【1】A Decade After SARS，China's Flu Response Wins Cautious Praise Science：SARS发生十年后，H7N9禽流感再次引起中国社会的高度警惕
Coming at the 10-year anniversary of the SARS outbreak， the Chinese government's announcement that a new influenza virus is killing people elicited suspicion from many Chinese. Why， some asked， did it take nearly 6 weeks after the first patient fell ill for the government to identify the H7N9 virus？ But many scientists say that， while there are plenty of questions surrounding the new virus， China has actually come a long way when it comes to monitoring health and has been forthcoming with the international health community—a sharp contrast with the SARS episode， when it was unable to identify the new pathogen and tried to sweep a deadly epidemic under the rug.
【2】New Flu Virus in China Worries and Confuses
A novel bird flu virus， designated H7N9， has infected three humans in China， killing two of them. While the Chinese government has won praise for aggressively pursuing this outbreak and openly discussing its findings， how the confirmed cases became infected is a mystery. Still， many researchers are guardedly optimistic： There is no persuasive evidence that the virus spreads between people， an ability it would need to set off the next flu pandemic
【3】H7N9 avian influenza virus - search and re-search
Emerging Microbes & Infections：对H7N9禽流感病毒的探索与研究
In February 2013， two patients with severe pneumonia and pulmonary dysfunction were admitted to Shanghai Fifth Hospital affiliated with Fudan University. The first patient， an 87-year-old man became ill on February 19th and died on February 27th. The second patient， also male and 27 years old， became ill on February 27th and died on March 4th. In both cases there were fever， cough， and respiratory tract infection during the early stages of the illness. Five to ten days later， the patients developed severe pneumonia and progressive respiratory distress with lethal outcome.
Following the guidelines of the nation-wide alert network for diagnosis of respiratory infectious diseases established in 2008， etiological studies were immediately carried out at the Laboratory of Pathogen Diagnosis and Biosafety of Shanghai Public Health Clinical Center， which is one of the 16 sites selected for survey in the alert network. Blood， throat swabs and sputum samples were collected and examined by polymerase chain reaction using primers for amplification of severe acute respiratory syndrome coronavirus， new corona virus， and H5N1 influenza virus， which all yielded negative results. The only positive results were observed by using universal primers for amplification of influenza A viruses. To identify the viral subtype， the gene segments were subjected to further amplification， sequencing and blast analysis. The results showed that the hemagglutinin fragment showed high homology to influenza A virus H7 (94.8%) while the neuraminidase fragment was high homologue to influenza A virus N9 (94.2%). MP， NP， PA， PB1， PB2 showed 97%–99% homology with H9N2 virus. Specimens were sent to the Chinese Center for Disease Control and Prevention for confirmation and H7N9 avian influenza viruses were isolated. China National Health and Family Planning Commission organized experts to do a comprehensive analysis based on the laboratory results， clinical manifestations of patients， epidemiological data， and concluded that the patients were infected with strains of H7N9 avian influenza virus. China National Health and Family Planning Commission notified the World Health Organization that a new H7N9 avian flu virus had caused lethal human infections in China (Gao RB et al.， unpublished). Epidemiological survey revealed no H7N9 infection occurred among close contacts of the lethal cases. Both lethal cases had a history of contacts with pigs， but not with chickens. In contrast， some of the H7N9 cases observed subsequently in Jiangsu province had a history of slaughtering chickens. The municipal government of Shanghai has implemented stage III regulations for survey and control for fever and acute respiratory infections in all hospitals， and up to April 4th， fourteen cases with six deaths have been reported.
Emerging viral diseases are a continuous threat to humans worldwide， and the majority of the emerging viruses originated from animal hosts. Of particular concern is the transmission of avian influenza viruses to humans with or without pigs as intermediate hosts. Though such zoonotic transmissions are usually self-limited， they always pose a pandemic threat， since the viruses may adapt to humans. The avian influenza viruses that have occasionally infected and caused disease in people without showing human adaptation comprise H5N1， H9N2， and a variety of H7 viruses.1，2 The H7 viruses isolated from humans include both highly pathogenic and low pathogenic avian viruses. Whereas highly pathogenic H5N1 and H7 viruses may cause fatal disease in people， all human infections caused by low pathogenic H7 viruses so far had been mild. It is therefore concerning to see that the new H7N9 virus which， according to the available evidence， is derived from a low pathogenic avian virus can be lethal for man. However， it has to be emphasized that it is not clear yet whether the H7N9 virus is transmitted directly from birds or pigs to people. So far， this virus as an agent not causing disease in animals may escape detection in an animal reservoir more easily than the highly pathogenic H5N1 viruses. It is also not clear whether the current H7N9 human infection is a rare event， or the severe cases observed are just the tip of an iceberg of many asymptomatic human infections as has been suggested for H9N23 and H7N34 viruses.
