Febrile events including convulsions following the administration of four brands of 2010 and 2011 inactivated seasonal influenza vaccine in NZ infants and children: the importance of routine active safety surveillance

Objective

To evaluate and compare rates of febrile events, including febrile convulsion, following immunisation with four brands of inactivated 2010 and 2011 influenza vaccine in NZ infants and children.

Design

Retrospective telephone surveys of parents of infants and children who received at least one dose of the vaccines of interest.

Setting

184 NZ General Practices who received the vaccines of interest.

Participants

Recipients of 4088 doses of trivalent inactivated vaccines Fluvax^®, Vaxigrip^®, Influvac^® and Fluarix^® and/or monovalent Celvapan. Vaccinees were identified via the electronic Practice Management System and contacted consecutively.

Main outcome measures

Primary outcome was febrile convulsive seizure. Secondary outcomes were presence of fever plus other organ system specific symptoms.

Results

The parental response rate was 99%. Of 4088 doses given, 865 were Fluvax^®, 2571 Vaxigrip^®, 204 Influvac^®, 438 Fluarix^® and 10 Celvapan. Three febrile convulsions followed Fluvax^®, a rate of 35 per 10,000 doses. No convulsions occurred following any dose of the other vaccines. There were nine febrile events that included rigors, all following Fluvax^®. Fever occurred significantly more frequently following administration of Fluvax^® compared with the other brands of vaccines (p < 0.0001) and Fluvax recipients were more likely to seek medical attention. Influvac^® also had higher rates of febrile reactions (OR 0.54, 0.36–0.81) than the other two brands Vaxigrip^® (OR 0.21, 0.16–0.27) and Fluarix^® (OR 0.10, 0.05–0.20). After multivariable analysis vaccine, European ethnicity and second dose of vaccine were significantly associated with reporting of fever within 24 h of vaccination.

Conclusions

Influenza vaccines have different rates of reactogenicity in children which varies between ethnic groups. High rates of febrile convulsions and reactions in children receiving Fluvax^® and to a lesser extent the higher fever rates in those receiving Influvac^® compared with the other two brands of influenza vaccines in this study suggests that reactogenicity profiles need to be considered prior to national policy advice each season. The risk-benefit profile in children might not be equally favourable for all licensed paediatric influenza vaccines. More attention needs to be given to comparative research for all trivalent seasonal vaccines, and with all strain changes.     

Trivalent influenza vaccine and febrile adverse events in Australia, 2010: clinical features and potential mechanisms

Introduction

Increased numbers of children presenting with febrile adverse events following trivalent influenza vaccine (TIV) were noted in Australia in 2010. We describe the epidemiology and clinical features of the adverse events and explore the biological basis for the adverse events using an in vitro model.

Materials and Methods

Children presenting to a tertiary paediatric hospital in 2010 with adverse events within 72 h of TIV were retrospectively reviewed. Demographics, clinical features, physiological variables and outcomes were examined. Plasma cytokine and chemokine levels were examined in a subgroup of children with vaccine-related febrile convulsions. Peripheral blood mononuclear cells of age-matched children were stimulated with different TIV preparations. Inflammatory cytokine and chemokine analysis was performed on cultured supernatants.

Results

Vaccine-related febrile adverse events were identified in 190 children. Most occurred in healthy children (median age: 1.5 years) within 12 h of vaccination. Twenty-eight (14.7%) required hospital admission. High temperature ≥39.0 °C (101/190; 53%), vomiting (120/190; 63%) and convulsions (38/190; 20%) were common. All children presenting had received Fluvax^® or Fluvax Junior^®.In the in vitro model, IFN-α, IL-1β, IL-6, IL-10, IP-10 and MIP-1α levels were significantly higher when measured at 6 and 24 h in cultures stimulated with Fluvax^® compared with alternative 2010 TIV preparations.

