2-Year GLOBE trial results: telbivudine Is superior to lamivudine in patients with chronic hepatitis B.

BACKGROUND & AIMS: The GLOBE trial has compared the efficacy and safety of telbivudine versus lamivudine treatment over 2 years in patients with chronic hepatitis B. METHODS: Hepatitis B e antigen (HBeAg)-positive (n = 921) and HBeAg-negative (n = 446) patients received telbivudine or lamivudine once daily for 104 weeks. The primary outcome, assessed in the intent-to-treat population, was therapeutic response (hepatitis B virus DNA <5 log(10) copies/mL and either HBeAg loss or normalization of alanine aminotransferase [ALT] level). RESULTS: The therapeutic response to telbivudine was superior to that of lamivudine in HBeAg-positive (63% vs 48%; P < .001) and HBeAg-negative (78% vs 66%; P = .007) patients. HBeAg-positive patients given telbivudine also had better outcomes compared with lamivudine in terms of nondetectable viremia (< 300 copies/mL) at 55.6% versus 38.5% (P < .001), HBeAg loss at 35.2% versus 29.2% (P = .056), and viral resistance at 25.1% versus 39.5% (P < .001). Hepatitis B e antigen seroconversion was 29.6% versus 24.7% (P = .095) in all patients and 36% versus 27% (P = .022) in patients with baseline ALT level > or = 2 times normal. Telbivudine-treated HBeAg-negative patients showed higher rates of nondetectable viremia compared with lamivudine at 82.0% versus 56.7% (P < .001) and less resistance at 10.8% versus 25.9% (P < .001). Adverse events occurred with similar frequency, whereas grade 3/4 increases in creatine kinase levels were more common in patients given telbivudine (12.9% vs 4.1%, P < .001). Multivariate logistic regression analyses identified telbivudine treatment, among other variables, as an independent predictor of better week 104 outcomes. CONCLUSIONS: Telbivudine is superior to lamivudine in treating patients with chronic hepatitis B over a 2-year period.

Outbreak of varicella at a day-care center despite vaccination.

BACKGROUND: In seven studies of the effectiveness of the varicella vaccine conducted since it was licensed, the effectiveness was 71 to 100 percent against disease of any severity and 95 to 100 percent against moderate and severe disease. We investigated an outbreak of varicella in a population of children with a high proportion of vaccinees who were attending a day-care center in a small community in New Hampshire. METHODS: Using standardized questionnaires, we collected information about the children's medical and vaccination history from parents and health care providers. The analysis of the effectiveness of the vaccine and of risk factors for vaccine failure was restricted to children who were enrolled in the day-care center continuously during the outbreak and attended for one week or more and who were cared for in the building that represented the epicenter of the outbreak, since transmission was not documented in a second building. RESULTS: Varicella developed in 25 of 88 children (28.4 percent) between December 1, 2000, and January 11, 2001. The index case occurred in a healthy child who had been vaccinated three years previously and who infected more than 50 percent of his classmates who had no history of varicella. The effectiveness of the vaccine was 44.0 percent (95 percent confidence interval, 6.9 to 66.3 percent) against disease of any severity and 86.0 percent (95 percent confidence interval, 38.7 to 96.8 percent) against moderate or severe disease. Children who had been vaccinated three years or more before the outbreak were at greater risk for vaccine failure than those who had been vaccinated more recently (relative risk, 2.6 [95 percent confidence interval, 1.3 to 5.3]). CONCLUSIONS: In this outbreak, vaccination provided poor protection against varicella, although there was good protection against moderate or severe disease. A longer interval since vaccination was associated with an increased risk of vaccine failure. Breakthrough infections in vaccinated, healthy persons can be as infectious as varicella in unvaccinated persons.

Hospitalizations for varicella in the United States, 1988 to 1999.

BACKGROUND: Varicella epidemiology is changing with increasing use of the varicella vaccine. METHODS: To describe the epidemiology of severe varicella disease before and after vaccine introduction, data from the National Hospital Discharge Survey (NHDS) for 1988 to 1999 were analyzed. Incidental cases of varicella in persons hospitalized for a different indication were excluded. RESULTS: In the prevaccination era (1988 to 1995), there were 10 632 varicella hospitalizations annually. The most common complications were viral pneumonitis (20.9%), fluid/electrolyte disturbances (19.3%) and soft tissue infections (17.8%). Most (89.1%) persons had no severe underlying immunocompromising conditions. The mean length of hospitalization was 5.4 days, corresponding to approximately 57 000 days of hospitalization annually. In the first years after vaccine licensure (1996 to 1999), vaccine coverage reached 59%. Although not statistically significant, there was a trend toward decreased hospitalizations and a decline in mean length of hospitalization. CONCLUSIONS: Varicella morbidity was higher in the prevaccination era than previously reported. Although no significant decline is evident, a trend toward decreased hospitalizations is emerging in the first years after vaccine introduction.

Postpartum varicella vaccination: is the vaccine virus excreted in breast milk?

OBJECTIVE: To evaluate whether the varicella vaccine virus is detected in breast milk after vaccination of breast-feeding women and whether there is serologic evidence of exposure of the infant to varicella virus after maternal vaccination. METHODS: We enrolled women identified as varicella seronegative during routine prenatal screening at Group Health Cooperative. Participants received the first dose of varicella vaccine at least 6 weeks postpartum and the second dose at least 4 weeks later. They collected ten breast milk samples after each vaccine dose. Breast milk samples were tested for varicella zoster virus by polymerase chain reaction (PCR). Serum specimens were collected from the mothers 1 month after each vaccine dose, and peripheral blood from their infants was collected onto filter spots 1 month after the mother's second dose. These samples were tested for varicella immunoglobulin (Ig) G by whole-virus enzyme-linked immunosorbent assay (ELISA), or by the more sensitive glycoprotein ELISA. When possible, filter spots from the infants were also tested by PCR for the presence of varicella zoster virus deoxyribonucleic acid (DNA). RESULTS: Twelve women were enrolled; all seroconverted after the first vaccine dose. Varicella DNA was not detected by PCR in any of the 217 postvaccination breast milk specimens. None of the infants was seropositive. Samples from six infants were tested for varicella zoster virus DNA by PCR, and all were negative. CONCLUSION: We found no evidence of varicella vaccine virus excretion in breast milk. These findings suggest that postpartum vaccination of varicella-susceptible women need not be delayed because of breast-feeding.

