Reflections on The Global Influenza Surveillance and Response System (GISRS) at 65 Years: An Expanding Framework for Influenza Detection, Prevention and Control

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142476/1/irv12511_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142476/2/irv12511.pd

EFFECT OF NEURAMINIDASE ANTIBODY ON HONG KONG INFLUENZA

The relation between antineuraminidase antibody (A.N.) and natural influenza infection in 1968 was investigated in the community of Tecumseh, Michigan. The outbreak was caused by Hong Kong influenza virus, which contained a new haemagglutinin antigen (H3), while the neuraminidase antigen (N2) was more closely related to that of Asian viruses circulating since 1957. In the study group of two hundred and seventy-four randomly selected adults (aged 20-45), titres of N2 neuraminidase antibody were detected in a hundred and fifteen (42%) serum samples collected before the outbreak. Influenza infection during the course of the outbreak was identified serologically. The frequency of infection decreased significantly at increasing levels of pre-existing A.N. antibody. In those subjects who were not protected from infection, A.N. antibody significantly suppressed the clinical expression of infection. It is concluded that antibody against the neuraminidase of the influenza virus prevented or modified infection in a situation in which haemagglutinin antibody had no effect.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33917/1/0000183.pd

Maximum likelihood estimation of influenza vaccine effectiveness against transmission from the household and from the community

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142449/1/sim7558_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142449/2/sim7558.pd

HAI and NAI titer correlates of inactivated and live attenuated influenza vaccine efficacy

Abstract Background High hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titers are generally associated with reduced influenza risk. While repeated influenza vaccination reduces seroresponse, vaccine effectiveness is not always reduced. Methods During the 2007-2008 influenza season, a randomized, placebo-controlled trial (FLUVACS) evaluated the efficacies of live-attenuated (LAIV) and inactivated influenza vaccines (IIV) among healthy adults aged 18-49 in Michigan; IIV vaccine efficacy (VE) and LAIV VE against influenza disease were estimated at 68% and 36%. Using the principal stratification/VE moderation framework, we analyzed data from this trial to assess how each VE varied by HAI or NAI responses to vaccination observed for vaccinated individuals and predicted counterfactually for placebo recipients. We also assessed how each VE varied with pre-vaccination/baseline variables including HAI titer, NAI titer, and vaccination history. Results IIV VE appeared to increase with Day 30 post-vaccination HAI titer, albeit not significantly (p=0.20 and estimated VE 14.4%, 70.5%, and 85.5% at titer below the assay lower quantification limit, 512, and 4096 (maximum)). Moreover, IIV VE increased significantly with Day 30 post-vaccination NAI titer (p=0.040), with estimated VE zero at titer 10 and 92.2% at highest titer 640. There was no evidence that fold-change in post-vaccination HAI or NAI titer associated with IIV VE (p=0.76, 0.38). For LAIV, there was no evidence that VE associated with post-vaccination or fold-rise HAI or NAI titers (p-values >0.40). For IIV, VE increased with increasing baseline NAI titer in those previously vaccinated, but VE decreased with increasing baseline NAI titer in those previously unvaccinated. In contrast, for LAIV, VE did not depend on previous vaccination or baseline HAI or NAI titer. Conclusions: Future efficacy trials should measure baseline and post-vaccination antibody titers in both vaccine and control/placebo recipients, enabling analyses to better elucidate correlates of vaccine- and natural-protection. Trial registration: ClinicalTrials.gov NCT00538512. October 1, 2007.https://deepblue.lib.umich.edu/bitstream/2027.42/149182/1/12879_2019_Article_4049.pd

Influenza vaccine effectiveness among outpatients in the US Influenza Vaccine Effectiveness Network by study site 2011‐2016

