Paediatric schistosomiasis: dynamics and consequences

Urogenital schistosomiasis, caused by the parasite helminth Schistosoma haematobium, is one of the major parasitic diseases affecting millions of preschool-aged children (PSAC), i.e. aged 5 years and below, in sub-Saharan Africa. Diagnosis is via microscopic detection of parasite eggs in urine, and treatment is by administration of the antihelminthic drug of choice, praziquantel. Epidemiological studies show that PSAC are infected as early as a year old, with negative impacts on nutrition, growth, cognition, and overall health. Despite recommendations to treat PSAC with schistosomiasis, this age group is still excluded from treatment programmes for various reasons including: a) the lack of a child-friendly formulation of praziquantel, b) lack of a coherent strategy to access PSAC for screening and treatment, and c) lack of compelling evidence on infection, disease and treatment dynamics. Currently, the global infection and disease burden is not fully known in this age group, and longitudinal studies to describe the incidence of infection and morbidity, especially the early events that occur during the very first infection and treatment in PSAC are lacking. In addition, the mechanistic pathways of disease, treatment, and immunity are poorly understood in this age group. Operational difficulties including obtaining parasitology samples for diagnosis, failure to detect light infections, and inadequate knowledge about risk factors have also contributed to a lower research focus on PSAC, relative to school-aged children and adults. To address these, I completed a series of studies, based on a larger longitudinal study on paediatric urogenital schistosomiasis (population age range: 6 months–5 years) conducted in the Shamva district of Zimbabwe. The aim was to determine the dynamics of infection, morbidity and treatment of the first S. haematobium infection, and to examine the impact of a regular screening and treatment strategy on (re)infections. I also determined the early host metabolic changes associated with the first S. haematobium infection as well as the impact of schistosome infection on the gut microbiome, and how these relate to disease progression, morbidity and overall health. I determined that 92% of microhaematuria, 38% of stunting, and between 9%–34% of malnutrition (depending on what index is used) are attributable to S. haematobium infection in PSAC; schistosome-positive children were more likely to present with microhaematuria (25 times) and stunting (2 times), compared to uninfected children. I demonstrated the annual incidence of first schistosome infections (17.4%) and urinary morbidity (microhaematuria; 20.4%), with significant incidences recorded every quarter. I showed that within 3 months of the first infection, a significant amount of urinary morbidity, i.e. microhaematuria (61%) occurs, and is resolved 3 months post-praziquantel treatment. In PSAC with no history of schistosome infection, regular quarterly screening and treatment of the first S. haematobium infection reduces the actual time at risk of infection in the population, and results in reduced rates of subsequent new infections. A single praziquantel treatment of schistosome infections (upon first infection) was associated with reduced reinfection rates and intensity a year later; an effect comparable to that observed post-treatment in chronically-infected children. In young children experiencing their first schistosome infection, there are significant increases (≥2-fold) in serum metabolites primarily linked with energy (glycolysis, pentose phosphate pathway, starch, and galactose) and purine metabolism. The observed changes were commensurate with increasing infection intensity and were restored 3 months post-curative antihelminthic treatment. The affected metabolic pathways and its implications on the natural adaptive metabolic responses were consistent with parasite survival and development of schistosome morbidity in PSAC, including malnutrition, stunting and poor physical and cognitive performance. Metagenomic analysis of the gut microbiota showed that the abundance of bacteria and fungi phyla from Proteobacteria, Ascomycota, and Basidiomycota, differed between schistosome-infected versus uninfected children. Specifically, infection was associated with increases in Pseudomonas, Stenotrophomonas, Derxia, Thalassospira, Aspergillus, Tricholoma, and Periglandula, and a decrease in Azospirillum. I found evidence of 262 antimicrobial resistance genes, from 12 functional drug classes, but these showed no association with individual-specific data, including schistosome infection. This points to microbiome dysbiosis as an additional consequence of schistosome infection, with implications for morbidity, immunity, and overall health. Taken together, the findings of this thesis show that early in the first S. haematobium infection, PSAC present with significant morbidity, and this resolves quickly with praziquantel treatment. A routine screen-and-treat strategy will optimise the chances of detecting and treating infections early, while reducing the risk of new and reinfections. The findings further highlight microbiome and metabolic alterations during schistosome infection, which may be relevant for disease pathogenesis. This thesis presents an integrative approach to schistosomiasis studies in PSAC, which contributes to evidence on infection/disease burden and dynamics, the applicability of currently available tools in the diagnosis, treatment and control of schistosomiasis, as well as the systemic impacts of infection on the host microbiome, metabolism, and overall health. It also adds to the repository of information, by providing a novel metagenomics and metabolomics dataset of PSAC from Zimbabwe. The findings reaffirm the need for early diagnosis and treatment of schistosome infections in PSAC to avert accumulative morbidity, and will inform stakeholders in providing new and appropriate interventions targeted at reducing schistosome-related pathology in young children

