Impact of Schistosoma sp., Infection on Biological, Feeding, Physiological, Histological, and Genotoxicological Aspects of Biomphalaria alexandrina and Bulinus truncatus Snails.

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

Prevalence and risk factors of schistosomiasis and hookworm infection in seasonal transmission settings in northern Côte d'Ivoire: A cross-sectional study.

BACKGROUND: Schistosomiasis and hookworm infection remain public health problems in large parts of sub-Saharan Africa. The epidemiology of schistosomiasis and hookworm was studied in seasonal transmission settings in the northern part of Côte d'Ivoire. METHODOLOGY: In August 2018, a cross-sectional study was conducted. Urine and stool samples were collected from 742 individuals aged 6-96 years in 16 localities from four departments in northern Côte d'Ivoire. Urine samples were examined by a filtration method for quantification of Schistosoma haematobium eggs. Stool samples were subjected to duplicate Kato-Katz thick smears and eggs of Schistosoma mansoni and soil-transmitted helminths (STHs) were counted. Additionally, a questionnaire was administered to determine demographic characteristics and to identify risk factors of schistosomiasis and STHs. Malacologic surveys were carried out at water points that are contacted by humans and animals. PRINCIPAL FINDINGS: The prevalence of schistosomiasis was very low. Only two cases of S. mansoni were found (0.3%, 95% confidence interval [CI]: 0.1-1.0%). The distribution of S. haematobium was focal, with cases found only in two departments; Ferkessédougou (5.4%, 95% CI: 2.5-9.9%) and Ouangolodougou (2.7%, 95% CI: 0.9-6.3%). Hookworm was the only STH species observed with a prevalence of 1.5% (95% CI: 0.8-2.8%). A higher risk of S. haematobium infection was observed in males compared to females, but the difference was not statistically significant (2.3% versus 1.3%, odds ratio [OR]: 1.5, 95% CI: 0.8-2.7). Participants aged 16-20 years showed the highest prevalence of S. haematobium. A total of 111 human- and animal-water contact points were identified at 47 water sources. Three potential intermediate host snails of schistosomes were collected; namely, Bulinus forskalii (n = 761), Bulinus truncatus (n = 205), and Biomphalaria pfeifferi (n = 1). Yet, only one specimen of Bu. truncatus was found to be shedding schistosome cercariae. CONCLUSIONS/SIGNIFICANCE: This study confirms very low transmission of schistosomiasis and hookworm in northern Côte d'Ivoire. The establishment and rigorous implementation of integrated surveillance-response systems could lead to the elimination of schistosomiasis and hookworm in this part of Côte d'Ivoire.

Gender-related differences in prevalence, intensity and associated risk factors of Schistosoma infections in Africa: A systematic review and meta-analysis.

BACKGROUND: Schistosomiasis remains a global-health problem with over 90% of its burden concentrated in Africa. Field studies reflect the complex ways in which socio-cultural and socio-economic variables, affect the distribution of Schistosoma infections across different populations. This review set out to systematically investigate and quantify the differences in Schistosoma infection burdens between males and females in Africa for two of the most prevalent Schistosoma species-Schistosoma mansoni and Schistosoma haematobium. METHODOLOGY: We searched (from inception to 11th March 2020) Embase, MEDLINE, PubMed, and Web of Science for relevant studies on schistosomiasis. We included studies that report S. mansoni and/or S. haematobium prevalence and/or intensity data distributed between males and females. We conducted meta-analyses on the male to female (M:F) prevalence of infection ratios. Subgroup analyses were performed according to study baseline prevalence, sample size and the lower and upper age limit of study participants. We also present a descriptive analysis of differential risk and intensity of infection across males and females. Evidence for differences in the prevalence of schistosomiasis infection between males and females is presented, stratified by Schistosoma species. RESULT: We identified 128 relevant studies, with over 200,000 participants across 23 countries. Of all the reported differences in the prevalence of infection between males and females, only 41% and 34% were statistically significant for S. mansoni and S. haematobium, respectively. Similar proportions of studies (27% and 34% for for S. haematobium and S. mansoni, respectively) of the reported differences in intensity of infection between males and females were statistically significant. The meta-analyses summarized a higher prevalence of infection in males; pooled random-effects weighted M:F prevalence of infection ratios were 1.20 (95% CI 1.11-1.29) for S. haematobium and 1.15 (95% CI 1.08-1.22) for S. mansoni. However, females are underrespresented in some of the studies. Additionally, there was significant heterogeneity across studies (Higgins I2 statistic (p-values < 0.001, I2values>95%)). Results of the subgroup analysis showed that the baseline prevalence influenced the M:F prevalence ratios for S. haematobium and S. mansoni, with higher M:F prevalence of infection ratios in settings with a lower baseline prevalence of infection. Across the studies, we identified four major risk factors associated with infection rates: occupational and recreational water contact, knowledge, socio-economic factors and demographic factors. The effect of these risk factors on the burden of infection in males and females varied across studies. CONCLUSIONS: We find evidence of differences in prevalence of infection between males and females which may reflect differences in gender norms and water contact activities, suggesting that policy changes at the regional level may help ameliorate gender-related disparities in schistosomiasis infection burden. Collecting, robustly analysing, and reporting, sex-disaggregated epidemiological data, is currently lacking, but would be highly informative for planning effective treatment programmes and establishing those most at risk of schistosomiasis infections.

