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Social outings can trigger influenza transmission, especially in children and elderly. In contrast, school closures are associated with reduced influenza incidence in school-aged children. While influenza surveillance modelling studies typically account for holidays and mass gatherings, age-specific effects of school breaks, sporting events and commonly celebrated observances are not fully explored. We examined the impact of school holidays, social events and religious observances for six age groups (all ages, ⩽4, 5–24, 25–44, 45–64, ⩾65 years) on four influenza outcomes (tests, positives, influenza A and influenza B) as reported by the City of Milwaukee Health Department Laboratory, Milwaukee, Wisconsin from 2004 to 2009. We characterised holiday effects by analysing average weekly counts in negative binomial regression models controlling for weather and seasonal incidence fluctuations. We estimated age-specific annual peak timing and compared influenza outcomes before, during and after school breaks. During the 118 university holiday weeks, average weekly tests were lower than in 140 school term weeks (5.93 vs. 11.99 cases/week, P < 0.005). The dampening of tests during Winter Break was evident in all ages and in those 5–24 years (RR = 0.31; 95% CI 0.22–0.41 vs. RR = 0.14; 95% CI 0.09–0.22, respectively). A significant increase in tests was observed during Spring Break in 45–64 years old adults (RR = 2.12; 95% CI 1.14–3.96). Milwaukee Public Schools holiday breaks showed similar amplification and dampening effects. Overall, calendar effects depend on the proximity and alignment of an individual holiday to age-specific and influenza outcome-specific peak timing. Better quantification of individual holiday effects, tailored to specific age groups, should improve influenza prevention measures.
We conducted probabilistic data linkage of three population datasets for the Northern Territory (NT), Australia, to describe the incidence of preterm births, stillbirths, low birthweight and small for gestational age (SGA) per 1000 NT births; and influenza and pertussis hospitalisations per 1 00 000 NT births in infants <7 months of age, in a pre-maternal vaccination era. The Perinatal Trends dataset (1994–2014) formed the cohort of 78 382 births. Aboriginal mother–infant pairs (37%) had disproportionately higher average annual rates (AR) for all adverse birth outcomes compared to their non-Aboriginal counterparts; rate ratios: preterm births 2.2 (AR 142.4 vs. 64.7); stillbirths 2.3 (AR 10.8 vs. 4.6); low birthweight 2.9 (AR 54 vs. 19); and SGA 1.7 (AR 187 vs. 111). Hospitalisation (2000–2015) and Immunisation Register datasets (1994–2015), showed that influenza hospitalisations (n = 53) and rates were 42.3 times higher in Aboriginal infants (AR 254 vs. 6); and that pertussis hospitalisations (n = 37) were 7.1 times higher in Aboriginal infants (AR 142.5 vs. 20.2) compared to non-Aboriginal infants. These baseline data are essential to assess the safety and effectiveness of influenza and pertussis vaccinations in pregnant women from the NT. Remote living Aboriginal women and infants stand to benefit the most from these vaccines.
Several studies have reported evidence of interference between respiratory viruses: respiratory viruses rarely reach their epidemic peak concurrently and there appears to be a negative association between infection with one respiratory virus and co-infection with another. We used results spanning 16 years (2002–2017) of a routine diagnostic multiplex panel that tests for nine respiratory viruses to further investigate these interactions in Victoria, Australia. Time series analyses were used to plot the proportion positive for each virus. The seasonality of all viruses included was compared with respiratory syncytial virus (RSV) and influenza A virus using cross-correlations. Logistic regression was used to explore the likelihood of co-infection with one virus given infection with another. Seasonal peaks were observed each year for influenza A and RSV and less frequently for influenza B, coronavirus and parainfluenza virus. RSV circulated an average of 6 weeks before influenza A. Co-infection with another respiratory virus was less common with picornavirus, RSV or influenza A infection. Our findings provide further evidence of a temporal relationship in the circulation of respiratory viruses. A greater understanding of the interaction between respiratory viruses may enable better prediction of the timing and magnitude of respiratory virus epidemics.
