Risk assessment of the newly emerged H7N9 avian influenza viruses.

Since the first human case in 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1500 human infections with a mortality rate of approximately 40%. Despite large-scale poultry vaccination regimes across China, the H7N9 AIVs continue to persist and evolve rapidly in poultry. Recently, several strains of H7N9 AIVs have been isolated and shown the ability to escape vaccine-induced immunity. To assess the zoonotic risk of the recent H7N9 AIV isolates, we rescued viruses with hemagglutinin (HA) and neuraminidase (NA) from these H7N9 AIVs and six internal segments from PR8 virus and characterized their receptor binding, pH of fusion, thermal stability, plaque morphology and in ovo virus replication. We also assessed the cross-reactivity of the viruses with human monoclonal antibodies (mAbs) against H7N9 HA and ferret antisera against H7N9 AIV candidate vaccines. The H7N9 AIVs from the early epidemic waves had dual sialic acid receptor binding characteristics, whereas the more recent H7N9 AIVs completely lost or retained only weak human sialic acid receptor binding. Compared with the H7N9 AIVs from the first epidemic wave, the 2020/21 viruses formed larger plaques in Madin-Darby canine kidney (MDCK) cells and replicated to higher titres in ovo, demonstrating increased acid stability but reduced thermal stability. Further analysis showed that these recent H7N9 AIVs had poor cross-reactivity with the human mAbs and ferret antisera, highlighting the need to update the vaccine candidates. To conclude, the newly emerged H7N9 AIVs showed characteristics of typical AIVs, posing reduced zoonotic risk but a heightened threat for poultry.

Benefit-cost analysis of a H7N9 vaccination program in poultry in Guangxi, China.

China launched a H7N9 vaccination program in poultry, starting from the Guangxi and Guangdong provinces in July 2017, followed by other provinces in September 2017, as a response to a steep increase of H7N9 influenza human infections from September 2016. Since then, H5-H7 bivalent vaccine has been used in the nationwide avian influenza compulsory vaccination program to replace the existing H5N1 vaccine. However, the economic returns of the H7N9 vaccination program in China have never been adequately assessed. This study was designed to evaluate the economic value of the H7N9 vaccination program in Guangxi by assessing the benefits and costs of the program compared to not vaccinating against H7N9. A benefit-cost analysis (BCA) was undertaken to evaluate the adoption of a vaccination program against H7N9 in each of three consecutive years from July 2017 to June 2020 with the baseline scenario (the absence of H7N9 vaccination in the 12-month period July 2016 to June 2017). Both animal and public health perspectives were included in the BCA framework and took account of both the private and public sectors. Benefit-Cost Ratio (BCR) of the three-year H7N9 vaccination program was 18.6 (90 %PI: 15.4; 21.8), and total Net Present Values reached to CNY 1.63 billion (90 %PI: 1.37 billion; 1.89 billion). The extra revenue generated by the yellow broiler industry comprised 93.8 % of the total benefits after adoption of H7N9 vaccination program in Guangxi. While cost-savings in public health and animal health expenditure avoided were 3.6 % and 2.6 %, respectively. Total costs arising from adoption of the revised vaccination program over the three years were CNY 12.46 million (90 %PI: 11.49 million; 14.14 million), CNY 34.87 million (90 %PI: 31.88 million; 40.06 million), and CNY 44.28 million (90 %PI: 39.66 million; 52.27 million), respectively. Sensitivity analysis found the yellow broiler wholesale prices contributed 97.7 % of the variance of the total NPV of three vaccination years. The study results demonstrate the significant economic advantage of implementing a vaccination program against H7N9 in Guangxi. It also offers a new set of evidence to China's H7N9 vaccination policy and debates around economic values of conducting routine avian influenza vaccination.

Spatial and temporal analysis of human infection with the avian influenza A (H7N9) virus in China and research on a risk assessment agent-based model.

OBJECTIVES: From 2013 to 2017, the avian influenza A (H7N9) virus frequently infected people in China, which seriously affected the public health of society. This study aimed to analyze the spatial characteristics of human infection with the H7N9 virus in China and assess the risk areas of the epidemic. METHODS: Using kernel density estimation, standard deviation ellipse analysis, spatial and temporal scanning cluster analysis, and Pearson correlation analysis, the spatial characteristics and possible risk factors of the epidemic were studied. Meteorological factors, time (month), and environmental factors were combined to establish an epidemic risk assessment proxy model to assess the risk range of an epidemic. RESULTS: The epidemic situation was significantly correlated with atmospheric pressure, temperature, and daily precipitation (P < 0.05), and there were six temporal and spatial clusters. The fitting accuracy of the epidemic risk assessment agent-based model for lower-risk, low-risk, medium-risk, and high-risk was 0.795, 0.672, 0.853, 0.825, respectively. CONCLUSIONS: This H7N9 epidemic was found to have more outbreaks in winter and spring. It gradually spread to the inland areas of China. This model reflects the risk areas of human infection with the H7N9 virus.

