Transmission potential of human schistosomes can be driven by resource competition among snail intermediate hosts.

Predicting and disrupting transmission of human parasites from wildlife hosts or vectors remains challenging because ecological interactions can influence their epidemiological traits. Human schistosomes, parasitic flatworms that cycle between freshwater snails and humans, typify this challenge. Human exposure risk, given water contact, is driven by the production of free-living cercariae by snail populations. Conventional epidemiological models and management focus on the density of infected snails under the assumption that all snails are equally infectious. However, individual-level experiments contradict this assumption, showing increased production of schistosome cercariae with greater access to food resources. We built bioenergetics theory to predict how resource competition among snails drives the temporal dynamics of transmission potential to humans and tested these predictions with experimental epidemics and demonstrated consistency with field observations. This resource-explicit approach predicted an intense pulse of transmission potential when snail populations grow from low densities, i.e., when per capita access to resources is greatest, due to the resource-dependence of cercarial production. The experiment confirmed this prediction, identifying a strong effect of infected host size and the biomass of competitors on per capita cercarial production. A field survey of 109 waterbodies also found that per capita cercarial production decreased as competitor biomass increased. Further quantification of snail densities, sizes, cercarial production, and resources in diverse transmission sites is needed to assess the epidemiological importance of resource competition and support snail-based disruption of schistosome transmission. More broadly, this work illustrates how resource competition can sever the correspondence between infectious host density and transmission potential.

Prevalence of Intestinal Parasites and Schistosoma mansoni and Associated Factors among Fishermen at Lake Tana, Northwest Ethiopia.

BACKGROUND: Intestinal parasites and Schistosoma mansoni infections adversely affect the health of humans in the world especially in sub-Saharan African countries including Ethiopia. Fishermen who spend most of their time in water bodies are supposed to be at high risk of schistosomiasis and other water-born parasites. However, the magnitude of these parasitic infections and their determinant factors are not well addressed. METHODS: A cross-sectional study was conducted at Lake Tana among 388 fishermen from March to May 2021. Questionnaire data was collected through face to face interview. Stool sample from each participant was processed by the Kato-Katz and spontaneous tube sedimentation techniques. Data were analyzed using SPSS version 26. RESULTS: One hundred sixty four (42.3%) and 88 (22.7%) participants were infected by intestinal parasites and Schistosoma mansoni, respectively. One hundred twenty two (31.4%) and 42 (10.8%) participants were infected by soil-transmitted helminths and intestinal protozoa, respectively. Attending only primary school (AOR = 2.02, p = 0.014) or being illiterate (AOR = 2.54, p = 0.004) and not washing hands before meal (AOR = 2.23, p = 0.007) were significantly associated with intestinal parasitic infections. Illiterate educational status (AOR = 2.37, p = 0.022), fishing by bargee (AOR = 2.43, p = 0.005), fishing ≥4 days per week (AOR = 2.27, p = 0.029), swimming habit (AOR = 3.03, p = 0.030), and participation in irrigation (AOR = 3.09, p ≤ 0.001) predispose fishermen to S. mansoni infection. CONCLUSION: Intestinal parasites and S. mansoni infections are highly prevalent among fishermen at Lake Tana basin. Low education level and frequent water contact predispose fishermen for intestinal parasites and S. mansoni. Therefore, health education to fishermen on intestinal parasites and S. mansoni infection and regular deworming should be advocated.

Association of IL-9, IL-10, and IL-17 Cytokines With Hepatic Fibrosis in Human Schistosoma mansoni Infection.

