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Background Varicella is a highly infectious disease, particularly affecting children, that can lead to complications requiring antibiotics or hospitalization. Antibiotic use for varicella management is poorly documented. This study assessed antibiotic use for varicella and its complications in a pediatric population in England. Methods Data were drawn from medical records in the Clinical Practice Research Datalink and Hospital Episode Statistics data sets. The study included patients <18 years old with varicella diagnosed during 2014–2018 and 3-month follow-up available. We determined varicella-related complications, medication use, healthcare resource utilization, and costs from diagnosis until 3 months after diagnosis. Results We identified 114 578 children with a primary varicella diagnosis. Of these, 7.7% (n = 8814) had a varicella-related complication, the most common being ear, nose, and throat related (37.1% [n = 3271]). In all, 25.9% (n = 29 706 of 114 578) were prescribed antibiotics. A higher proportion of patients with complications than without complications were prescribed antibiotics (64.3% [n = 5668 of 8814] vs 22.7% [n = 24 038 of 105 764]). Mean annualized varicella-related costs were £2 231 481 for the study cohort. Overall, antibiotic prescriptions cost approximately £262 007. Conclusions This study highlights high antibiotic use and healthcare resource utilization associated with varicella management, particularly in patients with complications. A national varicella vaccination program in England may reduce varicella burden and related complications, medication use, and costs. [ABSTRACT FROM AUTHOR]

Background We describe clinicoepidemiologic characteristics of mpox-chickenpox coinfection in Nigeria. Methods A retrospective cohort analysis was performed of confirmed mpox cases in Nigeria from January 2022 to March 2023. Mpox and chickenpox were confirmed by real-time polymerase chain reaction (RT-PCR). Results Of 94 (60.0%) suspected cases, 56 had confirmed mpox, of whom 16 (28.6%) had chickenpox coinfection. The median age of confirmed mpox cases was 29 years (interquartile range, 20–37 years), 24 were men (60.7%), 6 (10.7%) were bisexual, and 5 (8.9%) died. Mpox-chickenpox–coinfected patients had more complications than mpox-monoinfected cases (56.3% vs 22.5%, P =.015). Conclusions The high frequency of mpox-chickenpox coinfection argues for accelerated access to mpox and chickenpox vaccines in Africa. [ABSTRACT FROM AUTHOR]

Background Varicella causes a major health burden in many low- to middle-income countries located in tropical regions. Because of the lack of surveillance data, however, the epidemiology of varicella in these regions remains uncharacterized. In this study, based on an extensive dataset of weekly varicella incidence in children ≤10 during 2011–2014 in 25 municipalities, we aimed to delineate the seasonality of varicella across the diverse tropical climates of Colombia. Methods We used generalized additive models to estimate varicella seasonality, and we used clustering and matrix correlation methods to assess its correlation with climate. Furthermore, we developed a mathematical model to examine whether including the effect of climate on varicella transmission could reproduce the observed spatiotemporal patterns. Results Varicella seasonality was markedly bimodal, with latitudinal changes in the peaks' timing and amplitude. This spatial gradient strongly correlated with specific humidity (Mantel statistic = 0.412, P =.001) but not temperature (Mantel statistic = 0.077, P =.225). The mathematical model reproduced the observed patterns not only in Colombia but also México, and it predicted a latitudinal gradient in Central America. Conclusions These results demonstrate large variability in varicella seasonality across Colombia and suggest that spatiotemporal humidity fluctuations can explain the calendar of varicella epidemics in Colombia, México, and potentially in Central America. [ABSTRACT FROM AUTHOR]

Keywords: chickenpox; varicella; vaccine; VZV; program EN chickenpox varicella vaccine VZV program S375 S379 5 10/26/22 20221102 NES 221102 Varicella is an illness with a characteristic maculopapular, vesicular rash that, during the prevaccine era, infected almost everyone in the population during childhood. There were concerns raised before vaccine implementation that a universal childhood varicella vaccination program could shift the varicella burden to older ages and result in more severe disease and infections during pregnancy [[28]]. Monitoring varicella vaccine impact on varicella incidence in the United States: surveillance challenges and changing epidemiology, 1995-2019. Based on a documented continuing disease and societal burden, the United States was the first country to implement a routine varicella vaccination program following licensure of the live, attenuated varicella vaccine (VARIVAX, Merck & Co, Inc) in 1995. [Extracted from the article]

