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Background: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis. Methods: This was an open-label, randomised clinical trial involving 426 school-aged children (7–15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment. Results: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported. Conclusions: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. The intravascular worms acquire the nutrients necessary for their survival from host blood. Since all animals are auxotrophic for riboflavin (vitamin B2), schistosomes too must import it to survive. Riboflavin is an essential component of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD); these support key functions of dozens of flavoenzymes. Methods: Here, using a combination of metabolomics, enzyme kinetics and in silico molecular analysis, we focus on the biochemistry of riboflavin and its metabolites in Schistosoma mansoni (Sm). Results: We show that when schistosomes are incubated in murine plasma, levels of FAD decrease over time while levels of FMN increase. We show that live schistosomes cleave exogenous FAD to generate FMN and this ability is significantly blocked when expression of the surface nucleotide pyrophosphatase/phosphodiesterase ectoenzyme SmNPP5 is suppressed using RNAi. Recombinant SmNPP5 cleaves FAD with a Km of 178 ± 5.9 µM and Kcat/Km of 324,734 ± 36,347 M− 1.S− 1. The FAD-dependent enzyme IL-4I1 drives the oxidative deamination of phenylalanine to produce phenylpyruvate and H2O2. Since schistosomes are damaged by H2O2, we determined if SmNPP5 could impede H2O2 production by blocking IL-4I1 action in vitro. We found that this was not the case; covalently bound FAD on IL-4I1 appears inaccessible to SmNPP5. We also report that live schistosomes can cleave exogenous FMN to generate riboflavin and this ability is significantly impeded when expression of a second surface ectoenzyme (alkaline phosphatase, SmAP) is suppressed. Recombinant SmAP cleaves FMN with a Km of 3.82 ± 0.58 mM and Kcat/Km of 1393 ± 347 M− 1.S− 1. Conclusions: The sequential hydrolysis of FAD by tegumental ecto-enzymes SmNPP5 and SmAP can generate free vitamin B2 around the worms from where it can be conveniently imported by the recently described schistosome riboflavin transporter SmaRT. Finally, we identified in silico schistosome homologs of enzymes that are involved in intracellular vitamin B2 metabolism. These are riboflavin kinase (SmRFK) as well as FAD synthase (SmFADS); cDNAs encoding these two enzymes were cloned and sequenced. SmRFK is predicted to convert riboflavin to FMN while SmFADS could further act on FMN to regenerate FAD in order to facilitate robust vitamin B2-dependent metabolism in schistosomes. [ABSTRACT FROM AUTHOR]

Background: Hookworm infection and schistosomiasis are two of sub-Saharan Africa's most common neglected tropical diseases. An annual mass drug administration (MDA) program against schistosomiasis and soil-transmitted helminths (STHs), including hookworm, has been implemented in Mayuge district, Uganda, since 2003 to date. However, hookworm and schistosomiasis remain prevalent in Mayuge district. Understanding the factors that predispose children to these infections in the context of MDA could inform interventions to reduce prevalence in Uganda and similar settings. Method: This cross-sectional study took place in 33 randomly selected primary schools in the Mayuge district from January to February 2022. Children in primary classes 4 or 5, in the selected schools provided single stool samples and completed questionnaires. Stool specimens were examined using the Kato-Katz method to determine the prevalence of hookworm and schistosomiasis. We performed univariable and multivariable logistic regression to assess the associations of each infection with potential risk factors. Result: A total of 1,617 students (mean age 12.1 years, 50.1% male) were enrolled. The prevalence of hookworm infection and schistosomiasis was 21.8% (95% confidence interval (CI): 19.8–23.9%) and 18.7% (95% CI: 16.8–20.7%), respectively. In multivariable analysis, longer water fetching time (over 30 min versus less than 30 min) and working daily in the soil were associated with increased odds of hookworm infection (adjusted odds ratio (AOR): 1.49, 95% CI: 1.13–1.96 and 1.37, 95% CI: 1.03–1.82, respectively). Higher odds of schistosomiasis were linked to proximity to water bodies within a one-hour walking distance (AOR: 1.84, 95% CI: 1.35–2.50), and not always washing hands before eating (AOR: 2.00, 95% CI: 1.50–2.67). Swimming, bathing, or washing in water bodies twice a week, compared to never, also increased schistosomiasis odds (AOR: 2.91, 95% CI: 1.66–5.13). Conclusion: Consistent with the mechanisms of acquisition, hookworm infection increased with exposure to soil, and schistosomiasis increased with exposure to unclean water. Our findings highlight the importance of Water, Sanitation, and Hygiene programs and strategies aimed at reducing exposure within the framework of Neglected Tropical Disease elimination programs. [ABSTRACT FROM AUTHOR]

Background: Gastropods of the genus Biomphalaria (Family Planorbidae) are exploited as vectors by Schistosoma mansoni, the most common causative agent of human intestinal schistosomiasis. Using improved genomic resources, overviews of how Biomphalaria responds to S. mansoni and other metazoan parasites can provide unique insights into the reproductive, immune, and other systems of invertebrate hosts, and their responses to parasite challenges. Results: Using Illumina-based RNA-Seq, we compared the responses of iM line B. glabrata at 2, 8, and 40 days post-infection (dpi) to single infections with S. mansoni, Echinostoma paraensei (both digenetic trematodes) or Daubaylia potomaca (a nematode parasite of planorbid snails). Responses were compared to unexposed time-matched control snails. We observed: (1) each parasite provoked a distinctive response with a predominance of down-regulated snail genes at all time points following exposure to either trematode, and of up-regulated genes at 8 and especially 40dpi following nematode exposure; (2) At 2 and 8dpi with either trematode, several snail genes associated with gametogenesis (particularly spermatogenesis) were down-regulated. Regarding the phenomenon of trematode-mediated parasitic castration in molluscs, we define for the first time a complement of host genes that are targeted, as early as 2dpi when trematode larvae are still small; (3) Differential gene expression of snails with trematode infection at 40dpi, when snails were shedding cercariae, was unexpectedly modest and revealed down-regulation of genes involved in the production of egg mass proteins and peptide processing; and (4) surprisingly, D. potomaca provoked up-regulation at 40dpi of many of the reproduction-related snail genes noted to be down-regulated at 2 and 8dpi following trematode infection. Happening at a time when B. glabrata began to succumb to D. potomaca, we hypothesize this response represents an unexpected form of fecundity compensation. We also document expression patterns for other Biomphalaria gene families, including fibrinogen domain-containing proteins (FReDs), C-type lectins, G-protein coupled receptors, biomphalysins, and protease and protease inhibitors. Conclusions: Our study is relevant in identifying several genes involved in reproduction that are targeted by parasites in the vector snail B. glabrata and that might be amenable to manipulation to minimize their ability to serve as vectors of schistosomes. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the occurrence of Schistosoma mansoni and soil‐transmitted helminths in an endemic area in the Eastern Brazilian Amazon, analysing prevalence and spatial distribution. Methods: The study was conducted in four localities of Primavera Municipality, in Pará state. Data was obtained from the Decit 40/2012 project and the participants were divided into five age range categories for evaluation: children, adolescents, young adults, adults and elderly individuals. For the diagnostic tests, Kato–Katz slides were prepared to detect S. mansoni and soil‐transmitted helminths eggs. The spatial distribution map and the Kernel Density Estimation were performed to assess the presence and location of infections. Results: Stool samples revealed the presence of hookworms, S. mansoni, Ascaris lumbricoides and Trichuris trichiura eggs. Mono‐, bi‐ and poly‐parasitic infections were observed, with a significant prevalence of hookworm monoparasitism. Conclusions: The high frequency of children infected with soil‐transmitted helminths confirms their significance as an ongoing public health problem in the poorest municipalities of Brazil. The Geographic Information System plays a crucial role in environmental surveillance and in the control of epidemics and endemic diseases, enabling accurate assessment and informed decision‐making for their control. [ABSTRACT FROM AUTHOR]

[Display omitted] • Schistosoma mansoni lactate dehydrogenase (LDH) is allosterically regulated by ATP and FBP. • The active site of LDH from S. mansoni closely resembles that of prokaryotic LDHs. • The inhibition of LDH by ATP benefits the free-living, glycogen-consuming stages. • In the presence of glucose, FBP levels increase, neutralizing the inhibition by ATP. • This effect of FBP prevents fatally high FBP levels after entering the final host. Lactate dehydrogenase (LDH) from Schistosoma mansoni has peculiar properties for a eukaryotic LDH. Schistosomal LDH (SmLDH) isolated from schistosomes, and the recombinantly expressed protein, are strongly inhibited by ATP, which is neutralized by fructose-1,6-bisphosphate (FBP). In the conserved FBP/anion binding site we identified two residues in SmLDH (Val187 and Tyr190) that differ from the conserved residues in LDHs of other eukaryotes, but are identical to conserved residues in FBP-sensitive prokaryotic LDHs. Three-dimensional (3D) models were generated to compare the structure of SmLDH with other LDHs. These models indicated that residues Val187, and especially Tyr190, play a crucial role in the interaction of FBP with the anion pocket of SmLDH. These 3D models of SmLDH are also consistent with a competitive model of SmLDH inhibition in which ATP (inhibitor) and FBP (activator) compete for binding in a well-defined anion pocket. The model of bound ATP predicts a distortion of the nearby key catalytic residue His195, resulting in enzyme inhibition. To investigate a possible physiological role of this allosteric regulation of LDH in schistosomes we made a kinetic model in which the allosteric regulation of the glycolytic enzymes can be varied. The model showed that inhibition of LDH by ATP prevents fermentation to lactate in the free-living stages in water and ensures complete oxidation via the Krebs cycle of the endogenous glycogen reserves. This mechanism of allosteric inhibition by ATP prevents the untimely depletion of these glycogen reserves, the only fuel of the free-living cercariae. Neutralization by FBP of this ATP inhibition of LDH prevents accumulation of glycolytic intermediates when S. mansoni schistosomula are confronted with the sudden large increase in glucose availability upon penetration of the final host. It appears that the LDH of S. mansoni is special and well suited to deal with the variations in glucose availability the parasite encounters during its life cycle. [ABSTRACT FROM AUTHOR]

