Helminth egg derivatives as proregenerative immunotherapies.

The immune system is increasingly recognized as an important regulator of tissue repair. We developed a regenerative immunotherapy from the helminth Schistosoma mansoni soluble egg antigen (SEA) to stimulate production of interleukin (IL)-4 and other type 2-associated cytokines without negative infection-related sequelae. The regenerative SEA (rSEA) applied to a murine muscle injury induced accumulation of IL-4-expressing T helper cells, eosinophils, and regulatory T cells and decreased expression of IL-17A in gamma delta (γδ) T cells, resulting in improved repair and decreased fibrosis. Encapsulation and controlled release of rSEA in a hydrogel further enhanced type 2 immunity and larger volumes of tissue repair. The broad regenerative capacity of rSEA was validated in articular joint and corneal injury models. These results introduce a regenerative immunotherapy approach using natural helminth derivatives.

Cell therapy as a new approach on hepatic fibrosis of murine model of Schistosoma mansoni-infection.

BACKGROUND: Schistosomiasis is an acute and chronic disease of the genus Schistosoma triggered by blood flukes. Schistosomiasis is a disease occurring in, or endemic to, tropical and subtropical regions. A new concept was implemented to deal with schistosomiasis from natural plant sources. Curcumin's common name is Turmeric. Curcumin has proven to be main active component in Curcuma longa L. and has a wide range of anti-phrastic effects. Previous studies have shown the role of bone marrow mesenchymal stem cells (BMSCs) therapy in hepatic fibrosis recovery. OBJECTIVE: The current study was, therefore, intended to examine therapeutic role of BMSCs and Turmeric in murine schistosomiasis mansoni. ANIMALS: Mice were divided into five groups: a negative control group (non-infected non-treated), a positive control group (infected non-treated), a BMSCs treated group; Turmeric treated group, and untreated group. BMSCs derived from male mice were injected intraperitoneally into female mice receiving S. mansoni cercariae through the subcutaneous route. Liver histopathology and immuno-histochemical examinations were evaluated. RESULTS: BMSCs intraperitoneal injection resulted in a significant reduction of liver collagen, granuloma size, and significant increase of OV-6 expression in the Schistosomiasis-treated mice group. There was overall improvement in pathological changes of the liver. Unfortunately, group IV showed a mild improvement in the granuloma size and fibrosis compared to corresponding BMSCs treatment group, although with vacuolated liver cells. CONCLUSION AND CLINICAL RELEVANCE: BMSCs have a regenerative potential in liver tissue histopathology by decreasing liver fibrosis and granulomas. Turmeric, by contrast, could not be used as an anti-fibrotic, according to the findings.

Prophylactic versus therapeutic role of the transplanted CD34+ Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.

PURPOSE: Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34+ Umbilical Cord Blood Stem Cells (CD34+UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34+UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice. METHODS: Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34+UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed. RESULTS: Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34+UCBSCs and WJMSCs) & similarly the post-infection CD34+UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis. CONCLUSION: CD34+UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.

Delayed esophagopleural fistula after endoscopic injection sclerotherapy for esophageal varices: A case report.

RATIONALE: Esophagopleural fistula (EPF) is a rare critical life-threatening condition that features high misdiagnosis rate. Although various surgical and conservative techniques have been developed for the treatment of EPF, the mortality rate of EPF remains high. PATIENT CONCERNS: An 81-year-old man with hepatic cirrhosis caused by schistosomiasis was admitted with upper gastrointestinal bleeding. DIAGNOSES: Upper endoscopy revealed bleeding large esophageal varices, and endoscopic injection sclerotherapy (EIS) was performed. Two weeks after the EIS was performed, the patient developed pyrexia, left-sided pleuritic chest pain. Air and pleural effusion were showed in the left pleural cavity by high-resolution computed tomography (HRCT), and a linear fistulous communication was noticed from the distal esophagus. These findings were consistent with hepatic cirrhosis, esophageal varices, upper gastrointestinal bleeding, and esophagopleural fistula. INTERVENTIONS: The patient was intensively treated with endoscopic self-expandable metallic stent (covered-SEMS) implantation and comprehensive treatments (including thoracic closed drainage, antibiotics, nasojejunal nutrition, and antacids). OUTCOMES: The patient was completely cured without recurrence during a 6 months of follow-up by comprehensive conservative treatments. LESSONS: This case indicates that pleural effusion with food residue is a specific finding in EPF. Thorax CT exhibited high sensitivity for the diagnosis of EPF. Endoscopic self-expandable metallic stent implantation and comprehensive conservative treatments may be preferable for the severe liver disease with EPF.

