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Tuberculosis is certainly the disease that has provoked the most damage (diseases and deaths) to mankind throughout history. It has caused death and disease for perhaps more than 3 million years and, as a rule, has affected the poorest strata of society
J.A. Caminero. Eur Respir J 2004, 25: 895
Amenophis IV and
Nefertiti
(Deceased TB)
1360 b. c.
Mycobacterium tuberculosis
It is probably the infectious agent that has caused the greatest number of Deaths in the History of Humanity
Today it is still considered as the 2nd Greatest Murderer, out of all single Pathogens
50 40 30 20 10 0
* *
*
Cured
Positives
Dead
TB Smear + TB Smear -
INH-PAS-SM
ANTIMYCOBACTERIAL DRUGS
1. ISONIAZID 3. PYRAZINAMIDE 5. STREPTOMYCIN 7. KANAMYCIN 9. ETHION. PROTHIONAMIDE 11. P.A.S. 13. QUINOLONES:
- OFLOXACIN - LEVOFLOX. - GATIFLOXACIN - MOXIFLOX
2. RIFAMPICIN 4. ETHAMBUTOL 6. CAPREOMYCINE 8. AMIKACIN 10. CYCLOSERINE-TERIZ. 12. THIACETAZONE 14. CLOFAZIMIDE 15. Others:
- MACROLIDES, CLAVULANATE.,
Etc
TB An INCURABLE disease ?
Consequences of MDR/XDR-TB
Poor response to standardised treatment Long duration of contagiousness
8.7 million
(8.39.0 million)
990,000*
(840,0001.1 million)
1.1 million
(1.01.2 million)
430,000
(400,000460,000)
630,000
(460,000790,000)
- Between November 2009 and December 2010, 156 consecutively diagnosed new and 68 previously treated TB - MDR-TB was found in 35.3% (95% CI 27.742.8) of new patients and 76.5% (95% CI 66.186.8) of those previously treated. - Overall, nearly one in two patients enrolled had MDR-TB.
- Extensively drug-resistant TB was reported in 15 of the 107 MDR-TB patients (14.0%, 95% CI 7.320.7).
High prevalence of childhood multi-drug resistant tuberculosis in Johannesburg, South Africa: a cross sectional study
Lee Fairlie,Natalie C Beylis, Gary Reubenson, David P Moore,and Shabir A Madhi
- DST was performed in 148 (72.5%) of the 204 children who had culture-confirmed tuberculosis.
- The prevalence of isoniazid-resistance was 14.2% (n = 21) and the prevalence of MDR-TB 8.8% (n = 13) (95%CI, 4.8-14.6%). - The prevalence of HIV co-infection was 52.1% in children with drug susceptible-TB and 53.9% in children with MDR-TB. - Ten (76.9%) of the 13 children with MDR-TB received appropriate treatment and four (30.8%) died at a median of 2.8 months (range 0.1-4.0 months) after the date of tuberculosis investigation.
TB An INCURABLE disease ?
Mono - Resistance
Dr. Selman A. Waksman
- Discovered STREPTOMYCIN in 1943 - Together with his laboratory assistant A. Schatz
Poly - Resistance
INH-PAS-SM
ExtensivelyDrug-Resistance (XDR)
CONCLUSSIONS:
1. Only ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin have been tested in randomized controlled trials for treating tuberculosis. 2. We cannot recommend ciprofloxacin in treating tuberculosis. 3. Trials of newer fluoroquinolones for treating tuberculosis are needed and are on-going. 4. No difference has been demonstrated between sparfloxacin and ofloxacin in drug-resistant tuberculosis.
- In December 2011, clinicians in Mumbai, India, described four patients with TDR-TB (3). A few weeks later, the Times of India reported another eight cases in Mumbai.
1) Migliori GB, et al. Euro Surveill. 2007 May;12(5):E070517.1 2) Velayati AA, et al. Chest. 2009 Aug;136(2):4205. 3) Udwadia ZF, et al. Clin. Infect. Dis. 2012 Feb 15;54(4):57981.
1. 2. 3. 4. 5.
Is DR TB an Incurable Epidemic ?