The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg "losers" carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped "losers" instead of migrating intestinal "winners". This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite's eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized. Author summary: The egg of Schistosoma mansoni is the main causative agent of pathologies of chronic schistosomiasis, a neglected tropical disease with a significant global health burden. Pathology is primarily caused by a high number of eggs being lodged in host organs over time, causing inflammation and tissue damage. While trapped "loser" eggs causing the disease have been extensively studied, little attention has been paid to the successful "winner" eggs that pass through the intestinal wall and are responsible for the continuation of the life cycle. Here we provide a comprehensive analysis of the gene expression profiles of the parasite's eggs based on their maturity and, most importantly, their tissue localization. We revealed that eggs differ substantially based on their tissue localization from an early development. In addition to genes associated with development and metabolism, we have described differential expression of known immunomodulators, which may be reflected by the differential capacity of eggs to elicit a host immune response. Furthermore, we demonstrate that genes encoding proteins potentially involved in host-parasite interactions exhibit clear tissue-dependent expression patterns. Our research provides novel insights into the biology of S. mansoni eggs and provides a robust data source for new avenues of investigation related to this important pathogen. [ABSTRACT FROM AUTHOR]

Background: Snail-borne trematodes afflict humans, livestock, and wildlife. Recognizing their zoonotic potential and possible hybridization, a One Health approach is essential for effective control. Given the dearth of knowledge on African trematodes, this study aimed to map snail and trematode diversity, focusing on (i) characterizing gastropod snail species and their trematode parasites, (ii) determining infection rates of snail species as intermediate hosts for medically, veterinary, and ecologically significant trematodes, and (iii) comparing their diversity across endemic regions. Methods: A cross-sectional study conducted in 2021 in Chiredzi and Wedza districts in Zimbabwe, known for high human schistosomiasis prevalence, involved malacological surveys at 56 sites. Trematode infections in snails were detected through shedding experiments and multiplex rapid diagnostic polymerase chain reactions (RD-PCRs). Morphological and molecular analyses were employed to identify snail and trematode species. Results: Among 3209 collected snail specimens, 11 species were identified, including schistosome and fasciolid competent snail species. We report for the first time the invasive exotic snail Tarebia granifera in Zimbabwe, which was highly abundant, mainly in Chiredzi, occurring at 29 out of 35 sites. Shedding experiments on 1303 snails revealed a 2.24% infection rate, with 15 trematode species identified through molecular genotyping. Five species were exclusive to Chiredzi: Bolbophorus sp., Schistosoma mansoni, Schistosoma mattheei, Calicophoron sp., and Uvulifer sp. Eight were exclusive to Wedza, including Trichobilharzia sp., Stephanoprora amurensis, Spirorchid sp., and Echinostoma sp. as well as an unidentified species of the Plagiorchioidea superfamily. One species, Tylodelphys mashonensis, was common to both regions. The RD-PCR screening of 976 non-shedding snails indicated a 35.7% trematode infection rate, including the presence of schistosomes (1.1%) Fasciola nyanzae (0.6%). In Chiredzi, Radix natalensis had the highest trematode infection prevalence (33.3%), while in Wedza, R. natalensis (55.4%) and Bulinus tropicus (53.2%) had the highest infection prevalence. Conclusions: Our xenomonitoring approach unveiled 15 trematode species, including nine new records in Zimbabwe. Schistosoma mansoni persists in the study region despite six mass deworming rounds. The high snail and parasite diversity, including the presence of exotic snail species that can impact endemic species and biomedically important trematodes, underscores the need for increased monitoring. [ABSTRACT FROM AUTHOR]

Background: Community and individual participation are crucial for the success of schistosomiasis control. The World Health Organization (WHO) has highlighted the importance of enhanced sanitation, health education, and Mass Drug Administration (MDA) in the fight against schistosomiasis. These approaches rely on the knowledge and practices of the community to be successful; however, where the community knowledge is low and inappropriate, it hinders intervention efforts. Hence, it is essential to identify barriers and misconceptions related to awareness of schistosomiasis, sources of infection, mode of transmission, symptoms, and control measures. Methods: This was a mixed-method cross-sectional study involving 1200 pre-school children randomly selected and examined for Schistosoma mansoni infection using the Kato-Katz technique. All parents/guardians of selected children were enrolled for a pre-tested questionnaire survey, while 42 were engaged in focus group discussions (FGDs). The level of knowledge and awareness among parents/guardians about schistosomiasis was evaluated in relation to the infection status of their pre-school children. Results: Among pre-school children, the prevalence of intestinal schistosomiasis was 45.1% (95% CI 41.7–48.5). A majority of parents/guardians (85.5%) had heard about schistosomiasis, and this awareness was associated with the participant's level of education (OR = 0.16, 95% CI 0.08, 0.34). In addition, a positive association was observed between higher educational attainment and knowledge of the causative agent (OR = 0.69, 95% CI 0.49, 0.96). Low education level was significantly associated with limited knowledge of transmission through lake water contact (OR = 0.71, 95% CI 0.52, 0.97) and infection from the lake (OR = 0.33, 95% CI 0.19, 0.57). Notably, parents/guardians who have heard of schistosomiasis could not recognize symptoms of S. mansoni infection, such as abdominal pain (91.8%, 815/888) and blood in the stool (85.1%, 756/888). Surprisingly, 49.8% (442/888) incorrectly identified hematuria (blood in urine), a key sign of S. haematobium, but not S. mansoni, in an endemic area for S. mansoni infection. The majority (82.6%, 734/888) of parents/guardians were unaware that dams are potential infection sites, despite 53.9% (479/888) of their pre-school-aged children testing positive for schistosome infection. Conclusions: Despite the high level of awareness of intestinal schistosomiasis in the study area, we identified a low level of knowledge regarding its causes, modes of transmission, signs and symptoms and potential sites of transmission within the community. This study emphasizes the need for targeted educational interventions to address the misconceptions and knowledge gaps surrounding intestinal schistosomiasis through tailored community-based programs. [ABSTRACT FROM AUTHOR]

Background: The role of pathogen genotype in determining disease severity and immunopathology has been studied intensively in microbial pathogens including bacteria, fungi, protozoa and viruses but is poorly understood in parasitic helminths. The medically important blood fluke Schistosoma mansoni is an excellent model system to study the impact of helminth genetic variation on immunopathology. Our laboratory has demonstrated that laboratory schistosome populations differ in sporocyst growth and cercarial production in the intermediate snail host and worm establishment and fecundity in the vertebrate host. Here, we (i) investigate the hypothesis that schistosome genotype plays a significant role in immunopathology and related parasite life history traits in the vertebrate mouse host and (ii) quantify the relative impact of parasite and host genetics on infection outcomes. Methods: We infected BALB/c and C57BL/6 mice with four different laboratory schistosome populations from Africa and the Americas. We quantified disease progression in the vertebrate host by measuring body weight and complete blood count (CBC) with differential over a 12-week infection period. On sacrifice, we assessed parasitological (egg and worm counts, fecundity), immunopathological (organ measurements and histopathology) and immunological (CBC with differential and cytokine profiles) characteristics to determine the impact of parasite and host genetics. Results: We found significant variation between parasite populations in worm numbers, fecundity, liver and intestine egg counts, liver and spleen weight, and fibrotic area but not in granuloma size. Variation in organ weight was explained by egg burden and intrinsic parasite factors independent of egg burden. We found significant variation between infected mouse lines in cytokine levels (IFN-γ, TNF-α), eosinophils, lymphocytes and monocyte counts. Conclusions: This study showed that both parasite and host genotype impact the outcome of infection. While host genotype explains most of the variation in immunological traits, parasite genotype explains most of the variation in parasitological traits, and both host and parasite genotypes impact immunopathology outcomes. [ABSTRACT FROM AUTHOR]

Schistosomiasis is an old parasitic disease in Egypt primarily caused by Schistosoma mansoni, transmitted through infected water canals, and disproportionately affects rural areas. Despite substantial reductions in the disease prevalence over the years, it still affects more than 5% of the population in some governorates, highlighting the need for sustained control efforts. Among the recent control measures: (a) mass drug administration with large-scale, biannual administration of praziquantel, which remains the cornerstone of the control program targeting the interruption of vector transmission cycles. (b) Improving disease diagnostics, including point-of-care tests, which facilitate early detection and case management, particularly in remote areas. (c) Snail control using targeted mollusciciding aims to reduce parasite transmission by controlling intermediate snail hosts. And (d) behavioral change communication focusing on raising awareness regarding hygiene practices and safe water access. Even if control attempts have shown positive results, several challenges still exist, including (a) drug resistance, especially to praziquantel, the most commonly used drug, which calls for ongoing observation and monitoring. (b) Sustainability of funding to avoid program disruptions and setbacks. And (c) social and environmental factors like poverty, poor sanitation, and access to clean water. The transition from disease control to elimination requires meticulous planning and vigilance. Robust surveillance systems, enhanced case management, and continued community engagement are vital for such elimination. Strengthening research on drug resistance, snail control methods, and innovative diagnostics would further support elimination efforts. This report aims to address the most recent data regarding the prevalence and control measures for schistosomiasis in Egypt and provide the information required to lead the transition from disease control to elimination. [ABSTRACT FROM AUTHOR]