The identification of H7N9 virus as a cause of human disease is only the beginning of a long journey aimed at the elucidation of the epidemiology， the host range， and the pathogenicity of this virus， and at the development of efficient vaccines and antiviral therapeutics. Furthermore， adequate surveillance is the most important. The nation wide alert laboratory network established at 16 selected sites in China significantly contributed to the immediate identification of the emerging H7N9 virus， demonstrating that generous financial support from the government is necessary and fruitful. However， integrated surveillance of animal and human infections still needs to be improved. The barriers between physicians and veterinarians should be removed， and gaps should be filled between government agencies responsible for animal health (Ministry of Agriculture) and public health (Ministry of Health). While a close watch on H7N9 is going on in China， we expect that at the same time， basic research and international collaboration will be supported and encouraged.
While writing this news， up to April 6th， the number of patients infected with H7N9 in mainland China has increased to 16， with six deaths， distributed in Jiangsu and Zhejiang provinces， and all are in the eastern part of China. Only few patients had a history of contact with chickens. Among them， one is a four-year-old child with very mild respiratory infection symptoms but showed H9N7 positive by polymerase chain reaction in his throat swab. Currently in Shanghai and several other provinces， strict survey for H9N7 cases has been implemented in outpatients with fever and respiratory infections in all hospitals. At the same time survey for H9N7 among wild birds and poultries has been carried out by the animal Centers for Disease Control and Prevention， and confirmed by the National Key Laboratory of Avian Influenza Institute in Harbin. H7N9 isolates with high homology have been detected in pigeons from Songjiang district of Shanghai， and sanitary measures including slaughtering pigeons in that region and shutting down of markets trading live poultries in Shanghai have been implemented. Since this new virus is susceptible to antiviral drug oseltamivir， patients were treated with this drug as early as possible after the diagnosis.
【4】GENETIC ANALYSIS OF NOVEL AVIAN A(H7N9) INFLUENZA VIRUSES ISOLATED FROM PATIENTS IN CHINA，FEBRUARY TO APRIL 2013
Novel influenza viruses of the H7N9 subtype have infected 33 and killed nine people in China as of 10 April 2013. Their haemagglutinin (HA) and neuraminidase genes probably originated from Eurasian avian influenza viruses； the remaining genes are closely related to avian H9N2 influenza viruses. Several characteristic amino acid changes in HA and the PB2 RNA polymerase subunit probably facilitate binding to human-type receptors and efficient replication in mammals， respectively， highlighting the pandemic potential of the novel viruses.
【5】A fatal case caused by novel H7N9 avian influenza A virus in China
Emerging Microbes & Infections：对中国H7N9禽流感病毒感染者致死案例的分析研究
Since the highly pathogenic H5N1 avian influenza virus (AIV) was first transmitted from birds to humans in Hong Kong in 1997， other pathogenic AIVs， including H7N2， H7N3， H7N7， and H9N2 have been reported in China and other parts of the world.1，2，3，4 However， no human infections with the novel H7N9 virus have been reported until now from China. Here we report a fatal case caused by H7N9 AIV in the very early stage of this endemic.
A 52-year-old retired female resident in Shanghai was admitted to Fudan University affiliated Huashan Hospital due to 7-day history of pyrexia， accompanied by cough， chest stuffiness and dyspnea for the past two days. The patient had a sudden onset on March 27th， 2013 with rigors， and the highest temperature reached 40.6 °C but with no obvious symptoms of cough， pharyngalgia， stuffiness， dyspnea， nausea， vomiting， abdominal pain or diarrhea， and did not receive medication. The next day the patient visited emergency room and chest auscultation demonstrated rough breath sounds， absence of rales. Laboratory tests showed a leukocyte count of 5300/mm3， with 72% of neutrophils， and C reactive protein (CRP) of 26.8 mg/L. The patient was given antibiotics. On the third day， the patient took chest radiography and showed small patchy shadows in lower lobe of the right lung. The patient was given antibiotics intravenously for three consecutive days， still without cough， expectoration or shortness of breath， although her temperature was not resolved. On day 7 after onset of fever， due to quick progression of the symptoms， including cough， chest stuffiness and shortness of breath， the patient visited the emergency department of Fudan University affiliated Huashan Hospital again. Unfortunately， the arterial blood gas analysis showed severe hypoxemia， pH 7.54， PaCO2 4.33 kPa， PaO2 3.66 kPa， and saturation of oxygen 61.3% on room air. In the meantime， chest computed tomography (CT) demonstrated diffuse bilateral consolidation with right pleural effusion (Figure 1). Laboratory findings indicated a leukocyte count of 3290/mm3， with 92% of neutrophils and 5.5% of lymphocytes； platelets of 155 000/mm3； increased myocardial enzymes， prolonged prothrombin time and abnormal serum electrolytes. The patient was suspected severe flu with acute respiratory distress syndrome and thereafter was given endotracheal intubation and placed on a mechanical ventilator. Intravenous injection of methylprednisolone 40 mg was administered to inhibit inflammation and alleviate edema in the lung. On April 3rd (day 8)， antimicrobial regimen as well as immune globulin therapy and the methylprednisolone were maintained. However， the patient's condition worsened and died of acute respiratory distress syndrome.
