PMID: 

Clin Microbiol Infect. 2014 May ;20 Suppl 5:86-91. PMID: 24494784

Abstract Title: 

Varicella vaccination: a laboured take-off.

Abstract: 

Varicella vaccines are highly immunogenic, efficacious and safe in preventing varicella disease. The USA has been the first country recommending universal vaccination. In the European Union/European Economic Area countries, the use of varicella vaccine is heterogeneous, with some countries recommending universal vaccination in children at national or regional level, others only in high-risk groups and others having no recommendation at all. Uncertainties on the potential impact of varicella vaccination on the epidemiology of varicella and herpes zoster still exist. These uncertainties are the main reason behind the diverse vaccine recommendations. Surveillance systems and mathematical models could be useful to address these uncertainties. However, the lack of surveillance of varicella and herpes zoster in some countries, as well as the high variability of surveillance systems in the countries that have one, makes it difficult to assess the effect of the vaccine. On the other hand, mathematical models are based on assumptions and should be interpreted carefully. Continuous surveillance of varicella and herpes zoster is needed to identify any changes in the epidemiological presentation of the diseases. In any case, continuous surveillance will be needed to fully describe the impact of the programmes currently running and clarify some of the actual uncertainties in the near future. Additionally, increasing our understanding of the risk factors for development of herpes zoster is required.

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PMID: 

Vaccine. 2014 Feb 12 ;32(8):897-900. Epub 2014 Jan 9. PMID: 24412300

Abstract Title: 

Decline of varicella vaccination in German surveillance regions after recommendation of separate first-dose vaccination for varicella and measles-mumps-rubella.

Abstract: 

BACKGROUND: Germany introduced routine varicella (V) vaccination in 2004. Due to a slightly increased risk of febrile convulsions after first-dose application of combined measles-mumps-rubella-varicella (MMRV) vaccine separate first-dose vaccinations with MMR and monovalent V vaccine were recommended in September 2011.METHODS: We compared V and MMR vaccinations in paediatric practices from two surveillance regions (Munich and Würzburg) one year before and after the change in the recommendation.RESULTS: A total of 1405/326 monthly reports were provided by a monthly average of 79/14 practices participating in Munich/Würzburg. V first-dose vaccinations (monovalent V or MMRV vaccine) declined by 12% in Munich (from 10.1 to 8.9 vaccinations per month and practice; p

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PMID: 

Vaccine. 2014 Feb 3 ;32(6):645-50. Epub 2013 Dec 25. PMID: 24374498

Abstract Title: 

Risk of febrile convulsions after MMRV vaccination in comparison to MMR or MMR+V vaccination.

Abstract: 

BACKGROUND: In July 2006, Priorix-Tetra™, a combined measles-mumps-rubella-varicella (MMRV) vaccine, was licensed in Germany. Since a postlicensure study had shown a more than twofold elevated risk of febrile convulsions (FC) after first dose vaccination with the combined MMRV vaccine ProQuad(®) compared to separately administered MMRand V vaccines (MMR+V), the Paul-Ehrlich-Institute, the German regulatory agency for vaccine licensing and safety, requested a study investigating the risk of FC for Priorix-Tetra™.METHODS: We performed a matched cohort study based on claims data of more than 17 million insurees in the German Pharmacoepidemiological Research Database. All children born between 01.01.2004 and 31.12.2008 who received a 1st dose of MMRV vaccine were matched to children vaccinated with MMR, MMR+V and MMR or MMR+V (combined group), respectively, by sex, age, month of vaccination and statutory health insurance. The primary outcome was defined as hospitalization with a diagnosis of FC without any alternative plausible cause of FC, e.g. an infection or neurological condition, coded as main discharge diagnosis. The secondary outcome excluded only neurological conditions to provide a more comparable outcome definition to the one used in the ProQuad(®) study. Numbers needed to harm (NNH), risk ratios and confounder adjusted odds ratios (ORs) with 95% CIs were estimated to compare the exposure groups.RESULTS: In the main risk period 5-12 days after immunization, the adjusted ORs of the primary endpoint for immunization with MMRV vaccine relative to the comparator vaccine indicated in brackets were 4.1 [95% CI 1.3-12.7; MMR], 3.5 [0.7-19.0; MMR+V], and 4.1 [1.5-11.1; MMR and MMR+V]. The corresponding ORs for the secondary outcome were 2.3 [1.4-3.9; MMR], 1.5 [0.8-2.9; MMR+V] and 2.4 [1.5-3.9; MMR and MMR+V].CONCLUSIONS: This study in children younger than 5 years, 90% of them between 11 and 23 months, shows a risk of FC similar in magnitude for Priorix-Tetra™ as has previously been reported for ProQuad(®) suggesting a class effect for these quadrivalent vaccines.

