An integrated system of air sampling and simultaneous enrichment for rapid biosensing of airborne coronavirus and influenza virus.

Point-of-care risk assessment (PCRA) for airborne viruses requires a system that can enrich low-concentration airborne viruses dispersed in field environments into a small volume of liquid. In this study, airborne virus particles were collected to a degree above the limit of detection (LOD) for a real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). This study employed an electrostatic air sampler to capture aerosolized test viruses (human coronavirus 229E (HCoV-229E), influenza A virus subtype H1N1 (A/H1N1), and influenza A virus subtype H3N2 (A/H3N2)) in a continuously flowing liquid (aerosol-to-hydrosol (ATH) enrichment) and a concanavalin A (ConA)-coated magnetic particles (CMPs)-installed fluidic channel for simultaneous hydrosol-to-hydrosol (HTH) enrichment. The air sampler's ATH enrichment capacity (EC) was evaluated using the aerosol counting method. In contrast, the HTH EC for the ATH-collected sample was evaluated using transmission-electron-microscopy (TEM)-based image analysis and real-time qRT-PCR assay. For example, the ATH EC for HCoV-229E was up to 67,000, resulting in a viral concentration of 0.08 PFU/mL (in a liquid sample) for a viral epidemic scenario of 1.2 PFU/m3 (in air). The real-time qRT-PCR assay result for this liquid sample was "non-detectable" however, subsequent HTH enrichment for 10 min caused the "non-detectable" sample to become "detectable" (cycle threshold (CT) value of 33.8 ± 0.06).

Update: Influenza Activity in the United States During the 2018-19 Season and Composition of the 2019-20 Influenza Vaccine.

Influenza activity* in the United States during the 2018-19 season (September 30, 2018-May 18, 2019) was of moderate severity (1). Nationally, influenza-like illness (ILI)† activity began increasing in November, peaked during mid-February, and returned to below baseline in mid-April; the season lasted 21 weeks,§ making it the longest season in 10 years. Illness attributed to influenza A viruses predominated, with very little influenza B activity. Two waves of influenza A were notable during this extended season: influenza A(H1N1)pdm09 viruses from October 2018 to mid-February 2019 and influenza A(H3N2) viruses from February through May 2019. Compared with the 2017-18 influenza season, rates of hospitalization this season were lower for adults, but were similar for children. Although influenza activity is currently below surveillance baselines, testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round. Receiving a seasonal influenza vaccine each year remains the best way to protect against seasonal influenza and its potentially severe consequences.

EpiRank: Modeling Bidirectional Disease Spread in Asymmetric Commuting Networks.

Commuting network flows are generally asymmetrical, with commuting behaviors bi-directionally balanced between home and work locations, and with weekday commutes providing many opportunities for the spread of infectious diseases via direct and indirect physical contact. The authors use a Markov chain model and PageRank-like algorithm to construct a novel algorithm called EpiRank to measure infection risk in a spatially confined commuting network on Taiwan island. Data from the country's 2000 census were used to map epidemic risk distribution as a commuting network function. A daytime parameter was used to integrate forward and backward movement in order to analyze daily commuting patterns. EpiRank algorithm results were tested by comparing calculations with actual disease distributions for the 2009 H1N1 influenza outbreak and enterovirus cases between 2000 and 2008. Results suggest that the bidirectional movement model outperformed models that considered forward or backward direction only in terms of capturing spatial epidemic risk distribution. EpiRank also outperformed models based on network indexes such as PageRank and HITS. According to a sensitivity analysis of the daytime parameter, the backward movement effect is more important than the forward movement effect for understanding a commuting network's disease diffusion structure. Our evidence supports the use of EpiRank as an alternative network measure for analyzing disease diffusion in a commuting network.

Epidemiology and burden of influenza in healthy children aged 6 to 35 months: analysis of data from the placebo arm of a phase III efficacy trial.

