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Background: Surveillance programmes for influenza and other respiratory pathogens are important to generate vaccine effectiveness (VE) estimates and to inform vaccine composition. We aimed to explore the feasibility and acceptability of home-based testing., Methods: In three out of nine provinces in South Africa, we established a self-referral system for individuals aged ≥ 18 years with respiratory symptoms of ≤ 10 days duration. Following consent, swab collection material was delivered to participants who also completed a questionnaire including self-reported vaccination status. Swabs were tested by PCR for influenza, respiratory syncytial virus (RSV) and SARS-CoV-2. A test-negative methodology was used to estimate influenza VE., Results: Of 1456 samples collected between 19 November 2021 and 3 September 2022, 73 (5%) tested positive for influenza, 38 (3%) tested positive for RSV and 394 (27%) for SARS-CoV-2. We subtyped 55% (40/73) of the influenza positive specimens; 16/40 (40%) were influenza A(H1N1)pdm09; 10/40 (25%)A(H3N2)) and all 14/40(35%) influenza B were B/Victoria. Only 20% (279/1451) of participants reported influenza-like illness case definition symptoms of fever and cough. Influenza vaccine coverage was 11% (157/1454). The overall influenza VE was 26% (95% confidence interval: -73%, 69%). Of the completed acceptability questionnaires, 123/127 (97%) participants would make use of the service again; 90% (1306) were recruited via the COVID-19 testing centre (call in, social media, webpage), and 7% (99/1306) through CoughWatchSA., Conclusions: Home-based swabbing was feasible and acceptable. We were able to calculate an influenza VE, although a larger sample size and verification of vaccine status may improve the VE estimates in the future., (© 2024 The Author(s). Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point., Objective: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes., Design: Prespecified exploratory analysis of a nationwide randomized implementation trial. ( ClinicalTrials.gov: NCT05542004)., Setting: The 2022 to 2023 influenza season., Participants: 964 870 Danish citizens aged 65 years or older., Intervention: Usual care or 9 different electronically delivered behavioral nudging letters., Measurements: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023., Results: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care)., Limitation: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms., Conclusion: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended., Primary Funding Source: Sanofi., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2638.

Importance: Influenza vaccination is associated with a reduced risk of mortality in patients with diabetes, but vaccination rates remain suboptimal., Objective: To assess the effect of electronic nudges on influenza vaccination uptake according to diabetes status., Design, Setting, and Participants: The NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) trial was a nationwide clinical trial of Danish citizens 65 years or older that randomized participants at the household level to usual care or 9 different electronic nudge letters during the 2022 to 2023 influenza season. End of follow-up was January 1, 2023. This secondary analysis of the NUDGE-FLU trial was performed from May to July 2023., Intervention: Nine different electronic nudge letters designed to boost influenza vaccination were sent in September to October 2022. Effect modification by diabetes status was assessed in a pooled analysis of all intervention arms vs usual care and for individual letters., Main Outcomes and Measures: The primary end point was receipt of a seasonal influenza vaccine., Results: The trial included 964 870 participants (51.5% female; mean [SD] age, 73.8 [6.3] years); 123 974 had diabetes. During follow-up, 83.5% with diabetes vs 80.2% without diabetes received a vaccine (P < .001). In the pooled analysis, nudges improved vaccination uptake in participants without diabetes (80.4% vs 80.0%; difference, 0.37 percentage points; 99.55% CI, 0.08 to 0.66), whereas there was no evidence of effect in those with diabetes (83.4% vs 83.6%; difference, -0.19 percentage points; 99.55% CI, -0.89 to 0.51) (P = .02 for interaction). In the main results of NUDGE-FLU, 2 of the 9 behaviorally designed letters (cardiovascular benefits letter and a repeated letter) significantly increased uptake of influenza vaccination vs usual care; these benefits similarly appeared attenuated in participants with diabetes (cardiovascular gain letter: 83.7% vs 83.6%; difference, 0.04 percentage points; 99.55% CI, -1.52 to 1.60; repeated letter: 83.5% vs 83.6%; difference, -0.15 percentage points; 99.55% CI, -1.71 to 1.41) vs those without diabetes (cardiovascular gain letter: 81.1% vs 80.0%; difference, 1.06 percentage points; 99.55% CI, 0.42 to 1.70; repeated letter: 80.9% vs 80.0%; difference, 0.87 percentage points; 99.55% CI, 0.22 to 1.52) (P = .07 for interaction)., Conclusions and Relevance: In this exploratory subgroup analysis, electronic nudges improved influenza vaccination uptake in persons without diabetes, whereas there was no evidence of an effect in persons with diabetes. Trials are needed to investigate the effect of digital nudges specifically tailored to individuals with diabetes., Trial Registration: ClinicalTrials.gov Identifier: NCT05542004.

