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The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of −10.19 and −45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug. [ABSTRACT FROM AUTHOR]

Background Reasons for the high prevalence of Kaposi sarcoma–associated herpesvirus (KSHV) in sub-Saharan Africa, and risk factors leading to viral reactivation and shedding, remain largely undefined. Preliminary studies have suggested that schistosome infection, which has been associated with impaired viral control, is associated with KSHV. In this study we sought to determine the relationship between active Schistosoma mansoni or Schistosoma haematobium infection and KSHV shedding. Methods We quantified KSHV DNA in saliva and cervical swabs from 2 cohorts of women living in northwestern Tanzanian communities endemic for S mansoni or S haematobium by real-time polymerase chain reaction. χ2 and Fisher exact tests were used to determine differences in clinical and demographic factors between those who were and were not shedding KSHV. Results Among 139 total women, 44.6% were KSHV seropositive. Six percent of those with S mansoni and 17.1% of those with S haematobium were actively shedding KSHV in saliva and none in cervical samples. Women from the S mansoni cohort who were shedding virus reported infertility more frequently (80% vs 19.5%, P =.009). There was no difference in frequency of KSHV salivary shedding between schistosome-infected and -uninfected women. Conclusions In an area with high KSHV seroprevalence and endemic schistosome infections, we provide the first report with data demonstrating no association between schistosome infection and salivary or cervical herpesvirus shedding. KSHV salivary shedding was associated with infertility, a known effect of another herpesvirus, human herpesvirus 6. [ABSTRACT FROM AUTHOR]

Background. Schistosomiasis is caused by parasitic flatworms and the disease is endemic to most countries in sub-Saharan Africa including Ghana. The current therapeutic agent for managing this disease solely relies on praziquantel. The continual dependence on this single available drug could lead to possible drug resistance. This study seeks to evaluate the antischistosomal activity of the following Ghanaian medicinal plants: Khaya senegalensis, Vernonia amygdalina, Clausena anisata, and Bridelia ferruginea. Methodology. Two concentrations (100 μg/mL and 50 μg/mL) of each extract were tested in a 96-well plate containing 30 newly transformed schistosomula (NTS). Moreover, six worms of both sexes of adult Schistosoma mansoni were exposed to the extracts diluted in the RPMI medium. The assay was performed in a 24-well plate. The parasitic worms were examined using an inverted optical microscope. Results. At 100 μg/mL and 50 μg/mL, all extracts performed better and showed strong activity (p < 0.001) against NTS; thus, 98.08%, 100%, 80.77%, and 100% for Clausena, Vernonia, Bridelia, and Khaya, respectively, when compared to praziquantel. Strong activity was recorded when the extracts underwent testing against Schistosoma mansoni adults at 100 μg/mL; 96.35%, 100%, and 94.55% for Vernonia, Bridelia, and Khaya, respectively, except for Clausena which exhibited weak activity, i.e., 56.02%. There was no significant difference between Vernonia, Bridelia, and Khaya when compared to praziquantel. Conclusion. At 100 μg/mL, Khaya senegalensis, Vernonia amygdalina, and Bridelia ferruginea extracts demonstrated strong activity against both schistosomula and adult Schistosoma mansoni. These data can serve as baseline information in the quest to find alternative therapeutic agents to treat schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Malaria and schistosomiasis persist as major public health challenge in sub-Saharan Africa. These infections have independently and also in polyparasitic infection been implicated in anaemia and nutritional deficiencies. This study aimed at assessing asymptomatic malaria, intestinal Schistosoma infections and the risk of anaemia among school children in the Tono irrigation area in the Kassena Nankana East Municipal (KNEM) in the Upper East Region of Northern Ghana. Methods: A cross sectional survey of 326 school children was conducted in the KNEM. Kato Katz technique was used to detect Schistosoma eggs in stool. Finger-prick capillary blood sample was used for the estimation of haemoglobin (Hb) concentration and blood smear for malaria parasite detection by microscopy. Results: The average age and Hb concentration were 10.9 years (standard deviation, SD: ± 2.29) and 11.2 g/dl (SD: ± 1.39) respectively with 58.9% (n = 192) being females. The overall prevalence of infection with any of the parasites (single or coinfection) was 49.4% (n = 161, 95% confidence interval, CI [44.0–54.8]). The prevalence of malaria parasite species or Schistosoma mansoni was 32.0% (n = 104) and 25.2% (n = 82), respectively with 7.7% (n = 25) coinfection. The prevalence of anaemia in the cohort was 40.5% (95%CI [35.3–45.9]), of which 44.4% harboured at least one of the