Reported Global Avian Influenza Detections Among Humans and Animals During 2013-2022: Comprehensive Review and Analysis of Available Surveillance Data.

BACKGROUND: Avian influenza (AI) virus detections occurred frequently in 2022 and continue to pose a health, economic, and food security risk. The most recent global analysis of official reports of animal outbreaks and human infections with all reportable AI viruses was published almost a decade ago. Increased or renewed reports of AI viruses, especially high pathogenicity H5N8 and H5N1 in birds and H5N1, H5N8, and H5N6 in humans globally, have established the need for a comprehensive review of current global AI virus surveillance data to assess the pandemic risk of AI viruses. OBJECTIVE: This study aims to provide an analysis of global AI animal outbreak and human case surveillance information from the last decade by describing the circulating virus subtypes, regions and temporal trends in reporting, and country characteristics associated with AI virus outbreak reporting in animals; surveillance and reporting gaps for animals and humans are identified. METHODS: We analyzed AI virus infection reports among animals and humans submitted to animal and public health authorities from January 2013 to June 2022 and compared them with reports from January 2005 to December 2012. A multivariable regression analysis was used to evaluate associations between variables of interest and reported AI virus animal outbreaks. RESULTS: From 2013 to 2022, 52.2% (95/182) of World Organisation for Animal Health (WOAH) Member Countries identified 34 AI virus subtypes during 21,249 outbreaks. The most frequently reported subtypes were high pathogenicity AI H5N1 (10,079/21,249, 47.43%) and H5N8 (6722/21,249, 31.63%). A total of 10 high pathogenicity AI and 6 low pathogenicity AI virus subtypes were reported to the WOAH for the first time during 2013-2022. AI outbreaks in animals occurred in 26 more Member Countries than reported in the previous 8 years. Decreasing World Bank income classification was significantly associated with decreases in reported AI outbreaks (P<.001-.02). Between January 2013 and June 2022, 17/194 (8.8%) World Health Organization (WHO) Member States reported 2000 human AI virus infections of 10 virus subtypes. H7N9 (1568/2000, 78.40%) and H5N1 (254/2000, 12.70%) viruses accounted for the most human infections. As many as 8 of these 17 Member States did not report a human case prior to 2013. Of 1953 human cases with available information, 74.81% (n=1461) had a known animal exposure before onset of illness. The median time from illness onset to the notification posted on the WHO event information site was 15 days (IQR 9-30 days; mean 24 days). Seasonality patterns of animal outbreaks and human infections with AI viruses were very similar, occurred year-round, and peaked during November through May. CONCLUSIONS: Our analysis suggests that AI outbreaks are more frequently reported and geographically widespread than in the past. Global surveillance gaps include inconsistent reporting from all regions and human infection reporting delays. Continued monitoring for AI virus outbreaks in animals and human infections with AI viruses is crucial for pandemic preparedness.

Mild and asymptomatic influenza B virus infection among unvaccinated pregnant persons: Implication for effectiveness of non-pharmaceutical intervention and vaccination to prevent influenza.

BACKGROUND: We estimated symptomatic and asymptomatic influenza infection frequency in community-dwelling unvaccinated pregnant persons to inform risk communication. METHODS: We collected residue sera from multiple antenatal-care blood draws during October 2016-April 2017. We determined influenza infection as seroconversion with ≥ 4-fold rise in antibody titers between any two serum samples by improved hemagglutinin-inhibition assay including ether-treated B antigens. The serology data were linked to the results of nuclei acid testing (rRT-PCR) based on acute respiratory illness (ARI) surveillance. RESULTS: Among all participants, 43 %(602/1384) demonstrated serology and/or rRT-PCR evidenced infection, and 44 %(265/602) of all infections were asymptomatic. ARI-associated rRT-PCR testing identified only 10 %(61/602) of total infections. Only 1 %(5/420) of the B Victoria cases reported ARI and had a rRT-PCR positive result, compared with 33 %(54/165) of the H3N2 cases. Among influenza ARI cases with multiple serum samples, 19 %(11/58) had seroconversion to a different subtype prior to the illness. CONCLUSIONS: The incidence of influenza B infection in unvaccinated pregnant persons is under-estimated substantially. Non-pharmaceutical intervention may have suboptimal effectiveness in preventing influenza B transmission due to the less clinical manifestation compared to influenza A. The findings support maternal influenza vaccination to protect pregnant persons and reduce consequent household transmission.

