2006 National Guideline for the Management of Lymphogranuloma Venereum (LGV) Clinical Effectiveness Group of the British Association

for Sexual Health and HIV (CEG/BASHH) New information in this guideline since 2003 publication Aetiology and Epidemiology: latest data from LGV outbreaks in Western Europe (incl. UK) and USA epidemics have affected gay clubs sex scene, with no indication of contacts with endemic countries for LGV cases were White MSM, many of whom were also known to be HIV positive and co-infected with HCV Diagnosis: successful use of molecular diagnostic techniques to detect C trachomatis serovars: use of nested PCR for the detection of the major omp-1 gene of C trachomatis, and RFLP analysis to perform serovar typing on anorectal swabs. Clinical features have been diagnostic in recent outbreak in MSM with severe proctocolitis and rectal bleeding with history of genital ulcer and /or lymphadenopathy Management: UK cases have been successfully treated with doxycycline 100 mg BD for 3 weeks Dutch cases have been successfully treated with a single dose azithromycin 1.0 g Enhanced surveillance put in place by the Health Protection Agency Aetiology and Epidemiology Lymphogranuloma venereum (LGV) is a systemic disease caused by one of three invasive serovars L1, L2, or L3 of Chlamydia trachomatis, but other strains may occasionally be involved [1]. This disease has been known by a variety of terms including the DurandNicolas-Favres disease, lymphopatia venereum or lymphogranuloma inguinale [1]. LGV has been a rare occurrence in industrialised countries since the mid-1960's. For example, there had been only 65 reported cases of tropical genital ulcers (combining chancroid, LGV and donovanosis) in GUM clinics in England in 1998, with a steady decline since 1995 [2]. Since 2003, however, there have been a series of LGV outbreaks reported in several European cities, starting in The Netherlands, and occurring mostly among HIVpositive men who have sex with men (MSM) [3]. As a result, an international surveillance alert was launched in October 2004, including in the UK [4]. By January 2005, a total of 24 confirmed cases have been reported in the UK, with the first case retrospectively identified in January 2004 [5]. Following enhanced active surveillance and retrospective analysis of cases, more than 290 cases have been confirmed by December 2005, with exponential increases noted from June 2005. The majority of cases have been diagnosed in GUM clinics in London (72%), and Brighton (14%), with some cases in Scotland and Wales (4%) [6,7].

A notable feature of these outbreaks was that all cases occurred among White MSM belonging to large sexual networks associated with the sex party scene, and were not obviously linked with known endemic countries. The majority of cases (>75%) were already known to be HIV positive, and many patients had concomitant STIs (e.g. gonorrhoea) or infection with hepatitis C virus (HCV). Molecular epidemiological studies have identified L2 as the main serovar causing the current outbreaks in Europe and North America. The L2b strain has been identified as a dominant strain [8], although it appears through retrospective testing of archived samples that L2b type has been present as early as the 1980s in San Francisco [9]. Prior to 2003, most cases in industrialised settings tend to be imported via travelers, sailors or soldiers, as in the case of the USA during the wars in Korea or Vietnam [10]. By contrast, LGV is endemic in several tropical areas, including East, West and Southern Africa [11-14], Madagascar [15], India [16], South-East Asia [17], Papua New Guinea and some Caribbean islands [18]. A large epidemic has been reported recently among crack cocaine users in the Bahamas [19]. The proportion of genital ulcers that can be attributed to LGV in such settings varies between less than 1% to around 10%. The lack of specific diagnostic tools for LGV and the relatively poor degree of clinical suspicion for this condition even in endemic countries [12-14] may have biased these estimates. Since the development of the HIV epidemic in Africa, the epidemiology of aetiologies of genital ulcers has been changing. In general the prevalence of chancroid has decreased from 40-50% 10 years ago to 15% or less now, while HSV-2 has risen from 5-10% to 40% in the same period [20-23]. The prevalence of LGV however has remained stable and has not exceeded 5% of GUD, although a study from Durban based on nucleic acid detection techniques reported a rising prevalence of LGV from 2% to 10% over a 10-year period [24]. Clinical features The clinical course of LGV is classically divided into three stages. PRIMARY LESION The incubation period is extremely variable (range 3-30 days) from time of sexual contact with an infected individual; the primary lesion is transient and often imperceptible, in the form of a painless papule or pustule or shallow erosion; it is found on the coronal sulcus of males and on the posterior vaginal wall, fourchette or on the vulva, and occasionally on the cervix of females. Extra-genital lesions have been reported such as in the oral cavity (tonsil) and extra-genital lymph nodes. SECONDARY LESIONS, LYMPHADENITIS, OR LYMPHADENOPATHY OR BUBO Chlamydia trachomatis serovars L1-L3 are lymphotropic. The essential pathological process is thrombolymphangitis and perilymphangitis. Thus, regional dissemination will be characterised by inflammation and swelling of lymph nodes and surrounding tissue. The most common clinical manifestation of LGV (mostly found in heterosexual men) is tender inguinal and/or femoral lymphadenopathy that is typically unilateral (two thirds of cases). It may involve one lymph node or the entire chain, which can become matted

