Test-negative Case Control Research Articles

2746. Effectiveness of Influenza Vaccine for Prevention of Influenza-associated Hospitalizations Among Immunocompromised Adults—2017–2018

BackgroundImmunocompromised (IC) individuals are at higher risk for severe complications of influenza. Little literature describes vaccine effectiveness (VE) in this population. We evaluated VE for prevention of influenza-associated hospitalization among IC adults.MethodsWe analyzed data from adults hospitalized with acute respiratory illness (ARI) during the 2017–2018 FLU season at 9 hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Details of disease severity, underlying health status, and vaccination status were obtained through enrollment interviews and medical records. Prior year clinical encounter diagnoses and enrollment interviews were used to define IC groups. IC groups were mutually exclusive. VE was evaluated with a test-negative case–control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, race, and other factors, and stratifying by immunocompromising conditions.ResultsOf 3524 adults hospitalized with ARI, 1210 (34%) had an immunocompromising condition. Chronic steroid (n = 397), chemo/radiation therapy (n = 242), hematologic condition (n = 175), and organ transplant (n = 144) were most common. HIV (n = 45) and stem cell transplant (SCT) (n = 28) were least common. IC patients were more likely to be vaccinated than non-IC (60% vs. 55%, P = 0.002). Overall, vaccination reduced risk of influenza hospitalization by 36% (95% CI: 24,46). Among IC adults, VE was 9% (95% CI: −25,34). VE was 32% (95% CI: 5,51) for chemo/radiation therapy, 29% (95% CI: 6,47) for chronic steroids, 29% (95% CI: -6,52) for hematologic conditions, −1% (95% CI: −50,32) for organ transplant, −48% (95% CI: −190,25) for HIV, and −154% (95% CI = −458,−15) for SCT (Figure 1).ConclusionVaccination reduced risk of influenza hospitalization among adults with the most prevalent immunocompromising conditions in our cohort; however, it had little to no effect in other groups, such as in HIV and organ and stem cell transplant recipients. Results support using other preventative strategies in addition to vaccinating adults with immunocompromising conditions, such as vaccination of close contacts. Disclosures All authors: No reported disclosures.

Protection provided by influenza vaccine against influenza-related hospitalisation in ≥65 year olds: Early experience of introduction of a newly licensed adjuvanted vaccine in England in 2018/19

2018/19 was the first season of introduction in England of a newly licensed adjuvanted influenza vaccine (aTIV) for adults 65 years or older, who were previously offered standard-dose, non-adjuvanted vaccine, achieving uptake levels >70%, often with poor effectiveness. This paper presents the end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza hospitalisation in this population. A frequency-matched test negative case control approach was used to estimate aVE by influenza A subtype and vaccine type. Cases were influenza confirmed hospitalisations and controls influenza negative hospitalisations who were 65 years or more. Cases and controls were selected from a sentinel laboratory surveillance system which collates details of inpatients and outpatients routinely tested on clinical advice for influenza infection with reverse-transcription polymerase chain reaction (RT-PCR) on respiratory samples. Vaccine and clinical history was obtained from the general practitioners of study participants. A total of 428 cases and 1013 controls were included in the analysis. End-of-season any-influenza aVE against hospitalisation was 53.4% (95% CI: 39.9, 63.9). By influenza A subtype, aVE was 64.8% (95% CI: 49.6, 75.3) against influenza A(H1N1)pdm09 and 39.3% (95% CI: 6.5, 60.6) against influenza A(H3N2). There was insufficient data to estimate influenza B VE. aVE estimates for all influenza, influenza A(H1N1)pdm09 and influenza A(H3N2) for aTIV were 53.8% (39.8, 64.5); 65.9% (50.6, 76.4) and 39.5% (4.8, 61.5) respectively. We provide evidence of significant influenza VE in the elderly, most notably against influenza A(H1N1)pdm09, but also against A(H3N2) for aTIV.

