Discussion on the prevention and control related to influenza from WHO’s global influenza preplans

根据全球流行性感冒(简称流感)流行的历史和近年禽流感的流行状况,WHO在1999年就发布了指导全球流感大流行应对准备工作的计划,并在2005和2007年对此计划进行了更新和完善,并准备于2009年发布新版的计划.在第56届和第58届世界卫生大会上敦促成员国制定国家流感大流行应对准备计划及相应的应对准备策略,积极进行大流行的应对.     

Age-specific differences in influenza A epidemic curves: do children drive the spread of influenza epidemics?

There is accumulating evidence suggesting that children may drive the spread of influenza epidemics. The objective of this study was to quantify the lead time by age using laboratory-confirmed cases of influenza A for the 1995/1996-2005/2006 seasons from Canadian communities and laboratory-confirmed hospital admissions for the H1N1/2009 pandemic strain. With alignment of the epidemic curves locally before aggregation of cases, slight age-specific differences in the timing of infection became apparent. For seasonal influenza, both the 10-19- and 20-29-year age groups peaked 1 week earlier than other age groups, while during the fall wave of the 2009 pandemic, infections peaked earlier among only the 10-19-year age group. In the H3N2 seasons, infections occurred an average of 3.9 (95% confidence interval: 1.7, 6.1) days earlier in the 20-29-year age group than for youth aged 10-19 years, while during the fall pandemic wave, the 10-19-year age group had a statistically significant lead of 3 days compared with both younger children aged 4-9 years and adults aged 20-29 years (P < 0.0001). This analysis casts doubt on the hypothesis that younger school-age children actually lead influenza epidemic waves.     

Reasons given for not receiving an influenza vaccination, 2011–12 influenza season,United States

BackgroundInfluenza vaccination coverage in the United States remains below national targets and racial/ethnic differences persist.ObjectivesTo gain insights into potential strategies for improving influenza vaccination by examining reasons given for not receiving an influenza vaccination during the 2011–12 influenza season.MethodsData from the National Flu Survey were analyzed for the 2011–12 influenza season.Tests of association between reasons for non-vaccination and demographic variables were conducted using Wald chi-square tests. Multivariable logistic regression analyses were used to determine variables independently associated with each reason for non-vaccination.ResultsFor adults and children, there were no racial/ethnic differences in the overall most frequent reason for non-vaccination: “unlikely to get very sick from the flu”. Regarding adults, there were racial/ethnic differences in seven of the twelve reasons for non-vaccination in bivariate analyses, but only three remained significant in the multivariable models. Most notable of these was that blacks (40.9%) were more likely than Hispanics (27.0%), whites (25.2%), and adults of other/multiple races (21.2%) to report concerns about getting the flu from the vaccination and blacks (39.8%) were more likely than whites (28.4%) and adults of other/multiple races (29.3%) to report concerns about side effects from the vaccine. Regarding children, there were racial/ethnic differences for three of the reasons for non-vaccination, and these remained significant in the multivariable models. The most noteworthy of these was that more black (44.4%) than white (24.0%) and other/multiple race (19.0%) parents had concerns about their child getting the flu from the vaccination. Other demographic variables (age, gender income, MSA for adults and age and income for children) were also associated with reasons for non-vaccination based on the multivariable models.ConclusionsThere are racial/ethnic group differences in reasons for not receiving an influenza vaccination; recognition of these differences should guide the choice of interventions to increase vaccination rates.     

Seasonal influenza vaccine effectiveness against influenza in 2012–2013: A hospital-based case-control study in Lithuania

Background

Due to scarce information on seasonal influenza vaccine effectiveness (SIVE) against severe clinical influenza outcomes in risk populations, we conducted a case-control study to assess its effects against laboratory-confirmed influenza in hospitalized patients during the 2012–2013 influenza season.

Methods

We conducted a test-negative case-control study among ≥18 years old patients with influenza-like illness (ILI) hospitalized in two Lithuanian hospitals. Cases were influenza A(H1N1), A(H3) or influenza B positive by RT-PCR, and controls were influenza negative. Additional demographic and clinical data to assess the role of confounding were collected. SIVE and its confidence intervals (95% CI) were estimated by using multivariate logistic regression as (1 − OR) × 100%.

Results

The sample consisted of 185 subjects. Seasonal influenza vaccine uptake was 5%. Among 111 (60%) influenza positive cases, 24.3% were A(H1N1), 10.8% were A(H3) and 24.3% were influenza B cases. Unadjusted SIVE was 79% (95% CI −6% to 96%) and after the adjustment it increased to 86% (95% CI 19% to 97%).

