Schistosoma Mansoni Infection Research Articles

Schistosoma japonicum infection associated with membranous nephropathy: a case report

BackgroundSchistosomiasis is one of the most contagious parasitic diseases affecting humans; however, glomerular injury is a rare complication mainly described with Schistosoma mansoni infection. We report a case of membranous nephropathy associated with Schistosoma japonicum infection in a Chinese man.Case presentationA 51-year-old Chinese male with a long history of S. japonicum infection presented to the hospital with a slowly progressing severe lower limb edema and foaming urine for over 5 months. Serum S. japonicumantigen test was positive and immunohistochemistry showed that the glomeruli were positive for the antigens. The renal pathologic diagnosis was stage III membranous nephropathy. The patient was treated with glucocorticoid, praziquantel, and an angiotensin-converting enzyme inhibitor. The edema in both lower limbs disappeared within 2 weeks, but his renal function declined progressively and proteinuria persisted after 5 months of therapy.ConclusionsDifferent classes of schistosomal glomerulopathy have completely different clinical manifestation and prognosis. Therefore, efforts should focus on alleviating symptoms, prevention, and early detection. S. japonicumassociated with membranous nephropathy may show a good curative effect and prognosis. However, it is necessary to monitor the renal function in such patients.

Protective immune potential of multiple antigenic peptide (MAP) constructs comprising peptides that are shared by several cysteine peptidases against Schistosoma mansoni infection in mice

In vaccine trials, Schistosoma mansoni cathepsin B1 (SmCB1), helminth cathepsins of the L family (e.g., SmCL3), and papain consistently induce highly significant reductions in challenge worm burden and egg viability, but generated no additive protective effects when used in combination. The protective capacity of the cysteine peptidases is associated with modest (SmCB1) and poor (cathepsins L) production of cytokines and antibodies, essentially of the type 2 axis, and is only marginally reduced upon use of proteolytically inactive enzymes. In this work, peptides shared by SmCB1, cathepsins of the L family, papain and other allergens were selected, synthesized as tetrabranched multiple antigen peptide constructs (MAP-1 and MAP-2), and used in two independent experiments to immunize outbred mice, in parallel with papain. The two peptides elicited significant (P < 0.05) reduction in challenge worm burden when compared to unimmunized mice, albeit lower than that achieved by papain. Protection was associated with modest serum type 2 cytokines and antibody levels in MAP-, and papain-immunized mice. Immunization with papain also elicited a reduction in parasite egg load, viability, and granuloma numbers in liver and intestine. MAP-1 and MAP-2 immunogens displayed some opposite effects- MAP-1 leading to higher egg numbers with poor vitality, whereas MAP-2 immunization yielded fewer eggs. Cysteine peptidase thus appear to carry peptides that elicit opposing outcomes, highlighting the difficulty of reaching fully fledged protection, unless a vaccine is based on carefully selected peptides and combined with an effective adjuvant.

Alterations in blood glucose concentration in wild rodents, Holochilus sciureus, naturally infected with Schistosoma mansoni.

The present study aimed to evaluate the changes in peripheral blood glucose concentrations induced by Schistosoma mansoni infection in Holochilus sciureus rodents, a wild reservoir of the parasite. Glucose concentration was measured in the plasma of blood samples using a colorimetric enzymatic test. Biological parameters and S. mansoni burden in each rodent were also verified and correlated with glucose concentrations. A total of 76 H. sciureus were captured, out of which 20 (26%) were infected with S. mansoni (n=13 males and n=7 females). Although the parasite burden was comparable between the sexes, blood glucose concentration was lower in infected males and almost unchanged in females. Furthermore, histopathological data revealed that male rodents had a greater hepatic granulomatous inflammatory reaction than females. In addition, we also confirmed that the weight and total length of the analyzed animals had no effect on glucose levels. Therefore, natural infection with S. mansoni in H. sciureus may have a lower impact on glycemic homeostasis in females, which will help us understand the role of these rodents as reservoirs of S. mansoni.

Eosinophils participate in modulation of liver immune response and tissue damage induced by Schistosoma mansoni infection in mice.

The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-β and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.

Distinct Schistosoma mansoni-Specific Immunoglobulin Subclasses Are Induced by Different Schistosoma mansoni Stages-A Tool to Decipher Schistosoma mansoni Infection Stages.

