Schistosomiasis Research Articles

Impact of chemical snail control on intermediate host snail populations for urogenital schistosomiasis elimination in Pemba, Tanzania: findings of a 3-year intervention study.

The World Health Organization (WHO) has set the goal of eliminating schistosomiasis as a public health problem globally by 2030 and to interrupt transmission in selected areas. Chemical snail control is one important measure to reduce transmission and achieve local elimination. We aimed to assess the impact of several rounds of chemical snail control on the presence and number of the Schistosoma haematobium intermediate snail host (Bulinus spp.) in water bodies (WBs) on Pemba Island, Tanzania, a setting targeted for elimination of urogenital schistosomiasis. During the three annual intervention periods of the SchistoBreak study implemented in the north of Pemba from 2020 to 2024, malacological surveys were conducted up to four times per period in WBs of hotspot implementation units (IUs). Present freshwater snail species, vegetation, and WB characteristics were recorded. If Bulinus were found, the snails were inspected for Schistosoma infection and snail control with niclosamide was conducted. Across the three intervention periods, a total of 112 WBs were identified in 8 hotspots IUs. The spatial distribution of WBs with Bulinus per IU was heterogeneous, ranging from 0.0% (0/15) of WBs infested in one IU in 2022 to 80.0% (8/10) of WBs infested in one IU in 2021. Bulinus presence was significantly associated with lower pH values in WBs (odds ratio: 0.2, 95% confidence interval 0.1-0.4). A total of 0.2% (6/2360) of collected Bulinus were shedding Schistosoma cercariae. Following snail control, the number of Bulinus decreased or remained absent in 56.7% (38/67) of visits at WBs when compared with the previous visit in 2021, 54.9% (28/51) in 2022, and 33.3% (32/96) in 2023. In a total of 43.1% (22/55) of initially infested WBs, no Bulinus were found in the survey round conducted a few weeks after the first application of niclosamide. However, 25.4% (14/55) of WBs showed a pattern of recurring Bulinus presence. The distribution of WBs containing Bulinus was very heterogeneous. The percentage of Bulinus with patent Schistosoma infection in our study area was extremely low. Repeated niclosamide application reduced the number of Bulinus in WBs, but snails often recurred after one or multiple treatments. While chemical mollusciciding can reduce snail numbers, to fully break the S. haematobium transmission cycle, timely diagnosis and treatment of infected humans, access to clean water, sanitation, and health communication remain of prime importance. ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493.

Effect of preventive chemotherapy for neglected tropical diseases in Indonesia from 1992 to 2022: A systematic review and meta-analysis.

This study aimed to describe the prevalence of lymphatic filariasis (LF), soil-transmitted helminthiasis (STH) and schistosomiasis (SC) in Indonesia before and after PC implementation through a systematic review and meta-analysis. Embase, MEDLINE, PubMed, Scopus, Web of Science and Google Scholar were searched for articles published between 1 January 1992 and 31 December 2022, reporting LF, STH and SC in Indonesia. Using the Ministry of Health lists of districts receiving PC programs, we identified whether data collection was conducted before or after PC implementation in that particular district. A meta-analysis was performed with a random-effects model applied to pool pre- and post-PC prevalence of LF, STH and SC. Overall, 195 studies were included. The pooled prevalence of LF was 9.72% (95% CI, 5.56%-13.87%). The pre-PC pooled prevalence of LF was 11.48% (95% CI, 5.52%-17.45%). The prevalence decreased after PC implementation, and the pooled prevalence was 7.12% (95% CI, 1.79%-12.44%). The overall prevalence of STH was 35.16% (95% CI, 30.36%-39.96%). The pre-PC prevalence of STH was 36.29% (95% CI, 30.37%-42.20%). The post-PC prevalence of STH decreased at 31.93% (95% CI, 24.25%-39.62%), although the difference between before and after PC was not significant (p = 0.379). Only nine studies investigated the prevalence of SC; based on the random-effects model, the pooled prevalence was 21.90% (95% CI, 4.88%-38.92%). Owing to the scarcity of studies, we could not perform the funnel tests for publication bias and moderating variables of the pooled prevalence for SC. The prevalence of LF and STH decreased after PC implementation, although it was not significant. The difference for SC could not be assessed because of limited post-PC data. The uneven distribution of research and the lack of standardised sampling methods may not fully capture the situation.

