Laboratory-confirmed Influenza Illness Research Articles

Influenza Vaccine Effectiveness Against Illness and Asymptomatic Infection in 2022-2023: A Prospective Cohort Study.

Previous estimates of vaccine effectiveness (VE) against asymptomatic influenza virus infection based on seroconversion have varied widely and may be biased. We estimated 2022-2023 influenza VE against illness and asymptomatic infection in a prospective cohort. In the HEROES-RECOVER cohort, adults at increased occupational risk of influenza exposure across 7 US sites provided weekly symptom reports and nasal swabs for reverse transcription-polymerase chain reaction (RT-PCR) influenza testing. Laboratory-confirmed influenza virus infections were classified as symptomatic (≥1 symptom) or asymptomatic during the week of testing. Participants reported demographic information and vaccination through surveys; most sites verified vaccination through medical record and immunization registry review. Person-time was calculated as days from the site-specific influenza season start (September-October 2022) through date of infection, study withdrawal, or season end (May 2023). We compared influenza incidence among vaccinated versus unvaccinated participants overall, by symptom status, and by influenza A subtype, using Cox proportional hazards regression adjusted for site and occupation. We estimated VE as (1 - adjusted hazard ratio) × 100%. In total, 269 of 3785 (7.1%) participants had laboratory-confirmed influenza, including 263 (98%) influenza A virus infections and 201 (75%) symptomatic illnesses. Incidence of laboratory-confirmed influenza illness among vaccinated versus unvaccinated participants was 23.7 and 33.2 episodes per 100 000 person-days, respectively (VE: 38%; 95% CI: 15%-55%). Incidence of asymptomatic influenza virus infection was 8.0 versus 11.6 per 100 000 (VE: 13%; 95% CI: -47%, 49%). Vaccination reduced incidence of symptomatic but not asymptomatic influenza virus infection, suggesting that influenza vaccination attenuates progression from infection to illness.

Optimization of timing for maternal immunization to protect newborns from influenza infection

Objectives The primary objective of this systematic review was to identify the optimal timing for immunizing pregnant women to confer the most protection by reducing the incidence of laboratory-confirmed influenza or influenza-like illness in infants less than 6 months of age. Currently, there are gaps in research regarding the timing of administration during the gestational period to provide maximum immunogenicity to the infant. The research question being addressed is: ‘When considering immunization of pregnant mothers with the influenza vaccine, implementing a vaccination program during which trimester in pregnancy would optimize benefits for infants less than 6 months of age in terms of the incidence of laboratory-confirmed influenza and influenza-like illness?’ Design Systematic review/Meta-analysis Methods Randomized controlled trials (RCT’s) and observational studies comparing health outcomes of infants and children up to 6 months of age born to women who received inactivated influenza vaccine during pregnancy with mothers who did not receive the vaccine or received a control vaccine. The primary outcome was laboratory-confirmed influenza infection in infants. Secondary outcome measures included influenza –like illness diagnosed by a clinician and acute respiratory illness. Results 7 studies were included: 2 primary RCT’s and 5 observational studies (prospective and retrospective cohort studies).5 of the 7 studies were suitable to be included in the quantitative synthesis part and and were compared. Forrest plot analysis revealed that vaccinating pregnant mothers in the second and third trimester when compared with any trimester (1,2 and 3) (OR 0.18 vs. 0.65) conferred less protection, promoting vaccination in the first trimester. Conclusions Vaccinating pregnant mothers in the first trimester conferred greater protection to infants than any other trimester.

Optimization of timing for maternal immunization to protect newborns from influenza infection

