Prolonged Evolution of Virus-Specific Memory T Cell Immunity after Severe Avian Influenza A (H7N9) Virus Infection.

Since 2013, influenza A H7N9 virus has emerged as the most common avian influenza virus subtype causing human infection, and it is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of 45 H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5 to 4 months, 6 to 8 months, and 12 to 15 months postinfection. H7N9-specific antibody concentrations declined over time, and protective antibodies persisted longer in severely ill patients admitted to the intensive care unit (ICU) and patients presenting with acute respiratory distress syndrome (ARDS) than in patients with mild disease. Frequencies of virus-specific gamma interferon (IFN-γ)-secreting T cells were lower in critically ill patients requiring ventilation than in patients without ventilation within 4 months after infection. The percentages of H7N9-specific IFN-γ-secreting T cells tended to increase over time in patients ≥60 years or in critically ill patients requiring ventilation. Elevated levels of antigen-specific CD8+ T cells expressing the lung-homing marker CD49a were observed at 6 to 8 months after H7N9 infection compared to those in samples obtained at 1.5 to 4 months. Our findings indicate the prolonged reconstruction and evolution of virus-specific T cell immunity in older or critically ill patients and have implications for T cell-directed immunization strategies.IMPORTANCE Avian influenza A H7N9 virus remains a major threat to public health. However, no previous studies have determined the characteristics and dynamics of virus-specific T cell immune memory in patients who have recovered from H7N9 infection. Our findings showed that establishment of H7N9-specific T cell memory after H7N9 infection was prolonged in older and severely affected patients. Severely ill patients mounted lower T cell responses in the first 4 months after infection, while T cell responses tended to increase over time in older and severely ill patients. Higher levels of antigen-specific CD8+ T cells expressing the lung-homing marker CD49a were detected at 6 to 8 months after infection. Our results indicated a long-term impact of H7N9 infection on virus-specific memory T cells. These findings advance our understanding of the dynamics of virus-specific memory T cell immunity after H7N9 infection, which is relevant to the development of T cell-based universal influenza vaccines.

Variation in Influenza B Virus Epidemiology by Lineage, China.

We used national sentinel surveillance data in China for 2005-2016 to examine the lineage-specific epidemiology of influenza B. Influenza B viruses circulated every year with relatively lower activity than influenza A. B/Yamagata was more frequently detected in adults than in children.

Changing Geographic Patterns and Risk Factors for Avian Influenza A(H7N9) Infections in Humans, China.

The fifth epidemic wave of avian influenza A(H7N9) virus in China during 2016-2017 demonstrated a geographic range expansion and caused more human cases than any previous wave. The factors that may explain the recent range expansion and surge in incidence remain unknown. We investigated the effect of anthropogenic, poultry, and wetland variables on all epidemic waves. Poultry predictor variables became much more important in the last 2 epidemic waves than they were previously, supporting the assumption of much wider H7N9 transmission in the chicken reservoir. We show that the future range expansion of H7N9 to northern China may increase the risk of H7N9 epidemic peaks coinciding in time and space with those of seasonal influenza, leading to a higher risk of reassortments than before, although the risk is still low so far.

Preliminary Epidemiologic Assessment of Human Infections With Highly Pathogenic Avian Influenza A(H5N6) Virus, China.

BACKGROUND: Since 2014, 17 human cases of infection with the newly emerged highly pathogenic avian influenza A(H5N6) virus have been identified in China to date. The epidemiologic characteristics of laboratory-confirmed A(H5N6) cases were compared to A(H5N1) and A(H7N9) cases in mainland China. METHODS: Data on laboratory-confirmed H5N6, H5N1, and H7N9 cases identified in mainland China were analyzed to compare epidemiologic characteristics and clinical severity. Severity of confirmed H5N6, H5N1 and H7N9 cases was estimated based on the risk of severe outcomes in hospitalized cases. RESULTS: H5N6 cases were older than H5N1 cases with a higher prevalence of underlying medical conditions but younger than H7N9 cases. Epidemiological time-to-event distributions were similar among cases infected with the 3 viruses. In comparison to a fatality risk of 70% (30/43) for hospitalized H5N1 cases and 41% (319/782) for hospitalized H7N9 cases, 12 (75%) out of the 16 hospitalized H5N6 cases were fatal, and 15 (94%) required mechanical ventilation. CONCLUSION: Similar epidemiologic characteristics and high severity were observed in cases of H5N6 and H5N1 virus infection, whereas severity of H7N9 virus infections appeared lower. Continued surveillance of human infections with avian influenza A viruses remains an essential component of pandemic influenza preparedness.