parasites. The prevalence of anaemia in malaria parasite spp or S. mansoni mono-infections was 41.8% and 38.6%, respectively and 64.0% in coinfections. There was no statistically significant difference in the odds of being anaemic in mono-infection with malaria (OR = 1.22, 95% CI 0.71–2.11, p = 0.47) or S. mansoni (OR = 1.07, 95% CI 0.58–1.99, p = 0.83) compared to those with no infection. However, the odds of being anaemic and coinfected with malaria parasite species and S. mansoni was 3.03 times higher compared to those with no infection (OR = 3.03, 95% CI 1.26–7.28, p = 0.013). Conclusion The data show a high burden of malaria, S. mansoni infection and anaemia among school children in the irrigation communities. The risk of anaemia was exacerbated by coinfections with malaria parasite(s) and S. mansoni. Targeted integrated interventions are recommended in this focal area of KNEM. [ABSTRACT FROM AUTHOR]

Background. Schistosomiasis remains a major public health concern in sub-Saharan Africa. It has been associated to morbidity and mortality in developing countries including Cameroon, and Njombe-Penja health district is an endemic area. This study is aimed at determining the prevalence and risk factors of Schistosoma mansoni infection among patients attending the Saint Jean de Malte Hospital, Njombe. Methods. A cross-sectional study design was employed, with the enrolment of 300 participants using convenience sampling technique. Data were collected using a structured questionnaire. Stool specimens were collected and examined using direct microscopy, Kato-Katz's method, and formol ether concentration technique. Data were analyzed using SPSS, and chi-square test was used to assess the association. Risk factors for S. mansoni infection were assessed using multivariable logistic regression, and a p < 0.05 was considered significant. Results. The overall prevalence of Schistosoma mansoni infection was 13%. Schistosoma mansoni infection was mostly frequent among patients < 20 years and males. Stream usage (AOR = 2.15 , 95% CI. 1.32–3.50), always visiting the stream (AOR = 11.35 , 95% CI 2.33-55.33), always swimming and washing clothes in the stream (AOR = 7 : 10 , 95% CI 2.31-21.80), age group < 20 years (AOR = 3.7 , 95% CI 1.1-12.2), and age group 20-29 years (AOR = 2.58 , 95% CI 1.14-18.42) were significantly associated with increased risk of S. mansoni infection. Conclusion. These findings suggest that Schistosoma mansoni infection is of public health concern in Njombe and its environs. Age of <20 years and between 20 and 29 years, stream usage, always visiting the stream, and always swimming and washing clothes in the stream were the main risk factors of S. mansoni infection. Thus, mass drug administration and health education are required. [ABSTRACT FROM AUTHOR]

Background: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. Methods: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. Results: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). Conclusions: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission. Author summary: The standard method of control for intestinal worms, a common public health problem in sub-Saharan Africa, is distribution of deworming treatment on a mass scale. These infections are difficult to eliminate as re-infection is common due a combination of people not being treated and high exposure to the parasites through poor access to sanitation and clean water. The Geshiyaro project in Ethiopia has the ambitious goal of breaking the transmission cycle of such infections through treatment in combination with provision of water and sanitation services. The impact of these interventions is being measured using a unique approach, that is, using finger printing to evaluate prevalence of infection with compliance to treatment and access water or sanitation. [ABSTRACT FROM AUTHOR]

Background: Malaria and schistosomiasis persist as major public health challenge in sub-Saharan Africa. These infections have independently and also in polyparasitic infection been implicated in anaemia and nutritional deficiencies. This study aimed at assessing asymptomatic malaria, intestinal Schistosoma infections and the risk of anaemia among school children in the Tono irrigation area in the Kassena Nankana East Municipal (KNEM) in the Upper East Region of Northern Ghana. Methods: A cross sectional survey of 326 school children was conducted in the KNEM. Kato Katz technique was used to detect Schistosoma eggs in stool. Finger-prick capillary blood sample was used for the estimation of haemoglobin (Hb) concentration and blood smear for malaria parasite detection by microscopy. Results: The average age and Hb concentration were 10.9 years (standard deviation, SD: ± 2.29) and 11.2 g/dl (SD: ± 1.39) respectively with 58.9% (n = 192) being females. The overall prevalence of infection with any of the parasites (single or coinfection) was 49.4% (n = 161, 95% confidence interval, CI [44.0–54.8]). The prevalence of malaria parasite species or Schistosoma mansoni was 32.0% (n = 104) and 25.2% (n = 82), respectively with 7.7% (n = 25) coinfection. The prevalence of anaemia in the cohort was 40.5% (95%CI [35.3–45.9]), of which 44.4% harboured at least one of the parasites. The prevalence of anaemia in malaria parasite spp or S. mansoni mono-infections was 41.8% and 38.6%, respectively and 64.0% in coinfections. There was no statistically significant difference in the odds of being anaemic in mono-infection with malaria (OR = 1.22, 95% CI 0.71–2.11, p = 0.47) or S. mansoni (OR = 1.07, 95% CI 0.58–1.99, p = 0.83) compared to those with no infection. However, the odds of being anaemic and coinfected with malaria parasite species and S. mansoni was 3.03 times higher compared to those with no infection (OR = 3.03, 95% CI 1.26–7.28, p = 0.013). Conclusion The data show a high burden of malaria, S. mansoni infection and anaemia among school children in the irrigation communities. The risk of anaemia was exacerbated by coinfections with malaria parasite(s) and S. mansoni. Targeted integrated interventions are recommended in this focal area of KNEM. [ABSTRACT FROM AUTHOR]

Schistosoma haematobium is the most prevalent of the human-infecting schistosome species, causing significant morbidity in endemically exposed populations. Despite this, it has been relatively understudied compared to its fellow species, S. mansoni. Here we provide the first comprehensive characterization of the S. haematobium Tegument Allergen-Like protein family, a key protein family directly linked to protective immunity in S. mansoni infection. Comparable with observations for S. mansoni, parasite phylogenetic analysis and relative gene expression combined with host serological analysis support a cross-reactive relationship between S. haematobium TAL proteins, exposed to the host immune system as adult worms die, and closely related proteins, exposed during penetration by the infecting cercarial and early schistosomulae stages. Specifically, our results strengthen the evidence for host immunity driven by cross-reactivity between family members TAL3 and TAL5, establishing it for the first time for S. haematobium infection. Furthermore, we build upon this relationship to include the involvement of an additional member of the TAL protein family, TAL11 for both schistosome species. Finally, we show a close association between experience of infection and intensity of transmission and the development of protective IgE responses to these antigens, thus improving our knowledge of the mechanisms by which protective host immune responses develop. This knowledge will be critical in understanding how control efforts such as mass drug administration campaigns influence the development of host immunity and subsequent patterns of infection and disease within endemic populations. Author summary: S. haematobium is the most prevalent of the human infecting schistosomes. Along with S. mansoni, it is responsible for the majority of schistosomiasis cases that are borne by the populations of sub-Saharan Africa, where the global burden of this infection is centered. Here, we provide insight into the IgE antibody response that protects against these infections. Through utilization of in silico analysis in combination with immuno-epidemiological studies, we explore the relationship between host immune protection and a parasite protein family named the Tegument Allergen-Like (TAL) proteins. Our results show that several members of the TAL protein family are important in host protection to both these major schistosome species. For the first time we demonstrate that a progressive cross-reactive TAL-IgE response occurs against S. haematobium, similar to that previous observed in S. mansoni infection. We additionally expand upon previous knowledge for S. mansoni, identifying further complexity in the cross-reactive relationship between TAL family members, providing evidence of a key role for family member TAL11 in induction of the protective host immune response. [ABSTRACT FROM AUTHOR]

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment. Author summary: Schistosomiasis is caused by parasitic helminths of the genus Schistosoma. Schistosoma mansoni is the primary cause of intestinal schistosomiasis, a devastating and widespread parasitic infection that causes morbidity, death and socio-economic impact on endemic communities across the world and especially sub-Saharan Africa. Using whole-genome sequencing, we were able to elucidate the parasite population within Lake Victoria island fishing communities in Uganda which are among the major hotspots for schistosomiasis. We further assessed genetic markers that might be linked to recent observations concerning reduced susceptibility to praziquantel, the major drug used in the treatment of this disease. Whole-genome data on the population genetics of S. mansoni in an African setting will provide a strong basis for future functional genomics or transcriptomic studies that will be key to identifying drug targets, improving existing drugs or developing new therapeutic interventions. [ABSTRACT FROM AUTHOR]