Tracking vaccination coverage is a critical component of monitoring a vaccine program. Three different surveillance systems were used to examine trends in varicella vaccination coverage during the United States vaccination program: National Immunization Survey-Child, National Immunization Survey-Teen, and immunization information systems (IISs). The relationship of these trends to school requirements and disease decline was also examined. Among children aged 19-35 months, ≥1 dose of varicella vaccine increased from 16.0% in 1996 to 89.2% by the end of the 1-dose program in 2006, stabilizing around at least 90.0% thereafter. The uptake of the second dose was rapid after the 2007 recommendation. Two-dose coverage among children aged 7 years at 6 high-performing IIS sites increased from 2.6%-5.5% in 2006 to 86.0%-100.0% in 2020. Among adolescents aged 13-17 years, ≥2-dose coverage increased from 4.1% in 2006 to 91.9% in 2020. The proportion of adolescents with history of varicella disease declined from 69.9% in 2006 to 8.4% in 2020. In 2006, 92% of states and the District of Columbia (DC) had 1-dose daycare or school entry requirements; 88% of states and DC had 2-dose school entry requirements in the 2020-2021 school year. The successes in attaining and maintaining high vaccine coverage were paramount in the dramatic reduction of the varicella burden in the United States over the 25 years of the vaccination program, but opportunities remain to further increase coverage and decrease varicella morbidity and mortality. [ABSTRACT FROM AUTHOR]

After 25 years of varicella vaccination in the United States, classic varicella and its complications have become an uncommon occurrence. The clinical manifestation of varicella among vaccinated persons is usually modified, with fewer skin lesions, mostly maculopapular, and milder presentation. However, the potential for severe manifestations from varicella still exists among both vaccinated and unvaccinated persons, and thus healthcare providers should keep varicella in the differential diagnosis of a maculopapular or vesicular rash. The prompt recognition and diagnosis of varicella is important because when confirmed, clinical and public health measures need to be taken swiftly. [ABSTRACT FROM AUTHOR]

We summarize studies of varicella vaccine's effectiveness for prevention of varicella and lessons learned during the first 25 years of the varicella vaccination program in the United States. One dose of varicella vaccine provided moderate protection (82%-85%) against varicella of any severity and high protection (100%) against severe varicella, with some waning of protection over time. The 1-dose program (1995-2006) had a substantial impact on the incidence both of varicella and of severe outcomes (71%-90% decrease) although it did not prevent low-level community transmission and some outbreaks continued to occur in highly vaccinated populations. Two doses of varicella vaccine improved the vaccine's effectiveness by at least 10% against varicella of any severity, with further declines in the incidence both of varicella and of severe outcomes as well as in both number and size of outbreaks. There is no evidence for waning of the effectiveness of 2 doses of the vaccine. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the health and economic impact of the varicella vaccination program on varicella disease in the United States (US), 1996-2020.Methods: Analysis was conducted using the Centers for Disease Control and Prevention or published annual population-based varicella incidence, and varicella-associated hospitalization, outpatient visit, and mortality rates in the US population aged 0-49 years during 1996-2020 (range, 199.5-214.2 million persons) compared to before vaccination (1990-1994). Disease costs were estimated using the societal perspective. Vaccination program costs included costs of vaccine, administration, postvaccination adverse events, and travel and work time lost to obtain vaccination. All costs were adjusted to 2020 US dollars using a 3% annual discount rate. The main outcome measures were the number of varicella-associated cases, hospitalizations, hospitalization days, and premature deaths prevented; life-years saved; and net societal savings from the US varicella vaccination program.Results: Among US persons aged 0-49 years, during 1996-2020, it is estimated that more than 91 million varicella cases, 238 000 hospitalizations, 1.1 million hospitalization days, and almost 2000 deaths were prevented and 118 000 life-years were saved by the varicella vaccination program, at net societal savings of $23.4 billion.Conclusions: Varicella vaccination has resulted in substantial disease prevention and societal savings for the US over 25 years of program implementation. [ABSTRACT FROM AUTHOR]

We describe the changing epidemiology of varicella outbreaks informed by past and current active and passive surveillance in the United States by reviewing data published during 1995-2015 and analyzing new data from 2016 to 2019. Varicella outbreaks were defined as ≥5 varicella cases within 1 setting and ≥1 incubation period. During the 1-dose varicella vaccination program (1995‒2006), the number of varicella outbreaks declined by 80% (2003-2006 vs 1995-1998) in 1 active surveillance area where vaccination coverage reached 90.5% in 2006. During the 2-dose program, in 7 states with consistent reporting to the Centers for Disease Control and Prevention, the number of outbreaks declined by 82% (2016-2019 vs 2005-2006). Over the entire program (1995-2019), outbreak size and duration declined from a median of 15 cases/outbreak and 45 days duration to 7 cases and 30 days duration. The proportion of outbreaks with <10 cases increased from 28% to 73%. During 2016‒2019, most (79%) outbreak cases occurred among unvaccinated or partially vaccinated persons eligible for second-dose vaccination, highlighting the potential for further varicella control. [ABSTRACT FROM AUTHOR]

