Plasmodium falciparum artemisinin resistance monitoring in Sabah, Malaysia

In vivo therapeutic efficacy and kelch13 molecular marker surveillance

Matthew J. Grigg, Timothy William, Kim A. Piera, Giri S. Rajahram, Jenarun Jelip, Ammar Aziz, Jayaram Menon, Jutta Marfurt, Ric N. Price, Sarah Auburn, Bridget E. Barber, Tsin W. Yeo, Nicholas M. Anstey

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    Abstract

    Background: Spreading Plasmodium falciparum artemisinin drug resistance threatens global malaria public health gains. Limited data exist to define the extent of P. falciparum artemisinin resistance southeast of the Greater Mekong region in Malaysia.

    Methods: A clinical efficacy study of oral artesunate (total target dose 12 mg/kg) daily for 3 days was conducted in patients with uncomplicated falciparum malaria and a parasite count < 100,000/μL admitted to 3 adjacent district hospitals in Sabah, East Malaysia. On day 3 and 4 all patients were administered split dose mefloquine (total dose 25 mg/kg) and followed for 28 days. Twenty-one kelch13 polymorphisms associated with P. falciparum artemisinin resistance were also evaluated in P. falciparum isolates collected from patients presenting to health facilities predominantly within the tertiary referral area of western Sabah between 2012 and 2016.

    Results: In total, 49 patients were enrolled and treated with oral artesunate. 90% (44/49) of patients had cleared their parasitaemia by 48 h and 100% (49/49) within 72 h. The geometric mean parasite count at presentation was 9463/μL (95% CI 6757-13,254), with a median time to 50% parasite clearance of 4.3 h (IQR 2.0-8.4). There were 3/45 (7%) patients with a parasite clearance slope half-life of ≥ 5 h. All 278 P. falciparum isolates evaluated were wild-type for kelch13 markers.

    Conclusion: There is no suspected or confirmed evidence of endemic artemisinin-resistant P. falciparum in this pre-elimination setting in Sabah, Malaysia. Current guidelines recommending first-line treatment with ACT remain appropriate for uncomplicated malaria in Sabah, Malaysia. Ongoing surveillance is needed southeast of the Greater Mekong sub-region.

    Original languageEnglish
    Article number463
    Pages (from-to)1-8
    Number of pages8
    JournalMalaria Journal
    Volume17
    Issue number1
    DOIs
    Publication statusPublished - 10 Dec 2018

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    Malaysia
    Plasmodium falciparum
    Parasites
    Therapeutics
    Malaria
    Mefloquine
    Parasitemia
    District Hospitals
    artemisinine
    Falciparum Malaria
    Health Facilities
    Drug Resistance
    Half-Life
    Referral and Consultation
    Public Health
    Guidelines

    Cite this

    @article{ecbaf81119234a65ac2b02cc3a93e77d,
    title = "Plasmodium falciparum artemisinin resistance monitoring in Sabah, Malaysia: In vivo therapeutic efficacy and kelch13 molecular marker surveillance",
    abstract = "Background: Spreading Plasmodium falciparum artemisinin drug resistance threatens global malaria public health gains. Limited data exist to define the extent of P. falciparum artemisinin resistance southeast of the Greater Mekong region in Malaysia. Methods: A clinical efficacy study of oral artesunate (total target dose 12 mg/kg) daily for 3 days was conducted in patients with uncomplicated falciparum malaria and a parasite count < 100,000/μL admitted to 3 adjacent district hospitals in Sabah, East Malaysia. On day 3 and 4 all patients were administered split dose mefloquine (total dose 25 mg/kg) and followed for 28 days. Twenty-one kelch13 polymorphisms associated with P. falciparum artemisinin resistance were also evaluated in P. falciparum isolates collected from patients presenting to health facilities predominantly within the tertiary referral area of western Sabah between 2012 and 2016. Results: In total, 49 patients were enrolled and treated with oral artesunate. 90{\%} (44/49) of patients had cleared their parasitaemia by 48 h and 100{\%} (49/49) within 72 h. The geometric mean parasite count at presentation was 9463/μL (95{\%} CI 6757-13,254), with a median time to 50{\%} parasite clearance of 4.3 h (IQR 2.0-8.4). There were 3/45 (7{\%}) patients with a parasite clearance slope half-life of ≥ 5 h. All 278 P. falciparum isolates evaluated were wild-type for kelch13 markers. Conclusion: There is no suspected or confirmed evidence of endemic artemisinin-resistant P. falciparum in this pre-elimination setting in Sabah, Malaysia. Current guidelines recommending first-line treatment with ACT remain appropriate for uncomplicated malaria in Sabah, Malaysia. Ongoing surveillance is needed southeast of the Greater Mekong sub-region.",
    keywords = "Artemisinin-resistance, K13, kelch, Malaria, Plasmodium falciparum",
    author = "Grigg, {Matthew J.} and Timothy William and Piera, {Kim A.} and Rajahram, {Giri S.} and Jenarun Jelip and Ammar Aziz and Jayaram Menon and Jutta Marfurt and Price, {Ric N.} and Sarah Auburn and Barber, {Bridget E.} and Yeo, {Tsin W.} and Anstey, {Nicholas M.}",
    year = "2018",
    month = "12",
    day = "10",
    doi = "10.1186/s12936-018-2593-x",
    language = "English",
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    pages = "1--8",
    journal = "Malaria Journal",
    issn = "1475-2875",
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    }

    Plasmodium falciparum artemisinin resistance monitoring in Sabah, Malaysia : In vivo therapeutic efficacy and kelch13 molecular marker surveillance. / Grigg, Matthew J.; William, Timothy; Piera, Kim A.; Rajahram, Giri S.; Jelip, Jenarun; Aziz, Ammar; Menon, Jayaram; Marfurt, Jutta; Price, Ric N.; Auburn, Sarah; Barber, Bridget E.; Yeo, Tsin W.; Anstey, Nicholas M.

