ICAM-1 and VCAM-1 bind malaria parasite infected erythrocytes and their up-regulation by inflammatory cytokines may increase sequestration of parasites to endothelium in the brain, leading to severe malaria outcome [14]. In this study, the plasma concentrations of endothelial adhesion molecules; ICAM-1 and VCAM-1 were increased in cases with microscopic parasitaemia compared to uninfected controls. This finding aligns with previous studies [15, 16, 17], that reported an increase in ICAM-1 expression during malaria infections, and suggested its heightened binding with parasites displaying the appropriate Pf EMP-1 phenotype, indicating its potential significance in the development of cerebral malaria. It suggests that endothelial cells may react swiftly to the presence of the parasite in infected individuals, particularly when parasitaemia is visible by microscopy [15].
According to a study conducted by [18], higher levels of endothelial adhesion molecules were observed in a naïve population that developed sub-microscopic infections during a controlled human malaria infection. This indicates that naturally infected persons may develop some degree of tolerance towards Plasmodium parasites after repeated exposure, leading to little to no significant upregulation of endothelial adhesion molecules at the sub-patent level.
In this study, there was no association between parasite density and levels of ICAM-1 and VCAM-1. This is similar with the results of prior studies [15, 16, 19, 20] which reported significant variances between uninfected controls and children with microscopic parasitaemia, but no significant correlation between parasite levels and these molecules.
The mean PCV of the malaria cases in this study was significantly lower than malaria negative cases and, ICAM-1 and VCAM-I correlated negatively with PCV, in contrast, the study by [12], showed that ICAM-1 was significantly associated with increased risk of severe anaemia and that children with severe malarial anaemia relative to those without, showed significantly elevated levels of the ICAM-1, VCAM-1 and E-selectin.
According to a study conducted on animal models by [21], mice infected with malaria and lacking the ICAM-1 receptor experienced less anaemia and weight loss compared to mice with control infections. Despite developing a higher level of parasites in their peripheral blood, which continued for a longer duration, their reduced tissue cytoadherence was a contributing factor to their improved condition.
Severe malaria poses a higher risk for individuals of advanced age, while children residing in malaria-endemic regions acquire immunity against severe malaria more rapidly, although this immunity does not necessarily reduce the number of parasites in their system [22]. According to the findings of this study, levels of ICAM-1 and VCAM-1 were lower in individuals with microscopic parasitaemia as they grew older, with significant differences observed between various age groups. Conversely, a different study [23] observed that the binding of infected erythrocytes (IE) to ICAM-1 receptors was more prevalent in older individuals, while no significant change was noted in the adhesion of IE to VCAM-1 receptors over time. ICAM-1 expression has been associated with severe infections in children [9], while also found to have a negative correlation with malaria in a separate study that focused on Malawian childhood malaria [10]. This information explains why P. falciparum is accountable for only 2% of clinical malaria cases that result in severe illness in African children [24], but are responsible for the majority of malaria-related deaths [1]. The variant surface antigens (VSAs) in field isolates of P. falciparum that lead to severe malaria in children tend to express a subset of surface antigens that are not recognized by the immune systems of infants and young children [25].
Limitations of this study include our inability to measure plasma level of ICAM-1 and VCAM-1 in severe malaria cases for comparison with uncomplicated and malaria negative cases.