Browsing by Author "Mulindwa, Julius"

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    Gene Expression Changes in Mammalian Hosts during Schistosomiasis
    (Open Research Africa, 2021) Namulondo, Joyce; Mulindwa, Julius; Nyangiri, Oscar A.; Egesa, Moses; Noyes, Harry; Matovu, Enock
    Schistosomiasis affects over 250 million people worldwide with an estimated mortality of more than 200,000 deaths per year in sub-Saharan Africa. Efforts to control schistosomiasis in the affected areas have mainly relied on mass administration of praziquantel, which kills adult but not immature worms of all Schistosoma species. Mammalian hosts respond differently to Schistosoma infection with some being more susceptible than others, which is associated with risk factors such as sociodemographic, epidemiological, immunological and/or genetic. Host genetic factors play a major role in influencing molecular processes in response to schistosomiasis as shown in gene expression studies. These studies highlight gene profiles expressed at different time points of infection using model animals. Immune function related genes; cytokines (Th1 and Th17) are upregulated earlier in infection and Th2 upregulated later indicating a mixed Th1/Th2 response. However, Th1 response has been shown to be sustained in S. japonicum infection. Immune mediators such as matrix metalloproteinases (Mmps) and tissue inhibitors of matrix metalloproteinases (Timps) are expressed later in the infection and these are linked to wound healing and fibrosis. Downregulation of metabolic associated genes is recorded in later stages of infection. Most mammalian host gene expression studies have been done using rodent models, with fewer in larger hosts such as bovines and humans. The majority of these studies have focused on S. japonicum infections and less on S. haematobium and S. mansoni infections (the two species that cause most global infections). The few human schistosomiasis gene expression studies so far have focused on S. japonicum and S. haematobium infections and none on S. mansoni, as far as we are aware. This highlights a paucity of gene expression data in humans, specifically with S. mansoni infection. This data is important to understand the disease pathology, identify biomarkers, diagnostics and possible drug targets.
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    Molecular characterization of non‐polio enteroviruses isolated from acute flaccid paralysis patients in Uganda
    (Journal of Medical Virology, 2021) Tushabe, Phionah; Howard, Wayne; Bwogi, Josephine; Birungi, Molly; Eliku, James P.; Kakooza, Proscovia; Bukenya, Henry; Namuwulya, Prossy; Gaizi, Joseph; Tibanagwa, Mayi; Kabaliisa, Theopista; Mulindwa, Julius; Muhanguzi, Dennis; Suchard, Melinda; Gumede, Nicksy; Bakamutumaho, Barnabas
    Enteroviruses (EVs) are RNA viruses that can cause many clinical syndromes including acute flaccid paralysis (AFP). Within the global polio laboratory network, EVs are categorized either as polioviruses or non‐polio enteroviruses (NPEVs). Specific NPEVs have been described in polio‐like residual paralytic events in AFP patients. Retrospective analysis of 112 NPEV isolates from AFP patients was performed and thirty one NPEV types were identified of which 91% were Enterovirus B and 9% were Enterovirus A species. The NPEVs were distributed across the country with most patients in the eastern region (41/89; 46.1%). The highest proportion of patients were children less than 5 years (77/89; 86.5%) and male patients were more common (54/89; 60.7%). Echovirus 11 (11/89; 12.4%) was frequently observed and phylogenetic analysis of these sequences revealed high diversity. Coxsackievirus B5 (CV‐B5), CV‐B6, E21, and EV‐B69 were only seen in patients with residual paralysis. Analyses of the EV‐A71 sequence indicated a unique genogroup.