Assessing early child development and its association with stunting and schistosome infections in rural Zimbabwean children using the griffiths scales of child development

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

Dynamics of paediatric urogenital schistosome infection, morbidity and treatment:a longitudinal study among preschool children in Zimbabwe

Background Recent research has shown that in schistosome-endemic areas preschool-aged children (PSAC), that is, <=5 years, are at risk of infection. However, there exists a knowledge gap on the dynamics of infection and morbidity in this age group. In this study, we determined the incidence and dynamics of the first urogenital schistosome infections, morbidity and treatment in PSAC.Methods Children (6 months to 5 years) were recruited and followed up for 12 months. Baseline demographics, anthropometric and parasitology data were collected from 1502 children. Urinary morbidity was assessed by haematuria and growth-related morbidity was assessed using standard WHO anthropometric indices. Children negative for Schistosoma haematobium infection were followed up quarterly to determine infection and morbidity incidence.Results At baseline, the prevalence of S haematobium infection and microhaematuria was 8.5% and 8.6%, respectively. Based on different anthropometric indices, 2.2%–8.2% of children were malnourished, 10.1% underweight and 18.0% stunted. The fraction of morbidity attributable to schistosome infection was 92% for microhaematuria, 38% for stunting and malnutrition at 9%–34%, depending on indices used. S haematobium-positive children were at greater odds of presenting with microhaematuria (adjusted OR (AOR)=25.6; 95% CI 14.5 to 45.1) and stunting (AOR=1.7; 95% CI 1.1 to 2.7). Annual incidence of S haematobium infection and microhaematuria was 17.4% and 20.4%, respectively. Microhaematuria occurred within 3 months of first infection and resolved in a significant number of children, 12 weeks post-praziquantel treatment, from 42.3% to 10.3%; P<0.001.Conclusion We demonstrated for the first time the incidence of schistosome infection in PSAC, along with microhaematuria, which appears within 3 months of first infection and resolves after praziquantel treatment. A proportion of stunting and malnutrition is attributable to S haematobium infection. The study adds scientific evidence to the calls for inclusion of PSAC in schistosome control programmes

Coinfections and comorbidities in African health systems: At the interface of infectious and noninfectious diseases.

There is a disease epidemiological transition occurring in Africa, with increasing incidence of noninfectious diseases, superimposed on a health system historically geared more toward the management of communicable diseases. The persistence and sometimes emergence of new pathogens allows for the occurrence of coinfections and comorbidities due to both infectious and noninfectious diseases. There is therefore a need to rethink and restructure African health systems to successfully address this transition. The historical focus of more health resources on infectious diseases requires revision. We hypothesise that the growing burden of noninfectious diseases may be linked directly and indirectly to or further exacerbated by the existence of neglected tropical diseases (NTDs) and other infectious diseases within the population. Herein, we discuss the health burden of coinfections and comorbidities and the challenges to implementing effective and sustainable healthcare in Africa. We also discuss how existing NTD and infectious disease intervention programs in Africa can be leveraged for noninfectious disease intervention. Furthermore, we explore the potential for new technologies-including artificial intelligence and multiplex approaches-for diagnosis and management of chronic diseases for improved health provision in Africa

Schistosomiasis and the host metabolome in preschool-aged children: Schistosoma haematobium infection outcome data

