Age-Related Clinical Spectrum of Plasmodium knowlesi Malaria and Predictors of Severity
Matthew J Grigg1,2, Timothy William2,3,4, Bridget E Barber1,2
1Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
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/microL [interquartile range, 538-8481/microL]) than in falciparum (9600/microL; 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/microL 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/microL.
Insights
Plasmodium knowlesi malaria presents differently in children and adults in Malaysia. While adults experienced severe knowlesi malaria, children had higher rates of anemia despite lower parasitemia, highlighting distinct clinical patterns.
Area of Science:
- Tropical Medicine
- Infectious Diseases
- Parasitology
Background:
- Plasmodium knowlesi is an emerging cause of malaria in Southeast Asia.
- Prospective clinical spectrum studies in children and comparisons with human-only Plasmodium species are limited.
Purpose of the Study:
- To prospectively assess the clinical spectrum of Plasmodium knowlesi malaria in children and adults.
- To compare knowlesi malaria with Plasmodium vivax and Plasmodium falciparum in Malaysia.
Main Methods:
- Prospective assessment of patients with molecularly-confirmed Plasmodium monoinfection over 3.5 years.
- Data collected from three district hospitals in Sabah, Malaysia.
- Comparison of clinical features and outcomes across Plasmodium species and age groups.
Main Results:
- Of 481 knowlesi cases, 44% were children; 41% of vivax and 32% of falciparum cases were children.
- Lower median parasitemia in knowlesi malaria (2480/microL) compared to falciparum (9600/microL) and vivax malaria.
- Anemia was more frequent in children with knowlesi malaria (82%) than adults (36%). Severe knowlesi malaria occurred in 6.4% of adults but not in children. Acute kidney injury was a common severe criterion. Parasitemia >15000/microL best predicted severity (aOR, 16.1).
Conclusions:
- Knowlesi malaria exhibits distinct age-related differences in parasitemia and disease presentation compared to human-only Plasmodium species.
- Severe knowlesi malaria was observed only in adults, though anemia was more prevalent in children.
- High parasitemia (>15000/microL) independently predicted severe knowlesi malaria, suggesting a need for intravenous artesunate treatment.
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