Aims: Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE-FLU trial recently found two electronic behavioural nudging letter strategies - a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 -effective in increasing influenza vaccination in Denmark. The aims of this pre-specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off-target effects on guideline-directed medical therapy (GDMT) use., Methods and Results: The nationwide NUDGE-FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022-2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE-FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain-framed letter: p interaction  = 0.37; repeated letter: p interaction  = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (p interaction  = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain-framed letter (p interaction  = 0.07). The letters had no impact on longitudinal GDMT use., Conclusions: Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain-framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed., Clinical Trial Registration: ClinicalTrials.gov NCT05542004., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Annual influenza vaccination is widely recommended in older adults and other high-risk groups including patients with cardiovascular disease. The real-world effectiveness of influenza vaccination is limited by suboptimal uptake and effective strategies for increasing vaccination rates are therefore needed. The purpose of this trial is to investigate whether behavioral nudges digitally delivered via the Danish nationwide mandatory governmental electronic letter system can increase influenza vaccination uptake among older adults., Methods: The NUDGE-FLU trial is a randomized implementation trial randomizing all Danish citizens aged 65 years and above without an exemption from the Danish mandatory governmental electronic letter system to receive no digitally delivered behavioral nudge (usual care arm) or to receive one of 9 electronic letters (intervention arms) each leveraging different behavioral science strategies. The trial has randomized 964,870 participants with randomization clustered at the household level (n = 691,820 households). Intervention letters were delivered on September 16, 2022, and follow-up is currently ongoing. All trial data are captured using the nationwide Danish administrative health registries. The primary end point is the receipt of an influenza vaccine on or before January 1, 2023. The secondary end point is time to vaccination. Exploratory end points include clinical events such as hospitalization for influenza or pneumonia, cardiovascular events, all-cause hospitalization, and all-cause mortality., Discussion: The nationwide randomized NUDGE-FLU trial is one of the largest implementation trials ever conducted and will provide important insights into effective communication strategies to maximize vaccination uptake among high-risk groups., Trial Registration: Clinicaltrials.gov: NCT05542004, registered September 15, 2022, https://clinicaltrials.gov/ct2/show/NCT05542004., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: National Influenza Centers (NICs) have played a crucial role in the surveillance of SARS-CoV-2. The FluCov project, covering 22 countries, was initiated to monitor the impact of the SARS-CoV-2 pandemic on influenza activity., Methods: This project consisted of an epidemiological bulletin and NIC survey. The survey, designed to assess the impact of the pandemic on the influenza surveillance system, was shared with 36 NICs located across 22 countries. NICs were invited to reply between November 2021 and March 2022., Results: We received 18 responses from NICs in 14 countries. Most NICs (76%) indicated that the number of samples tested for influenza decreased. Yet, many NICs (60%) were able to increase their laboratory testing capacity and the "robustness" (e.g., number of sentinel sites) (59%) of their surveillance systems. In addition, sample sources (e.g., hospital or outpatient setting) shifted. All NICs reported a higher burden of work following the onset of the pandemic, with some NICs hiring additional staff or partial outsourcing to other institutes or departments. Many NICs anticipate the future integration of SARS-CoV-2 surveillance into the existing respiratory surveillance system., Discussion: The survey shows the profound impact of SARS-CoV-2 on national influenza surveillance in the first 27 months of the pandemic. Surveillance activities were temporarily disrupted, whilst priority was given to SARS-CoV-2. However, most NICs have shown rapid adaptive capacity underlining the importance of strong national influenza surveillance