Association of Intraleukocytic Plasmodium Falciparum Malaria Pigment With Disease Severity, Clinical Manifestations, and Prognosis in Severe Malaria

Abstract

Abstract. Peripheral parasite density of Plasmodium falciparum is used as an indicator of malaria disease severity, but does not quantify central sequestration, which is important in the pathogenesis of severe disease. Malaria pigment, recognizable within the cytoplasm of phagocytic cells by light microscopy may represent a peripheral marker for parasite biomass. One hundred seventy-two index cases of severe malaria and 172 healthy age-, residence-, and ethnicity-matched controls with uncomplicated malaria in Bandiagara, Mali were analyzed prospectively for presence of malaria pigment.

Blood group O protects against severe Plasmodium falciparum malaria through the mechanism of reduced rosetting

“…The healthy control children were asymptomatic and parasite-negative by thick blood smear (22). In classification of the severe malaria cases, cerebral malaria [unrousable coma with a Blantyre Coma Score (BCS) of Յ2 with other obvious causes of coma excluded] and severe anemia (Hb Ͻ5g/dl) were taken as primary defining criteria when they coexisted with other criteria, as described previously (22). The severe malaria cases (n ϭ 124) consisted of 32 children (25.8%) with cerebral malaria, 10 children (8.1%) with severe anemia, 9 children (7.3%) with cerebral malaria and severe anemia, 38 children (30.6%) with neurological impairment (impaired consciousness or prostration) but with a BCS of Ͼ2, 26 children (21.0%) with repeated seizures but no lasting neurological impairment, and 9 children (7.3%) with no neurological abnormalities or anemia but with evidence of renal or hepatic failure (anuria, hematuria, jaundice).…”

“…Uncomplicated malaria controls were children with P. falciparum infection and fever but with no symptoms or signs of severe malaria and no hyperparasitemia. The healthy control children were asymptomatic and parasite-negative by thick blood smear (22). In classification of the severe malaria cases, cerebral malaria [unrousable coma with a Blantyre Coma Score (BCS) of Յ2 with other obvious causes of coma excluded] and severe anemia (Hb Ͻ5g/dl) were taken as primary defining criteria when they coexisted with other criteria, as described previously (22).…”

“…Blood samples were collected in Bandiagara, Mali, an area with intense seasonal transmission of P. falciparum (20-60 infected bites per person per month at the peak of the July-December transmission season) (42). The samples were collected as part of the Bandiagara Malaria Project case-control study that has been described in detail previously (22). Blood samples were collected after informed consent from children's parents or guardians, and all protocols received institutional review board approval.…”

“…Some researchers (e.g., refs. 18 and 23) include hyperparasitemia as a criterion for severe disease; however, we have found that children with hyperparasitemia and no other symptoms or signs of severe malaria have an excellent prognosis (0% mortality) and can thus be considered as having a form of uncomplicated malaria with very high parasite burdens (22,24). The characteristics of the recruited children are shown in Table 1.…”

“…We therefore investigated the effect of ABO blood group on rosetting and malaria severity in a casecontrol study of African children. coma, severe anemia, neurological impairment, repeated seizures, or evidence of hepatic or renal failure; for full details see Materials and Methods) was matched by age, ethnicity, and place of residence to an uncomplicated malaria control and a healthy control child (22). Cases of nonsevere hyperparasitemia (Ͼ500,000 infected erythrocytes per l of blood) were also recruited and matched to uncomplicated malaria controls and healthy controls.…”