Plasmodium vivax Transmission Network and Population Structure through out Papua New Guinea: Implications for Malaria Control and Elimination.

Introduction: The Asia Pacific Leaders in Malaria Alliance (APLMA) have committed to eliminate malaria from the region by 2030. Although P. falciparum is prevalent, Plasmodium vivax is the most common malaria parasite in the region causing significant morbidity and mortality. Papua New Guinea (PNG) has the highest malaria burden in the Asia-Pacific region. With the intensification of control efforts since 2005, overall malaria rates have reduced however P. vivax is now dominant in some parts of country.To inform the control program, here we investigate the transmission networks and population structure of P. vivax throughout PNG. Methods: P. vivax isolates collected during a national malaria indicator survey in 2008 were selected from eight geographically distinct regions of PNG. A total of 219 P. vivax isolates (16-30 per population) were successfully genotyped using a well-validated panel of 10 microsatellites. For each population, genetic diversity was determined by calculating the expected heterozygosity (He) and allelic richness (Rs). Levels of linkage disequilibrium (IAS) and genetic differentiation (Jost’s D) were also quantified. Population structure was determined using Bayesian clustering, phylogenetic and network analyses. Results: The eight populations displayed a wide range of genetic diversity (He=0.36-0.87, 3.60-7.58) and significant linkage disequilibrium (IAS=0.16, p<0.001). Genetic differentiation between populations was variable (Jost’s D = 0.0306-0.206), and fits the isolation by distance model. P. vivax genotypes clustered into three genetically distinct populations segregating into mainland, island and highland regions. Phylogenetic and network analysis further revealed clonal clusters in the Western Province and connections between the islands and mainland via the National Capital District. Conclusion: High genetic diversity throughout most of the mainland and islands is consistent with endemic transmission, whilst there was lower diversity and evidence of clonal transmission in the Western province. Patterns of geographical population subdivision indicate that P. vivax populations circulating in PNG are isolated by distance. Populations may beconnected bymodern human movement viathe capital. These findings have implications for the design of effective strategies to control P. vivax and to prevent the spread of drug resistant parasites.