Healthcare personnel in 2016-2019 prospective cohort infrequently got vaccinated, worked while ill, and frequently used antibiotics rather than antivirals against viral influenza illnesses.

Background: Uncertainty about risk of illness and the value of influenza vaccines negatively affects vaccine uptake among persons targeted for influenza vaccination. Methods: During 2016-2019, we followed a cohort of healthcare personnel (HCP) targeted for free-of-charge influenza vaccination in five Lima hospitals to quantify risk of influenza, workplace presenteeism (coming to work despite illness), and absenteeism (taking time off from work because of illness). The HCP who developed acute respiratory illnesses (ARI) (≥1 of acute cough, runny nose, body aches, or feverishness) were tested for influenza using reverse-transcription polymerase chain reaction (rt-PCR). Findings: The cohort (2968 HCP) contributed 950,888 person-days. Only 36 (6%) of 605 HCP who participated every year were vaccinated. The HCP had 5750 ARI and 147 rt-PCR-confirmed influenza illnesses. The weighted incidence of laboratory-confirmed influenza was 10.0/100 person-years; 37% used antibiotics, and 0.7% used antivirals to treat these illnesses. The HCP with laboratory-confirmed influenza were present at work while ill for a cumulative 1187 hours. Interpretation: HCP were frequently ill and often worked rather than stayed at home while ill. Our findings suggest the need for continuing medical education about the risk of influenza and benefits of vaccination and stay-at-home-while-ill policies.

Knowledge, attitudes, and practices associated with frequent influenza vaccination among healthcare personnel in Peru, 2016─2018.

Introduction: Despite a government-subsidized vaccination program, healthcare personnel (HCP) influenza vaccination uptake remains low in Peru. Using three years of cross-sectional surveys and an additional five years of prior vaccination history of HCP in Peru, we explored HCP knowledge, attitudes, and practices (KAP) of influenza illness and its impact on vaccination frequency. Methods: In 2016, the Estudio Vacuna de Influenza Peru (VIP) cohort was initiated in Lima, Peru, which collected information about HCP KAP and influenza vaccination history from 2011─2018. HCP were classified by their 8-year influenza vaccination history as never (0 years), infrequently (1─4 years), or frequently (5─8 years) vaccinated. Logistic regression models were used to describe KAP associated with frequent compared to infrequent influenza vaccination, adjusted for each HCP's healthcare workplace, age, sex, preexisting medical conditions, occupation, and length of time providing direct patient care. Results: From 2016─2018, 5131 HCP were recruited and 3120 fully enrolled in VIP; 2782 consistently reported influenza vaccination status and became our analytic sample. From 2011─2018, 14.3% of HCP never, 61.4% infrequently, and 24.4% frequently received influenza vaccines. Compared to HCP who were infrequently vaccinated, frequently vaccinated HCP were more likely to believe they were susceptible to influenza (adjusted odds ratio [aOR]:1.49, 95% confidence interval [CI]:1.22─1.82), perceived vaccination to be effective (aOR:1.92, 95%CI:1.59─2.32), were knowledgeable about influenza and vaccination (aOR:1.37, 95%CI:1.06─1.77), and believed vaccination had emotional benefits like reduced regret or anger if they became ill with influenza (aOR:1.96, 95%CI:1.60─2.42). HCP who reported vaccination barriers like not having time or a convenient place to receive vaccines had reduced odds of frequent vaccination (aOR:0.74, 95%CI:0.61─0.89) compared to those without reported barriers. Conclusion: Few HCP frequently received influenza vaccines during an eight-year period. To increase HCP influenza vaccination in middle-income settings like Peru, campaigns could strengthen influenza risk perception, vaccine knowledge, and accessibility.

Effectiveness of Maternal Influenza Vaccination in Peru PRIME Cohort.