Schistosomiasis, also known as bilharzia or snail fever, is a debilitating neglected tropical disease (NTD), caused by parasitic trematode flatworms of the genus Schistosoma, that has an annual mortality rate of 280,000 people in sub-Saharan Africa alone. Schistosomiasis is transmitted via contact with water bodies that are home to the intermediate host snail which shed the infective cercariae into the water. Schistosome lifecycles are complex, and while not all schistosome species cause human disease, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform evidence-based local environmental, food security and health systems policy making. Crucially, schistosomiasis disproportionally affects low- and middle-income (LMIC) countries and for that reason, environmental screening of water bodies for schistosomes may aid with the targeting of water, sanitation, and hygiene (WASH) interventions and preventive chemotherapy to regions at highest risk of schistosomiasis transmission, and to monitor the effectiveness of such interventions at reducing the risk over time. To this end, we developed a DNA-based biosensor termed Specific Nucleic AcId Ligation for the detection of Schistosomes or 'SNAILS'. Here we show that 'SNAILS' enables species-specific detection from genomic DNA (gDNA) samples that were collected from the field in endemic areas. Author summary: Schistosomiasis is a neglected tropical disease, caused by the parasitic trematodes of the genus Schistosoma. Schistosomiasis is endemic to regions within Africa, Asia and South America with at least 250 million people infected and a further 779 million at risk of infection. The lifecycle of schistosomes are complex and involve specific freshwater intermediate snail hosts which shed infective cercariae into the waterbodies they inhabit. Schistosomiasis is subsequently transmitted to humans or animals that contact cercariae contaminated water. In Africa, human disease is largely caused by Schistosoma mansoni and Schistosoma haematobium. However, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform local environmental, food security and health programmes. To this end, we re-purposed a nucleic acid detection technology to enable the detection of different schistosome species. Our DNA-biosensor, abbreviated as 'SNAILS', employs carefully designed probes that recognise species-specific DNA sequences, coupled with enzymatic amplification steps, and a fluorescent signal-dye to indicate a positive detection. 'SNAILS' successfully differentiates between S. mansoni and S. haematobium samples and could conceivably be employed within future global health programmes. [ABSTRACT FROM AUTHOR]

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]

Human schistosomiasis is a disease that mostly plagues the destitute of various tropical and sub-tropical countries, particularly in sub-Saharan Africa (SSA) and South America. It has significant effects on various health and economic-related matters. Globally, the burden of schistosomiasis has been controlled with a single chemotherapeutic drug, praziquantel (PZQ), which has recently demonstrated several clinical issues, including its inability to destroy juvenile schistosome worms and drug resistance because of its extensive use. The use of organometallic moieties in biological and medicinal chemistry has developed greatly and has led to their use in various anti-cancer and anti-infectious agents. The abundance of a range of organometallic compounds that can cause damage to the parasite has received tremendous feedback, with many already at clinical trials. The distinct redox biology of the schistosome parasite is a vulnerable element to the survival of the worm and has steered attempts toward the use of redox-directed bioorganometallic compounds. Disruption of the schistosome redox homeostasis through organometallic ions provides a novel drug target that could be used in overcoming the drawbacks of the mainstream drug and one that could possibly bypass the emergence of drug resistance. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a potentially lethal parasitic disease that profoundly impacts systemic immune function in chronically infected hosts through mechanisms that remain unknown. Given the immunoregulatory dysregulation experienced in infected individuals, this study examined the impact of chronic schistosomiasis on the sustainability of vaccine-induced immunity in both children living in endemic areas and experimental infections in mice. Data show that chronic Schistosoma mansoni infection impaired the persistence of vaccine specific antibody responses in poliovirus-vaccinated humans and mice. Mechanistically, schistosomiasis primarily fostered plasmablast and plasma cell death in the bone marrow and removal of parasites following praziquantel treatment reversed the observed cell death and partially restored vaccine-induced memory responses associated with increased serum anti-polio antibody responses. Our findings strongly suggest a previously unrecognized mechanism to explain how chronic schistosomiasis