Polymerase Chain Reaction-confirmed Influenza Research Articles

Patients with influenza admitted to a tertiary-care hospital in Riyadh between 2018 and 2022: characteristics, outcomes and factors associated with ICU admission and mortality

BackgroundInfluenza is a common cause of hospital admissions globally with regional variations in epidemiology and clinical profile. We evaluated the characteristics and outcomes of patients with influenza admitted to a tertiary-care center in Riyadh, Saudi Arabia.MethodsThis was a retrospective cohort of adult patients admitted with polymerase chain reaction-confirmed influenza to King Abdulaziz Medical City-Riyadh between January 1, 2018, and May 31, 2022. We compared patients who required intensive care unit (ICU) admission to those who did not and performed multivariable logistic regression to assess the predictors of ICU admission and hospital mortality.ResultsDuring the study period, 675 adult patients were hospitalized with influenza (median age 68.0 years, females 53.8%, hypertension 59.9%, diabetes 55.1%, and chronic respiratory disease 31.1%). Most admissions (83.0%) were in the colder months (October to March) in Riyadh with inter-seasonal cases even in the summertime (June to August). Influenza A was responsible for 79.0% of cases, with H3N2 and H1N1 subtypes commonly circulating in the study period. Respiratory viral coinfection occurred in 12 patients (1.8%) and bacterial coinfection in 42 patients (17.4%). 151 patients (22.4%) required ICU admission, of which 62.3% received vasopressors and 48.0% mechanical ventilation. Risk factors for ICU admission were younger age, hypertension, bilateral lung infiltrates on chest X-ray, and Pneumonia Severity Index. The overall hospital mortality was 7.4% (22.5% for ICU patients, p < 0.0001). Mortality was 45.0% in patients with bacterial coinfection, 30.9% in those requiring vasopressors, and 29.2% in those who received mechanical ventilation. Female sex (odds ratio [OR], 2.096; 95% confidence interval [CI] 1.070, 4.104), ischemic heart disease (OR, 3.053; 95% CI 1.457, 6.394), immunosuppressed state (OR, 7.102; 95% CI 1.803, 27.975), Pneumonia Severity Index (OR, 1.029; 95% CI, 1.017, 1.041), leukocyte count and serum lactate level (OR, 1.394; 95% CI, 1.163, 1.671) were independently associated with hospital mortality.ConclusionsInfluenza followed a seasonal pattern in Saudi Arabia, with H3N2 and H1N1 being the predominant circulating strains during the study period. ICU admission was required for > 20%. Female sex, high Pneumonia Severity Index, ischemic heart disease, and immunosuppressed state were associated with increased mortality.

Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness.

Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2-49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2-9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42-49 (95% confidence interval (CI) 52-92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06-1.50, P = 0.010).

The Pregnancy and Influenza Multinational Epidemiologic (PRIME) study: a prospective cohort study of the impact of influenza during pregnancy among women in middle-income countries

BackgroundThe World Health Organization identifies pregnant women as at high-risk for severe influenza, but influenza vaccines are underutilized among pregnant women. Data on influenza burden during pregnancy are largely limited to high-income countries and data on the impact of influenza on birth and perinatal outcomes are scarce.Methods/designThis prospective, longitudinal cohort study of pregnant women in middle-income countries is designed to address three primary objectives: 1) to evaluate the effect of laboratory-confirmed influenza during pregnancy on pregnancy and perinatal outcomes; 2) to estimate the incidences of all-cause acute respiratory illness and laboratory-confirmed influenza during pregnancy; and 3) to examine the clinical spectrum of illness associated with influenza viruses. Through a multi-country network approach, three sites aim to enroll cohorts of 1500–3000 pregnant women just before local influenza seasons. Women aged ≥ 18 years with expected delivery dates ≥ 8 weeks after the start of the influenza season are eligible. Women are followed throughout pregnancy through twice weekly surveillance for influenza symptoms (≥ 1 of myalgia, cough, runny nose, sore throat, or difficulty breathing) and have mid-turbinate nasal swabs collected for influenza virus testing during illness episodes. Primary outcomes include relative risk of preterm birth and mean birth weight among term singleton infants of women with and without reverse transcription polymerase chain reaction-confirmed influenza during pregnancy. Gestational age is determined by ultrasound at < 28 weeks gestation and birth weight is measured by digital scales using standardized methods. Sites are primarily urban in Bangkok, Thailand; Lima, Peru; and Nagpur, India. All sites recruit from antenatal clinics at referral hospitals and conduct surveillance using telephone calls, messaging applications, or home visits. Nasal swabs are self-collected by participants in Thailand and by study staff in Peru and India. During the first year (2017), sites enrolled participants during March–May in Peru and May–July in India and Thailand; 4779 women were enrolled.DiscussionThis study aims to generate evidence of the impact of influenza during pregnancy to inform decisions by Ministries of Health, healthcare providers, and pregnant women in middle-income countries about the value of influenza vaccination during pregnancy.

