Extant interspecific hybridization among trematodes within the Schistosoma haematobium species complex in Nigeria.

BACKGROUND: Natural interspecific hybridization between the human parasite (Schistosoma haematobium [Sh]) and bovine parasites (Schistosoma bovis [Sb], Schistosoma curassoni [Sc]) is increasingly reported in Africa. We developed a multi-locus PCR DNA-Seq strategy that amplifies two unlinked nuclear (transITS, BF) and two linked organellar genome markers (CO1, ND5) to genotype S. haematobium eggs collected from infected people in Ile Oluji/Oke Igbo, Ondo State (an agrarian community) and Kachi, Jigawa State (a pastoral community) in Southwestern and Northern Nigeria, respectively. PRINCIPAL FINDINGS: Out of a total of 219 urine samples collected, 57 were positive for schistosomes. All patients from Jigawa state possessed an Sh mitochondrial genome and were infected with a genetic profile consistent with an Sh x Sb hybrid based on sequences obtained at CO1, ND5, transITS and BF nuclear markers. Whereas samples collected from Ondo state were more varied. Mitonuclear discordance was observed in all 17 patients, worms possessed an Sb mitochondrial genome but one of four different genetic profiles at the nuclear markers, either admixed (heterozygous between Sh x Sc or Sh x Sb) at both markers (n = 10), Sh at BF and admixed at transITS (Sh x Sc) (n = 5), admixed (Sh x Sc) at BF and homozygous Sc at transITS (n = 1) or homozygous Sh at BF and homozygous Sc at transITS (n = 1). SIGNIFICANCE: Previous work suggested that zoonotic transmission of S. bovis in pastoral communities, where humans and animals share a common water source, is a driving factor facilitating interspecific hybridization. However, our data showed that all samples were hybrids, with greater diversity identified in Southwestern Nigeria, a non-pastoral site. Further, one patient possessed an S. bovis mitochondrial genome but was homozygous for S. haematobium at BF and homozygous for S. curassoni at transITS supporting at least two separate backcrosses in its origin, suggesting that interspecific hybridization may be an ongoing process.

Human schistosomiasis in Nigeria: present status, diagnosis, chemotherapy, and herbal medicines.

Schistosomiasis is a neglected tropical disease caused by a parasitic, trematode blood fluke of the genus Schistosoma. With 20 million people infected, mostly due to Schistosoma haematobium, Nigeria has the highest burden of schistosomiasis in the world. We review the status of human schistosomiasis in Nigeria regarding its distribution, prevalence, diagnosis, prevention, orthodox and traditional treatments, as well as snail control strategies. Of the country's 36 states, the highest disease prevalence is found in Lagos State, but at a geo-political zonal level, the northwest is the most endemic. The predominantly used diagnostic techniques are based on microscopy. Other methods such as antibody-based serological assays and DNA detection methods are rarely employed. Possible biomarkers of disease have been identified in fecal and blood samples from patients. With respect to preventive chemotherapy, mass drug administration with praziquantel as well as individual studies with artemisinin or albendazole have been reported in 11 out of the 36 states with cure rates between 51.1 and 100%. Also, Nigerian medicinal plants have been traditionally used as anti-schistosomal agents or molluscicides, of which Tetrapleura tetraptera (Oshosho, aridan, Aidan fruit), Carica papaya (Gwanda, Ìbépe, Pawpaw), Borreria verticillata (Karya garma, Irawo-ile, African borreria), and Calliandra portoricensis (Tude, Oga, corpse awakener) are most common in the scientific literature. We conclude that the high endemicity of the disease in Nigeria is associated with the limited application of various diagnostic tools and preventive chemotherapy efforts as well as poor knowledge, attitudes, and practices (KAP). Nonetheless, the country could serve as a scientific base in the discovery of biomarkers, as well as novel plant-derived schistosomicides and molluscicides.

Differentiation between Bulinus truncatus and Bulinus hexaploidus by morphological characters, chromosomal study and compatibility with Schistosoma haematobium.

