Differential protective impact of peptide vaccine formulae targeting the lung- and liver-stage of challenge Schistosoma mansoni infection in mice.

The study aimed to elicit protective immune responses against murine schistosomiasis mansoni at the parasite lung- and liver stage. Two peptides showing amino acid sequence similarity to gut cysteine peptidases, which induce strong memory immune effectors in the liver, were combined with a peptide based on S. mansoni thioredoxin peroxidase (TPX), a prominent lung-stage schistosomula excretory-secretory product, and alum as adjuvant. Only one of the 2 cysteine peptidases-based peptides in a multiple antigenic peptide construct (MAP-3 and MAP-4) appeared to adjuvant protective immune responses induced by the TPX peptide in a MAP form. Production of TPX MAP-specific IgG1 serum antibodies, and increase in lung interleukin-1 (IL-1), uric acid, and reactive oxygen species (ROS) content were associated with significant (P < 0.05) 50 % reduction in recovery of lung-stage larvae. Increase in lung triglycerides and cholesterol levels appeared to provide the surviving worms with nutrients necessary for a stout double lipid bilayer barrier at the parasite-host interface. Surviving worms-released products elicited memory responses to the MAP-3 immunogen, including production of specific IgG1 antibodies and increase in liver IL-33 and ROS. Reduction in challenge worm burden recorded 45 days post infection did not exceed 48 % associated with no differences in parasite egg counts in the host liver and small intestine compared to unimmunized adjuvant control mice. Alum adjuvant assisted the second peptide, MAP-4, in production of IgG1, IgG2a, IgG2b and IgA specific antibodies and increase in liver ROS, but with no protective potential, raising doubt about the necessity of adjuvant addition. Accordingly, different vaccine formulas containing TPX MAP and 1, 2 or 3 cysteine peptidases-derived peptides with or without alum were used to immunize parallel groups of mice. Compared to unimmunized control mice, significant (P < 0.05 to < 0.005) 22 to 54 % reduction in worm burden was recorded in the different groups associated with insignificant changes in parasite egg output. The results together indicated that a schistosomiasis vaccine able to entirely prevent disease and halt its transmission still remains elusive.

Improving the Cost-efficiency of Preventive Chemotherapy: Impact of New Diagnostics on Stopping Decisions for Control of Schistosomiasis.

BACKGROUND: Control of schistosomiasis (SCH) relies on the regular distribution of preventive chemotherapy (PC) over many years. For the sake of sustainable SCH control, a decision must be made at some stage to scale down or stop PC. These "stopping decisions" are based on population surveys that assess whether infection levels are sufficiently low. However, the limited sensitivity of the currently used diagnostic (Kato-Katz [KK]) to detect low-intensity infections is a concern. Therefore, the use of new, more sensitive, molecular diagnostics has been proposed. METHODS: Through statistical analysis of Schistosoma mansoni egg counts collected from Burundi and a simulation study using an established transmission model for schistosomiasis, we investigated the extent to which more sensitive diagnostics can improve decision making regarding stopping or continuing PC for the control of S. mansoni. RESULTS: We found that KK-based strategies perform reasonably well for determining when to stop PC at a local scale. Use of more sensitive diagnostics leads to a marginally improved health impact (person-years lived with heavy infection) and comes at a cost of continuing PC for longer (up to around 3 years), unless the decision threshold for stopping PC is adapted upward. However, if this threshold is set too high, PC may be stopped prematurely, resulting in a rebound of infection levels and disease burden (+45% person-years of heavy infection). CONCLUSIONS: We conclude that the potential value of more sensitive diagnostics lies more in the reduction of survey-related costs than in the direct health impact of improved parasite control.

How Does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma mansoni Elimination as a Public Health Problem by 2030?

BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.

GLYCOLYTIC ENZYMES AS VACCINES AGAINST SCHISTOSOMIASIS: TESTING SCHISTOSOMA MANSONI PHOSPHOGLYCERATE MUTASE IN MICE.

