Translating Research into Policy: Rapid Diagnostic Tests (RDTs) for Malaria in Uganda Helen Counihan Malaria Consortium June 2007

Malaria Consortium in Uganda Malaria Consortium is: An implementing agency Works mainly in partnership with National Control Programmes and at international policy level Has the Africa Regional Office and many programmes in Uganda Objective: This presentation is on work on RDTs in Uganda to demonstrate process of translating research into policy

Introduction: Malaria diagnosis There is need for accurate diagnosis with advent of artemisinin-based combination therapies (ACTs) for malaria: cost, resistance, quality of care Diagnostic methods Clinical: over-treatment, missing true diagnosis Microscopy: infrastructure, training, quality assurance, still gold standard Rapid diagnostic tests: quick, relatively easy All 3 methods have limitations, need to understand when and where to use each one

Introduction: types of Rapid Diagnostic Test (RDT) HRP2 (histidine-rich protein II) pLDH (Plasmodium lactate dehydrogenase) Strengths/weaknesses: HRP2 is very heat stable but cannot diagnose non- falciparum species and has prolonged positivity after successful treatment which can last weeks – pLDH generally less heat stable but returns to negative rapidly after treatment

RDTs in Uganda: need for research Uganda has areas of varying malaria endemicity from very high to low transmission, predominantly P. falciparum Most research on RDTs done in Asia and South America Both HRP2 and pLDH tests are available in Uganda with very little regulation

RDTs in Uganda: Communication vacuum National Malaria Control Programme (NMCP) started developing policy for RDT use in late 2006 but without using evidence from Uganda Many research studies already completed in Uganda but results do not always reach NMCP

Evidence on RDTs from Uganda: 1. Epicentre/MSF studies Mbarara 2002: 5 different RDTs, all HRP2, found Paracheck best Mbarara 2005: 4 different RDTs, 3 pLDH and 1 HRP2 (Paracheck), pLDH test (Carestart) equal in sensitivity and specificity to Paracheck but returned to negative much more rapidly

2. Uganda Malaria Surveillance Project (UMSP): Study on RDTs (2006-7) Evaluation of different diagnostic methods for malaria 1000 consecutive patients at each of 7 UMSP sites  Blood smear for expert microscopy  HRP2 RDT - Paracheck  pLDH RDT – Parabank  Blood collected on filter paper for PCR Gold standard expert microscopy corrected by PCR for P. falciparum

UMSP Study Results: PPV Microscopy and pLDH: PPV excellent for all ages at all the sites HRP2: PPV poor at lowest transmission site but pretty good at other sites Compared to other tests, HRP2 will give positive results in a few more patients who don’t have malaria

Microscopy and pLDH: NPV worsens with ↑ transmission and younger ages HRP2: NPV excellent for all ages at all the sites Compared to HRP2, microscopy and pLDH miss an increasing number of sub-patent parasitemia cases according to age and transmission intensity UMSP Study Results: NPV

3. Malaria Consortium (MC) Study - ongoing Response to question from NMCP re most suitable test for Uganda Discussed requirements with NMCP, performed a situation analysis including availability, cost, suitability and ease-of-use Assessed a HRP2 test ICT (SA) in Soroti, holoendemic area Measured sensitivity and specificity compared to microscopy Currently assessing prolonged positivity

MC Study Results Result Below 5yr (%)n=163 Above 5 yr (%)n=194 Sensitivity (true + Ve) 98 Specificity (true –Ve) PPV7850 NPV9499

What to do with this information? What does it mean? What choices need to be made? The MC became aware that NMCP needed to be informed of the research results on RDTs The MC organised a workshop with WHO with international experts, researchers and MoH Two days in Kampala, including presentations and discussions on research in Uganda and other countries Resulting in specific recommendations for Uganda as requested by NMCP

Key recommendations for Uganda 1.HRP2 based tests recommended for Uganda 2.Modify policy framework to promote parasitological-based diagnosis for >5s and appropriate management of negative results 3.Training and guidelines with job aids in place before introduction of RDTs 4.Implementation phased starting in low-to- moderate transmission areas in health posts and health centres without microscopy

Key recommendations for Uganda (cont) 5.Community sensitisation about RDTs needed 6.Initiation of community level use of RDTs piloted for feasibility, safety and acceptability 7.National Drug Authority responsible for quality assurance 8.Operational research to continue

Lessons learnt on research into policy Important to develop policies that are evidence- based Need to have good communication between researchers and policy-makers (and researcher and researcher!) NMCPs should be involved in research choices at beginning Resources big influence on policy - research on cost-effectiveness vital Once policy is set there is a need for ongoing research to ensure best quality practice