Schistosomiasis is a snail-born, neglected tropical disease (NTD) caused by blood flukes (trematode worms) of the genusSchistosoma. It is the second most socioeconomically devastating parasitic disease after malaria. Urogenital schistosomiasis is caused by Schistosoma haematobium which is transmitted by snail intermediate host of the genus Bulinus. This genus is a model system for the study of polyploidy in animals. This study aims to investigate ploidy levels existing among the Bulinus species and their compatibility with S. haematobium. The specimens were collected from two governorates in Egypt. Chromosomal preparation was made from gonad tissue (ovotestis). This study found two ploidy levels (tetraploid, n = 36 and hexaploid, n = 54) of B. truncatus/tropicus complex in Egypt. Tetraploid B. truncatus was found in El-Beheira governorate while-unexpectedly and for the first time in Egypt, the hexaploid population was found in Giza governorate. This identification focused on shell morphology, chromosomal count, and spermatozoa of each species. Afterward, all species were exposed to S. haematobium miracidia where B. hexaploidus snails were the only refractory species. The histopathological study showed early destruction and abnormal development of S. haematobium in B. hexaploidus tissues. In addition, the hematological investigation showed increasing in the total hemocyte count, the formation of vacuoles, several pseudopodia, and more dense granules in the hemocytes of infected B. hexaploidus snails. In conclusion, there were two types of snails one was refractory and the other was susceptible.

Low doses and short duration of prednisolone administration in guinea pigs experimentally infected with Schistosoma haematobium: Histopathology of liver and lungs.

In our previous study, administration of 5 mg prednisolone for five days pre-Schistosoma haematobium infection in guinea pigs increased susceptibility and produced pathological reactions in the liver and bladder. Since corticosteroids can suppress granuloma formation, maturation, and size, this study sought to investigate if prednisolone given at low doses and short duration can produce granulomatous lesions in the tissues of guinea pigs experimentally infected with S. haematobium. Guinea pigs were shared into six groups: group I and II were the immunosuppressed-infected guinea pigs (I0.5 and I1.5- 20 animals each), group III was the unimmunosuppressed-infected guinea pigs (UI- 20 animals), and group IV, V and VI were the immunosuppressed-uninfected and normal guinea pigs (D0.5, D1.5, and normal- 10 animals each). Prednisolone was given in doses of 0.5 mg/kg and 1.5 mg/kg to the different groups, a day before infection and on day 5 post-infection. The infected groups were subcutaneously injected with 250-300 S. haematobium cercariae. Screening for S. haematobium eggs in urine and fecal samples of animals, and quantitative analysis for leukocyte and red blood cell (RBC) counts in urine samples of guinea pigs began nine weeks post-infection (WPI). Guinea pigs were killed, perfused, worms recovered and sections of the liver, lungs, and bladder excised for histopathological examination at 6, 8, 11, 14 and 16 WPI. S. haematobium eggs were only seen in urine samples of I1.5 at 15 and 16WPI. Although the parasite eggs were seen in fecal samples of all infected guinea pigs from 9WPI, those of UI were sparse and took longer time to hatch. High leukocyte counts were seen in all immunosuppressed groups at 6WPI, which returned to normal levels in D1.5 and D0.5 at 16WPI. At 16WPI, significant numbers of leukocyte and RBC counts were seen in urine samples of I1.5. The immunosuppressed-infected groups had significant numbers of mature and total worm loads than UI group (p > 0.05). However, the worm burden of I1.5 was higher than I0.5 at 14WPI and 16WPI. Non-granulomatous lesions were only recorded in the liver sections of the immunosuppressed-infected animals and in lung sections of UI and I1.5 guinea pigs. Liver lesions seen were hepatocyte degeneration; necrosis; Kupffer cell involvements as hyperplasia, phagocytosis, proliferation; hyperaemia and haemorrhage, and mononuclear leukocyte infiltration. Lung lesions seen in I1.5 at 11-16WPI were hemosiderin depositions and hyperaemia, emphysema and atelectasis, and mononuclear leukocyte infiltrations while in UI, emphysema and mononuclear leukocyte infiltration were seen only at 16WPI. In the immunosuppressed-infected groups, composite liver lesion scores showed that peak lesion severity was at 8WPI and 11WPI in I1.5 and I0.5, respectively. However, there was no significant difference (p = 0.105) in composite liver lesion scores of I1.5 and I0.5. Lung lesion score of UI at 16WPI was significantly higher (p > 0.05) than that of I1.5. Findings from this study show that even at low doses and short duration of administration, corticosteroids can only increase susceptibility of guinea pigs but cannot improve its suitability as experimental models of S. haematobium infection.

