Varicella Virus Vaccine Research Articles

AAP Issues Letter Regarding Vaccine Payment

The AAP has issued a letter to payers regarding payment for codes 90707 (measles, mumps, and rubella vaccine [MMR], live, for subcutaneous use) and 90716 (varicella virus vaccine, live, for subcutaneous use) when the 2 vaccines are administered separately rather than the combined vaccine listed under 90710 (measles, mumps, rubella, and varicella vaccine [MMRV], live, for subcutaneous use).

Developmental milestones as ACNS turns one year old

Developmental milestones as ACNS turns one year old

Meningitis caused by the varicella vaccine virus in 17 immunized children and adolescents from the United States, Europe, and Japan

AbstractThe varicella vaccination program has an excellent safety record. The vaccine virus, like its wild‐type counterpart, can enter latency and later reactivate as herpes zoster. A lesser known but serious adverse event following reactivation is varicella vaccine meningitis. We investigate that adverse event. We performed a literature search using the PubMed and Google Scholar search engines to locate all published cases of varicella vaccine meningitis. We continued the search through January 2023. We found 17 cases of varicella vaccine meningitis. The first case was published in 2003, and the last case was published in 2023. The children lived in the United States, Greece, Germany, Switzerland, and Japan. Among the 17 cases, 14 were immunocompetent; nine of the 17 were adolescents. One potential risk factor was the administration of corticosteroids three to four weeks before the onset of meningitis. Varicella vaccine meningitis is a rare but one of the more serious adverse events that occurs several years following varicella vaccination. In immunocompetent children, this complication is treatable with a single course of intravenous acyclovir after hospitalization.

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy infants, children, and adolescents

ABSTRACT Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV), which can result in bacterial superinfection, central nervous system complications, and hospitalization. Stage 2 of this Phase 3 open-label study (ClinicalTrials.gov identifier: NCT03843632) enrolled 100 healthy infants, children, and adolescents (12 months–6 years, n = 37; 7–12 years, n = 33; 13–17 years, n = 30) without a clinical history of varicella. Participants aged 12 months–12 years were administered 1 dose of VARIVAX™ 0.5 mL (Varicella Virus Vaccine Live [Oka/Merck]) and adolescents aged 13–17 years were administered 2 doses 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immunosorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and VZV antibody geometric mean titers 6 weeks after the final dose. For participants who were VZV seropositive at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by antibody titer geometric mean fold rise and percentage of participants with ≥4-fold rise in antibody titer 6 weeks after the final dose. A Vaccine Report Card was used to report solicited and unsolicited adverse events through 42 days post-vaccination. After series completion among seronegative participants across age groups (n = 74), 98.6% demonstrated seroconversion 6 weeks post-vaccination; among seropositive participants (n = 26), 65.4% had ≥4-fold rise in antibody titer 6 weeks post-vaccination. No new safety signals were observed. Administering VARIVAX to infants, children, and adolescents resulted in an acceptable immune response with a safety profile consistent with the licensed product.

Phase 3, open-label, Russian, multicenter, single-arm trial to evaluate the immunogenicity of varicella vaccine (VARIVAX™) in healthy adults

ABSTRACT Varicella (chickenpox) is a common, highly contagious disease caused by primary infection with varicella zoster virus (VZV). Adults typically experience more severe symptoms than children and have a higher risk of developing complications. Stage 1 of this Phase 3 open-label study enrolled healthy adults in Russia aged 18–75 years without a clinical history of varicella infection. Eligible participants (n = 50) were administered 2 doses of VARIVAX™ (Varicella Virus Vaccine Live [Oka/Merck]) 0.5 mL 6 weeks apart. For participants seronegative at baseline (VZV antibody titer <1.25 glycoprotein enzyme-linked immuno-sorbent assay [gpELISA] units/mL), immunogenicity was assessed by seroconversion (VZV antibody titer ≥5 gpELISA units/mL) and assessment of geometric mean titers of VZV antibody as measured by gpELISA 6 weeks after Dose 2. For VZV seropositive participants at baseline (VZV antibody titer ≥1.25 gpELISA units/mL), immunogenicity was assessed by geometric mean fold rise in antibody titer and percentage of participants with a ≥ 4-fold rise in antibody titer 6 weeks after Dose 2. A Vaccine Report Card was used to record solicited and unsolicited adverse events through 42 days post-vaccination. All participants who were seronegative (n = 26) at baseline demonstrated seroconversion 6 weeks after Dose 2. Among participants who were seropositive at baseline (n = 23), 60.9% had a ≥4-fold rise in antibody titer 6 weeks after Dose 2. Vaccination was generally well tolerated, with no new safety signals identified. Administration of 2 doses of VARIVAX in adults in Russia results in acceptable immune responses with safety data consistent with the licensed product (Clinicaltrials.gov identifier: NCT03843632).

