Safety and Immunogenicity of the Recombinant BCG Vaccine AERAS-422 in Healthy BCG-naïve Adults: A Randomized, Active-controlled, First-in-human Phase 1 Trial.

Background: We report a first-in-human trial evaluating safety and immunogenicity of a recombinant BCG, AERAS-422, over-expressing TB antigens Ag85A, Ag85B, and Rv3407 and expressing mutant perfringolysin.

Methods: This was a randomized, double-blind, dose-escalation trial in HIV-negative, healthy adult, BCG-naïve volunteers, negative for prior exposure to Mtb, at one US clinical site. Volunteers were randomized 2:1 at each dose level to receive a single intradermal dose of AERAS-422 (>10(5)-<10(6)CFU=low dose, ≥10(6)-<10(7)CFU=high dose) or non-recombinant Tice BCG (1-8×10(5)CFU).

The Ethics of Public Health Laws, and the Special Case of the New "Model Law".

The "model law" in Israel forbids underweight models (BMI below 18.5) to work. The stated goal of the law is to prevent eating disorders among the general audience of the models.

Disseminated, persistent, and fatal infection due to the vaccine strain of varicella-zoster virus in an adult following stem cell transplantation.

Live attenuated varicella vaccine is recommended for healthy individuals who are susceptible to varicella. Although the vaccine is safe, effective, and used worldwide, serious adverse events have been reported, mainly in immunocompromised patients who subsequently recovered. Here, we describe the fatality of an immunocompromised patient who received the varicella vaccine.

Detection of antibodies to varicella-zoster virus in recipients of the varicella vaccine by using a luciferase immunoprecipitation system assay.

A high-throughput test to detect varicella-zoster virus (VZV) antibodies in varicella vaccine recipients is not currently available. One of the most sensitive tests for detecting VZV antibodies after vaccination is the fluorescent antibody to membrane antigen (FAMA) test. Unfortunately, this test is labor-intensive, somewhat subjective to read, and not commercially available.

Deep sequencing of viral genomes provides insight into the evolution and pathogenesis of varicella zoster virus and its vaccine in humans.

Immunization with the vOka vaccine prevents varicella (chickenpox) in children and susceptible adults. The vOka vaccine strain comprises a mixture of genotypes and, despite attenuation, causes rashes in small numbers of recipients. Like wild-type virus, the vaccine establishes latency in neuronal tissue and can later reactivate to cause Herpes zoster (shingles).

Vaccine-related varicella-zoster rash in a hospitalized immunocompetent patient.

An immunocompetent health care worker with no known history of varicella-zoster virus (VZV) disease was exposed to a patient with herpes zoster and was immunized 2 days later. Twenty-seven days after receiving the varicella vaccine, while hospitalized, she developed a disseminated rash. This exposure and subsequent development of symptoms posed infection control challenges.

Effectiveness of 2 doses of varicella vaccine in children.

Background: Because of ongoing outbreaks of varicella, a second dose of varicella vaccine was added to the routine immunization schedule for children in June 2006 by the Centers for Disease Control and Prevention.

Methods: We assessed the effectiveness of 2 doses of varicella vaccine in a case-control study by identifying children ≥4 years of age with varicella confirmed by polymerase chain reaction assay and up to 2 controls matched by age and pediatric practice. Effectiveness was calculated using exact conditional logistic regression.

VZV meningitis following varicella vaccine.

Live attenuated varicella zoster virus is administered to prevent varicella in children and herpes zoster in the elderly. We report a case of disseminated herpes zoster in a previously healthy elderly woman hours after Oka strain vaccination. PCR and restriction enzyme analysis revealed that symptoms were caused by wild type virus.

A phase I-II study of live attenuated varicella-zoster virus vaccine to boost immunity in human immunodeficiency virus-infected children with previous varicella.

Herpes zoster, may be severe and recurrent in HIV-infected children. We determined the safety and immunogenicity of live attenuated varicella-zoster virus (VZV) vaccine in 46 HIV-infected children who had experienced varicella. There were no serious adverse events.

Risk of herpes zoster in adults immunized with varicella vaccine.

A program of routine varicella vaccination of children 12-18 months of age, begun in the United States in 1995, has been very successful in reducing the incidence of varicella. Varicella-zoster virus (VZV), in both wild-type and live attenuated forms, is notable for its ability to produce latent infection of sensory neurons from which it can later reactivate to cause herpes zoster (HZ). Therefore, the effects of vaccination on this secondary VZV-related disease are important to consider; in practice, however, such studies are complicated by the typically long delay between acquisition of the virus and its reactivation.

The safety profile of varicella vaccine: a 10-year review.

Varivax (varicella virus vaccine live [Oka/Merck]; Merck), a live attenuated varicella vaccine, is indicated for vaccination against varicella in appropriate individuals > or =12 months of age. The 10-year safety profile for Varivax is described using data submitted to Merck from routine global postmarketing surveillance, combined with information from a Varicella Zoster Virus Identification Program, which uses polymerase chain reaction (PCR) analysis to identify the presence and strain of VZV in selected specimens. There were 16,683 reports worldwide voluntarily submitted to Merck, for an overall reporting rate of 3.