Background: Universal varicella vaccination might reduce opportunities for varicella-zoster virus (VZV) exposure and protective immunological boosting, thus increasing herpes zoster incidence in latently infected adults. We assessed humoral and cell-mediated immunity (CMI), as markers of VZV exposure, in adults aged ≥50 years.Methods: We repurposed data from placebo recipients in a large multinational clinical trial (ZOE-50). Countries were clustered based on their varicella vaccination program characteristics, as having high, moderate, or low VZV circulation. Anti-VZV antibody geometric mean concentrations, median frequencies of VZV-specific CD4 T cells, and percentages of individuals with increases in VZV-specific CD4 T-cell frequencies were compared across countries and clusters. Sensitivity analyses using a variable number of time points and different thresholds were performed for CMI data.Results: VZV-specific humoral immunity from 17 countries (12 high, 2 moderate, 3 low circulation) varied significantly between countries (P < .0001) but not by VZV circulation. No significant differences were identified in VZV-specific CMI between participants from 2 high versus 1 low circulation country. In 3/5 sensitivity analyses, increases in CMI were more frequent in high VZV circulation countries (.03 ≤ P < .05).Conclusions: We found no consistent evidence of reduced VZV exposure among older adults in countries with universal varicella vaccination.Clinical Trials Registration: NCT01165177. [ABSTRACT FROM AUTHOR]

Michiaki Takahashi developed the live attenuated varicella vaccine in 1974 . This was the first, and is still the only, herpesvirus vaccine. Early studies showed promise, but the vaccine was rigorously tested on immunosuppressed patients because of their high risk of fatal varicella; vaccination proved to be lifesaving. Subsequently, the vaccine was found to be safe and effective in healthy children. Eventually, varicella vaccine became a component of measles mumps rubella vaccine, 2 doses of which are administered in the USA to ~90% of children. The incidence of varicella has dropped dramatically in the USA since vaccine-licensure in 1995. Varicella vaccine is also associated with a decreased incidence of zoster and is protective for susceptible adults. Today, immunocompromised individuals are protected against varicella due to vaccine-induced herd immunity. Latent infection with varicella zoster virus occurs after vaccination; however, the vaccine strain is impaired for its ability to reactivate. [ABSTRACT FROM AUTHOR]

Background: Risk factors for, and long-term outcomes following, detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown.Methods: We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemptiom of prescriptions for nervous system medicine prescribed for the nervous system, and social outcomes.Results: Prior hospital admission, redemption of immunosuppressive medicine, comorbidity, and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort.Conclusions: Immunosuppression and comorbidity are associated with increased risk of detection of VZV DNA in the CSF and the condition is associated with increased mortality and neurological morbidity. [ABSTRACT FROM AUTHOR]

Ileocolic intussusception is the invagination of ileum into the colon. In a subset of patients, the disease is caused by mesenteric lymphadenopathy in response to (viral) infection. We present a case of an ileocolic intussusception necessitating surgery in a 7-month-old immunocompetent infant with concurrent primary wild-type varicella-zoster virus (VZV) infection, in whom chickenpox rash developed 2 days after surgery. Detailed in situ analyses of resected intestine for specific cell type markers and VZV RNA demonstrated VZV-infected lymphocytes and neurons in the gut wall and in ganglion cells of the myenteric plexus. [ABSTRACT FROM AUTHOR]

Keywords: Varicella zoster virus (VZV); latency; VZV reactivation EN Varicella zoster virus (VZV) latency VZV reactivation 361 363 3 02/04/22 20220201 NES 220201 B (See the Major Article by Carryn et al, on pages 413-21.) Alternatively, vaccination might protect an individual exposed to wild-type VZV against clinical disease, but not against infection; therefore, wild-type VZV might be able to replace latent vaccine virus and later reactivate to cause zoster. This model does not take the phenomenon of "endogenous boosting" into account, and assumes that exogenous exposure to VZV shed by children with varicella is essential to maintain anti-VZV immunity and suppression of VZV reactivation and zoster. [Extracted from the article]

