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Background: Undernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a low-protein diet on the efficacy of praziquantel. Methodology/Principal findings: Thirty-day-old mice were fed with a low-protein diet, and 40 days later, they were individually infected with fifty Schistosoma mansoni cercariae. A 28-day-treatment with praziquantel at 100 mg/kg for five consecutive days followed by distilled water begins on the 36th day post-infection. Mice were sacrificed on the 64th day post-infection. We determined the parasitological burden, liver and intestine histomorphometry, liver injury, and immunomodulation parameters. Praziquantel treatment of infected mice fed with a standard diet (IN-PZQ) resulted in a significant reduction of worm and egg burdens and a normalization of iron and calcium levels. The therapy also improved schistosomiasis-induced hepatopathy and oxidative stress. The anti-inflammatory and immunomodulatory activities of praziquantel were also significant in these mice. When infected mice receiving the low-protein diet were treated with praziquantel (ILP-PZQ), the body weight loss and hepatomegaly were not alleviated, and the worm and liver egg burdens were significantly higher than those of IN-PZQ mice (P < 0.001). The treatment did not reduce the increased activities of ALT and γ-GGT, the high malondialdehyde concentration, and the liver granuloma volume. The iron and calcium levels were not ameliorated and differed from those of IN-PZQ mice (P < 0.001 and P < 0.05). Moreover, in these mice, praziquantel treatment did not reverse the high level of IL-5 and the low mRNA expression of CCL3/MIP-1α and CXCL-10/IP-10 induced by S. mansoni infection. Conclusion/Significance: These results demonstrated that a low-protein diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel. Author summary: Almost 90% of people requiring schistosomiasis preventive chemotherapy in 2018 lived in sub-Saharan Africa. Besides, 205.3 million children under five years suffer and die of undernutrition in low- and middle-income countries. The physiopathology of schistosomiasis mansoni involves liver damage, oxidative stress, and perturbation of the immune response. These disturbances are intensified by undernutrition. Praziquantel is used to treat schistosomiasis, but its efficacy on the comorbidity of S. mansoni infection and undernutrition has not been investigated. We conducted this study to assess the effectiveness of praziquantel on S. mansoni infection in mice fed with a low-protein diet. We recorded growth retardation, hepatomegaly, and high worm and egg burdens in mice fed with a low-protein diet and treated with PZQ. Moreover, the treatment did not reverse the liver function injury, oxidative stress, high iron level, and low calcium level. The proinflammatory cytokine IL-5 was still high, and the gene expression of some macrophage-associated chemokines was reduced. Therefore, this study demonstrated that in a murine model of a low-protein diet, the efficacy of praziquantel on S. mansoni infection was reduced. It also underlines the importance of targeting protein deficiency and malnutrition in populations living in schistosomiasis endemic areas for efficient disease control. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Schistosoma mansoni infection is usually assessed by the Kato-Katz diagnostic technique. However, Kato-Katz thick smears have low sensitivity, especially for light infections. Egg count models fitted on individual level data can adjust for the infection intensity-dependent sensitivity and estimate the 'true' prevalence in a population. However, application of these models is complex and there is need for adjustments that can be done without modelling expertise. This study provides estimates of the 'true' S. mansoni prevalence from population summary measures of observed prevalence and infection intensity using extensive simulations parametrized with data from different settings in sub-Saharan Africa. Methodology: An individual-level egg count model was applied to Kato-Katz data to determine the S. mansoni infection intensity-dependent sensitivity for various sampling schemes. Observations in populations with varying forces of transmission were simulated, using standard assumptions about the distribution of worms and their mating behavior. Summary measures such as the geometric mean infection, arithmetic mean infection, and the observed prevalence of the simulations were calculated, and parametric statistical models fitted to the summary measures for each sampling scheme. For validation, the simulation-based estimates are compared with an observational dataset not used to inform the simulation. Principal findings: Overall, the sensitivity of Kato-Katz in a population varies according to the mean infection intensity. Using a parametric model, which takes into account different sampling schemes varying from single Kato-Katy to triplicate slides over three days, both geometric and arithmetic mean infection intensities improve estimation of sensitivity. The relation between observed and 'true' prevalence is remarkably linear and triplicate slides per day on three consecutive days ensure close to perfect sensitivity. Conclusions/Significance: Estimation of 'true' S. mansoni prevalence is improved when taking into account geometric or arithmetic mean infection intensity in a population. We supply parametric functions and corresponding estimates of their parameters to calculate the 'true' prevalence for sampling schemes up to 3 days with triplicate Kato-Katz thick smears per day that allow estimation of the 'true' prevalence. Author summary: The World Health Organization (WHO) recommends the Kato-Katz diagnostic method, i.e., counting eggs in a thick-smear of stool using light microscopy, for estimation of Schistosoma mansoni infection prevalence. While the diagnostic specificity of Kato-Katz very high, the sensitivity varies strongly with infection intensity and the number of samples collected and thick smears per sample tested. Therefore, the performance of Kato-Katz in a population depends on the distribution of infections in the population and individual-level data is needed to determine the 'true' prevalence of infection. However, modelling capacity to determine 'true' prevalence from individual-level data is often not available to programme managers. In this study, we therefore provide simple equations to estimate the 'true' prevalence and associated uncertainty from observed prevalence and arithmetic or geometric mean infection intensity for a variety of common sampling schemes. We find that by including information about the mean infection intensity in a population the estimation of 'true' prevalence can be improved compared to assuming a constant value for the diagnostic sensitivity and supply parameters and functions to calculate the 'true' prevalence of infection. [ABSTRACT FROM AUTHOR]

Background: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19.Methods: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up.Findings: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19.Interpretation: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission.Funding: European Research Council and WHO. [ABSTRACT FROM AUTHOR]

Abstract: Schistosoma mansoni is a widespread human helminth and causes intestinal schistosomiasis in 54 countries, mainly across Africa but also in Madagascar, the Arabian Peninsula and the neotropics. The geographical range of this parasite relies on the distribution of certain species of freshwater pulmonate snails of the genus Biomphalaria. Whilst S. mansoni is known to exhibit high population diversity the true extent of this diversity is still to be fully elucidated as sampling of this taxon progressively accrues. Here a DNA ‘barcoding’ approach is taken using sequence analysis of a 450bp region within the mitochondrial cox1 gene to assess the genetic diversity within a large number of S. mansoni larval stages collected from their natural human hosts across sub-Saharan Africa. Five hundred and sixty one individual parasite samples were examined from 22 localities and 14 countries. Considerable within-species diversity was found with 120 unique haplotypes splitting geographically into five discrete lineages. The highest diversity was found in East Africa with samples forming three of the five lineages. Less diversity was found in the Far and Central Western regions of Africa with haplotypes from the New World showing a close affinity to the Far Western African S. mansoni populations supporting the hypothesis of a colonisation of South America via the West African slave trade. The data are discussed in relation to parasite diversity and disease epidemiology. [Copyright &y& Elsevier]

Despite the limited reports of praziquantel resistance, the relative success of chemotherapy-based control programmes for schistosomiasis has prompted overdue efforts to expand the use of cheap, generic, praziquantel in sub-Saharan Africa. The likely impact of such programmes on the development and spread of praziquantel resistance is uncertain, but this possibility reinforces the need for monitoring the spectrum of praziquantel sensitivity of schistosome populations and for an improved knowledge of the precise targets for the action of the drug. The search for alternatives to praziquantel and other tools for control of schistosomiasis must continue. [Copyright &y& Elsevier]