Human Infection with Influenza A(H7N9) Virus during 3 Major Epidemic Waves, China, 2013-2015.

Since March 2013, a novel influenza A(H7N9) virus has caused 3 epidemic waves of human infection in mainland China. We analyzed data from patients with laboratory-confirmed influenza A(H7N9) virus infection to estimate the risks for severe outcomes after hospitalization across the 3 waves. We found that hospitalized patients with confirmed infections in waves 2 and 3 were younger and more likely to be residing in small cities and rural areas than were patients in wave 1; they also had a higher risk for death, after adjustment for age and underlying medical conditions. Risk for death among hospitalized patients during waves 2 and 3 was lower in Jiangxi and Fujian Provinces than in eastern and southern provinces. The variation in risk for death among hospitalized case-patients in different areas across 3 epidemic waves might be associated with differences in case ascertainment, changes in clinical management, or virus genetic diversity.

Differences in the Epidemiology of Human Cases of Avian Influenza A(H7N9) and A(H5N1) Viruses Infection.

BACKGROUND: The pandemic potential of avian influenza viruses A(H5N1) and A(H7N9) remains an unresolved but critically important question. METHODS: We compared the characteristics of sporadic and clustered cases of human H5N1 and H7N9 infection, estimated the relative risk of infection in blood-related contacts, and the reproduction number (R). RESULTS: We assembled and analyzed data on 720 H5N1 cases and 460 H7N9 cases up to 2 November 2014. The severity and average age of sporadic/index cases of H7N9 was greater than secondary cases (71% requiring intensive care unit admission vs 33%, P = .007; median age 59 years vs 31, P < .001). We observed no significant differences in the age and severity between sporadic/index and secondary H5N1 cases. The upper limit of the 95% confidence interval (CI) for R was 0.12 for H5N1 and 0.27 for H7N9. A higher proportion of H5N1 infections occurred in clusters (20%) compared to H7N9 (8%). The relative risk of infection in blood-related contacts of cases compared to unrelated contacts was 8.96 for H5N1 (95% CI, 1.30, 61.86) and 0.80 for H7N9 (95% CI, .32, 1.97). CONCLUSIONS: The results are consistent with an ascertainment bias towards severe and older cases for sporadic H7N9 but not for H5N1. The lack of evidence for ascertainment bias in sporadic H5N1 cases, the more pronounced clustering of cases, and the higher risk of infection in blood-related contacts, support the hypothesis that susceptibility to H5N1 may be limited and familial. This analysis suggests the potential pandemic risk may be greater for H7N9 than H5N1.

Estimating the Distribution of the Incubation Periods of Human Avian Influenza A(H7N9) Virus Infections.

A novel avian influenza virus, influenza A(H7N9), emerged in China in early 2013 and caused severe disease in humans, with infections occurring most frequently after recent exposure to live poultry. The distribution of A(H7N9) incubation periods is of interest to epidemiologists and public health officials, but estimation of the distribution is complicated by interval censoring of exposures. Imputation of the midpoint of intervals was used in some early studies, resulting in estimated mean incubation times of approximately 5 days. In this study, we estimated the incubation period distribution of human influenza A(H7N9) infections using exposure data available for 229 patients with laboratory-confirmed A(H7N9) infection from mainland China. A nonparametric model (Turnbull) and several parametric models accounting for the interval censoring in some exposures were fitted to the data. For the best-fitting parametric model (Weibull), the mean incubation period was 3.4 days (95% confidence interval: 3.0, 3.7) and the variance was 2.9 days; results were very similar for the nonparametric Turnbull estimate. Under the Weibull model, the 95th percentile of the incubation period distribution was 6.5 days (95% confidence interval: 5.9, 7.1). The midpoint approximation for interval-censored exposures led to overestimation of the mean incubation period. Public health observation of potentially exposed persons for 7 days after exposure would be appropriate.

