Wild-type Varicella Research Articles

Herpes zoster virus sclerokeratitis and anterior uveitis in a child following varicella vaccination

PurposeTo report a case of herpes zoster virus sclerokeratitis with anterior uveitis following vaccination with live attenuated varicella vaccine (Oka strain). DesignCase report. MethodsThe case records of the patient were reviewed retrospectively. Pertinent literature citations were identified using MEDLINE. ResultsA 9-year-old boy presented with herpes zoster ophthalmicus 3 years following vaccination with live attenuated varicella vaccine (Oka strain). Examination of the affected eye revealed a moderate follicular response on the palpebral conjunctiva, decreased corneal sensation, mildly elevated intraocular pressure, diffuse anterior scleritis with marginal keratitis, and a moderately severe anterior uveitis. Amplified DNA from fluid taken from the base of a cutaneous vesicle produced wild-type varicella zoster virus (VZV) DNA, not Oka strain. ConclusionsHerpes zoster virus infection needs to be considered in all patients who present with scleritis, keratitis, or anterior uveitis, regardless of their varicella vaccination status.

Partial uptake of varicella vaccine and the epidemiological effect on varicella disease in 11 day-care centers in North Carolina.

The increasing use of varicella vaccine in children attending day care has rapidly decreased the incidence of wild-type varicella disease. The herd immunity noted is significant and will have an effect on the epidemiology of natural varicella. To monitor the change in varicella incidence in day-care attendees after the licensure of varicella vaccine. A prospective observational cohort study design. Eleven private day-care centers and preschools in North Carolina participated in the study from January 1, 1995, through December 31, 1999. All children in the 11 centers were eligible for participation. Some participated more actively, supplying information on a regular basis. Others participated passively. Day-care personnel provided information about all cases of varicella. None. The change in the incidence of varicella disease was documented as the use of varicella vaccine increased. Varicella vaccine coverage increased substantially from 4.4% in 1995 to 63.1% in December 1999. The vaccination rate accelerated dramatically in 1996 and 1997, leveled off in 1998, and rose again in 1999. Cumulative varicella incidence decreased from 16.74 cases per 1000 person-months in July 1996 to 1.53 cases per 1000 person-months in December 1999 in unvaccinated children. The varicella vaccination rate continued to increase slowly in the day-care population after an initial rapid uptake. The decrease in varicella disease is greater than the increase in varicella vaccination. This herd effect is welcome and even apparent in the unvaccinated children younger than 1 year.

Evidence for frequent reactivation of the Oka varicella vaccine strain in healthy vaccinees.

Serum antibody levels and infection rates were followed for 4 years in 4,631 children immunized with the recently licensed Oka strain varicella vaccine. Anti-VZV titers declined over time in high-responder subjects, but rose in vaccinees with low titers. Among subjects with low anti-VZV titers, the frequency of clinical sequelae and immunological boosting significantly exceeded the 13%/yr rate of exposure to wild type varicella. These findings indicate that the Oka strain of VZV persisted in vivo, and reactivated as serum antibody titers declined after vaccination. This mechanism may improve vaccine-associated long-term immunity.

Varicella Vaccination in Children

Varicella vaccines have been developed, studied, tested and used since the early 1970s, first in Japan and subsequently in Europe, the US, Asia and South and Central America. Varicella vaccination was first used to immunise Japanese children in cancer remission, as wild-type varicella disease is often fatal in immunocompromised individuals. Since then, it has been licensed for use in healthy children as well. There are 3 manufacturers of the vaccine: Biken (Japan), Merck and Co. (US) and SmithKline Beecham (Belgium). The Biken vaccine has been approved for use in Japan since 1986 (although it was developed and used for research purposes from 1974). The Merck and Co. vaccine was approved in the US in March 1995 and the SmithKline Beecham vaccine was first licensed for use in immunocompromised children in 1984 and for healthy children in Sweden in October 1994. All 3 vaccines are derived from the Oka (Japanese) strain obtained from an immunologically normal 3-year-old Japanese boy named Oka with wild-type disease. Aventis-Pasteur has also purchased the rights to the Oka strain but no published literature is available for review. Use of the varicella vaccine has been controversial because many argue that: (i) the disease is mild and not worth preventing; (ii) the long term immunity provided by the vaccine is unknown; and (iii) the average age of those with the disease will increase if the vaccine is used and hence there will be more complications in older patients and, therefore, more costs. Because of some outbreaks of secondary bacterial infections after varicella in children in US day care centres, vaccination of healthy children is required in some states. It will be interesting to see whether other countries adopt a similar recommendation as more families have 2 working parents. The financial benefit of the vaccine (keeping parents at work) may encourage more use of the vaccine and a subsequent recommendation for immunisation schedules.

Varicella vaccination: evidence for frequent reactivation of the vaccine strain in healthy children.

