Abstract: Aims: To estimate the annual incidence of hospitalisations due to severe complications of varicella, describe the complications and estimate annual mortality. Methods: Active surveillance throughout the UK and Ireland for 13 months by paediatricians notifying cases to the British Paediatric Surveillance Unit and completing a questionnaire. The case definition was any child aged Results: 188 cases were notified for the surveillance period, of which 112 (0.82/100 000 children/year) met the case definition and were not duplicates. Confirmed cases had a median age of 3 years (range 0–14). The complications were: bacteraemia/septic shock (n = 30), pneumonia (n = 30), encephalitis (n = 26), ataxia (n = 25), toxic shock syndrome/toxin-mediated disease (n = 14), necrotising fasciitis (n = 7), purpura fulminans/disseminated coagulopathy (n = 5), fulminant varicella (n = 5) and neonatal varicella (n = 3). 52 children (46%) had additional bacterial infections. Six deaths were due, or possibly due, to varicella, including one intrauterine death. Four of the other five children who died (ages 2–14 years) had a pre-existing medical condition. Sequelae on discharge were reported for 41 cases (40%), most frequently ataxia or skin scarring. The median length of hospital stay was 7 days (range 1–68). Conclusions: This study provides a minimum estimate of severe complications and death resulting from varicella in children in the UK and Ireland. Most complications, excluding deaths, occur in otherwise healthy children and thus would be preventable only through a universal childhood immunisation programme.

Abstract: Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5–10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasability of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible.

Abstract: 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. Indeed, most of the novel mutations distinguishing the Oka vaccine from the more virulent parental virus have not actually become fixed. Because the parental alleles are still present, the vaccine is polymorphic at >30 loci and therefore contains a mixture of related viruses. The inoculation of >40 million patients has consequently created a highly replicated evolutionary experiment that we have used to assess the competitive ability of these different viral genotypes in a human host. Using virus recovered from rash vesicles, we show that two vaccine mutations, causing amino acid substitutions in the major transactivating protein IE62, are outcompeted by the ancestral alleles. Standard interpretations of varicella disease severity concentrate on the undeniably important effects of host genotype and immune status, yet our results allow us to demonstrate that the viral genotype is associated with virulence and to identify the key sites. We propose that these loci have pleiotropic effects on the immunogenic properties of the virus, rash formation, and its epidemiological spread, which mould the evolution of its virulence. These findings are of practical importance for reducing the incidence of vaccine-associated rash and promoting public acceptance of the vaccine.

Abstract: The natural history of varicella zoster virus (VZV) infection and the molecular mechanisms of viral pathogenesis are incompletely understood. Although no animal model yet reproduces all aspects of VZV infection, recently developed models of VZV infection, and the creation of genetically altered VZV recombinants, are yielding new information about primary viraemia and latency. During viraemia, T-cells transport VZV to the skin, where cell-free viral replication facilitates person-to-person spread and transmission to the neurons where latency is established. The alternate viral pathways of lytic infection or latency appear to be cell-type determined and involve both host and viral components. Antiviral therapy for varicella is safe and efficacious, and as varicella in children is usually mild, treatment is generally recommended only for adolescents and adults with varicella. Treatment is recommended for all individuals with herpes zoster, especially those aged over 50 years. For some varicella and zoster cases, aciclovir, the original standard, is being replaced by valaciclovir and famciclovir as preferred therapies. For herpes zoster, bromovinyl deoxyuridine (brivudin) has been added to the list of treatment options for immunocompetent individuals, but is contraindicated in patients with cancer. Antiviral therapy will still have a role in the treatment of disease caused by VZV even after the widespread implementation of vaccination programmes for both chickenpox and herpes zoster.

Abstract: Background : Although Varicella Zoster virus (VZV) infections occur worldwide, the epidemiology is remarkably different in tropical and temperate climates. VZV infections result in significant morbidity and mortality among adults in Sri Lanka. Aims : For future VZV vaccination strategies, we set to determine the age-specific seroprevalence rate of VZV infections in Colombo, Sri Lanka. Materials and methods : The study was carried out from 1999 to 2000. Multi-stage cluster sampling technique was used to collect 913 blood samples, which were tested for the presence of VZV-specific IgG antibodies. Results :0 VZV seroprevalence rates were markedly lower in all age groups when compared to temperate climates. The seroprevalence rates increased with age in both the rural and urban populations. Of those aged 60 years, only 50% in the rural population and 78.9% in the urban population were immune to VZV. Seroprevalence rates of VZV infections were significantly different between the urban and rural populations (P Conclusions : These findings highlight the need for a VZV vaccination program, which is likely to have a huge impact on the incidence of chickenpox and its associated morbidity and mortality.

Abstract: 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.

Abstract: We investigated the comparative seroepidemiology of varicella zoster virus (VZV) in pregnant women of two ethnic groups, white British and Bangladeshi, living in an inner city area of London, United Kingdom. Women aged 16–45 years were recruited from antenatal clinics of the Royal London Hospital in the Borough of Tower Hamlets. Complete data were obtained from 275 white British and 765 Bangladeshi women. VZV antibody prevalence was 93·1% (95% CI 89·4–95·8) and 86·0% (95% CI 83·3–88·4) respectively. Women who were born in Bangladesh and lived there at least until the age of 15 years had the lowest odds of being immune (OR 0·37, 95% CI 0·22–0·63). This implies they will have an increased risk of varicella during pregnancy. Women arriving in the United Kingdom in adulthood should be screened routinely during pregnancy and vaccination offered postpartum if they are susceptible.

Abstract: Background: Although Varicella Zoster virus (VZV) infections occur worldwide, the epidemiology is remarkably different in tropical and temperate climates. VZV infections result in significant morbidity and mortality among adults in Sri Lanka. Aims : For future VZV vaccination strategies, we set to determine the age-specific seroprevalence rate of VZV infections in Colombo, Sri Lanka. Materials and methods : The study was carried out from 1999 to 2000. Multi-stage cluster sampling technique was used to collect 913 blood samples, which were tested for the presence of VZV-specific IgG antibodies. Results :VZV seroprevalence rates were markedly lower in all age groups when compared to temperate climates. The seroprevalence rates increased with age in both the rural and urban populations. Of those aged 60 years, only 50% in the rural population and 78.9% in the urban population were immune to VZV. Seroprevalence rates of VZV infections were significantly different between the urban and rural populations (P< 0.001), with VZV-specific IgG antibodies detected in 47.5% in the urban population and 27.9% in the rural population. It was found that 56.2% (131) of females of childbearing age were nonimmune to VZV. Conclusions : These findings highlight the need for a VZV vaccination program, which is likely to have a huge impact on the incidence of chickenpox and its associated morbidity and mortality.

Abstract: Objectives.Exposure to varicella zoster virus through close contact with people with chickenpox was suggested to boost specific immunity, reducing the risk of herpes zoster (HZ). Since the introduc...

Abstract: OBJECTIVE. To evaluate the correlation between self-report of a prior history of chickenpox and results of varicella-zoster virus (VZV) immunoglobulin (Ig) G serologic test results in an outbreak of VZV infection among Thai healthcare workers (HCWs) and to conduct a cost-benefit analysis of establishing routine VZV immunization as part of an occupational health program on the basis of the outbreak data. METHODS. All exposed patients received prophylaxis and the HCWs in our 3 intensive care units (ICUs) were prospectively evaluated. HCWs were assessed for disease history and serologic evidence of VZV IgG. A cost-benefit analysis was performed. RESULTS. After 140 HCWs and 18 ICU patients were exposed to VZV, 10 HCWs (7%) with active VZV infection were relieved from work until skin lesions were crusted. Acyclovir (ACV) was prescribed to all 10 HCWs with active disease, and all 18 exposed patients received prophylaxis with ACV. Of 140 HCWs, 100 consented to longitudinal follow-up. Twenty-three (100%) of the HCWs who reported a history of chickenpox also had serologic test results that were postive for VZV IgG, compared with 30 (39%) of 77 HCWs who reported no prior history of chickenpox, yet had test results that were positive for VZV IgG. Reported history of chickenpox had a sensitivity of 43%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 61% with respect to VZV infection immunity. The total cost estimate for this outbreak investigation was $23,087. CONCLUSIONS. An HCW's reported history of chickenpox was a reliable predictor of immunity; a report of no prior history of chickenpox was unreliable. Our cost-benefit analysis suggests that the costs of an occupational health program that included VZV surveillance and immunization for the next 323 HCWs would be approximately equal to the excess costs of $17,227 for the ACV therapy, HCW furloughs, and staff overtime associated with this outbreak.

Abstract: VZV is a human alphaherpesvirus that causes varicella (chickenpox) as the primary infection and establishes latency in sensory ganglia. VZV reactivation results in herpes zoster (shingles). During the course of varicella and zoster, VZV infects differentiated human cells that exist within unique tissue microenvironments in humans. The tropism of VZV for skin is the most obvious clinical manifestation of VZV infection, producing the vesicular cutaneous lesions that are associated with varicella and zoster. The site of initial VZV infection in naive hosts is thought to be mucosal epithelial cells of the upper respiratory tract. Entry is presumed to follow inoculation of the respiratory epithelium with infectious virus transmitted by aerosolized respiratory droplets or by contact with virus in varicella or zoster skin lesions (Arvin, ; Grose, 1981). VZV in respiratory or conjunctival mucosal cells has the opportunity to interact with and infect local immune system cells and those in adjacent lymphoid tissues. Trafficking of infected peripheral blood mononuclear cells (PBMC), which appear to be predominantly T-cells, to the skin is thought to give rise to crops of cutaneous vesicles. Skin lesions contain VZV material associated with necrotic debris and, unlike virus grown in vitro, cell-free, infectious particles are detected in vesicular fluid (Williams et al., 1962). The life cycle of VZV is completed upon its transmission to a susceptible host from an individual with varicella, or it can be postponed for decades by establishing latency in neurons and transmitting to future generations during episodes of zoster.

Abstract: Objective. The purpose of this study was to assess the validity of self-reported history for varicella disease relative to serological evidence of varicella immunity in pregnant women attending antenatal care at clinics located in two diverse geographical locations in the U.S. (Antelope Valley, California, and Philadelphia) with high varicella vaccination coverage. Methods. Pregnant women attending prenatal care appointments who needed blood drawn as part of their routine care were eligible to participate. Self-reported varicella disease history was obtained via questionnaire. Varicella serostatus was determined using a whole-cell enzyme-linked immunosorbent assay to test for varicella zoster virus-specific immunoglobulin G (VZV IgG) antibodies. Results. Of the 309 study participants from Antelope Valley and the 528 participants from Philadelphia who self-reported having had chickenpox disease, 308 (99.7%; 95% confidence interval [Cl]: 98.2, 100) and 517 (97.9%; 95% Cl: 96.3, 99.0), respectively, had serological evidence of immunity to varicella. Only 6.8% (95% Cl: 3.9, 11.0) and 17.4% (95% Cl: 13.1, 22.5) of women who self-reported having a negative or uncertain varicella disease history in Antelope Valley and Philadelphia, respectively, were seronegative for varicella antibodies. Conclusion. Despite the dramatic changes in the epidemiology of varicella that have occurred since 1995 due to the introduction and subsequent widespread use of the varicella vaccine, self-reported history of varicella continues to be a strong predictor of VZV IgG antibodies in pregnant women. Negative or uncertain history remains poorly predictive of negative serostatus.

Abstract: A retrospective study was conducted to provide epidemiological data on hospitalization for complicated and uncomplicated chickenpox in a pediatric population. The study analyzed hospitalization cases for chickenpox, among all the 31 Tuscan hospitals, during the period 1997–2003. Globally, 650 cases were recorded (306 = 47.07% for uncomplicated and 344 = 52.92% for complicated chickenpox). Total hospitalization rate was 22.66 per 100,000 living Tuscan children and 11.52 per 1,000 notified chickenpox cases. Hospitalization rates for complicated chickenpox were 12.00 per 100,000 living children and 6.09 per 1,000 notified cases. Notably, significantly increased hospitalization rates for complicated chickenpox were evidenced over years (p = 0.011 per 100,000 living children and p = 0.001 per 1,000 notified cases), due to the increased proportion of neurological (p = 0.043 per 100,000 living children and p = 0.025 per 1,000 notified cases) and respiratory (p = 0.021 per 100,000 living children and p = 0.008 per 1,000 notified cases) complications, whereas hospitalization rates for other complications as well as for uncomplicated chickenpox remained constant (p = 0.25 per 100,000 living children and p = 0.09 per 1,000 notified cases). Chickenpox complications, requiring hospitalization, occurred at a substantial rate in our pediatric population. In particular, increasing hospitalization rates for neurological and respiratory complications were evidenced over the study period. Our epidemiological data may provide additional information while planning a vaccination strategy for Italy.

Abstract: The general use of the varicella vaccine requires the surveillance of varicella-zoster virus (VZV) strains in patients infected with VZV. This paper reports the data achieved from a prospective study of genotyping VZV in Germany, analyzing the restriction fragment length polymorphism (RFLP) of the open reading frames (ORF) 38, 54, and 62 as well as the polymorphism of the R5 repeat region. The study included 177 patients with varicella. Seventy-eight patients with zoster served as controls. Results revealed that 78% of VZV strains in patients with varicella had the genetic profile of the dominant wild-genotype occurring in Europe and 22% had the markers of African or Asian strains. Varicella patients with the profile of African or Asian strains were significantly younger than patients with varicella caused by the dominant genotype. By contrast, all zoster patients exhibited strains representing the majority of wild-type strains in Europe. In conclusion, VZV strains from patients with varicella have a significantly higher genetic variability than viral strains from zoster patients. Since variants with the markers of African or Asian strains could only be found in young children with chickenpox, the results suggest a changing scene of VZV genotypes in Germany. As reasons, the spread of viruses, which may be imported originally by persons immigrating from warmer climates, or the recombination between wild-and vaccine-type viruses have to be considered.

Abstract: A total of 298 patients with herpes zoster were recruited as part of 2 community-based studies in East London between 1998 and 2003. Single nucleotide-polymorphism analysis of 4 regions (genes 1, 21, 37, and 60) found that most genotypes were European strains C and B, representing 58% and 21% of all samples collected. No change in the proportion of these European clades has occurred during the past 80 years, strongly supporting the hypothesis that these strains are indigenous to the United Kingdom. White patients almost exclusively had reactivation of genotypes C (66%) and B (21%), whereas patients from Africa, Asia, or the Caribbean mainly had reactivation of genotypes A and J. An increase in BglI-positive A and J genotypes in UK cases of zoster is only partly explained by immigration from endemic regions. The data presented provide a baseline against which to evaluate changes in the molecular epidemiology of varicella-zoster virus and the effect of immunization with the Japanese Oka vaccine strain.

Abstract: We report a case where acute varicella infection, chickenpox, mimics the findings of recurrent Hodgkin disease on F-18 FDG PET/CT. A 28-year-old man with a history of Hodgkin disease in remission had fatigue, pyrexia, and a raised ESR. His F-18 FDG PET/CT, performed to exclude lymphoma recurrence, demonstrated FDG-avid lymphadenopathy and increased FDG uptake in his spleen. A day later he developed the generalized rash of acute varicella infection. This was managed with valacyclovir. Repeat F-18 FDG PET/CT done 1 month later showed no evidence of FDG-avid disease. In this patient the stimulation of an immune response by the acute viral infection mimics recurrent lymphoma.

Abstract: Introduction: Varicella is an acute disease with significant morbidity. However, there is little knowledge on the seroepidemiology of the disease in Singapore. The objective of this study was to assess the seroprevalence of varicella zoster virus (VZV) antibodies in military recruits in Singapore and to ascertain the predictive value of a self-reported history of varicella. The latter is a possible proxy for seroprevalence, and may be used to provide efficient identification of candidates for vaccination. Materials and Methods: From September 2000 to October 2005, 2189 servicemen were selected during their pre-enlistment medical check-up. Blood samples were obtained to determine the varicella IgG levels via enzyme-linked immunosorbent assay (ELISA). Information about the participant's race, history of varicella and vaccination, and other clinical variables were obtained through a questionnaire. Results: The overall prevalence of VZV sero- positivity in military recruits was 76.0% (75.8% in the 16 years to 20 years age group). For the reported history, 73.7% of Chinese participants, 73.0% of Malays, and 63.6% of Indians reported having had varicella infection and/or vaccination. Overall, the sensitivity, specificity, positive and negative predictive values of a self-reported history of varicella for serologically confirmed immunity were 87.2%, 83.2%, 94.3% and 67.1% respectively. Conclusions: The prevalence of VZV antibodies in pre-enlistees to the Singapore Armed Forces (SAF) is high. Incidence of varicella in the SAF is on the wane, indicating an increase in herd immunity against VZV. A recalled history of varicella infection was also a good predictor of serological immunity and may be used for selection for vaccination. Ann Acad Med Singapore 2007;36:636-41

Abstract: OBJECTIVE. Extremely preterm infants mount lower antibody responses than term infants to several vaccines. The objective of this study was to measure the immunogenicity of measles-mumps-rubella and varicella vaccines in preterm and term children. METHODS. Immune status before immunization and immune response after immunization with measles-mumps-rubella and varicella vaccines at 15 months of age were compared in 32 infants, 16 of whom were preterm ( RESULTS. Preterm children had lower mumps and rubella geometric mean titers than did term children before vaccine, and nearly all children were seronegative for each of the 4 vaccine antigens before immunization. Measles, mumps, rubella, and varicella geometric mean titers were similar between groups after vaccine. All children were seropositive for measles after vaccine, whereas 13 of 14 preterm and 11 of 13 term children were seropositive for mumps, 13 of 14 preterm and 13 of 13 term children were seropositive for rubella, and 11 of 16 preterm and 9 of 15 term children were seropositive for varicella. CONCLUSIONS. Preterm children mounted antibody responses that were similar to those of term children after measles-mumps-rubella and varicella vaccines at 15 months of age.

Abstract: Ramsay Hunt syndrome is a disorder characterized by herpetic eruptions on the auricle, facial paralysis, and vestibulocochlear dysfunction, and is attributed to varicella zoster virus infection in the geniculate ganglion. Although it is a common cause of acute peripheral facial paralysis, children are not usually affected. We describe Ramsay Hunt syndrome in a 3-month-old infant who was referred because of a 2-day-old appearance of herpetic blisters on the right auricle and along the distribution of the right facial nerve. His mother had been infected with chickenpox during the second trimester of pregnancy. The infant presented with right facial palsy and was anxious, but had no fever. Otoscopy revealed herpetic eruptions in the right ear canal. Otoacoustic emissions were absent in the right ear and auditory brainstem responses confirmed moderate sensorineural hearing loss. Appropriate treatment resulted in slight improvement after the first week and complete recovery within 4 months. Infection with varicella zoster virus was proved by a significant increase in the serum anti-varicella zoster virus antibody titer during the convalescent phase of the disease.

Abstract: Objective: To report occupationally related outbreak of chickenpox in intensive care unit (ICU). Case Presentation and Intervention: The index patient was a 4-yea

Abstract: Chicken pox is a highly contagious infection, caused by the varicella zoster virus. Although generally a benign, self-limited disease, varicella may be associated with serious complications especially in adults. We present acute pancreatitis- a rare complication, in otherwise healthy patients suffering from chicken pox. The presence of pancreatitis in association with chickenpox in immunocompetent patients can influence the outcome of the latter. This interesting case will hopefully increase awareness about this complication and its fatality in chicken pox.

Abstract: We evaluated the seroprevalence of varicella-zoster virus (VZV) in the Finnish population among various age groups and genetically characterized VZV strains from documented cases of varicella and zoster. VZV-specific immunoglobulin G was measured in 2,842 serum samples that had been submitted for virological studies to the Department of Virology, University of Helsinki, from 1995 to 1996. Specimens for VZV genotyping were obtained from vesicular lesions from two pediatric patients and 26 adult patients. Seroprevalence to VZV varied markedly by age: 45% in children aged ≤2 months, 12.5% in children aged 6 to 8 months, and >90% in children near 10 years of age, plateauing thereafter into advanced age. The seroprevalence rates indicate that in Finland, as in other countries with temperate climates, primary VZV infection usually occurs during the first decade of life. Twenty-eight VZV DNA-positive specimens were analyzed to identify VZV vaccine and wild-type genotypes. All analyzed specimens were wild type and the European (E) genotype.

Abstract: OBJECTIVES To determine the seroprevalence of varicella antibody among recent Somali refugees living in Olmsted County, Minnesota, and to estimate the risk of varicella-zoster virus (VZV) infection in this group. SUBJECTS AND METHODS We obtained blood samples from the study subjects, along with demographic information, immunization records, and vaccine-preventable disease history. Serum samples were tested using a whole-virus IgG VZV-specific commercial enzyme-linked immunosorbent assay kit. This study was completed in 1998. RESULTS Overall, 200 Somali refugees, comprising 33 extended families, were interviewed, with 193 providing adequate blood samples. Thirty-five subjects (18%) were seronegative for varicella. Males had a significantly higher seronegativity rate (25% [n=23]) compared with females (12% [n=12]; P =.02); however, this association disappeared after adjustment for age and varicella infection history. Five percent (5/92) of adults were seronegative compared with 30% (30/101) of all children ( P P CONCLUSION These results demonstrate a high prevalence of varicella seronegativity among Somali refugees who have immigrated to an endemic area. We recommend instituting improved education regarding varicella among Somali communities and increasing vaccine uptake or routine testing for serum varicella antibody to prevent VZV-related morbidity and mortality, particularly in adolescents, adult refugees, and women of childbearing age.

Abstract: WEB This is a Web exclusive article. aricella pneumonia is a serious complication of chickenpox infection that in immunosuppressed individuals has a mortality rate of more than 20% [1]. The radiographic and highresolution CT appearances of varicella pneumonia have been described and include 1to 10-mm pulmonary nodules; hilar lymphadenopathy; ground-glass attenuation; consolidation; and, less commonly, pleural effusions [2–5]. This case report represents, to the best of our knowledge, the first description of the CT findings of varicella pneumonia occurring in a lung transplant recipient. The CT appearances in this case of varicella pneumonia differ from those previously reported in either immunocompetent or immunosuppressed individuals.