Schistosomiasis is a globally burdensome parasitic disease caused by flatworms (blood flukes) in the genus Schistosoma. The current standard treatment for schistosomiasis is the drug praziquantel, but there is an urgent need to advance novel interventions such as vaccines. Several glycolytic enzymes have been evaluated as vaccine targets for schistosomiasis, and data from these studies are reviewed here. Although these parasites are canonically considered to be intracellular, proteomic analysis has revealed that many schistosome glycolytic enzymes are additionally found at the host-interactive surface. We have recently found that the intravascular stage of Schistosoma mansoni (Sm) expresses the glycolytic enzyme phosphoglycerate mutase (PGM) on the tegumental surface. Live parasites display PGM activity, and suppression of PGM gene expression by RNA interference diminishes surface enzyme activity. Recombinant SmPGM (rSmPGM) can cleave its glycolytic substrate, 3-phosphoglycerate and can both bind to plasminogen and promote its conversion to an active form (plasmin) in vitro, suggesting a moonlighting role for this enzyme in regulating thrombosis in vivo. We found that antibodies in sera from chronically infected mice recognize rSmPGM. We also tested the protective efficacy of rSmPGM as a vaccine in the murine model. Although immunization generates high titers of anti-SmPGM antibodies (against both recombinant and native SmPGM), no significant differences in worm numbers were found between vaccinated and control animals.

Malacological, socio-environmental evaluation, and evidence of local transmission and maintenance of schistosomiasis in an urban area of Northeast Brazil.

To present the current epidemiological scenario of schistosomiasis related to urban transmission through an epidemiological risk assessment in Porto de Galinhas, a coastal area of Pernambuco, Brazil. Malacological and parasitological surveys were performed between the years 2018 and 2020. Snails were identified taxonomically and examined to confirm infection by Schistosoma mansoni, and so to identify Schistosomiasis Transmission Foci (STF) by the artificial light exposure technique. Stool samples were examined using the Kato-Katz method to identify schistosomiasis cases. Socioeconomic, environmental, behavioural and health data were collected by a questionnaire applied to participates in the survey and used to predict the schistosomiasis risk occurrence by multivariate logistic regression. In all, a total of 6466 snails of Biomphalaria glabrata were collected and 36 breeding sites were identified, of which 25 % were STF. A total of 2236 individuals took part of the survey which identified 187 cases of schistosomiasis, registering a positivity percentage of 8.36 %. The surveys identified the neighbourhoods with the highest risk for transmission while the socioenvironmental analysis identifies other risk factors for disease occurrence, such as gender, age range, level of education and absence of water drainage. We found that areas with poor sanitation, flooding during winter periods and dwellings located near mangroves should be treated by health authorities as priority areas for health interventions to minimize disease transmission. In addition, efforts to improve the population's educational level could certainly contribute to the adoption of measures to prevent and control this neglected tropical disease.

Temporal trends and spatial and spatiotemporal distribution of schistosomiasis mansoni in northeast Brazil between 2005 and 2016.

BACKGROUND: Schistosoma mansoni is a parasitic disease of great magnitude for Brazilian public health. We aimed to analyse the temporal trend and spatial and spatiotemporal distribution of positivity rates for schistosomiasis mansoni in northeast Brazil. METHODS: This is a descriptive study with an ecological approach, carried out between 2005 and 2016. We calculated the positivity rate for the disease and then performed a segmented trend analysis (Joinpoint). For spatial analysis, we smoothed the positivity rates using the local empirical Bayesian method. We checked for spatial autocorrelation using Moran's global and local. Subsequently, we performed Kulldorff's space time sweep analysis. RESULTS: In the period under review, 7 745 650 tests were performed in the northeast, of which 577 793 were positive for Schistosoma mansoni. In the historical series of positivities, it is noted that the highest rates were in Sergipe, Alagoas and Pernambuco. The states of Alagoas and Sergipe showed higher positivity in relation to the average positivity of the northeast and of Brazil. The spatial analysis maps identify clusters of high risk of schistosomiasis cases, mainly in coastal municipalities. There was also stability in positivity rates in some states and the maintenance of endemic areas. CONCLUSIONS: Thus effective public health policies are needed in health education in order to reduce schistosomiasis positivity and improve the health conditions of the northeastern population.

