Laboratory Biosafety: Summary of the NACI Supplemental Statement on Mammalian Cell Culture-Based Influenza Vaccines

BackgroundMammalian cell culture-based technology is an innovative technique for influenza vaccine manufacturing that may be a valuable alternative to overcome some of the problems and vulnerabilities associated with conventional egg-based influenza vaccine production. Flucelvax^® Quad (Seqirus, Inc.) is the first and only mammalian cell culture-based quadrivalent inactivated, subunit influenza vaccine (IIV4-cc) authorized for adult and pediatric use in Canada. The National Advisory Committee on Immunization (NACI) has not previously made a recommendation on cell culture-based influenza vaccines in any population.ObjectiveTo review the available evidence for the efficacy, effectiveness, immunogenicity, and safety of IIV4-cc, and to summarize the NACI recommendation regarding the use of Flucelvax Quad in Canada in adults and children.MethodsA systematic literature review on the vaccine efficacy, effectiveness, immunogenicity and safety of IIV4-cc in persons four years of age and older was performed. The systematic review’s methodology was specified a priori in a written protocol. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and develop a recommendation regarding the use of Flucelvax Quad in adults and children. The proposed recommendation was then considered and approved by NACI in light of the available evidence.ResultsThirteen eligible studies were included in the evidence synthesis. In the four observational studies that assessed vaccine effectiveness of IIV4-cc, there were some data indicating potentially improved protection against influenza compared to conventional egg-based quadrivalent inactivated influenza vaccines (IIV4) or trivalent inactivated influenza vaccine (IIV3), particularly against A(H3N2) virus infection. There was also some evidence that IIV4-cc may be more effective than egg-based trivalent or quadrivalent influenza vaccines against non-laboratory confirmed influenza-related outcomes, but there is insufficient evidence for laboratory-confirmed outcomes. Two randomized controlled trials assessed the immunogenicity and safety of IIV4-cc compared with mammalian cell culture-based trivalent inactivated, subunit influenza vaccine (IIV3-cc). The IIV4-cc was well-tolerated and the reported solicited local and systemic adverse events were generally mild to moderate in intensity, self-limited and did not precipitate sequelae. One clinical review of cases and six peer-reviewed randomized controlled trials (four in adults and two in children) that reported on the safety of IIV3-cc were included in the review. The evidence on immunogenicity and safety was consistent across these studies and showed that there was no significant difference in adults and children four years of age and older who had received IIV3-cc or an egg-based IIV3.ConclusionNACI concluded that there is fair evidence (Grade B Evidence) that Flucelvax Quad is effective, safe, and has non-inferior immunogenicity to comparable vaccines, based on direct evidence in adults and children nine years of age and older. NACI recommends that Flucelvax Quad may be considered among the IIV4 offered to adults and children nine years of age and older (Discretionary NACI Recommendation).     

Epidemiology and burden of illness of seasonal influenza among the elderly in Japan: A systematic literature review and vaccine effectiveness meta‐analysis

BackgroundElderly populations are particularly vulnerable to influenza and often require extensive clinical support. In Japan, nationwide passive surveillance monitors seasonal influenza but does not capture the full disease burden. We synthesized existing evidence on the epidemiology, vaccine effectiveness (VE), and economic burden of seasonal influenza in the elderly population.MethodsPubMed, EMBASE, and ICHUSHI were searched for articles on seasonal influenza in Japan, published between 1997 and 2018, in English or Japanese. Grey literature was also assessed. A random‐effects meta‐analysis characterized VE of influenza vaccines among studies reporting this information.ResultsOf 1,147 identified articles, 143 met inclusion criteria. Reported incidence rates varied considerably depending on study design, season, study setting and, most importantly, case definition. In nursing homes, the maximum reported attack rate was 55.2% and in the 16 articles reporting mortality rates, case fatality rates varied from 0.009% to 14.3%. Most hospitalizations were in people aged >60; healthcare costs were partially mitigated by vaccine administration. Meta‐analysis estimated overall VE of 19.1% (95% CI: 2.3% ‐ 33.0%) with a high proportion of heterogeneity (I²: 89.1%). There was a trend of lower VE in older people (40.1% [−57.3‐77.2] in the <65 group; 12.9% [−8.0‐29.8] in those 65; P = .21).ConclusionsDespite differences between studies that make comparisons challenging, the influenza burden in elderly Japanese is significant. While vaccines are effective, current vaccination programs offer suboptimal protection. Health economic data and cost‐effectiveness analyses were limited and represent areas for policy‐relevant future research.     

Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow‐fill‐seal device in adults: a randomized,active‐controlled study

Please cite this paper as: Sheldon et al. (2013) Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow‐fill‐seal device in adults: a randomized, active‐controlled study. Influenza and Other Respiratory Viruses 7(6), 1142–1150. Background  Influenza B strains from two distinct lineages (Yamagata and Victoria) have cocirculated over recent years. Current seasonal vaccines contain a single B lineage resulting in frequent mismatches between the vaccine strain and the circulating strain. An Ann Arbor strain quadrivalent live attenuated influenza vaccine (Q/LAIV) containing B strains from both lineages is being developed to address this issue. Objectives  The goal of this study was to evaluate whether Q/LAIV administered intranasally as a single dose to a single nostril, using a blow‐fill‐seal (BFS) delivery system had a similar immunogenicity and safety profile compared with the licensed trivalent vaccine delivered using the Accuspray device. Patients/Methods  Adults aged 18–49 years were randomized to receive one intranasal dose of Q/LAIV delivered using a BFS device (Q/LAIV‐BFS; n = 1202) or one of two trivalent live attenuated influenza vaccines (T/LAIV) containing one of the corresponding B strains (total T/LAIV, n = 598). Primary endpoints were the post‐vaccination strain‐specific serum hemagglutination inhibition antibody geometric mean titers for each strain. Secondary immunogenicity endpoints, safety, and acceptability of the BFS device were also assessed. Results  Q/LAIV was immunogenically non‐inferior to T/LAIV for all four influenza strains. Secondary immunogenicity outcomes were consistent with the primary endpoint. Solicited symptoms and AEs were comparable in both groups. Subjects considered the BFS device to be acceptable. Conclusions  Immune responses to vaccination with Ann Arbor strain Q/LAIV‐BFS were non‐inferior to those with T/LAIV. Q/LAIV may confer broader protection against seasonal influenza B by targeting both major influenza B lineages.     

Costs of seasonal influenza vaccination in South Africa

BackgroundInfluenza accounts for a substantial number of deaths and hospitalisations annually in South Africa. To address this disease burden, the South African National Department of Health introduced a trivalent inactivated influenza vaccination programme in 2010.MethodsWe adapted and populated the WHO Seasonal Influenza Immunization Costing Tool (WHO SIICT) with country‐specific data to estimate the cost of the influenza vaccination programme in South Africa. Data were obtained through key‐informant interviews at different levels of the health system and through a review of existing secondary data sources. Costs were estimated from a public provider perspective and expressed in 2018 prices. We conducted scenario analyses to assess the impact of different levels of programme expansion and the use of quadrivalent vaccines on total programme costs.ResultsTotal financial and economic costs were estimated at approximately USD 2.93 million and USD 7.91 million, respectively, while financial and economic cost per person immunised was estimated at USD 3.29 and USD 8.88, respectively. Expanding the programme by 5% and 10% increased economic cost per person immunised to USD 9.36 and USD 9.52 in the two scenarios, respectively. Finally, replacing trivalent inactivated influenza vaccine (TIV) with quadrivalent vaccine increased financial and economic costs to USD 4.89 and USD 10.48 per person immunised, respectively.ConclusionWe adapted the WHO SIICT and provide estimates of the total costs of the seasonal influenza vaccination programme in South Africa. These estimates provide a basis for planning future programme expansion and may serve as inputs for cost‐effectiveness analyses of seasonal influenza vaccination programmes.     

