Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow

Myo Win Htun, Nan Cho Nwe Mon, Khin Myo Aye, Chan Myae Hlaing, Myat Phone Kyaw, Irene Handayuni, Hidayat Trimarsanto, Dorina Bustos, Pascal Ringwald, Ric N. Price, Sarah Auburn, Kamala Thriemer

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    Abstract

    Background: Plasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts.

    Methods: Patients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and microsatellite diversity were assessed on samples from the patients enrolled in the clinical study and additional cross-sectional surveys undertaken in Myawaddy and Shwegyin in 2012.

    Results: A total of 85 patients were enrolled in the CQ clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy (1.2%) had an early treatment failure and two patients (2.3%) in Kawthoung presented with late treatment failures on day 28. The day 28 efficacy was 92.0% (95% CI 71.6-97.9) in Myawaddy and 98.3% (95% CI 88.7-99.8) in Kawthoung. By day 2, 92.2% (23/25) in Myawaddy and 85.0% (51/60) in Kawthoung were aparasitaemic. Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification was observed in 3.2% (1/31) of isolates in Myawaddy, 0% (0/49) in Kawthoung and 2.5% (1/40) in Shwegyin. Diversity was high in all sites (H E 0.855-0.876), with low inter-population differentiation (F ST 0.016-0.026, P < 0.05).

    Conclusions: Treatment failures after chloroquine were observed following chloroquine monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin. The results emphasize the importance of ongoing P. vivax drug resistance surveillance in Myanmar, particularly given the potential connectivity between parasite population at different sites.

    Original languageEnglish
    Article number281
    Pages (from-to)1-13
    Number of pages13
    JournalMalaria Journal
    Volume16
    DOIs
    Publication statusPublished - 10 Jul 2017

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    Myanmar
    Plasmodium vivax
    Gene Flow
    Chloroquine
    Parasites
    Treatment Failure
    Population
    Vivax Malaria
    Drug Resistance
    Microsatellite Repeats
    Public Health
    Cross-Sectional Studies
    Infection
    Clinical Studies

    Cite this

    Htun, Myo Win ; Mon, Nan Cho Nwe ; Aye, Khin Myo ; Hlaing, Chan Myae ; Kyaw, Myat Phone ; Handayuni, Irene ; Trimarsanto, Hidayat ; Bustos, Dorina ; Ringwald, Pascal ; Price, Ric N. ; Auburn, Sarah ; Thriemer, Kamala. / Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow. In: Malaria Journal. 2017 ; Vol. 16. pp. 1-13.
    @article{8a12007a75de4732a9682f744a805e4d,
    title = "Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow",
    abstract = "Background: Plasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts. Methods: Patients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and microsatellite diversity were assessed on samples from the patients enrolled in the clinical study and additional cross-sectional surveys undertaken in Myawaddy and Shwegyin in 2012. Results: A total of 85 patients were enrolled in the CQ clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy (1.2{\%}) had an early treatment failure and two patients (2.3{\%}) in Kawthoung presented with late treatment failures on day 28. The day 28 efficacy was 92.0{\%} (95{\%} CI 71.6-97.9) in Myawaddy and 98.3{\%} (95{\%} CI 88.7-99.8) in Kawthoung. By day 2, 92.2{\%} (23/25) in Myawaddy and 85.0{\%} (51/60) in Kawthoung were aparasitaemic. Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification was observed in 3.2{\%} (1/31) of isolates in Myawaddy, 0{\%} (0/49) in Kawthoung and 2.5{\%} (1/40) in Shwegyin. Diversity was high in all sites (H E 0.855-0.876), with low inter-population differentiation (F ST 0.016-0.026, P < 0.05). Conclusions: Treatment failures after chloroquine were observed following chloroquine monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin. The results emphasize the importance of ongoing P. vivax drug resistance surveillance in Myanmar, particularly given the potential connectivity between parasite population at different sites.",
    keywords = "Chloroquine, Copy number, Diversity, Efficacy, Genotyping, Malaria, Myanmar, Plasmodium, pvmdr1, Resistance, Transmission, Vivax",
    author = "Htun, {Myo Win} and Mon, {Nan Cho Nwe} and Aye, {Khin Myo} and Hlaing, {Chan Myae} and Kyaw, {Myat Phone} and Irene Handayuni and Hidayat Trimarsanto and Dorina Bustos and Pascal Ringwald and Price, {Ric N.} and Sarah Auburn and Kamala Thriemer",
    year = "2017",
    month = "7",
    day = "10",
    doi = "10.1186/s12936-017-1912-y",
    language = "English",
    volume = "16",
    pages = "1--13",
    journal = "Malaria Journal",
    issn = "1475-2875",
    publisher = "BioMed Central",

    }

    Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow. / Htun, Myo Win; Mon, Nan Cho Nwe; Aye, Khin Myo; Hlaing, Chan Myae; Kyaw, Myat Phone; Handayuni, Irene; Trimarsanto, Hidayat; Bustos, Dorina; Ringwald, Pascal; Price, Ric N.; Auburn, Sarah; Thriemer, Kamala.