Characterizing the epidemiology, virology, and clinical features of influenza in China's first severe acute respiratory infection sentinel surveillance system, February 2011-October 2013.

BACKGROUND: After the 2009 influenza A(H1N1)pdm09 pandemic, China established its first severe acute respiratory infections (SARI) sentinel surveillance system. METHODS: We analyzed data from SARI cases in 10 hospitals in 10 provinces in China from February 2011 to October 2013. RESULTS: Among 5,644 SARI cases, 330 (6%) were influenza-positive. Among these, 62% were influenza A and 38% were influenza B. Compared with influenza-negative cases, influenza-positive SARI cases had a higher median age (20.0 years vs.11.0, p=0.003) and were more likely to have at least one underlying chronic medical condition (age adjusted percent: 28% vs. 25%, p<0.001). The types/subtypes of dominant strains identified by SARI surveillance was almost always among dominant strains identified by the influenza like illness (ILI) surveillance system and influenza activity in both systems peaked at the same time. CONCLUSIONS: Data from China's first SARI sentinel surveillance system suggest that types/subtypes of circulating influenza strains and epidemic trends among SARI cases were similar to those among ILI cases.

[Clinical characteristics of hospitalized severe acute respiratory illnesses (SARI) in children and risk factors analysis of severe illness: results from SARI patients under 15-year-old of sentinel surveillance in 10 cities, China].

OBJECTIVE: To investigate clinical and epidemiological characteristics of hospitalized severe acute respiratory illnesses (SARI) patients under 15 years old registered by sentinel hospitals at 10 cities and risk factors analysis of severe illness. METHODS: The objects of this study were 2 937 SARI patients under 15 years old registered by sentinel surveillance in internal wards, pediatrics wards and intensive care units (ICU) of 10 sentinel hospitals in 10 cities during the period from December 2009 to June 2014. We also collected case report form (CRF) of them and their throat swabs for influenza testing. The inclusion criteria was hospitalized patients who were admitted by surveillance departments, registered by SARI surveillance system, under 15 years old, meeting SARI case definition and with complete CRF. Rank-sum test was used to compare the difference of age, the duration including from onset to admission, hospital stay and from onset to discharging/death between mild illness and severe illness. Chi-square test was used to compare the difference of demographic characteristics, influenza psoitive rate, vaccination rate of influenza, chronic medical conditions and clinical characteristics between mild illness and severe illness. Logistic regression was used to analysis risk factors associated with severe illness by two stratifications from SARI surveillance protocol (< 2 years old and ≥ 2 years old). RESULTS: Among 2 937 SARI patients under 15 years old, 97.7% (2 872/2 937) was mild illnesses, and 2.3% (65/2 937) was severe illnesses. 78.8% (2 315/2 937) was under 5 years old. The median ages of severe illness and mild illness were 0.4 and 2.0 years old (U = -6.23, P < 0.001). The proportions of severe illness and mild illness with at least one chronic medical condition were 32.3% (21/65) and 8.4% (240/2 872) (χ² = 45.03, P < 0.001). The positive rate of influenza virus was 6.5% (190/2 937), which was 6.5% (186/2 858) for mild illness and 6.2% (4/65) for severe illness (χ² = 0.08, P = 0.961). The proportion of seasonal influenza vaccination was 1.5% (42/2 853), which was 1.5% (42/2 788) for mild illness and higher than that for severe illness (0) (χ² = 6.09, P = 0.048). For under 2 years old patients, age < 11 months and with at least one chronic medical condition were risk factors for severe SARI illness, and the risk for SARI patients who was 12-23 months and without medical condition was 14.71 (5.35-40.44) and 5.61 (2.96-10.63). For ≥ 2 years old patients, age, with at least one chronic medical condition and seasonal influenza vaccination history have no association with severe illness, OR (95% CI) was 0.92 (0.80-1.05), 0.67 (0.09-5.05) and 0.85 (0.31-2.35), respectively. CONCLUSION: Most of SARI patients registered by 10 urban sentinel hospitals were patients under 5 years old. Age < 11 months and with at least chronic medical conditions were possible risk factors of severe illness of SARI patients.

