OBJECTIVES: Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables. METHODS: Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clínicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly. RESULTS: Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age>40 years (p<0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease. CONCLUSION: The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs.

Abstract Objective: The intravesical administration of hazardous drug products is a standard practice in the urology setting, which potentially exposing medical personnel to these drug products. It was deemed necessary to have a consensus document among the scientific societies involved (the Spanish Urological Association and the Spanish Society of Hospital Pharmacy) that collects the best available evidence on the safest handling possible of dangerous drug products in the setting of urology departments. Method: We reviewed the legislation and recommendations on the handling of dangerous drug products, both at the national and international level. Results: There is national legislation and regulations for protecting workers who handle dangerous drugs and products, as well as recommendations for handling to protect both the product and workers. Discussion: Following the strategic lines of the European Parliament for 2014-2020 in the chapter on occupational safety and health, the Spanish Urological Association and the Spanish Society of Hospital Pharmacy proposed a series of actions that decrease the risks of exposure for practitioners and caregivers involved in the handling of these products. Conclusions: After this review, 19 recommendations were established for handling dangerous drug products, which can be summarised as the need to train all individuals involved (from management teams to patients and caregivers), adopt systems that prevent contaminating leaks, implement exposure surveillance programmes and optimise available resources.

Resumen Objetivo: La administración intravesical de medicamentos peligrosos es una práctica habitual en el ámbito de la urología, con posible exposición del personal sanitario a dichos medicamentos. Se considera necesario disponer de un documento de consenso entre las sociedades científicas implicadas -Asociación Española de Urología y Sociedad Española de Farmacia Hospitalaria- que recoja la mejor evidencia disponible para el manejo, de la forma más segura posible, de medicamentos peligrosos en el ámbito de los servicios de Urología. Método: Se ha realizado una revisión de la legislación y de las recomendaciones sobre el manejo de medicamentos peligrosos tanto a nivel estatal como internacional. Resultados: Se dispone de legislación nacional y de normativas para la protección de los trabajadores que manipulen medicamentos y productos peligrosos, así como recomendaciones de manipulación para la protección tanto del producto, como de los trabajadores. Discusión: Siguiendo las líneas estratégicas del Parlamento Europeo para el período 2014-2020 en el capítulo de seguridad y salud laboral, la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria proponen una serie de actuaciones que hagan disminuir los riesgos de exposición de los profesionales y cuidadores implicados en su manejo. Conclusiones: Tras esta revisión se establecen 19 recomendaciones para el manejo de medicamentos peligrosos que pueden resumirse en la necesidad de formación de todas las personas implicadas (desde los equipos directivos hasta los pacientes y cuidadores), la adopción de sistemas que no permitan fugas contaminantes, programas de vigilancia de las exposiciones y optimización de los recursos disponibles.

Abstract: K-casein (CSN3) gene is of particular interest in goat production due to the effect of its polymorphisms on milk quality and composition. The objective of this study was to assess the genotypic and allelic frequencies in CSN3 gene in the Saanen goat breed and its effect on milk production and some of its compositional traits. Allelic discrimination assays were designed to determine the variants (A, B or C) using qPCR and allelic discrimination method. Allelic frequencies for A, B and C were 0.23, 0.64 and 0.13, respectively. Association analysis indicated that the CSN3 was significantly associated only with protein percentage (p = 0.006). Results indicated that animals with AC, BB and CC genotypes showed higher milk protein percentage than those with genotype AB. This evidence suggests that genotypes favorable to this associated trait could be included into Saanen goat breeding strategies.