Background: Few studies have examined influenza vaccine effectiveness (VE) among women during pregnancy in middle-income countries. We used data from a prospective cohort of women who were pregnant in Peru to estimate effectiveness of the 2018 Southern Hemisphere influenza vaccine. Methods: Women at <28 weeks gestation were enrolled from 4 tertiary level hospitals in Lima, Peru at the start of the 2018 influenza season and followed until the end of their pregnancies. Participants had mid-turbinate nasal swabs collected and tested for influenza by reverse-transcription polymerase chain reaction (RT-PCR) with onset of ≥1 of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing. Time-varying Cox proportional hazard regression models were used to estimate the risk of RT-PCR-confirmed influenza infection after adjusting for inverse probability treatment weight. Results: We followed 1896 women for a median of 127 days (interquartile range [IQR], 86-174). Participants had a median age of 29 years (IQR, 24-34). Among the 1896 women, 49% were vaccinated with the 2018 influenza vaccine and 1039 (55%) developed influenza-like illness, 76 (7%) of whom had RT-PCR-confirmed influenza. Incidence rates of RT-PCR-confirmed influenza were 36.6 and 15.3 per 100 000 person-days among women who were unvaccinated and vaccinated, respectively. Adjusted influenza VE was 22% (95% confidence interval, -64.1% to 62.9%). Conclusions: Participants vaccinated against influenza had more than 50% lower incidence of RT-PCR-confirmed influenza illness. Although the VE estimated through propensity weight-adjusted time-varying Cox regression did not reach statistical significance, our findings provide additional evidence about the value of maternal influenza vaccination in middle-income countries.

Incidence Rates of Medically Attended COVID-19 in Infants Less Than 6 Months of Age.

BACKGROUND: Studies suggest infants may be at increased risk of severe coronavirus disease 2019 (COVID-19) relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age. METHODS: We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from 3 health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses and severe acute respiratory syndrome coronavirus syndrome 2 (SARS-CoV-2) test results. Medically attended COVID-19 episodes were defined by positive SARS-CoV-2 clinical tests and/or COVID-19 diagnosis codes during medical care visits. Unadjusted and site-adjusted incidence rates by infant month of age, low and high SARS-CoV-2 circulation periods and maternal COVID-19 diagnosis were calculated. RESULTS: Among 18,192 infants <6 months of age whose mothers received prenatal care within the 3 systems, 173 (1.0%) had medically attended COVID-19 episodes. Incidence rates were highest among infants under 1 month of age (2.0 per 1000 person-weeks) and 1 month (2.0 per 1000 person-weeks) compared with older infants. Incidence rates were also higher for infants born to women with postpartum COVID-19 compared with women without known COVID-19 and women diagnosed with COVID-19 during pregnancy. CONCLUSIONS: Infants of women with postpartum COVID-19 had a higher risk of medically attended COVID-19 than infants born to mothers who were diagnosed during pregnancy or never diagnosed underscoring the importance of COVID-19 prevention measures for their household members and caregivers to prevent infections in infants.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Testing and Detection During Peripartum Hospitalizations Among a Multicenter Cohort of Pregnant Persons: March 2020-February 2021.

BACKGROUND: Identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during peripartum hospitalizations is important to guide care, implement prevention measures, and understand infection burden. METHODS: This cross-sectional analysis used electronic health record data from hospitalizations during which pregnancies ended (peripartum hospitalizations) among a cohort of pregnant persons at 3 US integrated healthcare networks (sites 1-3). Maternal demographic, medical encounter, SARS-CoV-2 testing, and pregnancy and neonatal outcome information was extracted for persons with estimated delivery and pregnancy end dates during March 2020-February 2021 and ≥1 antenatal care record. Site-stratified multivariable logistic regression was used to identify factors associated with testing and compare pregnancy and neonatal outcomes among persons tested. RESULTS: Among 17 858 pregnant persons, 10 863 (60.8%) had peripartum SARS-CoV-2 testing; 222/10 683 (2.0%) had positive results. Testing prevalence varied by site and was lower during March-May 2020. Factors associated with higher peripartum SARS-CoV-2 testing odds were Asian race (adjusted odds ratio [aOR]: 1.36; 95% confidence interval [CI]: 1.03-1.79; referent: White) (site 1), Hispanic or Latino ethnicity (aOR: 1.33; 95% CI: 1.08-1.64) (site 2), peripartum Medicaid coverage (aOR: 1.33; 95% CI: 1.06-1.66) (site 1), and preterm hospitalization (aOR: 1.69; 95% CI: 1.19-2.39 [site 1]; aOR: 1.39; 95% CI: 1.03-1.88 [site 2]). CONCLUSIONS: Findings highlight potential disparities in SARS-CoV-2 peripartum testing by demographic and pregnancy characteristics. Testing practice variations should be considered when interpreting studies relying on convenience samples of pregnant persons testing positive for SARS-CoV-2. Efforts to address testing differences between groups could improve equitable testing practices and care for pregnant persons with SARS-CoV-2 infections.

