Advances in the study of the interaction between schistosome infections and the host's intestinal microorganisms.

Schistosomiasis, also called bilharziasis, is a neglected tropical disease induced by schistosomes that infects hundreds of millions of people worldwide. In the life cycle of schistosomiasis, eggs are regarded as the main pathogenic factor, causing granuloma formation in the tissues and organs of hosts, which can cause severe gastrointestinal and liver granulomatous immune responses and irreversible fibrosis. Increasing evidence suggests that the gut microbiome influences the progression of schistosomiasis and plays a central role in liver disease via the gut-liver axis. When used as pharmaceutical supplements or adjunctive therapy, probiotics have shown promising results in preventing, mitigating, and even treating schistosomiasis. This review elucidates the potential mechanisms of this three-way parasite-host-microbiome interaction by summarizing schistosome-mediated intestinal flora disorders, local immune changes, and host metabolic changes, and elaborates the important role of the gut microbiome in liver disease after schistosome infection through the gut-liver axis. Understanding the mechanisms behind this interaction may aid in the discovery of probiotics as novel therapeutic targets and sustainable control strategies for schistosomiasis.

Knowledge, attitudes, and practices regarding schistosomiasis infection and prevention: A mixed-methods study among endemic communities of western Uganda.

INTRODUCTION: In Uganda, schistosomiasis (re)infections have continued to remain high despite the implementation of mass drug administration and sensitization campaigns aimed at controlling the disease. This could imply that there are some barriers to the implemented preventive measures. We conducted a mixed-methods study in Kagadi and Ntoroko districts around Lake Albert to assess knowledge, attitudes, and practices regarding schistosomiasis and to explore and understand perspectives regarding the disease. MATERIALS AND METHODS: Semi-structured survey questionnaires were administered to 337 household adults selected through systematic random sampling. We also interviewed 12 participants and held 28 focus-group discussion sessions with 251 individuals respectively. Quantitative data was analysed using frequencies, percentages, and chi-square tests for associations, while themes and sub-themes were used to analyse qualitative data respectively. FINDINGS: A total of 98.5%, 81.3%, and 78.5% had heard about schistosomiasis, and knew the main transmission modes and symptoms, respectively. The majority (75.8%) said avoiding contact with water was a preventative way, while 67.5% said observing signs and symptoms was a form of diagnosis. Furthermore, 98.4% and 73.4% said it was important to defecate in latrines and to avoid contact with contaminated water respectively. However, it is difficult to avoid contact with lake water because it is the only source of livelihood, especially for fisher communities. Open defecation is commonly practiced along the lake due to insufficient space and difficulties in the construction of latrines. Myths and misconceptions reported include; lake water is safe, gassing in water causes transmission, fetching water early in the morning and from deep water is safe, and feces in the lake water act as a bait for catching fish. CONCLUSIONS AND RECOMMENDATIONS: Despite adequate knowledge of schistosomiasis and a positive attitude towards its prevention, existing myths and misconceptions, coupled with persistent risky water, sanitation, and hygiene practices still pose a challenge. A more robust community-based awareness intervention using bottom-up participatory approaches, accompanied by the provision of clean and safe water sources and increasing latrine coverage, could provide lasting solutions to these barriers.

TIPS and splenorenal shunt for complications of portal hypertension in chronic hepatosplenic schistosomiasis-A case series and review of the literature.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) and shunt surgery are established treatment options for portal hypertension, but have not been systematically evaluated in patients with portal hypertension due to hepatosplenic schistosomiasis (HSS), one of the neglected tropical diseases with major impact on morbidity and mortality in endemic areas. METHODS: In this retrospective case study, patients with chronic portal hypertension due to schistosomiasis treated with those therapeutic approaches in four tertiary referral hospitals in Germany and Italy between 2012 and 2020 were included. We have summarized pre-interventional clinical data, indication, technical aspects of the interventions and clinical outcome. FINDINGS: Overall, 13 patients with confirmed HSS were included. 11 patients received TIPS for primary or secondary prophylaxis of variceal bleeding due to advanced portal hypertension and failure of conservative management. In two patients with contraindications for TIPS or technically unsuccessful TIPS procedure, proximal splenorenal shunt surgery in combination with splenectomy was conducted. During follow-up (mean follow-up 23 months, cumulative follow-up time 31 patient years) no bleeding events were documented. In five patients, moderate and transient episodes of overt hepatic encephalopathy were observed. In one patient each, liver failure, portal vein thrombosis and catheter associated sepsis occurred after TIPS insertion. All complications were well manageable and had favorable outcomes. CONCLUSIONS: TIPS implantation and shunt surgery are safe and effective treatment options for patients with advanced HSS and sequelae of portal hypertension in experienced centers, but require careful patient selection.

