Acute schistosomiasis diagnosis: a new tool for the diagnosis of schistosomiasis in a group of travelers recently infected in a new focus of Schistosoma mansoni

Introduction The diagnosis of schistosomiasis mansoni on early stages of infection is important to prevent late morbidity. A simple, cheap, sensitive and specific assay for routine diagnosis of schistosome infection based on the detection of specific IgG for schistosomula tegument antigens (ELISA-SmTeg) was developed by our group. Methods We describe here an acute outbreak involving a travel group of 80 individuals from a non-endemic area of the State of Minas Gerais, Brazil. These individuals were in contact with a freshwater pool where Biomphalaria glabrata was found. Results obtained from our new methodology were compared to IgG antibody titers against soluble worm antigenic preparation (SWAP) by ELISA and, also to parasitological examination, nuclear magnetic resonance and clinical findings. Results ELISA-SmTeg was capable of detecting 64 positive cases among the 80 individuals participating at the survey with a positivity ratio of 80% and a higher sensitivity than ELISA-SWAP that was only sensitive for 56% of positive cases. Besides, a significant correlation was found for the severity of the infection and the specific IgG titers against SmTeg. Conclusions Our data showed that ELISA-SmTeg might serve as the initial diagnostic tool for acute stages of the infection in community-based helminth control programs or for the surveillance of individuals from non-endemic areas. .

An outbreak of acute Schistosoma mansoni Schistosomiasis in a nonendemic area of Brazil: a report on 50 cases, including 5 with severe clinical manifestations.

BACKGROUND: Acute schistosomiasis is a systemic hypersensitivity reaction against the migrating schistosomula and eggs. In this report, we describe an atypical outbreak of the disease with severe cases. Transmission occurred in a nonendemic area of Brazil, which became a new focus of transmission due to the in-migration of infected workers. METHODS: From December 2009 to March 2010, the 50 patients with acute schistosomiasis (group 1) bathed in a swimming pool supplied by a brook on a country estate in the outskirts of São João del Rei, Brazil. Thirty other subjects (group 2) living in the same area, who denied having contact with the swimming pool, volunteered to participate in the study. All participants were submitted to clinical, laboratory, and ultrasound examinations. RESULTS: Five of 50 (10%) patients were admitted to the hospital: 1 with myeloradiculopathy, 1 with diffuse pulmonary micronodules, and 3 with diarrhea and dehydration. All 5 had hypereosinophilia and prolonged fever. Group 1 patients more frequently had cercarial dermatitis (P = .01), blood in the stool (P = .04), and intra-abdominal lymph nodes (P = .001). All group 1 patients were treated with praziquantel; 1 patient with myeloradiculopathy also received oral prednisone (60 mg/day) for 6 months with complete recovery. CONCLUSIONS: This report describes the first time that patients from an outbreak of acute schistosomiasis have been compared to controls. Five subjects (10%) had severe manifestations of schistosomiasis. Diagnosis of the disease and its severity was delayed because physicians did not consider that an epidemic of schistosomiasis might emerge in a nonendemic area.

Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni.

BACKGROUND: Schistosomiasis mansoni is a major cause of portal fibrosis and portal hypertension. The Hedgehog pathway regulates fibrogenic repair in some types of liver injury. AIMS: Determine if Hedgehog pathway activation occurs during fibrosis progression in schistosomiasis and to determine if macrophage-related mechanisms are involved. METHODS: Immunohistochemistry was used to characterize the cells that generate and respond to Hedgehog ligands in 28 liver biopsies from patients with different grades of schistosomiasis fibrosis staged by ultrasound. Cultured macrophages (RAW264.7 and primary rat Kupffer cells) and primary rat liver sinusoidal endothelial cells (LSEC) were treated with schistosome egg antigen (SEA) and evaluated using qRT-PCR. Inhibition of the Hedgehog pathway was used to investigate its role in alternative activation of macrophages (M2) and vascular tube formation. RESULTS: Patients with schistosomiasis expressed more ligands (Shh and Ihh) and target genes (Patched and Gli2) than healthy individuals. Activated LSEC and myofibroblasts were Hedgehog responsive [Gli2(+)] and accumulated in parallel with fibrosis stage (P < 0.05). Double IHC for Ihh/CD68 showed that Ihh(+) cells were macrophages. In vitro studies demonstrated that SEA-stimulated macrophages to express Ihh and Shh mRNA (P < 0.05). Conditioned media from such macrophages induced luciferase production by Shh-LightII cells (P < 0.001) and Hedgehog inhibitors blocked this effect (P < 0.001). SEA-treated macrophages also up-regulated their own expression of M2 markers, and Hh pathway inhibitors abrogated this response (P < 0.01). Inhibition of the Hedgehog pathway in LSEC blocked SEA-induced migration and tube formation. CONCLUSION: SEA stimulates liver macrophages to produce Hh ligands, which promote alternative activation of macrophages, fibrogenesis and vascular remodelling in schistosomiasis.

