Tracing evolution of virus yields insight into H7N9 origins

An international research team has shown how changes in a flu virus that has plagued Chinese poultry farms for decades helped create the novel H7N9 avian influenza A virus that has sickened more than 375 people since 2013. The research appears in the current online early edition of the scientific journal Proceedings of the National Academy of Sciences.
The results underscore the need for continued surveillance of flu viruses circulating on poultry farms and identified changes in the H9N2 virus that could serve as an early warning sign of emerging flu viruses with the potential to trigger a pandemic and global health emergency. The work focused on the H9N2 chicken virus, which causes egg production to drop and leaves chickens vulnerable to deadly co-infections. Scientists at St. Jude Children's Research Hospital and the China Agricultural University, Beijing, led the study.
Researchers used whole genome sequencing to track the evolution of the H9N2 chicken virus between 1994 and 2013. The analysis involved thousands of viral sequences and showed that the genetic diversity of H9N2 viruses fell sharply in 2009. From 2010 through 2013 an H9N2 virus emerged as the predominant subtype thanks to its genetic makeup that allowed it to flourish despite widespread vaccination of chickens against H9N2 viruses.
Evidence in this study suggests the eruptions set the stage for the emergence of the H7N9 avian virus that has caused two outbreaks in humans since 2013, with 115 confirmed deaths. The H9N2 infected chickens likely served as the mixing vessel where H9N2 and other avian flu viruses from migratory birds and domestic ducks swapped genes, researchers noted. The resulting H7N9 virus included six genes from the H9N2.
"Sequencing the viral genome allowed us to track how H9N2 evolved across time and geography to contribute to the H7N9 virus that emerged as a threat to human health in 2013," said Robert Webster, Ph.D., a member of the St. Jude Department of Infectious Diseases. He and Jinhua Liu, Ph.D., of the College of Veterinary Medicine at the China Agricultural University, are co-corresponding authors.
"The insights gained from this collaboration suggest that tracking genetic diversity of H9N2 on poultry farms could provide an early warning of emerging viruses with the potential to spark a pandemic," Webster said.
The analysis also provided insight into the creation of the H9N2 virus that emerged as the predominant subtype in 2010. Factors included widespread use of poultry vaccines and the natural tendency of flu to mutate, mix and swap genes.
Beginning in 1998, vaccinating poultry against H9N2 prevented flu outbreak for more than a decade. Vaccines work by recognizing and attaching to the spike-shaped hemagglutinin (HA) protein on the surface of the flu virus. That blocks the virus from infecting healthy cells. Changes in the HA gene that change the shape of the HA protein can reduce vaccine effectiveness and result in disease outbreaks. HA mutations occur naturally over time. Vaccines increase pressure for HA mutations that help the virus escape vaccine detection and cause infection.
Researchers at the China Agricultural University checked H9N2 vaccine effectiveness against the predominant H9N2 virus from 2010-11. Working in vaccinated and unvaccinated chickens, investigators found the vaccine neither protected vaccinated chickens from infection nor prevented spread of the virus in vaccinated chickens. Those failures suggest that due to HA mutations vaccines were less able to recognize the virus.
The tendency of flu viruses to swap genes also contributed to the enhanced ability of the predominant H9N2 subtype to spread. Researchers found that prior to the virus' emergence as the predominant H9N2 the virus had swapped genes with quail and duck influenza viruses.
The combination fueled the recent outbreaks of H9N2 on chicken farms by helping the virus escape vaccine detection and spread rapidly in vaccinated and unvaccinated poultry, said co-first author Juan Pu, Ph.D., a St. Jude visiting scientist from the China Agricultural University. The other first authors are Shuoguo Wang, Ph.D., of the St. Jude Department of Computational Biology, and Yanbo Yin, Ph.D., of Qingdao Agricultural University, Qingdao, China.
"The emergence of this dominant H9N2 virus was the first step in the genesis of the H7N9 viruses because it greatly increased the likelihood of reassortment between H9N2 and other flu subtypes," Liu said. Reassortment refers to the tendency of flu viruses to swap genes.
The other authors are Robert Carter, Yuannian Jiao, Susu Duan, Hui Zhang and Gang Wu, all of St. Jude; Gordon Lemmon, formerly of St. Jude; Guozhong Zhang, Jinliang Wang, Guanlong Xu, Honglei Sun, Min Wang, Chu Wen, Yandi Wei, Qian Wang, Qian Du, Meng Sun, Jinnan Bao, Yipeng Sun and Jixun Zhao, all of the China Agricultural University; Dongdong Wang, Qingdao Agricultural University; and Baoli Zhu, Chinese Academy of Sciences.
The research was funded in part by grants from the National Natural Science Foundation of China; the National Basic Research Program; the China Scholarship Foundation; Key Technologies Research and Development Program of China; the China Agriculture Research System; a contract (N266200700005C) from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health; and ALSAC.