H7N9 pandemic preparedness: A large-scale production of a split inactivated vaccine.

In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 µg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic.

Different intervention strategies toward live poultry markets against avian influenza A (H7N9) virus: Model-based assessment.

BACKGROUND: Different interventions targeting live poultry markets (LPMs) are applied in China for controlling avian influenza A (H7N9), including LPM closure and "1110" policy (i.e., daily cleaning, weekly disinfection, monthly rest day, zero poultry stock overnight). However, the interventions' effectiveness has not been comprehensively assessed. METHODS: Based on the available data (including reported cases, domestic poultry volume, and climate) collected in Guangdong Province between October 2013 and June 2017, we developed a new compartmental model that enabled us to infer H7N9 transmission dynamics. The model incorporated the intrinsic interplay among humans and poultry as well as the impacts of absolute humidity and LPM intervention, in which intervention strategies were parameterized and estimated by Markov chain Monte Carlo method. RESULTS: There were 258 confirmed human H7N9 cases in Guangdong during the study period. If without interventions, the number would reach 646 (95%CI, 575-718) cases. Temporal, seasonal and permanent closures of LPMs can substantially reduce transmission risk, which might respectively reduce human infections by 67.2% (95%CI, 64.3%-70.1%), 75.6% (95%CI, 73.8%-77.5%), 86.6% (95%CI, 85.7-87.6%) in total four epidemic seasons, and 81.9% (95%CI, 78.7%-85.2%), 91.5% (95%CI, 89.9%-93.1%), 99.0% (95%CI, 98.7%-99.3%) in the last two epidemic seasons. Moreover, implementing the "1110" policy from 2014 to 2017 would reduce the cases by 34.1% (95%CI, 20.1%-48.0%), suggesting its limited role in preventing H7N9 transmission. CONCLUSIONS: Our study quantified the effects of different interventions and execution time toward LPMs for controlling H7N9 transmission. The results highlighted the importance of closing LPMs during epidemic period, and supported permanent closure as a long-term plan.

Seroprevalence of H7N9 infection among humans: A systematic review and meta-analysis.

In spring 2013, a novel avian-origin influenza A (H7N9) virus emerged in mainland China. The burden of H7N9 infection was estimated based on systematic review and meta-analysis. The systematic search for available literature was conducted using Chinese and English databases. We calculated the pooled seroprevalence of H7N9 infection and its 95% confidence interval by using Freeman-Tukey double arcsine transformation. Out of 16 890 records found using Chinese and English databases, 54 articles were included in the meta-analysis. These included studies of a total of 64 107 individuals. The pooled seroprevalence of H7N9 infection among humans was 0.122% (95% CI: 0.023, 0.275). In high-risk populations, the highest pooled seroprevalence was observed among close contacts (1.075%, 95% CI: 0.000, 4.357). The seroprevalence among general population was (0.077%, 95% CI: 0.011, 0.180). Our study discovered that asymptomatic infection of H7N9 virus did occur, even if the seroprevalence among humans was low.

Biosafety risk assessment for production of candidate vaccine viruses to protect humans from zoonotic highly pathogenic avian influenza viruses.

A major lesson learned from the public health response to the 2009 H1N1 pandemic was the need to shorten the vaccine delivery timeline to achieve the best pandemic mitigation results. A gap analysis of previous pre-pandemic vaccine development activities identified possible changes in the Select Agent exclusion process that would maintain safety and shorten the timeline to develop candidate vaccine viruses (CVVs) for use in pandemic vaccine manufacture. Here, we review the biosafety characteristics of CVVs developed in the past 15 years to support a shortened preparedness timeline for A(H5) and A(H7) subtype highly pathogenic avian influenza (HPAI) CVVs. Extensive biosafety experimental evidence supported recent changes in the implementation of Select Agent regulations that eliminated the mandatory chicken pathotype testing requirements and expedited distribution of CVVs to shorten pre-pandemic and pandemic vaccine manufacturing by up to 3 weeks.

