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SASTM Newsflash - Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: Clinical analysis and characterisation of viral genome


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Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome


Source: The Lancet



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Human infection with avian influenza A H7N9 virus emerged in eastern China in February, 2013, and has been associated with exposure to poultry. We report the clinical and microbiological features of patients infected with influenza A H7N9 virus and compare genomic features of the human virus with those of the virus in market poultry in Zhejiang, China.



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Between March 7 and April 8, 2013, we included hospital inpatients if they had new-onset respiratory symptoms, unexplained radiographic infiltrate, and laboratory-confirmed H7N9 virus infection. We recorded histories and results of haematological, biochemical, radiological, and microbiological investigations. We took throat and sputum samples, used RT-PCR to detect M, H7, and N9 genes, and cultured samples in Madin-Darby canine kidney cells. We tested for co-infections and monitored serum concentrations of six cytokines and chemokines. We collected cloacal swabs from 86 birds from epidemiologically linked wet markets and inoculated embryonated chicken eggs with the samples.We identified and subtyped isolates by RT-PCR sequencing. RNA extraction, complementary DNA synthesis, and PCR sequencing were done for one human and one chicken isolate. We characterised and phylogenetically analysed the eight gene segments of the viruses in the patient's and the chicken's isolates, and constructed phylogenetic trees of H, N, PB2, and NS genes.



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We identified 4 patients (mean age 56 years), all of whom had contact with poultry 3 to 8 days before disease onset. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Patients were leucopenic and lymphopenic, and had impaired liver or renal function, substantially increased serum cytokine or chemokine concentrations, and disseminated intravascular coagulation with disease progression. 2 patients died. Sputum specimens were more likely to test positive for the H7N9 virus than were samples from throat swabs.


The viral isolate from the patient was closely similar to that from an epidemiologically linked market chicken.


All viral gene segments were of avian origin. The H7 of the isolated viruses was closest to that of the H7N3 virus from domestic ducks in Zhejiang, whereas the N9 was closest to that of the wild bird H7N9 virus in South Korea. We noted Gln226Leu and Gly186Val substitutions in human virus H7 (associated with increased affinity for α-2,6-linked sialic acid receptors) and the PB2 Asp701Asn mutation (associated with mammalian adaptation). Ser31Asn mutation, which is associated with adamantane resistance, was noted in viral M2.



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Cross species poultry-to-person transmission of this new reassortant

H7N9 virus is associated with severe pneumonia and multiorgan dysfunction in human beings. Monitoring of the viral evolution and further study of disease pathogenesis will improve disease management, epidemic control, and pandemic preparedness.


This study provides a detailed description of the results of haematological, biochemical, radiological, and microbiological investigations of confirmed cases of H5N7 virus infection. On the basis of comparison of one human case and an avian case it is concluded that the the patient isolate was closely similar to that from an epidemiologically linked market chicken. All viral gene segments were of avian origin.


Most H7N9 patients had underlying conditions, animal exposure

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The authors of a preliminary report on the epidemiology of the avian influenza A (H7N9) outbreak in China review data from 82 cases that were reported as of Apr 17. Since then, the outbreak total has grown to 109 illnesses, including 22 deaths. The country enhanced its surveillance for the disease after it identified the new virus in March. Among 664 hospitalized patients with unexplained pneumonia, 81 (12.2 percent) were infected with the new virus. Of 5551 respiratory specimens from outpatient surveillance for flulike illness, only 1 (0.02 percent) was positive for H7N9. Most of the patients who had confirmed infections were men (73 percent), and most lived in urban settings (84 percent). Of 71 patients with available information, 54 (76 percent) had underlying medical conditions. Among 46 of that group with available data, 40 (87 percent) were at increased risk due to their age -- either younger than 5 years or 65 or older. 4 of the patients were poultry workers: 3 slaughtered live-market poultry, and one transported poultry. All but one of the patients was hospitalized. As of the study cut-off date, 17 confirmed case-patients and 1 suspected case-patient had died of acute respiratory distress syndrome or multiorgan failure.


Animal exposure

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Details about animal exposure were available for 77 of the patients, and 59 (77 percent) said they had recent exposure to animals while working at or visiting a live-animal market: 45 to chickens, 12 to ducks, and 4 to swine. Other animals included pigeons, geese, quail, wild birds, pet birds, cats, and dogs. A history of animal exposure is unclear for 5 patients, and investigations are ongoing into their exposures.


The report also sheds new light on the type of contact and exposures that occurred in some of the family clusters, one of which involved some of the 1st patients who were reported in the outbreak, an 87-year-old man from Shanghai and his 2 sons.

The report said the index case in the cluster was a 57-year-old brother whose fatal infection was suspected but not confirmed. Within 2 weeks before he got sick, he had visited a live-poultry market where he bought a chicken, observed the slaughtering, brought it home, and cooked it. After he got sick, his father who lived with him and his 69-year-old brother who lived nearby cared for him, having prolonged unprotected contact before his hospitalization. The father and the brother got sick, and both had laboratory-confirmed H7N9 infections. The father died from his infection.


