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1
MacArthur J, Stennies GM, Macheso A, Kolczac MS, Green MD, Ali D, Barat LM, Kazembe PN, Ruebush TK 2nd, 2001. Efficacy of mefloquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum infection in Machinga District, Malawi, 1998. Am J Trop Med Hyg 65 :679–684.
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2
Ronn AM, Msangeni HA, Mhina J, Wernsdorfer WH, Bygbjerg IC, 1996. High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania. Trans R Soc Trop Med Hyg 90 :179–181.
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3
Kazadi WM, Vong S, Makina BN, Mantshumba JC, Kabuya W, Kebela BI, Ngimbi NP, 2003. Assessing the efficacy of chloroquine and sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in the Democratic Republic of Congo. Trop Med Int Health 8 :868–875.
-
4
Nsimba B, Malonga DA, Mouata AM, Mouata AM, Louva K, Kiori J, Malanda M, Yocka D, Oko-Ossho J, Ebata-Mongo S, Le Bras J, 2004. Efficacy of sulfadoxine/pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria in Republic of Congo. Am J Trop Med Hyg 70 :133–138.
-
5
Kublin JG, Witzig RS, Shankar AH, Zurita JQ, Gilman RH, Guarda JA, Cortese JF, Plowe CV, 1998. Molecular assays for surveillance of antifolate-resistant malaria. Lancet 351 :1629–1630.
-
6
Talisuna AO, Nalunkuma-Kazibwe A, Langi P, Mutabingwa TK, Watkins WW, Van Marck E, Egwang TG, D’Alessandro U, 2004. Two mutations in dihydrofolate reductase combined with one in the dihydropteroate synthase gene predict sulphadoxine-pyrimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria. Infect Genet Evol 4 :321–327.
-
7
Nagesha HS, Din S, Casey GJ, Susanti AI, Fryauff DJ, Reeder JC, Cowman AF, 2001. Mutations in the pfmdr1, dhfr and dhps genes of Plasmodium falciparum are associated with in-vivo drug resistance in West Papua, Indonesia. Trans R Soc Trop Med Hyg 95 :43–49.
-
8
Curtis J, Duraisingh MT, Warhurst DC, 1998. In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment. J Infect Dis 177 :1429–1433.
-
9
Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RA, Rogerson SJ, Lescano AG, Molyneux ME, Winstanley PA, Chimpeni P, Taylor TE, Plowe CV, 2002. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis 185 :380–388.
-
10
Plowe CV, Cortese JF, Djimde A, Nwanyanwu 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.
-
11
Plowe CV, Djimde A, Bouare M, Doumbo O, 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.
-
12
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.
-
13
Terlouw DJ, Nahlen BL, Courval JM, Kariuki SK, Rosenberg OS, Oloo AJ, Kolczak MS, Hawley WA, Lal AA, Kuile FO, 2003. Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing. Antimicrob Agents Chemother 47 :2929–2932.
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14
Basco LK, 2003. Molecular epidemiology of malaria in Cameroon. XVI. Longitudinal surveillance of in vitro pyrimethamine resistance in Plasmodium falciparum. Am J Trop Med Hyg 69 :174–178.
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15
Nzila AM, Mberu EK, Sulo J, Dayo H, Winstanley PA, Sibley CH, Watkins WM, 2000. Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother 44 :991–996.
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16
Alifrangis M, Enosse S, Khalil IF, Tarimo DS, Lemnge MM, Thompson R, Bygbjerg IC, Ronn AM, 2003. Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg 69 :601–606.
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17
World Health Organization. Position of WHO’s Roll Back Malaria Department on Malaria Treatment Policy. Geneva: World Health Organization, Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg 69: 2003.
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18
Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, Babigumira J, Kigozi I, Kiguli J, Kyomuhendo J, Ferradini L, Taylor W, Checchi F, Guthmann JP, 2005. Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365 :1467–1473.
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19
Olliaro P, Nevill C, LeBras J, Ringwald P, Mussano P, Garner P, Brasseur P, 1996. Systematic review of amodiaquine treatment in uncomplicated malaria. Lancet 348 :1196–1201.
| Past two years | Past Year | Past 30 Days | |
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| Abstract Views | 16 | 16 | 6 |
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MOLECULAR MARKERS ASSOCIATED WITH PLASMODIUM FALCIPARUM RESISTANCE TO SULFADOXINE-PYRIMETHAMINE IN THE DEMOCRATIC REPUBLIC OF CONGO
SANDRA COHUET
SANDRA COHUET
Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
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MARYLINE BONNET
MARYLINE BONNET
Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
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MICHEL VAN HERP
MICHEL VAN HERP
Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
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CHANTAL VAN OVERMEIR
CHANTAL VAN OVERMEIR
Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
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UMBERTO D’ALESSANDRO
UMBERTO D’ALESSANDRO
Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
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JEAN-PAUL GUTHMANN
JEAN-PAUL GUTHMANN
Epicentre, Paris, France; Médecins Sans Frontières, Brussels, Belgium; Prince Leopold Institute of Tropical Medicine, Antwerp, Belgium
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Sulfadoxine-pyrimethamine (SP) is the first line antimalarial treatment in the Democratic Republic of Congo. Using polymerase chain reaction, we assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulfadoxine, respectively. Four hundred seventy-four patients were sampled in Kilwa (N = 138), Kisangani (N = 112), Boende (N = 106), and Basankusu (N = 118). The proportion of triple mutations dhfr varied between sites but was always > 50%. The proportion of dhps double mutations was < 20%, with some sites as low as 0.9%. A quintuple mutation was present in 12.8% (16/125) samples in Kilwa; 11.9% (13/109) in Kisangani, 2.9% (3/102) in Boende, and 0.9% (1/112) in Basankusu. These results suggest high resistance to pyrimethamine alone or combined with sulfadoxine. Adding artesunate to SP does not seem a valid alternative to the current monotherapy.