Resumen: El gen de la к-caseína (CSN3) es de especial interés debido al efecto de sus polimorfismos sobre la calidad y composición de la leche. El objetivo de este estudio fue investigar las frecuencias genotípicas y alélicas del gen CSN3 en la raza caprina Saanen y su efecto sobre la producción de leche y algunas de sus características de composición. Se diseñaron diferentes ensayos de discriminación alélica para determinar las variantes (A, B y C) mediante qPCR. Las frecuencias alélicas para las variantes A, B y C fueron de 0.23, 0.64 y 0.13, respectivamente. El análisis de asociación indicó que el gen CSN3 esta asociado solamente al porcentaje de proteína en leche (p = 0.006). Los resultados mostraron que los animales con los genotipos AC, BB y CC producen leche con mayor porcentaje de proteína que aquellos con el genotipo AB. Esta evidencia sugiere que los genotipos favorables para la característica asociada podrían incluirse en estrategias de selección asistida por marcadores en cabras de la raza Saanen.

The hepatitis A virus (HAV) HAF-203 strain was isolated from an acute case of HAV infection. The primary isolation of HAF-203 in Brazil and its adaptation to the FRhK-4 cell lineage allowed the production of large amounts of viral particles enabling molecular characterization of the first HAV isolate in Brazil. The aim of our study was to determine the nucleotide sequence of the HAF-203 strain genome, compare it to other HAV genomes and highlight its genetic variability. The complete nucleotide sequence of the HAF-203 strain (7472 nucleotides) was compared to those obtained earlier by others for other HAV isolates. These analyses revealed 19 HAF-specific nucleotide sequence differences with 10 amino acid substitutions. Most of the non-conservative changes were located at VP1, 2C, and 3D genes, but the 3B region was the most variable. The availability of HAF-203 complementary DNA was useful for the production of the recombinant VP1 protein, which is a major determinant of viral infectivity. This recombinant protein was shown by enzyme-linked immunoassay and blotting, to be immunogenic and resemble the native protein, therefore suggesting its value as a reagent for incorporation into diagnostic tests.

A cross-sectional study was conducted in order to identify hepatitis A virus (HAV) serological markers in 418 individuals (mean age, 16.4 years; range, 1 month-80 years) at a public child care center in Rio de Janeiro, Brazil, as well as to analyze risk factors and determine circulating genotypes. Serum samples were tested using an enzyme immunoassay. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect and characterize HAV RNA, and sequencing was performed. Anti-HAV antibodies and IgM anti-HAV antibodies were detected, respectively, in 89.5% (374/418) and 10.5% (44/418) of the individuals tested. Acute HAV infection in children was independently correlated with crawling (p < 0.05). In 56.8% (25/44) of the IgM anti-HAV-positive individuals and in 33.3% (5/15) of the IgM anti-HAV-negative individuals presenting clinical symptoms, HAV RNA was detected. Phylogenetic analysis revealed co-circulation of subgenotypes IA and IB in 93.3% (28/30) of the amplified samples. In present study, we verify that 79% (30/38) of children IgM anti-HAV-positive were asymptomatic. In child care centers, this asymptomatic spread is a more serious problem, promoting the infection of young children, who rarely show signs of infection. Therefore, vaccinating children below the age of two might prevent the asymptomatic spread of hepatitis A.

The prevalence of hepatitis A virus (HAV) infection is high in developing countries, in which low standards of sanitation promote the transmission of the virus. In Latin America, which is considered an area of high HAV endemicity, most HAV-positive individuals are infected in early childhood. However, recent studies have shown that prevalence rates are decreasing. Herein, we review the data on HAV prevalence and outbreaks available in scientific databases. We also use official government data in order to evaluate mortality rates in Brazil over the last two decades. Studies conducted in the northernmost regions of Brazil have indicated that, although improved hygiene has led to a reduction in childhood exposure to HAV, the greatest exposure still occurs early in life. In the Southeastern region, the persistence of circulating HAV has generated outbreaks among individuals of low socioeconomic status, despite adequate sanitation. Nationwide, hepatitis A mortality rates declined progressively from 1980 to 2002. During that period, mortality rates in the Northern region consistently exceeded the mean national rate and those for other regions. Excluding the North, the rates in all regions were comparable. Nevertheless, the trend toward decline observed in the South was paralleled by a similar trend in the North.

