Background: A key objective in basic research on human African trypanosomiasis (HAT) is developing a cheap and reliable experimental model of the disease for use in pathogenesis and drug studies.Objective: With a view to improving current models, a study was undertaken to characterise the virulence and pathogenicity of three Trypanosoma brucei rhodesiense stabilates, labelled as International Livestock Research Institute (ILRI)-2918, ILRI-3953, and Institute of Primate Research (IPR)-001, infected into Swiss white mice.Methods: Swiss white mice were infected intraperitoneally with trypanosomes and observedfor parasitaemia using wet blood smears obtained by tail snipping. Induction of late-stagedisease was undertaken using diminazene aceturate (40 mg/kg, Berenil) with curativetreatment done using melarsoprol (3.6 mg/kg, Arsobal).Results: The prepatent period for the stabilates ranged from three to four days with mean peak parasitaemia ranging from Log10 6.40 to 8.36. First peak parasitaemia for all stabilates varied between six and seven days post infection (DPI) followed by secondary latency in ILRI-2918 (15–17 DPI) and IPR-001 (17–19 DPI). Survival times ranged from six DPI (ILRI-3953) to 86 DPI (IPR-001). Hindleg paresis was observed in both ILRI-3953 (at peak parasitaemia) and ILRI-2918 (after relapse parasitaemia). Mice infected with IPR-001 survived until 54 DPI when curative treatment was undertaken.Conclusions: This study demonstrated that the stabilates ILRI-2918 and ILRI-3953 were unsuitable for modelling late-stage HAT in mice. The stabilate IPR-001 demonstrated the potential to induce chronic trypanosomiasis in Swiss white mice for use in development of a late-stage model of HAT.
Background Follow-up of treated human African trypanosomiasis (HAT) patients has been a routine practice for confirming cure and early detection of treatment failure. Objective The aim of this study was to verify suitability of neopterin and CXCL13 as disease stage biomarkers and monitors of treatment efficacy in a vervet monkey model of HAT. Methods Six monkeys were infected with Trypanosoma brucei. Late stage disease was induced by sub-curative treatment with diminazene aceturate (DA) from 28 days post-infection (dpi). Upon relapse, the animals were treated curatively with melarsoprol (Mel B) from 82 dpi. Blood and cerebrospinal fluid (CSF) samples were collected weekly and assessed for parasitosis, as well as tested for neopterin and CXCL13 by ELISA, for a period of 39 weeks. Results Neopterin concentrations in serum increased rapidly after infection in early disease (stage 1), peaking at 14 dpi. Levels then dropped rapidly to pre-infection levels by 35 dpi. In contrast, there was a marginal increase in CSF neopterin during early infection, with a minor peak at 21 dpi. Serum CXCL13 increased rapidly from 7 dpi, peaking at 28 dpi. Levels dropped upon sub-curative treatment with DA. CXCL13 concentrations in CSF also increased gradually in early stage disease and continued to rise after sub-curative treatment with DA. Curative treatment with Mel B resulted in its gradual decline, reaching pre-infection levels 105 days later. Conclusions CSF neopterin and CXCL13 peak levels coinciding with time of relapses demonstrates the potential of these biomarkers in staging and detecting treatment failure. Moreover, the rapid fall in CSF neopterin after curative treatment confirms its great potential for use in development of a test of cure.
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