FAO rules out human-to-animal transmission of H7N9 avian influenza

The United Nations Food and Agriculture Organization (FAO) says there is no evidence that human patients infected with H7N9 avian influenza can transmit the virus to animals, including birds. FAO referred to the first human case of H7N9 outside China, which was recently detected in Malaysia.
The patient, originally from Guangdong Province in China, where she is thought to have contracted the infection, was visiting Malaysia as a tourist and has now been hospitalized there. Guangdong is one of the Chinese provinces most affected by the H7N9 virus in 2014.
"This case does not come as a surprise and should not be a cause for increased concern, but should remind the world to remain vigilant," said FAO Chief Veterinary Officer Juan Lubroth.
"Humans that become ill with (H7N9) constitute no threat to poultry populations," Lubroth underlined.
"In fact, we have no evidence that affected people could transmit the virus to other species, including birds. The highest risk of virus introduction is uncontrolled live poultry trade between affected and unaffected areas."
People, on the other hand, become infected following close contact with infected live poultry, mostly in live bird markets or when slaughtering birds at home.
WHO risk assessments show that should infected people from affected areas travel internationally, community level spread is unlikely since the virus does not have the ability to transmit easily among humans.
Lubroth observed that "Such 'imported' human cases, like the one reported in Malaysia last week, have been found in the past in previously unaffected areas of China, like Guizhou, Taiwan Province of China and Hong Kong SAR, and we will likely continue to see this in the not too distant future again. To date the virus has not been found in poultry populations outside affected areas in China."
Birds that have contracted H7N9 do not show clinical signs, which renders early detection of the virus in poultry populations more difficult. FAO therefore urges countries to adapt their surveillance programs to include this recently emerged virus.
One of the main recommendations is to target surveillance at critical points of entry, where direct or indirect live poultry trade with infected areas might occur.

In order to reduce human exposure to zoonotic pathogens in general, biosecurity measures should be introduced or reinforced at live bird markets, including frequent cleaning and disinfection, establishing market rest days with no poultry present and applying good hygiene standards.
With the strong support of the United States Agency for International Development (USAID), FAO is assisting a number of member countries to prepare for a potential introduction of H7N9 into their poultry populations.

FAO is focusing in particular on high risk countries, facilitating risk assessment, contingency planning, expansion of diagnostic capabilities and risk-based surveillance.

Vietnam bans poultry imports from China over H7N9 worries

Vietnam has banned poultry imports from China, citing fears of the spread of H7N9 avian influenza. To date, Vietnam has not had any reports of H7N9 avian influenza, though there have been confirmed cases of H5N1 avian influenza in Vietnam in recent months.
The fears of H7N9 avian influenza's spread are high, as two human cases of H7N9 avian influenza in Quangxi were confirmed. Quangxi is a Chinese province bordering Vietnam.
Cao Duc Phat, Vietnamese minister of agriculture and rural development, said the country is also cracking down on the illegal import of poultry from China. According to reports, there is no official tally on the amount of illegal poultry imports from China, but in one major poultry market in Hanoi, there could be as many as five metric tons of illegal poultry imports arriving daily.

Malaysia has first case of H7N9 avian influenza

Malaysia has experienced its first human case of H7N9 avian influenza, health officials announced on February 12. The patient has been identified as a 67-year-old woman, who had recently traveled to China.
The woman is believed to have contracted the H7N9 virus when she was part of a travel group visiting China's Guangdong province, an area that has seen multiple human cases of H7N9 avian influenza. She is presently being treated in the intensive care unit at a private hospital, according to the Center for Infectious Disease Research and Policy.
Malaysia's health minister, Datuk Seri Dr. S. Subramaniam, said it was the first case of H7N9 in Malaysia, and health officials are taking steps to limit other people's contact with the patient.