Glomerulonephritis in schistosomiasis mansoni: a time to reappraise.

INTRODUCTION: The current prevalence of glomerulonephritis in patients with hepatosplenic schistosomiasis mansoni in Brazil was evaluated. METHODS: Sixty three patients (mean age 45.5 ± 11 years) attending the outpatient infectious disease clinic of a University Hospital in Belo Horizonte, Brazil, from 2007 to 2009, were consecutively examined and enrolled in the present investigation. Diagnosis of hepatosplenic schistosomiasis was based on epidemiological, clinical and parasitological data and imaging techniques. Eight patients, who presented >30 mg/day albuminuria, were submitted to percutaneous ultrasound guided renal biopsy. Kidney tissue fragments were examined under light, direct immunofluorescence and electron microscopy. RESULTS: All patients showed mesangial enlargement. In five, mesangial hypercellularity was observed and four presented duplication of the glomerular basement membrane. Areas of glomerular sclerosis were diagnosed in four. Deposits of immunoglobulin M and C3 were present in six samples; deposits of IgG in four, IgA in three and C1q in two samples. In all patients, immunoglobulin A was reported in the lumen of renal tubules. Deposits of kappa and lambda were observed in six samples. Electron microscopy revealed dense deposits in the glomerular tissue of three patients. Arterial hypertension, small esophageal varices, slight increases in serum creatinine and decreases in serum albumin were associated with glomerular disease. CONCLUSIONS: Renal disease associated with hepatosplenic schistosomiasis was verified in 12.7% of patients and type I membranoproliferative glomerulonephritis was observed in 50% of them. Schistosomal glomerulopathy still is an important problem in patients with hepatosplenic schistosomiasis in Brazil.

Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity / Hepatotoxicidade induzida pelos tuberculostáticos: comparação em pacientes com e sem soropositividade para o vírus da imunodeficiência humana

INTRODUCTION: The prevalence and risk factors for rifampin, isoniazid and pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls. METHODS: Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007, were selected for this investigation. Three definitions of hepatotoxicity were used: I) a 3-fold increase in the lower limit of normal for alanine-aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN) for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in the ULN of total bilirubin. RESULTS: In groups with and without HIV infection the frequency of hepatotoxicity I was 77 percent and 46 percent, respectively (p < 0.01). Using hepatotoxicity II and III definitions no difference was observed in the occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with hepatotoxicity by definition III, 3 presented no side effects and treatment was well tolerated. In 8 (36.4 percent) out of 22, symptoms emerged and treatment was suspended. Alcohol abuse was related to hepatotoxicity only for definition I. CONCLUSIONS: Depending on the definition of drug-induced hepatitis, HIV infection may or may not be associated with hepatotoxicity. The impact that minor alterations in the definition had on the results was impressive. No death was related to drug-induced hepatotoxicity. The emergence of new symptoms after initiating antituberculosis therapy could not be attributed to hepatotoxicity in over one third of the cases.

INTRODUÇÃO: Avaliou-se a prevalência e os fatores de risco para hepatotoxicidade aos tuberculostáticos em pacientes HIV positivos e controles. MÉTODOS: Selecionou-se 162 pacientes com tuberculose, tratados com rifampicina, isoniazida e pirazinamida, na faixa etária de 18 a 80 anos, internados em hospital público no Brasil, entre 2005 e 2007. Eles foram divididos em dois grupos: 30 infectados pelo HIV e 132 controles. Adotou-se três definições para hepatotoxicidade: I) aumento de três vezes no valor inferior normal da alanina-aminotransferase (ALT); II) aumento de três vezes no valor superior normal (VSN) da ALT; III) aumento de três vezes no VSN da ALT e duas vezes no VSN da bilirrubina total. RESULTADOS: Nos grupos com e sem infecção pelo HIV, a frequência de hepatotoxicidade I foi de 77 por cento e 46 por cento, respectivamente (p<0,01). Para as definições II e III a frequência de hepatotoxicidade não diferiu entre os grupos estudados. De 17 pacientes com hepatotoxicidade induzida por droga (definição III), três não apresentaram sintomas e o tratamento foi mantido sem intercorrências. Oito (36,4 por cento) de 22 indivíduos apresentaram efeitos colaterais e interromperam o tratamento, mas não apresentavam hepatotoxicidade pela definição III. O abuso de álcool associou-se à hepatotoxicidade apenas para a definição I. CONCLUSÕES: Na dependência da definição escolhida, a infecção pelo HIV pode ou não associar-se à hepatotoxicidade. Foi grande o impacto que pequenas alterações na definição de hepatotoxicidade tiveram nos resultados. Nenhuma morte associou-se ao uso de tuberculostáticos. O surgimento de sintomas não pôde ser atribuído aos tuberculostáticos em um terço dos casos.