Influence of Birth Cohort on Effectiveness of 2015-2016 Influenza Vaccine Against Medically Attended Illness Due to 2009 Pandemic Influenza A(H1N1) Virus in the United States.

The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 × [1 - adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients. A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged ≥6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined. Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses.

Contribution of Serologic Assays in the Evaluation of Influenza Virus Infection Rates and Vaccine Efficacy in Pregnant Women: Report From Randomized Controlled Trials.

The utility of serologic testing to evaluate vaccine efficacy of seasonal inactivated influenza vaccine (IIV) is controversial. We aimed to evaluate the efficacy of IIV against serologically diagnosed influenza infection (SDI) and reverse-transcription polymerase chain reaction-confirmed influenza illness (PCR-CI) in women vaccinated during pregnancy. We undertook a post hoc analysis of 2 randomized clinical trials evaluating IIV efficacy among human immunodeficiency virus (HIV)-uninfected and HIV-infected pregnant women. SDI was defined as ≥4-fold increase in paired hemagglutinin antibody inhibition titers from 1 month postvaccination until end-of-study participation. PCR-CI was defined as molecular diagnostic evidence of influenza virus in pharyngeal specimens collected during clinical illness. Among placebo recipients, the respective incidence of PCR-CI and SDI was 5.6% and 35.0% in HIV-uninfected women and 20.5% and 43.6% among HIV-infected women. Vaccine efficacy in HIV-uninfected women was similar for PCR-CI (66.9%; 95% confidence interval [CI], -20.1% to 90.9%) and SDI (59.2%; 95% CI, 37.0%-73.5%); however, fewer women required vaccination to prevent 1 episode of SDI (5; 95% CI, 3-9) than PCR-CI (27; 95% CI, 12-∞). Also, vaccine efficacy was similar for PCR-CI (61.2%; 95% CI, 10.7%-83.2%) and SDI (60.9%; 95% CI, 33.9%-76.9%) in HIV-infected women, with 2-fold fewer women needing to be vaccinated to prevent SDI (4; 95% CI, 3-8) than PCR-CI (8; 95% CI, 4-52). Although vaccine efficacy was similar when measured for PCR-CI or SDI, IIV vaccination prevented a greater number of SDI than PCR-CI; the clinical relevance of the former warrants interrogation.Clinical Trials Registration. NCT01306669 and NCT01306682.

2014-2015 Influenza Vaccine Effectiveness in the United States by Vaccine Type.

Circulating A/H3N2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. Also in 2014-2015, the Advisory Committee on Immunization Practices recommended preferential use of live attenuated influenza vaccine (LAIV) over inactivated influenza vaccine (IIV) among children aged 2-8 years. Vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design, that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. Of 9311 enrollees with complete data, 7078 (76%) were influenza negative, 1840 (19.8%) were positive for influenza A (A/H3N2, n = 1817), and 395 (4.2%) were positive for influenza B (B/Yamagata, n = 340). The overall adjusted VE was 19% (95% confidence interval [CI], 10% to 27%) and was statistically significant in all age strata except those aged 18-64 years. The adjusted VE of 6% (95%CI, -5% to 17%) against A/H3N2-associated illness was not statistically significant, unlike VE for influenza B/Yamagata, which was 55% (95%CI, 43% to 65%). Among those aged 2-8 years, VE against A/H3N2 was 15% (95%CI, -16% to 38%) for IIV and -3% (CI, -50% to 29%) for LAIV; VE against B/Yamagata was 40% (95%CI, -20% to 70%) for IIV and 74% (95%CI, 25% to 91%) for LAIV. The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus but were effective against influenza B. Preferential use of LAIV among young children was not supported.

