Schistosoma Mansoni Research Articles

Residence Time, Water Contact, and Age-driven Schistosoma mansoni Infection in Hotspot Communities in Uganda.

ABSTRACT.Schistosomiasis is the second most important parasitic infection after malaria in terms of its socioeconomic impact and is endemic in 78 countries. It affects more than 240 million people worldwide, with 90% of cases occurring in sub-Saharan Africa. In Uganda, Schistosoma mansoni is the most common species, with more than seven million people infected and 17 million living at risk despite mass drug administration (MDA) of praziquantel initiated more than 16 years ago. There has been a shift in the WHO schistosomiasis goals from controlling morbidity to elimination as a public health problem. Understanding the drivers of infection in persistent transmission hotspots despite ongoing control interventions is paramount. We conducted a cross-sectional epidemiological study of 381 individuals in Bugoto community, Mayuge district, Eastern Uganda, along with a structured survey to ascertain drivers of S. mansoni infection. Bugoto has had community-wide MDA since 2004. We detected a S. mansoni prevalence of 52% across the whole community and a prevalence of 71% in school-age children. This qualifies Bugoto as a highly endemic community according to WHO guidelines. Using a multivariate logistic regression, we found that S. mansoni infection was best explained by age group, longer residence times, and any daily contact with lake water. Schistosoma mansoni infection remains a large burden across this community. This study identifies opportunities for interventions that reduce lake water contact, expand treatment eligibility to all at risk, and improve MDA coverage for long-term residents in these settings to control schistosomiasis in persistent transmission hotspots.

A proteomics evaluation of the primary and secondary immune response of Biomphalaria straminea challenged by Schistosoma mansoni.

Biomphalaria spp. snails are intermediary hosts of Schistosoma mansoni, etiologic agent of intestinal schistosomiasis, one of the most important neglected tropical diseases. Biomphalaria straminea is an important intermediary host that possess a different phenotype to parasite infection but shows a large geographic distribution and high capacity of new ecologic niche invasion. Our purpose was to characterize for the first time the differentially expressed proteome in B. straminea during two times intervals after primary and secondary exposure to S. mansoni. The hemolymph was collected at 1 and 15days after primary and secondary exposure of snails to the parasite. Total proteins were extracted and digested with trypsin. LC-MS/MS label-free quantification was performed and analyzed using Maxquant and Perseus software. Proteins were identified and annotated using Blast2GO tools. After 1day of exposure, most of upregulated proteins are hemoglobin type 2, C and H type lectins, molecules related to cell adhesion, and response to oxidative stress. After 15days, we found a similar pattern of upregulated proteins but some fibrinogen-related proteins (FREPs) and TEPs homologs were downregulated. Regarding the differentially expressed proteins during secondary response, the principal immune-related proteins upregulated were C and H type lectins, cellular adhesion molecules, biomphalysin, and FREP3. We noted a several upregulated biological processes during both responses that could be the one of the key points of efficacy in the immune response to parasite. Our data suggests different immune mechanisms used by B. straminea snails challenged with S. mansoni.

Environmental Drivers and Potential Distribution of Schistosoma mansoni Endemic Areas in Ethiopia.

In Ethiopia, human schistosomiasis is caused by two species of schistosome, Schistosoma mansoni and S. haematobium, with the former being dominant in the country, causing infections of more than 5 million people and more than 37 million at risk of infection. What is more, new transmission foci for S. mansoni have been reported over the past years in the country, raising concerns over the potential impacts of environmental changes (e.g., climate change) on the disease spread. Knowledge on the distribution of schistosomiasis endemic areas and associated drivers is much needed for surveillance and control programs in the country. Here we report a study that aims to examine environmental determinants underlying the distribution and suitability of S. mansoni endemic areas at the national scale of Ethiopia. The study identified that, among five physical environmental factors examined, soil property, elevation, and climatic factors (e.g., precipitation and temperature) are key factors associated with the distribution of S. mansoni endemic areas. The model predicted that the suitable areas for schistosomiasis transmission are largely distributed in northern, central, and western parts of the country, suggesting a potentially wide distribution of S. mansoni endemic areas. The findings of this study are potentially instrumental to inform public health surveillance, intervention, and future research on schistosomiasis in Ethiopia. The modeling approaches employed in this study may be extended to other schistosomiasis endemic regions and to other vector-borne diseases.