Not always!! With adequate Management it is curable, although the possibility of success can decrease notably
Patients with an Extensive pattern of Resistance has always existed , but with an Adequate Clinical Management and Enough Resources a good Rate of Success is Possible
2. Current Evidence
1. MDR-TB Patients (2 Meta-analysis) 2. XDR-TB Patients (1 Systematic Rev. and 1 Meta-analysis)
The MDR/XDR-TB patients of 1950-70s were those with Resistance to H+S+PAS (then there was not Rif nor Fq)
Reference
USA. Schwartz
JAMA 1962; 181:134
Drugs
Kn-Z-Eth-Cs
N Cases
64
Sm Conversion
57 %
100 %
UK. Pines
Chest 1962; 53: 163
Z-Eth-Cs-Vi-Th
12-24
39
Morocco. Chicou
RevTuberc1962;26:867
Kn-Eth-Cs-Vi-P
4-12
31
67,7 %
94,8 %
USA. Kass
Tubercle1965;46:151-80
21-37
98
Germany. Schtz
PraxisPneum1964;18:288
34
85 %
Reference
Hungary. Bszrmenyi
Tubercle 1965;46:143
Drugs
Z-Eth-Cs Kn-Z-Eth-Cs-
N Cases
31 146
Sm Conversion
51,6 %
83.5 % 92,4 % 96 %
USA. Lester
AmRevRespirDis1968;97:392-8
Poland. Zierski
Tubercle 1964;45:96
Z-Eth-Cs
3-9
65
Czechosl. Tousek
Tubercle 1967;48:27
Z-Eth-Cs
60-84
55
Spain. March
RevClinEsp1968;109:117
Z-Eth-Cs-Vi-E
6-18
33
93,4 %
2. Current Evidence
1. MDR-TB Patients (2 Meta-analysis) 2. XDR-TB Patients (1 Systematic Rev. and 1 Meta-analysis)
September 2009
- Systematic search (to December 2008) 36 met inclusion criteria, representing 31 treatment programmes from 21 Countries
62% [95% CI 5767] successful outcomes 13% [917] defaulted 11% [913] died 2% [14] were transferred out
- 34 clinical reports (mean 250 patients) met the inclusion criteria. - The proportion of patients treated successfully improved when: - Treatment duration was at least 18 months - Patients received DOT throughout treatment - Studies that combined both factors had significantly higher pooled success proportions (69%) than other studies of treatment outcomes (58%) - Individualized treatment regimens had higher treatment success (64%) than standardized regimens (54%), although the difference was not significant - Treatment approaches and study methodologies were heterogeneous across studies. - Many important variables, including patients HIV status, were inconsistently reported between studies.
- Longer treatment duration and delayed sputum smear conversion were reported in most studies among XDR-TB patients. - Median time to sputum Smear conversion ranged 41 56 days in MDR-TB patients, while it ranged 88110 days in XDR-TB cases. - The median time to Culture conversion ranged 5899 days in MDR-TB cases; it was substantially different in XDR-TB patients, ranging 60195 days.
- 13 observational studies covering 560 patients: - 43.7% (95% CI, 32.8%54.5%) favorable outcomes - 20.8% (95% CI, 14.2%27.3%) Died. - Studies in which a higher proportion of patients received a later-generation fluoroquinolone reported a higher proportion of favorable treatment outcomes (p= .012)
With each 10% increase in the proportion of patients receiving a latergeneration fluoroquinolone, there was a 4% increase in the proportion of patients with favorable outcomes.
Patients with an Extensive pattern of Resistance has always existed, but with Adequate Clinical Management and Enough Resources a good Rate of Success is Possible
M. tuberculosis Resistance
In TB, drug resistance is always the result of poor case management of drug sensitive tuberculosis cases
The first priority to fight against MDR/XDT-TB is to strengthen the NTP with a good management of
the susceptible TB
- 37 studies were included. Inappropriate treatment regimens were prescribed in 67% of studies. - The percentage of patients receiving inappropriate regimens varied between 0.4% and 100%. - In 19 studies the quality of treatment regimen reporting was low
Even for countries with unlimited resources, the time to generate a MDRTB case is less than the time required to cure it
1. To Avoid MDR-TB
4. To Avoid XDR-TB
1. To Avoid MDR-TB
4. To Avoid XDR-TB
2 HRZE / 4 HR
- Advisable Daily, at least in the Intensive Phase, but preferable along all the treatment
- EMB (or Intensive Phase) along all the treatment if Smear + at the end of the 2 month, or until knowing Susceptibility H+R
1. To Avoid MDR-TB
4. To Avoid XDR-TB
- Selection of the Best SLD Regimen according the Classification of the MDR-TB (New, never receiving previously
SLD and receiving previously SLD)
- To support in the selection of this Regimen is essential to know the possible Resistance to Fq+SLDI in MDR-TB
- Surveillance to address the best SLD Regimen - Genotype SLD in all the MDR-TB patients previous to start the SLD Regimen
Conclusions
1. MDR/XDR-TB is a global threat and a world challenge
pattern of resistance
3. The first priority to fight against MDR/XDT-TB is to strengthen