One-year impact of behavioural interventions on schistosomiasis-related knowledge, attitude and practices of primary schoolchildren in Pemba, Tanzania

BackgroundElimination of schistosomiasis as a public health problem and interruption of transmission in selected areas are goals set by the World Health Organization for 2030. Behaviour change communication (BCC), coupled with other interventions, is considered an essential measure to reduce the transmission of Schistosoma infection. Focusing on elimination, we assessed the 1-year impact of BCC interventions on schistosomiasis-related knowledge, attitude and practices (KAP) of schoolchildren in hotspot schools versus low-prevalence schools that did not receive the interventions.MethodsSchool-based cross-sectional surveys were implemented in 16 schools on Pemba Island, Tanzania, in 2020 and 2022, respectively. The schistosomiasis-related KAP were assessed in children attending grades 3–5, using pre-tested questionnaires. Between the surveys, in 2021, children from hotspot schools were exposed to BCC interventions. The difference in mean knowledge and attitude scores, respectively, between schoolchildren from hotspot and low-prevalence schools during the survey in 2022 was determined with a linear mixed-effect model.ResultsIn the five hotspot schools that received BCC interventions, 315 children participated in the survey in 2020 and 349 in 2022. There was a 21.0% increase in children with moderate knowledge and a 13.8% decrease in no knowledge; a 8.3% increase in good attitude and a 19.2% decrease in poor attitude; 3.4% and 3.2% fewer children reported to use waterbodies for washing clothes or body, respectively. In the 11 low-prevalence schools without BCC interventions, 778 children participated in 2020 and 732 in 2022. The percentage of children with poor knowledge (56.4% and 63.1%) and poor attitude (55.3% and 53.1%) remained relatively stable from 2020 to 2022, but 4.9% and 3.0% less children reported to use waterbodies for washing clothes or their body, respectively. In 2022, the difference in mean knowledge scores was 0.8 [95% confidence interval (CI): 0.5−1.1] and the difference in mean attitude scores was 0.6 (95% CI: 0.4−0.7) between children in hotspot compared with low-prevalence schools.ConclusionsAfter one year of implementation, the BCC interventions markedly improved the KAP of exposed children. Complemented by improved access to clean water and sanitation, BCC holds promise to contribute successfully to the achievement of schistosomiasis control and elimination targets.Trial registration ISRCTN, ISRCTN91431493. Registered 11 February. 2020, https://www.isrctn.com/ISRCTN91431493.Graphical

Awareness and knowledge about Female Genital Schistosomiasis among European healthcare workers

Abstract Background Female Genital Schistosomiasis (FGS) is a gynaecological manifestation of persistent infection with Schistosoma haematobium, which can lead to severe consequences, such as miscarriage and infertility. It is estimated to affect 56 million women globally, mostly in sub-Saharan Africa (SSA). Most migrants in Europe are female, often from SSA and therefore at risk of FGS, hence healthcare workers (HCWs) knowledge of FGS is essential for the provision of adequate care. This study aims to assess awareness and knowledge of FGS among European HCWs to inform strategies to improve the management of migrant health. Methods In June 2023 - January 2024 we conducted a cross-sectional online survey targeting medical doctors (MDs), nurses and midwives (NMs) working in fields of infectiology, gynaecology, urology, family, travel, internal or occupational medicine. The prevalence of FGS awareness and knowledge was estimated, Poisson regression was used to identify factors associated with MDs’ awareness of FGS. Results Among 922 surveyed HCWs, 43.7% (CI95%: 39.6-47.9) of MDs and 12.0% (CI95%: 8.8-16.0) NMs have heard about FGS. FGS awareness among MDs was associated with work in clinics for migrants (prevalence ratio (PR)=1.33, CI95%: 1.10-1.59) and specialization, being lower for gynaecology (PR = 0.67; CI95%:0.51-0.88), and family medicine (PR = 0.42, CI95%:0.30-0.59). Among MDs, 7.1% (CI95%: 5.1- 9.5) had medium knowledge, while 25.3% (CI95%: 21.8-29.0) had low, and 67.6% (CI95%: 63.7-71.4) no knowledge on symptoms, complications or diagnostic tools for FGS. FGS knowledge was mostly acquired through academic curricula (34.7%), scientific literature (28.4%) and conferences (25.6%). Conclusions The study shows limited awareness of FGS among European MDs and NMs, and highlights that European HCWs may not be adequately prepared to deal with diseases that are gaining relevance on the European continent due to the global connectivity and the dynamic nature of our societies. Key messages • In Europe, the health specialities that are the first point of patient access to the health system show a low level of awareness and knowledge of Female Genital Schistosomiasis. • Rising knowledge of FGS among European HCWs through academic curricula and continuous medical education is important to ensure adequate diagnosis and management of disease in migrant populations.

Single-Cell Analysis Reveals the Cellular and Molecular Changes of Liver Injury and Fibrosis in Mice During the Progression of Schistosoma japonicum Infection.