This is a case series study to evaluate immunological markers associated with schistosomiasis advanced fibrosis, including 69 patients from an endemic area from the State of Sergipe and from the Hepatology Service of the University Hospital in Sergipe, Brazil. Hepatic fibrosis was classified based on Niamey protocol for ultrasonography (US). Immune response to Schistosoma mansoni antigens was evaluated by stimulating peripheral blood mononuclear cells (PBMCs) from these patients with either adult worm (SWAP-10 µg/ml) or egg (SEA-10 µg/ml) antigens or purified protein derivative of turberculin (PPD-10 µg/ml) or phytohemagglutinin (PHA-1 µg/ml) for 72 h. The levels of IFN-γ, TNF-α, IL-5, IL-10, and IL-17 were measured in these supernatants by ELISA and IL-9 by Luminex. Single nucleotide polymorphisms in IL-17, IL10, and CD209 genes were genotyped using TaqMan probe by qPCR. Higher levels of IL-9, IL-10, and IL-17 were found in PBMC supernatants of patients with advanced hepatic fibrosis. Direct correlations were detected between IL-9 and IL-17 levels with US spleen sizes, portal vein diameters, and periportal thickening. The CD209 rs2287886 AG polymorphism patients produce higher IL-17 levels. Together, these data suggest a role of these cytokines in the immunopathogenesis of advanced fibrosis in human schistosomiasis.

Epidemiology of Schistosoma mansoni infection in Ituri Province, north-eastern Democratic Republic of the Congo.

BACKGROUND: Schistosomiasis, caused by Schistosoma mansoni, is of great significance to public health in sub-Saharan Africa. In the Democratic Republic of Congo (DRC), information on the burden of S. mansoni infection is scarce, which hinders the implementation of adequate control measures. We assessed the geographical distribution of S. mansoni infection across Ituri province in north-eastern DRC and determined the prevailing risk factors. METHODS/PRINCIPAL FINDINGS: Two province-wide, community-based studies were conducted. In 2016, a geographical distribution study was carried out in 46 randomly selected villages across Ituri. In 2017, an in-depth study was conducted in 12 purposively-selected villages, across the province. Households were randomly selected, and members were enrolled. In 2016, one stool sample was collected per participant, while in 2017, several samples were collected per participant. S. mansoni eggs were detected using the Kato-Katz technique. In 2017, a point-of-care circulating cathodic S. mansoni antigen (POC-CCA) urine test was the second used diagnostic approach. Household and individual questionnaires were used to collect data on demographic, socioeconomic, environmental, behavioural and knowledge risk factors. Of the 2,131 participants in 2016, 40.0% were positive of S. mansoni infection. Infection prevalence in the villages ranged from 0 to 90.2%. Of the 707 participants in 2017, 73.1% were tested positive for S. mansoni. Prevalence ranged from 52.8 to 95.0% across the health districts visited. Infection prevalence increased from north to south and from west to east. Exposure to the waters of Lake Albert and the villages' altitude above sea level were associated with the distribution. Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected (62.3%). Key risk factors were poor housing structure (odds ratio [OR] 2.1, 95% 95% confidence interval [CI] 1.02-4.35), close proximity to water bodies (OR 1.72, 95% CI 1.1-2.49), long-term residence in a community (OR 1.41, 95% CI 1.11-1.79), lack of latrine in the household (OR 2.00, 95% CI 1.11-3.60), and swimming (OR 2.53, 95% CI 1.20-5.32) and washing (OR 1.75, 95% CI 1.10-2.78) in local water bodies. CONCLUSIONS/SIGNIFICANCE: Our results show that S. mansoni is highly endemic and a major health concern in Ituri province, DRC. Infection prevalence and intensity, and the prevailing socioeconomic, environmental, and behavioural risk factors in Ituri reflect intense exposure and alarming transmission rates. A robust plan of action is urgently needed in the province.

Morbidity associated with Schistosoma mansoni infection in north-eastern Democratic Republic of the Congo.

BACKGROUND: Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. METHODS/PRINCIPAL FINDINGS: In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06-1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99-2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73-1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. CONCLUSIONS/SIGNIFICANCE: Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity.

Schistosoma mansoni infection risk for school-aged children clusters within households and is modified by distance to freshwater bodies.

