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H7N9 In China - MMWR March 3 Early Release

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Early Release / Vol. 66 March 3, 2017

U.S. Department of Health and Human Services Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report

Increase in Human Infections with Avian Influenza A(H7N9) Virus During the Fifth Epidemic — China, October 2016–February 2017

A. Danielle Iuliano, PhD1; Yunho Jang, PhD1; Joyce Jones, MS1; C. Todd Davis, PhD1; David E. Wentworth, PhD1; Timothy M. Uyeki, MD1; Katherine Roguski, MPH1; Mark G. Thompson, PhD1; Larisa Gubareva, PhD1; Alicia M. Fry, MD1; Erin Burns, MA1; Susan Trock, DVM1; Suizan Zhou, MPH2; Jacqueline M. Katz, PhD1; Daniel B. Jernigan, MD1


Edited by niman

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Posted (edited)

During March 2013–February 24, 2017, annual epidemics of avian influenza A(H7N9) in China resulted in 1,258 avian influenza A(H7N9) virus infections in humans being reported to the World Health Organization (WHO) by the National Health and Family Planning Commission of China and other regional sources (1). During the first four epidemics, 88% of patients developed pneumonia, 68% were admitted to an intensive care unit, and 41% died (2). Candidate vaccine viruses (CVVs) were developed, and vaccine was manufactured based on representative viruses detected after the emergence of A(H7N9) virus in humans in 2013. During the ongoing fifth epidemic (beginning October 1, 2016),* 460 human infections with A(H7N9) virus have been reported, including 453 in mainland China, six associated with travel to mainland China from Hong Kong (four cases), Macao (one) and Taiwan (one), and one in an asymptomatic poultry worker in Macao (1). Although the clinical characteristics and risk factors for human infections do not appear to have changed (2,3), the reported human infections during the fifth epidemic represent a significant increase compared with the first four epidemics, which resulted in 135 (first epidemic), 320 (second), 226 (third), and 119 (fourth epidemic) human infections (2). Most human infections continue to result in severe respiratory illness and have been associated with poultry exposure. Although some limited human-to-human spread continues to be identified, no sustained human-to-human A(H7N9) transmission has been observed (2,3).

CDC analysis of 74 hemagglutinin (HA) gene sequences from A(H7N9) virus samples collected from infected persons or live bird market environments during the fifth epidemic, which are available in the Global Initiative on Sharing All Influenza Data (GISAID) database (4,5), indicates that A(H7N9) viruses have diverged into two distinct genetic lineages. Available fifth epidemic viruses belong to two distinct lineages, the Pearl River Delta and Yangtze River Delta lineage, and ongoing analyses have found that 69 (93%) of the 74 HA gene sequences to date have been Yangtze River Delta lineage viruses. Preliminary antigenic analysis of recent Yangtze River Delta lineage viruses isolated from infections detected in Hong Kong indicate reduced cross-reactivity with existing CVVs, whereas viruses belonging to the Pearl River Delta lineage are still well inhibited by ferret antisera raised to CVVs. These preliminary data suggest that viruses from the Yangtze River Delta lineage are antigenically distinct from earlier A(H7N9) viruses and from existing CVVs. In addition, ongoing genetic analysis of neuraminidase genes from fifth epidemic viruses indicate that approximately 7%–9% of the viruses analyzed to date have known or suspected markers for reduced susceptibility to one or more neuraminidase inhibitor antiviral medications. The neuraminidase inhibitor class of antiviral drugs is currently recommended for the treatment of human infection with A(H7N9) virus. Antiviral resistance can arise spontaneously or emerge during the course of treatment. Many of the A(H7N9) virus samples collected from human infections in China might have been collected after antiviral treatment had begun.

Although all A(H7N9) viruses characterized from the previous four epidemics have been low pathogenic avian influenza viruses, analysis of human (three) and environmental (seven) samples from the fifth epidemic demonstrate that these viruses contain a four–amino acid insertion in a host protease cleavage site in the HA protein that is characteristic of highly pathogenic avian influenza (HPAI) viruses. Chinese authorities are investigating and monitoring closely for outbreaks of HPAI A(H7N9) among poultry.

