Effects of mycotoxins on the pathogenesis and efficacy of chemotherapy of trypanosoma brucei rhodesiense in mice
Kibugu, James Karuku
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Mycotoxins are secondary metabolites produced by toxigenic fungi that on ingestion induce mycotoxicosis in humans and animals. Among others, aflatoxins and ochratoxins are known to alter pathogenesis of diseases including parasitic infections and through their effects may render drugs ineffective. Such effects have not been evaluated in many tropical diseases including trypanosomiasis. The aim of the present work was to assess the effects of mycotoxins on the susceptibility of Swiss White mice and efficacy of chemotherapy to Trypanosoma brucei rhodesiense infection. Forty-nine days old male mice were given oral daily doses of 0.50 mg aflatoxin / kg b. wt. (12 mice) or 1.5 mg ochratoxin / kg b. wt. (12 mice) in vegetable oil for 30 days. These were then infected with T. b. rhodesiense on day 7 after commencement of mycotoxin feeding and compared to infected placebo-treated (12 mice), uninfected mycotoxin-fed (12 mice), infected nonmycotoxin-fed (6 mice) and uninfected non-mycotoxin-fed controls (6 mice). Parasitaemia development, clinical and pathological changes were determined. Analysis of variance and mean separation were used to determine differences between the test and control mice. Kaplan-Meier method was used to analyse and compare the survival between infected mycotoxin-fed mice and controls. In a separate study, aflatoxin-fed mice (6 groups of 6 mice) and placebo-treated controls (6 groups of 6 mice) were infected with T. b. rhodesiense and each treated with 4.0, 4.5, 5.0, 5.5, 6.0 or 6.5 mg suramin / kg b.wt. at the on-set of parasitaemia, and their curative dosage values determined and compared using a logistic linear regression model. Results showed that the two mycotoxins aggravate pathogenesis of T. b. rhodesiense infection in mice. Compared to the placebo-treated controls there was pronounced dyspnoea. Host survival was significantly (p<0.05) reduced in both mycotoxin-fed groups. There was extreme emaciation in the aflatoxin-fed and significantly (p<0.05) shorter pre-patent period in the ochratoxin-fed mice. Macrocytic normochromic anaemia characterized by significant (p<0.05) reduction in red cell count, packed cell volume, haemoglobin levels and significant (p<0.05) increase in mean corpuscular volume were observed in mycotoxinfed mice compared to controls. There were also massive hepatic haemorrhages and thrombosis, together with cardiac and hepatic embolism in the aflatoxin-fed mice while the ochratoxin-fed mice had massive hepatic-renal haemorrhages and congestion, and massive hepatic haemosiderosis. Kidneys and liver had massive peri-vascular inflammatory mononuclear cellular infiltration in both mycotoxin-fed groups, and inflammatory eosinophils in the ochratoxin-fed mice. Although both mycotoxins aggravated hepatitis, nephritis and heart inflammation, there was more exacerbated liver damage and pancarditis in aflatoxin-fed mice and more intense nephritis in the ochratoxin-fed mice. The ochratoxin-fed group had aggravated endocarditis and pericarditis with necrosis, fibrosis and hydropericardium. Both mycotoxin-fed groups also presented with exacerbated hydrothorax and ascites. These aggravated pathological lesions could have caused reduced survival in the mice. In addition, aflatoxicosis induced a consistent increase in curative dosages of suramin in mice that indicated reduced drug efficacy. It was concluded that aflatoxicosis and ochratoxicosis aggravated the pathogenesis of T, b. rhodesiense infection in mice reducing the host survival, and aflatoxicosis may hinder its chemotherapy. Mycotoxicosis should therefore be taken into consideration during trypanosomiasis control programs.