Artificial intelligence (AI) is reaching into every aspect of global health. In this essay, I examine one example of AI's potential contributions and limitations in global health: the prediction, treatment, and containment of a global influenza outbreak. The potential advantages are clear. AI can aid global influenza surveillance platforms by improving the capacity of organizations to look for novel influenza outbreak strains in the right places, to identify populations most likely to spread influenza, and to produce real-time information about the disease's spread by monitoring social media communications to track outbreak events. There are also very real limitations to what AI can do, and it is crucial that AI not be used as an excuse not to invest in strengthening health systems and other traditional components of global healthcare. AI may also be able to improve our understanding of who should receive a vaccine and what is most effective for large-scale vaccine delivery, but there will always be blind spots that the data cannot fill. Investment in healthcare, with attention to the danger of minimal access to care for minority groups that are at risk and in fragile situations, remains the best chance to prepare communities for outbreak detection, surveillance, and containment.
England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case–control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2–16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015–2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3–54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3–63.6) and 28.8% (95% CI −31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015–2016 and continues to support the rollout of the LAIV childhood programme.
The disease caused by the influenza virus is a global public health problem due to its high rates of morbidity and mortality. Thus, analysis of the information generated by epidemiological surveillance systems has vital importance for health decision making. A retrospective analysis was performed using data generated by the four molecular diagnostic laboratories of the Mexican Social Security Institute between 2010 and 2016. Demographics, influenza positivity, seasonality, treatment choices and vaccination status analyses were performed for the vaccine according to its composition for each season. In all cases, both the different influenza subtypes and different age groups were considered separately. The circulation of A/H1N1pdm09 (48.7%), influenza A/H3N2 (21.1%), influenza B (12.6%), influenza A not subtyped (11%) and influenza A/H1N1 (6.6%) exhibited well-defined annual seasonality between November and March, and there were significant increases in the number of cases every 2 years. An inadequate use of oseltamivir was determined in 38% of cases, and the vaccination status in general varied between 12.1 and 18.5% depending on the season. Our results provide current information about influenza in Mexico and demonstrate the need to update both operational case definitions and medical practice guidelines to reduce the inappropriate use of antibiotics and antivirals.
Introduction: Influenza is a preventable infectious disease that causes a yearly burden to Canada. While an influenza vaccine is available free of charge in most provinces, uptake is below target rates. 15% of Canadians who did not get the influenza vaccine reported that they “didn't get around to it”; this presents an opportunity to combine the task of influenza prevention with the logistical issue of another health system challenge: escalating emergency department (ED) wait times. At the Queen Elizabeth II Health Sciences Centre (QEII) in Halifax, NS, average wait time is 4.6 hours. Offering the influenza vaccine during this time could increase convenient access to health services, and ultimately, improve vaccination rates. Methods: This observational, cross-sectional design study is currently in progress. It aims to gauge public interest, health care provider (HCP) support, perceived barriers and perceived facilitators to influenza vaccine availability at the QEII ED. Data is being collected via short, anonymous, close-ended questionnaires over a 7-week period, set to end Dec 14, 2018. Client participants are a convenience sample of low-acuity (Canadian Triage and Acuity Scale score 4/5), adult clients who use the QEII ED during the study period, anticipated n = 150. Client questionnaires are completed, with the help of a research assistant, on an iPad that inputs data directly into a secure online data collection tool. The HCP group is a convenience sample of nurses, physicians and paramedics currently working in the QEII ED, anticipated n = 80. Questionnaires are available to HCPs either on paper outside the staff lounge, or online. Data is being collected via short, anonymous, close-ended questionnaires over a 7-week period, set to end Dec 14, 2018. Client participants are a convenience sample of low-acuity (Canadian Triage and Acuity Scale score 4/5), adult clients who use the QEII ED during the study period, anticipated n = 150. Client questionnaires are completed, with the help of a research assistant, on an iPad that inputs data directly into a secure online data collection tool. The HCP group is a convenience sample of nurses, physicians and paramedics currently working in the QEII ED, anticipated n = 80. Questionnaires are available to HCPs either on paper outside the staff lounge, or online. Results: Following completion of data collection, descriptive statistics, such as the frequency of support for ED influenza vaccination and the proportion of unvaccinated clients willing to receive the vaccine if available in the ED, will be calculated using IBM SPSS Statistics 25. This will provide meaningful data that can be used by the QEII to inform future program planning (i.e. should the influenza vaccine be made available in the ED). Conclusion: An ED vaccination program could add value to the hours clients spend waiting to be seen, and make ED care more cohesive. It is essential that clients and ED staff are approached prior to any new initiative; this study is one way we can lay the necessary groundwork for a public health program that would utilize patient “wait time” more effectively.
