Integrated Eco-Health approach significantly reduces helminth infections in endemic Khong islands with emphasis on Schistosoma mekongi.

BACKGROUND: Helminth infections, including Opisthorchis viverrini, hookworm, and Trichuris trichiura, are prevalent in Khong district, Champasack province, southern Lao People's Democratic Republic (PDR). Schistosomiasis caused by Schistosoma mekongi is of public health concern on the islands of the Khong district. This study aimed to assess the impact of an Eco-Health/One-Health approach in combination with mass drug administration (MDA) to reduce these helminth infections. METHODS: We conducted a community intervention using a stepped-wedge trial approach on two endemic islands (Donsom and Donkhone) of the Khong district, Champasack province, Lao PDR, between April 2012 and March 2013. In each study village, 30-40 households were randomly selected. All members of selected households, who were at home during the study period were invited to participate in the study. A baseline study was conducted to assess helminth infections, knowledge attitudes and practices toward Schistosoma mekongi infection, behavior of open defecation and availability of latrine at home. After the baseline (T0), the Eco-Health/One-Health approach was implemented on Donsom (intervention) and Donkhone island (control). An assessment was conducted in 2014 (T1), one year after the completion of intervention implementation, to assess the short-term impact of the Eco-Health/One-Health approach on helminth infections and compare intervention and control islands. Later in 2015, the Eco-Health/One-Health approach was implemented on control island (Donkhone). After the implementation of intervention, the parasitological assessments were conducted annually in humans in 2015 (T2), in 2016 (T3) and in 2017 (T4), and in dogs in 2017 (T4) to evaluate the long-term impact of the intervention on helminth infections. Frequency was used to describe the prevalence of helminth infections. Logistic regression was applied to associate the KAP (knowledge, attitudes, and practices and open defecation behavior) and the reduction of helminth infections between intervention and control islands. The reduction in prevalence pre- and post-intervention was associated using a McNemar test. A two-independent sample t-test was applied to compare the mean eggs per gram (EPG) of helminth infections between control and intervention islands. A paired t-test test was used to compare the mean EPG of stool samples before (baseline) and after (follow-up) interventions for the two islands separately. A P-value lower than 0.05 was considered statistically significant. RESULTS: Eco-Health/One-Health approach appears to be associated with reduction in prevalence of S. mekongi by 9.0% [odds ratio (OR) = 0.49, P = 0.003] compared to the use of mass drug administration alone (control island). Additionally, this intervention package significantly reduced O. viverrini infection by 20.3% (OR = 1.92, P < 0.001) and hookworm by 17.9% (OR = 0.71, P = 0.045), respectively. Annual parasitological assessments between 2012 and 2017 showed that the Eco-Health/One-Health approach, coupled with MDA, steadily reduced the prevalence of S. mekongi on the intervention island from 29.1% to 1.8% and on the control island from 28.4% to 3.1%, respectively. CONCLUSIONS: The study findings suggest that the Eco-Health/One-Health approach appears to be associated with a significant reduction in prevalence of S. mekongi and helminth co-infections, particularly hookworm and T. trichiura. Therefore, implementing the Eco-Health/One-Health approach in schistosomiasis-endemic areas could accelerate the achievement of national goals for transmission interruption by 2025 and elimination by 2030.

Detection of soil-transmitted helminths and Schistosoma spp. by nucleic acid amplification test: Results of the first 5 years of the only international external quality assessment scheme.