Conclusions

Numerous febrile adverse events (including febrile seizures) were observed following Fluvax^® or Fluvax Junior^® in 2010. Clear differences in cytokine production were observed when peripheral blood mononuclear cells were stimulated with Fluvax^® compared with alternate TIV preparations. Increased awareness of these potential adverse events is required to ensure earlier detection and prevention in the future.     

General practice encounters following seasonal influenza vaccination as a proxy measure of early-onset adverse events

Background

In 2010, use of seasonal trivalent influenza vaccine (TIV) in children <5 years of age was suspended in Australia following reports of vaccine-related febrile convulsions. We investigated the utility of data on primary care [general practice (GP)] consultations for any reason within three days of receipt of influenza vaccine as recorded on the Australian Childhood Immunisation Register (ACIR) as a means of signal detection.

Methods

Data on GP consultations were obtained from Medicare Australia (Australian Government Department of Human Services) for children recorded on the ACIR as receiving either TIV or monovalent influenza vaccine. Rates of GP consultation by day following ACIR-recorded receipt of influenza vaccine were compared by year (2008–2010), vaccine type, age and region.

Results

In 2010, GP encounter rates on the day after receipt of the TIV manufactured by bioCSL (formerly CSL Biotherapies (Fluvax^®) were significantly higher than both bioCSL TIVs in the previous two years [rate ratio (RR) 1.9; 95% CI: 1.7–2.2] and Sanofi Pasteur TIV, Vaxigrip^® [RR 1.6, 95% CI 1.4–1.7] in 2009–2010. Encounter rates were also higher than for CSL Monovalent influenza vaccine, Panvax^® [RR 1.9, 95% CI 1.7–2.2] in 2009–2010. These findings were robust to adjustment for age group (≤2, >2 years) and region (Western Australia vs other Australian states/territories).

Conclusions

A primary care consultation on the day after vaccine receipt is a reasonable proxy for early reactogenicity and has potential for use in various settings.     

Reactogenicity of two 2010 trivalent inactivated influenza vaccine formulations in adults

Objective

To assess the reactogenicity of two 2010 trivalent inactivated influenza vaccine (TIV) formulations among adults, including the formulation associated with febrile convulsions among children in Australia.

Design, setting and participants

We retrospectively interviewed persons aged ≥18 years who received TIV between 11 March and 24 April 2010 at a large general practice in Perth. All 160 persons who received Influvac® (Solvay) and a random sample of 190 of 451 persons who received Fluvax® (CSL Biotherapies) were included in the assessment; 127 (79%) recipients of Influvac® and 156 (82%) of the Fluvax® recipients completed the interview.

Main outcome measures

Patient demographics, the presence of underlying medical conditions, prior influenza vaccination history, self-reported onset of local and/or systemic symptoms within 72 h following receipt of 2010 TIV, and use of anti-fever/pain medication following TIV vaccination were examined.

Results

The mean age of the vaccinees was 54 years for both the Fluvax® and Influvac® brand cohorts and there was no significant difference between the cohorts with regard to gender or the presence of underlying medical conditions. In bivariate analyses, reported swelling (18% vs 7%, p = 0.009), muscle pain (12% vs 3%, p = 0.014) and use of anti-fever/pain medication after TIV vaccination (12% vs 2%, p = 0.008) were each significantly more common for patients who received Fluvax® compared to those who received Influvac®. In multivariate analyses simultaneously controlling for age, gender, receipt of seasonal influenza vaccine prior to 2010 and receipt of 2009 H1N1 pandemic vaccine, vaccination with Fluvax® TIV was a significant independent predictor of muscle pain and/or swelling (OR = 3.3, 95% CI 1.5-7.4 p = 0.004). No significant differences in the proportion of patients reporting systemic reactions were observed.

Conclusions

In this setting, 2010 Fluvax® was associated with a greater likelihood of local reactions among adults, compared to 2010 Influvac® TIV.     