The round trip model for severe herpes zoster caused by live attenuated varicella vaccine virus.

Highlights Varicella vaccine is a live attenuated varicella‐zoster virus. Varicella vaccine can enter latency and later reactivate as herpes zoster. Pseudorabies virus is another herpesvirus closely related to varicella‐zoster virus. The round trip model for pseudorabies virus explains pathogenesis of herpes zoster from vaccine virus.

Varicella Virus Vaccine Live: A 22-Year Review of Postmarketing Safety Data.

BackgroundVaricella, a contagious infectious disease caused by varicella zoster virus (VZV), can result in hospitalization and, occasionally, death. Varicella virus vaccine live (VVVL [VARIVAX]) was introduced in the United States in 1995.MethodsThis comprehensive review of the VVVL safety profile is based on 22 years of postmarketing adverse event (AE) data received through spontaneous and noninterventional study reports submitted by health care providers and on a review of the published literature (cumulatively from March 17, 1995, through March 16, 2017, during which period >212 million doses were distributed globally).ResultsThe VVVL safety profile was consistent with previous publications, with common AEs including varicella, rash, and pyrexia. AE reports have decreased over time, from ~500 per million doses in 1995 to ~40 per million doses in 2016; serious AEs comprise 0.8 reports per million doses. Secondary transmission was rare (8 confirmed cases); polymerase chain reaction analysis indicated that 38 of the 66 reported potential secondary transmission cases of varicella were attributable to wild-type VZV. The prevalence of major birth defects in the Pregnancy Registry was similar to that in the general US population. In total, 86 cases of death were reported after vaccination with VVVL; immunocompromised individuals appeared to be most at risk for a fatal varicella- or herpes zoster–related outcome.ConclusionsThis comprehensive 22-year review confirms the overall safety profile for VVVL, with no new safety concerns identified. Since VVVL’s introduction in 1995, notable declines in varicella cases and in varicella-related deaths have occurred compared with the prevaccination period.

A double-blind, randomized, controlled, multi-center safety and immunogenicity study of a refrigerator-stable formulation of VARIVAX®

ObjectiveVARIVAX® (varicella virus vaccine, live Oka/Merck, Merck & Co., Inc., Kenilworth, NJ, USA) was originally licensed as a frozen formulation. A refrigerator-stable formulation of VARIVAX was subsequently developed to allow for increased availability of the product around the world. The objective of this study (V210-051) was to demonstrate that the safety, tolerability and immunogenicity profile of the refrigerator-stable formulation of VARIVAX was similar to the frozen formulation. MethodsIn this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either a refrigerator-stable formulation of VARIVAX (at two dosage levels; 8000 PFU [N = 320] or 25,000 PFU [N = 315]) or the frozen formulation of VARIVAX (10,000 PFU, N = 323) given concomitantly with M-M-RII® (measles, mumps, and rubella virus vaccine live, Merck & Co., Inc., Kenilworth, NJ, USA). Children were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination. ResultsThe refrigerator-stable formulation of VARIVAX was generally well tolerated. The incidence of adverse experiences was similar between all three groups. No vaccine-related serious adverse experiences were reported with any of the vaccine formulations. The immune response (percentage of subjects with varicella antibody titers ≥5 gpELISA units) for both refrigerator-stable formulations of VARIVAX at 6 weeks postvaccination was similar to that of the frozen formulation. Administration of either refrigerator-stable formulation of VARIVAX with M-M-RII yielded seroconversion rates and GMTs for measles, mumps and rubella that were comparable to those achieved after administration of the frozen formulation of VARIVAX with M-M-RII. ConclusionThe safety, tolerability, and immunogenicity profile of the refrigerator-stable varicella vaccine was similar to that of the frozen formulation.

