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.

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.

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.

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.

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.

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.

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.

Cohort profile: China respiratory illness surveillance among pregnant women (CRISP), 2015-2018.

PURPOSE: We established the China Respiratory Illness Surveillance among Pregnant women (CRISP) to conduct active surveillance for influenza-associated respiratory illness during pregnancy in China from 2015 to 2018. Among annual cohorts of pregnant women, we assess the incidence of acute respiratory illness (ARI), influenza-like illness (ILI), laboratory-confirmed influenza virus infection and the seroconversion proportion during the winter influenza season. We also plan to examine the effect of influenza virus infection on adverse pregnancy, delivery and infant health outcomes with cumulative data from the three annual cohorts. PARTICIPANTS: Cohort nurses enrol pregnant women in different trimesters of pregnancy from prenatal care facilities in Suzhou, Jiangsu Province, eastern China. Pregnant women who plan to deliver in the study facilities are eligible. Pregnant women who are seeking care for anything other than routine prenatal care, such as confirmation of low progesterone and threatened miscarriage, are excluded. At enrolment, study nurses collect baseline information on demographics, education-level attained, underlying medical conditions, seasonal influenza vaccination receipt, risk factors for influenza infection, gravidity and parity and contact information. For each participant, cohort nurses conduct twice weekly follow-up contacts, one phone call and one WeChat message (free instant messaging), from the time of enrolment until delivery or termination of pregnancy. During follow-up, study nurses ask about symptoms, timing and characteristics of ARI, healthcare-seeking behaviour and medications taken for participants reporting respiratory illness since the last contact. In addition, we collect combined nasal and throat swabs for identified ARI to test for influenza viruses. We collect paired sera before and after the influenza season. Active respiratory illness surveillance and seroinfection data during pregnancy of participants are linked to their medical record and the Suzhou Maternal Child Information System for detailed information on clinical treatment for respiratory illness, pregnancy, delivery and infant health outcomes. FINDINGS TO DATE: In 2015-2016, of 4915 pregnant women approached, 192 (4%) refused to participate, 91 (2%) were ineligible because they did not plan to deliver in one of the study hospitals or because their visit was for anything other than routine prenatal care and 4632 (94%) were enrolled, 46% during their first trimester of pregnancy (range 5-12 weeks), 48% during the second trimester (range 13-27 weeks) and 6% during the third trimester (range 28-37 weeks). The median age of the enrollees was 27 years (range 16-45) and two (0.04%, 95% CI 0.01% to 0.17%) reported influenza vaccination in the previous 12 months before pregnancy, while zero reported influenza vaccination in the previous 12 months during pregnancy. During the observation time of 648 518 person-days, 1355 ARI episodes were identified. Among 1127 swabs collected (for 83% of all ARIs), 68 (6%) tested positive for influenza virus, for a laboratory-confirmed influenza incidence of 0.31 (95% CI 0.25 to 0.40) per 100 person-months during pregnancy in the study cohort. FUTURE PLANS: Results will be used to describe influenza disease burden in this population to model potential numbers of influenza illnesses averted if influenza vaccination coverage were increased and to support enhanced influenza prevention and control strategies among pregnant women in China. We also plan to enrol and follow three cohorts of pregnant women over three influenza seasons during 2015-2018 which will allow an analysis of the effect of influenza virus infection during pregnancy on adverse pregnancy, delivery and infant outcomes.

Innovations in adult influenza vaccination in China, 2014-2015: Leveraging a chronic disease management system in a community-based intervention.

OBJECTIVES: To evaluate a community-based intervention that leveraged the non-communicable disease management system to increase seasonal influenza vaccination coverage among older adults in Ningbo, China. METHODS: From October 2014 - March 2015, we piloted the following on one street in Ningbo, China: educating community healthcare workers (C-HCWs) about influenza and vaccination; requiring C-HCWs to recommend influenza vaccination to older adults during routine chronic disease follow-up; and opening 14 additional temporary vaccination clinics. We selected a non-intervention street for comparison pre- and post-intervention vaccine coverage. In April 2016, we interviewed a random sample of unvaccinated older adults on the intervention street to ask why they remained unvaccinated. RESULTS: Pre-intervention influenza vaccine coverage among adults aged 60 years and older on both streets was 0.3%. Post-intervention, coverage among adults 60 years and older was 19% (1338/7013) on the intervention street and 0.4% (20/5500) on the non-intervention street (p<0.01). Among vaccinated older adults, 98% reported their main reason for vaccination was receiving a C-HCW's recommendation, 90% were vaccinated at temporary vaccination clinics, and 53% paid for vaccine (10 USD) out-of-pocket. Reasons for not getting vaccinated among 150 unvaccinated adults (response rate = 75%) included: good health (39%); not trusting C-HCWs' recommendations (24%); not knowing where to get vaccinated (17%); and not wanting to pay (9%). CONCLUSIONS: Recommending influenza vaccination within a non-communicable disease management system, combined with adding vaccination sites, increased vaccine coverage among older adults in Ningbo, China.

Mortality burden from seasonal influenza and 2009 H1N1 pandemic influenza in Beijing, China, 2007-2013.