Knowledge, attitudes, and beliefs about seasonal influenza and H1N1 vaccinations in a low-income, public health clinic population

Objective

The Public Health Center Vaccine Survey (PHCVS) examines the knowledge, attitudes, and beliefs about seasonal influenza and H1N1 vaccinations in a largely low-income, urban, public health clinic population in Los Angeles County, USA.

Design

A cross-sectional survey of vulnerable individuals at risk for severe influenza infection was conducted in one of the nation's largest local public health jurisdictions.

Subjects

A total of 1541 clinic patients were recruited in the waiting rooms of five large public health centers in Los Angeles County from June to August, 2010.

Results

Among prospective respondents who met eligibility criteria, 92% completed the survey. The majority was black or Latino and most were between the ages of 18 and 44 years. More than half were unemployed; two-thirds had no health insurance; and nearly one-half reported having a high school education or less. About one-fifth reported they had received the H1N1 vaccine during the previous flu season. In comparative analyses, negative beliefs about vaccine safety and efficacy were highly predictive of H1N1 vaccination. Blacks were less likely than non-black respondents to report receiving the H1N1 vaccine (OR = 0.7, 95% CI = 0.6-1.0). Blacks were also less likely than other respondents to agree that vaccines can prevent disease (OR = 0.4, 95% CI = 0.3-0.5), that vaccines are safe (OR = 0.5, 95% CI = 0.4-0.6), and that they trust doctors/clinicians who recommend vaccines (OR = 0.5, 95% CI = 0.4-0.7).

Conclusions

Study findings provide a useful risk profile of vulnerable groups in Los Angeles County, which may be generalizable to other urban jurisdictions in the United States. They also describe real world situations that can be used to forecast potential challenges that vaccine beliefs may pose to national as well as local influenza pandemic planning and response, especially for communities with limited access to these preventive services.     

Comparing live attenuated and inactivated hepatitis A vaccines: an immunogenicity study after one single dose

Introduction

While three types of hepatitis A vaccines are available in China, little data are available to compare them in terms of early antibody response. We conducted a trial to compare antibody response at 7, 14 and 28 days.

Methods

We randomized primary school children in Gansu and Jilin provinces into four groups to receive either (1) Chinese live attenuated hepatitis A vaccine (H2 strain), (2) domestic inactivated hepatitis A vaccine (Healive^®), (3) imported inactivated hepatitis A vaccine (Havrix^®) or (4) hepatitis B vaccine (Control group). We compared groups at 7, 14 and 28 days in terms of proportion of sero-conversions (≥10 mUI/ml), and Geometric Mean Concentration (GMC) of antibodies measured with a Microparticle Enzyme Immunoassay (MEIA). We compared rates of self-reported adverse events following immunization (AEFI) in the first three days.

Results

204 children received the H2 vaccine, 208 received Healive^®, 214 received Havrix^®, and 215 received hepatitis B vaccine (no differences across groups in terms of age, sex, weight and height). At seven days, sero-conversion proportions were 25%, 35%, 27% and 2% (p < 0.0001) with GMC of 6 mIU/ml, 8 mIU/ml, 6 mIU/ml and 3 mIU/ml, respectively for the four groups. At 28 days, sero-conversion proportions were 98%, 100%, 93% and 3% (p < 0.0001) with GMC of 47 mIU/ml, 71 mIU/ml, 67 mIU/ml and 3 mIU/ml, respectively. AEFI were benign and did not differ across groups (p = 0.94).

Conclusions

While our study was not able to identify differences between Havrix^®, Healive^® and H2 vaccine in terms of sero-conversion proportion and GMC between seven and 28 days, further studies should evaluate non-inferiority or equivalence of the Chinese vaccines, particularly with respect to the GMC concentration for the H2 vaccine since it could affect long-term protection.     