systems. These developments have the potential to benefit global respiratory surveillance in the years to come; however, questions about sustainability remain., Competing Interests: JP, MDR, SC, and LS declare that Nivel has previously received RSV research grants from Sanofi Pasteur/AstraZeneca, the Foundation for Influenza Epidemiology, and the European Union's Innovative Medicines Initiative. CEG, ED, and MA are Sanofi employees and may hold shares and/or stock options in the company. The other authors have no conflicts of interest to declare., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Influenza vaccines have been demonstrated to effectively reduce the incidence of influenza infection and potentially associated risks of cardiovascular events in patients with cardiovascular disease (CVD). Despite strong guideline and public health endorsements, global influenza vaccination rates in patients with CVD are highly variable. This prespecified analysis of NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) examined the effect of digital behavioral nudges on influenza vaccine uptake based on the presence of CVD., Methods: NUDGE-FLU was a randomized, pragmatic, nationwide, register-based trial that included Danish citizens 65 years of age or older during the 2022 to 2023 influenza season. Households were randomized in a 9:1:1:1:1:1:1:1:1:1 ratio to usual care or 9 electronic letters with designs based on behavioral concepts. Danish nationwide registers were used to collect baseline and outcome data. The primary end point was receipt of an influenza vaccine on or before January 1, 2023. The effects of the intervention letters were examined according to the presence of CVD and across cardiovascular subgroups that included heart failure, ischemic heart disease, and atrial fibrillation., Results: Of 964 870 NUDGE-FLU participants from 691 820 households, 264 392 (27.4%) had CVD. During follow-up, 83.1% of participants with CVD versus 79.2% of participants without CVD received an influenza vaccination ( P <0.001). Compared with usual care, a letter emphasizing the potential cardiovascular benefits of influenza vaccination increased vaccination rates; this effect was consistent in participants with CVD (absolute difference, +0.60 percentage points [99.55% CI, -0.48 to 1.68]) and without CVD (+0.98 percentage points [99.55% CI, 0.27-1.70; P for interaction=0.41). A repeated letter strategy with a reminder follow-up letter 14 days later was also effective in increasing influenza vaccination, irrespective of CVD (CVD: absolute difference, +0.80 percentage points [99.55% CI, -0.27 to 1.86]; no CVD: +0.67 percentage points [99.55% CI, -0.06 to 1.40]; P for interaction=0.77). Effectiveness of both nudging strategies was consistent across all major CVD subgroups. None of the other 7 nudging strategies were effective, regardless of CVD status., Conclusions: Electronic letter interventions emphasizing the potential cardiovascular benefits of influenza vaccination and using a reminder letter strategy were similarly beneficial in increasing influenza vaccination rates among older adults with and without CVD and across cardiovascular subgroups. Electronic nudges may improve influenza vaccine uptake in individuals with CVD., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT05542004.

Background: Influenza vaccination rates remain suboptimal despite effectiveness in preventing influenza infection and related complications. We investigated whether behavioural nudges, delivered via a governmental electronic letter system, would increase influenza vaccination uptake among older adults in Denmark., Methods: We did a nationwide, pragmatic, registry-based, cluster-randomised implementation trial during the 2022-23 influenza season in Denmark. All Danish citizens aged 65 years or older or turning 65 years by Jan 15, 2023 were included. We excluded individuals living in nursing homes and individuals who had an exemption from the Danish mandatory governmental electronic letter system. Households were randomly assigned (9:1:1:1:1:1:1:1:1:1) to usual care or nine different electronic letters designed on the basis of different behavioural nudging concepts. Data were sourced from nationwide Danish administrative health registries. The primary endpoint was receipt of influenza vaccination on or before Jan 1, 2023. The primary analysis assessed an analytical set of one randomly selected individual per household, and a sensitivity analysis included all randomly assigned individuals and accounted for within-household correlation. The trial is registered with ClinicalTrials.gov, NCT05542004., Findings: We identified 1 232 938 individuals