Schistosomiasis is a parasitic disease that poses a serious threat to human health. However, the pathogenic mechanism during the progression of Schistosoma japonicum infection remains unclear. In order to elucidate this mechanism, we used single-cell RNA sequencing (scRNA-seq) to investigate the transcriptome characteristics of the cellular (single-cell) landscape in the livers of mice infected with Schistosoma japonicum, which were divided into three groups: uninfected mice (0 week (w)), infected mice at 6 w post-infection (the acute phase), and infected mice at 10 w post-infection (the chronic phase). A total of 31,847 liver cells were included and clustered into 21 groups. The cells and T-cells had high heterogeneity in the liver during the progression of schistosome infection. The number and intensity of the intercellular interactions significantly increased at 6 w after infection but decreased at 10 w. The inflammatory signaling pathways chemoattractant cytokine ligand (CCL)5-chemokine C-C-motif receptor (CCR)5 between macrophages and T-cells were predominant at 6 w post-infection; the CCL6-CCR2 signaling pathway between macrophages was predominant at 10 w. The CD80 signaling pathway related to T-cell activation was increased at 6 w after infection, and increased expression of its receptor CD28 on the surfaces of CD4+ and CD8+ T-cells was confirmed by flow cytometry, suggesting an increase in their activation. In addition, scRNA-seq and quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the intercellular communication between secretory phosphoprotein 1 (SPP1)-cluster of differentiation (CD44), insulin-like growth factor (IGF)-1-IGF1r and visfatin-insulin receptor (Insr) associated with bone metabolism and insulin metabolism was increased and enhanced in the liver at 6 w post-infection. Overall, we provide the comprehensive single-cell transcriptome landscape of the liver in mice during the progression of schistosome infection and delineate the key cellular and molecular events involved in schistosome infection-induced liver injury and fibrosis. The elevated CCL5-CCR5 and CCL6-CCR2 signaling pathways in the liver may be a drug target for liver injury and fibrosis caused by schistosome infection, respectively.

Schistosomiasis-Microbiota Interactions: A Systematic Review and Meta-Analysis.

Schistosomiasis, a tropical disease affecting humans and animals, affected 251.4 million people in 2021. Schistosoma mansoni, S. haematobium, S. intercalatum, and S. japonicum are primary human schistosomes, causing tissue damage, granulomas, ulceration, hemorrhage, and opportunistic pathogen entry. The gut and urinary tract microbiota significantly impact a host's susceptibility to schistosomiasis, disrupting microbial balance; however, this relationship is not well understood. This systematic review and meta-analysis explores the intricate relationship between schistosomiasis and the host's microbiota, providing crucial insights into disease pathogenesis and management. This systematic review used PRISMA guidelines to identify peer-reviewed articles on schistosomiasis and its interactions with the host microbiome, using multiple databases and Google Scholar, providing a robust dataset for analysis. The study utilized Meta-Mar v3.5.1; descriptive tests, random-effects models, and subgroups were analyzed for the interaction between Schistosomiasis and the microbiome. Forest plots, Cochran's Q test, and Higgins' inconsistency statistic (I2) were used to assess heterogeneity. The human Schistosoma species were observed to be associated with various bacterial species isolated from blood, stool, urine, sputum, skin, and vaginal or cervical samples. A meta-analysis of the interaction between schistosomiasis and the host microbiome, based on 31 studies, showed 29,784 observations and 5871 events. The pooled estimates indicated a significant association between schistosomiasis and changes in the microbiome of infected individuals. There was considerable heterogeneity with variance effect sizes (p < 0.0001). Subgroup analysis of Schistosoma species demonstrated that S. haematobium was the most significant contributor to the overall heterogeneity, accounting for 62.1% (p < 0.01). S. mansoni contributed 13.0% (p = 0.02), and the coinfection of S. haematobium and S. mansoni accounted for 16.8% of the heterogeneity (p < 0.01), contributing to the variability seen in the pooled analysis. Similarly, praziquantel treatment (RR = 1.68, 95% CI: 1.07-2.64) showed high heterogeneity (Chi2 = 71.42, df = 11, p < 0.01) and also indicated that Schistosoma infections in males (RR = 1.46, 95% CI: 0.00 to 551.30) and females (RR = 2.09, 95% CI: 0.24 to 18.31) have a higher risk of altering the host microbiome. Schistosomiasis significantly disrupts the host microbiota across various bodily sites, leading to increased susceptibility to different bacterial taxa such as E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Staphylococcus, Streptococcus, and Mycobacterium species (M. tuberculosis and M. leprae). This disruption enables these bacteria to produce toxic metabolites, which in turn cause inflammation and facilitate the progression of disease. The impact of schistosomiasis on the vaginal microbiome underscores the necessity for gender-specific approaches to treatment and prevention. Effective management of female genital schistosomiasis (FGS) requires addressing both the parasitic infection and the resulting microbiome imbalances. Additionally, praziquantel-treated individuals have different microbiome compositions compared to individuals with no praziquantel treatment. This suggests that combining praziquantel treatment with probiotics could potentially decrease the disease severity caused by an altered microbiome.

