Spatio-temporal variability in transmission risk of human schistosomes and animal trematodes in a seasonally desiccating East African landscape.

Different populations of hosts and parasites experience distinct seasonality in environmental factors, depending on local-scale biotic and abiotic factors. This can lead to highly heterogeneous disease outcomes across host ranges. Variable seasonality characterizes urogenital schistosomiasis, a neglected tropical disease caused by parasitic trematodes (Schistosoma haematobium). Their intermediate hosts are aquatic Bulinus snails that are highly adapted to extreme rainfall seasonality, undergoing prolonged dormancy yearly. While Bulinus snails have a remarkable capacity for rebounding following dormancy, we investigated the extent to which parasite survival within snails is diminished. We conducted an investigation of seasonal snail schistosome dynamics in 109 ponds of variable ephemerality in Tanzania from August 2021 to July 2022. First, we found that ponds have two synchronized peaks of schistosome infection prevalence and observed cercariae, though of lower magnitude in the fully desiccating than non-desiccating ponds. Second, we evaluated total yearly schistosome prevalence across an ephemerality gradient, finding ponds with intermediate ephemerality to have the highest infection rates. We also investigated dynamics of non-schistosome trematodes, which lacked synonymity with schistosome patterns. We found peak schistosome transmission risk at intermediate pond ephemerality, thus the impacts of anticipated increases in landscape desiccation could result in increases or decreases in transmission risk with global change.

Genetic profiles of Schistosoma haematobium parasites from Malian transmission hotspot areas.

BACKGROUND: Although schistosomiasis is a public health issue in Mali, little is known about the parasite genetic profile. The purpose of this study was to analyze the genetic profile of the schistosomes of Schistosoma haematobium group in school-aged children in various sites in Mali. METHODS: Urine samples were collected from 7 to 21 November 2021 and subjected to a filtration method for the presence S. haematobium eggs. The study took place in two schistosomiasis endemic villages (Fangouné Bamanan and Diakalèl), qualified as hotspots according to the World Health Organization (WHO) definition. Molecular genotyping on both Cox1 and ITS2/18S was used for eggs' taxonomic assignation. RESULTS: A total of 970 miracidia were individually collected from 63 school-aged children and stored on Whatman FTA cards for molecular analysis. After genotyping 42.0% (353/840) and 58.0% (487/840) of miracidia revealed Schistosoma bovis and S. haematobium Cox1 profiles, respectively; 95.7 (885/925) and 4.3% (40/925) revealed S. haematobium and S. haematobium/S. curassoni profiles for ITS/18S genes, respectively. There was a significant difference in the Cox1 and ITS2/18S profile distribution according to the village (P < 0.0001). Overall, 45.6% (360/789) were hybrids, of which 72.0% (322/447) were from Diakalèl. Three hybrids' profiles (Sb/Sc_ShxSc with 2.3%; Sb/Sc_ShxSh with 40.5%; Sh_ShxSc with 2.8%) and one pure profile (Sh_ShxSh with 54.4%) were identified. CONCLUSION: Our findings show, for the first time to our knowledge, high prevalence of hybrid schistosomes in Mali. More studies are needed on population genetics of schistosomes at the human and animal interface to evaluate the parasite's gene flow and its consequences on epidemiology of the disease as well as the transmission to humans.

Identification of Bulinus forskalii as a potential intermediate host of Schistosoma hæmatobium in Senegal.

Understanding the transmission of Schistosoma hæmatobium in the Senegal River Delta requires knowledge of the snails serving as intermediate hosts. Accurate identification of both the snails and the infecting Schistosoma species is therefore essential. Cercarial emission tests and multi-locus (COX1 and ITS) genetic analysis were performed on Bulinus forskalii snails to confirm their susceptibility to S. hæmatobium infection. A total of 55 Bulinus forskalii, adequately identified by MALDI-TOF mass spectrometry, were assessed. Cercarial shedding and RT-PCR assays detected 13 (23.6%) and 17 (31.0%), respectively, Bulinus forskalii snails parasitized by S. hæmatobium complex fluke. Nucleotide sequence analysis identified S. hæmatobium in 6 (11.0%) using COX1 and 3 (5.5%) using ITS2, and S. bovis in 3 (5.5%) using COX1 and 3 (5.5%) using ITS2. This result is the first report of infection of Bulinus forskalii by S. hæmatobium complex parasites in Senegal using innovative and more accurate identification methods to discriminate this snail and characterize its infection by S. hæmatobium.

