Malaria--Background Occurs in > 90 countries 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

Malaria-endemic Areas 2000

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

Drug Resistance

Resistance to Chloroquine

Resistance to Chloroquine

Resistance to Chloroquine

Resistance to Chloroquine

Intensification of Chloroquine Resistance in Africa

Antimalarial Resistence (excluding CQ) SP, Mefloquine, Halofantrine, Quinine SP Mefloquine SP, Mefloquine

Reports of Chloroquine Resistance in P.vivax

Surveillance for Drug Resistance The Peruvian Experience

History of Malaria in Peru Incidence of Malaria – ,000 cases – ,500 cases Remaining cases confined to northwestern coastal areas with occasional reports from border regions with Ecuador, Colombia, Brazil

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

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

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

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

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

Equador Pacific Ocean Columbia Bolivia Brazil Loreto Chile

North Region 1999 Data: INS

Amazon Region Iquitos Data: INS

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

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

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

COMBINATION THERAPY FOR MALARIA IN PERU

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)

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

Drug resistance in Thailand (sequential monotherapy) Year Cure Rate % Quinine Mefloquine Chloroquine SP Data: SMRU

Year Treatment efficacy at Thai-Burmese border MAS 3 M 15 M 25 Cured (%) Data: SMRU

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