Evaluation of schistosomula lung antigen preparation and soluble egg antigen vaccines on experimental schistosomiasis mansoni.

Schistosomiasis causes significant morbidity and mortality worldwide. This study aimed to assess the effect of schistosomula lung antigen preparation (SLAP) and soluble egg antigen (SEA) on a murine schistosomiasis mansoni model. Ninety laboratory-bred male Swiss albino mice were divided into 6 groups. Two doses of the vaccine were given at 2-week intervals. All mice were subcutaneously infected with 80±10 Schistosoma mansoni cercariae 2 weeks after the last vaccination dose. They were sacrificed 7 weeks post-infection. Parasitological and histopathological studies were conducted to assess the effect of inoculated antigens (single or combined). The results showed that the combination of SLAP and SEA (combination group) led to a significant reduction in worm burden (65.56%), and liver and intestine egg count (59% and 60.59%, respectively). The oogram pattern revealed a reduction in immature and mature eggs (15±0.4 and 10±0.8, respectively) and an increased number of dead eggs in the combination group (P<0.001). In terms of histopathological changes, the combination group showed notably small compact fibrocellular egg granuloma and moderate fibrosis in the liver. A high percentage of destroyed ova was observed in the intestine of the combination group. This study demonstrates for the first time the prophylactic effect of combined SLAP and SEA vaccine. The vaccine induced a significant reduction in the parasitological and pathological impacts of schistosomiasis mansoni in hepatic and intestinal tissues, making it a promising vaccine candidate for controlling schistosomiasis.

Effect of environmental factors in reducing the prevalence of schistosomiasis in schoolchildren: An analysis of three extensive national prevalence surveys in Brazil (1950-2018).

BACKGROUND: Over seven decades, Brazil has made admirable progress in controlling schistosomiasis, and a frequent question about the explanation for this reduction refers to the effect of improving environmental factors in the country. This article seeks to identify factors related to the change in the epidemiological situation of schistosomiasis mansoni infection by analyzing three national prevalence surveys conducted since 1950. METHODOLOGY/PRINCIPAL FINDINGS: This is an ecological study analyzing an unbalanced panel of data based on national surveys and considering the municipality as the unit of analysis. The sample consisted of 1,721 Brazilian municipalities, in which a total of 1,182,339 schoolchildren aged 7-14 were examined during the three periods corresponding to each survey (1947-1953, 1975-1979, and 2010-2015). The percentage of municipalities with zero cases of schistosomiasis was: 45.4%, 54.2% and 73.7%, respectively for those periods. A zero-inflated Poisson regression model, with fixed and random effects, was fitted to assess the association between candidate factors and disease prevalence using a significance level of 5%. There was a significant decrease in disease prevalence between the first and last periods analyzed (RR 0.214, CI 0.184-0.249), with a protective association with access to sanitation (RR 0.996, CI 0.994-0.998), urbanization (RR 0.991, CI 0.989-0.993), and living in own households (RR 0.986, CI 0.983-0.989); and an inverse association with piped water supply (RR 1.010, CI 1.008-1.011). CONCLUSION: The findings of this study indicate a decrease in the prevalence of schistosomiasis over seven decades in schoolchildren from the analyzed Brazilian municipalities, associated with environmental factors and social conditions. The increased access to piped water in the municipalities apparently triggers other ways of contact with unsafe water bodies, generating new transmission routes and suggesting the need for a systemic approach concerning contact with water.

Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells.

