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BACKGROUND: Schistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. Type 2 inflammation contributes to the development of Schistosoma-induced PH. Specifically, interstitial macrophages (IMs) derived from monocytes play a pivotal role by producing thrombospondin-1 (TSP-1), which in turn activates TGF-β, thereby driving the pathology of PH. Resident and recruited IM subpopulations have recently been identified. We hypothesized that in Schistosoma-PH, one IM subpopulation expresses monocyte recruitment factors, whereas recruited monocytes become a separate IM subpopulation that expresses TSP-1. METHODS: Mice were intraperitoneally sensitized and then intravenously challenged with S. mansoni eggs. Flow cytometry on lungs and blood was performed on wildtype and reporter mice to identify IM subpopulations and protein expression. Single-cell RNA sequencing (scRNAseq) was performed on flow-sorted IMs from unexposed and at day 1, 3 and 7 following Schistosoma exposure to complement flow cytometry based IM characterization and identify gene expression. RESULTS: Flow cytometry and scRNAseq both identified 3 IM subpopulations, characterized by CCR2, MHCII, and FOLR2 expression. Following Schistosoma exposure, the CCR2+ IM subpopulation expanded, suggestive of circulating monocyte recruitment. Schistosoma exposure caused increased monocyte-recruitment ligand CCL2 expression in the resident FOLR2+ IM subpopulation. In contrast, the vascular pathology-driving protein TSP-1 was greatest in the CCR2+ IM subpopulation. CONCLUSION: Schistosoma-induced PH involves crosstalk between IM subpopulations, with increased expression of monocyte recruitment ligands by resident FOLR2+ IMs, and the recruitment of CCR2+ IMs which express TSP-1 that activates TGF-β and causes PH.

Background: In Europe, avian schistosomes of the genus Trichobilharzia are the most common etiological agents involved in human cercarial dermatitis (swimmer's itch). Manifested by a skin rash, the condition is caused by an allergic reaction to cercariae of nonhuman schistosomes. Humans are an accidental host in this parasite's life cycle, while water snails are the intermediate, and waterfowl are the final hosts. The study aimed to conduct a molecular and phylogenetic analysis of Trichobilharzia species occurring in recreational waters in North-Eastern Poland. Methodology: The study area covered three water bodies (Lake Skanda, Lake Ukiel, and Lake Tyrsko) over the summer of 2021. In total, 747 pulmonate freshwater snails (Radix spp., Lymnaea stagnalis) were collected. Each snail was subjected to 1–2 h of light stimulation to induce cercarial expulsion. The phylogenetic analyses of furcocercariae were based on the partial sequence of the ITS region (ITS1, 5.8S rDNA, ITS2 and 28SrDNA). For Radix spp. phylogenetic analyses were based on the ITS-2 region. Results: The prevalence of the Trichobilharzia species infection in snails was 0.5%. Two out of 478 (0.4%) L. stagnaliswere found to be infected with Trichobilharzia szidati. Moreover, two out of 269 (0.7%) snails of the genus Radix were positive for schistosome cercariae. Both snails were identified as Radix auricularia. One of them was infected with Trichobilharzia franki and the other with Trichobilharzia sp. Conclusions: Molecular identification of avian schistosome species, both at the intermediate and definitive hosts level, constitutes an important source of information on a potential threat and prognosis of local swimmer's itch occurrence, and helps to determine species diversity in a particular area. [ABSTRACT FROM AUTHOR]

A fecal survey in Tamil Nadu, India, revealed 2 persons passed schistosome eggs, later identified as Schistosoma incognitum, a parasite of pigs, dogs, and rats. We investigated those cases and reviewed autochthonous schistosomiasis cases from India and Nepal. Whether the 2 new cases represent true infection or spurious passage is undetermined.

Schistosomiasis, acquired by skin-penetrating cercariae of dioecious digenean schistosomes during freshwater contact, afflicts nearly 260 and 440 million people with active infections and residual morbidity, respectively. About 10 million women at reproductive age contract schistosomiasis during gestation every year. Acute schistosomiasis is characterized by pre-patent pro-inflammatory CD4+ T-helper 1 or CD4+ Th1/T-helper 17 reactivity against immature schistosomulae. Chronic schistosomiasis is dominated by post-patent anti-inflammatory CD4+ T-helper 2 reactivity against ova epitopes. Flukes co-exist in immunocompetent definitive hosts as they are capable of evading their defense mechanisms. Preventive measures should be complemented by vaccination, inducing long-term protection against transmission, infection, and disease recurrence, given the latest advancements in schistosomal vaccines. Vaccines become pivotal when considering constraints of chemotherapy, i.e., lack of protection against re-infection, and evolving resistance or reduced sensitivity. Transmission models for human non-zoonotic schistosomiasis incorporating vaccination available in PubMed, Embase and Web of Science up to 31 December 2023 are presented. Besides conceptual model differences, predictions meant to guide decision- and policymaking reveal continued worm harboring that facilitates transmission besides residual infections. In addition, increased susceptibility to re-infection and rebound morbidity, both shifted to later life stages following the intervention, are forecasted. Consequently, a vaccination schedule is pivotal that considers the optimal age for initial immunization, i.e., pre-schoolchildren or schoolchildren in a cohort-based or population-based manner, while incorporating potential non-adherers promoting ongoing transmission. Longevity over magnitude of vaccine protection to antigenic schistosomal moieties is crucial. Accounting for pre-acquired immunity from natural exposure, in utero priming in addition to herd immunity, and induced by chemotherapy is crucial. Combining, as a multi-component approach, long-term effects of vaccination with short-term effects of chemotherapy as regular repeated vaccine-linked therapy seems most promising to achieve WHO’s endpoints of transmission elimination and morbidity control.

Background: Schistosomiasis is one of the endemic parasitic diseases in many developing countries. Despite this, appendicitis secondary to schistosomiasis is an uncommon condition even in some endemic areas. Schistosomal appendicitis, an incidentally discovered appendicitis associated with schistosomiasis histological findings, affects young males predominantly. Timely diagnosis and treatment, including appendectomy and anti-helminthic therapy, are crucial. Case report: A 24-year-old Sudanese male patient presented with abdominal pain. Diagnosed with acute appendicitis, he underwent appendectomy, revealing appendix inflammation with Schistosoma ova in histopathology. Abdominal ultrasound detected no complications. Weakly positive Schistosoma serology was noted, but stool and urine analysis showed no infection evidence. Prescribed praziquantel, patient had 3-year post-op follow-up without complications. Conclusions: This case report underscores the significance of including schistosomiasis in the differential diagnosis of appendicitis, particularly in regions where the disease is endemic. It underscores the necessity of histopathological evaluations for accurate diagnosis, emphasizing the potential implications for clinical practice in similar settings. [ABSTRACT FROM AUTHOR]