Millions of preschool-aged children (PSAC), i.e. aged 5 years and below, in sub-Saharan Africa suffer from a neglected tropical disease caused by helminth parasitic worms, known as schistosomiasis (commonly referred to as bilharzia or snail fever). This was a study to determine the changes in host metabolic profiles, in response to the first Schistosoma haematobium infection and treatment in Zimbabwean preschool-aged children. The species S. haematobium is the most common, and accounts for about two-thirds of all schistosomiasis cases in Africa. Eighty-three children (age range, 2–5 years old) confirmed schistosome-negative (as determined by parasitological diagnosis, guardian interviews and examination of medical records) were recruited at baseline (T0). Children were followed up after three months for parasitological diagnosis of their first S. haematobium infection, as determined by microscopic egg counts in urine (T2). Children positive for infection were treated with the antihelminthic drug praziquantel, and treatment efficacy was checked three months after treatment (T3). Blood samples were taken at each time point (i.e. T0, T2, and T3) and serum metabolite profiles were measured by capillary electrophoresis mass spectrometry. The change in serum metabolite profiles (∆T) were compared between schistosome-infected versus uninfected children. This dataset is linked as part of the manuscript “Schistosoma haematobium infection is associated with alterations in energy and purine-related metabolism in preschool-aged children”Osakunor, Derick Nii Mensah; Mutapi, Francisca. (2020). Schistosomiasis and the host metabolome in preschool-aged children: Schistosoma haematobium infection outcome data, [dataset]. University of Edinburgh. School of Biological Sciences. https://doi.org/10.7488/ds/2930

Renal function in Ghanaian HIV-infected patients on highly active antiretroviral therapy: a case-control study.

BACKGROUND: HAART is anticipated to result in an increase in long-term survival, but may present with the development of associated complications. The aim of this study was to assess the renal function of HIV-infected patients on antiretroviral therapy. METHODS: A case-control study (January to May 2013) conducted at the Suntreso Government Hospital, Kumasi, Ghana. A total of 163 HIV-infected patients (mean age 39.9±10.22) were studied, of which 111 were on HAART (HIV-HAART) and 52 were not (HIV-Controls). Serum urea, creatinine, potassium, sodium, chloride and CD4 counts were measured with the determination of eGFR (CKD-EPI and MDRD). Data was analysed using GraphPad Prism. The Chi-square, t-test, one-way ANOVA and Spearman's correlation were used. P values <0.05 were considered significant. RESULTS: Mean CD4 count of HIV-Controls was higher than that of HIV-HAART but was not significant (p = 0.304). But for sodium levels which were higher in HIV-Controls (p = 0.0284), urea (p = 0.1209), creatinine (p = 0.7155), potassium (p = 0.454) and chloride (p = 0.6282) levels did not differ significantly between both groups. All serum biochemical parameters did not differ significantly, irrespective of duration on therapy and CD4 counts. Based on regimen, sodium, chloride, urea and creatinine did not differ significantly between TDF, EVF and NVP-based therapies. Prevalence of CKD (eGFR <60 ml/min/1.73 m2) in the total population was 9.9% and 3.7% with the MDRD and EPI-CKD equations respectively. CONCLUSIONS: Renal insufficiency remains prevalent in HIV patients. Changes in renal function occur in HIV infection and over the course of HAART but the difference at either stage is not significant. This suggests the role of HIV infection, HAART and the presence of traditional risk factors but not HAART in itself, in renal dysfunction. We however recommend a close monitoring of patients before and during HAART, to aid in evaluating drug combinations and implement dose modifications when necessary

Anaemia and Iron Homeostasis in a Cohort of HIV-Infected Patients: A Cross-Sectional Study in Ghana

Aim. We determined the prevalence of anaemia and evaluated markers of iron homeostasis in a cohort of HIV patients. Methods. A comparative cross-sectional study on 319 participants was carried out at the Tamale Teaching Hospital from July 2013 to December 2013, 219 patients on HAART (designated On-HAART) and 100 HAART-naive patients. Data gathered include sociodemography, clinical history, and selected laboratory assays. Results. Prevalence of anaemia was 23.8%. On-HAART participants had higher CD4/CD3 lymphocyte counts, Hb, HCT/PCV, MCV, MCH, iron, ferritin, and TSAT (P<0.05). Hb, iron, ferritin, and TSAT decreased from grade 1 to grade 3 anaemia and CD4/CD3 lymphocyte count was lowest in grade 3 anaemia (P<0.05). Iron (P=0.0072) decreased with disease severity whilst transferrin (P=0.0143) and TIBC (P=0.0143) increased with disease severity. Seventy-six (23.8%) participants fulfilled the criteria for anaemia, 86 (26.9%) for iron deficiency, 41 (12.8%) for iron deficiency anaemia, and 17 (5.3%) for iron overload. The frequency of anaemia was higher amongst participants not on HAART (OR 2.6 for grade 1 anaemia; OR 3.0 for grade 3 anaemia). Conclusion. In this study population, HIV-associated anaemia is common and is related to HAART status and disease progression. HIV itself is the most important cause of anaemia and treatment of HIV should be a priority compared to iron supplementation

Hepatic Enzyme Alterations in HIV Patients on Antiretroviral Therapy: A Case-Control Study in a Hospital Setting in Ghana.

Diagnosing hepatic injury in HIV infection can be a herculean task for clinicians as several factors may be involved. In this study, we sought to determine the effects of antiretroviral therapy (ART) and disease progression on hepatic enzymes in HIV patients.A case-control study conducted from January to May 2014 at the Akwatia Government Hospital, Eastern region, Ghana, The study included 209 HIV patients on ART (designated HIV-ART) and 132 ART-naive HIV patients (designated HIV-Controls). Data gathered included demography, clinical history and results of blood tests for hepatic enzymes. We employed the Fisher's, Chi-square, unpaired t-test and Pearson's correlation in analysis, using GraphPad Prism and SPSS. A P value < 0.05 was considered significant.Median CD4 lymphocyte count of HIV-ART participants (604.00 cells/mm3) was higher than that of HIV-Controls (491.50 cells/mm3; P = 0.0005). Mean values of ALP, ALT, AST and GGT did not differ between the two groups compared (P > 0.05). There was a significant positive correlation between hepatic enzymes (ALP, ALT, AST and GGT) for both groups (p < 0.01 each). Duration of ART correlated positively with ALT (p < 0.05). The effect size of disease progression on hepatic enzymes for both groups was small.Antiretroviral therapy amongst this population has minimal effects on hepatic enzymes and does not suggest modifications in therapy. Hepatic injury may occur in HIV, even in the absence of ART and other traditional factors. Monitoring of hepatic enzymes is still important in HIV patients

Hepatic Enzyme Alterations in HIV Patients on Antiretroviral Therapy: A Case-Control Study in a Hospital Setting in Ghana.

Diagnosing hepatic injury in HIV infection can be a herculean task for clinicians as several factors may be involved. In this study, we sought to determine the effects of antiretroviral therapy (ART) and disease progression on hepatic enzymes in HIV patients.A case-control study conducted from January to May 2014 at the Akwatia Government Hospital, Eastern region, Ghana, The study included 209 HIV patients on ART (designated HIV-ART) and 132 ART-naive HIV patients (designated HIV-Controls). Data gathered included demography, clinical history and results of blood tests for hepatic enzymes. We employed the Fisher's, Chi-square, unpaired t-test and Pearson's correlation in analysis, using GraphPad Prism and SPSS. A P value < 0.05 was considered significant.Median CD4 lymphocyte count of HIV-ART participants (604.00 cells/mm3) was higher than that of HIV-Controls (491.50 cells/mm3; P = 0.0005). Mean values of ALP, ALT, AST and GGT did not differ between the two groups compared (P > 0.05). There was a significant positive correlation between hepatic enzymes (ALP, ALT, AST and GGT) for both groups (p < 0.01 each). Duration of ART correlated positively with ALT (p < 0.05). The effect size of disease progression on hepatic enzymes for both groups was small.Antiretroviral therapy amongst this population has minimal effects on hepatic enzymes and does not suggest modifications in therapy. Hepatic injury may occur in HIV, even in the absence of ART and other traditional factors. Monitoring of hepatic enzymes is still important in HIV patients

Serum biochemical parameters of HIV-HAART participants stratified by duration on HAART.

<p>All data are presented as mean ± SD. n = Number. p values <0.05 were considered significant.</p