Exposure, hazard, and vulnerability all contribute to Schistosoma haematobium re-infection in northern Senegal.

BACKGROUND: Infectious disease risk is driven by three interrelated components: exposure, hazard, and vulnerability. For schistosomiasis, exposure occurs through contact with water, which is often tied to daily activities. Water contact, however, does not imply risk unless the environmental hazard of snails and parasites is also present in the water. By increasing reliance on hazardous activities and environments, socio-economic vulnerability can hinder reductions in exposure to a hazard. We aimed to quantify the contributions of exposure, hazard, and vulnerability to the presence and intensity of Schistosoma haematobium re-infection. METHODOLOGY/PRINCIPAL FINDINGS: In 13 villages along the Senegal River, we collected parasitological data from 821 school-aged children, survey data from 411 households where those children resided, and ecological data from all 24 village water access sites. We fit mixed-effects logistic and negative binomial regressions with indices of exposure, hazard, and vulnerability as explanatory variables of Schistosoma haematobium presence and intensity, respectively, controlling for demographic variables. Using multi-model inference to calculate the relative importance of each component of risk, we found that hazard (Æ©wi = 0.95) was the most important component of S. haematobium presence, followed by vulnerability (Æ©wi = 0.91). Exposure (Æ©wi = 1.00) was the most important component of S. haematobium intensity, followed by hazard (Æ©wi = 0.77). Model averaging quantified associations between each infection outcome and indices of exposure, hazard, and vulnerability, revealing a positive association between hazard and infection presence (OR = 1.49, 95% CI 1.12, 1.97), and a positive association between exposure and infection intensity (RR 2.59-3.86, depending on the category; all 95% CIs above 1). CONCLUSIONS/SIGNIFICANCE: Our findings underscore the linkages between social (exposure and vulnerability) and environmental (hazard) processes in the acquisition and accumulation of S. haematobium infection. This approach highlights the importance of implementing both social and environmental interventions to complement mass drug administration.

Schistosome infection in Senegal is associated with different spatial extents of risk and ecological drivers for Schistosoma haematobium and S. mansoni.

Schistosome parasites infect more than 200 million people annually, mostly in sub-Saharan Africa, where people may be co-infected with more than one species of the parasite. Infection risk for any single species is determined, in part, by the distribution of its obligate intermediate host snail. As the World Health Organization reprioritizes snail control to reduce the global burden of schistosomiasis, there is renewed importance in knowing when and where to target those efforts, which could vary by schistosome species. This study estimates factors associated with schistosomiasis risk in 16 villages located in the Senegal River Basin, a region hyperendemic for Schistosoma haematobium and S. mansoni. We first analyzed the spatial distributions of the two schistosomes' intermediate host snails (Bulinus spp. and Biomphalaria pfeifferi, respectively) at village water access sites. Then, we separately evaluated the relationships between human S. haematobium and S. mansoni infections and (i) the area of remotely-sensed snail habitat across spatial extents ranging from 1 to 120 m from shorelines, and (ii) water access site size and shape characteristics. We compared the influence of snail habitat across spatial extents because, while snail sampling is traditionally done near shorelines, we hypothesized that snails further from shore also contribute to infection risk. We found that, controlling for demographic variables, human risk for S. haematobium infection was positively correlated with snail habitat when snail habitat was measured over a much greater radius from shore (45 m to 120 m) than usual. S. haematobium risk was also associated with large, open water access sites. However, S. mansoni infection risk was associated with small, sheltered water access sites, and was not positively correlated with snail habitat at any spatial sampling radius. Our findings highlight the need to consider different ecological and environmental factors driving the transmission of each schistosome species in co-endemic landscapes.

