title: Genetic evidence that the Makira region in northeastern Madagascar is a hotspot of malaria transmission.
abstract: BACKGROUND
  Encouraging advances in the control of Plasmodium falciparum malaria have been observed across much of Africa in the past decade. However, regions of high relative prevalence and transmission that remain unaddressed or unrecognized provide a threat to this progress. Difficulties in identifying such localized hotspots include inadequate surveillance, especially in remote regions, and the cost and labor needed to produce direct estimates of transmission. Genetic data can provide a much-needed alternative to such empirical estimates, as the pattern of genetic variation within malaria parasite populations is indicative of the level of local transmission. Here, genetic data were used to provide the first empirical estimates of P. falciparum malaria prevalence and transmission dynamics for the rural, remote Makira region of northeastern Madagascar.
  
  
  METHODS
  Longitudinal surveys of a cohort of 698 total individuals (both sexes, 0-74 years of age) were performed in two communities bordering the Makira Natural Park protected area. Rapid diagnostic tests, with confirmation by molecular methods, were used to estimate P. falciparum prevalence at three seasonal time points separated by 4-month intervals. Genomic loci in a panel of polymorphic, putatively neutral markers were genotyped for 94 P. falciparum infections and used to characterize genetic parameters known to correlate with transmission levels.
  
  
  RESULTS
  Overall, 27.8% of individuals tested positive for P. falciparum over the 10-month course of the study, a rate approximately sevenfold higher than the countrywide average for Madagascar. Among those P. falciparum infections, a high level of genotypic diversity and a high frequency of polygenomic infections (68.1%) were observed, providing a pattern consistent with high and stable transmission.
  
  
  CONCLUSIONS
  Prevalence and genetic diversity data indicate that the Makira region is a hotspot of P. falciparum transmission in Madagascar. This suggests that the area should be highlighted for future interventions and that additional areas of high transmission may be present in ecologically similar regions nearby.
authors.affiliation: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. benjaminrice@fas.harvard.edu.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Rice
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.|Harvard University Center for the Environment, Cambridge, MA, USA.|Madagascar Health and Environmental Research (MAHERY), Maroantsetra, Madagascar.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Golden
authors.affiliation: Madagascar Health and Environmental Research (MAHERY), Maroantsetra, Madagascar.
authors.forename: Evelin Jean Gasta
authors.initials: EJ
authors.lastname: Anjaranirina
authors.affiliation: Department of Pharmacy and Nutrition, Federal University of Espirito Santo, Alegre, ES, Brazil.
authors.forename: Carolina Mastella
authors.initials: CM
authors.lastname: Botelho
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Volkman
authors.affiliation: Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Hartl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018562:Disease Transmission, Infectious; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008270:Madagascar / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology* / Q000635:transmission; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D010963:Plasmodium falciparum / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D015995:Prevalence; D012424:Rural Population; D055815:Young Adult
keywords: Genetic diversity; Genetic surveillance; Madagascar; Plasmodium falciparum; Polygenomic infections