H7N9 avain flu, mutating

(News & Editorial/H7N9 avian flu, mutating)

A rhyme was used in 1918 to help people remember local mandates that compelled the wearing of face masks in public:
“Obey the laws
And wear the gauze
Protect your jaws
From septic paws”

H7N9 avain fluH7N9 Avian Influenza virus

A. The Elusive H7N9 Virus: Chinese Researchers Predict Future Pandemic
18 Jun 2013, Science20.com, by Jennifer Wong
Excerpt pasted from: http://www.science20.com/quotsciencequotstruck_bookworm/elusive_h7n9_virus_chinese_researchers_predict_future_pandemic-115063

Since February 2013, China experienced an outbreak of the novel H7N9 avian flu, causing 131 cases of infection, and a death toll of 39. This particular H7N9 strain is considered to be one of the most worrisome pathogens since the H5N1 pandemic in 1997; a reputation based on the virus’ ability to spread easily across species and to infect humans. According to the May 23, 2013 Science paper published by the Joint Influenza Research Centre (State Key Laboratory of Emerging Infectious Diseases, Shantou PR, China), Drs. Y. Guan and Y. Shu reported that H7N9 infects the upper respiratory tract of ferrets and pigs, and spreads via direct contact, suggesting that the rapid surge of H7N9 infections are likely caused by human’s direct contact with infected birds.

The source of the H7N9 virus is quite elusive, mainly because birds carrying the H7N9 virus appear to be unharmed by the infection. This is quite unlike the H5N1 outbreak in 1997, where H5N1-infected birds can succumb to the infection, and that the presence of dead ducks and poultry often indicates the presence of the H5N1 virus.

The Elusive Origin of H7N9
To solve the puzzle of H7N9’s origin, a group of scientists lead by Dr. Kwok Yung Yuen (University of Hong Kong) discovered that H7N9 virus was derived from two origins of ducks, a study the was published in the June 1, 2013 issue of the Lancet. The conclusion was based on the sequencing the hemagglutinin (H7) and neuraminidase (N9) viral genes in human patients that were infected with H7N9 (throat swabs, Zhejiang, China), and extensive analysis to determine whether similar H7 and N9 sequences can be found in duck and poultry samples from the Asian wet markets. Using this approach, Yuen reported that the H7 sequence found in domestic ducks in Zhejiang, and the N9 sequence found in wild ducks in Korea, were the closest match to the respective H7 and N9 protein sequences in H7N9-infected patients in Zhejiang. Yuen further highlighted that in contrast to the H7 proteins from domestic ducks, the H7 proteins in H7N9-infected patients carry several amino-acid mutations including the Gln226Leu, Gly186Val substitutions (associated with their ability to infect humans) and PB2 Asp701Asn mutation (associated with mammalian adaptation).

Further extrapolating the origin of H7N9 from an influenza sequence database (Global Initiative on Sharing Avian Influenza Data (GISAID) database), Dr. George Gao at the Chinese Center for Disease Control and Prevention (Beijing) demonstrated that the H7 gene is likely to have evolved from wild migratory ducks in Asia. Gao further found the H7N9 virus also shares internal genes that are similar to what is found in two lineages of H9N2 poultry influenza virus. In his report published in the June 1, 2013 issue of the Lancet, Gao further concluded that the H7N9 in humans is an evolutionary product that is likely created by multiple gene reassortment events between influenza viruses from at least four different migratory ducks and poultry lineages. According to Gao, H7N9 virus transmission and mutations in birds, and potentially in intermediate animals, should be watched closely to minimize the chances of a future pandemic.

The Ease of H7N9 Mutations and Human-Adaptation Points to the Possibility of a Future Pandemic
As quickly as the H7N9 outbreak emerged in China, the virus seemed to have rapidly disappeared, with no further cases of H7N9 infections since the end of May 2013. But whether the virus would reappear, and whether there might be a future pandemic, are crucial questions to which scientists can only surmise. According to Dr. Michael Gardam (Director of infection prevention and Control at University Health Network, Toronto General Hospital), a global pandemic is really triggered by human-to-human transmission.  “As long as it’s just in birds and hopping to humans on occasion, you’re going to get the same epidemiology that you have now. If [H7N9] can efficiently transfer from human to human, you’ll have a pandemic”, says Gardam. “Influenza is ‘very sloppy’ when it replicates itself – it’s always making mistakes. It could make a ‘good mistake’ for the virus and alter itself to make it easier to spread from person to person. It could also recombine with other viruses, picking up components, of say H3N1 or H1N1, making it easier for humans to contract,” Gardam further explains.

