Operational research to Policy and Practice: examples Anthony D Harries, The Union, Paris, France London School Hygiene & Tropical medicine

MALAWI 16 Million people GNP $380 1 Million PLHIV 20,000 TB cases per yr Life expectancy 59 years World Health Statistics 2014

Malawi TB Control Programme Nationwide coverage of “DOTS” by 1984 Initially very good progress Good case finding Good treatment outcomes THEN – along came HIV

Adult HIV-prevalence in Malawi Increased case numbers Increased case fatality

Notified TB cases in Malawi: %52% 67%75% HIV-prevalence rate in TB patients

Can HIV testing and cotrimoxazole preventive therapy (CPT) reduce TB treatment mortality?

Background and problem Cote d’Ivoire RCT: CPT associated with significant mortality reduction in HIV-infected TB patients (Wiktor et al, Lancet 1999) UNAIDS 2000 Provisional Recommendations Malawi Ministry of Health: CPT may not have the same efficacy in Malawi as Cote d’Ivoire because different resistance patterns and different spectrum of HIV-related illness Malawi not prepared to adopt UNAIDS Recommendations on CPT because no evidence of effectiveness and may be dangerous Strong endorsement for district operational research

Aim of district studies: Thyolo and Karonga To determine the feasibility and effectiveness of “HIV testing and CPT” in reducing case fatality in a cohort of TB patients registered under routine program conditions

Methods Patients: TB patients registered in DTO office TB treatment started - standardized regimens All patients offered HIV testing /counselling HIV-positive patients offered CPT End of Treatment Outcomes: Mortality

Analysis HIV test +CPT group: the cohort of all TB patients offered HIV testing and CPT and registered during a full 1 year period Control group: the cohort of all TB patients not offered HIV testing and CPT and registered the previous year during a full 1 year period Comparison of mortality at the end of treatment between the two groups

Results [1]: Registered cases Thyolo HIV test+CPT1061 Control925 Karonga HIV test+CPT362 Control355

Results [2]: Interventions in HIV+CPT group ThyoloKaronga Number enrolled HIV tested91%73% HIV-positive69%51% Started CPT94%96%

Results [3]: case fatality in all TB types Thyolo: HIV test+CPT 28% Control 36% p < Karonga: HIV test+CPT 29% Control 37% p < CPT safe in both districts with non-severe skin reactions at 2% and 5%

Number of TB patients that needed treatment with “HIV testing and CPT” to prevent one death = 12 in both Thyolo and Karonga “estimated cost to prevent one death = USD$100”

Conclusion and Policy In the two districts, the package of “HIV testing and CPT” given to TB patients at or shortly after registration was associated with a significant reduction in case fatality October 2002: Ministry of Health Meeting with national stakeholders – policy adopted to roll out the intervention Zachariah et al, AIDS 2003; Mwaungulu et al, Bulletin WHO 2004

HIV Testing and care in TB patients in Malawi: progress every 2 years MALAWI TB patients HIV tested26%66%84%88%93% HIV positive72%66%63%64%59% Start CPT97%98%96%94%88% Start ART<10%38% 54%81% Source: Malawi NTP

TB treatment outcomes in patients with new smear-positive PTB at national level YearTreatment SuccessDeathOther %19%10% %16%13% %13%8% %8%7% %8%4% Source: Malawi NTP

India

Screening TB patients for diabetes in India

Diabetes Mellitus increases the risk of TB by a factor of Dooley and Chaisson, Lancet Infectious Diseases, 2009 Ruslami et al, Tropical Medicine & International Health, 2010 Goldhaber-Fiebert et al, International Journal Epidemiology 2011 Some evidence that poor DM control increases TB risk (HbA 1c >7% = RR 2.56) [USA,UK, Canada, Mexico, Russia, India, Taiwan, South Korea, Indonesia] Stevenson et al, Chronic Illness 2007 Jeon and Murray, PLoS Medicine 2008

Framework for a public health approach to bi- directional screening and care for TB and diabetes Launched in August 2011

The recommendations available at:

Bi-Directional Screening and Care of TB and Diabetes Mellitus India World Diabetes Foundation Support National Stakeholders Meeting Training for implementers Implementation of screening Review of activities and data National Stakeholders Meeting

Screen TB patients for DM Is there is a known diagnosis of DM? No known diagnosis - screen first with RBG If RBG ≥ 6.1 mmol/l, screen with FBG If FBG ≥ 7.0 mmol/l, then diagnose DM and refer to DM care

Screening TB patients for DM in India IndicatorTOTAL Number of patients with TB registered and enrolled8269 Number (%) with known diagnosis of DM682 (8) Number needing to be screened with RBG7587 Number (%) actually screened with RBG7467 (98) Number with RBG >110 mg/dl and needing to be screened with FBG2838 Number (%) screened with FBG2703 (95) Number (%) with FBG ≥ 126 mg/dl (newly diagnosed with DM)402 (5) Number (%) with known and newly diagnosed DM1084 (13) Number (%) with known / newly diagnosed DM referred to DM care1033 (95) India TB-DM study group TMIH 2013: 18:

Screening TB patients for DM in India Policy decision from India RNTCP and NCD that all TB patients in India be routinely screened for DM

India TB-Diabetes Study Group

Back of the TB Treatment card used in India

Simple parameters added for routine recording in quarterly TB reports Number of TB patients registered Number of TB patients screened for DM Number of TB patients diagnosed with DM

Conclusion With the research think ahead to what you want to achieve Ensure that the research is done in close collaboration with the programme and with the decision makers Involve the decision makers at the beginning and at the end