Artemisinin-Combination Therapy Versus Chloroquine for The Treatment of Plasmodium Malariae in Sabah, Malaysia

A Randomized Controlled Trial

M. J. Grigg, T. William, B. E. Barber, G. S. Rajahram, J. Menon, C. S. Wilkes, K. Patel, A. Chandna, T. W. Yeo, N. M. Anstey

    Research output: Contribution to journalMeeting AbstractResearch

    Abstract

    Background: Human infection with Plasmodium malariae is uncommon but remains present in the Asia-Pacific region, Africa and South America, and can cause severe anaemia. There have been no previous randomised trials to evaluate the optimal treatment for uncomplicated malaria due to P. malariae.

    Methods: An open-label, randomised controlled trial was conducted at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P. malariae on screening microscopy were randomly assigned to receive oral artesunate–mefloquine (ASMQ; target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (CQ; target dose 25 mg/kg). The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. Secondary analysis 471astmh.orgincorporated additional patients separately randomised to artemether-lumefantrine (AL) or CQ.

    Findings: Between Jan 14, 2013, and Sep 20, 2014, admitted patients with PCR-confirmed P. malariae infection were allocated treatment with either ASMQ (n=6) or CQ (n=4). 24 h after treatment, we recorded parasite clearance in 3 (50% [95% CI 12-88]) of 6 patients in the ASMQ group versus none (0% [45–64]) of 4 patients in the CQ group (p=0.091). At 48 hours all ASMQ treated patients were negative for parasites versus none in the CQ arm (p=0.002), with this difference remaining at 72 hours with only 1 patient (25% [0-81]) in the CQ arm demonstrating parasite clearance (p=0.011). Fever clearance appeared faster in the ASMQ arm (median 6 hours [0-18]) versus 18.8 (3.8-42) following CQ (p=0.319). 1 patient in the ASMQ arm developed anaemia at day 28 during follow-up compared to none in the CQ arm (p=0.389). All patients had an adequate clinical and parasitological response to treatment at day 28 of follow-up. There were no serious adverse events due to either study medication. Results were consistent with the larger secondary analysis of patients treated with either ASMQ or AL (n=10) vs CQ (n=10).

    Interpretation: Artesunate–mefloquine demonstrated a rapid therapeutic response for P. malariae malaria, supporting a unified ACT treatment policy for for all Plasmodium species in co-endemic areas.
    Original languageEnglish
    Article number1501
    Pages (from-to)470-471
    Number of pages2
    JournalAmerican Journal of Tropical Medicine and Hygiene
    Volume95
    Issue numberSuppl. 5
    DOIs
    Publication statusPublished - Mar 2017
    Event65th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) - Atlanta, United States
    Duration: 13 Nov 201616 Nov 2016

    Fingerprint

    Plasmodium malariae
    Malaysia
    Chloroquine
    Randomized Controlled Trials
    Parasites
    Malaria
    Therapeutics
    Anemia
    artemisinine
    Mefloquine
    Plasmodium
    District Hospitals
    South America
    Microscopy
    Fever

    Cite this

    @article{0a41b7b12a0843edb5e61ee5e6cc8c5c,
    title = "Artemisinin-Combination Therapy Versus Chloroquine for The Treatment of Plasmodium Malariae in Sabah, Malaysia: A Randomized Controlled Trial",
    abstract = "Background: Human infection with Plasmodium malariae is uncommon but remains present in the Asia-Pacific region, Africa and South America, and can cause severe anaemia. There have been no previous randomised trials to evaluate the optimal treatment for uncomplicated malaria due to P. malariae. Methods: An open-label, randomised controlled trial was conducted at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P. malariae on screening microscopy were randomly assigned to receive oral artesunate–mefloquine (ASMQ; target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (CQ; target dose 25 mg/kg). The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. Secondary analysis 471astmh.orgincorporated additional patients separately randomised to artemether-lumefantrine (AL) or CQ. Findings: Between Jan 14, 2013, and Sep 20, 2014, admitted patients with PCR-confirmed P. malariae infection were allocated treatment with either ASMQ (n=6) or CQ (n=4). 24 h after treatment, we recorded parasite clearance in 3 (50{\%} [95{\%} CI 12-88]) of 6 patients in the ASMQ group versus none (0{\%} [45–64]) of 4 patients in the CQ group (p=0.091). At 48 hours all ASMQ treated patients were negative for parasites versus none in the CQ arm (p=0.002), with this difference remaining at 72 hours with only 1 patient (25{\%} [0-81]) in the CQ arm demonstrating parasite clearance (p=0.011). Fever clearance appeared faster in the ASMQ arm (median 6 hours [0-18]) versus 18.8 (3.8-42) following CQ (p=0.319). 1 patient in the ASMQ arm developed anaemia at day 28 during follow-up compared to none in the CQ arm (p=0.389). All patients had an adequate clinical and parasitological response to treatment at day 28 of follow-up. There were no serious adverse events due to either study medication. Results were consistent with the larger secondary analysis of patients treated with either ASMQ or AL (n=10) vs CQ (n=10). Interpretation: Artesunate–mefloquine demonstrated a rapid therapeutic response for P. malariae malaria, supporting a unified ACT treatment policy for for all Plasmodium species in co-endemic areas.",
    keywords = "Public, Environmental & Occupational Health Tropical Medicine",
    author = "Grigg, {M. J.} and T. William and Barber, {B. E.} and Rajahram, {G. S.} and J. Menon and Wilkes, {C. S.} and K. Patel and A. Chandna and Yeo, {T. W.} and Anstey, {N. M.}",
    year = "2017",
    month = "3",
    doi = "10.4269/ajtmh.abstract2016",
    language = "English",
    volume = "95",
    pages = "470--471",
    journal = "The American Journal of Tropical Medicine and Hygiene",
    issn = "0002-9637",
    publisher = "American Society of Tropical Medicine and Hygiene",
    number = "Suppl. 5",

    }

    Artemisinin-Combination Therapy Versus Chloroquine for The Treatment of Plasmodium Malariae in Sabah, Malaysia : A Randomized Controlled Trial. / Grigg, M. J.; William, T.; Barber, B. E.; Rajahram, G. S.; Menon, J.; Wilkes, C. S.; Patel, K.; Chandna, A.; Yeo, T. W.; Anstey, N. M.

