Medically Attended Acute Respiratory Illness Research Articles

P-1270. Using Machine Learning and ICD-10 Codes to Identify Cases of Laboratory-Confirmed Influenza, 2015-2020, US Flu VE Network

Abstract Background The International Classification of Diseases (ICD-10) has unique codes for influenza. Accurate classification of influenza is necessary to calculate unbiased vaccine effectiveness and typically requires laboratory testing. We used the US Influenza Vaccine Effectiveness (Flu VE) Network to determine if outpatient influenza-positive cases and influenza-negative controls could be identified by the presence or absence of certain codes to better understand the role of ICD-10 in estimating VE.Table:Twelve most common ICD-10 codes among influenza-positive outpatients in the US Flu VE Network and their corresponding rankings and frequencies among influenza-negative patients, 2015-16 through 2019-20 influenza seasons Methods During the 2015-16 through 2019-20 influenza seasons, 5 US Flu VE sites enrolled outpatients aged ≥6 months with medically attended acute respiratory illness (MAARI) defined as self-reported new or worsening cough lasting ≤7 days and tested patients for influenza by RT-PCR. We determined the frequencies of ICD-10 codes among influenza cases and controls. We also used classification and regression trees (CART) models to evaluate ICD-10 codes as predictors of influenza test results.Figure:Classification and Regression Tree using ICD-10 codes to determine influenza testing status for outpatients in the US Flu VE Network, 2015-16 through 2019-20 influenza seasons Results Over 5 seasons in the US Flu VE, we identified 2,711 ICD-10 codes assigned to enrollments among MAARI patients. Among 11,861 patients with laboratory-confirmed influenza, we identified a total of 1,234 unique ICD-10 codes versus 2,450 ICD-10 codes among 30,622 patients who tested negative for influenza. Codes for cases and controls overlapped substantially, with Diseases of the Respiratory system (J00-J99) being the most frequent (78%) among both. Among cases and controls, J06.9 (Acute upper respiratory infection, unspecified) and R05 (Cough) were the most frequent (Table). CART analysis identified a subset of 6 optimal MAARI-associated ICD-10 codes that identified 6,112 (52%) influenza cases, and these codes were absent for 25,518 (83%) test-negative controls totaling 31,630 (74%) cases and controls (Figure A). Conclusion Our findings show the importance of laboratory-confirmed influenza outcomes for influenza VE analyses; machine learning may be useful in identifying MAARI-associated ICD-10 diagnostic codes to define patients for inclusion in test-negative VE studies. In our study, we identified a restricted list of ICD-10 codes that could be used to improve VE estimates in electronic medical record systems with access to testing data. Disclosures Huong Nguyen, PhD, MPH, CSL Seqirus: Advisor/Consultant|CSL Seqirus: Grant/Research Support|GSK: Grant/Research Support|ModernaTX: Advisor/Consultant|ModernaTX: Grant/Research Support Mary Patricia Nowalk, PhD, AstraZeneca - Icosavax: Grant/Research Support|GSK: Advisor/Consultant|Merck & Co.: Grant/Research Support|Sanofi: Grant/Research Support Arnold Monto, MD, Roche: Advisor/Consultant

Epidemiology of RSV in Adults and Children with Medically-Attended Acute Respiratory Illness over Three Seasons.

Data on the true prevalence of RSV among medically-attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over three seasons, which is informative in light of the recommendations for shared decision-making for vaccination in older adults. Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated Multimorbidity-Weighted Index (MWI) were collected by in-person survey and electronic medical record review. Over three surveillance seasons (fall 2017 to spring 2020), 9.9% (n=441) of 4,442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months-4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision-making for vaccination.

The impact of repeated vaccination on relative influenza vaccine effectiveness among vaccinated adults in the United Kingdom.

Annual seasonal influenza vaccination is recommended for individuals at high risk of developing post-infection complications in many locations. However, reduced vaccine immunogenicity and effectiveness have been observed among repeat vaccinees in some influenza seasons. We investigated the impact of repeated influenza vaccination on relative vaccine effectiveness (VE) among individuals who were recommended for influenza vaccination in the United Kingdom with a retrospective cohort study using primary healthcare data from the Clinical Practice Research Datalink, a primary care database in the United Kingdom. Relative VE was estimated against general practitioner-diagnosed influenza-like illnesses (GP-ILI) and medically attended acute respiratory illnesses (MAARI) among participants who have been repeatedly vaccinated compared with first-time vaccinees using proportional hazards models. Relative VE against MAARI may be reduced for individuals above 65 years old who were vaccinated in the current and previous influenza seasons for some influenza seasons. However, these findings were not conclusive as we could not exclude the possibility of residual confounding in our dataset. The use of routinely collected data from electronic health records to examine the effects of repeated vaccination needs to be complemented with sufficient efforts to include negative control outcomes to rule out residual confounding.