BACKGROUND: Infections with soil-transmitted helminths (STH) and schistosomiasis (SCH) result in a significant global health burden, particularly in rural communities in low and middle-income countries. While microscopy remains the primary diagnostic method for STH and SCH in resource-limited settings, nucleic acid amplification tests (NAATs) are gaining prominence as tools for evaluation of public health control programs in endemic countries, and individual diagnosis in high-income countries. Despite the high sensitivity and specificity of NAATs, previous research has highlighted inter-laboratory variations, both in technical and clinical performance, justifying the need for continuous proficiency testing. METHODOLOGY: Results from 5 rounds over a 5-year period of the so far only longitudinal international Helminth External Molecular Quality Assessment Scheme (HEMQAS), coordinated by the Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), were examined in order to (i) assess the diagnostic proficiency of laboratories in detecting helminths in stool and (ii) identify potential factors contributing to variations in performance. OUTCOME AND CONCLUSIONS: Thirty-six laboratories, from 18 countries and 5 continents, participated in HEMQAS. The overall diagnostic performances were satisfying, with remarkably low numbers (<2%) of false-positive results. False-negative results were more often reported for stool (15%) than for DNA (5%) samples. False-negative results varied largely between targets (the highest number (29%) for Trichuris trichiura). Twenty-five laboratories provided a sufficient number of results for a robust comparison between participating laboratories, which confirmed substantial inter-laboratory variability in quantitative NAAT results (Cq-values). This variability likely arises from differences in pre-treatment, DNA isolation and DNA-target amplification procedures. This study emphasizes the complexity of molecular diagnosis for STH and SCH, highlighting the critical role of proper stool preparation and DNA isolation methods. The results underscore the necessity for laboratory professionals and public health decision-makers to recognize these complexities and continuously undertake external quality assessment schemes to ensure accurate and reliable performance in molecular diagnosis.

Detection of male genital schistosomiasis (MGS) associated with human, zoonotic and hybrid schistosomes in Southern Malawi.

BACKGROUND: Male Genital Schistosomiasis (MGS) remains an often-overlooked chronic sequela of urogenital schistosomiasis in endemic areas of sub-Saharan Africa. As part of a 2-year longitudinal study on Hybridization of UroGenital Schistosomiasis (HUGS) in Malawi, a MGS sub-study was conducted to assess whether hybrid schistosomes were incriminated. METHODS: During recruitment, demographic, health and socio-economic data were collected through individual questionnaire interviews in Mthawira community from Nsanje District along Shire River and Samama community from Mangochi District along Lake Malawi shoreline. Urine and semen samples were collected and analysed to determine the identity of schistosome infection. Urine filtration and microscopy, direct microscopy of semen and its sediments (after centrifugation) were performed. Thereafter, the sediments were examined by molecular DNA analysis with a novel two-tube real-time PCR assay. The participants were also screened for Human papilloma virus (HPV) and other sexually transmitted infections (STIs). RESULTS: Twenty-two men were recruited for the sub-study, 8 in Nsanje District and 14 in Mangochi District, with a median age of 22.0 years. By microscopy, ten (45.7%) participants had Schistosoma ova in their urine, 11 (50.0%) in semen while 16 (72.7%) were positive by real-time PCR. One participant had both S. haematobium and S. mattheei ova in his semen, three showed symptoms, and one had a mixed infection of S. mansoni and possible S. haematobium-S. mattheei hybrid. Twelve men had detectable high-risk HPV serotypes 16, 18 and others while six had Trichomonas vaginalis and other STIs. CONCLUSION: Zoonotic and hybrid schistosomes can cause MGS similar to human schistosomes, which can be co-infected with HPV and STIs, thereby posing a new challenge in diagnosis, management and control measures in resource poor settings. Increased awareness of these infections among local communities and primary healthcare workers and improvement of disease management are needed and advocated.

Schistosomiasis.

Schistosomiasis is a major cause of morbidity in the world and almost 800 million people worldwide are at risk for schistosomiasis; it is second only to malaria as a major infectious disease. Globally, it is estimated that the disease affects more than 250 million people in 78 countries of the world and is responsible for some 280,000-500,000 deaths each year. The three major schistosomes infecting humans are Schistosoma mansoni, S. japonicum, and S. haematobium. This chapter covers a wide range of aspects of schistosomiasis, including basic biology of the parasites, epidemiology, immunopathology, treatment, control, vaccines, and genomics/proteomics. In this chapter, the reader will understand the significant toll this disease takes in terms of mortality and morbidity. A description of the various life stages of schistosomes is presented, which will be informative for both those unfamiliar with the disease and experienced scientists. Clinical and public health aspects are addressed that cover acute and chronic disease, diagnosis, current treatment regimens and alternative drugs, and schistosomiasis control programs. A brief overview of genomics and proteomics is included that details recent advances in the field that will help scientists investigate the molecular biology of schistosomes. The reader will take away an appreciation for general aspects of schistosomiasis and the current research advances.