Influenza vaccine efficacy in young children attending childcare: A randomised controlled trial.

Influenza causes a substantial burden in young children. Vaccine efficacy (VE) data are limited in this age group. We examined trivalent influenza vaccine (TIV) efficacy and safety in young children attending childcare. A double-blind, randomised controlled trial in children aged 6 to <48 months was conducted with recruitment from Sydney childcare centres in 2011. Children were randomised to receive two doses of TIV or control hepatitis A vaccine. Efficacy was evaluated against polymerase chain reaction-confirmed influenza using parent-collected nose/throat swabs during influenza-like-illness. Safety outcomes were assessed during 6 months of follow-up. Fifty-seven children were allocated to influenza vaccine and 67 to control; all completed the study. The influenza attack rate was 1.8 vs 13.4% in the TIV and control groups, respectively; VE 87% (95%CI: 0-98%). For children aged 24 to <48 months, 0 vs 8 (18.6%) influenza infections occurred in the TIV and control groups respectively, giving a VE of 100% (16-100%). Efficacy was not shown in children 6 to <24 months, probably due to insufficient power. Injection site and systemic adverse events were mostly mild to moderate with no significant differences, apart from more mild diarrhoea following dose 2 in TIV recipients (11.8 vs 0%). Influenza vaccine appeared efficacious in the subgroup of children aged 24 to <48 months, although caution is required due to the small number of participants. There were no serious adverse events and most parents would vaccinate again. Influenza vaccination in a childcare setting could be valuable and a larger confirmatory study would be helpful.

Missed Opportunities for Influenza Vaccination Among Hospitalized Children With Influenza at a Tertiary Care Facility.

To identify the extent and characteristics of missed opportunities for influenza vaccination among children hospitalized with influenza at a tertiary children's hospital. We conducted a retrospective cohort study of hospitalized patients with polymerase chain reaction-confirmed influenza admitted to Children's Hospital Colorado from 2010 to 2014. We reviewed medical records for vaccination status and previous visits. The primary outcome was the proportion of underimmunized patients hospitalized with influenza with at least 1 missed opportunity visit (visit before influenza diagnosis in which an eligible patient did not receive the influenza vaccine). The relationship between sociodemographic characteristics and the primary outcome were examined using χ(2) tests and nonparametric tests, and variables with P < .2 were entered into a multivariate logistic regression model. Among 322 patients hospitalized with influenza, 199 (61%) were undervaccinated; 83 of 199 (42%) had at least 1 missed opportunity for influenza vaccination. Multivariate analysis demonstrated that high-risk status (adjusted odds ratio 6.9, 95% confidence interval 3.8-12.4) was associated with increased odds of having a missed opportunity visit. Most missed opportunity visits were to subspecialty clinics (42%), and most visits (71%) occurred from September to November. More than 40% of hospitalizations for influenza in children are associated with at least 1 missed opportunity visit at a tertiary center. Our findings highlight the potential role of tertiary care institutions in increasing influenza vaccination rates among children.

Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children

Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.

Evaluation of the New World Health Organization Case Definition of Severe Acute Respiratory Infection for Influenza Surveillance During the Peak Weeks of Two Influenza Seasons in Quebec, Canada

During the peak of the 2012-2013 and 2014-2015 influenza seasons in Quebec, Canada, the sensitivity of the new World Health Organization (WHO) case definition of severe acute respiratory infection (SARI) in <5-year-old children was 65% for polymerase chain reaction-confirmed influenza and 79% for other respiratory viruses (ORVs), whereas its specificity and positive predictive value were approximately 2- and 4-fold lower for influenza than ORVs (25% vs 40% and 18% vs 76%, respectively). The use of the WHO SARI definition for influenza surveillance in children should be interpreted with caution according to the specific surveillance goals.