Rectal Schistosomiasis and Adenocarcinoma

Abstract Introduction/Objective Schistosoma infestation has been implicated by the International Agency for Research on Cancer as an etiology for several cancers such as colon, liver, and bladder. S. japonicum is classified as a probable carcinogen in humans (class 2B). These trematodes may cause chronic infection in the affected organ leading to the trend of “inflammation-adenoma-carcinoma”. There is rising evidence that infection with Schistosoma japonicum is correlated with the liver and colorectal carcinoma in endemic Asian countries. We herein present a case of rectal adenocarcinoma associated with Schistosoma as a possible causal factor. Methods/Case Report An 88-year-old-woman from China, currently living in United States for past six years, presented with rectal bleeding. Colonoscopy showed evidence of a rectosigmoid mass 2.2 x 1.0 x 0.3 cm. She underwent trans-anal excision of the tumor. Microscopic examination showed moderately differentiated adenocarcinoma with tumor invading the muscularis propria (pT2). There were numerous oval / round calcified eggs (30 - 46 microns) with minute subterminal or no spine morphologically consistent with Schistosoma japonicum associated with granulomatous and foreign body giant cell reaction, fibrosis, and tissue eosinophilia. She was treated with Praziquantel and is currently undergoing endoscopic surveillance for recurrence. Results (if a Case Study enter NA) N/A Conclusion Patients with chronic Schistosoma japonicum infection have 3 times increased risk of developing colorectal cancer than those with no previous exposure to schistosomal infection. We believe that chronic S. japonicum infection is the likely etiology of rectal cancer in our patient. Physicians should be aware of such associations, especially for immigrants from endemic areas, to facilitate accurate diagnosis and management.

Mammary Schistosomiasis: Malignancy Mimicker or More?

Abstract Introduction/Objective Schistosomiasis is a neglected tropical disease (NTD) which affects more than 200 million people worldwide, with approximately 85% of cases occurring in sub-Saharan Africa. It serves both as an important etiologic agent in the development of carcinomas of many organ systems, as well as a common incidental histological finding in various organs, including the prostate, lung, spine, and liver. Detection of Schistosoma ova in the breast is rare. Here, we present a case of schistosomiasis of the breast in a patient concurrently diagnosed with breast carcinoma of the contralateral breast. Methods/Case Report A 48-year-old Mozambican female presented with a right breast mass, with suspicious microcalcifications detected in the contralateral breast on mammography. Biopsy confirmed invasive ductal carcinoma of no special type (NST) in the right breast and identified Schistosoma ova in the left, notably lacking an associated inflammatory response. A Ziehl-Neelsen special histochemical stain was negative, favoring schistosoma Hematobium species. Results (if a Case Study enter NA) NA Conclusion Our case marks the first in English literature where schistosomiasis was identified in the context of contralateral breast carcinoma, posing the question as to whether there is an association between schistosomiasis and breast carcinoma in our patient. One possible theory suggests hyperestrogenism secondary to Schistosoma infection in the liver. Breast schistosomiasis presenting as microcalcifications poses a diagnostic challenge, as it may clinically and radiologically resemble malignant breast disease. Histopathological diagnosis is crucial to confirm the diagnosis and prevent unnecessary procedures. Contrary to other organ systems, our case highlighted that schistosomiasis in the breast may not be accompanied by any inflammatory response. Definitive conclusions regarding the exact species of schistosomiasis cannot be drawn histologically based solely on H&amp;E findings due to the plane of sectioning; therefore, performing a Ziehl-Neelsen stain is beneficial. As screening mammography increases in endemic areas, a high index of suspicion and further research is warranted.

A holistic approach to address female genital schistosomiasis in Ghana and Madagascar: the FGS Accelerated Scale Together Package

Women and girls who have been infected with the blood fluke Schistosoma haematobium can experience the chronic form of urogenital schistosomiasis, called female genital schistosomiasis (FGS). Some FGS symptoms resemble sexually transmitted infections. As a result, women and girls seeking treatment are often misdiagnosed and stigmatized. The FGS Accelerated Scale Together (FAST) Package project implemented a holistic approach to address FGS combining proven interventions in training, mass drug administration, diagnosis, and treatment as well as community awareness to address FGS in four selected districts in Ghana and Madagascar. The FAST Package was supported by an FGS National Committee who provided guidance on integration at the national level. Using an implementation research design, researchers worked closely with government counterparts in the programs for neglected tropical diseases in both countries. Baseline cross-sectional surveys and qualitative methodologies collected information on schistosomiasis and FGS awareness, experience with health seeking behaviors and knowledge of schistosomiasis prevention amongst community members and teachers. FAST Package interventions included healthcare provider training delivered in online and in person formats; development of an Educators’ booklet to support schistosomiasis/FGS awareness creation among teachers, healthcare providers and community members; suspected FGS case detection; and advocacy for the provision of praziquantel in the primary health care system. Endline results included a cross-sectional survey and qualitative methodologies amongst community members and teachers, including Photovoice for women of reproductive health age exposed to FGS. This paper presents a description of the FAST Package project, the value of its holistic approach, and selected results from both countries. It discusses the lessons learnt highlighting some of the challenges and opportunities for integration within the health system.

Potential associations between Schistosoma mansoni infection and physico-chemical characteristics and water-related human activities in Côte d'Ivoire: a cross-sectional study.

