Malaria severity and c-c chemokines in children in Apac Hospital, Uganda

Abstract

Background Malaria poses a tremendous public health problem. Apac district has previously been reported to have the highest entomological inoculation rate in the world (39). Chemokines play a role in regulating innate and adaptive immunity in subsequent malaria infections. The immunological properties of the C-C chemokines can be exploited in the development of malaria vaccines as a malaria control strategy. Objective This study aimed at determining malaria prevalence, severity and its association with C-C chemokines (RANTES, MCP1 and MIP3α) in children aged 6-59 months in Apac hospital. Methods A cross-sectional study was conducted among 420 children aged 6-59 months in Apac Hospital outpatient department during March 2010. Stratified consecutive sampling was used to select participants for the study. Wilcoxon rank sum test was used to compare the chemokine levels in the independent groups of severe, uncomplicated and asymptomatic malaria and those children without malaria. A p-value ≤ 0.05 was considered significant. Risk estimation between chemokines (RANTES, MCP1 and MIP3α), and the several predictor variables was done using odds ratios and 95% confidence intervals. Confounders and effect modifiers were also controlled for. Results High levels of MIP-3α and MCP-1 were observed in children with severe and uncomplicated malaria 390.0 (IQR 210.9-1001.7), 299.4 (IQR 158.8-659.7) and 225.7 (IQR 92.9 -522.5), 121.59 (IQR 56.8 – 305.0) respectively. Severe malaria and uncomplicated malaria were also significantly positively associated with elevated levels of MIP-3α and MCP-1 OR=9.23 CI 4.24-20.09 (P<0.01), OR=7 CI 3.60-13.61 (P<0.01) and OR=16.9 CI 7.17-40.04 (P< 0.001), OR=7.5 CI 3.86-14.58 (P< 0.001) respectively. Significant positive correlations were observed between temperature, parasite density and MIP-3α and MCP-1 Spearman’s rho = 0.42 (P<0.0001), Spearman’s rho=0.32 (P<0.0001) and Spearman’s rho=0.39 (P<0.01), Spearman’s rho=0.28 (P<0.01) respectively. Children with no malaria and those with asymptomatic malaria had elevated levels of RANTES 170727.6 IQR 104043.1 – 223426.3 and 113185.8 IQR 64513.9 – 160523.4 respectively. Absence of malaria and having asymptomatic malaria was associated with high levels of RANTES OR=21.87 CI 7.82-61.15 (P<0.001) and OR=9.7 CI 3.49-27.21 (P<0.001) respectively. RANTES was significantly correlated with hemoglobin Spearman’s rho = 0.22 (P<0.001). Conclusion Elevated levels of MCP-1 and MIP-3α in children with severe malaria coupled with the significant correlations with parasite density and temperature indicates that MCP-1 and MIP- 3α might be important correlates of disease. On the other hand elevated levels of RANTES in children without malaria with significant correlations with hemoglobin levels probably provides indirect evidence of an association between RANTES and protection against severe malaria in children in a holoendemic region in Uganda. Recommendations Since many of the severe cases had high-density parasitaemia in the absence of severe anaemia a study investigating the role of MIP-3α and MCP-1 in the promotion of malarial anaemia in a pediatric population is recommended. MIP-3α attracts immunological effector cells implicated in malaria immunity and yet its levels are increased in clincal malaria. There is need to investigate further the paradoxical increase of this chemokine in malaria.