High prevalence of TT virus viremia in italian patients, regardless of age, clinical diagnosis, and previous interferon treatment.
(41/2101)
The pathogenic potential of the newly discovered TT virus (TTV) is currently a matter of conjecture. Its presence was investigated in the serum of 660 patients, by polymerase chain reaction. TTV was detected in 50% of 221 patients with unselected pathologies, and no significant differences related to age, sex, or organ disease were noted. TTV was present at a significantly higher rate in hemophiliacs (73%) and at lower rates in patients with cirrhosis (30%) and rheumatoid arthritis (28%). Patients with other liver diseases, systemic lupus erythematosus, or psoriasis or receiving hemodialysis had rates of infection similar to those in unselected patients. TTV-positive patients treated with interferon-alpha for underlying type C hepatitis showed no appreciable changes of TTV viremia levels. Type 1b was by far the most frequent viral genotype (92%), followed by types 2c (5%) and 1a (3%). (+info)
Factors associated with slow disease progression in macaques immunized with an adenovirus-simian immunodeficiency virus (SIV) envelope priming-gp120 boosting regimen and challenged vaginally with SIVmac251.
(42/2101)
Rhesus macaques were immunized with a combination vaccine regimen consisting of adenovirus type 5 host range mutant-simian immunodeficiency virus envelope (Ad5hr-SIVenv) recombinant priming and boosting with native SIV gp120. Upon intravaginal challenge with SIVmac251, both persistently and transiently viremic animals were observed (S. L. Buge, E. Richardson, S. Alipanah, P. Markham, S. Cheng, N. Kalyan, C. J. Miller, M. Lubeck, S. Udem, J. Eldridge, and M. Robert-Guroff, J. Virol. 71:8531-8541, 1997). Long-term follow-up of the persistently viremic immunized macaques, which displayed significantly reduced viral burdens during the first 18 weeks postchallenge compared to controls, has now shown that one of four became a slow progressor, clearing virus from plasma and remaining asymptomatic with stable CD4 counts for 134 weeks postchallenge. Reboosting of the transiently viremic macaques did not reactivate latent virus. Rechallenge with two sequential SIVmac251 intravaginal exposures again resulted in partial protection of one of two immunized macaques, manifested by viral clearance and stable CD4 counts. No single immune parameter was associated with partial protection. Development of a strong antibody response capable of neutralizing a primary SIVmac251 isolate together with SIV-specific cytotoxic T lymphocytes were implicated, while CD8(+) T-cell antiviral activity and mucosal immune responses were not associated with delayed disease progression. Our data show that even a third immunization with the same Ad5hr-SIVenv recombinant can elicit significant immune responses to the inserted gene product, suggesting that preexisting Ad antibodies may not preclude effective immunization. Further, the partial protection against a virulent, pathogenic SIV challenge observed in two of six macaques immunized with a vaccine regimen based solely on the viral envelope indicates that this vectored-vaccine approach has promise and that multicomponent vaccines based in the same system merit further investigation. (+info)
Longitudinal variation in hepatitis C virus (HCV) viraemia and early course of HCV infection after liver transplantation for HCV cirrhosis: the role of different immunosuppressive regimens.
(43/2101)
BACKGROUND: The role of the type of immunosuppression in the natural history of post-transplant hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate the fluctuation of HCV viraemia and the early course of infection, and their relation to the type of immunosuppression in HCV transplant patients. METHODS: In 47 HCV transplant patients, serum HCV RNA levels were determined pretransplant and at one and two weeks, and three and 12 months after transplant. Initial immunosuppression was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin, prednisolone) in five, and single (cyclosporin or tacrolimus) in 11 patients. Prednisolone was withdrawn at a median of six months. RESULTS: At three months, HCV RNA levels were higher in patients with single than with triple or double initial therapy. At 12 months, HCV RNA levels correlated only with duration of prednisolone treatment and were relatively higher in patients with triple compared with single initial immunosuppression. A higher necroinflammatory activity at 12 months post-transplant was found in patients with post-transplant acute hepatitis compared with those without. Extent of fibrosis at 12 months was associated with the 12 month HCV RNA level and occurrence of post-transplant acute hepatitis. CONCLUSIONS: HCV RNA levels at three months after transplant are higher in patients treated with single initial immunosuppressive therapy, but at 12 months are higher in patients with longer duration of steroid treatment. HCV viraemia at 12 months seems to be particularly important, as its levels are strongly correlated with the severity of fibrosis. (+info)
British HIV Association guidelines for prescribing antiretroviral therapy in pregnancy (1998).
(44/2101)
The aim of antiretroviral therapy in pregnancy is to deliver a healthy uninfected child to a healthy mother, without prejudicing the future treatment opportunities of the mother. The use of zidovudine monotherapy rapidly became standard practice once it had been shown to reduce by 67% mother to child transmission in women with CD4+ lymphocyte counts above 200 x 10(6)/l. High rates of transmission are seen when maternal disease is advanced (high viral load, low CD4+ lymphocyte counts) despite zidovudine. In these women highly active antiretroviral therapy gives the best prospect for prolonged health and it is anticipated that reducing plasma viral load below the limits of detection will further reduce transmission rates. However, safety data for antiretroviral therapy in pregnancy are limited and each additional treatment exposes a significant proportion of uninfected infants to potential long term hazards. Where maternal therapy is not indicated and the sole objective of treatment is to reduce mother to child transmission, recent data suggest that short course zidovudine (especially in conjunction with prelabour caesarean section) is a reasonable option. This may minimise the emergence of viruses with reduced sensitivity to zidovudine and preserve maternal options for later therapy. (+info)
The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.