Detecting influenza and emerging avian influenza virus by influenza and pneumonia surveillance systems in a large city in China, 2005 to 2016.

BACKGROUND: Detecting avian influenza virus has become an important public health strategy for controlling the emerging infectious disease. METHODS: The HIS (hospital information system) modified influenza surveillance system (ISS) and a newly built pneumonia surveillance system (PSS) were used to monitor the influenza viruses in Changsha City, China. The ISS was used to monitor outpatients in two sentinel hospitals and to detect mild influenza and avian influenza cases, and PSS was used to monitor inpatients in 49 hospitals and to detect severe and death influenza cases. RESULTS: From 2005 to 2016, there were 3,551,917 outpatients monitored by the ISS system, among whom 126,076 were influenza-like illness (ILI) cases, with the ILI proportion (ILI%) of 3.55%. After the HIS was used, the reported incident cases of ILI and ILI% were increased significantly. From March, 2009 to September, 2016, there were 5,491,560 inpatient cases monitored by the PSS system, among which 362,743 were pneumonia cases, with a proportion of 6.61%. Among pneumonia cases, about 10.55% (38,260/362,743) of cases were severe or death cases. The pneumonia incidence increased each year in the city. Among 15 avian influenza cases reported from January, 2005 to September, 2016, there were 26.7% (4/15) mild cases detected by the HIS-modified ISS system, while 60.0% (9/15) were severe or death cases detected by the PSS system. Two H5N1 severe cases were missed by the ISS system in January, 2009 when the PSS system was not available. CONCLUSIONS: The HIS was able to improve the efficiency of the ISS for monitoring ILI and emerging avian influenza virus. However, the efficiency of the system needs to be verified in a wider area for a longer time span in China.

Chinese poultry farmers' decision-making for avian influenza prevention: a qualitative analysis.

Poultry farmers faced dual risk when mutant avian influenza (AI) virus showed the zoonotic characteristics. A/H5N1 and A/H7N9 were two dominant AI virus strains that have captured the attention of the public over the years for they have been reported to bring about greater loss to poultry and human, respectively. Previous studies mainly used quantitative methods investigating either the means that poultry farmers adopted for protecting their poultry against A/H5N1 infection or the poultry farmers' self-protective behaviours against A/H7N9 infection. We sought insights into the underlying factors influencing Chinese poultry farmers' protective behaviours in response to the dual risk of AI by a qualitative way. Semi-structured in-depth interviews were conducted with 25 Chinese chicken farmers recruited by purposive sampling between November 2016 and May 2017, the peak season of AI. All interviews were audio-taped, transcribed and analysed using a grounded theory approach. From participants' experiences, we revealed five main themes: Measures adopted for protecting poultry and farmers, Emotional response to the AI epidemic, Perceived risk of AI, Perceived effectiveness of the preventive measures adopted and Perceived self-efficacy to take preventive measures. The information of AI outbreak directly triggered Chinese chicken farmers' emotional response and thereafter preventive actions. Compared to the perceived risk of poultry infection with A/H5N1 which mainly connected to economic loss, participants perceived much lower risk of human infection with A/H7N9. AI epidemic information played a key role triggering poultry farmers' response behaviours. Chinese poultry farmers weighted more attention on the risk of poultry infection which was highly associated with economic losses. The government should build and improve an early AI warning and information transmission network to poultry farmers. Further reinforcement of related self-protective and preventive knowledge training towards poultry farmers is necessary.

Risk Assessment of the Tropism and Pathogenesis of the Highly Pathogenic Avian Influenza A/H7N9 Virus Using Ex Vivo and In Vitro Cultures of Human Respiratory Tract.

