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Abstract Background Avian influenza A (H7N9) virus was first reported in mainland China in 2013, and alarming in 2016–17 due to the surge across a wide geographic area. Our study aimed to identify and explore the spatial and temporal variation across five epidemics to reinforce the epidemic prevention and control. Methods We collected spatial and temporal information about all laboratory-confirmed human cases of A (H7N9) virus infection reported in mainland China covering 2013–17 from the open source. The autocorrelation analysis and intensity of cases were used to analyse the spatial cluster while circular distribution method was used to analyse the temporal cluster. Results Across the five epidemics, a total of 1553 laboratory-confirmed human cases with A (H7N9) virus were reported in mainland China. The global Moran’s I index values of five epidemic were 0.610, 0.132, 0.308, 0.306, 0.336 respectively, among which the differences were statistically significant. The highest intensity was present in the Yangtze River Delta region and the Pearl River Delta region, and the range enlarged from the east of China to inner provinces and even the west of China across the five epidemics. The temporal clusters of the five epidemics were statistically significant, and the peak period was from the end of January to April with the first and the fifth epidemic later than the mean peak period. Conclusions Spatial and temporal clusters of avian influenza A (H7N9) virus in humans are obvious, moreover the regions existing clusters may enlarge across the five epidemics. Yangtze River Delta region and the Pearl River Delta region have the spatial cluster and the peak period is from January to April. The government should facilitate the tangible improvement for the epidemic preparedness according to the characteristics of spatial and temporal clusters of patients with avian influenza A (H7N9) virus.

Abstract Background With an increased incidence of viral zoonoses, there is an impetus to strengthen collaborations between public health, agricultural and environmental departments. This interdisciplinary cooperation, also known as the ‘One Health’ approach, has received significant support from various stakeholders. However, current efforts and policies still fall short of those needed for an effective One Health approach towards disease control and prevention. The avian-origin H7N9 influenza A virus outbreak in China serves as an ideal case study to emphasise this point. Discussion Here, we present the features and epidemiology of human infections with H7N9 influenza virus. At the early stages of the H7N9 epidemic, there was limited virus surveillance and limited prevention measures implemented in live poultry markets. As a result, zoonotic infections with H7N9 influenza viruses continued to enlarge in both numbers and geographic distribution. It was only after the number of human infections with H7N9 influenza virus spiked in the 5th wave of the epidemic that inter-departmental alliances were formed. This resulted in the rapid control of the number of human infections. We therefore further discuss the barriers that prevented the implementation of an effective One Health approach in China and what this means for other emerging, zoonotic viral diseases. Summary Effective implementation of evidence-based disease management approaches in China will result in substantial health and economic gains. The continual threat of avian influenza, as well as other emerging zoonotic viral infections, emphasizes the need to remove the barriers that prevent the effective implementation of One Health policies in disease management.

Abstract Background The emerging avian influenza A (H7N9) virus, a subtype of influenza viruses, was first discovered in March 2013 in China. Infected patients frequently present with pneumonia and acute respiratory disorder syndrome with high rates of intensive care unit admission and death. Neurological complications, such as Guillain–Barré syndrome(GBS), and intensive care unit-acquired weakness, including critical illness polyneuropathy and myopathy, have only rarely been reported previously. Case presentation In this study, we report on two Chinese patients with H7N9 severe pneumonia presenting neurological complications. These two patients had non-immune diseases prior to the onset of virus infection. A 56-year-old female patient (case 1) and a 78-year-old female patient (case 2) were admitted because of fever, cough, chest tightness and shortness of breath. These patients were confirmed to have H7N9 infection soon after admission followed by the development of acute respiratory distress syndrome and various severe bacterial and fungal infections. The case 1 patient was found to have muscle weakness in all extremities after withdrawing the mechanical ventilator, and the case 2 patient was found when withdrawing extracorporeal membrane oxygenation, both of these conditions prolonged ventilator-weaning time. Furthermore, the case 1 patient carried the H7N9 virus for a prolonged period, reaching 28 days, and both of them stayed in the hospital for more than two months. A clinical diagnosis of intensive care unit-acquired weakness could be confirmed. However, based on results from electrophysiological testing and needle electromyography of these 2 patients, it is difficult to differentiate critical illness polyneuropathy from GBS, since no lumbar puncture or muscle and nerve biopsy were conducted during hospitalization. Following a long-term comprehensive treatment, the patients’ neurological condition improved gradually. Conclusions Although there is great improvement in saving severe patients’ lives from fatal respiratory and blood infections, it is necessary to pay sufficient attention and to use more methods to differentiate GBS from intensive care unit-acquired weakness. This unusual neurological complication could result in additional complications including ventilator associated pneumonia, prolonged hospital stay and then would further increase the death rate, and huge costs.