BACKGROUND: The interaction of socio-demographic and ecological factors with Schistosoma mansoni (S. mansoni) infection risk by age and the household clustering of infections between individuals are poorly understood. METHODS: This study examined 1,832 individuals aged 5-90 years across 916 households in Mayuge District, Uganda. S. mansoni infection status and intensity were measured using Kato-Katz microscopy. Socio-demographic and ecological factors were examined as predictors of infection status and intensity using logistic and negative binomial regression models, respectively, with standard errors clustered by household. A subgroup analysis of children was conducted to examine the correlation of infection status between children and their caretakers. FINDINGS: Infection varied within age groups based on the distance to Lake Victoria. Children aged 9-17 years and young adults aged 18-29 years who lived ≤0.50km from Lake Victoria were more likely to be infected compared to individuals of the same age who lived further away from the lake. Infections clustered within households. Children whose caretakers were heavily infected were 2.67 times more likely to be infected. CONCLUSION: These findings demonstrate the focality of schistosome transmission and its dependence on socio-demographic, ecological and household factors. Future research should investigate the sampling of households within communities as a means of progressing towards precision mapping of S. mansoni infections.

Differential effects of asymptomatic Ascaris lumbricoides, Schistosoma mansoni or hook worm infection on the frequency and TGF-beta-producing capacity of regulatory T cells during active tuberculosis.

Helminth induced expansion of regulatory T cells (Tregs) may take part in suppressing protective host responses during tuberculosis (TB), although Tregs functionality and link to TB disease severity remains unexplored. We investigated the species-specific effect of helminths on frequency and TGF-ß producing capacity of Tregs, and possible connection to TB disease severity. 89 pulmonary TB patients (PTB) and 69 community controls (CCs) from Gondar, Ethiopia, were included. Clinical disease severity was graded by TB score, and flow cytometry used to characterize Treg frequency and functionality measured as their TGF-ß-producing capacity. In helminth positive PTB patients (Helminth+PTB+) compared to helminth negative PTB or CCs, TGF-ß+ Tregs were significantly increased mainly in hookworm coinfection whereas S. mansoni increased TGF-ß+ Tregs in CCs. Treatment of TB and helminths decreased TGF-ß+ Tregs in Helminth+PTB+ at 2 months follow-up. There were no overall differences in the frequency of Tregs in CCs or PTB unless stratification on TB disease severity was performed. At inclusion Helminth+PTB+ had increased frequency of Tregs already at low disease severity, and TGF-ß+ Tregs correlated to intermediate-to-high disease severity. In conclusion, helminth specific increase of TGF-ß+ Tregs in PTB patients was correlated to TB disease severity and was restored following anti-helminth treatment.

Does Schistosoma Mansoni Facilitate Carcinogenesis?

Schistosomiasis is one of the most prominent parasite-induced infectious diseases, causing tremendous medical and socioeconomic problems. Current studies have reported on the spread of endemic regions and the fear of development of resistance against praziquantel, the only effective drug available. Among the Schistosoma species, only S. haematobium is classified as a Group 1 carcinogen (definitely cancerogenic to humans), causing squamous cell carcinoma of the bladder, whereas infection with S. mansoni is included in Group 3 of carcinogenic hazards to humans by the International Agency for Research on Cancer (IARC), indicating insufficient evidence to determine its carcinogenicity. Nevertheless, although S. mansoni has not been discussed as an organic carcinogen, the multiplicity of case reports, together with recent data from animal models and cell culture experiments, suggests that this parasite can predispose patients to or promote hepatic and colorectal cancer. In this review, we discuss the current data, with a focus on new developments regarding the association of S. mansoni infection with human cancer and the recently discovered biomolecular mechanisms by which S. mansoni may predispose patients to cancer development and carcinogenesis.

Genetic architecture of transmission stage production and virulence in schistosome parasites.