During chronic schistosome infections, a complex regulatory network is induced to regulate the host immune system, in which IL-10-producing regulatory B (Breg) cells play a significant role. Schistosoma mansoni soluble egg antigens (SEA) are bound and internalized by B cells and induce both human and mouse IL-10 producing Breg cells. To identify Breg-inducing proteins in SEA, we fractionated SEA by size exclusion chromatography and found 6 fractions able to induce IL-10 production by B cells (out of 18) in the high, medium and low molecular weight (MW) range. The high MW fractions were rich in heavily glycosylated molecules, including multi-fucosylated proteins. Using SEA glycoproteins purified by affinity chromatography and synthetic glycans coupled to gold nanoparticles, we investigated the role of these glycan structures in inducing IL-10 production by B cells. Then, we performed proteomics analysis on active low MW fractions and identified a number of proteins with putative immunomodulatory properties, notably thioredoxin (SmTrx1) and the fatty acid binding protein Sm14. Subsequent splenic murine B cell stimulations and hock immunizations with recombinant SmTrx1 and Sm14 showed their ability to dose-dependently induce IL-10 production by B cells both in vitro and in vivo. Identification of unique Breg cells-inducing molecules may pave the way to innovative therapeutic strategies for inflammatory and auto-immune diseases.

School-based preventive chemotherapy program for schistosomiasis and soil-transmitted helminth control in Angola: 6-year impact assessment.

BACKGROUND: A school preventive chemotherapy (PC) program for soil-transmitted helminths (STHs) and schistosomiasis has operated in Huambo, Uige and Zaire provinces, Angola, since 2013 and 2014, respectively; complemented by a school water, sanitation and hygiene (WASH) program in a subset of schools from 2016. Conducted in 2021, this is the first impact assessment of the school program for the control of schistosomiasis and STHs. METHODOLOGY/PRINCIPAL FINDINGS: A two-stage cluster design was used to select schools and schoolchildren for parasitological and WASH surveys. The rapid diagnostic tests (RDTs), point of care circulating cathodic antigen (POC-CCA) and Hemastix, were used to estimate Schistosoma mansoni and Schistosoma haematobium prevalence, respectively. Kato Katz was used to detect STHs, and quantify STH and S. mansoni infections. Urine filtration was used to quantify S. haematobium infections. Prevalence, infection intensity, relative prevalence reduction and egg reduction rates were calculated for schistosomiasis and STHs. Cohen's Kappa co-efficient was used to assess agreement between RDTs and microscopy. Chi-square or Fisher's exact test was used to compare WASH indicators in WASH-supported and WASH-unsupported schools. Overall, 17,880 schoolchildren (599 schools) and 6,461 schoolchildren (214 schools) participated in the schistosomiasis and STH surveys, respectively. Prevalence of any schistosomiasis in Huambo was 29.6%, Uige 35.4%, and Zaire 28.2%. Relative reduction in schistosomiasis prevalence from 2014 for Huambo was 18.8% (95% confidence interval (CI) 8.6, 29.0), Uige -92.3% (95%CI -162.2, -58.3), and Zaire -14.0% (95%CI -48.6, 20.6). Prevalence of any STH in Huambo was 16.3%, Uige 65.1%, and Zaire 28.2%. Relative reduction in STH prevalence for Huambo was -28.4% (95%CI -92.1, 35.2), Uige -10.7% (95%CI -30.2, 8.8), and Zaire -20.9% (95%CI -79.5, 37.8). A higher proportion of WASH-supported schools had improved water sources, and toilet and handwashing facilities compared to WASH-unsupported schools. CONCLUSIONS/SIGNIFICANCE: The limited impact this school program has had in controlling schistosomiasis and STHs identifies the need for a comprehensive understanding of individual, community, and environmental factors associated with transmission, and consideration for a community-wide control program.

Prevalence and risk distribution of schistosomiasis among adults in Madagascar: a cross-sectional study.

