High Egg Reduction Rate but poor clearance of Circulating Cathodic Antigen three weeks after Praziquantel treatment among school children on Ijinga Island, north-western Tanzania.

Traditionally, efficacy of Praziquantel (PZQ) is monitored using Parasitological Cure Rates and Egg Reduction Rates applying Kato Katz (KK) technique. This parasitological technique has a number of limitations. Recently, the Point-of-Care Circulating Cathodic Antigen (POC-CCA) rapid test which is a highly sensitive technique, has emerged as a promising candidate to be used for evaluating the efficacy of PZQ. A prospective longitudinal study was conducted among 399 school children aged 7-17 years on Ijinga Island, north-western Tanzania. At baseline and three weeks after treatment, stool and urine samples were collected from participating school children and screened for S. mansoni infection using the KK technique as well as POC-CCA test. All S. mansoni infected children at baseline were treated with 40mg/kg of PZQ and followed up after three weeks. At baseline, the overall prevalence of S. mansoni infection was 56.6% (95%CI: 51.7-61.4) and 99.7% (95%CI: 98.2-99.9) (considering trace as positive) using KK technique and POC-CCA test, respectively. Three weeks after treatment, the prevalence of S. mansoni was 0.92% using the KK technique and 97.7% when applying the POC-CCA test. The parasitological cure rates based on KK technique and POC-CCA were 99.1% (95%CI: 97.5-99.8) and 2.3% (95%CI: 1.2-4.5). Egg Reduction Rate was 99.1%. Based on WHO guidelines using the KK technique, at three weeks point, the efficacy of PZQ is satisfactory. However, the assessment of the efficacy of PZQ using POC-CCA tests needs further evaluation.

Restaging Pulmonary Schistosomiasis.

Schistosomiasis is traditionally classified into an acute and a chronic phase, although a precise temporal distinction between the two phases has not been established. Lung involvement can be observed in both phases. We previously reported seven cases of pulmonary lesions due to chronic schistosomiasis in African immigrants. All cases were documented with CT scans and demonstrated complete resolution after treatment with praziquantel. Moreover, another case showed spontaneous disappearance of the nodule before treatment with praziquantel. These findings are similar to those observed in the acute phase of schistosomiasis, with well-defined or ground glass nodules that resolve spontaneously. According to these findings, we postulate the presence of an "intermediate" phase of schistosomiasis involving the lungs that can be defined as an "early chronic phase," and presents analogies to the acute phase. We also hypothesize that in the "early chronic phase," the female worms transit through the lungs where they may lay eggs. These passages not only cause transient, but also radiologically visible alterations. The pathophysiology of lung lesions in the late chronic phase is probably different: the adult worms settled in the mesenteric plexuses produce eggs for years. The eggs repeatedly migrate to the perialveolar capillary beds via portal-caval shunting. Thus, in this case it is the eggs and not the adult worms that reach the lungs in a scattered way. Based on our findings, we suggest the alternative hypothesis that the pulmonary involvement is a phase of the natural evolution of the infection, both from Schistosoma mansoni and Schistosoma haematobium.

Efficacy of artesunate with sulfalene plus pyrimethamine versus praziquantel for treatment of Schistosoma mansoni in Kenyan children: an open-label randomised controlled trial.

BACKGROUND: Schistosomiasis is an important parasitic disease in Kenya. Decreasing susceptibility of schistosomes to praziquantel, the major drug used to reduce disease morbidity, has made assessment of new antischistosomal drugs a priority. We aimed to assess the safety and efficacy of an artesunate-based combination drug in the treatment of schistosomiasis. METHODS: In this open-label randomised trial in Rarieda district of western Kenya, we enrolled school children (aged 6-15 years) who had Schistosoma mansoni infection according to duplicate Kato-Katz thick smears from a stool sample. Computer-generated block randomisation was used to assign children (1:1) to receive artesunate (100 mg) with sulfalene (also known as sulfamethoxypyrazine; 250 mg) plus pyrimethamine (12.5 mg) as one dose every 24 h for 3 days or one dose of praziquantel (40 mg/kg per day). The primary efficacy endpoint was the number of participants cured 28 days after treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01054651. RESULTS: Between October and December, 2009, 212 children were enrolled and assigned to receive artesunate with sulfalene plus pyrimethamine (n=106) or praziquantel (n=106). 69 patients (65%) were cured in the praziquantel treatment group compared with 15 (14%) in the artesunate with sulfalene plus pyrimethamine treatment group (p<0.0001). Adverse events were less common in patients taking artesunate with sulfalene plus pyrimethamine than in those taking praziquantel (22% [n=23] vs 49% [n=52], p<0.0001), and no drug-related serious adverse events occurred. INTERPRETATION: The standard treatment with praziquantel is more effective than artesunate with sulfalene plus pyrimethamine in the treatment of children with S mansoni infection in western Kenya. Whether artemisinin-based combination therapy has a role in the treatment of schistosomiasis is unclear.

