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Objective: To investigate the epidemiological characteristics of human infections with avian influenza A (H7N9) in China and to provide scientific evidence for the adjustment of preventive strategy and control measures., Methods: Demographic and epidemiologic information on human cases were collected from both reported data of field epidemiological investigation and the reporting system for infectious diseases., Results: A total of 433 cases including 163 deaths were reported in mainland China before June 4, 2014. Two obvious epidemic peaks were noticed, in March to April, 2013 and January to February, 2014. Confirmed cases emerged in 14 areas of China. Five provinces, including Zhejiang, Guangdong, Jiangsu, Shanghai, and Hunan, reported about 85% of the total cases. Median age of the confirmed cases was 58 years (range, 1-91), with 70% as males. Of the 418 cases with available data, 87% had ever exposed to live poultry or contaminated environments. 14 clusters were identified but human to human transmission could not be ruled out in 9 clusters., Conclusion: Human infections with avian influenza A (H7N9) virus showed the characteristics of obvious seasonal distribution, with certain regional clusters. The majority of confirmed cases were among the elderly, with more males seen than the females. Data showed that main source of infection was live poultry and the live poultry market had played a significant role in the transmission of the virus.

Background: The majority of human cases of novel avian influenza A(H7N9), which emerged in China in spring 2013, include reported exposure to poultry. However, specific host and exposure risk factors for disease are unknown, yet critical to design prevention measures., Methods: In April-June 2013, we conducted a case-control study in 8 Chinese provinces. Patients with laboratory-confirmed A(H7N9) (n = 89) were matched by age, sex, and neighborhood to controls (n = 339). Subjects completed a questionnaire on medical history and potential exposures, including poultry markets and other poultry exposure. We used conditional logistic regression to calculate matched and adjusted odds ratios (ORs) for the association of A(H7N9) virus infection with potential risk factors., Results: Fifty-five percent of patients compared with 31% of controls reported any contact with poultry (matched OR [mOR], 7.8; 95% confidence interval [CI], 3.3-18.8). Sixty-seven percent of patients compared with 35% of controls visited a live poultry market (mOR, 5.4; CI, 3.0-9.7). Visiting live poultry markets increased risk of infection even after adjusting for poultry contact and other confounders (adjusted OR, 3.4; CI, 1.8-6.7). Backyard poultry were not associated with increased risk; 14% of cases did not report any poultry exposure or market visit. Obesity (mOR, 4.7; CI, 1.8-12.4), chronic obstructive pulmonary disease (mOR, 2.7; CI, 1.1-6.9), and immunosuppressive medications (mOR, 9.0; CI, 1.7-47.2) were associated with A(H7N9) disease., Conclusion: Exposures to poultry in markets were associated with A(H7N9) virus infection, even without poultry contact. China should consider permanently closing live poultry markets or aggressively pursuing control measures to prevent spread of this emerging pathogen., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Problem: In 2003, China's handling of the early stages of the epidemic of severe acute respiratory syndrome (SARS) was heavily criticized and generally considered to be suboptimal., Approach: Following the SARS outbreak, China made huge investments to improve surveillance, emergency preparedness and response capacity and strengthen public health institutions. In 2013, the return on these investments was evaluated by investigating China's early response to the emergence of avian influenza A(H7N9) virus in humans., Local Setting: Clusters of human infection with a novel influenza virus were detected in China - by national surveillance of pneumonia of unknown etiology - on 26 February 2013., Relevant Changes: On 31 March 2013, China notified the World Health Organization (WHO) of the first recorded human infections with A(H7N9) virus. Poultry markets - which were rapidly identified as a major source of transmission of A(H7N9) to humans - were closed down in the affected areas. Surveillance in humans and poultry was heightened and technical guidelines were quickly updated and disseminated. The health authorities collaborated with WHO in risk assessments and risk communication. New cases were reported promptly and publicly., Lessons Learnt: The relevant infrastructures, surveillance systems and response capacity need to be strengthened in preparation for future emergencies caused by emerging or existing disease threats. Results of risk assessments and other data should be released promptly and publicly and such release should not jeopardize future publication of the data in scientific journals. Coordination between public health and veterinary services would be stronger during an emergency if these services had already undertaken joint preparedness planning.