Conclusions

Seasonal influenza vaccination in 2012–2013 was associated with reduced occurrence of laboratory-confirmed influenza, but due to low sample size the estimate of SIVE is imprecise. Given high prevalence of influenza in hospitalized ILI cases and low influenza vaccination coverage, there is a need to increase influenza vaccination rates.     

Reasons for low influenza vaccination coverage among adults in Puerto Rico,influenza season 2013–2014

BackgroundInfluenza vaccination is recommended annually for all persons 6 months and older. Reports of increased influenza-related morbidity and mortality during the 2013–2014 influenza season raised concerns about low adult influenza immunization rates in Puerto Rico. In order to inform public health actions to increase vaccination rates, we surveyed adults in Puerto Rico regarding influenza vaccination-related attitudes and barriers.MethodsA random-digit-dialing telephone survey (50% landline: 50% cellphone) regarding influenza vaccination, attitudes, practices and barriers was conducted November 19–25, 2013 among adults in Puerto Rico. Survey results were weighted to reflect sampling design and adjustments for non-response.ResultsAmong 439 surveyed, 229 completed the survey with a 52% response rate. Respondents’ median age was 55 years; 18% reported receiving 2013–2014 influenza vaccination. Among 180 unvaccinated respondents, 38% reported barriers associated with limited access to vaccination, 24% reported they did not want or need influenza vaccination, and 20% reported safety concerns. Vaccinated respondents were more likely to know if they were recommended for influenza vaccination, to report greater perceived risk of influenza illness, and to report being less concerned about influenza vaccine safety (p-value < 0.05). Of the 175 respondents who saw a healthcare provider (HCP) since July 1, 2013, 38% reported their HCP recommended influenza vaccination and 17% were offered vaccination. Vaccination rates were higher among adults who received a recommendation and/or offer of influenza vaccination (43% vs. 14%; p-value < 0.01).ConclusionsFailure of HCP to recommend and/or offer influenza vaccination and patient attitudes (low perceived risk of influenza virus infection) may have contributed to low vaccination rates during the 2013–2014 season. HCP and public health practitioners should strongly recommend influenza vaccination and provide vaccinations during clinical encounters or refer patients for vaccination.     

Comparison of vaccine effectiveness against influenza hospitalization of cell-based and egg-based influenza vaccines, 2017–2018

Egg-based influenza vaccines could be less effective than cell-based vaccine due to adaptive mutations acquired for growth. We conducted a test-negative case-control study at Kaiser Permanente Southern California to assess vaccine effectiveness (VE) against hospitalization for laboratory-confirmed influenza during 2017–2018. Among the 1186 cases and 6946 controls, 74% and 59%, respectively, were ages ≥ 65 years. For any influenza, the adjusted relative VE of cell-based vaccine versus egg-based vaccines was 43% (95% CI: −45% to 77%) for patients ages < 65 years and 6% (95% CI: −46% to 39%) for patients ages ≥ 65 years. For influenza A(H3N2), the adjusted relative VE was 61% (95% CI: −63% to 91%) for patients ages < 65 years and −4% (95% CI: −70% to 37%) for patients ages ≥ 65 years. Statistically significant protection against influenza hospitalization of cell-based vaccine compared to egg-based vaccines was not observed, but further studies in additional influenza seasons are warranted.     

A real-world study evaluating the relative vaccine effectiveness of a cell-based quadrivalent influenza vaccine compared to egg-based quadrivalent influenza vaccine in the US during the 2017–18 influenza season

BackgroundCell-based influenza vaccine manufacturing reduces egg adaptations that can decrease vaccine effectiveness. We evaluated the relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) compared to standard-dose egg-based quadrivalent influenza vaccines (QIVe-SD) against influenza-related and serious respiratory events among subjects 4–64 years of age during the 2017–18 influenza season.MethodsA retrospective cohort analysis was conducted using administrative claims data in the US (IQVIA PharMetrics Plus® database). Subjects vaccinated with QIVc or QIVe-SD from 8/2017–1/2018 were identified (date of vaccination termed the index date). Influenza-related hospitalizations/ER visits, all-cause hospitalizations and serious respiratory hospitalizations/ER visits were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of QIVc compared to QIVe-SD. In a subgroup analysis, rVE was assessed for several subgroups of interest (4–17, 18–64 and 50–64 years, and subjects with ≥1 high-risk condition). In a secondary economic analysis, annualized all-cause costs over the follow-up were compared using propensity score matching (PSM) and generalized estimating equation (GEE) models.ResultsThe study sample comprised 555,538 QIVc recipients and 2,528,524 QIVe-SD recipients. Prior to adjustment, QIVc subjects were older and had higher total costs in the 6-months pre-index. Following IPTW-adjustment and Poisson regression, QIVc was more effective in reducing influenza-related hospitalizations/ER visits, all-cause hospitalizations, and hospitalizations/ER visits related to asthma/COPD/bronchial events and other respiratory events compared to QIVe-SD. Similar trends were generally observed in the subgroup analysis. Following PSM adjustment and GEE regression, QIVe-SD was associated with significantly higher annualized all-cause total costs compared to QIVc, driven by higher costs for outpatient medical services and inpatient hospitalizations.ConclusionsAfter adjustment for confounders and selection bias, QIVc reduced influenza-related hospitalizations/ER visits, all-cause hospitalizations, and serious respiratory hospitalizations/ER visits compared to QIVe-SD. QIVc was associated with significantly lower all-cause total costs.     