Prevalence and risk factors of human Balantidium coli infection and its association with haematological and biochemical parameters in Ga West Municipality, Ghana

BackgroundIn Ghana, Balantidium coli (B. coli) has been identified in vegetables and in pigs, although there is a paucity of data regarding human balantidiosis. This study sought to assess human B. coli infection in Ghana, factors associated with the infection as well as its association with haematological and biochemical parameters.MethodsTwo pig rearing communities in the Ga West Municipality, Ghana, were involved in this study. Stool and blood samples were collected from pig farmers and their exposed household members as well as relevant information on potential associated factors. Eosin-saline wet preparation was done on the same day of stool samples were collected while formol ether concentration technique was performed later. Haematological, biochemical parameters and serum electrolytes were determined using Celltac MEK-6500 K, PKL-125 biochemical analyser, and FT-320 electrolyte analyser, respectively.ResultsThe overall prevalence of balantidiosis was 10.4 %, significantly higher among farmers (21.7 %) than in exposed household members (5.8 %) (x2 = 17.8, p = 0.000025). Of the 43 infected individuals, 20.9 % were co-infected with either Entamoeba histolytica, Giardia lamblia, or Schistosoma mansoni. In B. coli infection, mild to moderate anaemia together with a reduction in levels of platelet, albumin and, sodium, chloride, and bicarbonate ions were observed. However, white blood cells were significantly elevated in infected states. Poor farming practices such as free-range systems, improper disposal of pig faeces, lack of use of protective farming clothing, and unavailability of dedicated farming clothing were found to be associated with B. coli infection status. Finally, frequent diarrhea (OR = 12.30, p = 0.006) with occult blood (OR = 25.94, p < 0.0001) were found to be predictors of B. coli infection.ConclusionsHuman balantidiosis is endemic in Ga West Municipality, Ghana. Individuals living closed to pig rearing communities presenting with frequent diarrhea with occult blood in stool should be screened and treated for balantidiosis to mitigate the clinical consequences of the infection.

Schistosome-Associated Pulmonary Arterial Hypertension: A Review Emphasizing Pathogenesis.

Schistosomiasis, especially due to Schistosoma mansoni, is a well-recognized cause of pulmonary arterial hypertension (PAH). The high prevalence of this helminthiasis makes schistosome-related PAH (Sch-PAH) one of the most common causes of this disorder worldwide. The pathogenic mechanisms underlying Sch-PAH remain largely unknown. Available evidence suggests that schistosome eggs reach the lung via portocaval shunts formed as a consequence of portal hypertension due to hepatosplenic schistosomiasis. Once deposited into the lungs, the eggs elicit an immune response resulting in periovular granuloma formation. Immune mediators drive transforming growth factor-β (TGF-β) release, which gives rise to pulmonary vascular inflammation with subsequent remodeling and development of angiomatoid and plexiform lesions. These mechanisms elicited by the eggs seem to become autonomous and the vascular lesions progress independently of the antigen. Portopulmonary hypertension, which pathogenesis is still uncertain, may also play a role in the genesis of Sch-PAH. Recently, there have been substantial advances in the diagnosis and treatment of PAH, but it remains a difficult condition to recognize and manage, and patients still die prematurely from right-heart failure. Echocardiography is used for screening, and the formal diagnosis requires right-heart catheterization. The experience in treating Sch-PAH is largely limited to the phosphodiesterase type 5 inhibitors, with evidence suggesting that these vasodilators improve symptoms and may also improve survival. Considering the great deal of uncertainty about Sch-PAH pathogenesis, course, and treatment, the aim of this review is to summarize current knowledge on this condition emphasizing its pathogenesis.

Efficacy of carvacryl acetate in vitro and following oral administration to mice harboring either prepatent or patent Schistosoma mansoni infections.

