Receptor Antagonist of IL-13 Exerts a Potential Negative Regulation During Early Infection of Human Schistosomiasis.

The pathology of schistosomiasis is associated with the formation of granulomas, and this process is associated with liver fibrosis. Studies indicate that Th1 cytokines reduce fibrosis in schistosomiasis, while Th2 cytokines play a part in the progression of fibrosis, and IL-13 has a critical role in this process. The IL-13Rα2 receptor, known as a 'receptor antagonist' binds with high affinity to IL-13, and studies have identified that this plays a part in reducing fibrosis and the size of granulomas. The objective of this study was to evaluate the function of IL-13Rα2 and cellular immune response in hepatic fibrosis. A negative correlation between IL-13Rα2 and IL-13 was found, suggesting an increase in cytokine in early fibrosis. Initially, a negative correlation between IFN-γ and IL-13 was found in patients without fibrosis, and subsequently, this correlation was found to be positive in patients with severe fibrosis, thereby highlighting a new mechanism for regulating the progress of periportal fibrosis. There was a positive correlation between the profiles of Th1 and Th2 cytokines, suggesting the presence of both responses, thus regulating the disease. The results contribute to a better understanding of the immune mechanisms that control the process of hepatic fibrogenesis in schistosomiasis in humans.

Schistosomiasis mansoni: ultrasound-evaluated hepatic fibrosis and serum concentrations of hyaluronic acid.

Schistosomiasis mansoni is a fibrogenic liver disease that constitutes a major health problem in north-eastern Brazil. Although one common manifestation of the disease, periportal fibrosis (PPF), can be assessed by ultrasonography by well-trained physicians, the necessary equipment and personnel are not always readily available. Serum markers, including hyaluronic acid (HA), have been used as alternative means of measuring fibrosis. Recently serum concentrations of HA have been evaluated in 77 Brazilians (61 cases of schistosomiasis mansoni and 16 healthy controls) and compared against the ultrasound-evaluated PPF in the same subjects. The HA was measured using a non-competitive fluorescence-based assay, while the PPF was explored using a portable ultrasound scanner (SSD-500; Aloka, Tokyo) and graded, as patterns A-F, according to the World Health Organization's 'Niamey protocol'. In general, the serum concentrations of HA were found to be positively correlated with the severity of the PPF. The mean concentration of HA in the sera of the 16 controls was significantly lower than that recorded in the schistosomiasis cases who showed PPF of patterns D or E (P<0·001 for each). The cases who showed pattern-C PPF also had significantly less HA in their sera than the cases with PPF of patterns D or E (P<0·001 for each), and the cases with pattern-D fibrosis had significantly lower HA concentrations in their sera than the cases with PPF of pattern E (P<0·001). In an analysis based on a receiver-operating-characteristic (ROC) curve, an HA concentration of 20·2 µg/litre of serum was identified as a threshold that could be used to distinguish moderate cases of PPF (i.e. patterns C or D) from the more advanced cases (i.e. patterns E or F), with a sensitivity of 60% and specificity of 65%. In conclusion, it appears that serum concentrations of hyaluronic acid could be used as markers for periportal fibrosis in patients with schistosomiasis mansoni.

Rotavirus-associated infantile diarrhea in Uberaba, Minas Gerais, on the wake of the Brazilian vaccination program.

BACKGROUND: Rotaviruses are major causes of diarrhea in children for which vaccines were developed and are currently in use. OBJECTIVES: To investigate the genotypes of rotavirus strains causing dehydrating diarrhea in children in Uberaba, Triângulo Mineiro region, Minas Gerais, during 2005-2006. METHODS: Rotavirus-associated diarrhea was investigated in fecal specimens by PAGE and strains were characterized for their genotype by RT-PCR and PCR-typing assays. RESULTS: Rotavirus was detected in 15% (39/260) of the fecal specimens by PAGE: 64% of the specimens presented short electrophoretic patterns and G2P[4] genotype; and 36% presented long electropherotypes and G1P[8], G9P[8], G4P[9] and two strains with sill undetermined G and P[8] genotype. A change in the dominant electrophoretic pattern was observed, shifting from long to short patterns and coinciding with the highest incidence of diarrheal cases. CONCLUSIONS: Those are the first data on rotavirus strains circulating in the Triângulo Mineiro region. They were obtained over a 16-month period that included the first 10 months after the launch of the national rotavirus immunization program that uses a monovalent G1P[8] attenuated vaccine strain. These results should further our understanding of the dynamics of rotavirus strains and help interpreting the significance of the program.