Background: This national, sentinel prospective study aimed to identify children with severe hospitalized varicella, despite availability of universal 1-dose vaccination since 2005, and determine associations between virus genotypes and disease severity.Methods: Children with varicella or zoster from 5 Paediatric Active Enhanced Disease Surveillance hospitals were enrolled. Lesions were swabbed for genotyping. Associations with disease severity were analyzed using multiple regression.Results: From 2007 to 2015, 327 children with confirmed varicella (n = 238) or zoster (n = 89) were enrolled. Two hundred three (62%) were immunocompetent children; including 5 of 8 children who required intensive care unit management. Eighteen percent (36 of 203) of immunocompetent children had been previously vaccinated. Vaccinated children aged >18 months were less likely to have severe disease (9%; 5 of 56) than unvaccinated children (21%; 21 of 100; P = .05). Three of 126 children who had virus genotyping (2 immunocompromised) had varicella (n = 2) or zoster (n = 2) due to the Oka/vaccine strain. European origin clades predominated and were independently associated with more severe disease (odds ratio = 3.2; 95% confidence interval, 1.1- 9.5; P = .04).Conclusions: Severe hospitalized varicella still occurs with a 1-dose varicella program, although predominantly in unvaccinated children. Most 1-dose vaccine recipients were protected against severe disease. Viral genotyping in complex hospitalized cases is important to assist in monitoring disease due to Oka-vaccine strain. [ABSTRACT FROM AUTHOR]

We report the first use of whole viral genome sequencing to identify nosocomial transmission of varicella-zoster virus with fatal outcome. The index case patient, nursed in source isolation, developed disseminated zoster with rash present for 1 day before being transferred to the intensive care unit (ICU). Two patients who had received renal transplants while inpatients in an adjacent ward developed chickenpox and 1 died; neither patient had direct contact with the index patient. [ABSTRACT FROM AUTHOR]

Background: Although it is evident that zoster vaccination reduces postherpetic neuralgia (PHN) risk by reducing herpes zoster (HZ) occurrence, it is less clear whether the vaccine protects against PHN among patients who develop HZ despite previous vaccination.Methods: This cohort study included immunocompetent patients with HZ. The vaccinated cohort included 1155 individuals who were vaccinated against HZ at age ≥60 years and had an HZ episode after vaccination. Vaccinated patients were matched 1:1 by sex and age with unvaccinated patients. Trained medical residents reviewed the full medical record to determine the presence of HZ-related pain at 1, 2, 3, and 6 months after HZ diagnosis. The incidence of PHN was compared between vaccinated and unvaccinated -patients.Results: Thirty vaccinated women (4.2%) experienced PHN, compared with 75 unvaccinated women (10.4%), with an adjusted relative risk of 0.41 (95% confidence interval, .26-.64). PHN occurred in 26 vaccinated men (6.0%) versus 25 unvaccinated men (5.8%), with an adjusted relative risk of 1.06 (.58-1.94). These associations did not differ significantly by age.Conclusions: Among persons experiencing HZ, prior HZ vaccination is associated with a lower risk of PHN in women but not in men. This sex-related difference may reflect differences in healthcare-seeking patterns and deserve further investigation. [ABSTRACT FROM AUTHOR]

Background. The combined measles, mumps, and rubella (MMR) vaccine has been successfully administered for >20 years. Because of this, protection by maternal antibodies in infants born to vaccinated mothers might be negatively affected.Methods. A large cross-sectional serologic survey was conducted in the Netherlands during 2006–2007. We compared the kinetics of antibody concentrations in children and women of childbearing age in the highly vaccinated general population with those in orthodox Protestant communities that were exposed to outbreaks.Results. The estimated duration of protection by maternal antibodies among infants in the general population, most of whom were born to vaccinated mothers, was short: 3.3 months for measles, 2.7 months for mumps, 3.9 months for rubella, and 3.4 months for varicella. The duration of protection against measles was 2 months longer for infants born in the orthodox communities, most of whom had unvaccinated mothers. For rubella, mothers in the orthodox communities had higher concentrations of antibodies as compared to the general population.Conclusion. Children of mothers vaccinated against measles and, possibly, rubella have lower concentrations of maternal antibodies and lose protection by maternal antibodies at an earlier age than children of mothers in communities that oppose vaccination. This increases the risk of disease transmission in highly vaccinated populations. [ABSTRACT FROM AUTHOR]