BACKGROUND: Despite World Health Organization recommendations, in many countries young children are not targeted for influenza vaccination. To help inform influenza vaccination policy, we examined the occurrence and burden of influenza in healthy children aged 6 to 35 months using data from a recent phase III placebo-controlled influenza vaccine trial conducted in countries in the Northern and Southern Hemispheres. METHODS: This was an analysis of data from participants included in the placebo arm of a phase III clinical trial in healthy children aged 6 to 35 months (EudraCT no. 2013-001231-51). Included children had never been vaccinated for influenza and were observed for one influenza season. Outcome measures included the occurrence of influenza-like illness (ILI), laboratory-confirmed influenza, virus types/subtypes, severe symptoms and complications of confirmed influenza, and healthcare use associated with confirmed influenza. RESULTS: Data from 2210 participants were analysed. ILI was reported for 811 participants (36.7%). Of these, 255 participants (31.4%) had 263 virologically confirmed episodes of influenza. The overall influenza attack rate was 11.5%. The most common influenza virus detected was A(H3N2) (40.7%), followed by B/Yamagata (23.6%), A(H1N1) (18.6%), and B/Victoria (8.0%). Grade 3 fever was reported in 24.3% of confirmed episodes, acute lower respiratory infection in 8.7%, acute otitis media in 6.1%, and pneumonia in 1.9%. In most influenza episodes (93.2%), antipyretics, analgesics, or non-steroidal anti-inflammatory drugs were taken. Antibiotics were prescribed for 41.4% of influenza episodes. More than half of the influenza episodes (57.0%) resulted in outpatient visits. Influenza resulted in overnight hospitalisation in 1.1% of episodes. CONCLUSIONS: Influenza is associated with a significant burden of disease in healthy children. This analysis also revealed that antibiotics continue to be frequently used for young children with influenza. TRIAL REGISTRATION: EudraCT no. 2013-001231-51 .

Influenza A viruses in birds and humans: Prevalence, molecular characterization, zoonotic significance and risk factors' assessment in poultry farms.

This study aimed to investigate the prevalence of influenza A viruses in birds and humans residing in the same localities of Sharkia Province, Egypt and the risk factors' assessment in poultry farms. A total of 100 birds comprised of 50 chickens, 25 ducks and 25 wild egrets were sampled. Swab samples were collected from 65 people (50 poultry farm workers and 15 hospitalized patients). All samples were screened for the presence of influenza A viruses using isolation and molecular assays. Avian influenza viruses were only detected in chicken samples (18%) and molecularly confirmed as subtype H5. The infection rate was higher in broilers (40%) than layers (8.6%). Influenza A (H1) pdm09 virus was detected in a single human case (1.54%). All the isolated AI H5 viruses were clustered into clade (2.2.1.2) and shared a high similarity rate at nucleotides and amino acid levels. In addition, they had a multi-basic amino acid motif (ـــPQGEKRRKKR/GLFـــ) at the H5 gene cleavage site that exhibited point mutations. Chicken breed, movement of workers from one flock to another, lack of utensils' disinfection and the introduction of new birds to the farm were significant risk factors associated with highly pathogenic AI H5 virus infection in poultry farms (p ≤ 0.05). Other factors showed no significant association. The HPAI H5 viruses are still endemic in Egypt with continuous mutation. Co-circulation of these viruses in birds and pdm09 viruses in humans raises alarm for the emergence of reassortant viruses that are capable of potentiating pandemics.

Characteristics and mortality risk of children with life-threatening influenza infection admitted to paediatric intensive care in England 2003-2015.

BACKGROUND: Information is lacking about the severity of complications in children with influenza admitted to paediatric intensive care units (PICU) in the UK. In this study, we report risk factors for mortality, invasive ventilation and use of vasoactive drugs for children admitted to PICU with influenza. METHODS: We evaluated all admissions to PICUs in England for resident children with a recorded influenza diagnosis between September 2003 and March 2015. We used the Paediatric Intensive Care Audit Network (PICANet) database linked to hospital admission records to identify influenza cases, and high-risk comorbidities among admitted children. We used mixed effects logistic regression models to determine risk factors for mortality, use of invasive ventilation and vasoactive drugs. RESULTS: We identified 1961 influenza-related PICU admissions in 1778 children. Children with high-risk conditions accounted for 1540 admissions (78.5%). The odds of mortality were significantly higher for girls than boys (adjusted odds ratio 1.91; 95% confidence interval 1.31, 2.79), children from Asian/Asian British (2.70; 1.74, 4.20) or other minority ethnic groups (3.95; 1.65, 9.42) compared to white British children, and significantly increased before and during the A(H1N1)pdm 2009 pandemic compared to the post-pandemic period. Children required invasive ventilation in 1588 admissions (81.0%), and received vasoactive drugs in 586 admissions (29.9%). CONCLUSIONS: Nearly four fifths of influenza-related PICU admissions occurred in children with high-risk conditions, highlighting the burden of severe influenza in this vulnerable population Further research is required to explain sex and ethnic group differences in PICU mortality among children admitted with influenza.

Rapid detection and subtyping of multiple influenza viruses on a microfluidic chip integrated with controllable micro-magnetic field.

Influenza viruses have threatened animals and public health systems continuously. Moreover, there are many subtypes of influenza viruses, which have brought great difficulties to the classification of influenza viruses during any influenza outbreak. So it is crucial to develop a rapid and accurate method for detecting and subtyping influenza viruses. In this work, we reported a rapid method for simultaneously detecting and subtyping multiple influenza viruses (H1N1, H3N2 and H9N2) based on nucleic acid hybridization on a microfluidic chip integrated with controllable micro-magnetic field. H1N1, H3N2 and H9N2 could be simultaneously detected in 80min with detection limits about 0.21nM, 0.16nM, 0.12nM in order. Moreover, the sample and reagent consumption was as low as only 3µL. The results indicated that this approach possessed fast analysis and high specificity. Therefore, it is expected to be used to simultaneously subtype and detect multiple targets, and may provide a powerful technique platform for the rapid detection and subtyping analysis of influenza viruses.