BACKGROUND: The goal to eliminate the parasitic disease of poverty schistosomiasis as a public health problem is aligned with the 2030 United Nations agenda for sustainable development goals, including universal health coverage (UHC). Current control strategies focus on school-aged children, systematically neglecting adults. We aimed at providing evidence for the need of shifting the paradigm of schistosomiasis control programs from targeted to generalized approaches as key element for both the elimination of schistosomiasis as a public health problem and the promotion of UHC. METHODS: In a cross-sectional study performed between March 2020 and January 2021 at three primary health care centers in Andina, Tsiroanomandidy and Ankazomborona in Madagascar, we determined prevalence and risk factors for schistosomiasis by a semi-quantitative PCR assay from specimens collected from 1482 adult participants. Univariable and multivariable logistic regression were performed to evaluate odd ratios. RESULTS: The highest prevalence of S. mansoni, S. haematobium and co-infection of both species was 59.5%, 61.3% and 3.3%, in Andina and Ankazomborona respectively. Higher prevalence was observed among males (52.4%) and main contributors to the family income (68.1%). Not working as a farmer and higher age were found to be protective factors for infection. CONCLUSIONS: Our findings provide evidence that adults are a high-risk group for schistosomiasis. Our data suggests that, for ensuring basic health as a human right, current public health strategies for schistosomiasis prevention and control need to be re-addressed towards more context specific, holistic and integrated approaches.

Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Côte d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial.

BACKGROUND: WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children. METHODS: This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2-6 years were eligible. In cohort 1, participants aged 4-6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2-3 years) and 3 (aged 3 months to 2 years) infected with S mansoni, and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium, received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17-21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov, NCT03845140. FINDINGS: Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1-6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6-93·5] in cohort 1a vs 81·3% [67·4-91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]). INTERPRETATION: Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis. FUNDING: The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Understanding perceptions of schistosomiasis and its control among highly endemic lakeshore communities in Mayuge, Uganda.

BACKGROUND: Schistosomiasis is a neglected tropical disease and a serious global-health problem with over 230 million people requiring treatment, of which the majority live in Africa. In Uganda, over 4 million people are infected. Extensive parasitological data exist on infection prevalence, intensities and the impact of repeated praziquantel mass drug administration (MDA). However, how perceptions of schistosomiasis shape prevention and treatment practices and their implications for control measures are much less well understood. METHODS: Rapid ethnographic appraisals were performed for six weeks in each of three Schistosoma mansoni high endemicity communities on the shores of Lake Victoria, Mayuge District, Uganda. Data were collected between September 2017 and April 2018. Data were collected through structured observations, transect walks, and participant observation, and sixty in-depth interviews and 19 focus group discussions with purposively recruited participants. Data were analyzed thematically using iterative categorization, looking at five key areas: perceptions of 1) the symptoms of schistosomiasis; 2) the treatment of schistosomiasis; 3) how schistosomiasis is contracted; 4) how schistosomiasis is transmitted onwards and responsibilities associated with this; and 5) how people can prevent infection and/or onward transmission. RESULTS: Observations revealed open defecation is a common practice in all communities, low latrine coverage compared to the population, and all communities largely depend on lake water and contact it on a daily basis. Perceptions that a swollen stomach was a sign/symptom of 'ekidada' (caused by witchcraft) resulted in some people rejecting free praziquantel in favour of herbal treatment from traditional healers at a fee. Others rejected praziquantel because of its perceived side effects. People who perceived that schistosomiasis is caught from drinking unboiled lake water did not seek to minimize skin contact with infected water sources. Community members had varied perceptions about how one can catch and transmit schistosomiasis and these perceptions affect prevention and treatment practices. Open defecation and urinating in the lake were considered the main route of transmission, all communities attributed blame for transmission to the fishermen which was acknowledged by some fishermen. And, lastly, schistosomiasis was considered hard to prevent due to lack of access to safe water. CONCLUSION: Despite over 15 years of MDA and associated education, common misconceptions surrounding schistosomiasis exist. Perceptions people have about schistosomiasis profoundly shape not only prevention but also treatment practices, greatly reducing intervention uptake. Therefore, we advocate for a contextualized health education programme, alongside MDA, implementation of improved access to safe-water and sanitation and continued research.

Fine-scale mapping of Schistosoma mansoni infections and infection intensities in sub-districts of Makenene in the Centre region of Cameroon.