Schistosomiasis is a major public health problem that afflicts more than 240 million individuals globally, particularly in poor communities. Treatment of schistosomiasis relies heavily on a single oral drug, praziquantel, and there is interest in the search for new antischistosomal drugs. This study reports the anthelmintic evaluation of carvacryl acetate, a derivative of the terpene carvacrol, against Schistosoma mansoni ex vivo and in a schistosomiasis animal model harboring either adult (patent infection) or juvenile (prepatent infection) parasites. For comparison, data obtained with gold standard antischistosomal drug praziquantel are also presented. Initially in vitro effective concentrations of 50% (EC50) and 90% (EC90) were determined against larval and adult stages of S. mansoni. In an animal with patent infection, a single oral dose of carvacryl acetate (100, 200, or 400mg/kg) caused a significant reduction in worm burden (30-40%). S. mansoni egg production, a process responsible for both life cycle and pathogenesis, was also markedly reduced (70-80%). Similar to praziquantel, carvacryl acetate 400mg/kg had low efficacy in pre-patent infection. In tandem, although carvacryl acetate had interesting in vitro schistosomicidal activity, the compound exhibited low efficacy in terms of reduction of worm load in S. mansoni-infected mice.

Robust Immune Response Induced by Schistosoma mansoni TSP-2 Antigen Coupled to Bacterial Outer Membrane Vesicles.

PurposeThe use of adjuvants can significantly strengthen a vaccine’s efficacy. We sought to explore the immunization efficacy of bacterial outer membrane vesicles (OMVs) displaying the Schistosoma mansoni antigen, SmTSP-2, through a biotin-rhizavidin coupling approach. The rationale is to exploit the nanoparticulate structure and the adjuvant properties of OMVs to induce a robust antigen-specific immune response, in light of developing new vaccines against S. mansoni.Materials and MethodsOMVs were obtained from Neisseria lactamica and conjugated with biotin. The recombinant SmTSP-2 in fusion with the biotin-binding protein rhizavidin (rRzvSmTSP-2) was produced in E. coli and coupled to biotinylated OMVs to generate an OMV complex displaying SmTSP-2 on the membrane surface (OMV:rSmTSP-2). Transmission electron microscopy (TEM) and dynamic light scattering analysis were used to determine particle charge and size. The immunogenicity of the vaccine complex was evaluated in C57BL/6 mice.ResultsThe rRzvSmTSP-2 protein was successfully coupled to biotinylated OMVs and purified by size-exclusion chromatography. The OMV:rSmTSP-2 nanoparticles showed an average size of 200 nm, with zeta potential around – 28 mV. Mouse Bone Marrow Dendritic Cells were activated by the nanoparticles as determined by increased expression of the co-stimulatory molecules CD40 and CD86, and the proinflammatory cytokines (TNF-α, IL-6 and IL-12) or IL-10. Splenocytes of mice immunized with OMV:rSmTSP-2 nanoparticles reacted to an in vitro challenge with SmTSP-2 with an increased production of IL-6, IL-10 and IL-17 and displayed a higher number of CD4+ and CD8+ T lymphocytes expressing IFN-γ, IL-4 and IL-2, compared to mice immunized with the antigen alone. Immunization of mice with OMV:rSmTSP-2 induced a 100-fold increase in specific anti-SmTSP-2 IgG antibody titers, as compared to the group receiving the recombinant rSmTSP-2 protein alone or even co-administered with unconjugated OMV.ConclusionOur results demonstrate that the SmTSP-2 antigen coupled with OMVs is highly immunogenic in mice, supporting the potential effectiveness of this platform for improved antigen delivery in novel vaccine strategies.

Assessment of Ocimum basilicum Extracts on Schistosoma mansoni Infected Biomphalaria alexandrina Snails and Mice

Assessment of Ocimum basilicum Extracts on Schistosoma mansoni Infected Biomphalaria alexandrina Snails and Mice

Review: Schistosoma mansoni phosphatidylinositol 3 kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway.

Schistosoma mansoni worms are under a milieu of external and internal signaling pathways. The life-cycle stages are exposed to enormous stimuli within the mammalian and the snail hosts and as free-living stages in the fresh water. Furthermore, there is a unique interplay between the male and the female worms involving many stimuli from the male essential for full development of the female. PI3K/Akt/mTOR is an evolutionarily divergent signal transduction pathway universal to nearly every multicellular organism. This work reviews the Schistosoma mansoni PI3K/Akt/mTOR signal pathways and the involvement of the signal in the worms' physiology concerning the uptake of glucose, reproduction and survival. The inhibitors of the signal pathway used against Schistosoma mansoni were summarized. Given the importance of the PI3K/Akt/mTOR signal pathway, its inhibition could be a promising control strategy against schistosomiasis.