Prevalence and correlates of urogenital schistosomiasis in school-going children at Maramba Primary School in Livingstone District, Zambia.

OBJECTIVES: To determine the presence and correlates of S. haematobium in urine specimens of school-going children at Maramba Primary School in Livingstone, Zambia. METHODS AND SUBJECTS: A structured questionnaire was administered to children with signed consent from their guardians/parents, and spot urine specimens were collected in sterile containers for macroscopic/microscopic examination by an experienced laboratory technologist. RESULTS: A total of 173 school-going children participated in the study. Parasitic eggs were detected in six specimens with prevalence of 3.47 %, which was strongly associated with presence of microscopic red blood cells (p < 0.01) and washing clothes in a stream (p = 0.01). CONCLUSION: Low prevalence of urogenital schistosomiasis among school-going children was noted with correlates such as washing in a stream, while an older age group showed much stronger disease association.

Stakeholders' Perspectives on the Application of New Diagnostic Devices for Urinary Schistosomiasis in Oyo State, Nigeria: A Q-Methodology Approach.

Urinary schistosomiasis is a waterborne parasitic infection caused by Schistosoma haematobium that affects approximately 30 million people annually in Nigeria. Treatment and eradication of this infection require effective diagnostics. However, current diagnostic tests have critical shortcomings and consequently are of limited value to stakeholders throughout the health care system who are involved in targeting the diagnosis and subsequent control of schistosomiasis. New diagnostic devices that fit the local health care infrastructure and support the different stakeholder diagnostic strategies remain a critical need. This study focuses on understanding, by means of Q-methodology, the context of use and application of a new diagnostic device that is needed to effectively diagnose urinary schistosomiasis in Oyo State, Nigeria. Q-methodology is a technique that investigates subjectivity by exploring how stakeholders rank-order opinion statements about a phenomenon. In this study, 40 statements were administered to evaluate stakeholder perspectives on the context of use and application of potential new diagnostic devices and how these perspectives or viewpoints are shared with other stakeholders. Potential new diagnostic devices will need to be deployable to remote or distant communities, be affordable, identify and confirm infection status before treatment in patients whose diagnosis of urinary schistosomiasis is based on self-reporting, and equip health care facilities with diagnostic devices optimized for the local setting while requiring local minimal infrastructural settings. Similarly, the context of use and application of a potential new diagnostic device for urinary schistosomiasis is primarily associated with the tasks stakeholders throughout the health care system perform or procedures employed. These findings will guide the development of new diagnostic devices for schistosomiasis that match the contextual landscape and diagnostic strategies in Oyo.

Urinary Bladder Schistosomiasis Mimicking Neoplasm: A Case Report.

Schistosomiasis is a neglected disease that is prevalent in tropical and subtropical areas. A 20-year-old woman presented to the emergency room with a history of right flank pain and lower abdominal discomfort for one day, which coincided with the onset of menses. The patient did not provide any history of premenstrual hematuria. The physical examination revealed right costovertebral angle tenderness and was otherwise unremarkable. The urinalysis demonstrated a mild increase in red and white blood cells and no ova or parasite. The blood test was normal, except for eosinophilia. A right pedunculated intraluminal urinary bladder mass was detected by the computerized axial tomographic scan and ultrasonography, and after the transurethral resection of the mass, the patient was diagnosed with urinary schistosomiasis. The patient received two doses of oral praziquantel of 1200 mg every 12 h for one day. The cure was confirmed with a one-month post-treatment follow-up that revealed a normal urine microscope and eosinophil count. The S. haematobium infection should be evaluated as a possible cause of urinary bladder lesion in those who have travelled or lived in endemic areas.

Transmission and diversity of Schistosoma haematobium and S. bovis and their freshwater intermediate snail hosts Bulinus globosus and B. nasutus in the Zanzibar Archipelago, United Republic of Tanzania.