Despite the temporary absence of H7N9 infection in China, scientists are still concerned that the H7N9 viruses in asymptomatic birds could continue to evolve to give rise to viruses capable of human-to-human transmission. Indeed, this is exactly happened to the deadly H5N1 since its outbreak in 1997. According to the 2005 study published in the Journal of Virology, the World Health Organization reported that while the certain H5N1 strains can cause fatality in ducks, there are strains that remain asymptomatic in ducks, and contribute to the continual spread and evolution of the H5N1 strains in wild ducks and waterfowl in 10 Asian countries throughout late 2003 and early 2005 H5N1 in 10 Asian countries. The result was 53 human fatalities in Thailand, Vietnam, and Cambodia, and the death and slaughter of more than 150 million birds. A similar study published in 2005 in the New England Journal of Medicine suggests the possibility of human-to-human transmission of H5N1 in 2004-2005, specifically in house-hold clusters in Vietnam. Whether history would repeat itself in the evolution of H7N9 virus is a possibility that can have serious and immediate impact on public health.

The melting pot of influenza viruses carried in ducks and poultry is very likely the place where H7N9 might mutate by “picking up” viral components from other avian influenza strains. However, scientists are aware that H7N9 can just as likely to mutate in mammals and humans that are coinfected with H7N9 and other influenza strains. Indeed, a recent paper published in the June 15th issue of The Lancet reported a case of human coinfection, where a boy from Jiangsu, China was found to be infected by both the H7N9 and H3N2. According to Dr. Yefei Zhu and colleagues (who authored the paper), “the dual infections are a potential source of reassortment between human and avian viral strains, which could raise the risk of human-to-human transmission”.

Further concerning scientists is the relative ease of H7N9 in breaking the barrier to achieving human-to-human transmission, and acquiring resistance to antiviral drugs. In the two recent Cell papers (June 20, 2013) published by Dr. Ram Sasisekharan at the Massachusetts Institute of Technology, Sasisekharan reported that H7N9 and H5N1 require merely a single amino acid mutation in the hemagglutinin to dramatically enhance their ability to infect humans, and possibly enhance human-to-human transmission. In another study by Dr. Zhenghong Yuan at the Key Lab of Medical Molecular Virology (Shanghai Medical College of Fudan University), a single amino acid mutation (Arg292Lys mutation) in the neuramindase gene of H7N9 contributed to its ability to resist with oseltamivir (Tamiflu, Roche). The study, published in the May 28th online issue of The Lancet, was based on 14 human cases of H7N9 infection in Shanghai, China.

Indeed, the evidence so far indicates that the risk of a future H7N9 pandemic is very real. Yet despite scientist’s efforts in keeping track of the virus, there is really nothing scientists can do to stop a pandemic. According to Gardam, “If H7N9 is able to transmit from person to person, there really isn’t anything realistically that you can do, it’s just going to spread. I’ve likened it to a tidal wave – it’s about surfing the tidal wave than trying to stop the tidal wave.” Gardam further suggests that the most realistic strategy to “ride the tidal wave” is to take hygienic precautions to limit human-bird interactions, and to develop drugs and vaccines against the H7N9 virus.

Less than two months later…..

 B.  First probable person to person transmission of new bird flu virus in China
6  August 2013, ScienceCodex.com, Source: BMJ-British Medical Journal
Pasted from: http://www.sciencecodex.com/first_probable_person_to_person_transmission_of_new_bird_flu_virus_in_china-117111

The first report of probable person to person transmission of the new avian influenza A (H7N9) virus in Eastern China is published on bmj.com today.

The findings provide the strongest evidence yet of H7N9 transmission between humans, but the authors stress that its ability to transmit itself is “limited and non-sustainable.”

Avian influenza A (H7N9) virus was recently identified in Eastern China. As of 30 June 2013, 133 cases have been reported, resulting in 43 deaths.