Glomerulonephritis in schistosomiasis mansoni: a time to reappraise / Glomerulonefrite na esquistossomose mansônica: um tempo para reavaliar

INTRODUCTION: The current prevalence of glomerulonephritis in patients with hepatosplenic schistosomiasis mansoni in Brazil was evaluated. METHODS: Sixty three patients (mean age 45.5±11 years) attending the outpatient infectious disease clinic of a University Hospital in Belo Horizonte, Brazil, from 2007 to 2009, were consecutively examined and enrolled in the present investigation. Diagnosis of hepatosplenic schistosomiasis was based on epidemiological, clinical and parasitological data and imaging techniques. Eight patients, who presented >30mg/day albuminuria, were submitted to percutaneous ultrasound guided renal biopsy. Kidney tissue fragments were examined under light, direct immunofluorescence and electron microscopy. RESULTS: All patients showed mesangial enlargement. In five, mesangial hypercellularity was observed and four presented duplication of the glomerular basement membrane. Areas of glomerular sclerosis were diagnosed in four. Deposits of immunoglobulin M and C3 were present in six samples; deposits of IgG in four, IgA in three and C1q in two samples. In all patients, immunoglobulin A was reported in the lumen of renal tubules. Deposits of kappa and lambda were observed in six samples. Electron microscopy revealed dense deposits in the glomerular tissue of three patients. Arterial hypertension, small esophageal varices, slight increases in serum creatinine and decreases in serum albumin were associated with glomerular disease. CONCLUSIONS: Renal disease associated with hepatosplenic schistosomiasis was verified in 12.7 percent of patients and type I membranoproliferative glomerulonephritis was observed in 50 percent of them. Schistosomal glomerulopathy still is an important problem in patients with hepatosplenic schistosomiasis in Brazil.

INTRODUÇÃO: Avaliou-se a frequência de glomerulonefrite em pacientes com esquistossomose hepatosplênica no Brasil. MÉTODOS: Selecionou-se para o estudo, 63 pacientes (idade média de 45,5±11 anos) avaliados consecutivamente no ambulatório de doenças infecciosas de um hospital universitário de Belo Horizonte, Brasil, no período de 2007 a 2009. O diagnóstico da esquistossomose foi baseado em dados epidemiológicos, clínicos, parasitológicos e de imagem. Os oito pacientes que apresentaram albuminúria acima de 30mg em 24 horas submeteram-se a biópsia renal percutânea dirigida por ultrassonografia. As amostras de tecido renal foram analisadas à microscopia óptica, eletrônica e de fluorescência direta. RESULTADOS: Havia expansão do mesângio em todos. Em cinco, houve proliferação de células mesangiais e em quatro observou-se duplicação da membrana basal glomerular. Áreas de esclerose glomerular foram diagnosticadas em quatro. Depósitos de imunglobulinas M e C3 foram patentes em seis amostras; IgG em quatro, IgA em três e C1q em duas. Em todos os pacientes relatou-se fluorescência para IgA dentro dos túbulos renais. Depósitos de kappa e lambda foram vistos em seis amostras. A microscopia eletrônica demonstrou depósitos eletrondensos em tecido glomerular. A presença de hipertensão arterial, varizes do esôfago de pequeno calibre, pequenos aumentos de creatinina e diminuição de albumina sérica associaram-se à ocorrência de dano renal. CONCLUSÕES: A frequência de lesão renal foi de 12,7 por cento, no presente estudo, e a glomerulonefrite membranoproliferativa do tipo I foi encontrada em 50 por cento. A lesão renal associada à esquistossomose permanece um problema importante no Brasil.