Use of High-Dose Influenza and Live Attenuated Influenza Vaccines by US Primary Care Physicians

BackgroundSeveral different types of influenza vaccine are licensed for use in adults in the USA including high-dose inactivated influenza vaccine (HD-IIV) and live attenuated influenza vaccine (LAIV). HD-IIV is licensed for use in adults ≥ 65 years, and recommendations for use of LAIV have changed several times in recent years.ObjectiveWe sought to examine family physicians’ (FPs) and general internal medicine physicians’ (GIMs) perceptions, knowledge, and practices for use of HD-IIV and LAIV during the 2016–2017 and 2018–2019 influenza seasons.DesignE-mail and mail surveys conducted February–March 2017, January–February 2019.ParticipantsNationally representative samples of FPs and GIMs.Main MeasuresSurveys assessed HD-IIV practices (2017), knowledge and perceptions (2019), and LAIV knowledge and practices (2017, 2019).Key ResultsResponse rates were 67% (620/930) in 2017 and 69% (642/926) in 2019. Many physicians believed HD-IIV is more effective than standard dose IIV in patients ≥ 65 years (76%) and reported their patients ≥ 65 years believe they need HD-IIV (67%). Most respondents incorrectly thought ACIP preferentially recommends HD-IIV for adults ≥ 65 years (88%); 65% “almost always/always” recommended HD-IIV for adults ≥ 65 years. Some physicians incorrectly thought ACIP preferentially recommends HD-IIV for adults < 65 years with cardiopulmonary disease (38%) or immunosuppression (48%); some respondents recommended HD-IIV for these groups (25% and 28% respectively). In 2017, 88% of respondents knew that ACIP recommended against using LAIV during the 2016–2017 influenza season, and 4% recommended LAIV to patients. In 2019, 63% knew that ACIP recommended that LAIV could be used during the 2018–2019 influenza season, and 8% recommended LAIV.ConclusionsMany physicians incorrectly thought ACIP had preferential recommendations for HD-IIV. Physicians should be encouraged to use any available age-appropriate influenza vaccine to optimize influenza vaccination particularly among older adults and patients with chronic conditions who are more vulnerable to severe influenza disease.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06397-7.KEY WORDS: influenza vaccine, immunization, vaccination, influenza     

Seasonal influenza in children: Costs for the health system and society in Europe

BackgroundPediatric influenza causes significant morbidity annually, resulting in an increased economic burden. Therefore, we aimed to summarize existing literature regarding the costs of pediatric influenza in Europe, paying particular attention to the direct and indirect costs considered in the economic evaluations. Knowing health and social costs of childhood influenza is essential to support value‐based health decisions to implement effective immunization strategies.MethodsWe searched three databases for articles published to September 3, 2021. Eligible studies were those reporting the economic burden of influenza in the pediatric and youth population in European countries written in English language.ResultsOverall, 2225 records were screened, and 9 articles were included. Costs estimates are different across countries and in the age groups considered. Direct costs per episode, whose major expense driver are hospitalizations and pediatric examinations, range from about €74 in Italy to €252 in Germany. Important variations are observed based on age, with the youngest group absorbing in some cases double the resources of the older ones such as (in Italy, in France and in Germany). Regarding indirect costs, workdays lost by parents resulted in higher costs for children <2 years and 2–5 years than those >5 years of age and their economic impact was variable reaching €251 per week in Germany.ConclusionEvidence obtained in our review strengthened the awareness about the economic impact, in terms of direct and indirect costs, of pediatric influenza requiring, as a priority action in Europe, the implementation of influenza vaccination policies in this target population.     