BACKGROUND: Schistosomiasis control relies mainly on mass drug administration of Praziquantel (PZQ) to school aged children (SAC). Although precision mapping has recently guided decision making, the sub-districts and the epidemiological differences existing between bio-ecological settings in which infected children come from were not taken into consideration. This study was designed to fill this gap by using POC-CCA and KK to comparatively determine the prevalence and infection intensities of Schistosoma mansoni (S. mansoni) and to perform fine-scale mapping of S. mansoni infections and its infection intensities with the overarching goal of identifying sub-districts presenting high transmission risk where control operations must be boosted to achieve schistosomiasis elimination. METHODOLOGY: During a cross- sectional study conducted in Makenene, 1773 stool and 2253 urine samples were collected from SAC of ten primary schools. S. mansoni infections were identified using the point of care circulating cathodic antigen (POC-CCA) and Kato-Katz (KK) test respectively on urine and stool samples. Geographical coordinates of houses of infected SAC were recorded using a global position system device. Schistosome infections and infection intensities were map using QGIS software. RESULTS: The prevalence of S. mansoni inferred from POC-CCA and KK were 51.3% and 7.3% respectively. Most infected SAC and those bearing heavy infections intensities were clustered in sub-districts of Baloua, Mock-sud and Carrière. Houses with heavily-infected SAC were close to risky biotopes. CONCLUSION: This study confirms the low sensitivity of KK test compared to POC-CCA to accurately identify children with schistosome infection and bearing different schistosome burden. Fine-scale mapping of schistosome infections and infection intensities enabled to identify high transmission sub-districts where control measures must be boosted to reach schistosomiasis elimination.

New challenges for the control of human schistosomiasis: The possible impact of wild rodents in Schistosoma mansoni transmission.

Schistosomiasis is a neglected parasitic disease caused by digenean trematodes from the genus Schistosoma that affects millions of people worldwide. Despite efforts to control its transmission, this disease remains active within several endemic regions of Africa, Asia, and the Americas. In addition to the deficits in sanitation and educational structure, another major obstacle hindering the eradication of schistosomiasis is the ability of Schistosoma spp. to naturally infect multiple vertebrate hosts, particularly wild rodents. Due to climate change and other anthropogenic disturbances, contact between humans and wild animals has increased, and this has contributed to more frequent interactions between Schistosoma species that typically infect different hosts. This new transmission dynamic involving Schistosoma spp., humans, wild rodents, and livestock could potentially increase the frequency of Schistosoma hybridization and the establishment of new genotypes and strains. Although it is not currently possible to precisely measure how this biological phenomenon affects the epidemiology and morbidity of schistosomiasis, we speculate that these Schistosoma variants may negatively impact control strategies, treatment regimens, and disease burden in humans. In the present study, we discuss the natural infections of wild rodents with Schistosoma spp., the role of these animals as Schistosoma spp. reservoirs, and how they may select hybrids and strains of Schistosoma mansoni. We also discuss measures required to shed light on the actual role of the wild rodents Nectomys squamipes and Holochilus sciureus in the transmission and morbidity of schistosomiasis in Brazil.

Evidence for local transmission and maintenance of schistosomiasis in an urban neighbourhood in Northeast Brazil.

Schistosomiasis is a tropical neglected disease commonly associated with rural areas; however, urban schistosomiasis has been reported worldwide, and increasing urbanization is one of the most important demographic shifts of the 20th and now 21st centuries. The pattern of urbanization is not uniform so that within the same city the rates and sources of population increase vary. Here, we report on the parasite composition in one neighbourhood in the metropolitan area of Salvador, Bahia, Brazil. Using epidemiological data and population genetics, we find evidence for local transmission and maintenance of Schistosoma mansoni infection within an urban population and little contribution from rural-urban migration. Our findings provide direction for local mitigation strategies and to assist the public living in this neighbourhood to interrupt the local transmission cycle.

Determinants of Schistosoma mansoni transmission in hotspots at the late stage of elimination in Egypt.