Severity of influenza illness by seasonal influenza vaccination status among hospitalised patients in four South American countries, 2013-19: a surveillance-based cohort study.

BACKGROUND: Although several studies have reported attenuated influenza illness following influenza vaccination, results have been inconsistent and have focused predominantly on adults in the USA. This study aimed to evaluate the severity of influenza illness by vaccination status in a broad range of influenza vaccine target groups across multiple South American countries. METHODS: We analysed data from four South American countries (Argentina, Brazil, Chile, and Paraguay) participating in REVELAC-i, a multicentre, test-negative design, vaccine effectiveness network including 41 sentinel hospitals. Individuals hospitalised at one of these centres with severe acute respiratory infection were tested for influenza by real-time RT-PCR, and were included in the analysis if they had complete information about their vaccination status and outcomes of their hospital stay. We used multivariable logistic regression weighted by inverse probability of vaccination and adjusted for antiviral use, duration of illness before admission, and calendar week, to calculate the adjusted odds ratios (aORs) of intensive care unit (ICU) admission and in-hospital death (and combinations of these outcomes) among influenza-positive patients by vaccination status for three target groups: young children (aged 6-24 months), adults (aged 18-64 years) with pre-existing health conditions, and older adults (aged ≥65 years). Survival curves were used to compare length of hospital stay by vaccination status in each target group. FINDINGS: 2747 patients hospitalised with PCR-confirmed influenza virus infection between Jan 1, 2013, and Dec 8, 2019, were included in the study: 649 children (70 [10·8%] fully vaccinated, 193 [29·7%] partially vaccinated) of whom 87 (13·4%) were admitted to ICU and 12 (1·8%) died in hospital; 520 adults with pre-existing medical conditions (118 [22·7%] vaccinated), of whom 139 (26·7%) were admitted to ICU and 55 (10·6%) died in hospital; and 1578 older adults (609 [38·6%] vaccinated), of whom 271 (17·2%) were admitted to ICU and 220 (13·9%) died in hospital. We observed earlier discharge among partially vaccinated children (adjusted hazard ratio 1·14 [95% CI 1·01-1·29]), fully vaccinated children (1·24 [1·04-1·47]), and vaccinated adults with pre-existing medical conditions (1·78 [1·18-2·69]) compared with their unvaccinated counterparts, but not among vaccinated older adults (0·82 [0·65-1·04]). Compared with unvaccinated individuals, lower odds of ICU admission were found for partially vaccinated children (aOR 0·64 [95% CI 0·44-0·92]) and fully vaccinated children (0·52 [0·28-0·98]), but not for adults with pre-existing conditions (1·25 [0·93-1·67]) or older adults (0·88 [0·72-1·08]). Lower odds of in-hospital death (0·62 [0·50-0·78]) were found in vaccinated versus unvaccinated older adults, with or without ICU admission, but did not differ significantly in partially vaccinated (1·35 [0·57-3·20]) or fully vaccinated young children (0·88 [0·16-4·82]) or adults with pre-existing medical conditions (1·09 [0·73-1·63]) compared with the respective unvaccinated patient groups. INTERPRETATION: Influenza vaccination was associated with illness attenuation among those hospitalised with influenza, although results differed by vaccine target group. These findings might suggest that attenuation of disease severity might be specific to certain target groups, seasons, or settings. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Leveraging International Influenza Surveillance Systems and Programs during the COVID-19 Pandemic.

A network of global respiratory disease surveillance systems and partnerships has been built over decades as a direct response to the persistent threat of seasonal, zoonotic, and pandemic influenza. These efforts have been spearheaded by the World Health Organization, country ministries of health, the US Centers for Disease Control and Prevention, nongovernmental organizations, academic groups, and others. During the COVID-19 pandemic, the US Centers for Disease Control and Prevention worked closely with ministries of health in partner countries and the World Health Organization to leverage influenza surveillance systems and programs to respond to SARS-CoV-2 transmission. Countries used existing surveillance systems for severe acute respiratory infection and influenza-like illness, respiratory virus laboratory resources, pandemic influenza preparedness plans, and ongoing population-based influenza studies to track, study, and respond to SARS-CoV-2 infections. The incorporation of COVID-19 surveillance into existing influenza sentinel surveillance systems can support continued global surveillance for respiratory viruses with pandemic potential.

