Elevated levels of methaemoglobin in Tanzanian children with severe and uncomplicated malaria

Elevated levels of methaemoglobin, the ferric form of haemoglobin incapable of oxygen transport, have been previously found during Plasmodium vivax infections and in acidotic infants. We measured methaemoglobin in the following 5 groups of children with P. falciparum malaria admitted to Muhimbili Medical Centre, Dar es Salaam, Tanzania. (i) Cerebral malaria (CM) with unrousable coma (n = 50), including 32 with complete recovery (CMCR) and 18 with death or neurological sequelae (CMDS); (ii) malaria with severe anaemia but without severe respiratory distress (SA; n = 6); (iii) uncomplicated malaria (UM; n = 37); (iv) asymptomatic parasitaemia (AP; n = 5); and (v) healthy controls (HC; n = 34). Mean methaemoglobin levels were elevated in all groups with malaria, forming up to 16.4% of circulating haemoglobin. The degree of methaemoglobinaemia correlated with disease severity and severity of anaemia. Mean methaemoglobin levels in children with AP, UM, SA, CMCR and CMDS were 3.3%, 4.1%, 5.6%, 4.7% and 5.8% respectively; the mean levels in those with clinical disease were significantly higher than those in healthy controls (2.0%). Methaemoglobinaemia > 10% was found in 5.4%, 16.7%, 12.5%, and 22.2% of those with UM, SA, CMCR and CMDS, respectively. In the presence of parasite sequestration, impaired tissue perfusion, and a reduction in oxygen carrying capacity of blood due to anaemia, a further reduction in oxygen carrying capacity from even a modest concentration of methaemoglobin is likely to exacerbate tissue hypoxia, perhaps critically so in a minority of anaemic and acidotic patients with severe falciparum malaria.