Research on the drivers of vaccine acceptance has expanded but most interventions fall short of coverage targets. We explored whether vaccine uptake is driven directly or indirectly by disgust with attitudes towards vaccines acting as a possible mediator. An online cross-sectional study of 1007 adults of the USA via Amazon's Mechanical Turk was conducted in January 2017. The questionnaire consisted of four sections: (1) items assessing attitudes towards vaccines and vaccine uptake, (2) revised Disgust Scale (DS-R) to measure Disgust Sensitivity, (3) Perceived Vulnerability to Disease scale (PVD) to measure Germ Aversion and Perceived Susceptibility, and (4) socio-demographic information. Using mediation analysis, we assess the direct, the indirect (through Vaccine Attitudes) and the total effect of Disgust Sensitivity, Germ Aversion and Perceived Susceptibility on 2016 self-reported flu vaccine uptake. Mediation analysis showed the effect of Disgust Sensitivity and Germ Aversion on vaccine uptake to be twofold: a direct positive effect on vaccine uptake and an indirect negative effect through Vaccine Attitudes. In contrast, Perceived Susceptibility was found to have only a direct positive effect on vaccine uptake. Nonetheless, these effects were attenuated and small compared to economic, logistic and psychological determinants of vaccine uptake.
Influenza and respiratory syncytial virus (RSV) are common causes of respiratory tract infections and place a burden on health services each winter. Systems to describe the timing and intensity of such activity will improve the public health response and deployment of interventions to these pressures. Here we develop early warning and activity intensity thresholds for monitoring influenza and RSV using two novel data sources: general practitioner out-of-hours consultations (GP OOH) and telehealth calls (NHS 111). Moving Epidemic Method (MEM) thresholds were developed for winter 2017–2018. The NHS 111 cold/flu threshold was breached several weeks in advance of other systems. The NHS 111 RSV epidemic threshold was breached in week 41, in advance of RSV laboratory reporting. Combining the use of MEM thresholds with daily monitoring of NHS 111 and GP OOH syndromic surveillance systems provides the potential to alert to threshold breaches in real-time. An advantage of using thresholds across different health systems is the ability to capture a range of healthcare-seeking behaviour, which may reflect differences in disease severity. This study also provides a quantifiable measure of seasonal RSV activity, which contributes to our understanding of RSV activity in advance of the potential introduction of new RSV vaccines.
Increased social contact within school settings is thought to be an important factor in seasonal outbreaks of acute respiratory infection (ARI). To better understand the degree of impact, we analysed electronic health records and compared risks of respiratory infections within communities while schools were in session and out-of-session. A time series analysis of weekly respiratory infection diagnoses from 28 family medicine clinics in Wisconsin showed that people under the age of 65 experienced an increased risk of ARI when schools were in session. For children aged 5–17 years, the risk ratio for the first week of a school session was 1.12 (95% confidence interval (CI) 0.93–1.34), the second week of a session was 1.39 (95% CI 1.15–1.68) and more than 2 weeks into a session was 1.43 (95% CI 1.20–1.71). Less significant increased risk ratios were also observed in young children (0–4 years) and adults (18–64 years). These results were obtained after modelling for baseline seasonal variations in disease prevalence and controlling for short-term changes in ambient temperature and relative humidity. Understanding the mechanisms of seasonality make it easier to predict outbreaks and launch timely public health interventions.