Schistosomiasis remains a public health problem, particularly in sub-Saharan Africa. The disease is intimately connected to poverty and environmental factors. Our research was readily embedded into a multi-country schistosomiasis oversampling study. The aim of the study presented here was to determine the prevalence of Schistosoma mansoni and to investigate the role of water body characteristics and water-related human activities in disease transmission. In August and September 2022, a cross-sectional study was conducted in the western part of Côte d'Ivoire. Stool and urine samples were collected from 1602 and 1729 children aged 5-14years, respectively, in 65 villages in the health districts of Biankouma, Ouaninou and Touba. Additionally, data were collected from direct observation of water-related activities at water bodies and interviews conducted with community leaders and health workers. The prevalence and risk factors for Schistosoma infection were assessed using generalised estimating equation models. The prevalence ofS.mansoni and S.haematobium were 27.4% (95% confidence interval [CI] 21.5-34.3%) and 0.1% (95% CI 0.03-0.5%), respectively. Low prevalence of soil-transmitted helminths was observed with 2.4%, 0.4% and 0.2% for hookworm, Trichuris trichiura and Ascaris lumbricoides, respectively. At the health district level, we found S.mansoni prevalence of 34.4% (95% CI 25.0-45.3%), 34.3% (95% CI 24.0-46.2%) and 16.3% (95% CI 9.5-26.6%) for Biankouma, Ouaninou and Touba, respectively. Female and male participants were at a similar risk of infection (29.0% vs. 26.0%, odds ratio [OR]: 1.18, 95% CI 0.92-1.50). Children aged 9-14years showed a higher prevalence than their younger counterparts aged 5-8years (34.5% vs. 22.7%, OR: 1.80, 95% CI 1.42-2.27). High infection prevalence was observed in villages where children were washing clothes and dishes at open surface water sites and pursued recreational activities (e.g. swimming and playing in the water). The temperature, total dissolved solids and pH of water samples showed no significant association with S.mansoni infection at the village unit. Human water-related activities such as washing clothes and playing in the water are risk factors for S.mansoni transmission. Hence, preventive chemotherapy should be combined with information, education and communication to avoid or reduce the frequency of water exposure in children as part of a comprehensive package of interventions towards elimination of schistosomiasis as a public health problem.

Sex as a biological variable in HIV-1 and schistosome co-infection.

The sex of people living with HIV-1 infection, schistosome infection, or both, is a fundamental determinant of their clinical outcomes and of how these two infections interact in the host. Data from longitudinal and cross-sectional human studies and animal models indicate that males with HIV-1 and schistosome co-infection excrete fewer schistosome eggs and might have higher HIV-1 RNA viral loads and greater liver damage. Females with schistosome infection appear to have higher risk of HIV-1 acquisition than females without, particularly in Schistosoma haematobium infection, and a greater risk of death in HIV-1 and schistosome co-infection. Greater transmission of HIV-1 to partners has been shown in both sexes in those with schistosome infection. Biological sex is a consequential factor affecting pathophysiological and clinical responses in HIV-1 and schistosome co-infection. Designing future analyses to incorporate sex is vital to optimise research and care for people living with HIV-1, schistosomes, and HIV-1 and schistosome co-infection.

Epidemiology of periportal fibrosis and relevance of current Schistosoma mansoni infection within the context of repeated mass drug administration in rural Uganda: a population-based, cross-sectional study

WHO guidelines for schistosomiasis-related morbidity control and elimination rely on current infection as a proxy indicator for morbidity. We evaluated these guidelines within the context of repeated mass drug administration and periportal fibrosis attributable to chronic intestinal schistosomiasis. We examined 1442households randomly sampled from 38villages in Buliisa, Pakwach, and Mayuge districts of Uganda within the SchistoTrack cohort. Periportal fibrosis was diagnosed in 2834individuals aged 5-90years using ultrasound and image patterns C-F from the Niamey protocol. Schistosoma mansoni status and intensity were diagnosed by Kato-Katz microscopy and point-of-care circulating cathodic antigen tests. Schistosome infection, co-infections, and comorbidities were examined as exposures for periportal fibrosis. Multivariable logistic regressions were run with SEs clustered by household. Between Jan 6and Feb 3, 2022, 342 (12·1%) of 2834 participants were diagnosed with periportal fibrosis. ByKato-Katz microscopy, 1229 (43·4%) of 2834participants were infected. 1863 (65·7%) of 2834participants had trace positive point-of-care circulating cathodic antigen tests, which was higher than prevalence by Kato-Katz microscopy, and 1158 (40·9%) of 2834participants had trace negative point-of-care circulating cathodic antigen tests. Individual schistosome status, intensity, and prevalence of heavy intensity infections of less than 1% and less than 5% were not correlated with periportal fibrosis likelihood or village prevalence. Periportal fibrosis likelihood linearly increased with age from age 5 years to age 25years, non-linearly increased from age 26 years to age 45years, attenuated or remained unchanged from age 46 years to age 60years, and steadily decreased past 60years of age. History of liver diseases, HIV, and ultrasound-detected chronic hepatitis or early cirrhosis-like disease were associated with more than two-times increased periportal fibrosis likelihood. WHO guidelines reliant on current schistosome status and intensity are uninformative for identifying probable cases or communities with periportal fibrosis. History of HIV and underlying chronic hepatitis or early cirrhosis-like disease are risk factors that could be investigated for periportal fibrosis surveillance and management. NDPH Pump Priming Fund, Wellcome Trust, John Fell Fund, Robertson Foundation, and UK Research and Innovation Engineering and Physical Sciences Research Council.