COMMENTARY

COMMENTARY

Vaccine topics discussed at ACIP meeting

The following article covers vaccine topics discussed at the June 2012 Advisory Committee on Immunization Practices (ACIP) meeting. The article "ACIP meeting: Latest vaccine topics reviewed" on page 52 provides more information about this meeting. According to information presented at the meeting, Merck's hepatitis A vaccine Vaqta will be unavailable until mid-2012; however, production and supply of GlaxoSmithKline's adult hepatitis A vaccine (Havrix) and hepatitis A/hepatitis B combination vaccine (Twinrix) are sufficient to meet demand for routine adult usage. Sanofi Pasteur's Pentacel (tetanus, diphtheria, and pertussis [Tdap]; polio; and Haemophilus inBuenza type b [Hib]) and Daptacel (Tdap) are still on backorder; Merck's varicella virus vaccine Varivax is also backordered. In addition, it is anticipated that Merck's measles-mumpsrubella-varicella (MMRV) vaccine ProQuad will return to the market in October, and the backorder for its herpes zoster vaccine Zostavax has been resolved. Four meningococcal vaccines are now on the market: one polysaccharide (MPSV4 [Menomune—Sanofi Pasteur]), two conjugated quadrivalent (Menactra—Sanofi Pasteur and Menveo—Novartis), and a new combination of meningococcal groups C and Y and Hib-tetanus toxoid conjugate (MenHibrix—GlaxoSmithKline). This novel combination was approved by FDA in mid-June and is indicated in infants at age 2 months, 4 months, 6 months, and 12 months. ACIP has not recommended routine infant immunizations in the past due to the low incidence of disease in infants. Because the vaccine was approved shortly before the most recent ACIP meeting, the vaccine will be discussed at the group's October meeting. The 2010 Adult Vaccination Coverage schedule for patients 19 years to 64 years was recently published in CDC's Morbidity and Mortality Weekly Report. The report covers vaccines for Tdap, herpes zoster, human papillomavirus (HPV), and pneumococcal. Compared with 2009, there were only slight increases for Tdap (8.2% + 1.6%), zoster (14.4% + 4.4%), and HPV for women (20.7% + 3.6%), with the other vaccination rates remaining unchanged. The group concluded that all vaccination coverage remains low (far below 2020 targets). The improvement from 2009 was minimal, and racial and ethnic disparities remain. The inaugural National Adult Immunization Summit was held in conjunction with the National Influenza Vaccine Summit on May 15–17. The focus was increasing immunization rates in adults and reducing the burden of vaccine-preventable diseases. Major themes included improving communications and registries, decreasing policy and legal barriers for all providers, evaluating means to increase education of and incentivize providers, decreasing complexity of ACIP schedules, and engaging and encouraging immunization champions and leadership. The last time HPV was discussed by ACIP was October 2011, when the vaccine was approved for males. The National Immunization Survey for 2010 reported female coverage of the HPV vaccine to be 48.7% for one or more doses and 32% for all three doses. Data from eight Sentinel Immunization Information Systems sites funded by CDC showed only a slight increase in female coverage rates during the last 3 years. Only about 10% of males have received the HPV vaccine. Data on the impact of the HPV vaccine are currently being collected. One survey showed that the prevalence of anogenital warts in females aged 15 years to 19 years has decreased, whereas all other age groups increased. In addition, postlicensure monitoring for safety showed that the vaccine is safe but syncope remains a common problem. Currently, few trials are under way to evaluate the vaccine's efficacy with a decrease in the number of doses of vaccine needed. The last rubella pandemic was 1964–65 with 12.5 million cases in the United States. Following the development of the MMR vaccine, rubella was declared eliminated in 2004. An average of nine cases continue to occur each year, mostly in individuals older than 15 years, with onethird born in the United States. A total of 111,888 worldwide cases of congenital rubella syndrome (CRS) were reported in 2008. Six cases of CRS have been reported in the United States since 2005. Because wild measles has mostly disappeared from the American population, immunoglobulin levels of antibody against measles are also decreasing. The amount of antibody donated by people with previous MMR vaccination is lower that following natural disease. The recommended dose of intramuscular (I.M.) immunoglobulin for measles prophylaxis is 0.25 mL/kg (maximal dose is 15 mL). This dose is not adequate for measles prevention in most people. Doubling the dose would still give only minimal antibody concentrations; therefore, I.V. immunoglobulin may be needed to obtain an adequate dose. I.M. immunoglobulin is difficult to obtain because of supply issues. Discussion will continue. The ACIP working group has proposed policy changes for the MMR vaccine, including changing the definition of confirmation of disease and testing requirements, vaccination of patients with HIV, vaccination of household contacts of immunocompromised patients, and permissive use of a third dose in outbreaks. These ideas will be discussed further at future meetings. The next ACIP meeting is October 24–25 in Atlanta.