Neuronal signals mediated by the biogenic amine serotonin (5-HT) underlie critical survival strategies across the animal kingdom. This investigation examined serotonin-like immunoreactive neurons in the cerebral ganglion of the panpulmonate snail Biomphalaria glabrata, a major intermediate host for the trematode parasite Schistosoma mansoni. Five neurons comprising the cerebral serotonergic F (CeSF) cluster of B. glabrata shared morphological characteristics with neurons that contribute to withdrawal behaviors in numerous heterobranch species. The largest member of this group, designated CeSF-1, projected an axon to the tentacle, a major site of threat detection. Intracellular recordings demonstrated repetitive activity and electrical coupling between the bilateral CeSF-1 cells. In semi-intact preparations, the CeSF-1 cells were not responsive to cutaneous stimuli but did respond to photic stimuli. A large FMRF-NH2-like immunoreactive neuron, termed C2, was also located on the dorsal surface of each cerebral hemiganglion near the origin of the tentacular nerve. C2 and CeSF-1 received coincident bouts of inhibitory synaptic input. Moreover, in the presence of 5-HT they both fired rhythmically and in phase. As the CeSF and C2 cells of Biomphalaria share fundamental properties with neurons that participate in withdrawal responses in Nudipleura and Euopisthobranchia, our observations support the proposal that features of this circuit are conserved in the Panpulmonata. NEW & NOTEWORTHY: Neuronal signals mediated by the biogenic amine serotonin underlie critical survival strategies across the animal kingdom. This investigation identified a group of serotonergic cells in the panpulmonate snail Biomphalaria glabrata that appear to be homologous to neurons that mediate withdrawal responses in other gastropod taxa. It is proposed that an ancient withdrawal circuit has been highly conserved in three major gastropod lineages. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni “S. mansoni” cercariae (Egyptian strain), then they were divided into two major groups: Early- [3 weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes. [ABSTRACT FROM AUTHOR]

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

Schistosoma mansoni worms cause a waterborne parasitic disease called schistosomiasis. It commonly affects individuals in lack of sanitation structure. In Brazil, Pará state has Belém as one of the worst sanitation-ranking places in 2023, where schistosomiasis transmission was already documented. This study reports the occurrence of schistosomiasis in residents of Ilha das Onças, an island next to Belém. Stool samples were obtained from participants over 2 years old, all residents from Furo do Rio Grande, one of the rivers on the island. The Kato-Katz technique was performed for parasite investigation in the stool samples. Each participant responded to a sociodemographic and clinical questionnaire. The residences were georeferenced for map designing. Three out of 263 participants were S. mansoni positive, all men, ages ranging from 19 to 41 years old, with low parasitic load. Malacological surveys were carried out, but no Biomphalaria snails were found. Risk factors for schistosomiasis establishment are present on the island, and the lack of sanitation makes it a potential risk area. Malacological surveys are highly encouraged as preventive measures, as well as health surveillance for riverside populations, generating data that will help health authorities in the management and planning of preventive control actions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intestinal parasitic infection constitutes a global health burden; it has a high prevalence among children in Nigeria. The quest for control is still ongoing. Geographical Information Systems have contributed significantly to solving sundry real-world tasks, from agriculture to emergency planning and control. Therefore, this study was aimed at geo-mapping of intestinal parasites in a Southern community in Nigeria to identify the infection risk areas. METHODS: A cross-sectional survey and clustered random sampling method were used. Samples were analyzed by direct wet mount and formal ether concentration methods. Geostatistical analyses were done to determine the spatial distribution of these parasites. RESULTS: The overall prevalence of intestinal parasite in the community was 23.95% and parasites identified were: Ascaris lumbricoides 45(7.23%), Entamoeba histolytica 31(4.98%), Strongyloides stercoralis 13(2.09%), Gardia lambla 12(1.93%), Hookworm 11(1.77%), Trichuris trichiura 10(1.61%), Schistosoma mansoni 9(1.45%) and Diphyllobothrium latum 4(0.64%). The distribution and intensity of the parasites showed that Bolu-Orua, Tungbo, and Ogalawa communities had higher intestinal parasitic infection rates and needs urgent interventions. Part of Sagbama, Aguru, Toru-Orua to Toru-Eden had a moderate intestinal parasitic infection. CONCLUSION: An infection map was produced for each parasite, and visualizing the spatial distribution of intestinal parasites in these communities brings to bare health risk areas. It will help in the proper application of limited resources in the control and prevention of these parasites. [ABSTRACT FROM AUTHOR]

Abstract: Background: Intestinal schistosomiasis remains a worrying health problem, particularly in western Côte d'Ivoire, despite control efforts. It is therefore necessary to understand all the factors involved in the development of the disease, including biotic and abiotic factors. The aim of this study was to examine the factors that could support the maintenance of the intermediate host and its vectorial capacity in western Côte d'Ivoire. Methods: Data on river physicochemical, microbiological, and climatic parameters, the presence or absence of snails with Schistosoma mansoni, and human infections were collected between January 2020 and February 2021. Spearman rank correlation tests, Mann–Whitney, analysis of variance (ANOVA), and an appropriate model selection procedure were used to analyze the data. Results: The overall prevalence of infected snails was 56.05%, with infection reaching 100% in some collection sites and localities. Of 26 sites examined, 25 contained thermophilic coliforms and 22 contained Escherichia coli. Biomphalaria pfeifferi was observed in environments with lower land surface temperature (LST) and higher relative air humidity (RAH), and B. pfeifferi infection predominated in more acidic environments. Thermal coliforms and E. coli preferred higher pH levels. Lower maximum LST (LST_Max) and higher RAH and minimum LST (LST_Min) were favorable to E. coli, and lower LST_Max favored coliforms. The presence of B. pfeifferi was positively influenced by water temperature (T °C), LST_Min, RAH, and precipitation (Pp) (P < 0.05) and negatively influenced by pH, total dissolved solids (TDS), electrical conductivity (EC), LST_Max, and mean land surface temperature (LST). The parameters pH, TDS, EC, LST_Min, LST, and Pp had a positive impact on snail infection, while LST_Max had a negative impact on infection. Only pH had a positive effect on coliform and E. coli abundance. Of the 701 people examined for human schistosomiasis, 73.13% were positive for the point-of-care circulating cathodic antigen (POC-CCA) test and 12.01% for the Kato–Katz (KK) test. A positive correlation was established between human infections and the abundance of Biomphalaria (r2 = 0.879, P = 0.04959). Conclusions: The results obtained reflect the environmental conditions that are conducive to the maintenance of S. mansoni infection in this part of the country. To combat this infection as effectively as possible, it will be necessary not only to redouble efforts but also to prioritize control according to the level of endemicity at the village level. [ABSTRACT FROM AUTHOR]

Because of recent reports of praziquantel resistance in schistosome infections, there have been suggestions to employ ivermectin as a possible alternative, especially as its chemical composition is different from that of praziquantel, so cross-resistance is not expected. In order to ascertain possible damage and elimination of worms, we used ivermectin by oral gavage in infected mice, at a high dose (30.1 mg/kg, bordering toxicity). We also tested the efficacy of the drug at various times postinfection (PI), to check on possible effect on young and mature stages of the parasites. Thus, we treated mice on days 21 and 22 or on days 41 and 42 and even on days 21, 22, 41, and 42 PI. None of the treatment regimens resulted in cure rates or signs of lessened pathology in the mice. We also compared the effect of ivermectin to that of artemisone, an artemisinin derivative which had served us in the past as an effective anti-schistosome drug, and there was a stark difference in the artemisone’s efficacy compared to that of ivermectin; while ivermectin was not effective, artemisone eliminated most of the worms, prevented egg production and granulomatous inflammatory response. We assume that the reported lack of activity of ivermectin, in comparison with praziquantel and artemisinins, originates from the difference in their mode of action. In wake of our results, we suggest that ivermectin is not a suitable drug for treatment of schistosomiasis. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a neglected tropical disease caused by parasitic worms of the genus Schistosoma. In Brazil, there are reports of infection by the Schistosoma mansoni species, which has the Biomphalaria glabrata snail as one of its intermediate hosts. The present work aimed to test the effects of different Abelmoschus esculentus seed extracts and fractions on adults and embryos of B. glabrata and S. mansoni cercariae. A total of four crude extracts and thirteen fractions with different organic solvents were used for the bioassays. The extracts were analyzed using high-performance liquid chromatography coupled to mass spectrometry. Molluscicidal activity was assessed in 24-well plates, after which the LC50 and LC90 were calculated. Assays with B. glabrata embryos and S. mansoni cercariae were also performed. These findings indicate the presence of flavanoids in the hexane, ethyl acetate, and ethanol crude extracts. For the molluscicidal activity assays, eight fractions had an LC90 value less than that recommended by the WHO. The methanol fraction of the dichloromethane extract (FrMeOH EDM) had the most promising results, with an LC90 of 37.15 mg/L and 100% mortality in embryos of B. glabrata and cercariae. FrMeOH, EDM, and other fractions are possible candidates for new drugs for the combat of schistosomiasis. [ABSTRACT FROM AUTHOR]

