2. Malaria--Background Occurs in > 90 countries 300-500 million cases a year 2 million deaths a year –>90% deaths in sub-Saharan Africa –Most deaths in children <5 yrs of age –Risk factors for death – often delays in accurate diagnosis and effective treatment

3. Malaria-endemic Areas 2000

4. Africa vs. Americas Hyperendemic EIRs ~ 200 >90% Falciparum Acquired immunity Multidrug resistance Hypoendemic EIRs ~ 0.5 Vivax / Falciparum No immunity Multidrug resistance

5. Drug Resistance

6. Resistance to Chloroquine - 1960

7. Resistance to Chloroquine - 1970

8. Resistance to Chloroquine - 1980

9. Resistance to Chloroquine - 2000

10. Intensification of Chloroquine Resistance in Africa

11. Antimalarial Resistence - 1998 (excluding CQ) SP, Mefloquine, Halofantrine, Quinine SP Mefloquine SP, Mefloquine

12. Reports of Chloroquine Resistance in P.vivax 1989 1990 1995 1991 1995

13. Surveillance for Drug Resistance The Peruvian Experience

14. History of Malaria in Peru Incidence of Malaria –1944 - 95,000 cases –1965 - 1,500 cases Remaining cases confined to northwestern coastal areas with occasional reports from border regions with Ecuador, Colombia, Brazil

15. INS; PNCMyOEM; DISA Loreto; Proyecto Vigía; NAMRID; CDC

16. Resistance in Peru? Anectodal reports of –chloroquine (CQ) resistance in the north –CQ and sulfadoxine/pyrimethamine (SP) resistance in the Amazon Health Center “Cohorts” In vivo studies –various institutions –various protocols

17. In Vivo Capacity Building Decision to have Instituto Nacional de Salud (INS) perform In vivo studies to assess resistance in the Amazon region CDC team trained INS team in the use of WHO/PAHO In vivo protocol Study performed in Iquitos (1998) –CDC and INS together

18. In Vivo Sentinel Surveillance Inappropriate to continue using current first line therapies? Need for valid data –“Cohorts” data problematic –Available in vivo data from differing protocols –Policy makers asking for data prior to implementing changes in first line therapy

19. In Vivo Sentinel Surveillance 6 sites were chosen –3 in northern region –3 in Amazon region Standardized WHO/PAHO protocol Staffing –Health Center staff –INS –CDC

20. Equador Pacific Ocean Columbia Bolivia Brazil Loreto Chile

21. North Region 1999 Data: INS

22. Amazon Region Iquitos - 1999 Data: INS

23. Research into Policy Technical Meeting convened Aug.1999 –Attended by regional health officials and malaria control officers, MOH officials, INS scientists, Proyecto Vigia, Instituto de Medicina Tropical, CDC, NAMRD, PAHO Objective: to discuss the regional antimalarial drug resistance, present study results, discuss future directions

24. Research into Policy Technical Committee –endorsed the use of combination therapy (CT) [SP or mefloquine + artesunate] –baseline studies to ensure efficacy and safety prior to widespread implementation 2000 –2 in vivo studies occurring 1 in northern region 1 in Amazon region

25. Timeline of Activities Reemergence of malaria 19901992199419961998 2000 Policy Meeting Various non-MOH In vivo studies INS/CDC In vivo Studies Baseline CT Studies

26. COMBINATION THERAPY FOR MALARIA IN PERU

27. Combination Therapy A proposed strategy to delay antimalarial drug resistance Well established modality in TB, AIDS, Cancer Ideal drug is from the Artemisinin family combined with another (SP, MQ, AQ)

28. Combination Therapy Data from Thailand suggest that CT –Halts the progression of resistance –Decreases the transmission of malaria –No adverse side effects from artesunate/artemether –Safe for use in 2 nd /3 rd trimesters

29. Drug resistance in Thailand (sequential monotherapy) 0 20 40 60 80 100 120 19751976197819801982198419861988199019921994 Year Cure Rate % Quinine Mefloquine Chloroquine SP Data: SMRU

30. 40 60 80 100 1985 - 86 1990199119921993199419951996199719981999 Year Treatment efficacy at Thai-Burmese border MAS 3 M 15 M 25 Cured (%) Data: SMRU

31. Combination Therapy Will it work for Latin America? –Similar epidemiology –Similar vector activity –Similar species –Similar health infrastructure Peru now embarking on changing national policy to CT –Need for evaluation