City-wide school-located influenza vaccination: A retrospective cohort study

Background:We measured the effectiveness of a city-wide school-located influenza vaccination (SLIV) program implemented in over 102 elementary schools in Oakland, California.Methods:We conducted a retrospective cohort study among Kaiser Permanente Northern California (KPNC) members of all ages residing in either the intervention or a multivariate-matched comparison site from September 2011 - August 2017. Outcomes included medically attended acute respiratory illness (MAARI), influenza hospitalization, and Oseltamivir prescriptions. We estimated difference-in-differences (DIDs) in 2014–15, 2015–16, and 2016–17 using generalized linear models and adjusted for race, ethnicity, age, sex, health plan, and language.Results:Pre-intervention member characteristics were similar between sites. The proportion of KPNC members vaccinated for influenza by KPNC or the SLIV program was 8–11% higher in the intervention site than the comparison site during the intervention period. Among school-aged children, SLIV was associated with lower Oseltamivir prescriptions per 1,000 (DIDs: −3.5 (95% CI −5.5, −1.5) in 2015–16; −4.0 (95% CI −6.5, −1.6) in 2016–17) but not with other outcomes. SLIV was associated with lower MAARI per 1,000 in adults 65 + years (2014–15: −13.2, 95% CI −23.2, −3.2; 2015–16: −21.5, 95% CI −31.1, −11.9; 2016–17: −13.0, 95% CI −23.2, −2.9). There were few significant associations with other outcomes among adults.Conclusions:A city-wide SLIV intervention was associated with higher influenza vaccination coverage, lower Oseltamivir prescriptions in school-aged children, and lower MAARI among people over 65 years, suggesting possible indirect effects of SLIV among older adults.

The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review.

BackgroundRespiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking.MethodsThis systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as “Respiratory Syncytial Virus, Human,” “Respiratory Syncytial Virus Infections,” “Respiratory Syncytial Virus Vaccines,” “Immunization,” “Immunization Programs” and “Vaccines” and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV‐associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case.ResultsOf 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live‐attenuated/chimeric (n = 14), recombinant‐vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine‐related increased MAARI during RSV surveillance season.ConclusionLID ∆M2‐2, MEDI M2‐2, RSVcps2 and LID/∆M2‐2 /1030s (live‐attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.

1717. Relationship between Neighborhood Census-tract Level Poverty and Respiratory Syncytial Virus (RSV)-associated Hospitalizations in U.S. adults, 2015-2017

BackgroundIn the U.S., RSV is increasingly recognized as a cause of hospitalization for adults with respiratory illness. In adults > 50 years of age, it accounts for up to 12% of medically-attended acute respiratory illnesses and has a case fatality proportion of ~ 6–8%. Poverty can have important influences on health on both the individual level as well as the community level. Few studies have evaluated the relationship of RSV and poverty level, and no identified studies have evaluated this relationship among adults. We evaluated the incidence of RSV-associated hospitalizations in adults across multiple sites in the U.S. by census-tract (CT) level poverty.MethodsMedical record data abstraction was conducted for all adults with a laboratory-confirmed RSV infection admitted to a hospital within the Centers for Disease Control and Prevention’s Emerging Infections Program catchment areas within California, Georgia, Maryland, Minnesota, New York, and Tennessee during the 2015–2017 RSV seasons (October-April). Patient addresses were geocoded to their corresponding CT. CTs were divided into four levels of poverty, as selected in prior publications, based on American Community Survey data of percentage of people living below the poverty level: 0–4.9%, 5–9.9%, 10-19.9%, and ³20%. Incidence rates were calculated by dividing the number of RSV cases in each CT poverty-level (numerator) by the number of adults living in each CT poverty level (denominator), as determined from the 2010 US census, and standardized for age.ResultsThere were 1713 RSV case-patients with demographic characteristics (Table 1). The incidence of RSV-associated hospitalizations of adults increased with increasing CT level poverty (Figure 1 and Table 2). The risk of RSV-associated hospitalization was 2.58 times higher in census tracts with the highest (20%) versus the lowest (< 5%) percentages of individuals living below the poverty level.Table 1: Demographic characteristics of adults with an RSV-associated hospitalization, 2015-2017. Figure 1. Age-adjusted incidence rate of RSV-associated hospitalizations of adults by census-tract poverty level, 2015-2017 Table 2. Incidence rate ratios for RSV-associated hospitalizations of adults by census-tract poverty level, 2015-2017. ConclusionThe incidence rate of RSV-associated hospitalization in adults appears to have a positive association with increasing CT level of poverty; however, this trend reached significance only among cases living in CTs with higher percentages of poverty (≥ 10%).Disclosures Evan J. Anderson, MD, Sanofi Pasteur (Scientific Research Study Investigator)

Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children.

The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children. Respiratory syncytial virus-seronegative children ages 6-24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored. Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV. LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.

2325. Relationship Between Neighborhood Census-Tract-Level Poverty and Respiratory Syncytial Virus Infection in hospitalized Adults in the San Francisco Bay area, CA 2015–2017

BackgroundIn the United States, respiratory syncytial virus (RSV) is a leading cause of admission for adults with respiratory illness. In adults > 50 years of age, it accounts for up to 12% of medically-attended acute respiratory illnesses and has a case fatality proportion of ~6–8%. Poverty can have an important influence on health. Few studies have evaluated the relationship of RSV incidence and poverty level, and no identified studies have evaluated this relationship among adults. We evaluated the incidence of RSV-associated hospitalizations in adults in the San Francisco Bay Area, CA by census-tract-level poverty.MethodsMedical record data abstraction was conducted for all adults with a laboratory-confirmed RSV infection who were admitted to a hospital within the 3 counties comprising the catchment area (Alameda, Contra Costa, and San Francisco counties) during the 2015–2016 and 2016–2017 RSV seasons. Patient addresses were geocoded to their corresponding census-tract (CT). Census tracts were divided into four levels of poverty based on American Community Survey data of percentage of people living below the poverty level: 0–4.9%, 5–9.9%, 10-–9.9%, and ³20%. Incidence rates were calculated by dividing the number of RSV cases in each CT poverty-level (numerator) by the number of adults living in each CT poverty level (denominator), as determined from the 2010 US census, and standardized for age.ResultsThere were 526 RSV case-patients with demographic characteristics as outlined in Table 1. The highest incidence of RSV-associated hospitalization was in CTs associated with the highest levels of poverty (>20%). However, the second highest incidence of RSV-associated hospitalization occurred among adults living in CTs with <5% poverty (Figure 1 and Table 2).ConclusionThe incidence rate of RSV-associated hospitalization in adults appears to be positively correlated with highest census-tract level of poverty; however, there is a high incidence among adults living in the lowest poverty census-tracts. Disclosures All authors: No reported disclosures.

Statin use and medically attended acute respiratory illness among influenza vaccine recipients

Previous studies have suggested that statins decrease influenza vaccine effectiveness and increase risk of medically attended acute respiratory illness (MAARI). To examine the association of incident statin use and MAARI in a cohort of influenza vaccine recipients. This retrospective cohort study evaluated influenza vaccine recipients within the Tricare population. The primary outcome compared MAARI incidence during the follow-up period in a propensity score-matched cohort of incident statin users and statin non-users. Secondary analysis included propensity score-adjusted comparisons between incident statin users and statin non-users in the entire cohort and prespecified sub-cohorts with and without comorbidities. The propensity score was derived from 72 variables encompassing demographics, medical history, comorbidities, medication use, and healthcare utilization. MAARI incidence in statin users was similar to non-users in the propensity score-matched cohort (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.84-1.01). In contrast, statin users with lower comorbidity had lower OR for MAARI compared to non-users (Charlson Score zero cohort: 0.85 [CI 0.74-0.98]; No Diabetes cohort: 0.88 [CI 0.80-0.96]). Incident statin use was not associated with increased MAARI incidence and may be associated with lower incidence of MAARI in those with less comorbidity. This study thus offers reassurance regarding the effectiveness of the influenza vaccine in statin users.

Severe Illnesses Associated With Outbreaks of Respiratory Syncytial Virus and Influenza in Adults.