Immunometabolism: Towards a Better Understanding the Mechanism of Parasitic Infection and Immunity.

As a relatively successful pathogen, several parasites can establish long-term infection in host. This "harmonious symbiosis" status relies on the "precise" manipulation of host immunity and metabolism, however, the underlying mechanism is still largely elusive. Immunometabolism is an emerging crossed subject in recent years. It mainly discusses the regulatory mechanism of metabolic changes on reprogramming the key transcriptional and post-transcriptional events related to immune cell activation and effect, which provides a novel insight for understanding how parasites regulate the infection and immunity in hosts. The present study reviewed the current research progress on metabolic reprogramming mechanism exploited by parasites to modulate the function in various immune cells, highlighting the future exploitation of key metabolites or metabolic events to clarify the underlying mechanism of anti-parasite immunity and design novel intervention strategies against parasitic infection.

Mastomys natalensis (Smith, 1834) as a natural host for Schistosoma haematobium (Bilharz, 1852) Weinland, 1858 x Schistosoma bovis Sonsino, 1876 introgressive hybrids.

Cercarial emission of schistosomes is a determinant in the transmission to the definitive host and constitutes a good marker to identify which definitive host is responsible for transmission, mainly in introgressive hybridization situations. Our goal was to test the hypothesis that micro-mammals play a role in Schistosoma haematobium, S. bovis, and/or S. haematobium x S. bovis transmission. Small mammal sampling was conducted in seven semi-lacustrine villages of southern Benin. Among the 62 animals trapped, 50 individuals were investigated for Schistosoma adults and eggs: 37 Rattus rattus, 3 Rattus norvegicus, 9 Mastomys natalensis, and 1 Crocidura olivieri. Schistosoma adults were found in four R. rattus and two M. natalensis, with a local prevalence reaching 80% and 50%, respectively. Two cercarial chronotypes were found from Bulinus globosus experimentally infected with miracidia extracted from naturally infected M. natalensis: a late diurnal and nocturnal chronotype, and an early diurnal, late diurnal, and nocturnal chronotype. The cytochrome C oxidase subunit I mtDNA gene of the collected schistosomes (adults, miracidia, and cercariae) belonged to the S. bovis clade. Eleven internal transcribed spacer rDNA profiles were found; four belonged to S. bovis and seven to S. haematobium x S. bovis. These molecular results together with the observed multi-peak chronotypes add M. natalensis as a new host implicated in S. haematobium x S. bovis transmission. We discuss the origin of the new chronotypes which have become more complex with the appearance of several peaks in a 24-h day. We also discuss how the new populations of offspring may optimize intra-host ecological niche, host spectrum, and transmission time period.

Evidence of a Putative Novel Species of Avian Schistosome Infecting Planorbella trivolvis.

Freshwater gastropods of the genera Lymnaea Lamarck, 1799, Physa Draparnaud, 1801, Gyraulus Charpentier, 1837, Radix Montfort, 1810, and Stagnicola Jeffreys, 1830 are considered suitable intermediate hosts for avian schistosomes. A large trematode biodiversity survey performed across 3 yr on 6 lakes in Alberta confirmed 3 already-reported snail hosts for 7 North American avian schistosomes; however, the cytochrome c oxidase subunit 1 (COI) nucleotide sequence from 1 cercarial sample (from a single specimen of Planorbella trivolvis) was distinct from all other COI schistosome sequences. As part of a simultaneous, comparable study of P. trivolvis by us in Michigan, we collected another cercarial type from 6 lakes that was 99% similar (COI) to the aforementioned cercarial type. Phylogenetic analyses of the COI and 28S rDNA genes recovered the former cercaria in a clade of avian schistosomes. In Michigan, the feces of a Canada goose (Branta canadensis Linnaeus, 1758) had a miracidium with an identical COI nucleotide sequence. Preliminary swimmer's itch and cercarial emergence studies were performed to determine if the cercariae could cause swimmer's itch and to study the emergence pattern as compared with species of Trichobilharzia Skrjabin and Zakharow, 1920.

