Genomic characterization of recrudescent plasmodium malariae after treatment with artemether/lumefantrine

Gavin G. Rutledge, Ian Marr, G. Khai Lin Huang, Sarah Auburn, Jutta Marfurt, Mandy Sanders, Nicholas J. White, Matthew Berriman, Chris I. Newbold, Nicholas M. Anstey, Thomas D. Otto, Ric N. Price

    Research output: Contribution to journalReview articleResearchpeer-review

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    Abstract

    Plasmodium malariae is the only human malaria parasite species with a 72-hour intraerythrocytic cycle and the ability to persist in the host for life. We present a case of a P. malariae infection with clinical recrudescence after directly observed administration of artemether/lumefantrine. By using whole-genome sequencing, we show that the initial infection was polyclonal and the recrudescent isolate was a single clone present at low density in the initial infection. Haplotypic analysis of the clones in the initial infection revealed that they were all closely related and were presumably recombinant progeny originating from the same infective mosquito bite. We review possible explanations for the P. malariae treatment failure and conclude that a 3-day artemether/lumefantrine regimen is suboptimal for this species because of its long asexual life cycle.

    Original languageEnglish
    Pages (from-to)1300-1307
    Number of pages8
    JournalEmerging Infectious Diseases
    Volume23
    Issue number8
    DOIs
    Publication statusPublished - 1 Aug 2017

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    Plasmodium malariae
    Malaria
    Clone Cells
    Infection
    Bites and Stings
    Life Cycle Stages
    Culicidae
    Treatment Failure
    Parasites
    Genome
    Recurrence
    artemether
    lumefantrine

    Cite this

    Rutledge, Gavin G. ; Marr, Ian ; Huang, G. Khai Lin ; Auburn, Sarah ; Marfurt, Jutta ; Sanders, Mandy ; White, Nicholas J. ; Berriman, Matthew ; Newbold, Chris I. ; Anstey, Nicholas M. ; Otto, Thomas D. ; Price, Ric N. / Genomic characterization of recrudescent plasmodium malariae after treatment with artemether/lumefantrine. In: Emerging Infectious Diseases. 2017 ; Vol. 23, No. 8. pp. 1300-1307.
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    abstract = "Plasmodium malariae is the only human malaria parasite species with a 72-hour intraerythrocytic cycle and the ability to persist in the host for life. We present a case of a P. malariae infection with clinical recrudescence after directly observed administration of artemether/lumefantrine. By using whole-genome sequencing, we show that the initial infection was polyclonal and the recrudescent isolate was a single clone present at low density in the initial infection. Haplotypic analysis of the clones in the initial infection revealed that they were all closely related and were presumably recombinant progeny originating from the same infective mosquito bite. We review possible explanations for the P. malariae treatment failure and conclude that a 3-day artemether/lumefantrine regimen is suboptimal for this species because of its long asexual life cycle.",
    author = "Rutledge, {Gavin G.} and Ian Marr and Huang, {G. Khai Lin} and Sarah Auburn and Jutta Marfurt and Mandy Sanders and White, {Nicholas J.} and Matthew Berriman and Newbold, {Chris I.} and Anstey, {Nicholas M.} and Otto, {Thomas D.} and Price, {Ric N.}",
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    Genomic characterization of recrudescent plasmodium malariae after treatment with artemether/lumefantrine. / Rutledge, Gavin G.; Marr, Ian; Huang, G. Khai Lin; Auburn, Sarah; Marfurt, Jutta; Sanders, Mandy; White, Nicholas J.; Berriman, Matthew; Newbold, Chris I.; Anstey, Nicholas M.; Otto, Thomas D.; Price, Ric N.

    In: Emerging Infectious Diseases, Vol. 23, No. 8, 01.08.2017, p. 1300-1307.

    Research output: Contribution to journalReview articleResearchpeer-review

    TY - JOUR

    T1 - Genomic characterization of recrudescent plasmodium malariae after treatment with artemether/lumefantrine

    AU - Rutledge, Gavin G.

    AU - Marr, Ian

    AU - Huang, G. Khai Lin

    AU - Auburn, Sarah

    AU - Marfurt, Jutta

    AU - Sanders, Mandy

    AU - White, Nicholas J.

    AU - Berriman, Matthew

    AU - Newbold, Chris I.

    AU - Anstey, Nicholas M.

    AU - Otto, Thomas D.

    AU - Price, Ric N.

    PY - 2017/8/1

    Y1 - 2017/8/1

    N2 - Plasmodium malariae is the only human malaria parasite species with a 72-hour intraerythrocytic cycle and the ability to persist in the host for life. We present a case of a P. malariae infection with clinical recrudescence after directly observed administration of artemether/lumefantrine. By using whole-genome sequencing, we show that the initial infection was polyclonal and the recrudescent isolate was a single clone present at low density in the initial infection. Haplotypic analysis of the clones in the initial infection revealed that they were all closely related and were presumably recombinant progeny originating from the same infective mosquito bite. We review possible explanations for the P. malariae treatment failure and conclude that a 3-day artemether/lumefantrine regimen is suboptimal for this species because of its long asexual life cycle.

    AB - Plasmodium malariae is the only human malaria parasite species with a 72-hour intraerythrocytic cycle and the ability to persist in the host for life. We present a case of a P. malariae infection with clinical recrudescence after directly observed administration of artemether/lumefantrine. By using whole-genome sequencing, we show that the initial infection was polyclonal and the recrudescent isolate was a single clone present at low density in the initial infection. Haplotypic analysis of the clones in the initial infection revealed that they were all closely related and were presumably recombinant progeny originating from the same infective mosquito bite. We review possible explanations for the P. malariae treatment failure and conclude that a 3-day artemether/lumefantrine regimen is suboptimal for this species because of its long asexual life cycle.

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