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

Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156082/1/jiaa161.pdfSEL

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

Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

Abstract Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991 . Registered on November 6, 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/146186/1/12879_2018_Article_3444.pd

Home collection of nasal swabs for detection of influenza in the Household Influenza Vaccine Evaluation Study

BackgroundCommunity‐based studies of influenza and other respiratory viruses (eg, SARS‐CoV‐2) require laboratory confirmation of infection. During the current COVID‐19 pandemic, social distancing guidelines require alternative data collection in order to protect both research staff and participants. Home‐collected respiratory specimens are less resource‐intensive, can be collected earlier after symptom onset, and provide a low‐contact means of data collection. A prospective, multi‐year, community‐based cohort study is an ideal setting to examine the utility of home‐collected specimens for identification of influenza.MethodsWe describe the feasibility and reliability of home‐collected specimens for the detection of influenza. We collected data and specimens between October 2014 and June 2017 from the Household Influenza Vaccine Evaluation (HIVE) Study. Cohort participants were asked to collect a nasal swab at home upon onset of acute respiratory illness. Research staff also collected nose and throat swab specimens in the study clinic within 7 days of onset. We estimated agreement using Cohen’s kappa and calculated sensitivity and specificity of home‐collected compared to staff‐collected specimens.ResultsWe tested 336 paired staff‐ and home‐collected respiratory specimens for influenza by RT‐PCR; 150 staff‐collected specimens were positive for influenza A/H3N2, 23 for influenza A/H1N1, 14 for influenza B/Victoria, and 31 for influenza B/Yamagata. We found moderate agreement between collection methods for influenza A/H3N2 (0.70) and B/Yamagata (0.69) and high agreement for influenza A/H1N1 (0.87) and B/Victoria (0.86). Sensitivity ranged from 78% to 86% for all influenza types and subtypes. Specificity was high for influenza A/H1N1 and both influenza B lineages with a range from 96% to 100%, and slightly lower for A/H3N2 infections (88%).ConclusionsCollection of nasal swab specimens at home is both feasible and reliable for identification of influenza virus infections.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166444/1/irv12822_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166444/2/irv12822.pd

Respiratory syncytial virus hospitalization in middle-aged and older adults

BACKGROUND: The importance of Respiratory Syncytial Virus (RSV) is increasingly recognized in hospitalized adults, but mainly in those ≥ 65 years. OBJECTIVES: We sought to describe the epidemiology and clinical severity of RSV compared to influenza in hospitalized adults ≥18 years. STUDY DESIGN: Adults hospitalized with acute respiratory illnesses (ARI) of ≤10days duration were prospectively enrolled from two Michigan hospitals during two influenza seasons. Collected specimens were tested for RSV and influenza by real-time, reverse transcription polymerase chain reaction (RT-PCR). Viral load and subtype were determined for RSV-positive specimens. We evaluated factors associated with RSV and outcomes of infection using multivariable logistic regression. RSV-positive patients were separately compared to two reference groups: RSV-negative and influenza-negative, and influenza-positive patients. RESULTS: RSV was detected in 84 (7%) of 1259 hospitalized individuals (55 RSV-B, 29 RSV-A). The highest prevalence was found in 50-64year olds (40/460; 8.7%); 98% of RSV cases in this age group had at least one chronic comorbidity. RSV detection was associated with obesity (OR: 1.71 95% CI: 0.99-3.06, p=0.03). Individuals with RSV were admitted to the hospital later in their illness and had a higher median Charlson comborbidity index (3 vs 2 p\u3c0.001) compared to those with influenza. Clinical severity of RSV-associated hospitalizations was similar to influenza-associated hospitalizations. DISCUSSION: In this study we observed the highest frequency of RSV-associated hospitalizations among adult 50-64 years old; many of whom had chronic comorbidities. Our results suggest the potential benefit of including these individuals in future RSV vaccination strategies

Influenza Vaccine Effectiveness in the Inpatient Setting; Evaluation of Potential Bias in the Test Negative Design by use of Alternate Control Groups