Background: The first identified cases of avian influenza A(H7N9) virus infection in humans occurred in China during February and March 2013. We analyzed data obtained from field investigations to describe the epidemiologic characteristics of H7N9 cases in China identified as of December 1, 2013., Methods: Field investigations were conducted for each confirmed case of H7N9 virus infection. A patient was considered to have a confirmed case if the presence of the H7N9 virus was verified by means of real-time reverse-transcriptase-polymerase-chain-reaction assay (RT-PCR), viral isolation, or serologic testing. Information on demographic characteristics, exposure history, and illness timelines was obtained from patients with confirmed cases. Close contacts were monitored for 7 days for symptoms of illness. Throat swabs were obtained from contacts in whom symptoms developed and were tested for the presence of the H7N9 virus by means of real-time RT-PCR., Results: Among 139 persons with confirmed H7N9 virus infection, the median age was 61 years (range, 2 to 91), 71% were male, and 73% were urban residents. Confirmed cases occurred in 12 areas of China. Nine persons were poultry workers, and of 131 persons with available data, 82% had a history of exposure to live animals, including chickens (82%). A total of 137 persons (99%) were hospitalized, 125 (90%) had pneumonia or respiratory failure, and 65 of 103 with available data (63%) were admitted to an intensive care unit. A total of 47 persons (34%) died in the hospital after a median duration of illness of 21 days, 88 were discharged from the hospital, and 2 remain hospitalized in critical condition; 2 patients were not admitted to a hospital. In four family clusters, human-to-human transmission of H7N9 virus could not be ruled out. Excluding secondary cases in clusters, 2675 close contacts of case patients completed the monitoring period; respiratory symptoms developed in 28 of them (1%); all tested negative for H7N9 virus., Conclusions: Most persons with confirmed H7N9 virus infection had severe lower respiratory tract illness, were epidemiologically unrelated, and had a history of recent exposure to poultry. However, limited, nonsustained human-to-human H7N9 virus transmission could not be ruled out in four families.

Background: Published data on influenza in severe acute respiratory infection (SARI) patients are limited. We conducted SARI surveillance in central China and estimated hospitalization rates of SARI attributable to influenza by viral type/subtype., Methods: Surveillance was conducted at four hospitals in Jingzhou, China from 2010 to 2012. We enrolled hospitalized patients who had temperature ≥37·3°C and at least one of: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. A nasopharyngeal swab was collected from each case-patient within 24 hours of admission for influenza testing by real-time reverse transcription PCR., Results: Of 17 172 SARI patients enrolled, 90% were aged <15 years. The median duration of hospitalization was 5 days. Of 16 208 (94%) SARI cases tested, 2057 (13%) had confirmed influenza, including 1427 (69%) aged <5 years. Multiple peaks of influenza occurred during summer, winter, and spring months. Influenza was associated with an estimated 115 and 142 SARI hospitalizations per 100 000 during 2010-2011 and 2011-2012 [including A(H3N2): 55 and 44 SARI hospitalizations per 100 000; pandemic A(H1N1): 33 SARI hospitalizations per 100 000 during 2010-2011; influenza B: 26 and 98 hospitalizations per 100 000], with the highest rate among children aged 6-11 months (3603 and 3805 hospitalizations per 100 000 during 2010-2011 and 2011-2012, respectively)., Conclusions: In central China, influenza A and B caused a substantial number of hospitalizations during multiple periods each year. Our findings strongly suggest that young children should be the highest priority group for annual influenza vaccination in China., (© 2013 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China. A total of 132 confirmed cases and 39 deaths have been reported. Most patients presented with severe pneumonia and acute respiratory distress syndrome. Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (α2,3-linked sialic acid) and human-type (α2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1β, MCP-1, IL-6, IL-8 and IFN-α were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.