Abstract Background During the fifth wave of human H7N9 infections, a novel highly pathogenic (HP) H7N9 variant emerged with an insertion of multiple basic amino acids in the HA cleavage site. Moreover, a neuraminidase inhibitor (NAI) resistance (R292K in NA) mutation was found in H7N9 isolates from humans, poultry and the environment. In this study, we set out to develop and validate a multiplex quantitative reverse transcript polymerase chain reaction (qRT-PCR) to simultaneously detect the presence of H7N9 and further identify the HP and NAI-resistance mutations. Methods A quadruple qRT-PCR to simultaneously detect the presence of H7N9 and further identify the HP and NAI-resistance mutations was designed based on the analyses of the HA and NA genes of H7N9. This assay was further tested for specificity and sensitivity, and validated using clinical samples. Results The assay was highly specific and able to detect low pathogenic (LP)- or HP-H7N9 with/without the NAI-resistance mutation. The detection limit of the assay was determined to be 50 genome-equivalent copies and 2.8 × 10− 3 50% tissue culture infectious doses (TCID50) of live H7N9 per reaction. Clinical validation was confirmed by commercial kits and Sanger sequencing with ten clinical samples. Conclusions We developed and validated a rapid, single-reaction, one-step, quadruple real-time qRT-PCR to simultaneously detect the presence of H7N9 and further identify the HP- and NAI-resistance strains with excellent performance in specificity and sensitivity. This assay could be used to monitor the evolution of H7N9 viruses in the laboratory, field and the clinic for early-warning and the prevention of H7N9 infections.

Background: H7N9 human cases were first detected in mainland China in March 2013. Circulation of this virus has continued each year shifting to typical winter months. We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation. Methods: The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015. We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation. Results: In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively. The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves. Most reported cases were among men in all three waves. There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08). There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves. A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively). There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation. Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission. Conclusion: Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus. Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus. [ABSTRACT FROM AUTHOR]

Background H7N9 posed potentially serious health challenges for Chinese society. The previous SARS outbreak in this country was accompanied by contradictory information, while worries about wide-spread influenza led to discrimination worldwide. Early understanding of public threat perceptions is therefore important for effective public health communication and intervention. Methods We interviewed 1011 respondents by phone two weeks after the first case. Questions examined risk awareness and media use, beliefs about the emergence of the threat and those most at risk, anxiety about infection and preventive and avoidant behaviours. Results Results demonstrate moderate levels of anxiety but relatively high levels of trust towards government officials. Threat emergence was associated with hygiene levels, temperature change, floating pigs in the Huangpu River and migration to the city. Anxiety predicted both recommended and non-recommended behavioural changes. Conclusions Comparatively high levels of trust in Chinese government advice about H7N9 contrast positively with previous pandemic communications in China. Anxiety helped drive both recommended and non-recommended behaviours, with potentially important economic and social implications. This included evidence of 'othering' of those associated with the threat (e.g. migrants). Findings emphasise the need to manage public communications early during new influenza outbreaks. [ABSTRACT FROM AUTHOR]