Effectiveness of influenza vaccine in children in preventing influenza associated hospitalisation, 2018/19, England

2013/14 saw the start of the introduction of a new live attenuated influenza vaccine (LAIV) programme for children in England. 2018/19 saw co-circulation of both A(H1N1)pdm09 and A(H3N2), when LAIV was offered to all healthy children 2–9 years of age. LAIV effectiveness against influenza hospitalisation is not well described. This paper presents the 2018/19 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related hospitalisation in children aged 2–17. The test negative case control approach was used to estimate aVE by influenza A subtype and vaccine type. Cases and controls were selected from a sentinel laboratory surveillance system which collates details of individuals tested for influenza with reverse-transcription polymerase chain reaction (RT-PCR) on respiratory samples. Vaccine and clinical history was obtained from general practitioners of study participants. There were 307 hospitalised cases and 679 hospitalised controls. End-of-season influenza aVE was 53.0% (95% CI: 33.3, 66.8) against influenza confirmed hospitalisation; 63.5% (95% CI: 34.4, 79.7) against influenza A(H1N1)pdm09 hospitalisation and 31.1% (95% CI: −53.9, 69.2) against influenza A(H3N2). LAIV aVE was 49.1% (95% CI: 25.9, 65.0) for any influenza and 70.7% (95% CI: 41.8, 85.3) for A(H1N1)pdm09, whereas for those receiving quadrivalent inactivated influenza vaccine (QIV), aVE was 64.4% (95% CI: 29.4, 82.0) and 44.4% (95% CI: −51.9, 79.6) respectively. We provide evidence of overall significant VE for both LAIV and QIV against influenza associated hospitalisation in children 2–17 years of age, most notably against influenza A(H1N1)pdm09, with non-significant protection against A(H3N2).

End of season influenza vaccine effectiveness in adults and children in the United Kingdom in 2017/18.

BackgroundIn the United Kingdom (UK), in recent influenza seasons, children are offered a quadrivalent live attenuated influenza vaccine (LAIV4), and eligible adults mainly trivalent inactivated vaccine (TIV).AimTo estimate the UK end-of-season 2017/18 adjusted vaccine effectiveness (aVE) and the seroprevalence in England of antibodies against influenza viruses cultured in eggs or tissue.MethodsThis observational study employed the test-negative case–control approach to estimate aVE in primary care. The population-based seroprevalence survey used residual age-stratified samples.ResultsInfluenza viruses A(H3N2) (particularly subgroup 3C.2a2) and B (mainly B/Yamagata/16/88-lineage, similar to the quadrivalent vaccine B-virus component but mismatched to TIV) dominated. All-age aVE was 15% (95% confidence interval (CI): −6.3 to 32) against all influenza; −16.4% (95% CI: −59.3 to 14.9) against A(H3N2); 24.7% (95% CI: 1.1 to 42.7) against B and 66.3% (95% CI: 33.4 to 82.9) against A(H1N1)pdm09. For 2–17 year olds, LAIV4 aVE was 26.9% (95% CI: −32.6 to 59.7) against all influenza; −75.5% (95% CI: −289.6 to 21) against A(H3N2); 60.8% (95% CI: 8.2 to 83.3) against B and 90.3% (95% CI: 16.4 to 98.9) against A(H1N1)pdm09. For ≥ 18 year olds, TIV aVE against influenza B was 1.9% (95% CI: −63.6 to 41.2). The 2017 seroprevalence of antibody recognising tissue-grown A(H3N2) virus was significantly lower than that recognising egg-grown virus in all groups except 15–24 year olds.ConclusionsOverall aVE was low driven by no effectiveness against A(H3N2) possibly related to vaccine virus egg-adaption and a new A(H3N2) subgroup emergence. The TIV was not effective against influenza B. LAIV4 against influenza B and A(H1N1)pdm09 was effective.

Evaluation of the influenza vaccine effectiveness among children aged 6 to 72 months based on the test-negative case control study design