Immunomodulation and Immune Escape Strategies of Gastrointestinal Helminths and Schistosomes.

Parasitic worms (helminths) developed various immunoregulatory mechanisms to counteract the immune system of their host. The increasing identification and characterization of helminth-derived factors with strong immune modulatory activity provides novel insights into immune escape strategies of helminths. Such factors might be good targets to enhance anti-helminthic immune responses. In addition, immunosuppressive helminth-derived factors could be useful to develop new therapeutic strategies for treatment of chronic inflammatory conditions. This review will take an in depth look at the effects of immunomodulatory molecules produced by different helminths with a focus on schistosomes and mouse models of hookworm infections.

Prevalence and distribution of schistosomiasis in human, livestock, and snail populations in northern Senegal: a One Health epidemiological study of a multi-host system.

BACKGROUND: Schistosomiasis is a neglected tropical disease of global medical and veterinary importance. As efforts to eliminate schistosomiasis as a public health problem and interrupt transmission gather momentum, the potential zoonotic risk posed by livestock Schistosoma species via viable hybridisation in sub-Saharan Africa have been largely overlooked. We aimed to investigate the prevalence, distribution, and multi-host, multiparasite transmission cycle of Haematobium group schistosomiasis in Senegal, West Africa. METHODS: In this epidemiological study, we carried out systematic surveys in definitive hosts (humans, cattle, sheep, and goats) and snail intermediate hosts, in 2016-18, in two areas of Northern Senegal: Richard Toll and Lac de Guiers, where transmission is perennial; and Barkedji and Linguère, where transmission is seasonal. The occurrence and distribution of Schistosoma species and hybrids were assessed by molecular analyses of parasitological specimens obtained from the different hosts. Children in the study villages aged 5-17 years and enrolled in school were selected from school registers. Adults (aged 18-78 years) were self-selecting volunteers. Livestock from the study villages in both areas were also randomly sampled, as were post-mortem samples from local abattoirs. Additionally, five malacological surveys of snail intermediate hosts were carried out at each site in open water sources used by the communities and their animals. FINDINGS: In May to August, 2016, we surveyed 375 children and 20 adults from Richard Toll and Lac de Guiers, and 201 children and 107 adults from Barkedji and Linguère; in October, 2017, to January, 2018, we surveyed 386 children and 88 adults from Richard Toll and Lac de Guiers, and 323 children and 85 adults from Barkedji and Linguère. In Richard Toll and Lac de Guiers the prevalence of urogenital schistosomiasis in children was estimated to be 87% (95% CI 80-95) in 2016 and 88% (82-95) in 2017-18. An estimated 63% (in 2016) and 72% (in 2017-18) of infected children were shedding Schistosoma haematobium-Schistosoma bovis hybrids. In adults in Richard Toll and Lac de Guiers, the prevalence of urogenital schistosomiasis was estimated to be 79% (52-97) in 2016 and 41% (30-54) in 2017-18, with 88% of infected samples containing S haematobium-S bovis hybrids. In Barkedji and Linguère the prevalence of urogenital schistosomiasis in children was estimated to be 30% (23-38) in 2016 and 42% (35-49) in 2017-18, with the proportion of infected children found to be shedding S haematobium-S bovis hybrid miracidia much lower than in Richard Toll and Lac de Guiers (11% in 2016 and 9% in 2017-18). In adults in Barkedji and Linguère, the prevalence of urogenital schistosomiasis was estimated to be 26% (17-36) in 2016 and 47% (34-60) in 2017-18, with 10% of infected samples containing S haematobium-S bovis hybrids. The prevalence of S bovis in the sympatric cattle population of Richard Toll and the Lac de Guiers was 92% (80-99), with S bovis also found in sheep (estimated prevalence 14% [5-31]) and goats (15% [5-33]). In Barkedji and Linguère the main schistosome species in livestock was Schistosoma curassoni, with an estimated prevalence of 73% (48-93) in sheep, 84% (61-98) in goats and 8% (2-24) in cattle. S haematobium-S bovis hybrids were not found in livestock. In Richard Toll and Lac de Guiers 35% of infected Bulinus spp snail intermediate hosts were found to be shedding S haematobium-S bovis hybrids (68% shedding S haematobium; 17% shedding S bovis); however, no snails were found to be shedding S haematobium hybrids in Barkedji and Linguère (29% shedding S haematobium; 71% shedding S curassoni). INTERPRETATION: Our findings suggest that hybrids originate in humans via zoonotic spillover from livestock populations, where schistosomiasis is co-endemic. Introgressive hybridisation, evolving host ranges, and wider ecosystem contexts could affect the transmission dynamics of schistosomiasis and other pathogens, demonstrating the need to consider control measures within a One Health framework. FUNDING: Zoonoses and Emerging Livestock Systems programme (UK Biotechnology and Biological Sciences Research Council, UK Department for International Development, UK Economic and Social Research Council, UK Medical Research Council, UK Natural Environment Research Council, and UK Defence Science and Technology Laboratory).

Effectiveness analysis of spatially targeted mollusciciding for Oncomelania snail control.

A new developed spatially targeted mollusciciding technology for snail control was utilised in a research site. This study aims to analyse whether this technology can achieve rational effectiveness compared with the routine method. Snail density was monitored every spring and autumn from 2010 to 2017 at the research site and routine mollusciciding for snail control was then performed. After snail density monitoring in spring 2018, spatially targeted mollusciciding technology was adopted. Log-linear regression and nonlinear regression models were used for snail density prediction in autumn 2018 and the predicted value was compared with the actual snail density in autumn 2018 to verify the effectiveness of the spatially targeted mollusciciding. Monitoring results showed that overall snail density in the research site decreased from 2010 to 2018. The monitored snail density in autumn 2018 was 0.014/0.1 m2. Predicted by the log-linear regression model, the snail density in autumn 2018 would be 0.028 (95% CI 0.11-0.072)/0.1 m2. Predicted by the nonlinear regression model, the snail density growth in autumn 2018 in contrast to spring 2018 would be 79.79% (95% CI 54.81%-104.77%) and the actual value was 55.56%. Therefore, the effectiveness of the first application of spatially targeted mollusciciding was acceptable. However, the validation of its sustainable effectiveness still needs a replicated study comparing areas where targeted and untargeted methods are applied simultaneously and both snail abundance and human infection are monitored.

Effects of agrochemical pollution on schistosomiasis transmission: a systematic review and modelling analysis.

BACKGROUND: Agrochemical pollution of surface waters is a growing global environmental challenge, especially in areas where agriculture is rapidly expanding and intensifying. Agrochemicals might affect schistosomiasis transmission through direct and indirect effects on Schistosoma parasites, their intermediate snail hosts, snail predators, and snail algal resources. We aimed to review and summarise the effects of these agrochemicals on schistosomiasis transmission dynamics. METHODS: We did a systematic review of agrochemical effects on the lifecycle of Schistosoma spp and fitted dose-response models to data regarding the association between components of the lifecycle and agrochemical concentrations. We incorporated these dose-response functions and environmentally relevant concentrations of agrochemicals into a mathematical model to estimate agrochemical effects on schistosomiasis transmission. Dose-response functions were used to estimate individual agrochemical effects on estimates of the agrochemically influenced basic reproduction number, R0, for Schistosoma haematobium. We incorporated time series of environmentally relevant agrochemical concentrations into the model and simulated mass drug administration control efforts in the presence of agrochemicals. FINDINGS: We derived 120 dose-response functions describing the effects of agrochemicals on schistosome lifecycle components. The median estimate of the basic reproduction number under agrochemical-free conditions, was 1·65 (IQR 1·47-1·79). Agrochemical effects on estimates of R0 for S haematobium ranged from a median three-times increase (R0 5·05, IQR 4·06-5·97) to transmission elimination (R0 0). Simulations of transmission dynamics subject to interacting annual mass drug administration and agrochemical pollution yielded a median estimate of 64·82 disability-adjusted life-years (DALYs) lost per 100 000 people per year (IQR 62·52-67·68) attributable to atrazine use. In areas where aquatic arthropod predators of intermediate host snails suppress transmission, the insecticides chlorpyrifos (6·82 DALYs lost per 100 000 people per year, IQR 4·13-8·69) and profenofos (103·06 DALYs lost per 100 000 people per year, IQR 89·63-104·90) might also increase the disability burden through their toxic effects on arthropods. INTERPRETATION: Expected environmental concentrations of agrochemicals alter schistosomiasis transmission through direct and indirect effects on intermediate host and parasite densities. As industrial agricultural practices expand in areas where schistosomiasis is endemic, strategies to prevent increases in transmission due to agrochemical pollution should be developed and pursued. FUNDING: National Science Foundation, National Institutes of Health.

Aquatic macrophytes and macroinvertebrate predators affect densities of snail hosts and local production of schistosome cercariae that cause human schistosomiasis.

BACKGROUND: Schistosomiasis is responsible for the second highest burden of disease among neglected tropical diseases globally, with over 90 percent of cases occurring in African regions where drugs to treat the disease are only sporadically available. Additionally, human re-infection after treatment can be a problem where there are high numbers of infected snails in the environment. Recent experiments indicate that aquatic factors, including plants, nutrients, or predators, can influence snail abundance and parasite production within infected snails, both components of human risk. This study investigated how snail host abundance and release of cercariae (the free swimming stage infective to humans) varies at water access sites in an endemic region in Senegal, a setting where human schistosomiasis prevalence is among the highest globally. METHODS/PRINCIPAL FINDINGS: We collected snail intermediate hosts at 15 random points stratified by three habitat types at 36 water access sites, and counted cercarial production by each snail after transfer to the laboratory on the same day. We found that aquatic vegetation was positively associated with per-capita cercarial release by snails, probably because macrophytes harbor periphyton resources that snails feed upon, and well-fed snails tend to produce more parasites. In contrast, the abundance of aquatic macroinvertebrate snail predators was negatively associated with per-capita cercarial release by snails, probably because of several potential sublethal effects on snails or snail infection, despite a positive association between snail predators and total snail numbers at a site, possibly due to shared habitat usage or prey tracking by the predators. Thus, complex bottom-up and top-down ecological effects in this region plausibly influence the snail shedding rate and thus, total local density of schistosome cercariae. CONCLUSIONS/SIGNIFICANCE: Our study suggests that aquatic macrophytes and snail predators can influence per-capita cercarial production and total abundance of snails. Thus, snail control efforts might benefit by targeting specific snail habitats where parasite production is greatest. In conclusion, a better understanding of top-down and bottom-up ecological factors that regulate densities of cercarial release by snails, rather than solely snail densities or snail infection prevalence, might facilitate improved schistosomiasis control.

Cercarial swimming performance and its potential role as a key variable of trematode transmission.

Trematode transmission in aquatic habitats from molluscan intermediate host to vertebrate or invertebrate target host is typically undertaken by a free-living stage known as cercariae. Active locomotion by cercariae is a key aspect of the transmission process with the swimming speed potentially contributing to infection success. Individual cercarial species swim at different speeds but the significance of this to infection potential has not been determined. This study, using data from the scientific literature, investigates the role of swimming speed in relation to cercarial morphology, host-searching strategies and target host species. Larger cercariae swim faster than smaller ones with tail length being the principal factor controlling locomotion rates. Different cercarial morphotypes swim at different speeds, in particular, furcocercariae, with the exception of the schistosomes, being faster swimmers than mono-tailed cercariae. Host-searching behaviour has a significant influence on swimming speeds with 'active-searching' strategies swimming slower than those adopting 'active-waiting' or 'prey mimcry' strategies. Vertebrate-infecting cercariae swim faster than those infecting invertebrates with species targeting fish demonstrating the highest locomotion rates and those targeting arthropods the slowest speeds. The adaptions of individual cercarial swimming speeds to biological variables and their interactions with the physical processes of aquatic habitats are discussed.

Behind Enemy Lines: Immunomodulatory Armamentarium of the Schistosome Parasite.

The deeply rooted, intricate relationship between the Schistosoma parasite and the human host has enabled the parasite to successfully survive within the host and surreptitiously evade the host's immune attacks. The parasite has developed a variety of strategies in its immunomodulatory armamentarium to promote infection without getting harmed or killed in the battlefield of immune responses. These include the production of immunomodulatory molecules, alteration of membranes, and the promotion of granuloma formation. Schistosomiasis thus serves as a paradigm for understanding the Th2 immune responses seen in various helminthiases. This review therefore aims to summarize the immunomodulatory mechanisms of the schistosome parasites to survive inside the host. Understanding these immunomodulatory strategies not only provides information on parasite-host interactions, but also forms the basis in the development of novel drugs and vaccines against the schistosome infection, as well as various types of autoimmune and inflammatory conditions.

New Insights on Acute and Chronic Schistosomiasis: Do We Need a Redefinition?

A precise timeframe to differentiate acute schistosomiasis (AS) and chronic schistosomiasis (CS) is not well defined. Based on recent published literature, lung nodular lesions in AS and CS seem to have the same pathophysiology, that is, eggs laid in situ by adult worms, during an ectopic migration. Moreover, the occurrence of lung nodules due to clusters of eggs and the systemic immunoallergic reaction of AS (Katayama syndrome) may be two separate clinical entities, which may overlap during the early phase of infection. Consequently, the classical distinction between AS and CS loses much of its conceptual validity. If adult worms play a more important role in the early phase of the disease the clinical management of AS should probably be revised.

Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa.

Analyses of the population genetic structure of schistosomes under the "Schistosomiasis Consortium for Operational Research and Evaluation" (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent "biological hotspot" sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general.

Schistosome TRP channels: An appraisal.

Ion channels underlie electrical excitability in cells and are essential for a variety of functions, most notably neuromuscular and sensory activity. They are also validated targets for a preponderance of approved anthelmintic compounds. Transient receptor potential (TRP) channels constitute an ion channel superfamily whose members play important roles in sensory signaling, regulation of ion homeostasis, organellar trafficking, and other key cellular and organismal activities. Unlike most other ion channels, TRP channels are often polymodal, gated by a variety of mechanisms. Furthermore, TRP channels fall into several classes or subtypes based on sequence and structure. Until recently, there had been very little investigation of the properties and functions of TRP channels from parasitic helminths, including schistosomes, but that situation has changed in the past few years. Indeed, it is now clear that at least some schistosome TRP channels exhibit unusual pharmacological properties, and, intriguingly, both a mammalian and a schistosome TRP channel are activated by praziquantel, the current antischistosomal drug of choice. With the latest release of the Schistosoma mansoni genome database, several changes in predicted TRP channel sequences appeared, some of which were significant. This review updates and reassesses the TRP channel repertoire in S. mansoni, examines recent findings regarding these potential therapeutic targets, and provides guideposts for some of the physiological functions that may be mediated by these channels in schistosomes.

Current and Novel Therapies Against Helminthic Infections: The Potential of Antioxidants Combined with Drugs.

Infections caused by Schistosoma haematobium and Opisthorchisviverrini are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that might be considered as initiators of infection-associated carcinogenesis. Chemotherapy for these helminthic infections relies on a single drug, praziquantel, (PZQ) that mainly targets the parasite. Additionally, PZQ has some major drawbacks as inefficacy against juvenile form and alone it is not capable to counteract pathologies associated to infections or prevent carcinogenesis. There is an urgent need to develop novel therapeutic approaches that not only target the parasite but also improve the pathologies associated to infection, and ultimately, counteract or/and prevent the carcinogenesis processes. Repurposing the drug in combination of compounds with different modes of action is a promising strategy to find novel therapeutics approaches against these helminthic infections and its pathologies. Here, we emphasized that using antioxidants either alone or combined with anthelmintic drugs could ameliorate tissue damage, infection-associated complications, moreover, could prevent the development of cancer associated to infections. Hence, antioxidants represent a potential adjuvant approach during treatment to reduce morbidity and mortality. Despite the success of some strategies, there is a long way to go to implement novel therapies for schistosomiasis.