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

Objectives: Schistosomiasis is persistent in Lake Albert, Uganda, but local data are limited. This study aims to describe the local burden of moderate‐to‐heavy infection and associated morbidity in all ages and identify factors associated with these outcomes to guide further research. Methods: This cross‐sectional pilot study was conducted in July–August, 2022 in four village sites (Walukuba, Rwentale, Kyabarangwa and Runga) of the Praziquantel in Preschoolers (PIP) trial. Residents (approximately four per household) of any age of households of PIP participants were eligible, but individuals <10 years were only enrolled if no older individuals were available. Socio‐demographic information, household location, single stool Kato‐Katz and hepatic ultrasound results were obtained for a convenience sampled subset of trial households. The primary outcome, moderate‐to‐heavy infection (≥100 eggs per gram of faeces), was analysed using mixed‐effects logistic regression, with a household random effect. Univariate analyses were used for the secondary outcome, periportal fibrosis (Niamey protocol ultrasound image pattern C–F). Results: Of 243 participants with a median age of 22 (interquartile range 12–33) years from 66 households, 49.8% (103/207 with a Kato‐Katz result) had moderate‐to‐heavy infection and 11.2% (25/224 with ultrasound data) had periportal fibrosis. Moderate‐to‐heavy infection clustered by household (intraclass correlation coefficient = 0.11) and, in multivariable analysis, varied by village (Walukuba vs. Kyabarangwa adjusted odds ratio [aOR] 0.11, 95% CI 0.02–0.71), was highest in participants aged 10–15 years (vs. 5–9 years aOR 6.14, 95% CI 1.61–23.38) and lower in those reporting praziquantel treatment in the past year (aOR 0.39, 95% CI 0.18–0.88). Conclusions: In this setting, schistosome infection and morbidity are pervasive in all age groups. More intensive interventions are needed, for example more frequent praziquantel treatment, under investigation in the PIP trial and improved water and sanitation. More research is needed to understand local treatment barriers and optimal control strategies. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a disease caused by trematodes of the genus Schistosoma that affects over 200 million people worldwide. For decades, praziquantel (PZQ) has been the only available drug to treat the disease. Despite recent discoveries that identified a transient receptor ion channel as the target of PZQ, schistosome response to this drug remains incompletely understood, since effectiveness relies on other factors that may trigger a complex regulation of parasite gene expression. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that play important roles in S. mansoni homeostasis, reproduction, and fertility. Here, we show that in vivo PZQ treatment modulates lncRNA levels in S. mansoni. We re-analyzed public RNA-Seq data from mature and immature S. mansoni worms treated in vivo with PZQ and detected hundreds of lncRNAs differentially expressed following drug exposure, many of which are shared among mature and immature worms. Through RT-qPCR, seven out of ten selected lncRNAs were validated as differentially expressed; interestingly, we show that these lncRNAs are not adult worm stage-specific and are co-expressed with PZQ-modulated protein-coding genes. By demonstrating that parasite lncRNA expression levels alter in response to PZQ, this study unravels an important step toward elucidating the complex mechanisms of S. mansoni response to PZQ. [ABSTRACT FROM AUTHOR]

[Display omitted] • Recombinase Polymerase Amplification (RPA) is a simple and accurate tool for fast detection of Schistosoma mansoni DNA. • RPA targeting the S. mansoni mitochondrial minisatellite region (Sm MIT-RPA) can be used to detect infected snails. • Sm MIT-RPA detects S. mansoni early pre-patent infections in laboratory snails. • Sm MIT-RPA is a sensitive and specific tool for S. mansoni snail xenomonitoring. Improvements in diagnostics for schistosomiasis in both humans and snail hosts are priorities to be able to reach the World Health Organization (WHO) goal of eliminating the disease as a public health problem by 2030. In this context, molecular isothermal amplification tests, such as Recombinase Polymerase Amplification (RPA), are promising for use in endemic areas at the point-of-need for their accuracy, robustness, simplicity, and time-effectiveness. The developed recombinase polymerase amplification assay targeting the Schistosoma mansoni mitochondrial minisatellite region (Sm MIT-RPA) was used to detect S. mansoni DNA from both laboratory and field Biomphalaria snails. Laboratory snails were experimentally infected and used at one, seven, and 28 days post-exposure (dpe) to 10 S. mansoni miracidia to provide samples in the early pre-patent infection stage. Field samples of Biomphalaria spp. were collected from the Mucuri Valley and Jequitinhonha Valley regions in the state of Minas Gerais, Brazil, which are endemic for S. mansoni. The sensitivity and specificity of the Sm MIT-RPA assay were analysed and compared with existing loop-mediated isothermal amplification (LAMP), PCR-based methods, parasitological examination of the snails, and nucleotide sequencing. The Sm MIT-RPA assay was able to detect S. mansoni DNA in the experimentally infected Biomphalaria glabrata as early as one dpe to 10 miracidia. It also detected S. mansoni infections (55.5% prevalence) in the field samples with the highest accuracy (100% sensitivity and specificity) compared with the other molecular tests used as the reference. Results from this study indicate that the Sm MIT-RPA assay is a good alternative test to be used for snail xenomonitoring of S. mansoni due to its high sensitivity, accuracy, and the possibility of detecting early pre-patent infection. Its simplicity and portability also make it a suitable methodology in low-resource settings. [ABSTRACT FROM AUTHOR]

Schistosomiasis, otherwise known as bilharzia or snail fever, is a disease that usually affects poor people and people exposed to poor sanitation. The disease affects over 200 million people worldwide annually. Schistosomiasis has been treated using a single drug, praziquantel, since the 1970s and this is resulting in schistosomes becoming resistant. Therefore, there is an urgent need to develop new antischistosoma drugs and vaccines. This study focuses on identifying potential antischistosomal compounds from the plant Salvia fruticosa. We virtually screened a library of 163 S fruticosa compounds by docking against Schistosoma mansoni sulfotransferase (Sm SULT) using the PyRx software. Docking scores ranged from −4.7 to −9.3 kcal/mol. Compounds with binding affinity of −7.6 or stronger were subjected to drug-likeness assessments using the DataWarrior software. We also employed the PAINS removal tool to filter off false-positive results. Twelve compounds passed the drug-likeness screen, and these were subjected to in silico toxicity predictions to determine their mutagenic, tumorigenic and reproductive potential. Seven compounds were predicted to be nontoxic. After considering the toxicity analysis results and drug scores of the compounds, we identified rosmarinic acid and hispidulin as qualifying for further evaluation as potential drugs against schistosomiasis. Free energy calculations using the fastDRH webserver and molecular dynamics simulations using CABS-flex showed that the receptor-ligand complexes for the 2 lead compounds are stable under physiological conditions. We recommend that rosmarinic acid and hispidulin be used as hit compounds for the development of potential antischistosomal drugs. [ABSTRACT FROM AUTHOR]

Background. Malaria and schistosomiasis are infectious diseases that cause biochemical abnormalities. Malaria and Schistosoma mansoni coinfection causes exacerbations of health consequences and comorbidities. The study area is found in Ethiopia, where coinfection of malaria and S. mansoni is common. However, there is limited data on the biochemical profiles of patients coinfected with malaria and S. mansoni schistosomiasis in the study area. Hence, this study aimed to assess the effect of malaria and S. mansoni schistosomiasis coinfection on selected biochemical profiles. Methods. An institutional-based comparative cross-sectional study was conducted from March 30 to August 10, 2022. Using a convenient sampling technique, 70 participants (35 cases and 35 controls) were enrolled in the study. Schistosoma mansoni was detected in stool samples using the wet mount and the Kato Katz method. To detect Plasmodium, both thick and thin blood films were prepared and stained with Giemsa. The blood sample was processed for the analysis of biochemical profiles. All data were analyzed using SPSS version 25. A p value of less than 0.05 was considered statistically significant. Results. The mean values of alanine aminotransferase and aspartate aminotransferase (37.1 U/L and 41.9 U/L, respectively) in coinfected participants were significantly higher than in the healthy control participants (17.4 U/L and 22.0 U/L, respectively) p < 0.05 . Also, the median values of creatinine, total bilirubin, and direct bilirubin (1.51 mg/dL, 2.35 mg/dL, and 0.91 mg/dL, respectively) in coinfected participants were significantly higher than in the healthy control participants (0.85 mg/dL, 0.42 mg/dL, and 0.12 mg/dL, respectively) p < 0.05 . However, median values of total protein (4.82 g/dL) and mean values of glucose (66.6 mg/dL) in coinfected participants were significantly lower than in the healthy control participants (total protein (7.64 g/dL) and glucose (91.9 mg/dL)) p < 0.05 . The results of biochemical profiles in healthy participants were significantly different from those with light, moderate, and heavy S. mansoni infection intensity in malaria and S. mansoni coinfection p < 0.05 . Schistosoma mansoni infection intensity had a positive correlation with biochemical profiles except for total protein and glucose, which correlated negatively in coinfected participants p > 0.05 . Conclusion. Biochemical profiles in coinfection were significantly changed as compared to healthy individuals. As a result, biochemical profile tests should be utilized to monitor and manage coinfection-related problems, as well as to reduce coinfection-related morbidity and death. [ABSTRACT FROM AUTHOR]