Since April 2013, the Influenza Risk Assessment Tool has been used by CDC to assess the risk posed by certain novel influenza A viruses. Although the current risk to the public’s health from A(H7N9) viruses is low, among the 12 novel influenza A viruses evaluated with this tool, A(H7N9) viruses have the highest risk score and are characterized as posing moderate–high potential pandemic risk (6). Experts from the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS) met in Geneva, Switzerland, February 27–March 1, 2017, to review available epidemiologic and virologic data related to influenza A(H7N9) viruses to evaluate the need to produce additional CVVs to maximize influenza pandemic preparedness. Two additional H7N9 CVVs were recommended for development: a new CVV derived from an A/Guangdong/17SF003/2016-like virus (HPAI), which is a highly pathogenic virus from the Yangtze River Delta lineage; and a new CVV derived from A/Hunan/2650/2016-like virus, which is a low pathogenic virus also from the Yangtze River Delta lineage (1). At this time, CDC is preparing a CVV derived from an A/Hunan/2650/2016-like virus using reverse genetics. Further preparedness measures will be informed by ongoing analysis of genetic, antigenic, and epidemiologic data and how these data impact the risk assessment. CDC will continue to work closely with the Chinese Center for Disease Control and Prevention to support the response to this epidemic. Guidance for U.S. clinicians who might be evaluating patients with possible H7N9 virus infection and travelers to China is available online (https://www.cdc.gov/flu/avianflu/h7n9-virus.htm).

Edited by niman

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Acknowledgments Eduardo Azziz-Baumgartner, Stephen A. Burke, Douglas Jordan, CDC; Ying Song, Carolyn Greene, CDC, Beijing, China; National Influenza Center, CDC, Beijing, China; Prevention and Public Health Emergency Center, CDC, Beijing, China; Taiwan CDC, Taipei, Taiwan; Centre for Health Protection, Department of Health, Hong Kong SAR, China. 1CDC; 2CDC, Beijing, China. Corresponding author: A. Danielle Iuliano, aiuliano@cdc.gov, 404-639-5106.

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1. World Health Organization. Antigenic and genetic characteristics of zoonotic influenza viruses and development of candidate vaccine viruses for pandemic preparedness, March 2017. Geneva, Switzerland: World Health Organization; 2017. http://www.who.int/influenza/vaccines/ virus/201703_zoonotic_vaccinevirusupdate.pdf?ua=1

2. Xiang N, Li X, Ren R, et al. Assessing change in avian influenza A(H7N9) virus infections during the fourth epidemic—China, September 2015– August 2016. MMWR Morb Mortal Wkly Rep 2016;65:1390–4. http:// dx.doi.org/10.15585/mmwr.mm6549a2

3. Zhou L, Ren R, Yang L, et al. Sudden increase in human infection with avian influenza A(H7N9) virus in China, September–December 2016. Western Pac Surveill Response J 2017;8. http://dx.doi.org/10.5365/ wpsar.2017.8.1.001

4. Elbe S, Buckland-Merrett G. Data, disease and diplomacy: GISAID’s innovative contribution to global health. Global Challenges 2017;1:33–46. http://dx.doi.org/10.1002/gch2.1018

5. Federal Republic of Germany. The GISAID initiative. http://platform. gisaid.org/epi3/start

6. CDC. Influenza risk assessment tool (IRAT). Atlanta, GA: US Department of Health and Human Services, CDC; 2017. https://www.cdc.gov/flu/ pandemic-resources/national-strategy/risk-assessment.htm

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CDC Concerned by H7N9 Bird Flu’s Sudden Spread in China

A sudden surge in cases of H7N9 bird flu in China is a "cause for concern," the Centers for Disease Control and Prevention said Friday.

It's infected 460 people just since October, the CDC said in a report. "It's by far the largest epidemic wave since 2013," said CDC flu expert Dr. Tim Uyeki.