A duplex tetra-primer ARMS-PCR assay to discriminate three species of the Schistosoma haematobium group: Schistosoma curassoni, S. bovis, S. haematobium and their hybrids.

BACKGROUND: The use of applications involving single nucleotide polymorphisms (SNPs) has greatly increased since the beginning of the 2000s, with the number of associated techniques expanding rapidly in the field of molecular research. Tetra-primer amplification refractory mutation system-PCR (T-ARMS-PCR) is one such technique involving SNP genotyping. It has the advantage of amplifying multiple alleles in a single reaction with the inclusion of an internal molecular control. We report here the development of a rapid, reliable and cost-effective duplex T-ARMS-PCR assay to distinguish between three Schistosoma species, namely Schistosoma haematobium (human parasite), Schistosoma bovis and Schistosoma curassoni (animal parasites), and their hybrids. This technique will facilitate studies of population genetics and the evolution of introgression events. METHODS: During the development of the technique we focused on one of the five inter-species internal transcribed spacer (ITS) SNPs and one of the inter-species 18S SNPs which, when combined, discriminate between all three Schistosoma species and their hybrid forms. We designed T-ARMS-PCR primers to amplify amplicons of specific lengths for each species, which in turn can then be visualized on an electrophoresis gel. This was further tested using laboratory and field-collected adult worms and field-collected larval stages (miracidia) from Spain, Egypt, Mali, Senegal and Ivory Coast. The combined duplex T-ARMS-PCR and ITS + 18S primer set was then used to differentiate the three species in a single reaction. RESULTS: The T-ARMS-PCR assay was able to detect DNA from both species being analysed at the maximum and minimum levels in the DNA ratios (95/5) tested. The duplex T-ARMS-PCR assay was also able to detect all hybrids tested and was validated by sequencing the ITS and the 18S amplicons of 148 of the field samples included in the study. CONCLUSIONS: The duplex tetra-primer ARMS-PCR assay described here can be applied to differentiate between Schistosoma species and their hybrid forms that infect humans and animals, thereby providing a method to investigate the epidemiology of these species in endemic areas. The addition of several markers in a single reaction saves considerable time and is of long-standing interest for investigating genetic populations.

Molecular dynamics-derived pharmacophores of Schistosoma glutathione transferase in complex with bromosulfophthalein: Screening and analysis of potential inhibitors.

Schistosoma glutathione transferases (GSTs) have been identified as attractive drug targets for the design of novel antischistosomals. Here, we used in silico methods to validate the discriminative inhibitory properties of bromosulfophthalein (BSP) against the 26-kDa GST from S. japonicum (Sj26GST), and the 28-kDa GST from S. haematobium (Sh28GST), versus human GST (hGST) isoforms alpha (hGSTA), mu (hGSTM) and pi (hGSTP). The use of BSP as an archetypal selective inhibitor was harnessed to produce molecular dynamics-derived pharmacophores of the two targets. Pharmacophore-based screening using a large dataset of experimental and approved drug compounds was performed to produce a shortlist of candidates. The top candidate for each target was prioritised via molecular docking, yielding guanosine-3'-monophosphate-5'-diphosphate (G3D) for Sj26GST, and quercetin-3'-O-phosphate (Q3P) for Sh28GST. Comparative molecular dynamics studies of both candidates compared to BSP showed similar characteristics of binding stability and strength, suggesting their potential to emulate the inhibitory effects of BSP.

MALDI-TOF: A new tool for the identification of Schistosoma cercariae and detection of hybrids.

