Plasmodium Knowlesi Malaria in Children in Malaysia: No Severe Disease Despite an Increased Risk of Anaemia Compared to Adults

Plasmodium knowlesi is now the most common cause of malaria in Malaysia, but prospective studies describing the clinical spectrum have only detailed adult disease. In our prospective study (2012-ongoing) at 3 district hospitals in Sabah, Malaysia, previously untreated, non-pregnant patients of any age hospitalised with PCR-confirmed malaria includes: 500 P. knowlesi (49 [9.8%] children 12 yrs), 204 P. vivax (83 [40.7%] children), 103 P. falciparum (33 [32%] children), 26 P. malariae, 1 mixed Pk/Pf and 1 mixed Pv/Pf. Preliminary data include a lower baseline parasite count for P. knowlesi malaria patients (median 2480/μL, IQR 538-8481) than P. falciparum (9600/μL [IQR 1446-25440]; p<0.001), and P. vivax (3882/μL, [1454-9608]; p=0.016). Parasite counts were higher in adults with P. knowlesi compared to children (median 2800 vs. 1535/μL; p=0.019). Anaemia (WHO criteria) was present in 32% (95%CI 27-36) of adults vs. 81% (95%CI 70-93) of children with knowlesi malaria (p<0.001); comparable to that seen in children with P. vivax (82%; p=0.948) or P. falciparum (76%; p=0.551). Acute kidney injury (AKIN criteria and/or creatinine >132mmol/L) was found in 26% (95% CI 22-30) of those with P. knowlesi malaria including 111/437 (25%) of adults and 13/46 (26%) of children (p=0.673). There was a higher prevalence of acute kidney injury in children with P. knowlesi malaria (26%) compared to P. vivax(12.5%; p=0.027) but not P. falciparum (30.3%; p=0.844). Severe malaria (modified WHO 2010 criteria) was present in 6.4% (95%CI 2.4-9.6%) of those with P. knowlesi overall: 32/451 (7.1%) in adults but none in children. In comparison, severe disease was seen in 6/204 (2.9%; p=0.065) with P. vivax and 4/103 (3.9%; p=0.326) with P. falciparum. There were no treatment failures in knowlesi malaria patients seen at 28 days. There was one P. knowlesi malaria death, an adult (age 62) with delayed parenteral artesunate due to misreported hyperparasitaemia. Overall P. knowlesimalaria predominantly affected adults, and while anaemia was more common in children, parasitemia was lower and severe disease was not seen.