Disseminated Varicella Infection Caused by Varicella Vaccine Strain in a Child With Low Invariant Natural Killer T Cells and Diminished CD1d Expression

Live attenuated varicella vaccine is considered a safe vaccine with serious adverse effects reported only in immunocompromised children. We describe a severe life-threatening infection with varicella vaccine virus causing rash and pneumonitis in a 6-year-old boy with no apparent immunodeficiency. Polymerase chain reaction (PCR) analysis of vesicle swab samples demonstrated varicella zoster virus (VZV). Sequencing of the PCR product demonstrated 100% homology with human herpesvirus 3 strain VZV-Oka ORF62 gene. Routine immunologic investigations failed to demonstrate any abnormality. Total leukocyte, lymphocyte, and neutrophil counts and lymphocyte subsets were normal. Immunoglobulins, C3, C4, and CH50 were intact. Specific IgG to protein and polysaccharide antigens and to Epstein-Barr virus and cytomegalovirus were present. Normal lymphocyte proliferation to phytohemagglutinin and VZV antigens was detected. Neutrophil function and natural killer (NK) cell activity were normal. The analysis of invariant NK T (iNKT) cell numbers and function revealed diminished iNKT cells, reported once previously and unique to our patient, deficient expression of the cognate receptor, CD1d. This report provides a further link between deficiency of the iNKT/CD1d pathway and increased susceptibility to varicella vaccine virus, suggesting an important role of this innate pathway in host defense against yet another member of the herpesvirus family.

Safety of a second dose of varicella vaccine administered at 4 to 6 years of age in healthy children in Argentina

Varicela Biken [Live varicella Biken vaccine (strain Oka)] is an effective and safe vaccine for the prevention of varicella infection. Although the recommended schedule in all age groups (children, adolescents and adults) is a single dose, physicians in some countries follow the 2007 recommendation of the US Advisory Committee on Immunization Practices (ACIP) which recommends “implementation of a routine 2-dose varicella vaccination program for children, with the first dose administered at age 12--15 months and the second dose at age 4--6 years.”1 Therefore, cases can arise when two doses of Varicela Biken are given even though the ACIP guidelines are a response to the US epidemiological situation and for US licensed products based on the Oka/Merck and the Oka-RIT strains (Varicela Biken is not registered in US). The aim of this study is to ascertain the safety of a second dose of Varicela Biken in children who have been previously vaccinated with the same vaccine.In this study, children, 4-6 years of age who had been previously vaccinated with Varicela Biken, received a single 0.5mL dose of live attenuated varicella virus vaccine containing at least 1000 Plaque Forming Units (PFU) attenuated live Varicella-zoster virus (Oka strain). Participants were monitored for 30 minutes after vaccination. Predefined injection site and systemic reactions were solicited during the subsequent seven days. Unsolicited injection site reactions and unsolicited systemic events were collected throughout the study. Any serious adverse events occurring throughout the study were reported to the sponsor’s pharmacovigilance department.One hundred and twenty two children were recruited and all provided safety data. There were no immediate adverse events or injection site reactions. Forty three percent of participants reported injection site reactions and 22.1% reported systemic reactions on solicitation during the seven days after vaccination. During the 30 day monitoring period, 43 participants reported a total of 66 adverse events. Seven participants reported a total of eight unsolicited events that were assessed as related to the vaccine or where the relationship to vaccination was unknown. Five of these eight events were injection site reactions and all were mild, systemic reactions included mild rash (1 case) and fever (2 cases). There was a single serious adverse event that was not related to the study medication (subject was a passenger in a motor vehicle accident). A second dose of Varicela Biken was well tolerated and showed no significant safety issues in this population of previously vaccinated children.

Herpes zoster and meningitis due to reactivation of varicella vaccine virus in an immunocompetent child

Herpes zoster and meningitis due to reactivation of varicella vaccine virus in an immunocompetent child

Transmission of varicella vaccine virus to a non-family member in China

A 23-year-old teacher presented to hospital with a mild case of varicella. VZV vaccine strain vOka that resembles Varilrix but not Varivax or Biken strains was isolated from the skin lesion of the patient and was identified by single nucleotide polymorphism (SNP) analysis. The teacher denied having varicella vaccine before. Retrospective analysis suggests the transmission came from a pupil who developed zoster 13 months after varicella vaccine Varilrix. This is the first report in China in which an adult with varicella was attributable to vaccine virus and the 6th report of transmission of vaccine virus to a susceptible adult around the world.

