Aggravation of pathogenesis mediated by ochratoxin A in mice infected with Trypanosoma brucei rhodesiense

Abstract

Mice fed 1.5 mg ochratoxin A (OTA) per kg body weight and infected with Trypanosoma brucei rhodesiense were compared with trypanosome-infected placebo-fed and uninfected OTA-fed controls. Uninfected OTA-fed mice showed fever, lethargy, facial and eyelid oedemas, mild hepatitis and nephritis, and high survival. Infected placebo-fed controls had mean pre-patent period (PPP) of 3.26 days, lethargy, dyspnoea, fever, facial and scrotal oedema, survival of 33-65 days, reduced red cell counts (RCC: 10.96-6.87x106 cells/microl of blood), packed cell volume (PCV: 43.19-26.36%), haemoglobin levels (Hb: 13.37-7.92 g/dL) and mean corpuscular volume (MCV) of 37.96-41.31 fL, hepatosplenomegaly, generalized oedemas, heart congestion, hepatitis and nephritis. Compared to infected placebo-fed controls, infected OTA-fed mice had significantly (P<0.05) shorter mean PPP (2.58 days), reduced survival (6-47 days), more pronounced fever and dyspnoea. The latter had significantly (P<0.05) reduced RCC (10.74-4.56x106 cells/microl of blood), PCV (43.90-20.78%), Hb (13.06-5.74 g/dL), increased MCV (39.10-43.97 fL), severe generalized oedemas, haemorrhages, congestion, hepatic haemosiderosis, hepatitis, nephritis, endocarditis, pericarditis and exclusively, splenic macrophage and giant cell hyperplasia, expanded red pulp and splenic erythrophagocytosis. It was concluded that OTA aggravated the pathogenesis of T. b. rhodesiense infection in mice, and should therefore be taken into consideration during trypanosomosis control programmes.

Comparative pathogenicity of Trypanosoma brucei rhodesiense strains in Swiss white mice and Mastomys natalensis rats

“…Indeed, extremely high parasitaemia levels is one of the limitations of the mouse models of trypanosomiasis (Magez and Caljon, 2011). This agrees with earlier studies using EATRO 1989 and KETRI 3741 (Kibugu et al, 2009;Fink and Schmidt, 1979), the three trypanosome isolates used in the present study produced chronic infection in mice.…”

“…However, mice and rats infected with KETRI 3637 had similar high survival times. The host survival time has been estimated between 6 and 9 weeks for EATRO 1989- (Fink & Schmidt, 1979), 3-12 weeks ) and 3-7 weeks (Kibugu et al, 2009) for KETRI 3741-infected T. b. rhodesiense-infected mice. The present host survival data of 4-8 weeks for mice infected with the three trypanosome isolates and rats infected with KETRI 3622 or KETRI 3637 was consistent with the above earlier studies.…”

“…Three groups of 12 mice were infected with KETRI 3439 (Group A), KETRI 3622 (Group B) and KETRI 3637 (Group C) trypanosomes at 1 × 10 4 trypanosomes/0.2 mL per mouse (Gichuki and Brun, 1999; and monitored for 55 days. The pre-patent period (PP), parasitaemia development, survival times, clinical signs and gross pathology were recorded as previously described (Kibugu et al, 2009). This was repeated with 3 groups (Groups D, E and F, respectively) of Mastomys natalensis rats.…”

“…Survival times for each animal were monitored for 55 days post-trypanosome infection. This time was based on maximum survival time of 54-65 days observed in T. b. rhodesiense-infected laboratory rodents (Kibugu et al, 2009;Fink and Schmidt, 1979). For animals surviving beyond this period, the survival time was recorded as 55 days and categorized as censored data.…”

“…Emergence of drug resistance in sleeping sickness (Kagira and Maina, 2007;Nok, 2003), trypanocidal drug failure, lack of incentive for development of new trypanocides and unavailability of anti-trypanosomal vaccines (Geerts and Holmes, 1998;Gutterridge and Coombs, 1977) are major impediments to effective management of Rhodesian sleeping sickness. Murine models of HAT have been developed and used in research involving disease pathogenesis (Kibugu et al, 2009;Jennings et al, 1977), preclinical efficacy trials of novel drugs and evaluation of drug regimens (Thuita et al, 2008;Gichuki and Brun, 1999;Ndung'u and Akol, 1988), and validation of scientific innovations (Ndung'u et al, 2013). The development of these has been influenced by the variable infectivity patterns exhibited by trypanosomes.…”