Both theory and experimental data from pathogens suggest that the production of transmission stages should be strongly associated with virulence, but the genetic bases of parasite transmission/virulence traits are poorly understood. The blood fluke Schistosoma mansoni shows extensive variation in numbers of cercariae larvae shed and in their virulence to infected snail hosts, consistent with expected trade-offs between parasite transmission and virulence. We crossed schistosomes from two populations that differ 8-fold in cercarial shedding and in their virulence to Biomphalaria glabrata snail hosts, and determined four-week cercarial shedding profiles in F0 parents, F1 parents and 376 F2 progeny from two independent crosses in inbred snails. Sequencing and linkage analysis revealed that cercarial production is polygenic and controlled by five QTLs (i.e. Quantitative Trait Loci). These QTLs act additively, explaining 28.56% of the phenotypic variation. These results demonstrate that the genetic architecture of key traits relevant to schistosome ecology can be dissected using classical linkage mapping approaches.

New Insights Into Biomphalysin Gene Family Diversification in the Vector Snail Biomphalaria glabrata.

Aerolysins initially characterized as virulence factors in bacteria are increasingly found in massive genome and transcriptome sequencing data from metazoans. Horizontal gene transfer has been demonstrated as the main way of aerolysin-related toxins acquisition in metazoans. However, only few studies have focused on their potential biological functions in such organisms. Herein, we present an extensive characterization of a multigene family encoding aerolysins - named biomphalysin - in Biomphalaria glabrata snail, the intermediate host of the trematode Schistosoma mansoni. Our results highlight that duplication and domestication of an acquired bacterial toxin gene in the snail genome result in the acquisition of a novel and diversified toxin family. Twenty-three biomphalysin genes were identified. All are expressed and exhibited a tissue-specific expression pattern. An in silico structural analysis was performed to highlight the central role played by two distinct domains i) a large lobe involved in the lytic function of these snail toxins which constrained their evolution and ii) a small lobe which is structurally variable between biomphalysin toxins and that matched to various functional domains involved in moiety recognition of targets cells. A functional approach suggests that the repertoire of biomphalysins that bind to pathogens, depends on the type of pathogen encountered. These results underline a neo-and sub-functionalization of the biomphalysin toxins, which have the potential to increase the range of effectors in the snail's immune arsenal.

Schistosomiasis Morbidity Hotspots: Roles of the Human Host, the Parasite and Their Interface in the Development of Severe Morbidity.

Schistosomiasis is the second most important human parasitic disease in terms of socioeconomic impact, causing great morbidity and mortality, predominantly across the African continent. For intestinal schistosomiasis, severe morbidity manifests as periportal fibrosis (PPF) in which large tracts of macro-fibrosis of the liver, visible by ultrasound, can occlude the main portal vein leading to portal hypertension (PHT), sequelae such as ascites and collateral vasculature, and ultimately fatalities. For urogenital schistosomiasis, severe morbidity manifests as pathology throughout the urinary system and genitals, and is a definitive cause of squamous cell bladder carcinoma. Preventative chemotherapy (PC) programmes, delivered through mass drug administration (MDA) of praziquantel (PZQ), have been at the forefront of schistosomiasis control programmes in sub-Saharan Africa since their commencement in Uganda in 2003. However, despite many successes, 'biological hotspots' (as distinct from 'operational hotspots') of both persistent high transmission and morbidity remain. In some areas, this failure to gain control of schistosomiasis has devastating consequences, with not only persistently high infection intensities, but both "subtle" and severe morbidity remaining prevalent. These hotspots highlight the requirement to revisit research into severe morbidity and its mechanisms, a topic that has been out of favor during times of PC implementation. Indeed, the focality and spatially-structured epidemiology of schistosomiasis, its transmission persistence and the morbidity induced, has long suggested that gene-environmental-interactions playing out at the host-parasite interface are crucial. Here we review evidence of potential unique parasite factors, host factors, and their gene-environmental interactions in terms of explaining differential morbidity profiles in the human host. We then take the situation of schistosomiasis mansoni within the Albertine region of Uganda as a case study in terms of elucidating the factors behind the severe morbidity observed and the avenues and directions for future research currently underway within a new research and clinical trial programme (FibroScHot).

