The results of a randomized trial looking at 24 weeks vs 48 weeks of treatment with peginterferon alpha-2a (40 kDa) and ribavirin combination therapy in patients with chronic hepatitis C genotype 1.

Peginterferon-alpha plus ribavirin is the most effective therapy for chronic hepatitis C. This study was designed to evaluate the effect of peginterferon alpha-2a (40 kDa) plus ribavirin on sustained virological response (SVR) when administered for 24 vs 48 weeks in genotype 1 naïve patients. One hundred and seventeen patients were enrolled in this controlled trial. Genotype 1 patients were randomized to 24 weeks treatment vs 48 weeks treatment. Genotype non-1 patients received 24 weeks treatment as an observational group. Outcomes were SVR (defined by hepatitis C virus-RNA-negative at week 24 of follow-up) and tolerability across the study period. The end-of-treatment response was 59% for genotype 1 (24 weeks treatment), 80% for genotype 1 (48 weeks treatment) and 92% for genotype non-1 (24 weeks treatment). The end-of-follow-up response was 19% (95% confidence interval (CI): 7.2-36.4) (genotype 1, 24 weeks) and 48% (95% CI: 30.2-66.9; P = 0.0175) (genotype 1, 48 weeks). Among genotype non-1, SVR was 76% (95% CI: 62.3-86.5). There were no unexpected adverse events. Almost half of the genotype 1 patients achieved an SVR after 48 weeks treatment with peginterferon alpha-2a (40 kDa) and low-dose ribavirin and confirmed that they should be treated for 48 weeks. Safety profile was acceptable.

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil

Hepatitis C virus (HCV) infection is a serious public health problem, since 80 percent to 85 percent of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81 percent from public and 19 percent from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62 percent) and white patients (80 percent). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64 percent) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65 percent of the patients weighed less than 77kg. Overweight and obesity were observed in 37.8 percent and 13.6 percent of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65 percent of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

Demographic and anthropometrical analysis and genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil.

Hepatitis C virus (HCV) infection is a serious public health problem, since 80% to 85% of HCV carriers develop a persistent infection that can progress into liver cirrhosis and hepatocarcinoma. Considering that the response of hepatitis C patients to combination therapy with interferon and ribavirin depends on HCV characteristics as well as on host features, we made a retrospective analysis of demographic and anthropometrical data and HCV genotype distribution of chronic hepatitis C patients treated in public and private reference centers in Brazil. The medical records of 4,996 patients were reviewed, 81% from public and 19% from private institutions. Patients' median age was 46 years, and there was a higher prevalence of male (62%) and white patients (80%). The analysis of HCV-infecting strains showed a predominance of genotype 1 (64%) over genotypes 2 and 3. The patients' mean weight was 70.6 kg, and 65% of the patients weighed less than 77 kg. Overweight and obesity were observed in 37.8% and 13.6% of the patients, respectively. Since a body weight of 75 kg or less has been considered an independent factor that significantly increases the odds of achieving a sustained virological response, the Brazilian population seems to have a more favorable body weight profile to achieve a sustained response than the American and European populations. The finding that 65% of chronic hepatitis C patients have a body weight of 77 kg or less may have a positive pharmacoeconomic impact on the treatment of genotype 1 HCV patients with weight-based doses of peginterferon.

Prevalence of GB virus C (hepatitis G virus) and risk factors for infection in São Paulo, Brazil.

The prevalence of GB virus C (GBV-C) varies widely throughout the world. A cross-sectional study was conducted in the city of São Paulo, Brazil, to estimate the prevalence of GBV-C infection and to identify associated risk factors, using a large sampling of the general population rather than blood donors or an illness-related group of subjects. GBV-C RNA was detected by reverse-transcriptase polymerase chain reaction using primers directed to the 5' noncoding region (NCR) and nonstructural 5A region (NS5A) in serum samples from 1,039 healthy individuals 2 years of age or more. Fifty-two individuals were positive for both sets of primers and one was positive for NS5A only (prevalence of GBV-C infection, 5.1%; 95%CI, 3.9-6.7%). No child under 5 years of age was found positive. Among subjects aged 5 years or more, the prevalence of infection increased consistently with age, up to 30-39 years (8.3%), and decreased from then on. The number of sexual partners in the last 3 years (2 or more: OR, 2.6; 95%CI, 1.3-5.5) and history of contact with blood-sucking insects (OR, 2.5; 95%CI 1.2-5.4) were independently associated with GBV-C infection. In conclusion, the prevalence of GBV-C infection is high in São Paulo. In addition to parenteral transmission, another route, e.g. sexual or vertical, may be involved.