BackgroundRecent reports have described the contribution of adult respiratory syncytial virus (RSV) infections to the use of advanced healthcare resources and death.MethodsData regarding patients aged ≥18 years admitted to any of Maryland’s 50 acute-care hospitals were evaluated over 12 consecutive years (2001–2013). We examined RSV and influenza (flu) surveillance data from the US National Respiratory and Enteric Virus Surveillance System and the Centers for Disease Control and Prevention and used this information to define RSV and flu outbreak periods in the Maryland area. Outbreak periods consisted of consecutive individual weeks during which at least 10% of RSV and/or flu diagnostic tests were positive. We examined relationships of RSV and flu outbreaks to occurrence of 4 advanced medical outcomes (hospitalization, intensive care unit admission, intubated mechanical ventilation, and death) due to medically attended acute respiratory illness (MAARI).ResultsOccurrences of all 4 MAARI-related hospital advanced medical outcomes were consistently greater for all adult ages during RSV, flu, and combined RSV–flu outbreak periods compared to nonoutbreak periods and tended to be greatest in adults aged ≥65 years during combined RSV–flu outbreak periods. Rate ratios for all 4 MAARI-related advanced medical outcomes ranged from 1.04 to 1.38 during the RSV, flu, or combined RSV–flu outbreaks compared to the nonoutbreak periods, with all 95% lower confidence limits >1.ConclusionsBoth RSV and flu outbreaks were associated with surges in MAARI-related advanced medical outcomes (hospitalization, intensive care unit admission, intubated mechanical ventilation, and death) for adults of all ages.

Respiratory syncytial virus-associated illness in adults with advanced chronic obstructive pulmonary disease and/or congestive heart failure.

BackgroundRespiratory syncytial virus (RSV) is recognized as a serious pathogen in people with chronic cardiopulmonary conditions. Immunoprophylaxis might be considered for adults at high‐risk for frequent and severe RSV infection. Thus, we studied the incidence of RSV‐related medically attended acute respiratory illness (MARI) in adults with severe chronic obstructive pulmonary disease (COPD) and/or congestive heart failure (CHF).MethodsSubjects ≥50 years of age with Gold Class III/IV COPD and/or American Heart Association class III/IV CHF and exposure to children ≥once per month were recruited. Subjects were evaluated over 1.5 to 2.5 years for RSV‐associated MARI, defined as polymerase chain reaction (PCR) and/or seroresponse.ResultsFour hundred forty‐five subjects were enrolled between October 2011 and May 2012. Overall, 99 RSV infections were documented by PCR or serology for a cumulative incidence of 22.2%. Of these, 42 (9.4%) subjects had protocol‐specified RSV‐MARI for an incidence of 4.68/100 patient‐seasons. All‐cause MARI was common (63.85/100 patient‐seasons) with rhinovirus most commonly identified.ConclusionRSV infection was common in adults with severe COPD and/or advanced CHF. Given the severity of underlying cardiopulmonary diseases in the study population, most illnesses were surprisingly mild. Thus, active immunization rather than passive immunoprophylaxis with monoclonal antibodies may be a more cost‐effective strategy.

Effect of statin use on the risk of medically attended acute respiratory illness among influenza vaccinated elderly

The immunomodulatory effects of statins may reduce the immune response induced by influenza vaccines. However, evidence regarding the effect of statin use on the effectiveness of seasonal influenza vaccines against medically attended acute respiratory illness (MAARI) in the elderly remains scarce. We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. Elderly adults aged ≧ 66 years who were vaccinated with seasonal influenza vaccines during the 2007-2008 to 2012-2013 influenza seasons were enrolled for this analysis. We compared the risk of MAARI between statin and non-statin users. Propensity score matching and conditional logistic regression models were used to analyze the data. A total of 440,180 elderly were included in this study. In general, the risk of MAARI was higher in statin users than non-statin users (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.02-1.05). Statin exposure after vaccination was associated with a higher risk of MAARI (OR: 1.05, 95% CI: 1.02-1.07). Among different statin agents, simvastatin and lovastatin use was associated with a significant increase in the risk of MAARI (ORsimvastatin: 1.14, 95% CI: 1.10-1.18; ORlovastatin: 1.18, 95% CI: 1.12-1.25). Statin exposure, especially simvastatin and lovastatin, was associated with a higher risk of MAARI in the seasonal influenza vaccinated elderly. Future studies exploring the differences between individual statins and mechanisms of their immunomodulatory effects are necessary.