Burden of Influenza and Influenza-associated Pneumonia in the First Year of Life in a Prospective Cohort Study in Managua, Nicaragua.

Influenza is a major public health problem worldwide; however, relatively little is known about influenza in tropical regions, especially for infants. Additional information is required to inform public health policy making, in particular vaccination guidelines. Between September 2011 and July 2013, we enrolled newborns into the Nicaraguan Birth Cohort Study. Infants were provided primary medical care and actively followed for reverse-transcription polymerase chain reaction-confirmed influenza virus infection when presenting with influenza-like illness or undifferentiated fever. This report presents data pertaining to the first year of life. Of the 518 children enrolled in the study, 441 participated throughout their first year of life, 71 were withdrawn, and 6 died. Overall, 13% of the participants experienced at least 1 laboratory-confirmed influenza virus infection. The overall incidence of influenza was 15.5 cases per 100 person-years [95% confidence interval (CI): 12.2-19.5]. Infants aged 6-11 months experienced significantly higher rates of laboratory-confirmed influenza than infants aged 0-5 months (incidence rate ratio: 2.1; 95% CI: 1.3-3.4). The overall incidence of pneumonia was 52.6 cases per 100 person-years (95% CI: 46.3-59.6). Three percent of the pneumonia cases were influenza associated, and the incidence of influenza-associated pneumonia and hospitalization was 1.7 (95% CI: 0.9-3.5) and 0.22 (95% CI: 0.03-1.55) cases per 100 person-years, respectively. We found a significant burden of influenza and influenza-associated severe respiratory outcomes in infants. Our results support the need to explore the potential value of vaccinating pregnant women and infants aged >6 months, as recommended by the World Health Organization in 2012.

Impact of Late Oseltamivir Treatment on Influenza Symptoms in the Outpatient Setting: Results of a Randomized Trial.

We conducted a double-blind, randomized trial of 134 outpatients with polymerase chain reaction-confirmed influenza to assess the effects of oseltamivir initiated 48–119 hours after illness onset. Oseltamivir treatment did not reduce illness duration, severity, or duration of virus detection. However, the power of this study was limited due to lower than expected enrollment.

Does Influenza A Infection Increase Oxidative Damage?

Considerable data implicate oxidative damage in influenza pathogenesis. We examined temporal changes in oxidative damage using accurate biomarkers in an adult cohort with acute influenza infection and their relationships with clinical parameters. Clinical information and blood samples were collected during their acute illness and 3 months later. A fatigue questionnaire was administered 3 months following influenza infection. Thirty-five patients (mean age, 34 years) with polymerase chain reaction-confirmed influenza A infection were included; all patients returned for follow-up assessments. Adjusted levels of plasma F2-isoprostanes, total hydroxyeicosatetraenoic products (HETEs), 7β-hydroxycholesterol and 7-ketocholesterol, serum gamma-glutamyltransferase, and high-sensitivity C-reactive protein (hsCRP) were increased during the acute illness compared with age-matched controls. Despite clinical recovery, levels of these biomarkers remained higher at month 3 compared with controls. A proportion of patients had persistent symptoms such as fatigue (23%), myalgia (14%), and arthralgia (11%) at month 3. Patients with significant fatigue had higher baseline levels of plasma F2-isoprostanes, F4-neuroprostanes, and total HETEs compared to those without fatigue. By contrast, patients with persistent arthralgia and myalgia had higher baseline levels of serum hsCRP compared to those without these symptoms. Our observations lead to the hypothesis that oxidative damage participates in the pathogenesis of influenza infection and postinfectious fatigue.