Primary vaccine failure after 1 dose of varicella vaccine in healthy children.

Universal immunization of young children with 1 dose of varicella vaccine was recommended in the United States in 1995, and it has significantly decreased the incidence of chickenpox. Outbreaks of varicella, however, are reported among vaccinated children. Although vaccine effectiveness has usually been 85%, rates as low as 44% have been observed.

Severe varicella caused by varicella-vaccine strain in a child with significant T-cell dysfunction.

In March 1995, the US Food and Drug Administration approved a live attenuated varicella vaccine for use in healthy children 12 months to 12 years old. We report here an 18-month-old girl with cell-mediated immunodeficiency who developed a severe vaccine-associated rash and clinical evidence of vaccine-associated pneumonia 1 month after inadvertent receipt of varicella vaccine.

Integrating practice issues in managed care into the curriculum: a Delphi survey.

Purpose: This project evolved from a partnership between an advanced practice nurse (APN) graduate program and a care management insurer. The purpose of this Delphi survey was to identify (a) role components germane to the practice of APNs in managed care and (b) topics reflecting these components in the curriculum.

Data Sources: Data were gathered from two expert panels, clinician preceptors and faculty members.

Natural selection for rash-forming genotypes of the varicella-zoster vaccine virus detected within immunized human hosts.

The Oka vaccine strain is a live attenuated virus that is routinely administered to children in the United States and Europe to prevent chickenpox. It is effective and safe but occasionally produces a rash. The vaccine virus has accumulated mutations during its attenuation, but the rashes are not explained by their reversion, unlike complications reported for other viral vaccines.

Vaccine Oka varicella-zoster virus genotypes are monomorphic in single vesicles and polymorphic in respiratory tract secretions.

We previously found that, after immunization with vaccine Oka varicella-zoster virus, virus obtained from a single vesicle were monomorphic, and virus obtained from different individuals were heterogeneous. Here we show that virus obtained from the lungs of a patient were a mixture of vaccine Oka variants. We hypothesize that complications after immunization are unlikely to be caused by expansion of a single, biologically more virulent clone of virus that either pre-exists in the vaccine or develops after random mutation of different clones.

An evaluation of single nucleotide polymorphisms used to differentiate vaccine and wild type strains of varicella-zoster virus.

Rashes following immunization with the vaccine strain (vOka) of varicella-zoster virus (VZV) may occur in up to 5% of children and 10% of adults. In 40% of cases, the causative virus is the vaccine strain and in 60% wild type virus is found. Several reports have identified three restriction site polymorphisms in ORF 62 and the loss of one in ORF 6, which differentiate vOka from wild type VZV, including the parental wild type strain from which vOka, is derived.

Rashes occurring after immunization with a mixture of viruses in the Oka vaccine are derived from single clones of virus.

Vaccination against chickenpox causes a varicella-like rash in up to 5% of healthy children and 50% of children with leukemia. The vaccine may establish latency and reactivate to cause herpes zoster, albeit more rarely than wild-type virus. All vaccine preparations are composed of a mixture of varicella-zoster virus strains that show genotypic variation at several loci.

Effectiveness over time of varicella vaccine.

Context: Reports of outbreaks of varicella in highly immunized groups have increased concern about the effectiveness of varicella vaccine.

Objective: To assess whether the effectiveness of varicella vaccine is affected either by time since vaccination or by age at the time of vaccination.

Design: Case-control study conducted from March 1997 through June 2003.

Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cells.

An 11-year-old girl presented with a papulovesicular rash and severe respiratory distress 5 weeks after receiving varicella vaccine. Restriction fragment length-polymorphism analysis of virus isolated from an endotracheal-tube aspirate and from bronchoalveolar lavage revealed that this patient's illness was due to the Oka vaccine strain of varicella. An extensive immunologic analysis failed to identify a known diagnostic entity to explain her susceptibility to this attenuated vaccine strain.

Evaluations of clinical learning in a managed care environment.

Topic: Clinical learning in a managed-care environment.

Purpose: To obtain evaluative data about clinical learning experiences for graduate nursing students based on the domains of competence for successful practice in managed-care organizations.

Methods: A survey of 42 nurses (20 graduate students, 22 nurse practitioner preceptors) self-reported on two questionnaires.

Persistence of immunity to live attenuated varicella vaccine in healthy adults.

The varicella vaccine was approved in 1995 for use in healthy varicella-susceptible children and adults. Long-term immunity in 461 healthy adults who were enrolled in varicella vaccine trials in 1979-1999 were studied. Forty vaccinees (9%), including 19 (21%) of 89 vaccinees with household exposure (HHE) to chickenpox, developed breakthrough chickenpox 8 weeks to 11.