Background: Both high and low pathogenic subtype A avian influenza remain ongoing threats to the commercial poultry industry globally. The emergence of a novel low pathogenic H7N9 lineage in China presents itself as a new concern to both human and animal health and may necessitate additional surveillance in commercial poultry operations in affected regions. Methods: Sampling data was simulated using a mechanistic model of H7N9 influenza transmission within commercial poultry barns together with a stochastic observation process. Parameters were estimated using maximum likelihood. We assessed the probability of detecting an outbreak at time of slaughter using both real-time polymerase chain reaction (rt-PCR) and a hemagglutinin inhibition assay (HI assay) before considering more intense sampling prior to slaughter. The day of virus introduction and R0 were estimated jointly from weekly flock sampling data. For scenarios where R0 was known, we estimated the day of virus introduction into a barn under different sampling frequencies. Results: If birds were tested at time of slaughter, there was a higher probability of detecting evidence of an outbreak using an HI assay compared to rt-PCR, except when the virus was introduced <2 weeks before time of slaughter. Prior to the initial detection of infection Nsample = 50 (1%) of birds were sampled on a weekly basis once, but after infection was detected, Nsample = 2000 birds (40%) were sampled to estimate both parameters. We accurately estimated the day of virus introduction in isolation with weekly and 2-weekly sampling. Conclusions: A strong sampling effort would be required to infer both the day of virus introduction and R0. Such a sampling effort would not be required to estimate the day of virus introduction alone once R0 was known, and sampling Nsample = 50 of birds in the flock on a weekly or 2 weekly basis would be sufficient. [ABSTRACT FROM AUTHOR]

Background: A novel avian influenza A (H7N9) virus emerged in eastern China in February 2013. 413 confirmed human cases, including 157 deaths, have been recorded as of July 31, 2014. Methods: Clinical specimens, including throat swabs, sputum or tracheal aspirates, etc., were obtained from patients exhibiting influenza-like illness (ILIs), especially from those having pneumonia and a history of occupational exposure to poultry and wild birds. RNA was extracted from these samples and a multiplex one-step real-time RT-PCR assay was developed to specifically detect the influenza A virus (FluA). PCR primers targeted the conserved M and Rnase P (RP) genes, as well as the hemagglutinin and neuraminidase genes of the H7N9 virus. Results: The multiplex assay specifically detected the avian H7N9 virus, and no cross-reaction with other common respiratory pathogens was observed. The detection limit of the assay was approximately 0.05 50% tissue culture infective doses (TCID50), or 100 copies per reaction. Positive detection of the H7N9 virus in sputum/tracheal aspirates was higher than in throat swabs during the surveillance of patients with ILIs. Additionally, detection of the matrix (M) and Rnase P genes aided in the determination of the novel avian H7N9 virus and ensured the quality of the clinical samples. Conclusions: These results demonstrate that the multiplex assay detected the novel avian H7N9 virus with high specificity and sensitivity, which is essential for the early diagnosis and treatment of infected patients. [ABSTRACT FROM AUTHOR]

Background: Selective prophylactic decontamination of the digestive tract is a strategy for the prevention of secondary nosocomial infection in patients with avian influenza virus subtype H7N9 infection. Our aim was to summarize the effectiveness of these therapies in re-establishing a stable and diverse microbial community, and reducing secondary infections. Methods: Comprehensive therapies were dependent on the individual clinical situation of subjects, and were divided into antiviral treatment, microbiota-targeted therapies, including pro- or pre-biotics and antibiotic usage, and immunotherapy. Quantitative polymerase chain reaction and denaturing gradient gel electrophoresis (DGGE) were used for real-time monitoring of the predominant intestinal microbiome during treatment. Clinical information about secondary infection was confirmed by analyzing pathogens isolated from clinical specimens. Results: Different antibiotics had similar effects on the gut microbiome, with a marked decrease and slow recovery of the Bifidobacterium population. Interestingly, most fecal microbial DGGE profiles showed the relative stability of communities under the continual suppression of the same antibiotics, and significant changes when new antibiotics were introduced. Moreover, we found no marked increase in C-reactive protein, and no cases of bacteremia or pneumonia, caused by probiotic use in the patients, which confirmed that the probiotics used in this study were safe for use in patients with H7N9 infection. Approximately 72% of those who subsequently suffered exogenous respiratory infection by Candida species or multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae were older than 60 years. The combination of probiotics and prebiotics with antibiotics seemed to fail in these patients. Conclusions: Elderly patients infected with the influenza A (H7N9) virus are considered a high-risk group for developing secondary bacterial infection. Microbiota restoration treatment reduced the incidence of enterogenous secondary infection, but not exogenous respiratory infection. The prophylactic effects of microbiota restoration strategies for secondary infection were unsatisfactory in elderly and critically ill patients. [ABSTRACT FROM AUTHOR]