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

Background: Schistosoma mansoni causes intestinal schistosomiasis (SCH) in all regions of Ethiopia. Despite many years of mass treatment, the prevalence has not dropped significantly. The reduction of SCH transmission demands the integration of deworming with safe water, sanitation, and hygiene (WASH) activities. Adequate knowledge and a positive attitude towards SCH are critical to practicing those interventions. However, data on the knowledge, attitude, and practice (KAP) level in school and community settings is limited in Ethiopia. Methods: School and community-based cross-sectional studies were conducted from February to June 2023 among 634 school-aged children (SAC) and 558 adults. A pre-tested questionnaire was used to collect socio-demographic and KAP data. Records were entered and analyzed using SPSS software version 21. Correct responses for each of the KAP questions were scored as one, while incorrect or 'I don't know' responses were scored as zero. Good knowledge, a positive attitude and good practice were declared if percentage scores were ≥ 80%, ≥ 90% and ≥ 75%, respectively. Results: Only 229 (19.2%) respondents, comprising 91 (14.4%) SAC and 138 (24.7%) adults, had ever heard of SCH. Adults, males, and urban residents had higher awareness level compared to their respective counterparts (p < 0.05). Only 28.4% of aware respondents knew that swimming or bathing in freshwater is a risk factor for schistosoma infection; 10.9% knew the etiologic agent; and 14.4% mentioned at least one sign and symptom associated with SCH. The majority (97.8%) of the respondents were willing to take therapeutic drugs, but only 37.6% believed that SCH is a serious disease. Regarding risky practices, 89.5% practiced swimming or bathing in freshwater, and 25.3% had no access to piped water. Among the aware respondents, only 18 (7.9%) had good knowledge, while 30 (13.1%) had a positive attitude towards SCH. Ninety-nine (43.2%) respondents had good Schistosoma infection prevention practices. Conclusions: The knowledge, attitude, and preventive practice level towards schistosomiasis are low in the study area. Therefore, strengthening school and community-based health education, along with mass drug administration (MDA), WASH, and a vector control program, is recommended for preventing SCH. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni causes intestinal schistosomiasis (SCH) in all regions of Ethiopia. Despite many years of mass treatment, the prevalence has not dropped significantly. The reduction of SCH transmission demands the integration of deworming with safe water, sanitation, and hygiene (WASH) activities. Adequate knowledge and a positive attitude towards SCH are critical to practicing those interventions. However, data on the knowledge, attitude, and practice (KAP) level in school and community settings is limited in Ethiopia. Methods: School and community-based cross-sectional studies were conducted from February to June 2023 among 634 school-aged children (SAC) and 558 adults. A pre-tested questionnaire was used to collect socio-demographic and KAP data. Records were entered and analyzed using SPSS software version 21. Correct responses for each of the KAP questions were scored as one, while incorrect or 'I don't know' responses were scored as zero. Good knowledge, a positive attitude and good practice were declared if percentage scores were ≥ 80%, ≥ 90% and ≥ 75%, respectively. Results: Only 229 (19.2%) respondents, comprising 91 (14.4%) SAC and 138 (24.7%) adults, had ever heard of SCH. Adults, males, and urban residents had higher awareness level compared to their respective counterparts (p < 0.05). Only 28.4% of aware respondents knew that swimming or bathing in freshwater is a risk factor for schistosoma infection; 10.9% knew the etiologic agent; and 14.4% mentioned at least one sign and symptom associated with SCH. The majority (97.8%) of the respondents were willing to take therapeutic drugs, but only 37.6% believed that SCH is a serious disease. Regarding risky practices, 89.5% practiced swimming or bathing in freshwater, and 25.3% had no access to piped water. Among the aware respondents, only 18 (7.9%) had good knowledge, while 30 (13.1%) had a positive attitude towards SCH. Ninety-nine (43.2%) respondents had good Schistosoma infection prevention practices. Conclusions: The knowledge, attitude, and preventive practice level towards schistosomiasis are low in the study area. Therefore, strengthening school and community-based health education, along with mass drug administration (MDA), WASH, and a vector control program, is recommended for preventing SCH. [ABSTRACT FROM AUTHOR]

Background: Advanced schistosomiasis is the most serious outcome of infection and has a negative impact on both physical fitness and mental health of patients, the latter of which has long been overlooked. Therefore, we performed this systematic review and meta-analysis to estimate the overall prevalence of depressive symptoms, one of the most common mental problems, in patients with advanced schistosomiasis in China. Methods: Six electronic databases were searched for studies reporting the prevalence of depressive symptoms in the targeted patients. Assessments were pooled using a fixed- or random-effects model based on heterogeneity test. Subgroup analyses were further performed and differences between/among groups were examined using the chi-squared test. The protocol had previously been registered in PROSPERO (CRD42023406708). Results: A total of 11 studies with 1,673 participants were included. The pooled prevalence of depressive symptoms in advanced schistosomiasis in China was 62.01% (95% CI: 51.30% - 72.72%), with a significant heterogeneity among studies. Depressive symptoms were more prevalent in patients with complications and more than half of the patients suffered a mild- or moderate-level of depression. No publication bias was found, and sensitivity analysis showed a stable result. Conclusions: The overall prevalence of depressive symptoms in advanced schistosomiasis in China was high enough to warrant psychotherapeutic interventions, especially for patients with complications. This would greatly prevent or/and reduce depression and improve their quality of life. Author summary: Schistosomiasis is a neglected tropical disease (NTD) which affects more than 250 million people across 78 countries worldwide. The three major schistosomes infecting humans are Schistosoma mansoni, S. japonicum, and S. haematobium. In China, after 70 years of control efforts, tremendous progress has been made, and now the number of schistosomiasis japonica infections is at its lowest historical level. However, advanced schistosomiasis, which is the most serious outcome of schistosome infection, poses a great threat as an increasing number of the patients have been diagnosed. Depression is a frequently occurring mental health issue caused by the disease that has long been overlooked. Therefore, we performed this meta-analysis to estimate the overall prevalence of depressive symptoms in patients with advanced schistosomiasis in China and its possible influential factors. We found that the pooled prevalence was 62.01% (95% CI: 51.30% - 72.72%) in the targeted patients and the estimate was associated with complications of the disease. Our study would call for psychological interventions to improve quality of life for patients with advanced schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: Schistosoma mansoni and S. haematobium infections have been public health problems in Ethiopia, S. mansoni being more prevalent. To reduce the burden of schistosomiasis, a national school-based prazequantel (PZQ) mass drug administration (MDA) program has been implemented since November 2015. Nevertheless, S. mansoni infection is still a major public health problem throughout the country. Reduced efficacy of PZQ is reported by a few studies in Ethiopia, but adequate data in different geographical settings is lacking. Hence, this study aimed to assess the efficacy and safety of PZQ for the treatment of S. mansoni infection across different transmission settings in Amhara Regional State, northwest Ethiopia. Methods: A school-based single-arm prospective cohort study was conducted from February to June, 2023 among 130 S. mansoni-infected school-aged children (SAC). Forty-two, 37, and 51 S. mansoni-infected SAC were recruited from purposely selected schools located in low, moderate, and high transmission districts, respectively. School-aged children who were tested positive both by Kato Katz (KK) using stool samples and by the point of care circulating cathodic antigen (POC-CCA) test using urine samples at baseline were treated with a standard dose of PZQ and followed for 21 days for the occurrence of adverse events. After three weeks post-treatment, stool and urine samples were re-tested using KK and POC-CCA. Then the cure rate (CR), egg reduction rate (ERR), and treatment-associated adverse events were determined. The data were analyzed using SPSS version 21. Results: Out of the total 130 study participants, 110 completed the follow-up. The CR and ERR of PZQ treatment were 88.2% (95%CI: 82.7–93.6) and 93.5% (95%CI: 85.4–98.5), respectively, by KK. The CR of PZQ based on the POC-CCA test was 70.9% (95%CI: 62.7–79.1) and 75.5% (95%CI: 67.3–83.6) depending on whether the interpretation of 'trace' results was made as positive or negative, respectively. After treatment on the 21st day, 78 and 83 participants tested negative both by KK and POC-CCA, with respective interpretations of 'trace' POC-CCA test results as positive or negative. The CR in low, moderate and high transmission settings was 91.7%, 91.2% and 82.5%, respectively (p = 0.377) when evaluated by KK. The CR among SAC with a light infection at baseline (95.7%) by KK was higher than that of moderate (81.5%) and heavy (64.3%) infections (χ2 = 12.53, p = 0.002). Twenty-six (23.6%) participants manifested at least one adverse event. Eleven (10.0%), eight (7.3%), six (5.5%), and three (2.7%) participants complained about abdominal pain, nausea, headache, and anorexia, respectively. All adverse events were mild, needing no intervention. Occurrence of adverse events was slightly higher in high endemic areas (32.5%) than moderate (23.5%) and low endemic areas (p = 0.279). Conclusions: A single dose of 40 mg/kg PZQ was efficacious and safe for the treatment of S. mansoni infection when it was evaluated by the KK test, but a lower efficacy was recorded when it was evaluated by the POC-CCA test. However, the POC-CCA test's specificity, clearance time of CCA from urine after treatment, and interpretation of weakly reactive (trace) test results need further research. [ABSTRACT FROM AUTHOR]

