Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia

A longitudinal surveillance study

Enny Kenangalem, Jeanne Rini Poespoprodjo, Nicholas M. Douglas, Faustina Helena Burdam, Ketut Gdeumana, Ferry Chalfein, Prayoga, Franciscus Thio, Angela Devine, Jutta Marfurt, Govert Waramori, Shunmay Yeung, Rintis Noviyanti, Pasi Penttinen, Michael J. Bangs, Paulus Sugiarto, Julie A. Simpson, Yati Soenarto, Nicholas M. Anstey, Ric N. Price

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    Abstract

    Background: Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species.

    Methods and Findings: A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval [CI] -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = -0.21% [95% CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = -0.05% [95% CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48-0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71-0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy.

    Conclusions: In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.

    Original languageEnglish
    Article number1002815
    Pages (from-to)1-23
    Number of pages23
    JournalPLoS Medicine
    Volume16
    Issue number5
    DOIs
    Publication statusPublished - 29 May 2019

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    Indonesia
    Malaria
    Longitudinal Studies
    Morbidity
    Mortality
    Antimalarials
    Vivax Malaria
    Plasmodium
    Confidence Intervals
    Falciparum Malaria
    Therapeutics
    Incidence
    artemisinine
    Population Growth
    Plasmodium falciparum
    Drug Resistance
    Parasites

    Cite this

    Kenangalem, Enny ; Poespoprodjo, Jeanne Rini ; Douglas, Nicholas M. ; Burdam, Faustina Helena ; Gdeumana, Ketut ; Chalfein, Ferry ; Prayoga ; Thio, Franciscus ; Devine, Angela ; Marfurt, Jutta ; Waramori, Govert ; Yeung, Shunmay ; Noviyanti, Rintis ; Penttinen, Pasi ; Bangs, Michael J. ; Sugiarto, Paulus ; Simpson, Julie A. ; Soenarto, Yati ; Anstey, Nicholas M. ; Price, Ric N. / Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia : A longitudinal surveillance study. In: PLoS Medicine. 2019 ; Vol. 16, No. 5. pp. 1-23.
    @article{a1a4fb1ee4e24a50aeee83e6bb54bb69,
    title = "Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: A longitudinal surveillance study",
    abstract = "Background: Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. Methods and Findings: A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9{\%} (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0{\%} (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9{\%} (95{\%} confidence interval [CI] -13.5{\%} to -12.2{\%}). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53{\%} [100/18,965] versus 0.32{\%} [57/17,691]; difference = -0.21{\%} [95{\%} CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28{\%} [21/7,545] versus 0.23{\%} [28/12,397]; difference = -0.05{\%} [95{\%} CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1{\%} (30,444/69,098) to 53.3{\%} (29,934/56,125) in the community clinics and from 32.4{\%} (9,325/28,789) to 44.1{\%} (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95{\%} CI 0.48-0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95{\%} CI 0.71-0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy. Conclusions: In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.",
    author = "Enny Kenangalem and Poespoprodjo, {Jeanne Rini} and Douglas, {Nicholas M.} and Burdam, {Faustina Helena} and Ketut Gdeumana and Ferry Chalfein and Prayoga and Franciscus Thio and Angela Devine and Jutta Marfurt and Govert Waramori and Shunmay Yeung and Rintis Noviyanti and Pasi Penttinen and Bangs, {Michael J.} and Paulus Sugiarto and Simpson, {Julie A.} and Yati Soenarto and Anstey, {Nicholas M.} and Price, {Ric N.}",
    year = "2019",
    month = "5",
    day = "29",
    doi = "10.1371/journal.pmed.1002815",
    language = "English",
    volume = "16",
    pages = "1--23",
    journal = "PLoS Medicine",
    issn = "1549-1277",
    publisher = "Public Library of Science (PLoS)",
    number = "5",

    }

    Kenangalem, E, Poespoprodjo, JR, Douglas, NM, Burdam, FH, Gdeumana, K, Chalfein, F, Prayoga, Thio, F, Devine, A, Marfurt, J, Waramori, G, Yeung, S, Noviyanti, R, Penttinen, P, Bangs, MJ, Sugiarto, P, Simpson, JA, Soenarto, Y, Anstey, NM & Price, RN 2019, 'Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: A longitudinal surveillance study', PLoS Medicine, vol. 16, no. 5, 1002815, pp. 1-23. https://doi.org/10.1371/journal.pmed.1002815

    Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia : A longitudinal surveillance study. / Kenangalem, Enny; Poespoprodjo, Jeanne Rini; Douglas, Nicholas M.; Burdam, Faustina Helena; Gdeumana, Ketut; Chalfein, Ferry; Prayoga; Thio, Franciscus; Devine, Angela; Marfurt, Jutta; Waramori, Govert; Yeung, Shunmay; Noviyanti, Rintis; Penttinen, Pasi; Bangs, Michael J.; Sugiarto, Paulus; Simpson, Julie A.; Soenarto, Yati; Anstey, Nicholas M.; Price, Ric N.

    In: PLoS Medicine, Vol. 16, No. 5, 1002815, 29.05.2019, p. 1-23.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia

    T2 - A longitudinal surveillance study

    AU - Kenangalem, Enny

    AU - Poespoprodjo, Jeanne Rini

    AU - Douglas, Nicholas M.

    AU - Burdam, Faustina Helena

    AU - Gdeumana, Ketut

    AU - Chalfein, Ferry

    AU - Prayoga,

    AU - Thio, Franciscus

    AU - Devine, Angela

    AU - Marfurt, Jutta

    AU - Waramori, Govert

    AU - Yeung, Shunmay

    AU - Noviyanti, Rintis

    AU - Penttinen, Pasi

    AU - Bangs, Michael J.

    AU - Sugiarto, Paulus

    AU - Simpson, Julie A.

    AU - Soenarto, Yati

    AU - Anstey, Nicholas M.

    AU - Price, Ric N.

    PY - 2019/5/29

    Y1 - 2019/5/29

    N2 - Background: Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. Methods and Findings: A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval [CI] -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = -0.21% [95% CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = -0.05% [95% CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48-0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71-0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy. Conclusions: In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.

    AB - Background: Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species. Methods and Findings: A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval [CI] -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = -0.21% [95% CI -0.34 to -0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = -0.05% [95% CI -0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48-0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71-0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy. Conclusions: In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.

    UR - http://www.scopus.com/inward/record.url?scp=85067425102&partnerID=8YFLogxK

    U2 - 10.1371/journal.pmed.1002815

    DO - 10.1371/journal.pmed.1002815

    M3 - Article

    VL - 16

    SP - 1

    EP - 23

    JO - PLoS Medicine

    JF - PLoS Medicine

    SN - 1549-1277

    IS - 5

    M1 - 1002815

    ER -