Serum Levels of Pro-inflammatory Cytokines in relationship to outcomes in Children with P. falciparum malaria, in Nnewi-South east Nigeria

Abstract

Background and Objective: In P. falciparum malaria (PFM) infestation there are marked changes in cytokine production as the body mounts an immune response to it. Hence we set out to study these changes.
Methods: A total of 158 cases of PFM among children attending the paediatric unit of our hospital and 56 healthy controls were studied. Children with febrile illness were screened for malaria using 10% Giemsa stained blood smear. Patients with positive smears were recruited; co-infected patients – those infected by another organism in addition to plasmodium specie.- were excluded. Whole blood was collected, some into plain tubes for serum cytokine testing and some into EDTA bottles for complete blood count and parasite density (PD) determination. Controls with asymptomatic parasitaemia were excluded.
Results: Using the World Health Organization criteria for defining severe malaria; we identified 15 cases of severe and 143 cases of uncomplicated PFM. Significantly elevated levels of interleukin-1 (IL-1), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were seen in the uncomplicated and severe forms of PFM. It was observed that the elevated cytokine values correlated with PD (in uncomplicated PFM but not in the severe forms). The difference between PD/absolute monocyte count (AMC) ratio was not significant (p=0.13); while PD/platelet count (PC) and PC/ AMC ratios were significant (p=0.01, and 0.03 respectively) when compared between uncomplicated and severe disease.
Conclusion: Our data seems to suggest that subjects with an adequate immune response to the parasite density, in terms of pro-inflammatory cytokine levels, presented with uncomplicated disease; while those who have an inadequate response presented with severe disease. The ratios of (PD/PC) and (PC/AMC), in the positive and negative directions respectively, may be predictors of increased disease severity. These observations may have implications for predicting disease outcome and PFM therapy.

Key Words: plasmodium falciparum malaria, pro-inflammatory cytokines, Parasite density/Platelet count ratio, Platelet count/Absolute monocyte