Systems Biology Analysis of the Radiation-Attenuated Schistosome Vaccine Reveals a Role for Growth Factors in Protection and Hemostasis Inhibition in Parasite Survival.

In spite of several decades of research, an effective vaccine against schistosomiasis remains elusive. The radiation-attenuated (RA) cercarial vaccine is still the best model eliciting high protection levels, although the immune mechanisms have not yet been fully characterized. In order to identify genes and pathways underlying protection we investigated patterns of gene expression in PBMC and skin draining Lymph Nodes (LN) from mice using two exposure comparisons: vaccination with 500 attenuated cercariae versus infection with 500 normal cercariae; one versus three doses. Vaccinated mice were challenged with 120 normal parasites. Integration of PBMC and LN data from the infected group revealed early up-regulation of pathways associated with Th2 skewing and polarization of IgG antibody profiles. Additionally, hemostasis pathways were downregulated in infected mice, correlating with platelet reduction, potentially a mechanism to assist parasite migration through capillary beds. Conversely, up regulation of such mechanisms after vaccination may explain parasite blockade in the lungs. In contrast, a single exposure to attenuated parasites revealed early establishment of a Th1 bias (signaling of IL-1, IFN-γ; and Leishmania infection). Genes encoding chemokines and their receptors were more prominent in vaccinated mice, indicating an enhanced capacity for inflammation, potentially augmenting the inhibition of intravascular migration. Increasing the vaccinations from one to three did not dramatically elevate protection, but there was a clear shift towards antibody-mediated effectors. However, elements of the Th1 bias were still evident. Notable features after three vaccinations were markers of cytotoxicity (including IL-6 and NK cells) together with growth factors and their receptors (FGFR/VEGF/EGF) and the apoptosis pathway. Indeed, there is evidence for the development of anergy after three vaccinations, borne out by the limited responses detected in samples after challenge. We infer that persistence of a Th1 response puts a limit on expression of antibody-mediated mechanisms. This feature may explain the failure of multiple doses to drive protection towards sterile immunity. We suggest that the secretions of lung stage parasites would make a novel cohort of antigens for testing in protection experiments.

Current status of Schistosoma mansoni infection among previously treated rural communities in the Abbey and Didessa Valleys, Western Ethiopia: Implications for sustainable control.

BACKGROUND: Schistosoma constitutes a major public health problem and developmental challenges in the majority of developing and subtropical regions. The World Health Organization has set guidelines for the control and elimination of schistosomiasis. Ethiopia is providing school-based Mass Drug Administration (MDA) at the study areas of the Abbey and Didessa Valleys of western Ethiopian since 2015. Moreover, mass treatment was already done in the same villages 30 years ago. However, the current Schistosoma mansoni infection status among humans and snails in the study areas is not known. Hence, the present study aims to determine the current status. METHODS: A community-based cross-sectional study was conducted in the three communities; Chessega, Agallu Metti and Shimala in Schistosoma mansoni endemic areas of the Abbey and Didessa valleys in Western Ethiopia. Using the list of households obtained from the Kebele administration, a systematic sampling technique was used to select households in each village. RESULTS: Even though the area is under the Ethiopian national Mass Drug Administration campaign, the present study reports prevalence above 50%. Although the majority of the infections were moderate, we found that 13% had heavy infection, above 400 eggs per gram of stool, which is at the same level as before the treatment campaign 30 years ago. The infection was significantly higher among those below 12 years of age, among non-attending school-age children and daily laborers. CONCLUSION: Schistosoma mansoni infection is still a public health problem in the study areas, despite control efforts already 30 years ago and present mass treatment in the last years. We suggest making the mass treatment campaign just early after the rainy season, when the snails are washed away. This should be supplemented with provisions of clean water, sanitation, and hygiene (WASH) and reduction of water contact and possible snail control efforts' to prevent reinfection.