Revisiting density-dependent fecundity in schistosomes using sibship reconstruction.

The stability of parasite populations is regulated by density-dependent processes occurring at different stages of their life cycle. In dioecious helminth infections, density-dependent fecundity is one such regulatory process that describes the reduction in egg production by female worms in high worm burden within-host environments. In human schistosomiasis, the operation of density-dependent fecundity is equivocal and investigation is hampered by the inaccessibility of adult worms that are located intravascularly. Current understanding is almost exclusively limited to data collected from two human autopsy studies conducted over 40 years ago, with subsequent analyses having reached conflicting conclusions. Whether egg production is regulated in a density-dependent manner is key to predicting the effectiveness of interventions targeting the elimination of schistosomiasis and to the interpretation of parasitological data collected during monitoring and evaluation activities. Here, we revisit density-dependent fecundity in the two most globally important human Schistosoma spp. using a statistical modelling approach that combines molecular inference on the number of parents/adult worms in individual human hosts with parasitological egg count data from mainland Tanzania and Zanzibar. We find a non-proportional relationship between S. haematobium egg counts and inferred numbers of female worms, providing the first clear evidence of density-dependent fecundity in this schistosome species. We do not find robust evidence for density-dependent fecundity in S. mansoni because of high sensitivity to some modelling assumptions and the lower statistical power of the available data. We discuss the strengths and limitations of our model-based analytical approach and its potential for improving our understanding of density dependence in schistosomiasis and other human helminthiases earmarked for elimination.

Cervicovaginal Immune Activation in Zambian Women With Female Genital Schistosomiasis.

HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis (FGS), an inflammatory disease caused by S. haematobium egg deposition in the genital tract, has been associated with prevalent HIV-1 infection. Elevated levels of the chemokines MIP-1α (CCL-3), MIP-1ß (CCL-4), IP-10 (CXCL-10), and IL-8 (CXCL-8) in cervicovaginal lavage (CVL) have been associated with HIV-1 acquisition. We hypothesize that levels of cervicovaginal cytokines may be raised in FGS and could provide a causal mechanism for the association between FGS and HIV-1. In the cross-sectional BILHIV study, specimens were collected from 603 female participants who were aged 18-31 years, sexually active, not pregnant and participated in the HPTN 071 (PopART) HIV-1 prevention trial in Zambia. Participants self-collected urine, and vaginal and cervical swabs, while CVLs were clinically obtained. Microscopy and Schistosoma circulating anodic antigen (CAA) were performed on urine. Genital samples were examined for parasite-specific DNA by PCR. Women with FGS (n=28), defined as a positive Schistosoma PCR from any genital sample were frequency age-matched with 159 FGS negative (defined as negative Schistosoma PCR, urine CAA, urine microscopy, and colposcopy imaging) women. Participants with probable FGS (n=25) (defined as the presence of either urine CAA or microscopy in combination with one of four clinical findings suggestive of FGS on colposcope-obtained photographs) were also included, for a total sample size of 212. The concentrations of 17 soluble cytokines and chemokines were quantified by a multiplex bead-based immunoassay. There was no difference in the concentrations of cytokines or chemokines between participants with and without FGS. An exploratory analysis of those women with a higher FGS burden, defined by ≥2 genital specimens with detectable Schistosoma DNA (n=15) showed, after adjusting for potential confounders, a higher Th2 (IL-4, IL-5, and IL-13) and pro-inflammatory (IL-15) expression pattern in comparison to FGS negative women, with differences unlikely to be due to chance (p=0.037 for IL-4 and p<0.001 for IL-5 after adjusting for multiple testing). FGS may alter the female genital tract immune environment, but larger studies in areas of varying endemicity are needed to evaluate the association with HIV-1 vulnerability.

