Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya

• Published in: PloS one 2009-02, Vol.4 (2), p.e4364-e4364
• Main Authors: Oesterholt, Mayke J A M, Alifrangis, Michael, Sutherland, Colin J, Omar, Sabah A, Sawa, Patrick, Howitt, Christina, Gouagna, Louis C, Sauerwein, Robert W, Bousema, Teun
• Format: Article
• Language: English
• Subjects: Amodiaquine; Animals; Aquatic insects; Artemisinins - pharmacology; Artesunate; Carrier State - parasitology; Child, Preschool; Children; Chloroquine; Codons; Culicidae; Dihydrofolate reductase; Disease transmission; Drug Combinations; Drug resistance; Drug Resistance - drug effects; Erythrocytes; Evolutionary Biology/Microbial Evolution and Genomics; Folic Acid Antagonists - pharmacology; Gametocytes; Genes; Genetic aspects; Genotype; Germ Cells - cytology; Germ Cells - drug effects; Health aspects; Humans; Infant; Infections; Infectious Diseases/Epidemiology and Control of Infectious Diseases; Infectious Diseases/Protozoal Infections; Kenya; Malaria; Malaria, Falciparum - parasitology; Malaria, Falciparum - therapy; Malaria, Falciparum - transmission; Microscopy; Mosquitoes; Mutation; Mutation - genetics; Nuclear electric power generation; Nucleotide sequence; Parasite resistance; Parasitemia - parasitology; Parasites; Plasmodium falciparum; Plasmodium falciparum - cytology; Plasmodium falciparum - drug effects; Plasmodium falciparum - enzymology; Plasmodium falciparum - genetics; Population studies; Pyrimethamine; Pyrimethamine - pharmacology; Ribonucleic acid; RNA; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Sulfadoxine - pharmacology; Tetrahydrofolate dehydrogenase; Tetrahydrofolate Dehydrogenase - genetics; Tropical diseases; Vector-borne diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004364

Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites. In the present study, we determine the association between parasite mutations, submicroscopic P. falciparum gametocytemia and malaria transmission to mosquitoes. Samples from children treated with SP alone or in combination with artesunate (AS) or amodiaquine were genotyped for SNPs in the dhfr and dhps genes. Gametocytemia was determined by microscopy and Pfs25 RNA-based quantitative nucleic acid sequence-based amplification (Pfs25 QT-NASBA). Transmission was determined by membrane-feeding assays. We observed no wild type infections, 66.5% (127/191) of the infections expressed mutations at all three dhfr codons prior to treatment. The presence of all three mutations was not related to higher Pfs25 QT-NASBA gametocyte prevalence or density during follow-up, compared to double mutant infections. The proportion of infected mosquitoes or oocyst burden was also not related to the number of mutations. Addition of AS to SP reduced gametocytemia and malaria transmission during follow-up. In our study population where all infections had at least a double mutation in the dhfr gene, additional mutations were not related to increased submicroscopic gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites.