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

ABSTRACT: Helminths are parasitic worms that infect over a billion people worldwide. The pathological consequences from infection are due in part, to parasite-induced changes in host metabolic pathways. Here, we analyse the changes in host metabolic profiles, in response to the first Schistosoma haematobium infection and treatment in Zimbabwean children. A cohort of 83 schistosome-negative children (2-5 years old) as determined by parasitological examination, guardian interviews and examination of medical records, was recruited at baseline. Children were followed up after three months for parasitological diagnosis of their first S. haematobium infection, by detection of parasite eggs excreted in urine. Children positive for infection were treated with the antihelminthic drug praziquantel, and treatment efficacy checked three months after treatment. Blood samples were taken at each time point, and capillary electrophoresis mass spectrometry in conjunction with multivariate analysis were used to compare the change in serum metabolite profiles in schistosome-infected versus uninfected children. Following baseline at the three-month follow up, 11 children had become infected with S. haematobium (incidence = 13.3%). Our results showed that infection with S. haematobium was associated with significant increases (>2-fold) in discriminatory metabolites, linked primarily with energy (G6P, 3-PG, AMP, ADP) and purine (AMP, ADP) metabolism. These observed changes were commensurate with schistosome infection intensity, and levels of the affected metabolites were reduced following treatment, albeit not significantly. This study demonstrates that early infection with S. haematobium is associated with alterations in host energy and purine metabolism. Taken together, these changes are consistent with parasite-related clinical manifestations of malnutrition, poor growth and poor physical and cognitive performance observed in schistosome-infected children.

SUBMITTER: Osakunor DNM

PROVIDER: S-EPMC7735607 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Despite decades of experience with praziquantel treatment in school-aged children (SAC) and adults, we still face considerable knowledge gaps relevant to the successful treatment of preschool-aged children (PSAC). This study aimed to assess the efficacy and safety of escalating praziquantel dosages in PSAC infected with Schistosoma haematobium. METHODS:We conducted a randomised, dose-finding trial in PSAC (2-5 years) and as comparator a cohort of SAC (6-15 years) infected with S. haematobium in Côte d'Ivoire. A total of 186 PSAC and 195 SAC were randomly assigned to 20, 40 or 60 mg/kg praziquantel or placebo. The nature of the dose-response relationship in terms of cure rate (CR) was the primary objective. Egg reduction rate (ERR) and tolerability were secondary outcomes. CRs and ERRs were assessed using triplicate urine filtration over 3 consecutive days. Available-case analysis was performed including all participants with primary endpoint data. RESULTS:A total of 170 PSAC and 174 SAC received treatment. Almost 90% of PSAC and three quarters of SAC were lightly infected with S. haematobium. Follow-up data were available for 157 PSAC and 166 SAC. In PSAC, CRs of praziquantel were 85.7% (30/35), 78.0% (32/41) and 68.3% (28/41) at 20, 40 and 60 mg/kg and 47.5% (19/40) for placebo. In SAC, CRs were 10.8% for placebo (4/37), 55.6% for 20 mg/kg (25/45), 68.3% for 40 mg/kg (28/41) and 60.5% for 60 mg/kg (26/43). ERRs based on geometric means ranged between 96.5% (60 mg/kg) and 98.3% (20 mg/kg) in PSAC and between 97.6% (20 mg/kg and 60 mg/kg) and 98.6% (40 mg/kg) in SAC. Adverse events were mild and transient. CONCLUSIONS:Praziquantel revealed dose-independent efficacy against light infections of S. haematobium. Over the dose range tested, praziquantel displayed a ceiling effect with the highest response for 20 mg/kg in PSAC. In SAC maximum efficacy was obtained with 40 mg/kg praziquantel. Further investigations are required in children with moderate to heavy infections. TRIAL REGISTRATION:This trial is registered with International Standard Randomised Controlled Trial Number ISRCTN15280205 .

Project description:BackgroundIn sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied.MethodologyWe assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (<6 years) in the Azaguié district, south Côte d'Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians.Principal findingsOverall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children.Conclusions/significanceCrushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d'Ivoire. Further research is required with highly sensitive diagnostic tools and safety must be investigated in more depth.Trial registrationControlled-Trials.com ISRCTN53172722.

Project description:BackgroundSchistosomiasis remains a major public health concern in sub-Saharan Africa. Although schistosomiasis is well documented in school-aged children in Burkina Faso, prevalence data among preschool-aged children (PSAC) are limited and outdated, and its risk factors in this group remain poorly documented. The main objective of this study was to assess the prevalence and risk factors associated with Schistosoma (S.) mansoni infection among PSAC from Panamasso village, western Burkina Faso.MethodologyA cross-sectional study was carried out among 228 children under 6 years old from Panamasso village. Sociodemographic and water contact data were collected using a structured questionnaire. Kato-Katz and formol-ether concentration techniques were used to detect S. mansoni eggs in stool samples. Urine samples were subjected to a point-of-care circulating cathodic antigen (POC-CCA) cassette test and a centrifugation method to check for both S. mansoni and S. haematobium infection, respectively. Potential risk factors for S. mansoni infection were explored using multivariable logistic regression.ResultsThe mean age of children was 40.2 ± 15.0 months. The prevalence of S. mansoni infection as determined by Kato-Katz, formol-ether concentration and POC-CCA was 42.1%, 39.5% and 80.7%, respectively. Based on the combined results of the three methods, the overall prevalence of S. mansoni infection was 81.1%. No case of S. haematobium infection was found. The geometric mean intensity of S. mansoni infection was 107.2 eggs per gram of feces with 54.2%, 33.3% and 12.5% of the children having light, moderate and heavy infections, respectively. Girls (AOR = 2.9, 95% CI 1.3-6.1), a household located within 500 m from the pond (AOR = 3.0, 95% CI 1.0-8.6) or between 500 and 1000 m from the pond (AOR = 3.0, 95% CI 1.2-7.2), and the child's history of going to the pond (AOR = 5.0, 95% CI 1.7-14.3) were the variables significantly associated with S. mansoni infection.ConclusionS. mansoni was the sole species infecting a high proportion of PSAC in the study area. A mass drug administration program with praziquantel is therefore urgently required for those below 6 years old. Other control strategies should include increased community-awareness and provision of safe water.

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

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