Schistosomiasis is a neglected water-born parasitic disease caused by Schistosoma affecting more than 200 million people. Introgressive hybridization is common among these parasites and raises issues concerning their zoonotic transmission. Morphological identification of Schistosoma cercariae is difficult and does not permit hybrids detection. Our objective was to assess the performance of MALDI-TOF (Matrix Assistated Laser Desorption-Ionization-Time Of Flight) mass spectrometry for the specific identification of cercariae in human and non-human Schistosoma and for the detection of hybridization between S. bovis and S. haematobium. Spectra were collected from laboratory reared molluscs infested with strains of S. haematobium, S. mansoni, S. bovis, S. rodhaini and S. bovis x S. haematobium natural (Corsican hybrid) and artificial hybrids. Cluster analysis showed a clear separation between S. haematobium, S. bovis, S. mansoni and S. rodhaini. Corsican hybrids are classified with those of the parental strain of S. haematobium whereas other hybrids formed a distinct cluster. In blind test analysis the developed MALDI-TOF spectral database permits identification of Schistosoma cercariae with high accuracy (94%) and good specificity (S. bovis: 99.59%, S. haematobium 99.56%, S. mansoni and S. rodhaini: 100%). Most misidentifications were between S. haematobium and the Corsican hybrids. The use of machine learning permits to improve the discrimination between these last two taxa, with accuracy, F1 score and Sensitivity/Specificity > 97%. In multivariate analysis the factors associated with obtaining a valid identification score (> 1.7) were absence of ethanol preservation (p < 0.001) and a number of 2-3 cercariae deposited per well (p < 0.001). Also, spectra acquired from S. mansoni cercariae are more likely to obtain a valid identification score than those acquired from S. haematobium (p<0.001). MALDI-TOF is a reliable technique for high-throughput identification of Schistosoma cercariae of medical and veterinary importance and could be useful for field survey in endemic areas.

Addressing the oxamniquine in vitro-in vivo paradox to facilitate a new generation of anti-schistosome treatments.

The antischistosomal drug oxamniquine, OXA, requires activation by a sulfotransferase within the parasitic worm to enable killing. Examination of the pharmacokinetic/pharmacodynamic (PK/PD) relationship for OXA identified an in vitro-in vivo paradox with the maximal clinical plasma concentrations five-to ten-times lower than the efficacious concentration for in vitro schistosomal killing. The parasite resides in the vasculature between the intestine and the liver, and modeling the PK data to determine portal concentrations fits with in vitro studies and explains the required human dose. In silico models were used to predict murine dosing to recapitulate human conditions for OXA portal concentration and time course. Follow-up PK studies verified in mice that a 50-100 mg/kg oral gavage dose of OXA formulated in acetate buffer recapitulates the 20-40 mg/kg dose common in patients. OXA was rapidly cleared through a combination of metabolism and excretion into bile. OXA absorbance and tissue distribution were similar in wild-type and P-gp efflux transporter knockout mice. The incorporation of in vitro efficacy data and portal concentration was demonstrated for an improved OXA-inspired analog that has been shown to kill S. mansoni, S. haematobium, and S. japonicum, whereas OXA is only effective against S. mansoni. Second-generation OXA analogs should optimize both in vitro killing and physiochemical properties to achieve high portal concentration via rapid oral absorption, facilitated by favorable solubility, permeability, and minimal intestinal metabolism.

Frequency distribution of cytokine and associated transcription factor single nucleotide polymorphisms in Zimbabweans: Impact on schistosome infection and cytokine levels.

Cytokines mediate T-helper (TH) responses that are crucial for determining the course of infection and disease. The expression of cytokines is regulated by transcription factors (TFs). Here we present the frequencies of single nucleotide polymorphisms (SNPs) in cytokine and TF genes in a Zimbabwean population, and further relate SNPs to susceptibility to schistosomiasis and cytokine levels. Individuals (N = 850) were genotyped for SNPs across the cytokines IL4, IL10, IL13, IL33, and IFNG, and their TFs STAT4, STAT5A/B, STAT6, GATA3, FOXP3, and TBX21 to determine allele frequencies. Circulatory levels of systemic and parasite-specific IL-4, IL-5, IL-10, IL-13, and IFNγ were quantified via enzyme-linked immunosorbent assay. Schistosoma haematobium infection was determined by enumerating parasite eggs excreted in urine by microscopy. SNP allele frequencies were related to infection status by case-control analysis and logistic regression, and egg burdens and systemic and parasite-specific cytokine levels by analysis of variance and linear regression. Novel findings were i) IL4 rs2070874*T's association with protection from schistosomiasis, as carriage of ≥1 allele gave an odds ratio of infection of 0.597 (95% CIs, 0.421-0.848, p = 0.0021) and IFNG rs2069727*G's association with susceptibility to schistosomiasis as carriage of ≥1 allele gave an odds ratio of infection of 1.692 (1.229-2.33, p = 0.0013). Neither IL4 rs2070874*T nor IFNG rs2069727*G were significantly associated with cytokine levels. This study found TH2-upregulating SNPs were more frequent among the Zimbabwean sample compared to African and European populations, highlighting the value of immunogenetic studies of African populations in the context of infectious diseases and other conditions, including allergic and atopic disease. In addition, the identification of novel infection-associated alleles in both TH1- and TH2-associated genes highlights the role of both in regulating and controlling responses to Schistosoma.