BACKGROUND: Highly pathogenic avian influenza (HPAI)-H7N9 virus arising from low pathogenic avian influenza (LPAI)-H7N9 virus with polybasic amino acid substitutions in the hemagglutinin was detected in 2017. METHODS: We compared the tropism, replication competence, and cytokine induction of HPAI-H7N9, LPAI-H7N9, and HPAI-H5N1 in ex vivo human respiratory tract explants, in vitro culture of human alveolar epithelial cells (AECs) and pulmonary microvascular endothelial cells (HMVEC-L). RESULTS: Replication competence of HPAI- and LPAI-H7N9 were comparable in ex vivo cultures of bronchus and lung. HPAI-H7N9 predominantly infected AECs, whereas limited infection was observed in bronchus. The reduced tropism of HPAI-H7N9 in bronchial epithelium may explain the lack of human-to-human transmission despite a number of mammalian adaptation markers. Apical and basolateral release of virus was observed only in HPAI-H7N9- and H5N1-infected AECs regardless of infection route. HPAI-H7N9, but not LPAI-H7N9 efficiently replicated in HMVEC-L. CONCLUSIONS: Our findings demonstrate that a HPAI-H7N9 virus efficiently replicating in ex vivo cultures of human bronchus and lung. The HPAI-H7N9 was more efficient at replicating in human AECs and HMVEC-L than LPAI-H7N9 implying that endothelial tropism may involve in pathogenesis of HPAI-H7N9 disease.

Assessment of Human-to-Human Transmissibility of Avian Influenza A(H7N9) Virus Across 5 Waves by Analyzing Clusters of Case Patients in Mainland China, 2013-2017.

Background: The 2016-17 epidemic of human infections with avian influenza A(H7N9) virus was alarming, due to the surge in reported cases across a wide geographic area and the emergence of highly-pathogenic A(H7N9) viruses. Our study aimed to assess whether the human-to-human transmission risk of A(H7N9) virus has changed across the 5 waves since 2013. Methods: Data on human cases and clusters of A(H7N9) virus infection were collected from the World Health Organization, open access national and provincial reports, informal online sources, and published literature. We compared the epidemiological characteristics of sporadic and cluster cases, estimated the relative risk (RR) of infection in blood relatives and non-blood relatives, and estimated the bounds on the effective reproductive number (Re) across waves from 2013 through September 2017. Results: We identified 40 human clusters of A(H7N9) virus infection, with a median cluster size of 2 (range 2-3). The overall RR of infection in blood relatives versus non-blood relatives was 1.65 (95% confidence interval [CI]: 0.88, 3.09), and was not significantly different across waves (χ2 = 2.66, P = .617). The upper limit of Re for A(H7N9) virus was 0.12 (95% CI: 0.10, 0.14) and was not significantly different across waves (χ2 = 1.52, P = .822). Conclusions: The small cluster size and low Re suggest that human-to-human transmissibility of A(H7N9) virus has not changed over time and remains limited to date. Continuous assessment of A(H7N9) virus infections and human case clusters is of crucial importance for public health.

Needs Assessment for a Targeted Health Promotion Campaign.

ABSTRACTSince the first human A/H7N9 infection in Hong Kong, there has been an ongoing threat of human-to-human transmission, potentially causing a pandemic. Because there is no vaccine for A/H7N9, the individual preventive measures become all the more important for reducing transmission. However, due to the ongoing threat of numerous avian influenza viruses, the public may suffer from pandemic-media-fatigue. This study was done to assess the need for a targeted A/H7N9 health promotion campaign. Steven and Gillam's framework using epidemiological, comparative, and corporate approaches was used to assess the need for a targeted A/H7N9 health promotion campaign.Local surveillance data showed that Hong Kong faces a double burden of increasing seasonal influenza activity and threat of an avian influenza pandemic. Experts warned of potential severity and difficulties in A/H7N9 control. In contrast, surveys showed that the Hong Kong public were suffering from pandemic-media-fatigue, lacked anxiety, had misconceptions, and were not vigilant in preventive practices. This was more evident in certain demographics. Content analysis showed that health promotion materials were not targeted or tailored in countries with human A/H7N9 cases. Targeted health promotion campaigns and framing the issue to increase public and media awareness are crucial in preventing the current pandemic-media-fatigue. (Disaster Med Public Health Preparedness. 2019;13:596-604).

Risk Assessment of Fifth-Wave H7N9 Influenza A Viruses in Mammalian Models.