Objectives The primary objective of this systematic review was to identify the optimal timing for immunizing pregnant women to confer the most protection by reducing the incidence of laboratory-confirmed influenza or influenza-like illness in infants less than 6 months of age. Currently, there are gaps in research regarding the timing of administration during the gestational period to provide maximum immunogenicity to the infant. The research question being addressed is: ‘When considering immunization of pregnant mothers with the influenza vaccine, implementing a vaccination program during which trimester in pregnancy would optimize benefits for infants less than 6 months of age in terms of the incidence of laboratory-confirmed influenza and influenza-like illness?’ Design Systematic review/Meta-analysis Methods Randomized controlled trials (RCT’s) and observational studies comparing health outcomes of infants and children up to 6 months of age born to women who received inactivated influenza vaccine during pregnancy with mothers who did not receive the vaccine or received a control vaccine. The primary outcome was laboratory-confirmed influenza infection in infants. Secondary outcome measures included influenza –like illness diagnosed by a clinician and acute respiratory illness. Results 7 studies were included: 2 primary RCT’s and 5 observational studies (prospective and retrospective cohort studies).5 of the 7 studies were suitable to be included in the quantitative synthesis part and and were compared. Forrest plot analysis revealed that vaccinating pregnant mothers in the second and third trimester when compared with any trimester (1,2 and 3) (OR 0.18 vs. 0.65) conferred less protection, promoting vaccination in the first trimester. Conclusions Vaccinating pregnant mothers in the first trimester conferred greater protection to infants than any other trimester.

Neuropsychiatric outcomes in offspring after fetal exposure to maternal influenza infection during pregnancy: A systematic review

Increasing evidence suggests that influenza infection in pregnancy may disrupt fetal neurodevelopment. The impact of maternal influenza infection on offspring neuropsychiatric health has not been comprehensively reviewed. We systematically reviewed comparative studies evaluating associations between maternal influenza infection and neuropsychiatric health outcomes in offspring. We searched MEDLINE, EMBASE, CINAHL, and Web of Science for articles published until January 7, 2022. Included were English studies evaluating neuropsychiatric outcomes in offspring aged > 6 months born to women with and without influenza during pregnancy, defined as clinical or laboratory-confirmed influenza illness, or being pregnant during pandemics/epidemics. Of 12,010 records screened, 42 studies were included. Heterogeneity in study design, exposures, and outcome definitions precluded meta-analyses. Four of 14 studies assessing schizophrenia reported adjusted ratio estimates from 0.5 to 8.2; most 95% CIs contained the null value; study quality was high in three of four. Two studies reported an increased risk of schizophrenia with influenza exposure any time during pregnancy (adjusted incidence rate ratio 8.2, 95% CI: 1.4–48.8; adjusted odds ratio 1.3, 95% CI: 1.2–1.5); another reported a reduced risk with first-trimester exposure (adjusted risk ratio 0.5, 95% CI: 0.3–0.9). Seven studies of autism spectrum disorder reported adjusted ratio estimates from 0.9 to 4.0; all 95% CIs included the null value; study quality was high in four. No conclusions could be drawn about the association between exposure to maternal influenza and neuropsychiatric outcomes due to the limited quantity and quality of available research. Large observational studies with long-term follow-up are required to investigate these associations.

Cost-effectiveness of seasonal influenza vaccination in pregnant women, healthcare workers and adults >= 60 years of age in Lao People’s Democratic Republic

BackgroundPregnant women, healthcare workers (HW), and adults >= 60 years have shown an increased vulnerability to seasonal influenza virus infections and/or complications. In 2012, the Lao People's Democratic Republic (Lao PDR) initiated a national influenza vaccination program for these target groups. A cost-effectiveness evaluation of this program was undertaken to inform program sustainability. MethodsWe designed a decision-analytical model and collected influenza-related medical resource utilization and cost data, including indirect costs. Model inputs were obtained from medical record abstraction, interviews of patients and staff at hospitals in the national influenza sentinel surveillance system and/or from literature reviews. We compared the annual disease and economic impact of influenza illnesses in each of the target groups in Lao PDR under scenarios of no vaccination and vaccination, and then estimated the cost-effectiveness of the vaccination program. We performed sensitivity analyses to identify influential variables. ResultsOverall, the vaccination of pregnant women, HWs, and adults >= 60 years could annually save 11,474 doctor visits, 1,961 days of hospitalizations, 43,027 days of work, and 1,416 life-years due to laboratory-confirmed influenza illness. After comparing the total vaccination program costs of 23.4 billion Kip, to the 18.4 billion Kip saved through vaccination, we estimated the vaccination program to incur a net cost of five billion Kip (599,391 USD) annually. The incremental cost per life-year saved (ICER) was 44 million Kip (5,295 USD) and 6.9 million Kip (825 USD) for pregnant women and adults >= 60 years, respectively. However, vaccinating HWs provided societal cost-savings, returning 2.88 Kip for every single Kip invested. Influenza vaccine effectiveness, attack rate and illness duration were the most influential variables to the model. ConclusionProviding influenza vaccination to HWs in Lao PDR is cost-saving while vaccinating pregnant women and adults >= 60 is cost-effective and highly cost-effective, respectively, per WHO standards.