Africa must increase safeguards against avian influenza A(H7N9)

Following the emergence of the novel influenza A(H7N9) virus in birds in China, countries in Africa are being encouraged to increase their preparedness for the new, low-pathogenic strain of avian influenza.
The Food and Agriculture Organization (FAO) and the African Union's Interafrican Bureau for Animal Resources (AU-IBAR) have identified the need to invest in a project that would assist selected African countries to conduct regular H7N9 risk assessment, implement risk-based surveillance and update their contingency plans.
A number of countries have been identified due to their trade with China, their high density of poultry or a history of infection with H5N1.
Most of these countries have already established surveillance systems and contingency plans to combat the spread of highly pathogenic avian influenza H5N1, which hit Africa in 2006. However, with the advent of low-pathogenic A(H7N9), these surveillance and contingency measure need to be updated.

China closes poultry markets, culls 20,000 birds

Cheung Sha Wan Poultry Wholesale Market will be closed until February 18, 2014, after a batch of live chickens from Foshan, Guangdong, was confirmed to have the H7N9 avian influenza virus, according to a statement from Hong Kong's Secretary for Food and Health, Dr. Ko Wing-man. All live poultry in the market -- about 20,000 birds -- have been culled to prevent spread of the virus.
The city has also blocked live poultry imports from mainland China during the market closure.
Agriculture, Fisheries and Conservation Department officers will inspect local farms to collect samples for testing to monitor whether the local farms have been infected.
The ban is in place days before the start of Chinese New Year, when traders usually see a big boost in sales.

Live poultry trading halted in Hangzhou, China

Live poultry trading has been put to a stop in Hangzhou, the capital city of east China's Zhejiang province. The halt of live poultry trading in Hangzhou was announced on January 23 in an effort to help contain H7N9 avian influenza infections.
According to reports, city authorities ordered to disinfect live poultry markets in six districts and launched a widespread monitoring over domestic fowl and birds in poultry farms, habitats of migratory birds as well as parks. The government also banned the flying of carrier pigeons.
The ban of live trading comes on the heels of five new human cases of H7N9 avian influenza reported in Zhejiang. The mayor of the city announced there were two new avian influenza fatalities, but did not confirm with any further details.

Human cases of H7N9 on the rise again in southern and eastern China

Human infections with the H7N9 avian influenza virus are on the rise again in China and the upcoming Chinese New Year festivities provide opportunity for further spread and human exposure, the United Nations Food and Agriculture Organization (FAO) warned January 20.
Millions of people and poultry are expected to be on the move and many households will slaughter poultry at home to celebrate the new year on January 31. FAO called upon neighboring countries to remain vigilant in the face of H7N9 and other avian influenza viruses, such as highly pathogenic avian influenza H5N1.
The number of human infections with H7N9 has considerably increased since late December 2013 in East and Southeast China, according to the World Health Organization (WHO). The increase in cases was expected, as influenza viruses traditionally show increased activity during the winter months. So far, no other country has reported H7N9 in humans, animals or in the marketplace.

There is strong evidence that people become infected following close contact with infected live poultry, mostly in live bird markets or when slaughtering birds at home. According to WHO, no sustained human-to-human transmission has occurred so far. Genetic analysis by FAO reference centers has revealed that the virus has not changed significantly since its emergence in 2013.

"Chinese authorities are enforcing important measures to reduce the risk of human exposure to the (H7N9) virus," said FAO Chief Veterinary Officer Juan Lubroth. "This includes temporary closures of live bird markets, regular market rest days, improved hygiene in markets, heightened and ongoing surveillance in poultry and live bird market environment, and control of poultry movements."

Risk to humans remains
"But countries need to stay alert, as the virus continues to circulate in poultry without showing any visible clinical signs. The risk to humans remains, especially over the next few months and particularly during the Chinese New Year's holiday period," Lubroth said.

FAO is assisting a number of member countries, particularly those that are at high risk, in preventing and preparing for possible H7N9 introductions into their poultry populations, conducting  risk assessment, contingency planning and expansion of diagnostic capabilities, and risk based surveillance.

In South and South-East Asia, FAO, with strong support from the United States Agency for International Development (USAID), has assisted countries with the implementation of animal and environmental surveillance at live bird markets and on farms since June last year. FAO supported projects are also underway to assist some countries in Africa to prevent and be prepared for facing threats from avian influenza viruses, including H7N9.

It is essential to focus on good biosecurity standards on farms and markets, regular market cleaning and disinfection, and targeted surveillance in areas that have direct or indirect live poultry trade with infected areas. If infection in animals is shown or suspected to be confined to a specific area, culling should be considered as long as it performed in a humane way with appropriate compensation paid to producers and marketers.

