Jebet, Clarah2026-01-222026-01-222025http://41.89.96.81:4000/handle/123456789/3392The clinical manifestations of Rhodesian human African trypanosomiasis (rHAT), which is caused by T. b. rhodesiense, range from acute illness to chronic illness. The basis of this is poorly understood but is suggested to involve host and pathogen factors, and their interaction. Among other factors, host immune factors, including cytokines, play a role which has begun to unravel, and has been shown to vary depending on the host, pathogen species and strain, and mode of infection. These factors have also been suggested to be potential diagnostic biomarkers. With clinical diagnosis important in HAT, understanding the underlying basis of varying infection outcomes is important. In this study, the vervet monkey (Chlorocebus aethiops), a non-human primate (NHP) model of HAT, was employed to investigate the involvement of cytokines in the manifestation of different clinical outcomes of rHAT. The work utilised pathological data along with cryopreserved, archived S€l'l1IIl and cerebrospinal fluid (CSF) samples obtained from previously infected animals. Two groups of vervet monkeys were infected with strains KETRI 3801 and KETRI 3928 to represent acute and chronic disease forms, respectively, alongside an uninfected control group. Three animals per group (n=3) for plasma analysis and two animals per group(n=2) for CSF analysis were selected due to limited resources available. Quantities of immune modulators, namely INF-y, TGF-[3, TNF-(X, IL-113, IL-6, IL-10, IL-12, IL-13 and a brain damage biomarker protein, S100B were determined, and pathological data, including survival time, parasitaemia, packed cell volume (PCV), temperature, weight and food intake, were analysed. The levels of individual cytokines showed variations in the course of infection. Levels of IL-12, IL-6 and IL-l[5 cytokines were significantly increased (p<0.05) from the early stage through to the onset of late-stage disease. Additionally, cerebrospinal fluid (CSF) parasite counts and White blood cell (WBC) levels were higher in KETRI 3801 infections compared to KETRI 3928. IL-12, IL-6 and IL-1B cytokines were particularly higher in acute infection, possibly contributing to the severity of the disease in KETRI 3801 infections, while the interaction between IL-113, IL-6 and IL-10 played a typical pro- and counter-inflammatory response during infection progression. Fluctuations in parasitaemia were observed in infected animals, with the KETRI 3801 cohort exhibiting a higher parasitaemia (peak antilog 8.7) than KETRI 3928 (peak antilog 7.8). In addition, infected animals had higher febrile temperature, lower body weight and PCV, which these much pronounced in acute as compared to chronic infections. Monkeys infected with KETRI 3801 and KETRI 3928 had a mean survival time of 28 and 95 days, respectively. The findings suggest strain-directed and host-dependent immunomodulation as the basis of the different infection outcomes. Also, cytokines are key regulators of disease progression and severity in the NHP model of HAT, and they are essential for understanding the differences in infection outcomesenCytokinesVervet monkeysThesis