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.

Prevalence and distribution of schistosomiasis in human, livestock, and snail populations in northern Senegal: a One Health epidemiological study of a multi-host system.

BACKGROUND: Schistosomiasis is a neglected tropical disease of global medical and veterinary importance. As efforts to eliminate schistosomiasis as a public health problem and interrupt transmission gather momentum, the potential zoonotic risk posed by livestock Schistosoma species via viable hybridisation in sub-Saharan Africa have been largely overlooked. We aimed to investigate the prevalence, distribution, and multi-host, multiparasite transmission cycle of Haematobium group schistosomiasis in Senegal, West Africa. METHODS: In this epidemiological study, we carried out systematic surveys in definitive hosts (humans, cattle, sheep, and goats) and snail intermediate hosts, in 2016-18, in two areas of Northern Senegal: Richard Toll and Lac de Guiers, where transmission is perennial; and Barkedji and Linguère, where transmission is seasonal. The occurrence and distribution of Schistosoma species and hybrids were assessed by molecular analyses of parasitological specimens obtained from the different hosts. Children in the study villages aged 5-17 years and enrolled in school were selected from school registers. Adults (aged 18-78 years) were self-selecting volunteers. Livestock from the study villages in both areas were also randomly sampled, as were post-mortem samples from local abattoirs. Additionally, five malacological surveys of snail intermediate hosts were carried out at each site in open water sources used by the communities and their animals. FINDINGS: In May to August, 2016, we surveyed 375 children and 20 adults from Richard Toll and Lac de Guiers, and 201 children and 107 adults from Barkedji and Linguère; in October, 2017, to January, 2018, we surveyed 386 children and 88 adults from Richard Toll and Lac de Guiers, and 323 children and 85 adults from Barkedji and Linguère. In Richard Toll and Lac de Guiers the prevalence of urogenital schistosomiasis in children was estimated to be 87% (95% CI 80-95) in 2016 and 88% (82-95) in 2017-18. An estimated 63% (in 2016) and 72% (in 2017-18) of infected children were shedding Schistosoma haematobium-Schistosoma bovis hybrids. In adults in Richard Toll and Lac de Guiers, the prevalence of urogenital schistosomiasis was estimated to be 79% (52-97) in 2016 and 41% (30-54) in 2017-18, with 88% of infected samples containing S haematobium-S bovis hybrids. In Barkedji and Linguère the prevalence of urogenital schistosomiasis in children was estimated to be 30% (23-38) in 2016 and 42% (35-49) in 2017-18, with the proportion of infected children found to be shedding S haematobium-S bovis hybrid miracidia much lower than in Richard Toll and Lac de Guiers (11% in 2016 and 9% in 2017-18). In adults in Barkedji and Linguère, the prevalence of urogenital schistosomiasis was estimated to be 26% (17-36) in 2016 and 47% (34-60) in 2017-18, with 10% of infected samples containing S haematobium-S bovis hybrids. The prevalence of S bovis in the sympatric cattle population of Richard Toll and the Lac de Guiers was 92% (80-99), with S bovis also found in sheep (estimated prevalence 14% [5-31]) and goats (15% [5-33]). In Barkedji and Linguère the main schistosome species in livestock was Schistosoma curassoni, with an estimated prevalence of 73% (48-93) in sheep, 84% (61-98) in goats and 8% (2-24) in cattle. S haematobium-S bovis hybrids were not found in livestock. In Richard Toll and Lac de Guiers 35% of infected Bulinus spp snail intermediate hosts were found to be shedding S haematobium-S bovis hybrids (68% shedding S haematobium; 17% shedding S bovis); however, no snails were found to be shedding S haematobium hybrids in Barkedji and Linguère (29% shedding S haematobium; 71% shedding S curassoni). INTERPRETATION: Our findings suggest that hybrids originate in humans via zoonotic spillover from livestock populations, where schistosomiasis is co-endemic. Introgressive hybridisation, evolving host ranges, and wider ecosystem contexts could affect the transmission dynamics of schistosomiasis and other pathogens, demonstrating the need to consider control measures within a One Health framework. FUNDING: Zoonoses and Emerging Livestock Systems programme (UK Biotechnology and Biological Sciences Research Council, UK Department for International Development, UK Economic and Social Research Council, UK Medical Research Council, UK Natural Environment Research Council, and UK Defence Science and Technology Laboratory).

