1. DB. FIND 11 2009 1 Malaria diagnosis Removing the blindfold David Bell WHO – Global Malaria Programme LSHTM April 2010

2. DB. WHO/GMP Liu Bolin

3. DB. WHO/GMP Magnitude of over-diagnosis /over-treatment Before 2000 MEDIAN PR = 36% From 2000-2005 MEDIAN PR = 19% 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 PR = 26% Courtesy of: V. D’Acremont, C. Lengeler, B. Genton, Philadelphia, November 2007

4. DB. WHO/GMP Amexo M, Tolhurst R, Barnish G, Bates I. Malaria Misdiagnosis: effects on the poor and vulnerable. Lancet 2004; 364:1896-98

5. DB. WHO/GMP The importance of distinguishing malaria from other causes of fever Admissions for ‘malaria’ in 10 hospitals in NE Tanzania. High mortality for wrongly-diagnosed fever Admissions for malaria n=17,313 Severe disease n=4670 (27%) Readable slide results n=4474 (95%) No criteria for severe disease n=12,643 (73%) 120 deaths (1%) No criteria for severe disease n=12,643 (73%) 120 deaths (1%) Expert microscopy negative n=2412 (54%) Expert microscopy negative n=2412 (54%) Dead n=142 (7%) Dead n=142 (7%) Alive n=1920 (93%) Alive n=1920 (93%) Dead n=292 (12%) Dead n=292 (12%) Alive n=2120 (88%) Alive n=2120 (88%) Expert microscopy positive n=2062 (46%) Expert microscopy positive n=2062 (46%) Reyburn H et al. BMJ 2004

6. DB. WHO/GMP Diagnostic contrasts: Malaria and other diseases ? TB: Treat if disease is confirmed ? HIV: Treat if disease is confirmed ? Influenza: Treat if disease is confirmed ? Pneumonia: Treat if disease is confirmed (signs) ? Typhus: Treat if disease is confirmed ? ……… ? Malaria: Guess, treat, and hope ….

7. DB. WHO/GMP Malaria Diagnosis, WHO, 2009 Prompt parasitological confirmation by microscopy or alternatively by RDTs is recommended in all patients suspected of malaria before treatment is started. Treatment solely on the basis of clinical suspicion should only be considered when a parasitological diagnosis is not accessible. Symptom -based Micro- scopy RDT Symptom- based Micro- scopy RDT Referral Hospitals District Hospitals Health Centers Private Clinics Aid Posts/Volunteers Private Pharmacies Households?

8. DB. WHO/GMP Conventional microscopy for malaria detection

9. DB. WHO/GMP Malaria Rapid Diagnostic Tests (RDTs)

10. DB. WHO/GMP Courtesy: Malaria Consortium Accurate malaria diagnosis can now be accessible to all.

11. DB. WHO/GMP (% of RDT use by month in 2007 - 2008) Senegal RDT implementation Courtesy Babacar Faye and Senegal MoH Large-scale RDT introduction

12. DB. WHO/GMP Weekly Malaria Lab. Tests, 2008, Kabale District: Uganda Saving costs by treating only lab confirmed case! Uganda, RDT implementation Courtesy Uganda MoH, Uganda WHO office

13. DB. WHO/GMP Scale up of RDTs and ACTs in India Millions of kits/doses Source: personal communication: NMCP India, 2008

14. DB. WHO/GMP 12 month health worker follow-up Zambia 2007-8 Zambia NMCC, Mal Consortium, WHO, FIND, URC ACT

15. DB. WHO/GMP Challenges to ensuring access to accurate RDT-based diagnosis Sensitivity 20% to 99% in published studies Stability –Recommended storage temperature often inappropriate for rural health clinic in tropics (e.g. <30 ° C) User safety –Blood safety (gloves, sharps disposal, HIV risk) Programmatic –Managing negative results (non-malaria fever patients) –Logistics –Monitoring –Treatment ignoring diagnostic results

16. DB. WHO/GMP WHO, FIND, TDR, US CDC Product Testing Rnd 1 (2008) 41 products Rnd 2 (2009) 27 products Rnd 3 (2010): 47 products

17. DB. WHO/GMP HTD CDC ULIPB RITM IPC AMI IHRDC Collection and testing site Specimen characterization IPM DMR CIDEIM IMT KEMRI EHNRI UCAD Regional lot-testing site 2006: 41 lots 2007: 81 lots 2008: 167 lots 2009: 196 lots (?15% of public sector procurement) 2010: +++ Lot Testing

18. DB. WHO/GMP Community-level monitoring of RDT quality Now: Compare routinely with microscopy (often difficult) Future: Positive Control Wells Under development by FIND, WHO, and partners Field implementation trials planned Dried antigen Water added Contents placed on RDT 1 2 3 4 5 6 7 8 9 10 Antigen concentration Antigen types Future lot-testing panels

19. DB. WHO/GMP Taking heath-worker training seriously - Zambia Zambia MoH, URC, WHO, TDR, FIND, Malaria Consortium www.wpro.who.int/sites/rdt, Suite of products: Job-aid Training manual Photographic result guide Proficiency tests

20. DB. WHO/GMP Managing fever, not malaria Febrile patient RDT / microscopy Manage in community ? review ? Antibiotics ? Other Non-malaria Anti-malarial medicine Malaria Severe symptoms Refer Not severe Anti-malarial medicine ~20%~80% Can of worms…

21. DB. WHO/GMP Procurement of RDTs Training, drugs / supplies for non-malarial fever Community education Training and supervision Monitoring accuracy in field Lot-testing and laboratory monitoring Procurement of gloves, sharps disposal containers etc Transport and storage Minimum standard for funding a diagnostic programme? Need to build programmes, not just fund procurement

22. DB. WHO/GMP Where do we go after we are successful? … a larger can of worms… Successful intervention 10 cases per month. Malaria now down from 1 st to 16 th district health priority….other disease priorities are more urgent But the mosquitoes and the people are still there… We have the tools to identify and manage malaria as a common disease We need new tools and strategies to manage malaria as a rare disease

23. DB. WHO/GMP New diagnostic strategies to achieve and maintain elimination Finding and eliminating hidden parasite reservoirs Malaria LAMP Detects 1 parasite/µL Potential for district / clinic level use Find and treat malaria ‘carriers’ Serology Screen large populations for signs of recent malaria transmission

24. DB. WHO/GMP Current maps of malaria incidence www.map.ox.ac.uk 2009 WHO 2009

25. DB. WHO/GMP Polio case numbers 1988: 350,000 1999: 7,141 2000: 2,979 2001: 483 Possible future for malaria??

26. DB. WHO/GMP Summary: Parasite-based diagnosis and ACT If no parasite-based diagnosis: –Most recipients of ACT will not have malaria –Patients with non-malarial febrile illness will receive wrong or late treatment –Malaria incidence rates will be unavailable ( Poor resource allocation, poor planning, no elimination) However, delaying ACT raises malaria mortality: –Improving access to ACT is essential, should not be delayed Diagnosis needs to catch up to treatment.

27. DB. WHO/GMP Thank you Are we victims of a history? If malaria arose for the first time today…. would we consider routinely sending children home with 3 days of anti-malarial drugs when we know they probably have another, potentially fatal, illness?