Schistosomiasis diagnosis: Challenges and opportunities for elimination.

OVERVIEW: The roadmap adopted by the World Health Organization (WHO) for eliminating neglected tropical diseases aims to eliminate schistosomiasis, as a public health concern, by 2030. While progress has been made towards reducing schistosomiasis morbidity control in several sub-Saharan African countries, there is still more that needs to be done. Proper surveillance using accurate diagnostics with acceptable sensitivity and specificity is essential for evaluating the success of all efforts against schistosomiasis. Microscopy, despite its low sensitivity, remains the gold standard approach for diagnosing the disease. Although many efforts have been made to develop new diagnostics based on circulating parasite proteins, genetic markers, schistosome egg morphology, and their paramagnetic properties, none has been robust enough to replace microscopy. This review highlights common diagnostic approaches for detecting schistosomiasis in field and clinical settings, major challenges, and provides new and novel opportunities and diagnosis pathways that will be critical in supporting elimination of schistosomiasis. METHODS: We searched for relevant and reliable published literature from PubMed, Scopus, google scholar, and Web of science. The search strategies were primarily determined by subtopic, and hence the following words were used (schistosom*, diagnosis, Kato-Katz, antibody test, circulating antigen, POC-CCA, UCP-LF-CAA, molecular diagnostics, nucleic acid amplification test, microfluidics, lab-on a disk, lab-on chip, recombinase polymerase amplification (RPA), LAMP, portable sequencer, nanobody test, identical multi-repeat sequences, diagnostic TPPs, REASSURED, extraction free), and Boolean operators AND and/OR were used to refine the searching capacity. Due to the global public health nature of schistosomiasis, we also searched for reliable documents, reports, and research papers published by international health organizations, World Health Organization (WHO), and Center for Disease control and Elimination.

Schistosoma haematobium and Schistosoma bovis first generation hybrids undergo gene expressions changes consistent with species compatibility and heterosis.

When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To date, the extent of the transcriptomic changes in first hybrid generations, along with their functional outcome constitute an important knowledge gap, especially in parasite species. Here we explored the molecular and functional outcomes of hybridization in first-generation hybrids between the blood fluke parasites Schistosoma haematobium and S. bovis. Through a transcriptomic approach, we measured gene expression in both parental species and hybrids. We described and quantified expression profiles encountered in hybrids along with the main biological processes impacted. Up to 7,100 genes fell into a particular hybrid expression profile (intermediate between the parental expression levels, over-expressed, under-expressed, or expressed like one of the parental lines). Most of these genes were different depending on the direction of the parental cross (S. bovis mother and S. haematobium father or the reverse) and depending on the sex. For a given sex and cross direction, the vast majority of genes were hence unassigned to a hybrid expression profile: either they were differentially expressed genes but not typical of any hybrid expression profiles or they were not differentially expressed neither between hybrids and parental lines nor between parental lines. The most prevalent profile of gene expression in hybrids was the intermediate one (24% of investigated genes). These results suggest that transcriptomic compatibility between S. haematobium and S. bovis remains quite high. We also found support for an over-dominance model (over- and under-expressed genes in hybrids compared to parental lines) potentially associated with heterosis. In females in particular, processes such as reproductive processes, metabolism and cell interactions as well as signaling pathways were indeed affected. Our study hence provides new insight on the biology of Schistosoma hybrids with evidences supporting compatibility and heterosis.

Population genetic structure of Schistosoma bovis and S. curassoni collected from cattle in Mali.

Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies have been carried out to determine the role of animals in its transmission. In Mali, it has been over three decades since the last molecular study of animal schistosomes was carried out. It is now urgent to identify circulating strains of the parasite because of potential interactions with other schistosome species, which could complicate disease control. The aim of our work was to study the composition and genetic structure of schistosome populations collected from cattle. The prevalence of schistosome was 23.9%, with the prevalences of Schistosoma bovis (Sb) and S. curassoni (Sc) estimated at 12.6% and 9.8%, respectively. No hybrid strains or S. haematobium were found. The parasites displayed distinct geographical distribution with Sb dominant in Bamako (78.8% and 98% in Central Bamako Slaughterhouse and Sabalibougou Slaughterhouses, respectively) and Sc dominant in Kayes (95.3%). Of the 476 parasites with a complete genetic profile, 60.4% were pure Sc, and were mainly from Kayes. We identified two clusters at the site level (Fst of 0.057 and 0.042 for Sb and Sc, respectively). Cluster 1 was predominantly composed of pure Sb parasites and cluster 2 was mainly composed of pure Sc parasites, from Bamako and Kayes, respectively. Our study shows that cattle schistosomiasis remains endemic in Mali with S. bovis and S. curassoni. A robust genetic structure between the different schistosome populations was identified, which included two clusters based on the geographical distribution of the parasites.