Adoptive Transfer of Bone Marrow-Derived Monocytes Ameliorates Schistosoma mansoni -Induced Liver Fibrosis in Mice.

Liver diseases are a major health problem worldwide leading to high mortality rates and causing a considerable economic burden in many countries. Cellular therapies as potential treatments for liver diseases have proven beneficial in most of the conditions. In recent years, studies involving therapy with bone marrow cells have been implemented to promote liver regeneration and to reduce hepatic fibrosis, however identifying the cell population present in the bone marrow that is responsible for hepatic improvement after therapy is still necessary. The aim of the present study was the evaluation of the therapeutic efficacy of monocytes obtained from bone marrow in fibrosis resulting from S. mansoni infection in C57BL/6 mice. Monocytes were isolated by immunomagnetic separation and administered to the infected animals. The effects of treatment were evaluated through morphometric, biochemical, immunological and molecular analyzes. Monocyte therapy promoted reduction of liver fibrosis induced by S. mansoni infection, associated with a decrease in production of inflammatory and pro-fibrogenic mediators. In addition, monocyte infusion caused downregulation of factors associated with the M1 activation profile, as well as upregulation of M2reg markers. The findings altogether reinforce the hypothesis that the predominance of M2reg macrophages, producers of immunosuppressive cytokines, may favor the improvement of hepatic fibrosis in a preclinical model, through fibrous tissue remodeling, modulation of the inflammatory response and fibrogenesis.

[Etiological diagnosis of pulmonary hypertension: A cause of difficult diagnosis]. / Diagnostic étiologique de l'hypertension pulmonaire : une cause de diagnostic difficile.

INTRODUCTION: Schistosomiasis associated pulmonary arterial hypertension belongs to group 1 of the pulmonary hypertension classification and should be considered in any patient with pulmonary hypertension returning from an endemic area. CASE REPORT: A 17-year-old patient was hospitalized for pulmonary hypertension detected during the initial assessment of viral hepatitis B-related cirrhosis with portal hypertension. The initial assessment established the diagnosis of pulmonary hypertension secondary to viral hepatitis B-cirrhosis. The patient's hepatic and haemodynamic condition deteriorated and he was treated with intravenous epoprostenol. This allowed subsequent performance of a liver transplantation. Epoprostenol could then be discontinued. Unexpectedly, histology of the liver explant revealed florid schistosomiasis in addition to hepatitis B cirrhosis. CONCLUSION: The diagnosis of pulmonary arterial hypertension associated with schistosomiasis may be difficult. It is necessary to repeat the serological studies and, sometimes, to obtain a rectal biopsy. The treatment of pulmonary arterial hypertension associated with schistosomiasis is based on specific therapies and antiparasitic treatment.

The cost of a disease targeted for elimination in Brazil: the case of schistosomiasis mansoni

BACKGROUND Schistosomiasis mansoni is a poverty-related parasitic infection that has a variety of clinical manifestations. We consider the disability and deaths caused by schistosomiasis unacceptable for a tool-ready disease. Its condition in Brazil warrants an analysis that will enable better understanding of the local health losses and contribute to the complex decision-making process. OBJECTIVE This study estimates the cost of schistosomiasis in Brazil in 2015. METHODS We conducted a cost of illness study of schistosomiasis mansoni in Brazil in 2015 based on a prevalence approach and from a societal perspective. The study included 26,499 schistosomiasis carriers, 397 hepatosplenic cases, 48 cases with the neurological form, 284 hospitalisations, and 11,368.26 years of life lost (YLL) of which 5,187 years are attributable to economically active age groups. RESULTS The total cost of schistosomiasis mansoni in Brazil was estimated to be US$ 41,7million in 2015 with 94.61% of this being indirect costs. CONCLUSIONS The economic burden of schistosomiasis mansoni in Brazil is high and results in the loss of productivity. Its persistence in Brazil is a challenge to public health and requires inter-sectorial interventions in areas such as indoor water supply, basic sanitation, and education.

Clinical-epidemiological and laboratory profiles of severe Schistosomiasis mansoni infections at a university hospital.