Combined interventions for the testing and treatment of HIV and schistosomiasis among fishermen in Malawi: a three-arm, cluster-randomised trial

Undiagnosed HIV and schistosomiasis are highly prevalent among fishermen in the African Great Lakes region. We aimed to evaluate the efficacy of lakeside interventions integrating services for HIV and male genital schistosomiasis on the prevalence of schistosomiasis, uptake of antiretroviral therapy (ART) for HIV, and voluntary male medical circumcision (VMMC) among fishermen in Malawi. We conducted a three-arm, cluster-randomised trial in 45 lakeshore fishing communities (clusters) in Mangochi, Malawi. Clusters were defined geographically by their home community as the place where fishermen leave their boats (ie, a landing site). Eligible participants were male fishermen (aged ≥18 years) who resided in a cluster. Clusters were randomly allocated (1:1:1) through computer-generated random numbers to either enhanced standard of care (SOC), which offered invitation with information leaflets to a beach clinic offering HIV testing and referral, and presumptive treatment for schistosomiasis with praziquantel; peer education (PE), in which a nominated fisherman was responsible for explaining the study leaflet to promote services to his boat crew; or peer distribution education (PDE), in which the peer educator explained the leaflet and distributed HIV self-test kits to his boat crew. The beach clinic team and fishermen were not masked to intervention allocation; however, investigators were masked until the final analysis. Coprimary composite outcomes were the proportion of participants who had at least one Schistosoma haematobium egg observed on light microscopy from 10 mL of urine filtrate and the proportion who had self-reported initiating ART or scheduling VMMC by day 28. Outcomes were analysed by intention to treat; multiple imputation for missing outcomes was done; random-effect binomial models adjusting for baseline imbalance and clustering were used to compute unadjusted and adjusted risk differences, risk ratios (RRs) and 95% CIs, and intracluster correlation coefficients for each outcome. This trial is registered with ISRCTN, ISRCTN14354324. Between March 1, 2022, and Jan 29, 2023, 45 (65·2%) of 69 clusters assessed for eligibility were enrolled in the trial, with 15 clusters per arm. Of the 6036 fishermen screened at baseline, 5207 (86·3%) were eligible for participation: 1745 (87·6%) of 1991 in the enhanced SOC group, 1687 (81·9%) of 2061 in the PE group, and 1775 (89·5%) of 1984 in the PDE group. Compared with the prevalence of active schistosomiasis in the enhanced SOC group (292 [16·7%] of 1745), 241 (13·6%) of 1775 fishermen in the PDE group (adjusted RR 0·80 [95% CI 0·69-0·94]; p=0·0054) and 263 (15·6%) of 1687 fishermen in the PE group (0·92 [0·79-1·07]; p=0·28) had schistosomiasis at day 28. 230 (13·2%) in the enhanced SOC group, 281 (16·7%) in the PE group, and 215 (12·1%) in the PDE group initiated ART or were scheduled for VMMC. ART initiation or VMMC scheduling was not significantly increased with the PDE intervention (0·88 [0·74-1·05); p=0·15) and was marginally increased with the PE intervention (1·16 [0·99-1·37]; p=0·069) when compared with the enhanced SOC group. No serious adverse events were reported in this trial. We found weak evidence for the use of peer education to increase uptake of ART and VMMC, but strong evidence for the added distribution of HIV self-test kits to promote high engagement with services and reduce the prevalence of active schistosomiasis, suggesting a high potential for scale-up in hard-to-reach communities across Malawi. Wellcome Trust and the UK National Institute for Health Research.

Seroprevalence of Schistosoma japonicum Infection Among Dogs and Water Buffaloes Using Recombinant Antigen ELISA in New Corella, Davao del Norte, Philippines.