In previous studies, the inhibitory effect of chloroquine on NLRP3 inflammasome and heme production was documented. This may be employed as a double‐bladed sword in schistosomiasis (anti‐inflammatory and parasiticidal). In this study, chloroquine's impact on schistosomiasis mansoni was investigated. The parasitic load (worm/egg counts and reproductive capacity index [RCI]), i‐Nos/Arg‐1 expression, splenomegaly, hepatic insult and NLRP3‐immunohistochemical expression were assessed in infected mice after receiving early and late repeated doses of chloroquine alone or dually with praziquantel. By early treatment, the least RCI was reported in dually treated mice (41.48 ± 28.58) with a significant reduction in worm/egg counts (3.50 ± 1.29/2550 ± 479.58), compared with either drug alone. A marked reduction in the splenic index was achieved by prolonged chloroquine administration (alone: 43.15 ± 5.67, dually: 36.03 ± 5.27), with significantly less fibrosis (15 ± 3.37, 14.25 ± 2.22) than after praziquantel alone (20.5 ± 2.65). Regarding inflammation, despite the praziquantel‐induced significant decrease in NLRP3 expression, the inhibitory effect was marked after dual and chloroquine administration (liver: 3.13 ± 1.21/3.45 ± 1.23, spleen: 5.7 ± 1.6/4.63 ± 2.41). i‐Nos RNA peaked with early/late chloroquine administration (liver: 68.53 ± 1.8/57.78 ± 7.14, spleen: 63.22 ± 2.06/62.5 ± 3.05). High i‐Nos echoed with a parasiticidal and hepatoprotective effect and may indicate macrophage‐1 polarisation. On the flip side, the chloroquine‐induced low Arg‐1 seemed to abate immune tolerance and probably macrophage‐2 polarisation. Collectively, chloroquine synergised the praziquantel‐schistosomicidal effect and minimised tissue inflammation, splenomegaly and hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Gastropod molluscs, which serve as obligatory intermediate hosts for digenetic trematodes, possess an internal defense system (IDS) consisting of phagocytic hemocytes and plasma factors. This IDS is responsible for resistance to infection with larval trematodes, which are encapsulated and killed by hemocytes in incompatible snails. Like other physiological systems, the IDS probably undergoes maturation during early stages of life, and the relatively undeveloped state of the IDS in young snails has been hypothesized to be a factor in their increased susceptibility to infection with larval trematodes. In this study, hemocytes were examined in the BS‐90 laboratory strain of Biomphalaria glabrata that is resistant to infection with Schistosoma mansoni as adults but susceptible to infection as neonates. Compared with hemocytes from adults, hemocytes from neonates had a smaller perimeter and lower intrinsic directional motility on glass microscope slides. Additionally, in vitro assays showed a lower association with fucoidan‐linked polystyrene beads and less ability to produce superoxide anion in hemocytes from neonates compared to hemocytes from adults. These results support the hypothesis that the gastropod IDS undergoes maturation during growth. However, whether the observed differences between hemocytes of neonatal and adult BS‐90 snails play a role in the susceptibility of the former and resistance of the latter to infection with S. mansoni is not known. [ABSTRACT FROM AUTHOR]

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]

Aspergillus niger is a one-of-a-kind fungus with benefits for both terrestrial and aquatic species, although research on the effects of A. niger on aquatic animal species is limited. The present study investigated the impact of Aspergillus niger, A. flavus, and Alternaria alternate filtrates on Biomphalaria alexandrina snails (the main intermediate host of Schistosoma mansoni in Egypt). Moreover, the effect of A. niger (the most toxic fungus) filtrate was assessed against infected B. alexandrina snails with S. mansoni, in addition to its efficacy against S. mansoni free larval stages. Aspergillus niger had more toxicity (100 % mortality) than A. flavus (40% mortality), while Alternaria alternate did not affect B. alexandrina snails. Chronic exposure to sub-lethal concentrations of A. niger caused histopathological changes in the head-foot, digestive gland, kidney, and hermaphrodite gland of B. alexandrina snails. Furthermore, after exposure to the determined sub-lethal concentrations of A. niger, both uninfected and infected snails with S. mansoni showed low survival rates. In addition, the lethal time for miracidia and cercariae after exposure to LC25 of A. niger was 130 and 200 minutes, respectively. Additionally, exposure to sub-lethal A niger concentrations resulted in a significant decrease in the infection rate and mean total count of cercariae shed per snail, as well as the shed of aberrant cercariae. In conclusion, Aspergillus niger filtrate had a potent molluscicidal activity against B. alexandrina, and a damaging effect on cercariae, hence it can play a role in reducing schistosomiasis. [ABSTRACT FROM AUTHOR]

Schistosomiasis is a major neglected parasitic disease that affects more than 240 million people worldwide caused by Platyhelminthes of the genus Schistosoma. The treatment of schistosomiasis relies on the long-term application of a single safe drug, praziquantel (PZQ). Unfortunately, PZQ is very effective on adult parasites and poorly on larval stage and immature juvenile worms; this can partially explain the re-infection in endemic areas where patients are likely to host parasites at different developmental stages concurrently. Moreover, the risk of development of drug resistance because of the widespread use of a single drug in a large population is nowadays a serious threat. Hence, research aimed at identifying novel drugs to be used alone or in combination with PZQ is needed. Schistosomes display morphologically distinct stages during their life cycle and epigenetic mechanisms are known to play important roles in parasite growth, survival, and development. Histone deacetylase (HDAC) enzymes, particularly HDAC8, are considered valuable for therapeutic intervention for the treatment of schistosomiasis. Herein, we report the phenotypic screening on both larvae and adult Schistosoma mansoni stages of structurally different HDAC inhibitors selected from the in-house Siena library. All molecules have previously shown inhibition profiles on human HDAC6 and/or HDAC8 enzymes. Among them we identified a quinolone-based HDAC inhibitor, NF2839, that impacts larval and adult parasites as well as egg viability and maturation in vitro. Importantly, this quinolone-based compound also increases histone and tubulin acetylation in S. mansoni parasites, thus representing a leading candidate for the development of new generation anti-Schistosoma chemotherapeutics. Author summary: Neglected tropical diseases, such as schistosomiasis, which is caused by parasitic worms, represent serious public health problems in many countries around the world. Schistosoma mansoni is the major parasitic platyhelminth species causing intestinal schistosomiasis. Currently the control of schistosomiasis is heavily reliant on the drug praziquantel (PZQ) that it is unfortunately not highly effective against larval and immature worm stages. The use of PZQ in mass treatment programs means that the development of resistance is likely, therefore identifying novel drug targets and their associated compounds is critical. Drugs that inhibit enzymes that modify the chromatin structure have been developed for several diseases. We and others have shown that S. mansoni epigenetic enzymes are also potential therapeutic targets. Here, we evaluate and characterize several histone deacetylases (HDAC) inhibitors on the larval and adult stage of Schistosoma mansoni and report the anti-parasitic profile of these compounds. Some of the HDAC inhibitors tested showed potent effects, particularly NF2839, that impacts larval and adult parasites as well as egg viability and maturation. The findings of this study provide a starting point for the development of new HDAC-based schistosomicidal compounds. [ABSTRACT FROM AUTHOR]

Background: The genomic region that lies between the telomere and chromosome body, termed the subtelomere, is heterochromatic, repeat-rich, and frequently undergoes rearrangement. Within this region, large-scale structural changes enable gene diversification, and, as such, large multicopy gene families are often found at the subtelomere. In some parasites, genes associated with proliferation, invasion, and survival are often found in these regions, where they benefit from the subtelomere's highly plastic, rapidly changing nature. The increasing availability of complete (or near complete) parasite genomes provides an opportunity to investigate these typically poorly defined and overlooked genomic regions and potentially reveal relevant gene families necessary for the parasite's lifestyle. Results: Using the latest chromosome-scale genome assembly and hallmark repeat richness observed at chromosome termini, we have identified and characterised the subtelomeres of Schistosoma mansoni, a metazoan parasitic flatworm that infects over 250 million people worldwide. Approximately 12% of the S. mansoni genome is classified as subtelomeric, and, in line with other organisms, we find these regions to be gene-poor but rich in transposable elements. We find that S. mansoni subtelomeres have undergone extensive interchromosomal recombination and that these sites disproportionately contribute to the 2.3% of the genome derived from segmental duplications. This recombination has led to the expansion of subtelomeric gene clusters containing 103 genes, including the immunomodulatory annexins and other gene families with unknown roles. The largest of these is a 49-copy plexin domain-containing protein cluster, exclusively expressed in the tegument—the tissue located at the host-parasite physical interface—of intramolluscan life stages. Conclusions: We propose that subtelomeric regions act as a genomic playground for trial-and-error of gene duplication and subsequent divergence. Owing to the importance of subtelomeric genes in other parasites, gene families implicated in this subtelomeric expansion within S. mansoni warrant further characterisation for a potential role in parasitism. [ABSTRACT FROM AUTHOR]

