• 1

    WHO Study Group, 1995. WHO vector control for malaria and other mosquito borne diseases. World Health Organ Tech. Rep Ser :857.

  • 2

    Remme JHF, Binka F, Nabarro D, 2001. Toward a framework and indicators for monitoring role back malaria. Am J Trop Med Hyg 64 (suppl):76–84.

    • Search Google Scholar
    • Export Citation
  • 3

    White NJ, Nosten F, Looareesuwan S, Watkins WM, Marsh K, Snow RW, Kokwaro G, Ouma J, Hien TT, Molyneux ME, Taylor TE, Newbold CI, Ruebush TK II, Danis M, Greenwood BM, Anderson RM, Olliaro P, 1999. Averting a malaria disaster. Lancet 353 :1965–1967.

    • Search Google Scholar
    • Export Citation
  • 4

    Peters W, 1997. Chemotherapy and Drug resistance in Malaria. London: Academic Press.

  • 5

    Sibley CH, Hyde JE, Sims PFG, Plowe CV, Kublin JG, Mberu EK, Cowman AF, Winstanley PA, Watkins WM, Nzila AM, 2001. Pyrimethamine-sulfadoxine resistance in P. falciparum: what next? Trends Parasitol 17 :582–588.

    • Search Google Scholar
    • Export Citation
  • 6

    Plowe CV, Cortese JF, Djimde A, Nwanyanu OC, Watkins WM, Winstanley PA, Estrada-Franco JG, Mollinedo RE, Avila JC, Cespedes JL, Carter D, Doumbo OK, 1997. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 176 :1590–1596.

    • Search Google Scholar
    • Export Citation
  • 7

    Basco LK, Tahar R, Ringwald P, 1998. Molecular basis of in vivo resistance to sulfadoxine-pyrimethamine in African adult patients infected with Plasmodium falciparum parasites. Antimicrob. Agents Chemother 42 :1811–1814.

    • Search Google Scholar
    • Export Citation
  • 8

    Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RAG, Rogerson SJ, Lescano AG, Molyneux ME, Winstanley PA, Chimpeni P, Taylor TE, Plowe CV, 2002. Molecular markers for treatment failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone of falciparum malaria. J Infect Dis 185 :380–388.

    • Search Google Scholar
    • Export Citation
  • 9

    Thompson PE, Werbel LM, 1972. Chemistry and pharmacology. Medicinal Chemistry: Antimalarial Agents. New York: Academic Press.

  • 10

    Krungkrai J, Webster HK, Yothavong Y, 1989. De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. Mol Microbiol 23 :1254–1262.

    • Search Google Scholar
    • Export Citation
  • 11

    Stokstad ELR, Koch J, 1967. Folate acid metabolism. Physiol Rev 47 :83–116.

  • 12

    Russell RM, Ismail-Beigi F, Alfrasiabi K, Rahimifar, Pourkamal D, Ronaghy H, 1976. Folate levels among various populations in central Iran. Am J Clin Nutr 29 :794–798.

    • Search Google Scholar
    • Export Citation
  • 13

    White NJ, 2002. The assessment of antimalarial drug efficacy. Trends Parasitol. 18 :458–464.

  • 14

    Djimde AA, Doumbo OK, Traore O, Guindo AB, Kayentao K, Diourte Y, Niare-Doumbo S, Coulibaly D, Kone AK, Cissoko Y, Tekete M, Fofana B, Dicko A, Diallo DA, Wellems TE, Kwiatkowski D, Plowe CV, 2003. Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria. Am J Trop Med Hyg 69 :558–563.

    • Search Google Scholar
    • Export Citation
  • 15

    Kinyanjui SM, Mberu EK, Winstanley PA, Jacobus DP, Watkins WM, 1999. The antimalarial triazine WR99210 and the pro-drug PS-15: folate reversal of in vitro activity against Plasmodium falciparum and a non-antifolate mode of action of the prodrug. Am J Trop Med Hyg 60 :943–947.

    • Search Google Scholar
    • Export Citation
  • 16

    Watkins WM, Sixsmith DG, Chulay JD, Spencer HC, 1985. Antagonism of sulfadoxine and pyrimethamine antimalarial activity in vitro by p-aminobenzoic acid, p-aminobenzoylglutamic acid and folic acid. Mol Biochem Parasitol 14 :55–61.

    • Search Google Scholar
    • Export Citation
  • 17

    van Hensbroek MB, Morris-Jones S, Meisner S, Jaffar S, Bayo L, Dackour R, Phillips C, Greenwood BM, 1995. Iron, but not folic acid, combined with effective antimalarial therapy promotes haematological recovery in African children after acute falciparum malaria. Trans R Soc Trop Med Hyg 89 :672–676.

    • Search Google Scholar
    • Export Citation
  • 18

    Gail K, Herms V, 1969. Influence of pteroylglutamic acid (folic acid) on parasite density (Plasmodium falciparum) in pregnant women in West Africa. Z Trop Parasitol 20 :440–450.

