title: Prevalence and genetic variants of G6PD deficiency among two Malagasy populations living in Plasmodium vivax-endemic areas.
abstract: The prevalence and variants of G6PD deficiency in the Plasmodium vivax-endemic zones of Madagascar remain unknown. The admixed African-Austronesian origins of the Malagasy population make it probable that a heterogeneous mix of genetic variants with a spectrum of clinical severity will be circulating. This would have implications for the widespread use of P. vivax radical cure therapy. Two study populations in the P. vivax-endemic western foothills region of Madagascar were selected for G6PD screening. Both the qualitative fluorescent spot test and G6PD genotyping were used to screen all participants.
  
  
  
  A total of 365 unrelated male volunteers from the Tsiroanomandidy, Mandoto, and Miandrivazo districts of Madagascar were screened and 12.9% were found to be phenotypically G6PD deficient. Full gene sequencing of 95 samples identified 16 single nucleotide polymorphisms, which were integrated into a genotyping assay. Genotyping (n = 291) found one individual diagnosed with the severe G6PD MediterraneanC563Tmutation, while the remaining G6PD deficient samples had mutations of African origin, G6PD A- and G6PD A.
  
  
  
  Deployment of P. vivax radical cure in Madagascar must be considerate of the risks presented by the observed prevalence of G6PDd prevalence. The potential morbidity associated with cumulative episodes of P. vivax clinical relapses requires a strategy for increasing access to safe radical cure. The observed dominance of African G6PDd haplotypes is surprising given the known mixed African-Austronesian origins of the Malagasy population; more widespread surveying of G6PDd epidemiology across the island would be required to characterize the distribution of G6PD haplotypes across Madagascar.
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA. rosalind.howes@bdi.ox.ac.uk.|Nuffield Department of Medicine, Oxford Big Data Institute, University of Oxford, Oxford, UK. rosalind.howes@bdi.ox.ac.uk.
authors.forename: Rosalind E
authors.initials: RE
authors.lastname: Howes
authors.affiliation: Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Ernest R
authors.initials: ER
authors.lastname: Chan
authors.affiliation: National Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.|Faculty of Science, University of Antananarivo, Antananarivo, Madagascar.
authors.forename: Tovonahary Angelo
authors.initials: TA
authors.lastname: Rakotomanga
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Schulte
authors.affiliation: Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Zikursh
authors.affiliation: National Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.|Faculty of Science, University of Antananarivo, Antananarivo, Madagascar.
authors.forename: Thierry
authors.initials: T
authors.lastname: Franchard
authors.affiliation: National Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.
authors.forename: Brune
authors.initials: B
authors.lastname: Ramiranirina
authors.affiliation: National Malaria Control Programme, Ministry of Health, Antananarivo, Madagascar.|University of Antananarivo, Antananarivo, Madagascar.
authors.forename: Arsène
authors.initials: A
authors.lastname: Ratsimbasoa
authors.affiliation: Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA. paz@case.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Zimmerman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine; D019353:Endemic Diseases; D005838:Genotype; D060005:Genotyping Techniques; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008270:Madagascar / Q000453:epidemiology; D016780:Malaria, Vivax / Q000453:epidemiology*; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D015995:Prevalence; D017422:Sequence Analysis, DNA; D055815:Young Adult
keywords: G6PDd genotypes; Glucose-6-phosphate dehydrogenase deficiency; Madagascar; Plasmodium vivax; Primaquine