(45/2101)
BACKGROUND: Because many persons with chronic hepatitis C virus (HCV) infection are asymptomatic, population-based serologic studies are needed to estimate the prevalence of the infection and to develop and evaluate prevention efforts. METHODS: We performed tests for antibody to HCV (anti-HCV) on serum samples from 21,241 persons six years old or older who participated in the third National Health and Nutrition Examination Survey, conducted during 1988 through 1994. We determined the prevalence of HCV RNA by means of nucleic acid amplification and the genotype by means of sequencing. RESULTS: The overall prevalence of anti-HCV was 1.8 percent, corresponding to an estimated 3.9 million persons nationwide (95 percent confidence interval, 3.1 million to 4.8 million) with HCV infection. Sixty-five percent of the persons with HCV infection were 30 to 49 years old. Seventy-four percent were positive for HCV RNA, indicating that an estimated 2.7 million persons in the United States (95 percent confidence interval, 2.4 million to 3.0 million) were chronically infected, of whom 73.7 percent were infected with genotype 1 (56.7 percent with genotype 1a, and 17.0 percent with genotype 1b). Among subjects 17 to 59 years of age, the strongest factors independently associated with HCV infection were illegal drug use and high-risk sexual behavior. Other factors independently associated with infection included poverty, having had 12 or fewer years of education, and having been divorced or separated. Neither sex nor racial-ethnic group was independently associated with HCV infection. CONCLUSIONS: In the United States, about 2.7 million persons are chronically infected with HCV. People who use illegal drugs or engage in high-risk sexual behavior account for most persons with HCV infection. (+info)
Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group.
(46/2101)
Pig organs may offer a solution to the shortage of human donor organs for transplantation, but concerns remain about possible cross-species transmission of porcine endogenous retrovirus (PERV). Samples were collected from 160 patients who had been treated with various living pig tissues up to 12 years earlier. Reverse transcription-polymerase chain reaction (RT-PCR) and protein immunoblot analyses were performed on serum from all 160 patients. No viremia was detected in any patient. Peripheral blood mononuclear cells from 159 of the patients were analyzed by PCR using PERV-specific primers. No PERV infection was detected in any of the patients from whom sufficient DNA was extracted to allow complete PCR analysis (97 percent of the patients). Persistent microchimerism (presence of donor cells in the recipient) was observed in 23 patients for up to 8.5 years. (+info)
An intranasal challenge model for testing Japanese encephalitis vaccines in rhesus monkeys.
(47/2101)
Placebo-controlled field efficacy trials of new Japanese encephalitis (JE) vaccines may be impractical. Therefore, an animal model to evaluate efficacy of candidate JE vaccines is sought. Previous work has shown that exposure of monkeys to JE virus (JEV) via the intranasal route results in encephalitis. Here we report the further development of this model and the availability of titered virus stocks to assess the protective efficacy of JE vaccines. To determine the effective dose of our JE challenge virus, dilutions of a stock JEV (KE-93 isolate) were inoculated into four groups of three rhesus monkeys. A dose-dependent response was observed and the 50% effective dose (ED50) was determined to be 6.0 x 10(7) plaque forming units (pfu). Among animals that developed encephalitis, clinical signs occurred 9-14 days postinoculation. Infection with JEV was confirmed by detection of JEV in nervous tissues and IgM to JEV in the cerebrospinal fluid. Viremia with JEV was also detected intermittently throughout infection. Validation of the model was performed using a known effective JE vaccine and saline control. One ED90 of virus (2.0 x 10(9) pfu) was used as a challenge dose. Four of four animals that received saline control developed encephalitis while one of four monkeys administered the JE vaccine did so. This study demonstrates that the virus strain, route of inoculation, dose, and the outcome measure (encephalitis) are suitable for assessment of protective efficacy of candidate JE vaccines. (+info)
Production of lethal infection that resembles fatal human disease by intranasal inoculation of macaques with Japanese encephalitis virus.
(48/2101)
Twelve rhesus macaques (Macaca mulatta) challenged intranasally with a wild-type Japanese encephalitis virus (JEV) developed clinical signs 11-14 days later. Tissues from the cerebral cortex, cerebellum, brainstem, thalamus, meninges, and all levels of the spinal cord were stained for JEV antigen with hyperimmune mouse ascitic fluid and streptavidin-alkaline phosphatase; immunofluorescent staining was also done on frozen sections. Viral antigen was found in all cell layers of the cerebellum, the gray matter of the thalamus and brainstem, and the ventral horn of all levels of the spinal cord. Staining was limited to neurons and their processes. Histopathologic changes were limited to the nervous system and characterized by nonsuppurative meningoencephalitis. These results were comparable with those of previous studies done with human autopsy tissues. Intranasal inoculation of rhesus monkeys with JEV was effective in producing clinical disease comparable with natural disease in humans and may serve as a model to evaluate protective efficacy of candidate JEV vaccines. (+info)