Effectiveness of Whole-Virus COVID-19 Vaccine among Healthcare Personnel, Lima, Peru.

In February 2021, Peru launched a COVID-19 vaccination campaign among healthcare personnel using an inactivated whole-virus vaccine. The manufacturer recommended 2 vaccine doses 21 days apart. We evaluated vaccine effectiveness among an existing multiyear influenza vaccine cohort at 2 hospitals in Lima. We analyzed data on 290 participants followed during February-May 2021. Participants completed a baseline questionnaire and provided weekly self-collected nasal swab samples; samples were tested by real-time reverse transcription PCR. Median participant follow-up was 2 (range 1-11) weeks. We performed multivariable logistic regression and adjusted for preselected characteristics. During the study, 25 (9%) participants tested SARS-CoV-2-positive. We estimated adjusted vaccine effectiveness at 95% (95% CI 70%-99%) among fully vaccinated participants and 100% (95% CI 88%-100%) among partially vaccinated participants. These data can inform the use and acceptance of inactivated whole-virus vaccine and support vaccination efforts in the region.

Medically Attended Influenza During Pregnancy in the 2019-2020 and 2020-2021 Influenza Seasons.

Influenza testing and case-confirmation rates in pregnant populations have not been reported during the coronavirus disease 2019 (COVID-19) pandemic. Using electronic medical record data from a cohort of nearly 20,000 pregnancies in the United States, this retrospective cohort study examines the frequency of acute respiratory or febrile illness encounters, influenza testing, and influenza positivity during the 2020-2021 influenza season, which occurred during the COVID-19 pandemic, compared with the 2019-2020 influenza season, which largely did not. The ratios of influenza tests to acute respiratory or febrile illness visits were similar in the 2019-2020 and 2020-2021 influenza seasons (approximately 1:8 and 1:9, respectively) but were low and varied by study site. Although influenza testing in pregnant patients continued in the 2020-2021 season, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulation was widespread in the United States, no cases of influenza were identified in our study cohort.

Influenza Incidence and Vaccine Effectiveness During the Southern Hemisphere Influenza Season - Chile, 2022.

The COVID-19 pandemic has affected influenza virus transmission, with historically low activity, atypical timing, or altered duration of influenza seasons during 2020-22 (1,2). Community mitigation measures implemented since 2020, including physical distancing and face mask use, have, in part, been credited for low influenza detections globally during the pandemic, compared with those during prepandemic seasons (1). Reduced population exposure to natural influenza infections during 2020-21 and relaxed community mitigation measures after introduction of COVID-19 vaccines could increase the possibility of severe influenza epidemics. Partners in Chile and the United States assessed Southern Hemisphere influenza activity and estimated age-group-specific rates of influenza-attributable hospitalizations and vaccine effectiveness (VE) in Chile in 2022. Chile's most recent influenza season began in January 2022, which was earlier than during prepandemic seasons and was associated predominantly with influenza A(H3N2) virus, clade 3C.2a1b.2a.2. The cumulative incidence of influenza-attributable pneumonia and influenza (P&I) hospitalizations was 5.1 per 100,000 person-years during 2022, which was higher than that during 2020-21 but lower than incidence during the 2017-19 influenza seasons. Adjusted VE against influenza A(H3N2)-associated hospitalization was 49%. These findings indicate that influenza activity continues to be disrupted after emergence of SARS-CoV-2 in 2020. Northern Hemisphere countries might benefit from preparing for an atypical influenza season, which could include early influenza activity with potentially severe disease during the 2022-23 season, especially in the absence of prevention measures, including vaccination. Health authorities should encourage all eligible persons to seek influenza vaccination and take precautions to reduce transmission of influenza (e.g., avoiding close contact with persons who are ill).

Rates of Severe Influenza-Associated Outcomes Among Older Adults Living With Diabetes-Influenza Hospitalization Surveillance Network (FluSurv-NET), 2012-2017.