OBJECTIVE: Schistosomiasis remains a public health problem. This was a descriptive and retrospective study of 42 patients with a severe form of schistosomiasis who were admitted to the outpatient clinic of the Faculdade de Medicina da Universidade de São Paulo, São Paulo, in São Paulo, Brazil. METHODS: A data collection questionnaire was designed from the patient charts, and the following variables were evaluated: age, sex, place of birth, occupation, signs and symptoms of schistosomiasis, data from laboratory and imaging examinations, data regarding treatment outcomes, and the existence of comorbidities. Statistical analysis was carried out using Statistical Package for the Social Sciences 15.0 and Microsoft Excel 2003 software. The significance levels of the tests were fixed, accepting 5% type 1 error (α=0.05). Since this was a retrospective observational study, not all data were available for analysis. RESULTS: The mean age of the patients was 48.24 years; 57.1% were male. Statistically significant associations were observed between splenomegaly and thrombocytopenia (p=0.004) and between splenomegaly and leukopenia (p=0.046); however, only 4.5% of the patients had esophageal hemorrhage. Some patients received a specific treatment; of those, 42% took praziquantel, and 35.4% took oxamniquine. Nonspecific drug therapy was given as follows: 65% received propranolol, 90% omeprazole, and 43.6% aluminum hydroxide. The other treatments were as follows: 92.9% of patients underwent endoscopic treatment, 85% received sclerotherapy, and 62.5% used elastic bandages. CONCLUSION: This preliminary study presents a multidisciplinary outpatient follow-up associated with endoscopic and drug treatments that may be effective at preventing bleeding.

Sm-p80-based vaccine trial in baboons: efficacy when mimicking natural conditions of chronic disease, praziquantel therapy, immunization, and Schistosoma mansoni re-encounter.

Sm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm-p80-based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm-p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel-mediated parasite killing, and Sm-p80-mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm-p80 vaccine and provides insight into some of the epistatic interactions associated with protection.

Serine protease inhibitors containing a Kunitz domain: their role in modulation of host inflammatory responses and parasite survival.

Proteins containing a Kunitz domain have the typical serine protease inhibition function ranging from sea anemone to man. Protease inhibitors play major roles in infection, inflammation disorders and cancer. This review discusses the role of serine proteases containing a Kunitz domain in immunomodulation induced by helminth parasites. Helminth parasites are associated with protection from inflammatory conditions. Therefore, interest has raised whether worm parasites or their products hold potential as drugs for treatment of immunological disorders. Finally, we also propose the use of recombinant SmKI-1 from Schistosoma mansoni as a potential therapeutic molecule to treat inflammatory diseases.

Clinical-epidemiological and laboratory profiles of severe Schistosomiasis mansoni infections at a university hospital

OBJECTIVE: Schistosomiasis remains a public health problem. This was a descriptive and retrospective study of 42 patients with a severe form of schistosomiasis who were admitted to the outpatient clinic of the Faculdade de Medicina da Universidade de São Paulo, São Paulo, in São Paulo, Brazil. METHODS: A data collection questionnaire was designed from the patient charts, and the following variables were evaluated: age, sex, place of birth, occupation, signs and symptoms of schistosomiasis, data from laboratory and imaging examinations, data regarding treatment outcomes, and the existence of comorbidities. Statistical analysis was carried out using Statistical Package for the Social Sciences 15.0 and Microsoft Excel 2003 software. The significance levels of the tests were fixed, accepting 5% type 1 error (α=0.05). Since this was a retrospective observational study, not all data were available for analysis. RESULTS: The mean age of the patients was 48.24 years; 57.1% were male. Statistically significant associations were observed between splenomegaly and thrombocytopenia (p=0.004) and between splenomegaly and leukopenia (p=0.046); however, only 4.5% of the patients had esophageal hemorrhage. Some patients received a specific treatment; of those, 42% took praziquantel, and 35.4% took oxamniquine. Nonspecific drug therapy was given as follows: 65% received propranolol, 90% omeprazole, and 43.6% aluminum hydroxide. The other treatments were as follows: 92.9% of patients underwent endoscopic treatment, 85% received sclerotherapy, and 62.5% used elastic bandages. CONCLUSION: This preliminary study presents a multidisciplinary outpatient follow-up associated with endoscopic and drug treatments that may be effective at preventing bleeding.

Differential distribution and biochemical characteristics of hydrolases among developmental stages of Schistosoma mansoni may offer new anti-parasite targets.

