Jurnal Kusta Anak

VOLUME 73, NUMBER 4
DECEMBER 2005
INTERNATIONAL JOURNAL OF LEPROSY

And Other Mycobacterial Diseases
Ofcial Organ of the INTERNATIONAL LEPROSY ASSOCIATION (Association Internationale contre la Lpre) (Asociacin Internacional de la Lepra)
INTERNATIONAL JOURNAL OF LEPROSY and Other Mycobacterial Diseases CONTENTS Volume 73, Number 4, December 2005
Images from the History of Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Original Articles Bikash Ranjan Kar, and C. K. Job. Visible Deformity in Childhood LeprosyA Ten-Year Study. - - - - - - - - - - - - - - - - - Jan H. Richardus, Abraham Meima, Corine J. van Marrewijk, Richard P. Croft, and Trevor C. Smith. Close Contacts with Leprosy in Newly Diagnosed Leprosy Patients in a High and Low Endemic Area: Comparison between Bangladesh and Thailand. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Jos L. Alfonso, Fernando A. Vich, Juan J. Vilata, and J. Terencio de las Aguas. Factors Contributing to the Decline of Leprosy in Spain in the Second Half of the Twentieth Century. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - C. Ajith, Sachin Gupta, Bishan D. Radotra, Sunil K. Arora, Bhushan Kumar, Sunil Dogra, and Inderjeet Kaur. Study of Apoptosis in Skin Lesions of Leprosy in Relation to Treatment and Lepra Reactions. - - - - - - - - Clinical Notes G. N. Malaviya. Myiasis in Leprosy. Page 239 243
249 258 269 277
---------------------------------------------------------------------------------------------------------------
Correspondence L. Oskam and S. Bhrer-Skula. A Need for Clarication of the Classication Criteria for Leprosy Patients. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Dr. Gelber and Colleagues Reply. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - News and Notes Leprosy in the Era of AIDS. Report of a Meeting at Robben Island, SA. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 2005 U.S.-Japan Meeting, Seattle - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Editorial Elimination of (the International Journal of) Leprosy
280 281 283 297 303 304 306 307
---------------------------------------------------------------------------------
Reviewers - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Special Grantors Index 2005

----------------------------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------------------------------------------------------------------------------
Volume 73, Number 4 Printed in the U.S.A. (ISSN 0148-916X)

and Other Mycobacterial Diseases
VOLUME 73, NUMBER 4 DECEMBER 2005
Images from the History of Leprosy

Child patients and staff (also patients) at Robben Island Leprosy Hospital, South Africa, circa 1920. This photo is from an album that belonged to Dr. Hans Peter Lie (18621945), a distinguished Norwegian leprologist, founding member of the board of the ILA, and an Associate Editor of the JOURNAL. This is a digital copy of the original black and white print in the collection of the Leprosy Museum in Bergen, Norway, a part of the Bergen Leprosy Archives, and of the UNESCO program Memory of the World. It was made available courtesy of Sigurd Sandmo, Curator.
241

DECEMBER 2005
Visible Deformity in Childhood Leprosy A 10-Year Study

Bikash Ranjan Kar, M.D., and C. K. Job, M.D.1
ABSTRACT
Deformity seen in children with leprosy has not often been studied, as the disease itself is less common in children. Deformity, being synonymous with the stigma of leprosy, is a definite social problem in children. In this study we have focused on the burden of deformity in children with leprosy, and various factors responsible for the deformities are discussed. We have observed an incidence of 10.5% of Grade II deformities in children with leprosy, which is very high compared to the community rate of 1.4%. Various factors which contributed signicantly to the deformities in our study were: increasing age of children, delay in accessing health care, multiple skin lesions, multibacillary disease, smear positivity, multiple nerve involvement, and reaction at the time of presentation to the hospital. Logistic regression analysis showed that children with thickened nerve trunks had 6.1 times higher risk of developing deformities compared to those who did not have nerve enlargement. Children with the above risk factors should be followed up more frequently so as to detect any deformity as early as possible.
RSUM
Les dformations observes chez les enfants souffrant de lpre ne sont gure tudies, peut-tre parce que la maladie chez ces derniers est elle-mme moins frquente. Les dformations associes la lpre, synonymes de stigmatisation, sont accompagnes de problmes sociaux bien dnis chez les enfants. Dans cette tude, nous nous sommes attachs dnir la prvalence des dformations chez les enfants atteints de lpre, et discuter les divers facteurs associs ces dformations. Nous avons observ une incidence de 10,5 % de dformations de grade II chez les enfants souffrant de la lpre, ce qui est trs lev par rapport au taux de 1, 4 % pour la communaut. Les facteurs ayant contribu de faon signicative aux dformations observes dans notre tude ont t une corrlation positive avec lge, le dlai accder aux soins de sant, des lsions cutanes multiples, une forme multibacillaire, un examen bactrioscopique positif du suc dermique, des atteintes nerveuses multiples et des ractions immunopathologique au moment de la prsentation lhpital. Une analyse de rgression logistique a montr que les enfants prsentant des troncs nerveux paissis avaient
1 Address for correspondence: Dr. Bikash Ranjan Kar, Department of Dermatology, Schieffelin Leprosy Research and Training Centre, Karigiri, Vellore 632106, India; e-mail: karbikash@hotmail.com
243
244
International Journal of Leprosy

un risque 6,1 fois plus lev de dvelopper des dformations que les enfants sans paississements des nerfs. Les enfants avec les facteurs de risque analyss plus haut devraient tre suivi plus frquemment an de dtecter les dformations le plus prcocement possible.
2005
RESUMEN
Las deformidades en los nios con lepra son poco estudiadas porque la lepra en s, es menos comn en los nios que en los adultos. La deformidad, sinnimo de estigma de la lepra, es un verdadero problema social entre los nios. En este estudio enfocado al estigma de la deformidad en los nios con lepra, se discuten varios factores responsables de la deformidad. Observamos una incidencia del 10.5% de deformidades del Grado II en los nios con lepra. Esta incidencia es muy alta comparada con la incidencia del 1.4% en la comunidad general. Varios factores contribuyeron signicativamente a la alta incidencia de deformidades en nuestro estudio, entre ellos: incremento en la edad de los nios, retardo en la procuracin de atencin mdica, lesiones mltiples en la piel, enfermedad multibacilar, positividad bacilar en la linfa cutnea, afectacin nerviosa mltiple, y estados reaccionales al momento de su ingreso al hospital. Los anlisis de regresin logstica mostraron que los nios con troncos nerviosos engrosados tuvieron un riesgo 6.1 veces mayor de desarrollar deformidades que los nios sin engrosamiento de los nervios. Se concluye que los nios con los factores de riesgo antes mencionados deben vigilarse con mayor frecuencia con el n de detectar cualquier deformidad tan pronto como aparezca.
Childhood leprosy is an indicator of endemicity of the disease (13). To the common man leprosy is well known because of the stigma that is still prevalent in the society. This stigma is almost synonymous with visible deformity. Major factors that contribute to deformity in various studies in adult leprosy patients are delay in diagnosis (10, 20), high bacillary load (16), multiple nerve enlargements (16), occurrence of reaction (19), and delay in provision of proper care of the disease. Therefore deformity is a preventable complication in the majority of patients. Deformity occurring in children is more distressing both socially and psychologically, as they have to live their whole life with stigma and in a hostile environment. This study was carried out to document the number of children with Grade II deformity as well as to identify the role of various risk factors contributing to its development.
MATERIALS AND METHODS All the new childhood leprosy cases (<15 yrs) registering at Scheiffelin Leprosy Research & Training Center, Karigiri, for 10 yrs (from July 1994 through June 2003) were analyzed retrospectively. Details were collected concerning each patient on admission included sex, age, WHO classication (2), skin smear status, duration of disease, involvement of nerves, occurrence of reaction, presence and nature of deformities and
the distribution of any deformities. For the purpose of this study, deformity was graded according to the WHO classication (25) and only patients with Grade II deformities were considered for analysis of risk factors. Nerve involvement was recorded according to the examining physicians perception of thickened nerves. Details of any previous therapy received, as well as subsequent treatment received from this institute, were also noted. All the patients received multidrug therapy as per WHO schedule (26, 14) and the progress of the disease was assessed in each patient. The odds ratio was calculated with 95% CI for each parameter while analyzing relative risk. Logistic regression analysis was done to determine the signicance of individual risk factors.
RESULTS In all, 6031 new patients were registered during the 10 yr period, from July 1994 through June 2003, including 275 (4.5%) children with leprosy. Of these, 163 (59.2%) were male and 112 (41.8%) were females. In age distribution, 13 patients were below 4 yrs, 71 were between 59 yrs and 191 were between 1015 yrs (Table 1). Comparing both the groups, i.e., those with visible deformities to those without visible deformities (Table 2), the majority of the deformities were in the age group of 1015 yrs, followed by those in the age range of 59 yrs. Deformities affecting children
73, 4
Kar and Job: Visible Deformity in Childhood Leprosy
245
TABLE 1. Distribution of children with leprosy by age and sex.

Age Group 04 59 1015 Total F (%) 7 (96.2) 31 (27.7) 74 (66.1) 112 (40.7) M (%) 6 (3.6) 40 (24.6) 117 (71.8) 163 (59.3) Total (%) 13 (4.7) 71 (25.8) 191 (69.5) 275 (100)
1015 yrs old was statistically signicant when compared to the other age groups (p <0.05). Considering disease classication, 238 children (86.5%) had paucibacillary (PB) disease whereas 37 (13.4%) had multibacillary (MB) disease. Of the 238 PB patients, 20 (8.4%) had deformities, whereas 9 of the 37 MB cases (24.3%) had deformities (p = 0.007). One hundred twelve children (40.7%) presented with single patch, 126 (45.8%) with 14 patches and the remaining 37 patients (13.4%) had multiple (5) patches. Skin smears were negative at the time of presentation for 252 of the patients (91.6%), and 23 (8.4%) patients had a positive skin smear. Deformities were seen in 24 of 252 (9.5%) smear-negative patients, whereas 5 out of 23 (21.7%) smear-positive patients had deformities (p = 0.06). The average age of onset of the disease among children was 9.49 2.9 yrs. Average duration of disease at the time of diagnosis was (1.09 0.8) yrs. Two hundred eleven
(76.7%) children presented to the hospital within one year of onset of the disease, whereas 64 (23.2%) patients presented after one year of onset of the disease. The majority of the patients with deformities (58.6%) attended the hospital before one year of onset of the disease whereas 42.4% attended after one year of the onset of the disease. In the group without any deformities, 193 (78.4%) presented for health care before one year of onset of the disease and the rest 53 (21.5%) presented after one year of onset of the disease. This difference was statistically signicant (p = 0.03) The common peripheral nerve trunks involved in leprosy are the ulnar, radial, median, lateral popliteal, posterior tibial and the facial nerves (17). Thickened nerve trunks were present in 110 out of 275 patients (40%) at the time of presentation, out of which 60 (21.8%) had only one major nerve involved, 22 (8%) had thickening of two major nerve trunks, and 28 (8.3%) had multiple (3 nerves) nerve involvement. The ulnar nerve was the commonest nerve trunk involved in 93 patients (33.8%), followed by the lateral popliteal nerve in 51 (18.55%) and the posterior tibial nerve in 12 (4.3%). Of the 110 children who presented with thickened nerve trunks, 24 (21.8%) had deformities, whereas only 5 of 165 patients (3.0%) who presented without any nerve thickening had visible deformities (p <0.001).
TABLE 2. Risk factors for deformity in children. Odds rations of risk factors, adjusted and unadjusted by logistic regression.
Risk Group Factors Age (years) Sex 1015 09 M F Duration >1 yr <1 yr MB/PB MB PB Smear Skin Smear + Smear Reaction Yes No Nerve Yes Enlargement No With Deformity 26 3 16 13 11 18 9 20 5 24 11 18 24 5 Deformity 165 81 147 99 53 193 28 218 18 228 44 202 86 160 O.R. 4.255 0.829 2.225 3.504 2.639 2.806 8.930 95% C.I. 1.25114.473 0.3821.799 0.9914.999 1.4538.443 0.8897.743 1.2386.357 3.29024.239 Without Unadjusted Adjusted by Logistic Regression O.R. 2.563 0.757 2.048 1.914 0.814 1.546 6.134 Signicance (P) 0.1570 0.5173 0.1137 0.2124 0.7457 0.3459 0.0009
246
2005
A reaction was present in 55 (20%) of the children at the time of admission, and 11 (20%) of these patients had deformities compared to 18 of 220 patients (8.1%) without reaction at the time of presentation (p = 0.02). All but one of the children had Type I reactions. Grade II deformity (per WHO grading (1, 27)) was present in 29 patients (10.5%), of whom 16 (55.1%) were male and 13 (44.9%) were female, a male to female ratio of 1.2:1. There was not a single child with deformity below 4 yrs of age. Three children with deformities (10.3%) were in the 59 yr range and the remaining 26 (89.7%) were in the age range of 1015 yrs. The average age of onset of the disease among the deformed children was 12.2 2.3 yrs, and the average duration of disease was 1.5 1.2 yrs. In 24 patients (82.7%), deformities involved the upper limbs whereas the lower limbs were involved in only 3 (10.3%). Deformities of the right hand were seen in 16 (55.1%) patients and left hand involvement was present in 10 of the patients (34.4%). During the 10 yrs studied, the distribution of deformities had shown no signicant change, although a slight downward trend can be seen in the new millennium (Table 3). This could be due to the increasing awareness of the public regarding leprosy.
DISCUSSION This study reveals that 4.5% of the new cases seen in the outpatient department of a referral hospital during the years 1994 to 2003 were children and that 10.5% of these had visible deformities. Deformities due to leprosy in children were observed more frequently in boys than in girls, although the difference was not statistically signicant. It is well known that leprosy is prevalent more frequently among males than in females, on the order of 2:1. Other studies of leprosy in childhood have shown equal incidence, or a slight preponderance of males (6, 22). In the present study the male to female ratio in the deformity group is 1.2:1 which tallies well with the observations made by Meima (10), Kushwah (8), Nilkantha Rao (15) and Bravo (2). The overall consensus among leprosy workers is that the deformity rate increases with an increase in age, as noted down in various studies by Bravo (2) and Noordeen
TABLE 3. Distribution of Grade II deformities in children by year of diagnosis.

Year 1995 1996 1997 1998 1999 2000 2001 2002 Total Total number of Number of children children with leprosy with deformities 13 22 23 42 48 34 37 16 235 4 3 4 4 4 2 2 1 24
(12), though this has not been studied specifically in children, and there is a greater chance of exposure to the disease process with advancing age. In this study the disability rates were observed to increase with increasing age of the children. There was no deformity in the 04 yr age group and the maximum frequency of deformity was observed in the 1015 yrs age range, which agrees with the observations made in the previous studies. Deformity affecting children with MB disease was signicantly more frequent than in PB cases. Studies by Schreuder, et al. (20), Saunderson, et al. (19), and Saha, et al. (18) have also found a signicantly higher incidence of nerve function impairment (NFI) in MB as compared to PB leprosy patients. High disability rates among MB patients is explained by widespread nerve damage after several years of exposure in lepromatous cases and due to extensive large nerve involvement in borderline cases compared to localized nerve involvement in PB cases. Children with MB leprosy are found to be at higher risk of reversal reactions as observed by Selvasekar, et al. (22) and require a regular follow-up and prompt interventions for the prevention of deformities. A higher bacterial load increases the risk of reactions and nerve damage leading to deformities. Roche, et al. (16) has also shown high incidence of neuropathy in patients with high BI similar to those reported by Noordeen (12) and Zhang (28), and can be explained by the widespread and progressive nature of smear positive type of leprosy. Other types of leprosy are more local-
73, 4
Kar and Job: Visible Deformity in Childhood Leprosy
247
ized and have a shorter evolution. Therefore early detection of the disease and treatment along with health education are very important for disability control. However in our study smear positivity was not found to be a signicant risk factor for development of deformities, which could be attributed to the very low number of smear-positive cases in the cohort. In this study the deformity rate was observed to increase with increased duration of the disease. Studies by Meima (10), Schreuder (20), Wittenhorst (25), and Nichols (11) have reported on increased NFI in patients presenting late after developing skin lesions. In our study of children, the average duration of the disease in those with deformities was over one year, and 40% of the patients with deformities attended the hospital after one year of onset of their disease. Noordeen (12) and Thappa (24) made similar observations. Early detection and early access to the health care system would help to prevent such deformities. Leprosy is a disease that particularly affects peripheral nerves. In our study peripheral nerve trunk involvement was seen in 40% of the patients at the time of presentation. Deformities seen among those with nerve trunk involvement were signicantly more frequent compared to those without nerve trunk involvement. The risk of developing deformity in those with nerve enlargement in our study was 6.13 times greater than those who did not have nerve enlargement. The ulnar nerve, lateral popliteal nerve and the posterior tibial nerve are the common nerves involved in our patients. Saha (18) and Sharma (23 ) have reported similar observations. Saunderson and colleagues (19) in their study had reported a relative risk of 2.8 and 6.5 respectively in case of 15 and more than 5 thickened nerves. Roche, et al. (16) has also reported similar ndings. Reactional episodes are reportedly less frequent in children (7) but in our series 20% of the children presented with reversal reactions at the time of admission. This is less than the value of 30% reported by Hammond (5). In another study by Jain and colleagues (6), 29.7% of the children developed reaction. Patients with reaction at the time of presentation had more deformities compared to those without reactions. Bravo
(2), Thappa (24) and Gupte (4) also noted reactions as signicant risk factors in the development of deformities in their studies. Saunderson (19) has reported a relative risk of 14.7 to develop nerve function impairment in patients with reversal reaction. Reactions can be managed with prompt use of corticosteroids and hence effectively managing them would help to decrease the deformity load, athough steroid use in children is likely to lead to many complications and to growth retardation. In our series the majority of the deformities involved the upper limbs, lower limbs being involved only in 10% of the patients. Sehgal (21) reported deformities of the hands in 85.7% of patients compared to deformities of the feet in 48.5%. MartinezDominiqueez (9) and Thappa (24) have found the hands and feet to be affected with equal frequency. However the high frequency of right hand involvement in our patients has a denite socioeconomic impact, as the dominant hand is disabled.
CONCLUSIONS There is no previous study reporting the deformity rate in children with leprosy, and this study found an incidence of 10.5% of grade II deformity. This is high, compared to the overall deformity rate in the community (3), but the results of this hospital-based study may not be comparable with the outpatient community. The unadjusted results indicate an increase in risk of deformity for the following factors: increasing age of children, delay in accessing health care, multiple patches, multiple nerve involvement, and reaction at the time of presentation to the hospital. Logistic regression analysis, however, reveals that nerve enlargement is the most signicant risk factor in children for the development of deformities. Children with these risk factors must be followed-up more closely so as to prevent deformities. Children presenting late, with stigmatizing deformity, indicates inadequate early case detection activities as well as reluctance on the part of children and their parents to come forward to access the health system. Promoting various ways to motivate parents to bring their children to the hospital at the earliest sign of leprosy is of utmost importance in the present situation.
248

REFERENCES
2005
1. BRANDSMA, J. W., VAN BRAKEL, W. H. WHO deformity grading: operational denitions. Lepr. Rev. 74 (2003) 366373. 2. BRAVO, L. L., and RATARD, R. C. Leprosy disabilities in the New Hebrides. Lepr. Rev. 48 (1977) 247260. 3. Current leprosy situation in India as on 1st Apr 2004, NLEP, Central Leprosy Division, Directorate of General Health Services, Nirman Bhavan, New Delhi. 4. GUPTE, M. D. Dapsone treatment and deformities. Lepr. India 51 (1979) 218235 5. HAMMOND, P. J., and RAO, P. S. S. The tragedy of deformity in childhood leprosy. Lepr. Rev. 70 (1999) 217219. 6. JAIN, S., REDDY, R. G., OSMANI, S. N., LOCKWOOD, D. N., and SUNEETHA, S. Childhood leprosy in an urban clinic, Hyderabad, India: clinical presentation and the role of household contacts. Lepr. Rev. 73 (2002) 248253. 7. JAYALAXMI, P., TONG, M., SING, S., and GANESPILLAI, T. Leprosy in children. Int. J. Lep. Other Mycobact. Dis. (1997) 695697. 8. KUSHWAH, S. S., GOVILA, A. K., and KUSHWAH, J. An epidemiological study of disabilities among leprosy patients attending leprosy clinic in Gwalior. Lepr. India 53 (1981) 240248. 9. MARTINEZ-DOMINGUEZ, V., BECHELLI, L. M., and PATWARY, L. M. WHO survey of disabilities in leprosy in northern Nigeria, Cameroon and Thailand. Int. J. Lepr. Other Mycobact. Dis. 34 (1996) 244254. 10. MEIMA, A., SAUNDERSON, P. R., GEBRE, S., DESTA, K., VAN OORTMARSSEN, G. J., and HABBEMA, J. D. Factors associated with impairment in new leprosy patients, the AMFES cohort. Lepr. Rev. 70 (1999) 189203. 11. NICHOLAS, P. G., CROFT, R. P., RICARDUS, J. H., WITTINGTON, S. G., and SMITH, W. C. Delay in presentation, an indicator for nerve function status at registration and for treatment outcome. Lepr. Rev. 74 (2003) 349356. 12. NOORDEEN, S. K., and SRINIVASAN, H. Epidemiology of disability in leprosy. Int. J. Lepr. Other Mycobact. Dis. 34 (1966) 170174. 13. NOUSSITOU, F. M., SANSARRICQ, H., WALTERS, J. Leprosy in children. Geneva: WHO, 1976. 1921. 14. Operational guidelines on case detection, treatment, follow-up and reporting formsNLEP, Leprosy division, Directorate of General Health Services, New Delhi, 1992.
15. RAO, N., SHANKAR, S. V., NARASIMHAMURTHY, D. P., VOMSTEIN, E., and MEERMEIR, H. Lepr. India 52 (1980) 236244. 16. ROCHE, P. W., LE MASTER, J., and BUTLIN, C. R. Risk factors for type I reactions in leprosy. Int. J. Lepr. Other Mycobact. Dis. 65 (1997) 450456. 17. SABIN, T. D., HECKET, E. R., and BRAND, P. W. Temperature along the course of certain nerves often-affected in leprosy. Int. J. Lepr. Other Mycobact. Dis. 42 (1974) 3842. 18. SAHA, S. P., and DAS, K. K. Disability pattern amongst leprosy cases in an urban area (Calcutta). Indian J. Lepr. 65 (1993) 305314. 19. SAUNDERSON, P. R., GEBRE, S., DASTA, K., BYASS, P., and LOCKWOOD, D. N. The pattern of leprosy related neuropathy in the AMFES patients in Ethiopia, denitions, incidence, risk factors and outcome. Lepr. Rev. 71 (2000). 20. SCHREDUER, P. A. The occurrence of reaction and impairment in leprosy: experience in leprosy control programme of three provinces in Northeastern Thailand, 19781995, neural and other complications. Int. J. Lepr. Other Mycobact. Dis. 66 (1998) 170181. 21. SEHGAL, V. N., and SHARMA, P. K. Pattern of deformities/disabilities in urban leprosy. Ind. J. Lepr. 57 183192. 22. SELVASEKAR, A., JOSEPH, G., KURIAN, N., MANIMOZHI, N., JESUDASAN, K., and RAO, P. S. S. Childhood leprosy in an endemic area. Lepr. Rev. 70 (1999) 2127. 23. SHARMA, P., KAR, H. K., BEENA, K. R., KAUR, H., and NARAYANAN. Disabilities in multibacillary leprosy patients before, during and after multidrug therapy. Indian J. Lepr. 68 (1996) 127136. 24. THAPPA, D. M., KAUR, S., and SHARMA, V. K. Disability index of hands and feet in patients attending an urban leprosy clinic. Indian J. Lepr. 62 (1990) 328337. 25. WITTENHORST, B., VREE, M. L., TEN HAN, P. B., and VELEMA, J. P. The national leprosy control programme of Zimbawe. Lepr. Rev. 69 (1998) 4656. 26. WORLD HEALTH ORGANIZATION. Report of a study group: chemotherapy of leprosy for control programmes. World Health Organization, 1982. Tech. Rep. Ser. 675. 27. WHO EXPERT COMMITTEE ON LEPROSY. WHO, 1998. Tech. Rep. Ser. 874. 28. ZHANG, G., LI, W., YAN, L., YANG, Z., CHEN, X., ZHENG, T., ET AL. An epidemiological study of survey of deformities and disabilities among 14257 cases of leprosy in 11 countries. Lepr. Rev. 64 (1993) 143149.
Close Contacts with Leprosy in Newly Diagnosed Leprosy Patients in a High and Low Endemic Area: Comparison between Bangladesh and Thailand
Jan H. Richardus1, Abraham Meima1, Corine J. van Marrewijk1, Richard P. Croft2, and Trevor C. Smith3
ABSTRACT
Background: As part of a larger study of the role of close contacts in the transmission of M. leprae, we explored whether the proportion of newly detected cases with a family history of leprosy differs with different incidence rates of leprosy in a population. Methods: Retrospective analysis was performed of contacts of all new leprosy patients diagnosed during a 10-yr period in well-established leprosy control programs in Thailand and Bangladesh. By our denition, a contact group consisted of the new case and of past and present cases who were relatives and in-laws of the new case. For a new case, the nearest index case was dened on the basis of time of onset of symptoms for the cases in the contact group, in combination with the level of closeness of contact between these cases and the new case. Three contact levels were distinguished. In Bangladesh these levels were dened as kitchen contact; house contact; and non-house contact. In Thailand comparable levels were dened as house contact; compound contact; and neighbor contact. Results: In Bangladesh 1333, and in Thailand 129 new patients were included. The average new case detection rate over 10 yrs was 50 per 100,000 general population per year in Bangladesh, and 1.5 per 100,000 in Thailand. In the high endemic area 25% of newly detected cases were known to belong to a contact group and were not the index case of this group, whereas in the low endemic area 62% of newly detected cases had these characteristics. The distribution of the nearest index cases over the three contact levels was comparable in both areas. Just over half of the nearest index cases were found within the immediate family unit (kitchen in Bangladesh; house in Thailand). Conclusion: The results indicate that in a low endemic area a higher proportion of newly detected leprosy cases have a family history of leprosy compared to a high endemic area. Different contact levels and their relative risks to contract leprosy need to be established more precisely. In high endemic situations the circle of contacts that should be surveyed may need to be wider than currently practiced.
RSUM
Contexte: Cet article est publi dans le cadre dune tude plus large sur le rle des contacts troits dans la transmission de la lpre. Elle sest attache explorer si la proportion de nouveaux cas dtects dans une famille ayant un historique de lpre diffre des taux varis dincidence de lpre dans une population. Mthodes: Une analyse rtrospective fut entreprise sur les personnes au contact de tous les nouveaux cas diagnostiqus de lpre, pendant une priode de 10 ans au sein de programmes bien tablis de contrle de la lpre en Thalande et au Bengladesh. Selon notre dfinition, un groupe contact consiste du nouveau cas accompagn des cas prsents et passs qui taient membre de la famille par naissance ou alliance. Pour un nouveau cas, le cas index le plus proche fut dni par le temps dapparition des symptmes des cas dans le groupe
Department of Public Health, Erasmus MC, University Medical Center Rotterdam, The Netherlands. The Danish-Bangladesh Leprosy Mission, Nilphamari, Bangladesh. 3 McKean Rehabilitation Center, Chiang Mai, Thailand. Address for correspondence: Dr. J. H. Richardus, Department of Public Health, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; e-mail: j.richardus@erasmusmc.nl
2
249
250