Determinants of Helminthic Infections and Anemia among Schoolchildren in Bahir Dar Zuria District, Northwest Ethiopia.

Background Soil-transmitted helminths and Schistosoma mansoni are the major helminthic parasites that cause major public health problems among schoolchildren in developing countries. Infection with the above parasites decreases the hemoglobin level of children. However, information regarding the current status of helminthic infections and anemia is limited. Hence, this study aimed to assess the prevalence and determinants of helminthic infections and anemia among children. Methods A cross-sectional study was conducted among 394 schoolchildren at Sekelet primary school in northwest Ethiopia, from February to March 2017. Study participants were selected by a systematic random sampling technique. Stool samples were collected and processed via the modified Ritchie's concentration technique to detect parasites in stool. A HemoCue Hb 201 analyzer was used to determine the hemoglobin level. Data were analyzed using SPSS version 23 statistical software. Association of helminthic infections and anemia with independent variables was determined using logistic regression analysis. Variables with P < 0.05 were considered statistically significant. Results From the total of 394 participants, 185 (46.9%), 164 (41.6%), and 112 (28.4%) were infected with intestinal parasites, helminths, and STHs, respectively. The prevalence of hookworm and Schistosoma mansoni were 106 (25.6%) and 54 (13.7%), respectively. The prevalence of anemia among the schoolchildren was 278 (70.6%). Anemia was prevalent among 55 (51.9%) hookworm-infected and 19 (35.2%) S. mansoni-infected children. Not wearing shoes and improper utilization of latrine were significantly associated (P < 0.05) with hookworm infection, and frequent swimming in the river was also significantly associated (P ≤ 0.001) with Schistosoma mansoni infection. Schistosoma mansoni and hookworm infections were also significantly associated (P ≤ 0.001) with low levels of hemoglobin. Conclusion Hookworm and Schistosoma mansoni infections and anemia are highly prevalent among schoolchildren. Hookworm and Schistosoma mansoni infections are significantly associated with anemia. Therefore, helminthic detection and hemoglobin determination should be done simultaneously among schoolchildren.

The function of twister ribozyme variants in non-LTR retrotransposition in Schistosoma mansoni.

The twister ribozyme is widely distributed over numerous organisms and is especially abundant in Schistosoma mansoni, but has no confirmed biological function. Of the 17 non-LTR retrotransposons known in S. mansoni, none have thus far been associated with ribozymes. Here we report the identification of novel twister variant (T-variant) ribozymes and their function in S. mansoni non-LTR retrotransposition. We show that T-variant ribozymes are located at the 5′ end of Perere-3 non-LTR retrotransposons in the S. mansoni genome. T-variant ribozymes were demonstrated to be catalytically active in vitro. In reporter constructs, T-variants were shown to cleave in vivo, and cleavage of T-variants was sufficient for the translation of downstream reporter genes. Our analysis shows that the T-variants and Perere-3 are transcribed together. Target site duplications (TSDs); markers of target-primed reverse transcription (TPRT) and footmarks of retrotransposition, are located adjacent to the T-variant cleavage site and suggest that T-variant cleavage has taken place inS. mansoni. Sequence heterogeneity in the TSDs indicates that Perere-3 retrotransposition is not site-specific. The TSD sequences contribute to the 5′ end of the terminal ribozyme helix (P1 stem). Based on these results we conclude that T-variants have a functional role in Perere-3 retrotransposition.

Prevalence and Risk Factors Associated with Intestinal Parasitic Infection among Primary School Children in Dera District, Northwest Ethiopia.