Background. Because the varicella incidence has declined following varicella vaccine licensure, herpes zoster (HZ) cases may play a larger role in varicella zoster virus (VZV) transmission. We investigated how HZ and varicella cases contribute to the varicella incidence in schools and day care centers. Methods. Surveillance data collected in Philadelphia during September 2003-June 2010 were analyzed. A varicella case was considered to be sporadic if it was reported from a school or day care facility .6 weeks after or $10 days before other reports of VZV transmission. A varicella case was considered to be secondary if it occurred 10-21 days after report of a case of HZ or sporadic varicella. Analysis compared VZV transmission from individuals with HZ or sporadic varicella, stratified by varicella vaccination status and disease severity. Results. Of 290 HZ cases reported, 27 (9%) resulted in 84 secondary varicella cases. Of 1358 sporadic varicella cases reported, 205 (15%) resulted in 564 secondary varicella cases. Approximately half of the HZ and sporadic varicella cases resulted in single secondary cases. The proportion of individuals who had secondary cases with mild disease was similar for those exposed to HZ and those exposed to varicella (70% and 72%, respectively). VZV transmission was highest from unvaccinated individuals with sporadic varicella (P < .01). Conclusions. VZV transmission from individuals with HZ contributes to varicella morbidity. More research is needed to understand risk factors and guide recommendations for preventing VZV transmission from individuals with HZ. [ABSTRACT FROM AUTHOR]

In 2006, the Advisory Committee on Immunization Practices recommended that children routinely receive 2 varicella vaccine doses in place of the 1 dose previously recommended. This recommendation's initial impact on varicella epidemiology in Connecticut was assessed. Reported incidence and case-specific data were compared for 2005 and 2008. Varicella incidence decreased from 48.7 cases/100,000 persons in 2005 to 24.5 in 2008. Age-specific incidence decreased significantly (P < .05) among children aged 1-14 years. Reported varicella incidence has declined in Connecticut after implementation of routine 2-dose varicella vaccination for children. Continued surveillance is needed to determine the recommendation's full impact. [ABSTRACT FROM AUTHOR]

We investigated a varicella outbreak in a residential facility for adults with intellectual disabilities. A case of varicella was defined as a generalized maculopapular rash that developed in a facility resident or employee. Immunoglobulin M testing was conducted on serologic samples, and polymerase chain reaction testing was performed on environmental and skin lesion samples. Eleven cases were identified among 70 residents and 2 among ~145 staff. An unrecognized case of herpes zoster was the likely source. Case patients first entered any residential facility at a younger age than non-case residents (9.5 vs 15.0 years; P < .01). Varicella zoster virus DNA was detected 2 months after the outbreak in environmental samples obtained from case patients' residences. This outbreak exemplifies the potential for at-risk pockets of varicella-susceptible adults, especially among those who have lived in residential facilities from a young age. Evidence of immunity should be verified for all adults and healthcare staff in similar residential settings. [ABSTRACT FROM AUTHOR]

The authors reflect on the study conducted by Don Gilden and colleagues concerning the correlation between the presence of varicella zoster virus (VZV) DNA and VZV antigens in aortas with giant cell arteritis. They stated that when an effective vaccine is deployed in population, the infectious agent ought to disappear unless the vaccine is a live agent, which can become latent and reactive.

A previously healthy boy who had received varicella vaccine developed herpes zoster with meningitis. The vaccine strain recovered from scabs of 3 skin lesions had the wild-type allele at position 108111, a vaccine marker never previously associated with vaccine-associated adverse events. The vaccine strain from cerebrospinal fluid also contained mutations never previously observed at vaccine-associated single nucleotide polymorphisms that would alter amino acid sequences in ORF54 and ORF59. The presence of distinct strains in skin lesions and cerebrospinal fluid indicate that >1 variant strain may reactivate to cause herpes zoster. [ABSTRACT FROM AUTHOR]

Cell-mediated immunity (CMI) is critical for the prevention and control of varicella-zoster virus (VZV)-related disease.To assess CMI to VZV, a varicella skin test and interferon-γ enzyme-linked immunospot (ELISPOT) assay were both performed in healthy volunteers, and the results were compared. A total of 151 subjects were examined: 16 aged 20-29 years, 26 aged 30-39 years, 18 aged 40-49 years, 73 aged 50-59 years, and 18 aged 60-69 years. All were seropositive by a glycoprotein antigen- based enzyme-linked immunosorbent assay (gpELISA). Skin test reactivity was significantly correlated with the ELISPOT count, and both decreased with increasing age, indicating an age-dependent decline in CMI to VZV. In contrast, the antibody titer obtained by the gpELISA did not correlate with skin test reactivity. The results suggest that the skin test and ELISPOT assay are both reliable for assessing CMI to VZV and can easily be applied to screen individuals susceptible to the development of herpes zoster. [ABSTRACT FROM AUTHOR]