Title: Structure génétique des populations de Schistosoma bovis et S. curassoni collectées chez des bovins au Mali. Abstract: La schistosomiase revêt une grande importance médicale et vétérinaire. Malgré la situation critique de la schistosomiase en Afrique subsaharienne, peu d'études épidémiologiques moléculaires ont été réalisées pour déterminer le rôle des animaux dans sa transmission. Au Mali, cela fait plus de trois décennies que la dernière étude moléculaire des schistosomes animaux a été réalisée. Il est désormais urgent d'identifier les souches circulantes du parasite en raison des interactions potentielles avec d'autres espèces de schistosomes, ce qui pourrait compliquer la lutte contre la maladie. Le but de notre travail était d'étudier la composition et la structure génétique des populations de schistosomes collectées chez des bovins. La prévalence des schistosomes était de 23,9 %, celles de Schistosoma bovis (Sb) et de S. curassoni (Sc) étant respectivement estimées à 12,6 % et 9,8 %. Aucune souche hybride ni S. haematobium n'ont été trouvés. Les parasites présentaient une répartition géographique distincte avec Sb dominant à Bamako (respectivement 78,8 % et 98 % aux Abattoirs Centraux de Bamako et aux Abattoirs de Sabalibougou) et Sc dominant à Kayes (95,3 %). Sur les 476 parasites ayant un profil génétique complet, 60,4 % étaient des Sc purs, et provenaient principalement de Kayes. Nous avons identifié deux clusters au niveau du site (Fst de 0,057 et 0,042 pour Sb et Sc, respectivement). Le groupe 1 était principalement composé de parasites Sb purs et le groupe 2 était principalement composé de parasites Sc purs, provenant respectivement de Bamako et de Kayes. Notre étude montre que la schistosomiase bovine reste endémique au Mali, avec S. bovis and S. curassoni. Une structure génétique robuste entre les différentes populations de schistosomes a été identifiée, comprenant deux groupes basés sur la répartition géographique des parasites.

[Histone deacetylase and histone acetyltransferase inhibitors as antischistosomal agents: a review].

Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective chemical for treatment of schistosomiasis japonica. Since its introduction in the 1970s, praziquantel has been used for large-scale chemotherapy of schistosomiasis for over 40 years. However, there have been reports pertaining to the resistance to praziquantel in schistosomes. Therefore, development of novel antischistosomal agents as alternatives of praziquantel, is of great need. Histone deacetylases and histone acetyltransferases have been recently reported to play critical roles in the growth, development and reproduction of schistosomes, and are considered as potential drug targets for the treatment of schistosomiasis. This review summarizes the latest advances of histone deacetylase and histone acetyltransferase inhibitors in the research on antischistosomal drugs, so as to provide insights into research and development of novelantischistosomal agents.

A reanalysis and integration of transcriptomics and proteomics datasets unveil novel drug targets for Mekong schistosomiasis.

Schistosomiasis, caused by Schistosoma trematodes, is a significant global health concern, particularly affecting millions in Africa and Southeast Asia. Despite efforts to combat it, the rise of praziquantel (PZQ) resistance underscores the need for new treatment options. Protein kinases (PKs) are vital in cellular signaling and offer potential as drug targets. This study focused on focal adhesion kinase (FAK) as a candidate for anti-schistosomal therapy. Transcriptomic and proteomic analyses of adult S. mekongi worms identified FAK as a promising target due to its upregulation and essential role in cellular processes. Molecular docking simulations assessed the binding energy of FAK inhibitors to Schistosoma FAK versus human FAK. FAK inhibitor 14 and PF-03814735 exhibited strong binding to Schistosoma FAK with minimal binding for human FAK. In vitro assays confirmed significant anti-parasitic activity against S. mekongi, S. mansoni, and S. japonicum, comparable to PZQ, with low toxicity in human cells, indicating potential safety. These findings highlight FAK as a promising target for novel anti-schistosomal therapies. However, further research, including in vivo studies, is necessary to validate efficacy and safety before clinical use. This study offers a hopeful strategy to combat schistosomiasis and reduce its global impact.