A well-known feature of the great H1N1 influenza pandemic of a century ago is that the highest mortality rate was amongst young adults. The general explanation has been that they died from an over-reaction of their active immune systems. This explanation has never been very satisfactory because teenagers also have very active immune systems. Recent virological research provides a new perspective, which is important for life and health insurers. There is now strong recent scientific evidence for the principle of antigenic imprinting, where the highest antibody response is against influenza virus strains from childhood. The peak ages of 1918 pandemic mortality correspond to a cohort exposed to the H3N8 1889–1890 Russian influenza pandemic. The vulnerability of an individual depends crucially on his or her exposure to influenza during their lifetime, especially childhood. Date of birth is thus a key indicator of pandemic vulnerability. An analysis of the implications is presented, with focus on those now in their fifties, who were exposed to the H3N2 1968 Hong Kong influenza.
Low vaccine-effectiveness has been recognised as a key factor undermining efforts to improve strategies and uptake of seasonal influenza vaccination. Aiming to prevent disease transmission, vaccination may influence the perceived risk-of-infection and, therefore, alter the individual-level behavioural responses, such as the avoidance of contact with infectious cases. We asked how the avoidance behaviour of vaccinated individuals changes disease dynamics, and specifically the epidemic size, in the context of imperfect vaccination. For this purpose, we developed an agent-based simulation model, and parameterised it with published estimates and relevant databases for population demographics and agent characteristics. Encapsulating an age-stratified structure, we evaluated the per-contact risk-of-infection and estimated the epidemic size. Our results show that vaccination could lead to a larger epidemic size if the level of avoidance behaviour in vaccinated individuals reduces below that of susceptible individuals. Furthermore, the risk-of-infection in vaccinated individuals, which follows the pattern of age-dependent frailty index of the population, increases for older age groups, and may reach, or even exceed, the risk-of-infection in susceptible individuals. Our findings indicate that low engagement in avoidance behaviour can potentially offset the benefits of vaccination even for vaccines with high effectiveness. While highlighting the protective effects of vaccination, seasonal influenza immunisation programmes should enhance strategies to promote avoidance behaviour despite being vaccinated.
In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.
Purulent pericarditis occurs rarely in the current antibiotic era. We describe clinical and echocardiographic features of purulent pericarditis in a previously healthy child with influenza and community-acquired methicillin-resistant Staphylococcus aureus co-infection. The child was already on appropriate antibiotics and had a very subtle clinical presentation, with prominent abdominal symptoms. Timely surgical drainage led to complete recovery.
Febrile seizure (FS) in children is a common complication of infections with respiratory viruses and hand, foot and mouth disease (HFMD). We conducted a retrospective ecological time-series analysis to determine the temporal relationship between hospital attendances for FS and HFMD or respiratory virus infections. Epilepsy attendance was used as a control. Data from 2004 to 2012 FS and epilepsy hospital attendance, HFMD notifications to the Ministry of Health and from laboratory-confirmed viral respiratory infections among KK Women's and Children's Hospital inpatients were used. A multivariate linear regression analysis was conducted to evaluate the relationship between FS and the virus time series. Relative risks of FS by age were calculated using Bayesian statistical methods. Paediatric accident and emergency (A&E) attendances for FS were found to be associated with influenza A (extra 0.47 FS per influenza A case), B (extra 0.32 per influenza B case) and parainfluenza 3 (extra 0.35 per parainfluenza type 3 case). However, other viruses were not significantly associated with FS. None of the viruses were associated with epileptic seizure attendance. Influenza A, B and parainfluenza 3 viruses contributed to the burden of FS resulting in A&E attendance. Children at risk of FS should be advised to receive seasonal influenza vaccination.