contact, combin ltroitesse de contact entre ces cas et le nouveau cas. Trois niveaux de contact furent distingus. Au Bengladesh, trois niveaux furent dnis : les contacts la cuisine , les contacts la maison et les contacts hors maison . En Thalande, des niveaux comparables furent dnis comme contact de la maison , contact composite et contact de voisinage . Rsultats: Au Bengladesh furent incorpors dans ltude 1 333 nouveaux patients et en Thalande, 129. Le taux de dtection moyen a t durant les dix annes de 50 pour 100 000 personnes de la population gnrale et par an au Bengladesh, et de 1,5 pour 100 000 en Thalande. Dans la rgion hautement endmique, 25% des cas nouvellement dtects taient connus comme appartenant un groupe contact et ne furent pas le cas index pour ce groupe, tandis que dans la rgion faiblement endmique, 62% des cas nouvellement dtects avaient ces caractristiques. La distribution des cas index les plus proches parmi les 3 niveaux de personnes contacts tait comparable dans les deux rgions. Un peu plus de la moiti des cas index fut trouv dans lunit familiale immdiate (la cuisine au Bengladesh et la maison en Thalande). Conclusion: Ces rsultats suggrent que, dans une rgion faiblement endmique, la proportion de cas de lpre nouvellement diagnostique ayant une histoire familiale de lpre, est suprieure celle rencontre dans une rgion hautement endmique. Il sera important de plus prcisment tablir les niveaux de contact et leurs risques relatifs contracter la lpre. Dans les situations de haute endmicit, le cercle des contacts qui devrait tre le sujet de surveillance pidmiologique devra tre plus large que ce qui est couramment pratiqu.
2005
RESUMEN
Panorama: Como parte de un estudio ms extenso sobre el papel que juegan los contactos cercanos en la transmisin de M. leprae, en este estudio exploramos si la proporcin de nuevos casos con historia familiar de lepra, diere de la tasa de incidencia de lepra en la poblacin general. Mtodos: Se hizo un anlisis retrospectivo de contactos de todos los nuevos pacientes de lepra diagnosticados durante un periodo de 10 aos en los programas de control de la lepra en Tailandia y Bangladesh. En nuestra denicin, un grupo contacto consisti de los nuevos casos y de los casos pasados y presentes que fueron familiares y parientes de los nuevos casos. Para un nuevo caso, el caso ndice ms cercano se deni sobre la base del tiempo de aparicin de los sntomas en los casos del grupo de contactos en combinacin con el grado de contacto entre estos casos y el nuevo caso. Se denieron tres niveles comparables de contacto. En Bangladesh: contactos de cocina, contactos domsticos, y contactos no domsticos; en Tailandia: contactos domsticos, contactos compuestos y contactos vecinos. Resultados: Se incluyeron 1333 nuevos casos en Bangladesh y 129 en Tailandia. La tasa promedio de deteccin de casos nuevos en 10 aos fue de 50 por 100,000 por ao en Bangladesh, y de 1.5 por 100,000 en Tailandia. En el rea de alta endemia, el 25% de los nuevos casos detectados pertenecieron a un grupo de contactos y no fueron el caso ndice en este grupo; en el rea de baja endemia, el 62% de los nuevos casos detectados tuvieron estas caractersticas. La distribucin de los casos ndice ms cercanos en los tres niveles de contacto fueron comparables en ambas reas. Un poco ms de la mitad de los casos ndice ms cercanos se encontraron dentro de la unidad familiar inmediata: cocina en Bangladesh, domsticos en Tailandia). Conclusin: Los resultados indican que, en comparacin con un rea de alta endemia, en un rea de baja endemia la mayor proporcin de los nuevos casos detectados tienen una historia familiar de lepra. Se concluye que es necesario establecer con ms precisin, los diferentes niveles de los contactos y sus riesgos relativos de contraer la enfermedad. En las situaciones de alta endemia tambin se requiere una vigilancia dentro del crculo de contactos, mayor que la que se realiza actualmente.
The importance of close contact with a leprosy patient in the transmission of M. leprae is well established. (2, 3, 5, 8) The relative risk for contracting leprosy is increased in people with contacts to leprosy patients
in comparison to those in an endemic population without known contacts. The relative risk is higher for contacts of multibacillary (MB) leprosy patients than of paucibacillary (PB) patients. (2, 5, 13) Close contacts are
73, 4
Richardus, et al.: Close Contacts in Leprosy
251
usually, but not necessarily, relatives living in the same house or compound. For this reason, leprosy control programs often conduct contact surveys when new leprosy cases are detected. By examining family and household members of a new case, there is a fair chance to nd other cases of leprosy as well. But questions remains about the extent to which these contacts contribute to transmission of M. leprae in a community, and whether contact tracing and treatment contribute to interruption of transmission of the mycobacterium in that community. Field workers and control program managers often suggest that with declining leprosy endemicity, the incidence in contacts of leprosy patients appears to decrease less rapidly than in the surrounding population. Apparently risk factors for the development of leprosy are distributed differently in contact groups of leprosy patients and the general population. The suggested change in the importance of contact however, has never been substantiated. Yet in order to design effective leprosy control measures, it is necessary to know the relative importance of (close) contacts in the total transmission of leprosy in different populations and the underlying mechanisms of this transmission. As part of a larger program studying the transmission of M. leprae, the objective of this study was to explore whether the proportion of newly detected cases known to be a close contact of a leprosy patient differs with different incidence rates of leprosy in a population. To this end, a high endemic area in Bangladesh is compared with a low endemic area in Thailand. All new patients during a certain period of time were investigated retrospectively with respect to the presence of leprosy patients (past and present) among relatives. In doing so, different levels of closeness of contact were distinguished. The ndings of this exploration are intended to contribute to the interpretation of a prospective epidemiological study of the transmission of M. leprae and the role of close contacts therein. (7)
METHODS Study area and leprosy control program I. Bangladesh. The study was conducted in the subdistrict of Jaldhaka, a highly endemic
area in Nilphamari District in northwest Bangladesh, with a population of approximately 250,000. The Danish-Bangladesh Leprosy Mission (DBLM) has been involved in leprosy control activities in this area since the late 1970s, and virtually all leprosy patients in the area are registered with DBLM. (9, 10) Jaldhaka was selected because of relatively good quality of contact surveys, which were conducted frequently by experienced staff. DBLM started contact surveillance in 1980 and this reached a good level of completeness by 1985. From 1987 onward, all persons sharing a kitchen with a newly detected case were to be examined once a year, for a period of 5 yrs in PB cases, and 10 yrs in MB cases. In 1994, the lengths of these periods were reduced to 2 and 5 yrs respectively. Active case nding also included school surveys, mass surveys and village checks. The study period was between 1987 and 1996 (10 yrs). II. Thailand. The study was conducted in the Province of Chiang Mai in Northern Thailand. The following nine districts were selected: Chiang Mai city, Saraphi, Sansai, Doi Saket, Sankampaeng, Mae Rim, Mae Taeng, Hang Dong, and San Patong. The total population of the study area is approximately 850,000. Before the 1970s, almost all new leprosy cases in northern Thailand were detected by the McKean Rehabilitation Center in Chiang Mai, an institution of the Church of Christ in Thailand. With the integration of leprosy control in general health services, new cases in the area were also detected by the Leprosy Control Division of Northern Thailand or by Public Health Services since the 1970s. (12) Patient data were collected from both the McKean Rehabilitation Center and the Leprosy Control Division of Northern Thailand. The study districts were chosen because of the proximity to Chiang Mai city and good coverage of leprosy control activities in the past. These activities included health education, contact surveys, and school surveys. Contact surveys of new patients living in remote areas were not always performed in the house or village. These patients were advised to bring close relatives to the clinic for inspection on signs of leprosy. The study period was between 1988 and 1997 (10 yrs).
252
2005
Denitions Leprosy case denition. Leprosy control programs in both Bangladesh and Thailand adhered to the WHO denition for a leprosy case as a person showing clinical signs of leprosy, with or without bacteriological conrmation of the diagnosis, and requiring chemotherapy. Following ofcial guidelines, the program denitions for PB and MB changed several times in both countries during the study period. For consistency in data analysis, cases with Ridley Jopling classication BB, BL and LL and all cases with positive skin smears (BI >0) have in this study been dened as multibacillary (MB), and all other cases as paucibacillary (PB). All new leprosy cases who originated from the study area and who were detected during the study period were included in the study. Denition of contact group and closeness of contact. For each new case, the group of patients that was considered consisted of the new case and of relatives and family-in-law. The relation of a patient from this contact group to the new case was in both study areas dened as: husband, wife, father, mother, son, daughter, brother, sister, grandparent, grandchild, uncle, aunt, nephew, niece, and cousin. There was also an other category, in which other relationships could be specied, such as a stepparent or stepchild. Three contact levels were distinguished. In Bangladesh these levels were dened as kitchen contact (the new case ate from the same kitchen as a given case from the contact group); house contact (new case lived in the same house, but ate from a different kitchen: a house in this area of Bangladesh can have several kitchens); and non-house contact (new case lived in a different house, possibly in another village or town). In Thailand comparable levels were dened as house contact (the new case lived in the same house); compound contact (new case lived in a separate house, but on the same compound); and neighbor contact (new case lived in the same village or town, but not in the same compound). The contact level was taken to be that level of contact between the new case and a given case from the contact group at the time the given case was known to have leprosy. No time limit was set regarding the past duration of the contact.
Index denition. The index case of any group of cases with contact to one another was dened as the case with the earliest onset of symptoms, with time of onset calculated as registration date minus reported duration of symptoms at registration. In case of incomplete information, the registration date was used to determine the index case. For newly detected cases, the following procedure was adopted: First, it was determined whether the newly detected case was the index case of his/her contact group or not. If not, the index cases of the three closeness-of-contact circles around the newly detected case were determined, in widening order. Next, the nearest index case for a newly detected case was dened to be the rst index case found, other than the new case him/herself. The procedure implies that the index case of the contact group and the nearest index case of the newly detected case were not necessarily the same case. The term index case in this study does also not necessarily imply that this case was responsible for actual transmission. All individuals in a contact group might have been infected by other (possibly unknown) leprosy patients in the community.
Data collection and analysis For each study area, a data collection form was developed in order to collect information not available in the existing patient databases. The additionally collected data included information on the new patients themselves (such as registration number, duration of symptoms, leprosy type and mode of detection) and information on contact related variables (such as contact status which indicates whether the new case belonged to a contact group or not, level of closeness of contact to the contact group members, registration numbers of the group members and relationships). The additional patient information was extracted from patient cards. In Bangladesh, contact information on kitchen level was mainly extracted from contact surveillance cards. Information at house and non-house contact level was usually not recorded during contact surveillance, and information for identication of possible index cases at these levels was re-
73, 4
253
TABLE 1. Distribution of new leprosy cases, for which the contact status was known, in Bangladesh and Thailand, by leprosy type, age and sex.
Study cases Bangladesh Sex n Leprosy type PB MB Unknown Age (in years) 014 1529 3044 45 Total 608 134 2 Male % 82 18 0 Female n 388 64 1 % 86 14 0 n 996 198 3 Total % 83 17 0 n 25 40 0 Male % 38 62 Thailand Female n 9 26 0 % 26 74 n 34 66 0 Total % 34 66
107 210 247 180 744
14 28 33 24 100
77 122 161 93 453
17 27 36 21 100
184 332 408 273 1197
15 28 34 23 100
6 17 17 25 65
9 26 26 38 100
3 6 5 21 35
9 17 14 60 100
9 23 22 46 100
9 23 22 46 100
trieved from other sources with the help of the responsible leprosy control ofcers. In Thailand information on contact surveys was incomplete. Therefore an additional effort was made to retrieve the necessary data from the patients themselves or immediate relatives through follow-up visits. In total 90 out of 129 (70%) eligible patients or their relatives were visited for the purpose of this study and the contact survey forms completed. The primary objective of the study was to identify leprosy patients (past and present) who had had contact with the newly detected leprosy patients. Enumeration of all eligible contact group members was often impossible, especially outside the closest contact level considered (Bangladesh: kitchen; Thailand: house), because data were collected retrospectively and spanned a long period of time. Data analysis was carried out with SPSS 7.0 for windows. Proportions were compared using the Chi-square test (p = 0.05).
RESULTS In Jaldakha (Bangladesh), a total of 1333 new patients were detected between 1987 and 1996. The contact status was known for 1197 patients (90% of the included population). For these patients the distribution of leprosy type, age by sex is given in Table 1. Of the 1197 cases, 744 (62%) were male
and 453 (38%) female, giving a male:female ratio of 1.6:1. There were 996 PB cases (83%) and 198 MB cases (17%). In 3 cases the leprosy type was unknown. The average new case detection rate over the period was 50 per 100,000 general population per year. In Chiang Mai (Thailand) a total of 129 new cases were detected between 1988 and 1997. Of these, the contact status was known for 100 patients (78% of the included population). The distribution of leprosy type, age by sex for these patients is given in Table 1. Of these, 65 (65%) were male and 35 (35%) female, giving a male:female ratio of 1.9:1. There were 34 PB cases (34%) and 66 MB cases (66%). The average new case detection rate over the period was 1.5 per 100,000 general population per year. In Bangladesh, the overall percentage of newly detected cases with a known index case was 25% only (Table 2). The percentage was highest in the youngest age group of 014 yrs (48%), and decreased to 28% in the age group 1526 yrs, and 19% and 16% in the age groups 30 44 and 3 45 yrs respectively. In the remaining cases (75%), no leprosy patients were found within the three dened contact levels. Also included in Table 2 is the distribution of the nearest index cases over the three levels of closeness of contact for the newly detected pa-
254
2005
TABLE 2. Status of newly detected cases (by age) in Bangladesh and Thailand, according to closeness of family contact to the nearest index case.
Age (in years) 014 Bangladesh n % 48 68 18 14 52 100 % 67 100 0 0 22 100 n 92 47 29 16 240 332 n 18 10 6 2 5 23 1529 % 28 51 32 17 72 100 % 78 56 33 11 22 100 n 76 32 24 20 332 408 n 14 11 3 0 8 22 3044 % 19 42 32 26 81 100 % 64 79 21 0 36 100 n 44 19 8 17 229 273 n 24 10 7 7 22 46 45 % 16 43 18 39 84 100 % 52 42 29 29 48 100 n 300 158 77 65 897 1197 n 62 37 16 9 38 100 Total % 25 53 26 22 75 100 % 62 60 26 14 38 100
Contact to known index 88 Kitchen contact 60 House contact 16 Non-house contact 12 No contact to known index 96 Total 184 Thailand Contact to known index House contact Compound contact Neighbor contact No contact to known index Total n 6 6 0 0 3 9
tients with known positive family history. The nearest index cases were found at kitchen level in 53% of the cases. The percentage of kitchen contact was highest in the youngest age group (68%), and decreased to 51% in the age group 1529 yrs, and to 42% and 43% in the age groups 3044 and 45 yrs respectively. In Thailand, the overall percentage of newly detected cases with a known index case was as high as 62% (Table 2). The percentage was highest in the age groups 014 yrs (67%) and 1529 (78%), and decreased slightly to 64% and 52% in the age groups 30 44 and 45 yrs respectively. In the remaining cases (38%), no leprosy cases were found within the three dened contact levels. In cases with known positive family history, the nearest index cases were found at house level in 60% of the cases. The percentage of house contact was highest in the youngest age group (100%), and decreased to 56% in the age group 1529 yrs, to 79% in the age group 30 44 yrs, and to 42% in the group 45 yrs and older. The difference in percentage of newly detected leprosy cases with contact to a known index case between Bangladesh (overall
25%) and Thailand (overall 62%) is statistically signicant (Chi-square test: p < 0.05).
DISCUSSION The objective of this study was to explore whether the proportion of newly detected leprosy cases with a family history of leprosy is higher in a population with a lower incidence rate of leprosy. To this end, a retrospective study was undertaken in two areas; northwest Bangladesh with a high new case detection rate of approximately 50 per 100,000 per year, and northern Thailand with a low new case detection rate of approximately 1.5 per 100,000 per year. This study shows that in the chosen high endemic area approximately only 25% of newly detected cases have a known index case within the family, whereas in the chosen low endemic area this proportion is as high as 62%. The distribution of nearest index cases over three different contact levels was comparable in both areas. Just over half of the nearest index cases are found within the immediate family unit (kitchen in Bangladesh; house in Thailand). In Bangladesh, children aged 014 yrs most often have known index cases among rela-
73, 4
255
tives, with the nearest index primarily within the immediate family unit. The proportion with a known index case decreases over the age groups. Although less marked, in Thailand there is also a difference over the age groups. However, there is an important difference in age distribution of the newly diagnosed patients in both countries, with a higher average age in Thailand. This is probably a reection of the level of transmission. In Thailand transmission has been low in the past two decades, and many new patients are likely to have been infected in the past and have had long incubation periods. Increasing average age of newly detected patients with the decline of leprosy incidence has been described previously. (1, 4) Obviously, there are many limitations to direct comparisons between countries. There are geographical, socio-economic and cultural differences, as well as differences with regard to the provision of health services in general and leprosy control in particular. All these differences will have effect on transmission patterns and the detection of leprosy. An important difference, for instance, between the countries is the proportion of MB patients. In Bangladesh this is approximately 20%, while in Thailand over 60% are MB. Such differences between countries have been observed before, and are possibly explained by genetic differences. (1) With a higher proportion of patients with MB leprosy, one might expect transmission of M. leprae in the population to be more intensive, resulting in a higher endemic level of leprosy. However, this is not consistent with our ndings of proportion of MB and the leprosy incidence in the two populations studied, which perhaps might be due to a difference between the individuals in these populations with respect to susceptibility to developing leprosy. There are also important limitations in the methodology of the study. It is a retrospective analysis of routine data. The exact number of family members with past or present leprosy at the beginning of the observation period, or developing leprosy during this period, could not be established prospectively. Also denominator data, the total number of eligible family members within the dened contact levels per newly detected patient, are absent. Denominator information, however, is not strictly neces-
sary when establishing the presence of family members with past or present leprosy for a newly detected patient. There are differences in average size of the contact groups between the countries, with households in Bangladesh tending to be larger and thus theoretically with a higher chance of leprosy cases in households. This difference in fact strengthens our ndings. Lack of denominator information makes interpretation of relative risks for developing leprosy in and outside leprosy contact groups less straightforward, but this kind of calculation was outside the scope of the study. Finally, case detection efforts were more intensive at the closest contact level (Bangladesh: kitchen; Thailand: house) compared to the other levels, leading to a possible underestimation of numbers of cases at these other levels. While taking these limitations into account, we believe that the very large difference in newly detected leprosy patients with a known index case between both areas represents a valid observation regarding this proportion in different endemic situations. Differences in the leprosy control program and data collection between the two areas alone would not lead to such great difference in outcome (25% versus 62%), suggesting a genuine difference between the areas. However, the exact extent of the difference can only be established if adjustment for these factors would be possible. The implications of our ndings for transmission of M. leprae in general are important, but not easily interpreted. It is likely that in a high endemic area such as northwest Bangladesh, most transmission in the population occurs outside close contacts of known leprosy patients. Up to 75% of new patients in Jaldakha district did not have any known index case. But the contact denition used in this study was strict, consisting of (close) relatives only. In a retrospective study over 25 yrs in a high endemic village of 2283 inhabitants in Sulawesi, Indonesia, it was shown that new patients could also be linked to previous cases other than from their own household. Besides household index cases in 28% of new cases, there were rst neighbor cases in 24%; second neighbor cases in 12%; cases within the social network in 10%; and cases among relatives living elsewhere in
256
2005
5% of the new cases. Thus 79% of all new cases could be linked to an index case. (14) Leprosy cases are not distributed evenly among the population, but are known to cluster. Our observation of a high percentage of relatives with leprosy in Thailand compared to Bangladesh supports the hypothesis that the relative importance of clustering becomes stronger with declining endemicity of leprosy in a population. The challenge for leprosy control is to determine which contact levels need to be surveyed in order to signicantly interrupt transmission of M. leprae in the population. In order to do so, it appears that in high endemic situations, apart from early case nding, the circle of contacts to be surveyed needs to be wider than currently practiced. Also, the different contact levels and their relative risks to contract leprosy need to be dened more precisely. Lessons can possibly be learned from tuberculosis control, where contact tracing is performed according to the stone-in-the-pond principle.(6, 15) If the prevalence of tuberculosis within close proximity of a new case exceeds an expected level, the survey is extended to a next, wider range of contacts. This approach is continued until the prevalence of tuberculosis cases in the expanding circle of contacts reaches the prevalence level of the general population. The nding in Thailand that the nearest index case is most often found in very close proximity to the patient could indicate that with declining incidence of leprosy, the extent of contact surveys could be reduced. From a methodological point of view this study represents only a limited attempt to gain insight in the epidemiology of contact transmission. Further research, preferably prospective and with precise denitions of contact levels, is needed to understand the role of contact in leprosy under various endemic circumstances, underlying patterns of transmission, and implications for leprosy control. The effect of interventions targeting contacts such as chemoprophylaxis, on the overall transmission of M. leprae in a population also needs clarication.(11) Such a study is currently underway in Bangladesh.(7) The application of advanced techniques of epidemiological modeling is invaluable to help analyze and interpret existing and new data in this area. The result
of the present study is just one step towards this end.

Acknowledgment. We thank Mr. S. Chowdry of DBLM in Bangladesh, and Mrs. Orowan Buntham and Ms. Janet Greenleaf of McKean Rehabilitation Center in Thailand for their invaluable assistance in the eldwork of the study. This study was made possible by a grant from the American Leprosy Missions (ALM) and from Netherlands Leprosy Relief (NLR).
REFERENCES
1. FINE, P. E. Leprosy: the epidemiology of a slow bacterium. Epidemiol. Rev. 4 (1982) 161188. 2. FINE, P. E., STERNE, J. A., PONNIGHAUS, J. M., BLISS, L., SAUI, J., CHIHANA, A., MUNTHALI, M., and WARNDORFF, D. K. Household and dwelling contact as risk factors for leprosy in northern Malawi. Am. J. Epidemiol. 146 (1997) 91102. 3. GEORGE, K., JOHN, K. R., MULIYIL, J. P., and JOSEPH, A. The role of intrahousehold contact in the transmission of leprosy. Lepr. Rev. 61 (1990) 6063. 4. IRGENS, L. M. Leprosy in Norway. An epidemiological study based on a national patient registry. Lepr. Rev. 51 (1980) ixi, 1130. 5. JESUDASAN, K., BRADLEY, D., SMITH, P. G., and CHRISTIAN, M. Incidence rates of leprosy among household contacts of primary cases. Indian J. Lepr. 56 (1984) 600614. 6. MOET, F. J., MEIMA, A., OSKAM, L., and RICHARDUS, J. H. Risk factors for the development of clinical leprosy among contacts, and their relevance for targeted interventions. Lepr. Rev. 75 (2004) 310326. 7. MOET, F. J., OSKAM, L., FABER, R., PAHAN, D., and RICHARDUS, J. H. A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients: design, methodology and recruitment ndings of COLEP. Lepr. Rev. 75 (2004) 376383. 8. RAO, P. S., KARAT, A. B., KALIAPERUMAL, V. G., and KARAT, S. Transmission of leprosy within households. Int. J. Lepr. Other Mycobact. Dis. 43 (1975) 4554. 9. RICHARDUS, J. H., and CROFT, R. P. Estimating the size of the leprosy problem: the Bangladesh experience. Lepr. Rev. 66 (1995) 158164. 10. RICHARDUS, J. H., MEIMA, A., CROFT, R. P., and HABBEMA, J. D. Case detection, gender and disability in leprosy in Bangladesh: a trend analysis. Lepr. Rev. 70 (1999) 160173. 11. SMITH, C. M., and SMITH, W. C. Chemoprophylaxis is effective in the prevention of leprosy in endemic countries: a systematic review and metaanalysis. MILEP2 Study Group. Mucosal Immunology of Leprosy. J. Infect. 41 (2000) 137142. 12. SMITH, T. C., and RICHARDUS, J. H. Leprosy trends in northern Thailand: 19511990. South-
73, 4
257
east Asian J. Trop. Med. Public Health 24 (1993) 310. 13. SUNDAR RAO, P. S., JESUDASAN, K., MANI, K., and CHRISTIAN, M. Impact of MDT on incidence rates of leprosy among household contacts. Part 1. Baseline data. Int. J. Lepr. Other Mycobact. Dis. 57 (1989) 647651.
14. VAN BEERS, S. M., HATTA, M., and KLATSER, P. R. Patient contact is the major determinant in incident leprosy: implications for future control. Int. J. Lepr. Other Mycobact. Dis. 67 (1999) 119128. 15. VEEN, J. Microepidemics of tuberculosis: the stone-in-the-pond principle. Tuber. Lung Dis. 73 (1992) 7376.
Factors Contributing to the Decline of Leprosy in Spain in the Second Half of the Twentieth Century
Jos L. Alfonso1, Fernando A. Vich2, Juan J. Vilata3, J. Terencio de las Aguas4
ABSTRACT
Background: Leprosy is a chronic infectious disease that is considered to be declining, though it still remains prevalent in many parts of the world. A study was made to explore the health and socioeconomic factors that most inuenced the trend of the disease in a typical Mediterranean country. Materials and methods: An ecological study was conducted, investigating possible social, economic and health factors related to the evolution of leprosy incidence. The time period considered was 50 yearsthe second half of the twentieth century in Spain. Results: The variables showing the strongest correlation to evolution of the incidence of the disease were employment, the number of physicians, and the gross domestic product (GDP), with negative coefcientswhile tuberculosis showed a positive coefcient. However, the GDP showed the highest coefcient (0.5). The model that best explained the evolution of leprosy over the last 50 years comprised a 6-year lag period between the socioeconomic factors and the incidence of leprosyexplaining 57% of the data obtained. The annual decrease in leprosy incidence was 1.6%. Conclusions: Socioeconomic development, assessed in terms of the GDP, was the most important factor in explaining the evolution of leprosy incidence.
RSUM
Contexte: La lpre est une maladie chronique considre comme tant sur le dclin, bien quelle reste encore prvalente dans plusieurs rgions du monde. Le but de cette tude fut dexplorer dans un pays mditerranen typique, les facteurs sanitaires et socio-conomiques qui ont eu le plus dimpact sur lvolution pidmiologique de la maladie. Matriel et mthode: Une tude cologique tudiant les facteurs sanitaires, conomiques et sociaux en relation avec lvolution de lincidence de la lpre fut mene en considrant un intervalle de temps de 50 annes - la deuxime moiti du 20me sicle - en Espagne. Rsultats: Les variables qui ont montr les corrlations les plus robustes avec lvolution de lincidence de la maladie furent lactivit, le nombre de mdecins, et le Produit Intrieur Brut (PIB), avec des coefcients ngatifs - tandis que la tuberculose montrait un coefcient positif. Cependant le PIB a montr le plus haut coefcient (0,5). Le modle qui a le mieux prdit lvolution de la lpre au cours de ces 50 dernires annes fut celui ayant un dcalage de 6 annes entre les facteurs socio-conomiques et lincidence de la lpre - donnant une explication pour 57% des donnes acquises. Le taux de diminution annuel de lincidence de la lpre a t de 1,6%. Conclusions: Le dveloppement socio-conomique, valu laide du PIB, tait le facteur le plus important pour expliquer lvolution de lincidence de la lpre.
RESUMEN
Background: Aunque la lepra es una enfermedad infecciosa crnica en decaimiento, an permanece vigente en muchas partes del mundo. El presente, es un estudio realizado con el n de explorar los factores de salud y sanitarios que tienen ms inuencia en la tendencia de la enfermedad en un tpico pas Mediterrneo. Servicio de Medicina Preventiva, Consorcio Hospital General Universitario de Valencia. Centro Salud Pblica de Manises, Consellera de Sanidad de la Comunidad Valenciana. 3 Servicio de Dermatologa, Consorcio Hospital General Universitario de Valencia. 4 Advisor to the International Leprosy Association (ILA). Name and address to whom requests for reprints should be addressed: Jos L. Alfonso MD, Ph.D., Servicio de Medicina Preventiva, Consorcio Hospital General Universitario de Valencia, Departamento de Medicina Preventiva y Salud Pblica, Universidad de Valencia, Blasco Ibez 15, 46010 - Valencia (Spain); e-mail: jose.l.alfonso@uv.es
2 1
258
73, 4
Alfonso, et al.: Factors Contributing to the Decline of Leprosy

Material y Mtodos: Se realiz un estudio ecolgico en el cual se investigaron los posibles factores sociales, econmicos y sanitarios relacionados con la evolucin de la incidencia de la lepra. El periodo de tiempo considerado fue de 50 aos -la segunda mitad del siglo XX en Espaa. Resultados: Las variables que mostraron alta correlacin con la evolucin de la incidencia de la enfermedad fueron el desempleo, el nmero de mdicos, y el producto domstico bruto (PDB), con coecientes negativos -la tuberculosis, en cambio, mostr un coeciente positivo. El PDB mostr el coeciente ms alto (0.5). El modelo que mejor explic la evolucin de la lepra en el periodo de 50 aos analizado comprendi un periodo lag de 6 aos entre los factores socioeconmicos y la incidencia de lepra - explicando el 57% de los datos obtenidos. La disminucin anual en la incidencia de lepra fue del 1.6%. Conclusiones: El desarrollo Socioeconmico, medido en trminos del PDB, fue el factor ms importante para explicar la evolucin de la incidencia de lepra.
259
Leprosy is a chronic infectious disease produced by Mycobacterium leprae that results from an imbalance between the bacterium and the host immune response. With a history that goes back three thousand years, leprosy is one of the oldest diseases known. For centuries, the care of leprosy patients lacked a scientic basis. Affected individuals were isolated from society and from their couples, and diseased children were separated from their families. Later, scientic evidence came to show that in some cases isolation is not particularly effective, and that no more than 5% of exposed individuals actually develop the disease. In its third regional conference of leprosy, the World Health Organization (WHO) proposed elimination of the disease as a health problem in all countries by the year 2005. However, the number of new cases documented by the WHO in 2003 totaled 513,798, while the prevalence of the disease that same year was 457,792 cases. In other words, leprosy is still far from being controlled, and work remains to be done before the disease can be relegated to the history books. The majority of cases of leprosy are found in Southeast Asia. The present annual incidence of the disease worldwide is almost one new patient per minute, and is fundamentally attributable to developing countries like Indiawith 70% of all such cases. Some studies have even reported the incidence of the disease to be increasing in these parts of the world (25). One of the principal factors relating to control of the disease, and which was already suspected many years ago, is the social and economical development of society. In this context, it has been shown that economical development is accompanied by
important improvements in patient quality of life (QoL), and a decrease in mortality (3). Although the incidence of leprosy in Spain has decreased greatly, thanks to factors such as economical development, and the prevalence of the disease has also decreased in recent years, a minimum number of fundamentally imported cases remain (7, 21), as a result of which it is difcult to speak of actual eradication of the disease. The present study explores the inuence of socioeconomic factors in the evolution of leprosy in Spaina country illustrative of the Mediterranean setting of the disease in the last 50 years.
MATERIALS AND METHODS Two leprosy information sources have been used: the Spanish State Leprosy Registry (Registro Estatal de Lepra), a database of the National Epidemiology Center (Centro Nacional de Epidemiologa) (6), located in the Instituto de Salud Carlos III in Madrid, and which came into operation in 1991; and the Annual Statistical Bulletin (Anuario Estadstico) of the National Institute of Statistics (Instituto Nacional de Estadstica, INE) (11) for prior data up until the year 1950. Economic (national income) data and their provincial distribution were in turn obtained from the publications of the Service of Studies of the Banco de Bilbao Vizcaya (1) (presently BBVA). Demographic information was collected from the Natural Variations of the Spanish Population (Movimiento Natural de la Poblacin Espaola) (12), and from the Spanish population census (13), both being publications of the INE. The latter document reects the data corresponding to the population censuses conducted every decade.
260
2005
The variables derived from these information sources were classied into four groups. Variables to be included were required to remain stable in terms of both the information sources and the way in which they were obtained during the 50-year period covered by the study. The data were obtained at the provincial level, followed by grouping according to the different Spanish Autonomous Communities. The selected socio-demographic variables were: the proportion of rural population (i.e., the percentage of the population not living in the capital versus the total population), the employment rate with respect to the total population (per thousand), the emigration rate, the schooling rate (dened as the proportion of the population in the 614 years age range in school versus the total population), and the unemployment rate. As economical variables, the gross domestic product (GDP) per inhabitant was recorded, along with the product per educational and health sectors. The magnitudes of the economical variables were determined for each year at constant price, using the GDP deactor, and employing the 1986 prices as reference (expressed in euros). The variable corresponding to health care resources was the proportion of physicians per 1000 inhabitants, and the health variables were the infant mortality rate, the incidence of leprosy per 100,000 inhabitants, and the incidence of respiratory tuberculosis (TBC) per 1000. Base 100 index numbers were used for both the GDP and the incidence of leprosy and TBC. Retrospectively, the 5-year elasticity was calculated based on the ratio between the 5-year incidence variations and the economical variations corresponding to the same period. The statistical analyses included, a complete study of the type of distribution, followed by simple and multiple regression, residues analysis with the KolmogorovSmirnov test for one sample, and correlation between typied residues. Likewise, the co-linearity between variables was studied based on eigenvalues, the condition index and proportions of variance. Finally, tting was carried out based on logarithmic transformation of the data and co-linearity study via the tolerance, variance ination factor (VIF), and also the study of
residuesincluding histograms of typied residues and dispersion plots. In practice, exact co-linearity is rarely observed in studies of this kind, though socalled near co-linearity is seen with some frequency (i.e., some variable is found to be nearly a linear combination of another variable/s). We have jointly applied the method proposed by Kleimbaum (18) and the criteria of Belsley (2). The latter author proposes utilization of the condition indices and proportion of variance decomposition to conduct the analysis of co-linearityestablishing a value of 0.5 as the upper proportion threshold, as a result of which the conclusions are nally reached as follows: high condition indices (over 30) indicate the number of co-linearities, and their magnitude reects their relative importance. If a given component possesses a condition index of over 30, and two or more variables present a high proportion of variance in the latter, then these variables are considered to be co-linear. Taking into account the long incubation period of leprosy (generally between 210 years) (26), the incidence rates were studied with the socioeconomic status of the population 110 years previously, i.e., at the time of contagion.
RESULTS Regarding the mean annual incidence rates for leprosy, established for 5-year periods and 100,000 inhabitants during the period 19502000 (Fig. 1), and the interannual variations (Table 1), important differences are seen among the different regions. In effect, while most regions show reductions at a rate of 1% annually, some actually end up showing increasessuch as the Balearic Islands, Navarra, and the Basque Country. Andaluca, in the south of the country, for many years exhibited the highest leprosy incidence for that period, though it is also the Spanish Autonomous Community with the greatest interannual reductions (almost 4.5%), followed by Galiciawith reductions of 3%and the Canary Islands and Valencia (2%). Overall, Spain showed a decrease of 1.6% annually over this period of 50 years. In Table 2 the longitudinal study by regions presents the mean values from 1950 to 2000 for the variables considered in the study. Differences between regions are clearly seen, with important variability in
73, 4
TABLE 1. Mean annual incidence (per 100,000) and inter-annual variation of leprosy in Spain by communities and nationwide, 19502000.
5660 1.79 0.36 0.21 0 1.61 0 0.21 0.4 0.73 0.63 1.53 0.38 0.04 0.77 0.25 0.33 n.a. 0 0.75 1.24 0.18 0.2 0 0.42 0 0.25 0.46 0.13 0.24 0.94 0.19 0.04 0.5 0 0.36 n.a. 0 0.44 1.03 0.18 0.1 1.2 0.66 0 0.33 0.54 1.26 0.72 0.48 0 0.09 0 0 0.31 n.a. 0 0.58 0.23 0.09 0.1 0 0.09 0 0.04 0.12 1.09 0.33 0.35 0.08 0.11 0.12 0.22 0.11 n.a. 0 0.29 0.79 0 0 0.16 0.38 0 0.08 0.18 0.76 0.33 0.73 0.11 0.23 0.89 0.41 0.05 n.a. 0 0.4 1.38 0 0 0.15 2.08 0 0.12 0 0.62 0.99 0.48 0.15 0.02 0.52 0 0.14 n.a. 0 0.57 0.89 0.08 0 0 1.3 0 0 0.12 0.03 0.42 0.28 0.15 0.06 0.2 0 0 n.a. 2.25 0.3 0.38 0 0 0 0.31 0 0 0.18 0.02 0.23 0 0.11 0.04 0 0 0 n.a. 0.73 0.13 0.2 0.17 0 0.67 0.31 0 0 0.18 0.26 0.08 0 0.26 0.1 0.09 0.19 0.1 0.38 0 0.16 6165 6670 7175 7680 8185 8690 9195 962000 %Variation* 4.42 0.02 0 1.34 1.9 0.5 0.2 0.72 1.14 1.92 1.32 1.94 0.22 3 0.38 0.02 n.a. 0 1.6
5155
ANDALUCA ARAGN ASTURIAS BALEARIC ISLANDS CANARY ISLANDS CANTABRIA CASTILLA LEON CASTILLA LA MANCHA CATALONIA VALENCIAN COMMUNITY EXTREMADURA GALICIA MADRID MURCIA NAVARRA BASQUE COUNTRY RIOJA CEUTA/MELILLA SPAIN
2.41 0.18 0 0 1.26 0.25 0.1 0.54 0.83 1.04 0.66 1.23 0.21 1.59 0 0.09 n.a. 0 0.96
Note: * = % inter-annual variation; n.a. = not available.
261
262
2005
FIG. 1. Mean 5-yearly incidence rates for leprosy in Spain in the second half of the Twentieth Century. Note: Incidence rate = cases per 100,000.
both the economical values (with a nearly three-fold difference between minimum and maximum), and particularly the incidence of tuberculosis (with an up to 5.5fold difference) and leprosythe latter being the parameter showing the largest differences (up to 25-fold). In relation to this latter variable, the regions with the highest gures were Andaluca and Extremadura, along with Catalonia and the Canary Islands. On the other hand, in relation to the 5-year means of the variables considered in the study by regions (Table 3), all Autonomous Communities were seen to exhibit a relatively regular evolution with gradual decreases or increasesthe sole exception being emigration, which proved to be somewhat irregular. In reference to 100 base index numbers of the Gross Domestic Product (GDP) and incidences for leprosy and tuberculosis in
Spain (Table 4), a 7.23-fold economical increase was observed since the year 1950 this gure being similar to the reduction in the incidence of leprosy in the same period of time (7.4-fold). In turn, tuberculosis was seen to have decreased in incidence 3.7fold in the course of the period 19502000. On the other hand, the mean annual variation in GDP was seen to be 14%, while the mean variations for leprosy and tuberculosis were quite similar (1.66 and 1.57, respectively). The proportional variations taking economical growth as reference base revealed that leprosy varied 0.06 units for each proportional unit economical increment. The situation was similar in the case of tuberculosis (0.07). Considering that economical status exerts an inuence at the time of actual contagion, even though clinically manifest leprosy only appears some years later, we evaluated
73, 4
TABLE 2.
EmployInfant UnemSchooling Physicians ment mortality ployment GDP 3174 4503 4281 6217 4360 4442 3512 3037 5986 4738 2472 3382 6601 3682 5208 5719 4799 2952 70 54 85 60 64 68 69 85 63 70 86 85 28 70 69 63 63 0 87 124 98 190 125 109 103 67 193 123 69 89 246 87 179 168 125 99 30.78 38.8 38.61 44.54 34 39.1 37.41 34.33 40.38 38.58 32.42 41.7 37.76 33.68 40.04 37.92 41.65 22.03 12.59 10.69 10.82 12.14 12.68 12.07 12.84 11.99 10.72 11.65 11.7 11.69 10.84 12.86 11.78 11.38 11.86 10.86 2.02 2.87 2.21 2.19 1.79 2.34 2.29 1.59 2.57 2.15 1.56 1.72 3.45 1.89 2.7 2.48 2.25 1.63 0.49 0.35 0.34 0.25 0.45 0.4 0.64 0.62 0.21 0.28 0.69 0.43 0.31 0.45 0.41 0.27 0.44 0.47 40.01 19.47 28.63 31.31 37.97 25.75 21.28 22.39 27.8 34.23 32.86 24.52 29.17 24.22 24.15 32.31 16.99 27.33 Rural Health population product TBC 0.39 0.24 0.6 0.18 0.12 0.48 0.35 0.23 0.21 0.18 0.34 0.36 0.11 0.25 0.35 0.25 0.26 0.41
Annual rate per 100,000 inhabitants for all Spanish regions, 19502000.
Incidence of leprosy 1 0.12 0.06 0.22 0.82 0.02 0.12 0.29 0.54 0.47 0.58 0.26 0.09 0.43 0.11 0.13 0.04 0.29
Emigration
ANDALUCA ARAGN ASTURIAS BALEARIC ISLANDS CANARY ISLANDS CANTABRIA CASTILLA LEN CASTILLA LA MANCHA CATALONIA VALENCIAN COMMUNITY EXTREMADURA GALICIA MADRID MURCIA NAVARRA BASQUE COUNTRY RIOJA CEUTA/MELILLA
4.84 4.76 2.94 2.4 4.77 3.65 5.59 4.97 5.46 4.08 6.61 7.61 3.63 3.29 5.04 5.58 4.82 7.78
263
TABLE 3.
Infant Unemployment mortality GDP() 1583 1946 2279 2984 3619 4142 4613 5426 6203 9746 13027 72.14 70.43 68.86 66.31 64 63.37 62.8 63.09 63.36 64.29 66.01 62.78 72.29 81.03 107.17 130.71 150.68 168.63 166.45 164.36 184.92 215.7 0.89 0.59 0.31 0.21 0.12 0.13 0.15 0.16 0.18 0.2 0.194 TBC 1.28 1.01 0.76 0.56 0.37 0.22 0.09 0.08 0.08 0.06 0.04 6.25 5.22 4.26 4.59 4.88 26.63 46.2 54.51 59.59 62.16 38.45 %Rural population Health product() Incidence of leprosy 0.27 0.14 0.15 0.094 0.117 0.05 0.039 0.127 0.032 0.009 0.032
Corresponding annual rates for each of the factors analyzed in Spain, 19502000.
264
Year 7.38 9.92 12.27 11.68 11.16 13.1 14.85 13.59 12.38 9.51 6.32 1.04 1.1 1.15 1.25 1.34 1.98 2.56 3.24 3.89 4.12 4.42
Emigration
Employment
Schooling Physicians
1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000
1.97 1.51 1.09 8.17 14.55 9.52 5 2.57 0.23 4.65 4.27
41.09 40.43 39.83 39.04 38.33 35.73 33.4 33.69 33.97 35.82 37.79
Notes: Units as for Table 2. () = Euros. GDP and Health Product in constant prices based on 1986 and GDP deator.
TABLE 4. Index numbers corresponding to the evolution of leprosy and tuberculosis in relation to gross domestic product (GDP) in Spain, 19502000.
Incidence of leprosy 100 51.85 55.56 34.81 43.33 18.52 14.44 47.04 11.85 3.33 11.85 48.15 3.71 20.75 8.52 24.81 4.08 32.6 35.19 8.52 8.52 1.66 Leprosy Index number 2.10 0.18 0.47 0.21 0.75 0.14 0.64 0.72 0.04 0.04 0.06 Annual Leprosy variation variation/ecoleprosy nomic variation TBC TBC Index number 0.89 0.59 0.31 0.21 0.12 0.13 0.15 0.16 0.18 0.2 0.19 0.31 100 66.29 34.83 23.60 13.48 14.61 16.85 17.98 20.22 22.47 21.35 Annual TBC variation 33.71 31.46 11.24 10.11 1.12 2.25 1.12 2.25 2.25 1.12 1.57 Economic variation/ TBC variation 1.47 1.50 0.25 0.25 0.03 0.08 0.02 0.05 0.01 0.01 0.07
Year
TBC
GDP Index number 0.27 0.14 0.15 0.094 0.117 0.05 0.039 0.127 0.032 0.009 0.032 0.11
Annual GDP variation
1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 Mean
1583 1946 2279 2984 3619 4142 4613 5426 6203 9746 13027 5556
100 122.88 143.91 188.43 228.53 261.58 291.32 342.62 391.73 615.39 822.93
22.88 21.03 44.52 40.1 33.05 29.73 51.3 49.11 223.67 207.54 14.46
2005
73, 4