Most cases appear to have visited live poultry markets or had close contact with live poultry 7-10 days before illness onset. Currently no definite evidence indicates sustained human-to-human transmission of the H7N9 virus.

The study reports a family cluster of two patients (father and daughter) with H7N9 virus infection in Eastern China in March 2013.

The first (index) patient – a 60 year old man – regularly visited a live poultry market and became ill five to six days after his last exposure to poultry. He was admitted to hospital on 11 March.

When his symptoms became worse, he was transferred to the hospital’s intensive care unit (ICU) on 15 March. He was transferred to another ICU on March 18 and died of multi-organ failure on 4 May.

The second patient, his healthy 32 year old daughter, had no known exposure to live poultry before becoming sick. However, she provided direct and unprotected bedside care for her father in the hospital before his admission to intensive care.

She developed symptoms six days after her last contact with her father and was admitted to hospital on 24 March. She was transferred to the ICU on 28 March and died of multi-organ failure on 24 April.

Two almost genetically identical virus strains were isolated from each patient, suggesting transmission from father to daughter.

Forty-three close contacts of both cases were interviewed by public health officials and tested for influenza virus. Of these, one (a son in law who helped care for the father) had mild illness, but all contacts tested negative for H7N9 infection.

Environmental samples from poultry cages, water at two local poultry markets, and swans from the residential area, were also tested. One strain was isolated but was genetically different to the two strains isolated from the patients.

The researchers acknowledge some study limitations, but say that the most likely explanation for this family cluster of two cases with H7N9 infection is that the virus “transmitted directly from the index patient to his daughter.” But they stress that “the virus has not gained the ability to transmit itself sustained from person to person efficiently.”

They believe that the most likely source of infection for the index case was the live poultry market, and conclude: “To our best knowledge, this is the first report of probable transmissibility of the novel virus person to person with detailed epidemiological, clinical, and virological data. Our findings reinforce that the novel virus possesses the potential for pandemic spread.”

So does this imply that H7N9 has come one step closer towards adapting fully to humans, ask James Rudge and Richard Coker from the London School of Hygiene and Tropical Medicine, based in Bangkok, in an accompanying editorial?

Probably not, they say. Limited transmission between humans “is not surprising, and does not necessarily indicate that the virus is on course to develop sustained transmission among humans.”

Nevertheless, they point to several traits of H7N9 are of particular concern, and conclude that, while this study might not suggest that H7N9 is any closer to delivering the next pandemic, “it does provide a timely reminder of the need to remain extremely vigilant: the threat posed by H7N9 has by no means passed.”

The authors also summarise their findings in a video abstract. Dr Zhou says that the reason for carrying out this study was because there was “no definite evidence to show that the novel virus can transmit person-to-person”, plus she and her co-authors wanted to find out whether the novel avian influenza virus possesses the capability to transmit person-to-person. She concludes that “the infection of the daughter is likely to have resulted from her father during unprotected exposure” and suggest that the virus possesses the ability to transmit person-to-person in this cluster. She does add however that the infection was “limited and non-sustainable as there is no outbreak following the two cases”.
Source: BMJ-British Medical Journal

Now,  6 months later… 

C.  H7N9 Virus: One Of The Most Lethal We Have Seen So Far
30 January 2014, ModernSurvivalBlog.com, by Ken Jorgustin
Pasted from: http://modernsurvivalblog.com/pandemic/h7n9-virus-one-of-the-most-lethal-we-have-seen-so-far/#more-32197

UPDATE: A very deadly (bird flu) Avian Influenza ‘A’ virus (H7N9) — first reported in China during March 2013 — is now being confirmed to have ‘limited’ interhuman infection.