Salmonella is one of the most common foodborne pathogens in humans. Laboratory-based surveillance for non-typhoidal Salmonella infection was conducted in Guangdong Province, China to improve understanding about the disease burden and detection of dispersed outbreaks. Salmonella isolated from patients with diarrhea were sent from 16 sentinel hospitals to local public health laboratories for confirmation, serotyping, antimicrobial susceptibility testing, and pulsed-field gel electrophoresis (PFGE). PFGE patterns were analyzed to identify clusters representing potential outbreaks. Between September 2009 and October 2010, 352 (4%) Salmonella isolates were obtained from 9167 stool specimens. Salmonella enterica serotype Typhimurium (45%) and Salmonella enterica serotype Enteritidis (13%) were the most common serotypes, and multidrug resistance was high, especially in Salmonella Typhimurium isolates. PFGE patterns of obtained Salmonella isolates were found to be diverse, but a unique PFGE pattern comprising 53 Salmonella Typhimurium isolates were found to occur almost exclusively in infants. Epidemiologic studies are ongoing to determine whether a common exposure is the source of the Salmonella Typhimurium strain frequently isolated from infants.

Objective: To estimate influenza-associated mortality in urban China., Methods: Influenza-associated excess mortality for the period 2003-2008 was estimated in three cities in temperate northern China and five cities in the subtropical south of the country. The estimates were derived from models based on negative binomial regressions, vital statistics and the results of weekly influenza virus surveillance., Findings: Annual influenza-associated excess mortality, for all causes, was 18.0 (range: 10.9-32.7) deaths per 100,000 population in the northern cities and 11.3 (range: 7.3-17.8) deaths per 100,000 in the southern cities. Excess mortality for respiratory and circulatory disease was 12.4 (range: 7.4-22.2) and 8.8 (range: 5.5-13.6) deaths per 100,000 people in the northern and southern cities, respectively. Most (86%) deaths occurred among people aged ≥ 65 years. Influenza-associated excess mortality was higher in B-virus-dominant seasons than in seasons when A(H3N2) or A(H1N1) predominated, and more than half of all influenza-associated mortality was associated with influenza B virus., Conclusion: Between 2003 and 2008, seasonal influenza, particularly that caused by the influenza B virus, was associated with substantial mortality in three cities in the temperate north of China and five cities in the subtropical south of the country.

Background: Glucocorticoids increase the risk of developing critical disease from viral infections. However, primary care practitioners in China use them as antipyretics, potentially exposing hundreds of millions to this risk., Methods: We enrolled all patients with confirmed pandemic influenza A (pH1N1) virus infection aged ≥3 years with available medical records at 4 Shenyang City hospitals from 20 October to 30 November 2009. A critical patient was any confirmed, hospitalized pH1N1 patient who developed ≥1 of the following: death, respiratory failure, septic shock, failure or insufficiency of ≥2 nonpulmonary organs, mechanical ventilation, or ICU admission. In a retrospective cohort study, we evaluated the risk of developing critical illness in relation to early (≤72 hours of influenza-like illness [ILI] onset) glucocorticoids treatment., Results: Of the 83 hospitalized case-patients, 46% developed critical illness, 17% died, and 37% recovered and were discharged. Critically ill and other patients did not differ by underlying conditions and severity, median temperature at first clinic visit, and other measured risk factors. Of 17 patients who received early glucocorticoid treatment, 71% subsequently developed critical disease compared with 39% of 66 patients who received late (>72 hours) or no glucocorticoid treatment (RR(M-H) = 1.8, 95% CI = 1.2-2.8, after adjusting for 2 summary variables; ie, presence of underlying diseases and presence of underlying risk factors). Proportional hazards modeling showed that use of glucocorticoids tripled the hazard of developing critical disease (hazard ratio [HR] = 2.9, 95% CI = 1.3-6.2, after adjusting for the same summary variables)., Conclusions: Early use of parenteral glucocorticoids therapy for fever reduction and pneumonia prevention increases the risk for critical disease or death from pH1N1 infection. We recommend that guidelines on glucocorticoid use be established and enforced.

