Antibody Response against Conserved, Polymorphic and Variant Antigens in Severe falciparum Malaria in Gedarif State, Eastern Sudan

Abstract

The objectives of this study were to describe the clinico-epideiological feature of severe malaria in an area of markedly unstable and seasonal transmission. Also the interest was directed to characterize the immune response against merozoite surface proteins and variant surface antigens and to assess their impact on the development of different manifestation of severe malaria. The study was carried out in Gedarif area, Eastern Sudan during 2 successive malaria transmission seasons over the period 2000-2002. This is the first report about severe malaria in the Sudan and it is important for filling the paucity in the knowledge about the epidemiology of severe malaria. The incidence of severe malaria was 4.4%, and the mortality rate among the severe malaria (SM) patients was 6.4%, which accounts for 0.3% of all cases of malaria. Only four types of complications were recognized during the study period, the commonest was the severe malarial anemia (SMA) followed by convulsions (CAM), cerebral malaria (CM) and hypotension (HTN). Severe malaria was recognized in all age groups. The mean age for SM peaked at the age 2-4, while uncomplicated malaria peaked at 5-19 years. The 4 types of severe malaria significantly differ from each other in clinically important clinicoepidemiological indices, age, hemoglobin, blood glucose, parasite count and mortality rate. The antibody response directed against merozoite surface proteins (MSP119, MSP2A and MSP2B) revealed that, the three tested merozoite surface antigens were immunogenic. The MSP antibody response was age dependent in this setting. The antibody response against MSP119 was more significantly associated with protection from severe malaria but not uncomplicated malaria. More importantly, neither the prevalence nor the levels of MSP antibodies was associated with protection from fatal cerebral malaria. The study of the immune response against variant surface antigens (VSA) showed that the parasites obtained from patients with severe malaria, namely SMA and CM, displayed predominantly recognized VSA antigens compared to parasites obtained from patients with uncomplicated malaria (UM). On the other hand plasma from CM patients showed high or normal antibody response compared to the UM, while patients with SMA were found to have poor antibody response to VSA antigens expressed by parasites obtained from patients with different clinical grades of malaria. In addition it was found that, the plasma/parasite interaction is influenced by the intensity of malaria transmission in the place of the plasma donor (Sudan or Tanzania) rather than the place of parasite donor. On the contrary, the VSA antibody response was more affected by the age of parasite donor than the age of plasma donor.