title: Plasmodium vivax population structure and transmission dynamics in Sabah Malaysia.
abstract: Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A (S) >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A (S)  = 0.07 [P = 0.0076] in KM, and I A (S) = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for malaria elimination.
authors.affiliation: Herbal Medicine Research Centre, Institute for Medical Research, Kuala Lumpar, Malaysia.
authors.forename: Noor Rain
authors.initials: NR
authors.lastname: Abdullah
authors.affiliation: Infectious Diseases Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia ; Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Bridget E
authors.initials: BE
authors.lastname: Barber
authors.affiliation: Infectious Diseases Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia ; Sabah Department of Health, Kota Kinabalu, Sabah, Malaysia.
authors.forename: Timothy
authors.initials: T
authors.lastname: William
authors.affiliation: Herbal Medicine Research Centre, Institute for Medical Research, Kuala Lumpar, Malaysia.
authors.forename: Nor Azrina
authors.initials: NA
authors.lastname: Norahmad
authors.affiliation: Herbal Medicine Research Centre, Institute for Medical Research, Kuala Lumpar, Malaysia.
authors.forename: Umi Rubiah
authors.initials: UR
authors.lastname: Satsu
authors.affiliation: Herbal Medicine Research Centre, Institute for Medical Research, Kuala Lumpar, Malaysia.
authors.forename: Prem Kumar
authors.initials: PK
authors.lastname: Muniandy
authors.affiliation: Herbal Medicine Research Centre, Institute for Medical Research, Kuala Lumpar, Malaysia.
authors.forename: Zakiah
authors.initials: Z
authors.lastname: Ismail
authors.affiliation: Infectious Diseases Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia ; Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Grigg
authors.affiliation: Sabah Department of Health, Kota Kinabalu, Sabah, Malaysia.
authors.forename: Jenarun
authors.initials: J
authors.lastname: Jelip
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Piera
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Lorenz
authors.initials: L
authors.lastname: von Seidlein
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia ; Division of Medicine, Royal Darwin Hospital, Darwin, Australia.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia ; Division of Medicine, Royal Darwin Hospital, Darwin, Australia ; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Auburn
mesh_terms: D016054:DNA, Protozoan / Q000235:genetics; D019353:Endemic Diseases; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016780:Malaria, Vivax / Q000453:epidemiology / Q000235:genetics / Q000469:parasitology* / Q000635:transmission*; D008296:Malaysia / Q000453:epidemiology; D010966:Plasmodium vivax / Q000235:genetics* / Q000302:isolation & purification; D015995:Prevalence; D012008:Recurrence
chemical_list: D016054:DNA, Protozoan