    In: Malaria Journal, Vol. 16, 281, 10.07.2017, p. 1-13.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Chloroquine efficacy for Plasmodium vivax in Myanmar in populations with high genetic diversity and moderate parasite gene flow

    AU - Htun, Myo Win

    AU - Mon, Nan Cho Nwe

    AU - Aye, Khin Myo

    AU - Hlaing, Chan Myae

    AU - Kyaw, Myat Phone

    AU - Handayuni, Irene

    AU - Trimarsanto, Hidayat

    AU - Bustos, Dorina

    AU - Ringwald, Pascal

    AU - Price, Ric N.

    AU - Auburn, Sarah

    AU - Thriemer, Kamala

    PY - 2017/7/10

    Y1 - 2017/7/10

    N2 - Background: Plasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts. Methods: Patients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and microsatellite diversity were assessed on samples from the patients enrolled in the clinical study and additional cross-sectional surveys undertaken in Myawaddy and Shwegyin in 2012. Results: A total of 85 patients were enrolled in the CQ clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy (1.2%) had an early treatment failure and two patients (2.3%) in Kawthoung presented with late treatment failures on day 28. The day 28 efficacy was 92.0% (95% CI 71.6-97.9) in Myawaddy and 98.3% (95% CI 88.7-99.8) in Kawthoung. By day 2, 92.2% (23/25) in Myawaddy and 85.0% (51/60) in Kawthoung were aparasitaemic. Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification was observed in 3.2% (1/31) of isolates in Myawaddy, 0% (0/49) in Kawthoung and 2.5% (1/40) in Shwegyin. Diversity was high in all sites (H E 0.855-0.876), with low inter-population differentiation (F ST 0.016-0.026, P < 0.05). Conclusions: Treatment failures after chloroquine were observed following chloroquine monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin. The results emphasize the importance of ongoing P. vivax drug resistance surveillance in Myanmar, particularly given the potential connectivity between parasite population at different sites.

    AB - Background: Plasmodium vivax malaria remains a major public health burden in Myanmar. Resistance to chloroquine (CQ), the first-line treatment for P. vivax, has been reported in the country and has potential to undermine local control efforts. Methods: Patients over 6 years of age with uncomplicated P. vivax mono-infection were enrolled into clinical efficacy studies in Myawaddy in 2014 and Kawthoung in 2012. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. Pvmdr1 copy number (CN) and microsatellite diversity were assessed on samples from the patients enrolled in the clinical study and additional cross-sectional surveys undertaken in Myawaddy and Shwegyin in 2012. Results: A total of 85 patients were enrolled in the CQ clinical studies, 25 in Myawaddy and 60 in Kawthoung. One patient in Myawaddy (1.2%) had an early treatment failure and two patients (2.3%) in Kawthoung presented with late treatment failures on day 28. The day 28 efficacy was 92.0% (95% CI 71.6-97.9) in Myawaddy and 98.3% (95% CI 88.7-99.8) in Kawthoung. By day 2, 92.2% (23/25) in Myawaddy and 85.0% (51/60) in Kawthoung were aparasitaemic. Genotyping and pvmdr1 CN assessment was undertaken on 43, 52 and 46 clinical isolates from Myawaddy, Kawthoung and Shwegyin respectively. Pvmdr1 amplification was observed in 3.2% (1/31) of isolates in Myawaddy, 0% (0/49) in Kawthoung and 2.5% (1/40) in Shwegyin. Diversity was high in all sites (H E 0.855-0.876), with low inter-population differentiation (F ST 0.016-0.026, P < 0.05). Conclusions: Treatment failures after chloroquine were observed following chloroquine monotherapy, with pvmdr1 amplification present in both Myawaddy and Shwegyin. The results emphasize the importance of ongoing P. vivax drug resistance surveillance in Myanmar, particularly given the potential connectivity between parasite population at different sites.

    KW - Chloroquine

    KW - Copy number

    KW - Diversity

    KW - Efficacy

    KW - Genotyping

    KW - Malaria

    KW - Myanmar

    KW - Plasmodium

    KW - pvmdr1

    KW - Resistance

    KW - Transmission

    KW - Vivax

    UR - http://www.scopus.com/inward/record.url?scp=85022181729&partnerID=8YFLogxK

    U2 - 10.1186/s12936-017-1912-y

    DO - 10.1186/s12936-017-1912-y

    M3 - Article

    VL - 16

    SP - 1

    EP - 13

    JO - Malaria Journal

    JF - Malaria Journal

    SN - 1475-2875

    M1 - 281

    ER -