Enhanced environmental surveillance for avian influenza A/H5, H7 and H9 viruses in Guangxi, China, 2017-2019.

We conducted environmental surveillance to detect avian influenza viruses circulating at live poultry markets (LPMs) and poultry farms in Guangxi Autonomous Region, China, where near the China-Vietnam border. From November through April 2017-2018 and 2018-2019, we collected environmental samples from 14 LPMs, 4 poultry farms, and 5 households with backyard poultry in two counties of Guangxi and tested for avian influenza A, H5, H7, and H9 by real-time reverse transcription-polymerase chain reaction (rRT-PCR). In addition, we conducted four cross-sectional questionnaire surveys among stall owners on biosecurity practices in LPMs of two study sites. Among 16,713 environmental specimens collected and tested, the median weekly positive rate for avian influenza A was 53.6% (range = 33.5% - 66.0%), including 25.2% for H9, 4.9% for H5, and 21.2% for other avian influenza viruses A subtypes, whereas a total of two H7 positive samples were detected. Among the 189 LPM stalls investigated, most stall owners (73.0%) sold chickens and ducks. Therefore, continued surveillance of the avian influenza virus is necessary for detecting and responding to emerging trends in avian influenza virus epidemiology.

Incidence rates of influenza illness during pregnancy in Suzhou, China, 2015-2018.

BACKGROUND: Data on influenza incidence during pregnancy in China are limited. METHODS: From October 2015 to September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow-up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza. RESULTS: In total, we enrolled 18 724 pregnant women median aged 28 years old, 37% in first trimester, 48% in second trimester, and 15% in third trimester, with seven self-reported influenza vaccination during pregnancy. In the 18-week epidemic period during October 2015 to September 2016, influenza incidence was 0.7/100 person-months (95% CI: 0.5-0.9). In the cumulative 29-week-long epidemic during October 2016 to September 2017, influenza incidence was 1.0/100 person-months (95% CI: 0.8-1.2). In the 11-week epidemic period during October 2017 to September 2018, influenza incidence was 2.1/100 person-months (95% CI: 1.9-2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza-associated ARIs were mild, and <5.1% required hospitalization. CONCLUSIONS: Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy.

Estimated influenza illnesses and hospitalizations averted by influenza vaccination among children aged 6-59 months in Suzhou, China, 2011/12 to 2015/16 influenza seasons.

BACKGROUND: There are few estimates of vaccination-averted influenza-associated illnesses in China. METHODS: We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% confidence intervals (CI) of influenza-associated outcomes (hospitalization, illness, and medically-attended (MA) illness) averted by vaccination among children aged 6-59 months in Suzhou from October 2011-September 2016. Influenza illnesses included non-hospitalized MA influenza illnesses and non-MA influenza illnesses. The numbers of influenza-associated outcomes averted by vaccination were the difference between the expected burden if there were no vaccination given and the observed burden with vaccination. The model incorporated the disease burden estimated based on surveillance data from Suzhou University Affiliated Children's Hospital (SCH) and data from health utilization surveys conducted in the catchment area of SCH, age-specific estimates of influenza vaccination coverage in Suzhou from the Expanded Program on Immunization database, and influenza vaccine effectiveness estimates from previous publications. Averted influenza estimations were presented as absolute numbers and in terms of the prevented fraction (PF). A hypothetical scenario with 50% coverage (but identical vaccine effectiveness) over the study period was also modeled. RESULTS: In ~250,000 children, influenza vaccination prevented an estimated 731 (CI: 549-960) influenza hospitalizations (PF: 6.2% of expected, CI: 5.8-6.6%) and 10,024 (7593-12,937) influenza illnesses (PF: 6.5%, 6.4-6.7%), of which 8342 (6338-10,768) were MA (PF: 6.6%, 6.4-6.7%) from 2011 to 2016. The PFs declined each year along with decreasing influenza vaccination coverage. If 50% of the study population had been vaccinated over time, the estimated numbers of averted cases during the study period would have been 4059 (3120-5762) influenza hospitalizations (PF: 27.2%, 26.4-27.9%) and 56,215 (42,925-78,849) influenza illnesses (PF: 28.5%, 28.3-28.7%), of which 46,596 (35,662-65,234) would be MA (PF: 28.5%, 28.3-28.7%). CONCLUSION: Influenza vaccination is estimated to have averted influenza-associated illness outcomes even with low coverage in children aged 6-59 months in Suzhou. Increasing influenza vaccination coverage in this population could further reduce illnesses and hospitalizations.