DISCUSSION
265
TABLE 5. Logistic regression model for different forecast terms of leprosy in Spain, 19502000.
B Coefcient Lag 0 Lag 1 Lag 2 Lag 3 Lag 4 Lag 5 Lag 6 Lag 7 Lag 8 Lag 9 Lag 10 0.309 0.005 0.006 0.012 0.041 0.096 0.484 0.201 0.001 0.108 0.102 R2 0.145 0.284 0.286 0.291 0.303 0.312 0.568 0.282 0.166 0.192 0.157 Sig. 0.001 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.000 0.012 0.130
the data on economic growth corresponding to the preceding years (1, 2, 3, etc.) in relation to the incidence of Hansens Disease. To this effect we developed both simple and multiple regression models, using the annual information from all Spanish provinces. In this respect, Table 5 shows the results of multiple regression, tted by Naperian logarithmic transformation. The explanatory contribution, measured in terms of R2, is seen to increase until a 6-year lag was reached; at this point 57% of the incidence of leprosy was explained. Later, with increasing delays, the values began to decreasethough in an irregular manner. In the multiple regression analysis, based on the model involving a 6-year lag and using the annual and provincial data, we in turn developed a complete model (Table 6). The results revealed that the factors seen to inuence the incidence of leprosy were: employment, the number of physicians, and economic growth, all with negative coefcients, while tuberculosis was associated with a positive coefcient. Nevertheless, the GDP was found to yield the most important coefcient, with a value of 0.5, followed by infant mortality and the physician rate. In view of the similar behavior of tuberculosis as regards economic growth, a study was made of the interactions and resulting co-linearity. In this context, tolerance and the variance ination factor showed medium tolerance for the variables GDP, infant mortality and health education sector product, unemployment, and the number of physicianswhile high tolerance was recorded for the rest.
The main problem posed by studies of this kind is that the data corresponding to the factors analyzed must offer continuity and reliability. This prevented us from examining a large number of variables which logically should have been included in the study. The regions with the highest rate and most total cases of leprosy were Andaluca and Extremadura (both of which showed the lowest economic levels), followed by Catalonia and the Canary Islandspossibly due to the important number of immigrants found in these autonomous communities. Within Andaluca, the province of Crdoba clearly stands outwith a mean rate for the global study period of 0.6 new cases per 100,000 inhabitants per yeartogether with the province of Jan (7) . In sum, a preferentially though somewhat irregular Mediterranean distribution is observed, in coincidence with the ndings of other authors, in relation to the cases of leprosy (26). On the other hand, although the study has been carried out with delimitations in the form of provinces and/or regions, the distribution of Hansens disease is known to be extremely irregularwith marked intra-regional variations in Spain and also elsewhere in the world (35). Since 1981, the World Health Organization (WHO) has recommended multi-drug therapy for the management of leprosy, and has considered it possible to eliminate the disease as a public health problem worldwide. The leprosy-eliminating strategy proposed by the WHO has been based on the hypothesis that a reduction in the prevalence of the disease based on the administration of multi-drug regimens (dapsone, clofazimine and rifampicin) entails a low reservoir of cases in the community (fewer than 1/10,000 inhabitants)as a result of which the transmission cycle of the disease cannot be perpetuated (25, 32). The concept underlying this strategy is the so-called basic reproduction rate, R0 (the mean number of individuals directly infected by an infectious case). If R0 is >1, an epidemic may result, while if R0 is <1, the disease may disappear. In the case of leprosy, it has been estimated that R0 is <1 when the prevalence rate is less than 1/10,000a situation that has been applicable in Spain for many years. In our study the observed
266
2005
TABLE 6. Conditioned factors analysis of the trend of leprosy in Spain, 19502000 (logarithmic regression).
B COEFFICIENT Emigrant Employment Schooling Physician Infant mortality GDP Rural population Health product Tuberculosis 0.241 0.174 0.024 0.202 0.238 0.484 0.018 0.015 0.150 t 1.52 3.05 0.48 3.47 1.82 4.67 0.31 0.14 6.04 Sig. 0.129 0.002 0.631 0.001 0.068 0.000 0.754 0.886 0.000 ULCI 0.04 3.59 0.82 0.34 0.01 2.45 0.69 0.82 0.26 LLCI 0.27 0.78 1.36 0.09 0.04 1.01 0.96 0.95 0.51 TOLERANCE 0.35 0.56 0.73 0.80 0.99 0.17 0.53 0.16 0.23 VIF 2.88 1.78 1.37 1.25 1.01 5.91 1.87 6.25 4.40
Note: B = beta, t = t Student, Sig. = signicance, ULCI = upper limit condence interval, LLCI = lower limit condence interval, VIF = variance ination factor
annual reduction rate was 1.6%, while some sources in the literature conclude that countries with endemic disease have annual reduction rates of 4% (23). However, certain data and contradictions speak against the optimism of the WHO and raise doubts as to the evolution of the diseasequestioning the central argument of the elimination strategy whereby the only effective contagion source is the lepromatous patient, and a reduction in prevalence therefore necessarily implies a reduction in incidence. The principal unsettled questions refer to the evidence suggesting a slightly decreasing general incidence (though not in all countries); uncertainty over the true number of individuals with occult infection; a lack of knowledge of the magnitude of the problem posed by subclinical carriers of the disease (20); and the possible existence of animal reservoirs (5, 36). Many authors consider that the disease found in armadillos and monkeys is different from that seen in humans (27). Another important consideration is the present lack of an effective vaccine (10). In this context, and in an attempt to account for the evolution of leprosy, sociosanitary and economic considerations have been postulated to be of greater relevance than multitherapy. In favor of this hypothesis would be the declining trend of the disease in China and Spain starting before implementation of the WHO multi-drug strategy, and the spontaneous disappearance of the disease in Norway (24), Japan (15) and Hawaii (37), as well as its continued persistence in India, Brazil (17) and Cuba despite
application of the WHO program. In the case of Norway, the gradual decrease in leprosy incidence was accompanied by an increase in mean patient age at appearance of the disease, and a gradual prolongation of the incubation period (24). Leprosy prevalence data were not used in this study, because they posed concordance problems with the incidence data. Such discordance was mainly due to the repetition of individuals included in the prevalence lists. Moreover, while the incidence rate was not affected as a result, the prevalence rates were falsely elevated due to persistence in the prevalence lists of cases that had likely died or healed. Although the regression analysis cannot consider only the sum of the effects of variables, since the interference factors absorb part of the explanation or prediction of changes in the incidence of leprosy, the interactions among variables do not seem to be sufciently intense to compromise interpretation of the results. The same applies to the co-linearity among variables assessed by variance ination factors and tolerance. The confounding variables and resulting attributable bias always pose a considerable risk and are a source of imprecision in ecological studies, due to the scant control afforded by the use of population instead of individual measures (29). Although some authors have reported tuberculosis to be antagonistic to leprosy, attributing the almost total disappearance of the latter to the appearance of tuberculosis, it must be considered that this is an infectious disorder, and that the environmental
73, 4
267
conditions and factors of hygiene are therefore the bases for transmission. In this sense, socioeconomic status could be essential for creating a setting unfavorable for the transmission of both diseases, as observed in our study. Previous authors have addressed the possible relationship between socioeconomic development and concrete health aspects, e.g., mortality in the classical study of Krishnan (19) in India, or Mckeown (22) in England; or neonatal mortality in the study of Shah and Abbey (33) in Baltimore (United States), among many others. However, a review of the literature has yielded almost no studies relating socioeconomic development to the evolution of leprosy incidence. In contrast, analyses have been made of the social and economic variations observed in leprosy patients, and the need to restore such parameters to their previous levels in order to help heal the patients, as in a published Indian study (29). Other parameters investigated include crowding, domestic conditions, family size (31), and even the inverse relation between years of schooling and the incidence of leprosy in a study from Malawi (28). The present study made use of the gross domestic product (GDP), as recommended by some authors for conducting mediumand long-term studies (9). In this context, GDP was seen to be the factor exerting the greatest inuence upon leprosy evolution, according to the multiple regression analysis with a 6-year lag period. It should be taken into account that economic development is the fundamental factor inuencing family crowding conditions, schooling, and other factors such as nutritional status (33), likewise related to the incidence of leprosy. The family grouping of leprosy observed in some studies may also be a consequence of shared socioeconomic status (and therefore hygiene conditions) (16). Therefore some authors recommend considering this as a factor in chronic diseases (35). The other two factors with negative and statistically signicant coefcients were employment and the number of physicians, and the sum of their beta-coefcients was lower than that of GDPi.e., they were seen to jointly exert much less inuence upon leprosy incidence trends. The fourth signicant factor was tuberculosis; in effect, since the latter is also a transmissible disease, it is also affected by social and eco-
nomic development. Moreover, it should be taken into account that the results of the present study showed a similar interannual change for both transmissible diseases, and that Bacillus Calmette Gurin (BCG) vaccination produces a certain degree of immunity against leprosy as well (8, 38). In relation to the lag period used to explain the incubation period of leprosy, the estimated period is 2.9 to 5.3 years in the case of tuberculoid leprosy, and 9.3 to 11.6 years in the case of the lepromatous form of the diseasethough in our study a period of 6 years was seen to afford the best explanation for the observed statistical relationship. Other authors have reported periods of up to 30 years in veteransa situation not examined in the present study. It may have been advisable to separate the cases according to the type of leprosy, to establish the possible differences in the inuence of socioeconomic factors according to the type of disease involved. However, the incidence rates would have been zero or very close to zero in the last years of the study period. The declining tendency of leprosy in Spain was seen to be gradual since the 1950s, i.e., it started before the introduction of multi-drug therapy, and was more closely associated with the socioeconomic development of the country. Similar observations also apply to a number of other European countries (14), in addition to Norway as noted above (24). Our study illustrates the multicausal model of effects, whereby socioeconomic considerations can prove more important than the actual transmissibility conditions of leprosy.
REFERENCES
1. BANCO BILBAO VIZCAYA. Renta Nacional de Espaa y su Distribucin Provincial. Aos 1950 a 1995. Servicio de publicaciones. 2. BELSLEY, D. Detecting and assessing the problems caused by multi-collinearity: A use of the singular-value decomposition. No. 66 in NBER Working Papers, National Bureau of Economic Research, Inc., 1974. 3. BHATTACHARYA, S. N., and SEHGAL, V. N. Leprosy elimination campaign and its impending fallout. Int. J. Dermatol. 39(9) (2000) 667669. 4. BJARNASON, O. The last lepra patient in Iceland. Nord. Medicinhist. Arsb. (1989) 197203. 5. BRUCE, S., SCHROEDER, T. L., ELLNER, K., RUBIN, H., WILLIAMS, T., and WOLF, J. Armadillo exposure and Hansens disease: an epidemiologic sur-
268
2005
6.
7.
8.
9.
10.
11.
12.
13.
14.
15. 16.
17.
18.
19. 20.
21.
22.
vey in southern Texas. J. Am. Acad. Dermatol. 43(2 Pt. 1) (2000) 223228. CENTRO NACIONAL DE EPIDEMIOLOGA. Manual del registro estatal de lepra. Madrid. Instituto de Salud Carlos III. 1991. DELGADO-RODRIGUEZ, M., RODRIGUEZ-CONTRERAS PELAYO, R., EXTREMERA-CASTILLO, F., SERRANO-ORTEGA, S., and GALVEZ-VARGAS, R. Epidemiologic aspects of leprosy in the province of Jaen. Rev. Clin. Esp. 185(2) (1989) 99103. FINE, P. E. M. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346 (1995) 13391345. GETZEN, T. E. Forecasting health expenditures: short, medium, and long term. J. Health Care Finance 26(3) (2000 Spring) 5672. GUPTE, M. D., VALLISHAYEE, R. S., ANANTHARAMAN, D. S., NAGARAJU, B., SREEVATSA, BALASUBRAMANYAM S., DE BRITTO, R. L., ELANGO, N., UTHAYAKUMARAN, N., MAHALINGAM, V. N., LOURDUSAMY, G., RAMALINGAM, A., KANNAN, S., and AROKIASAMY, J. Comparative leprosy vaccine trial in south India. Indian J. Lepr. 70 (1998) 369388. INSTITUTO NACIONAL DE ESTADSTICA. Anuario estadstico Ministerio de Economa. Madrid. Aos 1950 hasta 2001. INSTITUTO NACIONAL DE ESTADSTICA. Censo de la poblacin espaola. Ministerio de Economa. Madrid. Aos 1950 hasta 2000. INSTITUTO NACIONAL DE ESTADSTICA. Movimiento natural de la poblacin espaola Ministerio de Economa. Madrid. Aos 1950 hasta 2001. IRGENS, L. M., MELO-CAEIRO, F., and LECHAT, M. F. Leprosy in Portugal 194680: epidemiologic patterns observed during declining incidence rates. Lepr. Rev. 61(1) (1990) 3249. ITO, I. The epidemiological situation in south east Asia. Lepr. Rev. 52 (1981) 4351. JAIN, S., REDDY, R. G., OSMANI, S. N., LOCKWOOD, D. N., and SUNEETHA, S. Childhood leprosy in an urban clinic, Hyderabad, India: clinical presentation and the role of household contacts. Lepr. Rev. 73 (2002) 248253. KLEINBAUM, D. G., KUPPER, LL., and MORGENSTERN, H. Epidemiologic research: Principles and quantitative methods. New York: Van Nostrand Reinhold. 1982. KRISHNAN, P. Mortality decline in India. 1951 1961: developmental versus public health program hypothesis. Soc. Sc. Med. 9 (1975) 475479. LECHAT, M. F. The source of infection: an unsolved issue. Indian J. Lepr. 72 (2000) 169173. LOCKWOOD, D. N., and SUNEETHA, S. Leprosy: too complex a disease for a simple elimination paradigm. Bull. World Health Organ. 83 (2005) 230235. LOPEZ-VELEZ, R., SAEZ-VAQUERO, T., BLANCOAREVALO, J. L., and GOMEZ-MAMPASO, E. Leprosy simulating other diseases. Rev. Clin. Esp. 199 (1999) 369372. MCKEOWN, T., and BROWN, R. G. Medical evi-
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34. 35.
36.
37.
38.
dence related to English populations change in the eighteenth century. Pop. Stud. 9 (1965) 119123. MEIMA, A., GUPTE, M. D., VAN OORTMARSSEN, G. J., and HABBEMA, J. D. F. Trends in leprosy case detection rates. Int. J. Lepr. Other Mycobact. Dis. 65 (1997) 305319. MEIMA, A., IRGENS, L. M., VAN OORTMARSSEN, G. J., RICHARDUS, J. H., and HABBEMA, J. D. Disappearance of leprosy from Norway: an exploration of critical factors using an epidemiological modelling approach. International Journal of Epidemiology 31 (2002) 9911000. MEIMA, A., RICHARDUS, J. H., and HABBEMA, J. D. Trends in leprosy case detection worldwide since 1985. Lepr. Rev. 75 (2004) 1933. NOORDEEN, S. K. Descriptive epidemiology of leprosy. In: Leprosy. Hasting eds. Edimburgh. Churchill Livingstone Publications, 1985. NOORDEEN, S. K. Toward the elimination of leprosy, the challenges and opportunities. Int. J. Lepr. Other Mycobact. Dis. 66 (1998) 218221. PONNIGHAUS, J. M., FINE, P. E., STERNE, J. A., MALEMA, S. S., BLISS, L., and WILSON, R. J. Extended schooling and good housing conditions are associated with reduced risk of leprosy in rural Malawi. Int. J. Lepr. Other Mycobact. Dis. 62 (1994 Sep) 345352. RAO, V. P., RAO, I. R., and PALANDE, D. D. Socioeconomic rehabilitation programmes of LEPRA Indiamethodology, results and application of needs-based socio-economic evaluation. Lepr, Rev. 71 (2000) 466471. ROTHMAN, K. J., and GREENLAND, S. Modern Epidemiology. Philadelphia. 2nd ed. Lippincott Williams & Wilkins, 1998. SAIKAWA, K. The effect of rapid socio-economic development on the frequency of leprosy in a population. Lepr. Rev. 52 (1981) 167175. SANSARRICQ, H. Epidmiologie de la lpre. In: La lpre. Chapitre 5. Paris. Edit Ellipses Universits francophones, 1995, pp. 5472. SHAH, F., and ABBEY, H. Effects of some factors on neonatal and postneonatal mortality. Milbank Mem. Fund Q 49 (1971) 3357. SKINSNES, O. K. Effect of malnutrition on leprosy. Int. J. Lepr. Other Mycobact. Dis. 44 (1976) 374375. TERENCIO DE LAS AGUAS, J. La lepra, pasado, presente y futuro. Valencia. Ed Generalitat Valenciana, 1999, pp. 5775. VALVERDE, C. R., CANFIELD, D., TARARA, R., ESTEVES, M. I., and GORMUS, B. J. Spontaneous leprosy in a wild-caught cynomolgus macaque. Int. J. Lepr. Other Mycobact. Dis. 66 (1998) 140148. WORTH, R. M. The disappearance of leprosy in a semi-isolated population (Nihau Island, Hawai). Int. J. Lepr. Other Mycobact. Dis. 31 (1963) 3435. ZODPEY, S. P., BANSOD, B. S., SHRIKHANDE, S. N., MALDHURE, B. R., and KULKARNI, S. W. Protective effect of Bacillus Calmette Gurin (BCG) against leprosy: a population-based case-control study in Nagpur, India. Lepr. Rev. 70 (1999) 287294.
Study of Apoptosis in Skin Lesions of Leprosy in Relation to Treatment and Lepra Reactions
C. Ajith1, Sachin Gupta2, Bishan D. Radotra3, Sunil K. Arora2, Bhushan Kumar1, Sunil Dogra1, and Inderjeet Kaur1
ABSTRACT
In leprosy on treatment, one factor contributing to the healing of skin lesions with minimal brosis may be apoptosis of inammatory cells, even though apoptosis is sparse in leprosy as compared to tuberculosis. The degree of apoptosis in skin lesions of leprosy was studied by histopathologic examination (HPE) and by DNA fragmentation and electrophoresis. The effect of various parameters on apoptosis was noted in untreated disease, during treatment at 3 and 6 months, and in lepra reactions in different parts of the spectrum of leprosy. Of the 31 patients, 13 had paucibacillary (PB) and 18 multibacillary (MB) disease. Twenty one patients were in reaction: 16 had type 1 reaction and 5 had type 2 reaction. The controls included patients with non-granulomatous skin diseases; there were no normal controls, and no separate controls for cases with reaction. Apoptosis occurred more frequently in patients with leprosy as compared to the controls. In both PB & MB lesions, apoptosis was observed to increase progressively with treatment at 3 and 6 months, and was more prominent in the MB cases at 6 months of treatment. When lesions in either type 1 or type 2 reaction were compared to lesions not in reaction, a signicant increase in apoptosis (p = 0.014) was found only in lesions with type 2 reaction and those which were at 6 months of treatment. The type of treatment regimen, or oral steroids given for reactions, did not signicantly alter the degree of apoptosis. Our observations indicate that increased apoptosis is present in leprosy lesions and that in leprosy it progressively increases with anti-leprosy treatment up to 6 months. If the process of apoptosis in skin lesions is followed up for a longer period of time, the degree of apoptosis may be expected to decline. The study of apoptosis may help to understand the mechanism of clearance of bacilli and resolution of granulomas in leprosy patients.
RSUM
Au cours du traitement de la lpre, un facteur contribuant la cicatrisation des lsions cutanes en labsence de brose signicative pourrait tre lapoptose des cellules inammatoires, mme si lapoptose est rapporte comme peu commune dans la lpre, compare la tuberculose. Le degr dapoptose dans les lsions cutanes de la lpre fut tudi lexamen histopathologique (HPE) et par examen de la fragmentation de lADN par lectrophorse. Leffet de divers paramtres sur lapoptose fut not lors de maladie non traite, en cours de traitement des temps de 3 et 6 mois et dans des ractions lpreuses pour diffrents points du spectre immunopathologique de la lpre. Parmi les 31 patients, 13 avaient la forme paucibacillaire (PB) et 18 la forme multibacillaire (MB). Vingt-et-un patients taient en raction, 16 ayant une raction de type 1 et 5 de type 2. Les contrles taient reprsents par des patients avec des maladies cutanes non granulomateuses, sans contrle avec peau normale, et sans contrle spar pour les cas avec ractions. Lapoptose tait plus frquente chez les
1 C. Ajith, M.D; B. Kumar, M.D., MNAMS; S. Dogra, M.D., DNB, MNAMS; I. Kaur, M.D., MNAMS; Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 2 Sachin Gupta M.Sc; Sunil K Arora, PhD, MNAMS; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 3 B. D. Radotra, M.D., PhD; Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Reprint requests to: Dr. Inderjeet Kaur, Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh-160012, India; e-mail: kaur_inderjeet@yahoo.com
269
270

patients atteints de la lpre que chez les contrles atteint de lsions cutanes non granulomateuses. A la fois dans les lsions PB et MB, il y eut un accroissement progressif de lapoptose aux temps de traitement de 3 et 6 mois, qui fut le plus net chez les cas MB 6 mois de traitement. Lorsque les lsions de type 1 ou de type 2 furent compares celles sans raction, une augmentation signicative de lapoptose (p = 0,014) fut observe dans les ractions de type 2 et celles qui furent 6 mois de traitement. Le type de traitement, ou bien les corticostrodes oraux administrs pendant les ractions nont pas altr de faon signicative le degr dapoptose. Nos observations indiquent quil existe une apoptose plus importante dans les lsions de lpre que dans celles de lsions cutanes non-granulomateuses et quelle augmente progressivement avec le traitement, et ce au moins jusqu 6 mois. Si lapoptose dans les lsions cutanes avait t suivie au-del de 6 mois, le degr dapoptose aurait probablement dclin. Ltude de lapoptose devrait pouvoir permettre de mieux comprendre les mcanismes dlimination des bacilles de Hansen et la rsolution des granulomes chez les patients souffrant de lpre.
2005
RESUMEN
En el tratamiento de la lepra, un factor contribuyente a la curacin de las lesiones de la piel, con mnima brosis, puede ser la apoptosis de las clulas inamatorias, aunque se piensa que la apoptosis en la lepra es rara comparada con la apoptosis en tuberculosis. En este estudio se examin el grado de apoptosis en las lesiones de la piel en la lepra por histopatologa (HP) y por fragmentacin y electroforesis del DNA. Se registr el efecto de varios parmetros sobre la apoptosis en la enfermedad no tratada, en la enfermedad con 3 y 6 meses de tratamiento, y en las reacciones de la lepra en diferentes partes del espectro de la lepra. De los 31 pacientes estudiados, 13 tenan lepra paucibacilar (PB) y 18 lepra multibacilar (MB). Veintin pacientes estaban en reaccin, 16 tenan reaccin leprosa tipo 1, y 5 reaccin leprosa tipo 2. Los controles incluyeron pacientes con enfermedad de la piel no granulomatosa; no hubo controles sanos ni controles separados para los casos en reaccin. La apoptosis ocurri ms frecuentemente en los pacientes con lepra que en los pacientes control. Tanto en los pacientes PB como en los MB la apoptosis aument progresivamente con el tratamiento a los 3 y 6 meses, y fue ms prominente en los casos MB a los 6 meses de tratamiento. Cuando se compararon las lesiones de las reacciones tipo 1 o tipo 2 con las lesiones de la lepra no reaccional, se encontr un signicante incremento en la apoptosis (p = 0.014) slo en las lesiones de las reacciones tipo 2 y en aquellas de los pacientes con 6 meses de tratamiento. El tipo del rgimen de tratamiento o los esteroides orales administrados para controlar las reacciones no alteraron signicativamente el grado de apoptosis. Nuestras observaciones indican que la apoptosis est incrementada en las lesiones de la lepra y que aumenta progresivamente con el tratamiento anti-leproso administrado durante 6 meses. Se esperara una disminucin en el grado de apoptosis en las lesiones seguidas por periodos ms prolongados de tiempo. El estudio de la apoptosis puede ayudar a entender el mecanismo de eliminacin de bacilos y la resolucin de los granulomas en los pacientes con lepra.
In leprosy, the clinical, bacteriological and histopathological manifestations are profoundly affected by the immunological status of the host, which determines the type of leprosy. The clinicopathologic bipolarity may stem from the dual response of lymphocytes, dendritic cells, monocytes and macrophages to M. leprae (1, 4, 14). Usually chronic granulomatous diseases of the skin heal with brosis, eg: the scarring left behind by lupus vulgaris or scrofuloderma. However, in leprosy, with proper treatment or spontaneously as in indeterminate leprosy, the majority of skin lesions heal without much brosis. One factor which may
contribute to this is thought to be apoptosis, a mechanism of cell death which has no accompanying inammatory component and thus may explain the relative lack of brosis mentioned above. Apoptosis is an active, self-destructive cellular process and is considered an integral part of the repertoire available to the cell to respond to deleterious stimuli from within and without (5, 7, 14). In tuberculosis, circulating polymorphonuclear neutrophils (PMN) show increased spontaneous apoptosis, and Mycobacterium tuberculosisinduced activation accelerates PMN apoptosis.(2)
73, 4
Ajith, et al.: Study of Apoptosis in Skin Lesions
271
In the resolution of leprosy granulomas with treatment, one mechanism of cell loss is believed to be apoptosis, especially for high turn-over granulomas. The number and density of apoptosis in leprosy may be affected by factors such as bacillary load and degree of cell mediated immunity (4, 10, 14). Since type1 and type 2 reactions in leprosy may be associated with changes in immune status, and the type 2 reaction is an acute inammatory state, the number and density of apoptosis is likely to vary in these states also. We have therefore studied the degree of apoptoses by two different standard laboratory techniques and observed the effect of various parameters on apoptosis in skin lesions in untreated leprosy, during treatment, and during reactions.
MATERIALS AND METHODS The study included 34 patients with leprosy attending the leprosy clinic at our center. Untreated, histopathologically conrmed leprosy patients were enrolled in the study, including patients with or without reactions, irrespective of sex, type and duration of disease. For controls, 20 patients from the general skin out-patient department were studied. Those with granulomatous skin disorders such as cutaneous tuberculosis and sarcoidosis were excluded. No normal skin samples were taken for control purposes. Also, there were no separate controls for those with reactions. Appropriate treatment regimen recommended by WHO, i.e., multi drug therapy (MDT), either multibacillary (MB) or paucibacillary (PB) regimen (15) was given to the patients according to the type of the disease. To study the apoptosis in the tissue specimens, biopsies were taken before starting treatment and at 3 and 6 months post-treatment, from the most active edge of the most prominent lesion, regardless of reactional state. All the initial biopsies were taken before the treatment started, and all subsequent biopsies were taken from the same lesion. For control purposes, biopsies were taken from 20 patients with skin diseases other than leprosy or other granulomatous disorders. From the tissue specimens, apoptosis was detected by two different methods for comparison i.e., histopathologic examination (HPE) and by DNA fragmentation and electrophoresis. All the biopsies
FIG. 1. Apoptotic cell depicting characteristic nuclear fragmentation (H&E stain 550).
were bisected, and the portion for HPE was xed in formalin, embedded in parafn, and 6 thick tissue sections were cut and stained by hematoxylin and eosin. By HPE, apoptotic bodies were identied by the following features: nuclear condensation, round to ovoid bodies, eosinophilia of the cytoplasm and karyorrhexis/karyolysis (7) (Fig. 1). The number of apoptotic bodies per 10 high power elds/sample was recorded. The readings were taken by an experienced histopathologist, who was unaware of the treatment status of the patient. The elds were within the granulomas, and in biopsies where the granulomas were not prominent, the elds chosen were among the inammatory inltrates. The other part of the bisected biopsy tissue was transported in normal saline for analysis of DNA fragmentation. DNA was isolated from all the samples by the method of Palmiter et al (14). Briey, the tissue was teased and suspended in 500l of lysis buffer containing 1% SDS and 0.01% protienase K in Tris-EDTA (TE) buffer (ph 8.0) and incubated at 55C overnight. After phe-
272
2005
FIG. 2 1% Agarose gel electrophoresis showing DNA fragmentation pattern; Lanes 1, 2, 3, 6, 7, 9 and 10 showing the typical ladder pattern of apoptoses.
nol-chloroform extraction, the DNA was precipitated with chilled isopropanol, and resuspended in TE buffer. The prepared DNA was run on 1% agarose gel, stained with ethidium bromide, and the gel was DNA viewed under ultraviolet light, to identify the typical ladder pattern of fragmented DNA specic to apoptosis. The pictures were captured using a gel documentation system (Image master, Pharmacia Biotech). Statistical analyses were done using non-parametric Chi-square tests and McNemars Chi-square tests.
RESULTS Of the 34 patients, 2 patients were lost to follow up and one patient died after 2 months of treatment due to dapsone hypersensitivity syndrome. Therefore, skin biopsy results from 31 patients were available for analysis. These were from 26 males and 5 females, having a mean age of 35.6 1.7 years. The majority of the patients (75%) were in the 1645 years age group followed by 4670 years (22%) and 1 (3%) was aged 14 years. Of the total patients 13 (42%) had paucibacillary (PB) and 18 (58%) had multibacillary (MB) disease. Twenty one patients were in reaction: 16
(76%) had type 1 reaction (9 in the PB and 7 in MB the group) and 5 (24%) had type 2 reaction. Skin biopsies were taken from the control group of 20 patients, (12 males, 8 females) who had a mean age of 34.8 1.8 years. The controls selected had various non-granulomatous dermatoses including lichen planus (5), discoid lupus erythematosus (4), pemphigus (4), warts (4), leiomyoma (2) and pseudopelade (1). The results obtained with both methods were compared in the PB and MB groups and controls at the start of the study, in relation to anti leprosy treatment, in Type 1 and Type 2 reactions, and in patients receiving corticosteroids for control of reaction. By the method of HPE, apoptotic bodies were detected in all the specimens at all the stages, whereas by DNA fragmentation and electrophoresis (Fig. 2), apoptosis was detected only in 9 (26%), 16 (52%) and 26 (87%) of patients at baseline (untreated) and at 3 and 6 months of treatment respectively. Detection of apoptosis by the method of HPE at baseline and at 3 months and 6 months after completing treatment is presented in Table 1. The detection of apoptosis by DNA fragmentation and elec-
73, 4
273
TABLE 1. Apoptoses by the method of HPE at baseline and at 3months and 6 months after completing treatment
Apoptoses (mean S.D.)/10hpf Diagnosis Number of cases Baseline PB with type 1 reaction PB without reaction MB with type 1 reaction MB with type 2 reaction MB without reaction 9 4 7 5 6 2.04 1.33 2 1.42 2.12 1.83 3.8 1.82 2.5 0.89 3 months after treatment 3 1.48 2.5 1.34 3.82 1.40 4.8 2.59 3.2 1.3 6 months after treatment 5 1.29 3.5 1.44 6 1.60 9.4 3.21 5.17 1.17
trophoresis in PB and MB disease at baseline and at 3 months and 6 months after treatment is presented in Table 2. A comparison of apoptosis by the method of HPE between the different groups is shown Table 3. Twenty two patients received MDT-MB therapy, 7 patients received MDT-PB therapy and 2 patients received rifampicin, ooxacin, and minocycline (ROM) therapy. Comparing the different treatment groups, apoptosis was found more frequently with treatment in all the groups. Comparing apoptosis between the groups, no signicant change in the apoptosis was observed at all the 3 stages of treatment. (The values from the two patients who received ROM therapy were not compared with other groups), Of the 31 patients, 23 (74%) patients received corticosteroids (19 for reactions and 4 for neuritis); the starting dose of prednisolone was 40 mg/day, which was then tapered over a period of 36 months. On comparing apoptoses between the steroidtreated and non-treated patients, both the groups showed an increase in apoptoses with the duration of treatment, but the effect of steroids on this trend was not statistically signicant in any of the groups at any period (p >0.05). In summary, apoptosis was found more frequently in patients with leprosy as compared to the controls. In both PB & MB portions of the leprosy spectrum, apoptosis progressively increased with treatment at 3 and 6 months, but it was more noticeable in the MB cases, especially at 6 months of treatment. When biopsies of either type 1 or type 2 reaction were compared to those not in reaction, a signicant increase in apo-
ptoses was found in cases with type 2 reactions, also at 6 months of treatment. All of the MDT regimens showed increased degrees of apoptosis, but the process was not affected by either of the regimens. The administration of corticosteroids did not appear to signicantly alter the degree of apoptosis.
DISCUSSION Apoptosis is one form of cell death which is non-inammatory, and it has been postulated to play a role in the resolution of leprosy granulomas as a mechanism of cell destruction. It might represent a strategy of the immune system to eliminate infected cells, but few studies have shown apoptosis to be present in leprosy lesions (1, 4, 15). One recent study assessing a small number of samples only from untreated patients found trends suggesting apoptosis in leprosy lesions might be more frequent in PB disease (15). However, sufcient information on apoptosis in various situations, such as during reactions, in different portions of the leprosy spectrum of disease (indirectly indi-
TABLE 2. Detection of apoptosis by electrophoresis to depict DNA fragmentation at various periods in PB and MB disease.
Number and % age of patients Disease spectrum Baseline 3 months after treatment 6 (46%) 10 (77%) 6 months after treatment 8 (61%) 18 (100%)
PB n = 13 (p >0.05) MB n = 18 (p <0.05)
3 (23%) 6 (33%)
274 TABLE 3. periods.