BackgroundInfluenza vaccination is recommended for all US residents aged ≥6 months. Vaccine effectiveness (VE) varies by age, circulating influenza strains, and the presence of high‐risk medical conditions. We examined site‐specific VE in the US Influenza VE Network, which evaluates annual influenza VE at ambulatory clinics in geographically diverse sites.MethodsAnalyses were conducted on 27 180 outpatients ≥6 months old presenting with an acute respiratory infection (ARI) with cough of ≤7‐day duration during the 2011‐2016 influenza seasons. A test‐negative design was used with vaccination status defined as receipt of ≥1 dose of any influenza vaccine according to medical records, registries, and/or self‐report. Influenza infection was determined by reverse‐transcription polymerase chain reaction. VE estimates were calculated using odds ratios from multivariable logistic regression models adjusted for age, sex, race/ethnicity, time from illness onset to enrollment, high‐risk conditions, calendar time, and vaccination status‐site interaction.ResultsFor all sites combined, VE was statistically significant every season against all influenza and against the predominant circulating strains (VE = 19%‐50%) Few differences among four sites in the US Flu VE Network were evident in five seasons. However, in 2015‐16, overall VE in one site was 24% (95% CI = −4%‐44%), while VE in two other sites was significantly higher (61%, 95% CI = 49%‐71%; P = .002, and 53%, 95% CI = 33,67; P = .034).ConclusionWith few exceptions, site‐specific VE estimates aligned with each other and overall VE estimates. Observed VE may reflect inherent differences in community characteristics of the sites and highlights the importance of diverse settings for studying influenza vaccine effectiveness.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155981/1/irv12741_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155981/2/irv12741.pd

Classification and Regression Tree (CART) analysis to predict influenza in primary care patients

Abstract Background The use of neuraminidase-inhibiting anti-viral medication to treat influenza is relatively infrequent. Rapid, cost-effective methods for diagnosing influenza are needed to enable appropriate prescribing. Multi-viral respiratory panels using reverse transcription polymerase chain reaction (PCR) assays to diagnose influenza are accurate but expensive and more time-consuming than low sensitivity rapid influenza tests. Influenza clinical decision algorithms are both rapid and inexpensive, but most are based on regression analyses that do not account for higher order interactions. This study used classification and regression trees (CART) modeling to estimate probabilities of influenza. Methods Eligible enrollees ≥ 5 years old (n = 4,173) who presented at ambulatory centers for treatment of acute respiratory illness (≤7 days) with cough or fever in 2011–2012, provided nasal and pharyngeal swabs for PCR testing for influenza, information on demographics, symptoms, personal characteristics and self-reported influenza vaccination status. Results Antiviral medication was prescribed for just 15 % of those with PCR-confirmed influenza. An algorithm that included fever, cough, and fatigue had sensitivity of 84 %, specificity of 48 %, positive predictive value (PPV) of 23 % and negative predictive value (NPV) of 94 % for the development sample. Conclusions The CART algorithm has good sensitivity and high NPV, but low PPV for identifying influenza among outpatients ≥5 years. Thus, it is good at identifying a group who do not need testing or antivirals and had fair to good predictive performance for influenza. Further testing of the algorithm in other influenza seasons would help to optimize decisions for lab testing or treatment.http://deepblue.lib.umich.edu/bitstream/2027.42/134640/1/12879_2016_Article_1839.pd

Facemasks, Hand Hygiene, and Influenza among Young Adults: A Randomized Intervention Trial

Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures for mitigating pandemic influenza. Our objective was to examine if the use of face masks and hand hygiene reduced rates of influenza-like illness (ILI) and laboratory-confirmed influenza in the natural setting. A cluster-randomized intervention trial was designed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007–2008 influenza season. Participants were assigned to face mask and hand hygiene, face mask only, or control group during the study. Discrete-time survival models using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined. A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study, with a maximum reduction of 75% during the final study week (rate ratio [RR] = 0.25, [95% CI, 0.07 to 0.87]). Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period, although results did not reach statistical significance. Generalizability limited to similar settings and age groups. Face masks and hand hygiene combined may reduce the rate of ILI and confirmed influenza in community settings. These non-pharmaceutical measures should be recommended in crowded settings at the start of an influenza pandemic

Vaccine effectiveness against COVID-19 among symptomatic persons aged ≥12 years with reported contact with COVID-19 cases, February-September 2021

BACKGROUND: Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19; protection offered by COVID-19 vaccines in the context of known exposure is poorly understood. METHODS: Symptomatic outpatients aged ≥12 years reporting acute onset of COVID-19-like illness and tested for SARS-CoV-2 between February 1 and September 30, 2021 were enrolled. Participants were stratified by self-report of having known contact with a COVID-19 case in the 14 days prior to illness onset. Vaccine effectiveness was evaluated using the test-negative study design and multivariable logistic regression. RESULTS: Among 2229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2-positive. Adjusted vaccine effectiveness was 71% (95% confidence interval [CI], 49%-83%) among fully vaccinated participants reporting a known contact versus 80% (95% CI, 72%-86%) among those with no known contact (p-value for interaction = 0.2). CONCLUSIONS: This study contributes to growing evidence of the benefits of vaccinations in preventing COVID-19 and support vaccination recommendations and the importance of efforts to increase vaccination coverage