Dose effect of influenza vaccine on protection against laboratory-confirmed influenza illness among children aged 6 months to 8 years of age in southern China, 2013/14-2015/16 seasons: a matched case-control study.

Background We conducted a matched case-control study in China during the 2013/14-2015/16 influenza seasons to estimate influenza vaccine effectiveness (VE) by dose among children aged 6 months to 8 years.Methods Cases were laboratory-confirmed influenza infections identified through the influenza-like illness sentinel surveillance network in Guangzhou. Age- and sex-matched community controls were randomly selected through the expanded immunization program database. We defined priming as receipt of ≥1 dose of influenza vaccine during the immediate prior season.Results In total, 4,185 case-control pairs were analyzed. Among children 6-35 months, VE for current season dose(s) across the three seasons during 2013/14-2015/16 were 59% (95% Confidence Interval: 44-71%), 12% (-11%,30%), 54% (32-69%); among unprimed children 6-35 months, VE for 1 vs 2 current season doses were 45% (8-67%) vs 65% (46-78%), -2% (-53%,32%) vs 19% (-11%,40%), and 37% (-24%,68%) vs 61% (32-78%). Among children aged 3-8 years, VE for current season dose(s) across study seasons were 62% (36-78%), 43% (22-58%), 32% (1-53%). VE for unprimed children receiving 1 dose only in current season was insignificant or lower than among all children.Conclusion Findings support utility of providing second dose ("booster dose") of seasonal influenza vaccine to unprimed children aged 6-35 months, and the need to study further dose effect of a booster dose among unprimed children aged 3-8 years in China.

Review of the status and challenges associated with increasing influenza vaccination coverage among pregnant women in China.

Influenza vaccination coverage in pregnant women in China remains low. In this review, we first provide an overview of the evidence for the use of influenza vaccination during pregnancy. Second, we discuss influenza vaccination policy and barriers to increased seasonal influenza vaccination coverage in pregnant women in China. Third, we provide case studies of successes and challenges of programs for increasing seasonal influenza vaccination in pregnant women from other parts of Asia with lessons learned for China. Finally, we assess opportunities and challenges for increasing influenza vaccination coverage among pregnant women in China.

Lessons from an active surveillance pilot to assess the pneumonia of unknown etiology surveillance system in China, 2016: the need to increase clinician participation in the detection and reporting of emerging respiratory infectious diseases.

BACKGROUND: We sought to assess reporting in China's Pneumonia of Unknown Etiology (PUE) passive surveillance system for emerging respiratory infections and to identify ways to improve the PUE surveillance system's detection of respiratory infections of public health significance. METHODS: From February 29-May 29, 2016, we actively identified and enrolled patients in two hospitals with acute respiratory infections (ARI) that met all PUE case criteria. We reviewed medical records for documented exposure history associated with respiratory infectious diseases, collected throat samples that were tested for seasonal and avian influenza, and interviewed clinicians regarding reasons for reporting or not reporting PUE cases. We described and analyzed the proportion of PUE cases reported and clinician awareness of and practices related to the PUE system. RESULTS: Of 2619 ARI admissions in two hospitals, 335(13%) met the PUE case definition; none were reported. Of 311 specimens tested, 18(6%) were seasonal influenza virus-positive; none were avian influenza-positive. < 10% PUE case medical records documented whether or not there were exposures to animals or others with respiratory illness. Most commonly cited reasons for not reporting cases were no awareness of the PUE system (76%) and not understanding the case definition (53%). CONCLUSIONS: Most clinicians have limited awareness of and are not reporting to the PUE system. Exposures related to respiratory infections are rarely documented in medical records. Increasing clinicians' awareness of the PUE system and including relevant exposure items in standard medical records may increase reporting.