Oseltamivir treatment of influenza A and B infections in infants

BackgroundOseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the effectiveness of the treatment in this age group.MethodsIn a prospective study, we enrolled 431 newborn infants and followed them up for 10 months during their first respiratory season (September 2017‐June 2018). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for determination of the viral etiology. Infants with influenza were re‐examined at short intervals, and additional nasopharyngeal specimens were obtained at each visit for measuring the viral load. All infants with symptoms <48 hours received oseltamivir treatment. The parents filled out daily symptom diaries.ResultsAmong 23 infants with influenza A, the mean total duration of illness in oseltamivir recipients was 82.1 hours, compared with 253.5 hours in infants without treatment (P = .0003). For infants with influenza B, the corresponding durations were 110.0 and 173.9 hours, respectively (P = .03). In infants with influenza A, total symptom scores were significantly lower in oseltamivir‐treated infants at all time points between days 3 and 11 after the onset of therapy. In most children with either influenza A or B, viral antigen concentrations declined rapidly within 1‐2 days after the initiation of oseltamivir treatment.ConclusionsOseltamivir treatment of infants with influenza rapidly decreased the viral load in nasopharyngeal secretions and shortened the duration and severity of symptoms. The clinical effectiveness of oseltamivir appeared to be greater against influenza A than against influenza B infections.     

Influenza Vaccine: Influenza vaccine during the 2019–2020 season and COVID-19 risk: A case-control study in Québec

BackgroundWe carried out a case-control study that examined whether receipt of the inactivated influenza vaccine during the 2019–2020 season impacted on the risk of coronavirus disease 2019 (COVID-19), as there was a concern that the vaccine could be detrimental through viral interference.MethodsA total of 920 cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (diagnosed between March and October 2020) and 2,123 uninfected controls were recruited from those who were born in Québec between 1956 and 1976 and who had received diagnostic services at two hospitals (Montréal and Sherbrooke, Québec). After obtaining consent, a questionnaire was administered by phone. Data were analyzed by logistic regression.ResultsAmong healthcare workers, inactivated influenza vaccine received during the previous influenza season was not associated with increased COVID-19 risk (AOR: 0.99, 95% CI: 0.69–1.41). Among participants who were not healthcare workers, influenza vaccination was associated with lower odds of COVID-19 (AOR: 0.73, 95% CI 0.56–0.96).ConclusionWe found no evidence that seasonal influenza vaccine increased the risk of developing COVID-19.     

Efficacy of live attenuated influenza vaccine in children 6 months to 17 years of age

Please cite this paper as: Belshe et al. (2010). Efficacy of live attenuated influenza vaccine in children 6 months to 17 years of age. Influenza and Other Respiratory Viruses 4(3), 141–145. Background  It has been suggested that live attenuated influenza vaccine (LAIV) may be less effective in older individuals because of prior wild‐type influenza infections. LAIV is currently approved in the United States, South Korea and Hong Kong for individuals 2–49 years of age. Objective  To examine data from previously published pediatric studies to determine the efficacy of LAIV in various age groups. Methods  Four studies in which the subject age range exceeded 36 months were identified: one 2‐year study comparing LAIV with placebo and three 1‐year studies comparing LAIV with trivalent inactivated influenza vaccine (TIV). Efficacy against any strain regardless of antigenic similarity to vaccine was analyzed by age; age groups were based on the study design and sample size. A logistic regression model was used to assess whether age, as a continuous variable, was an effect modifier on LAIV efficacy. Results  The efficacy of LAIV did not vary with age in children aged 15–84 months compared with placebo or in children aged 6 months to 17 years compared with TIV. Conclusions  The available data from prospective, randomized studies in children does not support the concept that prior repeated exposure to influenza, either through wild‐type infection or vaccination with live, attenuated or inactivated vaccines, reduces the efficacy of LAIV compared with placebo or TIV. The decreased immunologic responses to LAIV reported in older individuals or those with pre‐existing immunity do not appear to translate into reduced protection from influenza in children.     

