Severe malaria in children in areas with low, moderate and high transmission intensity in Uganda

OBJECTIVES Age and transmission intensity are known to influence the manifestations of severe falciparum malaria in African children. However, it is unclear how specific clinical features such as seizures, impairment of consciousness, or respiratory distress vary with the parasite load and transmission intensity. We examined how the peripheral parasite load varies with transmission intensity and how this influences the symptoms and manifestations of severe malaria in children under 5 years in three areas with different malaria transmission intensity across Uganda. METHODS We consecutively recruited 617 children with severe malaria presenting to three hospitals in areas with very low (51), moderate (367) and very high (199) transmission intensities and compared the age, admission parasite density and proportions of patients with different manifestations of severe disease. RESULTS The median age (months) was inversely proportional to transmission intensity and declined with rising transmission (26.4 in very low, 18.0 in moderate and 9.0 under very high transmission). The highest proportion of patients reporting previous malaria admissions came from the area with moderate transmission. The geometric mean parasite density (18 357, 32 508 and 95 433/mu l) and the proportion of patients with seizures (13.7%, 36.8% and 45.7%, P < 0.001) from very low, moderate and very high transmission respectively, increased with rising transmission. A linear increase with transmission was also observed in the proportion of those with repeated seizures (9.8%, 13.4% and 30.2%, P < 0.001) or impaired consciousness (7.8%, 12.8% and 18.1%, P = 0.029) but not respiratory distress. The proportion of patients with severe anaemia (19.6%, 24.8% and 37.7%, P = 0.002) mirrored that of patients with seizures. CONCLUSIONS These findings suggest that heavy Plasmodium falciparum parasitaemia may be important in development of seizures, severe malarial anaemia and impaired consciousness in children under 5 years of age but may not be important in the development of respiratory distress.