Interactions between Schistosoma haematobium group species and their Bulinus spp. intermediate hosts along the Niger River Valley.

BACKGROUND: Urogenital schistosomiasis, caused by infection with Schistosoma haematobium, is endemic in Niger but complicated by the presence of Schistosoma bovis, Schistosoma curassoni and S. haematobium group hybrids along with various Bulinus snail intermediate host species. Establishing the schistosomes and snails involved in transmission aids disease surveillance whilst providing insights into snail-schistosome interactions/compatibilities and biology. METHODS: Infected Bulinus spp. were collected from 16 villages north and south of the Niamey region, Niger, between 2011 and 2015. From each Bulinus spp., 20-52 cercariae shed were analysed using microsatellite markers and a subset identified using the mitochondrial (mt) cox1 and nuclear ITS1 + 2 and 18S DNA regions. Infected Bulinus spp. were identified using both morphological and molecular analysis (partial mt cox1 region). RESULTS: A total of 87 infected Bulinus from 24 sites were found, 29 were molecularly confirmed as B. truncatus, three as B. forskalii and four as B. globosus. The remaining samples were morphologically identified as B. truncatus (n = 49) and B. forskalii (n = 2). The microsatellite analysis of 1124 cercariae revealed 186 cercarial multilocus genotypes (MLGs). Identical cercarial genotypes were frequently (60%) identified from the same snail (clonal populations from a single miracidia); however, several (40%) of the snails had cercariae of different genotypes (2-10 MLG's) indicating multiple miracidial infections. Fifty-seven of the B. truncatus and all of the B. forskalii and B. globosus were shedding the Bovid schistosome S. bovis. The other B. truncatus were shedding the human schistosomes, S. haematobium (n = 6) and the S. haematobium group hybrids (n = 13). Two B. truncatus had co-infections with S. haematobium and S. haematobium group hybrids whilst no co-infections with S. bovis were observed. CONCLUSIONS: This study has advanced our understanding of human and bovid schistosomiasis transmission in the Niger River Valley region. Human Schistosoma species/forms (S. haematobium and S. haematobium hybrids) were found transmitted only in five villages whereas those causing veterinary schistosomiasis (S. bovis), were found in most villages. Bulinus truncatus was most abundant, transmitting all Schistosoma species, while the less abundant B. forskalii and B. globosus, only transmitted S. bovis. Our data suggest that species-specific biological traits may exist in relation to co-infections, snail-schistosome compatibility and intramolluscan schistosome development.

Parasite Population Genetic Contributions to the Schistosomiasis Consortium for Operational Research and Evaluation within Sub-Saharan Africa.

Analyses of the population genetic structure of schistosomes under the "Schistosomiasis Consortium for Operational Research and Evaluation" (SCORE) contrasting treatment pressure scenarios in Tanzania, Niger, and Zanzibar were performed to provide supplementary critical information with which to evaluate the impact of these large-scale control activities and guide how activities could be adjusted. We predicted that population genetic analyses would reveal information on a range of important parameters including, but not exclusive to, recruitment and transmission of genotypes, occurrence of hybridization events, differences in reproductive mode, and degrees of inbreeding, and hence, the evolutionary potential, and responses of parasite populations under contrasting treatment pressures. Key findings revealed that naturally high levels of gene flow and mixing of the parasite populations between neighboring sites were likely to dilute any effects imposed by the SCORE treatment arms. Furthermore, significant inherent differences in parasite fecundity were observed, independent of current treatment arm, but potentially of major impact in terms of maintaining high levels of ongoing transmission in persistent "biological hotspot" sites. Within Niger, naturally occurring Schistosoma haematobium/Schistosoma bovis viable hybrids were found to be abundant, often occurring in significantly higher proportions than that of single-species S. haematobium infections. By examining parasite population genetic structures across hosts, treatment regimens, and the spatial landscape, our results to date illustrate key transmission processes over and above that which could be achieved through standard parasitological monitoring of prevalence and intensity alone, as well as adding to our understanding of Schistosoma spp. life history strategies in general.