with considerable periadenitis and bubo formation, may ulcerate and discharge pus from multiple points, creating chronic fistulae. When both inguinal and femoral lymph nodes are involved, they may be separated by the so-called groove sign, which consists of the separation of these two lymph nodes systems by the inguinal ligament; though considered pathognomonic of LGV, the groove sign only occurs in 15-20% of cases. Lymphadenopathy commonly follows the primary lesion by a period of a few days to weeks (10-30 days, rarely months). The systemic spread of Chlamydia trachomatis may be associated with fever arthritis, pneumonitis and more rarely perihepatitis (Fitz-Hugh-Curtis syndrome), as was seen in a case in Sheffield [25].

TERTIARY STAGE OR THE GENITO-ANO-RECTAL SYNDROME The vast majority of patients recover after the secondary stage without sequelae, but in a few patients the persistence or progressive spread of Chlamydia trachomatis in anogenital tissues will incite a chronic inflammatory response, and destruction of tissue in the involved areas, including: proctitis, acute proctocolitis mimicking Crohn's disease, fistulae, strictures and chronic granulomatous disfiguring condition of the vulva (esthiomene, Greek word meaning eating away). These conditions occur most frequently among women, reflecting the involvement of retroperitoneal lymphatics (rather than inguinal), and the proximity of the rectal and vaginal tissue, or among homosexual men. LONG TERM COMPLICATIONS The destruction of lymph nodes may result in lymphoedema of genitals (elephantiasis) with persistent suppuration and pyoderma. An association with rectal cancer has been reported; certainly the two conditions can be confused and a differential diagnosis may be necessary. RECENT LGV IN THE UK In the recent outbreaks occurring among MSM in Western Europe and the USA (but a similar picture might present in case of rectal exposure in women), almost all cases presented with proctitis, and symptoms included severe rectal pain, mucoid and/or haemorragic rectal discharge, tenesmus, constipation and other signs of lower gastrointestinal inflammation, which can be very intense. Some patients reported systemic symptoms such as fever and malaise. Genital ulcers and inguinal symptoms were rare. Many patients had concomitant STI including hepatitis C infection [3,5,6]. Diagnosis The diagnosis of LGV is often differential, after other causes of genital ulcerations or inguinal lymphadenopathy have been ruled out. In the case of ano-rectal syndrome, diagnosis is based on clinical suspicion (eg. combination of signs of proctocolitis, inguinal lymphadenopathy and history of genital ulcer would be highly evocative) after the exclusion of other aetiologies of rectal bleeding. Even when LGV is suspected, investigations for other

potentially co-existing sexually transmitted infections must be undertaken, in particular for syphilis. Positive diagnosis of LGV is difficult, requiring a combination of good clinical acumen and supportive investigations. LGV can be suspected on positive chlamydial serology, isolation of Chlamydia trachomatis either from the infected site or histological identification of Chlamydia in infected tissue. Traditional methods for LGV diagnosis have been reviewed elsewhere [10,26,27], but the modern techniques are now based on nucleic acid amplification tests (NAATs) [28]. A surveillance and algorithm has been developed by the Health Protection Agency (HPA, UK) [29]. For more details consult: http://www.hpa.org.uk/infections/topics_az/hiv_and_sti/LGV/lgv.htm COLLECTION OF GENITAL SPECIMENS Chlamydiae are intracellular organisms so samples must contain cellular material which can be obtained: from the ulcer base exudate or from rectal tissue; by aspiration from fluctuant lymph nodes or buboes; after topical disinfection, a 20 gauge needle should be inserted into the lymph node through healthy adjacent tissue and the pus aspirated into a syringe; saline solution may be injected and re-aspirated; bubo pus is best homogenised in tissue culture medium before inoculation [26]; rectal swabs from MSM and women exposed rectally should be collected as recommended in the HPA guidelines [7]; a urethral swab or first-catch urine sample can be used when lymphadenopathy is present and LGV is suspected as the cause. MAIN DIAGNOSTIC TECHNIQUES (i) Detection of nucleic acid (DNA) by amplification techniques (NAATs) such as the ligase chain reaction (LCR) or the polymerase chain reaction (PCR); these methods are becoming established for routine testing of urethral, cervical or urine specimens but have rarely been used in the context of LGV [25,30], until the recent outbreaks in Western Europe [5]; they are highly sensitive and specific, and have now widely become available commercially. Positive samples should be confirmed by real-time PCR for LGV specific DNA. or (ii) Culture on cycloheximide-treated McCoy cells of material from suspected LGV lesion is the most specific method, but its sensitivity is 75-85% at best, and often closer to 30-50% in the case of bubo aspirate [10]; this is in part due to the toxic effect of the pus on the culture cells; the method is labour intensive, expensive and of restricted availability.