Foodborne infections are an important public health problem in China. In 2008, we conducted surveillance for laboratory-confirmed nontyphoidal Salmonella to monitor trends for this infection in China and to build capacity for rapid detection and response to foodborne outbreaks. Salmonella isolates from patients with diarrhea were sent from hospitals to local public health laboratories for confirmation, serotyping, and antimicrobial susceptibility testing. A total of 126 hospitals in 44 cities and counties from 8 provinces provided isolates and epidemiologic data for analysis. Of 23,140 stool specimens submitted to clinical laboratories, 662 (3%) grew Salmonella enterica. Salmonella were most commonly detected between April and October. The median age of infected patients was 27 years; 34% of infections occurred in patients <5 years old. Of the 662 isolates, we found 73 serotypes, of which serotype Enteritidis (31%) and serotype Typhimurium (26%) were the most common. The prevalence of resistance was high for clinically important antimicrobial agents, including ampicillin (41%) and ciprofloxacin (6%). More than 60% of isolates, including 35% of all Typhimurium, were resistant to three or more antimicrobial agents. In this first multiprovince surveillance report of laboratory-confirmed Salmonella infections in China, we found that Enteritidis and Typhimurium are the most common serotypes and that efforts to reduce antimicrobial resistance among Salmonella in China are needed. Although no outbreaks were detected using this system, efforts to improve this system's capacity to do so are underway.

Background: Data on risk factors for severe outcomes from 2009 pandemic influenza A (H1N1) virus infection are limited outside of developed countries., Methods: We reviewed medical charts to collect data from patients hospitalized with laboratory-confirmed 2009 H1N1 infection who were identified across China during the period from September 2009 through February 2010, and we analyzed potential risk factors associated with severe illness (defined as illness requiring intensive care unit admission or resulting in death)., Results: Among 9966 case patients, the prevalence of chronic medical conditions (33% vs 14%), pregnancy (15% vs 7%), or obesity (19% vs 14%) was significantly higher in those patients with severe illness than it was in those with less severe disease. In multivariable analyses, among nonpregnant case patients aged ≥ 2 years, having a chronic medical condition significantly increased the risk of severe outcome among all age groups, and obesity was a risk factor among those <60 years of age. The risk of severe illness among pregnant case patients was significantly higher for those in the second and third trimesters. The risk of severe illness was increased when oseltamivir treatment was initiated ≥ 5 days after illness onset (odds ratio, 1.42; 95% confidence interval, 1.20-1.67). For persons <60 years of age, the prevalence of obesity among case patients with severe illness was significantly greater than it was among those without severe illness or among the general population., Conclusions: Risk factors for severe 2009 H1N1 illness in China were similar to those observed in developed countries, but there was a lower prevalence of chronic medical conditions and a lower prevalence of obesity. Obesity was a risk factor among case patients < 60 years of age. Early initiation of oseltamivir treatment was most beneficial, and there was an increased risk of severe disease when treatment was started ≥ 5 days after illness onset.

Objective: To describe the clinical features and effectiveness of oseltamivir on disease progression and viral RNA shedding in patients with mild pandemic 2009 influenza A(H1N1) virus infection., Design: Opportunistic retrospective review of medical charts of patients with confirmed 2009 H1N1 identified through the national surveillance system in China from May to July 2009., Setting: Under coordination of the Ministry of Health, local health departments were asked to collect medical records of confirmed patients and send them to the Chinese Centre for Disease Control and Prevention on a voluntary basis as part of the public health response. Population 1291 patients with confirmed 2009 H1N1 infection and available data for chart review., Main Outcome Measures: Demographic characteristics, comorbidities, symptoms and signs, laboratory tests, findings on chest radiography, antiviral treatment, duration of fever, and duration of viral RNA shedding., Results: The median age of 1291 patients was 20 years (interquartile range 12-26); 701 (54%) were male. The most common symptoms were fever (820, 64%), cough (864, 67%), sore throat (425, 33%), sputum (239, 19%), and rhinorrhoea (228, 18%). Of 920 patients who underwent chest radiography, 110 (12%) had abnormal findings consistent with pneumonia. Some 983 (76%) patients were treated with oseltamivir from a median of the third day of symptoms (2-4). No patients required admission to the intensive care unit or mechanical ventilation. 2009 H1N1 was shed from one day before onset of symptoms to up to eight days after onset in most (91%) patients, with a median of 5 (3-6) days of shedding after onset. Treatment with oseltamivir significantly protected against subsequent development of radiographically confirmed pneumonia (odds ratio 0.12, 95% confidence interval 0.08 to 0.18), and treatment started within two days of symptom onset reduced the duration of fever and viral RNA shedding., Conclusions: Chinese patients with 2009 H1N1 infection predominantly presented with features of uncomplicated, self limiting acute respiratory illness. 2009 H1N1 might be shed longer than seasonal influenza virus. Treatment with oseltamivir was associated with a significantly reduced development of radiographically confirmed pneumonia and a shorter duration of fever and viral RNA shedding. Though these patients benefited from treatment, the findings should be interpreted with caution as the study was retrospective and not all patients underwent chest radiography.