aged 65 years or older in Denmark and excluded 56 436 (4·6%) individuals living in nursing homes and 211 632 (17·2%) with an exemption from the electronic letter system. We randomly assigned 964 870 (78·3%) participants across 691 820 households. Compared with usual care, influenza vaccination rates were higher in the group receiving an electronic letter highlighting potential cardiovascular benefits of vaccination (81·00% vs 80·12%; difference 0·89 percentage points [99·55% CI 0·29-1·48]; p<0·0001) and the group receiving repeated letters at randomisation and at day 14 (80·85% vs 80·12%; difference 0·73 percentage points [0·13-1·34]; p=0·0006). These strategies improved vaccination rates across major subgroups including those with and without established cardiovascular disease. The cardiovascular gain-framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season (p interaction =0·0002). A sensitivity analysis of all randomly assigned individuals accounting for within-household clustering yielded similar findings., Interpretation: Electronically delivered letters highlighting potential cardiovascular benefits of influenza vaccination or sent again as a reminder significantly increased vaccination uptake across Denmark. Although the magnitude of effectiveness was modest, the low-touch, inexpensive, and highly scalable nature of these electronic letters might be informative for future public health campaigns., Funding: Sanofi., Competing Interests: Declaration of interests MV has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; has speaker engagements with AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics; and participates on clinical trial committees for studies sponsored by AstraZeneca, Bayer AG, Galmed, Occlutech, Novartis, and Impulse Dynamics. ASB has received fees from Sanofi. SGL is supported by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI). BLC has received consulting fees from Amgen, Cardurion, Corvia, Myokardia, and Novartis. ELD, SIS, and MML are full-time employees of Sanofi and might own shares or have stock options in the company. LK has received speaker fees from Novo Nordisk, Novartis, AstraZeneca, Boehringer Ingelheim, and Bayer. SDS has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH and NHLBI, Neurotronik, Novartis, Novo Nordisk, Respicardia, Sanofi, Theracos, and US2.AI; and consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health. TB-S has served as a steering committee member of the Amgen financed GALACTIC-HF trial and the Boston Scientific financed LUX-Dx TRENDS trial; served on advisory boards for Sanofi, GSK, and Amgen; received speaker honoraria from Bayer, GSK, Novartis, and Sanofi; and received research grants from GE Healthcare and Sanofi. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Estimates of the burden of influenza are needed to inform prevention and control activities for seasonal influenza, including to support the development of appropriate vaccination policies. We used sentinel surveillance data on severe acute respiratory infection (SARI) to estimate the burden of influenza-associated hospitalizations in the Lao People's Democratic Republic., Methods: Using methods developed by the World Health Organization, we combined data from hospital logbook reviews with epidemiological and virological data from influenza surveillance from 1 January to 31 December 2016 in defined catchment areas for two sentinel sites (Champasack and Luang Prabang provincial hospitals) to derive population-based estimates of influenza-associated SARI hospitalization rates. Hospitalization rates by age group were then applied to national age-specific population estimates using 2015 census data., Results: We estimated the overall influenza-associated SARI hospitalization rate to be 48/100 000 population (95% confidence interval [CI]: 44-51) or 3097 admissions (95% CI: 2881-3313). SARI hospitalization rates were estimated to be as low as 40/100 000 population (95% CI: 37-43) and as high as 92/100 000 population (95% CI: 87-98) after accounting for SARI patient underascertainment in hospital logbooks. Influenza-associated SARI hospitalization rates were highest in children aged < 5 years (219; 95% CI: 198-241) and persons aged 3  65 years (106; 95% CI: 91-121)., Discussion: Our findings have identified age groups at higher risk for influenza-associated SARI hospitalization, which will support policy decisions for influenza prevention and control strategies, including for vaccination. Further work is needed to estimate the burdens of outpatient influenza and influenza in specific high-risk subpopulations., ((c) 2021 The authors; licensee World Health Organization.)