Schistosoma mansoni enzymes play important roles in host-parasite interactions and are potential targets for immunological and/or pharmacological attack. The aim of this study was to comparatively assess the presence of hydrolytic activities (phosphatases, glycosidases, aminopeptidases) in soluble (SF) and membrane (MF) fractions from different S. mansoni developmental stages (schistosomula 0 and 3h, juveniles, and adult worms of 28 and 45days-old, respectively), by using simple enzyme-substrate microassays. Our results show and confirm the prominent presence of alkaline phosphatase (AlP) activity in the MF of all the above parasite stages, highlighting also the relevant presence of MF-associated α-mannosidase (α-MAN) activity in juveniles. A soluble AlP activity, together with ß-N-D-acetylglucosaminidase (ß-NAG), and α-MAN activities, was detected in SF of schistosomulum 0h. Soluble ß-NAG, α-MAN, acid phosphatase (AcP), leucin (LAP) and alanine (AAP) aminopeptidase activities were also seen in the SF of the other different developmental stages. This work shows different soluble and membrane-associated hydrolytic capacities in each S. mansoni developmental stage from schistosomula to adults that might be exploitable as potential new targets for immune and/or chemoprophylactic strategies.

Estudo ecocardiográfico do ventrículo direito em pacientes com hipertensão pulmonar por esquistossomose mansoni / Echocardiography of right ventricle in patients with schistosomiasis-induced pulmonary hypertension

Introdução: A esquistossomose, parasitose tropical, pode provocar hipertensão pulmonar grave (HAPE), que leva a remodelamento e disfunção do ventrículo direito (VD), que pode ser detectada pela diminuição da excursão sistólica do anel tricúspide (TAPSE) e da variação de áreas do VD. No VD normal, rico em fibras longitudinais, predomina o strain longitudinal, sendo menor o strain transversal. Objetivo: Avaliar, com ecocardiografia convencional e com strain bidimensional do VD, pacientes portadores de HAPE, comparando os resultados com dados clínicos, hemodinâmicos e com parâmetros ecocardiográficos obtidos em controles sadios. Material: Trinta e dois pacientes com HAPE, média etária de 45 ± 12 anos. Vinte e três controles sadios, média etária de 48 ± 18 anos.Métodos: Foram avaliados os parâmetros de função do VD (variação de áreas e TAPSE) e o gradiente de refluxo tricúspide. Foi determinado o strain longitudinal e transversal do VD em pacientes com HAPE e em controles sadios. Resultados: Entre os pacientes com HAPE e os controles sadios, a variação das áreas foi, respectivamente, 28% e 46% (p = 0,0001), o TAPSE, 1,9 cm e 2,2 cm (p = 0,02); gradiente de regurgitação tricúspide, 76 mmHg e 28 mmHg (p = 0,0001); deformação longitudinal da parede lateral do VD -22% e -37% (p = 0,0001); e deformação transversal 39% e 21% (p = 0,001). Conclusão: Pacientes com HAPE modificaram o padrão de deformação do VD, com aumento do strain transversal, provavelmente por adaptação do VD à sobrecarga pressórica. O ecocardiograma convencional também foi útil paraavaliar a função do VD na HAPE.

Introduction: Schistosomiasis is a tropical parasitic disease may cause severe pulmonary hypertension (SIPH), which leads to right ventricular (RV) remodeling and dysfunction, which can be detected by decreased tricuspid annular plane systolic excursion (TAPSE) and variation of RV areas. In normal RV, rich in longitudinal fibers, longitudinal strain prevails, and transverse strain is smaller. Objective: To assess, using conventional echocardiography and two-dimensional RV strain, patients with SIPH, comparing the results with clinical and hemodynamic data and echocardiographic parameters obtained from healthy controls. Material: Thirty-two patients with SIPH, mean age 45 ± 12 years old. Twenty-three healthy controls, mean age 48 ± 18 years old. Methods: RV function parameters (range of areas and TAPSE) and the tricuspid regurgitation gradient were evaluated. Longitudinal and transverse RV strain RV were determined in patients with SIPH and in healthy controls. Results: Among SIPH patients and healthy controls, the variation of areas was 28% and 46%, respectively (p = 0.0001), TAPSE was 1.9 cm and 2.2 cm (p = 0.02); tricuspid regurgitation gradient was 76 mmHg and 28 mmHg (p = 0.0001); RV sidewall longitudinal strain -22% and -37%(p = 0.0001); and transverse strain of 39% and 21% (p = 0.001). Conclusion: Patients with SIPH changed the RV strain pattern with increased transverse strain, probably due to RV adaptation to pressure overload. Conventional echocardiography was also useful to assess RV function in SIPH.

