Browsing by Author "Mulindwa, Julius"
Now showing 1 - 11 of 11
Results Per Page
Sort Options
Item Candidate gene family-based and case-control studies of susceptibility to high Schistosoma mansoni worm burden in African children(AAS open research, 2021) Nyangiri, Oscar A.; Sokouri, A. Edwige; Koffi, Mathurin; Mewamba, Estelle; Simo, Gustave; Namulondo, Joyce; Mulindwa, Julius; Nassuuna, Jacent; Alison, Elliott; Karume, Kévin; Mumba, Dieudonne; M. Casacuberta-Partal; Dam, G. J. van; Bruno, Bucheton; Harry, Noyes; Matovu, EnockBackground: Approximately 25% of the risk of Schistosoma mansoni is associated with host genetic variation. We will test 24 candidate genes, mainly in the T h2 and T h17 pathways, for association with S. mansoni infection intensity in four African countries, using family based and case-control approaches. Methods: Children aged 5-15 years will be recruited in S. mansoni endemic areas of Ivory Coast, Cameroon, Uganda and the Democratic Republic of Congo (DRC). We will use family based (study 1) and case-control (study 2) designs. Study 1 will take place in Ivory Coast, Cameroon, Uganda and the DRC. We aim to recruit 100 high worm burden families from each country except Uganda, where a previous study recruited at least 40 families. For phenotyping, cases will be defined as the 20% of children in each community with heaviest worm burdens as measured by the circulating cathodic antigen (CCA) assay. Study 2 will take place in Uganda. We will recruit 500 children in a highly endemic community. For phenotyping, cases will be defined as the 20% of children with heaviest worm burdens as measured by the CAA assay, while controls will be the 20% of infected children with the lightest worm burdens. Deoxyribonucleic acid (DNA) will be genotyped on the Illumina H3Africa SNP (single nucleotide polymorphisms) chip and genotypes will be converted to sets of haplotypes that span the gene region for analysis. We have selected 24 genes for genotyping that are mainly in the Th2 and Th17 pathways and that have variants that have been demonstrated to be or could be associated with Schistosoma infection intensity. Analysis: In the family-based design, we will identify SNP haplotypes disproportionately transmitted to children with high worm burden. Case-control analysis will detect overrepresentation of haplotypes in extreme phenotypes with correction for relatedness by using whole genome principal components.Item Differences in gene expression profiles in early and late stage rhodesiense HAT individuals in Malawi(PLoS neglected tropical diseases, 2023) Nambala, Peter; Mulindwa, Julius; Harry, Noyes; Alibu, Vincent Pius; Nerima, Barbara; Namulondo, Joyce; Nyangiri, Oscar; Matovu, Enock; Annette, MacLeod; Musaya, JanelisaT. b. rhodesiense is the causative agent of Rhodesian human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected with T. b. rhodesiense was used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease foci. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R Studio using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 23 r-HAT case samples and 28 healthy controls with 7 controls excluded for downstream analysis as outliers. A total of 4519 genes were significant differentially expressed (p adjusted <0.05) in individuals with early stage 1 r-HAT disease (n = 12) and 1824 genes in individuals with late stage 2 r-HAT disease (n = 11) compared to controls. Enrichment of innate immune response genes through neutrophil activation was identified in individuals with both early and late stages of the disease. Additionally, lipid metabolism genes were enriched in late stage 2 disease. We further identified uniquely upregulated genes (log2 Fold Change 1.4–2.0) in stage 1 (ZNF354C) and stage 2 (TCN1 and MAGI3) blood. Our data add to the current understanding of the human transcriptome profiles during T. b. rhodesiense infection. We further identified biological pathways and transcripts enriched than were enriched during stage 1 and stage 2 r-HAT. Lastly, we have identified transcripts which should be explored in future research whether they have potential of being used in combination with other markers for staging or r-HAT.Item Gene Expression Changes in Mammalian Hosts during Schistosomiasis(Open Research Africa, 2021) Namulondo, Joyce; Mulindwa, Julius; Nyangiri, Oscar A.; Egesa, Moses; Noyes, Harry; Matovu, EnockSchistosomiasis 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.Item High prevalence of Schistosoma mansoni infection and stunting among school age children in communities along the Albert-Nile, Northern Uganda: A cross sectional study(PLoS neglected tropical diseases, 2022) Mulindwa, Julius; Namulondo, Joyce; Kitibwa, Anna; Nassuuna, Jacent; Asanya Nyangiri, Oscar; Kimuda, Magambo Phillip; Boobo, Alex; Nerima, Barbara; Busingye, Fred; Rowel, Candia; Namukuta, Annet; Ssenyonga, Ronald; Ukumu, Noah; Paul, Ajal; Adriko, Moses; Harry, Noyes; Claudia, J. de Dood; Paul, L. A. M. CorstjensBackground Knowing the prevalence of schistosomiasis is key to informing programmes to control and eliminate the disease as a public health problem. It is also important to understand the impact of infection on child growth and development in order to allocate appropriate resources and effort to the control of the disease. Methods We conducted a survey to estimate the prevalence of schistosomiasis among school aged children in villages along the Albert-Nile shore line in the district of Pakwach, North Western Uganda. A total of 914 children aged between 10–15 years were screened for Schistosoma mansoni using the POC-CCA and Kato Katz (KK) techniques. The infection intensities were assessed by POC-CCA and KK as well as CAA tests. The KK intensities were also correlated with POC-CCA and with CAA intensity. Anthropometric measurements were also taken and multivariate analysis was carried out to investigate their association with infection status. Results The prevalence of schistosomiasis using the POC-CCA diagnostic test was estimated at 85% (95% CI: 83–87), being highest amongst children living closer to the Albert-Nile shoreline. Visual scoring of the POC-CCA results was more sensitive than the Kato Katz test and was positively correlated with the quantified infection intensities by the CAA test. The majority of the children were underweight (BMI<18.5), and most notably, boys had significantly lower height for age (stunting) than girls in the same age range (p < 0.0001), but this was not directly associated with S. mansoni infection. Conclusion High prevalence of S. mansoni infection in the region calls for more frequent mass drug administration with praziquantel. We observed high levels of stunting which was not associated with schistosomiasis. There is a need for improved nutrition among the children in the area.Item 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, EnockBackground 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.Item 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, BarnabasEnteroviruses (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.Item 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, EnockHuman 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 wasItem 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 MackOver 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.Item 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.Item 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, RhonaFood 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 diseaseItem 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, RhonaFood 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.