Browsing by Author "Ssemaganda, Aloysious"

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    High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses
    (medRxiv, 2023) Namuniina, Annemarie; Muyanja, Enoch S.; Biribawa, Victoria M.; Ssemaganda, Aloysious; Nanteza, Ann; Bagaya, Bernard Ssentalo; Galwango, Ronald M.; Redd, Andrew D.
    The estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.
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    High Schistosoma mansoni infection intensity is associated with distinct gut microbiome and low levels of systemic cytokines in children along the Albert-Nile, Northern Uganda
    (Research Square, 2024) Mulindwa, Julius; Lujumba, Ibra; Musiime, Caroline; Namulondo, Joyce; Magambo, Phillip Kimuda; Nyangiri, Oscar; Gloria, Cuu; Mwubaha, Caroline; Tukwasibwe, Stephen; Ssemaganda, Aloysious; Ssewanyana, Isaac; Nerima , Barbara; Baingana, Rhona; Harry, Noyes; Annette, MacLeod; Matovu, Enock
    Background Schistosomiasis is a chronic neglected disease that affects millions of people in sub Saharan Africa, with a range of impacts on both host immune responses and the gut microbiome. The gut microbiota plays a fundamental in role in the host’s nutrition, metabolism, protection against pathogens, and modulation of host immunity. There is a need to understand the role of the gut microbiome in pathophysiology of Schistosoma mansoni infection and how this influences the host’s immune response. Methodology: A cross sectional study was carried out on 140 faecal samples collected from school children aged 10-15years residing in the schistosomiasis endemic hot spots of the Albert-Nile, Pakwach district, Northern Uganda. The samples were categorised by S. mansoni infection intensity based on the Kato Katz test. Faecal DNA was isolated and microbiome composition was determined by 16S rRNA V3-V4 sequencing. Plasma Th1/Th2 profiling of 13 cytokines was carried out on the Luminex platform and compared with respect to S. mansoni infection intensities. Results The genera Phascolarctobaterium and Prevotella_7 were significantly enriched (padj < 0.05, LDA > 3.0) in the high S. mansoni infection intensity group whereas, Ruminobacter and Alloprevotella were enriched in the Low infection intensity group. We observed significantly lower systemic Th1/Th2 cytokine levels between the high intensity infection and the control samples (padj < 0.05). Linear regression analysis using all cytokines as covariates showed that the genus Alloprevotella, Streptococcus, Gastranaerophilales and Ruminobacter were associated with systemic IL6 response. Conclusion There are alterations in the gut microbiome of S. mansoni infected children with distinct genera that discriminate the high and low infection intensity that could be potentially used as biomarkers. There is an association between the gut microbiome and systemic cytokine response whose mechanism in chronic disease pathophysiology can be further investigated.