Does influenza vaccination exacerbate asthma in children?

BACKGROUND: The risks of influenza vaccination in asthmatic children are still being discussed. Especially, the risk that influenza vaccination may exacerbate asthma is an issue in this debate. METHODS: We conducted a randomised double-blind placebo-controlled trial in 696 children 6-18 years of age with asthma recruited in general practice during two influenza seasons, 1999-2000 and 2000-2001. Children participated for only one season. During the first week after vaccination, participants recorded local, influenza like and asthma symptoms as well as use of medication, health care use and absenteeism. RESULTS: Except for cough during the day in the first season, favouring placebo, there were no differences indicating that vaccination exacerbates asthma. CONCLUSIONS: Influenza vaccination does not seem to exacerbate asthma.     

Vaccination against equine influenza: quid novi?

Equine influenza virus is a leading cause of respiratory disease in the horse. Equine influenza vaccines containing inactivated virus were first developed in the 1960s. Despite their intensive use, equine influenza outbreaks still continue to occur and therefore new strategies of vaccination are necessary to improve vaccine efficacy. Numerous methods of vaccination have been evaluated and commercialised in the horse, the most recent being the cold-adapted influenza virus and poxvirus-based vaccines. As a large animal model, the horse is also a useful species in which to evaluate the potential of new generations of influenza vaccine such as live-attenuated influenza virus engineered by reverse genetics. This report details the equine immune responses conferring protection against influenza. It then undertakes a selective review of different strategies of vaccination against equine influenza that have been developed over the last two decades and discusses factors that may influence the efficacy of vaccination. Finally it outlines progress in the development of a novel vaccination strategy against equine influenza using reverse genetics.     

Three-season effectiveness of inactivated influenza vaccine in preventing influenza illness and hospitalization in children in Japan, 2013–2016

ObjectivesWe assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age in 2015/16 season. In addition, based on the data obtained during the three seasons from 2013 to 2016, we estimated the three-season VE in preventing influenza illness and hospitalization.MethodsOur study was conducted according to a test-negative case-control design (TNCC) and as a case-control study based on influenza rapid diagnostic test results.ResultsDuring 2015/16 season, the quadrivalent IIV was first used in Japan. The adjusted VE in preventing influenza illness was 49% (95% confidence interval [CI]: 42–55%) against any type of influenza, 57% (95% CI: 50–63%) against influenza A and 34% (95% CI: 23–44%) against influenza B. The 3-season adjusted VE was 45% (95% CI: 41–49%) against influenza virus infection overall (N = 12,888), 51% (95% CI: 47–55%) against influenza A (N = 10,410), and 32% (95% CI: 24–38%) against influenza B (N = 9232). An analysis by age groups showed low or no significant VE in infants or adolescents. By contrast, VE was highest in the young group (1–5 years old) and declined with age thereafter. The 3-season adjusted VE in preventing hospitalization as determined in a case-control study was 52% (95% CI: 42–60%) for influenza A and 28% (95% CI: 4–46%) for influenza B, and by TNCC design, it was 54% (95% CI: 41–65%) for influenza A and 34% (95% CI: 6–54%) for influenza B.ConclusionWe demonstrated not only VE in preventing illness, but also VE in preventing hospitalization based on much larger numbers of children than previous studies.     

Intradermal and virosomal influenza vaccines for preventing influenza hospitalization in the elderly during the 2011–2012 influenza season: A comparative effectiveness study using the Valencia health care information system

Background

The use of intradermal vaccination or virosomal vaccines could increase protection against influenza among the vulnerable population of older adults. Studies assessing the comparative effectiveness of these two influenza vaccine types in this age group are lacking.

Methods

We conducted a retrospective cohort study to estimate the comparative effectiveness of intradermal seasonal trivalent-influenza vaccine (TIV) delivered by a microneedle injection system and a virosomal-TIV intramuscularly delivered for prevention of influenza hospitalization in non-institutionalized adults aged ≥65 years. We obtained administrative data on immunization status and influenza hospitalization for the 2011–2012 influenza season, and used Cox regression models to assess comparative effectiveness. We estimated crude and adjusted (age, sex, comorbidity, pharmaceutical claims, recent pneumococcal vaccination and number of hospitalizations for all causes other than influenza between the previous and current influenza seasons) hazard ratios (HR).