Characteristics of Vaccine Failures in a Randomized Placebo-controlled Trial of Inactivated Influenza Vaccine in Children

Infections occurring among vaccinated persons (vaccine failures) are known to occur in vaccines with imperfect efficacy. Failures among vaccinated children who were infected with vaccine-matched influenza B virus strain have not been adequately characterized. Taking advantage of a randomized controlled trial of trivalent seasonal influenza vaccine (TIV), the viral shedding and clinical symptoms associated with reverse transcriptase polymerase chain reaction-confirmed influenza B infection and serum hemaggluttination inhibiting antibody response to vaccine were compared between children 6 and 17 years receiving TIV and placebo. Vaccine failures were observed to show lower antibody response to TIV compared with other vaccine recipients. We did not find any evidence that vaccination reduced the severity or duration of clinical symptoms of reverse transcriptase polymerase chain reaction-confirmed vaccine-matched influenza B infections. Vaccination was not observed to alter viral load or shedding duration. TIV was not observed to ameliorate clinical symptoms or viral shedding among vaccine failures compared with infected placebo recipients. Lower antibody response might have explained vaccine failure and also lack of effect in reducing clinical symptoms and viral shedding upon infection. Our results are based on a randomized controlled trial of split virus inactivated vaccine and may not be applicable to other vaccine types. Further studies in vaccine failure among children will be important in future vaccine development.

Hospital‐acquired influenza in an Australian sentinel surveillance system

To review cases of nosocomial influenza and compare the epidemiology, clinical characteristics and outcomes with community-acquired cases. Prospective case series of adults hospitalised with influenza during April - November of 2010 and 2011 using a hospital-based sentinel surveillance system. A nosocomial case was defined as polymerase chain reaction-confirmed influenza where symptom onset was more than 2 15s after admission or, if this was not known, where the date of the positive test was more than 7 15s after admission. Demographic, clinical and outcome measures for patients with nosocomial influenza compared with patients admitted with community-acquired influenza. In 2010-2011, 598 cases of influenza were detected, of which 26 (4.3%) were nosocomial. All patients with nosocomial influenza had chronic comorbidities, compared with 71.7% of patients (410/572) with community-acquired influenza (P = 0.001). Similar proportions of community-acquired (32.5%) and nosocomial (36.4%) cases occurred in patients vaccinated in the current season. Clinical findings at time of enrollment did not differ between the two groups, with similar rates of fever, cough, chest pain and dyspnoea. Compared with community-acquired cases, a higher proportion of patients with nosocomial influenza received neuraminidase inhibitors within 2 15s of symptom onset (38.5% v 15.9%; P = 0.003). Admission to intensive care took place in 21.3% and 23.1% of community-acquired and nosocomial cases, respectively. One death from nosocomial influenza occurred in a patient with end-stage respiratory disease. Nosocomial influenza is uncommon but may be associated with severe disease. It may be partially preventable as patients frequently have comorbidities for which influenza vaccination is recommended. Patients, particularly those at high risk of complications, and their contacts (including health care workers) should be vaccinated to prevent severe disease.

Impact of swine influenza and quarantine measures on patients and households during the H1N1/09 pandemic

To assess the secondary attack rates (SAR) and impact of the 2009 H1N1 epidemic in Melbourne, Victoria, Australia, and the measures implemented to control household transmission. Patients with polymerase chain reaction-confirmed influenza A and pandemic H1N1 (pH1N1) were identified from hospital and microbiology laboratory records and asked to take part in a retrospective survey. Information obtained included: the constellation of symptoms, contact history, secondary infection, and household information, including adherence and attitudes towards quarantine measures. The overall SAR of pH1N1 index patients was 30.6%, but a significantly lower SAR was noted with oseltamivir treatment (36.6% vs 22.8%, p < 0.05). The greatest reduction in SAR was observed when index patients aged 0-4 y received oseltamivir (83.3% vs 22.2%, p < 0.01). Quarantine was requested of 65.8% of patients and 92.8% self-reported adhering to recommendations. pH1N1 index patients, the number of median days bed-bound is 2.5 days, being unable or too sick to work for a median of 5.0 days, and lost a median of 7.0 days of work for reasons related to an influenza-like illness. The pH1N1 influenza pandemic had a significant clinical impact on households. Public health interventions such as oseltamivir treatment of index cases were beneficial in reducing secondary attack rates, whilst quarantine measures were found to have high rates of self-reported compliance, understanding, and acceptability.