interferes with an otherwise effective vaccine regimen and further advocates for therapeutic intervention strategies that reduce schistosomiasis burden in endemic areas prior to vaccination. Author summary: Schistosoma mansoni (S. mansoni), a schistosomiasis disease-causing parasite species, is most common in sub-Saharan Africa. Schistosoma mansoni can influence immune responses and trigger physiological imbalances in their human and animal hosts, which improve their survival and multiplication in the host. These influences can disrupt the host's ability to maintain long term protective immunity mounted by vaccines for infectious diseases. Here, we investigated the impact of S. mansoni infection on poliovirus vaccine immunity in school-aged children and mice. We found that the parasite reduced its host's ability to maintain protective blood antibodies produced by immune responses to poliovirus vaccines. We also found that S. mansoni infection reduces the maintenance of antibody-producing plasma cells in the bone marrow of vaccinated mice. Our data showed that treating S. mansoni infected children and mice with praziquantel mitigated the parasite's negative influences on vaccine immunity. These findings suggest that in regions where schistosomiasis is endemic, the Schistosoma spp. parasites may be notable causes of suboptimal viral vaccine immunity maintenance by children, leaving them vulnerable to vaccine-preventable diseases. [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]

Background: Schistosomiasis, caused by Schistosoma mansoni, is of great significance to public health in sub–Saharan Africa. In the Democratic Republic of Congo (DRC), information on the burden of S. mansoni infection is scarce, which hinders the implementation of adequate control measures. We assessed the geographical distribution of S. mansoni infection across Ituri province in north-eastern DRC and determined the prevailing risk factors. Methods/Principal findings: Two province–wide, community–based studies were conducted. In 2016, a geographical distribution study was carried out in 46 randomly selected villages across Ituri. In 2017, an in–depth study was conducted in 12 purposively–selected villages, across the province. Households were randomly selected, and members were enrolled. In 2016, one stool sample was collected per participant, while in 2017, several samples were collected per participant. S. mansoni eggs were detected using the Kato–Katz technique. In 2017, a point–of–care circulating cathodic S. mansoni antigen (POC–CCA) urine test was the second used diagnostic approach. Household and individual questionnaires were used to collect data on demographic, socioeconomic, environmental, behavioural and knowledge risk factors. Of the 2,131 participants in 2016, 40.0% were positive of S. mansoni infection. Infection prevalence in the villages ranged from 0 to 90.2%. Of the 707 participants in 2017, 73.1% were tested positive for S. mansoni. Prevalence ranged from 52.8 to 95.0% across the health districts visited. Infection prevalence increased from north to south and from west to east. Exposure to the waters of Lake Albert and the villages' altitude above sea level were associated with the distribution. Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected (62.3%). Key risk factors were poor housing structure (odds ratio [OR] 2.1, 95% 95% confidence interval [CI] 1.02–4.35), close proximity to water bodies (OR 1.72, 95% CI 1.1–2.49), long-term residence in a community (OR 1.41, 95% CI 1.11–1.79), lack of latrine in the household (OR 2.00, 95% CI 1.11–3.60), and swimming (OR 2.53, 95% CI 1.20–5.32) and washing (OR 1.75, 95% CI 1.10–2.78) in local water bodies. Conclusions/Significance: Our results show that S. mansoni is highly endemic and a major health concern in Ituri province, DRC. Infection prevalence and intensity, and the prevailing socioeconomic, environmental, and behavioural risk factors in Ituri reflect intense exposure and alarming transmission rates. A robust plan of action is urgently needed in the province. Author summary: Intestinal schistosomiasis threatens many people in the tropical world, particularly those in Sub–Saharan Africa. Information on schistosomiasis in the Democratic Republic of Congo (DRC) is very scarce, which is a major barrier to planning and implementing efficient control programmes. We conducted two community–based studies with the objective of assessing the geographical distribution of S. mansoni infection across the Ituri province in north-eastern DRC and determining the prevailing risk factors. In 2016, a geographical distribution and in 2017, an in–depth studies were conducted in selected villages. Households were randomly selected and members, aged one year and older and present on the survey day, were enrolled. In 2016, one stool sample was examined per participant, whereas several stool samples were examined for each participant in 2017. S. mansoni eggs were detected using the Kato–Katz technique. A point–of–care circulating cathodic S. mansoni antigen (POC–CCA) urine test was also used in 2017. Household and individual questionnaires were used to collect demographic, socioeconomic, environmental, behavioural and knowledge data. In 2016, of the 2,131 participants, 40.0% of were infected with S. mansoni. Of the 707 participants in 2017, 73.1% were tested positive for S. mansoni. Infection prevalence increased from north to south and from west to east. Exposure to the Lake Albert and villages' altitude were main drivers of the distribution. Men and women had the same infection risk. Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected. Poor housing structure, proximity to water bodies, long–term residence in a community, lack of latrine in the household, and swimming and washing in local water bodies were the main risk factors. Our results confirm that S. mansoni is highly endemic in Ituri province, DRC. Both infection prevalence and intensity indicate intense exposure and alarming transmission. Control interventions are warranted and should pay attention to high–risk communities and population groups, including preschool children. [ABSTRACT FROM AUTHOR]

Background: Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. Methods/Principal findings: In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99–2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. Conclusions/Significance: Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity. Author summary: Schistosomiasis caused by Schistosoma mansoni is of great public health importance in sub-Saharan Africa. The World Health Organization (WHO) recommends that control efforts aim to reduce morbidity through large-scale intervention programmes. However, intestinal and liver morbidity is rarely assessed in such control programmes. Hence, little is known about (i) the magnitude of the intestinal and liver morbidity burden in the community, or about (ii) the morbidity associated with S. mansoni infection, specifically. We conducted a cross-sectional study in which we assessed intestinal morbidity by questionnaire and liver morbidity by abdominal ultrasonography. Additionally, we determined the infection status of the study participants using standard diagnostic procedures (Kato-Katz technique and point-of-care cathodic circulating S. mansoni antigen [POC-CCA] urine test). Among the 586 study participants, aged six years and older, from 13 villages in Ituri Province, DRC, we observed a high degree of intestinal (23.4% with diarrhoea; 21.5% with blood in stool) and hepatosplenic morbidity (42.8% with abnormal liver C, D, E, and F patterns; 26.5% with an enlarged liver; 25.3% with an enlarged spleen). S. mansoni infection was associated with liver and spleen enlargement. Likewise, S. mansoni infection intensity was linked to diarrhoea, to liver and spleen enlargement and to pathological changes in the liver parenchyma. At village level, we observed that the prevalence of an enlarged liver and spleen among patients increased with the prevalence of S. mansoni infection. We conclude that the population of Ituri Province carries an alarming burden of intestinal, liver and spleen morbidity associated with S. mansoni infection. A comprehensive control programme to address this infection and disease burden is urgently required. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis remains a global-health problem with over 90% of its burden concentrated in Africa. Field studies reflect the complex ways in which socio-cultural and socio-economic variables, affect the distribution of Schistosoma infections across different populations. This review set out to systematically investigate and quantify the differences in Schistosoma infection burdens between males and females in Africa for two of the most prevalent Schistosoma species—Schistosoma mansoni and Schistosoma haematobium. Methodology: We searched (from inception to 11th March 2020) Embase, MEDLINE, PubMed, and Web of Science for relevant studies on schistosomiasis. We included studies that report S. mansoni and/or S. haematobium prevalence and/or intensity data distributed between males and females. We conducted meta-analyses on the male to female (M:F) prevalence of infection ratios. Subgroup analyses were performed according to study baseline prevalence, sample size and the lower and upper age limit of study participants. We also present a descriptive analysis of differential risk and intensity of infection across males and females. Evidence for differences in the prevalence of schistosomiasis infection between males and females is presented, stratified by Schistosoma species. Result: We identified 128 relevant studies, with over 200,000 participants across 23 countries. Of all the reported differences in the prevalence of infection between males and females, only 41% and 34% were statistically significant for S. mansoni and S. haematobium, respectively. Similar proportions of studies (27% and 34% for for S. haematobium and S. mansoni, respectively) of the reported differences in intensity of infection between males and females were statistically