Results

Overall, 164,021 vaccinated subjects were evaluated. There were 127 hospitalizations for influenza among 62,058 subjects, contributing 914,740 person-weeks at risk in the virosomal-TIV group, and 133 hospitalizations for influenza among 101,963 subjects, contributing 1,504,570 person-weeks at risk in the intradermal-TIV group. The crude HR of intradermal-TIV relative to virosomal-TIV was 0.64 (95% confidence interval (CI): 0.50–0.81), and the adjusted Cox estimated HR was 0.67 (95% CI: 0.52–0.85).

Conclusions

During the 2011–2012 influenza season the risk of hospitalization for influenza was reduced by 33% in non-institutionalized elderly adults who were vaccinated with intradermal-TIV compared with virosomal-TIV.     

Estimated influenza illnesses and hospitalizations averted by influenza vaccination among children aged 6–59 months in Suzhou,China, 2011/12 to 2015/16 influenza seasons

BackgroundThere are few estimates of vaccination-averted influenza-associated illnesses in China.MethodsWe used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% confidence intervals (CI) of influenza-associated outcomes (hospitalization, illness, and medically-attended (MA) illness) averted by vaccination among children aged 6–59 months in Suzhou from October 2011–September 2016. Influenza illnesses included non-hospitalized MA influenza illnesses and non-MA influenza illnesses. The numbers of influenza-associated outcomes averted by vaccination were the difference between the expected burden if there were no vaccination given and the observed burden with vaccination. The model incorporated the disease burden estimated based on surveillance data from Suzhou University Affiliated Children’s Hospital (SCH) and data from health utilization surveys conducted in the catchment area of SCH, age-specific estimates of influenza vaccination coverage in Suzhou from the Expanded Program on Immunization database, and influenza vaccine effectiveness estimates from previous publications. Averted influenza estimations were presented as absolute numbers and in terms of the prevented fraction (PF). A hypothetical scenario with 50% coverage (but identical vaccine effectiveness) over the study period was also modeled.ResultsIn ~250,000 children, influenza vaccination prevented an estimated 731 (CI: 549–960) influenza hospitalizations (PF: 6.2% of expected, CI: 5.8–6.6%) and 10,024 (7593–12,937) influenza illnesses (PF: 6.5%, 6.4–6.7%), of which 8342 (6338–10,768) were MA (PF: 6.6%, 6.4–6.7%) from 2011 to 2016. The PFs declined each year along with decreasing influenza vaccination coverage. If 50% of the study population had been vaccinated over time, the estimated numbers of averted cases during the study period would have been 4059 (3120–5762) influenza hospitalizations (PF: 27.2%, 26.4–27.9%) and 56,215 (42,925–78,849) influenza illnesses (PF: 28.5%, 28.3–28.7%), of which 46,596 (35,662–65,234) would be MA (PF: 28.5%, 28.3–28.7%).ConclusionInfluenza vaccination is estimated to have averted influenza-associated illness outcomes even with low coverage in children aged 6–59 months in Suzhou. Increasing influenza vaccination coverage in this population could further reduce illnesses and hospitalizations.     

Survey of distribution of seasonal influenza vaccine doses in 201 countries (2004–2015): The 2003 World Health Assembly resolution on seasonal influenza vaccination coverage and the 2009 influenza pandemic have had very little impact on improving influenza control and pandemic preparedness

There is no global monitoring system for influenza vaccination coverage, making it difficult to assess progress towards the 2003 World Health Assembly (WHA) vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply International Task Force (IVS) developed a survey method to assess the global distribution of influenza vaccine doses as a proxy for vaccination coverage rates. The latest dose distribution data for 2014 and 2015 was used to update previous analyses. Data were confidentially collected and aggregated by the IFPMA Secretariat, and combined with previous IFPMA IVS survey data (2004–2013). Data were available from 201 countries over the 2004–2015 period. A “hurdle” rate was defined as the number of doses required to reach 15.9% of the population in 2008. Overall, the number of distributed doses progressively increased between 2004 and 2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses were distributed in 2015 than in 2011. Twenty–three countries were above the hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted for about 95% of doses distributed. But in EURO and WPRO, distribution rates in 2015 were only marginally higher than in 2004, and in EURO there was an overall downward trend in dose distribution. The vast majority of countries cannot meet the 2003 WHA coverage targets and are inadequately prepared for a global influenza pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the world’s population, there is urgency to redress the gross inequities in disease prevention and in pandemic preparedness. The 2003 WHA resolution must be reviewed and revised and a call issued for the renewed commitment of Member States to influenza vaccination coverage targets.