Factors Associated with Schistosoma mansoni Infestation in Northeast Brazil: A Need to Revisit Individual and Community Risk Factors.

In Brazil, schistosomiasis continues to be an important health issue. The aim of this study was to identify factors associated with Schistosoma mansoni infestation. A cross-sectional study was performed to assess factors associated with S. mansoni endemicity in a municipality in Northeast Brazil with a history of reporting schistosomiasis. Participants were divided into four groups: 1) new S. mansoni cases (n = 44), 2) past history of S. mansoni treatment (n = 78), 3) immediate neighbors (n = 158), and 4) nearby controls (n = 35). Multiple comparisons analysis was performed. Subjects had a mean of 6.6 ± 3.9 years of education, and no difference was observed regarding family income (one-way analysis of variance, P = 0.215). A total of 95.9% of the individuals had rudimentary cesspit as sanitary wastewater. The mean body mass index was 28.3 ± 5.1, with 41.0% and 24.1% overweight and obesity, respectively. Of note, 28.9% of adults had hypertension. Hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin were higher in the recent S. mansoni treated group (Wilks' lambda, P < 0.001). Male gender was more prevalent in new S. mansoni cases (likelihood ratio, P < 0.001), close proximity to water collections was a risk for S. mansoni infestation (likelihood ratio, P < 0.001), and a better hematological status was observed in individuals recently treated with praziquantel. This study indicates the need to maintain surveillance for S. mansoni in low-transmission areas and the need to establish community-based interventions to control transmission.

High rate of intestinal parasites among a closed community of Zay populations residing on three islands of Lake Ziway, Ethiopia.

BACKGROUND: Several factors including socio-economic and access to health facility influence burden of intestinal parasites. Epidemiological data from hard to reach areas will help to identify high-risk communities for targeted intervention. We, therefore, assessed the magnitude of intestinal parasites among Zay people residing in three islands of Lake Ziway in Ethiopia. METHODS: This cross-sectional survey was conducted in March 2013 on 444 individuals aged 6 months to 85 years. Stool samples were analyzed using wet mount and formol-ether concentration methods. Data were collected using interviewer-administered questionnaire and analyzed using STATA version 10. RESULTS: Among the study participants, 52% (321/444) were children under 15 years. While 72.8% were positive for at least one intestinal parasite, single, dual and triple infections were found in 42.1%, 23.9% and 6.3%, respectively. Four types of intestinal parasites were detected in two children. The commonest parasites were Entamoeba histolytica/dispar (51.4%), Schistosoma mansoni (17.8%), Giardia lamblia (14.4%), Trichuris trichiura (10.8%), Taenia species (5.6%), Hymenolopis nana (4.5%), Ascaris lumbricoides (4.1%), Entrobius vermicularis (0.9%), Hookworm (0.7%), and Strongyloides stercoralis (0.2%). Remarkable proportion of study participants (51.3%) had no latrine and >85% of the islanders use the lake water for drinking, cleaning or both. About 36% had no information about waterborne and related diseases, while 31% never heard about bilharziasis. Fishing and farming were the main source of income. In the multivariate model, being in the age group > 15 years (AOR = 0.49; 95%CI = 0.28-0.85) and not using lake water for drinking or washing (AOR = 0.52; 95%CI = 0.28-0.99) had protective effect, after adjusting for education, occupation and hand wash after latrine use. CONCLUSION: The observed high rate of intestinal parasites (72.8%) in these hard to reach Islanders of Lake Ziway, warrants targeted and sustainable intervention.

Diminished adherence of Biomphalaria glabrata embryonic cell line to sporocysts of Schistosoma mansoni following programmed knockout of the allograft inflammatory factor.