Disease groups
2005
Comparison of apoptoses by HPE between the various groups at different

p-value Baseline 0.55 (p >0.05) 0.56 (p >0.05) 1.00 (p >0.05) 0.07 (p >0.05) 0.13 (p >0.05) 0.52 (p >0.05) 3 months 0.16 (p >0.05) 0.68 (p >0.05) 0.57 (p >0.05) 0.16 (p >0.05) 0.26 (p >0.05) 0.14 (p >0.05) 6 months 0.20 (p >0.05) 0.19 (p >0.05) 0.32 (p >0.05) 0.014 (p <0.05) 0.03 (p <0.05) 0.17 (p >0.05)
PB with type 1 reaction vs. PB without reaction PB with type 1 reaction vs. MB with type 1 reaction MB with type 1 reaction vs. MB without reaction MB with type 2 reaction vs. MB without reaction MB with type 1 reaction vs. MB with type 2 reaction PB without reaction vs. MB without reaction
cating immune status), and the effects of treatment, are not available. Comparing two methods of apoptosis detection i.e., HPE and DNA fragmentation and electrophoresis, the HPE method was found to be more sensitive and provided a more exact quantitative difference in apoptosis at different stages. However, using the HPE method as a readout for apoptoses is not ideal because this method is subject to observer variability and incorrect interpretation if read by an observer not experienced in apoptoses (4, 15). The method of DNA fragmentation and electrophoresis is not subject to observer variation and the results are more reliable and probably of greater value than HPE, but in our study, which required a quantication of apoptoses, DNA fragmentation and electrophoresis was observed to be less sensitive. Using DNA fragmentation and electrophoresis, we could not detect the apoptotic process in expected numbers, but the trends in the detection of apoptoses between HPE and DNA fragmentation and electrophoresis were similar. In comparing the frequency of apoptosis in lesions across the disease spectrum, it was found that in all subsets of disease, there was progressive increase in apoptoses from baseline to 6 months of treatment. Our ndings of signicantly more apoptoses in patients with leprosy compared to controls supports the similar observation in previous studies (4, 10, 15). Walsh, et al. (15), using a well established TUNEL assay found apoptosis to be more frequent in untreated lesions of PB disease in comparison with MB disease; however we observed apoptosis to be greater in lesions of MB compared to PB group. Our observation supports a previous in vitro study in which apoptosis increased with in-
creasing concentration of M. leprae (6), although this was an in vitro study and did not involve skin lesion analysis. Generally, this suggests that apoptoses can be found in leprosy, but since it was not present in all the samples and the numbers of apoptoses were small, unlike in tuberculosis, the signicance of apoptoses in leprosy remains unclear. Regarding the effect of treatment, the number and density of apoptoses increased progressively with treatment in all the groups of patients. One previous study has shown that sulfonamides can induce apoptosis of circulating leukocytes, by their metabolites becoming attached to these cells and promoting up regulation of apoptosis inducing factors (9). Since sulfonamides are present in both MDT-MB and MDT-PB regimens and the effect of rifampicin and clofazimine on apoptosis is not known, an exact explanation of the role of MDT regimens in the increased apoptoses is not clear. With treatment, inammation subsides and the bacillary load also declines. Both of these effects should cause a fall in apoptosis. But we have found increasing apoptosis with both treatment regimens at 6 months. Since treatment results in the resolution of leprosy granulomas with a modest proportion of the inammatory cells undergoing apoptosis, this could explain the nding of increased apoptosis early in the treatment. Resolving granulomas initially show apoptoses of inammatory cells with treatment. In fully resolved granulomas the apoptosis may even cease completely and so there may occur a fall in apoptoses. Also, the apoptotic bodies are understood to be spontaneously cleared with time by phagocytosis. Hence, we speculate that studies carried out for a longer period may show decreasing apoptosis.
73, 4
275
In lesions of Type 2 reaction, a signicant increase in apoptosis was observed at 6 months of treatment when compared to non-reactional group as well as to the type 1 reactional group. Oliveira and colleagues found apoptosis to be greatly accelerated in circulating polymorphonuclear neutrophils in patients experiencing ENL (11). The increased expression of pro-apoptotic members of Bcl-2 protein family and of TNF- in type 2 reaction is likely to induce more apoptosis (11). Sampaio and colleagues have shown that neutrophils stimulated with M. leprae secrete large amounts of IL-8 and TNF-, and drugs with anti TNF- properties such as thalidomide given for severe ENL reaction may cause a decrease in apoptosis (13). Our ndings support the suggestions that greater bacillary load and type 2 reaction can lead to an increase in apoptosis. Though the number and density of apoptosis was more in the prednisolone treated group, the values were not statistically signicant when compared to the non-prednisolone treated group. Though corticosteroids are among the drugs that can induce apoptosis especially in thymic and circulating lymphocytes, no signicant association with corticosteroid treatment and apoptosis was found in this study. A previous study has shown differential effect of steroids on apoptosis, with apoptosis being inhibited in few specic tissues, especially glandular tissues (3). Also the pro-apoptotic effects of corticosteroids may have been offset by the effect of anti-leprosy treatment, with M. leprae induced inammation resolving and the corticosteroids further reducing the inammation. Apoptosis is the end point of an energy dependent cascade of molecular events and is regulated by several genes which induce p53, c-Myc, Bcl-2, CED-3 and Fas genes (7, 17, 18). M. leprae induced apoptosis of circulating monocytes has been shown to occur in vitro (6). Studies on blood mononuclear cells in leprosy patients have shown greatly increased apoptoses of lymphocytes especially the CD8+ and CD19+ cells compared to CD4+ cells (10). These results demonstrated that M. leprae can lead to apoptosis of macrophages through a mechanism that could be at least partially related to the expression of pro-apoptotic members of the Bcl-2 protein family and of TNF-. Apo-
ptosis may also have a role in nerve damage in leprosy, as shown by a recent study which investigated the possibility that human Schwann cells are susceptible to cell death through the activation of Toll like receptor 2 (TLR2), a pattern recognition receptor of the innate immune system (12). Hence, apoptosis promoted by M. leprae may induce damage in the affected tissues, also may act as a defense mechanism by shedding the infected and effete macrophages and lymphocytes. Further study of apoptosis may help to understand the method/mechanism of clearance of bacilli and resolution of granulomas in leprosy patients. It is expected that the degree of apoptosis will decrease in patients with resolving disease; however an increasing trend is likely to be seen in the initial period of therapy when immune response is being reconstituted and bacillary clearance is occurring. If the process of apoptosis in skin lesions is followed up for a longer period of time, the degree of apoptoses is expected to come down. From this study it is not possible to delineate the exact role of each of the factors like type of disease, reactions, treatment regimens and steroids, with each contributing directly or indirectly to the nal result. Hence further studies with larger number of patients and prolonged follow up designed to detect apoptosis for at least up to 1 year duration are warranted.
REFERENCES
1. ABULAFIA, J., and VIGNALE, R. A. Leprosy: pathogenesis updated. Int. J. Dermatol. 38 (1999) 321334. 2. ALEMAN, M., SCHIERLOH, P., DE LA BARRERA, S. S., MUSELLA, R. M., SAAB, M. A., BALDINI, M., ABBATE, E., and SASIAIN, M. C. Mycobacterium tuberculosis triggers apoptosis in peripheral neutrophils involving toll-like receptor 2 and p38 mitogen protein kinase in tuberculosis patients. Infect. Immun. 72 (2004) 51505158. 3. AMSTERDAM, A., TAJIMA, K., and SASSON, R. Cell-specic regulation of apoptosis by glucocorticoids: implications to their anti-inammatory action. Biochem. Pharmacol. 64 (2002) 843850. 4. CREE, I. A., GARDINER, C. A., BECK, J. S., and MEHTA, J. Studies of cell death (apoptosis) and cell division in leprosy granulomas. Int. J. Lepr. Other Mycobact. Dis. 54 (1986) 607613. 5. CREE, I. A., NURBHAI, S., MILNE, G., and BECK, J. S. Cell death in granulomata: the role of apoptosis. J. Clin. Pathol. 40 (1987) 13141319.
276
2005
6. HERNANDEZ, M. O., NEVES, I., SALES, J. S., CARVALHO, D. S., SARNO, L. N., and SAMPAIO, E. P. Induction of apoptosis in monocytes by Mycobacterium leprae in vitro: a possible role for tumor necrosis factor-alpha. Immunology 109 (2003) 156164. 7. HOCKENBERY, D. Dening Apoptosis. Am. J. Pathol. 146 (1995) 1619. 8. MUSTAFA, T., BJUNE, T. G., JONSSON, R., PANDO, R. H., and NILSEN, R. Increased expression of fas ligand in human tuberculosis and leprosy lesions: a potential novel mechanism of immune evasion in mycobacterial infection. Scand. J. Immunol. 54 (2001) 630639. 9. NAISBITT, D. J., HOUGH, S. J., GILL, H. J., PIRMOHAMED, M., KITTERINGHAM, N. R., and PARK, B. K. Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity. Br. J. Pharmacol. 126 (1999) 13931407. 10. NIANG, M. N., BALDE, A. T., PERRAUT, R., MANE, I., and CARTEL, J. L. Apoptosis in leprosy patients. Int. J. Lepr. Other Mycobact. Dis. 67 (1999) 473474. 11. OLIVEIRA, R. B., MORAES, M. O., OLIVEIRA, E. B., SARNO, E. N., NERY, J. A., and SAMPAIO, E. P. Neutrophils isolated from leprosy patients release TNF-alpha and exhibit accelerated apoptosis in vitro. J. Leukoc. Biol. 65 (1999) 364371. 12. OLIVEIRA, R. B., OCHOA, M. T., SIELING, P. A.,
13.
14.
15.
16. 17.
18.
REA, T. H., RAMBUKKANA, A., SARNO, E. N., and MODLIN, R. L. Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy. Infect. Immun. 71 (2003) 14271433. SAMPAIO, E. P., HERNANDEZ, M. O., CARVALHO, D. S., and SARNO, E. N. Management of erythema nodosum leprosum by thalidomide: thalidomide analogues inhibit M. leprae induced TNF alpha production in vitro. Biomed. Pharmacother. 56 (2002) 1319. PALMITER, R. D., CHEN, H. Y., MESSING, A., and BRINSTER, R. L. SV 40 enhancer and large-T antigen are instrumental in development of choroid plexus tumors in transgenic mice. Nature 316 (1985) 457460. WALSH, D. S., LANE, J. E., ABALOS, R. M., and MYINT, K. S. TUNEL and limited immunophenotypic analyses of apoptosis in paucibacillary and multibacillary leprosy lesions. FEMS Immunol. Med. Microbiol. 41 (2004) 265269. WHO EXPERT COMMITTEE ON LEPROSY. World Health Organ. Tech. Rep. Ser. 874 (1998) 143. WILLIAMS, G. T., and SMITH, C. A. Molecular regulation of apoptosis: genetic controls on cell death. Cell. 74 (1993) 777779. WYLLIE, A. H. Apoptosis: an overview. Br. Med. Bull. 53 (1997) 451465.
CLINICAL NOTES Myiasis in Leprosy

G. N. Malaviya1
Infestation of ulcers and invasion of nasal cavities of leprosy-affected persons by larvae of different ies is still seen in some patients today. Leprosy-affected persons, whether active or released from control, having residual problems like atrophic rhinitis or anesthesia of the hands and feet can acquire maggot infestations especially if they are from economically weaker strata of society, have poor hygiene, suffer from general debility and have poor near vision. The term myiasis is derived from Greek word Myia meaning a y. Infestation of living tissues by larvae of dipterans ies is called myiasis, and Goldstein (2) was probably the rst to report myiasis in human beings. The ies responsible for myiasis are grouped as obligatory, facultative and accidental parasites depending upon the ovi or larvipositing habits of the ies. Common genera causing myiasis in humans are Sarcophaga, Chrysomyia, Lucilla, and Calliphora. Occasionally common house ies (belonging to genus Musca) are also responsible for accidental myiasis. Based upon the affected organ, myiasis can also be classied as nasal, aural, ocular, anal, vaginal etc. Animal myiasis is well known. Human tissue myiasis involving the skin has been reported from Mexico, the Middle East, North Africa and the United States of America, but few documented reports are available (3, 7). The maggots of certain dipterans ies are merely scavengers and are sometimes found to be benecial. These surgical maggots are said to help in healing wounds (9,10). However it is difcult to predict cir-
1 Dr. G. N. Malaviya, Department of Plastic & Reconstructive Surgery, Central Jalma Institute for Leprosy, Tajganj, Agra (India) PIN 282 001; e-mail: govindmalaviya@rediffmail.com
cumstances under which they act as scavengers or as a serious parasite. It has been observed that once the wounds of the extremities are cleared of maggots they granulate faster. This has been attributed to the presence of allantoin which is excreted by maggots into the wound (11). Myiasis is more commonly seen in the tropics and subtropics where ies are present in abundance. These are the areas of the world where leprosy also exists. Myiasis causes distress, pain and increases tissue damage. Myiasis is a serious problem when it occurs, although Sreevatsa, et al. (12) found the incidence to be less than 0.5% in 3350 consecutive cases of leprosy of all types. Either sex can be affected but there has been a male predominance, probably due their involvement in outdoor activities. Poor personal hygiene as well as environmental conditions increase the risk of myiasis. Cases are more frequent during September to Novemberthe post monsoon season (mean temperatures around 25 Celsius and humidity 8090%)a favorable period for ies to breed. Reports in the literature about tissue myiasis are scanty; only nasal myiasis been extensively studied. The loss of capability to perceive sensory stimuli contributes significantly to such infestations. Atrophic rhinitis in BL-LL cases predisposes to nasal invasion, and 6070 % of lepromatous cases have ulcers of nasal mucosa during the course of illness (1). The suppurartive wounds of the nasal cavity and the resulting muco-purulent discharge provide an attractive and rather secure site for ies to breed. It is likely that ies lay their eggs in the vicinity of nostrils; eggs are subsequently pushed inside while wiping the nose. Larvipositing ies lay their larvae in the vicinity and they subsequently migrate into the nasal cavitya darker area.
277
278
2005
Wounds and ulcers in extremities, for various reasons, are seen in 1520% cases of all types leprosy (13). Infected suppurating wounds in these anatomical areas provide a congenial atmosphere for the ies to lay their eggs/larvae, and for larvae to grow and develop further. These larvae burrow deep into the wounds and damage tissues further. Clinical presentation of myiasis. Infestations of the nose and extremities produce several symptoms, some of which are common. Patients may have recurrent infestations, especially in nose. Nasal myiasis, usually seen in lepromatous (LL) and borderline lepromatous (BL) cases, gives rise to a feeling of uneasiness, nasal stufness and obstruction, headache, irritation, gnawing and/or insect crawling sensations in the nose, and sneezing. Associated features are blood-tinged nasal discharge or frank epistaxsis, swelling of the nose and nearby facial structures, and at times insects (maggots) dropping out of the nose, either spontaneously or on blowing the nose. Patients may appear to be disinterested and apathetic but are in severe agony. Sometimes tissue destruction is extensive and can lead to nasal perforation and other nasal deformities such as collapse of nasal architecture, partial absorption of nasal bones, and deviation of the nasal septum (4). Nasal perforation may result in a nasal stula when edema subsides and tissues begin healing. Occasionally the larvae burrow deep into the oor of the nasal cavity and erode the bony palate to produce a palatal perforation which may result in a permanent palatal stula. These stulae are difcult to treat because of intense brosis in the surrounding areas (8). Nasal myiasis can prove fatal if cavernous sinus thrombosis develops or the oor of the cranium is invaded. Many of the patients affected with nasal myiasis keep moustaches which, if not cleaned properly, can attract ies. The nasal discharges and food adhering to the hairs in moustaches and drying up, is again a source of attraction to ies. Patients having ulcers of the extremities complain of a feeling of insects crawling in areas around the wound, foul smelling discharge, swelling and insects in the wound. Many times patients try to treat their wounds themselves with available insecticides before presenting for treatment.
The bacterial ora seen in maggot-infested wounds of the extremities is mixed (6). Among gram-positive aerobes, Staphylococcus aureus, Staphylococcus albus and Streoptococcus pyogenes were more frequently isolated; gram-negative aerobes included Proteus spp. and Escherichia coli. Anaerobes which were isolated include Micrococcus and Bacteroids whereas Clostridia were seen infrequently (2% cases). Even after removal of maggots, Staphylococcus aureus persisted in the wound, though gram negative bacteria and anaerobes were dramatically reduced. These observations revealed only the spectrum of bacteria but not the quantum of bacterial load in maggot infested wounds. Sreevatsa, et al. (12) were able to culture the larvae obtained from the nose and wounds in laboratory and found that two ies were mainly involvedSarcophaga rucornis and Chrysomyia bezziana. Husain, et al. (5) in another study found Sarcophaga haemorrhoidalis, Chrysomiya bezziana, Callitroga americana and Musca domestica infested the nose and wounds of the extremities in leprosy affected persons. The former two were more frequent, and at times two or more species were infesting the same wound. Management of myiasis. The goal of management is to remove maggots as fast as one can, kill them to prevent maturation, promote wound healing and prevent secondary complications. Myiasis of the nose and that of the extremities require different approaches. Wounds of the extremities are washed with pure chloroform (Pharmacopoeia grade). About 5 to 10 ml is enough for an average size wound. Chloroform kills the maggots instantaneously (5) and is innocuous to the tissues. It must be stored in amber colored bottles away from sunlight because it decomposes in presence of sunlight to form a toxic product. It is better than ether (used in some clinics) which is more volatile and irritating and has a local freezing effect. Dead maggots can be manually removed or the wound can be lightly curetted, taking special care to remove maggots from under wound margins. Since maggots have a tendency to migrate quickly towards deep and darker areas, it is better to organize materials before opening the dressings. Wound
73, 4
Clinical Notes
279
debridement in the extremities should be limited to the essential minimum because the wound rapidly granulates and healing is faster if general debility is not severe. The wound is then dressed with uffed gauze soaked in a mixture of turpentine and water (1:10). This keeps the ies away, masks the bad odor and absorbs the discharges. Dressing changes are made after 24 hours and the wound is treated similarly removing dead tissues; additional chloroform treatment may be needed if some live maggots remain. The wound is usually free of maggots by the second or third day and then can be treated like any other infected wound. For nasal myiasis, the nasal cavity is copiously irrigated with a mixture of chloroform and water (1:2) two to three times a day and then is lightly packed with a ribbon gauze soaked in a mixture of turpentine and liquid parafn (1:15). The process is repeated until the nasal discharge subsides. Dead maggots are coughed out mixed with discharges. The patient should be advised to instill nasal drops made of turpentine oil and liquid parafn (1:20). Deep posterior burrowing of maggots makes their manual removal difcult. Patients are prescribed antibiotics and aspirin in suitable doses to control infection and prevent intracranial complications (i.e., cavernous sinus thrombosis). Patients are also given sedatives such as diazepam to reduce discomfort. The nasal cavity is usually free of maggots in 48 72 hours after starting treatment, and local cellulitis subsides in 7 to 10 days. Nasal myiasis usually does not require any surgical intervention except in cases where tissue destruction is extensive and nasal structures have been destroyed by maggots. There also the tissue excision should be done conservatively. Incisions on the nose to attempt manual removal of maggots should be avoided. In patients having recurrent infestations, partial closure of the nostrils using local mucosal aps can be performed (14). Myiasis is an avoidable problem. It can be prevented by proper ulcer care and by preventing ies from settling on ulcers by keeping the wounds well covered with
dressings and by painting the top-most layer with a turpentine water mixture (1:5), especially during the post monsoon season when ies tend to breed. To prevent nasal myiasis patients need to be educated about routine nasal care and hygiene.
REFERENCES
1. DAVEY, T. F., and BARTON, R. P. E. Leprous lesions of nose. In: Leprosy. Eds. Dharmendra; Kothari Publishing House: Bombay. Vol I. Chapter 12, 1978, pp. 168173. 2. GOLDSTEIN, M. A. The texas screw-worm and its invasion of the nasal cavities. Laryngoscope 3 (1897) 335340. (Quoted by Sahay L K. Ind. J. Otolaryngol.11: 146148, 1959). 3. GORDON, P. M., HEPBURN, N. C., WILLIAMS, A. E., and BUNNEY, M. H. Cutaneous myiasis due to Dermatobia hominis: a report of six cases. Br. J. Dermatol. 132 (1995) 811814. 4. HUSAIN, S., MALAVIYA, G. N., GIRDHAR, A., SREEVATSA, and GIRDHAR, B. K. Nasal Myiasis in Leprosy. Lepr. Review. 62 (1991) 389394. 5. HUSAIN, A., HUSAIN, S., MALAVIYA, G. N., and BAHADUR, R. R. Myiasis in leprosy. Acta Leprologica 8 (1993) 137141. 6. HUSAIN, A., SREEVATSA, MALAVIYA, G. N., HUSAIN, S., and BAHADUR, R. R. Characterization of microbial ora of leprous ulcers infested with maggots. Acta Leprologica 8 (1993) 143147. 7. KENNY, R. L., and BAKER, F. J. Boty (Dermatobia hominis) myiasis. Int . J. Dermatol. 23 (1984) 676677. 8. MALAVIYA, G. N., and HUSAIN, S. Repair of Nasal Fistulae in Leprosy. Euro. J. Plastic Surgery 14 (1991) 232234. 9. PECHTER, E. A., and SHERMAN, R. A. Maggot therapy: the surgical metamorphosis. Plastic & Reconstructive Surgery. 72 (1983) 567570. 10. REAMES, M. K., CHRISTENSEN, C., and LUCE, E. A. The use of maggots in wound debridement. Ann. Plast. Surg. 21 (1988) 388391. 11. ROBINSON, W. Stimulation of healing in non-healing wounds by allantoin (occurring in maggot secretions and of wide biological distribution). J. Bone Joint Surgery 17 (1935) 267271. 12. SREEVATSA, MALAVIYA, G. N., HUSAIN, S., GIRDHAR, A., BHAT, H. R., and GIRDHAR, B. K. Preliminary observations on myiasis in leprosy patients. Lepr. Review 61 (1990) 375378. 13. SRINIVASAN, H. Neuropathic ulceration. In: Leprosy. Eds. Dharmendra. Kothari Publishing House: Bombay. Vol I: Chapter 18. 1978, p. 225. 14. YOUNG, A. Closure of nostrils in atrophic rhinitis. J. Laryngol. Otol. 81 (1967) 514524.
CORRESPONDENCE
This department is for the publication of informal communications that are of interest because they are informative and stimulating, and for the discussion of controversial matters. The mandate of the JOURNAL is to disseminate information relating to leprosy in particular and also other mycobacterial diseases. Dissident comment or interpretation on published research is of course valid, but personality attacks on individuals would seem unnecessary. Political comments, valid or not, also are unwelcome. They might result in interference with the distribution of the JOURNAL and thus interfere with its prime purpose.
A Need for Clarication of the Classication Criteria for Leprosy Patients

TO THE EDITOR: We read with interest the article by Gelber et al. (1) in the December 2004 issue of THE JOURNAL, in which they observed high relapse rates in MB leprosy patients with high initial bacterial indices (BI). Even though we agree with the conclusions from the article, we were surprised to see the following phrase in the discussion: . . . classifying patients as MB or PB. This distinction is now determined simply by counting the number of skin lesions, MB being 5 or more (our emphasis) and PB being less. This is actually a misinterpretation of the WHO guidelines and our eld experience has indicated that this mistake is often made in leprosy control programmes: The actual WHO classication criteria are: more than 5 lesions for MB (27) and 5 lesions or less (24,6,7) or up to ve (5) for PB. As more than 5 in our experience is regularly interpreted as 5 or more by eld workers (and apparently also by the distinguished research group at the Leonard Wood Memorial Center in Cebu), we suggest that the recommendation be re-stated to state: 6 or more for MB leprosy and 5 or less for PB leprosy in all protocols and reports. In the case of the article by Gelber et al. (1) we are aware that the above misinterpretation of the WHO guidelines for classication had no inuence on the outcome or interpretation of the study results. This is because they made use of BI determinations
280
and Ridley and biopsies classied according to the Ridley-Jopling system. This lack of any effect on the results may make our point appear trivial, but if standard criteria are not used in published studies it undermines attempts to standardize criteria in the eld. The same phrase mentioned above also states that classication is determined by . . . simply counting the number of skin lesions (our emphasis). Actually, in our opinion the information provided by WHO is confusing on this point: In some documents (2,4,7), dating from 1995 and 2005, the inclusion of enlarged or damaged nerve trunks in the classication of leprosy is advised, with more than one involved nerve leading to classication as MB. In other documents (3,6), dating from 1997 and 2000, classication is solely based on counting skin lesions. We know from experience that in some leprosy control programs skin lesion counting is the only classication criterion used, while in other programs nerve involvement is included as well. Even within one country different control programs may use different classication criteria, making it extremely difcult to compare data from different programs, such as PB/MB ratios. The above observations emphasize the need that WHO gives clear and consistent criteria and that the those who collect and analyze the data (government ofcials, clin-
73, 4
Correspondence
281
icians, leprosy control ofcers and researchers) use unambiguous phrasing of classication criteria in protocols and reports to prevent misinterpretation, especially among people for whom English is not the rst language and/or for health workers in the eld who may have relatively limited education. It also emphasizes the importance of a detailed description of the exact classication criteria used in leprosy studies where classication of the leprosy patients is important for the interpretation of study results.
REFERENCES
1. GELBER, R. H., BALAGON, V. F., and CELLONA R. V. The relapse rate in MB leprosy patients treated with 2-years of WHO-MDT is not low. Int. J. Lepr. Other Mycobact. Dis. 72 (2004) 493500. 2. WORLD HEALTH ORGANIZATION. A guide to eliminating leprosy as a public health problem. Geneva: World Health Organization, 1995. WHO/LEP/95.1.
3. WORLD HEALTH ORGANIZATION. Guide to eliminate leprosy as a public health problem. World Health Organization, 2000. 4. WORLD HEALTH ORGANIZATION. 2005. URL: http://www.who.int/lep/disease/classication.htm 5. WORLD HEALTH ORGANIZATION. Global strategy for further reducing the leprosy burden and sustaining leprosy control activities 20062010. Geneva: World Health Organization, 2005. WHO/CDS/CPE/CEE/2005.53. 6. WHO EXPERT COMMITTEE ON LEPROSY. Seventh report. Geneva: World Health Organization, 1998. Tech. Rep. Ser. 874. 7. WHO REGIONAL OFFICE FOR THE WESTERN PACIFIC. 2005. URL: http://www.wpro.who.int/sites/ leprosy/leprosy_wpr/leprosy_classication.htm
Dr. Linda Oskam Dr. Samira Bhrer-Skula KIT (Royal Tropical Institute) KIT Biomedical Research Meibergdreef 39, 1105 AZ Amsterdam The Netherlands.
Dr. Gelber and Colleagues Reply

We entirely agree with the errors noted by Dr. Oskam and colleagues concerning our mistake regarding the number of skin lesions required by the WHO for the classication of MB leprosy, as well as their comments concerning the WHOs conicting statements concerning nerve trunk enlargement and damage in classifying leprosy cases. Furthermore, we agree that clarity in classication standards is necessary. In our report, the utility of counting lesions for classication, and not skin smears or histopathology, was criticized for its potential to fail to identify those leprosy cases with a high BI and who are BL or LL , these having been established as at high risk for relapse. Though Scollard (1) has recently and eloquently described in detail the importance of skin smears and proper histopathologic classication in research papers, there are 2 additional reasons clinicians require smears and biopsies for classication: 1. We have found over 1/3 of our patients who would be classied as PB by counting lesions are in fact BL or LL with an average BI (6 sites) of 2.3 (unpublished observations). Such patients at many centers would be treated, we believe inappropriately and to their detriment, with the PB regimen. Fortunately, in Cebu, we still use skin smears and biopsies for leprosy classication, and these patients are treated as MB leprosy. 2. In our MB patients an increasing BI is associated with an increased risk of reactional states after the completion of MDT, occurring particularly frequently in those treated with 1-year MDT as opposed to 2-year MDT and after 1-year MDT in 48% of patients in the rst 2 years after the competion of therapy (manuscript submitted for publication). Skin smears could thus prove particularly useful in assisting to re-dene when patients can safely be released from control. In conclusion, for those treating leprosy patients, skin smears and biopsies classied by the methods of Ridley and Jopling have are advantageous methods, compared to counting lesions, in predicting which patients are at risk for relapse and avoiding under-treatment, and in identifying patients
282
2005 Maria Balagon Rodolfo Abalos Tranquilino Fajardo Fe Pardillo
at high risk for reactional states after the completion of MDT.

1. SCOLLARD, D. M., Classication of leprosy: a full color spectrum, or black and white? Int J Lepr Other Mycbact Dis. (2004) 72:1668.
Robert Gelber Roland Cellona
The Leonard Wood Memorial Center for Leprosy Research Cebu City, Philippines
NEWS and NOTES

This department furnishes information concerning institutions, organizations, and individuals engaged in work on leprosy and other mycobacterial diseases, and makes note of scientic meetings and other matters of interest.
Stigma, Identity and Human Rights

The Experience of Leprosy in the Era of HIV/AIDS Robben Island, South Africa 46 February 2005 Sponsored by IDEA and the ILA Global Project on the History of Leprosy in Association with Robben Island Museum
Introduction to the History of Robben Island Dr. Harriet Deacon

The Graveyard Remembrance: IDEA Banner of Honor Rev. Albrecht Hahne, Dr. P.K. Gopal, Zilda Borges, Alhaji Shehu Sarkin Fada, William Malo Banishment: The Welfare of Society versus The Rights of Individual Freedom Chairs: Dr. Harriet Deacon & Anwei Law Sigurd Sandmo Norwegian segregation policies Jose Ramirez, Jr. Banishment versus imprisonment Ryohei & Suiko Shibata Japans absolute segregation policy Church of the Good Shepherd Isolation: The Experience of Isolation Chairs: Dr. Jo Robertson & William Malo William Malo, Former resident, Kalaupapa, Hawaii, USA Crescencio T. Rosello, Culion, Republic of the Philippines Keteng Feng, Guangdong Province, Peoples Republic of China Miyoji & Mieko Morimoto, Japan Dr. Michael Chen, Guangdong, Peoples Republic of China Dr. Arturo Cunanan, Culion, Republic of the Philippines ~ Clint Anabieza, Cebu, Republic of the Philippines
From February 46, 2005, individuals from 16 countries whose lives have been impacted by stigma, either as a result of leprosy or HIV/AIDS joined in discussion with historians specializing in the elds of leprosy, HIV/AIDS and human rights. The powerful backdrop of Robben Island, an international symbol of (in the words of the Robben Island Museum) the indestructibility of the spirit of resistance against colonialism, injustice and oppression, inspired discussions of how history can effect social change. At the same time, the legacy of Robben Island and all those who resisted its oppression empowered discussions on how stigma denies both identity and human rights with a view to developing concrete actions that can be used towards eliminating the power of stigma to destroy peoples lives.
PROGRAM Friday, February 4: Banishment, Isolation, Resistance & RemembranceTour and Discussions: Interacting With the History of Robben Island The Maximum Security Prison: WelcomeDr. Jo Robertson Opening RemarksDeirdre Prins-Solani and Richard Whiteing Remarks by Mr. Yohei Sasakawa, President, The Nippon Foundation
Saturday, February 5: Stigma & Identity

The Guesthouse Resistance: Retaining Identity in the Face of Oppression Chairs: Simonne Horwitz Panel: Arega Kassa Zelelew, Artur C.M. De Sousa (Zackie AchmatTreatment Ac283
284
2005
tion Campaign, South Africa, and Yasuji Hirasawa, Japan, were unable to participate at the last minute)
Stigma & Identity Culture, Identity & Stigma: The African Experience Chairs: Arega Kassa Zelelew and Dr. John Manton Panel: Dr. Jean-Paul Bado, Linda Beer Kumwenda, Jan Mahlangu, Bhekani Memela The Effect of Stigma on Individuals & Families Chairs: Jose Ramirez, Jr. and Ko Nyarko Panel: S.K. Jung, Jae Heung Kim, Magdalena Ramirez, Dr. Harriet Deacon, Ms. Inez Stephney, Amar Timilsina, Adi Yosep, Jaimie Tomas Cabeto, Rev. Albrecht Hahne, Breaking the Silence: Women & Stigma Chairs: Zilda Borges and Mimi Badamuti Panel: Natalia Isabel da Graca Marcal, Zoica Bakirtzief, Tiruwork Mengistu, Birke Nigatu, Saruto Labbo Illuminating Ourselves: Redening Traditional Images Open discussionThe role of images and language in the formation of attitudes. Achievements of people affected by leprosy or living with HIV/AIDS, past and present, as a means of challenging stereotypes and the stigma that is perpetuated by them. From Ingeborg Grytten (Author, Norway, 17th century) to Akashi Kaijin (Poet, Japan, early 1900s)
Excerpts from the meeting follow. Dr. Jo Robertson has provided summaries of the academic papers presented, and Anwei Law has provided transcripts of the other presentations and discussion. These have been combined and edited for brevity, attempting to preserve the sense and spirit of the discussions. Ed. Friday, February 4:
Banishment, Isolation, Resistance & RemembranceTour and Discussions: Interacting With the History of Robben Island The Maximum Security Prison Deirdre Prins-Solani, Manager, Education Department, Robben Island Museum: Robben Island represents the triumph of the human spirit against adversity. What does it mean for the spirit to triumph? One of the ways in which we have interpreted it is that we triumph through resistance; that an act of resistance against oppression, an act of resistance against stigma, an act of resistance against segregation, is a triumph of the spirit. When you came into prison, your name was written down into a book and you were given a number. You were told any communication that happened between you and the authorities would be done through your number. You lost your name, you lost your identity, your sense of belonging. So there was an attempt to erase an identity. . . So when we ght against oppression and segregation and we ght against erasure, the voices of people who have experiences of a particular condition should be the people who speak. And thats why when we learned who the participants in this workshop were, we were very excited. We said yes, this is in keeping with the mission of this institution. Eugene Mokgoasi, Former Political Prisoner, Robben Island: Coming to Robben Island . . . . you met people who had a common understanding, a common journey, and destiny like you. Robben Island was a learning institution. The rst morning here, it was kind of cold, and a guy said to me, Youre home now. Youre not going to live tomorrow, youre not going to live yesterday, youre going to live today and today only. Now look around. Youve got broth-
Sunday, February 6Human (Multi-Purpose Learning Center)