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PMID: 

Ann Intern Med. 2013 Dec 3 ;159(11):739-45. PMID: 24297190

Abstract Title: 

Examination of links between herpes zoster incidence and childhood varicella vaccination.

Abstract: 

BACKGROUND: Introduction of a universal varicella vaccine program for U.S. children in 1996 sparked concern that less-frequent exposure to varicella would decrease external boosting of immunity to varicella zoster virus and thereby increase incidence of herpes zoster (HZ).OBJECTIVE: To determine whether the varicella vaccination program has influenced trends in HZ incidence in the U.S. population older than 65 years.DESIGN: Retrospective study of Medicare claims.SETTING: Medicare, 1992 through 2010.PARTICIPANTS: 2 848 765 beneficiaries older than 65 years.MEASUREMENTS: Annual HZ incidence from 1992 through 2010; rate ratios (RRs) for HZ incidence by age, sex, and race or ethnicity; and state-level varicella vaccination coverage.RESULTS: 281 317 incident cases of HZ occurred. Age- and sex-standardized HZ incidence increased 39% from 10.0 per 1000 person-years in 1992 to 13.9 per 1000 person-years in 2010 with no evidence of a statistically significant change in the rate of increase after introduction of the varicella vaccination program. Before introduction of this program, HZ incidence was higher in women (RR, 1.21 [95% CI, 1.19 to 1.24]) than men and was lower in black persons (RR, 0.51 [CI, 0.48 to 0.53]) and Hispanic persons (RR, 0.76 [CI, 0.72 to 0.81]) than white persons. In a model adjusted for sex, age, and calendar year from 1997 to 2010, HZ incidence did not vary by state varicella vaccination coverage (RR, 0.9998 [CI, 0.9993 to 1.0003]).LIMITATION: Uncertain level and consistency of health-seeking behavior and access and uncertain accuracy of disease coding.CONCLUSION: Age-specific HZ incidence increased in the U.S. population older than 65 years even before implementation of the childhood varicella vaccination program. Introduction and widespread use of the vaccine did not seem to affect this increase. This information is reassuring for countries considering universal varicella vaccination.PRIMARY FUNDING SOURCE: None.

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PMID: 

Hum Vaccin Immunother. 2014 ;10(1):146-9. Epub 2013 Aug 27. PMID: 23982221

Abstract Title: 

Fatal varicella due to the vaccine-strain varicella-zoster virus.

Abstract: 

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.

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PMID: 

Med Microbiol Immunol. 2013 Aug ;202(4):257-8. Epub 2013 May 7. PMID: 23649706

Abstract Title: 

Progress in VZV vaccination? Some concerns.

Abstract: 

Since 1995, many countries have been aiming to replace the natural immunity against varicella by a vaccine-induced immunity to protect against varicella and herpes zoster. While the frequency of varicella in childhood has been significantly reduced, in future, herpes zoster morbidity might increase in the elderly due to the weaker immunity post-vaccination and the absence of immunity boosting silent reinfections. In countries, where less than 90 % of children are covered by universal vaccination, varicella zoster virus (VZV) infection is not completely eradicated, but might move from childhood to the age of young adults who suffer from more serious complications. A special VZV vaccine against herpes zoster in adults aged>60 years has proven to be effective in many cases, but not all vaccinees. This might lead to problems regarding the acceptance of vaccination and delay rapid antiviral therapy to prevent the post-zosteric neuralgia. An efficacious-inactivated VZV vaccine to protect immunocompromised patients is stillmissing. VZV vaccines and vaccination strategies have to be optimised to avoid that the quality of life and cost savings from varicella reduction in childhood are offset by more VZV diseases in adults.

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PMID: 

Pediatr Infect Dis J. 2013 Jul ;32(7):e305-13. PMID: 23838789

Abstract Title: 

Primary versus secondary failure after varicella vaccination: implications for interval between 2 doses.

Abstract: 

BACKGROUND: Two-dose varicella vaccination is recommended for optimal control of varicella in populations with high (>90%) 1-dose coverage. Optimal timing of the second dose may depend on whether breakthrough varicella results from primary vaccine failure (no protective immunity after vaccination) or secondary vaccine failure (waning protective immunity).METHODS: Published literature (1995 to 2012) on vaccine failure after varicella vaccination cited in PubMed and other online sources was reviewed.RESULTS: Nineteen publications detailed 21 varicella outbreaks with breakthrough varicella rates ranging from 0% to 42%; the publications showed no consistent trend between breakthrough varicella rate and time since vaccination.CONCLUSIONS: Literature to date indicates a relatively high rate of primary vaccine failure and limited evidence of secondary vaccine failure among 1-dose varicella vaccine recipients, suggesting that a short interval between 2 doses might be preferable in countries considering implementation of universal varicella vaccination to reduce breakthrough varicella. However, any potential disruption to well-established vaccination schedules should be considered.