Esquistosomiasis mansonica riesgo en la Cuenca del Plata / Esquistosomiasis mansonica risk in the Cuenca of the Plata

Visto el avance de 1000 km. de la esquistosomíasis en el cuenca del Plata, en los últimos años, el presente trabajo tiene el objetivo de efectuar un diagnostíco de situación y propuesta de soluciones de tan grave endemia. Con un impacto socioeconomic tan importante. En nuestro país ya hay registros de casos humanos en la provincia de Misiones.

Esquistosomiasis mansonica riesgo en la Cuenca del Plata / Esquistosomiasis mansonica risk in the Cuenca of the Plata

Visto el avance de 1000 km. de la esquistosomíasis en el cuenca del Plata, en los últimos años, el presente trabajo tiene el objetivo de efectuar un diagnostíco de situación y propuesta de soluciones de tan grave endemia. Con un impacto socioeconomic tan importante. En nuestro país ya hay registros de casos humanos en la provincia de Misiones.

Schistosomiasis mansoni - Clinical features

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In the present review, we will discuss the Schistosoma mansoni form, which is the most widely distributed schistosome in humans and is found both in the Old and New Worlds. The main features of the natural history of mansonic schistosomiasis are reviewed, with emphasis on the clinical forms of the disease, their diagnosis and treatment

Serum hyaluronic acid as a comprehensive marker to assess severity of liver disease in schistosomiasis.

Schistosomiasis mansoni is a non-cirrhotic fibrogenic disease model. The mild form shows normal liver function with slight or no liver fibrosis whereas in the periportal fibrosis form the manifestations of portal hypertension prevail over hepatocellular failure. We assessed serum hyaluronic acid as a marker of the course of the disease. We studied 24 patients presenting with pure chronic forms of schistosomiasis and seven with cirrhosis. In order to measure serum hyaluronic acid we developed a sandwich fluorescent ELISA-like assay. alpha2-Macroglobulin, prothrombin index, gamma-glutamyltransferase, platelets and ultrasound parameters were also assessed. The 20 micro g/l (ROC plot) hyaluronic acid level differentiated patients with the mild form (with no portal hypertension) from those with the severe form of schistosomiasis with 78% diagnostic efficacy. The 80 micro g/l cut-off value differentiated patients with the severe form of schistosomiasis from the cirrhotic group with similar diagnostic efficacy. alpha2-Macroglobulin provided no distinction between the groups studied. The hyaluronic acid serum concentration correlated positively with the splenic vein diameter (P=0.004) and marginally with alpha2-macroglobulin (P=0.059). Serum hyaluronic acid is a good marker for the initial phase of hepatic fibrosis and it was able to assess severity of liver disease in schistosomiasis.

Morbidity of schistosomiasis mansoni in the highlands of Madagascar and comparison of current sonographical classification systems.

To study the morbidity of schistosomiasis mansoni in the highlands of Madagascar, a cross-sectional study examined the extent to which liver fibrosis occurred in a rural community. The Managil and the Cairo classification systems were used. A second purpose was to investigate the effect of the measurements of 2 different branches of the portal vein (either segmental or sub-segmental branches) on the resulting staging of morbidity using the Cairo classification system. In a rice farmer village, 656 inhabitants (95% of the total population) were parasitologically examined; 561 patients underwent sonographic work-up based on the Managil scoring system, and in 307 randomized patients the outer to outer diameters of both the segmental and the sub-segmental branches of the portal vein were measured and scored by the Cairo classification system. Overall prevalence of schistosomiasis mansoni in the study area in 1994 was 68.3%. Upon sonographic examination and scoring by the Managil system 23.4% of the population showed liver changes (Managil degree I/II/III, 20%/2.5%/0.9%). Measuring the sub-segmental branches only and scoring by the Cairo classification, 19% of the study population were found to have liver changes, none with severe fibrosis. By contrast, 82% were found to have liver changes (Cairo degree 1/2/3, 70%/11%/2%) when the segmental branches were measured. The diameters of the sub-segmental branches were about two-thirds of those of the segmental branches. Both the Cairo- and the Managil-examination protocols have pitfalls. Using the Cairo classification, a considerable systematic error in classifying morbidity is created by measuring different branches of the portal vein.

[Ultrasonoic diagnosis of morbidity related to schistosomiasis due to Schistosoma mansoni and Schistosoma haematobium: epidemiological and individual value]. / Diagnostic échographique de la morbidité liée à la schistosomose à Schistosoma mansoni et à Schistosoma haematobium: intérêt épidémiologique, intérêt individuel.