or

(iii) Chlamydia trachomatis serology. Three types of techniques have been used: complement fixation (CF) test, the single L-type immunofluorescence test and the micro-immunofluorescence test (micro-IF), the latter one being the most accurate serologic assay. In general a four-fold rise of antibody (both IgM and IgG) in the course of suspected illness is diagnostic of active infection. Alternatively, single point titres of >1/64 [19] and >1/256 [31] have been considered positive, as only an invasive infection such as that caused by LGV could be responsible for such high titres. The test may lack sensitivity for the earlier manifestations of LGV such as ulcers [32], and a high titre in the absence of symptoms cannot confirm LGV. It is only performed in a few specialised laboratories. OTHER METHODS The original diagnostic method for LGV from the 1930s until 1970s was the Frei test which consisted of intradermal injections of purified Chlamydia trachomatis antigen obtained from culture in yolk sacs of chicken embryos. The test was reportedly positive in about 95% of bubonic LGV or late complications. Given its lack of sensitivity and specificity, the commercial manufacture of the test has been abandoned in 1974 [10]. Direct Immunofluorescence (DIF) of material from a suspected LGV lesion to demonstrate Chlamydia trachomatis elementary and inclusion bodies; this method can be sensitive but requires expertise (subjective interpretation) and is labour intensive. Enzyme immunoassay (EIA) sensitivity is lower than other methods and it is no longer recommended Histology of the lymph nodes show follicular hyperplasia and abscesses and is not specific. In a recent study of 12 anorectal biopsies from MSM with LGV, cryptitis and crypt abscesses, without distortion of crypt architecture, were the most common findings [33]. Typing to distinguish LGV strains from other chlamydial serotypes is becoming available. Investigators in Sheffield [25] and Durban [32] were able to combine several molecular diagnostic techniques, using PCR detecting the major outer membrane protein (momp-1) gene of Chlamydia trachomatis and restriction fragment length polymorphism (RFLP) analysis to perform serovar typing from the patients lymph node aspirates, or ulcers. Sequencing, which is increasingly widely available commercially, is the method now recommended by the HPA for genotyping [28]. These techniques have been applied with great success on anorectal swabs collected from patients with proctitis during the recent LGV outbreaks in Western Europe. All these patients have been confirmed to have L2 serovar [5]. Management General Advice (1) Patients should be advised to avoid unprotected sexual intercourse until they and their partners(s) have completed treatment and follow-up.