Wild-type varicella zoster virus (VZV) causes chickenpox, a common childhood illness characterized by fever and a vesicular rash and rare serious complications. Wild-type VZV persists in a latent form in the sensory ganglia, and can re-activate to cause herpes zoster. More than 10 million American children have received the live attenuated Oka strain VZV vaccine (OkaVZV) since its licensure in 1995. Pre-licensure clinical studies showed that mean serum anti-VZV levels among vaccinees continued to increase with time after vaccination. This was attributed to immunologic boosting caused by exposure to wild-type VZV in the community. Here, we examine the alternative, that large-scale asymptomatic reactivation of OkaVZV might occur in vaccinees. We analyzed serum antibody levels and infection rates for 4 years of follow-up in 4,631 children immunized with OkaVZV. Anti-VZV titers decreased over time in high-responder subjects, but rose in vaccinees with low titers. Among subjects with low anti-VZV titers, the frequency of clinical infection and immunological boosting substantially exceeded the 13%-per-year rate of exposure to wild-type varicella. These findings indicate that OkaVZV persisted in vivo and reactivated as serum antibody titers decreased after vaccination. This has salient consequences for individuals immunized with OkaVZV.

VARICELLA VACCINE

Varicella vaccine is safe, effective, and cost-effective in healthy children, adolescents, and adults. Breakthrough cases of MVLS are significantly milder than wild-type varicella infection. No severe adverse events have been reported following vaccination, and the incidence of herpes zoster is less in vaccinees than in individuals who have had natural varicella infections. To date, there is no evidence waning immunity following vaccination. "New and improved" varicella vaccines that may be more effective than the current vaccine and can be stored at refrigerator temperatures may soon become available in the United States.

Postlicensure study of varicella vaccine effectiveness in a day-care setting.

Varicella vaccine has been licensed for use in the United States since the spring of 1995. The acceptance of the vaccine and its effect on varicella incidence in children is important. To document the effectiveness of the varicella vaccine in children attending day care in 11 centers in North Carolina. A dynamic cohort study design was used in 11 day-care centers in North Carolina. Multiple cross-sectional evaluations were performed and children were noted to be vaccinated or not and diseased or not. Vaccine effectiveness was estimated by comparing the varicella attack rate in the vaccinated with the varicella attack rate in the unvaccinated. Person time was used as the denominator for all calculations. During the study period February 1, 1996, to September 1, 1997, 134 cases of varicella occurred in the unvaccinated and 11 cases occurred in the vaccinated children. The attack rates in the vaccinated and unvaccinated were 2.49 and 14.66, respectively, for an overall vaccine effectiveness of 83% for mild/moderate disease. In the day-care setting varicella vaccine demonstrated benefit in preventing and modifying wild-type varicella disease.

Varicella vaccine for immunocompromised children: results of collaborative studies in the United States and Canada.

Varicella vaccine in immunocompromised children was clinically evaluated in 575 US and Canadian children with leukemia in remission by the Varicella Vaccine Collaborative Study. Most children had chemotherapy stopped 1 week before and 1 week after immunization. Steroids were stopped for 3 weeks (1 week before to 2 weeks after vaccination). Varicella vaccine was safe, immunogenic, and effective in leukemic children at risk for serious disease or death from chickenpox. The major side effect was mild rash in 50% approximately 1 month after immunization. About 40% of children who developed rash were treated with acyclovir. Vaccine efficacy was judged by the degree of protection after a household exposure to varicella; of 123 exposed children, 17 (14%) developed a mild form of varicella. The vaccine protected completely against severe varicella. Leukemic vaccines were less likely to develop zoster than were comparable children with leukemia who had wild type varicella. Thus, varicella vaccine, administered carefully with close follow-up, is extremely beneficial for leukemic children.

Infection of human fetal dorsal root neurons with wild type varicella virus and the Oka strain varicella vaccine

The relative ability of a varicella-zoster virus (VZV) clinical isolate and a live attenuated VZV vaccine strain (Oka) to infect human neurons was determined in vitro. VZV infection of neurons prepared in culture from dorsal root ganglia of fetuses was assessed using an infectious center assay. Cultures were infected with 50-5,000 pfu of either VZV and assayed at either 24 or 48 hours post-VZV infection. Cultures infected with the clinical VZV isolate had seven-fold more infected neurons than cultures infected with the vaccine strain VZV.

Association of steroid therapy with vaccine-associated rashes in children with acute lymphocytic leukaemia who received Oka/Merck varicella vaccine

Oka strain varicella vaccine generally has been well tolerated by children with acute lymphocytic leukaemia (ALL) in remission and has induced protection against disease caused by wild-type varicella virus. At the end of 1985, four extensive vaccine-associated rashes were reported among children on maintenance chemotherapy. Steroid therapy in the week before vaccination or in the week following vaccination was significantly associated with rash in a retrospective analysis (odds ratio = 3.84, p = 0.0006). These findings were confirmed prospectively (OR = 2.38, p less than 0.05, one-sided) in a second smaller group of children with ALL on maintenance therapy who received varicella vaccination after the end of the data collection for the initial study but before the relationship between rash and steroids was discovered. As a result of these studies, investigators have been asked to withhold steroids for 1 week before vaccination and to delay resumption of steroid therapy for at least 2 weeks after vaccination. These results should serve as a caution that vaccination of these children should be undertaken only with full knowledge of their therapeutic regimen and a thorough clinical understanding of the competing risks of varicella, vaccination and modification of the child's chemotherapy.