Despite the existence of an effective medication against schistosomiasis, the disease remains a major health problem in affected areas, especially for those lacking appropriate sanitary facilities. Moreover, treatment cannot prevent re-infection since it is only effective on adult schistosome worms. Previous retrospective studies in the Sudan have discovered unique immuno-epidemiological profiles in uninfected individuals and those positive for Schistosoma mansoni via polymerase chain reaction (PCR) but egg-negative and those with eggs in their stool. Expanding on these data, serum samples from these individuals were further investigated for the presence of cercarial (SmCTF)-specific antibodies, which would indicate immune responses at the early stages of infection. Indeed, SmCTF IgG1, 2, 3 and 4 levels were significantly elevated in SmPCR+ individuals when compared to egg+ patients. Following multivariable regression analysis, including SmCTF-specific Igs, Schistosoma egg antigen (SEA)-specific and Schistosoma worm antigen (SWA)-specific immunoglobulins revealed a specific immunoglobulin (Ig) profile of individuals presenting different states of infection, which may be a useful future tool in order to identify egg− individuals and thereby prevent unnecessary treatments.

Morbidity associated with Schistosoma mansoni infection in north-eastern Democratic Republic of the Congo.

BackgroundReducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province.Methods/Principal findingsIn 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06–1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99–2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73–1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis.Conclusions/SignificanceOur study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity.

Infection of Plasmodium falciparum and helminths among school children in communities in Southern and Northern Ghana

BackgroundInfections of Plasmodium species, Schistosoma species and soil-transmitted helminths (STH) inflict a significant burden on children mostly in deprived communities in Ghana. Despite the deployment of malaria vector control and the annual Mass Drug Administration by National Control Programmes, these infections still pose major public health concerns in Ghana. Some remote communities which are hard-to-reach are not covered by MDA campaigns which is a major challenge to meeting elimination targets. Adequate data is necessary for formulating policies and strengthening interventions to mitigate transmission. This study assessed the infection burden of Plasmodium, Schistosoma species and STH infections among school children in communities in Southern and Northern Ghana.MethodSchool children living in communities in Southern (Ada Foah, Pediatorkope, Tuanikope) and Northern (Kpalsogu) Ghana were enrolled in a cross-sectional study. A total of 493 (241 males and 252 females) school children aged (2–15 years) were enrolled in the study. Stool samples were collected to screen for Schistosoma mansoni and STH infections using the formol-ether concentration technique and urine samples were also collected to screen for S. haematobium using the routine urine examination method. Plasmodium parasitaemia was determined from thick and thin finger-prick blood samples.ResultsOverall, the prevalence of P. falciparum, S. mansoni, S. haematobium, Trichuris trichiura and hookworm infections were 17.2% (95%CI 12.8–19.7), 22.6% (95%CI 25.2–32.7), 1.6% (95%CI 0.89–5.2), 1.2% (95%CI 0.78–4.8) and 1.2% (95%CI 0.78–4.8) respectively. Plasmodium falciparum infection was generally widespread in all the study sites with Ada Foah recording the highest prevalence (35.3%) and Kpalsogu recording the lowest (5.8%). Schistosoma mansoni was present in only two Southern communities with Tuanikope recording the highest prevalence of 70.3% as against 51.5% recorded in Pediatorkope. A total of 4.5% (95% CI 2.82–10.8) of the children were co-infected with P. falciparum, Schistosoma species and STHs. This occurred only in the Southern communities; of which combination of P. falciparum and S. mansoni were predominant (1.4%).ConclusionA relatively low burden of parasites co-infection among children only in the Southern communities was detected. However, there were a high prevalence of single infections of P. falciparum and S. mansoni in those communities. Control measures for the helminths needs to be restarted in the island communities with a high burden of S. mansoni infections and that of Plasmodium needs to be scaled up in Ada Foah where P. falciparum infections were high.

Risk Factors and Spatial Distribution of Schistosoma mansoni Infection among Preschool-Aged Children in Blapleu, Biankouma District, Western Côte d’Ivoire

