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. 2013 Dec 17;8(12):e82553.
doi: 10.1371/journal.pone.0082553. eCollection 2013.

Plasmodium Vivax Population Structure and Transmission Dynamics in Sabah Malaysia

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Free PMC article

Plasmodium Vivax Population Structure and Transmission Dynamics in Sabah Malaysia

Noor Rain Abdullah et al. PLoS One. .
Free PMC article

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Spatial distribution of P. vivax endemicity in 2010 in Malaysia.
This map was generated by Zhi Huang, Malaria Atlas Project, University of Oxford. The colour scale reflects the age-standardized P. vivax parasite rate (PvPR), which describes the estimated proportion of the general population that are infected with P. vivax at any one time, averaged over the 12 months of 2010 within the spatial limits of stable transmission . In this study, samples were collected from patients residing in all 5 of the Sabah divisions (illustrated in the square in the top left corner), but predominantly from Kota Marudu district in the Kudat Division and Kota Kinabalu district in the West Coast Division.
Figure 2
Figure 2. Population structure inferred by STRUCTURE software at K = 4.
Results presented with demarcations by district. KD  =  Kudat Division, WCD  =  West Coast Division, TD  =  Tawau Division. Each vertical bar represents an individual sample and each colour represents one of the 4 clusters (sub-populations) defined by STRUCTURE. For each sample, the predicted ancestry to each of the 4 sub-populations is represented by the colour-coded bars. K1  =  light green, K2  =  dark green, K3  =  red, K4  =  orange. Within each demarcation, samples are ordered according to their ancestral proportions from K1 to K4. Some isolates display predominant ancestry to a single sub-population (vertical lines with a single colour), and others appear to display ancestry to more than one sub-population (vertical lines split into multiple colour blocks).
Figure 3
Figure 3. Unrooted neighbour-joining trees illustrating genetic relatedness between isolates.
Tree generated with data from 92 isolates with no missing data at 6 loci. Branches are colour-coded by STRUCTURE clusters at K = 4 (see Figure 3). K1  =  light green, K2  =  dark green, K3  =  red, K4  =  orange. Black  =  samples with a maximum ancestry to any of the 4 clusters <75%. Grey  =  samples from the Sandakan or Interior Divisions (not included in the STRUCTURE analysis). KK  =  Kota Kinabalu, KM  =  Kota Marudu, KUD  =  Kudat, PG  =  Pulau Gaya, PIT  =  Pitas, PNM  =  Penampang, SDK  =  Sandakan, SPT  =  Sipitang, TRN  =  Tuaran, TWU  =  Tawau, RNA  =  Ranau. R  =  recurrent infection.
Figure 4
Figure 4. Temporal haplotype dynamics in independent samples.
Recurrent samples excluded. Dates split by yearly quarters. Note, 2010 Q3 and 2013 Q1 only comprise samples collected in September and January, respectively. Haplotypes with a minimum of 8 identical alleles at the 9 loci investigated and belonging to the same STRUCTURE sub-population (at K = 4) were grouped together as a single haplotype . Singleton haplotypes were grouped together for simple visual representation in the plot (black bars).

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