Examples of DR TB Treatment in Former Soviet Union

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