Influenza vaccine effectiveness within prospective cohorts of healthcare personnel in Israel and Peru 2016–2019

BackgroundThere are limited data on influenza vaccine effectiveness (IVE) in preventing laboratory-confirmed influenza illness among healthcare personnel (HCP). MethodsHCP with direct patient contact working full-time in hospitals were followed during three influenza seasons in Israel (2016–2017 to 2018–2019) and Peru (2016 to 2018). Trivalent influenza vaccines were available at all sites, except during 2018–2019 when Israel used quadrivalent vaccines; vaccination was documented by electronic medical records, vaccine registries, and/or self-report (for vaccinations outside the hospital). Twice-weekly active surveillance identified acute respiratory symptoms or febrile illness (ARFI); self-collected respiratory specimens were tested by real-time reverse transcription polymerase chain reaction (PCR) assay. IVE was 100 × 1-hazard ratio (adjusted for sex, age, occupation, and hospital). ResultsAmong 5,489 HCP who contributed 10,041 person-seasons, influenza vaccination coverage was 47% in Israel and 32% in Peru. Of 3,056 ARFIs in Israel and 3,538 in Peru, A or B influenza virus infections were identified in 205 (7%) in Israel and 87 (2.5%) in Peru. IVE against all viruses across seasons was 1% (95% confidence interval [CI] = −30%, 25%) in Israel and 12% (95% CI = −61%, 52%) in Peru. ConclusionEstimates of IVE were null using person-time models during six study seasons in Israel and Peru.

Changes in the incidence of seasonal influenza in response to COVID-19 social distancing measures: an observational study based on Canada\u2019s national influenza surveillance system

ObjectivesSeasonal influenza is an acute respiratory infection that presents a significant annual burden to Canadians and the Canadian healthcare system. Social distancing measures that were implemented to control the 2019–2020 novel coronavirus outbreak were investigated for their ability to lessen the incident cases of seasonal influenza.MethodsWe conducted an ecological study using data from Canada’s national influenza surveillance system to investigate whether social distancing measures to control COVID-19 reduced the incident cases of seasonal influenza. Data taken from three separate time frames facilitated analysis of the 2019–2020 influenza season prior to, during, and following the implementation of COVID-19-related measures and enabled comparisons with the same time periods during three preceding flu seasons. The incidence, which referred to the number of laboratory-confirmed cases of specific influenza strains, was of primary focus. Further analysis determined the number of new laboratory-confirmed influenza or influenza-like illness outbreaks.ResultsOur results indicate a premature end to the 2019–2020 influenza season, with significantly fewer cases and outbreaks being recorded following the enactment of many COVID-19 social distancing policies. The incidence of influenza strains A (H3N2), A (unsubtyped), and B were all significantly lower at the tail end of the 2019–2020 influenza season as compared with preceding seasons (p = 0.0003, p = 0.0007, p = 0.0019).ConclusionSpecific social distancing measures and behaviours may serve as effective tools to limit the spread of influenza transmission moving forward, as they become more familiar.

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults.

Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought correlates of protection against laboratory-confirmed influenza illness (LCII) in a 4-year randomized trial of standard versus high-dose influenza vaccination of adults 65 years and older. To this end, we quantified serum hemagglutination-inhibition (HAI) titers and interferon-gamma (IFNγ) and interleukin-10 (IL-10) secretion by virus-challenged peripheral blood mononuclear cells. Of the 608 participants included, 26 developed either A/H3N2-(n = 17) or B-LCII (n = 9) at 10–20 weeks post-vaccination. Antibody titres for A/H3N2 at 4-weeks post-vaccination were significantly associated with protection against LCII, where every 1-standard deviation increase reduced the odds of A/H3N2-LCII by 53%. Although B-titres did not correlate with protection against B-LCII, the fold-increase in IFNγ:IL-10 ratios from pre- to 4-weeks post-vaccination was significantly associated with protection against B-LCII, where every 1-standard deviation increase reduced the odds by 71%. Our results suggest that both antibody and cell-mediated immune measures are valuable and potentially complementary correlates of protection against LCII in vaccinated older adults, although this may depend on the viral type causing infection.