Ultrasonography of the liver and spleen in Brazilian patients with hepatosplenic schistosomiasis and cirrhosis.

Ultrasonography is now widely used in the diagnosis and management of patients with chronic Schistosoma mansoni infections. The present study was undertaken to evaluate the use of ultrasonography in patients with hepatosplenic schistosomiasis (HSS) with and without cirrhosis. Ninety-seven patients (52 males; median age 38 years, range 19-68 years) with HSS, 65 with well compensated (HSSC) and 32 with decompensated (HSSD) disease and cirrhosis, were systematically examined by ultrasound. Hepatic fibrosis was graded according to WHO recommendations. Typical atrophy of the right hepatic lobe accompanied by hypertrophy of the left lobe, with a rounded inferior marginal edge, was seen in 86 (88.7%) patients. Periportal fibrosis was observed in 83 (85.6%) cases and confirmed histologically in all. In 66 patients (68.0%) thickening of the gallbladder wall, associated with periportal fibrosis and extending from the branches of the porta hepatis, was noted. No evidence of biliary disease was found in these patients and gallstones were present in only 3 cases. Fourteen (43.8%) of the HSSD patients could not be classified for grade of fibrosis because of the advanced stage of cirrhosis related to hepatitis B or C viral infection. Of the remaining 18 HSSD patients, none had only grade I fibrosis (vs. 10.8% of HSSC, P = 0.054) and only 6 had grade II (vs. 67.7% of HSSC, P < 0.0005), while the frequency of grade III was significantly higher in the HSSD patients than in those with HSSC (37.5% vs. 21.5%, P = 0.049). These findings indicate that although ultrasonography is a very valid technique for assessing patients with pure HSS, and should be considered the 'gold standard', it is not reliable for assessing periportal fibrosis in patients with concomitant cirrhosis due to other causes.

An ultrasonographic study of liver fibrosis in patients infected with Schistosoma mansoni in north-east Brazil.

Between August 1988 and July 1990, 176 patients with Schistosoma mansoni infection attending the University Hospital, Recife, Brazil received a complete clinical examination including stool examination for intestinal parasites, liver function tests, and ultrasonography. The majority were also examined by upper digestive tract endoscopy. The clinical distribution of their disease was as follows: 26.7% intestinal, 13.6% hepato-intestinal, 53.4% compensated hepatosplenic and 6.3% decompensated hepatosplenic. Infection intensity was high, with a median of 360 eggs/g of faeces. Ultrasonography showed a good correlation between the degree of hepatic periportal fibrosis and the clinical stage of disease (P < 0.0001). Of the patients with the intestinal form of schistosomiasis, 12.8% had grade I fibrosis and the others had no fibrosis; 33.3% of patients with hepatointestinal schistosomiasis had grade I fibrosis, 8.3% had grade II fibrosis, and 58.4% had no fibrosis; all the patients with hepatosplenic disease had grade II or grade III fibrosis. The degree of liver fibrosis detected by ultrasonography correlated with the degree of oesophageal varices detected by endoscopy (P = 0.0001). The degree of oesophageal varices also correlated with the presence of haemorrhage (P < 0.0001). Ultrasonography is considered superior to liver biopsy, permitting a dynamic approach to the study of schistosomiasis morbidity with precise diagnosis and simple sequential follow-up of post-treatment results.

Molecular epidemiology of group A rotavirus causing acute diarrhea in infants and young children hospitalized in Rio de Janeiro, Brazil, 1995-1996.