Background: Multiple case definitions are used to identify hospitalized patients with community-acquired acute respiratory infections (ARI). We evaluated several commonly used hospitalized ARI case definitions to identify influenza cases., Methods: The study included all patients from a population-based surveillance site in Damanhour, Egypt hospitalized for a broad set of criteria consistent with community acquired ARIs. Naso- and oropharyngeal (NP/OP) swabs were tested for influenza using RT-PCR. Sensitivity, specificity and PPV for influenza identification was compared between the 2014 WHO Severe Acute Respiratory Infection (SARI) definition (fever ≥38°C and cough with onset within 10 days), the 2011 WHO SARI definition (fever ≥38°C and cough with onset within 7 days), the 2006 PAHO SARI definition, the International Emerging Infections Program (IEIP) pneumonia case definition, and the International Management of Childhood Illness (IMCI) case definitions for moderate and severe pneumonia., Results: From June 2009-December 2012, 5768 NP/OP swabs were obtained from 6113 hospitalized ARI patients; 799 (13.9%) were influenza positive. The 2014 WHO SARI case definition captured the greatest number of ARI patients, influenza positive patients and ARI deaths compared to the other case definitions examined. Sensitivity for influenza detection was highest for the 2014 WHO SARI definition with 88.6%, compared to the 2011 WHO SARI (78.2%) the 2006 PAHO SARI (15.8%) the IEIP pneumonia (61.0%) and the IMCI moderate and severe pneumonia (33.8% and 38.9%) case definitions (IMCI applies to <5 only)., Conclusions: Our results support use of the 2014 WHO SARI definition for identifying influenza positive hospitalized SARI cases as it captures the highest proportion of ARI deaths and influenza positive cases. Routine use of this case definition for hospital-based surveillance will provide a solid, globally comparable foundation on which to build needed response efforts for novel pandemic viruses., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The burden of influenza in Cambodia is not well known, but it would be useful for understanding the impact of seasonal epidemics and pandemics and to design appropriate policies for influenza prevention and control. The severe acute respiratory infection (SARI) surveillance system in Cambodia was used to estimate the national burden of SARI hospitalizations in Cambodia., Methods: We estimated age-specific influenza-associated SARI hospitalization rates in three sentinel sites in Svay Rieng, Siem Reap and Kampong Cham provinces. We used influenza-associated SARI surveillance data for one year to estimate the numerator and hospital admission surveys to estimate the population denominator for each site. A national influenza-associated SARI hospitalization rate was calculated using the pooled influenza-associated SARI hospitalizations for all sites as a numerator and the pooled catchment population of all sites as denominator. National influenza-associated SARI case counts were estimated by applying hospitalization rates to the national population., Results: The national annual rates of influenza-associated hospitalizations per 100 000 population was highest for the two youngest age groups at 323 for < 1 year and 196 for 1-4 years. We estimated 7547 influenza-associated hospitalizations for Cambodia with almost half of these represented by children younger than 5 years., Discussion: We present national estimates of influenza-associated SARI hospitalization rates for Cambodia based on sentinel surveillance data from three sites. The results of this study indicate that the highest burden of severe influenza infection is borne by the younger age groups. These findings can be used to guide future strategies to reduce influenza morbidity., ((c) 2018 The authors; licensee World Health Organization.)

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.

Background: Understanding the burden of influenza-associated severe acute respiratory infection (SARI) is important for setting national influenza surveillance and vaccine priorities. Estimating influenza-associated SARI rates requires hospital-based surveillance data and a population-based denominator, which can be challenging to determine., Objectives: We present an application of the World Health Organization's recently developed manual (WHO Manual) including hospital admission survey (HAS) methods for estimating the burden of influenza-associated SARI, with lessons learned to help others calculate similar estimates., Methods: Using an existing SARI surveillance platform in Cambodia, we counted influenza-associated SARI cases during 2015 at one sentinel surveillance site in Svay Rieng Province. We applied WHO Manual-derived methods to count respiratory hospitalizations at all hospitals within the catchment area, where 95% of the sentinel site case-patients resided. We used HAS methods to adjust the district-level population denominator for the sentinel site and calculated the incidence rate of influenza-associated SARI by dividing the number of influenza-positive SARI infections by the adjusted population denominator and multiplying by 100 000. We extrapolated the rate to the provincial population to derive a case count for 2015. We evaluated data sources, detailed steps of implementation, and identified lessons learned., Results: We estimated an adjusted influenza-associated 2015 SARI rate of 13.5/100 000 persons for the catchment area of Svay Rieng Hospital and 77 influenza-associated SARI cases in Svay Rieng Province after extrapolation., Conclusions: Methods detailed in the WHO Manual and operationalized successfully in Cambodia can be used in other settings to estimate rates of influenza-associated SARI., (© 2018 The Authors. Influenza and Other Respiratory Viruses. Published by John Wiley & Sons Ltd.)