Hepatitis C: a critical analysis of therapeutic response predictors.

Treatment of chronic hepatitis C is still unspecific. However, there is great expectancy concerning the new pegylated interferons. As there has been much controversy about the best parameters to determine whether treatment is effective, we analyzed several criteria currently used for evaluation, including serum alanine aminotransferase (ALT) normalization, viral load reduction and improvement of hepatic histology.

Hepatitis C: a critical analysis of therapeutic response predictors

Treatment of chronic hepatitis C is still unspecific. However, there is great expectancy concerning the new pegylated interferons. As there has been much controversy about the best parameters to determine whether treatment is effective, we analyzed several criteria currently used for evaluation, including serum alanine aminotransferase (ALT) normalization, viral load reduction and improvement of hepatic histology.

Estimated Prevalence of Viral Hepatitis in the General Population of the Municipality of São Paulo, Measured by a Serologic Survey of a Stratified, Randomized and Residence-Based Population.

The present study was done to estimate the prevalence of Hepatitis A (HAV), B (HBV), C (HCV), and E (HEV) infection in the general population residing in the municipality of São Paulo, and to evaluate the level of knowledge related to the various modes of infection transmission by and protection against the different viruses. Blood samples and health questionnaires were collected from 1,059 individuals. The study design used an inductive method of predictive statistical inferences through randomized sampling stratified by Sex, age and residence region. The estimated prevalence rated found were: Hepatitis A = 66.59% (63.75%-69.44% CI); Hepatitis B = 5.94% (4.50%-7.35%); Hepatitis C = 1.42% (0,70%-2.12%); Hepatitis E = 1.68% (0.91%-2.46%). The frequency of hepatitis was similar in males and females. HAV showed an estimated prevalence of 56.16% in the population up to 17 years old, increasing to 65.30% in individuals between 18 and 29 years. The infection reached its peak of 90% in individuals 40 years of age or older. The study showed a greater tendency of dissemination of HBV among the population between 15 and 17 years. This specific age group showed an estimated prevalence of active infection of 1.04% (0.43%-1.65% CI), and also demonstrated an ascending level of acquired immunity with an estimated prevalence of 4.90% (3.60%-6.20% CI). HCV demonstrated an estimated prevalence of 1.42% (0.70%-2.12% CI). This specific infection occurred more frequently among adults 30 years of age or older, with the prevalence reaching a peak of 3.80% among the group aged 50 to 59 years. HEV showed zero prevalence among the age group between 2 and 9 years. This was followed by a slightly ascending rate starting from age 10, with an estimated prevalence of 1.05% (0.94%-3.04% CI) among those 10 to 14 years of age. This infection reached its peak of 3.00% (0.55%-6.74% CI) at the age of 60 years or older. Individuals with lower educational levels had a higher tendency of acquiring HAV and HCV, while there was no statistically significant difference for this parameter related to HBV and HEV. HBV occurred more frequently among inhabitants of the northern region of the city. All other hepatitis forms occurred at similar frequencies among the five regions of the city. Among the population, 1.90% (1.08%-2.72% CI) demonstrated an elevated hepatic enzyme with no serologic evidence indicating the cause was the viruses studied. This observation suggests the presence of other hepatic diseases, possibly including other viral diseases. It was also estimated that 75.12% of the city's population did not know the modes of transmission of hepatitis viruses and 76.70% did not know how to prevent them. This clearly suggests the need for a full-scale education program combined with public health measures regarding prevention of all forms of vial hepatitis.