Mapping of intermediate host snails for schistosomiasis in the Democratic Republic of Congo: a systematic review.

Schistosomiasis is a snail-borne disease that has a considerable impact on human and animal health, particularly in sub-Saharan Africa. The intermediate hosts of the schistosome parasites are freshwater snails of the genera Biomphalaria Preston, 1910 and Bulinus Müller, 1781. In order to identify existing gaps in the spread of the disease in the Democratic Republic of Congo (DRC), this study compiled the available knowledge of the distribution, population dynamics and ecology of the intermediate hosts of schistosomiasis. A systematic literature search was conducted in PubMed, Embase and Scopus for all malacological studies on schistosoma intermediate hosts in DRC published between 1927 and October 2022. A total of 55 records were found, of which 31 met the inclusion criteria: these were published field and experimental studies conducted in the DRC and focused on snails as intermediate hosts of schistosomes. The analysis of these studies revealed that more up-to-date data on the distribution of snail intermediate hosts in the DRC are needed. Moreover, ecological factors have been less studied for Bulinus species than for Biomphalaria species. These factors play a crucial role in determining suitable snail habitats, and the lack of comprehensive information poses a challenge in snail control. This review makes it clear that there are no current malacological data in the DRC. There is a clear need for molecular and ecological research to update the exact species status and population dynamics of all potential intermediate host species. This will facilitate targeted snail control measures that complement drug treatment in the control of schistosomiasis in the country.

Aligning antimicrobial resistance surveillance with schistosomiasis research: an interlinked One Health approach.

One Health surveillance involves the analysis of human, animal and environmental samples, recognising their interconnectedness in health systems. Such considerations are crucial to investigate the transmission of many pathogens, including drug-resistant bacteria and parasites. The highest rates of antimicrobial resistance (AMR)-associated deaths are observed in sub-Saharan Africa, where concurrently the waterborne parasitic disease schistosomiasis can be highly endemic in both humans and animals. Although there is growing acknowledgment of significant interactions between bacteria and parasites, knowledge of relationships between schistosomes, microbes and AMR remains inadequate. In addition, newly emergent research has revealed the previously underappreciated roles of animals and the environment in both AMR and schistosomiasis transmission. We consider shared environmental drivers and colonisation linkage in this narrative review, with a focus on extended-spectrum beta-lactamase-mediated resistance among bacteria from the Enterobacteriaceae family, which is exceedingly prevalent and responsible for a high burden of AMR-associated deaths. Then we examine novel findings from Malawi, where the landscapes of AMR and schistosomiasis are rapidly evolving, and make comparisons to other geographic areas with similar co-infection epidemiology. We identify several knowledge gaps that could be addressed in future research, including the need to characterise the impact of intestinal schistosomiasis and freshwater contact on intestinal AMR colonisation, before proposing a rationale for connecting AMR surveillance and schistosomiasis research within a One Health framework.

Interstitial macrophage phenotypes in Schistosoma-induced pulmonary hypertension.

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-ß, 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-ß and causes PH.

Human Passage of Schistosoma incognitum, Tamil Nadu, India, and Review of Autochthonous Schistosomiasis, South Asia.

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.

An overview of qualitative and quantitative platelet abnormalities in schistosomiasis.