BACKGROUND: Larval development in an intermediate host gastropod snail of the genus Biomphalaria is an obligatory component of the life-cycle of Schistosoma mansoni. Understanding of the mechanism(s) of host defense may hasten the development of tools that block transmission of schistosomiasis. The allograft inflammatory factor 1, AIF, which is evolutionarily conserved and expressed in phagocytes, is a marker of macrophage activation in both mammals and invertebrates. AIF enhances cell proliferation and migration. The embryonic cell line, termed Bge, from Biomphalaria glabrata is a versatile resource for investigation of the snail-schistosome relationship since Bge exhibits a hemocyte-like phenotype. Hemocytes perform central roles in innate and cellular immunity in gastropods and in some cases can kill the parasite. However, the Bge cells do not kill the parasite in vitro. METHODS: Bge cells were transfected by electroporation with plasmid pCas-BgAIFx4, encoding the Cas9 nuclease and a guide RNA specific for exon 4 of the B. glabrata AIF (BgAIF) gene. Transcript levels for Cas9 and for BgAIF were monitored by reverse-transcription-PCR and, in parallel, adhesion of gene-edited Bge cells during co-culture with of schistosome sporocysts was assessed. RESULTS: Gene knockout manipulation induced gene-disrupting indels, frequently 1-2 bp insertions and/or 8-30 bp deletions, at the programmed target site; a range from 9 to 17% of the copies of the BgAIF gene in the Bge population of cells were mutated. Transcript levels for BgAIF were reduced by up to 73% (49.5 ± 20.2% SD, P ≤ 0.05, n = 12). Adherence by BgAIF gene-edited (ΔBgAIF) Bge to sporocysts diminished in comparison to wild type cells, although cell morphology did not change. Specifically, as scored by a semi-quantitative cell adherence index (CAI), fewer ΔBgAIF than control wild type cells adhered to sporocysts; control CAI, 2.66 ± 0.10, ΔBgAIF, 2.30 ± 0.22 (P ≤ 0.01). CONCLUSIONS: The findings supported the hypothesis that BgAIF plays a role in the adherence of B. glabrata hemocytes to sporocysts during schistosome infection in vitro. This demonstration of the activity of programmed gene editing will enable functional genomics approaches using CRISPR/Cas9 to investigate additional components of the snail-schistosome host-parasite relationship.

Schistosoma mansoni infection affects the proteome and lipidome of circulating extracellular vesicles in the host.

Eggs, schistosomula and adult Schistosoma worms are known to release extracellular vesicles (EV) during in vitro incubations and these EVs are postulated to affect the host responses. So far only those EVs released during in vitro incubations of schistosomes have been studied and it is unknown whether in blood of infected hosts the schistosomal EVs can be detected amidst all the circulating EVs of the host itself. In this study we analyzed the protein as well as the phospholipid composition of EVs circulating in blood plasma of S. mansoni infected hamsters and compared those with the EVs circulating in blood of non-infected hamsters. Although neither proteins nor lipids specific for schistosomes could be detected in the circulating EVs of the infected hamsters, the infection with schistosomes had a marked effect on the circulating EVs of the host, as the protein as well as the lipid composition of EVs circulating in infected hamsters were different from the EVs of uninfected hamsters. The observed changes in the EV lipid and protein content suggest that more EVs are released by the diseased liver, the affected erythrocytes and activated immune cells.

Therapeutic efficacy of a newly synthesized benzimidazole compound BTP-OH against murine schistosomiasis mansoni.