Comparative incidence and burden of respiratory viruses associated with hospitalization in adults in New York City

BackgroundAlthough the burden of influenza is well characterized, the burden of community‐onset non‐influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non‐influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines.MethodsFrom October 2017 to September 2019, a retrospective study was performed in a pre‐defined catchment area to estimate the population‐based incidence of community‐onset respiratory viruses associated with hospitalization. Included patients were ≥18 years old, resided in New York City, were hospitalized for ≥24 hours, and had a respiratory virus detected within 3 calendar‐days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in‐hospital mortality and compared among those with laboratory‐confirmed influenza versus those with laboratory‐confirmed non‐influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus).ResultsDuring the study period, 4232 eligible patients were identified of whom 50.9% were ≥65 years of age. For each virus, the population‐based incidence was highest for those ≥80 years of age. When compared to those with influenza viruses detected, those with non‐influenza respiratory viruses detected (combined) had higher population‐based incidence, significantly more ICU admissions, and higher in‐house mortality.ConclusionsThe burden of non‐influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non‐influenza respiratory viruses, particularly for older adults.     

Immunogenicity and safety of a 2009 pandemic influenza A (H1N1) monovalent vaccine in Chinese infants aged 6–35?months: a randomized,double‐blind,controlled phase I clinical trial

Please cite this paper as: Li et al. (2012) Immunogenicity and safety of a 2009 pandemic influenza A (H1N1) monovalent vaccine in Chinese infants aged 6–35 months: a randomized, double‐blind, controlled phase I clinical trial. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12028. Objectives  The goal of this double‐blind, randomized, controlled clinical trial was to assess the safety and immunogenicity of two different doses of a monovalent split‐virion 2009 pandemic influenza A/H1N1 vaccine without adjuvant in Chinese infants aged 6‐35 months. Design and setting  Subjects were randomly assigned to receive either a 2009 pandemic (H1N1) vaccine containing 7.5 or 15 μg haemagglutinin (HA) or a seasonal influenza vaccine. 2 doses of the H1N1 vaccines or the seasonal influenza vaccine were given 21 days apart in younger infants aged 6‐23 months or older infants aged 24‐35 months. Sample  Serum samples were collected immediately before the first injection and before and 21 days after the second injection. Main outcome measures  Primary outcomes were haemagglutinin inhibition (HI) antibody responses 21 days following each vaccination. Safety was monitoring throughout the study. Results  The first vaccination of 7.5 μg and 15 μg H1N1 vaccine induced seroprotective antibody titers (HI titers ≥ 1: 40) in 42.9‐57.4% of younger infants and 49.1‐61.0% older infants. Immune responses after completion of the two dose schedule were comparable in both age groups with seroprotective rates of 91‐98% in each vaccine and age group and GMTs of 173‐263. The H1N1 vaccine elicited similar rates of local and systemic adverse reactions as the seasonal influenza vaccine. Conclusions  The 2009 pandemic influenza A /H1N1 vaccine were highly immunogenic in infants aged 6‐35 months, and displayed a safety and reactogenicity profile similar to the seasonal influenza vaccine. Trial registration  ClinicalTrial.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT01047202","term_id":"NCT01047202"}}NCT01047202     

Using the health belief model to identify barriers to seasonal influenza vaccination among Australian adults in 2019

BackgroundEach year tens of thousands of Australians become ill with influenza, resulting in thousands of severe infections that require hospitalisation. However, only 40% of adults receive the annual influenza vaccine. We surveyed Australian adults to provide up to date, population‐specific data on the predictors and barriers of seasonal influenza vaccination.MethodsWe administered an online survey to a nationally representative sample of Australian adults. We designed survey questions using the theoretical constructs of the health belief model. Using simple and multivariable Poisson regression, we identified attitudes and beliefs associated with influenza vaccination in 2019.ResultsAmong 1,444 respondents, 51.7% self‐reported influenza vaccination in 2019. We estimated vaccine coverage to be 44% for adults under 45, 46% for adults aged 45 to 64 and 77% for adults aged 65 and over. The strongest individual predictors of self‐reported vaccination were believing the vaccine is effective at preventing influenza (APR = 3.71; 95% CI = 2.87‐4.80), followed by recalling their doctor recommending the vaccine (APR = 2.70; 95% CI = 2.31‐3.16). Common perceived barriers that predicted self‐reported vaccination included believing the vaccine could give you influenza (APR = 0.59; 95% CI = 0.52‐0.67), believing the vaccine can make you ill afterwards (APR = 0.68; 95% CI = 0.62‐0.74) and preferring to develop immunity “naturally” (APR = 0.38; 95% CI = 0.32‐0.45).ConclusionAlthough vaccine uptake in 2019 appears to be higher than previous years, there are perceived barriers which may limit uptake among Australians. Tailored interventions are needed to combat widespread influenza vaccine hesitancy, particularly among high‐risk groups.     