Schistosoma mansoni infection is common among school-age children (SAC) in western Côte d'Ivoire. Little is known on the infection rate of preschool-aged children (PSAC) due to epidemiological data deficiency and nonappropriate formulation of the drug. Thus, mass drug administration for schistosomiasis control mainly targets SAC. This study aims to identify the risk factors and spatial distribution of S. mansoni infection among PSAC in Blapleu, endemic foci of S. mansoni. We carried out a cross-sectional study in households with PSAC aged 1–6 years. A structured questionnaire was administered to mothers/guardians to obtain data on sociodemographics and water contact behaviour of children. Point-of-care circulating cathodic antigen (POC-CCA) immunodiagnostic test in urine and Kato-Katz (K-K) method with stool were used for S. mansoni infection diagnosis. Multiple logistic regression analysis was performed to determine the relationship between S. mansoni infection and sociodemographic data. Coordinates recorded by a Global Positioning System of households, water source points, and infected PSAC were used to map the spatial distribution of S. mansoni infection cases. This study was conducted with 350 PSAC aged 1–6 years. The overall infection prevalence of S. mansoni varies from 31.43% with the K-K method to 62.86% with the POC-CCA. PSAC aged 2–6 years were highly infected with S. mansoni than those aged 1-2 years (OR = 14.24, 95% CI: 5.85–34.64). PSAC who did not have access and who do not live close to the infected water source were at a significant lower risk of S. mansoni infection (OR = 0.13, 95% CI: 0.057–0.30). The main purpose of water contact of PSAC was to help their mother for laundry that occurs weekly. In Blapleu, a high risk of S. mansoni infection was observed among PSAC. Schistosomiasis control effort in such localities should include information, education, and communication, water, sanitation, and hygiene, and particularly chemotherapy targeting PSAC, reinforcing the need of the paediatric praziquantel formulation.

ABO Blood Groups Do Not Predict Schistosoma mansoni Infection Profiles in Highly Endemic Villages of Uganda.

Schistosoma mansoni is a parasite which causes significant public-health issues, with over 240 million people infected globally. In Uganda alone, approximately 11.6 million people are affected. Despite over a decade of mass drug administration in this country, hyper-endemic hotspots persist, and individuals who are repeatedly heavily and rapidly reinfected are observed. Human blood-type antigens are known to play a role in the risk of infection for a variety of diseases, due to cross-reactivity between host antibodies and pathogenic antigens. There have been conflicting results on the effect of blood type on schistosomiasis infection and pathology. Moreover, the effect of blood type as a potential intrinsic host factor on S. mansoni prevalence, intensity, clearance, and reinfection dynamics and on co-infection risk remains unknown. Therefore, the epidemiological link between host blood type and S. mansoni infection dynamics was assessed in three hyper-endemic communities in Uganda. Longitudinal data incorporating repeated pretreatment S. mansoni infection intensities and clearance rates were used to analyse associations between blood groups in school-aged children. Soil-transmitted helminth coinfection status and biometric parameters were incorporated in a generalised linear mixed regression model including age, gender, and body mass index (BMI), which have previously been established as significant factors influencing the prevalence and intensity of schistosomiasis. The analysis revealed no associations between blood type and S. mansoni prevalence, infection intensity, clearance, reinfection, or coinfection. Variations in infection profiles were significantly different between the villages, and egg burden significantly decreased with age. While blood type has proven to be a predictor of several diseases, the data collected in this study indicate that it does not play a significant role in S. mansoni infection burdens in these high-endemicity communities.

Feasibility of near-infrared spectroscopy for species identification and parasitological diagnosis of freshwater snails of the genus Biomphalaria (Planorbidae).

Near Infrared Spectroscopy (NIRS) has been applied in epidemiological surveillance studies of insect vectors of parasitic diseases, such as the Dengue’s mosquitoes. However, regarding mollusks, vectors of important worldwide helminth diseases such as schistosomiasis, fascioliasis and angiostrongyliasis, NIRS studies are rare. This work proposes to establish and standardize the procedure of data collection and analysis using NIRS applied to medical malacology, i.e., to mollusk vectors identifications. Biomphalaria shells and live snails were analyzed regarding several operational aspects, such as: moisture, shell side and position of the live animal for acquisition of NIR spectra. Representative spectra of Biomphalaria shells and live snails were collected using an average of 50 scans per sample and resolution of 16 cm-1. For shells, the sample should first be dried for a minimum of 15 days at an average temperature of 26±1°C, and then placed directly in the equipment measurement window with its left side facing the light beam. Live animals should be dried with absorbent paper; placed into a glass jar, and analyzed similarly to the shells. Once standardized, the technique was applied aiming at two objectives: identification of Biomphalaria using only the shells and parasitological diagnosis for Schistosoma mansoni infection. The discrimination of the three Biomphalaria species intermediate hosts of S. mansoni only by shell has technical limit due to the scarcity of organic material. Nevertheless, it was possible to differentiate B. straminea from B. tenagophila and B. glabrata with 96% accuracy. As for the parasitological diagnosis, it was possible to differentiate infected mollusks shedding S. mansoni cercariae from the non-infected ones with 82, 5% accuracy. In conclusion, the Near Infrared Spectroscopy (NIR’s) technique has proven to be an innovative and sound tool to detect infection by S. mansoni in the different species of Biomphalaria intermediate hosts.