BACKGROUND: The Zanzibar Archipelago (Pemba and Unguja islands) is targeted for the elimination of human urogenital schistosomiasis caused by infection with Schistosoma haematobium where the intermediate snail host is Bulinus globosus. Following multiple studies, it has remained unclear if B. nasutus (a snail species that occupies geographically distinct regions on the Archipelago) is involved in S. haematobium transmission on Zanzibar. Additionally, S. haematobium was thought to be the only Schistosoma species present on the Zanzibar Archipelago until the sympatric transmission of S. bovis, a parasite of ruminants, was recently identified. Here we re-assess the epidemiology of schistosomiasis on Pemba and Unguja together with the role and genetic diversity of the Bulinus spp. involved in transmission. METHODOLOGY/PRINCIPAL FINDINGS: Malacological and parasitological surveys were conducted between 2016 and 2019. In total, 11,116 Bulinus spp. snails were collected from 65 of 112 freshwater bodies surveyed. Bulinus species identification were determined using mitochondrial cox1 sequences for a representative subset of collected Bulinus (n = 504) and together with archived museum specimens (n = 6), 433 B. globosus and 77 B. nasutus were identified. Phylogenetic analysis of cox1 haplotypes revealed three distinct populations of B. globosus, two with an overlapping distribution on Pemba and one on Unguja. For B. nasutus, only a single clade with matching haplotypes was observed across the islands and included reference sequences from Kenya. Schistosoma haematobium cercariae (n = 158) were identified from 12 infected B. globosus and one B. nasutus collected between 2016 and 2019 in Pemba, and cercariae originating from 69 Bulinus spp. archived in museum collections. Schistosoma bovis cercariae (n = 21) were identified from seven additional B. globosus collected between 2016 and 2019 in Pemba. By analysing a partial mitochondrial cox1 region and the nuclear ITS (1-5.8S-2) rDNA region of Schistosoma cercariae, we identified 18 S. haematobium and three S. bovis haplotypes representing populations associated with mainland Africa and the Indian Ocean Islands (Zanzibar, Madagascar, Mauritius and Mafia). CONCLUSIONS/SIGNIFICANCE: The individual B. nasutus on Pemba infected with S. haematobium demonstrates that B. nasutus could also play a role in the local transmission of S. haematobium. We provide preliminary evidence that intraspecific variability of S. haematobium on Pemba may increase the transmission potential of S. haematobium locally due to the expanded intermediate host range, and that the presence of S. bovis complicates the environmental surveillance of schistosome infections.

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.

Nuclear genome of Bulinus truncatus, an intermediate host of the carcinogenic human blood fluke Schistosoma haematobium.

Some snails act as intermediate hosts (vectors) for parasitic flatworms (flukes) that cause neglected tropical diseases, such as schistosomiases. Schistosoma haematobium is a blood fluke that causes urogenital schistosomiasis and induces bladder cancer and increased risk of HIV infection. Understanding the molecular biology of the snail and its relationship with the parasite could guide development of an intervention approach that interrupts transmission. Here, we define the genome for a key intermediate host of S. haematobium-called Bulinus truncatus-and explore protein groups inferred to play an integral role in the snail's biology and its relationship with the schistosome parasite. Bu. truncatus shared many orthologous protein groups with Biomphalaria glabrata-the key snail vector for S. mansoni which causes hepatointestinal schistosomiasis in people. Conspicuous were expansions in signalling and membrane trafficking proteins, peptidases and their inhibitors as well as gene families linked to immune response regulation, such as a large repertoire of lectin-like molecules. This work provides a sound basis for further studies of snail-parasite interactions in the search for targets to block schistosomiasis transmission.

Chromosome-level genome of Schistosoma haematobium underpins genome-wide explorations of molecular variation.

Urogenital schistosomiasis is caused by the blood fluke Schistosoma haematobium and is one of the most neglected tropical diseases worldwide, afflicting > 100 million people. It is characterised by granulomata, fibrosis and calcification in urogenital tissues, and can lead to increased susceptibility to HIV/AIDS and squamous cell carcinoma of the bladder. To complement available treatment programs and break the transmission of disease, sound knowledge and understanding of the biology and ecology of S. haematobium is required. Hybridisation/introgression events and molecular variation among members of the S. haematobium-group might effect important biological and/or disease traits as well as the morbidity of disease and the effectiveness of control programs including mass drug administration. Here we report the first chromosome-contiguous genome for a well-defined laboratory line of this blood fluke. An exploration of this genome using transcriptomic data for all key developmental stages allowed us to refine gene models (including non-coding elements) and annotations, discover 'new' genes and transcription profiles for these stages, likely linked to development and/or pathogenesis. Molecular variation within S. haematobium among some geographical locations in Africa revealed unique genomic 'signatures' that matched species other than S. haematobium, indicating the occurrence of introgression events. The present reference genome (designated Shae.V3) and the findings from this study solidly underpin future functional genomic and molecular investigations of S. haematobium and accelerate systematic, large-scale population genomics investigations, with a focus on improved and sustained control of urogenital schistosomiasis.