A study of Chitosan and c‐di‐GMP as mucosal adjuvants for intranasal influenza H5N1 vaccine

Please cite this paper as: Svindland et al. (2012) A study of Chitosan and c‐di‐GMP as mucosal adjuvants for intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses 10.1111/irv.12056000(000), 000–000. Background  Highly pathogenic avian influenza A/H5N1 virus remains a potential pandemic threat, and it is essential to continue vaccine development against this subtype. A local mucosal immune response in the upper respiratory tract may stop influenza transmission. It is therefore important to develop effective intranasal pandemic influenza vaccines that induce mucosal immunity at the site of viral entry. Objectives  We evaluated the humoral and cellular immune responses of two promising mucosal adjuvants (Chitosan and c‐di‐GMP) for intranasal influenza H5N1 vaccine in a murine model. Furthermore, we evaluated the concept of co‐adjuvanting an experimental adjuvant (c‐di‐GMP) with chitosan. Methods  BALB/c mice were intranasally immunised with two doses of subunit NIBRG‐14 (H5N1) vaccine (7·5, 1·5 or 0·3 μg haemagglutinin (HA) adjuvanted with chitosan (CSN), c‐di‐GMP or both adjuvants. Results  All adjuvant formulations improved the serum and local antibody responses, with the highest responses observed in the 7·5 μg HA CSN and c‐di‐GMP‐adjuvanted groups. The c‐di‐GMP provided dose sparing with protective single radial haemolysis (SRH), and haemagglutination inhibition (HI) antibody responses found in the 0·3 μg HA group. CSN elicited a Th2 response, whereas c‐di‐GMP induced higher frequencies of virus‐specific CD4⁺ T cells producing one or more Th1 cytokines (IFN‐γ⁺, IL‐2⁺, TNF‐α⁺). A combination of the two adjuvants demonstrated effectiveness at 7·5 μg HA and triggered a more balanced Th cytokine profile. Conclusion  These data show that combining adjuvants can modulate the Th response and in combination with ongoing studies of adjuvanted intranasal vaccines will dictate the way forward for optimal mucosal influenza vaccines.     

Global patterns of seasonal influenza activity,duration of activity and virus (sub)type circulation from 2010 to 2020

BackgroundSeasonal influenza viruses undergo unpredictable changes, which may lead to antigenic mismatch between circulating and vaccine strains and to a reduced vaccine effectiveness. A continuously updated knowledge of influenza strain circulation and seasonality is essential to optimize the effectiveness of influenza vaccination campaigns. We described the global epidemiology of influenza between the 2009 A(H1N1)p and the 2020 COVID‐19 pandemic.MethodsInfluenza virological surveillance data were obtained from the WHO‐FluNet database. We determined the median proportion of influenza cases caused by the different influenza virus types, subtypes, and lineages; the typical timing of the epidemic peak; and the median duration of influenza epidemics (applying the annual average percentage method with a 75% threshold).ResultsWe included over 4.6 million influenza cases from 149 countries. The median proportion of influenza cases caused by type A viruses was 75.5%, highest in the Southern hemisphere (81.6%) and lowest in the intertropical belt (73.0%), and ranged across seasons between 60.9% in 2017 and 88.7% in 2018. Epidemic peaks typically occurred during winter months in Northern and Southern hemisphere countries, while much more variability emerged in tropical countries. Influenza epidemics lasted a median of 25 weeks (range 8–42) in countries lying between 30°N and 26°S, and a median of 9 weeks (range 5–25) in countries outside this latitude range.ConclusionsThis work will establish an important baseline to better understand factors that influence seasonal influenza dynamics and how COVID‐19 may have affected seasonal activity and influenza virus types, subtypes, and lineages circulation patterns.     

