Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia

Noor Abdullah, Bridget Barber, Timothy William, Nor Norahmad, Umi Satsu, Prem Muniandy, Zakiah Ismail, Matthew Grigg, Jenarun Jelip, Kim Piera, Lorenz Von Seidlein, Tsin Yeo, Nicholas Anstey, Ric Price, Sarah Auburn

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    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 (FST = 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 (HE = 0.583 in KM and HE = 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 (IA 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 IA 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. 
    Original languageEnglish
    Article numbere82553
    Pages (from-to)1-10
    Number of pages10
    JournalPLoS One
    Volume8
    Issue number12
    DOIs
    Publication statusPublished - 2013

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    Plasmodium vivax
    Malaysia
    Borneo
    population structure
    Recurrence
    malaria
    Population
    haplotypes
    Haplotypes
    Malaria
    Parasites
    parasites
    relapse
    disease transmission
    linkage disequilibrium
    Infectious Disease Transmission
    Linkage Disequilibrium
    Microsatellite Repeats
    microsatellite repeats
    duration

    Cite this

    Abdullah, Noor ; Barber, Bridget ; William, Timothy ; Norahmad, Nor ; Satsu, Umi ; Muniandy, Prem ; Ismail, Zakiah ; Grigg, Matthew ; Jelip, Jenarun ; Piera, Kim ; Von Seidlein, Lorenz ; Yeo, Tsin ; Anstey, Nicholas ; Price, Ric ; Auburn, Sarah. / Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia. In: PLoS One. 2013 ; Vol. 8, No. 12. pp. 1-10.
    @article{12222051c47f4d7ebc4f9207874dcc1f,
    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 (FST = 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 (HE = 0.583 in KM and HE = 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 (IA 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 IA 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. ",
    keywords = "adolescent, adult, aged, article, child, endemic disease, haplotype, human, major clinical study, Malaysia, microbial diversity, nonhuman, parasite isolation, parasite migration, parasite transmission, Plasmodium vivax, Plasmodium vivax malaria, population differentiation, population structure, prevalence, recurrent disease, relapse, short tandem repeat, DNA, Protozoan, Endemic Diseases, Genetic Variation, Genotype, Humans, Linkage Disequilibrium, Malaria, Vivax, Prevalence, Recurrence",
    author = "Noor Abdullah and Bridget Barber and Timothy William and Nor Norahmad and Umi Satsu and Prem Muniandy and Zakiah Ismail and Matthew Grigg and Jenarun Jelip and Kim Piera and {Von Seidlein}, Lorenz and Tsin Yeo and Nicholas Anstey and Ric Price and Sarah Auburn",
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    language = "English",
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    Abdullah, N, Barber, B, William, T, Norahmad, N, Satsu, U, Muniandy, P, Ismail, Z, Grigg, M, Jelip, J, Piera, K, Von Seidlein, L, Yeo, T, Anstey, N, Price, R & Auburn, S 2013, 'Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia', PLoS One, vol. 8, no. 12, e82553, pp. 1-10. https://doi.org/10.1371/journal.pone.0082553

    Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia. / Abdullah, Noor; Barber, Bridget; William, Timothy; Norahmad, Nor; Satsu, Umi; Muniandy, Prem; Ismail, Zakiah; Grigg, Matthew; Jelip, Jenarun; Piera, Kim; Von Seidlein, Lorenz; Yeo, Tsin; Anstey, Nicholas; Price, Ric; Auburn, Sarah.

    In: PLoS One, Vol. 8, No. 12, e82553, 2013, p. 1-10.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - Plasmodium vivax Population Structure and Transmission Dynamics in Sabah Malaysia

    AU - Abdullah, Noor

    AU - Barber, Bridget

    AU - William, Timothy

    AU - Norahmad, Nor

    AU - Satsu, Umi

    AU - Muniandy, Prem

    AU - Ismail, Zakiah

    AU - Grigg, Matthew

    AU - Jelip, Jenarun

    AU - Piera, Kim

    AU - Von Seidlein, Lorenz

    AU - Yeo, Tsin

    AU - Anstey, Nicholas

    AU - Price, Ric

    AU - Auburn, Sarah

    PY - 2013

    Y1 - 2013

    N2 - 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 (FST = 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 (HE = 0.583 in KM and HE = 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 (IA 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 IA 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. 

    AB - 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 (FST = 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 (HE = 0.583 in KM and HE = 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 (IA 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 IA 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. 

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