Assessing the efficacy of an integrated intervention to create demand for fishermen's schistosomiasis and HIV services (FISH) in Mangochi, Malawi: Study protocol for a cluster randomized control trial.

BACKGROUND: Both HIV and schistosomiasis are major public health problems worldwide with 1.8 million new HIV infections, and up to 110 million untreated schistosomiasis cases globally. Although a causal link has not been established, there are strong suggestions that having schistosomiasis increases onward transmission of HIV from co-infected men to women. With both HIV and schistosomiasis treatment readily available in Malawi, there is a need to investigate the feasibility, acceptability and health impacts of joint management of these two hazards, with special focus on health education and demand-creation for fishermen. The aim of this project is to identify optimal models of delivering integrated HIV and schistosomiasis services for fishermen, particularly investigating the effect of using social networks, HIV self-test kits and beach clinic services in Mangochi, Malawi. METHODS: We have mapped 45 boat teams or landing sites for a 3-arm cluster randomized trial using "boat team" as the unit of randomization. The three arms are: 1) Standard of care (SOC) with leaflets explaining the importance of receiving presumptive treatment for schistosomiasis (praziquantel) and HIV services for fishermen, and two intervention arms of 2) SOC + a peer explaining the leaflet to his fellow fishermen in a boat team; and 3) arm 2 with HIV self-test kits delivered to the boat team fishermen by the peer. The primary outcomes measured at 9 months of trial delivery will compare differences between arms in the proportions of boat-team fishermen: 1) who self-report starting antiretroviral therapy or undergoing voluntary medical male circumcision; and 2) who have ≥1 S. haematobium egg seen on light microscopy of the filtrate from 10mls urine ("egg-positive"). DISCUSSION: This is the first evaluation of an integrated HIV and schistosomiasis services intervention for fishermen, particularly investigating the effect of using social networks, HIVST kits and beach clinic services. The findings will support future efforts to integrate HIVST with other health services for fishermen in similar settings if found to be efficacious. TRIAL REGISTRATION: This trial is registered in the ISRCTN registry: ISRCTN14354324; date of registration: 05 October 2020. https://www.isrctn.com/ISRCTN14354324?q=ISRCTN14354324&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search. Linked to protocol version number 1.4 of 11 January 2021.

Association of schistosome infection with adiposity in Tanzania.

Background: Observational studies in humans have reported a link between schistosome infection and lower adiposity, but this may be explained by socioeconomic and demographic factors, intensity of infection, or common co-infections such as HIV. Methods: This was a cross-sectional study that investigated the relationship between schistosome infection and adiposity in a large, well-described cohort of Tanzanian adults living with and without HIV. Cross-sectional data were collected among adults living in Mwanza, Tanzania who were enrolled in the Chronic Infections, Co-morbidities and Diabetes in Africa (CICADA) cohort study. Schistosome circulating anodic antigen, secreted by both Schistosoma mansoni and haematobium which are endemic to Tanzania, was quantified from stored samples. Schistosome infection diagnosed by serum circulating anodic antigen levels. The primary outcome was fat mass measured by bioimpedance analysis. Secondary outcomes included fat-free mass, waist circumference, mid-upper arm circumference, and body mass index. Results: The study enrolled 1,947 adults, of whom 1,923 (98.8%) had serum available for schistosome testing. Of these, 873 (45.4%) had a serum circulating anodic antigen ≥30 pg/mL, indicating schistosome infection. Compared to uninfected individuals, those with schistosome infections had -1.1 kg [95% CI -1.9 to -0.3] lower fat mass after adjusting for age, sex, physical activity, tobacco use, education level, and socioeconomic status. Infected participants also had lower waist circumference, mid-upper arm circumference, and body mass index. Fat-free mass was not different between the two groups. Neither being HIV-infected, nor receiving antiretroviral therapy, modified associations between schistosome infection and adiposity. These associations were also not affected by Schistosoma worm burden. Conclusions: Schistosome infection was associated with lower fat mass and less central adiposity without a difference in muscle mass, irrespective of confounders, HIV status, or the intensity of schistosome infection. Future studies should adjust for socioeconomic and demographic factors that are associated with schistosome infection and adiposity. Identifying mechanistic pathways by which schistosome infection reduces adiposity while preserving muscle mass could yield new strategies for obesity control and cardiovascular disease prevention.