Background: Timely diagnosis of Toxoplasma gondii infection is necessary to prevent and control toxoplasmosis transmission. The gold immunochromatographic assay (GICA) is a means of rapidly detecting pathogen in samples. GICA-based diagnostic methods have been developed to accurately detect pathogens with high sensitivity and specificity, and their application in T. gondii diagnosis is expected to yield good results. Methods: Colloidal gold test strips were produced using T. gondii C-terminal truncated apical membrane antigen 1 (AMA1C). Colloidal gold-AMA1C and colloidal gold-murine protein conjugate were synthesized under optimal conditions. A nitrocellulose membrane was treated with AMA1C and goat anti-mouse antibody as the test line and control line, respectively. In total, 90 cat serum samples were tested using AMA1C-GICA and a commercial enzyme linked immunosorbent assay (ELISA) kit. The GICA results were digitally displayed using a portable colloidal gold immunochromatographic test strip analyzer (HMREADER). The sensitivity, specificity, and stability of AMA1C-GICA were assessed, and this was then used to examine clinical samples, including 203 human sera, 266 cat sera, and 81 dog sera. Results: AMA1C-GICA had a detection threshold of 1:32 for T. gondii-positive serum. The GICA strips specifically detected T. gondii antibodies and exhibited no reactivity with Plasmodium vivax, Paragonimus kellicotti, Schistosoma japonicum, Clonorchis sinensis, and Schistosoma mansoni. Consequently, 15 (16.7%) positive samples were detected using the AMA1C-GICA and commercial ELISA kits for each of the assays. The receiver-operating characteristic curve showed that GICA had a relative sensitivity of 85.3% and specificity of 92%, with an area under the curve of 98%. After analyzing clinical samples using HMREADER, 1.2%–23.4% of these samples were found to be positive for T. gondii. Conclusions: This study presents a novel assay that enables timely and efficient detection of serum antibodies against T. gondii, thereby allowing for its early clinical diagnosis. Furthermore, the integration of digital detection using HMREADER can enhance the implementation of GICA. [ABSTRACT FROM AUTHOR]

Schistosomiasis is one of the most devastating human diseases worldwide. The disease is caused by six species of Schistosoma blood fluke; five of which cause intestinal granulomatous inflammation and bleeding. The current diagnostic method is inaccurate and delayed, hence, biomarker identification using metabolomics has been applied. However, previous studies only investigated infection caused by one Schistosoma spp., leaving a gap in the use of biomarkers for other species. No study focused on understanding the progression of intestinal disease. Therefore, we aimed to identify early gut biomarkers of infection with three Schistosoma spp. and progression of intestinal pathology. We infected 3 groups of mice, 3 mice each, with Schistosoma mansoni, Schistosoma japonicum or Schistosoma mekongi and collected their feces before and 1, 2, 4 and 8 weeks after infection. Metabolites in feces were extracted and identified using mass spectrometer-based metabolomics. Metabolites were annotated and analyzed with XCMS bioinformatics tool and Metaboanalyst platform. From >36,000 features in all conditions, multivariate analysis found a distinct pattern at each time point for all species. Pathway analysis reported alteration of several lipid metabolism pathways as infection progressed. Disturbance of the glycosaminoglycan degradation pathway was found with the presence of parasite eggs, indicating involvement of this pathway in disease progression. Biomarkers were discovered using a combination of variable importance for projection score cut-off and receiver operating characteristic curve analysis. Five molecules met our criteria and were present in all three species: 25-hydroxyvitamin D2, 1α-hydroxy-2β-(3-hydroxypropoxy) vitamin D3, Ganoderic acid Md, unidentified feature with m/z 455.3483, and unidentified feature with m/z 456.3516. These molecules were proposed as trans-genus biomarkers of early schistosomiasis. Our findings provide evidence for disease progression in intestinal schistosomiasis and potential biomarkers, which could be beneficial for early detection of this disease. Author summary: Schistosomiasis is a parasitic disease caused by the blood fluke Schistosoma. Five species of Schistosoma cause intestinal damage and inflammation, but the current method of diagnosis is not satisfactory because it lacks sensitivity and timeliness. Therefore, we applied metabolomics to identify the overall types and abundance of compounds in biological samples to discover new markers. Previous metabolomic studies focused only on infection with one species, making it difficult to detect disease caused by other species. Moreover, no study examined progression of intestinal disease. In this study, we used a mouse model and metabolomics to investigate changes in the gut environment from the early stage of the disease and identify markers of early infection caused by three different species of Schistosoma. We found that changes in compounds related to lipid metabolism since early infection and some pathways, such as glycosaminoglycan degradation, might be related to intestinal disease. We identified five compounds as early biomarkers of schistosomiasis, which were shared among the three species. These compounds could be used for future biomarker development, which could facilitate diagnosis of schistosomiasis. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends the use of Schisto point-of-care circulating cathodic antigens (Schisto POC-CCA) for screening of Schistosoma mansoni as it offers better sensitivity than microscopy. However, there are limitation facing the use of this method including timely availability of the test cassettes. The aim of this study was to determine the reliability of dried urine spot (DUS) method for collection of urine and detection of S. mansoni using Schisto POC-CCA cassettes in a resource-limited settings. Methods: A cross-sectional study was conducted between October and November 2022 among 250 primary school children in Sengerema District, northwestern Tanzania. S. mansoni CCA was detected in filter paper-based DUS, liquid urine using DUS Schisto POC-CCA (index), and direct urine Schisto POC-CCA (comparator) methods respectively. S. mansoni eggs in stool were detected using duplicate Kato-Katz (KK) method. The measures of accuracy were computed and compared between the index and comparator methods. The strength of agreement between inter-raters precisions was tested using Cohen’s kappa (k). Results: This study revealed S. mansoni prevalence rates of 28.8%, 54.0% and 50.8% by duplicate KK, direct urine Schisto POC-CCA and DUS Schisto POC-CCA methods respectively. The mean intensity of infection among infected participants was 86.3 eggs per gram of stool (EPG) ranging from 12.0 EPG to 824.0 EPG. The sensitivity of DUS Schisto POC-CCA and direct urine Schisto POC-CCA was 94.44% (95% CI: 89.15–99.74%) and 97.22% (95% CI: 93.43–100.00%) respectively. The DUS Schisto POC-CCA method had slightly higher specificity (66.85%) than direct urine Schisto POC-CCA method (63.48%). The accuracy of the DUS Schisto POC-CCA was found to be slightly high (74.80%, 95% CI: 68.94–79.06%) compared to that of direct urine Schisto POC-CCA (73.20%, 95% CI: 67.25–78.59%). There was good agreement between two laboratory technologists who performed the DUS Schisto POC-CCA method on similar samples (k = 0.80, 95% CI: 0.59–0.95). Conclusions: The DUS Schisto POC-CCA method had comparable S. mansoni detection accuracy to direct urine Schisto POC-CCA. This suggests that the method could be a potential alternative to direct urine Schisto POC-CCA for screening S. mansoni in resource-limited situations. [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]

The quantification of parasite forces during migration in host environments elucidates critical biophysical mechanisms that support parasite survival and dissemination. Traction force microscopy (TFM) has been a crucial tool. It is highly adaptive in experimental settings and adjustable to various scales for quantifying forces across parasite species and developmental stages. TFM enriches the current understanding of parasite locomotion. It not only refines long-standing protozoan migration theories, but also uncovers novel metazoan motility models, shedding light on fundamental parasite biology. Advances in techniques that measure mechanical forces at the parasite–host interface, especially in 3D and in vivo , will expand our knowledge of adaptation of parasites to their environments, and possibly suggest new intervention strategies. The dissemination of protozoan and metazoan parasites through host tissues is hindered by cellular barriers, dense extracellular matrices, and fluid forces in the bloodstream. To overcome these diverse biophysical impediments, parasites implement versatile migratory strategies. Parasite-exerted mechanical forces and upregulation of the host's cellular contractile machinery are the motors for these strategies, and these are comparably better characterized for protozoa than for helminths. Using the examples of the protozoans, Toxoplasma gondii and Plasmodium , and the metazoan, Schistosoma mansoni , we highlight how quantitative tools such as traction force and reflection interference contrast microscopies have improved our understanding of how parasites alter host mechanobiology to promote their migration. [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]

Liebold et al. recently revealed how the identity of dying cells drives distinct changes to the macrophages which engulf and clear them, a process known as efferocytosis. During infection with the helminth Schistosoma mansoni , liver macrophages recapitulate these phenotypes, mediated by Axl/MerTK receptors and regulating egg burdens. [ABSTRACT FROM AUTHOR]

Background: Healthy eating habits are essential for improving nutritional status and strengthening immunity against infectious diseases. This study examined the relationship between diet quality and stunting in school-aged children in an infectious disease-endemic area of western Kenya. Methods: This cross-sectional study included 260 school-aged children (age 9–17 years) enrolled in primary schools in Mbita Sub-county, western Kenya. The nutritional status was assessed using anthropometric measurements. Dietary intake was measured using food frequency questionnaires and evaluated using the Food Pyramid (FP) score, which indicates adherence to the Kenyan food-based dietary guideline. Information on the children's age, sex, maternal education, and household wealth index was collected using a household-based questionnaire. Infections with the predominant parasites, such as Schistosoma (S.) mansoni, were detected via microscopy. The trend associations of the FP score with food group intake were examined to characterize the dietary intake of this population. Logistic regression analysis was performed to investigate the relationship between stunting and FP score tertiles, adjusted for sociodemographic and economic indicators and parasitic infection status. Results: Among the studied schoolchildren, 15.0% exhibited stunting, while 76.2% were infected with S. mansoni. The mean FP score was 25.6 out of 50 points. A higher FP score was characterized by a high intake of roots and tubers, dairy products, pulses, and fruits and a low intake of cereals and animal-source foods. The analysis revealed a trend: a lower risk of stunting was evident in groups with elevated FP scores (p for trend = 0.065). However, these trend associations were observable among subjects with either negative or light S. mansoni infection (p for trend = 0.016). Conclusions: A higher quality diet, as evaluated by FP scores, was associated with a low risk of stunting among school-aged children. Notably, this association seemed to weaken in the presence of a high burden of S. mansoni infection. It highlights the importance of enhancing dietary quality through the promotion of diverse nutrient-dense foods alongside effective S. mansoni infection control for improved growth. This study contributes fundamental knowledge for understanding the diet–malnutrition relationship in areas endemic for S. mansoni infection. [ABSTRACT FROM AUTHOR]