Connecting Female Genital Schistosomiasis and Menstrual Hygiene Initiatives.

Effective future control of female genital schistosomiasis (FGS) requires an integrated and multisectoral approach, bringing together HIV, sexual and reproductive health, and reproductive rights sectors. In this article, an underappreciated but important connection between FGS and menstrual hygiene initiatives in Africa is highlighted.

Schistosome migration in the definitive host.

Schistosomes are parasitic blood flukes that infect >200 million people around the world. Free-swimming larval stages penetrate the skin, invade a blood vessel, and migrate through the heart and lungs to the vasculature of the liver, where maturation and mating occurs. From here, the parasite couples migrate to their preferred egg laying sites. Here, we compare and contrast what is known about the migration patterns within the definitive host of the three major species of human schistosome: Schistosoma mansoni, S. japonicum, and S. haematobium. We conclude that intravascular schistosomes are inexorable colonizers whose migration and egg laying strategy is profligate; all three species (and their eggs) can be found throughout the mesenteric venules, the rectal venous plexus, and, to a greater or lesser extent, the urogenital venous plexuses. In addition, it is common for parasite eggs to be deposited in locations that lack easy access to the exterior, further demonstrating the relentless exploratory nature of these intravascular worms.

High prevalence of Schistosoma haematobium × Schistosoma bovis hybrids in schoolchildren in Côte d'Ivoire.

Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been reported in West Africa, no data about Schistosoma hybrids in humans are available from Côte d'Ivoire. This study aimed to identify and quantify S. haematobium-bovis hybrids among schoolchildren in four localities of Côte d'Ivoire. Urine samples were collected and examined by filtration to detect Schistosoma eggs. Eggs were hatched and 503 miracidia were individually collected and stored on Whatman® FTA cards for molecular analysis. Individual miracidia were molecularly characterized by analysis of mitochondrial cox1 and nuclear internal transcribed spacer 2 (ITS 2) DNA regions. A mitochondrial cox1-based diagnostic polymerase chain reaction was performed on 459 miracidia, with 239 (52.1%) exhibiting the typical band for S. haematobium and 220 (47.9%) the S. bovis band. The cox1 and ITS 2 amplicons were Sanger sequenced from 40 randomly selected miracidia to confirm species and hybrids status. Among the 33 cox1 sequences analysed, we identified 15 S. haematobium sequences (45.5%) belonging to seven haplotypes and 18 S. bovis sequences (54.5%) belonging to 12 haplotypes. Of 40 ITS 2 sequences analysed, 31 (77.5%) were assigned to pure S. haematobium, four (10.0%) to pure S. bovis and five (12.5%) to S. haematobium-bovis hybrids. Our findings suggest that S. haematobium-bovis hybrids are common in Côte d'Ivoire. Hence, intense prospection of domestic and wild animals is warranted to determine whether zoonotic transmission occurs.

Persistent establishment of a tropical disease in Europe: the preadaptation of schistosomes to overwinter.

BACKGROUND: Global changes promote the spread of infectious diseases worldwide. In this context, tropical urogenital schistosomiasis is now permanently established in Corsica since its first emergence in 2013. The local persistence of the tropical pathogens (schistosomes) responsible for urogenital schistosomiasis at such latitudes might be explained by (i) the presence of its intermediate host, the snail Bulinus truncatus, (ii) the recurrent local reseeding of schistosomes by their vertebrate hosts (either human or animal) every summer, and/or (iii) the maintenance and survival of schistosomes within their snail hosts over winter. METHODS: In this study we conducted an ecological experiment to assess the ability of temperate and tropical schistosome strains to survive in classical winter temperatures in Corsican rivers when infecting temperate (local) snail strains. We also quantified the ability of the schistosomes to complete their life-cycle post-overwintering when returned to classical summer water temperatures. RESULTS: Our results show that Mediterranean molluscs are locally adapted to winter conditions compared to tropical molluscs. Moreover, temperate and tropical schistosome strains equally survived the cold and produced viable offspring when returned to optimal temperatures. These results indicate that schistosomes can overwinter under temperate climates when infecting locally adapted snails and might partly explain the establishment and maintenance of schistosomes in Corsica from year to year. CONCLUSIONS: The observed broader thermal range of schistosomes compared to that of their snail hosts was unexpected and clearly indicates that the spread and establishment of schistosomiasis in temperate countries relies primarily on the presence of the locally adapted snail host lineages, currently known to be present in France, Italy, Portugal, Spain and Greece.