National burden of influenza-associated hospitalizations in Cambodia, 2015 and 2016.

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.

Burden of influenza among hospitalized febrile children in Ghana.

BACKGROUND: Influenza surveillance data from Africa indicate a substantial disease burden with high mortality. However, local influenza data from district hospitals with limited laboratory facilities are still scarce. OBJECTIVES: To identify the frequency and seasonal distribution of influenza among hospitalized febrile children in a rural hospital in Ghana and to describe differential diagnoses to other severe febrile infections. METHODS: Between January 2014 and April 2015, all children with a temperature of ≥38°C admitted to a district hospital in Ghana were screened for influenza A and B by RT-PCR and differentiated to subtypes A(H1N1)pdm09 and A(H3N2). Malaria microscopy and blood cultures were performed for each patient. RESULTS: A total of 1063 children with a median age of 2 years (IQR: 1-4 years) were recruited. Of those, 271 (21%) were classified as severe acute respiratory infection (SARI) and 47 (4%) were positive for influenza, namely 26 (55%) influenza B, 15 (32%) A(H1N1)pdm09, and 6 (13%) A(H3N2) cases. Influenza predominantly occurred in children aged 3-5 years and was more frequently detected in the major rainy season (OR = 2.9; 95% CI: 1.47-6.19) during the first half of the year. Two (4%) and seven (15%) influenza-positive children were co-diagnosed with an invasive bloodstream infection or malaria, respectively. CONCLUSION: Influenza contributes substantially to the burden of hospitalized febrile children in Ghana being strongly dependent on age and corresponds with the major rainy season during the first half-year.

The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection.

Severe influenza infection represents a leading cause of global morbidity and mortality. Although influenza is primarily considered a viral infection that results in pathology limited to the respiratory system, clinical reports suggest that influenza infection is frequently associated with a number of clinical syndromes that involve organ systems outside the respiratory tract. A comprehensive MEDLINE literature review of articles pertaining to extra-pulmonary complications of influenza infection, using organ-specific search terms, yielded 218 articles including case reports, epidemiologic investigations, and autopsy studies that were reviewed to determine the clinical involvement of other organs. The most frequently described clinical entities were viral myocarditis and viral encephalitis. Recognition of these extra-pulmonary complications is critical to determining the true burden of influenza infection and initiating organ-specific supportive care.

Estimation of influenza-attributable medically attended acute respiratory illness by influenza type/subtype and age, Germany, 2001/02-2014/15.

BACKGROUND: The total burden of influenza in primary care is difficult to assess. The case definition of medically attended "acute respiratory infection" (MAARI) in the German physician sentinel is sensitive; however, it requires modelling techniques to derive estimates of disease attributable to influenza. We aimed to examine the impact of type/subtype and age. METHODS: Data on MAARI and virological results of respiratory samples (virological sentinel) were available from 2001/02 until 2014/15. We constructed a generalized additive regression model for the periodic baseline and the secular trend. The weekly number of influenza-positive samples represented influenza activity. In a second step, we distributed the estimated influenza-attributable MAARI (iMAARI) according to the distribution of types/subtypes in the virological sentinel. RESULTS: Season-specific iMAARI ranged from 0.7% to 8.9% of the population. Seasons with the strongest impact were dominated by A(H3), and iMAARI attack rate of the pandemic 2009 (A(H1)pdm09) was 4.9%. Regularly the two child age groups (0-4 and 5-14 years old) had the highest iMAARI attack rates reaching frequently levels up to 15%-20%. Influenza B affected the age group of 5- to 14-year-old children substantially more than any other age group. Sensitivity analyses demonstrated both comparability and stability of the model. CONCLUSION: We constructed a model that is well suited to estimate the substantial impact of influenza on the primary care sector. A(H3) causes overall the greatest number of iMAARI, and influenza B has the greatest impact on school-age children. The model may incorporate time series of other pathogens as they become available.

Real-time real-world analysis of seasonal influenza vaccine effectiveness: method development and assessment of a population-based cohort in Stockholm County, Sweden, seasons 2011/12 to 2014/15.