(2) Patients should be given a detailed explanation of their condition with particular emphasis on the long-term implications for the health of themselves and their partners(s). This should be reinforced by giving them clear and accurate written information. Further investigations Screening for other possible causes of genital ulcerative disease should be arranged, i.e. diagnosis of Haemophilus ducreyi, Treponema pallidum, Herpes simplex and Klebsiella/Calymmatobacterium granulomatis (see BASHH guidelines on chancroid, syphilis, genital herpes and donovanosis, respectively). Many cases of the recent LGV outbreaks in Europe were associated with HIV and hepatitis C infection and other STIs (eg. Gonorrhoea), and screening for these infections (and possibly also for syphilis) is therefore strongly encouraged, after appropriate counseling. Lymph node biopsy may be used to make differential diagnoses with atypical infections and neoplasia. Treatment No controlled double-blind treatment trials have been published on LGV. The low incidence of the disease, its complex presentation and its natural history, marked by spontaneous remissions and exacerbations, have precluded any rigorous evaluation of management. Only one single comparative trial published in 1957, had demonstrated that the duration of buboes in patients receiving tetracycline, sulfadiazine or chloramphenicol was significantly shorter than in symptomatically treated patients [34]. Subsequent observations have reported the successful use of tetracycline, minocycline, rifampicin [35,36]. Early treatment is important to reduce the chronic phase. Prolonged treatment (at least 3 weeks) is the norm and more than one course of therapy, alternating some of the above antibiotics may be necessary for chronic cases [18,37]. On the basis of the known response of Chlamydia trachomatis to antibiotics such as doxycycline, tetracycline, erythromycin in uncomplicated infections, the following recommendations have been made (summarised in Table 1): Recommended Regimens 1st choice: Doxycycline 100mg twice daily orally for 21 days (or tetracycline 2g daily or minocycline 300mg loading dose followed by 200mg twice daily) (level of evidence III or IV, grading B) [10,18,34,37,38]. 2nd choice: Erythromycin 500mg four times daily orally for 21 days (IV, B) [18,38,39]. Alternative Regimens The activity of azithromycin against Chlamydia trachomatis suggests that it may be effective in multiple doses over 2-3 weeks but clinical data on its use are lacking.

These treatment regimens are identical to those of CDC guidelines 2002 [31]. The Sheffield case was treated with a 3-week course of minocycline [25]. Cases during the recent LGV outbreaks were successfully treated with standard 3-week courses of doxycycline [5,6] and in some instances with azithromycin 1.0 g as a single dose [40] (level of evidence IV, grading C). Clearly, the current outbreaks afford the opportunity to conduct randomized comparative trials of newer/shorter drug regimens. Special mention should be made of the treatment of non-LGV Chlamydia strains found on rectal samples, sometimes among asymptomatic patients. There are currently no specific guidelines for the management of such patients. Discussions held at the recent BASHH meeting among GUM physicians in the UK [BASHH Spring Meeting, Nottingham, 17-19 May 2006] suggested that prolonged treatment with doxycycline could be provided. Allergy Patients allergic to tetracyclines should be treated with the erythromycin regimen. Treatment for pregnant or lactating mothers Pregnant and lactating women should be treated with the erythromycin regimen. Accompanying measures Fluctuant buboes should be aspirated through healthy adjacent skin and surgical incision is usually contra-indicated by fear of complications. Sexual partner(s) management Persons who have had sexual contact with a patient who has LGV within the 30 days 1 before onset of the patients symptoms should be examined, tested for rectal, urethral or cervical chlamydial infection (as applicable) and treated, or receive presumptive treatment (eg. azithromycin 1.0g orally or doxycycline 100mg twice daily for 7 days have been used). Follow-up Patients should be followed clinically until signs and symptoms have resolved. This may occur within 3-6 weeks. However, there is also evidence of spontaneous remission within 8 weeks. Routine microbiological TOC will depend on locally available resources. Specific NAAT tests can be used, although their use has not yet been rigorously evaluated. The optimum time for testing is not yet known. Patients with fibrotic lesions or fistulae are beyond the stage where chemotherapy can be used and surgical repair, including reconstructive genital surgery, often must be considered.

Note: an extended period up to 6 months was proposed in the European outbreaks investigations, resulting however in little success in terms of increased number of partners traced.

Special considerations Latent LGV may be reactivated in patients with HIV infection with development of multiple abscesses [26]. HIV infected patients should be treated following the regimens previously cited. It had been suggested that prolonged therapy may be required and delay in resolution may occur. However, data from the recent LGV epidemics in Europe [5,40] and data from South Africa [24] showed that HIV-1 coinfection was not associated with a decreased response to treatment. Auditable Outcome Measures All cases of suspected LGV should be subjected to laboratory investigations. Target 100%. Sexual partners should be treated. HIV, syphilis, and HCV serological testing should be offered, as well as screening for concomitant STI (eg. gonorrhoea). Important diagnosis and surveillance guidelines and forms have been developed by the HPA and are regularly updated for the reporting of suspected or confirmed cases of LGV, and should be adhered to [29]. Intended Audience Clinicians working in Genito-Urinary Medicine clinics in UK. Applicability Suggestions for diagnostic approach made in this guideline should be tailored to local resources. DNA amplification tests and the serological tests recommended may not be available in all laboratories. Additional testing may be available from the Sexually Transmitted Bacteria Reference Laboratory. Stakeholder involvement Microbiologists, clinicians and epidemiologists at the Health Protection Agency in Colindale, London, the Regional Microbiology Laboratory, Plymouth, Devon, the HIV/STI Centre at University College London Medical School (UCLMS), and the London School of Hygiene & Tropical Medicine (LSHTM) have been consulted. The guidelines were posted for three months for general consultation on the BASHH website (www.bashh.org) before finalization by the CEG. The rare nature of this disease precluded patients consultation. Authors and Centre Philippe Mayaud, Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine. Membership of the CEG Clinical Effectiveness Group: Chairman Keith Radcliffe, Imtyaz Ahmed-Jushuf, David Daniels, Mark FitzGerald, Neil Lazaro, Guy Rooney.

