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

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 - 1960

Resistance to Chloroquine - 1970

Resistance to Chloroquine - 1980

Resistance to Chloroquine - 2000

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

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

Surveillance for Drug Resistance

The Peruvian Experience

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

Malaria Cases in Peru 1944 - 2000 300000 250000 200000 150000 100000 50000 0 1944 1948 1952 1956 1960 1964 1968 1972

Year

1976 1980 1984 1988 1992 1996 2000 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 Columbia Loreto Brazil Pacific Ocean Bolivia Chile

RIII RII RI S/RI(T) Total

North Region 1999

CQ n=27(%)

6(22.2)

SP n=32(%)

0(0) 13(48.1) 0(0) 5(18.5) 0(0) 3(11.1) 26(100) 32(100) 32(100)

MQ n=14(%)

0(0) 0(0) 0(0) 14(100) 14(100) Data: INS

Data: INS

RIII RII RI S/RI(T) Total

Amazon Region Iquitos - 1999

SP n=26(%)

6(23.1) 7(26.9) 5(19.2) 8(30.8) 26(100)

MQ n=16(%)

0(0.0) 0(0.0) 0(0.0) 16(100) 41(100)

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

INS/CDC In vivo Studies 1990 Reemergence of malaria 1992 1994 1996 Various non-MOH In vivo studies 1998 2000 Policy Meeting 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)

Cure Rate %

120 100

Quinine Mefloquine

80

SP

60 40 20

Chloroquine

0 1975 1976 1978 1980 1982 1984 Year 1986 1988 1990 1992 1994 Data: SMRU

Treatment efficacy at Thai-Burmese border 100 Cured (%) 80 60 40

M 15 M 25 MAS 3 Year

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