Background: Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes. Methods: We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized. Results: We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries. Conclusions: This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a parasitic disease characterized by liver fibrosis, a process driven by the activation of hepatic stellate cells (HSCs) and subsequent collagen production. Previous studies from our laboratory have demonstrated the ability of Schistosoma japonicum protein P40 (SjP40) to inhibit HSCs activation and exert an antifibrotic effect. In this study, we aimed to elucidate the molecular mechanism underlying the inhibitory effect of recombinant SjP40 (rSjP40) on HSCs activation. Using a cell model in which rSjP40 inhibited LX‐2 cell activation, we performed RNA‐seq analyses and identified ATF3 as the most significantly altered gene. Further investigation revealed that rSjP40 inhibited HSCs activation partly by suppressing ATF3 activation. Knockdown of ATF3 in mouse liver significantly alleviated S. japonicum‐induced liver fibrosis. Moreover, our results indicate that ATF3 is a direct target of microRNA‐494‐3p, a microRNA associated with anti‐liver fibrosis effects. rSjP40 was found to downregulate ATF3 expression by upregulating microRNA‐494‐3p in LX‐2 cells. This downregulation led to the inhibition of the expression of liver fibrosis proteins α‐SMA and COL1A1, ultimately alleviating liver fibrosis caused by S. japonicum. [ABSTRACT FROM AUTHOR]

Schistosomiasis, acquired by skin-penetrating cercariae of dioecious digenean schistosomes during freshwater contact, afflicts nearly 260 and 440 million people with active infections and residual morbidity, respectively. About 10 million women at reproductive age contract schistosomiasis during gestation every year. Acute schistosomiasis is characterized by pre-patent pro-inflammatory CD4+ T-helper 1 or CD4+ Th1/T-helper 17 reactivity against immature schistosomulae. Chronic schistosomiasis is dominated by post-patent anti-inflammatory CD4+ T-helper 2 reactivity against ova epitopes. Flukes co-exist in immunocompetent definitive hosts as they are capable of evading their defense mechanisms. Preventive measures should be complemented by vaccination, inducing long-term protection against transmission, infection, and disease recurrence, given the latest advancements in schistosomal vaccines. Vaccines become pivotal when considering constraints of chemotherapy, i.e., lack of protection against re-infection, and evolving resistance or reduced sensitivity. Transmission models for human non-zoonotic schistosomiasis incorporating vaccination available in PubMed, Embase and Web of Science up to 31 December 2023 are presented. Besides conceptual model differences, predictions meant to guide decision- and policymaking reveal continued worm harboring that facilitates transmission besides residual infections. In addition, increased susceptibility to re-infection and rebound morbidity, both shifted to later life stages following the intervention, are forecasted. Consequently, a vaccination schedule is pivotal that considers the optimal age for initial immunization, i.e., pre-schoolchildren or schoolchildren in a cohort-based or population-based manner, while incorporating potential non-adherers promoting ongoing transmission. Longevity over magnitude of vaccine protection to antigenic schistosomal moieties is crucial. Accounting for pre-acquired immunity from natural exposure, in utero priming in addition to herd immunity, and induced by chemotherapy is crucial. Combining, as a multi-component approach, long-term effects of vaccination with short-term effects of chemotherapy as regular repeated vaccine-linked therapy seems most promising to achieve WHO's endpoints of transmission elimination and morbidity control. [ABSTRACT FROM AUTHOR]

Background: The role of parasitic infections in acute appendicitis is still debatable. We aimed to investigate the role of parasitic infections in acute appendicitis as a neglected risk factor in an attempt to early recognition and treatment. Patients and Methods: A retrospective study included 1365 patients who underwent appendectomy. Demographic data, presentation, complications, investigation, and pathological reports were obtained from patients' records. Patients were categorized into two groups: group I (n=37), with parasitic infections present, and group II (n=1328) absent parasitic infections. Results: The prevalence of acute parasitic appendicitis was 2.7%. The mean age group of patients with appendiceal parasitic infections was 23.86±10.1 years with a male/female ratio of 1.6:1. The detected parasites were 21 (56.8%) Enterobius vermicularis, 9 (24.3%) Ascaris lumbricoides, 7 (18.9%) Schistosoma mansoni. The histopathological examination of acute appendicitis with parasitic infections revealed non-complicated histopathology in 62.2% of specimens, acute catarrhal inflammation in 13.5% of specimens, acute suppurative appendicitis in 16.2%, acutely gangrenous appendicitis in 5.4% of specimens and with schistosomiasis infection there was acutely gangrenous appendicitis with perforation in 2.7% of specimens. Common presenting symptoms in acute appendicitis with parasitic infections were nausea in 86.5%, and periumbilical pain in 78.3%. The complications were significantly common among acute appendicitis patients with parasitic infections (13.5%) compared to those without parasitic infections (4.1%) (p=0.006). There is no reported mortality among studied cases. Conclusions: The current study demonstrated that acute parasitic infection is one of the infectious agents that may increase the risk of appendicitis and can be identified postoperatively in the resected appendix. These findings emphasize the importance of considering the neglected role of parasites in acute appendicitis. As a result, early detection and treatment of parasites are recommended for complete eradication. [ABSTRACT FROM AUTHOR]

The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents of schistosomiasis. Indeed, the peptide tag of the hybrid compounds can be hydrolyzed by worm's digestive enzymes to afford a highly labile alkoxyamine which homolyzes spontaneously and instantaneously into radicals—which are then used as a drug against Schistosome adult parasites. This approach is nicely summarized as digging their graves with their forks. Several hybrid peptide-alkoxyamines were prepared and clearly showed an activity: two of the tested compounds kill 50% of the parasites in two hours at a concentration of 100 µg/mL. Importantly, the peptide and alkoxyamine fragments that are unable to generate alkyl radicals display no activity. This strong evidence validates the proposed mechanism: a specific activation of the prodrugs by the parasite proteases leading to parasite death through in situ alkyl radical generation. [ABSTRACT FROM AUTHOR]

Schistosomiasis, a neglected tropical disease, caused by blood flukes belonging to the genus Schistosoma; it persists as a public health problem in selected regions throughout Africa, South America, and Asia. Schistosoma mekongi, a zoonotic schistosome species endemic to the Mekong River in Laos and Cambodia, is one of the significant causes of human schistosomiasis along with S. japonicum, S. mansoni, S. haematobium and S. intercalatum. Since its discovery, S. mekongi infection has been highly prevalent in communities along the Mekong River. Although surveillance and control measures have shown success in recent years, more robust diagnostic tools are still needed to establish more efficient control and prevention strategies to achieve and sustain an elimination status. Diagnosis of S. mekongi infection still relies on copro-parasitological techniques, commonly made by Kato-Katz stool examination. Serological techniques such as enzyme-linked immunosorbent assay (ELISA) may also be applicable but in a limited setting. Targeted molecular and serological tools specific to the species, on the other hand, have been limited. This is due, in part, to the limited research and studies on the molecular biology of S. mekongi since genome information of this species has not yet been released. In this review, current advances, and gaps and limitations in the molecular and immunological diagnosis of S. mekongi are discussed. [ABSTRACT FROM AUTHOR]

A laboratory-based lateral flow (LF) test that utilizes up-converting reporter particles (UCP) for ultrasensitive quantification of Schistosoma circulating anodic antigen (CAA) in urine is a well-accepted test to identify active infection. However, this UCP-LF CAA test requires sample pre-treatment steps not compatible with field applications. Flow, a new low-cost disposable, allows integration of large-volume pre-concentration of urine analytes and LF detection into a single field-deployable device. We assessed a prototype Flow-Schistosoma (Flow-S) device with an integrated UCP-LF CAA test strip, omitting all laboratory-based steps, to enable diagnosis of active Schistosoma infection in the field using urine. Flow-S is designed for large-volume (5–20 mL) urine, applying passive paper-based filtration and antibody-based CAA concentration. Samples tested for schistosome infection were collected from women of reproductive age living in a Tanzania region where S. haematobium infection is endemic. Fifteen negative and fifteen positive urine samples, selected based on CAA levels quantified in paired serum, were analyzed with the prototype Flow-S. The current Flow-S prototype, with an analytical lower detection limit of 1 pg CAA/mL, produced results correlated with the laboratory-based UCP-LF CAA test. Urine precipitates occurred in frozen banked samples and affected accurate quantification; however, this should not occur in fresh urine. Based on the findings of this study, Flow-S appears suitable to replace the urine pre-treatment required for the laboratory-based UCP-LF CAA test, thus allowing true field-based applications with fresh urine samples. The urine precipitates observed with frozen samples, though less important given the goal of testing fresh urines, warrant additional investigation to evaluate methods for mitigation. Flow-S devices permit testing of pooled urine samples with applications for population stratified testing. A field test with fresh urine samples, a further optimized Flow-S device, and larger statistical power has been scheduled. [ABSTRACT FROM AUTHOR]