Safety profile of live varicella virus vaccine (Oka/Merck): Five-year results of the European Varicella Zoster Virus Identification Program (EU VZVIP)

Background VARIVAX ® (Oka/Merck) is a live varicella vaccine, licensed in Europe since 2003. In addition to routine safety surveillance, the Varicella Zoster Virus Identification Program (VZVIP) analyzes clinical samples to establish whether adverse events (AEs) are associated with wild-type (wt) or vaccine varicella zoster virus (vVZV) strain. The European VZVIP provides data on VZV clade distribution. Methods Samples were collected from patients with selected AEs; the VZV strain was determined using polymerase chain reaction. Results From October 2003 to September 2008, 1006 spontaneous AE reports were analyzed (88% non-serious). Samples from 76/585 cases with selected AEs were collected. Of 55 VZV-positive/typable samples, wtVZV was detected in 40 and vVZV in 15 samples. Most rashes (32/44) ≤42 days postvaccination were associated with wtVZV. For breakthrough varicella, 6/9 cases were wtVZV-positive; none were vVZV-positive. For herpes zoster 9/17 cases were VZV-positive: eight vVZV, one wtVZV. One case of mild encephalitis was associated with vVZV. One of three cases of suspected secondary vVZV transmission was confirmed. Most wtVZV was clade 3 and clade 1. Conclusions European experience confirms that Oka/Merck vaccine is generally well tolerated. wtVZV genotypes were consistent with the molecular epidemiology of VZV in Europe.

Long Term Persistence of IgE Anti-Varicella Zoster Virus in Pediatric and Adult Serum Post Chicken Pox Infection and after Vaccination with Varicella Virus Vaccine

The production of IgE specific to different viruses (HIV-1, Parvovirus B19, RSV), and the ability for IgE anti-HIV-1 to suppress HIV-1 production in vitro, strongly suggest an important role for IgE and/or anti viral specific IgE in viral pathogenesis. Previous studies in our laboratory were the first to report the presence of IgE anti-varicella zoster virus (VZV) in an adolescent patient with shingles. However, the presence and long term persistence of IgE anti VZV antibodies has not been studied in adults. The presence of serum IgE in addition to IgE and IgG anti-VZV antibody in sera were studied in children (N=12) (0-16 y/o) and adults (N=9) (32-76 y/o) with either a past history of (wild type) chicken pox (N=7 children, 9 adults) or 5 years after vaccination with varicella zoster (N=2 children) (Varicella virus vaccine live, Oka/Merck), as well as in non-infected subjects (N=3 children). Of the patients who had a positive history of chicken pox 13 of 16 (81%) contained IgE anti–VZV antibodies; they were both serum IgEHi (&gt;100 IU/ml) and IgELo (&lt;100 IU/ml). Of the patients who were vaccinated, IgE anti-VZV antibodies were undetected. In contrast, serum from the patients without a history of chicken pox or vaccination did not make either IgE or IgG anti-VZV antibodies. This is the first demonstration of the existence of IgE anti-VZV antibodies, and its long-term persistence in serum of previously infected subjects. Future studies regarding the functional role of anti-viral IgE and its relationship to VZV are warranted.

The Incidence and Clinical Characteristics of Herpes Zoster Among Children and Adolescents After Implementation of Varicella Vaccination

The varicella-zoster virus (VZV) vaccine strain may reactivate to cause herpes zoster. Limited data suggest that the risk of herpes zoster in vaccinated children could be lower than in children with naturally acquired varicella. We examine incidence trends, risk and epidemiologic and clinical features of herpes zoster disease among children and adolescents by vaccination status. Population-based active surveillance was conducted among <20 years old residents in Antelope Valley, California, from 2000 through 2006. Structured telephone interviews collected demographic, varicella vaccination and disease histories, and clinical information. From 2000 to 2006, the incidence of herpes zoster among children<10 years of age declined by 55%, from 42 cases reported in 2000 (74.8/100,000 persons; 95% confidence interval [95% CI]: 55.3-101.2) to 18 reported in 2006 (33.3/100,000; 95% CI: 20.9-52.8; P<0.001). During the same period, the incidence of herpes zoster among 10- to 19-year-olds increased by 63%, from 35 cases reported in 2000 (59.5/100,000 persons; 95% CI: 42.7-82.9) to 64 reported in 2006 (96.7/100,000; 95% CI: 75.7-123.6; P<0.02). Among children aged<10 years, those with a history of varicella vaccination had a 4 to 12 times lower risk for developing herpes zoster compared with children with history of varicella disease. Varicella vaccine substantially decreases the risk of herpes zoster among vaccinated children and its widespread use will likely reduce overall herpes zoster burden in the United States. The increase in herpes zoster incidence among 10- to 19-year-olds could not be confidently explained and needs to be confirmed from other data sources.

