title: Subtle changes in Plasmodium falciparum infection complexity following enhanced intervention in Malawi.
abstract: With support from the Global Fund, the United States President's Malaria Initiative (PMI) and other cooperating partners, Malawi is implementing a comprehensive malaria control programme involving indoor residual spraying in targeted districts, universal coverage with insecticide-treated bed nets, use of rapid diagnostic tests to confirm the clinical diagnosis of malaria and use of the highly effective artemisinin-based combination therapy, artemether-lumefantrine (AL), as the first-line treatment for malaria. We genotyped 24 genome-wide single nucleotide polymorphisms (SNPs) in Plasmodium falciparum infections (n=316) sampled from a single location in Malawi before (2006 and 2007) and after enhanced intervention (2008 and 2012). The SNP data generated were used to examine temporal changes in the proportion of multiple-genotype infections (MIs), mean number of heterozygous SNPs within MIs, parasite genetic diversity (expected heterozygosity and genotypic richness), multilocus linkage disequilibrium and effective population size (N(e)). While the proportion of MIs, expected heterozygosity, genotypic richness, multilocus linkage disequilibrium and Ne were unchanged over time, the mean number (±standard deviation) of heterozygous SNPs within MIs decreased significantly (p=0.01) from 9(±1) in 2006 to 7(±1) in 2012. These findings indicate that the genetic diversity of P. falciparum malaria parasites in this area remains high, suggesting that only subtle gains, if any, have been made in reducing malaria transmission. Continued surveillance is required to evaluate the impact of malaria control interventions in this area and the rest of Malawi, and to better target control interventions.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Tamika J
authors.initials: TJ
authors.lastname: Sisya
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Raphael M
authors.initials: RM
authors.lastname: Kamn'gona
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Jimmy A
authors.initials: JA
authors.lastname: Vareta
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Fulakeza
authors.affiliation: Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Mavuto F J
authors.initials: MF
authors.lastname: Mukaka
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
authors.forename: Karl B
authors.initials: KB
authors.lastname: Seydel
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Miriam K
authors.initials: MK
authors.lastname: Laufer
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi; Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
authors.forename: Terrie E
authors.initials: TE
authors.lastname: Taylor
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA Liverpool, UK. Electronic address: snkhoma@mlw.medcol.mw.
authors.forename: Standwell C
authors.initials: SC
authors.lastname: Nkhoma
mesh_terms: D037621:Artemisinins; D002675:Child, Preschool; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D057148:Insecticide-Treated Bednets; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology / Q000517:prevention & control; D008295:Malawi / Q000453:epidemiology; D009032:Mosquito Control; D010963:Plasmodium falciparum / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D011156:Population Density
chemical_list: D037621:Artemisinins; C031327:artemisinin
keywords: Effective population size; Genetic differentiation; Genetic diversity; Malaria control interventions; Multiple-genotype infections; Plasmodium falciparum