Co-exposure to multiple parasites can alter parasite success and host life history when compared to single infections. These infection outcomes can be affected by the order of parasite arrival, the host immune response, and the interspecific interactions among co-infecting parasites. In this study, we examined how the arrival order of two trematode parasites, Schistosoma mansoni and Echinostoma caproni, influenced parasite ecology and the life history of their snail host, Biomphalaria glabrata. Snail hosts were exposed to E. caproni cercariae before, with, and after their exposure to S. mansoni miracidia. We then measured the effects of this timing on infection prevalence, infection intensity of E. caproni metacercariae, and cercarial output of S. mansoni, as well as on snail reproduction and survival. Snails infected only with S. mansoni and snails exposed to E. caproni after S. mansoni both shed more cercariae than simultaneously exposed snails. Additionally, S. mansoni prevalence was lower in snails that were first exposed to E. caproni compared to snails that were exposed to E. caproni after S. mansoni. Moreover, snails exposed to E. caproni before S. mansoni did not differ in their survival compared to control snails, whereas simultaneously exposed snails and snails exposed to E. caproni after S. mansoni had lower survival than control snails. Combined, this prevalence and survival data suggest a potential protective role of early E. caproni exposure. The timing of E. caproni exposure impacts S. mansoni establishment and reproduction, but host survival patterns are likely driven by S. mansoni prevalence alone. [ABSTRACT FROM AUTHOR]

In September 2022, the Drug Discovery Unit at the University of Dundee, UK, organised an international meeting at the Wellcome Collection in London to explore the current clinical situation and challenges associated with treating schistosomiasis. The aim of this meeting was to discuss the need for new treatments in view of the clinical situation and to ascertain what the key requirements would be for any potential new anti-schistosomals. This information will be essential to inform ongoing drug discovery efforts for schistosomiasis. We also discussed the potential drug discovery pathway and associated criteria for progressing compounds to the clinic. To date, praziquantel (PZQ) is the only drug available to treat all species causing schistosomiasis, but it is often unable to completely clear parasites from an infected patient, partially due to its inactivity against juvenile worms. PZQ-mediated mass drug administration campaigns conducted in endemic areas (e.g., sub-Saharan Africa, where schistosomiasis is primarily prevalent) have contributed to reducing the burden of disease but will not eliminate the disease as a public health problem. The potential for Schistosoma to develop resistance towards PZQ, as the sole treatment available, could become a concern. Consequently, new anthelmintic medications are urgently needed, and this Perspective aims to capture some of the learnings from our discussions on the key criteria for new treatments.

Background: Species hybridization represents a real concern in terms of parasite transmission, epidemiology and morbidity of schistosomiasis. It is greatly important to better understand the impact of species hybridization for the clinical management. Methods: A prospective observational study was carried out in sub-Saharan migrants who were diagnosed with confirmed genitourinary schistosomiasis. A tailored protocol was applied, including Schistosoma serology, a specific urine LAMP tests for schistosomiasis and an ultrasound examination before treatment with praziquantel. A scheduled follow-up was performed at 3, 6 and 12 months to monitor treatment response, comparing patients carriers of Schistosoma hybrids with carriers of only genetically pure forms. Results: A total of 31 male patients from West Africa were included in the study with a mean age of 26.5 years. Twelve (38.7 %) of the patients were carriers of Schistosoma hybrids. As compared with patients infected with S. haematobium alone, hybrid carriers had lower haemoglobin levels (13.8 g/dL [SD 1.8] vs 14.8 g/dL [SD 1.4], p = 0.04), a greater frequency of hematuria (100 % vs 52.6 %, p = 0.005), a higher ultrasound score (2.64, SD 2.20 vs 0.89, SD 0.99; p = 0.02). However, the presence of hybrids did not result in differences in clinical and analytical responses after treatment. Conclusions: The presence of Schistosoma hybrids seems to cause increased morbidity in infected individuals. However, it does not appear to result in differences in diagnostic tests or in clinical and analytical responses after treatment.

Schistosomiasis causes over 200,000 deaths annually. The current treatment option, praziquantel, presents limitations, including low bioavailability and resistance. In this context, nanoparticles have emerged as a promising option for improving schistosomiasis treatment. Several narrative reviews have been published on this topic. Unfortunately, the lack of clear methodologies presented in these reviews leads to the exclusion of many important studies without apparent justification. This integrative review aims to examine works published in this area with a precise and reproducible method. To achieve this, three databases (i.e., Pubmed, Web of Science, and Scopus) were searched from March 31, 2022, to March 31, 2023. The search results included only original research articles that used nanoparticles smaller than 1 µm in the treatment context. Additionally, a search was conducted in the references of the identified articles to retrieve works that could not be found solely using the original search formula. As a result, 65 articles that met the established criteria were identified. Inorganic and polymeric nanoparticles were the most prevalent nanosystems used. Gold was the primary material used to produce inorganic nanoparticles, while poly(lactic-co-glycolic acid) and chitosan were commonly used to produce polymeric nanoparticles. None of these identified works presented results in the clinical phase. Finally, based on our findings, the outlook appears favorable, as there is a significant diversity of new substances with schistosomicidal potential. However, financial efforts are required to advance these nanoformulations.

The Grand Round concerns a 24-year-old man from Zimbabwe who was studying and living in Poland. The patient had been complaining of abdominal pain, fatigue, alternating diarrhoea and constipation, and presence of blood in his stool for 3 years. The patient had the following diagnostic tests: colonoscopy, CT scan, histopathology, and parasitological and molecular tests. Results of the examinations showed that the cause of the patient's complaints was chronic intestinal schistosomiasis due to the co-infection with Schistosoma intercalatum and Schistosoma mansoni. The patient had two cycles of praziquantel therapy (Biltricide) and responded well to the treatment. In the Grand Round, we describe full diagnostics as well as clinical and therapeutic management in the patient with S intercalatum and S mansoni co-infection. This case allows us to draw attention to cases of forgotten chronic tropical diseases (including rare ones) in patients from regions with a high endemic index staying in non-endemic regions of the world for a long time. Co-infection with S intercalatum and S mansoni should be considered as a very rare clinical case. [ABSTRACT FROM AUTHOR]

Microbiota in intermediate hosts of human schistosomes play a significant role in various aspects of snail biology, such as growth and development. Understanding the potential impact of microbiota on snail–schistosome interactions and snail competence is crucial for future research and requires omics-based approaches. Successfully developing axenic and gnotobiotic models is a significant step that involves proper isolation of snail eggs, effective sterilization methods, suitable nutrition, and husbandry practices. And more axenic snail species are needed to cover diverse schistosome species. Advancing axenic and gnotobiotic snail systems and combining them with advanced technologies can offer insights into the role of snail microbiota and uncover intricate microbiota–snail and snail–parasite interactions, leading to the development of new strategies for controlling schistosomiasis. The microbiota in the intermediate snail hosts of human schistosomes can significantly affect host biology. For decades, researchers have developed axenic snails to manipulate the symbiotic microbiota. This review summarizes the characteristics of symbiotic microbes in intermediate snail hosts and describes their interactions with snails, affecting snail growth, development, and parasite transmission ability. We focus on advances in axenic and gnotobiotic technologies for studying snail–microbe interactions and exploring the role of microbiota in snail susceptibility to Schistosoma infection. We discuss the challenges related to axenic and gnotobiotic snails, possible solutions to address these challenges, and future research directions to deepen our understanding of snail–microbiota interactions, with the aim to develop microbiota-based strategies for controlling snail populations and reducing their competence in transmitting parasites. [ABSTRACT FROM AUTHOR]

Human schistosomiasis, a neglected tropical disease affecting millions of people, mainly in sub-Saharan Africa, is caused by a parasitic worm of the Schistosoma genus that resides in the veins of its host for many years. In parasite-host interactions, there is competition for survival between the parasite and its host because the parasite depends completely on the host for the maintenance of homeostasis. The host must protect itself from the harm caused by parasites in the process of obtaining food and shelter by attacking parasites with a strong immune defence system. Parasites have evolved strategies to survive in these unfavourable conditions created by the host. In this review, we examined the host immune response in Schistosoma parasite infection, the immune evasion mechanisms of Schistosoma parasites, nutrients, and the metabolic dependency of the parasite on the host. [ABSTRACT FROM AUTHOR]

Background: Trematode infections of the genus Schistosoma can induce physiological and behavioral changes in intermediate snail hosts. This is because the parasite consumes essential resources necessary for the host's survival, prompting hosts to adapt their behavior to maintain some level of fitness before parasite-induced mortality occurs. Methods: In this study, the reproductive and biochemical parameters of Biomphalaria alexandrina and Bulinus truncatus were examined during the cercareal shedding stage of infection with Schistosoma mansoni and Schistosoma haematobium, respectively, compared with controls. Results: The study revealed an infection rate of 34.7% for S. mansoni and 30.4% for S. haematobium. In B. alexandrina infected with S. mansoni, a survival rate of 65.2% was recorded, along with a mean prepatent period of 30.3 ± 1.41 days, a mean shedding duration of 14.2 ± 0.16 days, and a mean lifespan of 44.1 ± 0.24 days. Meanwhile, in B. truncatus infected with S. haematobium, a survival rate of 56.4% was observed, with a mean prepatent period of 44.3 ± 1.41 days, a mean shedding duration of 22.6 ± 2.7 days, and a mean lifespan of 66.9 ± 1.6 days. Feeding increased in both infected species of snails, while the net reproductive rate (Ro) of the infected snails decreased. Total antioxidant (TAO) and lipid peroxidation activity increased in the two infected snail species during shedding, while Glutathione-S-transferase levels decreased. Lipid peroxidase activity and nitrogen oxide levels significantly decreased in infected B. alexandrina and increased in infected Bulinus. Steroid hormone levels were elevated in infected Biomphalaria, whereas they were reduced in infected Bulinus. Comet assay parameters showed an increase in the two infected genera after infection compared to control snails, indicating genotoxic damage and histopathological damage was observed. Conclusions: These findings demonstrate that infection with larva species diverse biochemical, hormonal, genotoxic, and histopathological changes in the tissues responsible for fecundity and reproduction in B. alexandrina and B. truncates comparing with controls. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis significantly impacts public health, as it causes severe morbidity. Infections caused by Schistosoma mansoni (S. mansoni) can be treated with gold nanoparticles (AuNPs). This study aims to determine the most effective route of AuNPs administration and the magnitude of its anti-fibrotic effect. Methods: In the five groups' in vivo assay design, AuNPs were administered intraperitoneally (1 mg/kg) and orally (1 mg/100 g) to S. mansoni-infected mice. Biochemical parameters (serum levels of albumin and liver enzymes alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured. The histological changes of the liver in distinct groups were evaluated using Hematoxylin and Eosin, Masson's trichrome, and immunohistochemical stains. Results: Infection with S. mansoni was associated with substantial changes in the histological architecture of liver tissue and abnormal levels of hepatic function tests (albumin, AST, and ALT). Schistosoma infected hepatocytes exhibited an abnormal microscopic morphology, granuloma formation and aggressive fibrosis. AuNPs restored the liver histological architecture with a highly significant anti-fibrotic effect and significantly corrected hepatic function test levels. Intraperitoneal administration of AuNPs resulted in the most significant anti-fibrotic effect against hepatic S. mansoni infection as observed in all histological sections with Masson's trichrome being the best stain to represent this fact. Conclusion: For treating S. mansoni-induced chronic liver fibrosis, intraperitoneal administration of AuNPs is a successful and effective route of administration that can be recommended. [ABSTRACT FROM AUTHOR]

Background Female genital schistosomiasis (FGS) is a chronic gynaecological disease affecting girls and women in sub-Saharan Africa (SSA), caused by the parasite Schistosoma (S.) haematobium. FGS is associated with sexual dysfunction, reproductive tract morbidity and increased prevalence of HIV and cervical precancer lesions. Source of data Key peer-reviewed published literature. Areas of agreement FGS screening and diagnosis require costly equipment and specialized training, seldom available in resource-limited settings. FGS surveillance is not included in wider schistosomiasis control strategies. The interplay of FGS with other SRH infections is not fully understood. Integration of FGS within sexual and reproductive health (SRH) control programmes needs to be explored. Areas of controversy There are no standardized methods for individual or population-based FGS screening and diagnosis, hindering accurate disease burden estimates and targeted resource allocation. Treatment recommendations rely on public health guidelines, without rigorous clinical evidence on efficacy. Growing points Integrating FGS screening with SRH programmes offers an opportunity to reach at-risk women with limited access to healthcare services. Home-based self-sampling coupled with handheld colposcopes operated by primary healthcare workers show promise for FGS diagnosis and surveillance at scale. Areas timely for developing research There is growing interest in decentralizing strategies for FGS screening and diagnosis. The accurate predictions on the 'cost-effectiveness' of these approaches will determine their affordability and feasibility within the overburdened health systems in SSA. Clinical trials are needed to optimize FGS treatment. Longitudinal studies can expand on the epidemiological knowledge on co-morbidities and integration within other SRH interventions. [ABSTRACT FROM AUTHOR]

Background and Aim: Freshwater snails belonging to the family Planorbidae serve as the first intermediate hosts of many species of important parasitic flukes of animals and humans. Information regarding the occurrence of planorbid snail larval trematode infection is limited in Northern Thailand. Thus, this study aimed to estimate the prevalence of larval trematode infection of the freshwater snail Indoplanorbis exustus in Uttaradit, Thailand, and to identify trematode species based on their morphological and molecular characteristics. Materials and Methods: Planorbid snail specimens were collected from a water reservoir in Uttaradit, Thailand, from June to August 2023. Snails were assessed for larval trematode infection through cercarial shedding and crushing methods. The released cercariae were preliminarily identified on the basis of their morphological characteristics. In addition, species identification of the detected cercariae was conducted using 28S ribosomal RNA and cytochrome c oxidase subunit 1 gene sequence analyses. Results: The overall prevalence of cercarial infection was 61.5% (107/174) in planorbid snails in Uttaradit province. Two species of cercarial trematodes, Schistosoma spindale (106/174, 60.9%) and Artyfechinostomum malayanum (1/174, 0.6%), were identified using morphological and molecular analyses, of which S. spindale was the most abundant species. Our studied snails did not have mixed infection with more than two cercarial species. Conclusion: Our findings reveal a remarkably high prevalence of S. spindale cercariae infecting planorbid snails in Uttaradit, indicating that humans and animals across the study area are at risk of infection. Our data may contribute to the development of effective strategies to control this zoonotic infectious disease. [ABSTRACT FROM AUTHOR]

Background The conventional diagnostic for Schistosoma mansoni infection is stool microscopy with the Kato-Katz (KK) technique to detect eggs. Its outcomes are highly variable on a day-to-day basis and may lead to biased estimates of community infection used to inform public health programs. Our goal is to develop a resampling method that leverages data from a large-scale randomized trial to accurately predict community infection. Methods We developed a resampling method that provides unbiased community estimates of prevalence, intensity and other statistics for S mansoni infection when a community survey is conducted using KK stool microscopy with a single sample per host. It leverages a large-scale data set, collected in the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) project, and allows linking single—stool specimen community screening to its putative multiday "true statistics." Results SCORE data analysis reveals the limited sensitivity of KK stool microscopy and systematic bias of single-day community testing versus multiday testing; for prevalence estimate, it can fall up to 50% below the true value. The proposed SCORE cluster method reduces systematic bias and brings the estimated prevalence values within 5%–10% of the true value. This holds for a broad swath of transmission settings, including SCORE communities, and other data sets. Conclusions Our SCORE cluster method can markedly improve the S mansoni prevalence estimate in settings using stool microscopy. [ABSTRACT FROM AUTHOR]

Hepatic schistosomiasis is a prevalent form of chronic liver disease that drastically affects human health. Nevertheless, an antifibrotic drug that could suppress the development of hepatic fibrosis does not exist yet. The current study aimed to evaluate the effect of resveratrol, a natural polyphenol with multiple biological activities, on Schistosoma mansoni (S. mansoni)-induced hepatic fibrosis and delineate the underlying molecular mechanism. Swiss male albino mice were randomly assigned into infected and non-infected groups. Hepatic schistosomiasis infection was induced via exposure to S. mansoni cercariae. 6 weeks later, resveratrol was administrated either as 20 mg/kg/day or 100 mg/kg/day for 4 weeks to two infected groups. Another group received vehicle and served as infected control group. At the end of the study, portal hemodynamic, biochemical, and histopathological evaluation of liver tissues were conducted. Remarkably, resveratrol significantly reduced portal pressure, portal and mesenteric flow in a dose-dependent manner. It improved several key features of hepatic injury as evidenced biochemically by a significant reduction of bilirubin and liver enzymes, and histologically by amelioration of the granulomatous and inflammatory reactions. In line, resveratrol reduced the expression of pro-inflammatory markers; TNF-α, IL-1β and MCP-1 mRNA, together with fibrotic markers; collagen-1, TGF-β1 and α-SMA. Moreover, resveratrol restored SIRT1/NF-κB balance in hepatic tissues which is the main switch-off control for all the fibrotic and inflammatory mechanisms. Taken together, it can be inferred that resveratrol possesses a possible anti-fibrotic effect that can halt the progression of hepatic schistosomiasis via targeting SIRT1/ NF-κB signaling. [ABSTRACT FROM AUTHOR]

Schistosoma mekongi, a significant schistosome parasite, has various life stages, including egg, cercaria, female, and male, that play crucial roles in the complex life cycle. This study aimed to explore the microRNA (miRNA) profiles across these developmental stages to understand their potential functions and evolutionary significance, which have not been studied. Pre-processed sequencing reads of small RNA (sRNA) were obtained, and annotations were performed against the S. japonicum reference miRNA database. Results indicated marked variations in miRNA profiles across different life stages, with notable similarities observed between female and male S. mekongi. Principal Coordinate Analysis (PCoA) and unsupervised clustering revealed distinct miRNA signatures for each stage. Gene ontology (GO) analysis unveiled the potential roles of these miRNAs in various biological processes. The differential expression of specific miRNAs was prominent across stages, suggesting their involvement in crucial developmental processes. Furthermore, orthologous miRNA analysis against various worm species revealed distinct presence–absence patterns, providing insights into the evolutionary relationships of these miRNAs. In conclusion, this comprehensive investigation into the miRNA profiles of S. mekongi offers valuable insights into the functional and evolutionary aspects of miRNAs in schistosome biology. [ABSTRACT FROM AUTHOR]

Background: Despite the functions of TLRs in the parasitic infections have been extensively reported, few studies have addressed the role of TLR3 in the immune response to Schistosoma japonicum infections. The aim of this study was to investigate the properties of TLR3 in the liver of C57BL/6 mice infected by S. japonicum. Methods: The production of TLR3+ cells in CD4+T cells (CD4+CD3+), CD8+T cells (CD8+CD3+), γδT cells (γδTCR+CD3+), NKT cells (NK1.1+CD3+), B cells (CD19+CD3−), NK (NK1.1−CD3+) cells, MDSC (CD11b+Gr1+), macrophages (CD11b+F4/80+), DCs (CD11c+CD11b+) and neutrophils (CD11b+ Ly6g+) were assessed by flow cytometry. Sections of the liver were examined by haematoxylin and eosin staining in order to measure the area of granulomas. Hematological parameters including white blood cell (WBC), red blood cell (RBC), platelet (PLT) and hemoglobin (HGB) were analyzed. The levels of ALT and AST in the serum were measured using biochemical kits. The relative titers of anti-SEA IgG and anti-SEA IgM in the serum were measured by enzyme-linked immunosorbent assay (ELISA). CD25, CD69, CD314 and CD94 molecules were detected by flow cytometry. Results: Flow cytometry results showed that the expression of TLR3 increased significantly after S. japonicum infection (P < 0.05). Hepatic myeloid and lymphoid cells could express TLR3, and the percentages of TLR3-expressing MDSC, macrophages and neutrophils were increased after infection. Knocking out TLR3 ameliorated the damage and decreased infiltration of inflammatory cells in infected C57BL/6 mouse livers.,The number of WBC was significantly reduced in TLR3 KO-infected mice compared to WT-infected mice (P < 0.01), but the levels of RBC, platelet and HGB were significantly increased in KO infected mice. Moreover, the relative titers of anti-SEA IgG and anti-SEA IgM in the serum of infected KO mice were statistically decreased compared with the infected WT mice. We also compared the activation-associated molecules expression between S.japonicum-infected WT and TLR3 KO mice. Conclusions: Taken together, our data indicated that TLR3 played potential roles in the context of S. japonicum infection and it may accelerate the progression of S. japonicum-associated liver pathology. [ABSTRACT FROM AUTHOR]

Cancer involves a major aberration in the normal behaviour of cells, making them divide continuously, which interferes with the normal physiology of the body. The link between helminths and their cancer-inducing potential has been proposed in the last century. The exact pathway is still not clear but chronic inflammation in response to the deposited eggs, immune response against soluble egg antigens, and co-infection with a third party (a bacteria, a virus, or infection leading to a change in microbiome) seems to be the reasons for cancer induction. This review looks into the historical outlook on helminths along with their epidemiology, morphology, and life cycle. It then focuses on providing correlations between helminth infection and molecular mechanism of carcinogenesis by elaborating upon epidemiological, clinical, and surgical studies. While the cancer-inducing potential has been convincingly established only for a few helminths and studies point out towards possible cancer-inducing ability of the rest of the helminths elucidated in this work, however, more insights into the immunobiology of helminths as well as infected patients are required to conclusively comment upon this ability of the latter. [ABSTRACT FROM AUTHOR]

Whether all Schistosoma species cause pulmonary hypertension (PH) is unclear. Experimentally exposing mice to Schistosoma haematobium eggs caused PH, which was less severe than that induced by S. mansoni exposure. These findings align with the relatively uncommon reports of pulmonary arterial hypertension associated with S. haematobium. [ABSTRACT FROM AUTHOR]

Schistosomiasis, one of the neglected tropical diseases which affects both humans and animals, is caused by trematode worms of the genus Schistosoma. The disease is caused by several species of Schistosoma which affect several organs such as urethra, liver, bladder, intestines, skin and bile ducts. The life cycle of the disease involves an intermediate host (snail) and a mammalian host. It affects people who are in close proximity to water bodies where the intermediate host is abundant. Common clinical manifestations of the disease at various stages include fever, chills, headache, cough, dysuria, hyperplasia and hydronephrosis. To date, most of the control strategies are dependent on effective diagnosis, chemotherapy and public health education on the biology of the vectors and parasites. Microscopy (Kato-Katz) is considered the golden standard for the detection of the parasite, while praziquantel is the drug of choice for the mass treatment of the disease since no vaccines have yet been developed. Most of the previous reviews on schistosomiasis have concentrated on epidemiology, life cycle, diagnosis, control and treatment. Thus, a comprehensive review that is in tune with modern developments is needed. Here, we extend this domain to cover historical perspectives, global impact, symptoms and detection, biochemical and molecular characterization, gene therapy, current drugs and vaccine status. We also discuss the prospects of using plants as potential and alternative sources of novel anti-schistosomal agents. Furthermore, we highlight advanced molecular techniques, imaging and artificial intelligence that may be useful in the future detection and treatment of the disease. Overall, the proper detection of schistosomiasis using state-of-the-art tools and techniques, as well as development of vaccines or new anti-schistosomal drugs may aid in the elimination of the disease.

Right ventricular (RV) failure is the primary cause of death in pulmonary hypertension (PH), but the mechanisms of RV failure are not well understood. We hypothesized macrophages in the RV contribute to the RV response in PH. We induced PH in mice with hypoxia (FiO2 10%) and Schistosoma mansoni exposure, and in rats with SU5416-hypoxia. We quantified cardiac macrophages in mice using flow cytometry. Parabiosis between congenic CD45.1/.2 mice or Cx3cr1-green fluorescent protein and wild-type mice was used to quantify circulation-derived macrophages in experimental PH conditions. We administered clodronate liposomes to Sugen hypoxia (SU-Hx) exposed rats to deplete macrophages and evaluated the effect on the extracellular matrix (ECM) and capillary network in the RV. In hypoxia exposed mice, the overall number of macrophages did not significantly change but two macrophage subpopulations increased. Parabiosis identified populations of RV macrophages that at steady state is derived from the circulation, with one subpopulation that significantly increased with PH stimuli. Clodronate treatment of SU-Hx rats resulted in a change in the RV ECM, without altering the RV vasculature, and correlated with improved RV function. Populations of RV macrophages increase and contribute to RV remodeling in PH, including through regulation of the RV ECM.

The rising migration and travel from and towards endemic areas has brought renewed concerns about many parasitic infections, including neglected tropical diseases, such as schistosomiasis. Although serology is the most widely used method for the screening of schistosomiasis in non-endemic countries, this technique lacks sensitivity, especially to distinguish between past and ongoing infections. More recently, a molecular test based on the detection of Schistosoma cell-free DNA in the serum has been proposed as a diagnostic procedure for parasitosis. To test the performance of a blood PCR assay, this work investigated 102 serum samples collected from migrants coming from endemic areas by using primers specific to genomic regions of S. mansoni and S. haematobium patients. The results were then compared with the detection of specific IgG Abs with serological tests. Molecular analysis detected Schistosoma DNA in 32 patients. Among them, we characterized nine S. haematobium, 20 S. mansoni, and three coinfections. Compared with molecular assay, serological analysis detected specific antibodies against Schistosoma antigens in 52 out of 102 patients. Concordance between the two tests was found in 76 out of 102 patients (74.51%): in particular, both diagnostic tests were positive in 29 patients (28.43%) and negative in 47 (46.08%). The specificity of the molecular test was 94%. Overall, our data suggest that serological diagnosis could be combined with the molecular approach, providing the clinician with the serotyping of the parasite and useful information about the infection as well as the required further diagnostic procedures.

Schistosomiasis is considered as a significant public health problem, imposing a deeper understanding of the intricate interplay between parasites and their hosts. Unfortunately, current invasive methodologies employed to study the compatibility and the parasite development impose limitations on exploring diverse strains under various environmental conditions, thereby impeding progress in the field. In this study, we demonstrate the usefulness for the trematode parasite Schistosma mansoni, leveranging a fluorescence-imagingbased approach that employs fluorescein 5-chloromethylfluorescein diacetate (CMFDA) and 5-chloromethylfluorescein diacetate (CMAC) as organism tracker for intramolluscan studies involving the host snail Biomphalaria glabrata. These probes represent key tools for qualitatively assessing snail infections with unmatched accuracy and precision. By monitoring the fluorescence of parasites within the snail vector, our method exposes an unprecedented glimpse into the host-parasite compatibility landscape. The simplicity and sensitivity of our approach render it an ideal choice for evolutionary studies, as it sheds light on the intricate mechanisms governing host-parasite interactions. Fluorescent probe-based methods play a pivotal role in characterizing factors influencing parasite development and phenotype of compatibility, paving the way for innovative, effective, and sustainable solutions to enhance our understanding host-parasite immunobiological interaction and compatibility. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has recently published a draft definition of a persistent schistosomiasis hotspot, referring to, in brief, a location which satisfies specific prevalence and treatment intervention targets, but where transmission persists. Inconsistencies between this draft WHO definition and those already used in published research and implementation manuals could, however, lead to confusion for program managers, with potential implications for who gets treated and how. Using a comprehensive review of the literature, combined with interviews with stakeholders and an evaluation of each of the criteria in the draft WHO definition, we propose modifications to the definition of a persistent hotspot. We suggest regional flexibility in some of the thresholds and highlight areas where more research is needed to enable a universal standardised definition. The World Health Organization (WHO) recently proposed a new operational definition which designates communities with ≥10% prevalence of Schistosoma spp. infection as a persistent hotspot, when, after at least two rounds of high-coverage annual preventive chemotherapy, there is a lack of appropriate reduction. However, inconsistencies and challenges from both biological and operational perspectives remain, making the prescriptive use of this definition difficult. Here, we present a comprehensive analysis of the use of the term 'hotspot' across schistosomiasis research over time, including both literature searches and opinions from a range of stakeholders, to assess the utility and generalisability of the new WHO definition of a persistent hotspot. Importantly, we propose an updated definition based on our analyses. [ABSTRACT FROM AUTHOR]

The rising migration and travel from and towards endemic areas has brought renewed concerns about many parasitic infections, including neglected tropical diseases, such as schistosomiasis. Although serology is the most widely used method for the screening of schistosomiasis in non-endemic countries, this technique lacks sensitivity, especially to distinguish between past and ongoing infections. More recently, a molecular test based on the detection of Schistosoma cell-free DNA in the serum has been proposed as a diagnostic procedure for parasitosis. To test the performance of a blood PCR assay, this work investigated 102 serum samples collected from migrants coming from endemic areas by using primers specific to genomic regions of S. mansoni and S. haematobium patients. The results were then compared with the detection of specific IgG Abs with serological tests. Molecular analysis detected Schistosoma DNA in 32 patients. Among them, we characterized nine S. haematobium, 20 S. mansoni, and three coinfections. Compared with molecular assay, serological analysis detected specific antibodies against Schistosoma antigens in 52 out of 102 patients. Concordance between the two tests was found in 76 out of 102 patients (74.51%): in particular, both diagnostic tests were positive in 29 patients (28.43%) and negative in 47 (46.08%). The specificity of the molecular test was 94%. Overall, our data suggest that serological diagnosis could be combined with the molecular approach, providing the clinician with the serotyping of the parasite and useful information about the infection as well as the required further diagnostic procedures. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mekongi is a human blood fluke causing schistosomiasis that threatens approximately 1.5 million humans in the world. Nonetheless, the limited available S. mekongi genomic resources have hindered understanding of its biology and parasite-host interactions for disease management and pathogen control. The aim of our study was to integrate multiple technologies to construct a high-quality chromosome-level assembly of the S. mekongi genome. Methods: The reference genome for S. mekongi was generated through integrating Illumina, PacBio sequencing, 10 × Genomics linked-read sequencing, and high-throughput chromosome conformation capture (Hi-C) methods. In this study, we conducted de novo assembly, alignment, and gene prediction to assemble and annotate the genome. Comparative genomics allowed us to compare genomes across different species, shedding light on conserved regions and evolutionary relationships. Additionally, our transcriptomic analysis focused on genes associated with parasite-snail interactions in S. mekongi infection. We employed gene ontology (GO) enrichment analysis for functional annotation of these genes. Results: In the present study, the S. mekongi genome was both assembled into 8 pseudochromosomes with a length of 404 Mb, with contig N50 and scaffold N50 lengths of 1168 kb and 46,759 kb, respectively. We detected that 43% of the genome consists of repeat sequences and predicted 9103 protein-coding genes. We also focused on proteases, particularly leishmanolysin-like metalloproteases (M8), which are crucial in the invasion of hosts by 12 flatworm species. Through phylogenetic analysis, it was discovered that the M8 gene exhibits lineage-specific amplification among the genus Schistosoma. Lineage-specific expansion of M8 was observed in blood flukes. Additionally, the results of the RNA-seq revealed that a mass of genes related to metabolic and biosynthetic processes were up-regulated, which might be beneficial for cercaria production. Conclusions: This study delivers a high-quality, chromosome-scale reference genome of S. mekongi, enhancing our understanding of the divergence and evolution of Schistosoma. The molecular research conducted here also plays a pivotal role in drug discovery and vaccine development. Furthermore, our work greatly advances the understanding of host-parasite interactions, providing crucial insights for schistosomiasis intervention strategies. [ABSTRACT FROM AUTHOR]

Malacological and parasitological studies were conducted from April 2020 to March 2021 to determine the abundance and distribution of molluscs and cercariae of Schistosoma spp and Fasciola gigantica. Collected molluscs are exposed to strong light to induce cercarial release. Mollusc densities were higher at station 1 (Gamak) than in station 8 (Patakai), with Bellamya unicolor and Biomphalaria pfeifferi more abundant and Bulinus truncatus, B. tropicus, and B. globosus less abundant. The overall prevalence of cercariae (19.87%) is higher in station 3 (Yaye orchard), station 9 (Gougni), station 4 (Madiogo), station 5 (Madiogo pasture), and station 6 (Ziam 3). It varies significantly between 15.76% in station 8 and 25.77% in station 3, between 8.48% in B. truncatus and 25.53% in B. globosus, and between 19.27% for cercariae of Schistosoma spp and 21.60% for those of F. gigantica. Cercarial emissions in L. natalensis and B. pfeifferi were higher in hot and cold dry seasons; on the other hand, cercarial emissions in B. globosus were higher in hot dry seasons (31.48%) and rainy seasons (23.38%). Emissions of cercariae from S. haematobium are related to areas of human activity and defecation, while those of F. gigantica in L. natalensis, Schistosoma haematobium in B. tropicus, and S. mansoni in B. pfeifferi are related to grazing areas. Mayo-Vreck is a site that favors the endemicity of fascioliasis and human schistosomiasis. [ABSTRACT FROM AUTHOR]

Objective: Galectins are sugar-binding proteins that participate in many biological processes, such as immunity, by regulating host immune cells and their direct interaction with pathogens. They are involved in mediating infection by Schistosoma mansoni, a parasitic trematode that causes schistosomiasis. However, their direct effects on schistosomes have not been investigated. Results: We found that galectin-2 recognizes S. mansoni glycoconjugates and investigated whether galectin-1, 2, and 3 can directly affect S. mansoni in vitro. Adult S. mansoni were treated with recombinant galectin-1, 2, and 3 proteins or praziquantel, a positive control. Treatment with galectin-1, 2, and 3 had no significant effect on S. mansoni motility, and no other differences were observed under a stereoscopic microscope. Hence, galectin-1, 2, and 3 may have a little direct effect on S. mansoni. However, they might play a role in the infection in vivo via the modulation of the host immune response or secretory molecules from S. mansoni. To the best of our knowledge, this is the first study to investigate the direct effect of galectins on S. mansoni and helps in understanding the roles of galectins in S. mansoni infection in vivo. [ABSTRACT FROM AUTHOR]

In 1971, scientists from Mahidol University in Thailand and the Smithsonian Institution in the USA formed a research team to study a new species of Schistosoma in the Mekong River in Thailand and Laos. The studies, completed during 1971–1973, prior to the construction of any dams or restrictions to the natural flow regime of the Mekong River, provide a unique description of the natural ecological state of the river that can serve as a baseline for current research. The natural transmission of Schistosoma japonicum, Mekong Strain, was first reported on Khong Island, Laos in 1973 using sentinel mice. The first detailed description of the habitat ecology of the snail vector Neotricula aperta was done on-site in 1971 simultaneously with that research and is unique in providing the only description of the river shoreline habitat before any dams were built and any alteration of the natural flow regime was in place. Aggregating current information in a Place-Based Conceptual Model (PBCM) as an organizing template, along with current habitat models that combine ecological data with e-flows, can be developed and used as a tool to predict suitable habitats for snails. The natural flow regime of the Mekong River prior to any impoundments is described with current updates on the potential impacts of climate change and dams with flow-related snail habitat characteristics, including sediment drift and water quality. The application of the PBCM to describe and compare descriptive information on current and potential future N. aperta/S. mekongi habitat is discussed. Author summary: We provide a unique profile of Neotricula aperta habitat in the Mekong River in Laos and Thailand during the transmission of Schistosoma mekongi prior to the construction of any dams on the river. A Place-Based Conceptual Model (PBCM) is described to help identify potential new areas, with suitable habitats for snails and disease transmission. The natural flow regime of the Mekong River prior to any impoundments is described with current updates on the potential impacts of climate change and flow-related snail habitat characteristics, including sediment drift and water quality. Environmental management strategies are outlined, emphasizing environmental flow (e-flow) and habitat models, with the potential to mitigate N. aperta distribution and S. mekongi disease transmission. The PBCM can serve as a template to aggregate and compare historical baseline information (Before dams) with current data (After dams) to create predictive models describing suitable habitats for N. aperta and other snail intermediate hosts and vectors along shoreline areas of the Mekong River continuum. The PBCM model could be a powerful management tool when combined with habitat suitability and e-flow models. Adding schistosome biomarkers currently under development in a One Health context to select possible areas of a river likely to support disease transmission could extend the value of the model. [ABSTRACT FROM AUTHOR]

Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis, exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca2+/NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control. [ABSTRACT FROM AUTHOR]

After many decades of research, a schistosome vaccine still looks to be a distant prospect. These helminths can live in the human bloodstream for years, even decades, surrounded by and feeding on the components of the immune response they provoke. The original idea of a vaccine based on the killing of invading cercariae in the skin has proven to be illusory. There has also been a realisation that even if humans develop some protection against infection over a protracted period, it very likely involves IgE-mediated responses that cannot provide the basis for a vaccine. However, it has also become clear that both invasive migrating larvae and adult worms must expose proteins and release secretions into the host environment as part of their normal biological activities. The application of modern 'omics approaches means that we now have a much better idea of the identity of these potential immune targets. This review looks at three animal models in which acquired immunity has been demonstrated and asks whether the mechanisms might inform our vaccine strategies to achieve protection in model hosts and humans. Eliciting responses, either humoral or cellular, that can persist for many months is a challenge. Arming of the lungs with effector T cells, as occurs in mice exposed to the radiation-attenuated cercarial vaccine, is one avenue. Generating IgG antibody titres that reach levels at which they can exert sustained immune pressure to cause worm elimination, as occurs in rhesus macaques, is another. The induction of memory cell populations that can detect trickle invasions of larval stages remains to be explored. One promising approach is the analysis of protective antibodies using high-density peptide arrays of target proteins to identify reactive regions. These can be combined in multi-epitope constructs to immunise a host against many targets simultaneously and cheaply. [ABSTRACT FROM AUTHOR]

Schistosomiasis is common in many tropical regions and poses a risk for the local population and travelers. In travelers, most of schistosomiasis are described as acute. We report the epidemiological, clinical, and laboratory characteristics associated with an outbreak of asymptomatic schistosomiasis among nonimmune Belgian school travelers in Rwanda. Schistosomiasis was diagnosed by serology in 12 out of the 15 (80%) travelers who swam in the lake nearly 2 years after a single exposure to freshwater at Kivu Lake, Rwanda. None showed signs of acute or chronic schistosomiasis. Eosinophilia was present in only 1 of them. Schistosoma mansoni eggs were not found in any infected patient. This report of an outbreak of asymptomatic schistosomiasis imported from Lake Kivu highlights the risk for travelers of acquiring the infection with only a short and single exposure, and provides strong arguments for routine serological screening for schistosomiasis in all individuals who have had any freshwater contact in endemic areas, irrespective of symptoms or laboratory findings.

The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems. Experimental animal models that recapitulate schistosomiasis immunology, disease progression, and pathology observed in humans are important in testing and validation of control interventions. We discuss the pivotal value of these models in contributing to elimination of schistosomiasis. Treatment of schistosomiasis relies heavily on mass drug administration of praziquantel whose efficacy is comprised due to re-infections and experimental systems have revealed the inability to kill juvenile schistosomes. In terms of diagnosis, nonhuman primate models have demonstrated the low sensitivity of the gold standard Kato Katz smear technique. Antibody assays are valuable tools for evaluating efficacy of candidate vaccines, and sera from graded infection experiments are useful for evaluating diagnostic sensitivity of different targets. Lastly, the presence of Schistosomes can compromise the efficacy of vaccines to other infectious diseases and its elimination will benefit control programs of the other diseases. As the focus moves towards schistosomiasis elimination, it will be critical to integrate treatment, diagnostics, novel research tools such as sequencing, improved understanding of disease pathogenesis and utilization of experimental models to assist with evaluating performance of new approaches.

BackgroundReliable and field-applicable diagnosis of schistosome infections in non-human animals is important for surveillance, control, and verification of interruption of human schistosomiasis transmission. This study aimed to summarize uses of available diagnostic techniques through a systematic review and meta-analysis.Methodology and principal findingsWe systematically searched the literature and reports comparing two or more diagnostic tests in non-human animals for schistosome infection. Out of 4,909 articles and reports screened, 19 met our inclusion criteria, four of which were considered in the meta-analysis. A total of 14 techniques (parasitologic, immunologic, and molecular) and nine types of non-human animals were involved in the studies. Notably, four studies compared parasitologic tests (miracidium hatching test (MHT), Kato-Katz (KK), the Danish Bilharziasis Laboratory technique (DBL), and formalin-ethyl acetate sedimentation-digestion (FEA-SD)) with quantitative polymerase chain reaction (qPCR), and sensitivity estimates (using qPCR as the reference) were extracted and included in the meta-analyses, showing significant heterogeneity across studies and animal hosts. The pooled estimate of sensitivity was 0.21 (95% confidence interval (CI): 0.03-0.48) with FEA-SD showing highest sensitivity (0.89, 95% CI: 0.65-1.00).Conclusions/significanceOur findings suggest that the parasitologic technique FEA-SD and the molecular technique qPCR are the most promising techniques for schistosome diagnosis in non-human animal hosts. Future studies are needed for validation and standardization of the techniques for real-world field applications.

In all 592 mesenteries and 368 intestinal contents were randomly screened to record the prevalence of visceral schistosomes and gastrointestinal (GI) parasites, respectively, in buffaloes slaughtered at Mumbai abattoir from March 2022 to February 2023. Out of 592 mesenteries, 95 (16.05%) were positive for Schistosoma spp., while intestinal contents of 38 out of 368 (10.32%) animals were positive for gastrointestinal parasites. The prevalence of schistosomes was highest in winter followed by summer and monsoon. Mild intensity of infection was predominant in 36.84% buffaloes, while 5.26% buffaloes showed moderate infection. Schistosomes recovered from the mesenteries were identified as Schistsoma spindale based on their morphometry with male flukes predominating the females. In slaughtered buffaloes, the highest incidence was from Thane followed by Mumbai and Satara districts of Maharashtra. Highest prevalence of GI parasites was recorded in summer followed by winter and monsoon. Considering the prevalence rate of visceral schistosomosis, it is concluded that animals and human in these regions are sub-clinically at risk, and therefore effective control strategies need to be implemented. [ABSTRACT FROM AUTHOR]

The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents of schistosomiasis. Indeed, the peptide tag of the hybrid compounds can be hydrolyzed by worm’s digestive enzymes to afford a highly labile alkoxyamine which homolyzes spontaneously and instantaneously into radicals—which are then used as a drug against Schistosome adult parasites. This approach is nicely summarized as digging their graves with their forks. Several hybrid peptide-alkoxyamines were prepared and clearly showed an activity: two of the tested compounds kill 50% of the parasites in two hours at a concentration of 100 µg/mL. Importantly, the peptide and alkoxyamine fragments that are unable to generate alkyl radicals display no activity. This strong evidence validates the proposed mechanism: a specific activation of the prodrugs by the parasite proteases leading to parasite death through in situ alkyl radical generation.