Because of the increasingly emerging praziquantel resistance, there is a crucial need to develop new anti-schistosomal agents. This work was conducted to assess the therapeutic efficacy of a new benzimidazole compound (BTP-OH) in mice experimentally infected with Schistosoma mansoni. A total of 40 Swiss albino female mice were divided into an infected untreated group and three infected treated groups (using praziquantel and BTP-OH). The compound activity was evaluated through parasitological, histopathological and scanning electron microscopy studies. Praziquantel and BTP-OH at both doses significantly reduced male (75%, 42.67% and 61.08%, respectively), female (71.45%, 48.94% and 68.13%, respectively) and total worm burden (75.21%, 42.42% and 62.28%, respectively), as well as tissue egg load in the liver (71.22%, 42.12% and 66.04%, respectively). In oogram, praziquantel significantly increased the percentage of dead eggs (65.89%), while BTP-OH significantly reduced the percentage of immature eggs (30.43% and 19.64%). BTP-OH significantly diminished granuloma count (33.87% and 44.77%) and diameter (39.23% and 49.40%), and caused ultrastructural changes in the tegument of adult schistosomes. This study provides evidence for the schistosomicidal efficacy of BTP-OH. However, future studies are needed to elucidate the full mechanisms of action and effects of BTP-OH on other human schistosomes.

Genetic diversity of Biomphalaria pfeifferi, the intermediate host of Schistosoma mansoni in Shamva district, Zimbabwe: role on intestinal schistosomiasis transmission.

The fresh water snail Biomphalaria pfeifferi is the intermediate host for Schistosoma mansoni, which causes human intestinal schistosomiasis in Zimbabwe. Despite the medical importance of this intermediate host, there are no current data on its molecular characterization in Zimbabwe. In 2016, human water contact sites were identified in four communities in Madziwa area, Shamva district, Zimbabwe. The survey sites were recorded and mapped using a global positioning system. A 655 bp region of the mitochondrial cytochrome oxidase subunit I gene was amplified in 70 B. pfeifferi snails. The sequence data were analysed to determine the relationships between the individual snails, their inter, intra population diversity and structure. Overall, four unique cox1 haplotypes, with a haplotype diversity of 0.608, were identified in the snails. One haplotype spanned across most of the sites. There was no clear geographical clustering of haplotypes. The mean diversity among the haplotypes was very low (0.009), while the net divergence among the collection sites ranged from 0.000 to 0.026. The diversity within and between the sites was 0.017 and 0.012 respectively. This data advances our knowledge of the understanding of the population structure of B. pfeifferi in Madziwa area, Zimbabwe, with the high occurrence of one haplotype indicating the possibility of a recent bottleneck followed by population expansion. The population genetic structure of B. pfeifferi snails described here has provided an opportunity to investigate the contribution of snail genetics to variation in disease burden; and development of control strategies that exploit genetic differences in susceptibility to parasites.

SCORE Studies on the Impact of Drug Treatment on Morbidity due to Schistosoma mansoni and Schistosoma haematobium Infection.

The Schistosomiasis Consortium for Operational Research (SCORE) was funded in 2008 to improve the evidence base for control and elimination of schistosomiasis-better understanding of the systemic morbidities experienced by children in schistosomiasis-endemic areas and the response of these morbidities to treatment, being essential for updating WHO guidelines for mass drug administration (MDA) in endemic areas. This article summarizes the SCORE studies that aimed to gauge the impact of MDA-based treatment on schistosomiasis-related morbidities. Morbidity cohort studies were embedded in the SCORE's larger field studies of gaining control of schistosomiasis in Kenya and Tanzania. Following MDA, cohort children had less undernutrition, less portal vein dilation, and increased quality of life in Year 5 compared with baseline. We also conducted a pilot study of the Behavioral Assessment System for Children (BASC-2) in conjunction with the Kenya gaining control study, which demonstrated beneficial effects of treatment on classroom behavior. In addition, the SCORE's Rapid Answers Project performed systematic reviews of previously available data, providing two meta-analyses related to morbidity. The first documented children's infection-related deficits in school attendance and achievement and in formal tests of learning and memory. The second showed that greater reductions in egg output following drug treatment correlates significantly with reduced odds of most morbidities. Overall, these SCORE morbidity studies provided convincing evidence to support the use of MDA to improve the health of school-aged children in endemic areas. However, study findings also support the need to use enhanced metrics to fully assess and better control schistosomiasis-associated morbidity.