Schistosomiasis is a neglected tropical disease referring to the infection with blood parasitic trematodes of the genus Schistosoma. It impacts millions of people worldwide, primarily in low-to-middle-income countries. Patients infected with schistosomiasis often exhibit a distinct hematological profile, including anemia, eosinophilia, thrombocytopenia, and coagulopathy. Platelets, essential components of the hemostatic system, play a crucial role in the pathogenesis of schistosomiasis. Schistosomes secrete serine proteases and express ectoenzymes, such as calpain protease, alkaline phosphatase (SmAP), phosphodiesterase (SmNPP5), ATP diphosphohydrolase (SmATPDase1), serine protease Sk1, SmSP2, and Sm22.6, which can interfere with platelet normal functioning. This report provides comprehensive, up-to-date information on platelet abnormalities observed in patients with schistosomiasis, highlighting their importance in the disease progression and complications. It delves into the interactions between platelets and schistosomes, including the impact of platelet dysfunction on hemostasis and immune responses, immune-mediated platelet destruction, and the potential mechanisms by which schistosome tegumental ectoenzymes affect platelets. Furthermore, the report clarifies the relationship between platelet abnormalities and clinical manifestations such as thrombocytopenia, coagulation disorders, and the emergence of portal hypertension and gastrointestinal bleeding. Understanding the complex interplay between platelets and schistosomes is crucial for improving patient management and outcomes in schistosomiasis, particularly for those with platelet alterations. This knowledge contributes to improved diagnostic methods, innovative treatment strategies, and global efforts to control and eliminate schistosomiasis.

Comparison of tissue biomarkers between non-schistosoma and schistosoma-associated urothelial carcinoma.

BACKGROUND: High-grade urothelial carcinoma either non-Schistosoma (NS-UBC) or Schistosoma (S-UBC)-associated is the tenth cause of death worldwide and represents a serious therapeutic problem. AIM: Evaluation of the immmunohistochemical expression of tumor necrosis factor-alpha (TNFα), epidermal growth factor receptor (EGFR), programmed cell death protein-1 (PDL1), estrogen receptor-alpha (ERα) and UroplakinIII, in the high-grade in NS-UBC and S-UBC as potential prognostic and therapeutic targets analyzed through estimation of area percentage, optical density and international pathological scoring system for each marker. MATERIAL AND METHODS: Sixty high grade urothelial carcinoma cases were enrolled in the study (30 cases of NS-UBC and 30 cases of S-UBC). The cases were immunohistochemically-assessed for TNFα, EGFR, PDL1, ERα and Uroplakin III expression. In S-UBC, parasite load was also evaluated for correlation with the immunohistochemical markers' expression in S-UBC. RESULTS: The area percentage of immune-expression of TNFα and EGFR was higher in S-UBC compared to NS-UBC. On the other hand, the NS-UBC displayed statistically-higher expression of PDL1 and uroplakinIII (p-value <0.001). ERα revealed higher, yet, non-significant expressions in S-UBC compared to NS-UBC (p-value =0.459). PDL1 expression showed the most superior record regarding area percentage (64.6± 34.5). Regarding optical density, TNF-α showed the highest transmittance expression (2.4 ± 0.9). EGFR positively correlated with PDL1 in S-UBC (r= 0.578, p-value =0.001) whereas in NS-UBC, TNFα and PDL1 (r=0.382, p-value=0.037) had positive correlation. Schistosoma eggs in tissues oppose uroplakin III expression and trigger immunomodulation via PDL1. CONCLUSION: Due to lower UroplakinIII expression, S-UBC is supposed to have a poorer prognosis. Hormonal therapy is not hypothesized due to a very minimal ERα expression in both NS-UBC and S-UBC. Regarding immunotherapy, anti-TNF-α is suggested for S-UBC whilst in NS-UBC, blockading PDL1 might be useful. Targeted EGFR therapy seems to carry emphasized outcomes in S-UBC. Correlations encourage combined immune therapy in NS-UBC; nevertheless, in S-UBC, combined anti-EGFR and PDL1 seem to be of benefit.

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.

Metalloenzyme Inhibitors against Zoonotic Infections: Focus on Leishmania and Schistosoma.