BACKGROUND: In certain settings, the prevalence and severity of schistosoma infection do not lessen despite repeated rounds of preventative chemotherapy; these areas are known as hotspots. This study aimed to investigate the role of human practices, besides environmental and malacological factors, in the maintenance of the Schistosoma mansoni infection transmission chain in hotspot areas in Egypt. METHODS: This cross-sectional study was conducted between July and November 2019 in Kafr El-Sheikh Governorate, Egypt. A pre-designed structured interviewing questionnaire was used to collect humanitarian data. Stool samples were collected from children aged 6-15 years on three successive days and examined using the Kato-Katz technique. Simultaneously, water and snail samples were taken from watercourses surrounding houses. Snails were identified based on their shell morphology and structure and tested for cercaria shedding. Water samples were analyzed for their physicochemical and biological characteristics. RESULTS: A total of 2259 fecal samples (1113 in summer and 1146 in fall) were collected from 861 children. About 46.9% of the participants were males, and 31.8% were aged 6-10 years. The prevalence of S. mansoni infection was higher during the summer than during the fall (19.1% vs 7.2%, respectively, P < 0.01). The intensity of infection (light, moderate, and heavy) during summer versus fall was (93.55 vs 89.38%, 6.45 vs 8.85%, and 0.00% vs 1.77%), respectively (P < 0.05). A higher prevalence of human infection was observed among males than females [OR = 1.63, 95% confidence interval (CI):1.10-2.40, P = 0.015], children aged 11-15 years than among their counterparts aged 6-10 years (OR = 2.96, 95% CI: 1.72-5.06, P < 0.001), and mothers with a low level of education (OR = 3.33, 95% CI: 1.70-6.52, P < 0.001). The main identified risk factors were contacting the main body of water-canal for washing clothes (OR = 1.81, 95% CI: 1.12-2.49, P = 0.015), land irrigation (OR = 2.56, 95% CI: 1.32-4.96, P = 0.004), water collection (OR = 2.94, 95% CI: 1.82-4.73, P < 0.001), bathing (OR = 2.34, 95% CI: 1.21-4.31, P = 0.009), and garbage disposal (OR = 2.38, 95% CI:1.38-4.12, P < 0.001). The count of Biomphalaria alexandrina was distinct between seasons (P < 0.01) in consistent with statistically significant differences in water temperature, salinity, turbidity, the total concentration of coliforms, depth, velocity, and water level (P < 0.01). The presence of grasses and duckweeds was significantly associated with snail infection (P = 0.00 l). Significant effects of water depth, pH, temperature, and total dissolved solids on snail count were also observed (P < 0.05). CONCLUSIONS: The persistence of the infection is due to adoption of risky behaviors and environmental factors that enhance snail survival and infection. Schistosomiasis elimination in hotspots requires an integrated control approach that combines preventive chemotherapy with other complementary measures.

Clustered Regularly Interspaced Short Palindromic Repeats/ CRISPR associated protein 9-mediated editing of Schistosoma mansoni genes: Identifying genes for immunologically potent drug and vaccine development.

Schistosomiasis is a neglected acute and chronic tropical disease caused by intestinal (Schistosoma mansoni and Schistosoma japonicum) and urogenital (Schistosoma haematobium) helminth parasites (blood flukes or digenetic trematodes). It afflicts over 250 million people worldwide, the majority of whom reside in impoverished tropical and subtropical regions in sub-Saharan Africa. Schistosomiasis is the second most common devastating parasitic disease in the world after malaria and causes over 200,000 deaths annually. Currently, there is no effective and approved vaccine available for human use, and treatment strongly relies on praziquantel drug therapy, which is ineffective in killing immature larval schistosomula stages and eggs already lodged in the tissues. The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9)-mediated gene editing tool is used to deactivate a gene of interest to scrutinize its role in health and disease, and to identify genes for vaccine and drug targeting. The present review aims to summarize the major findings from the current literature reporting the usage of CRISPR/Cas9-mediated gene editing to inactivate genes in S. mansoni (acetylcholinesterase (AChE), T2 ribonuclease omega-1 (ω1), sulfotransferase oxamniquine resistance protein (SULT-OR), and α-N-acetylgalactosaminidase (SmNAGAL)), and freshwater gastropod snails, Biomphalaria glabrata (allograft inflammatory factor (BgAIF)), an obligatory component of the life cycle of S. mansoni, to identify their roles in the pathogenesis of schistosomiasis, and to highlight the importance of such studies in identifying and developing drugs and vaccines with high therapeutic efficacy.