Human Rights Professor Bernardino Fantini
Rights
Ensuring the Rights of Humanity Chairs: Professor Bernardino Fantini & Dr. P.K. Gopal Panel: Alhaji Shehu Sarkin Fada, Chamada Abibo In Conclusion: History as an Agent for Social Change Prof. Megan Vaughan, Zilda Borges and Anwei Law
73, 4
News and Notes
285
The IDEA Banner of Honor is displayed at the cemetery where people who had leprosy were buried on Robben Island. The Banner of Honor recognizes individuals who have had leprosy who have made signicant contributions to their own countries. Photo by Pamela Parlapiano
ers, youve got fathers, youve got uncles, youve got everything you need. Whatever you need, approach any one of us. And I felt safe, for the rst time. Richard Whiteing, Robben Island Museum: We can see the prison, but when we go back to the hospital period and . . . we nd an erasure that Deirdre mentioned. One of the unique aspects of the people living with leprosy and the buildings they lived in is that theres been an attempt to obliterate the built fabric. We have but one building that remains that was used by people with leprosy, and that is a church. The rest of the buildings were burned because of the fear of infection. But they cant obliterate the cultural landscape, so we still have trees that were planted at that time. We have a shpond that was built for the children in the childrens section. We have the graveyard. . . So often there has been a silencing, but what we will try and do is to help you imagine . . .
The Graveyard: Remembrance: The IDEA Banner of Honor Banishment: The Welfare of Society versus The Rights of Individual Freedom
Sigurd Sandmo, Curator, The Leprosy Museum, Bergen. Norwegian segregation policies. The Norwegian contributions to the struggle against leprosy worldwide are famous, partly because of Hansens discovery of the leprosy bacillus in 1873, partly because the Norwegian leprosy policies of the 19th century served as models for other countries, especially in terms of legislation. The idea that the Norwegian policies were rather humane and rational, like Hansen saw them, seems however still widespread, but I think we lose an important opportunity to understand the dynamics of banishment if we attribute the building of modern leprosaria to a theory of contagion, disconnected from public stigma. In the golden age of Norwegian leprosy work, the physicians contributed willingly to the social banishment of leprosy sufferers outside the institutions, to make them easier to collect, and to make it more difcult for them to escape the modern leprosaria. In order to demonstrate both the connections and lack of connectedness between the theory of contagion and the Norwegian model of segregation, four examples of how the medical
286
2005
Norway fraternity tried out different strategies in order to direct sufferers towards hospitalization from the 1840s to the 1880s, in the golden age of Norwegian leprology, are discussed. In 1877 the Norwegian parliament passed an act making provision for those suffering from leprosy, which practically forced this group into hospital. And in 1885, the parliament passed a much stricter act On Segregation. Outside the inner circles of leprologists, many considered this act as being a terrible mistake and perhaps even against the constitution. The segregationists and the contagionists won the dispute and the last obstinate cases of leprosy could nally be collected.
REFERENCES
SIGURD SANDMO. The Politics of a Bacillus in Krasner, Robert: Meeting the Microbial Challenge. American Society for Microbiology Press. New York, 2002. SIGURD SANDMO. En hovedstad for spedalske. Bergens bermte leprahistorie. (Printed radio lecture for Norways National Broadcasting) P2akademiet, Vol. Y. Oslo, 2002. s 163175.
these places dealt with people who were affected by leprosy in the same way. Some were much more absolute in terms of the isolation than others. Some of the places in Africa were more treatment places than anything else. Going through this list alphabetically, it may seem as though the list is endless . . . . What surprised me when I looked at the register from Culion were the ages of the people . . . . youd be surprised how young they were and I think this is true of many places, 15 yr olds, 11, yr olds, very, very young people.
Church of the Good Shepherd: The Experience of Isolation Dr. Harriet Deacon, Consultant, Human Sciences Research Council, Cape Town, South Africa: This building is very symbolic for this meeting; to be speaking in this building about the history of leprosy and its relationship to other forms of stigmatization. I think its really essential, when we talk about Robben Island as a leprosarium, to understand the difference between the isolation of patients in the pre-1891 period, before the Leprosy Repression Act was passed, and the situation after1891, where people were forcibly institutionalized once theyd been identied as people with leprosy. In 1891, you had a huge inux of patients coming, largely involuntarily, to the island and often they felt that they were tricked into coming to the island. This church dates from 1895, from the period in which the leprosy patients were moved out of the village, and further isolated even from the staff on the island. Jose Ramirez, Jr., M.S.W., IDEA USA: People oftentimes think of banishment as the same as imprisonment. But for many of us, we think of banishment in terms of leprosy, because there has been banishment . . . . With imprisonment you nd that persons end up with a particular term to describe them political prisoners, jailbirds, etc. But when theres banishment of a person with Hansens Disease, theres the brand of the word leper that we all dislike, so its never a multitude of words to describe those with leprosy, its only one word. When you talk about the laws related to leprosy, what youre really talking about are the laws of silence. People were not speak-
Ryohei Shibata, IDEA Japan: The main idea of the absolute segregation policy in Japan was to abolish and eliminate the patients; it was not to cure them. I was diagnosed with leprosy in 1947. I was shunned by society and segregated in a sanatorium on an isolated island. There, I was forced to wait for my life to end. A poet living in the sanatorium on the island where I was sent once said: Like those luminescent sh dwelling in the sunless depths of the sea, I will nd no light until I light myself up from within. . . . After 21 long years, I nally returned to society. In Johannesburg I went to an Apartheid Museum. There I saw the history of the men who were put in jail for no reason other than being black. That particular image overlapped with my own experience. In this sense, apartheid, the Japanese segregation laws and segregation policy, were similar. One was for racial discrimination and the other was discrimination against those people who have leprosy. Dr. Jo Robertson, Coordinator, ILA Global Project on the History of Leprosy, UK: I dont think any of us have any idea how many places there were in the world where leprosy work was done. Not all of
73, 4
News and Notes
287
William Malo, who was isolated at Kalaupapa, Hawaii as a young man but has lived in the community for the last 40 years, presents his experiences in the panel discussion The Experience of Isolation. To his left are Dr. Jo Robertson and Dr. Harriet Deacon. To his right are Mr. Feng Keteng and Dr. Michael Chen. Photo by Henry Law.
ing out about the injustices of banishment for those persons affected by leprosy in the last 3000 years. It has only been very, very recently that this has occurred. Persons with leprosy did not have an opportunity to be defended as do most who are imprisoned. So, what has happened is that banishment continues until death. Cresenciano T. Rosello, Culion, IDEA Philippines: . . . the very close family ties of the Filipinos made them regard segregation as an unmerited punishment that lasted for life. This condition triggered anti-segregation feelings and the families hid the aficted family members in the forest and in caves . . . . The people who were banished to Culion for the last 98 years their bones are crying for justice, justice that they did not have during their lifetime. William Malo, IDEA, Hawaii: The people of Hawaii knew that if you were taken and sent to Molokai, you would never be seen again. So, they were not afraid to hide you and to keep you at home as long as possible. They would continue to have your love at home. Thats why when I was asked
why the mothers were doing that, I said Love was greater than fear. The love for their children or husband or wife who had the disease was greater than any fear and so they hid their family members in order to keep them at home. Mieko Morimoto, IDEA Japan: When you got leprosy in Japan you just basically had to throw away every single thing you had. Because of leprosy, I had to give up my education, job opportunities, and to see my family. I regret that I could not have children. I have always, always wanted to have children. I was young then and I just couldnt cope with the fact that I couldnt have children and it was almost like a sickness I had in my heart. However, I have to say that since I got leprosy I have learned a lot. I have also stood up throughout the country to regain our humanity. Keteng Feng, Handa/IDEA China: If you go to our village you cannot see any children because even now we are still not allowed to get married and have children. I was sent to this leprosy village in 1963. Many decades have passed. We have suf-
288
2005
fered many difculties and in 1968 some people around our village came to attack us. Some people also committed suicide because their family wouldnt accept them. I was sent to the village in 1963 and I have only gone back home two times. I had to walk because we are not allowed to ride on the public bus. I had to spend more than 10 hours to walk back home. When I got there, my family didnt allow me to go into the house because they were afraid that I would bring them trouble. Miyoji Morimoto, IDEA Japan: Frankly speaking, and to be honest with you, I really do not want to look back . . . . But, I was specically asked to talk about banishment and also about stigma and discrimination. From the age 14, my life was as leprosy patient Myoji Morimoto and I was never able to live as Myoji Morimoto alone. This is something that I still hold in my heart. Japanese law had it that you couldnt go to college; you couldnt even go out of the Sanatorium. Against all advice and recommendations from the doctors and nurses and everyone in Sanatorium, I left the Sanatorium and went to college for four years. Now, there are 13 national sanatoria in Japan and about 3,500 people live in them. The average age is 78 years old. We were discarded from our hometowns and families and also by the government. Clint Aabieza, IDEA Philippines: When I graduated in 1994, I was also diagnosed as a person with Hansens Disease. Through the discrimination in society, the stigma comes. I decided to isolate myself because my family would face difculties because of my situation. At that time the doctor did not conne me at the hospital and said it was okay to take your medicine outside. But I faced discriminationsometimes the taxi driver would not allow me to ride in the car when they saw I had some patches on my face and hands. Thats one reason that I isolated myself in a small house beside in the sea. Some of my brothers and sisters brought me food to eat, but later I managed to cook on my own. At that time, many people told me that Im a person with leprosy, hopeless in this world. Some people told me that even though you are graduated from college, you will not be employed. I took my medicine almost two years but the stigma cannot be
erased in 10 years or 20 yearsit goes from generation to generation. Dr. Michael Chen, Handa/IDEA China: In China we still have more than 600 leprosy villages around the whole country and probably more than 60,000 people are isolated in these leprosy villages. Many of these places are in very, very remote areas, in mountainous areas that are not accessible by a vehicle. Some are even on an island like Robben Island and you have to go by boat. This is only the physical part of isolation and there are many, many difculties from the psychological part. For example, if a chair is sat in by a person who has the disease, other people wont touch it again. This still happens in some of the general hospitals. If the hospital has treated people who had leprosy, then they have to destroy all the instruments and equipment after that. Im glad to say that in China were getting more and more members of the younger generation as volunteers. They go to leprosy villages and try to break the world of isolation and develop more contact between people affected by the disease and the community. I think we can have a better future and reach our goals of a world without discrimination and stigma in the future. Dr. Arturo Cunanan, Jr, Culion, IDEA Philippines: I was born and grew up in Culion. I am a third generation descendent of Culion . . . . If you review most of the history of isolation, its never been towards the patients themselves, but towards the protection of the healthy individuals. Isolation was not for the purpose of curing the sick. In the past, there was no cure, but only care. Unfortunately, our policy makers and decision makers approached the issue of leprosy on medical aspects, whether unknowingly or knowingly, and the social aspects of leprosy were left to the religious side or non-governmental organizations . . . . I am very, very happy that during the last few congresses we are now hearing and learning that leprosy control should not simply be based on a medical approach. Saturday, February 5: Stigma & Identity
The Guesthouse: Resistance: Retaining Identity in the Face of Oppression Dr. Harriet Deacon: There were various kinds of resistance that both political pris-
73, 4
News and Notes
289
Participants in the Robben Island Conference (left to right): Simonne Horwitz, Wellcome Unit for the History of Medicine, Oxford; Mimi Badamuti, The Sinikithemba HIV+ Choir, South Africa; Ms. Inez Stephney, Human Sciences Research Council, South Africa; and Saruto Labbo, IDEA Nigeria. Photo by Pamela Parlapiano
oners in the post-1960 period and leprosy patients engaged in. For example, some people just buckled down and concentrated on education programs and developing a community among the patients. They collected lobster and craysh on the beaches, smuggled contraband and alcohol, and smuggled newspapers in . . . . With the 1892 rebellion led by Franz Jacobs, there was active resistance against institutionalization on the island. The way in which Franz Jacobs rebellion was silenced is interesting. There is almost nothing in the colonial archive here in Cape Town about the rebellion. The only place Ive found any record of it was in London at the Public Records ofce. It has been wiped off the face of the colonial archive and theres only one printed reference to it that talks about a smoking gun . . . . The way in which the patients resisted was that they actually de-
manded the things that they felt should go with a humanitarian segregation of themselves and they resisted being treated like slaves or prisoners. Simonne Horwitz, Wellcome Unit for the History of Medicine, Oxford University, U.K.: Its very tting that we are here in site thats linked to rebellion and resistance. In my own work on Westfort . . . . (a leprosy hospital thats just outside of Pretoria) from about 18901948, one of the themes that I constantly nd is that the authorities tried to segregate and oppress people by gender, by race and by their disease. They were constantly trying to segregate them, to take away their identity. Yet, it was very clear that people fought against that . . . . Yesterday there was talk about the political prisoners signing their names and its the same with Mr. Pipe who was at Westfort . . . . a
290
2005
man who wrote to the newspapers . . . . not as a person affected by leprosy, but as a person telling about how he was feeling, how he was treated in those early years. Because he spoke out about his oppression, he was forced to leave Westfort because they thought he was creating too much of an uproar. But he had created a sense of optimism amongst people who were ghting for their identity. There are a number of occasions where the women patients, for example, had a sit down strike and refused to work until they were called by their names, until they were recognized, until they were given some of the same things that Harriet was talking about on Robben Island. These were people who were very actively engaged in maintaining their identity and whether that was writing a newsletter about their lives or whether that was through strikes, [they] . . . actively tried to shape an identity that was not around their disease . . . . Zackie Achmat from the Treatment Action Campaign [in South Africa] is a person whos led a regeneration of civil society around issues of HIV and AIDS and hes taken an identity that has been stigmatized, an identity that was hidden around HIV/AIDS, and made it very public. Arega Kassa Zelelew, IDEA Ethiopia: When I remember 39 years back, my life was turned upside down. After facing repeated discrimination, I started to drink; I was a chain smoker. One day I thought, What am I doing? So I started to think beyond disability, beyond stigma, beyond the disease. My life started to change. I started to resist. I helped found ENAELP, the Ethiopian National Association for Persons Affected by Leprosy, and also the Ethiopian Federation for Persons with Disabilities. If you ght, if you struggle, we can win, we will win. Now we have got the international organization IDEA and we have to resist social stigma, discrimination, isolation . . . . Our colleagues, our companions on Robben Island from 18461931, they were ghting alone here on this island. Now we are united and this gives us strength. Anwei Law: International Coordinator, IDEA: We all know that resistance takes a lot of different forms. There are lawsuits but there is also the creative expression of resistance through music and art and poetry.
Certainly in Japan there is this wealth of poetry and creative expression that I think represented strong resistance during those very hard times. Within the oral history project and within IDEA, we are very much looking for the creative resistance and we encourage you to help us identify examples of this creative resistance. Dr. Wim Van Brakel, Royal Tropical Institute (KIT) Leprosy Unit, The Netherlands: I want to mention another side of the legal aspect. One is the repealing of any laws that might still be there that actively repress people affected by leprosy. On the other side, there may be some countries where there isnt a law like there was in Japan, but still you nd that people with leprosy and people perhaps with other disabilities have been marginalized very seriously, either by civil society, or just by the community. And, you would also nd that those countries have also signed disability acts as part of an international effort to try and raise the status of people with disabilities. So . . . . [we can] see if there is pro-disability legislation which would provide, for example, quotas for jobs or education. If that is there, it is important to ght to get that enforced . . . . for example, in India, part of the struggle is to actually get people to recognize that people with leprosy related disability come under that act and should have the right to have the same facilities that people with other disabilities would be accorded.
Stigma & Identity The Effect of Stigma on Individuals & Families Jose Ramirez, Jr.: I can trace my family history all the way back to a small shing village in Spain. That is very important to me and to my family . . . . When a person is diagnosed with Hansens Disease, oftentimes that persons history is taken away . . . . whether its through laws or through practices of different countries . . . . If you look at all of this collectively, the stigma throughout the world becomes a very powerful force . . . . Im hoping that you will go ahead and focus, not so much on what we have lost, but on what we have gained and continue to gain. Bhekani Memela, Sinikithemba HIV+ Choir, South Africa: I am HIV positive. I
73, 4
News and Notes
291
am part of the choir which is called the Sinikithemba HIV+ choir. Our mission is to educate and help people to be in a position to disclose their status and to check their status, especially in the rural areas. In South Africa we are still facing the serious problem of stigma. . . .[which] is very high in our country. There are many, many, many dangers which you face when you disclose your status. We have people who have been killed because they disclosed their status . . . . staying quiet and not discussing or sharing your problems that you are facing with your disease doesnt help; instead it perpetuates the stigma. Ignorance becomes a barrier for people to help other people. We are trying right now to educate people, to make them aware, to share our stories. We are HIV+. HIV is here. Its real and it kills. There is help. Its only that people . . . . dont want to come forward to go to the counsellors, to go to the clinics, to say Im having this problem with my life. If I myself and the other 14 members of the choir can go public and tell people that we are HIV positive but we are still living a fruitful and a healthy life, then we think . . . . that we will be in a position to reduce the level of death, to reduce the level of ignorance and to reduce the level of stigma.
Dr. Harriet Deacon and Inez Stephney and Sandra Prosalendis: Understanding HIV/AIDS stigma: a theoretical and methodological analysis. This theoretical and methodological analysis is the rst phase of a project initiated by the HSRCs Social Cohesion and Integration programme in Cape Town, in collaboration with the HSRCs Social Aspects of HIV/AIDS programme (SAHA). The larger project will develop ideas and test methodologies that can shed light on research on stigma in other contexts. We will also make recommendations about interventions to reduce the impact of HIV/AIDS-related stigma. This can support and inform the work of government and NGOs in managing the effects of the HIV/AIDS epidemic. Most of the research on HIV/AIDS stigma has been done in the US, a country with large research resources, an early epidemic and pronounced stigmatisation of
gay men, African-Americans and Haitian immigrants as carriers of HIV/AIDS. Considerable research attention is now being focused on HIV/AIDS research in general in Africa because of the severity of the African epidemic, the politics of the HIV/AIDS issue, and the fact that HIV/AIDS seems to be highly stigmatised in the region. However, the relative lack of scientic research on the manifestations of HIV/AIDS-related stigma in [Sub-Saharan Africa still] presents a serious challenge to the understanding, alleviation and prevention of HIV/AIDS related stigma (Lorentzen & Morris 2004:27). The problem of HIV/AIDS stigma in Africa has been raised in related research on barriers to testing, treatment, care and adherence, on quality of life, and on social responses to HIV/AIDS. It is important to understand HIV/AIDS stigma in relation to the broader social, political, economic and cultural context, and to address stigma as one of a number of causes of discrimination, reluctance to test, therapeutic noncompliance, and so on. First, however, it is, however, essential to clarify exactly what we mean by stigma, how it arises, and how it works, so that we can suggest ways of reducing its negative impact on society. Important recent work on HIV/AIDS stigma in South Africa includes Posel (2004), Kalichman & Simbayi (2003, 2004), Patient & Orr (2003), POLICY project (2003a), Stein (2003), Shisana & Simbayi (2002), Jennings et al. (2002). Research on HIV/AIDS stigma in other African countries includes ICRW 2002, Muyinda et al. 1997, Bond et al. 2002, and several Bergen University theses: Lie (1996 cited in Lorentzen & Morris 2004), Oduroh (2002 cited in Lorentzen & Morris 2004), and Lorentzen & Morris 2004. In order to conduct this literature review, we compiled a database of recent academic work on disease stigma across various disciplines and across different medical conditions (although we focused on HIV/AIDS). Our database (which currently stands at over 3,000 entries) is not yet fully comprehensive, nor yet fully representative of the admittedly meagre amount of current African research, but it provides a good general overview of the available material. This paper critically reviews academic
292
2005
literature on disease stigma that can help us to: 1. Develop more sophisticated theoretical approaches to understanding stigma in southern Africa, 2. Develop research methodologies to better understand the historical and cultural specicity of stigma, and its impact on the treatment and care of PLHAs in southern Africa, and 3. Inform the development of better antistigma interventions in southern Africa.
REFERENCES
1. DEACON, H. J., VAN HEYNINGEN, E., DIGBY, A., and PHILLIPS, H. (EDS.). The Cape Doctor (Rodopi, forthcoming) 2. DEACON, H. J. Patterns of exclusion on Robben Island, 16541992 in C Strange and A Bashford (eds.) Isolation: Places and practices of exclusion (Routledge, 2003) 3. DEACON, H. J. Racism and Medical Science in the Cape Colony, Osiris 15 (2000), 190206 reprinted in J P Jackson (ed.) Science, Race and Ethnicity: readings from Isis and Osiris (University of Chicago Press, 2002) 4. DEACON, H. J. Midwives and Medical Men in the Cape Colony before 1860, Journal of African History, 1998 5. DEACON, H. J. Cape Town and Country Doctors in the Cape Colony During the First Half of the Nineteenth Century, Social History of Medicine, 10(1) (1997), 2552 6. DEACON, H. J. (ED.). The Island: a History of Robben Island, 14881992 (David Philip and Mayibuye Books, 1996) 7. DEACON, H. J. Racial Segregation and Medical Discourse in Nineteenth-Century Cape Town, Journal of Southern African Studies, 22(2) (1996), 287308 8. DEACON, H. J. Leprosy and Racism at Robben Island in E van Heyningen (ed.) Studies in the History of Cape Town, vol.7 (Cape Town, 1994), pp.4583 9. JENNINGS, R., MULAUDZI, J., DAVID EVERATT, HEYWOOD, M., and RICHTER, M. 2002. Discrimination and HIV/AIDS, paper for the Department of Health written by Strategy & Tactics and the AIDS Law Project. 10. KALICHMAN, S. C., and SIMBAYI, L. 2004. Traditional beliefs about the cause of AIDS and AIDSrelated stigma in South Africa, AIDS Care, vol. 16, no. 5, pp. 572580. 11. KALICHMAN, S. C., and SIMBAYI, L. C. 2003. HIV testing attitudes, AIDS stigma, and voluntary HIV counselling and testing in a black township in Cape Town, South Africa. Sex Transm.Infect. 79 (6):442447. 12. POSEL, D. 1983. Rethinking the race-class debate
in South African historiography, Social Dynamics 9(1). 13. STEIN, J. 2003. HIV/AIDS stigma: the latest dirty secret, CSSR working paper no.46, University of Cape Town. 14. SHISANA, ET AL. 2003. The Impact of HIV/AIDS on the Health Sector: National survey of health personnel, ambulatory and hospitalised patients and health facilities, Pretoria: National Department of Health 15. SHISANA, O., and SIMBAYI, L. 2002. Nelson Mandela/HSRC Study of HIV/AIDS: South African National HIV Prevalence, Behavioral Risks and Mass Media, Household Survey 2002. Human Sciences Research Council.
Anwei Law, IDEA: One of the things Ive noticed, and we brought it up in Brazil, too, was that when people do social science research papers, they use quotations from people who have had leprosy, but usually dont use their names. Usually this is said to be out of ethical considerations. However, I think that when dealing with issues of stigma, one has to rethink this. I just saw a paper on stigma and HIV/AIDS that identied someone simply as a woman from Thailand its possible that the women requested this, but equally likely that the researcher suggested this. In any case, it serves to increase anonymity, which perpetuates stigma. I think that the people doing social science research need to really think about this. We have seen that identity is a critical part of eliminating the stigma and when you do not attribute a quote to a person, you are taking away their identity, which might also be regarded as unethical. Its a challenge. Its important to guard privacy as requested by a person, but important not to encourage anonymity, which only adds to the stigma. Jose Ramirez, Jr., IDEA USA: A scientic . . . method [hasnt been] developed yet that will measure stigma because there are so many differences in language, in culture, in geography, in laws, so its really very hard. In my opinion, stigma is actually an act of rejection or labelling or unexplained fear of a person or even of oneself because . . . . we learn about stigma even before were diagnosed. Amar Timilsina, IDEA Nepal: When I was nine years old and was going to school, I used to have needle pricking competitions among my friends, because of my loss of
73, 4
News and Notes
293
sensation . . . . When I eventually started the treatment, my suffering started because other people came to know that I was suffering from the disease. When I went back home and started going back to school again, they refused to have me in the class. So I was thrown out of the school as well as from the community. I was compelled to forsake my family and the love of the village where I was born and brought up . . . . I made up mind to commit suicide several times, but by the grace of love and good support from the hospital and staff I got additional energy to tolerate the pain and wait for the bright future . . . . Slowly I started getting the dignity back into my life. I got married, I have two children and am now the General Secretary of IDEA Nepal. Jaimie Tomas Cabeto, ARPAL/IDEA Angola: In 1978 I started hearing and learning about people affected by leprosy. We were children and as we saw those people in the leprosarium we thought that was something very odd, very strange . . . . It took a long time for the doctors to nd out what I had. I went to several clinics, saw several doctors but they couldnt tell what I had . . . . When the health professional told me the diagnosis, I was crushed. I started taking the treatment but I was afraid of telling my family I had the disease. As time went by and as I got involved in the Association of People Affected by Leprosy, ARPAL, in Angola, I started feeling courage to speak about the disease and to tell my family about the diagnosis. Rev. Albrecht Hahne, South Africa: If you look at the term stigma, it is a mark. If I look at my hands, they are marked hands. If I look at my face, its a marked face. In other words, I can say whatever Id like, but I will always have to live with this mark. I can tell other people that that mark is nothing, but every morning I get up I see that mark. Every day that I get dressed, I am reminded of that mark. The stigma is part of my life, of my existence. If I try to shy away from that, I actually need to try to shy away from a part of my existence . . . . Thatll to my mind be a decimation of my own life. I would return my life to nothingness . . . . I myself have come to this point that I accept the stigma of my life. . . My life is a life marked by leprosy . . . . If society is not prepared to accept us as
what we are, society is not worthy of us . . . . I rmly believe that this, my life as it is, is a unique life given to me by my Creator, I call him God. He said this life is going to be so valuable that I will put everything into this life that is necessary for this life to develop to what it is . . . . All of you know Im a pastor of a Christian Church. Ive led three churches, one church of over a thousand people and I must tell you, there was not one house into which I couldnt go. At the moment Im leading a church of over 500 people; theres not one house that I cannot enter. I believe the main thing . . . . is to say I accept what I am and with what I am, I will move out into society. If you have to run away, run away. Are we going to return into a cocoon of silence, cover everything up, dont talk about it, or are we going to share it with the society where were going to live. We share it. Let us bear this mark, this stigma, with courage. Lets face the world with courage. And we can help others to come to terms with the facts of their lives.
Breaking the Silence: Women & Stigma Zoica Bakirtzief, American Leprosy Missions, IDEA Brazil: Lets say a woman is dependent on her husband for income, dependent on her husband for housing and for providing for her children and her future and old age. If that husband rejects her and shes also unskilled and doesnt have other resources, thats a survival threat. Its not a simple threat. So would you ask her to disclose her diagnosis? Im just posing a question. Maybe the issue, perhaps, is not to have women so vulnerable to such situations, such as a disease. Economic power and independence, the possibility to not depend upon others for ones own survival, its a basic need for women and for men. So we have to consider the economic aspect of rehabilitation as an important issue in human rights because it has to do with survival, and if you are faced with the threat of survival, its very hard to cope with anything else. Its a burden too hard to bear. Zilda Borges, Brazil, IDEA Latin America: We know that women have been discriminated against in many parts of the world . . . . in relation to employment, income, and participation. We also know that many women have fought for their rights all
294
2005
over the world to overcome discrimination. I have met women with their heads bowed down, women who are part of the womens movement, or other social movements, but who do not speak about their experience with Hansens Disease. I have also met women with their heads held up high, who speak with people in the community about the disease. But the number of women who have their heads held up high is much smaller those who bow their heads. In the work I do amongst women, I give priority to the women who are living in silence. The methodology that I found to address their silence was to promote meetings. One woman, two women, three, four, ve, thats all. The groups are different, one from the other, and weve had groups that merged into other groups. The goal is to get the women involved and engaged and merged into other social movement groups. Mimi Badamuti, Sinikithemba HIV+ Choir, South Africa: The question is, is the stigma ever going to end? Thats the question I ask myself every day. Every time you are talking about HIV and AIDS, people, they think you are talking about a wild animal that can pounce on them, attack them and kill them instantly. But its not. Ive got a great experience about stigma, because in our country, here in South Africa, we are labelled. Its none of anybodys business that you are HIV positive or HIV negative, but people think its their own business . . . . the main problem is with us women. Once you disclose your status to your partner it is the last time you hear from him. He goes, he disappears. Sometimes, most of us women, we nd out when we are pregnant that we are HIV positive, and the man is leaving you because you just told him that you are HIV positive . . . . Once the man is gone, sometimes you are not working, you are unemployed. You have no one else to buy formula for the child. You are not supposed to breast feed the child, what will happen after that? The child will be malnourished and she or he will have nothing to take into her stomach or his stomach. For me, I was fortunate enough that my family was so supportive to me and even now they are so supportive to me even though I am HIV positive. And I was fortunate enough that the girl that I give birth to is HIV negative. She is now 7 years old and she is healthy, she
looks nice, she is big, she is beautiful like her mother. So for us women, we must stand up, we must break the chains, we must break the silence, and speak out . . . . For me, I live positively with my status, I reduce stress, I talk to my virus. I tell my virus that if it kills me, we are both going down together . . . . So women, men with HIV/AIDS and leprosy, let us stand up and ght together, and ght these diseases . . . . and ght stigma, discrimination.
Culture, Identity & Stigma: The African Experience Dr. Jean-Paul Bado: French Colonial Africa In the nineteenth century, many explorers in their reports pointed out that they discovered many affected by leprosy in Western Africa who carried out different social activities, and even married (sometimes with many wives). For many ethnic groups, those with leprosy lived in societies without ostracism, except in some region of Dahomey (currently Benin and the northern Ivory Coast) where those with the signs of the disease were banished by their societies and more directly by their family. With the development of the colonial economy, the colonial administration decided that those with the disease became more and more an obstacle to its development plans. In French Sudan (and other colonies, just after the International Conference of Leprosy in Strasbourg), certain administrations expelled many affected by leprosy from colonial towns for different reasons. They were arrested for begging, which was forbidden by the colonial administration. Dr Marchoux, who had been studying the disease since 1897, managed to convince those in charge of health in the French colonies to build a modern leprosarium for people with leprosy in French Africa. In 1931, the French Western Africa health policy makers created service de lutte contre lepr. Three years later, they built the Institut Central de la Lepr which was unveiled in 1935. Those affected by leprosy had a centre where specialists in biomedicine tried to understand all the mechanisms of their disease and treat it. The ght against leprosy was also a ght for everyone. REFERENCES
JEAN-PAUL BADO, Mdecine coloniale et grandes endmics en Afrique, Paris: Karthala, 1996.
73, 4
News and Notes
295
Linda Beer Kumwenda. To save our Empires Children . Mission Leprosy Settlements in Northern Rhodesia.
community around Fiwila was such that, on being called to sort out a marital dispute Chief Shaiwila remarked, These people are already dead. How can a dead man or woman be divorced or marry?
REFERENCES
1. From paper by Major-General Sir Leonard Rogers, read to the Commonwealth section of British Empire Leprosy Relief Association (BELRA), 25th June 1954: Progress towards the eradication of leprosy from the British Commonwealth. National Archives of Zimbabwe F122 455/1, Leprosy Surveys, 19411956 2. ILIFFE J. Leprosy in The African Poor. Cambridge University Press, 1987, p215. 3 NAZ SEC2/622 Mkushi District Tour Report 193339. Tour Report 3/1938 Sub Chief Mondoka and Chief Shaiwila. Lala-Luano Reserve. DC John Gaunt. Appendix 3 Health.
This image, taken from a missionary journal published in 1907, portrays the accepted view of the engagement of missionaries with leprosy: the necessity for a dual healing, and the association of leprosy with sin. Whilst this image and much other archival evidence can lead to the conclusion that missionaries did target people with leprosy, placing them within what has been described as a total institution, and thereafter attempted to reconstruct them, a closer examination reveals a more nuanced trajectory in Zambia. In this brief presentation, I show through the examination of specic stations involved in such work such as that carried out at Chitokoloki, by the Christian Missions in Many Lands; Mbereshi, where leprosy work was forced upon the London Missionary Society; and Fiwila the village of mercy run by the Universities Mission to Central Africa that missionaries in Zambia did not target Africans suffering from leprosy. Additionally, whilst they did use the opportunity provided by settlements for evangelism, they generally found that the work was, evangelically speaking, uneconomic and did not enlarge their settlements until 100% funding was provided by government and this at a time when treatment could be given on an outpatient basis, and opportunities for social reconstruction no longer available. Indeed, whilst some missionaries applied damaging labels to those under their care, others saw beyond the disease to the person. Yet others changed their stance over time. Local attitudes to leprosy conrm Iliffes statement that African reactions are diverse. The Luvale people in the area around Chitokoloki, for example, did not appear to have negative attitudes towards leprosy, whilst the marginality experienced within the Lala
Illuminating Ourselves: Redening Traditional Images Open discussion The role of images and language in the formation of attitudes. Achievements of people affected by leprosy or living with HIV/AIDS, past and present, as a means of challenging stereotypes and the stigma that is perpetuated by them. From Ingeborg Grytten (Author, Norway, 17th century), to Akashi Kaijin (Poet, Japan, early 20th century) to the Music of Bacurau (Brazil) and the Poetry of Antonio Borges, Jr. (Brazil) to the Sinikithemba HIV+ Choir. Images of Dignity Pamela Parlapiano Sunday, February 6 Human Rights Alhaji Shehi s/Fada, IDEA Nigeria: This is the new era for people affected by leprosy that is marked by freedom, from hardship to freedom: What I will say is that in every country we [must] unite ourselves, help each other, cooperate. In Nigeria before, we were not cooperating . . . . but as IDEA came, we began to cooperate amongst ourselves. So let us cooperate, unite, and then face the government . . . . to ght for our own rights. Artur C.M. de Sousa, MORHAN, Brazil: Bacarau was one of our founding members. His vision was that of a humanitarian nature. So when he founded MORHAN, 25 years ago . . . . He used to say that we were supposed to bring other social issues to be
296
2005
discussed within the movement . . . . When I met him in Rio De Janeiro, it was a cold, rainy evening. And he pointed at a child who was covered under newspaper sheets on the street. And he also pointed to a car that had had a rain protection cover. And he saidWe were supposed to ght against any form of social injustice. Because the same situation, same conditions that cause leprosy discrimination, were the same conditions that made our society protect a car more than a child. We have 40,000 new leprosy cases per year [in Brazil]. And we have to think that Hansens disease is part of a group of diseases that are neglected. They have the following characteristics low political engagement, little information, little power by the groups of affected persons . . . . the poorest or the lowest social strata are the most affected by these diseases, and they are more de-habilitating or incapacitating than deadly. Professor Bernardino Fantini, Director, Institute of History of Medicine & Health, University of Geneva. Health and Human Rights. This paper discusses the history of relationships between health, disease, and human rights, and divergent ideas about what human rights are, and how history can integrate personal experiences and the memory of individuals, groups, and institutions. It started with a denition of history as a way to build up our personal and social identity, to preserve our memory, which is the basis of our personal and collective identity, to recognize our being part of a social group and of the whole humanity, to acknowledge that we all share ideas, ways of thinking, psychological attitudes, theoretical constructs, artistic perceptions, and moral and religious beliefs. It acknowledged that for the whole of human history, infectious diseases killed, disabled, and disgured. They had and have the capacity to destroy, destabilise, and profoundly modify populations, but they also produced and still produce psychological and moral consequences such as fear or terror, abandonment, exclusion, discrimination, and stigma, but also solidarity, compassion, and mutual help. Leprosy is a paradigm of a global disease, a paradigmatic experience for looking to the relation between global health and human rights. The memories of what the disease has been and of the human experi-
ences of diseased persons are of fundamental importance in the understanding of the social attitudes towards other diseases, like HIV/AIDS. Many historical examples, including the history of leprosy, show that global health (health for all in the world) will be the result of social action and the empowering of individuals to pursue their own safety and self determination. Human rights are not abstract nor only the result of legislation or public statements. They refer to the respect for the individual as a person, for his or her dignity, and the right to pursue his or her life. The right to health means the right of each member of humanity to realise his or her own potential in life, and this means also the obligation of the national and international authorities to ensure this realisation of potential, even in conditions created by disease or disability. In centuries past, health was considered as a product of other, more fundamental rights. It was believed that economic growth, scientic progress, education, information would be enough to ensure health for everybody (for example the hygienic movement of the nineteenth and twentieth centuries). Once considered as disappearing threats, infectious diseases have come into prominence in global health with the emergence of new viral and bacterial agents; the spread of resistance to common antibiotics; the devastating impacts of new epidemics from old enemies such as cholera, plague, dengue, foot-and-mouth disease, BSE; and resurgent infections of silent or neglected diseases such as malaria and tuberculosis. Those active in health care can no longer simply act alone without regard for the many other issues and others involved. Health inequities are widening and in global health, millions continue to die from diseases of poverty, despite the accumulation of impressive knowledge and modern technologies. Historians want to know the social and cultural determinants of this tragic paradox. Human rights are not only the world of the individual person, but are the result of social conquest, collective initiatives, as the potential for life of each individual becomes connected to interpersonal relationships and social contexts. A human right is individual, but the defence and implementation of those rights are necessarily collective. Strategies for health and human secu-
73, 4
News and Notes
297
rity depend upon individual and collective action. Health equity is the fundamental value underpinning global health; it is both intrinsically valuable, as well as instrumental in achieving human freedom. The globalisation of health responses must be based on the value of equity, on the diffusion and application of knowledge, and on moral indignation over injustices associated with health.
Ensuring the Rights of Humanity: Discussion Chairs: Professor Bernardino Fantini & Dr. P.K. Gopal Panel: Alhaji Shehu Sarkin Fada, Chamada Abibo In Conclusion: History as an Agent for Social Change Chairs: Prof. Megan Vaughan, Zilda Borges and Anwei Law Professor Megan Vaughan, Smuts Professor of Commonwealth History, Cambridge University, U.K.: . . . though Ive spent some years reading in the history of medicine and the history of leprosy, it really is genuinely true, I couldnt have learned anything that Ive learned in the last 2 days if I hadnt been here, listening to peoples stories, so its really a privilege for me . . . . when you hear about the history, the stories that weve been listening to, you wonder if we learn anything from history at all . . . . Its really rather depressing in some ways but there are also some more positive aspects of this. I want to start by just saying something about the history of slavery, partly because were here on Robben Island, but also because I think there are some parallels . . . . one might draw. We all know that in the history of slavery is a history of struggle. It is a history of struggle against the deprivations and stigmatization . . . . What slaves were deprived of were their names, their
families, their languages . . . . [and] perhaps most importantly of all, their histories. So part of the struggle against slavery and within slavery was to recover a history, but integral to the struggle against slavery was always in the telling of stories. It was always telling your story, telling the story of your people, telling the story of your resistance. And again these stories took different forms but they were very important in the struggle, in the oppositionist movement, in the struggle in slavery. People who had been slaves whose ancestors had been slaves felt they carried a stigma of slavery. Slavery is not a disease but its a social condition that can give you a stigma. And they also found that there were other more complex forms of social and economic discrimination that they were faced with. They were faced with racism . . . . they were faced with economic deprivation, they were faced with the fact that they couldnt get proper jobs, they were faced with a lack of education, all those things we know about. If there are any lessons to be drawn from this then I think for me what Ive learned from listening to you all is how you found strength in unity within this organization, IDEA. And I think this is a very interesting case of a very successful, political and advocacy organization from which other organizations dealing with other issues may well want to learn. Ive also been incredibly impressed by the ability of people from such diverse places facing quite diverse kinds of struggles to come together and give each other support and move forward.
Acknowledgment. This conference was made possible by support from The Nippon Foundation, The Leprosy Mission International, The German Leprosy Relief Association, the Sasakawa Memorial Health Foundation, and Fontilles.
US-Japan Meeting, 2005