Background: Diabetes mellitus (DM) is common among older adults hospitalized with influenza, yet data are limited on the impact of DM on risk of severe influenza-associated outcomes. Methods: We included adults aged ≥65 years hospitalized with influenza during 2012-2013 through 2016-2017 from the Influenza Hospitalization Surveillance Network (FluSurv-NET), a population-based surveillance system for laboratory-confirmed influenza-associated hospitalizations conducted in defined counties within 13 states. We calculated population denominators using the Centers for Medicare and Medicaid Services county-specific DM prevalence estimates and National Center for Health Statistics population data. We present pooled rates and rate ratios (RRs) of intensive care unit (ICU) admission, pneumonia diagnosis, mechanical ventilation, and in-hospital death for persons with and without DM. We estimated RRs and 95% confidence intervals (CIs) using meta-analysis with site as a random effect in order to control for site differences in the estimates. Results: Of 31 934 hospitalized adults included in the analysis, 34% had DM. Compared to those without DM, adults with DM had higher rates of influenza-associated hospitalization (RR, 1.57 [95% CI, 1.43-1.72]), ICU admission (RR, 1.84 [95% CI, 1.67-2.04]), pneumonia (RR, 1.57 [95% CI, 1.42-1.73]), mechanical ventilation (RR, 1.95 [95% CI, 1.74-2.20]), and in-hospital death (RR, 1.48 [95% CI, 1.23-1.80]). Conclusions: Older adults with DM have higher rates of severe influenza-associated outcomes compared to those without DM. These findings reinforce the importance of preventing influenza virus infections through annual vaccination, and early treatment of influenza illness with antivirals in older adults with DM.

Incidence and seasonality of respiratory viruses among medically attended children with acute respiratory infections in an Ecuador birth cohort, 2011-2014.

BACKGROUND: Ecuador annually has handwashing and respiratory hygiene campaigns and seasonal influenza vaccination to prevent respiratory virus illnesses but has yet to quantify disease burden and determine epidemic timing. METHODS: To identify respiratory virus burden and assess months with epidemic activity, we followed a birth cohort in northwest Ecuador during 2011-2014. Mothers brought children to the study clinic for routine checkups at ages 1, 2, 3, 5, and 8 years or if children experienced any acute respiratory illness symptoms (e.g., cough, fever, or difficulty breathing); clinical care was provided free of charge. Those with medically attended acute respiratory infections (MAARIs) were tested for common respiratory viruses via real-time reverse-transcription polymerase chain reaction (rRT-PCR). RESULTS: In 2011, 2376 children aged 1-4 years (median 35 months) were enrolled in the respiratory cohort and monitored for 7017.5 child-years (cy). The incidence of respiratory syncytial virus (RSV) was 23.9 (95% CI 17.3-30.5), influenza 10.6 (2.4-18.8), adenoviruses 6.7 (4.6-28.0), parainfluenzas 5.0 (2.3-10.5), and rhinoviruses, bocaviruses, human metapneumoviruses, seasonal coronaviruses, and enteroviruses <3/100 cy among children aged 12-23 months and declined with age. Most (75%) influenza detections occurred April-September. CONCLUSION: Cohort children frequently had MAARIs, and while the incidence decreased rapidly among older children, more than one in five children aged 12-23 months tested positive for RSV, and one in 10 tested positive for influenza. Our findings suggest this substantial burden of influenza occurred more commonly during the winter Southern Hemisphere influenza season.

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

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

What do pregnant women think about influenza disease and vaccination practices in selected countries.

Introduction: We evaluated knowledge, attitudes, and practices (KAP) related to influenza and influenza vaccination among pregnant women in three selected countries.Methods: During 2017, pregnant women seeking antenatal care at hospitals at participating sites were enrolled. We described characteristics and responses to KAP questions. We also evaluated predictors associated with influenza vaccination during pregnancy at sites with substantial influenza vaccine uptake by multivariable logistic regression.Results: Overall, 4,648 pregnant women completed the survey. There were substantial differences among the three survey populations; only 8% of the women in Nagpur had heard of influenza, compared to 90% in Lima and 96% in Bangkok (p-value<0.01). Despite significant differences in sociodemographic characteristics in the three populations, most participants across sites who were aware of influenza prior to study enrollment believe they and their infants are at risk of influenza and related complications and believe influenza vaccination is safe and effective. Half of women in Lima had verified receipt of influenza vaccine compared to <5% in Bangkok and Nagpur (p < .05). For further analysis conducted among women in Lima only, household income above the poverty line (aOR: 1.38; 95%CI: 1.01, 1.88), having 8+ antenatal visits, compared to 0-4 (aOR: 2.41; 95%CI: 1.39, 2.87, respectively), having 0 children, compared to 2+ (aOR: 1.96; 95%CIs: 1.23, 3.12), and vaccination recommended by a health-care provider (aOR: 8.25; 95%CI: 6.11, 11.14) were strongly associated with receipt of influenza vaccine during pregnancy.Conclusions: Our findings identify opportunities for targeted interventions to improve influenza vaccine uptake among pregnant women in these settings.