Author Notes
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-
1
MacArthur J, Stennies GM, Macheso A, Kolczac MS, Green MD, Ali D, Barat LM, Kazembe PN, Ruebush TK 2nd, 2001. Efficacy of mefloquine and sulfadoxine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum infection in Machinga District, Malawi, 1998. Am J Trop Med Hyg 65 :679–684.
-
2
Ronn AM, Msangeni HA, Mhina J, Wernsdorfer WH, Bygbjerg IC, 1996. High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania. Trans R Soc Trop Med Hyg 90 :179–181.
-
3
Kazadi WM, Vong S, Makina BN, Mantshumba JC, Kabuya W, Kebela BI, Ngimbi NP, 2003. Assessing the efficacy of chloroquine and sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in the Democratic Republic of Congo. Trop Med Int Health 8 :868–875.
-
4
Nsimba B, Malonga DA, Mouata AM, Mouata AM, Louva K, Kiori J, Malanda M, Yocka D, Oko-Ossho J, Ebata-Mongo S, Le Bras J, 2004. Efficacy of sulfadoxine/pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria in Republic of Congo. Am J Trop Med Hyg 70 :133–138.
-
5
Kublin JG, Witzig RS, Shankar AH, Zurita JQ, Gilman RH, Guarda JA, Cortese JF, Plowe CV, 1998. Molecular assays for surveillance of antifolate-resistant malaria. Lancet 351 :1629–1630.
-
6
Talisuna AO, Nalunkuma-Kazibwe A, Langi P, Mutabingwa TK, Watkins WW, Van Marck E, Egwang TG, D’Alessandro U, 2004. Two mutations in dihydrofolate reductase combined with one in the dihydropteroate synthase gene predict sulphadoxine-pyrimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria. Infect Genet Evol 4 :321–327.
-
7
Nagesha HS, Din S, Casey GJ, Susanti AI, Fryauff DJ, Reeder JC, Cowman AF, 2001. Mutations in the pfmdr1, dhfr and dhps genes of Plasmodium falciparum are associated with in-vivo drug resistance in West Papua, Indonesia. Trans R Soc Trop Med Hyg 95 :43–49.
-
8
Curtis J, Duraisingh MT, Warhurst DC, 1998. In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment. J Infect Dis 177 :1429–1433.
-
9
Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RA, Rogerson SJ, Lescano AG, Molyneux ME, Winstanley PA, Chimpeni P, Taylor TE, Plowe CV, 2002. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis 185 :380–388.
-
10
Plowe CV, Cortese JF, Djimde A, Nwanyanwu 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.
-
11
Plowe CV, Djimde A, Bouare M, Doumbo O, 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.
-
12
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.
-
13
Terlouw DJ, Nahlen BL, Courval JM, Kariuki SK, Rosenberg OS, Oloo AJ, Kolczak MS, Hawley WA, Lal AA, Kuile FO, 2003. Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing. Antimicrob Agents Chemother 47 :2929–2932.
-
14
Basco LK, 2003. Molecular epidemiology of malaria in Cameroon. XVI. Longitudinal surveillance of in vitro pyrimethamine resistance in Plasmodium falciparum. Am J Trop Med Hyg 69 :174–178.
-
15
Nzila AM, Mberu EK, Sulo J, Dayo H, Winstanley PA, Sibley CH, Watkins WM, 2000. Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother 44 :991–996.
-
16
Alifrangis M, Enosse S, Khalil IF, Tarimo DS, Lemnge MM, Thompson R, Bygbjerg IC, Ronn AM, 2003. Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg 69 :601–606.
-
17
World Health Organization. Position of WHO’s Roll Back Malaria Department on Malaria Treatment Policy. Geneva: World Health Organization, Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg 69: 2003.
-
18
Piola P, Fogg C, Bajunirwe F, Biraro S, Grandesso F, Ruzagira E, Babigumira J, Kigozi I, Kiguli J, Kyomuhendo J, Ferradini L, Taylor W, Checchi F, Guthmann JP, 2005. Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial. Lancet 365 :1467–1473.
-
19
Olliaro P, Nevill C, LeBras J, Ringwald P, Mussano P, Garner P, Brasseur P, 1996. Systematic review of amodiaquine treatment in uncomplicated malaria. Lancet 348 :1196–1201.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 16 | 16 | 6 |
| Full Text Views | 251 | 92 | 1 |
| PDF Downloads | 47 | 23 | 0 |