Estimates of Inactivated Influenza Vaccine Effectiveness Among Children in Senegal: Results From 2 Consecutive Cluster-Randomized Controlled Trials in 2010 and 2011.

We report results of years 2 and 3 of consecutive cluster-randomized controlled trials of trivalent inactivated influenza vaccine (IIV3) in Senegal. We cluster-randomized (1:1) 20 villages to annual vaccination with IIV3 or inactivated poliovirus vaccine (IPV) of age-eligible residents (6 months-10 years). The primary outcome was total vaccine effectiveness against laboratory-confirmed influenza illness (LCI) among age-eligible children (modified intention-to-treat population [mITT]). Secondary outcomes were indirect (herd protection) and population (overall community) vaccine effectiveness. We vaccinated 74% of 12 408 age-eligible children in year 2 (June 2010-April 11) and 74% of 11 988 age-eligible children in year 3 (April 2011-December 2011) with study vaccines. Annual cumulative incidence of LCI was 4.7 (year 2) and 4.2 (year 3) per 100 mITT child vaccinees of IPV villages. In year 2, IIV3 matched circulating influenza strains. The total effectiveness was 52.8% (95% confidence interval [CI], 32.3-67.0), and the population effectiveness was 36.0% (95% CI, 10.2-54.4) against LCI caused by any influenza strain. The indirect effectiveness against LCI by A/H3N2 was 56.4% (95% CI, 39.0-68.9). In year 3, 74% of influenza detections were vaccine-mismatched to circulating B/Yamagata and 24% were vaccine-matched to circulating A/H3N2. The year 3 total effectiveness against LCI was -14.5% (95% CI, -81.2-27.6). Vaccine effectiveness varied by type/subtype of influenza in both years. IIV3 was variably effective against influenza illness in Senegalese children, with total and indirect vaccine effectiveness present during the year when all circulating strains matched the IIV3 formulation. NCT00893906.

Assessment of indirect protection from maternal influenza immunization among non-vaccinated household family members in a randomized controlled trial in Sarlahi, Nepal

Influenza is a significant cause of morbidity and mortality worldwide, and the World Health Organization highly recommends maternal vaccination during pregnancy. The indirect effect of maternal vaccination on other close contacts other than newborns is unknown. To evaluate this, we conducted a nested substudy between 2011 and 2012 of influenza and acute respiratory illness (ARI) among household members of pregnant women enrolled in a randomized placebo-controlled trial of antenatal influenza vaccination in the rural district of Sarlahi, Nepal. Women were assigned to receive influenza vaccination or placebo during pregnancy and then they and their household members were followed up to 6 months postpartum with weekly symptom surveillance and nasal swab collection. Swabs were tested by RT-PCR for influenza. Rates of laboratory-confirmed influenza and of ARI were compared between vaccine and placebo groups using generalized estimating equations with a Poisson link function. Overall, 1752 individuals in 520 households were eligible for inclusion. There were 82 laboratory-confirmed influenza illness episodes, for a rate of 7.0 per 100 person-years overall. Of the influenza strains able to be typed, 29 were influenza A, 40 were influenza B, and 6 were coinfections with influenza A and B. The rate did not differ significantly whether the household was in the vaccine or placebo group (rate ratio (RR) 1.37, 95% confidence interval (CI) 0.83–2.26). The rate of ARI was 28.5 per 100 person-years overall and did not differ by household group (RR 0.99, 95% CI 0.72–1.36). Influenza vaccination of pregnant women did not provide indirect protection of unvaccinated household members.