Schistosoma mansoni infection risk for school-aged children clusters within households and is modified by distance to freshwater bodies.

BackgroundThe interaction of socio-demographic and ecological factors with Schistosoma mansoni (S. mansoni) infection risk by age and the household clustering of infections between individuals are poorly understood.MethodsThis study examined 1,832 individuals aged 5–90 years across 916 households in Mayuge District, Uganda. S. mansoni infection status and intensity were measured using Kato-Katz microscopy. Socio-demographic and ecological factors were examined as predictors of infection status and intensity using logistic and negative binomial regression models, respectively, with standard errors clustered by household. A subgroup analysis of children was conducted to examine the correlation of infection status between children and their caretakers.FindingsInfection varied within age groups based on the distance to Lake Victoria. Children aged 9–17 years and young adults aged 18–29 years who lived ≤0.50km from Lake Victoria were more likely to be infected compared to individuals of the same age who lived further away from the lake. Infections clustered within households. Children whose caretakers were heavily infected were 2.67 times more likely to be infected.ConclusionThese findings demonstrate the focality of schistosome transmission and its dependence on socio-demographic, ecological and household factors. Future research should investigate the sampling of households within communities as a means of progressing towards precision mapping of S. mansoni infections.

Thymol as Molluscicidal Agent Against Biomphalaria alexandrina, Intermediate Host of Schistosoma mansoni

Biomphalaria alexandrina snails have received much concern due to their great medical importance as vectors for transmitting Schistosoma mansoni infection to humans. Sustainable control of B. alexandrina snails represents a logical approach to achieve its elimination targets. This work aimed to evaluate the efficacy of the monoterpenoid thymol as a plant molluscicide in the control of this schistosomiasis vector snail. The molluscicidal activity of thymol was determined according to the WHO method. The results showed that the lethal concentration LC50 and LC90 values of thymol were 21.90 and 34.06 ppm, respectively. Also, it was observed that the accumulative effect of sublethal concentration LC25 (15.94 ppm) of thymol for 4 successive weeks had destructive effects on the survival rate, egg-laying capacity, reproduction rate, and biochemical parameters of exposed snails. Our results demonstrated that thymol showed an oviposition inhibitory activity against B. alexandrina snails. Furthermore, the sublethal toxicity of thymol induced a significant increase in levels of total proteins and glucose as well as in enzyme activities of alkaline phosphatase and acid phosphatase of hemolymph of exposed snails, whereas a significant inhibition in aspartate aminotransferase and alanine aminotransferase activities was recorded. These significant biochemical disorders in turn explained noticeable changes in reproduction and other biological activities of treated snails. It was concluded that thymol can be used as a safe promising plant molluscicide for B. alexandrina snails’ control as it interferes with the snails’ biology and physiology. So thymol can be effectively used in the National S. mansoni control programs.

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.

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.

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.

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.

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.

Mitochondria as a Potential Target for the Development of Prophylactic and Therapeutic Drugs against Schistosoma mansoni Infection.

The emergence of parasites resistant to praziquantel, the only therapeutic agent, and its ineffectiveness as a prophylactic agent (inactive against the migratory/juvenile Schistosoma mansoni), make the development of new antischistosomal drugs urgent. The parasite's mitochondrion is an attractive target for drug development, because this organelle is essential for survival throughout the parasite's life cycle. We investigated the effects of 116 compounds against Schistosoma mansoni cercaria motility that have been reported to affect mitochondrion-related processes in other organisms. Next, eight compounds plus two controls (mefloquine and praziquantel) were selected and assayed against the motility of schistosomula (in vitro) and adults (ex vivo). Prophylactic and therapeutic assays were performed using infected mouse models. Inhibition of oxygen consumption rate (OCR) was assayed using Seahorse XFe24 analyzer. All selected compounds showed excellent prophylactic activity, reducing the worm burden in the lungs to less than 15% of that obtained in the vehicle control. Notably, ascofuranone showed the highest activity, with a 98% reduction of the worm burden, suggesting the potential for the development of ascofuranone as a prophylactic agent. The worm burden of infected mice with S. mansoni at the adult stage was reduced by more than 50% in mice treated with mefloquine, nitazoxanide, amiodarone, ascofuranone, pyrvinium pamoate, or plumbagin. Moreover, adult mitochondrial OCR was severely inhibited by ascofuranone, atovaquone, and nitazoxanide, while pyrvinium pamoate inhibited both mitochondrial and nonmitochondrial OCRs. These results demonstrate that the mitochondria of S. mansoni are a feasible target for drug development.