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. Whether this is from primary or secondary vaccine failure— or both—is unclear. We tested serum samples from 148 healthy children immunized against varicella in New York, Tennessee, and California to determine their seroconversion rates, before and after 1 dose of Merck/Oka varicella vaccine. The median age at vaccination was 12.5 months; postvaccination serum samples were obtained on average 4 months later. Serum was tested for antibodies against varicella-zoster virus (VZV) by use of the previously validated sensitive and specific fluorescent antibody to membrane antigen (FAMA) assay. Of 148 healthy child vaccinees, 113 (76%) seroconverted, and 24% had no detectable VZV FAMA antibodies. Our data contrast with reported seroconversion rates of 86%-96% by other VZV antibody tests and suggest that many cases of varicella in immunized children are due to primary vaccine failure. A second dose of varicella vaccine is expected to increase seroconversion rates and vaccine effectiveness. [ABSTRACT FROM AUTHOR]

The attenuation of varicella-zoster virus (VZV) by Takahashi in 1974 was a remarkable achievement. It swiftly led to development of a live vaccine against chickenpox, which was initially tested in Japan. With its successful employment in immunocompromised children to prevent morbidity and mortality due to varicella, the vaccine began to be tested in healthy children in Japan and elsewhere. In the United States, vaccine use progressed from extensive clinical trials that demonstrated safety and efficacy to universal immunization of healthy infants and children. In the past 10 years, >30 million healthy American individuals, mostly children, have been vaccinated. With increasing use of vaccine, there has been a concomitant decrease in the incidence of disease, along with decreases in hospitalizations and deaths due to VZV. To improve protection, however, a 2-dose schedule of immunization was recommended for routine use in all children by the Centers for Disease Control and Prevention in June 2006. At roughly the same time, licensure of the combined measles-mumps-rubella- varicella vaccine was completed, which allowed harmonization of immunization against these 4 viruses with 1 injection given twice in childhood. Concomitantly, a version of the varicella vaccine with 10 times the titer was developed for immunization of healthy individuals >60 years of age against herpes zoster (HZ). Although elimination of VZV from human populations may not yet be possible, the combined approach of immunization against both varicella in childhood and HZ in adulthood in the developed world are predicted to dramatically increase our control of this troublesome virus. [ABSTRACT FROM AUTHOR]

Background. Varicella vaccine currently is recommended for children between 12 and 18 months of age. However, rates of breakthrough varicella have been reported to be higher among children vaccinated before 14 or 15 months of age and to increase with time since vaccination. Methods. An ongoing study at the Northern California Kaiser Permanente Medical Care Program is evaluating vaccine efficacy in 7585 children vaccinated with Varivax in 1995, when they were between 12 and 23 months of age. Cases of chickenpox are identified by telephone interviews with each child's parent(s) every 6 months. Mean age at varicella onset and mean time from vaccination to onset were calculated on the basis of age, in months, at vaccination. Logistic regression was used to test for trend, and the χ² test was used to test for differences in rates of breakthrough varicella by age. Results. Over the first 8 years of the study, a total of 1161 cases of breakthrough varicella were reported, for an average rate of 21.7 cases/1000 person-years. Vaccine effectiveness was 83.6% at year 8. The rate of breakthrough varicella did not change for each additional month of age at vaccination (P = .864), and no difference in the rate of breakthrough varicella was found between children vaccinated at <15 months of age and those vaccinated at ⩾15 months of age. Conclusions. Our data do not show a difference in vaccine effectiveness with age at vaccination and thus support the current recommendations for initial vaccination between 12 and 18 months of age. [ABSTRACT FROM AUTHOR]

A plethora of tests for determining the presence of antibodies to varicella-zoster virus (VZV) have been developed over the years, with a wide range of performance standards. There is general agreement that the presence of VZV antibodies in serum indicates immunity to varicella and protection from chickenpox, although the role of specific antibody in mediating protection remains unclear. Both antibodies and cellular immunity probably interact to mediate immunity to the virus. In any case, VZV-specific serum antibody is a useful indicator of protection against chickenpox in patients and persons at high risk of exposure, whether they have been immunized or naturally infected. Serological tests are also a useful implement for evaluating the length of time that immunity to varicella persists after vaccination and whether waning of vaccine-induced immunity occurs. The purpose of this review is to contrast the strengths and weaknesses of currently available VZV antibody assays. Although several of these methods are useful for various specific applications, simpler and more accurate tests to measure antibodies to VZV are a high priority for future research and development. [ABSTRACT FROM AUTHOR]

