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. InP. 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 commonest severity criterion was acute kidney 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. InP. 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 commonest severity criterion was acute kidney 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
UR - http://www.scopus.com/inward/record.url?scp=85045925819&partnerID=8YFLogxK
U2 - 10.1093/cid/ciy065
DO - 10.1093/cid/ciy065
M3 - Article
C2 - 29873683
AN - SCOPUS:85045925819
SN - 1058-4838
VL - 67
SP - 350
EP - 359
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 3
ER -