Association of influenza outbreaks with advanced pediatric medical support.

Retrospective data evaluated increases in advanced medical support for children with medically attended acute respiratory illness (MAARI) during influenza outbreak periods (IOP). Advanced support included hospitalisation, intensive care unit admission, or mechanical ventilation, for children aged 0-17 years hospitalised in Maryland's 50 acute-care hospitals over 12 influenza seasons. Weekly numbers of positive influenza tests in the Maryland area defined IOP for each season as the fewest consecutive weeks, including the peak week containing at least 85% of positive tests with a 2-week buffer on either side of the IOP. Peak IOP (PIOP) was defined as four consecutive weeks containing the peak week with the most number of positive influenza tests. Off-PIOP was defined as the 'shoulder' weeks during each IOP. Non-influenza season (NIS) was the remaining weeks of that study season. Rate ratios of mean daily MAARI-related admissions resulting in advanced medical support outcomes during PIOP or Off-PIOP were compared with the NIS and were significantly elevated for all 12 study seasons combined. The results suggest that influenza outbreaks are associated with increased advanced medical support utilisation by children with MAARI. We feel that this data may help preparedness for severe influenza epidemics or pandemic.

Influenza vaccine effectiveness in older adults compared with younger adults over five seasons

There have been inconsistent reports of decreased vaccine effectiveness (VE) against influenza viruses among older adults (aged ≥ 65 years) compared with younger adults in the United States. A direct comparison of VE over multiple seasons is needed to assess the consistency of these observations. We performed a pooled analysis of VE over 5 seasons among adults aged ≥ 18 years who were systematically enrolled in the U.S. Flu VE Network. Outpatients with medically-attended acute respiratory illness (cough with illness onset ≤ 7 days prior to enrollment) were tested for influenza by reverse transcription polymerase chain reaction. We compared differences in VE and vaccine failures among older adult age group (65-74, ≥75, and ≥ 65 years) to adults aged 18-49 years by influenza type and subtype using interaction terms to test for statistical significance and stratified by prior season vaccination status. Analysis included 20,022 adults aged ≥ 18 years enrolled during the 2011-12 through 2015-16 influenza seasons; 4,785 (24%) tested positive for influenza. VE among patients aged ≥ 65 years was not significantly lower than VE among patients aged 18-49 years against any subtype with no significant interaction of age and vaccination. VE against A(H3N2) viruses was 14% (95% confidence interval [CI] -14% to 36%) for adults ≥ 65 years and 21% (CI 9-32%) for adults 18-49 years. VE against A(H1N1)pdm09 was 49% (95% CI 22-66%) for adults ≥ 65 years and 48% (95% CI 41-54%) for adults 18-49 years and against B viruses was 62% (95% CI 44-74%) for adults ≥ 65 years and 55% (95% CI 45-63%) for adults 18-49 years. There was no significant interaction of age and vaccination for separate strata of prior vaccination status. Over 5 seasons, influenza vaccination provided similar levels of protection among older and younger adults, with lower levels of protection against influenza A(H3N2) in all ages.

Surges of advanced medical support associated with influenza outbreaks.

We utilized de-identified data to evaluate increases in four outcomes during influenza outbreak periods (IOPs) including: hospitalization, intensive care unit admission, mechanical ventilation or death for adults aged 18 years or older with medically attended acute respiratory illnesses (MAARI) admitted to any of Maryland's 50 acute-care hospitals over 12 years. Weekly numbers of positive influenza tests in the Maryland area were obtained from the US Center for Disease Control and Prevention interactive website. The fewest consecutive weeks around the peak week containing at least 85% of the positive tests defined the IOP. Weekly counts of individual study outcomes were positively correlated with regional weekly counts of positive influenza tests during all the IOPs over 12 years. Also, rate ratios comparing daily occurrences of each study outcome between the IOP and non-IOP were significantly elevated. These results confirm conclusions of previous studies that influenza outbreaks are clearly associated with deaths and increased use of advanced medical resources by patients with MAARI. These data analyses suggest that increased efforts to develop more effective influenza vaccines and therapeutics should be a priority.

Enterovirus D68 Infection Among Children With Medically Attended Acute Respiratory Illness, Cincinnati, Ohio, July-October 2014.