Beijing confirmed for the first time that H7N9 bird flu has spread from person to person.
 While Chinese government controlled media has made it difficult to understand the full impact that is underway, and while some reports downplay the potential of a human-to-human pandemic outbreak of the killer virus, there are new reports which are alarming…
•   “…more human H7N9 infections and deaths have been reported in several provinces.”
“(Shanghai)…has reported eight human H7N9 infections in January, four of whom died, including one doctor.”
•   “It deserves high attention when the infection cases increase by dozens or hundreds of times.”
•   “There is no evidence of regular inter-human transmission,” “there has been no evidence for consistent human-to-human infection, but limited, single human-to-human transmission cases cannot be ruled out.”
– (China) xinhuanet.com Jan. 27, 2014 “China goes on high H7N9 bird flu alert”

•   The fact that officials in China are using phrases such as “no evidence of ‘regular’ inter-human transmission” implies that it is indeed occurring. To what extent is subject to interpretation.
•   They are saying that it is not ‘consistent’, but again this implies that it is indeed occurring.
•   They say human-to-human transmission is ‘limited’, but this implies that it is occurring…

During the spring of 2013, the World Health Organization (WHO) reported 132 human H7N9 infections, with 44 deaths. One out of three people died from it.

The Asahi Shimbun, a Japanese national newspaper, recently reported Jan. 29, 2014, that there have been 260 people infected with 71 casualties (27% mortality).

They also said,
“Already this year, 111 infection cases have been confirmed in China – 22 fatalities.”
…in just one month!

In another Xinhua report from Shenyang China on Jan. 28, “A man from northeast China’s Liaoning Province was detained by police after he allegedly spread rumors about H7N9 bird flu on the Internet,” …apparently indicating the degree to which the Chinese government is attempting to suppress related information.

Headlines from China in just the past 2 days include the following…
1.  Chinese family of three infected with H7N9
2.  Bird flu costs China’s farmers 20 bln
3.  HK confirmed latest fatal case of human infected with H7N9
4.  Live poultry markets should close if H7N9 detected
5.  China reports 8 new human H7N9 cases
6.  Experts call for detailed H7N9 rules
7.  HK confirms H7N9 bird flu, to cull about 20,000 poultry
8.  China Focus: China goes on high H7N9 bird flu alert
9.  19 H7N9 deaths in China
10.  12 H7N9 deaths in Chinese province
11.  China reports 6 new human H7N9 cases
12.  China steps up bird flu monitoring at customs
13.  China reports 3 new human H7N9 cases
14.  Five more cases of bird flu reported on Saturday in China
15.  China’s Zhejiang reports 3 new H7N9 cases
16.  China reports 10 new H7N9 human cases
17.  Resurgent bird flu epidemic pains poultry industry
18.  Hangzhou halts live poultry trading; Shanghai reports deaths
19.  China’s health authorities on alert against H7N9

 Last year, the outbreak decreased during the warmer summer months, but the virus is now picking up again…

More recently, the frequency of reports of human infection with H7N9 has increased; since the beginning of October, WHO and China have reported more new H7N9 cases in China per month relative to previous months.
Epidemiological investigations are ongoing for some of the more recent cases, and the CDC says “…currently no evidence has been found that indicates sustained human-to-human transmission is occurring.”

However, the World Health Organization (WHO) has identified H7N9 as…
“…an unusually dangerous virus for humans.”
“This is definitely one of the most lethal influenza viruses that we’ve seen so far.”
Source: Keiji Fukuda, WHO’s assistant director-general for health – news conference in Beijing (CNN)

Even during 2013, s study group headed by one of the world’s leading experts on avian flu reported that several instances of human-to-human infection are suspected.

Their efforts revealed the H7N9 virus’s ability to infect and replicate suggests H7N9 viruses have the potential to become a worldwide threat to human health.
•  “H7N9 viruses have several features typically associated with human influenza viruses and therefore possess pandemic potential and need to be monitored closely,”
•   “If H7N9 viruses acquire the ability to transmit efficiently from person to person, a worldwide outbreak is almost certain since humans lack protective immune responses to these types of viruses,”
Source: Yoshihiro Kawaoka of UW-Madison and the University of Tokyo

 According to the World Health Organization, symptoms include fever, cough, and shortness of breath, which may progress to severe pneumonia. The virus can also overload the immune system, causing blood poisoning and organ failure.

In an article in The New England Journal of Medicine, doctors reported that most of the H7N9 patients had died of acute respiratory distress syndrome (ARDS) or multiorgan failure.

 While there is no major outbreak at this time, the situation warrants your attention. If and when the alarm sounds, there will be little or no time to prepare without risking exposure. The time to prepare is (as always) …now.


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