The term "zoonosis" denotes diseases transmissible among vertebrate animals and humans. These diseases constitute a significant public health challenge, comprising 61% of human pathogens and causing an estimated 2.7 million deaths annually. Zoonoses not only affect human health but also impact animal welfare and economic stability, particularly in low- and middle-income nations. Leishmaniasis and schistosomiasis are two important neglected tropical diseases with a high prevalence in tropical and subtropical areas, imposing significant burdens on affected regions. Schistosomiasis, particularly rampant in sub-Saharan Africa, lacks alternative treatments to praziquantel, prompting concerns regarding parasite resistance. Similarly, leishmaniasis poses challenges with unsatisfactory treatments, urging the development of novel therapeutic strategies. Effective prevention demands a One Health approach, integrating diverse disciplines to enhance diagnostics and develop safer drugs. Metalloenzymes, involved in parasite biology and critical in different biological pathways, emerged in the last few years as useful drug targets for the treatment of human diseases. Herein we have reviewed recent reports on the discovery of inhibitors of metalloenzymes associated with zoonotic diseases like histone deacetylases (HDACs), carbonic anhydrase (CA), arginase, and heme-dependent enzymes.

Praziquantel as the preferred treatment for schistosomiasis.

Schistosomiasis, caused by Schistosoma trematode worms, represents a significant global health challenge. This review offers a thorough examination of the disease's epidemiology, transmission dynamics, diagnostic modalities, and treatment options. Diagnostic techniques encompass direct parasitological methods, immunological assays, DNA/RNA detection, and biomarker utilization, each with distinct advantages and limitations. There is an urgent need for improved diagnostic tools with enhanced sensitivity and specificity. Praziquantel remains the cornerstone of treatment, exhibiting efficacy against all Schistosoma species, while the potential of artemisin derivatives in combination therapy is also explored. In this review, we focus on the importance of praziquantel administration as the central aspect of schistosomiasis treatment, highlighting ongoing efforts to optimize its utilization for improved patient outcomes.

Harnessing Schistosoma-associated metabolite changes in the human host to identify biomarkers of infection and morbidity: Where are we and what should we do next?

Schistosomiasis is the second most widespread parasitic disease affecting humans. A key component of today's infection control measures is the diagnosis and monitoring of infection, informing individual- and community-level treatment. However, newly acquired infections and/or low parasite burden are still difficult to diagnose reliably. Furthermore, even though the pathological consequence of schistosome egg sequestration in host tissues is well described, the evidence linking egg burden to morbidity is increasingly challenged, making it inadequate for pathology monitoring. In the last decades, omics-based instruments and methods have been developed, adjusted, and applied in parasitic research. In particular, the profiling of the most reliable determinants of phenotypes, metabolites by metabolomics, emerged as a powerful boost in the understanding of basic interactions within the human host during infection. As such, the fine detection of host metabolites produced upon exposure to parasites such as Schistosoma spp. and the ensuing progression of the disease are believed to enable the identification of Schistosoma spp. potential biomarkers of infection and associated pathology. However, attempts to provide such a comprehensive understanding of the alterations of the human metabolome during schistosomiasis are rare, limited in their design when performed, and mostly inconclusive. In this review, we aimed to briefly summarize the most robust advances in knowledge on the changes in host metabolic profile during Schistosoma infections and provide recommendations for approaches to optimize the identification of metabolomic signatures of human schistosomiasis.

Current drug strategies for the treatment and control of schistosomiasis.

INTRODUCTION: Schistosomiasis, one of the current Neglected Tropical Diseases (NTDs) affects over 230 million people globally, with nearly 700 million at risk in more than 74 countries. Praziquantel (PZQ) has served as the primary treatment for the past four decades; however, its effectiveness is limited as it solely eliminates adult worms. In regions where infections are frequent, PZQ exhibits only temporary efficacy and has restricted potential to disrupt the prolonged transmission of the disease. AREAS COVERED: A comprehensive exploration using the PubMed database was conducted to review current pharmacotherapy approaches for schistosomiasis. This review also encompasses recent research findings related to potential novel therapeutics and the repurposing of existing drugs. EXPERT OPINION: Current schistosoma treatment strategies, primarily relying on PZQ, face challenges like temporary effectiveness and limited impact on disease transmission. Drug repurposing, due to economic constraints, is decisive for NTDs. Despite PZQ's efficacy, its failure to prevent reinfection highlights the need for complementary strategies, especially in regions with persistent environmental foci. Integrating therapies against diverse schistosome stages boosts efficacy and impedes resistance. Uncovering novel agents is essential to address resistance concerns in tackling this neglected tropical disease. Integrated strategies present a comprehensive approach to navigate the complex challenges.