Image: Health officials in protective suits put a goose into a sack as part of preventive measures against the H7N9 bird flu at a poultry market in Zhuji
Health officials in protective suits put a goose into a sack as part of preventive measures against the H7N9 bird flu at a poultry market in Zhuji, Zhejiang province on Jan. 5, 2014. Reuters file

The CDC has been working on a vaccine against H7N9 just in case it's ever needed and is starting work on a second one now because it's started to mutate.

"It's a cause for concern, that's for sure," Uyeki told NBC News. "The surge in numbers of human H7N9 cases in China is definitely a concern."

The CDC issued a travel notice in January, cautioning travelers to China to stay away from live bird markets. Uyeki said travelers do not need to avoid China but they should be aware that poultry can spread the virus.

Related: WHO Says Watch Out for Bird Flu

Since 2013, H7N9 bird flu has infected 1,258 people, the CDC said. So 460 cases in just five months account for a third of all the cases over four years.

Earlier this week the World Health Organization held a meeting on H7N9 and then issued public reassurances, saying the virus did not appear to have changed in a way that would make it more likely to spread to people or to make it more dangerous to people.

Instead, the changes make the virus more dangerous to birds — which could be a good thing.

"These changes make the virus highly pathogenic in birds, meaning that it can cause some severe disease in birds," Dr. Wenqing Zhang, head of WHO's global influenza program, told reporters.

"Previously, H7N9 had only been observed to be 'low pathogenic' in birds, meaning the virus did not cause visible outbreaks of disease in birds," Zhang said.

If an avian influenza virus kills birds, it's bad for poultry farmers but it can give a warning that the virus is spreading. The problem with H7N9 has been that it does not make poultry sick, so it can spread among flocks without people knowing it.

 Can You Catch Bird Flu? 0:42

Uyeki is worried that H7N9 has become more widespread in China, spreading silently and infecting more people because it's infecting more birds.

"You could have more cases of human infection even if the risk of poultry-to-human transmission has not changed," he said.

China has been publishing genetic sequences of the H7N9 virus in public databases, but it has not been sharing actual samples of the virus, so it's not possible for U.S. labs to test the virus themselves to see whether it's changed and if so, whether it's more dangerous.

But it's already dangerous. H7N9 is considered a moderate to high pandemic threat, although the CDC and WHO do not think an H7N9 pandemic is about to happen, or even that it is certain to happen.

Related: CDC Issues H7N9 Travel Warning

H7N9 is one of several strains of bird flu that officials are watching because they have the potential to cause a human pandemic.

So far, H7N9 doesn't seem to infect people easily and people who are infected do not seem to spread it to others much. But influenza viruses change quickly and unpredictably, and if one starts passing easily from one person to another it could spread.

"From what we understand, there have been no real changes in the epidemiology or mortality of hospitalized H7N9 cases," Uyeki said.

H7N9 can be deadly when people do get it. It kills more than 40 percent of people who get sick enough to go to the hospital.

Related: H7N9 has cost billions

"Early symptoms are similar to those of seasonal flu and may include fever, cough, sore throat, muscle aches and fatigue, loss of appetite, and runny or stuffy nose," CDC said.

It often progresses to pneumonia. And hospitals or clinics treating people infected with H7N9 need to take precautions to make sure patients do not infect anyone else.

"Clinicians should consider the possibility of avian influenza A (H7N9) virus infection in people presenting with respiratory illness within 10 days of travel to China, particularly if the patient reports exposure to birds or poultry markets," the CDC says.

The CDC and WHO are watching the spread of several bird flu viruses that are known to infect people, including H5N1 and H7N2.

Related: Vet Catches Bird Flu From Cats

"Although the current risk to the public's health from A(H7N9) viruses is low, among the 12 novel influenza A viruses evaluated ... A(H7N9) viruses have the highest risk score and are characterized as posing moder­ate-high potential pandemic risk," the CDC team said in the report released Friday. 


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