As with most live attenuated viral vaccines, varicella vaccine comprises a mixture of variant strains. Knowledge about the pathogenic potential of individual strains in the varicella vaccine is limited. Vaccination against chickenpox causes a usually modified varicella-like rash in a small percentage of healthy children, and vaccine virus reactivates on rare occasions to cause herpes zoster (HZ). In several published studies, our respective laboratories have analyzed genomic variation among specimens from cases of postvaccination rash and HZ in vaccine recipients, focusing on polymorphisms between vaccine Oka strains and the parental Oka strain. In most respects, these studies were in close agreement, identifying the set of wild-type markers among vaccine adverse event isolates, each occurring at similar frequencies. The same 3 universally present vaccine markers, at positions 106262, 107252, and 108111, were also identified by both laboratories. One notable difference has been the observation of mostly clonal vaccine virus among isolates examined by one laboratory and mostly mixed viruses in isolates examined by the other. In addition to reviewing and comparing our combined observations, we propose possible explanations for our contrasting findings and propose future studies to reconcile them. [ABSTRACT FROM AUTHOR]

We investigated a small outbreak of varicella in a long-term-care facility after a case of herpes zoster. Clinical specimens and environmental samples were collected from all case patients and from surfaces in the case patients' rooms and other common-use areas. Wild-type varicella-zoster virus (VZV) DNA was identified in all 3 varicella case patients, and high concentrations of VZV DNA were detected in environmental samples from the room of the herpes zoster case patient. Genotypic analysis showed that the identical VZV strain was present in all samples; moreover, the strain was a unique Mosaic genotype isolate that included a stable Oka vaccine marker that had hitherto never been observed in a wild-type strain of VZV. This study provides evidence for the value of including environmental sampling during the investigation of varicella outbreaks and illustrates the importance of evaluating multiple vaccine-associated markers for the discrimination of vaccine virus from wild-type VZV. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. We have shown, by DNA sequencing of 40 polymorphic loci, that viruses sampled from vesicles in varicella-like and herpes zoster rashes are single clones. This finding suggests that, between the time of inoculation of the vaccine and development of rash, selection of single strains occurs. The results have general implications for the pathogenesis of varicella-zoster virus. [ABSTRACT FROM AUTHOR]

Background. Since licensure in the United States, studies have shown that varicella vaccine's overall effectiveness ranges from 44% to 100%, with substantial protection against moderate and severe varicella; however, breakthrough illness has been documented in up to 56% of vaccinated individuals. Methods. A varicella outbreak occurred in a Minnesota school with 319 students. Phone surveys were conducted with students' parents. Information was collected on students who had recent varicella infections, including onset date, rash characteristics, duration, and underlying medical conditions. Results. Fifty-four cases occurred after a primary breakthrough case. Twenty-nine (53%) students had been vaccinated. Unvaccinated students had an increased risk of moderate varicella, compared with vaccinated students (relative risk [RR], 4.4 [95% confidence interval {CI}, 2.2-9.1]; P<.001). The vaccine was 56% effective at preventing any varicella and 90% effective against moderate illness. Students vaccinated ≥5 years before the outbreak had a greater risk of breakthrough varicella than did those vaccinated within ≤4 years (RR, 2.6 [95% CI, 1.3-5.4]; P<.01). Conclusions. Vaccinated students presented with milder varicella symptoms than did unvaccinated students. Individuals with breakthrough illness can be highly infectious. Time since varicella vaccination was associated with illness. Despite 29 breakthrough cases, the varicella vaccine conferred a high degree of protection against moderate illness. [ABSTRACT FROM AUTHOR]

We examined the excretion of varicella zoster virus (VZV) in hospitalized patients with herpes zoster localized to the thoracic region whose skin lesions were covered with either hydrocolloid dressing agents (hydrocolloid group) or conventional gauze bandages (gauze group). The presence of VZV DNA in swab samples from lesion coverings, the throat, and filters of air purifiers was examined by use of a sensitive polymerase chain reaction assay. For the hydrocolloid group, VZV was detected in none of the samples from lesion coverings or air purifier filters; for the gauze group, VZV DNA was detected in samples from gauze coverings and air purifier filters for all 6 patients. VZV DNA was detected less frequently in throat samples from patients in the hydrocolloid group than in those from patients in the gauze group. The results of the present study suggest that hydrocolloid dressing agents prevent excretion of aerosolized VZV DNA from skin lesions of patients with localized herpes zoster. [ABSTRACT FROM AUTHOR]

Discusses a case of disseminated varicella infection due to the vaccine strain of varicella-zoster virus in a patient with a novel deficiency in natural killer T (NKT) cells. Oka vaccine strain of varicella; Suggestion that NKT cells contribute to host defense against varicella virus.

