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, Halofantrine, Quinine

SP

Mefloquine

SP, Mefloquine

Reports of Chloroquine Resistance in P.vivax

19891990

1995

1995

19911995

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

0

50000

100000

150000

200000

250000

300000

1944 1948 1952 1956 1960 1964 1968 1972 1976 1980 1984 1988 1992 1996 2000

Year

# C

as

es

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 Region1999

CQn=27(%)

SPn=32(%)

MQn=14(%)

RIII 6(22.2) 0(0) 0(0)

RII 13(48.1) 0(0) 0(0)

RI 5(18.5) 0(0) 0(0)

S/RI(T) 3(11.1) 32(100) 14(100)

Total 26(100) 32(100) 14(100)

Data: INS

Amazon Region Iquitos - 1999

SPn=26(%)

MQn=16(%)

RIII 6(23.1) 0(0.0)

RII 7(26.9) 0(0.0)

RI 5(19.2) 0(0.0)

S/RI(T) 8(30.8) 16(100)

Total 26(100) 41(100)

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

Reemergenceof malaria

1990 1992 1994 1996 1998 2000

PolicyMeeting

Various non-MOHIn vivo studies

INS/CDC In vivo Studies

Baseline CTStudies

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 2nd/3rd trimesters

Drug resistance in Thailand (sequential monotherapy)

0

20

40

60

80

100

120

1975 1976 1978 1980 1982 1984 1986 1988 1990 1992 1994Year

Cure Rate %

Quinine

Mefloquine

Chloroquine

SP

Data: SMRU

40

60

80

100

1985

- 86

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

Year

Treatment efficacy at Thai-Burmese border

MAS3M15 M25

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