Efficacy and safety of a live attenuated influenza vaccine in Chinese healthy children aged 3–17 years in one study center of a randomized, double-blind, placebo-controlled phase 3 clinical trial, 2016/17 season

BackgroundNo data on the safety and efficacy of a live attenuated influenza vaccine in China have ever been reported. MethodsAt a site of a phase 3 randomized, double-blind, placebo-controlled clinical trial in eastern China, eligible healthy children aged 3–17 years underwent randomization to receive live attenuated vaccine or placebo at a ratio of 1:1. The primary objective of the study was the prevention of laboratory-confirmed influenza illness during the surveillance period, starting on day 15 after vaccination. ResultsA total of 2000 participants were enrolled, with 998 receiving the vaccine and 1001 receiving placebo. Sixty-four cases of influenza-like illness were observed, of which, 44 were laboratory-confirmed (12 in vaccine group versus 32 in placebo group). Vaccine efficacy was 62.5% (95%CI: 27.6–80.6) against all types of influenza and 63.3% (95%CI: 27.5–81.5) against influenza H3N2 illness. 11 severe adverse events reported (7 in LAIV group versus 4 in placebo group) were all deemed to be non-vaccine-related. Adverse events occurred in 412 (41.3%) participants in the vaccine group versus 389 (38.9%; p = 0.274) participants in the placebo group. Significant increase incidence of fever was observed in participants in the vaccine group, especially in those aged 3–9 years. ConclusionsThe live attenuated influenza vaccine showed good efficacy and safety among 3- to 17-year-olds children during the 2016–2017 season at a site in eastern China.Clinical Trial Registry Number: NCT02964065.

Serious outcomes of medically attended, laboratory-confirmed influenza illness among school-aged children with and without asthma, 2007-2018.

BackgroundAsthma was associated with influenza hospitalizations in children during the 2009 pandemic, but it is unclear if asthma is associated with serious illness during seasonal epidemics. Little is known regarding the effect of vaccination on influenza severity in children with asthma.MethodsChildren aged 5‐17 years in a community cohort presenting with acute respiratory illness were prospectively enrolled and tested for influenza from 2007‐08 through 2017‐18 (excluding the 2009‐10 pandemic season). Data from the electronic health record were extracted to determine asthma status and serious outcomes associated with influenza infection. A serious outcome was defined as hospitalization, emergency department visit, and/or pneumonia diagnosis within 30 days of symptom onset. Multivariable logistic regression models were used to assess asthma status and effect of vaccination on odds of a serious outcome.ResultsOne thousand seven hundred and sixty four medically‐attended influenza infections among school‐aged children were included. Asthma was confirmed in 287 (16%) children. A serious influenza‐associated outcome occurred in 104 (6%) children. The odds of a serious outcome did not differ between those with confirmed asthma and those without asthma [adjusted odds ratio (aOR): 1.35, 95% confidence interval (CI): (0.77‐2.35), P = .3]. The effect of vaccination on serious outcomes was not modified by asthma status [aOR for children without asthma: 0.55 (95% CI: 0.28‐1.07), children with asthma: 1.39 (95% CI: 0.53‐3.69); interaction P‐value = .12].ConclusionsAsthma was not a risk factor for serious illness among children with influenza. Additional studies are needed to better understand the role of influenza vaccination in preventing serious outcomes among children with asthma.

Influenza vaccine effectiveness estimates against influenza A(H3N2) and A(H1N1) pdm09 among children during school-based outbreaks in the 2016–2017 season in Beijing, China

ABSTRACT Background Since 2007, trivalent inactivated influenza vaccine (TIV) has been provided free-of-charge to primary, middle school and high school students in Beijing. However, there have been few school-based studies on influenza vaccine effectiveness (VE). In this report, we estimated influenza VE against laboratory-confirmed influenza illness among school children in Beijing, China during the 2016–2017 influenza season. Methods The VE of 2016–2017 TIV against laboratory-confirmed influenza virus infection among school-age children was assessed through a case–control design. Conditional logistic regression was conducted on matched case–control sets to estimate VE. The effect of prior vaccination on current VE was also examined. Results All 176 samples tested positive for influenza A virus with the positive rate of 55.5%. The average coverage rate of 2016–2017 TIV among students across the 37 schools was 30.6%. The fully adjusted VE of 2016–2017 TIV against laboratory-confirmed influenza was 69% (95% CI: 51 to 81): 60% (95% CI: −15 to 86) for influenza A(H1N1)pdm09 and 73% (95% CI: 52 to 84) for influenza A(H3N2). The overall VE for receipt of 2015–2016 vaccination only, 2016–2017 vaccination only, and vaccinations in both seasons was 46% (95% CI: −5 to 72), 77% (95% CI: 58 to 87), and 57% (95%CI: 17 to 78), respectively. Conclusions Our study during school outbreaks found that VE of 2016–2017 TIV was moderate against influenza A(H3N2) as well as A(H1N1)pdm09 viruses.