Background: Influenza vaccination is recommended by the World Health Organization for high risk groups, yet few data exist on influenza disease burden in West Africa., Methods: We estimated medically attended influenza-associated illness rates among residents of Shai-Osudoku and Ningo Pram-Pram Districts (SONPD), Ghana. From May 2013 to April 2015, we conducted prospective surveillance for severe acute respiratory illness (SARI) and influenza-like illness (ILI) in 17 health facilities. In 2015, we conducted a retrospective assessment at an additional 18 health facilities to capture all SONPD SARI and ILI patients during the study period. We applied positivity rates to those not tested to estimate total influenza cases., Results: Of 612 SARI patients tested, 58 (9%) were positive for influenza. The estimated incidence of influenza-associated SARI was 30 per 100,000 persons (95% CI: 13-84). Children aged 0 to 4 years had the highest influenza-associated SARI incidence (135 per 100,000 persons, 95% CI: 120-152) and adults aged 25 to 44 years had the lowest (3 per 100,000 persons, 95% CI: 1-7) (p < 0.01). Of 2,322 ILI patients tested, 407 (18%) were positive for influenza. The estimated incidence of influenza-associated ILI was 844 per 100,000 persons (95% CI: 501-1,099). The highest incidence of influenza-associated ILI was also among children aged 0 to 4 years (3,448 per 100,000 persons, 95% CI: 3,727 - 3,898). The predominant circulating subtype during May to December 2013 and January to April 2015 was influenza A(H3N2) virus, and during 2014 influenza B virus was the predominant circulating type., Conclusions: Influenza accounted for 9% and 18% of medically attended SARI and ILI, respectively. Rates were substantive among young children and suggest the potential value of exploring the benefits of influenza vaccination in Ghana, particularly in this age group.

Background: Influenza epidemiology in Africa is generally not well understood. Using syndrome definitions to screen patients for laboratory confirmation of infection is an established means to effectively conduct influenza surveillance., Methods: To compare influenza-related epidemiologic data, from October 2010 through March 2013, we enrolled hospitalized severe acute respiratory infection (SARI; fever with respiratory symptoms) and acute febrile illness (AFI; fever without respiratory or other localizing symptoms) patients from three referral hospitals in Ghana. Demographic and epidemiologic data were obtained from enrolled patients after which nasopharyngeal and oropharyngeal swabs were collected, and processed by molecular methods for the presence of influenza viruses., Results: Of 730 SARI patients, 59 (8%) were influenza positive; of 543 AFI patients, 34 (6%) were positive for influenza. Both SARI and AFI surveillance yielded influenza A(H3N2) (3% versus 1%), A(H1N1)pdm09 (2% versus 1%), and influenza B (3% versus 4%) in similar proportions. Data from both syndromes show year-round influenza transmission but with increased caseloads associated with the rainy seasons., Conclusions: As an appreciable percentage of influenza cases (37%) presented without defined respiratory symptoms, and thus met the AFI but not the SARI definition, it is important to consider broader screening criteria (i.e., AFI) to identify all laboratory-confirmed influenza. The identified influenza transmission seasonality has important implications for the timing of related public health interventions., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: Acute respiratory infections (ARIs) are a major cause of morbidity and mortality worldwide. Influenza typically contributes substantially to the burden of ARI, but only limited data are available on influenza activity and seasonality in Jordan., Methods: Syndromic case definitions were used to identify individuals with severe acute respiratory infections (SARI) admitted to four sentinel hospitals in Jordan. Demographic and clinical data were collected. Nasopharyngeal and oropharyngeal swabs were tested for influenza using real-time reverse transcription polymerase chain reaction and typed as influenza A or B, with influenza A further subtyped., Results: From January 2008-February 2014, 2891 SARI cases were tested for influenza, and 257 (9%) were positive. While 73% of all SARI cases were under 5 years of age, only 57% of influenza-positive cases were under 5 years of age. Eight (3%) influenza-positive cases died. An annual seasonal pattern of influenza activity was observed. The proportion of influenza-positive cases peaked during November-January (14-42%) in the non-pandemic years., Conclusions: Influenza is associated with substantial morbidity and mortality in Jordan. The seasonal pattern of influenza aligns with known Northern Hemisphere seasonality. Further characterization of the clinical and financial burden of influenza in Jordan will be critical in supporting decisions regarding disease control activities., (© 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Introduction: Acute respiratory infections (ARI), including influenza, comprise a leading cause of morbidity and mortality worldwide. Influenza surveillance provides important information to inform policy on influenza control and vaccination. While