    • Search Google Scholar
    • Export Citation
  • 19

    World Health Organization, 2002. Monitoring Antimalarial Resistance. Geneva: World Health organization. Report of a WHO consultation, WHO/CDS/CSR/EPH/2002.17.

  • 20

    Winstanley PA, Watkins WM, Newton CRJC, Nevill C, Mberu E, Warns PA, Waruiru CM, Mwangi IN, Warrell DA, Marsh K, 1992. The disposition of oral and intramuscular pyrimethamine/sulfadoxine in Kenyan children with high parasitaemia but clinically non-severe falciparum malaria. Br J Clin Pharmacol 33 :143–148.

    • Search Google Scholar
    • Export Citation
  • 21

    Plowe CV, Djimde A, Bouare M, Doumbo OK, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52 :565–568.

    • Search Google Scholar
    • Export Citation
  • 22

    Baird JK, Jones TR, Danudirgo EW, Annis BA, Bangs MJ, Basri H, Purnomo, Masbar S, 1991. Age-dependent acquired protection against Plasmodium falciparum in people having two years exposure to hyperendemic malaria. Am J Trop Med Hyg 45 :65–76.

    • Search Google Scholar
    • Export Citation
  • 23

    Wang P, Brobey RK, Horii T, Sims PF, Hyde JE, 1999. Utilization of exogenous folate in the human malaria parasite Plasmodium falciparum and its critical role in antifolate drug synergy. Mol Microbiol 32 :1254–1262.

    • Search Google Scholar
    • Export Citation
  • 24

    U.S. Department of Agriculture, Agricultural Research Service 1999. USDA Nutrient Database for Standard Reference, Release13. Nutrient Data Lab Home Page, http://www.nal.usda.gov/fnic/foodcomp

  • 25

    Diem K, Lentner C, eds, 1970. Scientific Tables. Seventh edition. Basel, Switzerland: Geigy Pharmaceuticals.

  • 26

    Tsui JC, Nordstrom JW, 1990. Folate status of adolescence: effects of folic acid supplementation. J Am Diet Assoc 90 :1551–1556.

  • 27

    Wang P, Wang Q, Aspinall TV, Sims PF, Hyde JE, 2004. Transfection studies to explore essential folate metabolism and antifolate drug synergy in the human malaria parasite Plasmodium faciparum. Mol Microbiol 51 :1425–1438.

    • Search Google Scholar
    • Export Citation
  • 28

    Nzila A, Mberu E, Bray P, Kokwaro G, Winstanley P, Marsh K, Ward S, 2003. Chemosensitization of Plasmodium falciparum by Probenecid in vitro. Antimicrob Agents Chemother 47 :2108–2112.

    • Search Google Scholar
    • Export Citation
  • 29

    Chanarin I, 1979. The Megaloblastic Anaemias. Oxford, United Kingdom: Blackwell Scientific Publications.

  • 30

    Gregory JF, 1997. Bio-availability of folate. Eur J Clin Nutr 51 :554–559.

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BLOOD FOLATE CONCENTRATIONS AND IN VIVO SULFADOXINE-PYRIMETHAMINE FAILURE IN MALAWIAN CHILDREN WITH UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA

FRACTION K. DZINJALAMALADivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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ALLAN MACHESODivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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JAMES G. KUBLINDivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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TERRIE E. TAYLORDivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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KAREN I. BARNESDivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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MALCOM E. MOLYNEUXDivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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CHRISTOPHER V. PLOWEDivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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PETER J. SMITHDivision of Pharmacology, University of Cape Town, Cape Town, South Africa; Ministry of Health, Lilongwe, Malawi; Department of Community Health, Malawi College of Medicine, Blantyre, Malawi; College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland

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Folate antagonizes the antimalarial action of sulfadoxine-pyrimethamine (SP) in vitro, but its role in vivo is not well understood. We measured blood folate concentrations and SP therapeutic outcomes in Malawian children. Children with late treatment failure and those with adequate clinical and parasitologic responses had similar demographic characteristics, prevalence of parasite mutations conferring resistance to SP, and blood concentrations of anti-malarial drugs following treatment. However, a higher folate concentration was associated with late treatment failure. Patients from a low malaria transmission site had higher blood folate concentrations than those in a higher transmission site (mean ± SEM = 39 ± 9.3 ng/mL versus 29 ± 10 ng/mL; P < 0.0001), and there was a higher rate of late treatment failure in the low transmission area (54.4% versus 40.2%; P = 0.010). This study also provides the first evidence of the independent role of physiologic folate concentrations in in vivo SP therapeutic efficacy, and the critical role of pyrimethamine concentrations in the therapeutic efficacy of SP when one controls physiologic folate levels and the frequency of critical dihydrofolate reductase/dihydropteroate synthase mutations.

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