The report described another family cluster, a 60-year old man with a suspected infection and his 32-year-old daughter who lived in the same house with other family members. The father got sick, and his daughter cared for him at home and in the hospital before she got sick. Both of the patients are still critically ill. Tests confirmed H7N9 in the daughter and are still under way on the father. The woman did not raise poultry and had not had any animal exposures.


Contact tracing

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Today's report also fleshes out more details about contact tracing. Of 1689 close contacts, excluding the cluster cases, 19 had respiratory symptoms during the 7-day surveillance period; 15 were healthcare workers, 1 was a patient in the same ward, 2 were household members, and 1 was a medical intern.


The investigators wrote that the current mortality rate is 21 percent, but they expect it to increase, given that many of the patients are still critically ill. So far the H7N9 virus appears more virulent to humans than are other H7 viruses, the group noted. Though extensive testing is needed to verify the source of H7N9, the Chinese authors strongly suspect poultry that don't show signs of disease. Until the source is confirmed, they said, control measures -- such as banning the sale of live birds at markets -- could help control the spread of the virus to humans.


Limited human-to-human contact remains a possibility, the scientists wrote, especially in blood relatives. Paired serum samples are being collected from contacts during the case-patients' acute and convalescent illness stages, they added. They recommend enhanced surveillance to clarify the clinical spectrum of the disease and the extent of asymptomatic infection, along with case-control studies to reveal more about the possible animal and environmental source.


China's bird flu outbreak: 3 good signs, 3 bad signs and 3 very bad signs

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Since the new avian flu strain H7N9 began appearing in China earlier this year, it's infected over 100 people, killed 22, spread to five provinces plus Beijing and Shanghai and, as of Wednesday, is confirmed to have spread abroad to Taiwan. How worried should you be about this? How serious is the H7N9 outbreak? The simplest and most honest answer is that we don't know what's going to happen next, either with the virus, which may or may not mutate and become more transmittable, or

with Chinese and international health-care authorities responsible for tamping it down. But there are some good signs, some bad signs and some very bad signs. Here are a few.


Three good signs:

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1. China is being unusually transparent so far. Ten years ago, as the deadly viral respiratory illness known as SARS first spread across China, the government did not respond well. It suppressed information about the outbreak, making it that much harder to contain and study the disease, ultimately costing lives. This time, though, Chinese authorities have been sharing information about the disease's spread,

and state media appear to be freely reporting on new cases. Chinese officials seem to take the disease seriously and want to combat its rise, even if it means overcoming more secretive instincts. All health care for H7N9 is now free in China, for example, to help encourage people to report cases.


2. The number of cases has largely flatlined in the last week. After weeks of rising cases, the number seems to have stayed stable at around 110 over the last week. Big caveats here that there might be cases we don't know about, and the count could change at any moment.


3. Shanghai has found some success limiting new cases. A lot of the cases started around Shanghai, but the city was able to reduce the number of new infections after it closed poultry markets, according to Laurie Garrett, a senior fellow at the Council on Foreign Relations covering health-care policy. The Wall Street Journal found the same thing.


Three bad signs:

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1. It's spreading. With cases recently reported in Shandong province and now in Taiwan, the virus seems to be moving outward.


2. No verified human-to-human transmissions, but it's possible. Neither China nor the World Health Organization has documented human-to-human transmission, which would allow the virus to spread far more quickly and widely, but nor have they ruled it out. The Taiwanese case had no known exposure to poultry.


3. Tough to identify birds with the virus. World Health Organization officials say the virus is more difficult to detect in sick poultry than were previous strains because the birds do not show symptoms that are as clearly identifiable. This makes it tougher to keep sick birds off the market.


Three very bad signs:

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1. It's very deadly, with 18 percent mortality so far. For comparison, tuberculosis has a mortality rate of about 4 or 5 percent in China. Still, the avian flu virus that had its first outbreaks in China in 2006, known as H5N1, has a mortality rate of 60 percent and has killed hundreds of people on multiple continents. It's way too early to tell

H7N9′s mortality rate, given that many infected patients have not yet fully recovered, but it's so far killed about 18 percent of patients.


2. "This is definitely one of the most lethal influenza viruses that we have seen so far." That's according to Keiji Fukuda, the World Health Organization's assistant director general for health, security and the environment, who added, "This is an unusually dangerous virus for humans." Fukuda said the WHO is still struggling to understand the disease, but he certainly seems to be sounding the alarm.


3. More easily transmitted than the 2006 avian flu outbreak. That's alsoaccording to the WHO's Fukuda, who says this new strain is more easily contracted than the H5N1 virus.


Communicated by: Promed Mail



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