Age-related clinical spectrum of plasmodium knowlesi malaria and predictors of severity

Matthew J. Grigg, Timothy William, Bridget E. Barber, Giri S. Rajahram, Jayaram Menon, Emma Schimann, Kim Piera, Christopher S. Wilkes, Kaajal Patel, Arjun Chandna, Christopher J. Drakeley, Tsin W. Yeo, Nicholas M. Anstey

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    Abstract

    Background: Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking.

    Methods: Over 3.5 years, we prospectively assessed patients of any age with molecularly–confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia.

    Results: Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9%), 71 (41%), and 31 (32%) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range, 538–8481/μL]) than in falciparum (9600/μL; P < .001) and vivax malaria. In P. knowlesi, World Health Organization–defined anemia was present in 82% (95% confidence interval [CI], 67%–92%) of children vs 36% (95% CI, 31%–41%) of adults. Severe knowlesi malaria occurred in 6.4% (95% CI, 3.9%–8.3%) of adults but not in children; the commenst severity criterion was acute kideny injury. No patient had coma. Age, parasitemia, schizont proportion, abdominal pain, and dyspnea were independently associated with severe knowlesi malaria, with parasitemia >15000/μL the best predictor (adjusted odds ratio, 16.1; negative predictive value, 98.5%; P < .001). Two knowlesi-related adult deaths occurred (fatality rate: 4.2/1000 adults).

    Conclusions: Age distribution and parasitemia differed markedly in knowlesi malaria compared to human-only species, with both uncomplicated and severe disease occurring at low parasitemia. Severe knowlesi malaria occurred only in adults; however, anemia was more common in children despite lower parasitemia. Parasitemia independently predicted knowlesi disease severity: Intravenous artesunate is warranted initially for those with parasitemia >15000/μL.

     

    Original languageEnglish
    Pages (from-to)350-359
    Number of pages10
    JournalClinical Infectious Diseases
    Volume67
    Issue number3
    Early online date5 Mar 2018
    DOIs
    Publication statusPublished - 18 Jul 2018

    Fingerprint

    Plasmodium knowlesi
    Plasmodium malariae
    Parasitemia
    Malaria
    Malaysia
    Confidence Intervals
    Anemia
    Vivax Malaria
    Schizonts
    Southeastern Asia
    Plasmodium
    Falciparum Malaria
    Age Distribution
    Coma
    Abdominal Pain
    Odds Ratio
    Prospective Studies
    Wounds and Injuries

    Cite this

    Grigg, Matthew J. ; William, Timothy ; Barber, Bridget E. ; Rajahram, Giri S. ; Menon, Jayaram ; Schimann, Emma ; Piera, Kim ; Wilkes, Christopher S. ; Patel, Kaajal ; Chandna, Arjun ; Drakeley, Christopher J. ; Yeo, Tsin W. ; Anstey, Nicholas M. / Age-related clinical spectrum of plasmodium knowlesi malaria and predictors of severity. In: Clinical Infectious Diseases. 2018 ; Vol. 67, No. 3. pp. 350-359.
    @article{d11f6518c8374faab2bbf6df0fa35bb0,
    title = "Age-related clinical spectrum of plasmodium knowlesi malaria and predictors of severity",
    abstract = "Background: Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking. Methods: Over 3.5 years, we prospectively assessed patients of any age with molecularly–confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia. Results: Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9{\%}), 71 (41{\%}), and 31 (32{\%}) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range, 538–8481/μL]) than in falciparum (9600/μL; P < .001) and vivax malaria. In P. knowlesi, World Health Organization–defined anemia was present in 82{\%} (95{\%} confidence interval [CI], 67{\%}–92{\%}) of children vs 36{\%} (95{\%} CI, 31{\%}–41{\%}) of adults. Severe knowlesi malaria occurred in 6.4{\%} (95{\%} CI, 3.9{\%}–8.3{\%}) of adults but not in children; the commenst severity criterion was acute kideny injury. No patient had coma. Age, parasitemia, schizont proportion, abdominal pain, and dyspnea were independently associated with severe knowlesi malaria, with parasitemia >15000/μL the best predictor (adjusted odds ratio, 16.1; negative predictive value, 98.5{\%}; P < .001). Two knowlesi-related adult deaths occurred (fatality rate: 4.2/1000 adults). Conclusions: Age distribution and parasitemia differed markedly in knowlesi malaria compared to human-only species, with both uncomplicated and severe disease occurring at low parasitemia. Severe knowlesi malaria occurred only in adults; however, anemia was more common in children despite lower parasitemia. Parasitemia independently predicted knowlesi disease severity: Intravenous artesunate is warranted initially for those with parasitemia >15000/μL.  ",
    keywords = "children, clinical epidemiology, district, malaria, Plasmodium knowlesi",
    author = "Grigg, {Matthew J.} and Timothy William and Barber, {Bridget E.} and Rajahram, {Giri S.} and Jayaram Menon and Emma Schimann and Kim Piera and Wilkes, {Christopher S.} and Kaajal Patel and Arjun Chandna and Drakeley, {Christopher J.} and Yeo, {Tsin W.} and Anstey, {Nicholas M.}",
    year = "2018",
    month = "7",
    day = "18",
    doi = "10.1093/cid/ciy065",
    language = "English",
    volume = "67",
    pages = "350--359",
    journal = "Clinical Infectious Diseases",
    issn = "1058-4838",
    publisher = "Oxford University Press",
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    }