Incidence of influenza during pregnancy and association with pregnancy and perinatal outcomes in three middle-income countries: a multisite prospective longitudinal cohort study.

BACKGROUND: Influenza vaccination during pregnancy prevents influenza among women and their infants but remains underused among pregnant women. We aimed to quantify the risk of antenatal influenza and examine its association with perinatal outcomes. METHODS: We did a prospective cohort study in pregnant women in India, Peru, and Thailand. Before the 2017 and 2018 influenza seasons, we enrolled pregnant women aged 18 years or older with expected delivery dates 8 weeks or more after the season started. We contacted women twice weekly until the end of pregnancy to identify illnesses with symptoms of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing and collected mid-turbinate nasal swabs from symptomatic women for influenza real-time RT-PCR testing. We assessed the association of antenatal influenza with preterm birth, late pregnancy loss (≥13 weeks gestation), small for gestational age (SGA), and birthweight of term singleton infants using Cox proportional hazards models or generalised linear models to adjust for potential confounders. FINDINGS: Between March 13, 2017, and Aug 3, 2018, we enrolled 11 277 women with a median age of 26 years (IQR 23-31) and gestational age of 19 weeks (14-24). 1474 (13%) received influenza vaccines. 310 participants (3%) had influenza (270 [87%] influenza A and 40 [13%] influenza B). Influenza incidences weighted by the population of women of childbearing age in each study country were 88·7 per 10 000 pregnant woman-months (95% CI 68·6 to 114·8) during the 2017 season and 69·6 per 10 000 pregnant woman-months (53·8 to 90·2) during the 2018 season. Antenatal influenza was not associated with preterm birth (adjusted hazard ratio [aHR] 1·4, 95% CI 0·9 to 2·0; p=0·096) or having an SGA infant (adjusted relative risk 1·0, 95% CI 0·8 to 1·3, p=0·97), but was associated with late pregnancy loss (aHR 10·7, 95% CI 4·3 to 27·0; p<0·0001) and reduction in mean birthweight of term, singleton infants (-55·3 g, 95% CI -109·3 to -1·4; p=0·0445). INTERPRETATION: Women had a 0·7-0·9% risk of influenza per month of pregnancy during the influenza season, and antenatal influenza was associated with increased risk for some adverse pregnancy outcomes. These findings support the added value of antenatal influenza vaccination to improve perinatal outcomes. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Thai, Hindi, Marathi and Spanish translations of the abstract see Supplementary Materials section.

Performance of Symptom-Based Case Definitions to Identify Influenza Virus Infection Among Pregnant Women in Middle-Income Countries: Findings From the Pregnancy and Influenza Multinational Epidemiologic (PRIME) Study.

BACKGROUND: The World Health Organization (WHO) recommends case definitions for influenza surveillance that are also used in public health research, although their performance has not been assessed in many risk groups, including pregnant women in whom influenza may manifest differently. We evaluated the performance of symptom-based definitions to detect influenza in a cohort of pregnant women in India, Peru, and Thailand. METHODS: In 2017 and 2018, we contacted 11 277 pregnant women twice weekly during the influenza season to identify illnesses with new or worsened cough, runny nose, sore throat, difficulty breathing, or myalgia and collected data on other symptoms and nasal swabs for influenza real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing. We calculated sensitivity, specificity, positive-predictive value, and negative-predictive value of each symptom predictor, WHO respiratory illness case definitions, and a de novo definition derived from results of multivariable modeling. RESULTS: Of 5444 eligible illness episodes among 3965 participants, 310 (6%) were positive for influenza. In a multivariable model, measured fever ≥38°C (adjusted odds ratio [95% confidence interval], 4.6 [3.1-6.8]), myalgia (3.0 [2.2-4.0]), cough (2.7 [1.9-3.9]), and chills (1.6 [1.1-2.4]) were independently associated with influenza illness. A definition based on these 4 (measured fever, cough, chills, or myalgia) was 95% sensitive and 27% specific. The WHO influenza-like illness (ILI) definition was 16% sensitive and 98% specific. CONCLUSIONS: The current WHO ILI case definition was highly specific but had low sensitivity. The intended use of case definitions should be considered when evaluating the tradeoff between sensitivity and specificity.

