Pamela Chauvin1, Sandie Menard2, Xavier Iriart3, Sandrine E Nsango4, Majoline T Tchioffo5, Luc Abate6, Parfait H Awono-Ambéné7, Isabelle Morlais5, Antoine Berry8. 1. Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France. 2. Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, CNRS UMR5282, Université de Toulouse, Toulouse, France. 3. Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, CNRS UMR5282, Université de Toulouse, Toulouse, France. 4. Faculté de Médecine et des Sciences Pharmaceutiques, Université de Douala, Douala, Cameroon Laboratoire d'Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon. 5. Laboratoire d'Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon UMR MIVEGEC, IRD, 224-CNR, 5290-UM1-UM2, Institut de Recherche pour le Développement, Montpellier, France. 6. UMR MIVEGEC, IRD, 224-CNR, 5290-UM1-UM2, Institut de Recherche pour le Développement, Montpellier, France. 7. Laboratoire d'Entomologie Médicale, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale, Yaoundé, Cameroon. 8. Service de Parasitologie-Mycologie, CHU Toulouse, Toulouse, France Centre de Physiopathologie de Toulouse Purpan, INSERM U1043, CNRS UMR5282, Université de Toulouse, Toulouse, France berry.a@chu-toulouse.fr.
Abstract
OBJECTIVES: To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles. METHODS: pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP- group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced. RESULTS: The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP- group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant. CONCLUSIONS: Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.
OBJECTIVES: To determine, 6 years after the adoption of intermittent preventive treatment of pregnant women with sulfadoxine/pyrimethamine (IPTp-SP) in Cameroon, (i) the polymorphism and prevalence of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) gene mutations associated with sulfadoxine/pyrimethamine resistance and (ii) the consequences of sulfadoxine/pyrimethamine use in the selection of pfdhfr/pfdhps alleles. METHODS: pfdhfr and pfdhps genes from P. falciparum isolates collected in Yaoundé (Cameroon) from pregnant women with symptomatic malaria before taking IPTp-SP [SP- group (control) (n = 51)] or afterwards [SP+ group (n = 49)] were sequenced. RESULTS: The pfdhfr N51I, C59R, S108N triple mutant had a prevalence close to 100% (96/100) and no mutations at codons 50 and 164 were detected in either of the groups. The most frequent pfdhps mutation was A437G with a prevalence of 76.5% (39/51) in the SP- group, which was significantly higher in pregnant women who took sulfadoxine/pyrimethamine [95.9% (47/49)] (P = 0.012). Our study confirmed the presence of the pfdhps K540E mutation in Cameroon, but it remained rare. The prevalence of pfdhps A581G and A613S mutations had increased [5.9% (3/51) and 11.8% (6/51) in the control group, respectively] since the last studies in 2005. Surprisingly, the new pfdhps I431V mutation was detected, at a prevalence of 9.8% (5/51), and was found to be associated with other pfdhfr/pfdhps alleles to form an octuple N51I, C59R, S108N/I431V, S436A, A437G, A581G, A613S mutant. CONCLUSIONS: Significant changes were found in pfdhps polymorphism. In particular, we observed several parasites carrying eight mutations in pfdhfr/pfdhps genes, which are very susceptible to having a high level of resistance to sulfadoxine/pyrimethamine.
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