Drug Discovery and Target Identification against Schistosomiasis: A Reality Check on Progress and Future Prospects.

Schistosomiasis ranks among the most important infectious diseases, with over 200 million people currently being infected and > 280,000 deaths reported annually. Chemotherapeutic treatment has relied on one drug, praziquantel, for four decades, while other drugs, such as oxamniquine and metrifonate, are no longer preferred for clinical use due to their narrow spectrum of activity - these are only active against S. mansoni and S. haematobium, respectively. Despite being cheap, safe, and effective against all schistosome species, praziquantel is ineffective against immature worms, which may lead to reinfections and treatment failure in endemic areas; a situation that necessitates repeated administration besides other limitations. Therefore, novel drugs are urgently needed to overcome this situation. In this paper, an up to date review of drug targets identified and validated against schistosomiasis while also encompassing promising clinical and preclinical candidate drugs is presented. While there are considerable efforts aimed at identifying and validating drug targets, the pipeline for new antischistosomals is dry. Moreover, the majority of compounds evaluated preclinically are not really advanced because most of them were evaluated in very small preclinical species such as mice alone. Overall, it appears that although a lot of research is going on at discovery phases, unfortunately, it does not translate to advanced preclinical and clinical evaluation.

Morphological and genomic characterisation of the Schistosoma hybrid infecting humans in Europe reveals admixture between Schistosoma haematobium and Schistosoma bovis.

Schistosomes cause schistosomiasis, the world's second most important parasitic disease after malaria in terms of public health and social-economic impacts. A peculiar feature of these dioecious parasites is their ability to produce viable and fertile hybrid offspring. Originally only present in the tropics, schistosomiasis is now also endemic in southern Europe. Based on the analysis of two genetic markers the European schistosomes had previously been identified as hybrids between the livestock- and the human-infective species Schistosoma bovis and Schistosoma haematobium, respectively. Here, using PacBio long-read sequencing technology we performed genome assembly improvement and annotation of S. bovis, one of the parental species for which no satisfactory genome assembly was available. We then describe the whole genome introgression levels of the hybrid schistosomes, their morphometric parameters (eggs and adult worms) and their compatibility with two European snail strains used as vectors (Bulinus truncatus and Planorbarius metidjensis). Schistosome-snail compatibility is a key parameter for the parasites life cycle progression, and thus the capability of the parasite to establish in a given area. Our results show that this Schistosoma hybrid is strongly introgressed genetically, composed of 77% S. haematobium and 23% S. bovis origin. This genomic admixture suggests an ancient hybridization event and subsequent backcrosses with the human-specific species, S. haematobium, before its introduction in Corsica. We also show that egg morphology (commonly used as a species diagnostic) does not allow for accurate hybrid identification while genetic tests do.

Species diversity and distribution of schistosome intermediate snail hosts in The Gambia.