【6】Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus
Infection of poultry with influenza A subtype H7 viruses occurs worldwide， but the introduction of this subtype to humans in Asia has not been observed previously. In March 2013， three urban residents of Shanghai or Anhui， China， presented with rapidly progressing lower respiratory tract infections and were found to be infected with a novel reassortant avian-origin influenza A (H7N9) virus.
We obtained and analyzed clinical， epidemiologic， and virologic data from these patients. Respiratory specimens were tested for influenza and other respiratory viruses by means of real-time reverse-transcriptase–polymerase-chain-reaction assays， viral culturing， and sequence analyses.
A novel reassortant avian-origin influenza A (H7N9) virus was isolated from respiratory specimens obtained from all three patients and was identified as H7N9. Sequencing analyses revealed that all the genes from these three viruses were of avian origin， with six internal genes from avian influenza A (H9N2) viruses. Substitution Q226L (H3 numbering) at the 210-loop in the hemagglutinin (HA) gene was found in the A/Anhui/1/2013 and A/Shanghai/2/2013 virus but not in the A/Shanghai/1/2013 virus. A T160A mutation was identified at the 150-loop in the HA gene of all three viruses. A deletion of five amino acids in the neuraminidase (NA) stalk region was found in all three viruses. All three patients presented with fever， cough， and dyspnea. Two of the patients had a history of recent exposure to poultry. Chest radiography revealed diffuse opacities and consolidation. Complications included acute respiratory distress syndrome and multiorgan failure. All three patients died.
Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.)
【7】Origins and evolutionary genomics of the novel 2013 avian-origin H7N9 influenza A virus in China：Early findings
In March and early April 2013， a new avian-origin influenza A (H7N9) virus (A-OIV) emerged in the eastern China. During the first week of April， the 18 infection cases have been confirmed and 6 people have died since March. This virus has caused global concern as a potential pandemic threat. Here we use evolutionary analysis to reconstruct the origins and early development of the A-OIV viruses. We found that A-OIV was derived from a reassortment of three avian flu virus strains， and substantial mutations have been detected. Our results highlight the need for systematic surveillance of influenza in birds， and provide evidence that the mixing of new genetic elements in avian can result in the emergence of viruses with pandemic potential in humans.
【8】Pathogenesis and transmissibility of highly (H7N1) and low (H7N9) pathogenic avian influenza virus infection in red-legged partridge (Alectoris rufa)
An experimental infection with highly pathogenic avian influenza virus (HPAIV) and low pathogenic avian influenza virus (LPAIV) was carried out in red-legged partridges (Alectoris rufa) in order to study clinical signs， gross and microscopic lesions， and viral distribution in tissues and viral shedding. Birds were infected with a HPAIV subtype H7N1 (A/Chicken/Italy/5093/1999) and a LPAIV subtype H7N9 (A/Anas crecca/Spain/1460/2008). Uninoculated birds were included as contacts in both groups. In HPAIV infected birds， the first clinical signs were observed at 3 dpi， and mortality started at 4 dpi， reaching 100% at 8 dpi. The presence of viral antigen in tissues and viral shedding were confirmed by immunohistochemistry and quantitative real time RT-PCR (qRRT-PCR)， respectively， in all birds infected with HPAIV. However， neither clinical signs nor histopathological findings were observed in LPAIV infected partridges. In addition， only short-term viral shedding together with seroconversion was detected in some LPAIV inoculated animals. The present study demonstrates that the red-legged partridge is highly susceptible to the H7N1 HPAIV strain， causing severe disease， mortality and abundant viral shedding and thus contributing to the spread of a potential local outbreak of this virus. In contrast， our results concerning H7N9 LPAIV suggest that the red-legged partridge is not a reservoir species for this virus.