Reduction in Severity of All-Cause Gastroenteritis Requiring Hospitalisation in Children Vaccinated against Rotavirus in Malawi

Rotavirus is the major cause of severe gastroenteritis in children aged <5 years. Introduction of the G1P[8] Rotarix^® rotavirus vaccine in Malawi in 2012 has reduced rotavirus-associated hospitalisations and diarrhoeal mortality. However, the impact of rotavirus vaccine on the severity of gastroenteritis presented in children requiring hospitalisation remains unknown. We conducted a hospital-based surveillance study to assess the impact of Rotarix^® vaccination on the severity of gastroenteritis presented by Malawian children. Stool samples were collected from children aged <5 years who required hospitalisation with acute gastroenteritis from December 2011 to October 2019. Gastroenteritis severity was determined using Ruuska and Vesikari scores. Rotavirus was detected using enzyme immunoassay. Rotavirus genotypes were determined using nested RT-PCR. Associations between Rotarix^® vaccination and gastroenteritis severity were investigated using adjusted linear regression. In total, 3159 children were enrolled. After adjusting for mid-upper arm circumference (MUAC), age, gender and receipt of other vaccines, all-cause gastroenteritis severity scores were 2.21 units lower (p < 0.001) among Rotarix^®-vaccinated (n = 2224) compared to Rotarix^®-unvaccinated children (n = 935). The reduction in severity score was observed against every rotavirus genotype, although the magnitude was smaller among those infected with G12P[6] compared to the remaining genotypes (p = 0.011). Each one-year increment in age was associated with a decrease of 0.43 severity score (p < 0.001). Our findings provide additional evidence on the impact of Rotarix^® in Malawi, lending further support to Malawi’s Rotarix^® programme.     

A mixed methods study of seasonal influenza vaccine hesitancy in adults with chronic respiratory conditions

BackgroundSeasonal influenza vaccination is recommended for patients with chronic respiratory conditions, but uptake is suboptimal. We undertook a comprehensive mixed methods study in order to examine the barriers and enablers to influenza vaccination in patients with chronic respiratory conditions.MethodsMixed methods including a survey (n = 429) which assessed sociodemographics and the psychological factors associated with vaccine uptake (ie confidence, complacency, constraints, calculation and collective responsibility) with binary logistic regression analysis. We also undertook focus groups and interviews (n = 59) to further explore barriers and enablers to uptake using thematic analysis.ResultsThe survey analysis identified that older participants were more likely to accept the vaccine, as were those with higher perceptions of collective responsibility around vaccination, lower levels of complacency and lower levels of constraints. Thematic analysis showed that concerns over vaccine side effects, lack of tailored information and knowledge, and a lack of trust and rapport with healthcare professionals were key barriers. In contrast, the importance of feeling protected, acceptance of being part of an at‐risk group and feeling a reduced sense of vulnerability after vaccination were seen as key enablers.ConclusionsOur findings showed that the decision to accept a vaccine against influenza is influenced by multiple sociodemographic and psychological factors. Future interventions should provide clear and transparent information about side effects and be tailored to patients with chronic respiratory conditions. Interactions between patients and their healthcare providers have a particularly important role to play in helping patients address their concerns and feel confident in vaccination.     