Objective: To assess the effectiveness of seasonal influenza vaccine among children aged 6 to 72 months. Methods: The test-negative case control study was conducted based on available surveillance data which was from China Influenza Surveillance Information system (CSIS). From October 2016 to April 2017 and from October 2017 to April 2018,1 161 cases aged 6-72 months with influenza-like illness in Yongkang and Yiwu city, were selected as the study subjects, and the cases with influenza test-positive were selected as the case group (403 cases). Test-negative subjects were selected as control group (758 cases). The etiology and immunization data of the subjects were obtained from CSIS and Immune Information and Management System (IIMS) respectively. Vaccine effectiveness was estimated using multivariate logistic regression model,and the mixed effects of non-randomized control in TNCC study were equalized by using the propensity score (PS) method in the statistical analysis. Results: The age of the subjects was (2.44±1.60) years,and there were 681 boys (58.66%). The age of case group was (2.62±1.58) years, and there were 246 boys (61.04%). The case group was including of 237 cases (58.81%) of influenza A (H3N2), 92 cases (22.83%) of influenza A (H1N1) pmd09, 62 cases (15.38%) of influenza B(Victoria) lineage, 11 cases (2.73%) of influenza B (Yamagata) lineage and one case (0.25%) co-infection of influenza [A(H(3)N(2))+B (Victoria)]. The mean age of the control group was (2.35±1.61) years,and there were 435 boys (57.39%). Overall vaccine effectiveness (VE) against all type influenza for two seasons combined was 58% (95%CI: 31%-74%). An analysis by age groups showed 68% (95%CI:41%-82%) of the VE estimate among children aged 36-72 months while it was 28%(95%CI:-80%-71%)of the VE estimate among children aged 6-35 months. The VE estimate value was 54% (95%CI:16%-75%) against all type influenza and 65% (95%CI:24%-83%) against influenza A (H(3)N(2)) during the 2016-2017 season. During the 2017-2018 season, the VE estimate value was 69% (95%CI:18%-88%) against all type influenza. Conclusion: Influenza vaccine is effective in preventing influenza virus infection during the flu season,especially the effect among children aged 36-72 months is higher compared to that among children aged 6-35 months.

Influenza vaccine effectiveness against hospitalisation due to laboratory-confirmed influenza in children in England in the 2015-2016 influenza season - a test-negative case-control study.

England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case-control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2-16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015-2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3-54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3-63.6) and 28.8% (95% CI -31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015-2016 and continues to support the rollout of the LAIV childhood programme.

1973. A Meta-Analysis of the Effectiveness of LAIV4 and IIV against Influenza A/H3N2 Strains in Children 2–18 Years of Age During the 2016–2017 Season

BackgroundThe effectiveness of the quadrivalent live attenuated influenza vaccine (LAIV4) and inactivated influenza vaccines (IIV) has been evaluated in recent seasons using a number of different study designs (e.g., randomized controlled studies [RCT], cohort studies and test-negative case–control [TNCC] studies). Effectiveness estimates from these studies have, in general, had very broad confidence intervals reflecting the small numbers of cases reported. We conducted a meta-analysis to more precisely estimate the effectiveness of both vaccine types for the 2016–2017 season.MethodsLAIV4 and IIV efficacy and effectiveness studies conducted over the 2016–2017 influenza season were identified from the published literature and through personal communication with the study investigators. Effectiveness estimates from all available study designs were included in the meta-analysis to maximize use of all available data and because all studies included methods to minimize bias. The analysis provided average estimates of the LAIV4 and IIV efficacy across countries. A sensitivity analysis limited to TNCC studies was also conducted. Only effectiveness results for A/H3N2 strains were combined as circulation of other strains was minimal. The meta-analyses used a random effects model. Heterogeneity testing was performed.ResultsSeven studies conducted in children in the United States, Japan, Finland, Germany, thr UK, and Canada were identified including four TNCC studies, one cohort study and one RCT (Figure 1). Individual effectiveness estimates ranged from 29% to 74% for LAIV4 and from 31% to 56% for IIV. Heterogeneity testing for H3N2 strains was not statistically significant. The consolidated effectiveness estimate across studies for LAIV4 was 44% (95% CI: 24, 58) and for IIV was 45% (95% CI: 29, 58). Estimates for the sensitivity analysis limited to TNCC studies were 61% (95% CI: 40, 74) and 43% (95% CI: 32, 52) for LAIV4 and IIV, respectively. ConclusionDespite variability in estimates across studies, both LAIV4 and IIV showed moderate and comparable effectiveness in children for circulating H3N2 strains during the 2016–2017 influenza season.Disclosures R. Mallory, MedImmune: Employee, Salary. A. Bandell, AstraZeneca: Employee, Salary. C. S. Ambrose, AstraZeneca: Employee, Salary. J. Yu, GSK: Employee, Salary and Stockholder.

Effectiveness of influenza vaccine in preventing medically-attended influenza virus infection in primary care, Israel, influenza seasons 2014/15 and 2015/16.