Knowing the burden of influenza is helpful for policy decisions. Here we estimated the contribution of influenza-like illness (ILI) visits associated with laboratory-confirmed influenza among all clinic visits in a Senegal sentinel network. ILI data from ten sentinel sites were collected from January 2013 to December 2015. ILI was defined as an axillary measured fever of more than 37.5 °C with a cough or a sore throat. Collected nasopharyngeal swabs were tested for influenza viruses by rRT-PCR. Influenza-associated ILI was defined as ILI with laboratory-confirmed influenza. For the influenza disease burden estimation, we used all-case outpatient visits during the study period who sought care at selected sites. Of 4030 ILI outpatients tested, 1022 were influenza positive. The estimated proportional contribution of influenza-associated ILI was, per 100 outpatients, 1.2 (95% CI 1.1–1.3), 0.32 (95% CI 0.28–0.35), 1.11 (95% CI 1.05–1.16) during 2013, 2014, 2015, respectively. The age-specific outpatient visits proportions of influenza-associated ILI were higher among children under 5 years (0.68%, 95% CI: 0.62–0.70). The predominant virus during years 2013 and 2015 was influenza B while A/H3N2 subtype was predominant during 2014. Influenza viruses cause a substantial burden of outpatient visits particularly among children under 5 of age in Senegal and highlight the need of vaccination in risk groups.
Knowledge about the infection transmission routes is significant for developing effective intervention strategies. We searched the PubMed databases and identified 10 studies with 14 possible inflight influenza A(H1N1)pdm09 outbreaks. Considering the different mechanisms of the large-droplet and airborne routes, a meta-analysis of the outbreak data was carried out to study the difference in attack rates for passengers within and beyond two rows of the index case(s). We also explored the relationship between the attack rates and the flight duration and/or total infectivity of the index case(s). The risk ratios for passengers seated within and beyond the two rows of the index cases were 1.7 (95% confidence interval (CI) 0.98–2.84) for syndromic secondary cases and 4.3 (95% CI 1.25–14.54) for laboratory-confirmed secondary cases. Furthermore, with an increase of the product of the flight duration and the total infectivity of the index cases, the overall attack rate increased linearly. The study indicates that influenza A(H1N1)pdm09 may mainly be transmitted via the airborne route during air travel. A standardised approach for the reporting of such inflight outbreak investigations would help to provide more convincing evidence for such inflight transmission events.
The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015–2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015–2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015–2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.
Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014–2015 and 2015–2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0–2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2–0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2–1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0–2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.
Retrospective data evaluated increases in advanced medical support for children with medically attended acute respiratory illness (MAARI) during influenza outbreak periods (IOP). Advanced support included hospitalisation, intensive care unit admission, or mechanical ventilation, for children aged 0–17 years hospitalised in Maryland's 50 acute-care hospitals over 12 influenza seasons. Weekly numbers of positive influenza tests in the Maryland area defined IOP for each season as the fewest consecutive weeks, including the peak week containing at least 85% of positive tests with a 2-week buffer on either side of the IOP. Peak IOP (PIOP) was defined as four consecutive weeks containing the peak week with the most number of positive influenza tests. Off-PIOP was defined as the ‘shoulder’ weeks during each IOP. Non-influenza season (NIS) was the remaining weeks of that study season. Rate ratios of mean daily MAARI-related admissions resulting in advanced medical support outcomes during PIOP or Off-PIOP were compared with the NIS and were significantly elevated for all 12 study seasons combined. The results suggest that influenza outbreaks are associated with increased advanced medical support utilisation by children with MAARI. We feel that this data may help preparedness for severe influenza epidemics or pandemic.