Browsing by Author "Mugasa, Claire M."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Interleukin (IL)-6 and IL-10 Are Up Regulated in Late Stage Trypanosoma brucei rhodesiense Sleeping Sickness
    (PLoS Neglected Tropical Diseases, 2015) Kato, Charles D.; Alibu, Vincent P.; Nanteza, Ann; Mugasa, Claire M.; Matovu, Enock
    Sleeping sickness due to Trypanosoma brucei rhodesiense has a wide spectrum of clinical presentations coupled with differences in disease progression and severity across East and Southern Africa. The disease progresses from an early (hemo-lymphatic) stage to the late (meningoencephalitic) stage characterized by presence of parasites in the central nervous system. We hypothesized that disease progression and severity of the neurological response is modulated by cytokines.
  • Thumbnail Image
    Item
    Plasma Neuron-Specifc Enolase is not a reliable biomarker for staging Trypanosoma brucei rhodesiense sleeping sickness patients
    (BMC Research Notes, 2022) Kato, Charles D.; Twesigye, Dorothy; Alibu, Vincent P.; Nanteza, Ann; Nsubuga, Julius; Mugasa, Claire M.; Matovu, Enock
    Currently, the only available staging criterion for T. b. rhodesiense requires a lumber puncture to collect and later examine cerebrospinal fluid (CSF). This study examined the potential of plasma Neuron-Specific Enolase (NSE) in discriminating between early and late-stage patients. When median NSE levels were compared between early and late-stage patients, results showed a significant (P < 0.02) upregulation among late-stage patients (599.8 ng/mL). No significant differences (P > 0.9) in NSE levels were observed between early-stage patients (300 ng/mL) and controls (454 ng/mL). We used Receiver Operator Characteristic (ROC) curves to explore the likelihood of using plasma NSE as a potential stage biomarker in discriminating between early and late-stage HAT patients. Our results showed that NSE demonstrated an area under the curve (AUC) of 0.702 (95% CI 0.583–0.830). A high staging accuracy for NSE was obtained by using a cutoff of > 346.5 ng/mL with a sensitivity of 68.6% (95% CI 55–79.7%) and a specificity of 93.3% (95% CI 70.2–99.7%). Although our results demonstrate that plasma NSE is upregulated in T. b. rhodesiense sleeping sickness patients, its value in discriminating between late and early-stage patients is limited. However, future studies could consider improving its specificity by combining it with other identified plasma biomarkers.
  • Thumbnail Image
    Item
    Population genetic structure and temporal stability among Trypanosoma brucei rhodesiense isolates in Uganda
    (Parasites & Vectors, 2016) Kato, Charles D.; Alibu, Vincent P.; Nanteza, Ann; Mugasa, Claire M.; Matovu, Enock
    The population structure and role of genetic exchange in African trypanosomes have been previously analyzed albeit with contradictory findings. To further investigate the role of genetic polymorphism on the population genetic structure of Trypanosoma b. rhodesiense, we hypothesized that parasite genotypes are clonal and stable over time. We have undertaken a microsatellite marker analysis of T. b. rhodesiense isolates in a relatively new active HAT focus in Uganda (Kaberamaido-Dokolo-Amolatar) over a six-year period (2006–2012). We amplified six microsatellite markers by PCR directly from blood spotted FTA cards following whole genome amplification. The majority of loci demonstrated an excess of heterozygosity (Ho > He, FIS < 0). We identified 26 unique genotypes among the 57 isolates, accounting for 45.6 % genotypic polymorphism. The presence of a high proportion of samples with repeated genotypes (54.4 %, 31/57), disagreement with Hardy-Weinberg equilibrium, and significant linkage disequilibrium between loci pairs, provide evidence that T. b. rhodesiense isolates from this focus are clonal. Our results show low values of FST’ (0–0.115) indicating negligible genetic differentiation across temporal isolates. Furthermore, predominant genotypes isolated in 2006 were still detectable in 2012. Our findings confirm the notion that endemicity is maintained by stable genotypes rather than an influx of new genotypes. Our results have considerable importance in understanding and tracking the spread of sleeping sickness with significant implication to disease control.
  • Thumbnail Image
    Item
    Relationship between Trypanosoma brucei rhodesiense genetic diversity and clinical spectrum among sleeping sickness patients in Uganda
    (BMC Research Notes, 2017) Kato, Charles D.; Mugasa, Claire M.; Nanteza, Ann; Matovu, Enock; Alibu, Vincent P.
    Human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense in East and southern Africa is reported to be clinically diverse. We tested the hypothesis that this clinical diversity is associated with a variation in trypanosome genotypes. Trypanosome DNA isolated from HAT patients was genotyped using 7 microsatellite markers directly from blood spotted FTA cards following a whole genome amplification. All markers were polymorphic and identified 17 multi-locus genotypes with 56% of the isolates having replicate genotypes. We did not observe any significant clustering between isolates and bootstrap values across major tree nodes were insignificant. When genotypes were compared among patients with varying clinical presentation or outcome, replicate genotypes were observed at both extremes showing no significant association between genetic diversity and clinical outcome. Our study shows that T. b. rhodesiense isolates are homogeneous within a focus and that observed clinical diversity may not be associated with parasite genetic diversity. Other factors like host genetics and environmental factors might be involved in determining clinical diversity. Our study may be important in designing appropriate control measures that target the parasite.