Schistosoma mansoni and soil-transmitted helminths among schoolchildren in An-Nadirah District, Ibb Governorate, Yemen after a decade of preventive chemotherapy.

The Ministry of Public Health in Yemen continues the implementation of school and community-based preventive chemotherapy with praziquantel and albendazole for the control and elimination of schistosomiasis and soil-transmitted helminths (STH). The latest remapping to update the distribution of schistosomiasis and STH was conducted seven years ago. This study aimed to estimate the prevalence, intensity and associated risk factors of Schistosoma mansoni and STH among schoolchildren in An-Nadirah District, Ibb Governorate, Yemen. A cross-sectional study was carried out among schoolchildren aged 6-15 years in four selected schools. Biological, demographic, socioeconomic and environmental data were collected using a pre-tested questionnaire. S. mansoni and STH eggs were detected and counted by the microscopic examination of Kato-Katz fecal smears. Out of 417 schoolchildren, 17.0% were infected with at least one intestinal helminth. Prevalence of S. mansoni and STH were 6.5% and 9.1%, respectively. The most prevalent parasite among STH was Ascaris lumbricoides (8.4%). Unemployed fathers (Adjusted Odds Ratio (AOR) = 3.2; 95% Confidence interval (CI): 1.23, 8.52; P = 0.018), eating exposed food (AOR: 2.9; 95%CI = 1.24, 6.89; P = 0.014), not washing hands before eating and after defecation (AOR: 4.8; 95%CI = 1.77, 12.81; P = 0.002), and schools located close to water stream (AOR: 22.1; 95%CI = 5.12, 95.46; P <0.001) were independent risk factors of ascariasis. Swimming in ponds/stream (AOR: 3.9; 95%CI = 1.63, 9.55; P = 0.002), and schools close to the stream (AOR: 24.7; 95%CI = 3.05, 200.07; P = 0.003) were independent risk factors of intestinal schistosomiasis. The present study does not indicate a reduction in the prevalence of intestinal schistosomiasis in this rural area since the latest remapping conducted in 2014, although ascariasis was reduced by half. The prevalence of the two parasites was highly focal in areas close to the valley, suggesting a significant role of the stream in sustaining and accelerating the parasitic infection. Children practicing swimming and having poor hygienic practices were at high exposure to S. mansoni and A. lumbricoides, respectively. Water, Sanitation and Hygiene intervention, school-based health education, and snail control, in addition to mass drug administration, will help in the interruption of transmission of schistosomiasis and STH.

The prophylactic and anti-fibrotic activity of phthalimido-thiazole derivatives in schistosomiasis mansoni.

Schistosomiasis mansoni is considered a serious public health problem. As praziquantel is the only drug recommended by the World Health Organization for the treatment and control of schistosomiasis, the development of new drugs is of great significance. In this work, we present the antischistosomal activity of a small set of phthalimido-thiazole derivatives against Schistosoma mansoni. The effects of those derivatives on the viability of larvae juveniles and adult parasites, production and development of eggs, mortality of schistosomules in vitro by counting worms, and stages of eggs of infected animals in acute and chronic phases were evaluated, resulting in the identification of new multistage antischistosomal compounds. Additionally, a study of liver fibrogenesis was released. The phthalimido-thiazole derivatives, compounds 2b-d, 2h-j, had shown activity on schistosomules, achieving 100% mortality even at 5 mg/mL, in the first 24 h. In the chronic phase of schistosomiasis infection, compound 2i promoted a reduction in the number of immature eggs, an increase in the number of non-viable parasite eggs, a reduction in the average number of eggs in the liver and intestine, decrease in the levels of hydroxyproline in the liver, and a reduction in the areas of hepatic fibrosis. This compound also promoted an increase of IL-10 and a reduction in the level of TNF-α in the liver. Accordingly, the phthalimide-thiazole scaffold is a new starting point for the development of multistage compounds that affect S. mansoni viability, egg formation, and production.