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    No evidence for association between APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations
    (PLoS neglected tropical diseases, 2018) Magambo, Phillip K.; Noyes, Harry; Mulindwa, Julius; Enyaru, John; Alibu, Vincent P.; Sidibe, Issa; Mumba Ngoyi, Dieuodonne; Hertz-Fowler, Christiane; MacLeod, Annette; Tastan Bishop, Ozlem; Matovu, Enock
    Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT. Methodology and results We included 238 and 202 participants from the Busoga Tbr and Northwest Uganda Tbg endemic areas respectively. Single Nucleotide Polymorphism (SNP) genotype data were analysed in the CGAS. The study was powered to find odds ratios > 2 but association testing of the SNPs with HAT yielded no positive associations i.e. none significant after correction for multiple testing. However there was strong evidence for no association with Tbr HAT and APOL1 G2 of the size previously reported in the Kabermaido district of Uganda. Conclusions/Significance A recent study in the Soroti and Kaberamaido focus in Central Uganda found that the APOL1 G2 allele was strongly associated with protection against Tbr HAT (odds ratio = 0.2, 95% CI: 0.07 to 0.48, p = 0.0001). However, in our study no effect of G2 on Tbr HAT was
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    Transcriptome analysis of peripheral blood of Schistosoma Mansoni Infected Children from the Albert Nile Region in Uganda Reveals Genes Implicated in Fibrosis Pathology.
    (bioRxiv, 2023) Namulondo, Joyce; Nyangiri, Oscar Asanya; Kimuda, Magambo Phillip; Nambala, Peter; Nassuuna, Jacent; Egesa, Moses; Nerima, Barbara; Biryomumaisho, Savino; Nabukenya, Immaculate; Drago, Kato; Tweyongyere, Robert; Matovu, Enock; Mulindwa, Julius; Mugasa, Claire Mack
    Over 290 million people are infected by schistosomes worldwide. Schistosomiasis control efforts focus on mass drug treatment with praziquantel (PZQ), a drug that kills the adult worm of all Schistosoma species. Nonetheless, re-infections have continued to be detected in endemic areas with individuals living in the same area presenting with varying infection intensities. Our objective was to characterize the transcriptome profiles in peripheral blood of children between 10 - 15 years with varying intensities of Schistosoma mansoni infection living along the Albert Nile in Uganda. RNA extracted from peripheral blood collected from 44 S. mansoni infected (34 high and 10 low by circulating anodic antigen [CAA] level) and 20 uninfected children was sequenced using Illumina NovaSeq S4 and the reads aligned to the GRCh38 human genome. Differential gene expression analysis was done using DESeq2 and enriched pathways in differentially expressed genes (DEGs) were identified using REACTOME. Principal component analysis revealed clustering of gene expression by gender when S. mansoni infected children were compared with uninfected children. In addition, we identified 14 DEGs between S. mansoni infected and uninfected individuals, 56 DEGs between children with high infection intensity and uninfected individuals, 33 DEGs between those with high infection intensity and low infection intensity and no DEGs between those with low infection and uninfected individuals. We also observed upregulation and downregulation of some DEGs that are associated with fibrosis and its regulation. These data suggest expression of fibrosis associated genes as well as genes that regulate fibrosis in S. mansoni infection. The relatively few significant DEGS observed in children with schistosomiasis suggests that chronic S. mansoni infection is a stealth infection that does not stimulate a strong immune response.
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    Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression
    (NPJ Genomic Medicine, 2021) Mwesigwa, Savannah; Williams, Lesedi; Retshabile, Gaone; Katagirya, Eric; Mboowa, Gerald; Mlotshwa, Busisiwe; Kyobe, Samuel; Kateete, David P.; Mujjwiga Wampande, Eddie; Wayengera, Misaki; Wata Mpoloka, Sununguko; Mirembe, Angella N.; Kasvosve, Ishmael; Morapedi, Koketso; Kisitu, Grace P.; Kekitiinwa, Adeodata R.; Anabwani, Gabriel; Joloba, Moses L.; Matovu, Enock; Mulindwa, Julius; Noyes, Harry; Botha, Gerrit; Brown, Chester W.; Mardon, Graeme; Matshaba, Mogomotsi; Hanchard, Neil A.
    Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%; p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), with Anelloviridae showing strong association with LTNP status (p = 3 × 10−4; q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02; q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of the Anelloviridae reads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.