The test negative design is validated in outpatient but not inpatient studies of influenza vaccine effectiveness. The prevalence of chronic pulmonary disease among inpatients may lead to nonrepresentative controls. Test negative design estimates are biased if vaccine administration is associated with incidence of non-influenza viruses. We evaluated whether control group selection and effects of vaccination on non-influenza viruses biased vaccine effectiveness in our study. Subjects were enrolled at the University of Michigan and Henry Ford hospitals during the 2014-15 and 2015-16 seasons. Patients presenting with acute respiratory infection were enrolled and tested for respiratory viruses. Vaccine effectiveness was estimated using three control groups: influenza negative, other respiratory virus positive, and pan-negative individuals; it was also estimated for other common respiratory viruses. In 2014-15, vaccine effectiveness was 41.1% (95% CI: 1.7%, 64.7%) using influenza negative, 24.5% (95% CI: -42.6%, 60.1%) using other-virus positive, and 45.8% (95% CI: 5.7%, 68.9%) using pan-negative controls. In 2015-16, vaccine effectiveness was 68.7% (95% CI: 44.6%, 82.5%) using influenza negative, 63.1% (95% CI: 25.0%, 82.2%) using other-virus positive, and 71.1% (46.2%, 84.8%) using pan-negative controls. Vaccination did not alter odds of other respiratory viruses. Results support use of the test negative design among inpatients

Distinct influenza surveillance networks and their agreement in recording regional influenza circulation: Experience from Southeast Michigan

IntroductionIn Southeast Michigan, active surveillance studies monitor influenza activity in hospitals, ambulatory clinics, and community households. Across five respiratory seasons, we assessed the contribution of data from each of the three networks towards improving our overall understanding of regional influenza circulation.MethodsAll three networks used case definitions for acute respiratory illness (ARI) and molecularly tested for influenza from research-collected respiratory specimens. Age- and network-stratified epidemic curves were created for influenza A and B. We compared stratified epidemic curves visually and by centering at seasonal midpoints.ResultsAcross all seasons (from 2014/2015 through 2018/2019), epidemic curves from each of the three networks were comparable in terms of both timing and magnitude. Small discrepancies in epidemics recorded by each network support previous conclusions about broader characteristics of particular influenza seasons.ConclusionInfluenza surveillance systems based in hospital, ambulatory clinic, and community household settings appear to provide largely similar information regarding regional epidemic activity. Together, multiple levels of influenza surveillance provide a detailed view of regional influenza epidemics, but a single surveillance system—regardless of population subgroup monitored—appears to be sufficient in providing vital information regarding community influenza epidemics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172297/1/irv12944.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172297/2/irv12944_am.pd

Influenza Vaccine Effectiveness Against Antigenically Drifted Influenza Higher Than Expected in Hospitalized Adults: 2014-2015

BACKGROUND: The 2014-2015 influenza season was severe, with circulating influenza A (H3N2) viruses that were antigenically drifted from the vaccine virus. Reported vaccine effectiveness (VE) estimates from ambulatory care settings were markedly decreased. METHODS: Adults, hospitalized at 2 hospitals in southeast Michigan for acute respiratory illnesses, defined by admission diagnoses, of ≤10 days duration were prospectively enrolled. Throat and nasal swab specimens were collected, combined, and tested for influenza by real-time reverse transcription polymerase chain reaction. VE was estimated by comparing the vaccination status of those testing positive for influenza with those testing negative in logistic regression models adjusted for age, sex, hospital, calendar time, time from illness onset to specimen collection, frailty score, and Charlson comorbidity index (CCI). RESULTS: Among 624 patients included in the analysis, 421 (68%) were vaccinated, 337 (54%) were female, 220 (35%) were age ≥65 years, and 92% had CCI \u3e 0, indicating ≥1 comorbid conditions. Ninety-eight (16%) patients tested positive for influenza A (H3N2); among 60 (61%) A (H3N2) viruses tested by pyrosequencing, 53 (88%) belonged to the drifted 3C.2a genetic group. Adjusted VE was 43% (95% confidence interval [CI], 4-67) against influenza A (H3N2); 40% (95% CI, -13 to 68) for those \u3c65 \u3eyears, and 48% (95% CI, -33 to 80) for those ≥65 years. Sensitivity analyses largely supported these estimates. CONCLUSIONS: VE estimates appeared higher than reports from similar studies in ambulatory care settings, suggesting that the 2014-2015 vaccine may have been more effective in preventing severe illness requiring hospitalization