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

Research output: Contribution to journalArticleResearchpeer-review

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.

 

LanguageEnglish
Pages350-359
Number of pages10
JournalClinical Infectious Diseases
Volume67
Issue number3
Early online date5 Mar 2018
DOIs
StatePublished - 18 Jul 2018

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Plasmodium knowlesi
Plasmodium malariae
Parasitemia
Malaria
Surgical Instruments
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",
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doi = "10.1093/cid/ciy065",
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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. DOI: 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.  

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KW - clinical epidemiology

KW - district

KW - malaria

KW - Plasmodium knowlesi

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DO - 10.1093/cid/ciy065

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Grigg MJ, William T, Barber BE, Rajahram GS, Menon J, Schimann E et al. Age-related clinical spectrum of plasmodium knowlesi malaria and predictors of severity. Clinical Infectious Diseases. 2018 Jul 18;67(3):350-359. Available from, DOI: 10.1093/cid/ciy065