Real-world estimates of seasonal influenza vaccine effectiveness (VE) are important for early detection of vaccine failure. We developed a method for evaluating real-time in-season vaccine effectiveness (IVE) and overall seasonal VE. In a retrospective, register-based, cohort study including all two million individuals in Stockholm County, Sweden, during the influenza seasons from 2011/12 to 2014/15, vaccination status was obtained from Stockholm's vaccine register. Main outcomes were hospitalisation or primary care visits for influenza (International Classification of Disease (ICD)-10 codes J09-J11). VE was assessed using Cox multivariate stratified and non-stratified analyses adjusting for age, sex, socioeconomic status, comorbidities and previous influenza vaccinations. Stratified analyses showed moderate VE in prevention of influenza hospitalisations among chronically ill adults ≥ 65 years in two of four seasons, and lower but still significant VE in one season; 53% (95% confidence interval (CI): 33-67) in 2012/13, 55% (95% CI: 25-73) in 2013/14 and 18% (95% CI: 3-31) in 2014/15. In conclusion, seasonal influenza vaccination was associated with substantial reductions in influenza-specific hospitalisation, particularly in adults ≥ 65 years with underlying chronic conditions. With the use of population-based patient register data on influenza-specific outcomes it will be possible to obtain real-time estimates of seasonal influenza VE.

Modelling of seasonal influenza and estimation of the burden in Tunisia.

The burden of influenza was estimated from surveillance data in Tunisia using epidemiological parameters of transmission with WHO classical tools and mathematical modelling. The incidence rates of influenza-associated influenza-like illness (ILI) per 100 000 were 18 735 in 2012/2013 season; 5536 in 2013/14 and 12 602 in 2014/15. The estimated proportions of influenza-associated ILI in the total outpatient load were 3.16%; 0.86% and 1.98% in the 3 seasons respectively. Distribution of influenza viruses among positive patients was: A(H3N2) 15.5%; A(H1N1)pdm2009 39.2%; and B virus 45.3% in 2014/2015 season. From the estimated numbers of symptomatic cases, we estimated that the critical proportions of the population that should be vaccinated were 15%, 4% and 10% respectively. Running the model for the different values of R0, we quantified the number of symptomatic clinical cases, the clinical attack rates, the symptomatic clinical attack rates and the number of deaths. More realistic versions of this model and improved estimates of parameters from surveillance data will strengthen the estimation of the burden of influenza.

Burden of acute respiratory disease of epidemic and pandemic potential in the WHO Eastern Mediterranean Region: A literature review.

There are gaps in the knowledge about the burden of severe respiratory disease in the Eastern Mediterranean Region (EMR). This literature review was therefore conducted to describe the burden of epidemicand pandemic-prone acute respiratory infections (ARI) in the Region which may help in the development of evidence-based disease prevention and control policies. Relevant published and unpublished reports were identified from searches of various databases; 83 documents fulfilled the search criteria. The infections identified included: ARI, avian influenza A(H5N1), influenza A(H1N1)pdm09 and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Pneumonia and ARIs were leading causes of disease and death in the Region. Influenza A(H1N1) was an important cause of morbidity during the 2009 pandemic. This review provides a descriptive summary of the burden of acute respiratory diseases in the Region, but there still remains a lack of necessary data.

The H1N1 influenza pandemic of 2009 in the Eastern Mediterranean Region: lessons learnt and future strategy.

A novel strain of influenza A virus H1N1 surfaced in Mexico in April 2009 and quickly spread across the globe, turning an epidemic into a pandemic. Within two months, the World Health Organization (WHO) declared an international health emergency and raised the threat bar from level V to level VI, i.e. containment to mitigation. During this time, the WHO Regional Office for the Eastern Mediterranean worked closely with its Member States, other stakeholders and WHO headquarters to manage the situation. This report examines the steps taken as part of this response. Programme documents were reviewed and key personnel interviewed for this study. A hallmark of the response was the establishment of the Strategic Health Operations Centre to bring together experts from different technical backgrounds at regional level. Several lessons were learnt that can provide the basis for standard operating procedures, protocols and guidelines for emergency events in future.

Integrated microfluidic system for rapid detection of influenza H1N1 virus using a sandwich-based aptamer assay.

The rapid spread of influenza-associated H1N1 viruses has caused serious concern in recent years. Therefore, there is an urgent need for the development of automatic, point-of-care devices for rapid diagnosis of the influenza virus. Conventional approaches suffer from several critical issues; notably, they are time-consuming, labor-intensive, and are characterized by relatively low sensitivity. In this work, we present a new approach for fluorescence-based detection of the influenza A H1N1 virus using a sandwich-based aptamer assay that is automatically performed on an integrated microfluidic system. The entire detection process was shortened to 30min using this chip-based system which is much faster than the conventional viral culture method. The limit of detection was significantly improved to 0.032 hemagglutination unit due to the high affinity and high specificity of the H1N1-specific aptamers. The results showed that the two-aptamer microfluidic system had about 10(3) times higher sensitivity than the conventional serological diagnosis. It was demonstrated that the developed microfluidic system may play as a powerful tool in the detection of the H1N1 virus.