Raiva humana tratada com interferon por via intratecal / Human rabies treated with interferon by intramuscular way

Relata-se um caso de raiva humana submetido a tratamento com interferon leucocitário humano injetado por via ventricular, através de reservatório de Rickham, e parte por via intramuscular. As doses diárias injetadas foram de 5 x10**6 unidades por via intraventricular e de 20 x 10**6 unidades por via intramuscular, a partir do 7§ dia de doença durante nove dias, quando entäo ocorreu o óbito em conseqüência de sepse por Klebsiella pneumoniae (16§ dia de doença). O vírus da raiva foi isolado inicialmente através de biopsia do tecido nervoso cerebral. O nível de interferon no sangue e no líquor era inferior a 10 U/ml antes do início do tratamento. O esquema terapêutico utilizado propiciou títulos elevados de interferon no sangue e no líquor 10 a 2.000 vezes maiores que aqueles atingidos usualmente na infecçäo natural. O nível residual, após 24 horas, foi de 212 ñ 14 U no sangue e 451 ñ 81 U no líquor. Foi observada menor soroconversäo (anticorpos neutralizantes) contra o vírus rábico (1/75 a partir do 13§ dia), em conseqüência da imunossupressäo induzida pelo interferon, provavelmente

[Pathogenesis of AIDS: possible role of co-factors in HIV reactivation]. / Patogênese da AIDS: possível papel dos co-fatores na reativação do HIV.

One of the most intriguing aspects concerning the pathogenesis of AIDS is the long period of latency of the HIV in human cells, not causing any cytopatic effect in some and, on the other hand, causing cell destruction, at short periods, in others. The various agents and the mechanisms they adopt to reactivate the latente HIV, were described. Also the frequent epidemiological observation on the presence of both such agents and the HIV in AIDS patients allowed the authors to speculate on the probable important role of a cohort of co-factors which determine the destiny of such individuals. Special considerations were made in respect to the hepatitis B virus, cytomegalovirus, herpesviruses (HHV-1, e and 6), EB virus, HTLV-1 and 2 retroviruses, group B arbovirus Maguary, malaria and other endemic infectious diseases which victimize millions of Brazilians. Accepting the importance of such co-factors acting on the viral gens that regulate the HIV expression in the host cell, it was speculated on the possible role of vaccines, such as the hepatitis B vaccine, and some antiviral drugs which could be useful in the indirect prevention of AIDS-disease in both HIV-carriers and those practising AIDS-high-risk-activities.

Naturally acquired antibodies to tetanus toxin in humans and animals from the galápagos islands.

A serologic survey using a highly sensitive enzyme-linked immunosorbent assay confirmed the anticipated finding of naturally acquired antibodies to tetanus toxin both in humans and animals on the Galápagos Islands. In 57 inhabitants (mean age, 31.3 years) who had not been vaccinated against tetanus, antibody to tetanus toxin was detected in the blood in varying titers (geometric mean [reciprocal] titer [GMT], 0.015 international units [IU]/ml). In one individual the titer of antibody was greater than 12.5 IU/ml. Two individuals who had never been vaccinated against tetanus but who had reported having had clinical tetanus had titers of antibody to tetanus toxin of 0.02 IU/ml and 0.3 IU/ml, respectively. All nine of the animals studied showed antibody to tetanus toxin (GMT, 0.028 IU/ml).

Tratamento especifico do tetano com uma fracao - F(ab') - da imunoglobulina antitetanica injetada por via raquidiana. / Specific treatment of tetanus with a fraction - F(ab') - of the antitetanic immunoglobulin injected intrathecally

Sao apresentados os resultados preliminares do tratamento especifico de 26 casos de tetano humano com a fracao F(ab') da antitoxina tetanica equina injetada por via intratecal. O indice de letalidade observado foi de 3,8%. Considerando-se apenas os casos de maior gravidade (grau III) o indice de letalidade foi de 10%. Tais resultados encorajadores vem corroborar os resultados de experimentacoes previas em animais de laboratorio, realizados por outros pesquisadores, onde a importancia da via sub-aracnoidea e de fracoes de baixo peso molecular de gamaglobulina antitetanica foram demonstradas importantes para permitir o acesso da antitoxina aos neuronios das membranas pre-sinapticas da medula espinal a fim de deslocar e neutralizar a toxina fixada aos receptores dos gangliosideos