Background Globally, over 600 million school children are living with intestinal parasites. The prevalence of intestinal parasitic infections (IPIs) among school children in Ethiopia and the Amhara region is 52% and 51%, respectively. The present study aimed to determine the prevalence and associated risk factors of IPIs among primary school children in Dera district, Northwest Ethiopia. Methods A school-based cross-sectional study was conducted from December 2019 to February 2020. The study used a structured pretested questionnaire and stool tests to obtain epidemiological and disease data. Data were analyzed using appropriate univariate and multivariable logistic regression methods by statistical package for social science (SPSS) version 25.0. Results Of the 382 students who were examined for IPIs, 238 (62.3%) (61.8% males, 62.8% females) were positive for one or more IPIs. One hundred thirty-six (35.6%), 98 (25.7%), and 4 (1.05%) were single, double, and triple infections, respectively. Out of the nine species of IPIs detected, Entamoeba sp. was the predominant species (29.6%) followed by hookworm (21.7%), Schistosoma mansoni (11.3%), Taenia sp. (9.2%), Giardia lamblia (5.2%), and Ascaris lumbricoides, Hymenolepis nana, and Enterobius vermicularis (4.2%) each, and Trichuris trichiura (0.5%). Family size greater than five (AOR = 1.8; 95% CI: 1.004, 3.13), open field school waste disposal (AOR = 15.88; 95% CI: 1.91, 132.1), and lack of knowledge about intestinal parasitic infection (AOR = 1.8; 95% CI: 1.1, 3.2) were the independent risk factors associated with the overall prevalence of IPIs. Conclusions The prevalence of intestinal parasitic infection was high in the Dera district. Health education, extending school-based deworming, and mass treatments are recommended.

Intestinal schistosomiasis among schoolchildren in Sana'a Governorate, Yemen: Prevalence, associated factors and its effect on nutritional status and anemia.

Intestinal schistosomiasis is a neglected tropical disease, causing morbidity and mortality in tropical and subtropical countries. Despite the frequent implementation of mass drug administration with praziquantel, the reinfection with Schistosoma mansoni is still common in Yemen. In addition, there is a scarcity of information on the impact of S. mansoni on nutritional status and anemia among schoolchildren. The present study aimed to determine prevalence and risk factors of intestinal schistosomiasis and investigate its impact on nutritional status and anemia among schoolchildren in Sana’a Governorate, Yemen. It was conducted in 2018 on 445 schoolchildren aged 5–15 years. Biodata, socio-economic, demographic, behavioral and environmental data were collected using a standard questionnaire. S. mansoni was identified and quantified by microscopic examination of Kato-Katz fecal smear. Hemoglobin concentration and anthropometric measurements were estimated using standard methods. The prevalence of S. mansoni was higher in Al-Haimah Al-Dakheliah (33.9%) than Bani Mater (1.4%). Household without tap water (Adjusted Odds Ratio (AOR) = 2.9, 95% Confidence interval (CI): 1.12, 7.55, P = 0.028) was the independent risk factor of the infection. The prevalence of wasting and stunting was 25.0% (95%CI: 21.2%, 29.2%) and 45.8% (95%CI: 41.2%, 50.5%), respectively. The prevalence of underweight among schoolchildren aged 5–10 years was 27.3% (95%CI: 21.9%, 33.4%). The prevalence of anemia was 31.7% (95%CI: 27.5%, 36.2%) with 0.5%, 21.1% and 10.1% being severe, moderate and mild anemia, respectively. S. mansoni (AOR = 4.1, 95%CI: 2.16, 7.84, P < 0.001) and early adolescence (AOR = 6.8, 95%CI: 4.26, 10.82, P < 0.001) were independent predictors of stunting among schoolchildren. The early adolescent schoolchildren (AOR = 3.1, 95%CI: 1.86, 4.97, P < 0.001) and children from families with low (AOR = 2.1, 95%CI: 1.01, 4.15, P = 0.046) or moderate wealth (AOR = 2.3, 95%CI: 1.11, 4.77, P = 0.026) were significantly more wasted.Early adolescence (AOR = 1.8, 95%CI:1.14, 2.78, P = 0.011), female (AOR = 1.6, 95%CI: 1.03, 2.43, P = 0.038) and Al-Haimah Al-Dakheliah District (AOR = 3.4, 95%CI: 1.20, 9.55, P = 0.021) were independent risk factors for anemia. The study findings indicate highly focal prevalence of schistosomiasis in Sana’a Governorate with a public health significance that varies from low to high risk. Approximately half of schoolchildren were stunted, which was associated with S. mansoni infection and early adolescence. One quarter of schoolchildren were wasted with early adolescent schoolchildren and children from poor families being at high risk of wasting. Anemia was a moderate public health threat affecting the female and the early adolescent schoolchildren. The study suggests the implementation of control measures to combat schistosomiasis and integrated diseases control programmes to improve the health status of schoolchildren in Sana’a Governorate.