IntroductionInfluenza vaccine is recommended for the entire population in Israel. We assessed influenza vaccine effectiveness (VE) for the 2014/15 and 2015/16 seasons in Israel, for the first time. Methods: Combined nose and throat swab specimens were collected from patients with influenza-like illness (ILI) presenting to sentinel primary care clinics and tested for influenza virus by RT-PCR. VE of the trivalent inactivated vaccine (TIV) was assessed using test-negative case–control design. Results: During the 2014/15 season 1,142 samples were collected; 327 (28.6%) were positive for influenza, 83.8% A(H3N2), 5.8% A(H1N1)pdm09, 9.2% B and 1.2% A un-subtyped. Adjusted VE against all influenza viruses for this influenza season was −4.8% (95% confidence interval (CI): −54.8 to 29.0) and against influenza A(H3N2), it was −15.8% (95% CI: −72.8 to 22.4). For the 2015/16 season, 1,919 samples were collected; 853 (44.4%) were positive for influenza, 43.5% A(H1N1)pdm09, 57% B, 0.7% A(H3N2) and 11 samples positive for both A(H1N1)pdm09 and B. Adjusted VE against all influenza viruses for this influenza season was 8.8% (95% CI: −25.1 to 33.5), against influenza A(H1N1)pdm09, it was 32.3% (95% CI: (−4.3 to 56.1) and against influenza B, it was −2.2% (95% CI: (−47.0 to 29.0). Conclusions: Using samples from patients with ILI visiting sentinel clinics in Israel, we demonstrated the feasibility of influenza VE estimation in Israel.

End-of-season influenza vaccine effectiveness in adults and children, United Kingdom, 2016/17.

IntroductionThe United Kingdom is in the fourth season of introducing a universal childhood influenza vaccine programme. The 2016/17 season saw early influenza A(H3N2) virus circulation with care home outbreaks and increased excess mortality particularly in those 65 years or older. Virus characterisation data indicated emergence of genetic clusters within the A(H3N2) 3C.2a group which the 2016/17 vaccine strain belonged to. Methods: The test-negative case–control (TNCC) design was used to estimate vaccine effectiveness (VE) against laboratory confirmed influenza in primary care. Results: Adjusted end-of-season vaccine effectiveness (aVE) estimates were 39.8% (95% confidence interval (CI): 23.1 to 52.8) against all influenza and 40.6% (95% CI: 19.0 to 56.3) in 18–64-year-olds, but no significant aVE in ≥ 65-year-olds. aVE was 65.8% (95% CI: 30.3 to 83.2) for 2–17-year-olds receiving quadrivalent live attenuated influenza vaccine. Discussion: The findings continue to provide support for the ongoing roll-out of the paediatric vaccine programme, with a need for ongoing evaluation. The importance of effective interventions to protect the ≥ 65-year-olds remains.

Seasonal influenza vaccine effectiveness against laboratory-confirmed influenza in 2015–2016: a hospital-based test-negative case–control study in Lithuania

ObjectiveA case–control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015–2016 influenza season.MethodsA study was performed in three departments in Lithuania between 1 December 2015 and...

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza A(H1N1)pdm09 and B among elderly people in Europe: results from the I-MOVE+ project.

We conducted a multicentre test-negative case–control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged ≥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases.

Repeated seasonal influenza vaccination among elderly in Europe: Effects on laboratory confirmed hospitalised influenza.

In Europe, annual influenza vaccination is recommended to elderly. From 2011 to 2014 and in 2015-16, we conducted a multicentre test negative case control study in hospitals of 11 European countries to measure influenza vaccine effectiveness (IVE) against laboratory confirmed hospitalised influenza among people aged ≥65years. We pooled four seasons data to measure IVE by past exposures to influenza vaccination. We swabbed patients admitted for clinical conditions related to influenza with onset of severe acute respiratory infection ≤7days before admission. Cases were patients RT-PCR positive for influenza virus and controls those negative for any influenza virus. We documented seasonal vaccination status for the current season and the two previous seasons. We recruited 5295 patients over the four seasons, including 465A(H1N1)pdm09, 642A(H3N2), 278 B case-patients and 3910 controls. Among patients unvaccinated in both previous two seasons, current seasonal IVE (pooled across seasons) was 30% (95%CI: -35 to 64), 8% (95%CI: -94 to 56) and 33% (95%CI: -43 to 68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Among patients vaccinated in both previous seasons, current seasonal IVE (pooled across seasons) was -1% (95%CI: -80 to 43), 37% (95%CI: 7-57) and 43% (95%CI: 1-68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Our results suggest that, regardless of patients' recent vaccination history, current seasonal vaccine conferred some protection to vaccinated patients against hospitalisation with influenza A(H3N2) and B. Vaccination of patients already vaccinated in both the past two seasons did not seem to be effective against A(H1N1)pdm09. To better understand the effect of repeated vaccination, engaging in large cohort studies documenting exposures to vaccine and natural infection is needed.