the epidemiology of influenza has been well characterized in western countries, few data exist on influenza epidemiology in the Eastern Mediterranean Region. We describe the epidemiology of influenza virus in Oman., Methods: Using syndromic case definitions and protocols, patients from four regional hospitals in Oman were enrolled in a descriptive prospective study to characterize the burden of severe acute respiratory infections (SARI) and influenza. Eligible patients provided demographic information as well as oropharyngeal (OP) and nasopharyngeal (NP) swabs. Specimens were tested for influenza A and influenza B; influenza A viruses were subtyped using RT-PCR., Results: From January 2008 through June 2013, a total of 5,147 cases were enrolled and tested for influenza. Influenza strains were detected in 8% of cases for whom samples were available. Annual incidence rates ranged from 0.5 to 15.4 cases of influenza-associated SARI per 100,000 population. The median age of influenza patients was 6 years with children 0-2 years accounting for 34% of all influenza-associated hospitalizations. By contrast, the median age of non-influenza SARI cases was 1 year with children 0-2 years comprising 59% of SARI. Compared to non-influenza SARI cases, a greater proportion of influenza cases had pre-existing chronic conditions and underwent ventilation during hospitalization., Conclusions: Influenza virus is associated with a substantial proportion of SARI in Oman. Influenza in Oman approximately follows northern hemisphere seasonality, with major peaks in October to December and a lesser peak around April. The burden of influenza was greatest in children and the elderly. Future efforts should examine the burden of influenza in other potential risk groups such as pregnant women to inform interventions including targeted vaccination.

Vaccination uptake of pregnant women in Morocco during the A (H1N1) pdm09 pandemic was lower than expected. A qualitative study using open-ended questions was developed to explore the main determinants of acceptance and non-acceptance of the monovalent A (H1N1) pdm09 vaccine among pregnant women in Morocco and to identify information sources that influenced their decision-making process. The study sample included 123 vaccinated and unvaccinated pregnant women who were in their second or third trimester between December 2009 and March 2010. They took part in 14 focus group discussions and eight in-depth interviews in the districts of Casablanca and Kenitra. Thematic qualitative analysis identified reasons for vaccine non-acceptance: (1) fear of the monovalent A (H1N1) pdm09 vaccine, (2) belief in an A (H1N1) pdm09 pandemic conspiracy, (3) belief in the inapplicability of the monovalent A (H1N1) pdm09 vaccine to Moroccans, (4) lack of knowledge of the monovalent A (H1N1) pdm09 vaccine, and (5) challenges of vaccination services/logistics. Reasons for vaccine acceptance included: (1) perceived benefits and (2) modeling. Decision-making was strongly influenced by family, community, mass media, religious leaders and health providers suggesting that broad communication efforts should also be used to advocate for vaccination. Meaningful communication for future vaccine campaigns must consider these context-specific findings. As cultural and religious values are shared across many Arab countries, these findings may also provide valuable insights for seasonal influenza vaccine planning in the Middle East and North Africa region at large.

Background: At the onset of an influenza pandemic, when the severity of a novel strain is still undetermined and there is a threat of introduction into a new environment, e.g., via the deployment of military troops, sensitive screening criteria and conservative isolation practices are generally recommended., Objectives: In response to elevated rates of influenza-like illness among U.S. military base camps in Kuwait, U.S. Naval Medical Research Unit No. 3 partnered with local U.S. Army medical units to conduct an A(H1N1) pdm09 outbreak investigation., Patients/methods: Initial clinical data and nasal specimens were collected via the existent passive surveillance system and active surveillance was conducted using a modified version of the World Health Organization/U.S. Centers for Disease Control and Prevention influenza-like illness case definition [fever (T > 100.5˚F/38˚C) in addition to cough and/or sore throat in the previous 72 hours] as the screening criteria. Samples were tested via real-time reverse-transcription PCR and sequenced for comparison to global A(H1N1) pdm09 viruses from the same time period., Results: The screening criteria used in Kuwait proved insensitive, capturing only 16% of A(H1N1) pdm09-positive individuals. While still not ideal, using cough as the sole screening criteria would have increased sensitivity to 73%., Conclusions: The results of and lessons learned from this outbreak investigation suggest that pandemic influenza risk management should be a dynamic process (as information becomes available regarding true attack rates and associated mortality, screening and isolation criteria should be re-evaluated and revised as appropriate), and that military operational environments present unique challenges to influenza surveillance.