Prostatic schistosomosis by Schistosoma Mansoni in a patient with prostatic adenocarcinoma: case report / Esquistossomose prostática por Schitosoma Mansoni em paciente com adenocarcinoma prostático: relato de caso

Schistosomiasis is a parasitic infectious disease of global relevance and endemic in Brazil, especially in the state of Minas Gerais. However, genitourinary involvement by Schistosoma mansoni is not frequent, with S. haematobium being the primary cause for this ectopic infection. In the present study, we report a case of prostatic schistosomiasis identified incidentally in a biopsy of a patient with prostatic adenocarcinoma. Current studies show that the inflammation resulting from the presence of the parasite's eggs generates an oncogenic environment and indicates a possible association of schistosomiasis with the development of adenocarcinoma-however, few cases are described in world literature.

Unprotected water sources and low latrine coverage are contributing factors to persistent hotspots for schistosomiasis in western Kenya.

BackgroundEvidence indicates that whereas repeated rounds of mass drug administration (MDA) programs have reduced schistosomiasis prevalence to appreciable levels in some communities referred to here as responding villages (R). However, prevalence has remained high or less than anticipated in other areas referred to here as persistent hotspot villages (PHS). Using a cross-sectional quantitative approach, this study investigated the factors associated with sustained high Schistosoma mansoni prevalence in some villages despite repeated high annual treatment coverage in western Kenya.MethodWater contact sites selected based on observation of points where people consistently go to collect water, wash clothes, bathe, swim or play (young children), wash cars and harvest sand were mapped using hand-held smart phones on the Commcare platform. Quantitative cross-sectional surveys on behavioral characteristics were conducted using interviewer-based semi-structured questionnaires administered to assess water usage/contact patterns and open defecation. Questionnaires were administered to 15 households per village, 50 pupils per school and 1 head teacher per school. One stool and urine sample was collected from 50 school children aged 9–12 year old and 50 adults from both responding (R) and persistent hotspot (PHS) villages. Stool was analyzed by the Kato-Katz method for eggs of S. mansoni and soil-transmitted helminths. Urine samples were tested using the point-of-care circulating cathodic antigen (POC-CCA) test for detection of S. mansoni antigen.ResultsThere was higher latrine coverage in R (n = 6) relative to PHS villages (n = 6) with only 33% of schools in the PHS villages meeting the WHO threshold for boy: latrine coverage ratio versus 83.3% in R, while no villages met the girl: latrine ratio requirement. A higher proportion of individuals accessed unprotected water sources for both bathing and drinking (68.5% for children and 89% for adults) in PHS relative to R villages. In addition, frequency of accessing water sources was higher in PHS villages, with swimming being the most frequent activity. As expected based upon selection criteria, both prevalence and intensity of S. mansoni were higher in the PHS relative to R villages (prevalence: 43.7% vs 20.2%; P < 0.001; intensity: 73.8 ± 200.6 vs 22.2 ± 96.0, P < 0.0001), respectively.ConclusionUnprotected water sources and low latrine coverage are contributing factors to PHS for schistosomiasis in western Kenya. Efforts to increase provision of potable water and improvement in latrine infrastructure is recommended to augment control efforts in the PHS areas.

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

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

Endoparasites of Dominant Rattus rattus frugivorus (Rafinesque, 1814) In Sohag Area, Egypt

In this study, an inventory of the types of rodents in the study area was conducted, and a survey of internal parasites was done for the most important types of rodents prevalent in Sohag region during the year 2020. The results showed that four types of climbing rodents were present. Those rodents were the white-bellied rat (the most dominant in the region), the gray-bellied climber rat, field rat and brown Norwegian rat. The results showed the absence of many species. By studying the internal parasites of the most common species in the study area. we found 3 trematodes (Echinostoma liei Jeyarasasingam &Heyneman,1972, Schistosoma mansoni (Bilharzia), and Fasciola hepatica Linnaeus,1758),two nematodes (Angiostrongylus cantoniensis Chen,1935, and Trichuris sp.) and one cestode (Hymenolepis sp.) of the white-bellied climbing rat Rattus rattus frugivorus, which is the dominant species in this study.