During 1995-1996, an epidemiological survey was conducted at Fernandes Figueira Institute (Rio de Janeiro, DC) on group A rotavirus strains causing acute diarrhea in infants and young children. Rotaviruses were detected in 15.7% of examined specimens. Among the rotavirus strains tested for dsRNA by PAGE, 70% belonged to the long pattern and 30% to the short pattern. A long pattern classified as LA was the prevalent electropherotype among all of the types, and the prevalent short pattern was a unique SA type. Fifteen years ago, LA type was prevalent in the city among long patterns, and a SB type among short patterns, showing a substitution of circulating electropherotypes. The long pattern occurred throughout the period studied and in all age ranges studied (0-5 years old), but the short pattern occurred only in young children (age range 0-11 months) in May 1995, and September 1996. The data demonstrate epidemiologic differences between long and short electropherotypes incidence; the long electropherotype strains circulate throughout the community and the short electropherotype strains appear only in young children. Rotavirus was observed throughout the period studied but there were peaks of infection in the months of May and September.

Reduction of morbidity in hepatosplenic schistosomiasis mansoni after treatment with praziquantel: a long term study.

Forty-two with hepatosplenic patients treated with praziquantel and followed up for 5 years. One half of the patients received a single 30 mg/kg dose and the other half, two doses of 25 mg/kg given 4 hrs apart. According to Hoffman and Kato-Katz stool exams, an 83.3% cure rate, was observed after twelve months. Stool egg counts in cases of incomplete cure were greatly reduced. Liver function, as assessed by serum levels of aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase and alkaline phosphatase activities as well as albumin and gamma globulin showed marked improvement after one year. Hepatomegaly was reduced in 81.0% of patients and splenomegaly in 78.8%. Spleen regression was complete in 15.1% of the total, and in 18.5% of those with compensated hepatosplenic disease. As a result of these observations, the authors recommend early treatment with anti-schistosomal medication, either oxamniquine or praziquantel, to halt progression of disease and reduce splenomegaly.

[An outbreak of acute schistosomiasis at Porto de Galinhas beach, Pernambuco, Brazil]. / Epidemia de esquistossomose aguda na praia de Porto de Galinhas, Pernambuco, Brasil.

We recently confirmed several cases of acute schistosomiasis in Porto de Galinhas beach, Northeast Brazil. A total of 662 patients were diagnosed by parasitological and clinical examinations. The infection likely occurred during the September 7 national holiday, when heavy rainfall flooded the Ipojuca River and people were infected when the water covered their yards. Families were continuously exposed to infection for a period of three weeks until the water had completely dried up. Previous investigation suggests that snail vectors were introduced as a result of landfill in marshy areas. The swamp-flooding of such areas facilitated the emergence of slums surrounded by snail breeding sites. Heavy rainfall caused open-air sewage ditches to overflow, allowing for infection of snails by Schistosoma mansoni. Thus, continuous floods were responsible for the spread of human infection. Clinical and laboratory results identified 62% of acute cases of S. mansoni. Complementary studies are being conducted to define the impact and epidemiological meaning of the acute schistosomiasis outbreak.

Changes in epidemiology of rotavirus in the Triângulo Mineiro region of Brazil: lack of two consecutive rotavirus seasons.

Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.

Splenosis after splenectomy and spleen tissue autoimplantation: Late followup study.

AIM: In children suffering from severe hepatosplenic schistosomiasis, the surgical protocol includes splenectomy and autoimplantation of spleen morsels in the major omentum, which has the potential of reducing the overwhelming postsplenectomy infection (OPSI). The purpose of the study was to evaluate the remaining splenosis, with the mean postoperative followup of 12.1 ± 5.6 years; to compare the efficacy of the 2 evaluation tools. MATERIALS AND METHODS: Nineteen patients underwent, when they were children, portal decompression and autoimplantation of spleen. After a mean age of 23.4 ± 5.3 years, they were investigated regarding the number of infections and OPSI. They had undergone hepatosplenic scintigraphy with labeled colloidal SnTc(99m) and abdominal ultrasound. It was considered efficient splenosis when the patients presented with 5 or more spleen nodules. The evaluation was performed by 3 observers. RESULTS: None of the patients had increased infection rate or developed OPSI. Sixteen (84.2%) presented efficient splenosis. CONCLUSIONS: The remaining postoperative splenosis was considered efficient in the majority of patients in the long-term followup; and nuclear medicine was considered the gold standard for splenosis evaluation.

Distribution of rotavirus genotypes after vaccine introduction in the Triângulo Mineiro region of Brazil: 4-Year follow-up study.