Reduce Disease Burden of Human Schistosomiasis in Asia Through Biological Control.

Schistosomiasis is a chronic parasitic disease caused by a trematode blood fluke of the genus Schistosoma that belongs to the Schistosomatidae family. It is a neglected disease in different regions of Asia. In this review, 218 articles (between 2000 and 2017) related to the topic were collected from PubMed and Google scholar and reviewed. After thoroughly reading collected articles, due to irrelevant topic requirements, 94 articles were excluded. Articles that have data associated with Asian regions are considered. In Asia, the disease is prevalent in China, Philippines, Indonesia, Yemen, Nepal and Laos, etc. While in Pakistan, India and Bangladesh, the disease is not endemic and very few cases were reported. The disease was eliminated from Japan and Iran. The current review highlights the geographical distribution among Asian countries, transmission patterns, diagnosis, control strategies based on the use of anthelmintic plants and management practices implemented in Asia for the control of schistosomiasis. However, new implementations to treat schistosomiasis in humans should be proved to eliminate the disease finally in the future. This review emphasizes the biological control of schistosomiasis for the eradication of the disease from Asia in the near future.

Interactions of Schistosoma and HIV in Sub-Saharan Africa: A Systematic Review.

Schistosomiasis is an acute and chronic parasitic disease caused by blood flukes of the genus Schistosoma. More than 220 million people worldwide were estimated to have active schistosomiasis in 2017, 90% of whom live on the African continent, but only 102 million were reported to have received treatment. Africa is also disproportionately burdened by HIV, with an estimated 26 million people living with HIV in 2017. Given these overlapping epidemics, we conducted a systematic review to ascertain the contribution of schistosomes to HIV acquisition risk, the contribution of HIV to schistosome acquisition, the impact of HIV on schistosomiasis-related morbidity, the impact of schistosomes on HIV disease progression and immune response, the impact of HIV on the efficacy of praziquantel treatment, and the impact of HIV on egg shedding. We reviewed studies of people living in sub-Saharan Africa coinfected with HIV and Schistosoma spp. between January 1996 and July 2018. We found that 1) infection with Schistosoma haematobium increases the risk of HIV acquisition, 2) there is currently a lack of data on whether HIV infection increases the risk of Schistosoma acquisition, 3a) HIV coinfection was not an accelerating factor for adverse Schistosoma outcomes, 3b) schistosomiasis may be an important contributor to immune activation in HIV coinfected people, 4) praziquantel use in coinfected people may improve immune reconstitution on antiretroviral therapy for HIV, and 5) there is evidence that HIV infection reduces egg excretion in individuals infected with Schistosoma mansoni.

High prevalence of Schistosoma haematobium × Schistosoma bovis hybrids in schoolchildren in Côte d'Ivoire.

Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been reported in West Africa, no data about Schistosoma hybrids in humans are available from Côte d'Ivoire. This study aimed to identify and quantify S. haematobium-bovis hybrids among schoolchildren in four localities of Côte d'Ivoire. Urine samples were collected and examined by filtration to detect Schistosoma eggs. Eggs were hatched and 503 miracidia were individually collected and stored on Whatman® FTA cards for molecular analysis. Individual miracidia were molecularly characterized by analysis of mitochondrial cox1 and nuclear internal transcribed spacer 2 (ITS 2) DNA regions. A mitochondrial cox1-based diagnostic polymerase chain reaction was performed on 459 miracidia, with 239 (52.1%) exhibiting the typical band for S. haematobium and 220 (47.9%) the S. bovis band. The cox1 and ITS 2 amplicons were Sanger sequenced from 40 randomly selected miracidia to confirm species and hybrids status. Among the 33 cox1 sequences analysed, we identified 15 S. haematobium sequences (45.5%) belonging to seven haplotypes and 18 S. bovis sequences (54.5%) belonging to 12 haplotypes. Of 40 ITS 2 sequences analysed, 31 (77.5%) were assigned to pure S. haematobium, four (10.0%) to pure S. bovis and five (12.5%) to S. haematobium-bovis hybrids. Our findings suggest that S. haematobium-bovis hybrids are common in Côte d'Ivoire. Hence, intense prospection of domestic and wild animals is warranted to determine whether zoonotic transmission occurs.