Changes in genetically drifted H3N2 influenza A viruses and vaccine effectiveness in adults 65 years and older during the 2016/17 season in Denmark

BackgroundIn Denmark, influenza A virus of the subtype H3N2 has been dominating the 2016/17 season, as in most countries of the Northern Hemisphere. ObjectivesThis study was conducted as part of the Danish seasonal influenza surveillance programme to genetically characterize circulating H3N2 viruses and determine the seasonal vaccine effectiveness (VE) overall in the Danish population and further on the virus cluster level. Study designInfluenza virus positive samples submitted for the national surveillance programme were genetically characterized by sequencing. VE estimates against influenza A and the circulating virus clusters were determined in patients above 65 years using the test-negative case–control design. ResultsThe genetic characterization revealed several genetically drifted viruses, which could be divided into four main clusters by the defining amino acid substitutions: 3C.2a/N121K/S144K, 3C.2a/T131K/R142K, 3C.2a1, and 3C.2a1/N121K. Some of the drifted viruses appeared to be more prominent in vaccinated or non-vaccinated individuals, respectively. Overall the adjusted VE was 7.4% (95% confidence interval (CI): −6.0–19.2) among inpatients and 19.3% (95% CI: −5.7–38.4) among outpatients, respectively. VE for the four main virus clusters was; cluster 3C.2a1: 38.8% (95% CI: −29.8–71.1), cluster 3C.2a/N121K/S144K: 9.2% (95% CI: −63.0–49.4), cluster 3C.2a/T131K/R142K: 19.0% (95% CI: −85.3–64.6), and cluster 3C.2a1/N121K: −12.2% (95%CI: −129.7–45.2). ConclusionsSeveral genetically drifted H3N2 viruses have been circulating in Denmark in the 2016-17 influenza season. An overall low VE was estimated and VE for the four main virus cluster indicate different VEs between the circulating drifted H3N2 viruses.

Effectiveness of rotavirus pentavalent vaccine under a universal immunization programme in Israel, 2011–2015: a case–control study

ObjectivesThe use of rotavirus pentavalent vaccine (RotaTeq®) as a sole vaccine within rotavirus universal immunization programmes remains limited. We examined the effectiveness of RotaTeq in preventing rotavirus gastroenteritis (RVGE) hospitalization in Israel, after the introduction of universal immunization against the disease. MethodsA test-negative case–control study included age-eligible children for universal RotaTeq immunization (aged 2–59 months, born in 2011–2015). Cases (n = 98) were patients who tested positive for rotavirus by immunochromatography; those who tested negative (n = 628) comprised the control group. Information on rotavirus immunization history was obtained through linkage with a national immunization registry. Vaccination status was compared between cases and controls, adjusted odds ratios (aORs) were obtained from logistic regression models, and vaccine effectiveness calculated as (1 − aOR)*100. ResultsImmunization with RotaTeq was less frequent in RVGE cases (73.5%) than in controls (90.1%), p < 0.001; this association persisted after controlling for potential confounders. Effectiveness of the complete vaccine series was estimated at 77% (95% confidence interval (CI): 49–90) in children aged 6–59 months, and 86% (95% CI: 65–94) in children aged 6–23 months; whereas for the incomplete series, the respective estimates were 72% (95% CI: 28–89) and 75% (95% CI: 30–91). Vaccine effectiveness was estimated at 79% (95% CI: 45–92) against G1P[8]-associated RVGE hospitalizations and 69% (95% CI: 11–89) against other genotype-RVGE hospitalizations. ConclusionsHigh effectiveness of RotaTeq as the sole rotavirus vaccine in a universal immunization programme was demonstrated in a high-income country. Although partial vaccination conferred protection, completing the vaccine series is warranted to maximize the benefit.