Conflict of interest None. Evidence Base The previous guidelines (1998, 2000) were largely based on the published CDC Guidelines for Treatment of Sexually Transmitted Diseases of 1993 and 1997, and on a Medline search spanning the years 1966-2000. The review has been updated by searching Medline from 2000-2005 using the search terms: Lymphogranuloma venereum; Chlamydia trachomatis diagnosis; and Chlamydia trachomatis treatment. The most recent CDC guidelines (2002) have also been consulted. There were no entries in the Cochrane Library of any randomized clinical trials on lymphogranuloma venereum. In addition, abstracts and proceedings from the International Conferences on AIDS, Symposia on Human Chlamydial Infections, Meetings of the International Society for STD Research (ISSTDR), including the most recent meeting held in Amsterdam (July 2005), or the BASHH Spring Meeting held in Nottingham, May 2006, were reviewed.

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16. Ray K, Latha R, Sachdeva KG, et al. Usefulness of immunoperoxidase for serodiagnosis of genital chlamydial infections. Indian J Med Res 1993; 97: 67-71. 17. Viravan C, Dance DA, Ariyarit C, et al. A prospective clinical and bacteriological study of inguinal buboes in Thai men. Clin Infect Dis 1996; 22 (2): 233-9. 18. Piot P, Holmes KK. Sexually transmitted diseases. In: Warren KS & Mahmoud AAF, eds. Tropical and Geographical Medicine. New York: McGraw-Hill, 2nd edition, 1990, Chapter 96, pp 894-910 19. Bauwens JE, Orlander H, Gomez MP, et al. Epidemic lymphogranuloma venereum during epidemics of crack cocaine use and HIV infection in the Bahamas. Sex Transm Dis 2002; 29: 255-8. 20. Malonza IM, Tyndall MW, Ndinya-Achola JO, et al. A randomized, double-blind, placebo-controlled trial of single-dose ciprofloxacin versus erythromycin for the treatment of chancroid in Nairobi, Kenya. J Infect Dis 1999; 180: 1886-1893. 21. O'Farrell N. Increasing prevalence of genital herpes in developing countries: implications for heterosexual HIV transmission and STI control programmes. Sex Trans Inf 1999; 75: 377-384. 22. Htun Y, Morse SA, Dangor Y, et al. Comparison of clinically directed, disease specific, and syndromic protocols for the management of genital ulcer disease in Lesotho. Sex Transm Infect 1998; 74(suppl 1): S23-S28. 23. Lai W, Chen CY, Morse SA, et al. Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa. Sex Transm Infect. 2003; 79(3):202-7. 24. Moodley P, Sturm PD, Vanmali T, Wilkinson D, Connolly C, Sturm AW. Association between HIV-1 infection, the etiology of genital ulcer disease, and response to syndromic management. Sex Transm Dis. 2003; 30(3): 241-5. 25. Kellock DJ, Barlow R, Suvarna SK, Green S, Eley A, Rogstad KE. Lymphogranuloma venereum: biopsy, serology, and molecular biology. Genitourin Med 1997; 73: 399-401. 26. Van Dyck E, Piot P. Laboratory techniques in the investigation of chancroid, lymphogranuloma venereum and donovanosis. Genitourin Med 1992; 68: 130-3. 27. Mabey D, Peeling RW. Lymphogranuloma venereum. Sex Transm Infect 2002; 78: 90-2. 28. Bacterial Special Interest Group of the British Association for Sexual Health and HIV (Bacterial SIG/BASHH) (Richens & Herring). Sexually transmitted infections screening guidelines: lymphogranuloma venereum (in preparation). 29. Health Protection Agency. Improving case ascertainment and awareness raising of Lymphogranuloma Venereum (LGV) in the United Kingdom amongst men who have sex with men. Protocol for UK LGV enhanced surveillance March 2005. (available at: http://www.hpa.org.uk/infections/topics_az/hiv_and_sti/LGV/publications/LGV_enh anced_surveillance_March_2005.pdf) 30. Hadfield TL, Lamy Y, Wear DJ. Demonstration of Chlamydia trachomatis in inguinal lymphadenitis of lymphogranuloma venereum: a light microscopy, electron microscopy and polymerase chain reaction study. Mod Pathol 1995; 8(9): 924-9. 31. Centers for Disease Control and Prevention. 2002 Sexually Transmitted Diseases Treatment Guidelines. MMWR 2002; 51(RR 6): 1-84.