BACKGROUND: Rotaviruses are the major cause of diarrhea in children for which a monovalent G1P[8] vaccine has been provided free for all Brazilian infants since March 2006. OBJECTIVES: To investigate prevalence and genotypes of rotavirus strains causing diarrhea in children in Triângulo Mineiro, Minas Gerais, during 2007-2010, and to assess local vaccine impact. STUDY DESIGN: Fecal specimens were analyzed for rotavirus detection and characterization by PAGE, RT-PCR and PCR-genotyping assays. RESULTS: Overall, rotavirus was diagnosed in 12.1% (76/630) cases, accounting for 35.8% of the hospitalizations and 6.5% of outpatient attendance due to diarrhea. A trend in rotavirus disease reduction occurred in both cities (71.8% and 83.4% in Uberaba; 95.3% in Uberlândia) up to 2009, but it reversed in 2010 with increased rotavirus cases in Uberlândia. Short pattern G2P[4] strains were detected in all but three (96%) cases of mixed/P[NT] infections with long electropherotypes. CONCLUSIONS: This 4-year follow-up study showed a reduction in rotavirus-related diarrhea and even skipped a rotavirus season, which is consistent with vaccine mediated protection. The 2007-2010 rotavirus epidemic curve reflected the natural cyclic fluctuation of the single G2P[4] genotype, with sharp reduction of cases in 2008 leading to lack of a rotavirus 2009 season (both cases and hospitalizations) followed by its come back in 2010. Diarrhea cases related to either vaccine serotype/genotype (G1 or P[8]) were not detected. Thus, a new scenario emerged with a single epidemic genotype replacing the cocirculation of great diversity of genotypes, thus far, a hallmark of the epidemiology of rotavirus in Brazil.

Analysis of bovine rotavirus strains circulating in diarrheic dairy calves in Uberaba, Minas Gerais, Brazil, during 2008-2009 / Análise de cepas de rotavírus bovino circulantes em bezerros leiteiros com diarreia em Uberaba, Minas Gerais, Brasil, durante 2008-2009

O objetivo deste estudo foi detectar rotavírus em fezes de bezerros com diarreia em Uberaba, MG, e caracterizar os genes VP7 e VP4 por meio da genotipagem e da análise filogenética. Setenta e quatro amostras foram coletadas entre novembro de 2008 e setembro de 2009. A detecção do vírus foi feita por teste de aglutinação e as amostras positivas foram submetidas à transcrição reversa, seguida de reação em cadeia da polimerase (RT-PCR), tipagem por PCR e sequenciamento. A taxa de detecção de rotavírus foi de 6,8% e todas as amostras apresentaram o genótipo G6P[5]. A análise filogenética mostrou que as amostras do genótipo G6 pertencem à linhagem IV e que, para ambos os genes (VP7 e VP4), as amostras deste estudo compõem um sub-cluster à parte daquele das cepas referências e das amostras campo mais similares. O alinhamento das sequências de aminoácidos deduzidas mostrou substituições em regiões antigênicas quando comparadas com as sequências das cepas bovinas UK e NCDV, presentes nas vacinas disponíveis no Brasil. Uma nova sublinhagem genética de G6P[5] foi evidenciada neste estudo. Substituições de aminoácidos nas regiões antigênicas dos rotavírus e a circulação de novas variantes podem representar desafios para as vacinas utilizadas atualmente. O presente estudo contribui para a compreensão da epidemiologia dos rotavírus bovinos no Brasil.(AU)

Long-term response of isolated limb perfusion with hyperthermia and chemotherapy for Merkel cell carcinoma.

INTRODUCTION: Merkel cell carcinoma (MCC) is a very rare and aggressive neoplasm. Due to its rarity, therapeutic guidelines are not well established, especially for regionally advanced disease. Hyperthermic isolated limb perfusion (HILP) with Melphalan and either with or without tumor necrosis factor-alpha (TNF-alpha) is becoming more common in clinical practice, yet the long-term response is not clear. Previous reports have established indications for treatment of unresectable MCC as well as the outcome of MCC patients receiving perfusion treatment in combination with other therapies (e.g., radiation). METHOD: A review was performed of the most important articles in MEDLINE from the last 20 years related to HILP and MCC. It was possible to collect all cases of HILP from the literature. Details of one case of MCC where HILP was administered was included in the literature review. RESULTS: A total of nine cases of MCC receiving ILP were identified in the literature; of these, seven achieved a complete response, one a partial response and one no response. All five patients treated without TNF-alpha had a complete response. Of the four patients treated with TNF-alpha, two had complete, one partial and one no response. CONCLUSION: Based on the cases described, isolated limb perfusion is an acceptable option to treat regional advanced cases of MCC, and the use of TNF-alpha does not impact the overall response.