FAO continues to recommend producers and consumers the following standard precautions:
• Close contact with infected animals can put people at risk. Since H7N9 causes little or no signs of disease in birds, it is crucial to separate living areas for animals from those of people.
• Seek immediate advice from your doctor if you show signs of fever after being in contact with poultry, farmed birds, wild birds or other animals.
• Wash your hands often to kill and remove microbes such as bacteria or viruses. You should always do so after handling birds or other animals, before and after preparing food, and before eating.
• Observe good hygiene practices such as keeping raw meat separate from cooked or ready-to-eat foods to avoid contamination, using separate utensils to prepare raw meats and other foods (e.g. chopping boards and other surfaces, knives, and plates, for instance) and washing and disinfecting all surfaces and utensils that have been in contact with raw meat.
• Eat only well-cooked meat products (food reaches 70C or more in all parts). Influenza viruses are not transmitted through consumption of well-cooked food. The consumption of raw meat and uncooked blood-based dishes is a high-risk practice.
• Keep different types of birds and other species of domestic animals apart. Screens, fencing or nets can be used to separate species from each other and help prevent possible transmission.
• Even though wild birds do not seem to be implicated in the spread of H7N9 avian influenza, it is still considered good practice to limit access of wild birds to poultry and other domestic animals.
• Report sick or dead animals to the local veterinary (or public health) authorities. If this is not possible, tell your community leaders. Even though currently, H7N9 does not cause illness in poultry, H5N1 does and it remains important that all signs of illness or sudden and unexplained deaths in poultry, farmed birds, wild birds or other animals are reported to the authorities so that they can deal with them safely and help stop any potentially damaging disease from spreading and limit/avoid subsequent human exposures.
• Do not eat sick or dead animals and do not give or sell them to others. Such animals, also, should not be fed to other animals.

H7N9 avian influenza claims second human life in Hong Kong

A 65-year-old man infected with the H7N9 avian influenza virus has died in Hong Kong. He was the third person to be diagnosed with H7N9 avian influenza in Hong Kong, and the second person to die after contracting the virus.
The man, according to a Reuters report, came from the southern Chinese city of Shenzhen and had eaten poultry there.
The other person to suffer a death from avian influenza in Hong Kong, was an 80-year-old man, who on December 3, 2013, sought diabetes and heart treatment at Tuen Mun Hospital on December 3, but three days later he had flu symptoms. His death was confirmed later in the month. He was the second person in Hong Kong reported to have been stricken by H7N9 avian influenza.
Hong Kong's first human victim of H7N9, a 36-year-old domestic worker who had travelled from Indonesia, was last reported in stable condition.

Second human avian influenza case, 19 people quarantined in Hong Kong

Health officials in Hong Kong have put 19 people under quarantine because they were in contact with an 80-year-old man sickened by avian influenza. The victim is the second human to be infected with H7N9 avian influenza in Hong Kong.
According to a statement from the Centre for Health Protection's Department of Health, the man lives in Shenzhen and was admitted to a hospital on November 13. Among the people who had contact with the patient are family members, a cab driver and other patients at the Tuen Mun Hospital, where the avian influenza patient has been treated, according to a Bloomberg report.
It is not yet known whether the man had contact with live poultry to catch the H7N9 avian influenza virus.
Hong Kong's first case of H7N9 avian influenza was reported in early December. The first of the two Hong Kong avian influenza patients was a 36-year-old woman.

Food and Agriculture Organization launches emergency H7N9 avian influenza projects in Asia

Two emergency regional projects aimed at containing avian influenza in the Asia-Pacific region were launched by the UN Food and Agriculture Organization's Regional Office for Asia and the Pacific during September.
The projects will promote coordinated sub-regional preparedness, surveillance and response to avian influenza H7N9 in poultry and other animal populations in Asian countries at risk. Conducted in coordination with development partners, such as the United States Agency for International Development, the World Organization for Animal Health and the World Health Organization, the projects will assist countries in the region to better detect, control and respond to the virus.
FAO said these initiatives will boost epidemiologic knowledge, surveillance and diagnostic capacity, and risk management, including preparedness and response, and risk communication, as well as coordination and collaboration among Association of Southeast Asian Nations members and members of the South Asian Association for Regional Cooperation.
Speaking at the project launch, Hiroyuki Konuma, FAO assistant director-general and regional representative for Asia and the Pacific warned the region that the "virus in China is still present and there is still a great deal not yet understood about this H7N9 virus. Other influenza viruses that circulate in poultry often decrease dramatically during the summer months, only to reappear later in the year during the cold season. Also, many low-pathogenic influenza viruses in poultry have transformed into highly pathogenic viruses."
Konuma called on the region's countries to ensure that they are prepared should the N7N9 virus follow a similar path. "This means that countries in Asia need to be vigilant - both for incursion and spread of the virus, and possible evolution to highly pathogenic type," Konuma said. 

