Prevalence of Plasmodium ovale and Plasmodium malariae Mixed Infections and Associated Mortality in Children with Severe Falciparum Malaria

The prevalence and clinical significance of mixed Plasmodium infections in children with severe Plasmodium falciparum (P. falciparum) malaria are not well characterized. In a cohort of 440 Ugandan children hospitalized with severe malaria who were diagnosed with Plasmodium species via microscopy, nested polymerase chain reaction (nPCR) testing was used to detect P. falciparum, Plasmodium ovale (P. ovale), Plasmodium malariae (P. malariae), and Plasmodium vivax (P. vivax) infections and assess their association with adverse clinical outcomes during hospitalization. Using nPCR testing, the Plasmodium 18S small-subunit ribosomal RNA gene was detected in 440 children. Plasmodium falciparum mono-infection was identified in 329 (74.8%) children, P. malariae mono-infection was detected in one (0.2%), P. falciparum and P. ovale mixed infections were detected in 100 (22.8%), P. falciparum and P. malariae mixed infection was detected in one (0.2%), and P. falciparum, P. ovale, and P. malariae triple infections were detected in nine (2.1%). Children with triple infections of P. falciparum, P. ovale, and P. malariae exhibited higher mortality rates than those with P. falciparum mono-infection (3/9 [33%] versus 23/329 [7%]; odds ratio = 7.0; 95% CI = 1.8-28; P = 0.005). They were also more likely to experience respiratory distress (6/9 [67%] versus 115/329 [35%]; P = 0.08). In the present study, a high proportion of children with severe falciparum malaria had mixed P. ovale infections, and P. falciparum, P. ovale, and P. malariae triple infections were associated with increased mortality. Improved detection and broader surveillance of non-falciparum malaria may help identify epidemiologic patterns associated with adverse outcomes in severe malaria.