    In: American Journal of Tropical Medicine and Hygiene, Vol. 95, No. Suppl. 5, 1501, 03.2017, p. 470-471.

    Research output: Contribution to journalMeeting AbstractResearch

    TY - JOUR

    T1 - Artemisinin-Combination Therapy Versus Chloroquine for The Treatment of Plasmodium Malariae in Sabah, Malaysia

    T2 - A Randomized Controlled Trial

    AU - Grigg, M. J.

    AU - William, T.

    AU - Barber, B. E.

    AU - Rajahram, G. S.

    AU - Menon, J.

    AU - Wilkes, C. S.

    AU - Patel, K.

    AU - Chandna, A.

    AU - Yeo, T. W.

    AU - Anstey, N. M.

    PY - 2017/3

    Y1 - 2017/3

    N2 - Background: Human infection with Plasmodium malariae is uncommon but remains present in the Asia-Pacific region, Africa and South America, and can cause severe anaemia. There have been no previous randomised trials to evaluate the optimal treatment for uncomplicated malaria due to P. malariae. Methods: An open-label, randomised controlled trial was conducted at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P. malariae on screening microscopy were randomly assigned to receive oral artesunate–mefloquine (ASMQ; target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (CQ; target dose 25 mg/kg). The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. Secondary analysis 471astmh.orgincorporated additional patients separately randomised to artemether-lumefantrine (AL) or CQ. Findings: Between Jan 14, 2013, and Sep 20, 2014, admitted patients with PCR-confirmed P. malariae infection were allocated treatment with either ASMQ (n=6) or CQ (n=4). 24 h after treatment, we recorded parasite clearance in 3 (50% [95% CI 12-88]) of 6 patients in the ASMQ group versus none (0% [45–64]) of 4 patients in the CQ group (p=0.091). At 48 hours all ASMQ treated patients were negative for parasites versus none in the CQ arm (p=0.002), with this difference remaining at 72 hours with only 1 patient (25% [0-81]) in the CQ arm demonstrating parasite clearance (p=0.011). Fever clearance appeared faster in the ASMQ arm (median 6 hours [0-18]) versus 18.8 (3.8-42) following CQ (p=0.319). 1 patient in the ASMQ arm developed anaemia at day 28 during follow-up compared to none in the CQ arm (p=0.389). All patients had an adequate clinical and parasitological response to treatment at day 28 of follow-up. There were no serious adverse events due to either study medication. Results were consistent with the larger secondary analysis of patients treated with either ASMQ or AL (n=10) vs CQ (n=10). Interpretation: Artesunate–mefloquine demonstrated a rapid therapeutic response for P. malariae malaria, supporting a unified ACT treatment policy for for all Plasmodium species in co-endemic areas.

    AB - Background: Human infection with Plasmodium malariae is uncommon but remains present in the Asia-Pacific region, Africa and South America, and can cause severe anaemia. There have been no previous randomised trials to evaluate the optimal treatment for uncomplicated malaria due to P. malariae. Methods: An open-label, randomised controlled trial was conducted at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P. malariae on screening microscopy were randomly assigned to receive oral artesunate–mefloquine (ASMQ; target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (CQ; target dose 25 mg/kg). The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. Secondary analysis 471astmh.orgincorporated additional patients separately randomised to artemether-lumefantrine (AL) or CQ. Findings: Between Jan 14, 2013, and Sep 20, 2014, admitted patients with PCR-confirmed P. malariae infection were allocated treatment with either ASMQ (n=6) or CQ (n=4). 24 h after treatment, we recorded parasite clearance in 3 (50% [95% CI 12-88]) of 6 patients in the ASMQ group versus none (0% [45–64]) of 4 patients in the CQ group (p=0.091). At 48 hours all ASMQ treated patients were negative for parasites versus none in the CQ arm (p=0.002), with this difference remaining at 72 hours with only 1 patient (25% [0-81]) in the CQ arm demonstrating parasite clearance (p=0.011). Fever clearance appeared faster in the ASMQ arm (median 6 hours [0-18]) versus 18.8 (3.8-42) following CQ (p=0.319). 1 patient in the ASMQ arm developed anaemia at day 28 during follow-up compared to none in the CQ arm (p=0.389). All patients had an adequate clinical and parasitological response to treatment at day 28 of follow-up. There were no serious adverse events due to either study medication. Results were consistent with the larger secondary analysis of patients treated with either ASMQ or AL (n=10) vs CQ (n=10). Interpretation: Artesunate–mefloquine demonstrated a rapid therapeutic response for P. malariae malaria, supporting a unified ACT treatment policy for for all Plasmodium species in co-endemic areas.

    KW - Public, Environmental & Occupational Health Tropical Medicine

    U2 - 10.4269/ajtmh.abstract2016

    DO - 10.4269/ajtmh.abstract2016

    M3 - Meeting Abstract

    VL - 95

    SP - 470

    EP - 471

    JO - The American Journal of Tropical Medicine and Hygiene

    JF - The American Journal of Tropical Medicine and Hygiene

    SN - 0002-9637

    IS - Suppl. 5

    M1 - 1501

    ER -