Schistosoma haematobium infection is associated with alterations in energy and purine-related metabolism in preschool-aged children

Osakunor, Derick Nii Mensah; Mduluza, Takafira; Osei‐Hyiaman, Douglas; Burgess, Karl; Woolhouse, Mark E. J.; Mutapi, Francisca

doi:10.1371/journal.pntd.0008866

Cited by 16 publications

(18 citation statements)

References 91 publications

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“…In the current study we observed an upregulation of the TBC1 domain family member 4 ( Tbc1d4 ), which is known to enhance glucose uptake and insulin sensitivity in tissues [ 80 ]. Our findings confirm the role of such proteomic pathways in enhancing host glucose uptake to compensate for the nutrient-poor-conditions in the host, often associated with schistosome infection [ 81 , 82 ].…”

Section: Discussionsupporting

confidence: 86%

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

et al. 2022

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Urogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology are not well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology. Purified S. haematobium eggs or control vehicle were microinjected into the bladder walls of mice. Mice were sacrificed seven days post-injection and bladder proteins isolated and processed for proteome profiling using mass spectrometry. We demonstrate that biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism were significantly enriched in S. haematobium infection. S. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Our findings highlight the potential bladder protein indicators for host-parasite interplay and provide new insights into the complex dynamics of pathology and characteristic bladder tissue changes in urogenital schistosomiasis. The findings will be relevant for development of improved interventions for disease control.

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Section: Discussionsupporting

confidence: 86%

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

et al. 2022

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“…In the current study we observed an upregulation of the TBC1 domain family member 4 (Tbc1d4), which is known to enhance glucose uptake and insulin sensitivity in tissues [79]. Our findings confirm the role of such proteomic pathways in enhancing host glucose uptake to compensate for the nutrient-poor-conditions in the host, often associated with schistosome infection [80,81].…”

Section: Discussionsupporting

confidence: 85%

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Osakunor

Ishida

Lamanna

et al. 2021

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BackgroundUrogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology have not been well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology.MethodsPurified S. haematobium eggs or control vehicle were microinjected into the bladder walls of mice. Mice were sacrificed seven days post-injection and bladder proteins isolated and processed for proteome profiling using mass spectrometry.ResultsWe demonstrate that biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism were significantly enriched in S. haematobium infection.ConclusionS. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Our findings highlight the potential bladder protein indicators for host-parasite interplay and provide new insights into the complex dynamics of pathology and characteristic bladder tissue changes in urogenital schistosomiasis. The findings will be relevant for development of improved interventions for disease control.Author summaryThe molecular mechanisms underlying the urinary and genital pathology from urogenital schistosomiasis have not been well-defined. This has mainly been due to limited mechanistic studies and the lack of a suitable animal model for S. haematobium infection. We leveraged a mouse model of urogenital schistosomiasis, along with proteomics analysis, to determine the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to define protein pathways that may be involved in morbidity from urogenital schistosomiasis infection. Our results show that S. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism are significantly enriched in S. haematobium infection. Our findings highlight important protein indicators of host-parasite interactions in the bladder and their association with tissue changes in urogenital schistosomiasis. The findings presented here will be relevant for development of improved interventions for disease control, and contribute to realizing the 2021-2030 NTD goals by demonstrating evidence on the early events that occur during schistosome infection..

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“…In addition to nutrition, other factors such as childhood infections [ 38 ] also affect early child development. We have recently reported that early childhood infections with schistosomes affect metabolism in children aged 5 years and below, [ 39 ], which may have a subsequent impact on ECD. Whilst the detrimental effects of helminth infections (both STH [ 4 ] and schistosomes [ 7 ]) have been previously reported, to date there has been no study investigating the impact of schistosome infection on ECD focusing on children aged 5 years and below.…”

Section: Discussionmentioning

confidence: 99%

Assessing early child development and its association with stunting and schistosome infections in rural Zimbabwean children using the Griffiths Scales of Child Development

et al. 2021

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There is a paucity of reference early childhood development (ECD) data at community level in rural Africa. Our objective was to conduct a comprehensive assessment of ECD in rural Zimbabwe and determine the impact of stunting and schistosome infections on ECD. Using the Griffiths Scales of Child Development, we conducted a cross sectional assessment of Eye and Hand Coordination (EHC), Personal-Social-Emotional (PSE), Language and Communication (LC), Foundations of Learning (FL) and Gross Motor (GM) domains and the summary General Development (GD) in 166 children aged 6–72 months. The effects of stunting, malnutrition and Schistosoma haematobium infection on ECD was determined. The impact of praziquantel curative treatment of schistosome infection on the developmental scores was determined through a longitudinal follow up at 6 and 12 months. From an initial 166 children, 11 were found to have developmental deficits warranting further investigation. Of the remaining 155, 58.7% recorded a good (≥ average) score for the overall General Development (GD). Proportions of children scoring above the cut-off (≥ average) for each domain were GM (84.5%), PSE (80.6%), EHC (61.9%), FL (43.9%) and LC (44.5%). The prevalence of stunting was 26.8% (95% CI = 20.1%–34.8%) Scores for stunted children were significantly lower for EHC (p = 0.0042), GM (p = 0.0099), and GD (p = 0.0014) with the fraction of lower scores attributable to stunting being GM = 63.4%, GD = 46.6%, EHC = 45%, and LC = 21%. S. haematobium infection prevalence was 39.7% and mean infection intensity was 5.4 eggs/10 ml urine. Infected children had poorer cognitive performance scores for the FL (p = 0.0005) with 30.8% of poor FL attributable to the infection. Performance in all domains improved to the expected normal or above reference levels at 6 and 12 months post curative treatment of schistosome infections. Our study documented reference values for ECD in rural Zimbabwean children. The study detected deficiencies in the FL domain, which were more pronounced in children, infected with schistosomes, highlighting the need for provision of cognitive stimulation tools and access to early childhood foundation education. There is also need for improved child nutrition and treatment of schistosome infections to improve child development outcomes.

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Schistosoma haematobium infection is associated with alterations in energy and purine-related metabolism in preschool-aged children

Cited by 16 publications

References 91 publications

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Assessing early child development and its association with stunting and schistosome infections in rural Zimbabwean children using the Griffiths Scales of Child Development

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