A ten-year China-US laboratory collaboration: improving response to influenza threats in China and the world, 2004-2014.

The emergence of severe acute respiratory syndrome (SARS) underscored the importance of influenza detection and response in China. From 2004, the Chinese National Influenza Center (CNIC) and the United States Centers for Disease Control and Prevention (USCDC) initiated Cooperative Agreements to build capacity in influenza surveillance in China.From 2004 to 2014, CNIC and USCDC collaborated on the following activities: 1) developing human technical expertise in virology and epidemiology in China; 2) developing a comprehensive influenza surveillance system by enhancing influenza-like illness (ILI) reporting and virological characterization; 3) strengthening analysis, utilization and dissemination of surveillance data; and 4) improving early response to influenza viruses with pandemic potential.Since 2004, CNIC expanded its national influenza surveillance and response system which, as of 2014, included 408 laboratories and 554 sentinel hospitals. With support from USCDC, more than 2500 public health staff from China received virology and epidemiology training, enabling > 98% network laboratories to establish virus isolation and/or nucleic acid detection techniques. CNIC established viral drug resistance surveillance and platforms for gene sequencing, reverse genetics, serologic detection, and vaccine strains development. CNIC also built a bioinformatics platform to strengthen data analysis and utilization, publishing weekly on-line influenza surveillance reports in English and Chinese. The surveillance system collects 200,000-400,000 specimens and tests more than 20,000 influenza viruses annually, which provides valuable information for World Health Organization (WHO) influenza vaccine strain recommendations. In 2010, CNIC became the sixth WHO Collaborating Centre for Influenza. CNIC has strengthened virus and data sharing, and has provided training and reagents for other countries to improve global capacity for influenza control and prevention.The collaboration's successes were built upon shared mission and values, emphasis on long-term capacity development and sustainability, and leadership commitment.

Influenza-associated Hospitalization in Children Younger Than 5 Years of Age in Suzhou, China, 2011-2016.

BACKGROUND: Studying the burden and risk factors associated with severe illness from influenza infection in young children in eastern China will contribute to future cost-effectiveness analyses of local influenza vaccine programs. METHODS: We conducted prospective, severe acute respiratory infection (SARI) surveillance at Suzhou University-Affiliated Children's Hospital to estimate influenza-associated hospitalizations in Suzhou University-Affiliated Children's Hospital by month in children younger than 5 years of age from October 2011 to September 2016. SARI was defined as fever (measured axillary temperature ≥ 38°C) and cough or sore throat or inflamed/red pharynx in the 7 days preceding hospitalization. We combined SARI surveillance data with healthcare utilization survey data to estimate and characterize the burden of influenza-associated SARI hospitalizations in Suzhou within this age group in the 5-year period. RESULTS: Of the 36,313 SARI cases identified, 2,297 from respiratory wards were systematically sampled; of these, 259 (11%) were influenza positive. Estimated annual influenza-associated SARI hospitalization rates per 1,000 children younger than 5 years of age ranged from 4 (95% confidence interval [CI], 2-5) in the 2012-2013 season to 16 (95% CI, 14-19) in the 2011-2012 season. The predominant viruses were A/H3N2 (59%) in 2011-12, both A/H1N1pdm09 (42%) and B (46%) in 2012-13, A/H3N2 (71%) in 2013-14, A/H3N2 (55%) in 2014-15 and both A/H1N1pdm09 (50%) and B (50%) in 2015-16. The age-specific influenza-associated SARI hospitalization rates for the 5-year period were 11 (95% CI, 8-15) per 1,000 children 0-5 months of age; 8 (95% CI, 7-10) per 1,000 children 6-23 months of age and 5 (95% CI, 4-5) per 1,000 children 24-59 months of age, respectively. CONCLUSIONS: From 2011 to 2016, influenza-associated SARI hospitalization rates in children aged younger than 5 years of age in Suzhou, China, were high, particularly among children 0-5 months of age. Higher hospitalization rates were observed in years where the predominant circulating virus was influenza A/H3N2. Immunization for children > 6 months, and maternal and caregiver immunization for those < 6 months, could reduce influenza-associated hospitalizations in young children in Suzhou.