Field assessment in Cameroon of a reader of POC-CCA lateral flow strips for the quantification of Schistosoma mansoni circulating cathodic antigen in urine.

Determining Schistosoma mansoni infection rate and intensity is challenging due to the low sensitivity of the Kato-Katz (KK) test that underestimates the true disease prevalence. Circulating cathodic antigen (CCA) excreted in urine is constantly produced by adult worms and has been used as the basis of a simple, non-invasive point of care test (POC-CCA) for Schistosoma mansoni infections. Although the abundance of CCA in urine is proportional to worm burden, the POC-CCA test is marketed as a qualitative test, making it difficult to investigate the wide range of infection intensities. This study was designed to compare the prevalence and intensity of S. mansoni by KK and POC-CCA and quantify, on fresh and frozen (<-20°C) urine samples, CCA using the visual scores and the ESEquant LR3 reader. Stool and urine samples were collected from 759 school-aged children. The prevalence and intensity of S. mansoni were determined using KK and POC-CCA. The degree of the positivity of POC-CCA was estimated by quantifying CCA on fresh and frozen urine samples using visual scores and strip reader. The prevalence, the infection intensity as well the relative amounts of CCA were compared. The S. mansoni infection rates inferred from POC-CCA and KK were 40.7% and 9.4% respectively. Good correlations were observed between infection intensities recorded by; i) the reader and visual scoring system on fresh (Rho = 0.89) and frozen samples (Rho = 0.97), ii) the reader on fresh urine samples and KK (epg) (Rho = 0.44). Nevertheless, 238 POC-CCA positive children were negative for KK, and sixteen of them had high levels of CCA. The correlation between results from the reader on fresh and frozen samples was good (Rho = 0.85). On frozen samples, CCA was not detected in 55 samples that were positive in fresh urine samples. This study confirmed the low sensitivity of KK and the high capacity of POC-CCA to provide reliable data on the prevalence and intensity of S. mansoni infections. The lateral flow reader enabled accurate quantification of CCA under field conditions on fresh and frozen urine samples with less time and effort than KK.

Schistosoma mansoni infection is associated with decreased risk of respiratory allergy symptoms and low production of CCL2.

We measured the production of cytokines, chemokines and antibodies involved in allergic responses and sCD23 levels during Schistosoma mansoni infection. Individuals (n=164) were selected using the ISAAC questionnaire and parasitological exams. The subjects were divided as follows: those infected individuals with allergy-related symptoms (A-I), those with allergy-related symptoms only (A-NI); those only infected (NA-I); and those non-infected individuals without allergy-related symptoms (NA-NI). We used supernatants from cell culture (mitogenic stimulation) to measure cytokine and chemokine levels using cytometric bead arrays. Serum levels of anti-Ascaris lumbricoides (Asc) and anti-Blomia tropicalis IgE were measured using ImmunoCAP, and sCD23 was measured using ELISA. Schistosoma mansoni infection was associated with a lower risk of allergy-related symptoms. In A-I, there were higher levels of TNF-α, IL-10, IL-6, IFN-γ and CXCL8 than in NA-NI group, with TNF-α and IL-6 also at higher levels compared to A-NI group. Levels of IL-6, CXCL8, total and anti-Asc IgE, as well as the numbers of eosinophils, were higher in NA-I than in NA-NI, and the antibodies were also lower in A-NI than in NA-I group. In AI and NA-I, there was less production of CCL2 than in NA-NI. There were no differences in the levels of IL-2, IL-4, IL-17, CCL5, sCD23 and anti-Blomia IgE. Patients with allergy-related symptoms and infected (simultaneously) had higher levels of IL-10; due to the infection, there was increased production of IL-6 and CXCL8 and less CCL2. These data may characterize deviation to Th1 or attenuation of the Th2 response in allergy sufferers in areas endemic for schistosomiasis.