To understand 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) circulation in West Africa, we collected influenza surveillance data from ministries of health and influenza laboratories in 10 countries, including Cameroon, from 4 May 2009 through 3 April 2010. A total of 10,203 respiratory specimens were tested, of which 25% were positive for influenza virus. Until the end of December 2009, only 14% of all detected strains were A(H1N1)pdm09, but the frequency increased to 89% from January through 3 April 2010. Five West African countries did not report their first A(H1N1)pdm09 case until 6 months after the emergence of the pandemic in North America, in April 2009. The time from first detection of A(H1N1)pdm09 in a country to the time of A(H1N1)pdm09 predominance varied from 0 to 37 weeks. Seven countries did not report A(H1N1)pdm09 predominance until 2010. Introduction and transmission of A(H1N1)pdm09 were delayed in this region.

Background: In response to the potential threat of an influenza pandemic, several international institutions and governments, in partnership with African countries, invested in the development of epidemiologic and laboratory influenza surveillance capacity in Africa and the African Network of Influenza Surveillance and Epidemiology (ANISE) was formed., Methods: We used a standardized form to collect information on influenza surveillance system characteristics, the number and percent of influenza-positive patients with influenza-like illness (ILI), or severe acute respiratory infection (SARI) and virologic data from countries participating in ANISE., Results: Between 2006 and 2010, the number of ILI and SARI sites in 15 African countries increased from 21 to 127 and from 2 to 98, respectively. Children 0-4 years accounted for 48% of all ILI and SARI cases of which 22% and 10%, respectively, were positive for influenza. Influenza peaks were generally discernible in North and South Africa. Substantial cocirculation of influenza A and B occurred most years., Conclusions: Influenza is a major cause of respiratory illness in Africa, especially in children. Further strengthening influenza surveillance, along with conducting special studies on influenza burden, cost of illness, and role of other respiratory pathogens will help detect novel influenza viruses and inform and develop targeted influenza prevention policy decisions in the region.

Background: The global burden of disease attributable to seasonal influenza virus in children is unknown. We aimed to estimate the global incidence of and mortality from lower respiratory infections associated with influenza in children younger than 5 years., Methods: We estimated the incidence of influenza episodes, influenza-associated acute lower respiratory infections (ALRI), and influenza-associated severe ALRI in children younger than 5 years, stratified by age, with data from a systematic review of studies published between Jan 1, 1995, and Oct 31, 2010, and 16 unpublished population-based studies. We applied these incidence estimates to global population estimates for 2008 to calculate estimates for that year. We estimated possible bounds for influenza-associated ALRI mortality by combining incidence estimates with case fatality ratios from hospital-based reports and identifying studies with population-based data for influenza seasonality and monthly ALRI mortality., Findings: We identified 43 suitable studies, with data for around 8 million children. We estimated that, in 2008, 90 million (95% CI 49-162 million) new cases of influenza (data from nine studies), 20 million (13-32 million) cases of influenza-associated ALRI (13% of all cases of paediatric ALRI; data from six studies), and 1 million (1-2 million) cases of influenza-associated severe ALRI (7% of cases of all severe paediatric ALRI; data from 39 studies) occurred worldwide in children younger than 5 years. We estimated there were 28,000-111,500 deaths in children younger than 5 years attributable to influenza-associated ALRI in 2008, with 99% of these deaths occurring in developing countries. Incidence and mortality varied substantially from year to year in any one setting., Interpretation: Influenza is a common pathogen identified in children with ALRI and results in a substantial burden on health services worldwide. Sufficient data to precisely estimate the role of influenza in childhood mortality from ALRI are not available., Funding: WHO; Bill & Melinda Gates Foundation., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

To evaluate the effectiveness of an intensive hand hygiene campaign on reducing absenteeism caused by influenza-like illness (ILI), diarrhea, conjunctivitis, and laboratory-confirmed influenza, we conducted a randomized control trial in 60 elementary schools in Cairo, Egypt. Children in the intervention schools were required to wash hands twice each day, and health messages were provided through entertainment activities. Data were collected on student absenteeism and reasons for illness. School nurses collected nasal swabs from students with ILI, which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group, in the intervention group, overall absences caused by ILI, diarrhea, conjunctivitis, and laboratory-confirmed influenza were reduced by 40%, 30%, 67%, and 50%, respectively (p<0.0001 for each illness). An intensive hand hygiene campaign was effective in reducing absenteeism caused by these illnesses.