Uptake and impact of vaccinating primary school children against influenza: Experiences in the fourth season of the live attenuated influenza vaccination programme,England, 2016/2017

BackgroundIn the 2016/2017 influenza season, England was in its fourth season of the roll‐out of a live‐attenuated influenza vaccine (LAIV) targeted at healthy children aged two to less than 17 years. For the first time, all healthy children aged 2 to 8 years were offered LAIV at national level in 2016/2017. Since the commencement of the programme in 2013/2014, a series of geographically discrete pilot areas have been in place where quadrivalent LAIV was also offered to all school age children. In 2016/2017, these were children aged 8 to 11 years, other than those targeted by the national programme.MethodsWe evaluated the overall and indirect impact of vaccinating primary school age children, on the population of England, by measuring vaccine uptake levels and comparing cumulative disease incidence through various influenza surveillance schemes, in targeted and non‐targeted age groups in pilot and non‐pilot areas in 2016/2017.ResultsOur findings indicate that cumulative primary care influenza‐like consultations, primary and secondary care swab positivity, influenza confirmed hospitalisations and emergency department attendances in pilot areas were overall lower than those observed in non‐pilot areas; however, significant differences were not always observed in both targeted and non‐targeted age groups. Excess mortality was higher in pilot areas compared with non‐pilot areas.ConclusionsThese results are similar to earlier seasons of the programme indicating the importance and continuing support of vaccinating all primary school children with LAIV to reduce influenza related illness across the population, although further work is needed to understand the differences in excess mortality.     

An overview of the regulation of influenza vaccines in the United States

Influenza virus vaccines are unique among currently licensed viral vaccines. The vaccines designed to protect against seasonal influenza illness must be updated periodically in an effort to match the vaccine strain with currently circulating viruses, and the vaccine manufacturing timeline includes multiple, overlapping processes with a very limited amount of flexibility. In the United States (U.S.), over 150 million doses of seasonal trivalent and quadrivalent vaccine are produced annually, a mammoth effort, particularly in the context of a vaccine with components that usually change on a yearly basis. In addition, emergence of an influenza virus containing an HA subtype that has not recently circulated in humans is an ever present possibility. Recently, pandemic influenza vaccines have been licensed, and the pathways for licensure of pandemic vaccines and subsequent strain updating have been defined. Thus, there are formidable challenges for the regulation of currently licensed influenza vaccines, as well as for the regulation of influenza vaccines under development. This review describes the process of licensing influenza vaccines in the U.S., the process and steps involved in the annual updating of seasonal influenza vaccines, and some recent experiences and regulatory challenges faced in development and evaluation of novel influenza vaccines.     

Live‐attenuated influenza vaccine effectiveness against hospitalization in children aged 2–6 years,the first three seasons of the childhood influenza vaccination program in England, 2013/14–2015/16

IntroductionIn 2013, the United Kingdom began to roll‐out a universal annual influenza vaccination program for children. An important component of any new vaccination program is measuring its effectiveness. Live‐attenuated influenza vaccines (LAIVs) have since shown mixed results with vaccine effectiveness (VE) varying across seasons and countries elsewhere. This study aims to assess the effectiveness of influenza vaccination in children against severe disease during the first three seasons of the LAIV program in England.MethodsUsing the screening method, LAIV vaccination coverage in children hospitalized with laboratory‐confirmed influenza infection was compared with vaccination coverage in 2–6‐year‐olds in the general population to estimate VE in 2013/14–2015/16.ResultsThe overall LAIV VE, adjusted for age group, week/month and geographical area, for all influenza types pooled over the three influenza seasons was 50.1% (95% confidence interval [CI] 31.2, 63.8). By age, there was evidence of protection against hospitalization from influenza vaccination in both the pre‐school (2–4‐year‐olds) (48.1%, 95% CI 27.2, 63.1) and school‐aged children (5–6‐year‐olds) (62.6%, 95% CI 2.6, 85.6) over the three seasons.ConclusionLAIV vaccination in children provided moderate annual protection against laboratory‐confirmed influenza‐related hospitalization in England over the three influenza seasons. This study contributes further to the limited literature to date on influenza VE against severe disease in children.