The fifth wave of the H7N9 influenza epidemic in China was distinguished by a sudden increase in human infections, an extended geographic distribution, and the emergence of highly pathogenic avian influenza (HPAI) viruses. Genetically, some H7N9 viruses from the fifth wave have acquired novel amino acid changes at positions involved in mammalian adaptation, antigenicity, and hemagglutinin cleavability. Here, several human low-pathogenic avian influenza (LPAI) and HPAI H7N9 virus isolates from the fifth epidemic wave were assessed for their pathogenicity and transmissibility in mammalian models, as well as their ability to replicate in human airway epithelial cells. We found that an LPAI virus exhibited a similar capacity to replicate and cause disease in two animal species as viruses from previous waves. In contrast, HPAI H7N9 viruses possessed enhanced virulence, causing greater lethargy and mortality, with an extended tropism for brain tissues in both ferret and mouse models. These HPAI viruses also showed signs of adaptation to mammalian hosts by acquiring the ability to fuse at a lower pH threshold than other H7N9 viruses. All of the fifth-wave H7N9 viruses were able to transmit among cohoused ferrets but exhibited a limited capacity to transmit by respiratory droplets, and deep sequencing analysis revealed that the H7N9 viruses sampled after transmission showed a reduced amount of minor variants. Taken together, we conclude that the fifth-wave HPAI H7N9 viruses have gained the ability to cause enhanced disease in mammalian models and with further adaptation may acquire the ability to cause an H7N9 pandemic.IMPORTANCE The potential pandemic risk posed by avian influenza H7N9 viruses was heightened during the fifth epidemic wave in China due to the sudden increase in the number of human infections and the emergence of antigenically distinct LPAI and HPAI H7N9 viruses. In this study, a group of fifth-wave HPAI and LPAI viruses was evaluated for its ability to infect, cause disease, and transmit in small-animal models. The ability of HPAI H7N9 viruses to cause more severe disease and to replicate in brain tissues in animal models as well as their ability to fuse at a lower pH threshold than LPAI H7N9 viruses suggests that the fifth-wave H7N9 viruses have evolved to acquire novel traits with the potential to pose a higher risk to humans. Although the fifth-wave H7N9 viruses have not yet gained the ability to transmit efficiently by air, continuous surveillance and risk assessment remain essential parts of our pandemic preparedness efforts.

[Semi-quantitative risk assessment of human infection with H7N9 avian influenza epidemic in Zhejiang province].

OBJECTIVE: To assess the risk of local outbreaks of H7N9 avian influenza infection in Zhejiang province and to explore the semi-quantitative assessment method for public health risks in emergency. METHODS: Risk index system of human infection with H7N9 avian influenza caused by local transmission were reviewed. The weights of indexes were calculated by analytic hierarchy process, which was combined with the TOPSIS method to calculate the risk comprehensive index. RESULTS: Four primary indexes and 23 secondary indexes were identified for risk assessment in local outbreaks of H7N9 avian influenza infection. The weights ranked on the top five were:morbidity (0.0972), closure measures (0.0718), sterilization measures (0.0673), fatality rate (0.0651), and epidemic spread (0.0616). The comprehensive index of the risk of local outbreaks of H7N9 avian influenza ranged from high to low were Hangzhou (0.5910), Shaoxing (0.5711), Jiaxing (0.5199), Taizhou (0.5198), Huzhou (0.4662), Ningbo (0.3828), Wenzhou (0.3719), Jinhua (0.3392), Lishui (0.2727), Quzhou (0.2001) and Zhoushan (0.0508). CONCLUSIONS: A semi-quantitative method has been established in this study, which provides scientific basis for prevention and control of H7N9 avian influenza epidemic in Zhejiang province.

The Impacts on Health, Society, and Economy of SARS and H7N9 Outbreaks in China: A Case Comparison Study.

Background: Epidemics such as SARS and H7N9 have caused huge negative impacts on population health and the economy in China. Aims: This article discusses the impacts of SARS in 2003 and H7N9 in 2013 in China, in order to provide a better understanding to government and practitioners of why improving management of response to infectious disease outbreaks is so critical for a country's economy, its society, and its place in the global community. Methods: To provide the results of an analysis of impacts of SARS and H7N9 based on feedback from documents, informants, and focus groups on events during the SARS and H7N9 outbreaks. Results: Both outbreaks of SARS and H7N9 have had an impact on China, causing significant negative impacts on health, the economy, and even national and even international security. Conclusions: Both SARS coronavirus and H7N9 viruses presented a global epidemic threat, but the social and economic impacts of H7N9 were not as serious as in the case of SARS because the response to H7N9 was more effective.

Simple Strategy for Rapid and Sensitive Detection of Avian Influenza A H7N9 Virus Based on Intensity-Modulated SPR Biosensor and New Generated Antibody.