Enterovirus D68 (EV-D68) caused a widespread outbreak of respiratory illness in the United States in 2014, predominantly affecting children. We describe EV-D68 rates, spectrum of illness, and risk factors from prospective, population-based acute respiratory illness (ARI) surveillance at a large US pediatric hospital. Children <13 years of age with ARI and residence in Hamilton County, Ohio were enrolled from the inpatient and emergency department (ED) settings at a children's hospital in Cincinnati, Ohio, from 1 July to 31 October 2014. For each participant, we interviewed parents, reviewed medical records, and tested nasal and throat swabs for EV-D68 using real-time reverse- transcription polymerase chain reaction assay. EV-D68 infection was detected in 51 of 207 (25%) inpatients and 58 of 505 (11%) ED patients. Rates of EV-D68 hospitalization and ED visit were 1.3 (95% confidence interval [CI], 1.0-1.6) and 8.4 per 1000 children <13 years of age, respectively. Preexisting asthma was associated with EV-D68 infection (adjusted odds ratio, 3.2; 95% CI, 2.0-5.1). Compared with other ARI, children with EV-D68 were more likely to be admitted from the ED (P ≤ .001), receive supplemental oxygen (P = .001), and require intensive care unit admission (P = .04); however, mechanical ventilation was uncommon (2/51 inpatients; P = .64), and no deaths occurred. During the 2014 EV-D68 epidemic, high rates of pediatric hospitalizations and ED visits were observed. Children with asthma were at increased risk for medically attended EV-D68 illness. Preparedness planning for a high-activity EV-D68 season in the United States should take into account increased healthcare utilization, particularly among children with asthma, during the late summer and early fall.

Intraseason waning of influenza vaccine protection: Evidence from the US Influenza Vaccine Effectiveness Network, 2011-12 through 2014-15.

Recent studies suggest that influenza vaccine effectiveness (VE) may wane over the course of an influenza season, leading to suboptimal VE during late influenza seasons. We examined the association between influenza VE and time since vaccination among patients ≥9 years old with medically-attended acute respiratory illness in the US Influenza Vaccine Effectiveness Network using data pooled from the 2011-12 through 2014-15 influenza seasons. We used multivariate logistic regression with PCR-confirmed influenza infection as the outcome and vaccination status defined by days between vaccination and symptom onset as the predictor. Models were adjusted for calendar time and other potential confounding factors. We observed decreasing VE with increasing time since vaccination for influenza A(H3N2) (p=0.004), influenza A(H1N1)pdm09 (p=0.01), and influenza B viruses (p=0.04). Maximum VE was observed shortly after vaccination, followed by a decline in VE of about 7% (absolute) per month for influenza A(H3N2) and influenza B and 6% - 11% per month for influenza A(H1N1)pdm09 viruses. VE remained greater than zero for at least six months for influenza A(H1N1)pdm09 and influenza B and at least five months for influenza A(H3N2) viruses. Decline in VE was more pronounced among patients with prior season influenza vaccination. A similar pattern of increasing influenza risk with increasing time since vaccination was seen in analyses limited to vaccinees. We observed decreasing influenza vaccine protection with increasing time since vaccination across influenza types/subtypes. This association is consistent with intraseason waning of host immunity, but bias or residual confounding could explain these findings.

A UK general practice population cohort study investigating the association between lipid lowering drugs and 30-day mortality following medically attended acute respiratory illness.

