ABSTRACT
Use of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) during pregnancy (IPTp-SP) has become policy in much of sub-Saharan Africa but crucially depends on the efficacy of SP. We assessed the frequency of the dhfr triple mutation among Plasmodium falciparum isolates obtained from pregnant Ghanaian women in 1998, 2000, and 2006. The prevalence of the triple mutation, which confers resistance to SP, doubled from 36% to 73% during the study period (P<.001). In 2006, the prevalence was virtually identical among women of early gestation and delivering women with or without a history of IPTp-SP use, indicating that such treatment did not select for mutant parasites. Nevertheless, IPTp-SP may be outdated by drug resistance before it is fully implemented.
Subject(s)
DNA, Protozoan/genetics , Drug Resistance/genetics , Malaria, Falciparum/parasitology , Plasmodium falciparum/genetics , Pregnancy Complications, Parasitic/parasitology , Adolescent , Adult , Animals , Antimalarials/therapeutic use , Drug Combinations , Female , Gene Frequency , Ghana/epidemiology , Humans , Malaria, Falciparum/drug therapy , Middle Aged , Mutation/genetics , Pregnancy , Pregnancy Complications, Parasitic/drug therapy , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Tetrahydrofolate Dehydrogenase/genetics , Young AdultABSTRACT
BACKGROUND: Intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) has been adopted as policy by many countries in sub-Saharan Africa. However, data on the post-implementation effectiveness of this measure are scarce. METHODS: Clinical and parasitological parameters were assessed among women delivering at a district hospital in rural southern Ghana in the year 2000 when pyrimethamine chemoprophylaxis was recommended (n = 839) and in 2006 (n = 226), approximately one year after the implementation of IPTp-SP. Examinations were performed in an identical manner in 2000 and 2006 including the detection of placental Plasmodium falciparum infection by microscopy, histidine-rich protein 2, and PCR. RESULTS: In 2006, 77% of the women reported to have taken IPTp-SP at least once (26%, twice; 24%, thrice). In 2006 as compared to 2000, placental P. falciparum infection was reduced by 43-57% (P < 0.0001) and maternal anaemia by 33% (P = 0.0009), and median birth weight was 130 g higher (P = 0.02). In 2006, likewise, women who had taken > or = 1 dose of IPTp-SP revealed less infection and anaemia and their children tended to have higher birth weights as compared to women who had not used IPTp-SP. However, placental P. falciparum infection was still observed in 11% (microscopy) to 26% (PCR) of those women who had taken three doses of IPTp-SP. CONCLUSION: In southern Ghana, placental malaria and maternal anaemia have declined substantially and birth weight has increased after the implementation of IPTp-SP. Likely, these effects can further be increased by improving IPTp-SP coverage and adherence. However, the remnant prevalence of infection in women having taken three doses of IPTp-SP suggests that additional antimalarial measures are needed to prevent malaria in pregnancy in this region.
Subject(s)
Antimalarials/therapeutic use , Malaria, Falciparum/epidemiology , Placenta Diseases/epidemiology , Plasmodium falciparum/drug effects , Pregnancy Complications, Parasitic/epidemiology , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Adolescent , Adult , Anemia/epidemiology , Animals , Antimalarials/administration & dosage , Birth Weight/drug effects , Chemoprevention , Drug Administration Schedule , Drug Combinations , Female , Ghana/epidemiology , Humans , Infant, Newborn , Malaria, Falciparum/parasitology , Malaria, Falciparum/prevention & control , Middle Aged , Placenta/parasitology , Placenta Diseases/parasitology , Placenta Diseases/prevention & control , Plasmodium falciparum/classification , Plasmodium falciparum/genetics , Plasmodium falciparum/isolation & purification , Pregnancy , Pregnancy Complications, Parasitic/parasitology , Pregnancy Complications, Parasitic/prevention & control , Pyrimethamine/administration & dosage , Rural Population , Sulfadoxine/administration & dosage , Treatment OutcomeABSTRACT
Placental sequestration of Plasmodium falciparum in pregnancy may impair the usefulness of molecular markers of sulfadoxine-pyrimethamine resistance. In 300 infected, delivering women, the concordance of PCR-restriction fragment length polymorphism-derived parasite resistance alleles in matched samples from placenta and circulation was 83 to 98%. Sulfadoxine-pyrimethamine resistance typing in peripheral blood is reasonably representative of P. falciparum infecting pregnant women.