The human respiratory tract is a major site of avian influenza A(H5N1) infection. However, many humans infected with H5N1 present with gastrointestinal tract symptoms, suggesting that this may also be a target for the virus. In this study, we demonstrated that the human gut expresses abundant avian H5N1 receptors, is readily infected ex vivo by the H5N1 virus, and produces infectious viral particles in organ culture. An autopsy colonic sample from an H5N1-infected patient showed evidence of viral antigen expression in the gut epithelium. Our results provide the first evidence, to our knowledge, that H5N1 can directly target human gut tissues.

Background: In China, 30 human cases of avian influenza A (H5N1) virus infection were identified through July 2008. We conducted a retrospective case-control study to identify risk factors for influenza H5N1 disease in China., Methods: A questionnaire about potential influenza H5N1 exposures was administered to 28 patients with influenza H5N1 and to 134 randomly selected control subjects matched by age, sex, and location or to proxies. Conditional logistic regression analyses were performed., Results: Before their illness, patients living in urban areas had visited wet poultry markets, and patients living in rural areas had exposure to sick or dead backyard poultry. In multivariable analyses, independent risk factors for influenza H5N1 were direct contact with sick or dead poultry (odds ratio [OR], 506.6 [95% confidence interval {CI}, 15.7-16319.6]; P<.001), indirect exposure to sick or dead poultry (OR, 56.9 [95% CI, 4.3-745.6]; P=.002), and visiting a wet poultry market (OR, 15.4 [95% CI, 3.0-80.2]; P=.001)., Conclusions: To prevent human influenza H5N1 in China, the level of education about avoiding direct or close exposures to sick or dead poultry should be increased, and interventions to prevent the spread of influenza H5N1 at live poultry markets should be implemented.

Objective: To investigate the application of prospective permutation space-time scan statistic in the early detection of infectious disease outbreaks., Methods: The prospective permutation space-time scan statistic was tested by mimicking daily prospective analyses of measles data of Chengdu city in 2005., Results: The prospective space-time permutation scan statistic could timely detect the outbreaks that start locally., Conclusion: The early warning system based on prospective space-time permutation scan statistic and geographical information system could work efficiently.

Objective: To study the safety and immunogenicity of the measles-mumps-rubella combined vaccine (MMR) produced by Beijing Biological Product Institute., Methods: Children aged 10-12 years, 2-2.5 years and 8-12 months were selected to be vaccinated with Beijing MMR vaccine (test vaccine). Other groups of children with similar nature were vaccinated with measles vaccine, mumps vaccine and rubella vaccine while using imported MMR vaccine (control vaccine) as controls., Results: The safety of the Beijing MMR vaccine was confirmed after vaccinating 32 children above 2 years old. Among 104 children of 8-12 months were vaccinated with Beijing MMR vaccine, only 6.7% of the children had transient fever and 1.9% had signs of rashes but with no other signs observed. The positive seroconversion rates of measles, rubella and mumps anti-HI were 100%, 100% and 85.7% respectively. GMT also showed high lever., Conclusion: The MMR vaccine (Beijing) had good safety and immunogenicity which might be used to be the bases enhance immunization of measles.