Dynamics in Morbidity Markers and Cytological Observations Made in Urine of Schistosoma haematobium-Infected Children: Pre- and Post-Praziquantel Treatment in an Endemic Setting.

BACKGROUND: Schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. Morbidity markers and cytological observations such as squamous metaplastic cells, inflammatory cells, and hyperkeratotic cells in the urine of S. haematobium-infected children may suggest disease severity. They may also help predict severe forms of clinical presentation, such as bladder cancer in later years, among infected ones who miss out on early detection and treatment. Insights into possible changes in the morbidity markers and cytological observations in the urine of these S. haematobium-infected children before and after treatment would be of high clinical importance. AIM: The aim of this study was to identify changes/dynamics in morbidity markers and cytological abnormalities in the urine deposits of S. haematobium-infected children, pre- and post-praziquantel treatment. METHODOLOGY: This was a longitudinal study involving baseline and follow-up sampling among basic school children living in schistosomiasis-endemic communities. Urine samples were collected from 520 children at baseline and examined for S. haematobium ova by microscopy, while urine chemistry analyses were used for the examination of morbidity markers. The cytological analyses involved cytopathological examination of the urine deposits. Children whose urine showed positivity for S. haematobium eggs were treated with a single oral dose of praziquantel (40 mg/kg), after which urine chemistry and cytological analyses were repeated weekly for comparison with baseline, until the eighth week. RESULTS: Morbidity markers such as hematuria, proteinuria, and leukocyturia were detected both at baseline and post-treatment among the infected children (30/520). Hematuria was the predominant parameter (90%, 27/30) detected at baseline, followed by proteinuria (53.3%, 16/30). Leukocyturia was the rarest parameter detected at baseline (13.3%, 4/30). However, almost all these parameters declined gradually post-treatment. Regarding cytological analyses, inflammatory cells were observed most (70.0%, 21/30) at baseline. For hyperkeratotic cells and squamous metaplastic cells, 46.7% and 26.7% were respectively observed at baseline, all of which gradually declined during the weekly follow-ups. Notably, squamous metaplastic cells persisted in all the participants from Week 1 through Week 3 post-treatment, but declined gradually thereafter. CONCLUSIONS: Morbidity markers and cytological observations in the children gradually decreased after treatment. Therefore, we continue to recommend routine cytological screening for urogenital schistosomiasis patients at hospitals in S. haematobium-endemic locations using both baseline and follow-up samples to detect these abnormalities early and monitor changes that may be occurring after treatment. Such changes may be useful in assessing treatment progress in infected persons.

Urogenital schistosomiasis outbreak in a basic school, Volta Region, Ghana: a case-control study.

Introduction: schistosomiasis is a neglected parasitic infection caused by nematode worms. It affects approximately 200 million people globally. Prevalence in Ghana is 23.3%, mostly affecting school children. On November 28th 2018, the Disease Surveillance Department received reports of increase in occurrence of bloody urine among students of a basic school in the Volta Region. We investigated to identify the agent and source, to determine the magnitude, risk factors and to implement control measures. Methods: we conducted a case-control study. A suspected case was any student of the school, who has bloody urine with or without: dysuria, itching of the skin, frequent urination or lower abdominal pain from September 2018 to November 2018. A confirmed case was one with laboratory-isolation of Schistosoma ova in appropriate urine sample. We identified cases from the school and hospital records. We collected socio-demographic, clinical and exposure data from cases and controls. Descriptive and inferential analysis were performed to estimate odds ratios at 95% confidence intervals (CI) to determine associations. Results: of 880 students, 112 suspected cases were identified (attack rate = 12.7%). Mean age of suspected cases was 14-years (standard deviation = ±3.5). Confirmed cases were 76.8%(86/112). Males had twice odds of becoming cases (cOR = 2.3, 95% CI = 1.35-3.96). Fishing (cOR = 7.29, 95% CI = 4.08-13.04) and swimming (aOR = 44.63, 95% CI = 4.73-420.86) were factors significantly associated with infection. Students with previous history of bloody urine had greater odds of being cases (aOR = 47.9, 95% CI = 4.19-546.55). Conclusion: Schistosoma haematobium was isolated in this outbreak. Fishing and swimming were risky water-related activities. WASH education and mass drug administration with Praziquantel were control measures.