    Grigg, MJ, William, T, Barber, BE, Rajahram, GS, Menon, J, Schimann, E, Piera, K, Wilkes, CS, Patel, K, Chandna, A, Drakeley, CJ, Yeo, TW & Anstey, NM 2018, 'Age-related clinical spectrum of plasmodium knowlesi malaria and predictors of severity', Clinical Infectious Diseases, vol. 67, no. 3, pp. 350-359. https://doi.org/10.1093/cid/ciy065

    Age-related clinical spectrum of plasmodium knowlesi malaria and predictors of severity. / Grigg, Matthew J.; William, Timothy; Barber, Bridget E.; Rajahram, Giri S.; Menon, Jayaram; Schimann, Emma; Piera, Kim; Wilkes, Christopher S.; Patel, Kaajal; Chandna, Arjun; Drakeley, Christopher J.; Yeo, Tsin W.; Anstey, Nicholas M.

    In: Clinical Infectious Diseases, Vol. 67, No. 3, 18.07.2018, p. 350-359.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Age-related clinical spectrum of plasmodium knowlesi malaria and predictors of severity

    AU - Grigg, Matthew J.

    AU - William, Timothy

    AU - Barber, Bridget E.

    AU - Rajahram, Giri S.

    AU - Menon, Jayaram

    AU - Schimann, Emma

    AU - Piera, Kim

    AU - Wilkes, Christopher S.

    AU - Patel, Kaajal

    AU - Chandna, Arjun

    AU - Drakeley, Christopher J.

    AU - Yeo, Tsin W.

    AU - Anstey, Nicholas M.

    PY - 2018/7/18

    Y1 - 2018/7/18

    N2 - Background: Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking. Methods: Over 3.5 years, we prospectively assessed patients of any age with molecularly–confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia. Results: Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9%), 71 (41%), and 31 (32%) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range, 538–8481/μL]) than in falciparum (9600/μL; P < .001) and vivax malaria. In P. knowlesi, World Health Organization–defined anemia was present in 82% (95% confidence interval [CI], 67%–92%) of children vs 36% (95% CI, 31%–41%) of adults. Severe knowlesi malaria occurred in 6.4% (95% CI, 3.9%–8.3%) of adults but not in children; the commenst severity criterion was acute kideny injury. No patient had coma. Age, parasitemia, schizont proportion, abdominal pain, and dyspnea were independently associated with severe knowlesi malaria, with parasitemia >15000/μL the best predictor (adjusted odds ratio, 16.1; negative predictive value, 98.5%; P < .001). Two knowlesi-related adult deaths occurred (fatality rate: 4.2/1000 adults). Conclusions: Age distribution and parasitemia differed markedly in knowlesi malaria compared to human-only species, with both uncomplicated and severe disease occurring at low parasitemia. Severe knowlesi malaria occurred only in adults; however, anemia was more common in children despite lower parasitemia. Parasitemia independently predicted knowlesi disease severity: Intravenous artesunate is warranted initially for those with parasitemia >15000/μL.  

    AB - Background: Plasmodium knowlesi is increasingly reported in Southeast Asia, but prospective studies of its clinical spectrum in children and comparison with autochthonous human-only Plasmodium species are lacking. Methods: Over 3.5 years, we prospectively assessed patients of any age with molecularly–confirmed Plasmodium monoinfection presenting to 3 district hospitals in Sabah, Malaysia. Results: Of 481 knowlesi, 172 vivax, and 96 falciparum malaria cases enrolled, 44 (9%), 71 (41%), and 31 (32%) children aged ≤12 years. Median parasitemia was lower in knowlesi malaria (2480/μL [interquartile range, 538–8481/μL]) than in falciparum (9600/μL; P < .001) and vivax malaria. In P. knowlesi, World Health Organization–defined anemia was present in 82% (95% confidence interval [CI], 67%–92%) of children vs 36% (95% CI, 31%–41%) of adults. Severe knowlesi malaria occurred in 6.4% (95% CI, 3.9%–8.3%) of adults but not in children; the commenst severity criterion was acute kideny injury. No patient had coma. Age, parasitemia, schizont proportion, abdominal pain, and dyspnea were independently associated with severe knowlesi malaria, with parasitemia >15000/μL the best predictor (adjusted odds ratio, 16.1; negative predictive value, 98.5%; P < .001). Two knowlesi-related adult deaths occurred (fatality rate: 4.2/1000 adults). Conclusions: Age distribution and parasitemia differed markedly in knowlesi malaria compared to human-only species, with both uncomplicated and severe disease occurring at low parasitemia. Severe knowlesi malaria occurred only in adults; however, anemia was more common in children despite lower parasitemia. Parasitemia independently predicted knowlesi disease severity: Intravenous artesunate is warranted initially for those with parasitemia >15000/μL.  

    KW - children

    KW - clinical epidemiology

    KW - district

    KW - malaria

    KW - Plasmodium knowlesi

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    U2 - 10.1093/cid/ciy065

    DO - 10.1093/cid/ciy065

    M3 - Article

    VL - 67

    SP - 350

    EP - 359

    JO - Clinical Infectious Diseases

    JF - Clinical Infectious Diseases

    SN - 1058-4838

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    ER -