In this report, we examine the adaptability of commercially available serological kits to detect antibodies markers for viral hepatitis in oral fluid samples. We also assessed the prevalence of hepatitis A, B, and C virus-specific antibodies, and related risk factors for these infectious diseases through sensitivity of the tests in saliva samples to evaluate if oral fluid can be an alternative tool to substitute serum in diagnosis of acute viral hepatitis and in epidemiological studies. One hundred and ten paired serum and saliva specimens from suspect patients of having acute hepatitis were collected to detect antibodies to hepatitis A (total and IgM), hepatitis B (anti-HBs, total anti-HBc and IgM anti-HBc), and hepatitis C (anti-HCV) using commercially available enzyme-linked immunossorbent assay (EIA). In relation to serum samples, oral fluid assay sensitivity and specificity were as follows: 87 and 100% for total anti-HAV, 79 and 100% for anti-HAV IgM, 6 and 95% for anti-HBs, 13 and 100% for total anti-HBc, 100 and 100% for anti-HBc IgM, and 75 and 100% for anti-HCV. The consistency observed between antibodies tests in saliva and expected risk factors for hepatitis A and C suggests that the saliva method could replace serum in epidemiological studies for hepatitis A and C.

Serological evidence of hepatitis E virus infection (HEV) has been observed in both humans and different animal species living in non-endemic areas, suggesting that animals could be important reservoir for virus transmission to man. Antibodies to HEV have been detected in some Brazilian population groups. Nevertheless, sporadic cases of acute HEV infection have never been reported. We collected 271 serum samples from several domestic animals and also from pig handlers from Southeast of Brazil in order to investigate the seroprevalence of HEV infection. Anti-HEV IgG was detected in cows (1.42%), dogs (6.97%), chickens (20%), swines (24.3%), and rodents (50%), as well as in pig handlers (6.3%). The recognition of swine HEV infections in pigs in many countries of the world led us to investigate a larger sample of pigs (n = 357) from the same Brazilian region with ages ranging from 1 to > 25 weeks. IgG anti-HEV was detected in 100% of 7-day old pigs. Following a gradual decline between weeks 2 and 8 (probably due to loss of maternal IgG), the prevalence then steady increased until it reached 97.3% of animals older than 25 weeks. Besides the detection of anti-HEV antibodies in different animal species, the results showed that swine HEV infection seems to be almost universal within this Brazilian pig population. This is the first report that shows evidences of HEV circulation in Brazilian animal species and pig handlers.

A seroprevalence study was carried out among a group of women in Rio de Janeiro to determine the prevalence of different markers for viral hepatitis given the limited data among healthy populations. Blood samples collected and tested from 874 women before or after delivery in a public county maternity hospital demonstrated age to be directly related to markers for hepatitis A virus and hepatitis B virus (HBV) infection. The prevalence of HBV and hepatitis C virus infection were lower than that observed in the blood donor population and might be explained by the younger age group and gender.

Hepatitis B and C virus markers were assessed during a survey on malaria in gold mine camps in southern Brazilian Amazon in order to identify risk factors associated to these viral diseases. The study comprised 520 subjects, most of them were gold miners. Missing subjects totaled 49 (8.6%). Among these 520, 82.9% had HBV markers and 7.1% were HBsAg positive. Previous hospitalization, surgery, sexually transmitted diseases and incarceration were quite common among surveyed people, but there is no association between total HBV markers and these factors. On other hand, HBsAg was independently associated to history of sexually transmitted diseases and history of surgery after adjustment. The most frequent HBsAg subtypes identified, adw2 (59%), predominates in populations of Northeast Brazil. The most surveyed people were immigrants coming from that area suggesting that immigrants carried HBV themselves to the study area. Immunoblot (RIBA) confirmed-anti-HCV were found in 2.1%. The only variable associated to anti-HCV in multivariate analysis was illicit intravenous drug. Lack of HCV infection in subjects with such a high HBV markers prevalence reinforces the opinion that HCV is transmitted by restricted routes when compared to HBV. Furthermore, gold miners in Amazon may be considered as a risk group for HBV infection, but not for HCV.