Epidemiological characteristics of breakthrough varicella infection during varicella outbreaks in Shanghai, 2008-2014.

The outbreaks of varicella occurring in kindergartens and schools are increasingly notified in Shanghai despite the implementation of one-dose varicella vaccination. We analyzed surveillance data on the notified outbreaks of varicella in Minhang District of Shanghai during 2008-2014. A total of 13 511 varicella cases and 154 outbreaks involving 1558 (11·5%) cases were reported. Annual attack rates of outbreak-associated varicella in outbreak classes were 5·5%-12%. The mean age of the outbreak-associated cases was 8·6 ± 3·1 years. Among 1558 outbreak cases, 660 (42·4%) received one-dose varicella vaccine previously. The proportions of breakthrough varicella infection during outbreaks ranged from 21·5% in 2008 to 86·1% in 2014. Annual breakthrough infection rates in outbreak classes ranged from 5·4% to 7·4%. Breakthrough cases as index cases results in 9·7% of outbreaks, and the average duration of outbreaks was significantly longer in vaccinated cases as index cases than in unvaccinated cases as index cases (11·3 ± 5·8 days vs. 8·6 ± 6·1 days, P < 0·05). The mean time of breakthrough infection since vaccination was 6·2 ± 2·3 years (range 0·6-13·4 years). One-dose varicella vaccination cannot prevent the varicella outbreaks in kindergartens and schools. A second dose of varicella vaccine should be recommended for children.

[The epidemiology of varicella disease in Germany after introduction of a vaccination recommendation : Analysis of mandatory and sentinel data between 2002 and 2014]. / Die Epidemiologie der Varizellen in Deutschland unter Einfluss der Varizellen-Impfempfehlung : Auswertung der Sentinel- und Meldepflichtdaten 2002­2014.

BACKGROUND: Since 2004 a single varicella vaccination for all infants aged 11-14 months has been recommended in Germany and since 2009 a second dose at the age of 15-23 months is recommended. Vaccination coverage after 24 months rose from 43% in 2006 to 87.5% in 2012. A mandatory notification system was introduced in the New Federal States (NFS) between 2002 and 2009 and nationwide in 2013. A national sentinel system has been in place since 2005. OBJECTIVE AND METHOD: We analyzed both data sources to describe the varicella epidemiology related to vaccination coverage after initiation of routine childhood varicella vaccination and to evaluate both notification systems regarding informative value and data quality. We looked at trends, age distribution and incidences using Microsoft Excel and Stata12. Vaccination coverage data were available from health insurance claims data. RESULTS: By 2013 a decrease of cases/medical practice/month from 3.47 to 0.43 was observed. The incidence in the NFS declined from 32 to 12 out of 100,000. Sentinel and mandatory notification data showed the largest decrease among the 1-4 year-olds (-94 and -90% resp.). In 2014, varicella incidences increased in all age groups, but not the cases/medical-practice/month by age in the sentinel. DISCUSSION: Increasing vaccination coverage and decreasing varicella cases demonstrate the success of routine childhood varicella vaccination. Mandatory notification data allow incidence calculation; The sentinel system has been providing more detailed information about vaccination status, better data quality and continuous national data since 2005, irrespective of the Infectious disease protection act. Trends and age distribution can be continuously calculated, whereas the nationwide mandatory data collected in the short period since April 2013 can only be evaluated to a limited extent.

Control of varicella in the post-vaccination era in Australia: a model-based assessment of catch-up and infant vaccination strategies for the future.

In Australia, varicella vaccine was universally funded in late 2005 as a single dose at 18 months. A school-based catch-up programme for children aged 10-13 years without a history of infection or vaccination was funded until 2015, when those eligible for universal infant vaccination would have reached the age of high school entry. This study projects the impact of discontinuing catch-up vaccination on varicella and zoster incidence and morbidity using a transmission dynamic model, in comparison with alternative policy options, including two-dose strategies. At current vaccine coverage (83% at 2 years and 90% at 5 years), ceasing the adolescent catch-up programme in 2015 was projected to increase varicella-associated morbidity between 2035 and 2050 by 39%. Although two-dose infant programmes had the lowest estimated varicella morbidity, the incremental benefit from the second dose fell by 70% if first dose coverage increased from 83% to 95% by age 24 months. Overall zoster morbidity was predicted to rise after vaccination, but differences between strategies were small. Our results suggest that feasibility of one-dose coverage approaching 95% is an important consideration in estimating incremental benefit from a second dose of varicella vaccine.

[Varicella vaccine potency and stability during transport and delivery].

Oka varicella vaccine was developed to confer active immunity to varicella-zoster virus (VZV) in immunocompromized and immunocompetent children. It is now used to prevent varicella in about 20 million people worldwide. Although VZV infectivion is relatively unstable compared to other viruses, cell-free virus is stabilized and lyophilized vaccine has been developed. Virus titers were evaluated in vaccine distributed to six clinics in 5 years. Yearly mean virus titers at the vaccine producer were 42,000-67,000 plaque-forming units per dose, corresponding to Oka varicella vaccine (Zostavax) used to prevent zoster and postherpetic neuralgia by Oxman et al. Virus titer was found to be stable during delivery to clinics. Virus titers of varicella vaccine were equivalent to Zostavax and vaccine delivered to clinics had enough virus titer to confer active immunity to VZV in this study.

Routine Childhood Vaccines Given From 1 through 18 Years of Age.

In addition to the vaccines due in the first year of life, the US Advisory Committee on Immunization Practices recommends that children continue to receive vaccines regularly against a variety of infectious diseases. Starting at 12 to 15 months of life, these include the two-dose measles-mumps-rubella vaccine series and the two-dose varicella vaccine series. Also in the second year of life, infants should begin the two-dose hepatitis A vaccine series and complete the Haemophilus influenzae type B vaccine series as well as the pneumococcal conjugate vaccine series. Before 19 months of life, infants should receive the third dose of the poliovirus vaccine and the fourth dose of diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The final doses of poliovirus and tetanus-diphtheria-acellular pertussis vaccines are both due at 4 to 6 years of life. Before each influenza season, every child should receive the influenza vaccine. Those less than 9 years of age who previously received less than two doses need two doses a month apart. At 11 to 12 years of life, all should get two doses of the human papillomavirus vaccine, the adolescent/adult version of the tetanus-diphtheria-acellular pertussis vaccine, and begin a two-dose series of meningococcal ACWY vaccine. Each of these vaccines is due when the vaccine works to protect against both an immediate risk as well as to provide long-term protection. Each vaccine-preventable disease varies in terms of the nature of exposure, the form of the morbidity, the risk of mortality, and potential to prevent or ameliorate its harm.

Safety, immunogenicity, and lot-to-lot consistency of live attenuated varicella vaccine in 1-3 years old children: a double-blind, randomized phase III trial.

The study was to evaluate the safety, immunogenicity and lot-to-lot consistency of live attenuated varicella vaccine in Chinese population aged 1-3 years. The double-blind, randomized phase III trial was conducted in Henan Province, China. In total, 1197 subjects were included in this study. Subjects were randomly assigned into four groups in a 2:2:2:1 ratio to receive one of the three lots of commercial scale (CS) vaccine or the licensed pilot scale (LPS) vaccine. Seroconversion rate and neutralizing antibody titers (NATb) were assessed at day 0 pre-vaccination and at day 30 post-vaccination. Safety data were recorded for 30 days post-vaccination. After vaccination, the geometric mean titers (GMTs) of the three CS groups were 25.04 (95% confidence interval [CI], 22.85 to 27.44), 24.47 (95% CI, 22.35 to 26.78) and 25.88 (95% CI, 23.61 to 28.36), respectively (P= 0.6928). The ratio of GMTs adjusted for covariates of each pair of lots were all between 0.67 to 1.50 in susceptible subjects. The difference of seroconversion rate between pooled CS group and LPS group was 3.82 (95% CI, 0.55 to 8.81). Meanwhile, the percentage of solicited local, systemic and unsolicited adverse reactions showed no difference across the four groups, and most of the adverse reactions were mild or moderate in intensity. The CS group was comparable to the LPS group in safety and immunogenicity. The consistency of three consecutive CS lots was reliable. Moreover, the CS group was non-inferior to the LPS group.

[Awareness and application of vaccine recommendations for chickenpox in French Nurse Schools]. / Connaissance et application des recommandations vaccinales concernant la varicelle en institut de soins infirmiers en France.

Since 2004, the French High Committee on Public Hygiene has recommended chickenpox vaccination for first-year medical or paramedical students with no history of chickenpox and with negative serology. A survey was carried out among directors of nurse schools to evaluate both their awareness of these new recommendations and the way in which they had been applied. A questionnaire was sent by mail to each of the directors of the 332 nurse schools identified throughout France. Less than half (41%) of the 147 directors who responded said they were aware of recommendations, and 31% stated they had real knowledge of the recommendations. Only 21% enquire about chickenpox history of students enrolling in their school, and 9% undertake serological assessment of students with no known history of varicella or zoster. More needs to be done both to inform nurse school directors of the vaccine recommendations and to ensure their application.

Update From the Advisory Committee on Immunization Practices.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts, meets 3 times per year to develop recommendations for vaccine use in the United States. The group has 15 voting members, and each member's term is 4 years. ACIP members and Centers for Disease Control and Prevention (CDC) staff discuss the epidemiology of vaccine-preventable diseases and vaccine research, effectiveness, safety data, and clinical trial results. Representatives from the American Academy of Pediatrics (Carrie L. Byington and D. W. K.) and the Pediatric Infectious Diseases Society (S. T. O.) are present as liaisons to the ACIP. The ACIP met on June 21 to 22, 2017, to discuss catch-up vaccination for hepatitis A vaccine, influenza surveillance, influenza vaccine effectiveness, herpes zoster vaccine, the effect of varicella vaccination on the incidence of herpes zoster, meningococcal disease in patients taking eculizumab, and considerations for a potential third dose of measles, mumps, and rubella (MMR) vaccine to combat ongoing mumps outbreaks. Updates on dengue virus epidemiology, Zika virus vaccines, anthrax vaccine, yellow fever vaccine, and the Vaccine Adverse Event Reporting System were given also.

The safety and immunogenicity of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children: a study of manufacturing consistency and persistence of antibody.

BACKGROUND: This clinical trial was conducted to demonstrate that each of 3 consistency lots of a combined measles, mumps, rubella and varicella vaccine (MMRV) would be well tolerated, induce clinically acceptable and similar immune responses to each antigen and induce immune responses similar to measles, mumps and rubella vaccine (MMR) administered concomitantly with varicella vaccine (V). An additional objective was to evaluate the persistence of antibodies 1 year postvaccination. METHODS: Study participants 12 to 23 months of age received a single injection of either one of 3 consistency lots of MMRV or MMR + V administered at separate injection sites. RESULTS: A total of 3,928 healthy children were enrolled at study sites in the United States and Canada. Immune responses to measles, mumps, rubella and varicella in children immunized with each of 3 lots of MMRV were similar and the combined response to all 3 lots was comparable to that of the control group. The 1-year antibody persistence rates for measles, mumps, rubella and varicella viruses were each greater than 95% and comparable among the recipients of the 3 consistency lots of MMRV and the control group. All vaccines were generally well tolerated during the 42 days after vaccination and the overall incidence of adverse experiences was comparable between recipients of MMRV and MMR + V. Rates of fever (temperature >or=38.9 degrees C oral equivalent or tactile) were greater in recipients of MMRV than in recipients of MMR + V (39.1% versus 33.1%, P = 0.001). Fevers were transient and there was no difference in the incidence of febrile seizures. CONCLUSIONS: MMRV was generally well tolerated and had comparable immunogenicity and overall safety profiles to MMR + V administered concomitantly. Long-term persistence of antibodies after receipt of MMRV is expected based on similar antibody titers against all 4 antigens 1 year postvaccination compared with recipients of MMR and V.

Susceptibility to varicella-zoster among pregnant women in the province of Lecce, Italy.

BACKGROUND: Varicella is predominantly a childhood disease, considered a mild self-limiting disease that can have serious complications for a pregnant woman and her developing fetus. OBJECTIVES: We investigated the susceptibility to varicella-zoster Virus (VZV) among pregnant women in the province of Lecce. STUDY DESIGN: A cross-sectional study was carried out in Departments of Gynecology and Obstetrics of the Province of Lecce, where 539 pregnant women were recruited, and face-to-face interviews were conducted. Varicella IgG tests were performed. RESULTS: The prevalence of varicella susceptibility among pregnant mothers was 10.6%. The prevalence of IgG antibodies increases significantly with increasing age, from 62.5% in the age group 15-19 years to 94.4% in the age group 40-49 years. DISCUSSION: In the Italian National Vaccination Plan 2005-2007, varicella vaccine is only recommended for childbearing women. A safe and effective vaccine is available and no abnormalities have been observed among infants born to susceptible women who received varicella vaccines during pregnancy. Such a high number of susceptible women indicates that preventive and informative programs should be introduced, even among those who do not plan to become pregnant. Routine counselling, varicella IgG antibody screening and varicella vaccination should be considered if they have no history of the infection, to reduce the risk of fetal complications and the cost of healthcare associated with the infection.

Rapid and accurate determination of the potency of varicella vaccine by quantitative polymerase chain reaction.

The potency of varicella vaccines is currently determined by a plaque assay technique, which usually takes seven days and is laborious and has considerable inter- and intra-assay variability. Here, we report a new potency assay for varicella vaccine based on quantitative polymerase chain reaction in conjunction with a much more efficient virus infection step. Potency results can be obtained within 24h of infection and demonstrates acceptable accuracy and reproducibility when compared with the plaque assay, which relies on manual counting of plaques formed one week after viral infection. Using multiple vaccine lots from 7 manufacturers, we found no significant difference in infectivity determined between the new assay and plaque assay. The optimized conditions for viral infection and polymerase chain reaction are of significant value for the potency determination of the vaccine due to its rapidity, accuracy and the high throughput capacity of the assay.

Establishment of the Ph. Eur. BRP for varicella vaccine batch 1.

The European Pharmacopoeia (Ph. Eur.) monograph for varicella vaccine (live) (0648) requires a vial of an appropriate reference material to be titred in triplicate to validate each assay and the virus concentration of the reference preparation is monitored using a control chart to determine the assay consistency. An international collaborative study involving 9 participants from 7 countries and including both OMCLs and manufacturers was carried out to establish a common reference material for this purpose and establish a Ph. Eur. Biological Reference Preparation. Two candidate reference preparations (X and Y), obtained from 2 different EU manufacturers, were assayed by the participants using their in-house PFU assay methods. Both candidates were found to be suitable for this purpose. Based on logistical considerations, candidate X (4.37 log(10)0 PFU/vial) has been established as BRP batch 1 of varicella vaccine (live) and was adopted at the June 2009 session of the European Pharmacopoeia Commission for immediate use. Candidate Y (3.82 log(10) PFU/vial) will be established as BRP batch 2 upon depletion of BRP batch 1 provided that the stability data supports this.

Impact of vaccination against varicella on the reduction of the disease incidence in children and adolescents from Florianópolis, Brazil.

OBJECTIVE: To evaluate the impact of universal early childhood vaccination against varicella on the reduction of its incidence in a state capital in southern Brazil. METHODS: Official epidemiologic surveillance data from the SINAN database for the 1997-2007 period were used to evaluate the impact of varicella vaccination targeting all children < 2 years of age in Florianópolis (the capital city of the state of Santa Catarina), Brazil, since 2002, thus comprising 5 years before and 6 years after the vaccination. Varicella incidence in Florianópolis was compared with the incidence in the rest of the state for four age groups (< 1, 1-4, 5-9, and 10-14 years). RESULTS: Among the 135,311 cases of varicella in the state of Santa Catarina during the 1997-2007 period, 70% were children under 10 years of age. The effectiveness of varicella vaccine ranged from 27 to 38% among the age groups but reached statistical significance only for children 1-4 years old. CONCLUSION: The vaccine was effective in reducing varicella incidence in Florianópolis for children 1-4 years old.

Comparison of the safety and immunogenicity of a refrigerator-stable versus a frozen formulation of ProQuad (measles, mumps, rubella, and varicella virus vaccine live).

OBJECTIVE: A refrigerator-stable formulation of ProQuad has been developed to expand the utility of ProQuad to areas in which maintenance of a frozen cold chain (-15 degrees C or colder) during storage and transport may not be feasible. The objective of this study was to demonstrate that the immunogenicity and safety profiles of a refrigerator-stable formulation of ProQuad are similar to the recently licensed frozen formulation. METHODS: In this double-blind, randomized, multicenter study, healthy 12- to 23-month-old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either the refrigerator-stable formulation of ProQuad (N = 1006) or the frozen formulation of ProQuad (N = 513). Patients were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination. RESULTS: The refrigerator-stable formulation of ProQuad was generally well tolerated. The incidence of adverse experiences was similar between groups. No vaccine-related serious adverse experiences were reported. For both groups, the response rate was > or = 97.7% for measles, mumps, and rubella, and the percentage of patients with a varicella zoster virus antibody titer of > or = 5 U/mL glycoprotein antigen-based enzyme-linked immunosorbent assay after vaccination was > or = 88.8%. The geometric mean titers for all antigens were numerically slightly higher in patients who received the refrigerator-stable formulation. CONCLUSIONS: The refrigerator-stable formulation of ProQuad is generally well tolerated, highly immunogenic, and noninferior in terms of postvaccination antibody responses. This refrigerator-stable formulation may improve ease of vaccine administration, increase use of the vaccine throughout the world because of its improved storage conditions, and replace the frozen formulation of ProQuad or any dose of M-M-RII and Varivax in routine practice.

Impacto da vacinação contra varicela na redução da incidência da doença em crianças e adolescentes de Florianópolis (SC) / Impact of vaccination against varicella on the reduction of the disease incidence in children and adolescents from Florianópolis, Brazil

OBJETIVO: Avaliar o impacto da vacinação universal infantil precoce contra a varicela sobre a redução da incidência da doença em uma capital da Região Sul do Brasil. MÉTODOS: Dados oficiais de vigilância epidemiológica obtidos do banco de dados do SINAN para o período de 1997-2007 foram utilizados para avaliar o impacto da vacinação contra a varicela direcionada a todas as crianças menores de 2 anos de idade em Florianópolis desde 2002, incluindo assim 5 anos antes e 6 anos após a vacinação. A incidência de varicela em Florianópolis foi comparada com a incidência no interior do estado para quatro faixas etárias (< 1, 1-4, 5-9 e 10-14 anos). RESULTADOS: Entre os 135.311 casos de varicela no estado de Santa Catarina durante o período de 1997-2007, 70 por cento eram crianças com menos de 10 anos. A eficiência da vacina da varicela variou de 27 a 38 por cento entre as faixas etárias, mas alcançou significância estatística somente para a faixa etária de 1 a 4 anos. CONCLUSÃO: A vacina foi eficaz na redução da incidência da varicela em Florianópolis para a faixa etária entre 1 e 4 anos de idade.

OBJECTIVE: To evaluate the impact of universal early childhood vaccination against varicella on the reduction of its incidence in a state capital in southern Brazil. METHODS: Official epidemiologic surveillance data from the SINAN database for the 1997-2007 period were used to evaluate the impact of varicella vaccination targeting all children < 2 years of age in Florianópolis (the capital city of the state of Santa Catarina), Brazil, since 2002, thus comprising 5 years before and 6 years after the vaccination. Varicella incidence in Florianópolis was compared with the incidence in the rest of the state for four age groups (< 1, 1-4, 5-9, and 10-14 years). RESULTS: Among the 135,311 cases of varicella in the state of Santa Catarina during the 1997-2007 period, 70 percent were children under 10 years of age. The effectiveness of varicella vaccine ranged from 27 to 38 percent among the age groups but reached statistical significance only for children 1-4 years old. CONCLUSION: The vaccine was effective in reducing varicella incidence in Florianópolis for children 1-4 years old.