Malaria--Background

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Malaria--Background

• Occurs in gt 90 countries
• 300-500 million cases a year
• 2 million deaths a year
• gt90 deaths in sub-Saharan Africa
• Most deaths in children lt5 yrs of age
• Risk factors for death often delays in accurate
  diagnosis and effective treatment

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Malaria-endemic Areas 2000
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Africa vs. Americas

• Hyperendemic
• EIRs 200
• gt90 Falciparum
• Acquired immunity
• Multidrug resistance

• Hypoendemic
• EIRs 0.5
• Vivax / Falciparum
• No immunity
• Multidrug resistance

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Drug Resistance
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• Resistance to Chloroquine - 1960

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• Resistance to Chloroquine - 1970

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• Resistance to Chloroquine - 1980

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• Resistance to Chloroquine - 2000

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• Intensification of Chloroquine
• Resistance in Africa

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• Antimalarial Resistence - 1998
• (excluding CQ)

SP
SP, Mefloquine
Mefloquine
SP, Mefloquine, Halofantrine, Quinine
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• Reports of Chloroquine Resistance
• in P.vivax

1995
1995
1991
1990
1989
1995
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Surveillance for Drug Resistance

• The Peruvian Experience

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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

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INS PNCMyOEM DISA Loreto Proyecto Vigía
NAMRID CDC
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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

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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

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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

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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

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Columbia
Equador
Loreto
Brazil
Pacific Ocean
Bolivia
Chile
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North Region1999
Data INS
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Amazon Region Iquitos - 1999
Data INS
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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

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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

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Timeline of Activities
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COMBINATION THERAPY FOR MALARIA IN PERU
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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)

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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

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Drug resistance in Thailand (sequential
monotherapy)
Cure Rate
120
Mefloquine
100
Quinine
80
SP
60
40
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Chloroquine
0
1975
1976
1978
1980
1982
1984
1986
1988
1990
1992
1994
Year
Data SMRU
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Treatment efficacy at Thai-Burmese border
Cured ()
100
80
60
40
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
1985 - 86
Year
Data SMRU
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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