THE IMPACT OF SCHISTOSOMA MANSONI ON DISEASE SEVERITY OF SECONDARY INFECTION WITH TRYPANOSOMA BRUCEI RHODESIENSE IN A MOUSE MODEL

Abstract

Human African Trypanosomiasis (HAT) and Schistosomiasis are neglected parasitic diseases found in the African continent. There’s paucity of data on the outcome during co-infection of S. mansoni and Trypanosoma brucei rhodesiense. This study was conducted to determine how primary infection with Schistosoma mansoni affects HAT diseases progression with a secondary infection with Trypanosoma brucei rhodesiense (T.b.r) in a mouse model. Female BALB-c mice (6-8 weeks old) were randomly divided into four groups of 12 mice each. The different groups were infected with Schistosoma mansoni (100 cercariae) and Trypanosoma brucei rhodesiense (5.0x104 ) separately or together. Twenty-one days’ post infection with T.b.r, mice were sacrificed and samples collected for analysis. The primary infection with S. mansoni significantly enhanced successive infection by T.b.r; consequently, promoting HAT disease severity and curtailing host survival time. T.b.r-induced neurological integrity impairment and breach of the blood brain barrier were markedly pronounced on co-infection with S. mansoni. Co-infection with S. mansoni and T.b.r resulted in microcytic hypochromic anemia characterized by suppression of RBCs, hematocrit, hemoglobin and red cell indices. Moreover, co-infection of the mice with the two parasites resulted in leukocytosis which was accompanied with elevation of basophils, neutrophils, lymphocytes, monocytes, and eosinophils. More importantly, co-infection resulted in significant elevation of alanine amino transferase (ALT), alkaline phosphatase (ALP), aspartate amino transferase (AST), total bilirubin, creatinine, urea and uric acid, markers of liver and kidney damage. Meanwhile, S. mansoni-driven dyslipidemia was significantly enhanced by co-infection of mice with T.b.r. Moreover, co-infection with S. mansoni and T.b.r led to a strong immune response characterized by significant increase in serum IFN-γ and TNF-α. T.b.r infection enhanced S. mansoni-induced depletion of cellular reduced glutathione (GSH) in the brain and liver tissues, indicative of lethal oxidative damage. Similarly, co-infection resulted in significant rise in nitric oxide (NO) and malondialdehyde (MDA) levels. In conclusion, primary infection with S. mansoni exacerbates disease severity of secondary infection with T.b.r in a mouse model that is linked with harmful inflammatory response, oxidative stress and organ injury