Prevalência e carga parasitária da esquistossomose mansônica antes e depois do tratamento coletivo em Jaboatão dos Guararapes, Pernambuco / Prevalence and worm burden of Schistosomiasis mansoni before and after collective treatment in Jaboatão dos Guararapes, Pernambuco, Brazil / Prevalencia y carga parasitaria de Esquistosomiasis mansónica antes y después del tratamiento colectivo en Jaboatão dos Guararapes, Pernambuco, Brasil

OBJETIVO: avaliar a efetividade do tratamento coletivo para esquistossomose mansônica em duas localidades endêmicas do município de Jaboatão dos Guararapes-PE. MÉTODOS: foram descritas a prevalência de esquistossomose e a carga média parasitária antes e após tratamento coletivo, no período 2011-2013; foram utilizados dados do Sistema de Informações da Esquistossomose e de relatórios de conclusão dos inquéritos amostrais. RESULTADOS: observou-se redução no percentual de positividade de 8,9% para 2,3% em Barra de Jangada e de 15,7% para 3,5% em Novo Horizonte; ocorreu diminuição da carga média parasitária em Novo Horizonte (de 67,0 para 52,7 ovos/grama de fezes) e incremento em Barra de Jangada (de 23,8 para 91,7 ovos/grama de fezes). CONCLUSÃO: o tratamento coletivo contribuiu para a redução do percentual de positividade nas áreas endêmicas.

OBJECTIVE: to evaluate the effectiveness of collective treatment for Schistosomiasis mansoni in two endemic localities in Jaboatão dos Guararapes-PE. METHODS: we described the prevalence of Schistosomiasis mansoni and the average parasite load before and after collective treatment in the period 2011-2013; data from the Schistosomiasis mansoni Information System and completion of sample surveys reports were used. RESULTS: there is a reduction in 8.9% positivity rate to 2.3% in Barra de Jangada and from 15.7% to 3.5% in Novo Horizonte; there was a decrease of the parasitic load average in Novo Horizonte (67.0 to 52.7 eggs/gram of feces) and increase in Barra de Jangada (23.8 to 91.7 eggs/gram of feces). CONCLUSION: the collective treatment contributed to reducing the rate of positivity in endemic areas.

OBJETIVO: evaluar la efectividad del tratamiento colectivo para Esquistosomiasis mansónica en dos localidades endémicas del municipio de Jaboatão dos Guararapes-PE. MÉTODOS: describimos la prevalencia de Esquistosomiasis mansónica y la carga parasitaria antes y después del tratamiento colectivo en el período 2011-2013; se utilizaron los datos del Sistema de Información de la esquistosomiasis y la finalización de los informes de encuestas por muestreo. RESULTADOS: observamos una reducción de 8,9% para 2,3% en la tasa de positividad en Barra de Jangada y de 15,7% para 3,5% en Novo Horizonte; hubo una disminución del promedio de carga parasitaria en Nuevo Horizonte (de 67,0 para 52,7 huevos/gramo de heces) y un aumento en Barra de Jangada (de 23,8 a 91,7 huevos/gramo de heces). CONCLUSIÓN: el tratamiento colectivo ayudó a reducir la tasa de positividad en las zonas endémicas.

Garlic attenuates histological and histochemical alterations in livers of Schistosoma mansoni infected mice.

Interest in screening for new anti-schistosomal agents is growing because of increased concerns about resistance to and safety of praziquantel. We investigated the anti-schistosomal action of prophylactic and therapeutic doses of garlic on the histological and histochemical alterations caused by Schistosoma mansoni infection. Livers of infected mice were characterized by granulomas, periportal inflammation and fibrosis, hepatocyte vacuolation, fatty degeneration and necrosis, and hypertrophy and pigmentation of Kupffer cells. Significant depletion of carbohydrates and increased lipid vacuoles also were observed. All garlic regimens caused suppression of granuloma formation and amelioration of histological and histochemical changes; the continuous treatment protocol produced the best results. Garlic appears to be a safe and economical anti-schistosomal adjuvant for attenuating the pathogenicity of schistosomiasis.

Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis.

Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton's jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8(th) week post infection) and late (16(th) week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10(th) month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone.

IMMUNOGENICITY ASSESSMENT FOR LUNG-STAGE AND BIOMPHALARIA ALEXANDRINA COCKTAIIVACCINE IN SCHISTOSOMA MANSONI INFECTED MICE.

