Examples of DR TB Treatment in Former Soviet Union
Dr Philipp du Cros Head of the Manson Unit, MSF UK
Overview • Global TB Cascade • Uzbekistan – Ambulatory MDR TB day 1
• Tajikistan – Pediatric TB diagnosis
Global TB Treatment Cascade (2011) 500000 450000 400000 350000 300000 250000 200000 150000
100000 50000 0 Estimated new cases
Estimated cases amongst notified cases
Notified
Start Adherent to Treatment treatment
Success
Global TB Treatment Cascade (2011) 500000 450000 400000
Loss to follow up =28% (WHO 2009 cohorts)
350000 300000 250000 200000 150000
100000 50000 0 Estimated new cases
Estimated cases amongst notified cases
Notified
Start Adherent to Treatment treatment
Success
Global TB Treatment Cascade (2011) 500000 450000 400000
Success = 48% (WHO 2009 cohorts)
350000 300000 250000 200000 150000
100000 50000 0 Estimated new cases
Estimated cases amongst notified cases
Notified
Start Adherent to Treatment treatment
Success
MDR TB and default: Philippines • Retrospective analysis: 583 MDR-TB patients (1999 to 2006) • 88 (15%) patients defaulted • Multivariate analysis adjusted for age, sex and previous TB treatment, – Greater number of treatment drugs (⩾5vs. 2–3 drugs, HR 7.2, 95%CI 3.3–16.0, P < 0.001) – decentralization reduced the risk of default (HR 0.3, 95%CI 0.2–0.7, P < 0.001).
Impact of patient and program factors on default during treatment of multidrugresistant tuberculosis M. T. Gler, L. J. Podewils, N. Munez, M. Galipot, M. I. D. Quelapio, T. E. Tupasi. INT J TUBERC LUNG DIS 16(7):955–960
• 75 studies describing interventions to support DR TB treatment • Default rates: 0.5% to 56%, pooled proportion 14.8% (95%CI 12.4–17.4)
Strategies identified to be associated with lower default rates: • • • •
Engagement of community health workers for DOT Provision of DOT throughout treatment Provision of patient education Smaller cohort sizes
Challenges of Retention • Support patient to start treatment • Ensure patient takes all treatment correctly • Ensure patient remains in care until cured
TB in Uzbekistan • TB incidence Uzbekistan 101 / 100,000 • Case detection 52% • New cases treatment success = 76% • MDR TB New cases: 23% (95% CI: 18-30%) WHO. Global tuberculosis report 2012.
DR TB enrolment 800 700
TAK TAH
600
SHU
500
NUK NKR
400
KUN
300
KEG KAR
200
HOJ
100
CHM
0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Outcomes • 1448 patients MDR TB enrolled b/w 2003 -2010 • The overall rate of success = 62%, • New patients (74%) 80%
70% 60% 50%
Success
40%
Died
30%
Failure Default
20% 10%
0% 2003
2004
2005
2006
2007
2008
2009
2010
Cross-Transmission? 87 patients MDR TB no Ofx resistance
18 developed Ofx resistance during treatment
4 infected with different strains
1 with mixed strain
13 infected with same strain
Cox et al. Emergence of Extensive Drug Resistance during Treatment for Multidrug-Resistant Tuberculosis. n engl j med 359;22 nov 27, 2008
Comprehensive TB Care • Rapid molecular diagnosis & culture for all possible TB cases (new and retreatment) • Treatment for all drug sensitive and DR TB patients (MDR, pre-XDR and XDR) • Ambulatory treatment from start of treatment • Investing in improved psychosocial support • Improving infection control
Simplified Guidelines for Comprehensive TB Care • Simplified choice of regimens • 70 9 regimens • Standard side effect protocols • Molecular diagnosis
70.0
Proportion of pts (DR, DS) started tx on ambulatory basis 64.8
60.0
66.3 60.7
% of DR started as ambulatory
50.0
48.9
40.0 36.0
30.0
29.2
20.0 17.2
10.0 3.6
0.0 2011q1
2011q2
2011q3
2011q4
2012q1
2012q2
2012q3
2012q4
Ambulatory versus Hospitalised: Interim outcomes for MDR TB patients enrolled Mar 2011- Oct 2012 Ambulatory Day 1 Deaths at 6 months 4.7% Default at 6 12.3% months Culture conversion 87.5% at 4 months
IPD 5.2% 6.8% 80.5%
Ambulatory Day 1 MDR TB Treatment • Allowed increase in enrolments • Has not improved interim outcomes – Decentralisation requires attention to retention
• For those remaining on treatment has improved culture conversion rates by 4 months
Paediatric TB in Tajikistan
Case Report II – Primary MDR TB in a Baby
9 months old girl, two month history of cough, fever, weight loss, loss of appetite
Received antibiotic treatment prior to referral to TB hospital
Nutritional status good (8 kg)
No known TB contact in household
Case Report II – Primary MDR TB in a Baby
Induced sputum after admission
Xpert MTB/Rif showed resistance to rifampicin
Started on empiric regimen with Z – Am – Lfx – Cs – Pto – PAS
Syrup formulations for Z, Lfx, Pto
Ad hoc formulation for Cs
Pediatric TB Tajikistan • • • •
Household Contact tracing Access to appropriate diagnostics Simplified guidelines – empiric treatment Age specific support
Important Vulnerable Groups • • • •
Children Prisoners HIV / TB infected Diabetics
Conclusions • Scale up of comprehensive TB care requires: – simplified comprehensive TB guidelines – decentralization and involvement of GPs. – Attention to Retention – Inclusion vulnerable groups
Conclusions • Universal access to high-quality care for all? – Urgent need for shorter, more effective and better tolerated MDR-TB regimens – Need for pediatric formulations