Schistosomiasis is caused by parasites of the genus Schistosoma, which infect more than 200 million people. Praziquantel (PZQ) has been the main drug for controlling schistosomiasis for over four decades, but despite that it is ineffective against juvenile worms and size and taste issues with its pharmaceutical forms impose challenges for treating school-aged children. It is also important to note that PZQ resistant strains can be generated in laboratory conditions and observed in the field, hence its extensive use in mass drug administration programs raises concerns about resistance, highlighting the need to search for new schistosomicidal drugs. Schistosomes survival relies on the redox enzyme thioredoxin glutathione reductase (TGR), a validated target for the development of new anti-schistosomal drugs. Here we report a high-throughput fragment screening campaign of 768 compounds against S. mansoni TGR (SmTGR) using X-ray crystallography. We observed 49 binding events involving 35 distinct molecular fragments which were found to be distributed across 16 binding sites. Most sites are described for the first time within SmTGR, a noteworthy exception being the "doorstop pocket" near the NADPH binding site. We have compared results from hotspots and pocket druggability analysis of SmTGR with the experimental binding sites found in this work, with our results indicating only limited coincidence between experimental and computational results. Finally, we discuss that binding sites at the doorstop/NADPH binding site and in the SmTGR dimer interface, should be prioritized for developing SmTGR inhibitors as new antischistosomal drugs. [ABSTRACT FROM AUTHOR]

A role of IL‐10 is down‐regulating T‐cell responses to schistosome antigens. Since SmATPDases can be correlated to modulation of the immune response, we evaluated the expression of enzymes in S. mansoni eggs. Faecal samples were collected from 40 infected individuals to detect coding regions of the SmATPDases. The cytokines were measured in supernatants of PBMC. The analysis was performed by the global median determination and set up high producers (HP) of cytokines. Six individuals expressed SmATPDase1, six expressed SmATPDase2 and six expressed both enzymes. The group who expressed only SmATPDase1 showed a high frequency of IFN‐γ, TNF IL‐4 HP; individuals who expressed only SmATPDase2 showed a high frequency of IFN‐γ, IL‐6 and IL‐4 HP; and individuals who expressed both enzymes showed a high frequency of IL‐10 HP. The comparison of the IFN‐γ/IL‐10 ratio presented higher indices in the group who had SmATPDase 2 expression than those who had the expression of both enzymes. The positive correlation between infection intensity and IL‐10 levels remained only in the positive SmATPDase group. The IL‐10 is the only cytokine induced by the expression of both enzymes. Our data suggest that the expression of both enzymes seems to be a factor that modulates the host immune response by inducing high IL‐10 production. [ABSTRACT FROM AUTHOR]

Probiotics contribute to the integrity of the intestinal mucosa and preventing dysbiosis caused by opportunistic pathogens, such as intestinal helminths. Bacillus cereus GM obtained from Biovicerin® was cultured to obtain spores for in vivo evaluation on experimental schistosomiasis. The assay was performed for 90 days, where all animals were infected with 50 cercariae of Schistosoma mansoni on the 15th day. Three experimental groups were formed, as follows: G1—saline solution from the 1st until the 90th day; G2—B. cereus GM (105 spores in 300 μL of sterile saline) from the 1st until the 90th day; and G3—B. cereus GM 35th day (onset of oviposition) until the 90th day. G2 showed a significant reduction of 43.4% of total worms, 48.8% of female worms and 42.5% of eggs in the liver tissue. In G3, the reduction was 25.2%, 29.1%, and 44% of the total number of worms, female worms, and eggs in the liver tissue, respectively. G2 and G3 showed a 25% (p < 0.001) and 22% (p < 0.001) reduction in AST levels, respectively, but ALT levels did not change. ALP levels were reduced by 23% (p < 0.001) in the G2 group, but not in the G3. The average volume of granulomas reduced (p < 0.0001) 65.2% and 46.3% in the liver tissue and 83.0% and 53.2% in the intestine, respectively, in groups G2 and G3. Th1 profile cytokine (IFN-γ, TNF-α, and IL-6) and IL-17 were significantly increased (p < 0.001) stimulated with B. cereus GM in groups G2 and G3. IL-4 showed significant values when the stimulus was mediated by ConA. By modulating the immune response, B. cereus GM reduced the burden of worms, improved some markers of liver function, and reduced the granulomatous inflammatory reaction in mice infected with S. mansoni, especially when administered before infection. [ABSTRACT FROM AUTHOR]

Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a neglected tropical disease caused by parasitic blood flukes. Schistosomiasis is treated with praziquantel (PZQ), an old drug introduced over 40 years ago. New drugs are urgently needed, as while PZQ is broadly effective it suffers from several limitations including poor efficacy against juvenile worms, which may prevent it from being completely curative. An old compound that retains efficacy against juvenile worms is the benzodiazepine meclonazepam (MCLZ). However, host side effects caused by benzodiazepines preclude development of MCLZ as a drug and MCLZ lacks an identified parasite target to catalyze rational drug design for engineering out human host activity. Here, we identify a transient receptor potential ion channel of the melastatin subfamily, named TRPMMCLZ, as a parasite target of MCLZ. MCLZ potently activates Schistosoma mansoni TRPMMCLZ through engagement of a binding pocket within the voltage-sensor-like domain of the ion channel to cause worm paralysis, tissue depolarization, and surface damage. TRPMMCLZ reproduces all known features of MCLZ action on schistosomes, including a lower activity versus Schistosoma japonicum, which is explained by a polymorphism within this voltage-sensor-like domain-binding pocket. TRPMMCLZ is distinct from the TRP channel targeted by PZQ (TRPMPZQ), with both anthelmintic chemotypes targeting unique parasite TRPM paralogs. This advances TRPMMCLZ as a novel druggable target that could circumvent any target-based resistance emerging in response to current mass drug administration campaigns centered on PZQ. [ABSTRACT FROM AUTHOR]

Schistosomes are blood flukes with specialised tissues and organs, each one playing a pivotal role in perpetuating the parasite life cycle. Herein, we describe a detailed methodology for preserving the proteome of adult Schistosoma mansoni worms during manual dissection for enrichment of tissues associated with the parasite's alimentary tract. We provide step‐by‐step directions for specimen storage and dissection while in preservative solution, tissue homogenisation, protein extraction and digestion using a methodology fully compatible with downstream quantitative liquid chromatography–mass spectrometry analysis. Our methodology uses label‐free and QconCAT‐based absolute quantification for detection of S. mansoni oesophageal gland products proposed as vaccine candidates. Through stabilisation of the proteome and minimising sample degradation during dissection our approach has allowed us to access the hidden proteome of target tissues not readily available from total lysates because of their small volume. This protocol can be replicated or adapted to other Schistosoma species lacking quantitative proteomics characterisation of specialised tissues for discovery of proteins with potential diagnostic and therapeutic utility. [ABSTRACT FROM AUTHOR]

Background: Preventive chemotherapy with a single dose of praziquantel given to an all-at-risk population through mass drug administration is the cornerstone intervention to control and eliminate schistosomiasis as a public health problem. This intervention mainly targets school age children, and pre-school age children (pre-SAC) are excluded from receiving preventive chemotherapy, partly due to scarcity of data on praziquantel treatment outcomes. Methods: We conducted active efficacy and safety surveillance of praziquantel treatment among 240 Schistosoma mansoni-infected pre-SAC who received a single dose of praziquantel (40 mg/kg) in southern Ethiopia. The study outcomes were egg reduction rates (ERR) and cure rates (CRs) four weeks after treatment using the Kato–Katz technique and treatment-associated adverse events (AEs) that occurred within 8 days post-treatment. Results: The overall ERR was 93.3% (WHO reference threshold ≥ 90%), while the CR was 85.2% (95% CI = 80.0–89.5%). Baseline S. mansoni infection intensity was significantly associated with CRs, 100% among light infected than moderate (83.4%) or heavy (29.4%) infected children. An increase of 100 in baseline S. mansoni egg count per gram of stool resulted in a 26% (95% CI: 17%, 34%) reduction in the odds of cure. The incidence of experiencing at least one type of AE was 23.1% (95% CI: 18.0%, 29.0%). Stomachache, diarrhea, and nausea were the most common AEs. AEs were mild-to-moderate grade and transient. Pre-treatment moderate (ARR = 3.2, 95% CI: 1.69, 6.14) or heavy infection intensity (ARR = 6.5, 95% CI: 3.62, 11.52) was a significant predictor of AEs (p < 0.001). Sex, age, or soil-transmitted helminth coinfections were not significant predictors of CR or AEs. Conclusions: Single-dose praziquantel is tolerable and effective against S. mansoni infection among pre-SAC, and associated AEs are mostly mild-to-moderate and transient. However, the reduced CR in heavily infected and AEs in one-fourth of S. mansoni-infected pre-SAC underscores the need for safety and efficacy monitoring, especially in moderate-to-high infection settings. Integrating pre-SACs in the national deworming programs is recommended to accelerate the elimination of schistosomiasis as a public health problem. [ABSTRACT FROM AUTHOR]