Imaging techniques and histology in the evaluation of liver fibrosis in hepatosplenic schistosomiasis mansoni in Brazil: a comparative study.

Few publications have compared ultrasound (US) to histology in diagnosing schistosomiasis-induced liver fibrosis (LF); none has used magnetic resonance (MR). The aim of this study was to evaluate schistosomal LF using these three methods. Fourteen patients with hepatosplenic schistosomiasis admitted to hospital for surgical treatment of variceal bleeding were investigated. They were submitted to upper digestive endoscopy, US, MR and wedge liver biopsy. The World Health Organization protocol for US in schistosomiasis was used. Hepatic fibrosis was classified as absent, slight, moderate or intense. Histology and MR confirmed Symmers' fibrosis in all cases. US failed to detect it in one patient. Moderate agreement was found comparing US to MR; poor agreement was found when US or MR were compared to histology. Re-classifying LF as only slight or intense created moderate agreement between imaging techniques and histology. Histomorphometry did not separate slight from intense LF. Two patients with advanced hepatosplenic schistosomiasis presented slight LF. Our data suggest that the presence of the characteristic periportal fibrosis, diagnosed by US, MR or histology, associated with a sign of portal hypertension, defines the severity of the disease. We conclude that imaging techniques are reliable to define the presence of LF but fail in grading its intensity.

Imaging techniques and histology in the evaluation of liver fibrosis in hepatosplenic schistosomiasis mansoni in Brazil: a comparative study

Few publications have compared ultrasound (US) to histology in diagnosing schistosomiasis-induced liver fibrosis (LF); none has used magnetic resonance (MR). The aim of this study was to evaluate schistosomal LF using these three methods. Fourteen patients with hepatosplenic schistosomiasis admitted to hospital for surgical treatment of variceal bleeding were investigated. They were submitted to upper digestive endoscopy, US, MR and wedge liver biopsy. The World Health Organization protocol for US in schistosomiasis was used. Hepatic fibrosis was classified as absent, slight, moderate or intense. Histology and MR confirmed Symmers' fibrosis in all cases. US failed to detect it in one patient. Moderate agreement was found comparing US to MR; poor agreement was found when US or MR were compared to histology. Re-classifying LF as only slight or intense created moderate agreement between imaging techniques and histology. Histomorphometry did not separate slight from intense LF. Two patients with advanced hepatosplenic schistosomiasis presented slight LF. Our data suggest that the presence of the characteristic periportal fibrosis, diagnosed by US, MR or histology, associated with a sign of portal hypertension, defines the severity of the disease. We conclude that imaging techniques are reliable to define the presence of LF but fail in grading its intensity.

Schistosoma mansoni: magnetic resonance analysis of liver fibrosis according to WHO patterns for ultrasound assessment of schistosomiasis-related morbidity

For the last two decades, ultrasound (US) has been considered a surrogate for the gold standard in the evaluation of liver fibrosis in schistosomiasis. The use of magnetic resonance imaging (MRI) is not yet standardised for diagnosing and grading liver schistosomal fibrosis. The aim of this paper was to analyse MRI using an adaptation of World Health Organization (WHO) patterns for US assessment of schistosomiasis-related morbidity. US and MRI were independently performed in 60 patients (42.1 ± 13.4 years old), including 37 men and 23 women with schistosomiasis. Liver involvement appraised by US and MRI was classified according to the WHO protocol from patterns A-F. Agreement between image methods was evaluated by kappa index (k). The correlation between US and MRI was poor using WHO patterns [k = 0.14; confidence interval (CI) 0.02; 0.26]. Even after grouping image patterns as "A-D", "Dc-E" and "Ec-F", the correlation between US and MRI remained weak (k = 0.39; CI 0.21; 0.58). The magnetic resonance adaptation used in our study did not confirm US classification of WHO patterns for liver fibrosis.