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32. Sturm PD, Moodley P, Govender K, Bohlken L, Vanmali T, Sturm AW. Molecular diagnosis of lymphogranuloma venereum in patients with genital ulcer disease. J Clin Microbiol. 2005; 43(6):2973-5. 33. White JA, Soni S, Lucas SB. Twelve men with proctitis: a case series of rectal biopsies from male patients diagnosed subsequently with lymphogranuloma venereum (LGV) proctitis. Poster 17. BASHH Spring Meeting, Nottingham, 17-19 May 2006. 34. Greaves AB, Hilleman MR, Taggart SR, Bankhead AB, Feld M. Chemotherapy in bubonic lymphogranuloma venereum: a clinical and serological evaluation. Bull World Health Org 1957; 16: 277-89. 35. Sowmini CN, Gopalan KN, Rao GC. Minocycline in the treatment of lymphogranuloma venereum. J Am Vener Dis Assoc 1976; 2(4): 19-22. 36. Centers for Disease Control and Prevention. Recommendations for the prevention and management of Chlamydia trachomatis infections. MMWR 1993; 42(RR-12):1-39. 37. Toomey KE & Barnes RC. Treatment of Chlamydia trachomatis genital infection. Rev Infect Dis 1990; 12 (suppl .6): S645-55. 38. Osoba AO. Lymphogranuloma venereum. In: Holmes KK, Mardh PA, eds. International perspectives on neglected sexually transmitted diseases: impact on venereology, infertility, and maternal and infant health. Washington, DC, Hemisphere Publishing Corporation, 1983: 193-204. 39. Bowie WR. In vitro and in vivo efficacy of antimicrobials against Chlamydia trachomatis. Infection 1982; 10 (suppl 1): S46-52. 40. Nieuwenhuis RF, Ossewaarde JM, van der Meijden WI, Neumann HAM. Unusual presentation of early lymphogranuloma venereum in an HIV-1 infected patient: effective treatment with 1 g azithromycin. Sex Transm Infect 2003; 79:453-5.

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Table 1. Drugs shown to be effective in the treatment of Lymphogranuloma venereum (LGV) Route evidence** IV Osoba, 1983 [38] Piot & Holmes, 1990 [18] Toomey & Barnes, 1990 [37] O 6.5 C Cost 2 of treatment Grading of recommendation Level of Reference

Drug

Dose

Co-trimoxazole

80/400mg twice daily O 13.0 B/C IV

x 21 days

Doxycyline*

100mg twice daily

x 21 days O 18.5 C IV

Osoba, 1983 [38] Piot & Holmes, 1990 [18] Toomey & Barnes, 1990 [37]

Erythromycin*

500mg four times daily

x 21 days O 35.4 C IV

Bowie, 1982 [39] Osoba, 1983 [38] Piot & Holmes, 1990 [18] Toomey & Barnes, 1990 [37] Sowmini et al, 1976 [35] reported by Perine & Stamms, 1999 [10]

Minocycline

300mg loading dose, followed by 200mg twice daily O 6.1

x 21 days C/B III Greaves, 1957 [34]

Tetracycline hydrochloride

500mg four times daily

Costs from British National Formulary Number 50 (November 2005) * Currently recommended by CDC. ** There have been numerous randomized trials to prove the equivalent efficacies of doxycyline, erythromycine, tetracycline, minocycline, etc for the management uncomplicated Chlamydia trachomatis infections, however these are lacking for LGV; a B grade is conferred for simplicity of use for doxycycline

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x 21 days O O 188.0 C IV CDC, 2002 [31] 8.95 C IV Nieuwenhuis, 2003 [40]

Azithromycin

1.0 g STAT

1.0 g daily

x 21 days

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