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PMID: 

Vaccine. 2012 Nov 6 ;30(48):6935-9. Epub 2012 Aug 8. PMID: 22884663

Abstract Title: 

Challenges in confirming a varicella outbreak in the two-dose vaccine era.

Abstract: 

BACKGROUND: A second dose of varicella vaccine was recommended for U.S. children in 2006. We investigated a suspected varicella outbreak in School District X, Texas to determine 2-dose varicella vaccine effectiveness (VE).METHODS: A varicella case was defined as an illness with maculopapulovesicular rash without other explanation with onset during April 1-June 10, 2011, in a School District X student. We conducted a retrospective cohort in the two schools with the majority of cases. Lesion, saliva, and environmental specimens were collected for varicella-zoster virus (VZV) PCR testing. VE was calculated using historic attack rates among unvaccinated.RESULTS: In School District X, 82 varicella cases were reported, including 60 from Schools A and B. All cases were mild, with a median of 14 lesions. All 10 clinical specimens and 58 environmental samples tested negative for VZV. Two-dose varicella vaccination coverage was 66.4% in Schools A and B. Varicella VE in affected classrooms was 80.9% (95% CI: 67.2-88.9) among 1-dose vaccinees and 94.7% (95% CI: 89.2-97.4) among 2-dose vaccinees in School A, with a second dose incremental VE of 72.1% (95% CI: 39.0-87.3). Varicella VE among School B students did not differ significantly by dose (80.1% vs. 84.2% among 1-dose and 2-dose vaccinees, respectively).CONCLUSION: Laboratory testing could not confirm varicella as the etiology of this outbreak; clinical and epidemiologic data suggests varicella as the likely cause. Better diagnostics are needed for diagnosis of varicella in vaccinated individuals so that appropriate outbreak control measures can be implemented.

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PMID: 

Pediatr Infect Dis J. 2012 Nov ;31(11):1148-52. PMID: 22863912

Abstract Title: 

Serologic analysis of the IgG antibody response in children with varicella zoster virus wild-type infection and vaccination.

Abstract: 

INTRODUCTION: In contrast to varicella zoster virus (VZV) primary infection, VZV vaccination does not seem to provide lifelong immunity against varicella. Because more people get vaccinated every year, the development of sensitive serological test systems for the detection of protective anti-VZV IgG will become important in the future.METHODS: We have previously developed a novel VZV line assay based on 5 different recombinant VZV antigens. In this study, we compared this novel assay with a commercially available glycoprotein enzyme immunoassay (RIDASCREEN VZV IgG) in detecting anti-VZV IgG of children with previous varicella infection and VZV vaccination.RESULTS: One hundred twenty-five children were included in this study, 72 with a history of varicella infection and 53 with VZV vaccination. Both assays detected anti-VZV IgG antibodies in both study groups with similar sensitivities. The VZV line assay revealed striking differences in the anti-VZV IgG composition against the VZV open reading frames, 4, 14 and 49, between both study groups, indicating that wild-type varicella infection causes a more diverse immune response against VZV than does vaccination. The exploitation of these results enabled the discrimination of both study groups with a sensitivity of 0.93 and a specificity of 0.83, indicating that the serologic differentiation of children with previous varicella infection and VZV vaccination might be possible.CONCLUSION: The VZV line assay enables the detection of anti-VZV IgG with sensitivities comparable to glycoprotein enzyme immunoassays and might be suitable for the serologic discrimination between children with a history of varicella infection and VZV vaccination.

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PMID: 

Pediatr Infect Dis J. 2013 Feb ;32(2):183-5. PMID: 22982982

Abstract Title: 

Fatal wild-type varicella-zoster virus encephalitis without a rash in a vaccinated child.

Abstract: 

Encephalitis associated with varicella-zoster virus, rare among children in the varicella vaccine era, has generally been associated with a rash. We report fatal wild-type varicella-zoster virus encephalitis without a rash in a child who had received 1 dose of varicella vaccine. Varicella-zoster virus encephalitis should be considered in the differential diagnosis for children presenting with acute neurologic symptoms, even vaccine recipients.

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