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

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

0.16

1985 1990 1995 2000 2005

Adult HIV prevalence

Adult HIV-prevalence in Malawi

Increased case numbersIncreased case fatality

Notified TB cases in Malawi: 1985 - 2005

0

5000

10000

15000

20000

25000

30000

1985 1989 1993 1997 2001 2005

Sm-TBSm+PTB

26% 52% 67% 75% 75%

HIV-prevalence rate in TB patients

0

5

10

15

20

25

% deaths

86 88 90 92 94 96 98

Year

Deaths in New Sm+ve PTB patients in Malawi

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

Control 925

Karonga

HIV test+CPT 362

Control 355

Results [2]: Interventions in HIV+CPT group

Thyolo Karonga

Number enrolled 1061 362

HIV tested 91% 73%

HIV-positive 69% 51%

Started CPT 94% 96%

Results [3]: case fatality in all TB types

Thyolo:

HIV test+CPT 28%

Control 36%

p < 0.001

Karonga:

HIV test+CPT 29%

Control 37%

p < 0.001

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 = 12in 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 2004 2006 2008 2010 2012

TB patients 26136 26659 25688 22536 20463

HIV tested 26% 66% 84% 88% 93%

HIV positive 72% 66% 63% 64% 59%

Start CPT 97% 98% 96% 94% 88%

Start ART <10% 38% 38% 54% 81%

Source: Malawi NTP

TB treatment outcomes in patients with new smear-positive PTB at national level

Year Treatment Success Death Other

2002 71% 19% 10%

2004 71% 16% 13%

2006 79% 13% 8%

2008 85% 8% 7%

2010 88% 8% 4%

Source: Malawi NTP

India

Screening TB patients for diabetes in India

Diabetes Mellitus increases the risk of TB by a factor of 2 - 3

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 (HbA1c >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

http://www.who.int/tb/publications/2011/en/index.html Document 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

 Indicator TOTAL

Number of patients with TB registered and enrolled 8269

Number (%) with known diagnosis of DM 682 (8)

Number needing to be screened with RBG 7587

Number (%) actually screened with RBG 7467 (98)

Number with RBG >110 mg/dl and needing to be screened with FBG 2838

Number (%) screened with FBG 2703 (95)

Number (%) with FBG ≥ 126 mg/dl (newly diagnosed with DM) 402 (5)

Number (%) with known and newly diagnosed DM 1084 (13)

Number (%) with known / newly diagnosed DM referred to DM care 1033 (95)

India TB-DM study group TMIH 2013: 18: 636-45

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