Current Organisation

First Technical University

Current Job Title

Senior Lecturer

Biography

Project Title

Role of Schistosomiasis in dysbiosis, inflammation and bacterial translocation in children from Nigeria

EDCTP Project Call

Career Development Fellowship (CDF)

Host Organisation

Project Objectives

1. Characterise the microbiome and gut barrier function of Schistosoma, Salmonella and SchistosomaSalmonella co-morbid infections in Nigerian children 2. Evaluate the temporal changes in microbiome structure after praziquantel administration 3. Determine the impact of S. haematobium-infected microbiome on Salmonella colonization and shedding by utilizing gnotobiotic mouse faecal microbiome transplant model

Study Design

Observational

Project Summary

Schistosoma infections are most prevalent and intense in children. Salmonella is another infection that can impact this population and it has similar modes of transmission as schistosomiasis, due to a lack of good hygiene practices, access to clean water, and poor health care facilities in affected countries. Since S. Typhi, the causative agent of typhoid fever is a human host-restricted pathogen a comprehensive understanding of the co-morbid risk factors associated with infection and bacterial shedding is critical for disease control. Schistosomiasis has been long recognized for establishing a symbiotic relationship with Salmonella, yet its contribution to the epidemiology of Salmonella and asymptomatic shedding is unknown. There is evidence to demonstrate that schistosomiasis infection modulates the gut microbiome causing dysbiosis and a bloom in Proteobacteria. Based on this evidence, I aim to determine the impact of Schistosoma infection on the gut microbiome, gut barrier function and Salmonella translocation. To achieve this aim, this study is investigating three objectives (i) Characterise the microbiome and gut barrier function of Schistosoma, Salmonella and Schistosoma-Salmonella co-morbid infections in Nigerian children (ii) Evaluate the temporal changes in microbiome structure after praziquantel administration (iii) Determine the impact of S. haematobium-infected microbiome on Salmonella colonization and shedding by utilizing fecal microbiome transplant mice models. We obtained relevant ethics approval from the Kebbi State Ethics Research Committee and began sample collection in December 2020 with a cross-sectional survey to identify children aged between 11-15 years that were infected with urogenital schistosomiasis. From our community survey, we sampled 196 children within the age bracket and we were able to recruit 46 that were positive for urogenital schistosomiasis. These children have been followed up every three months for 1 year, and we collected our last data point in December 2021. We have experienced about 15% drop out in the children being followed up due to relocation out of their communities for various reasons such as farming or visiting family members. An interesting observation from the children infected was that there was epidemiological clustering of the infected children; i.e. they all seemed to live near each other surrounded by water bodies even though we did not do a house to house survey. This clustering pattern was achieved through application of remote sensing and geographic Information System tools through a new collaboration with Prof Samuel Adelabu of Free State University, South Africa. Next, we started the clinical collection at the hospital from April 2021 onwards and met our recruitment target of 370 febrile patients. We have analysed the samples to determine the bacteria species present and antibiotic sensitivity patterns of the isolates. The fecal DNA extracted from urogenital schistosomiasis infected and uninfected kids longitudinally over one year at 3 months interval was sequenced to determine the temporal impacts of urogenital schistosomiasis on the gut microbiome of the kids. I spent 6 months at Brown University in the lab of Prof Peter Belenky that is well known for carrying out work on the microbiome. The focus of my training was on learning how to use R, analysing 16S sequencing data, and use of sequencing technologies like Nanopore and Illumina technologies. We observed using Bray Curtis similarity index that the microbiome profile at 9 and 12 months was different from the earlier time points. We also observed that praziquantel treatment seemed to have an impact on the gut microbiome of the kids within the first three months. Overall, at baseline, we observed a state of dysbiosis as described by differences in the ratio of Firmicutes and Bacteriodes community in the gut of the kids. Further, I gavaged gnotobiotic (germ free) mice with frozen fecal pellets to determine the impacts of S. haematobium infection on susceptibility to a bacteria- Salmonella infection. Initial pilot studies carried out suggests that infection does not alter the hosts susceptibility to Salmonella inoculation. Through engagement with the community, we have carried out community sensitisations on the importance of our findings, submitted manuscripts for publications and trained students in using 16S sequencing techniques and data analyses. These findings have important implications in the elimination of schistosomiasis from endemic communities, clearly mass drug chemotherapy without provision of alternative sources of clean water and good education on sanitary and hygiene practices will continue to yield minimal success. Country programmes targeting schistosomiasis elimination should endeavour to incorporate measures such as sanitation, hygiene and provision of alternative sources of water for domestic uses. This will prevent reinfection of subjects at risk which we observed in our follow-up studies so far. In all, we observed that 3 of the 46 kids that were infected and treated with praziquantel in our study were reinfected during our follow up visits. For more information on our project, please visit: www.sidicnigeria.com.

Results & Outcomes