There is a need for recent information on intermediate snail hosts of schistosomes in The Gambia; the previous studies were conducted over three decades ago. This study assessed the incidence, species diversity, distribution and infection status of schistosome intermediate snail hosts in the country. Malacological surveys were conducted in all 5 regions of The Gambia: Central River Region (CRR), Upper River Region (URR), Western Region (WR), Lower River Region (LRR) and North Bank Region (NBR). Sampling of snails was undertaken at 114 sites that included permanent water bodies such as streams (bolongs), rice fields, irrigation canals and swamps; and temporal (seasonal) laterite pools. Ecological and physicochemical factors of sites were recorded. Snails were identified morphologically and screened for schistosome infections using molecular techniques. Freshwater snails were found at more than 50% (60/114) of sites sampled. While three species of Bulinus were collected, no Biomphalaria snails were found in any of the sites sampled. Of the total 2877 Bulinus snails collected, 75.9% were identified as Bulinus senegalensis, 20.9% as Bulinus forskalii and 3.2% as Bulinus truncatus. Seasonal pools produced the largest number of snails, and CRR was the region with the largest number of snails. Bulinus senegalensis was found more in seasonal pools as opposed to permanent sites, where B. forskalii and B. truncatus were observed to thrive. Bulinus snails were more common in seasonal sites where aquatic vegetation was present. In permanent sites, the abundance of snails increased with increase in water temperature and decrease in water pH. Bulinus senegalensis was found infected with both S. haematobium and S. bovis, while B. forskalii and B. truncatus had only S. bovis infection. While the human parasite S. haematobium was restricted to just four sites, the livestock parasite S. bovis had a much more widespread geographical distribution across both CRR and URR. This new information on the distribution of intermediate snail hosts of schistosomes in The Gambia will be vital for the national schistosomiasis control initiative.

Lactate dehydrogenase and malate dehydrogenase: Potential antiparasitic targets for drug development studies.

Parasitic diseases remain a major public health concern for humans, claiming millions of lives annually. Although different treatments are required for these diseases, drug usage is limited due to the development of resistance and toxicity, which necessitate alternative therapies. It has been shown in the literature that parasitic lactate dehydrogenases (LDH) and malate dehydrogenases (MDH) have unique pharmacological selective and specificity properties compared to other isoforms, thus highlighting them as viable therapeutic targets involved in aerobic and anaerobic glycolytic pathways. LDH and MDH are important therapeutic targets for invasive parasites because they play a critical role in the progression and development of parasitic diseases. Any strategy to impede these enzymes would be fatal to the parasites, paving the way to develop and discover novel antiparasitic agents. This review aims to highlight the importance of parasitic LDH and MDH as therapeutic drug targets in selected obligate apicoplast parasites. To the best of our knowledge, this review presents the first comprehensive review of LDH and MDH as potential antiparasitic targets for drug development studies.

Identification of Snails and Schistosoma of Medical Importance via Convolutional Neural Networks: A Proof-of-Concept Application for Human Schistosomiasis.

In recent decades, computer vision has proven remarkably effective in addressing diverse issues in public health, from determining the diagnosis, prognosis, and treatment of diseases in humans to predicting infectious disease outbreaks. Here, we investigate whether convolutional neural networks (CNNs) can also demonstrate effectiveness in classifying the environmental stages of parasites of public health importance and their invertebrate hosts. We used schistosomiasis as a reference model. Schistosomiasis is a debilitating parasitic disease transmitted to humans via snail intermediate hosts. The parasite affects more than 200 million people in tropical and subtropical regions. We trained our CNN, a feed-forward neural network, on a limited dataset of 5,500 images of snails and 5,100 images of cercariae obtained from schistosomiasis transmission sites in the Senegal River Basin, a region in western Africa that is hyper-endemic for the disease. The image set included both images of two snail genera that are relevant to schistosomiasis transmission - that is, Bulinus spp. and Biomphalaria pfeifferi - as well as snail images that are non-component hosts for human schistosomiasis. Cercariae shed from Bi. pfeifferi and Bulinus spp. snails were classified into 11 categories, of which only two, S. haematobium and S. mansoni, are major etiological agents of human schistosomiasis. The algorithms, trained on 80% of the snail and parasite dataset, achieved 99% and 91% accuracy for snail and parasite classification, respectively, when used on the hold-out validation dataset - a performance comparable to that of experienced parasitologists. The promising results of this proof-of-concept study suggests that this CNN model, and potentially similar replicable models, have the potential to support the classification of snails and parasite of medical importance. In remote field settings where machine learning algorithms can be deployed on cost-effective and widely used mobile devices, such as smartphones, these models can be a valuable complement to laboratory identification by trained technicians. Future efforts must be dedicated to increasing dataset sizes for model training and validation, as well as testing these algorithms in diverse transmission settings and geographies.