Serum hyaluronan and collagen IV as non-invasive markers of liver fibrosis in patients from an endemic area for schistosomiasis mansoni: a field-based study in Brazil

Non-invasive markers of fibrosis have been used to diagnose liver fibrosis in a variety of diseases. Hyaluronic acid (HA) and collagen IV (C-IV) levels were measured in the sera of patients from an endemic area for schistosomiasis in Brazil to diagnose and to rank the intensity of liver fibrosis. Seventy-nine adult patients with schistosomiasis, in the age range of 21-82 years (49 ± 13.4) were submitted to clinical and ultrasonographic examinations. Ultrasound was employed to diagnose and categorise liver fibrosis according to World Health Organization patterns. Serum HA and C-IV levels were measured using commercial ELISA kits. Ultrasound revealed six patients with intense liver fibrosis, 21 with moderate, 23 with light and 29 without. Serum HA was able to separate individuals with fibrosis from those without (p < 0.001) and light from intense fibrosis (p = 0.029), but C-IV was not (p = 0.692). The HA diagnostic accuracy for fibrosis was 0.89. The 115.4 ng/mL cut-off level diagnosed patients with fibrosis (sensitivity 0.98, specificity 0.64). HA correlated positively with portal hypertension. Periportal fibrosis (subjective evaluation), age and collateral circulation predicted HA increase. In conclusion, we propose that serum HA can be used to identify patients with liver fibrosis in an endemic area for schistosomiasis mansoni in Brazil.

Comparison between clinical and ultrasonographic findings in cases of periportal fibrosis in an endemic area for schistosomiasis mansoni in Brazil / Comparação entre achados clínicos e ultrassonográficos no diagnóstico da fibrose periportal em uma área endêmica de esquistossomose no Brasil

INTRODUCTION: Abdominal palpation and ultrasound findings among patients from an endemic area for schistosomiasis in Brazil who had been followed up for 27 years were compared. METHODS: In 2004, 411 patients from Brejo do Espírito Santo, in the State of Bahia, were selected for the present investigation after giving their written informed consent. Based on clinical data, they were divided into three groups: 41 patients with evidence of liver fibrosis in 2004 (Group 1); 102 patients with evidence of liver fibrosis in the past (1976-1989) but not in 2004 (Group 2); and 268 patients without evidence of liver fibrosis at any time during the 27-year follow-up (Group 3). All of the patients underwent abdominal ultrasound in which the examiner did not know the result from the clinical examination. The data were stored in a database. RESULTS: The prevalence of periportal fibrosis on ultrasound was 82.9 percent, 56.9 percent and 13.4 percent in Groups 1, 2 and 3, respectively. In the presence of hard, nodular liver or prominent left lobe and a hard palpable spleen, ultrasound revealed periportal fibrosis in 70.9 percent. However, periportal fibrosis was diagnosed using ultrasound in 25.4 percent of the patients in the absence of clinical evidence of liver involvement. Thus, ultrasound diagnosed periportal fibrosis 3.1 times more frequently than clinical examination did. CONCLUSIONS: Although clinical examination is important in evaluating morbidity due to Manson's schistosomiasis in endemic areas, ultrasound is more accurate in diagnosing liver involvement and periportal fibrosis.

INTRODUÇÃO: Neste estudo, se comparou os achados da palpação abdominal e do ultrassom em pacientes de área endêmica de esquistossomose que foram acompanhados por 27 anos no Brasil. MÉTODOS: Em 2004, 411 pacientes de Brejo do Espírito Santo, no estado da Bahia, após consentimento informado e por escrito foram selecionados para o presente estudo. Baseando-se no exame clínico eles foram divididos em 3 grupos: 41 (Grupo 1) com evidência de fibrose hepática no ano de 2004; 102 (Grupo 2) com evidência de fibrose hepática no passado (1976-1989) mas não em 2004; e 268 (Grupo 3) sem evidência de fibrose hepática em 27 anos de seguimento. Todos foram submetidos a exame ultrassonográfico do abdome em que o examinador não sabia o resultado do exame clínico. Os dados foram armazenados em banco de dados. RESULTADOS: A prevalência de fibrose periportal ao ultrassom foi de 82,9 por cento, 56,9 por cento e 13,4 por cento nos Grupos 1, 2 e 3, respectivamente. Na presença de fígado duro, nodular ou lobo esquerdo proeminente e baço palpável duro, o ultra-som revelou fibrose periportal em 70,9 por cento. Porém, fibrose periportal foi diagnosticada através do ultrassom em 25,4 por cento dos pacientes, na ausência de evidência clínica de envolvimento hepático. Assim, o ultrassom diagnosticou fibrose periportal 3,1 vezes mais frequentemente que o exame clínico. CONCLUSÕES: O exame clínico tem importância na avaliação da morbidade da esquistossomose mansônica em áreas endêmicas, mas o ultrassom mostra-se mais preciso quando se pretende diagnosticar o envolvimento hepático e a fibrose periportal.