Varicella-zoster virus (VZV) is the etiologic agent of varicella (primary infection) and herpes zoster (reactivation of latent infection). Although varicella is most often a relatively benign and self-limited childhood illness, the disease can be associated with a variety of serious and potentially lethal complications in both immunocompetent and immunocompromised persons. One complication of varicella that appears to be increasing in frequency is serious bacterial soft tissue infections caused by group A streptococci. Issues related to management of varicella become especially complex when varicella involves pregnant women or susceptible neonates. Herpes zoster can be associated with a variety of neurologic complications, including a syndrome of delayed contralateral hemiparesis. Neurologic complications of herpes zoster, including chronic encephalitis, occur with increased frequency in AIDS patients. VZV retinitis is a potentially sight-threatening complication that occurs in both immunocompetent and immunocompromised persons. Current knowledge regarding pathogenesis and antiviral therapy is reviewed. [ABSTRACT FROM AUTHOR]

Evaluates the epidemiology and costs of hospitalization with primary varicella and herpes zoster in the prevaccine era and the usefulness of hospital discharge data to determine the population impact of vaccination on these conditions. Analysis of statewide hospital discharge data in Connecticut from 1986 to 1995; Patient and temporal characteristics; Underlying conditions and complications.

Examines the varicella-zoster virus-specific cellular immunity among persons who received acyclovir following exposure to household chickenpox. Factor that influenced the effectiveness of varicella vaccine in preventing the onset of varicella symptoms; Effect of acyclovir on the subjects.

Techniques for assay of in vitro lymphocyte transformation (LTF) were used with varicella-zoster virus (VZV) as the antigen to study the temporal characteristics of the VZV-specific cellular immune response in children with varicella and in normal subjects with a history of the illness. The LTF response in children with only vesicular eruptions was prompt, and individual peak activity was detected within one to two weeks after the onset of illness, followed by a gradual decrease of the activity to lower levels. Patients with a complication of meningoencephalitis showed a marked delay in the development of peak activity. No consistent difference in the development of complement-fixing antibody to VZV was observed in these patients with different clinical manifestations. The LTF response of normal subjects with remote clinical evidence of varicella was characterized by occasional high activity, a finding that suggests reinfection with VZV. These observations provide additional evidence that the specific cellular immune response is heavily involved in the pathogenesis of VZV infection. [ABSTRACT FROM PUBLISHER]

The author conveys his response to a feedback about his report on whether exogenous boosting can explain the increase in herpes zoster (HZ) incidence in the U.S. Topics discussed include the real-life increase of HZ incidence, whether the launch of a childhood varicella zoster vaccination (VZV) program in other countries is an appropriate idea, and the annual number of prevented VZV cases because of the vaccination program.

The author reflects on the epidemiology and transmissibility of disease varicella and herpes zoster (HZ) caused by the Varicella Zoster Virus (VZV), with reference to a study on pediatric population. According to him, varicella vaccine was tested on several school children during the study to determine its efficacy which leads to the reduction in the hospitalization and death of children due to varicella infection. He further talks about the HZ which perpetuates the VZV infections in children.

Discusses a study on the pathogenetic tropism of Varicella-Zoster Virus (VZV) to primary human hepatocytes and attenuating tropism of Oka Varicella vaccine strain to neonatal dermal fibroblasts. Pathogenesis of VZV characterized by the cell tropism of the original Oka and attenuated Oka varicella vaccine strains; Replication of VZV in hepatocytes and in lung fibroblasts.

Editorial. Focuses on the complications associated with varicella vaccines. Zoster infection after vaccinatino with the Oka strain of varicella-zoster virus; Diagnosis of the Oka-strain infection on the basis of polymerase chain reaction analysis.

The author discusses a study that proposes that exogenous boosting may help explain growth in zoster taking place in the absence of vaccination and following it, with topics mentioned such as varicella vaccination, Hope-Simpson's exogenous hypothesis, and live attenuated zoster vaccine.