Cytoadherence in paediatric malaria:ABOblood group,CD36, andICAM1 expression and severePlasmodium falciparuminfection

Abstract

As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies.

ABO blood group distribution among endemic Burkitt’s lymphoma patients in Nigeria: Further evidence for the aetiological role of malaria

“…These changes were associated with significant Odds ratios suggesting decreased and increased risks of eBL among individuals with O and non-O blood groups respectively. These findings are interpreted to be a reflection of decreased and increased risks of severe malaria in individuals with O and non-O blood groups respectively as previously reported in earlier studies [3,4,12,13]. Previous studies have shown that malaria was associated with immune suppression, increased EBV load and polyclonal B cell activation, all of which are important in the pathogenesis of eBL [1,7].…”

“…Previous studies have shown that malaria was associated with immune suppression, increased EBV load and polyclonal B cell activation, all of which are important in the pathogenesis of eBL [1,7]. These malaria induced immune deregulations would be greater in persons with non-O blood groups because of their vulnerability to severe malaria [3,4,12,13]. Conversely, persons with O blood group, which is associated with non-severe malaria, would incur milder malaria associated pathology because of their reduced vulnerability to severe malaria [3,4,12,14].…”

Functional Roles for C5a and C5aR but Not C5L2 in the Pathogenesis of Human and Experimental Cerebral Malaria

“…Between 15 October 2007 and 30 October 2009, children aged 0.6 to 10.6 years living in an area in Uganda where malaria transmission is holoendemic and presenting to the Acute Care Unit of Mulago Hospital in Kampala with fever and Plasmodium falciparum malaria were eligible for enrollment in a nested case-control study, as described previously (33,34). Briefly, children were diagnosed with uncomplicated (UM) or cerebral (CM) malaria according to World Health Organization criteria (35).…”

Inter-Relationships of Cardinal Features and Outcomes of Symptomatic Pediatric Plasmodium falciparum Malaria in 1,933 Children in Kampala, Uganda

“…Children 6 months to 12 years of age with either uncomplicated or severe malaria were enrolled in a prospective observational study conducted at the Acute Care Unit of Mulago Hospital in Kampala, Uganda 26. Mulago Hospital is a 1,500 bed national referral center and teaching hospital of Makerere University College of Health Sciences where a previous study documented a 4.2% case-fatality rate among 23,342 children with malaria 27.…”