1. Moving forward in the diagnosis of infectious diseases in developing countries: a focus on malaria Forum organized by Fondation Mérieux & the Roll Back Malaria Partnership 22 June 2009 Dr Sergio Spinaci Global Malaria Programme

2. 2 | GLOBAL MALARIA PROGRAMME Estimated number of cases and deaths Approximately 250 million cases per year: 85% in Africa, 9% in South-East Asia Approximately 900 000 deaths: 91% in Africa, 85% in children under 5 years of age Source: World Malaria Report, 2008 Africa 21280188% Americas 3329% Eastern Mediterranean 83876% Europe 000% South-East Asia 213635% Western Pacific 2 440% World24788185% Cases (millions) Deaths (thousands) % deaths under 5

3. 3 | GLOBAL MALARIA PROGRAMME Laboratory-confirmed diagnosis of malaria Africa Western Pacific Eastern Mediterranean South-East Asia AmericasEurope 0 20 40 60 80 100 Malaria patients with confirmed diagnosis (%)

4. 4 | GLOBAL MALARIA PROGRAMME Health centres in sub-district District health system in Ghana... District level Sub-district level Community level District health management teams (DHMT) Sub-district health management teams (SDHMT) Community health committees District hospital supervision Health centres in sub-district CHPS zones with community support systems CHPS zones with community support systems CHPS zones with community support systems CHPS zones with community support systems... supervision patient referral supervision patient referral supervision patient referral

5. 5 | GLOBAL MALARIA PROGRAMME Trend of malaria cases compared to total OPD in Sene District, 2005–2008 Malaria cases Total OPD cases Number of malaria cases 0 20 000 40 000 60 000 2005200620072008

6. 6 | GLOBAL MALARIA PROGRAMME Trend of laboratory-confirmed malaria cases in the Sene District, 2005–2008 1484 5463 4183 0 1000 2000 3000 4000 5000 6000 2005200620072008 Number of laboratory-confirmed malaria cases

7. 7 | GLOBAL MALARIA PROGRAMME Reduction in prescription of antimalarials after RDT implementation A mean of 6-fold decrease in ALu consumption was observed (range: 2–26) in intervention facilities and 1.7-fold decrease in control health facilities Proportion of patients tested negative who were still prescribed antimalarials decreased from 67% to 7% Fever patients tested for malaria increased from 73% to 90%

8. 8 | GLOBAL MALARIA PROGRAMME Mean test positivity rates in intervention and control health facilities Routine microscopy: 41% in hospitals; 49% in health centres; 65% in dispensaries (range: 13–90%) Routine RDTs: 7% in hospitals; 10% in health centres; 9% in dispensaries (range: 6–12%) 200620072008 Malaria test positivity rate before and after RDT implementation

9. 9 | GLOBAL MALARIA PROGRAMME New development in 2007–2009 Malaria decrease due to effective control Systematic review: 24 studies conducted between 1989 and 2005 in 15 different African countries including 15 331 patients Proportion of malaria among fevers highly variable: 2% to 81% Median parasite rate = 26% Median PfPR 1985-1999 2-10 = 37% Median PfPR 2000-2007 2-10 = 17% D'Acrémont et. al. (2009). PLoS Med, 6 (1) : e252

10. 10 | GLOBAL MALARIA PROGRAMME New development in 2007–2009 Evidence of benefits of health outcomes 1887 patients studied in Zanzibar in non randommized four-centre clinical trial with weekly cross-over validation comparing RDT-aided malaria diagnosis with symptom-based clinical diagnosis (CD) RDT was associated with lower prescription rates of antimalarial treatment than CD alone, 361/1005 (36%) compared with 752/882 (85%). Prescriptions of antibiotics were higher after RDT than CD alone, i.e., 372/1005 (37%) and 235/882 (27%); re-attendance due to perceived unsuccessful clinical cure was lower after RDT 25/1005 (2.5%), than CD alone 43/882 (4.9%). Total average cost per patient was similar: US$ 2.47 and 2.37 after RDT and CD alone, respectively Msellem et. al. (2009). PLoS Med, 6 (4) : e1000070

11. 11 | GLOBAL MALARIA PROGRAMME Debate on abandoning presumptive antimalarial treatment for febrile African children Time to move to laboratory confirmed diagnosis Proportion of fevers due to malaria has become significantly lower We now have reliable RDTs (comparable to expert microscopy) Risk of false negative test is smaller than risk of patient dying due to another severe disease because of the focus on malaria Against rapid abandoning of presumptive treatment Health systems and health workers not ready for this change – Prescription of antimalarial to negative – Problematic drug supply system – No resources for treating other causes of non-malaria fevers Pre-requirements – More data on local epidemiology – Improved implementation in > 5 years – Evidence of safety of new policy D'Acrémont V et. al. (2009). PLoS Med, 6 (1) : e252English M et. al. (2009). PLoS Med, 6 (1) : e1000015

12. 12 | GLOBAL MALARIA PROGRAMME New diagnostics at different levels of the health system Reference labs Regional labs District level Sub-district level Recombinant panel TB Malaria HAT Infant HIV Dx Malaria HAT TB Community level TB Malaria HAT LAMP Malaria RDT lot testing RTD lot testing Malaria Improved RDTs LAMP iLED PCWs Specimen bank Drug resistance surveillance FIND: Foundation for innovative new diagnostics

13. 13 | GLOBAL MALARIA PROGRAMME Conclusions The quality of routine microscopy was as poor in hospitals and health centres as in dispensaries Routine RDT implementation minimized over-diagnosis and significantly reduced ALu consumption Without appropriate diagnosis the true burden of disease cannot be estimated Well-trained clinicians with adequate supportive supervision comply with RDT results and improve on practice RDTs should be used as first-line diagnostic tool for malaria in all settings and all health facility levels, including hospitals where the potential for saving lives is the greatest