Background. Cholesterol lowering drugs HMG-CoA reductase inhibitors (statins) and PPARα activators (fibrates) have been shown to reduce host inflammation via non-disease specific immunomodulatory mechanisms. Recent studies suggest that commonly prescribed drugs in general practice, statins and fibrates, may be beneficial in influenza-like illness related mortality. This retrospective cohort study examines the association between two lipid lowering drugs, statins and fibrates, and all-cause 30-day mortality following a medically attended acute respiratory illness (MAARI).Methods. Primary care patient data were retrospectively extracted from the UK Clinical Practice Research Datalink (CPRD) database. The sample comprised 201,179 adults aged 30 years or older experiencing a MAARI episode. Patient exposure to statins or fibrates was coded as separate dichotomous variables and deemed current if the most recent GP prescription was issued in the 30 days prior to MAARI diagnosis. Multivariable logistic regression and Cox regression were used for analyses. Adjustment was carried out for chronic lung disease, heart failure, metformin and glitazones, comorbidity burden, socio-demographic and lifestyle variables such as smoking status and body mass index (BMI). Statistical interaction tests were carried out to check for effect modification by gender, body mass index, smoking status and comorbidity.Results. A total of 1,096 (5%) patients died within the 30-day follow up period. Of this group, 213 (19.4%) were statin users and 4 (0.4%) were fibrate users. After adjustment, a significant 35% reduction in odds [adj OR; 0.65 (95% CI [0.52–0.80])] and a 33% reduction in the hazard [adj HR: 0.67 (95% CI [0.55–0.83])] of all-cause 30-day mortality following MAARI was observed in statin users. A significant effect modification by comorbidity burden was observed for the association between statin use and MAARI-related mortality. Fibrate use was associated with a non-significant reduction in 30-day MAARI-related mortality.Conclusion. This study suggests that statin use may be associated with a reduction in 30-day mortality following acute respiratory illness that is severe enough to merit medical consultation. Findings from this study support and strengthen similar observational research while providing a strong rationale for a randomised controlled trial investigating the potential role of statins in acute respiratory infections.

The Impact of Statin on Influenza Vaccine Efficacy in the Elderly and Patients With Acute Respiratory Illness

Copyright © 2016, Infectious Diseases and Tropical Medicine Research Center. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited. Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reeducates. Considering the association between elevated cholesterol levels and the risk of cardiovascular diseases and because of studies show that statins can lower this risk, it is given to a large number of adults (1). In fact, it is estimated that more than one billion people worldwide take statins (2). Although the primary goal of statin therapy was to lower cholesterol levels, it was recognized that this drug class had other effects, including suppression of T-cell activation and immunomodulatory and anti-inflammatory effects (3, 4). Many patients who routinely take statins are the elderly who are at higher risk for the complications of influenza (5). Statins are beneficial for cardiovascular diseases due to their lipid-lowering effect (6). They also exhibit anti-inflammatory and immunomodulatory properties, which not only contribute to their impact on cardiovascular disease, but can also affect the clinical course of a variety of infectious processes, including sepsis, bacteremia, communityacquired pneumonia and laboratory-confirmed influenza. Furthermore, statins affect vaccine responsiveness in individuals, and their widespread use could influence overall vaccine effectiveness (VE) in a population (7-11). Based on a study, the immunosuppressive effect of statins on the vaccine immune response was most dramatic in individuals receiving synthetic statins. These effects were observed in both the adjuvanted and nonadjuvanted vaccine groups in the clinical trial. These results, if confirmed, could have implications both for future clinical trial designs, as well as vaccine use recommendations for the elderly (12). Also in another study, statin therapy was associated with reduced influenza VE against medically attended acute respiratory illness (MAARI). Many cases of MAARI are not caused by influenza; studies on the impact of statins on influenza VE against laboratory-confirmed influenza are needed (13). Researchers observed that statin users had a significantly reduced to immune response to vaccination compared to those not taking statins, as measured by the level of antibodies to the flu vaccine strains in the patients’ blood three weeks after vaccination. The effect was most dramatic in patients on synthetic statins, rather than naturally derived statins (14). Apparently, statins interfere with the response to influenza vaccine and lower the immune response, and it seems to also result in a lower effectiveness of influenza vaccines. If confirmed, the findings could support the preferential use of high-dose flu vaccine or vaccines containing adjuvants to boost immune response in the elderly, in an attempt to counteract the apparent effect (15, 16). Researchers in a study observed that vaccine effectiveness, to prevent serious respiratory illness, was lower among the patients taking statins compared to the ones not on statins, particularly when flu was widespread in the region. The findings have potential implications for guidelines regarding statin use in older adults around the vaccination time, but additional studies, including researches examining laboratory-confirmed cases of flu, are needed to provide more guidance (12, 13). In conclusion the results of these studies should be viewed as hypothesis-generating and should prompt further investigations on whether statins reduce inactivated influenza vaccine immunogenicity and, if so, the mechanisms by which immune responses and associated vaccine effectiveness are adversely affected.

Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States.

The predominant strain during the 2013-2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009. The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2-17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed. We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR-confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%-61%). Among fully vaccinated children aged 2-17 years, the effectiveness of LAIV4 was 17% (95% CI, -39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%-74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season. During 2013-2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States.