Population Dynamics of Intermediate-Host Snails in the White Nile River, Sudan: A Year-Round Observational Descriptive Study.

We aimed to explore the population dynamics of snail in 3 sites of the White Nile in Sudan. More specifically, we aimed to investigate the annual patterns of snail populations that act as intermediate hosts of schistosomes and monthly snail infection rates and ecological characteristics presumably related to snail populations. We collected snails for 1 year monthly at 3 different shore sites in the vicinity of El Shajara along the White Nile river in Khartoum State, Sudan. In addition, we measured air and water temperatures, water turbidities, vegetation coverages, and water depths and current speeds. Most of the collected snails were Biomphalaria pfeifferi and Bulinus truncatus. The population densities of snails and their infection rates varied across survey sites. The collected snails liberated S. mansoni and S. haematobium cercariae as well as Amphistome and Echinostome cercariae. Infected snails were found during March-June. The ecological characteristics found to be associated with the absence of snails population were: high turbidity, deep water, low vegetation coverage (near absence of vegetation), high water temperature, and high current speed. To our knowledge, this is the first longitudinal study of the snail population and ecological characteristics in the main basin of the White Nile river.

Orbital migration of schistosome eggs: a case report.

BACKGROUND: Ocular damage, including damage to the conjunctiva, lacrimal gland, eyelids, and orbit, caused by Schistosoma haematobium is sporadic. We report a clinical case of orbital migration of schistosome eggs. CASE PRESENTATION: A 14-year-old boy of Malian nationality presented with a painless swelling of the upper right eyelid, which had been gradually increasing for approximately 3 months. Visual acuity was logMAR 0.10 and 0.00 in the right and left eye, respectively. External examination revealed a right palpebral mass, pushing the globe slightly downward and inward. Computed tomography revealed a mass of the right lacrimal gland. Total excision of the mass was performed by transpalpebral orbitotomy. Pathological examination revealed an inflammatory granulomatous infiltrate of the lacrimal gland consisting of lymphocytes, eosinophils, giant cells, epithelioid cell, histiocytes and calcified Schistosoma eggs with terminal spine. Urine examination revealed eggs of S. haematobium. Praziquantel 40 mg/kg was administered to the patient. The hematuria stopped after 1 week. After 3 years of follow-up, no recurrence was noted. CONCLUSIONS: The bilharzian granuloma of the lacrimal gland is an ectopic site of the parasite. In this case, the granuloma was cured by surgical excision followed by a course of Praziquantel.

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

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

The Genetics of Human Schistosomiasis Infection Intensity and Liver Disease: A Review.

Schistosomiasis remains the fourth most prevalent parasitic disease affecting over 200 million people worldwide. Control efforts have focussed on the disruption of the life cycle targeting the parasite, vector and human host. Parasite burdens are highly skewed, and the majority of eggs are shed into the environment by a minority of the infected population. Most morbidity results from hepatic fibrosis leading to portal hypertension and is not well-correlated with worm burden. Genetics as well as environmental factors may play a role in these skewed distributions and understanding the genetic risk factors for intensity of infection and morbidity may help improve control measures. In this review, we focus on how genetic factors may influence parasite load, hepatic fibrosis and portal hypertension. We found 28 studies on the genetics of human infection and 20 studies on the genetics of pathology in humans. S. mansoni and S. haematobium infection intensity have been showed to be controlled by a major quantitative trait locus SM1, on chromosome 5q31-q33 containing several genes involved in the Th2 immune response, and three other loci of smaller effect on chromosomes 1, 6, and 7. The most common pathology associated with schistosomiasis is hepatic and portal vein fibroses and the SM2 quantitative trait locus on chromosome six has been linked to intensity of fibrosis. Although there has been an emphasis on Th2 cytokines in candidate gene studies, we found that four of the five QTL regions contain Th17 pathway genes that have been included in schistosomiasis studies: IL17B and IL12B in SM1, IL17A and IL17F in 6p21-q2, IL6R in 1p21-q23 and IL22RA2 in SM2. The Th17 pathway is known to be involved in response to schistosome infection and hepatic fibrosis but variants in this pathway have not been tested for any effect on the regulation of these phenotypes. These should be priorities for future studies.