Epidemiology of varicella hospitalizations in the United States, 1995-2005.

To describe the impact of the varicella vaccination program on varicella-related hospitalizations (VRHs) in the United States, data from the Varicella Active Surveillance Project (VASP) were used to compare rates of hospitalization and rates of complications among patients hospitalized for varicella-related conditions from 1995 to 2005. Of the 26,290 varicella cases reported between 1995 and 2005, 170 cases resulted in VRHs, including 1 case that resulted in death. Both VRH rates per 100,000 population and complications during VRH per 100,000 population decreased significantly between the early vaccination period (1995-1998) and the middle/late vaccination period (1999-2005). Infants and adults were at highest risk for VRH, and having been vaccinated against varicella was a protective factor. Varicella vaccination may have prevented a significant number of VRHs. The fact that 4 vaccinated children required hospitalization for varicella-related complications demonstrates that 1 dose of varicella vaccine does not prevent serious disease in all cases, even among previously healthy children.

Incidence of herpes zoster, before and after varicella-vaccination-associated decreases in the incidence of varicella, 1992-2002.

BACKGROUND: Varicella zoster virus (VZV) causes varicella and, later in the life of the host, may reactivate to cause herpes zoster (HZ). Because it is hypothesized that exposure to varicella may boost immunity to latent VZV, the vaccination-associated decrease in varicella disease has led some to suggest that the incidence of HZ might increase. We assessed the impact that varicella vaccination has on the incidence of varicella and of HZ. METHODS: Codes for cases of varicella and of HZ in an HMO were determined in automated databases of inpatients and outpatients, on the basis of the Ninth Revision of the International Classification of Diseases. We calculated the incidence, during 1992-2002, of varicella and of HZ. RESULTS: The incidence of HZ remained stable as the incidence of varicella decreased. Age-adjusted and -specific annual incidence rates of varicella decreased steadily, starting with 1999. The age-adjusted rates decreased from 2.63 cases/1000 person-years during 1995 to 0.92 cases/1000 person-years during 2002; among children 1-4 years old, there was a 75% decrease between 1992-1996 and 2002. Age-adjusted and -specific annual incidence rates of HZ fluctuated slightly over time; the age-adjusted rate was highest, at 4.05 cases/1000 person-years, in 1992, and was 3.71 cases/1000 person-years in 2002. CONCLUSIONS: Our findings revealed that the vaccination-associated decrease in varicella disease did not result in an increase in the incidence of HZ. These early findings will have to be confirmed as the incidence of varicella disease continues to decrease.

Younger age at vaccination may increase risk of varicella vaccine failure.

To determine vaccine effectiveness (VE), a varicella outbreak in a highly vaccinated day-care center (DCC) population in Pennsylvania was investigated. In Pennsylvania, proof of immunity is required for children >or=12 months old for DCC enrollment. Questionnaires were administered to parents of children who had attended the DCC continuously during the study period (1 November 1999-9 April 2000) to determine history of varicella disease or vaccination and for information about any recent rash illnesses. VE was calculated for children >or=12 months old without a history of varicella. There were 41 cases of varicella among 131 attendees, with 14 cases (34%) among vaccinated children. VE was 79% against all varicella and 95% against moderate or severe varicella. Vaccination at <14 months was associated with an increased risk of breakthrough disease (relative risk, 3.0; 95% confidence interval, 0.9-9.9). Despite varicella vaccination coverage of 80%, a sizeable outbreak occurred. Early age at vaccination may increase the risk of vaccine failure.

Resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study.

BACKGROUND: Previous studies have reported age-dependent development of resistance to reinfection by schistosomes and identified immunological correlates of this resistance. However, whether resistance exists that is independent of age effects has been questioned. We did a longitudinal investigation of reinfection by Schistosoma mansoni in an adult population with high occupational exposure. METHODS: We monitored a cohort of 96 male car washers working along the shores of Lake Victoria, Kenya during 349.7 person-years for frequency of water contact and infection with S mansoni. Patients were treated with praziquantel upon study entry and after reinfection with S mansoni. Bivariate analyses and a multivariate proportional hazards model were used to assess the effects of water contact, previous infections, and HIV-1 on S mansoni reinfection rates. FINDINGS: 13 car washers did not get reinfected or only became reinfected after an extended time (91 weeks). 47 initially had a short time to reinfection (15 weeks) but on subsequent treatments showed increased time to reinfection (29-38 weeks). 36 consistently displayed short times to reinfection (<15 weeks) despite multiple reinfection and treatment cycles. Decreased CD4 T-cell counts in HIV-1-positive individuals corresponded to increased susceptibility to S mansoni reinfection. INTERPRETATION: Adults similarly exposed to schistosomiasis are either resistant to reinfection; susceptible, but develop resistance to reinfection after multiple treatments; or remain susceptible to reinfection. Thus, immunological resistance to reinfection with S mansoni exists or can develop independent of age effects. The consequence of HIV-1 co-infection suggests that CD4 T cells contribute to this resistance.