The availability of a new vaccine is usually needed as an additional component to chemotherapy for control of schistosomiasis. Different strategies of different types of vaccines were assessed to decrease morbidity but did not give the best protection. The study assessed the efficacy of BAAP, SLAP and their combined preparations together with BCG adjuvant as an effective anti-schistosomal vaccine. METHODOLOGY: Six groups of Swiss albino mice were used; (Gl) as a control, (G2) infected non immunized; (G3) infected and supported by Adj.; (G4) infected; vaccinated with BAAP and supported by Adj.; (G5) infected, vaccinated with SLAP and supported by Adj. and the target group (G6) infected, vaccinated with combined antigens (BAAP + SLAP) and supported by Adjuvant. Mice were sacrificed 8 weeks post infection for assessment the effect of our vaccine through parasitological, histopathological, serological and immunohisto- chemical study. The vaccination of mice with BAAP, SLAP and Adjuvant followed by challenge S. mansoni infection resulted in highest reduction percentages (92% & 86%) for mean numbers of adult burdens and fecal egg counts respectively,(82.4%, 81%) for granuloma number and diameter respectively compared with other groups. The improvement % of all measured enzymes was higher in G6 than other groups.IL1O was significantly increased in G6 than other groups; also, TNF was significantly decreased in G6 than other groups.

Therapeutic Potential of Mesenchymal Stem Cells on Early and Late Experimental Hepatic Schistosomiasis Model.

Cell-based therapy is emerging as a promising therapeutic approach for a wide range of liver diseases. This study aimed to investigate the regenerative and antifibrotic therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in an early and late experimental hepatic schistosomiasis model. BM-MSCs were isolated from 6-wk-old BALB/c donor male mice, then grown and propagated in culture until cell count was 5-8 × 10(6)/ml. MSCs were then separated and injected into Schistosoma mansoni -infected female BALB/c mice on their 6, 10, 14, and 18 wk post-infection. Mice were sacrificed on the fourth and eighth week after BM-MSCs transplantation in each group. Homing of BM-MSCs was confirmed by PCR detection of male Y-chromosome gene (sry) in the liver tissue of the recipient female mice. The regenerative and antifibrotic potential of BM-MSCs was assessed by histopathological examination, morphometric analysis, electron microscopy, and liver function tests. Schistosoma-infected mice, which were treated with BM-MSCs, showed a decrease in the granuloma size, percentage and density of the fibrotic area, formation of new hepatocytes, and improvement of the liver function tests. Immunohistochemical examination of alpha-smooth muscle actin revealed a significant decrease in the immunoreactive hepatic stellate cells in mice treated with MSCs. Early granulomas (acute infection) showed better response to MSC injection than did later granulomas (chronic infection). Dosing and timing of MSCs transplantation should undergo more investigations in long-term experiments before application to the clinical field. This study is the first to assess and compare the effect of MSCs treatment on early and late granulomas.

Understanding low uptake of mass treatment for intestinal schistosomiasis among school children: a qualitative study in Jinja district, Uganda.

Despite attempts to control intestinal schistosomiasis through school-based mass drug administration (MDA) with praziquantel using school teachers in Uganda, less than 30% of the school children take the treatment in some areas. The aim of the study was to understand why the uptake of praziquantel among school children is low and to suggest strategies for improved uptake. This was a cross-sectional qualitative study in which 24 focus group discussions and 15 key informant interviews were conducted 2 months after MDA. The focus group discussions were held with school children in twelve primary schools and the key informant interviews were held with school teachers, sub-county health assistants and the District Vector Control Officer. The study shows that the low uptake of praziquantel among school children is a result of a complex interplay between individual, interpersonal, institutional, community and public policy factors. The individual and interpersonal factors underpinning the low uptake include inadequate information about schistosomiasis prevention, beliefs and attitudes in the community about treatment of schistosomiasis and shared concerns among children and teachers about the side-effects of praziquantel, especially when the drug is taken on an empty stomach. The institutional, policy and community factors include inadequate preparation and facilitation of teachers and the school feeding policy, which requires parents to take responsibility for providing their children with food while at school, yet many parents cannot meet the cost of a daily meal due to the prevailing poverty in the area. It is concluded that strategies to improve uptake of praziquantel among school children need to be multi-pronged addressing not only the preparation and motivation of teachers and health education for children, but also the economic and political aspects of drug distribution, including the school feeding policy.