Dose effect of influenza vaccine on protection against laboratory-confirmed influenza illness among children aged 6 months to 8 years of age in southern China, 2013/14–2015/16 seasons: a matched case–control study

ABSTRACT Background We conducted a matched case–control study in China during the 2013/14–2015/16 influenza seasons to estimate influenza vaccine effectiveness (VE) by dose among children aged 6 months to 8 years. Methods Cases were laboratory-confirmed influenza infections identified through the influenza-like illness sentinel surveillance network in Guangzhou. Age- and sex-matched community controls were randomly selected through the expanded immunization program database. We defined priming as receipt of ≥1 dose of influenza vaccine during the immediate prior season. Results In total, 4,185 case–control pairs were analyzed. Among children 6–35 months, VE for current season dose(s) across the three seasons during 2013/14–2015/16 were 59% (95% Confidence Interval: 44–71%), 12% (−11%,30%), 54% (32–69%); among unprimed children 6–35 months, VE for 1 vs 2 current season doses were 45% (8–67%) vs 65% (46–78%), −2% (−53%,32%) vs 19% (−11%,40%), and 37% (−24%,68%) vs 61% (32–78%). Among children aged 3–8 years, VE for current season dose(s) across study seasons were 62% (36–78%), 43% (22–58%), 32% (1–53%). VE for unprimed children receiving 1 dose only in current season was insignificant or lower than among all children. Conclusion Findings support utility of providing second dose (“booster dose”) of seasonal influenza vaccine to unprimed children aged 6–35 months, and the need to study further dose effect of a booster dose among unprimed children aged 3–8 years in China.

Influenza Vaccine Effectiveness and Statin Use Among Adults in the United States, 2011-2017.

Statin medications have immunomodulatory effects. Several recent studies suggest that statins may reduce influenza vaccine response and reduce influenza vaccine effectiveness (VE). We compared influenza VE in statin users and nonusers aged ≥45 years enrolled in the US Vaccine Effectiveness Network study over 6 influenza seasons (2011-2012 through 2016-2017). All enrollees presented to outpatients clinics with acute respiratory illness and were tested for influenza. Information on vaccination status, medical history, and statin use at the time of vaccination were collected by medical and pharmacy records. Using a test-negative design, we estimated VE as (1 - OR) × 100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated vs unvaccinated participants. Among 11692 eligible participants, 3359 (30%) were statin users and 2806 (24%) tested positive for influenza virus infection; 78% of statin users and 60% of nonusers had received influenza vaccine. After adjusting for potential confounders, influenza VE was 36% (95% confidence interval [CI], 22%-47%) among statin users and 39% (95% CI, 32%-45%) among nonusers. We observed no significant modification of VE by statin use. VE against influenza A(H1N1)pdm09, A(H3N2), and B viruses were similar among statin users and nonusers. In this large observational study, influenza VE against laboratory-confirmed influenza illness was not affected by current statin use among persons aged ≥45 years. Statin use did not modify the effect of vaccination on influenza when analyzed by type and subtype.

Moderate influenza vaccine effectiveness against influenza A(H1N1)pdm09 virus and low effectiveness against A(H3N2) virus among older adults during 2013–2014 influenza season in Beijing, China