Influenza Vaccine Effectiveness in the Netherlands from 2003/2004 through 2013/2014: The Importance of Circulating Influenza Virus Types and Subtypes.

Influenza vaccine effectiveness (IVE) varies over different influenza seasons and virus (sub)types/lineages. To assess the association between IVE and circulating influenza virus (sub)types/lineages, we estimated the overall and (sub)type specific IVE in the Netherlands. We conducted a test-negative case control study among subjects with influenza-like illness or acute respiratory tract infection consulting the Sentinel Practices over 11 influenza seasons (2003/2004 through 2013/2014) in the Netherlands. The adjusted IVE was estimated using generalized linear mixed modelling and multiple logistic regression. In seven seasons vaccine strains did not match the circulating viruses. Overall adjusted IVE was 40% (95% CI 18 to 56%) and 20% (95% CI -5 to 38%) when vaccine (partially)matched and mismatched the circulating viruses, respectively. When A(H3N2) was the predominant virus, IVE was 38% (95% CI 14 to 55%). IVE against infection with former seasonal A(H1N1) virus was 83% (95% CI 52 to 94%), and with B virus 67% (95% CI 55 to 76%). In conclusion IVE estimates were particularly low when vaccine mismatched the circulating viruses and A(H3N2) was the predominant influenza virus subtype. Tremendous effort is required to improve vaccine production procedure and to explore the factors that influence the IVE against A(H3N2) virus.

Trivalent inactivated influenza vaccine effective against influenza A(H3N2) variant viruses in children during the 2014/15 season, Japan

The 2014/15 influenza season in Japan was characterised by predominant influenza A(H3N2) activity; 99% of influenza A viruses detected were A(H3N2). Subclade 3C.2a viruses were the major epidemic A(H3N2) viruses, and were genetically distinct from A/New York/39/2012(H3N2) of 2014/15 vaccine strain in Japan, which was classified as clade 3C.1. We assessed vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children aged 6 months to 15 years by test-negative case–control design based on influenza rapid diagnostic test. Between November 2014 and March 2015, a total of 3,752 children were enrolled: 1,633 tested positive for influenza A and 42 for influenza B, and 2,077 tested negative. Adjusted VE was 38% (95% confidence intervals (CI): 28 to 46) against influenza virus infection overall, 37% (95% CI: 27 to 45) against influenza A, and 47% (95% CI: -2 to 73) against influenza B. However, IIV was not statistically significantly effective against influenza A in infants aged 6 to 11 months or adolescents aged 13 to 15 years. VE in preventing hospitalisation for influenza A infection was 55% (95% CI: 42 to 64). Trivalent IIV that included A/New York/39/2012(H3N2) was effective against drifted influenza A(H3N2) virus, although vaccine mismatch resulted in low VE.

Letter to the editor: Regarding the editorial by Penttinen and Friede

To the editor: In the editorial by Penttinen and Friede, the authors summarised data from 2015 to 2016 on live attenuated influenza vaccine (LAIV) effectiveness in a Table and used the data in the Table to make several conclusions [1]. Unfortunately, the Table has several errors and, therefore, misrepresents the available data and studies. On 26 June 2016, the United States (US) Advisory Committee for Immunization Practices (ACIP) recommended that LAIV not be used during the 2016/17 season in the US [2]. Among all studies using a test-negative case–control design (TNCCD), the study from the US Centers for Disease Control and Prevention (CDC) (US Influenza Vaccine Effectiveness (VE) network) and the US Department of Defence (DoD) study (US Air Force School of Aerospace Medicine (USAFSAM) Sentinel Provider network) had the largest number of influenza A(H1N1)pdm09-infected children aged 2–17 years and larger or comparable numbers of children who received LAIV; these numbers were not correctly shown in the Table in the editorial. The US CDC study included 133 children aged 2–17 years who received LAIV (23 LAIV-vaccinated children had influenza A(H1N1)pdm09 infection) and 1,078 children who were unvaccinated. The US DoD study included 93 children vaccinated with LAIV (23 LAIV-vaccinated children had influenza A(H1N1)pdm09 infection) and 338 unvaccinated children (personal communication September 2016, Susan Federinko, USAFSAM). The youngest age for which LAIV is licensed for use in the US is two years; the US CDC VE estimates refer to children aged 2–17 years. The sample sizes for the other studies in the Table should also be consistently reported so that the same numerical comparisons are available for each study.

Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States

PurposeThis analysis examined potential causes of the lack of vaccine effectiveness (VE) of live attenuated influenza vaccine (LAIV) against A/H1N1pdm09 viruses in the United States (US) during the 2013–2014 season. Laboratory studies have demonstrated reduced thermal stability of A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through 2013–2014. MethodsPost hoc analyses of a 2013–2014 test-negative case-control (TNCC) effectiveness study investigated associations between vaccine shipping conditions and LAIV lot effectiveness. Investigational sites provided the LAIV lot numbers administered to each LAIV recipient enrolled in the study, and the vaccine distributor used by the site for commercially purchased vaccine. Additionally, a review was conducted of 2009–2014 pediatric observational TNCC effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season, and geographic location. ResultsFrom the 2013 to 2014 TNCC study, the proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly higher among children who received a lot released between August 1 and September 15, 2013, compared with a lot shipped either earlier or later (21% versus 4%; P<0.01). A linear relationship was observed between the proportion of subjects testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at distributors’ central locations. The review of LAIV VE studies showed that in the 2010–2011 and 2013–2014 influenza seasons, no significant effectiveness of LAIV against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations of LAIV in the US, respectively, in contrast to significant effectiveness against A/H3N2 and B strains during 2010–2014. ConclusionsThis study showed that the lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated with exposure of some LAIV lots to temperatures above recommended storage conditions during US distribution, and is likely explained by the increased susceptibility of the A/California/7/2009 (H1N1pdm09) LAIV strain to thermal degradation.Clinical trial registry: NCT01997450

Epidemiological risk factors for adult dengue in Singapore: an 8-year nested test negative case control study.

BackgroundUnderstanding changes in the ecology and epidemiology of dengue is important to ensure resource intensive control programmes are targeted effectively as well as to inform future dengue vaccination strategies.MethodsWe analyzed data from a multicentre longitudinal prospective study of fever in adults using a nested test negative case control approach to identify epidemiological risk factors for dengue disease in Singapore. From April 2005 to February 2013, adult patients presenting with fever within 72 h at selected public primary healthcare clinics and a tertiary hospital in Singapore were recruited. Acute and convalescent blood samples were collected and used to diagnose dengue using both PCR and serology methods. A dengue case was defined as having a positive RT-PCR result for DENV OR evidence of serological conversion between acute and convalescent blood samples. Similarly, controls were chosen from patients in the cohort who tested negative for dengue using the same laboratory methods.ResultsThe host epidemiological factors which increased the likelihood of dengue disease amongst adults in Singapore were those aged between 21 and 40 years old (2 fold increase) while in contrast, Malay ethnicity was protective (OR 0.57, 95%CI 0.35 to 0.91) against dengue disease. Spatial factors which increased the odds of acquiring dengue was residing at a foreign workers dormitory or hostel (OR 3.25, 95 % CI 1.84 to 5.73) while individuals living in the North-West region of the country were less likely to get dengue (OR 0.50, 95%CI 0.29 to 0.86). Other factors such as gender, whether one primarily works indoors or outdoors, general dwelling type or floor, the type of transportation one uses to work, travel history, as well as self-reported history of mosquito bite or household dengue/fever were not useful in helping to inform a diagnosis of dengue.ConclusionsWe have demonstrated a test negative study design to better understand the epidemiological risk factors of adult dengue over multiple seasons. We were able to discount other previously speculated factors such as gender, whether one primarily works indoors or outdoors, dwelling floor in a building and the use of public transportation as having no effect on one’s risk of getting dengue.

Influenza vaccine effectiveness in adults 65 years and older, Denmark, 2015/16 - a rapid epidemiological and virological assessment.

In Denmark, both influenza A(H1N1)pdm09 and influenza B co-circulated in the 2015/16 season. We estimated the vaccine effectiveness (VE) of the trivalent influenza vaccine in patients 65 years and older using the test-negative case-control design. The adjusted VE against influenza A(H1N1)pdm09 was 35.0% (95% confidence interval (CI): 11.1-52.4) and against influenza B 4.1% (95% CI: -22.0 to 24.7). The majority of influenza A(H1N1)pdm09 circulating in 2015/16 belonged to the new genetic subgroup subclade 6B.1.