Vaccination after stem cell transplant: a review of recent developments and implications for current practice

We have seen significant advances in the fields of stem cell transplantation and vaccinology. However, vaccination practices after transplantation remain varied and data sparse. We review recent changes in adult stem cell transplantation that pertain to vaccination practice, and discuss the evidence guiding the use of established and newly approved vaccines. Infection remains an important cause of morbidity and mortality in the stem cell transplant population. To extend stem cell transplantation to an increased number of patients and to widen the sources of donor cells, nonmyeloablative stem cell transplantation and cord blood transplantation have been used with increased frequency. These newer modalities differ in their immunological deficits, risk of infection and response to vaccination. Alternate vaccination regimens such as vaccination of either donors or recipients or both prior to stem cell harvest and early repeated vaccination after transplantation have been investigated. The full utility of these methods has yet to be delineated. The safety and benefit of new vaccines such as the acellular pertussis, human papilloma virus or varicella virus vaccine have yet to be formally investigated. We would argue that their use may be appropriate in the right setting. The complexity of stem cell transplantation continues to evolve and so must vaccine practices in this population. New vaccines that have the potential to improve long-term outcome should be investigated.

Varicella Vaccine Exposure During Pregnancy: Data From 10 Years of the Pregnancy Registry

Varivax (Merck), or varicella virus vaccine, is a live, attenuated viral vaccine intended to prevent varicella disease. Its use is contraindicated in pregnant women, and current recommendations are that pregnancy be avoided for 1 to 3 months after vaccination. Nevertheless, some women have inadvertently been vaccinated while pregnant. The investigators reviewed information in the Pregnancy Registry for Varivax, which was established to monitor the offspring of pregnant women exposed to varicella vaccine. The registry receives voluntary reports from health care providers or consumers about women given the vaccine 3 months before or during pregnancy. A total of 981 women were enrolled in the Registry in the years 1995–2005. Pregnancy outcomes were available for 629 prospectively enrolled women. No evidence of congenital varicella syndrome was obtained in 131 live births to varicella-zoster virus (VZV)-seronegative women. Three infants (3.7%) had major birth defects (95% confidence interval, 0.8%–10.7%). Approximately two-thirds of VZV-seronegative women in this study were vaccinated during the first or second trimester—thought to be a high-risk period. All 18 live-born infants whose mothers inadvertently received varicella vaccine rather than VZV immunoglobulin were reportedly healthy and without birth defects. Eight of these infants were born to VZV-seronegative mothers. The number of exposures analyzed is not great enough to rule out a very low risk, but they fail to support a relationship between exposure to varicella vaccine during pregnancy and either congenital varicella syndrome or other birth defects. Even so, women of reproductive age who are vaccinated should be advised to avoid becoming pregnant for 1–3 months afterward.

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 3.4 reports/10,000 doses of vaccine distributed. PCR analysis of vesicular rashes that occurred within the first 2 weeks after vaccination was more likely to identify wild-type varicella-zoster virus (VZV), whereas the presence of Oka VZV was generally associated with vesicular rashes that occurred 15-42 days after vaccination. Reports of breakthrough varicella that occurred >42 days after vaccination were associated with wild-type VZV. Among 697 herpes zoster reports, PCR analysis identified Oka VZV in 57 reports and wild-type VZV in 38 reports. There were no primary neurologic adverse events associated with Oka VZV. Secondary transmission of Oka VZV from vaccine recipients with postvaccination vesicular rashes was identified in 3 susceptible household contacts. Disseminated Oka VZV was identified in 6 immunocompromised patients and 1 patient with Down syndrome. This review has shown that the vaccine is generally safe and well tolerated.