Poultry market closures and human infection with influenza A(H7N9) virus, China, 2013-14.

Closure of live poultry markets was implemented in areas affected by the influenza virus A(H7N9) outbreak in China during winter, 2013-14. Our analysis showed that closing live poultry markets in the most affected cities of Guangdong and Zhejiang provinces was highly effective in reducing the risk for H7N9 infection in humans.

Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: a population-based study of laboratory-confirmed cases.

BACKGROUND: The novel influenza A H7N9 virus emerged recently in mainland China, whereas the influenza A H5N1 virus has infected people in China since 2003. Both infections are thought to be mainly zoonotic. We aimed to compare the epidemiological characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China so far. METHODS: An integrated database was constructed with information about demographic, epidemiological, and clinical variables of laboratory-confirmed cases of H7N9 (130 patients) and H5N1 (43 patients) that were reported to the Chinese Centre for Disease Control and Prevention until May 24, 2013. We described disease occurrence by age, sex, and geography, and estimated key epidemiological variables. We used survival analysis techniques to estimate the following distributions: infection to onset, onset to admission, onset to laboratory confirmation, admission to death, and admission to discharge. FINDINGS: The median age of the 130 individuals with confirmed infection with H7N9 was 62 years and of the 43 with H5N1 was 26 years. In urban areas, 74% of cases of both viruses were in men, whereas in rural areas the proportions of the viruses in men were 62% for H7N9 and 33% for H5N1. 75% of patients infected with H7N9 and 71% of those with H5N1 reported recent exposure to poultry. The mean incubation period of H7N9 was 3·1 days and of H5N1 was 3·3 days. On average, 21 contacts were traced for each case of H7N9 in urban areas and 18 in rural areas, compared with 90 and 63 for H5N1. The fatality risk on admission to hospital was 36% (95% CI 26-45) for H7N9 and 70% (56-83%) for H5N1. INTERPRETATION: The sex ratios in urban compared with rural cases are consistent with exposure to poultry driving the risk of infection--a higher risk in men was only recorded in urban areas but not in rural areas, and the increased risk for men was of a similar magnitude for H7N9 and H5N1. However, the difference in susceptibility to serious illness with the two different viruses remains unexplained, since most cases of H7N9 were in older adults whereas most cases of H5N1 were in younger people. A limitation of our study is that we compared laboratory-confirmed cases of H7N9 and H5N1 infection, and some infections might not have been ascertained. FUNDING: Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.

A clinical prediction rule for diagnosing human infections with avian influenza A(H7N9) in a hospital emergency department setting.

BACKGROUND: Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance. METHODS: Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping. RESULTS: In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96. CONCLUSIONS: A simple decision rule based on data readily obtainable in the setting of patients' first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement.

Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China.

BACKGROUND: Appropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of 'line lists' with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus. METHODS: We collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure. RESULTS: Demographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou. CONCLUSIONS: We demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.

Clinical and epidemiologic characteristics of respiratory syncytial virus infection among children aged <5 years, Jingzhou City, China, 2011.

Severe acute respiratory illness (SARI) surveillance began in Jingzhou City, China, in 2010. A subset of 511 children aged <5 years enrolled in the SARI study during 2011 were tested for influenza and noninfluenza respiratory viral infection by real-time reverse-transcription polymerase chain reaction. Respiratory syncytial virus (RSV) was most commonly detected. Children aged 12-23 and 24-60 months were equally likely to test positive for RSV. Although cases of RSV infection could be detected throughout the year, the greatest numbers were detected from autumn to early winter.

Influenza's Plummeting During the COVID-19 Pandemic: The Roles of Mask-Wearing, Mobility Change, and SARS-CoV-2 Interference.