    In: Malaria Journal, Vol. 17, No. 1, 463, 10.12.2018, p. 1-8.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Plasmodium falciparum artemisinin resistance monitoring in Sabah, Malaysia

    T2 - In vivo therapeutic efficacy and kelch13 molecular marker surveillance

    AU - Grigg, Matthew J.

    AU - William, Timothy

    AU - Piera, Kim A.

    AU - Rajahram, Giri S.

    AU - Jelip, Jenarun

    AU - Aziz, Ammar

    AU - Menon, Jayaram

    AU - Marfurt, Jutta

    AU - Price, Ric N.

    AU - Auburn, Sarah

    AU - Barber, Bridget E.

    AU - Yeo, Tsin W.

    AU - Anstey, Nicholas M.

    PY - 2018/12/10

    Y1 - 2018/12/10

    N2 - Background: Spreading Plasmodium falciparum artemisinin drug resistance threatens global malaria public health gains. Limited data exist to define the extent of P. falciparum artemisinin resistance southeast of the Greater Mekong region in Malaysia. Methods: A clinical efficacy study of oral artesunate (total target dose 12 mg/kg) daily for 3 days was conducted in patients with uncomplicated falciparum malaria and a parasite count < 100,000/μL admitted to 3 adjacent district hospitals in Sabah, East Malaysia. On day 3 and 4 all patients were administered split dose mefloquine (total dose 25 mg/kg) and followed for 28 days. Twenty-one kelch13 polymorphisms associated with P. falciparum artemisinin resistance were also evaluated in P. falciparum isolates collected from patients presenting to health facilities predominantly within the tertiary referral area of western Sabah between 2012 and 2016. Results: In total, 49 patients were enrolled and treated with oral artesunate. 90% (44/49) of patients had cleared their parasitaemia by 48 h and 100% (49/49) within 72 h. The geometric mean parasite count at presentation was 9463/μL (95% CI 6757-13,254), with a median time to 50% parasite clearance of 4.3 h (IQR 2.0-8.4). There were 3/45 (7%) patients with a parasite clearance slope half-life of ≥ 5 h. All 278 P. falciparum isolates evaluated were wild-type for kelch13 markers. Conclusion: There is no suspected or confirmed evidence of endemic artemisinin-resistant P. falciparum in this pre-elimination setting in Sabah, Malaysia. Current guidelines recommending first-line treatment with ACT remain appropriate for uncomplicated malaria in Sabah, Malaysia. Ongoing surveillance is needed southeast of the Greater Mekong sub-region.

    AB - Background: Spreading Plasmodium falciparum artemisinin drug resistance threatens global malaria public health gains. Limited data exist to define the extent of P. falciparum artemisinin resistance southeast of the Greater Mekong region in Malaysia. Methods: A clinical efficacy study of oral artesunate (total target dose 12 mg/kg) daily for 3 days was conducted in patients with uncomplicated falciparum malaria and a parasite count < 100,000/μL admitted to 3 adjacent district hospitals in Sabah, East Malaysia. On day 3 and 4 all patients were administered split dose mefloquine (total dose 25 mg/kg) and followed for 28 days. Twenty-one kelch13 polymorphisms associated with P. falciparum artemisinin resistance were also evaluated in P. falciparum isolates collected from patients presenting to health facilities predominantly within the tertiary referral area of western Sabah between 2012 and 2016. Results: In total, 49 patients were enrolled and treated with oral artesunate. 90% (44/49) of patients had cleared their parasitaemia by 48 h and 100% (49/49) within 72 h. The geometric mean parasite count at presentation was 9463/μL (95% CI 6757-13,254), with a median time to 50% parasite clearance of 4.3 h (IQR 2.0-8.4). There were 3/45 (7%) patients with a parasite clearance slope half-life of ≥ 5 h. All 278 P. falciparum isolates evaluated were wild-type for kelch13 markers. Conclusion: There is no suspected or confirmed evidence of endemic artemisinin-resistant P. falciparum in this pre-elimination setting in Sabah, Malaysia. Current guidelines recommending first-line treatment with ACT remain appropriate for uncomplicated malaria in Sabah, Malaysia. Ongoing surveillance is needed southeast of the Greater Mekong sub-region.

    KW - Artemisinin-resistance

    KW - K13

    KW - kelch

    KW - Malaria

    KW - Plasmodium falciparum

    UR - http://www.scopus.com/inward/record.url?scp=85058298684&partnerID=8YFLogxK

    U2 - 10.1186/s12936-018-2593-x

    DO - 10.1186/s12936-018-2593-x

    M3 - Article

    VL - 17

    SP - 1

    EP - 8

    JO - Malaria Journal

    JF - Malaria Journal

    SN - 1475-2875

    IS - 1

    M1 - 463

    ER -