BACKGROUND: Data about influenza mortality burden in northern China are limited. This study estimated mortality burden in Beijing associated with seasonal influenza from 2007 to 2013 and the 2009 H1N1 pandemic. METHODS: We estimated influenza-associated excess mortality by fitting a negative binomial model using weekly mortality data as the outcome of interest with the percent of influenza-positive samples by type/subtype as predictor variables. RESULTS: From 2007 to 2013, an average of 2375 (CI 1002-8688) deaths was attributed to influenza per season, accounting for 3% of all deaths. Overall, 81% of the deaths attributed to influenza occurred in adults aged ≥65 years, and the influenza-associated mortality rate in this age group was higher than the rate among those aged <65 years (113.6 [CI 49.5-397.4] versus 4.4 [CI 1.7-18.6] per 100 000, P < .05). The mortality rate associated with the 2009 H1N1 pandemic in 2009/2010 was comparable to that of seasonal influenza during the seasonal years (19.9 [CI 10.4-33.1] vs 17.2 [CI 7.2-67.5] per 100 000). People aged <65 years represented a greater proportion of all deaths during the influenza A(H1N1)pdm09 pandemic period than during the seasonal epidemics (27.0% vs 17.7%, P < .05). CONCLUSIONS: Influenza is an important contributor to mortality in Beijing, especially among those aged ≥65 years. These results support current policies to give priority to older adults for seasonal influenza vaccination and help to define the populations at highest risk for death that could be targeted for pandemic influenza vaccination.

Potential impact of B lineage mismatch on trivalent influenza vaccine effectiveness during the 2015-2016 influenza season among nursery school children in Suzhou, China.

BACKGROUND: We actively followed a cohort of nursery school children in Suzhou, China to assess the impact of vaccination with trivalent influenza vaccine on the prevention of influenza like illness (ILI). METHODS: We enrolled children aged 36 to 72 months from 13 nursery schools in Suzhou starting two weeks after vaccination during October 2015-February 2016. Every school-day, teachers reported the names of students with ILI to study clinicians, who collected the student's nasopharyngeal swab or throat swab, either at a study clinic or the child's home. Swabs were sent to the Suzhou Center for Disease Control and Prevention's laboratory for influenza testing by RT-PCR. RESULTS: In total, 3278 children were enrolled; 83 (3%) were lost to follow-up, while 3195 (vaccinated: 1492, unvaccinated: 1703) were followed for 24 weeks. During the study, 40 samples tested positive; 17 in the vaccinated (B Victoria: 12; A(H1N1)pdm09: 5) and 23 in the unvaccinated group (B Victoria: 10; B Yamagata: 2; A(H1N1)pdm09: 11). The VE estimates were: 16% overall (95%CI:-58%,56%), 48% (-47%,84%) for influenza A(H1N1)pdm09, 43% (-650%,98%) for influenza B Yamagata, and -37% (-227%,42%) for influenza B Victoria. Data were analyzed by vaccinated and unvaccinated groups based on enrollees' vaccination records. CONCLUSIONS: The VE for A(H1N1)pdm09 was moderate but not significant. Mismatching of B lineage may have compromised trivalent influenza vaccine effectiveness during the 2015-2016 influenza season among nursery school children in Suzhou, China. Additional larger studies are warranted to inform policy related to quadrivalent influenza vaccine licensure in China in the future.

Clusters of Human Infection and Human-to-Human Transmission of Avian Influenza A(H7N9) Virus, 2013-2017.

To detect changes in human-to-human transmission of influenza A(H7N9) virus, we analyzed characteristics of 40 clusters of case-patients during 5 epidemics in China in 2013-2017. Similarities in number and size of clusters and proportion of clusters with probable human-to-human transmission across all epidemics suggest no change in human-to-human transmission risk.

Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic - China, October 1, 2016-August 7, 2017.

Among all influenza viruses assessed using CDC's Influenza Risk Assessment Tool (IRAT), the Asian lineage avian influenza A(H7N9) virus (Asian H7N9), first reported in China in March 2013,* is ranked as the influenza virus with the highest potential pandemic risk (1). During October 1, 2016-August 7, 2017, the National Health and Family Planning Commission of China; CDC, Taiwan; the Hong Kong Centre for Health Protection; and the Macao CDC reported 759 human infections with Asian H7N9 viruses, including 281 deaths, to the World Health Organization (WHO), making this the largest of the five epidemics of Asian H7N9 infections that have occurred since 2013 (Figure 1). This report summarizes new viral and epidemiologic features identified during the fifth epidemic of Asian H7N9 in China and summarizes ongoing measures to enhance pandemic preparedness. Infections in humans and poultry were reported from most areas of China, including provinces bordering other countries, indicating extensive, ongoing geographic spread. The risk to the general public is very low and most human infections were, and continue to be, associated with poultry exposure, especially at live bird markets in mainland China. Throughout the first four epidemics of Asian H7N9 infections, only low pathogenic avian influenza (LPAI) viruses were detected among human, poultry, and environmental specimens and samples. During the fifth epidemic, mutations were detected among some Asian H7N9 viruses, identifying the emergence of high pathogenic avian influenza (HPAI) viruses as well as viruses with reduced susceptibility to influenza antiviral medications recommended for treatment. Furthermore, the fifth-epidemic viruses diverged genetically into two separate lineages (Pearl River Delta lineage and Yangtze River Delta lineage), with Yangtze River Delta lineage viruses emerging as antigenically different compared with those from earlier epidemics. Because of its pandemic potential, candidate vaccine viruses (CVV) were produced in 2013 that have been used to make vaccines against Asian H7N9 viruses circulating at that time. CDC is working with partners to enhance surveillance for Asian H7N9 viruses in humans and poultry, to improve laboratory capability to detect and characterize H7N9 viruses, and to develop, test and distribute new CVV that could be used for vaccine production if a vaccine is needed.