Il-1 at the Early Stage of Monocyte Differentiation to Dendritic Cells Impairs Functional Activities of Dendritic Cells Masahiko Makino, Yumi Maeda, and Tetsu Mukai
Department of Microbiology, Leprosy Research Center, National Institute of Infectious Diseases, Japan
ABSTRACT
Mycobacterium leprae initially infects monocytes and produces various cytokines, but the role of these cytokines on the precursors of dendritic cells (DCs) is unclear. M. leprae-infected DCs were differentiated from monocytes treated with low levels of IL-1 (100 pg/ml), and the functions of
298
2005
these DCs were evaluated. IL-1 treated DCs were inefcient in activating autologous T cells. Although these DCs presented M. leprae antigens, the percentage of DCs expressing high levels of CD86 and CD83 Ag was reduced. When LPS, peptidoglycan or M. bovis BCG was used as stimulator, IL-12 production from these DCs was signicantly reduced, although monocytes treated with other cytokines (TNF-, IL-6 or IL-10) did not have such effect. We can conclude the IL-1, at the early stage of DC differentiation, impairs DC function. Therefore, clear understanding of the immune responses will be vital to the design of vaccines against mycobacterial infection.
Dendritic Cell Maturation is Suppressed by Mycobacterium Leprae Rose Ann Murray and Gilla Kaplan
Public Health Research Institute, Newark, N.J.
ABSTRACT
Oyama5, Masako Namisato6, Nahoko Kogoe1, Naoko Yamada1, Nobuyuki Terada1, Sho Matushita4
1 3
Hyogo College of Medicine, 2Shimadzu Corporation, Okayama University Graduate School of Medicine and Dentistry, 4Saitama Medical School, 5Nagasaki University Graduate School of Biomedical Sciences, 6 National Sanatorium KuryuRakusenen
ABSTRACT
To better understand the host innate immune response to mycobacterial infections, we are exploring the effect of M. leprae, M. bovis bacillus Calmette-Guerin (BCG) and M. tuberculosis (TB) on antigen presenting cell (APC) maturation. Dendritic cells (DC) are especially good APC, being able to prime nave T lymphocytes against particular antigens at proximal lymph nodes. However, to function optimally, blood DC must be matured by exposure to stimulatory cytokines and/or the antigens that induce these molecules. We have infected monocyte-derived immature DC with M. leprae, BCG or TB and examined the extent of DC maturation, as evaluated by phenotypic surface changes and immune response gene expression. Our results suggest that BCG and TB both stimulate phenotypic and genotypic DC maturation but BCG is much more efcient. In contrast, M. leprae appears to inhibit DC genotypic maturation without affecting DC maturation marker expression.
Polymorphism of the 5 Flanking Region of the Il-12 Receptor 2 Gene Partially Determines the Clinical Types of Leprosy through Impaired Transcriptional Activity Hideki Ohyama1, Koretsugu Ogata2, Tazu Takeuchi3, Yasushi Uemura4, Masataka
Polymorphisms on the 5 anking region of IL12RB2 were analyzed to determined possible immunogenetical factors affecting the establishment of clinical types of leprosy. Several SNPs, including 1035A>G, 1023A>G, 650delG and 465A>G SNPs, were detected on the 5 anking region of IL12RB2. Frequency of haplotype 1 (1035A, 1023A, 650G, 464A), which exhibited the highest frequency in the general Japanese population, was signicantly lower in lepromatous patients as compared with ndings in tuberculoid patients and healthy controls. Reporter gene assays using Jurkat T cells revealed that all haplotypes carrying one or more SNPs exhibited lower transcriptional activity as compared with haplotype 1. These results suggest that SNPs in the 5 anking region of IL12RB2 affect the level of expression and may be implicated in individual differences in cellmediated immune responsiveness to mycobacterial antigens, leading to lepromatous or tuberculoid leprosy.
Inhibition of TNF or LTa Impairs Mycobacterium Leprae Growth in Mouse Foot Pads and Is Accompanied by Dysregulated Granuloma Formation Deanna A. Hagge1, Bernadette M. Saunders2, Gig Ebenezer3, Vilma Tulaga1, Nashone A. Ray1, Warwick J. Britton2, James L. Krahenbuhl1 and Linda B. Adams1
1
National Hansens Disease Programs Laboratory, Louisiana State University, Baton Rouge, LA, 2Centenary Institute and Department of Medicine, University of Sydney, Sydney, New South Wales, Australia, and 3Johns Hopkins University, Baltimore, MD
ABSTRACT
TNF and lymphotoxin-alpha (LT) are key cytokines in cell mediated immunity against intracellular pathogens. To study their role in experimental leprosy, My-
73, 4
News and Notes
299
cobacterium leprae foot pad (FP) infection was evaluated in TNF knockout (TNF/) and LT-decient chimeric (LT/) mice. In both TNF/ and LT/ mice, M. leprae growth was augmented compared to control mice. Histopathologically, TNF/ mice developed more extensive and diffuse lymphocytic inltration compared to control mice. In contrast, few lymphocytes were present in LT/ mice. Upon M. leprae inoculation, there was a delayed early response in FP induration in both strains; however, induration in TNF/ mice rapidly increased to levels higher than controls while LT/ mice could not sustain induration. Flow cytometric analyses of isolated FP cells demonstrated elevated percentages of CD3+ T cells in TNF/ mice many of which expressed CD69. Expression of various Th1 cytokines and chemokines in established granulomas were similar or elevated in TNF/ compared to control mice, but LT/ mice demonstrated 525 fold lower levels of expression. These studies indicate the critical but independent roles for TNF and LT in orchestrating and maintaining an appropriate T cell accumulation within the microenvironment of the M. leprae-induced granuloma.
Nerve Damage in a Mouse Model of Mycobacterium ulcerans Infections Detection of M. ulcerans-specic DNA from micro-dissected nerve tissue Masamichi Goto1, Kazue Nakanaga2, Junichiro En1, Thida Aung1, Tomofumi Hamada1, Shinichi Kitajima1, Norihisa Ishii2, Suguru Yonezawa1, Hajime Saito3
1
were proven to possess M. ulcerans-specic DNA sequences, but not M. lepraespecic DNA sequences.
Advances in Molecular Epidemiology of Leprosy Miyako Kimura1, Nathan A. Groathouse1, Kiran Madanahally1, Becky Rivoire1, Xiaoman Weng2, Huan-Ying Li2, Juan Camilo Beltran Alzate3, Nora CardonaCastro3, Robert H. Gelber4, Sang-Nae Cho5, William C. Black1, Patrick J. Brennan1 and Varalakshmi D. Vissa1
Department of Microbiology, Immunology and Pathology, Colorado State University (CSU), Fort Collins, U.S.A.; 2Beijing Tropical Medicine Research Institute (BTMRI), Beijing, Peoples Republic of China; 3Instituto Colombiana de Medicina Tropical (ICMT), Sabaneta, Colombia; 4Leonard Wood Memorial (LWM), Center for Biomedical Research, Cebu City, Philippines; 5Yonsei University, Seoul, Republic of Korea
ABSTRACT
1
Kagoshima University, 2National Institute of Infectious Diseases Leprosy Research Center, 3Hiroshima Environment and Health Association
ABSTRACT
Buruli ulcer is a chronic painless ulcerative skin disease in tropical and subtropical zone caused by Mycobacterium ulcerans. Recent histological and ultrastructural studies have claried direct intraneural invasion of acidfast bacilli and vacuolar change of Schwann cells in M. ulcerans-inoculated mice. In order to further investigate the mechanism of painlessness, nerve tissues were selectively cut out from the histological specimens by a UV-laser micro-dissection system, and PCR technique was applied. Intraneural bacilli
In order to monitor and break the cycle of transmission of leprosy, a better understanding of the source and chains of M. leprae infection by means of molecular epidemiology is necessary. Since M. leprae cannot be grown in vitro and the DNA recovered from clinical samples such as skin biopsy is valuable, we rst established multiple locus variable number of tandem repeats analysis (MLVA) as a method of strain typing in four clinical M. leprae strains grown in armadillo host. This approach involved the screening of 25 short tandem repeat (STR) loci, resulting in the discovery of polymorphisms at 13 loci. Subsequently, MLVA was applied to additional archived armadillo-derived clinical isolates from leprosy patients from eight countries for a total of 21 reference strains, and to recent clinical isolates from Colombia, the Philippines and China. These data were analyzed according to parsimony principles to discern genetic diversity and phylogenetic relationships. MLVA has been shown to be a practical and effective method for M. leprae strain typing and classication.
What is Needed to Improve Diagnostics for TB and eprosy? Mark Perkins
Foundation for Innovative Diagnostics
300
ABSTRACT
2005
Case detection is a major problem for the control of both leprosy and tuberculosis, and the need to detect drug resistance continues to rise. In countries where these diseases are coming under control, the need for accurate tests for latent infection is also pressing. Signicant advances have been made in unraveling the genome and proteome of both M. leprae and M. tuberculosis, and a number of promising new diagnostic targets have been identied. These targets are now being explored for their relevance to the development of clinical tools for the detection of latent infection, active disease, and pathogen drug resistance. The path from reagent discovery to useable diagnostic is a long one, however, blocked by a number of nancial and logistic as well as technical obstacles. This talk will put the search for novel TB and leprosy diagnostics into context, highlight the priority needs, and discuss knowledge gaps that stand in the way of development of tests that are ideally suited for the intended settings of use.
Genotyping of Mycobacterium leprae by variable number tandem repeats and its application for molecular epidemiology Masanori Matsukoa1, Zhang Liangfen1 and Teky Budiawan2
Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan 2)Leprosy-TB Program, Health Service, North Sulawesi, Indonesia
ABSTRACT
1)
submitted to molecular typing. Two M. leprae isolates obtained from one family contact cases could be divided into different genotypes by these polymorphic loci. The transmission of leprosy by some infectious sources other than the multi-bacillary case in the same dwelling was strongly suggested.
Identication of Specic Proteins and Peptides in Mycobacteruim Leprae Suitable for the Selective Diagnosis of Leprosy John S. Spencer1, Hazel M. Dockrell2, Hee Jin Kim1, Maria A. M. Marques1, Diana L. Williams3, Marcia V. S. B. Martins4, Marcio L. F. Martins4, Monica C. B. S. Lima4, Maria C. V. Pessolani4, Euzenir N. Sarno5, Elisabeth P. Sampaio5, Thomas H. M. Ottenhoff6, Sang-Nae Cho7, Neil G. Stoker8, Stewart T. Cole9, and Patrick J. Brennan1
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA, 2Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK, 3Laboratory Research Branch, Division of the National Hansens Disease Programs, Louisiana State University, Baton Rouge, LA, USA, 4Laboratory of Cellular Microbiology and 5Leprosy Laboratory, Department of Mycobacterial Diseases, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil, 6Department of Immunohematology & Blood Transfusion, Leiden University medical Center, Leiden, The Netherlands, 7Department of Microbiology, Yonsei University College of Medicine, Seoul, Republic of Korea, 8Department of Pathology and Infectious Diseases, Royal Veterinary College, London, UK, 9Unit de Gntique Molculaire Bacterienne, Institut Pasteur, Paris, France.
ABSTRACT
1
The transmission mode of leprosy was examined by application of polymorphism of short tandem repeat (STR) in Mycobacterium leprae genome. To substantiate polymorphic loci from STR as promising candidates applied for the molecular typing tools in leprosy epidemiology, 44 STR loci including 33 microsatellites and 11 minisatellites were investigated among the 27 laboratory maintained strains. Not all STRs were expectedly polymorphic. Thirty-two out of the 44 loci were polymorphic. Nine polymorphic loci were suitable for identifying genotypes according to the discriminatory capacity, stability and reproducibility. All the strains were classied into independent genotypes by the selected 9 polymorphic loci. Three multicase households were
Abstract. Comparative genomic analysis of the M. leprae genome has identied 1604 open reading frames, as well as 1,130 inactivated genes (pseudogenes), and up to 165 genes with no homologues in M. tuberculosis. Diagnosis of leprosy is a major obstacle to disease control, and has been compromised in the past by the lack of specic reagents. We have used comparative genome analysis to identify genes that are specic to M. leprae, and tested both recombinant proteins and synthetic peptides from a subset of these for immunological
73, 4
News and Notes
301
reactivity. Four of the unique recombinant proteins (ML0008, ML0126, and ML2567) and a panel of 58 peptides were tested for IFN- responses in PBMC from leprosy patients and contacts, TB patients and endemic and non-endemic controls. The responses to the four recombinant proteins gave higher levels of IFN- production, but less specicity, than the peptides. Of the 58 peptides tested, 35 have showed IFN- responses only in the paucibacillary leprosy and household contact groups, with no responses in the TB or endemic control groups. Four of the six 9mer peptides tested also showed promising specicity, indicating that CD8 T cells epitopes may also have diagnostic potential. Those peptides that provide specic responses in leprosy patients from an endemic setting could potentially be developed into a rapid diagnostic test for the early detection of leprosy and epidemiological surveys of the incidence of leprosy, of which little is known.
Isothermal Amplication and Molecular Typing of the Obligate Intracellular Pathogen Mycobacterium leprae from Tissues of Unknown Origins Nathan A. Groathouse1, Susan E. Brown2, Dennis L. Knudson2, Patrick J. Brennan1 and Richard A. Slayden1*
Department of Microbiology, Immunology and Pathology1 and Bioagricultural Science and Pest Management2, Colorado State University, Fort Collins, CO 80523
ABSTRACT
unaltered and while regional differences in global amplication efciency were seen using comparative microarray analysis, a signicant degree of concordance of amplied genomic DNA was observed. This method was also applied directly to archived tissues for the purpose of molecular typing via short tandem repeats. This study demonstrated that whole genome amplication can be coupled with error-sensitive molecularbased typing methods on low copy number sequences from clinical biopsies of obligate intracellular pathogens, such as M. leprae. *Corresponding Author: Richard Slayden, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523-1682, USA. Phone: (970) 491-1925, Fax: (970) 491-1815, Email: richard.slayden@colostate.edu
The Alternative Sigma Factor sigE and Stress Responses in Mycobacterium Leprae 1 Diana L. Williams, 1Tana Pittman, 2 Mike Deshotel, 3Sandra Oby-Robinson, 4 Issar Smith
Molecular Biology Research Dept., Laboratory Research Branch, Division of the National Hansens Disease Programs @ SVM-LSU, Baton Rouge, LA, USA, 2Dept. of Microbiology, Immunology and Parasitology, LSU Health Sciences Ctr., School of Medicine, New Orleans, LA, USA, 3Dept. of Veterinary Clinical Sciences, SVM-LSU, Baton Rouge, LA, USA, 4TB Center, Public Health Research Institute, Newark, NJ, USA
ABSTRACT
1
Molecular based diagnostic and epidemiology studies require sufcient amounts of high quality DNA. Routine molecular-based epidemiologic methods have not been applied to the obligate intracellular organism Mycobacterium leprae because it is difcult to obtain genomic DNA template from clinical materials. Accordingly, we have developed a method based on isothermic multiple displacement amplication, which will nally allow access to quality DNA template. In this report, we evaluated the usefulness of this method in error-sensitive, multiple feature molecular analyses. Using test samples isolated from host tissue, we also evaluated amplication delity, genome coverage and regional amplication bias. The delity of amplied genomic material was
Mycobacterium leprae lacks a functional heat shock response mechanism which appears to relegate it to peripheral regions of the body including peripheral nerves. The alternative sigma factor SigH orchestrates the heat shock response by inducing sigE and sigB gene transcription and their respective heat shock regulons in M. tuberculosis (Mtb). However, M. lepraes sigE and sigB genes are transcriptional unresponsive during heat shock conditions. A likely mechanism for this heat shock defect is the lack of a functional sigH. However, no recombinant protocols exist for M. leprae to directly test this hypothesis. Therefore, we studied the functional capability of SigE of M. leprae, using surrogate genetics in a sigE knock-out mutant of Mtb (ST28) con-
302
2005
taining a functional sigH. The SigE of M. leprae restored the ability of ST28 to respond to heat shock and detergent stress and restored its ability to grow in human macrophages providing direct evidence that the SigE of M. leprae is functionally capable of regulating specic stress responses and indirect evidence that the lack of a protective heat shock response and potentially other environmental stress responses in M. leprae is at least partly due to the lack of a functional sigH.
Lepra Reactions After Multidrug Therapy for Multibacillary (MB) Leprosy Ma. Victoria Balagon, Roland Cellona, Rodolfo Abalos, Robert Gelber
Leonard Wood Memorial Center for Leprosy Research, Cebu, Republic of the Philippines
ABSTRACT
There are two distinct, commonly occurring, immunologically-mediated reactional states in leprosy which complicate its course, account for considerable morbidity, including neuropathy, and are the major reason for patients on chemotherapy to seek
medical attentionlepra type 1 reactions, reversal reaction (RR), and lepra type 2 reactions, ENL, mediated respectively by Th1 and Th2 responses. In this study we evaluated in MB patients the incidence, severity, and duration of lepra reactions one and two years after the completion of 1-year WHO MDT (139 patients) and 2-year WHOMDT (295 patients) and compared those results. We have found for the rst time that in MB patients lepra reactions commonly persist even after the completion of MDT, occurring 48% of the time in the rst 2 years after the currently recommended 1year regimen and are of considerable severity and duration. Also, the incidence, severity and duration of lepra reactions and the frequency of neuritis were consistently greater after the completion of 1-year MDT than 2-year MDT, and lepra reactions and these complications more frequent in those with a high bacterial burden. Since a major goal of WHO MDT is to reduce the duration needed to care for leprosy patients to a period sufcient to complete MDT, our ndings suggest this is not feasible without courting the signicant morbidity from lepra reactions observed in this study.
EDITORIAL
Elimination of (the International Journal of) Leprosy.
We regret to inform our readers that this 73rd volume of THE INTERNATIONAL JOURNAL OF LEPROSY is the last and nal volume of the JOURNAL. We have been gratied to observe that that the JOURNAL has had a dedicated readership and has had the condence of veteran as well as new authors submitting their work to the JOURNAL right up to the end of its long and distinguished career. A number of manuscripts awaiting review, or in revision, have unfortunately been returned to their authors. Closure of the JOURNAL was, ultimately, a business decision. The publication of a high quality, professional, peer-reviewed journal is a costly undertaking. To the best of our knowledge, this JOURNAL, unique to its origins and purpose, has never been fully funded by memberships in the International Leprosy Association, of which it is the ofcial organ. Rather, the JOURNAL has always depended upon the generosity of leprosy-oriented charitable organizations which have, in recent years, considered the cost of this JOURNAL to be excessive. In spite of diligent efforts on the part of the ofcers of the ILA to trim costs and to nd additional revenue, a satisfactory solution was not forthcoming. Many factors underlie the decision to close the JOURNAL, and we are probably not aware of all of them. It would be a mistake, however, not to see this development as representative of the broader international decline of resources allocated to efforts to deal with leprosy. While commendable progress has been made to control leprosy in many countries, approximately 500,000 new patients are still being diagnosed annually worldwide, most of them in the several regions of the world that remain highly endemic. Even in these highly endemic regions, however, pressures are being applied to reduce the resources available to diagnose and treat leprosy. Some details of these policies have been presented by Drs. Rao and Pratap earlier in this volume ([vol. 73:225]). The details vary, but diminished resources lead to cuts of all kinds. The result is that a clinic is closed in one district, clinics are merged elsewhere, and in other districts patients are referred to a general health center that lacks specialized expertise in leprosy. In this way, a small light is extinguished here and there, but the loss is almost imperceptible (except to the patients in that locale). The closure of this JOURNAL, however, represents the extinction of a larger, more conspicuous light that has been of value to leprosy workers worldwide for many decades. This is a clear sign of the current trend in all aspects of leprosy work. Some individuals are condent that current elimination policies are scientically sound and are being implemented appropriately; for these individuals, the closure of the JOURNAL should be cause for neither surprise nor dismay, but will be seen as a logical, natural development. Others are highly skeptical of the scientic basis for current elimination policies, and think that implementation of these policies is being unnecessarily and prematurely rushed to meet arbitrary bureaucratic goals, to the detriment of patient care. For many of these individuals the closure of the JOURNAL will probably come as a surprise and a disappointment. The work will go on, of course, as resources permit. Other leprosy-oriented journals will continue, and we wish them well. Much remains to be learned about this disease and much remains to be done to control it. We will not be surprised, however, ifa few decades hencethose who look back to review leprosy elimination efforts at the beginning of this millennium should reach the conclusion that we have been following the mistaken paths already well trod in the recent history of programs to eliminate other diseases such as tuberculosis and malaria. David Scollard
303
REVIEWERS 2005
The Editor, on behalf on the INTERNATIONAL JOURNAL OF LEPROSY and the membership of the International Leprosy Association, expresses his deepest appreciation to the following reviewers who have provided invaluable expertise, criticism, and advice in preparing Volume 73. David Baker Mirjam Bakker Lucia Barker Patrick Brennan Jack Cohen Ian Cree Graca Cunha Ebenezer Daniel Gigi Ebenezer Katrien Fransen Robert H. Gelber Thomas Gillis James Harnisch Robert Hastings Robert Jacobson C.K. Job Paul Klatser Jim Krahenbuhl Wayne Meyers Sam Moschella S.K. Noordeen Gift Norman Winnie Ooi Thomas Rea Paul Saunderson David Scollard Vanaja Shetty Mariane Stefani Richard Truman Wim van Brakel Marcos Virmond Douglas Walsh Cornelius Walter Leo Yoder
304
ACKNOWLEDGMENT
The Board of Directors of the INTERNATIONAL JOURNAL OF LEPROSY gratefully acknowledges the nancial assistance from special grantors and sustaining members which, with the special donations of certain members, has made possible the continuation of publication of the JOURNAL directly by the International Leprosy Association. Without this assistance the ofcial organ of the ILS, so essential to leprosy workers everywhere, could not be published.
SPECIAL GRANTORS
*Aide aux Lepreux Emmaus-Suisse, Spitalgasse, CH-3011 Berne, Switzerland. *American Leprosy Missions, One ALM Way, Greenville, South Carolina 29601, U.S.A. *Amici dei Lebbrosi, Foundazione Italiana Raoul Follereau, Via Borselli 4, 40135 Bologna, Italy. Damien-Dutton Society, 616 Bedford Avenue, Bellmore, New York 11710, U.S.A. *Damien Foundation (DF/APD), 16 Rue Stevin, B-1040 Bruxelles, Belgium. *Deutsches Aussatzigen-Hilfswerk e. V., Postfach 9062, D-97090 Wrzberg 11, Germany. *Le Secours aux Lpreux (Canada), 1275 Rue Hodge Bureau 12, Montreal H4N 3H4, Canada *Netherlands Leprosy Relief, Wibautstraat 137K, 1097 DN Ansterdam, The Netherlands. *Pacic Leprosy Foundation, 115 Sherborne Street, Bag 4730, Christchurch, New Zealand. *Sasakawa Memorial Health Foundation, Senpaku Shinko Bldg., 1-15-16 Toranomon, Minato-ku, Tokyo 105, Japan.
305
VOLUME 73
2005

Ofcial Organ of the INTERNATIONAL LEPROSY ASSOCIATION (Association Internationale contre la Lpre) (Asociacin Internacional de la Lepra)
Contents
INTERNATIONAL JOURNAL OF LEPROSY and Other Mycobacterial Diseases CONTENTS Volume 73, Number 1, March 2005
Page 1
Images from the History of Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Original Articles Novales-Santa Coloma, J., Navarrete-Franco, G., Iribe, P., and Lpez-Cepeda, L. D. Ulcerative Cutaneous Mycobacteriosis Due to Mycobacterium ulcerans: Report of Two Mexican Cases - - - - - - - - - - - - - - - - - - - - - - - - - - Cross, H. A Delphi Consensus on Criteria for Contraindications, Assessment Indicators and Expected Outcomes Related to Tibialis Posterior Transfer Surgery - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Case Report Daniel, E., and G. Ebenezer. Anesthesia of Face Uncovered by Histopathology
------------------------------------------
5 13 22 25 28 32 33 34 36 37 39 41 42 43 46 52 58 61 67 67 69 71 76 77 78 84 87
Editorial Scollard, D. M. Leprosy Research Declines, but Most of the Basic Questions Remain Unanswered
------------
Commentaries Cross, H. Consensus Methods: A Bridge Between Clinical Reasoning and Clinical Research? - - - - - - - - - - - - - - - - - - - - Franzblau, S. A Potentially New Treatment for Tuberculosis; Will a Diarylquinoline Work for Leprosy? - - - - - - - - - Correspondence Opromolla, D.V.A. Some Considerations on the Origin of Type 1 Reactions in Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Malaviya, G. N. Neuropathic Pain in Leprosy Patients - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Book Reviews Anderson, G. A. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Mathews, R. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - News and Notes Calendar
-----------------------------------------------------------------------------------------------------------------------------------------------
-----------------------------------------------------------------------------------------------------------------------------------------------------------
Current Literature General and Historical - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Chemotherapy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Clinical Sciences - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Immunopathology - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Tuberculosis - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Microbiology - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Tuberculosis - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Experimental Infections and Vaccines - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Epidemiology and Prevention - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Rehabilitation - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Other Mycobacterial Diseases - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Molecular and Genetic Studies - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Special Grantors and Sustaining Members
---------------------------------------------------------------------------------------------------
INTERNATIONAL JOURNAL OF LEPROSY and Other Mycobacterial Diseases CONTENTS Volume 73, Number 2, June 2005
Page 89
Images from the History of Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Original Articles Hussain, Tahziba, Sinha, Shikha, Kulshreshtha, K. K., Katoch, Kiran, Yadav, V. S., Sengupta, U., and Katoch, V. M. Seroprevalence of HIV Infection among Leprosy Patients in Agra, India: Trends and Perspective Gupta, U. D., Katoch, K., Singh, H. B., Natrajan, M., and Katoch, V. M. Persister Studies in Leprosy Patients after Multi-Drug Treatment - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Narang, Tarun, Kaur, Inderjeet, Kumar, Bhushan, Radotra, Bishan Dass, and Dogra, Sunil. Comparative Evaluation of Immunotherapeutic Efcacy of BCG and Mw Vaccines in Patients of Borderline Lepromatous and Lepromatous Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Kumar, Anil, Girdhar, Anita, and Girdhar, B. K. Prevalence of Leprosy in Agra District (U.P.) India from 2001 to 2003 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Case Report Pandhi, Deepika, Mehta, Shilpa, Agrawal, Subhav, and Singal, Archana. Erythema Nodosum Leprosum Necroticans in a ChildAn Unusual Manifestation - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Correspondence Burdick, Anne E., and Ramirez, Claudia C. The Role of Mycophenolate Mofetil in the Treatment of Leprosy Reactions - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Asilian, A., Faghihi, G., Momeni, A., Radan, M. R., Meghdadi, M., and Shariati, F. Leprosy Prole in Isfahan (A Province of Iran) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Commentaries Nelson, Kenrad E. Leprosy and HIV Infection (Rarely the Twain Shall Meet?) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Steinhoff, Ulrich, and Visekruna, Alexander. Leprosy SusceptibilityA Matter of Protein Degradation? The Role of Proteasomes in Infection and Disease - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Obituary Diltor Vladmir Araujo Opromolla (19342004) by Marcos Virmond - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - African Leprosy Congress
-------------------------------------------------------------------------------------------------------------------------------
93 100
105 115
122
127 129 131 135 138 140 162 163 164
News and Notes Damien-Dutton Award - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Calendar - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Special Grantors

----------------------------------------------------------------------------------------------------------------------------------------------
INTERNATIONAL JOURNAL OF LEPROSY and Other Mycobacterial Diseases CONTENTS Volume 73, Number 3, September 2005
Page 165
Images from the History of Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Original Articles Thomas H. Rea and Robert S. Jerskey. Clinical and Histologic Variations Among Thirty Patients with Lucios Phenomenon and Pure and Primitive Diffuse Lepromatosis (Latapis Lepromatosis) - - - - - - - - - - - - - - - - - - - - - - - - Nand Lal Sharma, Vikram K. Mahajan, Vikas C. Sharma, Sandip Sarin, and Ramesh Chander Sharma. Erythema Nodosum Leprosum and HIV Infection: A Therapeutic Experience - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Ramanuj Lahiri, Baljit Randhawa, and James L. Krahenbuhl. Effects of Purication and Fluorescent Staining on Viability of Mycobacterium leprae - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Case Reports Tarun Narang, Sunil Dogra, and Inderjeet Kaur. Borderline Tuberculoid Leprosy with Type 1 Reaction in an HIV PatientA Phenomenon of Immune Reconstitution - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Tarun Narang, Sunil Dogra, and Inderjeet Kaur. Co-localization of Pityriasis Versicolor and BT Hansens Disease - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Commentary Ottenhoff, Tom H.M., and Klein, Michl R. Leprosy Bacillus Triggers the Wrong Cells
--------------------------------
169 189 194
203 206 208 211 216
Editorials Rao, P. Narasimha. Leprosy Program in India at the Crossroads - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Ji, Baohong. Comments on WHO/AFROs Post-Elimination Strategy Paper: A New Bottle with Old Wine of the Final Push - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Correspondence Premkumar, Ramaswamy, Rajan, Pichaimuthu, and Daniel, Ebenezer. Quantitative Measurement of Sensory Impairment in Referral Centers - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Rada, Elsa Mara, Zambrano, Edgar A., Aranzazu, Nacarid, and Convit, Jacinto. Serologic Recognition of Low Molecular Weight Mycobacterial Protein Fractions in Lepromatous Patients with Type II Reactions (ENL) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Santos, Mnica Nunes Souza, Ferreira, Luis Carlos de Lima, and Talhari, Sinsio. Paucibacillary Treatment for Large Tuberculoid Lesions of Leprosy? - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Kumarasinghe, S. Prasad W., and Kumarasinghe, M. P. Reply to the Editor - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Ganapati, R., and Pai, V. V. Has the Term Elimination Outlived Its Utility? - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - News and Notes - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - U.S.-Japan Meeting, 2004 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Special Grantors
----------------------------------------------------------------------------------------------------------------------------------------------
219
222 225 227 229 230 230 238
INTERNATIONAL JOURNAL OF LEPROSY and Other Mycobacterial Diseases CONTENTS Volume 73, Number 4, December 2005
Page 239 243
Images from the History of Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Original Articles Bikash Ranjan Kar, and C. K. Job. Visible Deformity in Childhood LeprosyA Ten-Year Study. - - - - - - - - - - - - - - - - - Jan H. Richardus, Abraham Meima, Corine J. van Marrewijk, Richard P. Croft, and Trevor C. Smith. Close Contacts with Leprosy in Newly Diagnosed Leprosy Patients in a High and Low Endemic Area: Comparison between Bangladesh and Thailand. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Jos L. Alfonso, Fernando A. Vich, Juan J. Vilata, and J. Terencio de las Aguas. Factors Contributing to the Decline of Leprosy in Spain in the Second Half of the Twentieth Century. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - C. Ajith, Sachin Gupta, Bishan D. Radotra, Sunil K. Arora, Bhushan Kumar, Sunil Dogra, and Inderjeet Kaur. Study of Apoptosis in Skin Lesions of Leprosy in Relation to Treatment and Lepra Reactions. - - - - - - - - Clinical Notes G. N. Malaviya. Myiasis in Leprosy.
249 258 269 277
---------------------------------------------------------------------------------------------------------------
Correspondence L. Oskam and S. Bhrer-Skula. A Need for Clarication of the Classication Criteria for Leprosy Patients. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Dr. Gelber and Colleagues Reply. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - News and Notes Leprosy in the Era of AIDS. Report of a Meeting at Robben Island, SA. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - 2005 U.S.-Japan Meeting, Seattle - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Editorial Elimination of (the International Journal of) Leprosy
280 281 283 297 303 304 306 307
---------------------------------------------------------------------------------
Reviewers - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Special Grantors Index 2005

----------------------------------------------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------------------------------------------------------------------------------
INTERNATIONAL JOURNAL OF LEPROSY Printed in the U.S.A.
Volume 73, Number 4
Index to Volume 732005

AUTHOR INDEX
An original article is indicated by (O), editorial (E), correspondence (C), news and notes (N), abstract (A), book review (B), obituary (Ob), supplement (S).
Abalos, R. M., (A) 58 Actor, J. K., (A) 71 Adachi, J. A., (A) 82 Adekambi, T., (A) 77, 78 Agrawal, S. K., (A) 46 Agrawal, Subhav, (O) 122 Aguiar, J., (A) 79 Aguilar-Leon, D., (A) 161 Ahlem, C., (A) 161 Ajith, C., (O) 269 Alcaide, F., (A) 78, 83 Alderson, M. R., (A) 70 Alfonso, Jose L., (O) 258 Allix, C., (A) 66 Almeida, E. C., (A) 75, 83 Alt, J., (A) 62 Andersen, P., (A) 74 Anderson, George A., (B) 36 Andries, K., (A) 44 Antia, N. H., (A) 60 Appelberg, R., (A) 53 Aranzazu, Nacarid, (C) 222 Araujo Filho, J. A., (A) 50 Arduino, M. J., (A) 80 Armitige, L. Y., (A) 71 Arora, Sunil K., (O) 269 Asilian, A., (C) 127 Astarie-Dequeker, C., (A) 57 Bagwan, I. N., (A) 58 Bahrmand, A. R., (A) 83 Bajaj, P., (A) 49 Barletta, R. G., (A) 79 Barreto, M. L., (A) 76 Barrow, R. R., (A) 44 Barry, C. E., III, (A) 69 Basak, C., (A) 55 Basaraba, R. J., (A) 70 Bastos, A. P., (A) 59 Basu, J., (A) 55 Bautista-Lorite, J., (A) 52
Bay, M. L., (A) 63 Beery, D., (A) 65 Behar, S. M., (A) 62, 62 Belisle, J. T., (A) 84 Bennedsen, J., (A) 83 Berchel, M., (A) 80 Bermudez, L. E., (A) 44, 79 Besedovsky, H., (A) 63 Beveridge, T. J., (A) 65 Bhattacharyya, A., (A) 55 Blau, S., (A) 42, 42 Boldsen J. L., (A) 42 Bonato, V. L., (A) 74 Bonatti, H., (A) 168 Bonilla, F. A., (A) 79 Bonnet, D., (A) 52 Boom, W. H., (A) 63 Bosch, S., (A) 51 Boshoff, H. I., (A) 69 Bottasso, O. A., (A) 63 Bouchot, A., (A) 74 Bozza, V., (A) 63 Bradbury, A. R., (A) 84 Bradbury, E. M., (A) 84 Brandt, L., (A) 70 Brennan, P. J., (A) 64, 69 Breton, G., (A) 52 Brooks, D. E., (A) 65 Brown, J., (A) 55 Buckley, H. R., (A) 43 Buhrer-Sekula, S., (C) 280 Burdick, Anne E., (C) 129 Butlin, C. R., (A) 50 Buxton, M., (A) 76 Calatayud, L., (A) 78 Calza, L., (A) 166 Cambau, E., (A) 44 Canaday, D. H., (A) 63 Carvalho, A. A., (A) 49 Cecilia, G. V., (A) 60
313
314

Duerksen, F., (A) 47 Dunst, K. R., (A) 168 Duppre, N. C., (A) 75, 83 Duval, X., (A) 52 de Chaffoy, D., (A) 44 de Paula, F. J., (A) 47 de St Groth, B. F., (A) 73 de las Aguas, J. Terencio, (O) 258 deSauvage, F., (A) 56 Ebenezer, Gigi, (O) 22 Eluru, H. B., (A) 53 Enciso-Moreno, J. A., (A) 65 Espitia, C., (A) 72 Estellat, C., (A) 52 Estrada-Garcia, I., (A) 65 Estrada-Parra, S. A., (A) 65 Etienne, G., (A) 46, 57 Faber, R., (A) 149 Faber, W. R., (A) 58 Faccioli, L. H., (A) 74 Faghihi, G., (C) 127 Fajardo, T. T., (A) 58 Faria, S. C., (A) 48 Farroni, M. A., (A) 63 Farshchian, M., (A) 47 Fauville-Dufaux, M., (A) 66, 83 Fazio, J. A., (A) 52 Feldman, K., (A) 83 Feldmeier, H., (A) 76 Ferdinand, S., (A) 80 Ferguson, D. D., (A) 80 Fernandes, P. V., (A) 48 Ferraz, J. C., (A) 72 Ferreira, Luis Carlos de Lima, (C) 225 Ferri, M., (A) 166 Fine, P. E., (A) 84 Fitness, J., (A) 84 Fletcher, H. A., (A) 82 Florido, M., (A) 53 Florquin, S., (A) 63 Floyd, S., (A) 84 Forst, C. V., (A) 84 Foss, N. T., (A) 47 Franzblau, Scott, (C) 32 Fremond C. M., (A) 61 Fremond, C., (A) 74 Frincke, J., (A) 161 Fu, Z. J., (A) 61 Ganapati, R., (C) 229 Gandhi, G., (A) 59 Garcia, V. E., (A) 60 Garcia-Tapia, A., (A) 69 Geha, R. S., (A) 79 Gellis, S. E., (A) 79 Germano, S., (A) 73 Gershman, K., (A) 80 Gevaudan, M. J., (A) 78 Ghadiali, A. H., (A) 80 Ghilardi, N., (A) 56 Ghosh, S., (A) 72
2005
Chacon, O., (A) 79 Chacon-Salinas, R., (A) 65 Chae, G. T., (A) 68, 85 Chambers, M., (A) 75 Chang, J. C., (A) 65 Chapman, P. L., (A) 70 Cheers, C., (A) 73 Chen, H. H., (A) 79 Chen, J., (A) 84 Chen, X., (A) 84 Chen, Z. W., (A) 56 Chico-Ortiz, M., (A) 73 Chimelli, L., (A) 48 Chinchon, D., (A) 52 Chinchon, I., (A) 52 Chiu, H. C., (A) 79 Chua, J., (A) 52, 57 Church, J. A., (A) 81 Clay, H., (A) 65 Co, D. O., (A) 52 Coade, S., (A) 72 Coelho-Castelo, A. A., (A) 74 Colford, J. M., Jr., (A) 54 Coloma, Josefa, (O) 5 Colombo, M. I., (A) 155 Colston, M. J., (A) 71, 72, 75 Convit, Jacinto, (C) 222 Cooksey, R. C., (A) 80 Cooper, A. M., (A) 56 Copenhaver, R. H., (A) 71 Cordeiro, R. S., (A) 59 Couri, C. E., (A) 47 Crampin, A. C., (A) 84 Crick, D. C., (A) 69 Croft, Richard P., (O) 249 Cross, Hugh, (C) 28, (O) 13 Curcio, M., (A) 83 Da Costa Neri, J. A., (A) 48 Daffe, M., (A) 46, 57 Dahl, J. L., (A) 69 Dai, Y. S., (A) 79 Dalemans, W., (A) 70 Daniel, Ebenezer, (C) 219, (O) 22 Das, P. K., (A) 58 Dawes, S., (A) 54, 84 De Souza, A. O., (A) 74 Debacker, M., (A) 79 Debbabi, H., (A) 62 Dekker, T., (A) 58 Del Rey, A., (A) 63 Deng, J. Y., (A) 61 Deretic, V., (A) 52, 57, 155 Deshmukh, S. D., (A) 58 Dobos, K. M., (A) 84 Dogra, Sunil, (A) 105, (O) 203, 206, 269 Dos Santos, C. S., (A) 47 Doxsee, D., (A) 65 Dramaix, M., (A) 79 Drancourt, M., (A) 77, 78 Du, G., (A) 56
73, 4
Gilbert, S. C., (A) 82 Gilbertson, B., (A) 73 Giles, M., (A) 52 Gilleron, M., (A) 57 Gilmartin, L., (A) 56 Girdhar, Anita, (A) 115 Girdhar, B. K., (A) 67, 115 Goh, K. S., (A) 80 Gohlmann, Neefs, J. M., (A) 44 Gomes Antunes, S. L., (A) 48 Gomez-Aranda, F., (A) 52 Gomez-Mampaso, E., (A) 70 Goodworth, K. J., (A) 71 Gopinath, D. V., (A) 48 Greub, G., (A) 78 Guillemont, J., (A) 44 Gupta, Sachin, (O) 269 Gupta, U. D., (A) 100 Gupte, M. D., (A) 76 Gutierrez, M. G., (A) 155 Hailes, H. C., (A) 71 Han, J. Y., (A) 81 Han, X. Y., (A) 82 Hanney, S., (A) 76 Harding, C. V., (A) 63 Hart, P. D., (A) 71 Hatch, G., (A) 74 Havelkova, M., (A) 83 Hendster, P., (A) 168 Henriques, M. G., (A) 59 Hernandez-Pando, R., (A) 161 Herrewegh, A., (A) 84 Herve, A. C., (A) 71 Herve, G., (A) 71 Hewinson, G., (A) 75 Hill, A. M., (A) 71 Hill, A. V., (A) 84 Hill, A. V. S., (A) 82 Hoeve, M. A., (A) 57, 85 Hoffner, S., (A) 44 Hogan, L. H., (A) 52 Holland, S. M., (A) 81 Hollis, G., (A) 53 Hsiao, C. H., (A) 79 Huang, D., (A) 56 Huitric, E., (A) 44 Hunter, R. L., (A) 71 Hussain, Tahziba, (O) 93 Huygem, K., (A) 82 Iribe, Pedro, (O) 5 Ishii, N., (A) 43 Iyer, A. M., (A) 58 Izzo, A. A., (A) 70, 73 Izzo, L. S., (A) 73 Jacobs, M., (A) 61 Jacobs, M. R., (A) 45 Jadhav, M. V., (A) 58 Jagannath, C., (A) 71 Jain, S., (A) 68, 85 Jaishankar, T. J., (A) 48
Author IndexVolume 73
Jardim, M. R., (A) 48 Jarlier, V., (A) 44 Jenner, P., (A) 71 Jensen, B., (A) 80 Jerskey, Robert S., (O) 169 Ji, Baohong, (E) 216 Jianping, S., (A) 76 Jing, G., (A) 53 Joaquin, G. E., (A) 60 Job, C. K., (O) 243 Jogi, R., (A) 81 Jones, J. M., (A) 55 Jones, T., (A) 76 Joshua, J., (A) 49 Kadam, P., (A) 58 Kai, M., (A) 67 Kamath, A. B., (A) 62, 62 Kang, T. J., (A) 68, 85 Kapur, M., (A) 45 Kar, Bikash Ranjan, (O) 243 Kasimos, J., (A) 73 Katila, M. L., (A) 83 Katoch, K., (A) 100 Katoch, Kiran, (O) 93 Katoch, V. M., (A) 67, 81, 100, (O) 93 Kaur, D., (A) 69 Kaur, Inderjeet, (A) 105, (O) 203, 206, 269 Kawakami, K., (A) 66 Keating, S. M., (A) 82 Kerr-Pontes, L. R. S., (A) 76 Kessler, A. T., (A) 81 Khader, S. A., (A) 56 Khan, A., (A) 49 Khandekar, M. M., (A) 58 Kheirandish, A., (A) 47 Khuller, G. K., (A) 45, 45, 75 Kim, S. I., (A) 52 Kim, S. K., (A) 68, 85 Kinjo, T., (A) 66 Kinkle, B., (A) 53 Kishore, B. N., (A) 50 Klatser, P., (A) 55 Klein, Michel R., (C) 208 Kobayashi, K., (A) 54 Koksalan, K., (A) 83 Koranne, R. V., (A) 49 Kourtis, A. P., (A) 81 Krahenbuhl, James L., (O) 194 Kulshreshtha, K. K., (O) 93 Kumar, Anil, (A) 115 Kumar, Bhushan, (A) 105, (O) 269 Kumarasinghe, M. P., (C) 227 Kumarasinghe, S., (C) 227 Kundu, M., (A) 55 Kyei, G., (A) 52 La Scola, B., (A) 78 Lahiri, Ramanuj, (O) 194 Lasco, T. M., (A) 70 Lasuncion, M. A., (A) 70 Laverde, C., (A) 51
315
316
Lee, E., (A) 44 Lee, S. A., (A) 82 Lee, S. B., (A) 68 Leemans, J. C., (A) 63 Legrand, E., (A) 80 Leport, C., (A) 52 Letvin, N. L., (A) 56 Liang, M. G., (A) 79 Liangbin, Y., (A) 76 Lima, K. M., (A) 74 Liu, Q., (A) 61 Lobet, Y., (A) 70 Lockwood, D. N., (A) 68, 85 Longuet, P., (A) 52 Lopez-Cepeda, Larissa, (O) 5 Lopez-Marin, L. M., (A) 73 Lounis, N., (A) 44 Lowrie, D. B., (A) 72, 75 Lu, H. B., (A) 61 la Mora Pedro, G. D., (A) 60 lee, S. B., (A) 85 Macdonald, M., (A) 51 Machowski, E. E., (A) 54, 84 Maeda, S., (A) 67 Magan, N., (A) 55 Mahajan, Vikram K., (O) 189 Mahalingam, M., (A) 68 Mahmmod, N., (A) 84 Mahuad, C., (A) 63 Mailaender, C., (A) 46 Maillet, I., (A) 74 Majka, S., (A) 73 Malaviya, G. N., (C) 34 Malaviya, G. N., (O) 277 Maldonado-Garcia, G., (A) 73 Malema, S., (A) 84 Mandal, D., (A) 55 Manfredi, R., (A) 166 Manickam, P., (A) 76 Maniero, V. C., (A) 75, 83 Manning, E. J., (A) 80 Maridonneau-Parini, I., (A) 57 Martelli, C. M., (A) 50 Martin, R., (A) 78 Martin-Casabona, N., (A) 83 Martinez, A. N., (A) 75, 83 Martinez, G. J., (A) 60 Martins, R. S., (A) 49 Mast, D., (A) 53 Master, S., (A) 52 Master, S. S., (A) 155 Mateo, L., (A) 83 Mathew, D., (A) 50 Mathews, Ronnie, (B) 37 Matilla, J., (A) 70 Mawuenyega, K. G., (A) 84 Mazzarelli, G., (A) 80 McShane, H., (A) 82 Meghdadi, M., (C) 127 Mehta, Shilpa, (O) 122

Meima, Abraham, (O) 249 Meiwen, Y., (A) 76 Meyers, W. M., (A) 79 Miyagi, K., (A) 66 Mizrahi, V., (A) 54, 84 Moel, F. J., (A) 149 Momeni, A., (C) 127 Montenegro, A. C. D., (A) 76 Montero, M. T., (A) 70 Moraes, M. O., (A) 75, 83 Morelli, S., (A) 166 Mori, S., (A) 43 Moura, A. C., (A) 59 Munoz-Cruz, S., (A) 65 Mvondo, D., (A) 52 Nakajima, H., (A) 43 Nakamura, K., (A) 66 Nanetti, A., (A) 166 Narang, Tarun, (A) 105, (O) 203, 206 Naser, S. A., (A) 80 Natrajan, M., (A) 100 Navarrete-Franco, Gisela, (O) 5 Nelson, Kenrad E., (C) 133 Ngai, P., (A) 57 Nicolle, D., (A) 74 Nicolle, D. M., (A) 61 Niederweis, M., (A) 46 Nienhuis, W. A., (A) 50 Nolla, J. M., (A) 83 Norris, S. J., (A) 71 Norris-Jones, R., (A) 65 Oberoi, S., (A) 46 Oerther, D. B., (A) 53 Okkels, L. M., (A) 74 Olsen, A. W., (A) 74 Opromolla, D. V. A., (C) 33 Orange, J. S., (A) 79 Ordonez, N., (A) 51 Orme, I. M., (A) 70 Orozco, H., (A) 161 Oskam, L., (A) 149, (C) 280 Ottenhoff, T. H., (A) 85 Ottenhoff, T. H., (A) 57 Ottenhoff, Tom H. M., (C) 208 Overduin, P., (A) 84 Pahan, D., (A) 149 Pai, M., (A) 54 Pai, R. K., (A) 63 Pai, V. V., (C) 229 Pandey, A., (A) 67 Pandey, R., (A) 45, 75 Pandhi, D., (A) 46 Pandhi, Deepika, (O) 122 Papautsky, I., (A) 53 Parkash, O., (A) 67 Pasquinelli, V., (A) 60 Pathak, S., (A) 55 Pathak, S. K., (A) 55 Pathan, A. A., (A) 82 Pavlou, A. K., (A) 55
2005
73, 4
Pearl, J. E., (A) 56 Pennini, M. E., (A) 63 Pereira, G. A., (A) 50 Pereira, M. F., (A) 83 Pfausler, B., (A) 51 Pfyffer, G. E. & Portaels, F., (A) 83 Pichon, X., (A) 74 Pinto, R., (A) 51 Poaletti, X., (A) 52 Polaczyk, A., (A) 53 Portaels, R., (A) 79 Prasad, W., (C) 227 Premkumar, Ramaswamy, (C) 219 Qiu, L., (A) 56 Quesniaux, V. F., (A) 61 Quesniaux, V. J., (A) 74 Quiroga, M. F., (A) 60 Raad, I. I., (A) 82 Rada, Elsa Maria, (C) 222 Radan, M. R., (C) 127 Radotra, Bishan Dass, (A) 105 Ragno, S., (A) 75 Rai, S., (A) 67 Raja, A., (A) 64 Rajan, Pichaimuthu, (C) 219 Ramakrishnan, L., (A) 65 Ramalingam, B., (A) 64 Ramirez, Claudia C., (C) 129 Randhawa, Baljit, (O) 194 Rao, P. Narasimha, (E) 211 Raoult, D., (A) 78 Rastogi, N., (A) 80 Ravi, B., (A) 49 Rea, Thomas H., (O) 169 Reading, C., (A) 161 Redotra, Bishan D., (O) 269 Reed, S. G., (A) 70 Reid, C. A., (A) 43 Reid, S. E., (A) 43 Reynaud-Gaubert, M., (A) 78 Richardus, J. H., (A) 149 Richardus, Jan H., (O) 249 Riley, L. W., (A) 54 Rivera-Marrero, C. A., (A) 64 Riveros, A., (A) 51 Rodrigues, F., (A) 83 Rodrigues, J. M., (A) 74 Rodriguez, G., (A) 51 Rodriguez, J. C., (A) 69 Roholl, P., (A) 84 Roman, J., (A) 64 Rook, G. A., (A) 161 Rosenzweig, S. D., (A) 81 Ross, L. A., (A) 81 Royo, G., (A) 69 Ru, G., (A) 83 Ruiz, M., (A) 69 Ryffel, B., (A) 61, 74 Saito, A., (A) 66 Sales, A. M., (A) 48, 75, 83
Author IndexVolume 73
Sanchez-Garcia, F. J., (A) 73 Sander, C. R., (A) 82 Sandor, M., (A) 52 Santin, M., (A) 78 Santos, A. R., (A) 75, 83 Santos, Monica Nunes Souza, (C) 225 Santos, S. A., (A) 74 Santosuosso, M., (A) 57 Sarin, Sandip, (O) 189 Sarkar, S., (A) 49 Sarmiento, M., (A) 51 Sarno, E. N., (A) 48, 75, 83 Save, M. P., (A) 60 Saxena, R. K., (A) 72 Schmutzhard, E., (A) 51 Schneider, L. C., (A) 79 Schouls, L., (A) 84 Schramm, B., (A) 161 Schwarz, R. J., (A) 51 Scollard, D. M., (E) 25 Scollard, David M., (E) 303 Scott, J. T., (A) 79 Sehgal, P., (A) 56 Sengupta, U., (O) 93 Sepp, N., (A) 51 Sepulveda, E., (A) 71 Seran-Lopez, J., (A) 65 Sergio, N. F., (A) 60 Serrano, A., (A) 161 Serrano-Pozo, A., (A) 52 Shafer, W. M., (A) 64 Shariati, F., (C) 127 Sharma, A., (A) 45 Sharma, Nand Lal, (O) 189 Sharma, Ramesh Chander, (O) 189 Sharma, S., (A) 45, 45 Sharma, Vikas C., (O) 189 Shen, L., (A) 56 Shen, Y., (A) 56 Shenoy, A. R., (A) 68 Sherman, D. R., (A) 65 Shetty, K. T., (A) 60 Shetty, N. J., (A) 50 Shetty, V. P., (A) 60 Shwethadri, G. K., (A) 50 Sichali, L., (A) 84 Silva, C. L., (A) 74 Singal, A., (A) 46 Singal, Archana, (O) 122 Singh, B., (A) 59 Singh, H. B., (A) 67, 100 Singh, S. B., (A) 155 Singh, S. B., (A) 52, 57 Sinha, Shikha, (O) 93 Siqueira, M. G., (A) 49 Skeiky, Y. A., (A) 70 Smith, Trevor C., (O) 249 Sola, C., (A) 80 Solache, A., (A) 56 Sonia, L., (A) 60
317
318