By allowing study of large population samples, ultrasonography has revolutionized assessment of schistosomiasis-related morbidity. Previous clinical or parasitological parameters provided poor documentation of the public health impact of schistosomiasis. Thanks to a WHO-coordinated drive to standardize examination protocols and severity scores, comparison of data from different regions is now much easier. The latest "Niamey" methodology has eliminated the major shortcomings of earlier methods. Detection of periportal fibrosis is the cardinal diagnostic feature for Schistosoma mansoni. Ultrasonographic evidence has been validated by correlation with hepatic biopsy findings from hospitalized patients with severe disease. The specificity of ultrasonography is poor in low- or moderate-grade disease for which different methodologies give discordant results. Ultrasonography is highly sensitive for assessment of morbidity related to Schistosoma haematobium infection, which is associated with typical bladder lesions. Lesions involving the upper urinary tract are also well visualized but do not constitute a specific finding. The best applications for which ultrasonographic investigation of schistomsomiasis is now considered as mandatory are community-based studies and post-therapeutic follow-up of populations. In contrast ultrasonography is not well suited to individual diagnosis. In endemic areas, ultrasonography may be used for individual diagnosis if more effective methods are unavailable. However the poor specificity of some images is a major limitation for use in zones of low transmission.

Schistosomiasis mansoni: immunoblot analysis to diagnose and differentiate recent and chronic infection.

One hundred seven patients classified into three different groups (11 with acute schistosomiasis, 58 with chronic schistosomiasis, and 38 children with high IgM-specific antibody titers against schistosome gut-associated antigens living in an endemic schistosomiasis area) were studied by immunoblotting for the presence of IgG, IgM, and IgA antibodies against Schistosoma mansoni soluble adult worm antigen preparation. We used sera from 15 individuals infected with various intestinal parasites, as well as sera from 19 uninfected individuals, as controls. An immunogenic fraction with a molecular weight of 31-32 kD (Sm31/32) was the most frequently recognized by the different antibody isotypes. In the group with acute disease, this fraction was recognized by IgG and IgM antibodies of all patients, and by 10 (90.9%) of 11 samples for IgA antibodies. Approximately 98% of the patients with chronic infections had IgG antibodies against Sm31/32, but only about 10% had IgM and IgA antibodies against this fraction. The IgG immunoblot profiles of the children from the endemic area were similar to those obtained for the group with acute schistosomiasis. This observation suggests recent infection of these children. Our data show that the Sm31/32 protein fraction is highly immunogenic and may be a useful serologic marker for diagnosing and differentiating between acute and chronic schistosomiasis infection.

Efficacy of an enzyme-linked immunosorbent assay in the diagnosis of and serologic distinction between acute and chronic Schistosoma mansoni infection.

To determine the efficacy of an ELISA to diagnose and differentiate the clinical phases of schistosomiasis, serum from patients with acute (11) and chronic schistosomiasis (58), from individuals infected with other parasites (53), and from uninfected individuals (40) was analyzed for the presence of anti-schistosomal of IgG, IgM, and IgA antibodies. Immunofluorescence for IgM and IgA antibodies was also performed on serum from all patients and controls. The IgG antibodies against worm antigen (ELISA-w) were detected in all schistosomiasis patients, with only one false-positive result. The IgA antibodies were detected by ELISA-w in 81.8% of patients with acute disease and in only 5.9% of patients with chronic disease. In addition, the mean optical density values for IgM and IgA antibodies was statistically higher in the patients with acute disease than in those with chronic disease. The results of this study show that the use of a crude adult worm extract as an ELISA antigen can provide a serologic method with high sensitivity and specificity for 1) the diagnosis of acute and chronic schistosomiasis and (2) the serologic distinction between the two forms of the disease.

Flow cytometric study of blood leucocytes in clinical forms of human schistosomiasis.

The aim of this study was to examine three distinct groups of schistosomiasis patients and to determine whether cell phenotype profiles could be correlated with the different clinical forms of the disease. The data obtained indicate that Schistosoma mansoni infected patients have a lower percentage of CD3+ T cells than do non-infected individuals. Interestingly, infected patients presented more than twice the mean percentage of circulating activated T cells (CD3+HLA-DR+) when compared to the control group. Examination of T lymphocyte subpopulations showed that patients with the severe hepatosplenic form (HS) of the disease had lower levels of both CD8High+ and CD8Low+ cells when compared to the other groups of patients. All infected individuals had a higher percentage of circulating B cells, with an increase in the CD5+ B cell population that was more evident in the HS group. The data presented here are evidence to support a relationship between the hepatosplenic form of the disease, a decrease on the CD8+ cell population and an elevation on CD5+ B cells.

Evidence that cellular immune responses to soluble and membrane associated antigens are independently regulated during human schistosomiasis mansoni.

