Izabela Voieta

Macrophage‐derived hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni

Schistosomiasis mansoni is a major cause of portal fibrosis and portal hypertension. The Hedgehog pathway regulates fibrogenic repair in some types of liver injury.

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.

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.

Schistosomiasis mansoni of the prostate

A 56-year-old man came to hospital for a routine checkup. His medical history and physical examination wereunremarkable. Laboratory evaluation was normal, except for aserum prostate specific antigen (PSA) of 6.5ng/mL (referencevalues: 0-3.5ng/mL). Digital rectal examination revealed anenlarged well-delimitated prostate. Transrectal ultrasonographywas normal. A biopsy retrieved 9 fragments of prostate tissueand histology showed no alterations. He was followed at theoutpatient clinic for another 3 months and a second PSA showedincreasing levels (7.2ng/mL). A second transrectal biopsy showedno malignant infiltration of the prostate, but eggs of S. mansonisurrounded by characteristic granulomata were described(Figure A shows a granuloma surrounding an egg shell with aremnant miracidium and Figure B shows normal prostate tissue).The patient was treated with praziquantel (60mg/kg, body weight,divided in two equal doses given at 4 hour intervals) and is beingfollowed at the outpatient clinic. A diagnosis of adenocarcinomaof the prostate has not been discarded.O paciente, de 56 anos, veio ao hospital para exame de rotina.A sua historia medica e o exame fisico nao revelaram alteracoesde importância. Os exames de laboratorio mostraram-se normais,exceto pela elevacao do nivel do antigeno prostatico especifico nosoro (PSA = 6,5ng/mL – valores de referencia = 0-3,5 ng/mL).O toque retal revelou aumento da prostata e contornos bemdelimitados. A ultra-sonografia transretal mostrou uma prostatade aspecto normal. Nao houve alteracoes histologicas em novefragmentos de tecido prostatico obtido por biopsia. O pacientefoi acompanhado em ambulatorio por tres meses e o segundoPSA aumentou para 7,2ng/mL. A segunda biopsia da prostatanao revelou sinais de malignidade, mas evidenciou ovos de S.mansoni dentro de granulomas bem formados (Figura A:granuloma ao redor de casca de ovo contendo restos de ummiracidio; Figura B: tecido prostatico normal). O paciente foitratado com praziquantel na dose de 60mg/kg de peso, divididoem duas tomadas com intervalo de quatro horas. Ele continuasendo acompanhado em ambulatorio. O diagnostico deadenocarcinoma da prostata nao foi descartado.

Cerebral schistosomiasis mansoni.

1. Curso de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 2. Serviço de Anatomia Patológica, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG. Address to: Dr. José Roberto Lambertucci. Faculdade de Medicina/UFMG. Av. Alfredo Balena 190, 30130-100 Belo Horizonte, MG, Brasil. email: lamber@uai.com.br Recebido para publicação em 03/11/2008 Aceito em 10/11/2008 A IMAGENS EM DIP/IMAGES IN INFECTIOUS DISEASE

Comparison between clinical and ultrasonographic findings in cases of periportal fibrosis in an endemic area for schistosomiasis mansoni in Brazil.

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%, 56.9% and 13.4% 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%. However, periportal fibrosis was diagnosed using ultrasound in 25.4% 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 Mansons schistosomiasis in endemic areas, ultrasound is more accurate in diagnosing liver involvement and periportal fibrosis.

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni

Schistosomal egg antigens induce host bile ductular cells to proliferate and produce osteopontin (OPN), a pro-fibrogenic factor that stimulates hepatic stellate cells to become myofibroblasts. The numbers of OPN-producing bile ductules correlate with fibrogenesis and portal hypertension in humans and mice.

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.

Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity

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% and 46%, 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%) 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.