Preliminary Epidemiology of Human Infections with Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2017.

We compared the characteristics of cases of highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI) A(H7N9) virus infections in China. HPAI A(H7N9) case-patients were more likely to have had exposure to sick and dead poultry in rural areas and were hospitalized earlier than were LPAI A(H7N9) case-patients.

Innovations in Population Health Surveillance: Using Electronic Health Records for Chronic Disease Surveillance.

With 87% of providers using electronic health records (EHRs) in the United States, EHRs have the potential to contribute to population health surveillance efforts. However, little is known about using EHR data outside syndromic surveillance and quality improvement. We created an EHR-based population health surveillance system called the New York City (NYC) Macroscope and assessed the validity of diabetes, hyperlipidemia, hypertension, smoking, obesity, depression, and influenza vaccination indicators. The NYC Macroscope uses aggregate data from a network of outpatient practices. We compared 2013 NYC Macroscope prevalence estimates with those from a population-based, in-person examination survey, the 2013-2014 NYC Health and Nutrition Examination Survey. NYC Macroscope diabetes, hypertension, smoking, and obesity prevalence indicators performed well, but depression and influenza vaccination estimates were substantially lower than were survey estimates. Ongoing validation will be important to monitor changes in validity over time as EHR networks mature and to assess new indicators. We discuss NYC's experience and how this project fits into the national context. Sharing lessons learned can help achieve the full potential of EHRs for population health surveillance.

Sero-epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013-2014.

BACKGROUND: The first human infections of novel avian influenza A(H7N9) virus were identified in China in March 2013. Sentinel surveillance systems and contact tracing may not identify mild and asymptomatic human infections of influenza A(H7N9) virus. OBJECTIVES: We assessed the seroprevalence of antibodies to influenza A(H7N9) virus in three populations during the early stages of the epidemic. PATIENTS/METHODS: From March 2013 to May 2014, we collected sera from the general population, poultry workers, and contacts of confirmed infections in nine Chinese provinces reporting human A(H7N9) infections and, for contacts, second sera 2-3 weeks later. We screened for A(H7N9) antibodies by advanced hemagglutination inhibition (HI) assay and tested sera with HI titers ≥20 by modified microneutralization (MN) assay. MN titers ≥20 or fourfold increases in paired sera were considered seropositive. RESULTS: Among general population sera (n=1480), none were seropositive. Among poultry worker sera (n=1866), 28 had HI titers ≥20; two (0.11%, 95% CI: 0.02-0.44) were positive by MN. Among 61 healthcare and 117 non-healthcare contacts' sera, five had HI titers ≥20, and all were negative by MN. There was no seroconversion among 131 paired sera. CONCLUSIONS: There was no evidence of widespread transmission of influenza A(H7N9) virus during March 2013 to May 2014, although A(H7N9) may have caused rare, previously unrecognized infections among poultry workers. Although the findings suggest that there were few undetected cases of influenza A(H7N9) early in the epidemic, it is important to continue monitoring transmission as virus and epidemic evolve.

Assessing Change in Avian Influenza A(H7N9) Virus Infections During the Fourth Epidemic - China, September 2015-August 2016.

Since human infections with avian influenza A(H7N9) virus were first reported by the Chinese Center for Disease Control and Prevention (China CDC) in March 2013 (1), mainland China has experienced four influenza A(H7N9) virus epidemics. Prior investigations demonstrated that age and sex distribution, clinical features, and exposure history of A(H7N9) virus human infections reported during the first three epidemics were similar (2). In this report, epidemiology and virology data from the most recent, fourth epidemic (September 2015-August 2016) were compared with those from the three earlier epidemics. Whereas age and sex distribution and exposure history in the fourth epidemic were similar to those in the first three epidemics, the fourth epidemic demonstrated a greater proportion of infected persons living in rural areas, a continued spread of the virus to new areas, and a longer epidemic period. The genetic markers of mammalian adaptation and antiviral resistance remained similar across each epidemic, and viruses from the fourth epidemic remained antigenically well matched to current candidate vaccine viruses. Although there is no evidence of increased human-to-human transmissibility of A(H7N9) viruses, the continued geographic spread, identification of novel reassortant viruses, and pandemic potential of the virus underscore the importance of rigorous A(H7N9) virus surveillance and continued risk assessment in China and neighboring countries.