Background: With an increased incidence of viral zoonoses, there is an impetus to strengthen collaborations between public health, agricultural and environmental departments. This interdisciplinary cooperation, also known as the 'One Health' approach, has received significant support from various stakeholders. However, current efforts and policies still fall short of those needed for an effective One Health approach towards disease control and prevention. The avian-origin H7N9 influenza A virus outbreak in China serves as an ideal case study to emphasise this point.Discussion: Here, we present the features and epidemiology of human infections with H7N9 influenza virus. At the early stages of the H7N9 epidemic, there was limited virus surveillance and limited prevention measures implemented in live poultry markets. As a result, zoonotic infections with H7N9 influenza viruses continued to enlarge in both numbers and geographic distribution. It was only after the number of human infections with H7N9 influenza virus spiked in the 5th wave of the epidemic that inter-departmental alliances were formed. This resulted in the rapid control of the number of human infections. We therefore further discuss the barriers that prevented the implementation of an effective One Health approach in China and what this means for other emerging, zoonotic viral diseases. Effective implementation of evidence-based disease management approaches in China will result in substantial health and economic gains. The continual threat of avian influenza, as well as other emerging zoonotic viral infections, emphasizes the need to remove the barriers that prevent the effective implementation of One Health policies in disease management. [ABSTRACT FROM AUTHOR]

Background: H7N9 human cases were first detected in mainland China in March 2013. Circulation of this virus has continued each year shifting to typical winter months. We compared the clinical and epidemiologic characteristics for the first three waves of virus circulation., Methods: The first wave was defined as reported cases with onset dates between March 31-September 30, 2013, the second wave was defined as October 1, 2013-September 30, 2014 and the third wave was defined as October 1, 2014-September 30, 2015. We used simple descriptive statistics to compare characteristics of the three distinct waves of virus circulation., Results: In mainland China, 134 cases, 306 cases and 219 cases were detected and reported in first three waves, respectively. The median age of cases was statistically significantly older in the first wave (61 years vs. 56 years, 56 years, p < 0.001) compared to the following two waves. Most reported cases were among men in all three waves. There was no statistically significant difference between case fatality proportions (33, 42 and 45%, respectively, p = 0.08). There were no significant statistical differences for time from illness onset to first seeking healthcare, hospitalization, lab confirmation, initiation antiviral treatment and death between the three waves. A similar percentage of cases in all waves reported exposure to poultry or live poultry markets (87%, 88%, 90%, respectively). There was no statistically significant difference in the occurrence of severe disease between the each of the first three waves of virus circulation. Twenty-one clusters were reported during these three waves (4, 11 and 6 clusters, respectively), of which, 14 were considered to be possible human-to-human transmission., Conclusion: Though our case investigation for the first three waves found few differences between the epidemiologic and clinical characteristics, there is continued international concern about the pandemic potential of this virus. Since the virus continues to circulate, causes more severe disease, has the ability to mutate and become transmissible from human-to-human, and there is limited natural protection from infection in communities, it is critical that surveillance systems in China and elsewhere are alert to the influenza H7N9 virus.