We have made a comparative analysis of human cellular and antibody responses to membrane associated adult worm antigens (Mb-A), soluble adult worm antigens (SWAP) and soluble egg antigens (SEA) derived from Schistosoma mansoni. Chronically infected patients with the intestinal (I) and hepatosplenic (HS) forms of the disease as well as non-infected putative immune 'endemic normals' (EN), were studied. We observed that the cellular responses, of individuals, to the two adult worm preparations, SWAP and Mb-A, may be distinct and can be related to the occurrence of resistance or pathology. The resistant group (EN) presented higher levels of both cellular proliferation, and IFN-gamma production, in response to Mb-A as compared with SWAP whereas HS individuals presented higher levels of cellular proliferation to SWAP as compared with Mb-A. Individuals with intestinal disease had similar levels of proliferation to both antigens. The response to SEA by all groups was generally similar, and not predictive of any clinical form. The specific antibody response to the three antigens were in general higher among infected patients than in resistant EN individuals. These results support the hypothesis that the response to adult worm antigens may be pivotal in determining both the development of resistance and severity of disease.

[Use of ultrasonography in Schistosoma mansoni infections: from the past to the present and future perspectives]. / Utilisation de l'échographie dans l'infection à Schistosoma mansoni: du passé au présent, perspectives d'avenir.

Before the sonographic era, clinics or parasitology even autopsy have been the only sources of basic principles on the morbidity due to Schistosoma mansoni. The exploration of inner organs and their pathologies became easier. The organ's size as well as their echogenicity permit grading. Up till now, any classification is not appropriate. Attempts of standardization haven't yet succeeded, thus any comparison among different endemic regions is not possible. A simple method based on qualitative observation of the periportal fibrosis is proposed to help sonographist for the diagnosis of presumption in front of evocative image and to be a guideline for later investigation.

[Ultrasonographic evaluation of Schistosoma mansoni morbidity: comparison of Cairo/WHO and Managil-Hannover classifications]. / Evaluation échographique de la morbidité liée à Schistosoma mansoni: comparaison des classifications Cairo/OMS et Managil-Hannover.

A ultrasonographical survey of morbidity in schistosomiasis mansoni was carried out in two villages of an endemic area of Madagascar. Using the Managil-Hannover classification, the overall prevalence of morbidity in the first village was of 49.4% and of 39.4% in the second one, while modified Cairo/WHO classification found 9.1% and 1.9% respectively. Thus, results given by the two classifications for a same individual are often discordant. This discrepancy is essentially observed in the lower stage of morbidity while advanced cases are generally well-staged by either of these two methods. These differences in the sonographical assessment of morbidity related to hepatosplenic schistosomiasis make it necessary to continue investigations in order to establish a classification that will have the agreement of everybody.

[Presence of urinary Sm28GST antigen in Madagascar patients with Schistosomiasis mansoni]. / Présence d'antigène Sm28GST urinaire chez des patients malgaches atteints de bilharziose à Schistosoma mansoni.

Using an ELISA method, we quantitated the level of glutathion S-transferase 28 kDa (Sm28GST), specific of Schistosoma mansoni, in the urine of 13 malagasy patients. The presence of Sm28GST antigen has been demonstrated for the first time, in 8 patients (69%). No significant correlation could be found between antigen level and the parasitological burden in the feces. The use of an immunocapture ELISA technic on a larger number of samples will be necessary to assess if this test could be quantitative and reliable enough for the diagnosis or the follow up of patients infected with Schistosoma mansoni.

Aspects of the granulomatous reaction in the liver of mice infected and reinfected with two different geographical strains of schistosoma mansoni

In this study, which was undertaken in relation to the histopathologic behavior of two different strains (LE - Belo Horizonte, MG and SJ - Sao José dos Campos, SP) in infections and reinfections (homologous or heterologous) with Schistosoma mansoni, the authors confirmed a more accentuated pathogenicity of the SJ strain. All the reinfections showed the presence of typical granulomas of the acute phase, when performed either with the same strain (homologous) or with a different strain (heterologous) of the parasite of the primo infection. The possible mechanisms responsible for reactivation of the immunopathologic response in reinfections are discussed.

Aspects of the granulomatous reaction in the liver of mice infected and reinfected with two different geographical strains of Schistosoma mansoni.

In this study, which was undertaken in relation to the histopathologic behavior of two different strains (LE-Belo Horizonte, MG and SJ-São José dos Campos, SP) in infections and reinfections (homologous or heterologous) with Schistosoma mansoni, the authors confirmed a more accentuated pathogenicity of the SJ strain. All the reinfections showed the presence of typical granulomas of the acute phase, when performed either with the same strain (homologous) or with a different strain (heterologous) of the parasite of the primo infection. The possible mechanisms responsible for reactivation of the immunopathologic response in reinfections are discussed.