Seasonal influenza activity typically peaks in the winter months but plummeted globally during the current coronavirus disease 2019 (COVID-19) pandemic. Unraveling lessons from influenza's unprecedented low profile is critical in informing preparedness for incoming influenza seasons. Here, we explored a country-specific inference model to estimate the effects of mask-wearing, mobility changes (international and domestic), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interference in China, England, and the United States. We found that a one-week increase in mask-wearing intervention had a percent reduction of 11.3%-35.2% in influenza activity in these areas. The one-week mobility mitigation had smaller effects for the international (1.7%-6.5%) and the domestic community (1.6%-2.8%). In 2020-2021, the mask-wearing intervention alone could decline percent positivity by 13.3-19.8. The mobility change alone could reduce percent positivity by 5.2-14.0, of which 79.8%-98.2% were attributed to the deflected international travel. Only in 2019-2020, SARS-CoV-2 interference had statistically significant effects. There was a reduction in percent positivity of 7.6 (2.4-14.4) and 10.2 (7.2-13.6) in northern China and England, respectively. Our results have implications for understanding how influenza evolves under non-pharmaceutical interventions and other respiratory diseases and will inform health policy and the design of tailored public health measures.

Attitudes Regarding Influenza Vaccination Among Public Health Workers during COVID-19 Pandemic - China, September 2022.

What is already known about this topic?: Public health workers (PHWs) were listed as a priority group recommended for influenza vaccination during the coronavirus disease 2019 (COVID-19) pandemic. Understanding the drivers of influenza vaccine hesitancy among PHWs can promote influenza vaccination in the COVID-19 pandemic. What is added by this report?: The study found that 10.7% of PHWs were hesitant to get an influenza vaccination. Drivers associated with vaccine hesitancy were assessed based on "3Cs model." The absence of a government or workplace requirement and concerns about vaccine safety were the biggest obstacles for PHWs to recommend influenza vaccination. What are the implications for public health practice?: Interventions are needed to improve PHWs' influenza vaccine coverage to prevent the co-circulation of influenza and COVID-19.

Healthcare Workers' Attitudes toward Influenza Vaccination: A Behaviour and Social Drivers Survey.

This study aimed to understand the intention and correlation of receiving and recommending influenza vaccine (IV) among healthcare workers (HCWs) in China during the 2022/2023 season using the behavior and social drivers (BeSD) tools. A self-administered electronic survey collected 17,832 participants on a media platform. We investigated the willingness of IV and used multivariate logistic regression analysis to explore its associated factors. The average scores of the 3Cs' model were compared by multiple comparisons. We also explored the factors that potentially correlated with recommendation willingness by partial regression. The willingness of IV was 74.89% among HCWs, and 82.58% of the participants were likely to recommend it to others during this season. Thinking and feeling was the strongest domain independently associated with willingness. All domains in BeSD were significantly different between the hesitancy and acceptance groups. Central factors in the 3Cs model were significantly different among groups (p < 0.01). HCWs' willingness to IV recommendation was influenced by their ability to answer related questions (r = 0.187, p < 0.001) after controlling for their IV willingness and perceived risk. HCWs' attitudes towards IV affect their vaccination and recommendation. The BeSD framework revealed the drivers during the decision-making process. Further study should classify the causes in detail to refine HCWs' education.

Transmission dynamics, border entry screening, and school holidays during the 2009 influenza A (H1N1) pandemic, China.

Pandemic influenza A (H1N1) 2009 virus spread rapidly around the world in 2009. We used multiple data sources from surveillance systems and specific investigations to characterize the transmission patterns of this virus in China during May-November 2009 and analyze the effectiveness of border entry screening and holiday-related school closures on transmission. In China, age distribution and transmission dynamic characteristics were similar to those in Northern Hemisphere temperate countries. The epidemic was focused in children, with an effective reproduction number of ≈1.2-1.3. The 8 days of national holidays in October reduced the effective reproduction number by 37% (95% credible interval 28%-45%) and increased underreporting by ≈20%-30%. Border entry screening detected at most 37% of international travel-related cases, with most (89%) persons identified as having fever at time of entry. These findings suggest that border entry screening was unlikely to have delayed spread in China by >4 days.