ABSTRACTBackground: Since 2007, trivalent inactivated influenza vaccine has been provided free-of-charge to older adults aged ≥60 years in Beijing, China, but the data regarding influenza vaccine effectiveness (VE) among these people are very limited so far. We sought to estimate influenza VE against medically-attended laboratory-confirmed influenza illness among older adults during the 2013–2014 season.Methods: The influenza-like illness (ILI) patients aged 60 years and older who participated in the influenza virological surveillance of Beijing during 2013–2014 influenza season were recruited in this study. A test-negative design was employed to estimate influenza VE among older adults by using logistic regression models. VE was estimated using logistic regression, adjusted for sex, age, interval (days) between illness onset and specimen collection, and week of illness onset.Results: Between 1 November, 2013 and 30 April, 2014, a total of 487 elderly ILI patients were enrolled in the study, including 133 influenza-positive cases (of whom 6.8% were vaccinated) and 354 influenza-negative controls (of whom 10.2% were vaccinated). Among 133 influenza-positive cases, 51 tested positive for A(H1N1)pdm09 virus, 22 positive for A(H3N2) virus, 52 tested positive for B/Yamagata-lineage virus, 2 positive for B/Victoria-lineage virus, 1 positive for both A(H1N1)pdm09 and A(H3N2) viruses, and 5 tested positive for viruses of unknown subtype or lineage. The adjusted overall VE was estimated as 32% (95% CI:-48-69), with 59% (95% CI: −79–90) against A(H1N1)pdm09, 22% (95% CI: −253-83) against A(H3N2) and −20% (95% CI: −239-58) against B/Yamagata-lineage viruses.Conclusions: These results suggested a modest protective effect of the 2013–2014 influenza vaccine among older adults in Beijing which was not statistically significant, with higher VE against the A(H1N1)pdm09 viruses compared to A(H3N2) and B viruses.

Impact of Human Immunodeficiency Virus on the Burden and Severity of Influenza Illness in Malawian Adults: A Prospective Cohort and Parallel Case-Control Study

The impact of human immunodeficiency virus (HIV) infection on influenza incidence and severity in adults in sub-Saharan Africa is unclear. Seasonal influenza vaccination is recommended for HIV-infected persons in developed settings but is rarely implemented in Africa. We conducted a prospective cohort study to compare the incidence of laboratory-confirmed influenza illness between HIV-infected and HIV-uninfected adults in Blantyre, Malawi. In a parallel case-control study, we explored risk factors for severe influenza presentation of severe (hospitalized) lower respiratory tract infection, and mild influenza (influenza-like illness [ILI]). The cohort study enrolled 608 adults, of whom 360 (59%) were HIV infected. Between April 2013 and March 2015, 24 of 229 ILI episodes (10.5%) in HIV-infected and 5 of 119 (4.2%) in HIV-uninfected adults were positive for influenza by means of polymerase chain reaction (incidence rate, 46.0 vs 14.5 per 1000 person-years; incidence rate ratio, 2.75; 95% confidence interval, 1.02-7.44; P = .03; adjusted for age, sex, household crowding, and food security). In the case-control study, influenza was identified in 56 of 518 patients (10.8%) with hospitalized lower respiratory tract infection, and 88 or 642 (13.7%) with ILI. The HIV prevalence was 69.6% and 29.6%, respectively, among influenza-positive case patients and controls. HIV was a significant risk factor for severe influenza (odds ratio, 4.98; 95% confidence interval, 2.09-11.88; P < .001; population-attributable fraction, 57%; adjusted for season, sanitation facility, and food security). HIV is an important risk factor for influenza-associated ILI and severe presentation in this high-HIV prevalence African setting. Targeted influenza vaccination of HIV-infected African adults should be reevaluated, and the optimal mechanism for vaccine introduction in overstretched health systems needs to be determined.

Influenza vaccine-mediated protection in older adults: Impact of influenza infection, cytomegalovirus serostatus and vaccine dosage