Animal reservoirs are important targets for controlling and eliminating schistosomiasis. Prevalence studies showed that dogs (Canis familiaris) and water buffaloes (Bubalus bubalis) are important reservoirs of S. japonicum. Previous studies have validated the use of the recombinant proteins Sj1TR, Sj7TR, and SjTPx-1 in ELISA as diagnostics for dogs and water buffaloes from schistosomiasis-endemic areas. In this study, we aimed to determine the seroprevalence of S. japonicum among dogs and water buffaloes in New Corella, Davao del Norte, Philippines, using the recombinant proteins Sj1TR, Sj7TR, and SjTPx-1 in ELISA format. Fecal and serum samples were collected from dogs (n = 63) and water buffaloes (n = 57). Schistosome-positive samples were detected using formalin-ether concentration technique (FECT), stool polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) using soluble egg antigen (SEA), rSj1TR, rSj7TR, and rSjTPx-1. Positivity rates, sensitivity, specificity, predictive values, accuracy, and kappa values were calculated. Mean positivity rates for schistosome infection were high for both dogs (x = 15.40%) and water buffaloes (x = 6.32%). On dogs, the sensitivity and specificity of the tests are as follows: 66.67% and 100% for rSj7TR-ELISA, while 100% and 93.33% for rSjTPx-1-ELISA, respectively. rSjTPx-1-ELISA showed the highest agreement with stool PCR among all diagnostic tests, with an overall kappa value of 0.824. On water buffaloes, the sensitivity and specificity of both rSj1TR-ELISA and rSjTPx-1-ELISA are 100.0% and 98.15%. Both tests also had an overall kappa value of 0.84. To ensure elimination and prevention of schistosomiasis in humans, the use of validated serological diagnostics such as recombinant antigen ELISA is preferable for field detection in animals, especially in resource-limited areas.

Breaking the silence of female genital schistosomiasis in Ghana's health system: A case of health workers within the FAST project.

Female Genital Schistosomiasis (FGS) remains a critical and yet neglected topics in Neglected Tropical Diseases (NTDs), significantly affecting the health of women and girls worldwide. Health workers' knowledge of FGS is vital to the prevention and management of the disease. This study adopted an implementation research approach to identify and address the existing knowledge gap regarding FGS among healthcare workers in Ghana. This study was a 3-year (2020-2022) implementation research applying a pragmatic uncontrolled quasi-experimental study design. The study involved a baseline assessment, FGS training intervention for health workers and student nurses, distribution of FGS educational materials, and an endline assessment. A mixed-method approach was applied to data collection involving health workers from two schistosomiasis endemic districts and across the country. NVIVO 12 and STATA 14 were used for qualitative and quantitative data analysis, respectively. Prior to the intervention, the level of awareness about FGS among health workers was less than 8%, and most participants only understood FGS as merely urogenital schistosomiasis in females. In response to this gap, an FGS education intervention in the form of training of health workers, student nurses alongside the distribution of FGS educational materials were carried out. The intervention enhanced health workers' awareness of FGS to more than 61%, encompassing an enhanced understanding of the disease's signs and symptoms to more than 60%, as well as its management strategies. However, access to praziquantel, the primary treatment, remained a significant challenge. The FGS intervention effectively raised healthcare workers' awareness and knowledge. Expanding training and improving praziquantel access are essential for optimal FGS management. A multi-faceted approach involving individuals, communities, and the healthcare system is necessary for comprehensive FGS prevention and control.

Deep humoral profiling coupled to interpretable machine learning unveils diagnostic markers and pathophysiology of schistosomiasis.

Schistosomiasis, a highly prevalent parasitic disease, affects more than 200 million people worldwide. Current diagnostics based on parasite egg detection in stool detect infection only at a late stage, and current antibody-based tests cannot distinguish past from current infection. Here, we developed and used a multiplexed antibody profiling platform to obtain a comprehensive repertoire of antihelminth humoral profiles including isotype, subclass, Fc receptor (FcR) binding, and glycosylation profiles of antigen-specific antibodies. Using Essential Regression (ER) and SLIDE, interpretable machine learning methods, we identified latent factors (context-specific groups) that move beyond biomarkers and provide insights into the pathophysiology of different stages of schistosome infection. By comparing profiles of infected and healthy individuals, we identified modules with unique humoral signatures of active disease, including hallmark signatures of parasitic infection such as elevated immunoglobulin G4 (IgG4). However, we also captured previously uncharacterized humoral responses including elevated FcR binding and specific antibody glycoforms in patients with active infection, helping distinguish them from those without active infection but with equivalent antibody titers. This signature was validated in an independent cohort. Our approach also uncovered two distinct endotypes, nonpatent infection and prior infection, in those who were not actively infected. Higher amounts of IgG1 and FcR1/FcR3A binding were also found to be likely protective of the transition from nonpatent to active infection. Overall, we unveiled markers for antibody-based diagnostics and latent factors underlying the pathogenesis of schistosome infection. Our results suggest that selective antigen targeting could be useful in early detection, thus controlling infection severity.