Prospective cohort study of influenza vaccine effectiveness among healthcare personnel in Lima, Peru: Estudio Vacuna de Influenza Peru, 2016-2018.

BACKGROUND: The Estudio Vacuna de Influenza Peru (VIP) cohort aims to describe the frequency of influenza virus infection, identify predictors of vaccine acceptance, examine the effects of repeated influenza vaccination on immunogenicity, and evaluate influenza vaccine effectiveness among HCP. METHODS: The VIP cohort prospectively followed HCP in Lima, Peru, during the 2016-2018 influenza seasons; a fourth year is ongoing. Participants contribute blood samples before and after the influenza season and after influenza vaccination (for vaccinees). Weekly surveillance is conducted to identify acute respiratory or febrile illnesses (ARFI). When an ARFI is identified, participants self-collect nasal swabs that are tested for influenza viruses by real-time reverse transcriptase-polymerase chain reaction. Influenza vaccination status and 5-year vaccination history are ascertained. We analyzed recruitment and enrollment results for 2016-2018 and surveillance participation for 2016-2017. RESULTS: In the first 3 years of the cohort, VIP successfully contacted 92% of potential participants, enrolled 76% of eligible HCP, and retained >90% of participants across years. About half of participants are medical assistants (54%), and most provide "hands-on" medical care (76%). Sixty-nine percent and 52% of participants completed surveillance for >70% of weeks in years 1 and 2, respectively. Fewer weeks of completed surveillance was associated with older age (≥50 years), being a medical assistant, self-rated health of fair or poor, and not receiving the influenza vaccine during the current season (P-values < .05). CONCLUSIONS: The VIP cohort provides an opportunity to address knowledge gaps about influenza virus infection, vaccination uptake, effectiveness and immunogenicity among HCP.

Estimated Burden of Community-Onset Respiratory Syncytial Virus-Associated Hospitalizations Among Children Aged <2 Years in the United States, 2014-15.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of hospitalizations in young children. We estimated the burden of community-onset RSV-associated hospitalizations among US children aged <2 years by extrapolating rates of RSV-confirmed hospitalizations in 4 surveillance states and using probabilistic multipliers to adjust for ascertainment biases. METHODS: From October 2014 through April 2015, clinician-ordered RSV tests identified laboratory-confirmed RSV hospitalizations among children aged <2 years at 4 influenza hospitalization surveillance network sites. Surveillance populations were used to estimate age-specific rates of RSV-associated hospitalization, after adjusting for detection probabilities. We extrapolated these rates using US census data. RESULTS: We identified 1554 RSV-associated hospitalizations in children aged <2 years. Of these, 27% were admitted to an intensive care unit, 6% needed mechanical ventilation, and 5 died. Most cases (1047/1554; 67%) had no underlying condition. Adjusted age-specific RSV hospitalization rates per 100 000 population were 1970 (95% confidence interval [CI],1787 to 2177), 897 (95% CI, 761 to 1073), 531 (95% CI, 459 to 624), and 358 (95% CI, 317 to 405) for ages 0-2, 3-5, 6-11, and 12-23 months, respectively. Extrapolating to the US population, an estimated 49 509-59 867 community-onset RSV-associated hospitalizations among children aged <2 years occurred during the 2014-2015 season. CONCLUSIONS: Our findings highlight the importance of RSV as a cause of hospitalization, especially among children aged <2 months. Our approach to estimating RSV-related hospitalizations could be used to provide a US baseline for assessing the impact of future interventions.

Influenza vaccine effectiveness against hospitalizations in children and older adults-Data from South America, 2013-2017. A test negative design.

BACKGROUND: In 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults. METHODS: We used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6─24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013-December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults. RESULTS: We included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: -16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: -40%, 54%) against influenza B viruses. CONCLUSIONS: Our results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults.