Project description:Live vaccines usually provide robust immunity but can transmit the vaccine virus. To assess the characteristics of secondary transmission of the vaccine-strain varicella-zoster virus (Oka strain; vOka) on the basis of the published experience with use of live varicella and zoster vaccines. Systematic review of Medline, Embase, the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and Scopus databases for articles published through 2018. Articles that reported original data on vOka transmission from persons who received vaccines containing the live attenuated varicella-zoster virus. We abstracted data to describe vOka transmission by index patient's immune status, type (varicella or herpes zoster) and severity of illness, and whether transmission was laboratory confirmed. Twenty articles were included. We identified 13 patients with vOka varicella after transmission from 11 immunocompetent varicella vaccine recipients. In all instances, the vaccine recipient had a rash: 6 varicella-like and 5 herpes zoster. Transmission occurred mostly to household contacts. One additional case was not considered direct transmission from a vaccine recipient, but the mechanism was uncertain. Transmission from vaccinated immunocompromised children also occurred only if the vaccine recipient developed a rash postvaccination. Secondary cases of varicella caused by vOka were mild. It is likely that other vOka transmission cases remain unpublished. Healthy, vaccinated persons have minimal risk for transmitting vOka to contacts and only if a rash is present. Our findings support the existing recommendations for routine varicella vaccination and the guidance that persons with vaccine-related rash avoid contact with susceptible persons at high risk for severe varicella complications.
Project description:We describe a death in a 15-mo-old girl who developed a varicella-like rash 20 d after varicella vaccination that lasted for 2 mo despite acyclovir treatment. The rash was confirmed to be due to vaccine-strain varicella-zoster virus (VZV). This is the first case of fatal varicella due to vaccine-strain VZV reported from the United States. The patient developed severe respiratory complications that worsened with each new crop of varicella lesions; vaccine-strain VZV was detected in the bronchial lavage specimen. Sepsis and multi-organ failure led to death. The patient did not have a previously diagnosed primary immune deficiency, but her failure to thrive and repeated hospitalizations early in life (starting at 5 mo) for presumed infections and respiratory compromise treated with corticosteroids were suggestive of a primary or acquired immune deficiency. Providers should monitor for adverse reactions after varicella vaccination. If severe adverse events develop, acyclovir should be administered as soon as possible. The possibility of acyclovir resistance and use of foscarnet should be considered if lesions do not improve after 10 d of treatment (or if they become atypical [e.g., verrucous]). Experience with use of varicella vaccine indicates that the vaccine has an excellent safety profile and that serious adverse events are very rare and mostly described in immunocompromised patients. The benefit of vaccination in preventing severe disease and mortality outweigh the low risk of severe events occurring after vaccination.
Project description:This study aimed at establishing baseline key epidemiological parameters for varicella zoster virus (VZV) infection in Vojvodina, Serbia, with the ultimate goal to quantify the VZV transmission potential in the population. Seroprevalence data generated during the first large cross-sectional VZV serosurvey were modelled, using a two-tiered modelling approach to calculate age-specific forces of infection (FOI), the basic reproduction number (R0) and herd immunity threshold (H). Seroprevalence and modelling data were compared with corresponding pre-vaccination epidemiological parameters from 11 countries participating in the European Sero-Epidemiology Network 2 (ESEN2) project. Serbia fits into the general dynamic VZV transmission patterns in Europe in the pre-vaccine era, with estimated R0 = 4.12, (95% CI: 2.69-7.07) and H = 0.76 (95% CI: 0.63-0.86). The highest VZV transmission occurs among preschool children, as evidenced by the estimation of the highest FOI (0.22, 95% CI: 0.11-0.34) in the 0.5-4 age group, with a peak FOI of 0.25 at 2.23 years. Seroprevalence was consistently lower in 5-14 year-olds, resulting in considerable shares of VZV-susceptible adolescents (7.3%), and young adults (6%), resembling the situation in a minority of European countries. The obtained key epidemiological parameters showed most intense VZV transmission in preschool children aged <4 years, justifying the consideration of universal childhood immunization in the future. National immunization strategy should consider programs for VZV serologic screening and immunization of susceptible groups, including adolescents and women of reproductive age. This work is an important milestone towards the evaluation of varicella immunization policy options in Serbia.
Project description:To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.
Project description:BackgroundIn Japan, routine two-dose immunization against varicella has been conducted among children at ages of 12 and 36 months since 2014, and the vaccination coverage has reached around 90%. To understand the impact of routine varicella vaccination, we reconstructed the epidemiological dynamics of varicella in Japan.MethodsEpidemiological and demographic datasets over the past three decades were analyzed to reconstruct the number of susceptible individuals by age and year. To estimate the annual risk of varicella infection, we fitted a balance equation model to the annual number of cases from 1990 to 2019. Using parameter estimates, we reconstructed varicella dynamics starting from 1990 and modeled future dynamics until 2033.ResultsOverall varicella incidence declined over time and the annual risk of infection among children younger than 10 years old decreased monotonically starting in 2014. Conversely, varicella incidence among teenagers (age 10 to 14 years) has increased each year since 2014. A substantial number of unvaccinated individuals born before the routine immunization era remained susceptible and aged without contracting varicella, while the annual risk of infection among teenagers aged 10 to 14 years increased starting in 2011 despite gradual expansion of varicella vaccine coverage. The number of susceptible individuals decreased over time in all age groups. Modeling indicated that susceptibility rates among pre-school children aged 1 to 4 years will remain low.ConclusionRoutine varicella vaccination has successfully reduced infections in pre-school and early primary school age children, but has also resulted in increased infection rates among adolescents. This temporary increase was caused both by the increased age of susceptible individuals and increased transmission risk among adolescents resulting from the dynamic nature of varicella transmission. Monitoring susceptibility among adolescents will be important to prevent outbreaks over the next decade.
Project description:BackgroundVaricella-zoster virus (VZV) causes chickenpox in children and shingles in older people. Currently, live attenuated vaccines based on the Oka strain are available worldwide. In Korea, an attenuated VZV vaccine has been developed from a Korean isolate and has been commercially available since 1994. Despite this long history of use, the mechanism for the attenuation of the vaccine strain is still elusive. We attempted to understand the molecular basis of attenuation mechanism by full genome sequencing and comparative genomic analyses of the Korean vaccine strain SuduVax.ResultsSuduVax was found to contain a genome that was 124,759 bp and possessed 74 open reading frames (ORFs). SuduVax was genetically most close to Oka strains and these Korean-Japanese strains formed a strong clade in phylogenetic trees. SuduVax, similar to the Oka vaccine strains, underwent T- > C substitution at the stop codon of ORF0, resulting in a read-through mutation to code for an extended form of ORF0 protein. SuduVax also shared certain deletion and insertion mutations in ORFs 17, 29, 56 and 60 with Oka vaccine strains and some clinical strains.ConclusionsThe Korean VZV vaccine strain SuduVax is genetically similar to the Oka vaccine strains. Further comparative genomic and bioinformatics analyses will help to elucidate the molecular basis of the attenuation of the VZV vaccine strains.
Project description:We studied the relationship between varicella-zoster virus (VZV) DNAemia and development of VZV-specific immunity after administration of live-attenuated zoster vaccine. VZV-DNAemia, detected by polymerase chain reaction (PCR), and VZV-specific effector (Teff) and memory (Tmem) T cells, was measured in 67 vaccinees. PCR was positive in 56% (9 direct, 28 nested) on day 1 and in 16% (1 direct, 10 nested) on day 14. Teff progressively increased in direct-PCR-positive vaccinees up to day 30, but Tmem did not. Conversely, Tmem, but not Teff, increased in direct-PCR-negative vaccinees on day 7. The kinetics of these immune responses and VZV DNAemia suggested that direct-PCR sample positive represented viremia.
Project description:Varicella, 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. This 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). The 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. This 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.
Project description:We report the first laboratory-documented case of herpes zoster caused by the attenuated varicella zoster virus (VZV) contained in Zostavax in a 68-year-old immunocompetent adult with strong evidence of prior wild-type VZV infection. The complete genome sequence of the isolate revealed that the strain carried 15 of 42 (36%) recognized varicella vaccine-associated single-nucleotide polymorphisms, including all 5 of the fixed vaccine markers present in nearly all of the strains in the vaccine. The case of herpes zoster was relatively mild and resolved without complications.
Project description:A high-throughput test to detect varicella-zoster virus (VZV) antibodies in varicella vaccine recipients is not currently available. One of the most sensitive tests for detecting VZV antibodies after vaccination is the fluorescent antibody to membrane antigen (FAMA) test. Unfortunately, this test is labor-intensive, somewhat subjective to read, and not commercially available. Therefore, we developed a highly quantitative and high-throughput luciferase immunoprecipitation system (LIPS) assay to detect antibody to VZV glycoprotein E (gE). Tests of children who received the varicella vaccine showed that the gE LIPS assay had 90% sensitivity and 70% specificity, a viral capsid antigen enzyme-linked immunosorbent assay (ELISA) had 67% and 87% specificity, and a glycoprotein ELISA (not commercially available in the United States) had 94% sensitivity and 74% specificity compared with the FAMA test. The rates of antibody detection by the gE LIPS and glycoprotein ELISA were not statistically different. Therefore, the gE LIPS assay may be useful for detecting VZV antibodies in varicella vaccine recipients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00921999.).