Epidemiological and etiological characteristics of mild hand, foot and mouth disease in children under 7 years old, Nanjing, China, 2010-2019.

BACKGROUND: Mild hand, foot and mouth disease (HFMD) cases make up a relatively high proportion of HFMD while have often been overlooked. This study aimed to investigate the epidemiological and etiological characteristics of mild HFMD in Nanjing. METHODS: Data on mild HFMD cases, during 2010-2019 in Nanjing, were collected from the China Information System for Disease Control and Prevention. This study mainly focused on mild cases aged < 7 years. Descriptive analysis was used to summarize epidemiological and etiological characteristics of mild cases. Flexible spatial scan statistic was used to detect spatial clusters of mild cases. RESULTS: A total of 175,339 mild cases aged < 7 years were reported, accounting for 94.4% of all mild cases. There was a higher average annual incidence of mild HFMD in children aged < 7 years (4,428 cases/100,000) compared with children aged ≥ 7 years (14 cases/100,000, P < 0.001), and especially children aged 1-year-old (7,908 cases/100,000). Mild cases showed semi-annual peaks of activity, including a major peak (April to July) and a minor peak (September to November). The average annual incidence was higher in males (5,040 cases/100,000) than females (3,755 cases/100,000). Based on the cumulative reported cases, the most likely cluster was detected, including Yuhuatai District, Jiangning District, Jiangbei new Area, and Pukou District. The annual distribution of enterovirus serotypes showed a significant difference. During 2010-2016, Enterovirus 71 (EV71), Coxsackievirus A16 (Cox A16), and other non-EV71/Cox A16 EVs, accounted for 29.1%, 34.6%, 36.3% of all the enterovirus test positive cases, respectively. Moreover, during 2017-2019, Cox A6, Cox A16, EV71, and other non-EV71/Cox A16/Cox A6 EVs, accounted for 47.3%, 32.5%, 10.7%, 9.5%, respectively. CONCLUSIONS: Children under 7 years old are at higher risk of mild HFMD. Regions with high risk are mainly concentrated in the areas surrounding central urban areas. Cox A16 and Cox A6 became the dominant serotypes and they alternated or were co-epidemic. Our findings could provide valuable information for improving the regional surveillance, prevention and control strategies of HFMD.

Characterization of influenza seasonality in China, 2010-2018: Implications for seasonal influenza vaccination timing.

BACKGROUND: Optimizing the timing of influenza vaccination based on regional temporal seasonal influenza illness patterns may make seasonal influenza vaccination more effective in China. METHODS: We obtained provincial weekly influenza surveillance data for 30 of 31 provinces in mainland China from the Chinese Center for Disease Control and Prevention for the years 2010-2018. Influenza epidemiological regions were constructed by clustering analysis. For each region, we calculated onset date, end date, and duration of seasonal influenza epidemics by the modified mean threshold method. To help identify initial vaccination target populations, we acquired weekly influenza surveillance data for four age groups (0-4, 5-18, 19-59, and ≥60 years) in each region and in 171 cities of wide-ranging size. We used linear regression analyses to explore the association of epidemic onset dates by age group, city, and epidemiological region and provide evidence for initial target populations for seasonal influenza vaccination. RESULTS: We determined that northern, mid, southwestern, southeast regions of mainland China have distinct seasonal influenza epidemic patterns. We found significant regional, temporal, and spatial heterogeneity of seasonal influenza epidemics. There were significant differences by age group and city size in the interval between epidemic onset in the city or age group and regional spread (epidemic lead time), with longer epidemic lead times for 5- to 18-year-old children and larger cities. CONCLUSIONS: Knowledge of influenza epidemic characteristics may help optimize local influenza vaccination timing and identify initial target groups for seasonal influenza vaccination in mainland China. Similar analyses may help inform seasonal influenza vaccination strategies in other regions and countries.