Changes in epidemiology of rotavirus in the Triângulo Mineiro region of Brazil: lack of two consecutive rotavirus seasons

Rotaviruses are the main cause of infantile acute diarrhea, and a monovalent (G1P[8]) vaccine against the virus was introduced into the Brazilian National Immunization Program for all infants in March 2006. The objectives of this study were to determine the rate and genotype distribution of rotavirus causing infantile diarrhea in the Triângulo Mineiro region of Brazil during 2011-2012 and to assess the impact of local vaccination. Fecal specimens were analyzed for detection and characterization of rotavirus using polyacrylamide gel electrophoresis, reverse transcription followed by polymerase chain reaction (PCR), and PCR-genotyping assays. Overall, rotavirus was diagnosed in 1.7% (6/348) of cases. Rotavirus positivity rates decreased 88% [95% confidence intervals (CI)=15.2, 98.3%; P=0.026] in 2011 and 78% (95%CI=30.6, 93.0%; P=0.007) in 2012 when compared with available data for baseline years (2005/2006) in Uberaba. In Uberlândia, reductions of 95.3% (95%CI=66.0, 99.4%; P=0.002) in 2011, and 94.2% (95%CI=56.4, 99.2%; P=0.004) in 2012 were also observed compared with data for 2008. The circulation of rotavirus G2P[4] strains decreased during the period under study, and strains related to the P[8] genotype reemerged in the region. This study showed a marked and sustained reduction of rotavirus-related cases, with a lack of rotavirus in the 2011 and 2012 seasons, suggesting a positive impact of the vaccination program.

Prevalence of pulmonary hypertension in patients with schistosomal liver fibrosis.

Between the April and July of 2007, patients undergoing treatment for schistosomal liver fibrosis, at a university hospital in north-eastern Brazil, were examined by transthoracic Doppler echocardiography (TTE). The main aim was to determine the prevalence of pulmonary hypertension in the patients. The thorax of each patient who had such hypertension, as indicated by an estimated pulmonary arterial systolic pressure (PASP) in excess of 35 mmHg, was then investigated by contrast-enhanced multidetector-row computed tomography (MDCT). The 84 patients (53 women and 31 men) enrolled in the study had a mean (S.D.) age of 50.06 (12.25) years. Nine (10.7%, with a 95% confidence interval of 5.0%-19.4%) of the patients were found to have pulmonary hypertension, with PASP ranging from 40-126 mmHg, and a median (S.D.) PASP of 58.78 (28.01) mmHg. The contrast-enhanced thoracic MDCT indicated that most of the patients with pulmonary hypertension had a pulmonary artery trunk that was unusually wide (67%) and more than 1.1-fold wider than the ascending aorta (56%), dilatation of the main pulmonary arteries (100%), a segmental artery that, in diameter, was more than 1.1-fold larger than the adjacent bronchi (89%), tapering of the peripheral pulmonary arteries (78%), and cardiac enlargement (78%). No patient suffered pulmonary embolism as a result of the investigations. The prevalence of pulmonary hypertension in the patients with schistosomal liver fibrosis (10.7%) justifies the screening of such patients by TTE.

Specific treatment of advanced schistosomiasis liver disease in man: favourable results.

One hundred eighty-four patients with hepatosplenic schistosomiasis mansoni from the northeast of Brazil were studied. All were treated with a single dose of Oxamniquine or Praziquantel, and were observed over 6 to 12 months. Special attention was given to the evolution of severe hepatopathy. Favourable results were obtained, particularly with the compensated hepatosplenic form. Hepatic function showed great improvement. Hepatomegaly and splenomegaly were significantly reduced in size, to a greater or lesser extent, in the great majority of patients. The implications of the results obtained are considered below.