China allows transport of qualified breeding birds nationwide

Qualified breeding birds or young breeders from quarantined producing areas but proved to H7N9-free by lab testing are now being allowed to be distributed and delivered throughout China. This follows a May 10 announcement by six departments of the Chinese government that banned provinces with confirmed H7N9 avian influenza infections or where H7N9 virus was found from animals and environmental samples from transporting live poultry across provincial borders.
The notification also requires effective safety measures to encourage slaughtering of live poultry at areas close to farming lands. The government departments, including China's Ministry of Agriculture, Ministry of Public Security, Ministry of Transport, State Administration for Industry and Commerce, and State Food and Drug Administration, also set measures to lead consumers to buy chilled poultry products in the notification.

Poultry markets in Shanghai to reopen by late June

Shanghai will reopen its market for live poultry by the end of June, but it could be reduced by 50 percent, authorities said. All live poultry markets there have been closed since April 6 after a deadly outbreak of H7N9 avian influenza.
"The city is considering reopening some live poultry trading markets," Shao Linchu, deputy director of Shanghai Agriculture Commission, told the People's Daily. "But these markets will adhere to stricter requirements, such as sterilization and environment."
In addition, the city also advocated the consumption of chilled and frozen chicken, which are processed under strict quarantine supervision.
According to the city's agriculture department, Shanghai consumes between 170 million and 180 million chickens annually, with more than 70 percent purchased live. 

International Poultry Council stresses food products are safe

Even though a new strain of Type A H7N9 influenza that apparently originated in a live bird market in China has infected more than 100 Chinese people, consumers can be confident in eating properly cooked poultry meat, according to the International Poultry Council.
The International Poultry Council, an organization comprised of poultry industry associations from more than 20 major poultry-producing countries around the world, is closely monitoring developments in China regarding the spread of this new strain of Type A H7N9 influenza. Numerous human cases have occurred and have resulted in at least 10 deaths, most of which occurred in people who were exposed to the virus by handling infected birds.
Thus far, Chinese authorities have worked diligently and vigorously to contain the spread of the virus, have closed live bird markets in Shanghai and in other affected areas, and have destroyed infected birds. Although Chinese officials have found no Type A H7N9 influenza infections in any commercial poultry farms or in poultry processing plants in China, the situation has caused many consumers in China to refrain from eating poultry products. This anxiety among consumers has cost the Chinese poultry industry millions of dollars in lost sales as a result.
The World Health Organization and leading influenza experts agree that proper cooking is the best defense against foodborne illnesses, including influenza. In fact, Dr. Michael O'Leary, who heads the World Health Organization's office in Beijing, said he eats chicken every day.
Cooking to an internal temperature of 74 degrees Celsius destroys any residual viruses that may in the meat. In other words, there is no risk of contracting influenza from eating properly cooked poultry meat.
Chinese consumers can be assured that all poultry products they get in the market, regardless of origin, can be eaten safely when they are properly cooked.
"The global poultry industry has been impressed with the growth in per capita poultry consumption in China, which is eclipsing pork," said International Poultry Council President Jim Sumner. "In fact, since 1990, China's per capita poultry consumption has increased nearly five-fold, to more than 10 kilograms."
Sumner also said that, while poultry consumption dipped during previous influenza occurrences in China, consumers quickly realized that properly cooked and prepared poultry meat is safe, and consumption rebounded.
He said that the reaction of consumers to previous incidents prompted the International Poultry Council to adopt the slogan: "Poultry is safe. Just cook it.!"

Avian flu found in Minnesota turkeys

An unidentified commercial turkey flock in central Minnesota has been quarantined by the Board of Animal Health after routine testing discovered a strain of the avian flu virus, labeled H7N9, according to an Associated Press news report.
Minnesota Board of Animal Health Assistant Director Dale Lauer stressed that the avian flu strain found at the Meeker County farm was different from the strain that has caused problems in birds and humans mostly in Asia.
Lauer, a veterinarian, went on to inform that the strain of virus found at the farm didn't pose a threat to the general public but could cause mild symptoms in poultry workers, including mild eye infections and mild respiratory problems.
According to him, the quarantined flock was showing no signs of illness, but if left unchecked the virus could morph into a form that could be more pathogenic to the state's commercial poultry flocks. Minnesota is the nation's top turkey producing state.
Surrounding poultry farms in a three-mile radius have also been quarantined and will undergo the same routine testing and observation as the primary site.