Methodological assessment for efficient collection of Schistosoma mansoni environmental DNA and improved schistosomiasis surveillance in tropical wetlands

Schistosomiasis, caused by trematodes of genus Schistosoma, is among the most seriously neglected tropical diseases. Although rapid surveillance of risk areas for Schistosoma transmission is vital to control schistosomiasis, the habitat and infection status of this parasite are difficult to assess. Environmental DNA (eDNA) analysis, involving the detection of extra-organismal DNA in water samples, facilitates cost-efficient and sensitive biomonitoring of aquatic environments and is a promising tool to identify Schistosoma habitat and infection risk areas. However, in tropical wetlands, highly turbid water causes filter clogging, thereby decreasing the filtration volume and increasing the risk of false negatives. Therefore, in this study, we aimed to conduct laboratory experiments and field surveys in Lake Victoria, Mbita, to determine the appropriate filter pore size for S. mansoni eDNA collection in terms of particle size and filtration volume. In the laboratory experiment, aquarium water was sequentially filtered using different pore size filters. Targeting >3 µm size fraction was found to be sufficient to capture S. mansoni eDNA particles, regardless of their life cycle stage (egg, miracidia, and cercaria). In the field surveys, GF/D (2.7 µm nominal pore size) filter yielded 2.5-times the filtration volume obtained with a smaller pore size filter and pre-filtration methods under the same time constraints. Moreover, a site-occupancy model was applied to the field detection results to estimate S. mansoni eDNA occurrence and detection probabilities and assess the number of water samples and PCR replicates necessary for efficient eDNA detection. Overall, this study reveals an effective method for S. mansoni eDNA detection in turbid water, facilitating the rapid and sensitive monitoring of its distribution and cost-effective identification of schistosomiasis transmission risk areas.

Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review.

Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome. We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently. We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts. S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection.

A Mixed-Methods Evaluation of Mainstreaming Mass Drug Administration for Schistosomiasis and Soil-Transmitted Helminthiasis in Four Districts of Nigeria.

In Nigeria, mass drug administration (MDA) for schistosomiasis (SCH) and soil-transmitted helminthiasis (STH) has often been coordinated with other programs that receive greater external funding. As these programs reach stop MDA milestones, SCH and STH programs will likely need to transition implementation, or "mainstream," to domestic support. A mixed-methods study was conducted in four districts before (2021) and after (2022) mainstreaming to evaluate its impact on MDA coverage. Household surveys were done in 30 villages per district pre- and post-mainstreaming. All selected communities were eligible for STH treatment; around a third were eligible for SCH treatment. Mass drug administration was primarily conducted in schools. A total of 5,441 school-aged children were included in pre-mainstreaming and 5,789 were included in post-mainstreaming. Mass drug administration coverage was heterogeneous, but overall, mebendazole coverage declined nonsignificantly from 81% pre-mainstreaming to 76% post-mainstreaming (P = 0.09); praziquantel coverage declined significantly from 73% to 55% (P = 0.008). Coverage was significantly lower among unenrolled children or those reporting poor school attendance in nearly every survey. For the qualitative component, 173 interviews and 74 focus groups were conducted with diverse stakeholders. Respondents were deeply pessimistic about the future of MDA after mainstreaming and strongly supported a gradual transition to full government ownership. Participants formulated recommendations for effective mainstreaming: clear budgetallocation by governments, robust and targeted training, trust building, and comprehensive advocacy. Although participants lacked confidence that SCH and STH programs could be sustained after reductions in external support, initial results indicate that MDA coverage can remain high 1 year into mainstreaming.

Integrated Serosurveillance for Onchocerciasis, Lymphatic Filariasis, and Schistosomiasis in North Darfur, Sudan.

Sudan is endemic for multiple neglected tropical diseases, including trachoma, onchocerciasis (OV), lymphatic filariasis (LF), and schistosomiasis (SCH). In 2019, dried blood spot samples were collected for a baseline trachoma serosurvey in three localities (El Seraif, Kotom, and Saraf Omrah) in North Darfur State. None were classified previously as OV- or LF-endemic, although low levels of SCH had been identified in all three. Approximately 30 households from 25 communities in each locality were selected by multistage cluster random sampling. Collections of DBSs were analyzed by multiplex bead assay for antibodies to multiple pathogens. This paper presents data on OV (Ov16), LF (Wb123, Bm14, Bm33), and SCH (soluble egg antigen [SEA], Sm25) antibodies among 8,322 individuals from 2,119 households. The survey-adjusted seroprevalence estimates for Ov16 were <0.3% in all localities. Lymphatic filariasis-antigen seroprevalences were discordant. Seroprevalence estimates ranged from 4.6-6.0% (Wb123), 0.99-1.4% (Bm14), and 29.2-33.3% (Bm33). Schistosomiasis seroprevalence estimates among school-aged children ranged from 2.7-8.0% (SEA) and 10.9-15.6% (Sm25). Ov16 seropositivity was low and supported the localities' classification as nonendemic. The results suggested LF exposure, but discordance between antigens, challenges defining seropositivity thresholds, and the absence of programmatic guidance based on antibody serology alone for Wuchereria bancrofti indicate a need for remapping surveys to confirm transmission. Schistosomiasis antibody levels were high enough to warrant further mapping to guide treatment decisions. The lack of gold standards limited interpretation of results, particularly for LF, but in resource-challenged areas, integrated serological surveillance offers the possibility of efficient monitoring of exposure to multiple diseases.