An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (Kinrix™) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children

Background

In the US, it is recommended that 4-6 year old children receive diphtheria-tetanus-acellular pertussis (DTaP), inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella (V), and influenza vaccines. Data relating to the concomitant administration of combination DTaP-IPV vaccine (Kinrix™; GlaxoSmithKline Biologicals) and influenza or V vaccines are currently limited. This study was undertaken to evaluate the immunogenicity and reactogenicity of Kinrix™ when co-administered with MMR (M-M-RII^®, Merck & Co.) and Varivax™ (Merck & Co.) in 4-6 year old children.

Methods

Phase IIIb, open-label, non-inferiority study (NCT00871117). We randomized (1:1) healthy 4-6 year olds to receive Kinrix™ + MMR + V on day 0 (Group 1), or Kinrix™ + MMR on day 0, followed by V at month 1 (Group 2). We measured DTaP-IPV immunogenicity before and 1 month post-vaccination (prior to V vaccination in Group 2). We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events (SAEs) through 6 months post-vaccination.

Results

We enrolled 478 subjects. One month post-vaccination, >95% of subjects in both groups had booster responses to diphtheria, tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers. Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre-specified criteria. Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups, as was reporting of solicited general adverse events within 4 days of vaccination; no vaccine related SAEs were reported.

Conclusion

Concomitant administration of varicella vaccine with Kinrix™ and MMR did not impact the immunogenicity of diphtheria, tetanus, pertussis or poliovirus antigens. Both vaccine regimens were well tolerated. These results support the co-administration of DTaP-IPV, MMR, and V vaccines in 4-6-year-old children, providing protection against multiple diseases in a timely and efficient manner.     

Financing and systems barriers to seasonal influenza vaccine delivery in community settings

Background

Recommendations for annual seasonal influenza vaccination have expanded to now include >300 million children and adults each year. Community settings have become increasingly important venues for influenza vaccination. We sought to identify barriers to and solutions for expanding influenza vaccination in community settings.

Methods

Semi-structured telephone interviews were conducted from 01/09 to 06/10 with a range of stakeholders involved in influenza vaccination, including health plans, medical services firms, retail based clinics, pharmacies, schools, and state and local public health immunization programs. Participants (n = 65) were asked about barriers and feasible solutions to influenza vaccine delivery to children and adults in community settings. Key themes were identified through iterative coding using a grounded theory approach.

Results

Stakeholders identified specific financial barriers to influenza vaccine delivery in 3 major areas: purchase and distribution, delivery, and reimbursement. Limited purchasing power, the uncertain nature of public demand, and unpredictable timing of influenza vaccine supply were important barriers to enhance delivery in community settings. Barriers to delivery included complexities in running off-site clinics, especially in school settings, the need to manage publicly vs. privately purchased vaccines separately, and state-to-state variability in requirements for credentialing, physician oversight, and reporting. Reimbursement barriers included a protracted credentialing process, the need to determine insurance eligibility at point-of-service, and lack of a billing infrastructure in off-site clinics. Opportunities to mitigate financial barriers to influenza vaccine delivery in community settings focused on coordination across providers and the role of public health as a “trusted broker” to overcome existing challenges.

Conclusions

Financial and systems barriers hamper the optimal use of community settings to effectively deliver influenza vaccines. Public health partners at the federal, state, and local levels are well-positioned to facilitate the engagement of all stakeholders in this important and complex vaccine delivery system.     

Vaccination and risk of type 1 diabetes mellitus in active component U.S. Military, 2002-2008

Aims/hypothesis

To evaluate whether vaccination increases the risk of type 1 diabetes mellitus in active component U.S. military personnel.

Methods

We conducted a retrospective cohort study among active component U.S. military personnel age 17-35 years. Individuals with first time diagnoses of type 1 diabetes between January 1, 2002 and December 31, 2008 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We used Poisson regression to estimate risk ratios between individual vaccine exposures and type 1 diabetes. Secondary analyses were performed controlling for receipt of multiple vaccines and available demographic variables.

Results

Our study population consisted of 2,385,102 individuals followed for approximately 7,644,098 person-years of service. This included 1074 incident type 1 diabetes cases. We observed no significant increased risk of type 1 diabetes after vaccination with anthrax vaccine adsorbed (AVA) [RR = 1.00; 95% CI (0.85, 1.17)], smallpox vaccine [RR = 0.84; 95% (CI 0.70, 1.01)], typhoid vaccine [RR = 1.03; 95% CI (0.87, 1.22)], hepatitis B vaccine [RR = 0.83; 95% CI (0.72, 0.95)], measles mumps rubella vaccine (MMR) [RR = 0.71, 95% CI (0.61, 0.83)], or yellow fever vaccine [RR = 0.70; 95% CI (0.59, 0.82)].

Conclusions

We did not find an increased risk of diagnosed type 1 diabetes and any of the study vaccines. We recommend that follow-up studies using medical record review to confirm case status should be considered to corroborate these findings.     

Acute disseminated encephalomyelitis following influenza vaccination

Introduction

Approximately 5% of cases of acute disseminated encephalomyelitis are preceded by vaccination within 1 month prior to symptom onset. This occurs rarely following influenza immunization.

Methods

Case presentation and literature review.

Results

A 75-year-old woman developed acute disseminated encephalomyelitis within 3 weeks of receiving the seasonal influenza vaccine. The patient subsequently passed away, despite treatment with methylprednisolone and plasma exchange therapy.

Conclusions

The literature on post-influenza vaccination encephalomyelitis is limited. The majority of published cases had favourable outcomes following treatment with intravenous methylprednisolone. Given the limited number of cases, no incidence estimates have been published.     

Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: A phase I–II randomized trial

Objective

Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children.

Methods

An open-labelled phase I trial was conducted in children aged 3–11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5–30 μg) and in children aged 12–17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5–15 μg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3–11 years received the split-virion vaccine (10 or 15 μg) and 280 children aged 12–17 years received the split-virion vaccine (10–30 μg) or the whole-virion vaccine (5 μg). Serum samples were collected for hemagglutination-inhibition (HI) assays.

Findings

5–15 μg adjuvated split-virion vaccines were well tolerated in children aged 3–11 years and 5–30 μg adjuvated split-virion vaccines and 5 μg adjuvated whole-virion vaccine were well tolerated in children aged 12–17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3–11 years children, the 10 and 15 μg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer ≥1:40) rates. In 12–17 years children, the 30 μg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 μg whole-virion vaccine induced higher response than the 10 μg split-virion vaccine did.

Interpretation

The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in children and 30 μg dose induced immune response complying with European Union licensure criteria. [ClinicalTrials.gov identifiers: NCT00900588 and NCT00900991].     

Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok®) against influenza in healthy adults: a randomized, placebo-controlled trial

Background

Development of influenza vaccines that do not use embryonated eggs as the substrate for vaccine production is a high priority. We conducted this study to determine the protective efficacy a recombinant, baculovirus-expressed seasonal trivalent influenza virus hemagglutinin (rHA0) vaccine (FluBlok^®).

Methods

Healthy adult subjects at 24 centers across the US were randomly assigned to receive a single injection of saline placebo (2304 subjects), or trivalent FluBlok containing 45 mcg of each rHA0 component (2344 subjects). Serum samples for assessment of immune responses by hemagglutination-inhibition (HAI) were taken from a subset of subjects before and 28 days after immunization. Subjects were followed during the 2007-2008 influenza season and combined nasal and throat swabs for virus isolation were obtained from subjects reporting influenza-like illness.

Results

Rates of local and systemic side effects were low, and the rates of systemic side effects were similar in the vaccine and placebo groups. HAI antibody responses were seen in 78%, 81%, and 52% of FluBlok recipients to the H1, H3, and B components, respectively. FluBlok was 44.6% (95% CI, 18.8%, 62.6%) effective in preventing culture-confirmed influenza meeting the CDC influenza-like illness case definition despite significant antigenic mismatch between the vaccine antigens and circulating viruses.

Conclusions

Trivalent rHA0 vaccine was safe, immunogenic and effective in the prevention of culture confirmed influenza illness, including protection against drift variants.     

Live attenuated seasonal and pandemic influenza vaccine in school-age children: A randomized controlled trial

Background

The novel influenza A(H1N1pdm09) virus emerged in North America in early 2009 and rapidly spread worldwide. In this study we report the efficacy of the live attenuated monovalent H1N1pdm09 vaccine and 2009–10 seasonal influenza vaccine in a randomized double-blind placebo-controlled trial.

Methods

We enrolled 703 children aged 7–11. Each child was randomly allocated in the ratio 3:2 to receive one dose of live attenuated monovalent H1N1pdm09 vaccine or saline placebo between November 2009 and January 2010, followed after 3–10 weeks by independent random allocation to one dose of live attenuated trivalent 2009–10 seasonal influenza vaccine or saline placebo in the same ratio. Children were followed up through September 2010 with biweekly telephone calls and symptom diaries. Seasonal and pandemic influenza infections were confirmed by virologic testing of nose and throat swabs collected during acute respiratory illnesses.

Results

Overall, 30 children had confirmed influenza including 3 (0.43%) H1N1pdm09, 10 (1.4%) seasonal A(H3N2), and 17 (2.4%) influenza B. There were no significant differences in incidence rates of H1N1pdm09 or A(H3N2) between the four study arms, but receipt of the seasonal influenza vaccine was associated with a significant reduction in risk of influenza B (p < 0.01). Vaccine efficacy against confirmed H1N1pdm09 infection associated with receipt of the monovalent H1N1pdm09 vaccine was 65% (95% confidence interval, CI: −281%, 97%). Vaccine efficacies against confirmed seasonal influenza A(H3N2) and B infection associated with receipt of the seasonal influenza vaccine were 31% (95% CI: −138%, 80%) and 96% (95% CI: 67%, 99%) respectively.

Conclusions

Vaccine efficacy was consistent with other studies of the monovalent H1N1pdm09 vaccine and seasonal influenza vaccines. Our study was underpowered to provide precise estimates of vaccine efficacy due to low incidence of influenza A viruses during the study period.     

A comparative study to evaluate the safety and immunogenicity of two lots of Haemophilus influenzae type-B conjugate vaccine manufactured at different scales

Objective

To compare the immunogenicity and safety of two different lots of SII Haemophilus influenzae type-B-tetanus toxoid conjugate (SII HibP_RO) vaccine manufactured at different scales when given in 3-dose schedule.

Design

Phase IV, open label, comparative, randomized parallel group study.

Setting

Shirdi Sai Baba Hospital, Vadu Budruk, Pune and Pediatrics Department of King Edward Memorial Hospital Research Centre, Pune.

Subjects

204 normal healthy infants of age 6-8 weeks at the time of first vaccination.

Methods

The eligible subjects received 3 doses of 0.5 ml of SII HibP_RO vaccine of either lot depending upon randomization number, intramuscularly in right thigh in the EPI schedule of 6, 10 and 14 weeks. They also received concomitantly DTP-HB vaccine intramuscularly on left thigh and Oral Polio vaccine (OPV). Solicited reactions were captured for 7 days following each vaccination; the events beyond 7 days till day 28 were captured as unsolicited adverse events. Serious Adverse Events (SAEs) were looked for throughout the subject participation. Blood samples were collected at baseline (before the first dose) and one month after the third dose for anti-PRP (polyribosylribitol phosphate) antibodies.

Results

In both groups, more than 98% subjects achieved short-term seroprotection (anti-PRP ≥ 0.15 μg/ml) after 3 doses. The long-term seroprotection (anti-PRP ≥ 1 μg/ml) was 87% and 80% in infants receiving lot manufactured at industrial scale and small scale respectively. Short and long term seroprotection and GMTs increased significantly as compared to baseline in both the groups. Overall local pain (52% and 58%), redness (30% and 41%), swelling (34% and 44%), fever (6% and 6%) and irritability (52% and 50%) were reported in infants receiving lot manufactured at industrial scale and small scale respectively. Majority of the reactions were mild and resoled without any sequelae. Four SAEs, none of them causally related to the study vaccine, occurred during study.

Conclusion

SII HibP_RO vaccines manufactured in small and industrial scale are equally immunogenic, safe and confer adequate seroprotection to infants of 6-14 weeks of age. Scaling up production process has not affected the safety and immune response in the target population.     

Non-adjuvanted 2009 influenza A (H1N1)v vaccine in pregnant women: the results of a French prospective descriptive study

In 2009, during the influenza A (H1N1)v pandemic, the French Health authorities recommended influenza immunisation for pregnant women because of the higher risk of serious influenza outcomes in that population. Thus, the non-adjuvanted inactivated influenza vaccine Panenza^® was administered to French women from the second trimester of pregnancy. Several studies suggest that inactivated seasonal influenza vaccines are safe during pregnancy but there are few data about the effects of new A (H1N1)vaccines (new antigen) on pregnant women.

Objective

The aim of the present prospective study was to describe pregnancy outcomes among women vaccinated with non-adjuvanted influenza vaccines in South Western France.

Methods

the study ran from November 2009 to February 2010 and included, on a voluntary basis, pregnant women who were vaccinated against A (H1N1) influenza in vaccination clinics or maternity wards.

Results

569 pregnant women were monitored until delivery. Compared with the general population, the risks of maternal conditions, malformations and neonatal conditions were not statistically different.

Conclusion

This study does not reveal any sign of safety concerns regarding the effects of the vaccine on pregnancy outcomes.     

Comparative varicella vaccine effectiveness during outbreaks in day-care centres

Background

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC).

Methods

Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age < 11 months, vaccinated at age < 11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC).

Findings

Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57–81, p < 0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix^® (RR = 2.8, 95%CI 1.0–7.8, p = 0.05) or Priorix-Tetra^® (RR = 2.4, 95%CI 0.7–8.3, p = 0.18) but lower for 2 doses of Priorix-Tetra^® (RR = 0.5, 95%CI 0.1–2.7, p = 0.41) than for 1 dose of Varivax^®.

Interpretation

Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.     

The effectiveness of influenza vaccination in preventing hospitalizations in children in Hong Kong, 2009–2013

Background

Influenza vaccination is widely recommended every year to protect individuals against influenza virus infection and illness. There are few published estimates of influenza vaccine effectiveness against hospitalization in children or from subtropical regions.

Methods

We conducted a test-negative year-round study between October 2009 and September 2013, recruiting children 6 months to 17 years of age admitted to two hospitals in Hong Kong with a febrile acute respiratory infection. Cases were tested for influenza A and B and conditional logistic regression was used to estimate vaccine effectiveness comparing influenza vaccination history of the trivalent influenza vaccine (TIV) among patients testing positive versus negative for influenza, adjusting for age and sex and matching by calendar week of recruitment.

Results

Overall vaccine effectiveness against hospitalization with laboratory-confirmed influenza A and B was estimated to be 61.7% (95% CI: 43.0%, 74.2%). The estimated vaccine effectiveness against A(H3N2) was 36.6% (95% CI: −25.5%, 67.9%) compared to 71.5% (95% CI: 39.4%, 86.6%) for A(H1N1)pdm09 and 68.8% (95% CI: 41.6%, 83.3%) for B.

Conclusions

Vaccine effectiveness against hospitalization in children varied from year to year, but was moderate to high overall even in an area with influenza activity throughout the year.