Haematological and tissue enzyme changes in a sheep model infected with Trypanosoma brucei rhodesiense

Abstract

Control and management of human African trypanosomosis faces many challenges including limited available drugs that are stage specific and also toxic, treatment failures and post treatment CNS and cardiac pathology which might be fatal. Because of ethical considerations, trypanosomosis and drug trial studies are conducted using animal models which have drawbacks. It is therefore important to develop models that can address the current drawbacks and also develop enzymatic disease staging markers to detect CNS and cardiac involvement in order to institute correct choice of trypanosome drugs and/or use of adjunct to mitigated conditions. The current study evaluated a sheep model infected with Trypanosoma brucei rhodesiense as a cheap and reliable model of human trypanosomosis. In addition the model was used to asses clinical signs, haematological changes and the use of total and isoenzyme CK and LDH levels in serum and CSF as markers of cardiac and staging of CNS infection, respectively. Eight sheep were infected with 1 × 10 4 T.b rhodesiense and two were uninfected controls. Blood was collected from the ear and jugular vein for parasitemia and for haematological and biochemical changes, respectively. CSF was also collected for cells and biochemical changes while total CK and LDH plus their respective isoenzymes were done by using starch gel electrophoresis and their quantification by a UN-SCAN IT densitometry. Infected sheep developed acute infection accompanied by clinical signs and haematological changes that mimicked infections in humans, including loss of body weight and fever.The infection was also characterized by an increase in MCH and MCHC. However, there was a decline in the levels of PCV, HCT, Hb, MCV and RBC counts. All parameters however recovered to control levels after treatment.This study also showed an increase in total protein, total LDH and total CK activities in both serum and CSF of infected compared to uninfected sheep. At the same time LDH and CK total enzyme and isoenzyme changes indicated cardiac involvement suggesting the diagnostic potential of the enzymes. However the infection did not develop a chronic CNS infection since following humane treatment of the infected sheep with berenil this resulted in cure of the infection and thus did not lead to late stage CNS infection. The study indicated that the T. b.rhodesiense sheep model can be a useful animal model of human African trypanosomosis. However, the study needs to be repeated using a less virulent or low dose of trypanosome to ensure the disease develops to the chronic stage.