Anti-schistosomal activities of quinoxaline-containing compounds: From hit identification to lead optimisation

Schistosomiasis is a neglected disease of poverty that is caused by infection with blood fluke species contained within the genus Schistosoma. For the last 40 years, control of schistosomiasis in endemic regions has predominantly been facilitated by administration of a single drug, praziquantel. Due to limitations in this mono-chemotherapeutic approach for sustaining schistosomiasis control into the future, alternative anti-schistosomal compounds are increasingly being sought by the drug discovery community. Herein, we describe a multi-pronged, integrated strategy that led to the identification and further exploration of the quinoxaline core as a promising anti-schistosomal scaffold.Firstly, phenotypic screening of commercially available small molecules resulted in the identification of a moderately active hit compound against Schistosoma mansoni (1, EC50 = 4.59 μM on schistosomula). Secondary exploration of the chemical space around compound 1 led to the identification of a quinoxaline-core containing, non-genotoxic lead (compound 22). Compound 22 demonstrated substantially improved activities on both intra-mammalian (EC50 = 0.44 μM, 0.20 μM and 84.7 nM, on schistosomula, juvenile and adult worms, respectively) and intra-molluscan (sporocyst) S. mansoni lifecycle stages. Further medicinal chemistry optimisation of compound 22, resulting in the generation of 20 additional analogues, improved our understanding of the structure-activity relationship and resulted in considerable improvements in both anti-schistosome potency and selectivity (e.g. compound 30; EC50 = 2.59 nM on adult worms; selectivity index compared to the HepG2 cell line = 348). Some derivatives of compound 22 (e.g. 31 and 33) also demonstrated significant activity against the two other medically important species, Schistosoma haematobium and Schistosoma japonicum. Further optimisation of this class of anti-schistosomal is ongoing and could lead to the development of an urgently needed alternative to praziquantel for assisting in schistosomiasis elimination strategies.

Spatial analysis of areas at risk for schistosomiasis in the Alto Tietê Basin, São Paulo, Brazil

The present study identified locations with the presence of Biomphalaria and the areas at risk for Schistosoma mansoni, the etiological agent of schistosomiasis, in the Metropolitan Region of São Paulo (MRSP), located in the Alto Tietê Basin (ATB), São Paulo, Brazil. The study area comprises floodplains of the Tietê River from its source, in Salesópolis, to Rasgão Dam, in Pirapora do Bom Jesus, covering 39 municipalities. Data from the planorbidic chart of the malacology laboratory of the Endemic Control Superintendence for 2008–2016 were used, as well as data from the notification forms of cases of human schistosomiasis in 2006–2015 made available by the Epidemiological Surveillance Groups of Mogi das Cruzes and Osasco, and by the Health and Surveillance Coordination of São Paulo. These data were used to generate maps of the distribution of Biomphalaria, of the scanning analysis, of the Gi statistics of the autochthonous and imported schistosomiasis cases, and of the flow of cases imported from other Brazilian states and municipalities in the state of São Paulo to the study area. A total of 21,618 specimens of the genus Biomphalaria were captured and six species were identified. Biomphalaria tenagophila was the predominant species in the region and of greatest epidemiological importance as it is the main responsible for the transmission of the disease in the state of São Paulo. A total of 3,623 cases of schistosomiasis were reported in the study area, and São Paulo and Guarulhos were the municipalities with the highest number of autochthonous and imported cases during the study period. The imported cases originated from 21 Brazilian states plus the Federal District and from 51 municipalities in São Paulo state located outside the study area. Autochthonous clusters with high risk for the occurrence of schistosomiasis were identified in the municipalities of São Paulo, Guarulhos, Santa Isabel/Mogi das Cruzes/Arujá, and Cotia/Itapevi. Clusters of imported cases were also identified in Itaquaquecetuba, at the border of Cotia/Itapevi and Suzano/São Paulo/Mogi das Cruzes. The presence of B. tenagophila in the ATB and in the clusters of autochthonous cases herein identified, although not carrying schistosome larvae, represents a risk for the transmission of infectious agents. The human population in the MRSP mainly occupies the lowlands of the Tietê River, which are locations with poor coverage of basic sanitation. Therefore, measures for the control and surveillance of schistosomiasis such as educational actions, improvements in basic sanitation, and the malacological and epidemiological monitoring of these areas are extremely important.

Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade

ABSTRACT Schistosoma mansoni infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187–2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.