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.

Association between cervical dysplasia and female genital schistosomiasis diagnosed by genital PCR in Zambian women.

BACKGROUND: Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium, a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. METHODS: Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18-31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. RESULTS: VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58-23.37, P = 0.02). CONCLUSIONS: This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed.

Molecular approach to the epidemiology of urinary schistosomiasis in France.

BACKGROUND: The diagnosis of urogenital schistosomiasis is based on the complementarity of serological technique and microscopic examination (ME). Between 2015 and 2019, the number of urinary schistosomiasis tests received in our laboratory increased sharply from 300 to 900 per year. Therefore, we wanted to evaluate the reliability of urine microscopic examination (ME, reference and routine technique) from urine sample by comparing it to other techniques (antigenic technique and PCR). To this end, we optimized two real-time PCRs targeting respectively Schistosoma haematobium (Sh) and Schistosoma mansoni (Sm). METHODOLOGY/PRINCIPAL FINDINGS: 914 urine samples from 846 patients suspected of urogenital schistosomiasis were prescribed and analyzed by PCR and also by antigenic technique for the first 143 samples. The antigenic technique evaluated was Schisto POC-CCA, Rapid Medical Diagnostics. These results (antigenic technique and PCR) were compared to ME which was performed from all urines. The percentage of 14% (128/914) positive cases with the PCR technique and the percentage of 6.0% (54/914) positive cases with ME is significantly different (Chi 2 test, p<0.001). These 128 positive PCRs correspond to 120 different patients, 88.3% (106/120) of them were young migrants and 11.7% (14/120) were French patients returning from travel. Among these migrants, more than 75% (80/106) came from French-speaking West Africa. In addition, the Schisto POC-CCA showed a specificity of 39% (46/117), too poor to be used as a screening tool in low or non-endemic areas. CONCLUSION/SIGNIFICANCE: Targeted Sh and Sm PCRs in urine are reliable techniques compared to ME (reference technique). In view of our results, we decided to screen urinary schistosomiasis by direct ME always coupled by the PCR technique, which has shown better reliability criteria.

Immunomics-Guided Antigen Discovery for Praziquantel-Induced Vaccination in Urogenital Human Schistosomiasis.

Despite the enormous morbidity attributed to schistosomiasis, there is still no vaccine to combat the disease for the hundreds of millions of infected people. The anthelmintic drug, praziquantel, is the mainstay treatment option, although its molecular mechanism of action remains poorly defined. Praziquantel treatment damages the outermost surface of the parasite, the tegument, liberating surface antigens from dying worms that invoke a robust immune response which in some subjects results in immunologic resistance to reinfection. Herein we term this phenomenon Drug-Induced Vaccination (DIV). To identify the antigenic targets of DIV antibodies in urogenital schistosomiasis, we constructed a recombinant proteome array consisting of approximately 1,000 proteins informed by various secretome datasets including validated proteomes and bioinformatic predictions. Arrays were screened with sera from human subjects treated with praziquantel and shown 18 months later to be either reinfected (chronically infected subjects, CI) or resistant to reinfection (DIV). IgG responses to numerous antigens were significantly elevated in DIV compared to CI subjects, and indeed IgG responses to some antigens were completely undetectable in CI subjects but robustly recognized by DIV subjects. One antigen in particular, a cystatin cysteine protease inhibitor stood out as a unique target of DIV IgG, so recombinant cystatin was produced, and its vaccine efficacy assessed in a heterologous Schistosoma mansoni mouse challenge model. While there was no significant impact of vaccination with adjuvanted cystatin on adult worm numbers, highly significant reductions in liver egg burdens (45-55%, P<0.0001) and intestinal egg burdens (50-54%, P<0.0003) were achieved in mice vaccinated with cystatin in two independent trials. This study has revealed numerous antigens that are targets of DIV antibodies in urogenital schistosomiasis and offer promise as subunit vaccine targets for a drug-linked vaccination approach to controlling schistosomiasis.

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.