A 5-Year intervention study on elimination of urogenital schistosomiasis in Zanzibar: Parasitological results of annual cross-sectional surveys.

BACKGROUND: The Zanzibar Elimination of Schistosomiasis Transmission (ZEST) project aimed to eliminate urogenital schistosomiasis as a public health problem from Pemba and to interrupt Schistosoma haematobium transmission from Unguja in 5 years. METHODOLOGY: A repeated cross-sectional cluster-randomized trial was implemented from 2011/12 till 2017. On each island, 45 shehias were randomly assigned to receive one of three interventions: biannual mass drug administration (MDA) with praziquantel alone, or in combination with snail control or behavior change measures. In cross-sectional surveys, a single urine sample was collected from ~9,000 students aged 9- to 12-years and from ~4,500 adults aged 20- to 55-years annually, and from ~9,000 1st year students at baseline and the final survey. Each sample was examined for S. haematobium eggs by a single urine filtration. Prevalence and infection intensity were determined. Odds of infection were compared between the intervention arms. PRINCIPAL FINDINGS: Prevalence was reduced from 6.1% (95% confidence interval (CI): 4.5%-7.6%) to 1.7% (95% CI: 1.2%-2.2%) in 9- to 12-year old students, from 3.9% (95% CI: 2.8%-5.0%) to 1.5% (95% CI: 1.0%-2.0%) in adults, and from 8.8% (95% CI: 6.5%-11.2%) to 2.6% (95% CI: 1.7%-3.5%) in 1st year students from 2011/12 to 2017. In 2017, heavy infection intensities occurred in 0.4% of 9- to 12-year old students, 0.1% of adults, and 0.8% of 1st year students. Considering 1st year students in 2017, 13/45 schools in Pemba and 4/45 schools in Unguja had heavy infection intensities >1%. There was no significant difference in prevalence between the intervention arms in any study group and year. CONCLUSIONS/SIGNIFICANCE: Urogenital schistosomiasis was eliminated as public health problem from most sites in Pemba and Unguja. Prevalence was significantly reduced, but transmission was not interrupted. Continued interventions that are adaptive and tailored to the micro-epidemiology of S. haematobium in Zanzibar are needed to sustain and advance the gains made by ZEST.

In vitro effect of curcumin on Schistosoma species viability, tegument ultrastructure and egg hatchability.

Schistosomiasis remains a severe problem of public health in developing countries. The development of resistance to praziquantel (PZQ) has justified the search for new alternative chemotherapies with new formulations, more effective, and without adverse effects. Curcumin (CUR), the major phenolic compound present in rhizome of turmeric (Curcuma longa L.), has been traditionally used against various diseases including parasitic infections. Here, the antischistosomal activity of CUR (50-500 µM), evaluated in parallel against S. mansoni and S. haematobium adult worms, appeared significant (P < 0.05 to < 0.0001) in a time- and dose-dependent manner. Two h incubation with CUR (500 µM) caused 100% irreversible killing of both schistosomal species. CUR (250 µM) caused the death of S. haematobium and S. mansoni worms after 2 h and 4 h, respectively. As CUR concentration decreases (50 µM), all coupled adult worms were separated into individual male and female but the worms remained viable up to 4 h. Scanning and transmission electron microscopy revealed that S. haematobium are more sensitive than S. mansoni to CUR schistosomicidal effects. In support, CUR was found to affect the antigenicity of surface membrane molecules of S. haematobium, but not S. mansoni. Of importance, CUR significantly (P < 0.05 to < 0.0001) affected S. mansoni eggs hatchability and viability, a ground for its use in chemotherapy of schistosomiasis mansoni and japonicum because of its increased bioavailability in the gastrointestinal tract. The data together emphasize that CUR is a promising potential schistosomicidal drug.