Villenuve, C., (A) 57 Virmond, Marcos, (Ob) 137 Visekruna, Alexande, (C) 131 Visweswariah, S. S., (A) 68 Volkman, H. E., (A) 65 Vordermeier, M., (A) 75 van Brakel, W. H., (A) 50 van Gestel, J., (A) 44 van Marrewijk, Corine J., (O) 249 van Rooijen, N., (A) 63 van Soolingen, D., (A) 84 van de Vosse, E., (A) 57, 85 van de Winkel, J. G., (A) 63 van der Poll, T., (A) 63 van der Werf, T. S., (A) 50 van der Zanden, A., (A) 84 Wang, J., (A) 57 Wanger, A., (A) 71 Warndorff, D. K., (A) 84 Watt, B., (A) 83 Weijer, S., (A) 63 Weng, Y., (A) 62 Wenzhong, L., (A) 76 Werneck, G. L., (A) 76 Wiesmayr, S., (A) 168 Williams, A., (A) 74 Williams, P., (A) 44 Winkler, H., (A) 44 Woodworth, J., (A) 62 Xie, W. H., (A) 61 Xing, Z., (A) 57 Xiong, X., (A) 62 Xue, T., (A) 75 Yadav, V. S., (O) 93 Yagodin, V., (A) 42, 42 Yakrus, M. A., (A) 80 Yamashiro, S., (A) 66 Yamazaki, Y., (A) 44 Yang, M., (A) 72, 75 Yeremeev, V., (A) 61 You, E. Y., (A) 68, 85 Young, D. B., (A) 68, 85 Young, S. K., (A) 68, 85 Zambrano, Edgar A., (C) 222 Zangerle, R., (A) 168 Zganiacz, A, (A) 57 Zhang, X. E., (A) 61 Zhang, Y., (A) 46 Zhang, Z. P., (A) 61 Zhou, Y. F., (A) 61 Zhu, M., (A) 44 Zinsou, C., (A) 79
2005
Souza, L. C., (A) 50 Sp. Grp Non Tuber. Mycobacteria, (A) 83 Sreenath, N. P., (A) 68 Sreevatsan, S., (A) 80 Srinivasan, A., (A) 80 Stavropoulos, E., (A) 71, 72, 75 Steele, P., (A) 73 Stefani, G. P., (A) 50 Stefani, M. M., (A) 50 Steinhoff, Ulrich, (C) 131 Stelzmueller, I., (A) 168 Stephan, J., (A) 46 Steunous, C., (A) 79 Stewart, J., (A) 64 Stokes, R. W., (A) 65 Strother, M., (A) 80 Sukumar, , (A) 50 Suneetha, L. M., (A) 68, 85 Suneetha, S., (A) 68, 85 Supply, P., (A) 66 Talhari, Sinesio, (C) 225 Tascon, R. E., (A) 71, 72, 75 Tayles, N., (A) 43 Taylor, C., (A) 62, 62 Taylor, G. A., (A) 155 Taylor, G. M., (A) 68, 85 Thappa, D. M., (A) 48 Thepen, T., (A) 63 Thomsen, V. O., (A) 83 Thorson, L. M., (A) 65 Timmerman, P., (A) 44 Tobian, A. A., (A) 63 Tortoli, E., (A) 80 Tortoli, E. & Vincent, V., (A) 83 Trauger, R. ., (A) 161 Truffot-Pernot, C., (A) 44 Turner, A. P., (A) 55 Turner, O. C., (A) 70 Turner, S., (A) 73 Tyring, S. K., (A) 81 Uezu, K., (A) 66 Uma Devi, K. R., (A) 64 Urgell, J. R. & Rusch-Gerdes, S, (A) 83 Valderrama, J., (A) 51 Valentini, R., (A) 166 Vergne, I., (A) 52, 57 Verhasselt, P., (A) 44 Verma, I., (A) 75 Vermund, S. H., (A) 43 Vich, Fernando A., (O) 258 Vilata, Juan J., (O) 258 Vilde, J. L., (A) 52 Villahermosa, L. G., (A) 58
Volume 73, Number 4 Printed in the U.S.A.
SUBJECT INDEX
This Subject Index is compiled from key words in the title of each entry. An original article is indicated by (O), editorial (E), correspondence (C), news and notes (N), obituary (Ob), abstract (A), book review (B), supplement (S), image from the history of leprosy (I).
Acquired immunodeciency syndrome (AIDS), Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al. . . . (A) Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) Leprosy in the Era of AIDS. Report of a meeting at Robben Island, SA. . . . . . . . . . . . . . . . . . (N) Adenosine triphosphate (ATP), A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries, K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Africa, ALERT Training Courses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy Reid, S.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Images from the History of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..(I) Antibody(ies), Improved diagnosis of pulmonary tuberculosis by detection of free and immune complexbound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Antigen(s), A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . . (A) Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) Electrochemical antigen-retrieval of formaldehyde xed and parafn-embedded archived leprosy skin biopsies. Sergio, N.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) RNA encoding the MPT83 antigen induces protective immune responses against mycobacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Recombinant modied vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. (A) Apoptosis, Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions. Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Asia, International Course on rehabilitation and prevention of disability (RPOD) and course in community based rehabilitation (CBR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) Osteoarchaeological evidence for leprosy from western Central Asia. Blau, S. and Yagodin, V. . (A) Osteoarchaeological evidence for leprosy from western Central Asia. Blau, S. and Yagodin, V. . (A)
56 166 283
44 40 43 89
64
72 71 63 60 74 75 82 62
269
39 43 42 42
319
320
2005
Assay(s) (see also ELISA), Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) Bacilli, The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Bacteriology, Utility of fast mycobacerial interspersed repetitive unit variable number tandem repeat genotyping in clinical mycobacteriological analysis. Allix, C., et al. . . . . . . . . . . . . . . . . . . (A) Bangladesh, Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic area: Comparison between Bangladesh and Thailand. Richardus, Jan H., et al. . . . . . . . . . (O) BCG (bacille Calmette-Guerin), A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Gutierrez, M.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Comparative evaluation of immunotherapeutic efcacy of BCG and Mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Long term control of mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-decient mice. Nicolle, D., et al. (A) Recombinant modied vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . (A) Biopsy, Electrochemical antigen-retrieval of formaldehyde xed and parafn-embedded archived leprosy skin biopsies. Sergio, N.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Blood, Catheter-related bloodstream infection caused by mycobacterium brumae. Lee, S.A., et al. . . . (A) Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Borderline leprosy, Borderline tuberculoid leprosy with Type 1 reactiion in an HIV patientA phenomenon of immune reconstitution. Narang, Tarun, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Co-localization of pityriasis versicolor and BT Hansens Disease. Narang, Tarun, et al. . . . . . (O) Comparative evaluation of immunotherapeutic efcacy of BCG and Mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) Brazil, Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A)
54 61
64
66
249
72 155 105 59 74 82
70
60 82 63 75 83
203 206 105
48 75 83
73, 4
Subject IndexVolume 73
321
Human immunodeciency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic proles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Inequality and leprosy in Northeast Brazil: an ecological study. Kerr-Pontes, L.R.S., et al. . . . (A) Case detection, Trends in case detection inuenced by leprosy elimination campaigns in certain areas of China. Jianping, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cell(s), 16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis. Hernandez-Pando, R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy. Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cell biology of mycobacterium tuberculosis phagosome. Vergne, I., et al. . . . . . . . . . . . . . . . . (A) Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprosy bacillus triggers the wrong cells. Ottenhoff, Tom H.M. and Klein, Michel R. . . . . . . (C) Mycobacterium tuberculosis functional network analysis by global subcellular protein proling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The glycan-rich outer layer of the cell wall of mycobacterium tuberculosis acts as an antiphagocytic capsule limiting the association of the bacterium with macrophages. Stokes, R.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cells, mononuclear, Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) Cells, T, A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy. Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cell-mediated immunity (CMI) (see also Immunology), Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
50 76
76
161 58 57 57 63 62 59 69 57 85 208 84
64
65
62
63
58 57 62
62
57 85
322
2005
Chemotherapy (see also Multidrug therapy), 16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis. Hernandez-Pando, R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Chemotherapeutic efcacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Fluoroquinolones as chemotherapeutics against mycobacterial infections. Jacobs, M.R . . . . . (A) Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Microsphere technology for chemotherapy of mycobacterial infections. Barrow, R.R . . . . . . . (A) China, Peoples Republic of, Trends in case detection inuenced by leprosy elimination campaigns in certain areas of China. Jianping, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Classication, A need for clarication of the classication criteria for leprosy patients Oskam, L. and Buhrer-Sekula, S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Dr. Gelber and Colleagues Reply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Clinic(s), A clinical study of the involvement of cranial nerves in leprosy. Gopinath, D.V., et al. . . . . . . (A) An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of xed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Clinical and histologic variations among thiry patients with Lucios phenomenon and pure and primitive diffuse lepromatosis (Latapis Lepromatosis). Rea, Thomas H. and Jerskey, Robert S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al . . . (A) Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) Clinico-pathological study of 12 cases of patients with leprosy admitted to Sina Hospital, Hamadan, Iran, from 1991 2000. Farshchian, M. and Kheirandish, A. . . . . . . . . . . . . . . . . (A) Consensus methods: A bridge between clinical reasoning and clinical research. Cross, Hugh . (C) Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) Human immunodeciency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic proles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Hypercalcemia secondary to leprosy Couri, C.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprous neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multibacillary leprosy in Tyrol Pfausler, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Utility of fast mycobacerial interspersed repetitive unit variable number tandem repeat genotyping in clinical mycobacteriological analysis. Allix, C., et al. . . . . . . . . . . . . . . . . . . (A) Clinical, A clinical study of the involvement of cranial nerves in leprosy. Gopinath, D.V., et al. . . . . . . (A) An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of xed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Clinical and histologic variations among thiry patients with Lucios phenomenon and pure and primitive diffuse lepromatosis (Latapis Lepromatosis). Rea, Thomas H. and Jerskey, Robert S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al . . . (A) Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Consensus methods: A bridge between clinical reasoning and clinical research. Cross, Hugh . (C) Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A)
161
45 45
74 44
76
280 281 48 50
169 56 48 49 47 28 166
50 47 47 51 61 277 66 48 50
169 56 48 28 166
73, 4
323
Human immunodeciency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic proles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Hypercalcemia secondary to leprosy Couri, C.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprous neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multibacillary leprosy in Tyrol Pfausler, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Utility of fast mycobacerial interspersed repetitive unit variable number tandem repeat genotyping in clinical mycobacteriological analysis. Allix, C., et al. . . . . . . . . . . . . . . . . . . (A) Control of leprosy, Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . (A) IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Long term control of mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-decient mice. Nicolle, D., et al. (A) Cutaneous, A case of isolated tuberculoid leprosy of antebrachial medial cutaneous nerve. Martins, R.S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Successive development of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and Sweets syndrome in a patient with cervical lymphadenitis caused by mycobacterium fortuitum. Chen, H.H., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Ulcerative cutaneous mycobacteriosis due to report of two mexican cases. Coloma, Josefa, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Cytokine, Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Yamashiro, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions. Faber, W.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The effect of iron on the expression of cytokines in macrophages infected with mycobacterium tuberculosis. Seran-Lopez, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Deformity, disability, International Course on rehabilitation and prevention of disability (RPOD) and course in community based rehabilitation (CBR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Measuring impairment caused by leprosy: inter-tester reliability of the WHO disability grading system. Nienhuis, W.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Visible deformity in childhood leprosyA ten-year study. Kar, Bikash Ranjan and Job, C.K. (O) Dermal, Characteristics of mycobacterial infection in patients with immunodeciency and nuclear factor-kappaB essential modulator mutation, with or without ectodermal dysplasis. Dai, Y.S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Diabetes, Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Yamashiro, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) DNA, A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) DNA damage studies in untreated and treated leprosy patients. Gandhi, G. and Singh, B. . . . (A) Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A)
50 47 47 51 61 277 66
71 56 74
49
79 5
66 58 65
39 50 243
79
66
72 59 75 83
324
2005
67
Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) Drugs (see also Multidrug therapy and specic drugs), A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries, K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Chemotherapeutic efcacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levooxacin, moxioxacin, and four conventional antimycobacterial drugs against mycobacterium kansasii. Alcaide, F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. (A) Multi drug resistant mycobacterium leprae from patients with leprosy. Maeda, S . . . . . . . . . . (A) Multidrug resistance of a porin deletion mutant of mycobacterium smegmatis. Stephan, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Persister studies in leprosy patients after multi-drug treatment. Gupta, U.D., et al. . . . . . . . . . (A) The magic bullets and tuberculosis drug targets. Zhang, Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Electron microscopy (see also Ultrastructure), Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) Elimination, Trends in case detection inuenced by leprosy elimination campaigns in certain areas of China. Jianping, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Comments on WHO/AFROs Post-Elimination strategy paper: A new bottle with old wine of the Final Push. Ji, Baohong . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (E) Elimination of the International Journal of Leprosy Scollard, David M . . . . . . . . . . . . . . . . . . . (E) Epidemiology, Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) Factors contributing to the decline of leprosy in Spain in the second half of the twentieth century. Alfonso, Jose L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Erythema nodosum leprosum (ENL), Erythema nodosum leprosum and HIV infection: A therapeutic experience. Sharma, Nand Lal, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Erythema nodosum leprosum necroticans in a childan unusual manifestation. Pandhi, Deepika, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) Face, Anesthesia of face uncovered by histopathology. Daniel, Ebenezer and Ebenezer, Gigi . . . . . (O) Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the receptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Family, Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Variable presentation of disseminated nontuberculous mycobacterial infections in a family with an interferon gamma receptor mutation. Han, J.Y., et al . . . . . . . . . . . . . . . . . . . . . . . . (A)
74 61
44
45
78 45 67 46 68 85 100 46 69
76 216 303
166 258
189 122 222 22
57
68 81
73, 4
325
Genetics, A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Gutierrez, M.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Comparative evaluation of immunotherapeutic efcacy of BCG and Mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) Dissection of phylogenetic relationships among 19 rapidly growing mycobacterium species by 16S rRNA, hsp65, sodA, recA and rpoB gene sequencing. Adekambi, T. and Drancourt, M. . . . (A) Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Long term control of mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-decient mice. Nicolle, D., et al. (A) Recombinant modied vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) TB tools to tell the talemolecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) TB tools to tell the tale-molecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Taxonomic and phylogenetic status of non-tuberculous mycobacteria in a Carribbean setting. Ferdinand, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . (A) Genital, Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal, S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Granuloma(s), A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy. Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Granuloma necrosis during Mycobacterium avium infection does not require tumor necrosis factor. Florido, M. and Appelberg, R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterial granulomas: keys to a long lasting host-pathogen relationship. Co, D.O., et al. (A) Tuberculous granuloma formation is enhanced by a mycobacerium virulence determinant. Volkman, H.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Hand(s), Mycobacterium chelonae tenosynovitis of the hand. Mateo, L., et al. . . . . . . . . . . . . . . . . . . . (A) Histopathology, An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of xed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Anesthesia of face uncovered by histopathology. Daniel, Ebenezer and Ebenezer, Gigi . . . . . (O) Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) Human immunodeciency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic proles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) History of leprosy, Images from the History of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I) Images from the History of Leprosy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I) Images from the History of Leprosy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I)
72 155
68 105 77 59 57 85 74 82 54 84 80
70
46
73 58 53 52 65 83
50 22 49
50 1 89 241
326
2005
167 42 25
Images from the History of Leprosy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (I) Leprosy and mortality in the Medieval Danish village of Tirup Boldsen J.L . . . . . . . . . . . . . . . (A) Leprosy research declines, but most of the basic questions remain unanswered Scollard, D.M (E) Human immunodeciency virus (HIV), Borderline tuberculoid leprosy with Type 1 reactiion in an HIV patientA phenomenon of immune reconstitution. Narang, Tarun, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Determinants of immune reconstitution inammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) Endosomal membrane trafc: convergence point targeted by mycobacterim tuberculosis and HIV. Deretic, V., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) Erythema nodosum leprosum and HIV infection: A therapeutic experience. Sharma, Nand Lal, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Human immunodeciency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic proles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprosy and HIV infection (Rarely the Twain shall meet?). Nelson, Kenrad E . . . . . . . . . . . . . (C) Seroprevalence of HIV infection among leprosy patients in Agra, India: Trends and perspective. Hussain, Tahziba, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Immune complexes, Improved diagnosis of pulmonary tuberculosis by detection of free and immune complexbound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Immune responses, Fatal mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. Fremond C.M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) RNA encoding the MPT83 antigen induces protective immune responses against mycobacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Immunology, Human immunodeciency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic proles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Immunotherapy, Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) India, Leprosy program in India at the Crossroads. Rao, P. Narasimha . . . . . . . . . . . . . . . . . . . . . . . . (E) Management of 34 chronic heel sinuses in leprosy, using a modicatiion of a local rotation ap in Kolkata, India. Joshua, J. and Sarkar, S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Prevalence of leprosy in Agra District (U.P.) India from 2001 to 2003. Kumar, Anil, et al. . . . (A) Seroprevalence of HIV infection among leprosy patients in Agra, India: Trends and perspective. Hussain, Tahziba, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Interferon, Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy. Quiroga, M.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Variable presentation of disseminated nontuberculous mycobacterial infections in a family with an interferon gamma receptor mutation. Han, J.Y., et al . . . . . . . . . . . . . . . . . . . . . . . . (A) Interleukin(s), IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
203 52 52 166 189
50 133 93
64
61 75
50
74 211 49 115 93
54
63 60 81
56
73, 4
327
303 304 177 87 238 305
INTERNATIONAL JOURNAL OF LEPROSY (IJL), Elimination of the International Journal of Leprosy Scollard, David M . . . . . . . . . . . . . . . . . . . (E) Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) Special Grantors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) Special Grantors and Sustaining Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) Special Grantors and Sustaining Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) Special Grantors and Sustaining Members . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) Intestine(s), Johnes disease, inammatory bowel disease, and mycobacterium paratuberculosi. Chacon, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Iran, Clinico-pathological study of 12 cases of patients with leprosy admitted to Sina Hospital, Hamadan, Iran, from 1991 2000. Farshchian, M. and Kheirandish, A. . . . . . . . . . . . . . . . . (A) Leprosy prole in Isfahan (A province of Iran). Asilian, A., et al. . . . . . . . . . . . . . . . . . . . . . . (C) Japan, 2005 U.S.-Japan Meeting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Summary of questionnaires on leprosy in Yokohama City area and university hospitals Ishii, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) U.S.-Japan cooperative medical science program. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) U.S.-Japan meeting, 2004. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Kidney(s), Mycobacterium chelonae skin infection in kidney-pancreas recipient. Stelzmueller, I., et al. (A)
79
47 127 297 43 139 230 168
Korea, Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Lepromatous leprosy, Comparative evaluation of immunotherapeutic efcacy of BCG and Mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal, S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Lesion(s), A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy. Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal, S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Reply to the Editor Kumarasinghe, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions. Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Lipid(s), Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) High-polarity Mycobacterium avium-derived lipids interact with murine macrophage lipid rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the receptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. (A) Lipoprotein, Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Liposome, Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. . . . . (A) Liver, Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. . . . . (A)
68 85
105 46
58 46 227 269
59 73 57
63 45 45
328
2005
Lucio phenomenon, Clinical and histologic variations among thiry patients with Lucios phenomenon and pure and primitive diffuse lepromatosis (Latapis Lepromatosis). Rea, Thomas H. and Jerskey, Robert S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Lymphocyte(s), Bystander activation of CD8+ T lymphocytes during experimental mycobacterial infection. Gilbertson, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Macrophage(s), Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . (A) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Gutierrez, M.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) High-polarity Mycobacterium avium-derived lipids interact with murine macrophage lipid rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . (A) Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the receptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The effect of iron on the expression of cytokines in macrophages infected with mycobacterium tuberculosis. Seran-Lopez, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The glycan-rich outer layer of the cell wall of mycobacterium tuberculosis acts as an antiphagocytic capsule limiting the association of the bacterium with macrophages. Stokes, R.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Toll-like receptor 2 and mitogen and stress-activated kinase 1 are effectors of Mycobacterium avium induced cyclooxygenase 2 expression in macrophages. Pathak, S.K., et al. . . . . . . . (A) Malawi, Large scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Fitness, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Metabolism, Hypercalcemia secondary to leprosy Couri, C.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Tuberculosis-metabolism and respiration in the absence of growth. Boshoff, H.I. and Barry, C.E., III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mexico, Ulcerative cutaneous mycobacteriosis due to report of two mexican cases. Coloma, Josefa, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Mice, murine, A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . (A) Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . (A) Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) High-polarity Mycobacterium avium-derived lipids interact with murine macrophage lipid rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
169
73
71 155 72 73 63
63
57 65
65 55
84 47 69
72 71 71 72 59 73 56
73, 4
329
Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Long term control of mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-decient mice. Nicolle, D., et al. . (A) Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Yamashiro, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . . . (A) The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Microscopy, Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) Molecular biology (see also DNA, Genetics), Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Molecular pathogenesis of mycobacterial diseases. Kobayashi, K . . . . . . . . . . . . . . . . . . . . . . (A) Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) TB tools to tell the talemolecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) TB tools to tell the tale-molecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Monocyte(s), The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Morbidity, Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity. Debacker, M., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Morphology, Alterations in neurolament protein(s) in human leprous nerves: morphology, immunohistochemistry and Western immunoblot correlative study. Save, M.P., et al. . . . . . . . . . . . (A) Mycobacteria (see also individual species), A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) Amoebal coculture of mycobacterium massiliense sp. nov. from the sputum of a patient with hemoptoic pneumonia Adekambi, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . . (A) Bystander activation of CD8+ T lymphocytes during experimental mycobacterial infection. Gilbertson, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Characteristics of mycobacterial infection in patients with immunodeciency and nuclear factor-kappaB essential modulator mutation, with or without ectodermal dysplasis. Dai, Y.S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Clinical latency and reactivation of AIDS-related mycobacterial infections. Shen, Y., et al . . . (A) Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levooxacin,
74 74
66 63
62 69
57 85 54 222 54 84
64
79
60
72 57 78 71 73
79
68 56
330
2005
78 63 53 44 45 57 85 56
moxioxacin, and four conventional antimycobacterial drugs against mycobacterium kansasii. Alcaide, F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) Developing rapid detection of mycobacteria using microwaves. Jing, G., et al. . . . . . . . . . . . . (A) Effects of macrolides and ketolides on mycobacterial infections. Bermudez, L.E. and Yamazaki, Y. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Fluoroquinolones as chemotherapeutics against mycobacterial infections. Jacobs, M.R . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. van de Vosse, E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. Pearl, J.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Infections due to non tuberculous mycobacteria (NTM). Katoch, V.M . . . . . . . . . . . . . . . . . . . (A) Liposome technology for drug delivery against mycobacterial infections. Khuller, G.K., et al. (A) Lipsomes as adjuvant for anti-mycobacterial vaccine development. Verma, I., et al. . . . . . . . . (A) Microsphere technology for chemotherapy of mycobacterial infections. Barrow, R.R . . . . . . . (A) Molecular pathogenesis of mycobacterial diseases. Kobayashi, K . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterial granulomas: keys to a long lasting host-pathogen relationship. Co, D.O., et al. (A) Non tuberculous mycobacteria: patterns of isolation. A multi country retrospective survey. Martin-Casabona, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Recombinant modied vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) Surface exposed glycopeptidolipids and phosphatidylinositol mannosides participate in the receptor-dependent phagocytosis of mycobacterial by human macrophages. Villenuve, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) TB tools to tell the talemolecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) TB tools to tell the tale-molecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Taxonomic and phylogenetic status of non-tuberculous mycobacteria in a Carribbean setting. Ferdinand, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Therapy of nontuberculous mycobacterial infections. Jogi, R. and Tyring, S.K. . . . . . . . . . . . (A) Variable presentation of disseminated nontuberculous mycobacterial infections in a family with an interferon gamma receptor mutation. Han, J.Y., et al . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium abscessus, Mycobacterium abscessus as a cause of pacemaker infection. Kessler, A.T. and Kourtis, A.P. (A) Mycobacterium avium, Granuloma necrosis during mycobacterium avium infection does not require tumor necrosis factor. Florido, M. and Appelberg, R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) High-polarity mycobacterium avium-derived lipids interact with murine macrophage lipid rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacerium avium subsp. paratuberculosis strains isolated from Crohns disease patients and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) Toll-like receptor 2 and mitogen and stress-activated kinase 1 are effectors of mycobacterium avium induced cyclooxygenase 2 expression in macrophages. Pathak, S.K., et al. . . . . . . . (A) Use of multilocus variable number tandem-repeat analysis for typing mycobacterium avium subsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
74 81 45 75 44 54 52 83 82 222
57 54 84 80
62 81 81 81
53 73 80 55 84
73, 4
331
Mycobacterium avium complex, Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium bovis (see also BCG), A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Long term control of mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-decient mice. Nicolle, D., et al. (A) The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium cheloni (chelonae), Mycobacterium chelonae skin infection in kidney-pancreas recipient. Stelzmueller, I., et al. . . . (A) Mycobacterium chelonae tenosynovitis of the hand. Mateo, L., et al. . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium fortuitum, Successive development of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and Sweets syndrome in a patient with cervical lymphadenitis caused by mycobacterium fortuitum. Chen, H.H., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium goodii, Mycobacterium goodii infections associated with surgical implants at Colorado hospital. Ferguson, D.D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium kansasii, Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levooxacin, moxioxacin, and four conventional antimycobacterial drugs against mycobacterium kansasii. Alcaide, F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Epidemiological, clinical and therapeutic features of AIDS related mycobacterium kansasii infectiion during the HIV pandemic: an 11 year follow up study. Manfredi, R., et al. . . . . . (A) Mycobacterium leprae, Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Diaminodiphenylsulfone resistance of mycobacterium leprae due to mutations in the dihydropteroate synthase gene. Kai, M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Effect of mycobacterium leprae lipids on BCG- and carrageenan induced cellular recruitment in mouse pleurisy. Moura, A.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Effects of purication and uorescent staining on viability of mycobacterium leprae. Lahiri, Ramanuj, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Human immunodeciency virus type 1 (HIV-1) and mycobacterium leprae co-infection: HIV-1 subtypes and clinical, immunologic, and histopathologic proles in a Brazilian cohort. Pereira, G.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Microsatellite mapping of mycobacterium leprae populations in infected humans. Young, S.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Microsatellite mapping of mycobacterium leprae populations in infected humans. Young, S.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multi drug resistant mycobacterium leprae from patients with leprosy. Maeda, S . . . . . . . . . . (A) Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mutations in genes related to drug resistance in mycobacterium leprae isolates from leprosy patients in Korea. You, E.Y., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
72
72 74
70 168 83
79
80
78 166
68 75 83 67 67 59 194
50 68 85 67 68 85
332
2005
Mycobacterium paratuberculosis, Mycobacerium avium subsp. paratuberculosis strains isolated from Crohns disease patients and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) Use of multilocus variable number tandem-repeat analysis for typing mycobacterium avium subsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium smegmatis, Multidrug resistance of a porin deletion mutant of mycobacterium smegmatis. Stephan, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium tuberculosis, 16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis. Hernandez-Pando, R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries, K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . (A) A potentially new treatment for tuberculosis; Will a diarylquinoline work for leprosy?. Franzblau, Scott . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Action of uoroquinolones and Linezolid on logarithmic- and stationary-phase culture of mycobacterium tuberculosis. Garcia-Tapia, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . (A) Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy. Reid, S.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Gutierrez, M.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cell biology of mycobacterium tuberculosis phagosome. Vergne, I., et al. . . . . . . . . . . . . . . . . (A) Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Chemotherapeutic efcacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated anti tubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Decaprenyl diphosphate synthesis in mycobacterim tuberculosis. Kaur, D., et al. . . . . . . . . . . (A) Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A) Determinants of immune reconstitution inammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) Endosomal membrane trafc: convergence point targeted by mycobacterim tuberculosis and HIV. Deretic, V., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Fatal mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. Fremond C.M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Geranylgeraniol regulates negatively caspase-1 autoprocessing: implication in the TH1 response against mycobacterium tuberculosis. Montero, M.T., et al. . . . . . . . . . . . . . . . . . . (A) Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with
80 84
46
161 44
72 73 71 32 69 57 71 43 155 57
68
45 63 62 69 55 52 72 69 52 61 70
73, 4
333
74 64 54 84 43
chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Improved diagnosis of pulmonary tuberculosis by detection of free and immune complexbound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Large scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Fitness, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Yamashiro, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . . (A) Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) Mycobacerium avium subsp. paratuberculosis strains isolated from Crohns disease patients and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) Mycobacterium tuberculosis functional network analysis by global subcellular protein proling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) RNA encoding the MPT83 antigen induces protective immune responses against mycobacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The effect of iron on the expression of cytokines in macrophages infected with mycobacterium tuberculosis. Seran-Lopez, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The glycan-rich outer layer of the cell wall of mycobacterium tuberculosis acts as an antiphagocytic capsule limiting the association of the bacterium with macrophages. Stokes, R.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The magic bullets and tuberculosis drug targets. Zhang, Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Tuberculosis-metabolism and respiration in the absence of growth. Boshoff, H.I. and Barry, C.E., III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Use of multilocus variable number tandem-repeat analysis for typing mycobacterium avium subsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Mycobacterium ulcerans, Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity. Debacker, M., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Nerve(s) (see also Neuritis, Neuropathy), A case of isolated tuberculoid leprosy of antebrachial medial cutaneous nerve. Martins, R.S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A clinical study of the involvement of cranial nerves in leprosy. Gopinath, D.V., et al. . . . . . . (A) Alterations in neurolament protein(s) in human leprous nerves: morphology, immunohistochemistry and Western immunoblot correlative study. Save, M.P., et al. . . . . . . . . . . . . . . . (A) Clinical, electroneuromyographic and morphological studies of pure neural leprosy in a Brazilian referral centre. Jardim, M.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A)
66 63 61 80 84
63 74 75
64 65
65 46
62
70 69 84
79
49 48 60 48 49 55
334
2005
46
Involvement of genitofemoral nerve with genital lesions in lepromatous leprosy. Agrawal, S.K., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Neuropathy (see also Nerve(s), Neuritis), Factors contributing to the decline of leprosy in Spain in the second half of the twentieth century. Alfonso, Jose L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Leprosy and neuropathy seen from the perspective of a surgeon. Duerksen, F . . . . . . . . . . . . . (A) Leprous neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Multibacillary leprosy in Tyrol Pfausler, B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Neuropathic Pain in Leprosy Patients. Malaviya, G. N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Quantitative measurement of sensory impairment in referral centers Premkumar, Ramaswamy, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Sensory polyneuropathy as initial manifestation of endemic leprosy in Spain. Serrano-Pozo, A., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Nose, A rational approach to nasal reconstruction in leprosy. Schwarz, R.J. and Macdonald, M. . . . (A) Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic area: Comparison between Bangladesh and Thailand. Richardus, Jan H., et al. . . . . . . . . . (O) Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A) Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Workshop on Hansens Disease: The challenge to integrate diagnose and treatment activities into basic care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Obituaries, Diltor Vladmir Araujo Opromolla (1934-2004) Virmond, Marcos . . . . . . . . . . . . . . . . . . . . . (Ob) Ooxacin, Comparative in vitro activities of linezolid, telithromycin, clarithromycin, levooxacin, moxioxacin, and four conventional antimycobacterial drugs against mycobacterium kansasii. Alcaide, F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Persisters, Persister studies in leprosy patients after multi-drug treatment. Gupta, U.D., et al. . . . . . . . . . (A) Polymerase chain reaction (PCR), Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Prevalence, Prevalence of leprosy in Agra District (U.P.) India from 2001 to 2003. Kumar, Anil, et al. . . . (A) Seroprevalence of HIV infection among leprosy patients in Agra, India: Trends and perspective. Hussain, Tahziba, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Prophylaxis, A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients: design, methodology and recruitment ndings of COLEP. Moel, F.J., et al. . . . . . . . . . . . . (A) Protein(s), A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) Alterations in neurolament protein(s) in human leprous nerves: morphology, immunohistochemistry and Western immunoblot correlative study. Save, M.P., et al. . . . . (A) Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprosy SusceptibilityA matter of protein degradation? The role of proteasomes in infection and disease. Steinhoff, Ulrich and Visekruna, Alexande . . . . . . . . . . . . . . . . . . . . . . . . (C)
258 47 47 51 34 219 52 51 249 75 83 55 277 40 137
78 100
75 83 115 93
149
73 60 67 131
73, 4
335
84
Mycobacterium tuberculosis functional network analysis by global subcellular protein proling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) The SLAM-associated protein (SAP) regulates IFN-gamma expression in leprosy. Quiroga, M.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Purication, Effects of purication and uorescent staining on viability of mycobacterium leprae. Lahiri, Ramanuj, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Reaction, leprosy, Detection of mycobacerium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Detection of mycobacterium leprae DNA by polymerase chain reaction in the blood and nasal secretion of Brazilian household contacts. Almeida, E.C., et al. . . . . . . . . . . . . . . . . . . . . . (A) Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions. Faber, W.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Serologic recognition of low molecular weight mycobacterial protein fractions in lepromatous patients with Type II reactions (ENL). Rada, Elsa Maria, et al. . . . . . . . . . . . . . . . . . . . . . . (C) Some considerations on the origin of Type 1 reactions in leprosy. Opromolla, D.V.A . . . . . . . (C) Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions. Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) The role of mycophenolate mofetil in the treatment of leprosy reactions. Burdick, Anne E. and Ramirez, Claudia C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Rehabilitation, International Course on rehabilitation and prevention of disability (RPOD) and course in community based rehabilitation (CBR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Anderson, George A (B) Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Mathews, Ronnie . (B) Relapse(s), Relapses after multibacillary leprosy treatment. Rodriguez, G., et al. . . . . . . . . . . . . . . . . . . . (A) Review, Estimating the economic value to societies of the impact of health research: a critical review. Buxton, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprosy research declines, but most of the basic questions remain unanswered.Scollard, D.M (E) Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (Ob) Rifampin, Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) Serum, Serial measurement of serum cytokines, cytokine receptors and neopterin in leprosy patients with reversal reactions. Faber, W.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Skin, A study of mast cells in granulomatous lesions of skin, with special emphasis on leprosy. Bagwan, I.N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Clinico-histopathological correlation of skin and nerve in leprosy. Khan, A., et al. . . . . . . . . . (A) Electrochemical antigen-retrieval of formaldehyde xed and parafn-embedded archived leprosy skin biopsies. Sergio, N.F., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
63 222 60
70
194
75 83 58 222 33 269 129
39 36 37 51
76 54 25 304
61
58
58 49 60
336
2005
168 269
Mycobacterium chelonae skin infection in kidney-pancreas recipient. Stelzmueller, I., et al. . (A) Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions. Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Social, Summary of questionnaires on leprosy in Yokohama City area and university hospitals Ishii, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Social aspects, Summary of questionnaires on leprosy in Yokohama City area and university hospitals Ishii, N., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) South America, Workshop on Hansens Disease: The challenge to integrate diagnose and treatment activities into basic care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Southeast Asia, Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) Spain, Factors contributing to the decline of leprosy in Spain in the second half of the twentieth century. Alfonso, Jose L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Sensory polyneuropathy as initial manifestation of endemic leprosy in Spain. Serrano-Pozo, A., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Stain(s), Effects of purication and uorescent staining on viability of mycobacterium leprae. Lahiri, Ramanuj, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Sulfone(s), Diaminodiphenylsulfone resistance of mycobacterium leprae due to mutations in the dihydropteroate synthase gene. Kai, M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Surgery, A Delphi Consensus on criteria for contraindications, assessment indicators and expected outcomes related to tibialis posterior transfer surgery. Cross, Hugh . . . . . . . . . . . . . . . . . . . (O) Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Anderson, George A (B) Reconstructive surgery & rehabilitation in leprosy and other neuropathies. Mathews, Ronnie . (B) Synovitis, Mycobacterium chelonae tenosynovitis of the hand. Mateo, L., et al. . . . . . . . . . . . . . . . . . . . (A) Thailand, Close contacts with leprosy in newly diagnosed leprosy patients in a high and low endemic area: Comparison between Bangladesh and Thailand. Richardus, Jan H., et al. . . . . . . . . . (O) Therapy (see also Chemotherapy and Multidrug therapy), 16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis. Hernandez-Pando, R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of xed duration therapy. Mathew, D., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy. Reid, S.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Determinants of immune reconstitution inammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Microsphere technology for chemotherapy of mycobacterial infections. Barrow, R.R . . . . . . . (A) Therapy of nontuberculous mycobacterial infections. Jogi, R. and Tyring, S.K. . . . . . . . . . . . (A) Toll-like receptors, Long term control of mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2 , TLR6-, or TLR2-Tlr4-decient mice. Nicolle, D., et al. . . . (A)
43
43
40 43
258 52
194
67
13 36 37 83
249
161 50 43 52
74 44 81
74
73, 4
337
40
Training, ALERT Training Courses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Transmission, A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients: design, methodology and recruitment ndings of COLEP. Moel, F.J., et al. . . . . . . . . . . . . (A) Treatment, A potentially new treatment for tuberculosis; Will a diarylquinoline work for leprosy?. Franzblau, Scott . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Paucibacillary treatment for large tuberculoid lesiions of leprosy. Santos, Monica Nunes Souza, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Persister studies in leprosy patients after multi-drug treatment. Gupta, U.D., et al. . . . . . . . . . (A) Relapses after multibacillary leprosy treatment. Rodriguez, G., et al. . . . . . . . . . . . . . . . . . . . (A) Study of Apoptosis in skin lesions of leprosy in relation to treatment and lepra reactions. Ajith, C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) The role of mycophenolate mofetil in the treatment of leprosy reactions. Burdick, Anne E. and Ramirez, Claudia C. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Workshop on Hansens Disease: The challenge to integrate diagnose and treatment activities into basic care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (N) Trial(s), A study on transmission and a trial of chemoprophylaxis in contacts of leprosy patients: design, methodology and recruitment ndings of COLEP. Moel, F.J., et al. . . . . . . . . . . . . (A) Tuberculoid leprosy, A case of isolated tuberculoid leprosy of antebrachial medial cutaneous nerve. Martins, R.S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Borderline tuberculoid leprosy with Type 1 reactiion in an HIV patientA phenomenon of immune reconstitution. Narang, Tarun, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Tuberculosis, 16alpha-Bromoepiandrosterone restores T helper cell type 1 activity and accelerates chemotherapy-induced bacterial clearance in a model of progressive pulmonary tuberculosis. Hernandez-Pando, R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A Diaryquinoline Drug Active on the ATP Synthase of mycobacterium tuberculosis. Andries, K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A heterologous DNA priming-mycobacterium bovis BCG boosting immunization strategy using mycobacterial Hsp70, Hsp65 and Apa antigens improves protection against tuberculosis in mice. Ferraz, J.C., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of mycobacterium tuberculosis pulmonary infection. Izzo, A.A., et al. . . . . . . . . . . . . . . . . . . (A) A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . (A) A potentially new treatment for tuberculosis; Will a diarylquinoline work for leprosy?. Franzblau, Scott . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Action of uoroquinolones and Linezolid on logarithmic- and stationary-phase culture of mycobacterium tuberculosis. Garcia-Tapia, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . . (A) Antiretroviral therapy in sub-Saharan Africa: adherence lessons from tuberculosis and leprosy. Reid, S.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Gutierrez, M.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cell biology of mycobacterium tuberculosis phagosome. Vergne, I., et al. . . . . . . . . . . . . . . . . (A) Characterization of phylogenetically distant members of the adenylyl cyclase family from mycobacteria: Rv1647 from M.tuberculosis and its ortholog ML1399 from M. leprae. Shenoy, A.R., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
149
32
74 225 100 51 269 129 40
149
49 203
161 44
72 73 71 32 69 57 71 43 155 57
68
338
2005
Chemotherapeutic efcacy of poly (DL-lactide-co-glycolide) nanoparticle encapsulated antitubercular drugs at sub therapeutic dose against experimental tuberculosis. Sharma, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Cortisol and dehydroepiandrosterone affect the response of peripheral blood mononuclear cells to mycobacterial antigens during tuberculosis. Mahuad, C., et al. . . . . . . . . . . . . . . . . (A) Cytolytic CD8+ T cells recognizing CFP10 are recruited to the lung after mycobacterium tuberculosis infection. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Decaprenyl diphosphate synthesis in mycobacterim tuberculosis. Kaur, D., et al. . . . . . . . . . . (A) Detection of mycobacterium tuberculosis (TB) in vitro and in situ using an electronic nose in combination with a neural network system. Pavlou, A.K., et al. . . . . . . . . . . . . . . . . . . . . . (A) Determinants of immune reconstitution inammatory syndrome in HIV type 1-infected patients with tuberculosis after initiation of antiretroviral therapy. Breton, G., et al. . . . . . (A) Early effect of mycobacterium tuberculosis infection on Mac-1 and ICAM-1 expression on mouse peritoneal macrophages. Ghosh, S. and Saxena, R.K. . . . . . . . . . . . . . . . . . . . . . . . . (A) Electron microscopy analysis of mycobacterium tuberculosis cell division. Dahl, J.L . . . . . . . (A) Endosomal membrane trafc: convergence point targeted by mycobacterim tuberculosis and HIV. Deretic, V., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Fatal mycobacterium tuberculosis infection despite adaptive immune response in the absence of MyD88. Fremond C.M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Geranylgeraniol regulates negatively caspase-1 autoprocessing: implication in the TH1 response against mycobacterium tuberculosis. Montero, M.T., et al. . . . . . . . . . . . . . . . . . . (A) Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efcient form of treatment for tuberculosis in mice. Silva, C.L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Improved diagnosis of pulmonary tuberculosis by detection of free and immune complexbound anti-30 kDa antibodies. Raja, A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Pai, M., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Large scale candidate gene study of tuberculosis susceptibility in the Karonga district of northern Malawi. Fitness, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Leprosy and tuberculosis in Iron Age Southeast Asia?. Tayles, N. and Buckley, H.R. . . . . . . . (A) Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with mycobacterium tuberculosis. Yamashiro, S., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Macrophages play a dual role during pulmonary tuberculosis in mice. Leemans, J.C., et al. . . . . (A) Multiplex detection of mutations in clinical isolates of rifampin-resistant mycobacterium tuberculosis by short oligonucleotide ligation assay on DNA chips. Deng, J.Y., et al. . . . . (A) Mycobacerium avium subsp. paratuberculosis strains isolated from Crohns disease patients and animal species exhibit similar polymorphic locus patterns. Ghadiali, A.H., et al. . . . . (A) Mycobacterium tuberculosis functional network analysis by global subcellular protein proling. Mawuenyega, K.G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Prolonged toll-like receptor signaling by mycobacterium tuberculosis and its 19-kilodalton lipoprotein inhibits gamma interferon-induced regulation of selected genes in macrophages. Pai, R.K., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) RNA encoding the MPT83 antigen induces protective immune responses against mycobacterium tuberculosis infection. Xue, T., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) TB tools to tell the talemolecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) TB tools to tell the tale-molecular genetic methods for mycobacterial research. Machowski, E.E., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The down-regulation of cathepsin G in THP-1 monocytes after infection with mycobacterium tuberculosis is associated with increased intracellular survival of bacilli. Rivera Marrero, C.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The effect of iron on the expression of cytokines in macrophages infected with mycobacterium tuberculosis. Seran-Lopez, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The glycan-rich outer layer of the cell wall of mycobacterium tuberculosis acts as an antiphagocytic capsule limiting the association of the bacterium with macrophages. Stokes, R.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The magic bullets and tuberculosis drug targets. Zhang, Y . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
45 63 62 69 55 52 72 69 52 61 70
74 64 54 84 43
66 63 61 80 84
63 74 75 54 84
64 65
65 46
73, 4
339
The major histocompatibility complex haplotype affects T-cell recognition of mycobacterial antigens but not resistance to mycobacterium tuberculosis in C3H mice. Kamath, A.B., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Tuberculosis-metabolism and respiration in the absence of growth. Boshoff, H.I. and Barry, C.E., III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Use of multilocus variable number tandem-repeat analysis for typing mycobacterium avium subsp. paratuberculosis. Overduin, P., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Ulcer(s), Mycobacterium ulcerans disease: role of age and gender in incidence and morbidity. Debacker, M., et al . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Myiasis in leprosy Malaviya, G.N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Ulcerative cutaneous mycobacteriosis due to report of two mexican cases. Coloma, Josefa, et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (O) Urine, Antimycobacterial calixarenes enhance innate defense mechanisms in murine macrophages and induce control of mycobacterium tuberculosis infection in mice. Colston, M.J., et al. . . . (A) Detection of mycobacterium leprae DNA for 36kDa protein in urine from leprosy patients: a preliminary report. Parkash, O., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) High-polarity mycobacterium avium-derived lipids interact with murine macrophage lipid rafts. Maldonado-Garcia, G., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Vaccine(s), Vaccination, A mutant of mycobacterium tuberculosis H37Rv that lacks expression of antigen 85A is attenuated in mice but retains vaccinogenic potential. Copenhaver, R.H., et al. . . . . . . . . . (A) Activation of CD8 T cells by mycobacterial vaccination protects against pulmonary tuberculosis in the absence of CD4 T cells. Wang, J., et al. . . . . . . . . . . . . . . . . . . . . . . . . . (A) Comparative evaluation of immunotherapeutic efcacy of BCG and Mw vaccines in patients of borderline lepromatous and lepromatous leprosy. Narang, Tarun, et al . . . . . . . . . . . . . . (A) Lipsomes as adjuvant for anti-mycobacterial vaccine development. Verma, I., et al. . . . . . . . . (A) Protective effect of a tuberculosis subunit vaccine based on a fusion of antigen 85B and ESAT6 in the aerosol guinea pig model. Olsen, A.W., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Recombinant modied vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. McShane, H., et al. . . . . . . . . . (A) The protective effect of the mycobacterium bovis BCG vaccine is increased by coadministration with the mycobacterium tuberculosis 72-kilodalton fusion polyprotein Mtb72F in M. tuberculosis-infected guinea pigs. Brandt, L., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) Vasculitis, Successive development of cutaneous polyarteritis nodosa, leucocytoclastic vasculitis and Sweets syndrome in a patient with cervical lymphadenitis caused by mycobacterium fortuitum. Chen, H.H., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A) World Health Organization (WHO), A need for clarication of the classication criteria for leprosy patients Oskam, L. and Buhrer-Sekula, S. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Comments on WHO/AFROs Post-Elimination strategy paper: A new bottle with old wine of the Final Push. Ji, Baohong . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (E) Dr. Gelber and Colleagues Reply . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (C) Has the Term Elimination outlived its utility? Ganapati, R. and Pai, V.V. . . . . . . . . . . . . . . . (C) Measuring impairment caused by leprosy: inter-tester reliability of the WHO disability grading system. Nienhuis, W.A., et al. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . (A)
62
70 69 84
79 277 5
71 67 73
71 57 105 75 74 82
70
79
280 216 281 229 50

Jurnal Kusta Anak

Transféré par

Informations du document

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Jurnal Kusta Anak

Transféré par

Droits d'auteur :

Formats disponibles

VOLUME 73, NUMBER 4

INTERNATIONAL JOURNAL OF LEPROSY

249 258 269 277

280 281 283 297 303 304 306 307

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 4 Printed in the U.S.A. (ISSN 0148-916X)

INTERNATIONAL JOURNAL OF LEPROSY

Images from the History of Leprosy

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 4 Printed in the U.S.A. (ISSN 0148-916X)

INTERNATIONAL JOURNAL OF LEPROSY

Visible Deformity in Childhood Leprosy A 10-Year Study

International Journal of Leprosy

Kar and Job: Visible Deformity in Childhood Leprosy

TABLE 1. Distribution of children with leprosy by age and sex.

International Journal of Leprosy

TABLE 3. Distribution of Grade II deformities in children by year of diagnosis.

Kar and Job: Visible Deformity in Childhood Leprosy

International Journal of Leprosy

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 4 Printed in the U.S.A. (ISSN 0148-916X)

International Journal of Leprosy

Richardus, et al.: Close Contacts in Leprosy

International Journal of Leprosy

Richardus, et al.: Close Contacts in Leprosy

107 210 247 180 744

77 122 161 93 453

184 332 408 273 1197

International Journal of Leprosy

Richardus, et al.: Close Contacts in Leprosy

International Journal of Leprosy

of the present study is just one step towards this end.

Richardus, et al.: Close Contacts in Leprosy

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 4 Printed in the U.S.A. (ISSN 0148-916X)

Alfonso, et al.: Factors Contributing to the Decline of Leprosy

International Journal of Leprosy

Alfonso, et al.: Factors Contributing to the Decline of Leprosy

Note: * = % inter-annual variation; n.a. = not available.

International Journal of Leprosy

Alfonso, et al.: Factors Contributing to the Decline of Leprosy

International Journal of Leprosy

Annual GDP variation

Alfonso, et al.: Factors Contributing to the Decline of Leprosy

International Journal of Leprosy

Alfonso, et al.: Factors Contributing to the Decline of Leprosy

International Journal of Leprosy

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 4 Printed in the U.S.A. (ISSN 0148-916X)

International Journal of Leprosy

Ajith, et al.: Study of Apoptosis in Skin Lesions

International Journal of Leprosy

Ajith, et al.: Study of Apoptosis in Skin Lesions

274 TABLE 3. periods.

International Journal of Leprosy

Comparison of apoptoses by HPE between the various groups at different

Ajith, et al.: Study of Apoptosis in Skin Lesions

International Journal of Leprosy

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 4 Printed in the U.S.A. (ISSN 0148-916X)

CLINICAL NOTES Myiasis in Leprosy

International Journal of Leprosy

INTERNATIONAL JOURNAL OF LEPROSY