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    Value Chain Hygiene Practices and Microbial Contamination of Street and Market Vended Ready-to- Eat grasshopper, Ruspolia differens in Uganda: Implications for food safety and public health
    (Research Square, 2022) Rutaro, Karlmax; Hawumba, Joseph; Nakimuli, Jane; Mulindwa, Julius; Malinga, Geoffrey M.; Baingana, Rhona
    Food safety is a major public health issue, particularly in developing countries. Ready-to-eat street-vended foods contribute to daily dietary life, but with elevated food safety burden. Here, hygiene and food safety practices as well as the microbial contamination in Uganda's edible grasshopper value chain was evaluated. Methods This was a cross-sectional mixed methods study with both qualitative and quantitative approaches. A face-toface administered questionnaire and observational checklists were used to collect data. A total of 29 households (Kampala; 12 and Masaka; 17) participated, and grasshopper samples collected along the value chain. Indicator pathogens were analysed using standard microbiological methods. Results Sociodemographic characteristics reveal that two-thirds of households in Kampala and 53% in Masaka were female headed. In Kampala and Masaka, respectively, 50% and 12% of households had earth or sand floors. All households in Kampala were one or two-roomed dwellings with no separate room as a kitchen, and shared a toilet compared to 43%, 65% and 53%, respectively, in Masaka. 83% households in Kampala and 56% in Masaka obtained drinking water from public taps. Handwashing was inadequate and none of the actors was observed to wash their hands after taking a break or handling waste. Only 8.3% respondents had raised racks for drying utensils. For vendors, wearing protective clothing was not common, with only 28.5% in Kampala and 30.8% in Masaka wearing an apron. Containers for vending grasshoppers were largely uncovered and the utensils (spoon or cup) for measuring the grasshoppers were left mainly uncovered during the observation period. Indicator organisms, E. coli and Salmonella typhimurium, were detected. E. coli was the most common contaminant, but with lower levels in Masaka compared to Kampala. Salmonella typhimurium was mainly a burden in Kampala. Conclusions Our findings demonstrate that there are enormous contributors to poor hygiene and sanitation along the value chain. The existence of pathogenic bacteria such as E. coli in ready-to-eat foods imply that their consumption pose a health risk. There is an urgent need to create awareness among the actors,through regular trainings on food safety and personal hygiene practices in food handling and inspection to prevent foodborne disease
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    Value chain hygiene practices and microbial contamination of street and market vended ready-to-eat grasshopper, Ruspolia differens in Uganda: Implications for food safety and public health
    (Elsevier Ltd, 2024-02) Rutaro, Karlmax; Hawumba, Joseph; Nakimuli, Jane; Mulindwa, Julius; Malinga, Geoffrey M; Baingana, Rhona
    Food safety is a major public health issue particularly in developing countries. Ready-to-eat street-vended foods contribute significantly to dietary intake in urban and peri-urban areas, but with elevated public health risk. In this study, hygiene and food safety practices as well as the microbial contamination in Uganda's edible grasshopper value chain were evaluated.''A total of 29 grasshopper-processing households participated, and grasshopper samples collected. Indicator pathogens were analyzed using standard microbiological methods. In Kampala 50% and in Masaka 12% households had earth floors. All households in Kampala were one or two-roomed dwellings with no separate room as a kitchen, and shared a toilet. In contrast, 59% of households in Masaka had three or more rooms, 35% had a separate room for a kitchen and 47% did not share a toilet. 83% households in Kampala and 56% in Masaka obtained drinking water from public taps. Handwashing was inadequate and none of the actors was observed to wash their hands after taking a break or handling waste. For vendors, wearing protective clothing was not common, with only 28.5% in Kampala and 30.8% in Masaka wearing an apron. Containers for vending grasshoppers were largely uncovered and the utensils for measuring the grasshoppers were left mainly uncovered. Indicator organisms, Escherichia coli and Salmonella typhimurium, were detected. E. coli was the most common contaminant, but with lower levels in Masaka compared to Kampala. S. typhimurium was mainly a burden in Kampala. Our findings demonstrate that there are enormous contributors to poor hygiene and sanitation along the edible grasshopper value chain. The existence of pathogenic bacteria such as E. coli in ready-to-eat foods imply that their consumption poses a health risk.