Restaging Pulmonary Schistosomiasis.

Schistosomiasis is traditionally classified into an acute and a chronic phase, although a precise temporal distinction between the two phases has not been established. Lung involvement can be observed in both phases. We previously reported seven cases of pulmonary lesions due to chronic schistosomiasis in African immigrants. All cases were documented with CT scans and demonstrated complete resolution after treatment with praziquantel. Moreover, another case showed spontaneous disappearance of the nodule before treatment with praziquantel. These findings are similar to those observed in the acute phase of schistosomiasis, with well-defined or ground glass nodules that resolve spontaneously. According to these findings, we postulate the presence of an "intermediate" phase of schistosomiasis involving the lungs that can be defined as an "early chronic phase," and presents analogies to the acute phase. We also hypothesize that in the "early chronic phase," the female worms transit through the lungs where they may lay eggs. These passages not only cause transient, but also radiologically visible alterations. The pathophysiology of lung lesions in the late chronic phase is probably different: the adult worms settled in the mesenteric plexuses produce eggs for years. The eggs repeatedly migrate to the perialveolar capillary beds via portal-caval shunting. Thus, in this case it is the eggs and not the adult worms that reach the lungs in a scattered way. Based on our findings, we suggest the alternative hypothesis that the pulmonary involvement is a phase of the natural evolution of the infection, both from Schistosoma mansoni and Schistosoma haematobium.

The Effect of Climate Change and the Snail-Schistosome Cycle in Transmission and Bio-Control of Schistosomiasis in Sub-Saharan Africa.

In the next century, global warming, due to changes in climatic factors, is expected to have an enormous influence on the interactions between pathogens and their hosts. Over the years, the rate at which vector-borne diseases and their transmission dynamics modify and develop has been shown to be highly dependent to a certain extent on changes in temperature and geographical distribution. Schistosomiasis has been recognized as a tropical and neglected vector-borne disease whose rate of infection has been predicted to be elevated worldwide, especially in sub-Saharan Africa; the region currently with the highest proportion of people at risk, due to changes in climate. This review not only suggests the need to develop an efficient and effective model that will predict Schistosoma spp. population dynamics but seeks to evaluate the effectiveness of several current control strategies. The design of a framework model to predict and accommodate the future incidence of schistosomiasis in human population dynamics in sub-Saharan Africa is proposed. The impact of climate change on schistosomiasis transmission as well as the distribution of several freshwater snails responsible for the transmission of Schistosoma parasites in the region is also reviewed. Lastly, this article advocates for modelling several control mechanisms for schistosomiasis in sub-Saharan Africa so as to tackle the re-infection of the disease, even after treating infected people with praziquantel, the first-line treatment drug for schistosomiasis.

Ultrasound Evolution of Pediatric Urinary Schistosomiasis after Treatment with Praziquantel in a Highly Endemic Area.

Urinary schistosomiasis causes damage to the urological system. Ultrasound is a method that detects the burden of secondary disease, individually and in epidemiological studies. In this study, the Schistosoma haematobium-associated urinary tract pathology is analyzed before and after treatment in a short period of time. Seventy children who had previously participated in an epidemiological study on schistosomiasis in the city of Cubal, Angola, and had also performed urinary ultrasound between August 2013 and February 2014 were cited 6-8 months later to assess the possible reinfection and repeat new urinary ultrasound, analyzing changes at the level of urinary pathology. The presence of hematuria and proteinuria was also analyzed. Of the 70 children analyzed, 29 (41.4%) were girls, with an average age of 10.4 years (standard deviation 2.3). Fifty-three (75.7%) had an improvement in their bladder and/or kidney scores, whereas 12 (17.1%) had no change and five (7.1%) had progression of the disease. None of the parameters analyzed completely disappeared. After one single course of treatment with praziquantel, all the analyzed parameters showed regression. Improvement was greater in the urinary bladder than in the upper urinary tract, though these lesions also reversed; the reversion of all parameters was greater among children older than 10 years old than the younger ones. Proteinuria was the parameter with a smaller reduction. Ultrasound should be a usual tool for diagnosis and follow-up in urinary schistosomiasis, particularly in children; more accurate recommendations about follow-up in the case of children whose lesions do not reverse should be established.