significant. The meta-analyses summarized a higher prevalence of infection in males; pooled random-effects weighted M:F prevalence of infection ratios were 1.20 (95% CI 1.11–1.29) for S. haematobium and 1.15 (95% CI 1.08–1.22) for S. mansoni. However, females are underrespresented in some of the studies. Additionally, there was significant heterogeneity across studies (Higgins I2 statistic (p-values < 0.001, I2values>95%)). Results of the subgroup analysis showed that the baseline prevalence influenced the M:F prevalence ratios for S. haematobium and S. mansoni, with higher M:F prevalence of infection ratios in settings with a lower baseline prevalence of infection. Across the studies, we identified four major risk factors associated with infection rates: occupational and recreational water contact, knowledge, socio-economic factors and demographic factors. The effect of these risk factors on the burden of infection in males and females varied across studies. Conclusions: We find evidence of differences in prevalence of infection between males and females which may reflect differences in gender norms and water contact activities, suggesting that policy changes at the regional level may help ameliorate gender-related disparities in schistosomiasis infection burden. Collecting, robustly analysing, and reporting, sex-disaggregated epidemiological data, is currently lacking, but would be highly informative for planning effective treatment programmes and establishing those most at risk of schistosomiasis infections. Author summary: Schistosomiasis is a parasitic waterborne disease affecting more than 240 million people worldwide every year, especially in sub-Saharan Africa. The difference in schistosoma infection prevalence, infection intensity and risk between males and females has rarely been quantified. In this study, we aim to qualitatively and quantitatively synthesise published studies that present sex-disaggregated epidemiological data and investigate gender differences (e.g. those driven by social and cultural norms) that predispose males or females to higher risk of infection. Based on the 123 studies included in our meta-analysis, we found a higher prevalence of Schistosoma (S. mansoni and S. haematobium) in males. [ABSTRACT FROM AUTHOR]

Background: Schsistosomiasis is endemic in sub-Saharan Africa. It is transmitted by intermediate host snails such as Bulinus and Biomphalaria. An understanding of the abundance and distribution of snail vectors is important in designing control strategies. This study describes the spatial and seasonal variation of B. globosus and Bio. pfeifferi and their schistosome infection rates between May 2014 and May 2015 in Ingwavuma, uMkhanyakude district, KwaZulu-Natal province, South Africa. Methods: Snail sampling was done on 16 sites once every month by two people for 30 min at each site using the scooping and handpicking methods. Snails collected from each site were screened for schistosome mammalian cercariae by the shedding method. The negative binomial generalised linear mixed model (glmm) was used to determine the relationship between abundances of the intermediate host snails and climatic factors [rainfall, land surface temperatures (LST), seasons, habitats, sampling sites and water physico-chemical parameters including pH and dissolved oxygen (DO)]. Results: In total, 1846 schistosomiasis intermediate host snails were collected during the study period. Biompharia pfeifferi was more abundant (53.36%, n = 985) compared to B. globosus (46.64%, n = 861). Bulinus globosus was recorded at 12 sites (75%) and Bio. pfeifferi was present at 7 sites (43.8%). Biompharia pfeifferi cohabited with B. globosus at all the sites it was present. High numbers of Bio. pfeifferi (n = 872, 88.5%) and B. globosus (n = 705, 81.9%) were found between winter and mid-spring. Monthly rainfall showed a statistically significant negative relationship with the abundance of B. globosus (p < 0.05). Dissolved oxygen (DO) had a statistically significant positive relationship with the abundance of Bio. pfeifferi (p < 0.05) while (LST) had a statistically significant negative relationship (p < 0.05). More B. globosus (8.9%, n = 861) were shedding schistosome mammalian cercariae compared to Bio. pfeifferi (0.1%, n = 985) confirming the already documented high prevalence of S. haematobium in Ingwavuma compared to S. mansoni. Conclusion: Results of this study provide updated information on the distribution of schistosomiasis intermediate host snails in the study area and contributes towards the understanding of the transmission dynamics of schistosomiasis at the micro-geographical scale in this area. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis 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. Methodology: A 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. Results: The 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. Conclusion: S. 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. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis 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. Methodology: A 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. Results: The 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. Conclusion: S. 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. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is one of the widely distributed neglected tropical diseases. It is a serious public health problem in sub-Saharan Africa. The disease is highly prevalent and widely distributed in Ethiopia due to suitable environmental factors and human activities. The prevalence and infection intensity varied from locality to locality in the country. This study aimed to assess the prevalence and intensity of S. mansoni infection and associated risk factors among schoolchildren around Lake Tana. Methods: A school-based cross-sectional study was conducted among 710 schoolchildren from February to April 2021 in eight selected primary schools around Lake Tana. A questionnaire was used to collect data on socio-demographic information and potential risk factors of S. mansoni infection. After collecting socio-demographic information, students were requested to bring about 2grams of stool specimens for parasitological examination. The collected stool samples were processed using a single Kato-Katz and Ritchie's concentration techniques. The data were analyzed using SPSS software version 23 and factors with a p-value < 0.05 were considered as statistically significant. Results: The overall prevalence of S. mansoni was 34.9% (95% CI: 31.4–38.7) among schoolchildren in the study area. The eggs per gram (EPG) of stool ranged from 24 to 1659 with arithmetic and geometric mean values of 138.1 EPG and 85.1 EPG, respectively. The majority of S. mansoni infections (61.4%) were classified as low infection intensity. Among the different determinant factors being male (AOR = 1.74; 95%CI = 1.233–2.457; P-value = 0.002), bathing habits (AOR = 1.494; 95%CI = 1.013–2.199; P-value = 0.043) and students attending at Qunzela primary school (AOR = 10.545; 95%CI = 3.264–34.067; P-value = 0.001), Alabo primary school (AOR = 3.386; 95%CI = 1.084–10.572; P-value = 0.036) were significantly associated with S. mansoni infection. Conclusion: This study revealed that more than one-third of schoolchildren were infected by S. mansoni in the study area. The majority of the infections were classified as low infection intensity. Being male, bathing habits and schools in which students attended were independent explanatory factors for S. mansoni infection. Therefore, integrated control strategies are needed to improve the health conditions of schoolchildren in the study area. Author summary: We conducted a school-based cross-sectional study to assess the prevalence and intensity of Schistosoma mansoni infection and associated risk factors. Stool samples were collected from 681 schoolchildren and processed using Kato-Katz and Ritchie's concentration techniques. Among those students, 238 (34.9%) were infected with S. mansoni. Kato-Katz and Ritchie's concentration detect 220 (92.4%) and 165 (69.3%) of the total positive cases, respectively. Most of the S. mansoni infections were categorized as low infection intensity based on egg per gram of stool. Among the potential risk factors assessed; being male, bathing habits in open water and schools in which students attended were independent predictors for S. mansoni infection. [ABSTRACT FROM AUTHOR]

Schistosomiasis remains a worldwide public health problem, especially in sub-Saharan Africa. The World Health Organization targets the goal for its elimination as a public health problem in the 2030 Neglected Tropical Diseases (NTDs) Roadmap. Concerted action and agile responses to challenges will be necessary to achieve the targets. Better diagnostic tests can accelerate progress towards the elimination by monitoring disease trends and evaluating the effectiveness of interventions; however, current examinations such as Kato–Katz technique are of limited power to detect light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) test shows a higher sensitivity compared to the reference standard, Kato-Katz technique, but it still lacks sufficient sensitivity with low infection intensity. In this study, we examined antibody reactions against recombinant protein antigens; Schistosoma mansoni serine protease-inhibitor (SmSerpin) and RP26, by enzyme-linked immunosorbent assay (ELISA) in plasma samples with light-intensity infection. The sensitivity using the cocktail antigen of recombinant SmSerpin and RP26 showed 83.7%. The sensitivity using S. mansoni soluble egg antigen (SmSEA) was 90.8%, but it showed poor specificity (29.7%), while the cocktail antigen presented improved specificity (61.4%). We conclude that antibody detection to the SmSerpin and RP26 protein antigens is effective to detect S. mansoni light-intensity infections. Our study indicates the potential of detecting antibody against recombinant protein antigens to monitor the transmission of schistosomiasis in low endemicity contexts. [Display omitted] [ABSTRACT FROM AUTHOR]