In 2013 a new reassortant avian influenza A H7N9 virus emerged in China, causing human infection with high mortality. An accurate and timely diagnosis is crucial for controlling the outbreaks of the disease. We therefore propose a simple strategy for rapidly and sensitively detecting the H7N9 virus using an intensity-modulated surface plasmon resonance (IM-SPR) biosensor integrated with a new generated monoclonal antibody. The novel antibody exhibits significant specificity to recognize H7N9 virus compared with other clinical human influenza isolates (p < 0.01). Experimentally, the detection limit of the proposed approach for H7N9 virus detection is estimated to be 144 copies/mL, which is a 20-fold increase in sensitivity compared with homemade target-captured ELISA using the identical antibody. For the measurement of mimic clinical specimens containing the H7N9 virus mixed with nasal mucosa from flu-like syndrome patients, the detection limit is calculated to be 402 copies/mL, which is better than conventional influenza detection assays; quantitative reverse transcription polymerase chain reaction (qRT-PCR) and rapid influenza diagnostic test (RIDT). Most importantly, the assay time took less than 10 min. Combined, the results of this study indicate that the proposed simple strategy demonstrates high sensitivity and time-saving in H7N9 virus detection. By incorporating a high specific recognizer, the proposed technique has the potential to be used in applications and development of other emerging or re-emerging microbe detection platforms.

A Comparison of China's Risk Communication in Response to SARS and H7N9 Using Principles Drawn From International Practice.

BACKGROUND: China's emergency management of severe acute respiratory syndrome (SARS) was heavily criticized, whereas the H7N9 response was praised by the international community.AimsThe aims of this study were to examine and compare the strengths and weaknesses of risk communication conducted in response to SARS and H7N9 and their associated social impacts on affected communities in China. METHOD: A qualitative comparative case study approach was employed in the present study, using a set of 8 risk communication principles selected from international literature to suit the Chinese context for the comparative analysis of emergency responses of SARS and H7N9. RESULTS: The study found significant differences in the risk communication conducted in the 2 cases. The SARS outbreak fully exposed China's lack of experience in public health risk communication. By contrast, the Chinese government's risk communication strategies had improved significantly during the H7N9 outbreak.DiscussionTrust is the basis for communication. Maintaining an open and honest attitude and actively engaging stakeholders to address their risk information needs will serve to build trust and facilitate multi-sector collaborations in dealing with a public health crisis. CONCLUSIONS: From SARS to H7N9, risk communication practices in China greatly improved, which, in turn, lessened adverse social impacts and improved outcomes in emergency management of public health crises. (Disaster Med Public Health Preparedness. 2018;12:587-598).

Economic burden and its associated factors of hospitalized patients infected with A (H7N9) virus: a retrospective study in Eastern China, 2013-2014.

BACKGROUND: H7N9 continues to cause human infections and remains a pandemic concern. Understanding the economic impacts of this novel disease is important for making decisions on health resource allocation, including infectious disease prevention and control investment. However, there are limited data on such impacts. METHODS: Hospitalized laboratory-confirmed H7N9 patients or their families in Jiangsu Province of China were interviewed. Patients' direct medical costs of hospitalization were derived from their hospital bills. A generalized linear model was employed to estimate the mean direct medical costs of patients with different characteristics. RESULTS: The mean direct cost of hospitalization for H7N9 was estimated to be ¥ 71 060 (95 % CI, 48 180-104 820), i.e., US$ 10 996 (95 % CI, 7 455-16 220), and was ¥12 060 (US$ 1 861), ¥136 120 (US$ 21 001) and ¥218 610 (US$ 33 728) for those who had mild or severe symptoms or who died, respectively. The principal components of the total fees differed among patients with different disease severity, although medication fees were always the largest contributors. Disease severity, proportion of reimbursement and family member monthly average income were identified as the key factors that contributed to a patient's direct medical cost of hospitalization. CONCLUSIONS: The direct medical costs of hospitalized patients with H7N9 are significant, and far surpass the annual per capita income of Jiangsu Province, China. The influencing factors identified should be taken into account when developing related health insurance policies and making health resource allocation. TRIAL REGISTRATION: Not applicable. This is a survey study with no health care intervention implemented on human participants.

Assessment of Antiviral Properties of Peramivir against H7N9 Avian Influenza Virus in an Experimental Mouse Model.

The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avian influenza virus infection. The data show that repeated administration of peramivir at 30 mg/kg of body weight successfully eradicated the virus from the respiratory tract and extrapulmonary tissues during the acute response, prevented clinical signs of the disease, including neuropathy, and eventually protected mice against lethal H7N9 influenza virus infection. Early treatment with peramivir was found to be associated with better disease outcomes.