Age-related changes in T-cell function are associated with a loss of influenza vaccine efficacy in older adults. Both antibody and cell-mediated immunity plays a prominent role in protecting older adults, particularly against the serious complications of influenza. High dose (HD) influenza vaccines induce higher antibody titers in older adults compared to standard dose (SD) vaccines, yet its impact on T-cell memory is not clear.The aim of this study was to compare the antibody and T-cell responses in older adults randomized to receive HD or SD influenza vaccine as well as determine whether cytomegalovirus (CMV) serostatus affects the response to vaccination, and identify differences in the response to vaccination in those older adults who subsequently have an influenza infection.Older adults (≥65years) were enrolled (n=106) and randomized to receive SD or HD influenza vaccine. Blood was collected pre-vaccination, followed by 4, 10 and 20weeks post-vaccination. Serum antibody titers, as well as levels of inducible granzyme B (iGrB) and cytokines were measured in PBMCs challenged ex vivo with live influenza virus. Surveillance conducted during the influenza season identified those with laboratory confirmed influenza illness or infection.HD influenza vaccination induced a high antibody titer and IL-10 response, and a short-lived increase in Th1 responses (IFN-γ and iGrB) compared to SD vaccination in PBMCs challenged ex vivo with live influenza virus. Of the older adults who became infected with influenza, a high IL-10 and iGrB response in virus-challenged cells was observed post-infection (week 10 to 20), as well as IFN-γ and TNF-α at week 20. Additionally, CMV seropositive older adults had an impaired iGrB response to influenza virus-challenge, regardless of vaccine dose.This study illustrates that HD influenza vaccines have little impact on the development of functional T-cell memory in older adults. Furthermore, poor outcomes of influenza infection in older adults may be due to a strong IL-10 response to influenza following vaccination, and persistent CMV infection.

Granzyme B: a biomarker of influenza infection in older adults

Abstract The importance of a T-cell mediated response against influenza infection in older adults has growing support. It has been previously shown that effector cells in older adults challenged with influenza virus produce granzyme B (GrB) in the absence of perforin. This lack of perforin could impair CTL directed killing and result in high extracellular GrB levels. GrB has been associated with various inflammatory and age related conditions and could also play an important role in influenza infection severity. We postulate that GrzB is a key mediator of inflammatory processes involved in severe influenza illness and could be used as a marker of influenza infection in older adults. Subjects over the age of 65 admitted to hospital with influenza like symptoms were recruited and grouped into cases of laboratory confirmed influenza illness (LCII) and influenza like illness (ILI). PBMCs were isolated from blood samples collected from participants on hospital admission and one month post-discharge. PBMCs were challenge with live influenza virus. Real-time PCR was used to quantify IFNγ, GrB and IL10 in PBMCs and isolated T-cells. We found that in vivo GrB levels in T-cells at the time of influenza infection in older adults were significantly higher in the LCII than the ILI group. Furthermore, ex vivo influenza virus challenge resulted in higher IFNγ, GrB and IL10 responses in subjects with LCII than ILI. Our study supports the association of elevated GrB and influenza infection status as well as the importance of T-cell mediated responses to infection. Future work will characterize GrB levels in older adults with varying severities of influenza illness with the aim to develop a point of care test to identify patients likely to develop serious outcomes.

Efficacy of a Russian-backbone live attenuated influenza vaccine among young children in Bangladesh: a randomised, double-blind, placebo-controlled trial.

SummaryBackgroundThe rates of influenza illness and associated complications are high among children in Bangladesh. We assessed the clinical efficacy and safety of a Russian-backbone live attenuated influenza vaccine (LAIV) at two field sites in Bangladesh.MethodsBetween Feb 27 and April 9, 2013, children aged 2–4 years in urban Kamalapur and rural Matlab, Bangladesh, were randomly assigned in a 2:1 ratio, according to a computer-generated schedule, to receive one intranasal dose of LAIV or placebo. After vaccination, we monitored children in weekly home visits until Dec 31, 2013, with study clinic surveillance for influenza illness. The primary outcome was symptomatic, laboratory-confirmed influenza illness due to vaccine-matched strains. Analysis was per protocol. The trial is registered with ClinicalTrials.gov, number NCT01797029.FindingsOf 1761 children enrolled, 1174 received LAIV and 587 received placebo. Laboratory-confirmed influenza illness due to vaccine-matched strains was seen in 93 (15·8%) children in the placebo group and 79 (6·7%) in the LAIV group. Vaccine efficacy of LAIV for vaccine-matched strains was 57·5% (95% CI 43·6–68·0). The vaccine was well tolerated, and adverse events were balanced between the groups. The most frequent adverse events were tachypnoea (n=86 in the LAIV group and n=54 in the placebo group), cough (n=73 and n=43), and runny nose (n=68 and n=39), most of which were mild.InterpretationThis single-dose Russian-backbone LAIV was safe and efficacious at preventing symptomatic laboratory-confirmed influenza illness due to vaccine-matched strains. LAIV programmes might reduce the burden of influenza illness in Bangladesh.FundingThe Bill & Melinda Gates Foundation.