ESA: Epidemiological Update On H5N8/H5N5 In Europe - Feb 28th

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Throughout this winter's remarkable avian flu epizootic in Europe,  three entities have provided us with the most detailed accounts and summaries; The UK's DEFRA, Germany's FLI (Friedrich-Loeffler-Institut), and France's ESA (Epidemiosurveillance Santé Animale).

Reporting 373 HPAI H5N8 outbreaks in less than 90 days, France has been perhaps the hardest hit nation.

Today, the ESA has published their latest summary for France - and the rest of Europe. I've translated and excerpted only portions of the full report.

Follow the link below for the full report including graphs, maps, and links.

HPAI epidemiological situation in Europe since October 2016: point situation 27/02/2017

Submitted by Alizé MERCIER on 28. February 2017 - 3:33 p.m..

International Health Surveillance (IVS) ESA platform - France

NRL avian influenza laboratory ANSES Ploufragan - France
National Office for Hunting and Wildlife - France

Source: Data updated on 02.26.2017 (inclusive) ADNS / OIE / EB The Minister of Agriculture

Two virus highly pathogenic avian influenza (HPAI) - H5N5 and H5N8- currently circulating in Europe. The ADNS tool was not adapted to the notification of new subtypes H5N8 and H5N5, leading the country to notify the homes as "H5Nx" with possibility of adding comments in free subtype, which is what certain countries.

In light of these comments, the ADNS statements are distributed as follows: H5Nx (n = 361), H5N5 (n = 18), H5N8 (n = 1600) and Joint H5N5 / H5N8 (n = 1). The HPAI viruses are treated in their entirety in this note. Data analysis takes into account the sometimes changes the ADNS alerts after the first statement, including the accuracy of some serotype H5Nx homes (which are then taken in H5N5 or H5N8 outbreaks).

Since the latter situation on 20 February, 202 new outbreaks of HPAI were reported in Europe (European Union - EU - plus Switzerland), mainly in Germany (66 H5N8 outbreaks in wild birds and 2 farms) and France (39 H5N8 outbreaks in livestock and 6 in the avifauna).

The total number of outbreaks and cases of reported HPAI continues to increase and is now 1 980 1 082 of which in wild birds (73 species affected), 861 livestock and 37 in the captive birds (Tables 1 and 2). For cons, the number of affected countries remains the same.

Several countries reported the presence of virus of subtype H5N5 in wild birds (1 in Germany, 1 case in the Netherlands, 1 case in Montenegro, 2 in Italy, 1 in Croatia, 1 case in Greece, 2 in Poland, Slovenia 3, and since the last update, 1 case in Hungary), in farms with three outbreaks of H5N5 in Germany, and in the captive birds (1 case in Italy, 1 case in the Republic Czech). In addition, the Netherlands reported a mixed case of H5N8 infection / H5N5 in wild birds in November, 2016.

The interactive map of HPAI outbreaks is available on the ESA platform site ( link ).

The HPAI situation in France is detailed every two weeks (last note dated February 24: link ).

HP H5N8 virus is also present beyond Europe in the following countries: Uganda, Cameroon, Nigeria, Tunisia, Egypt, Israel, Kuwait, Iran, Ukraine, Kazakhstan, Russia, India, China, Chinese Taipei South Korea (source: OIE / FAO). A review of the HPAI situation in Africa February 21, 2017 is available on the Platform website ( link ).

Figure 1 shows the evolution of the number of weekly returns and outbreaks of HPAI cases in Europe. Aggregate data for Europe (Switzerland included), with situations very different country from the standpoint surveillance and epidemiology, provide overall indications. At the macroscopic scale, it is interesting to note that the curves "farms" and "savages" have similar developments until the third week in 2017, generally parallel, and with a time lag of two weeks, the curve " wild "before the" farms "curve. We find the same gap between farmed and wild compartments in the aggregate representing the number of new countries reporting their first home / cases of HPAI (Figure 2).

The evolution of these curves would be consistent with contamination of livestock by wildlife and suggests a lack of proper development of the disease in the livestock compartment, overall on the European continent (which does not preclude situations particular where locally there might be an important secondary distribution between farms). However, this interpretation must be taken with caution, variations being a dependent of pressure from oversight in different populations, and the other hand certainly different in different countries (for Hungary and France who said a large number of cases in livestock but not in wild birds and in contrast to Germany and Switzerland reporting a large number of cases in wild birds and little or no animal husbandry). In the last notes, the number of cases observed in the last week is adjusted from one week to the other by late returns. so it should not draw conclusions from the data last week.

The reported mortality in livestock vary according to species, but also within the same species, and is only available for a limited number of households. For mono-specific farming, the mortality ranges from 0.06 to 33% to the species Gallus gallus , around 20% in turkey farms (but with a 100% mortality rate reported in a home in France) and from 0 to 70% in waterfowl. Despite all the caution that one must have in interpreting (time of intervention in relation to infection, farms in epidemiological link could be the beginning of infection, etc.), it should be noted that this strain appears to have an unusual virulence in domestic waterfowl.

The 73 different species of birds in affected wild birds in Europe with their families are:

    Accipitridae  : Goshawk, spp Eagle, Harris Hawk, Rough-legged Hawk, Buzzard, Sparrowhawk, White-tailed Eagle.
    Anatidae: Red-breasted Goose, Brent Goose, Canada Goose, Barnacle Goose, Gadwall, Mallard, Muscovy Duck, Northern Pintail, Wigeon, Whooper Swan, Black Swan, Mute Swan, Common Eider, Common Pochard, Scaup , tufted Duck, Common Goldeneye eye, Common Merganser, Common Scoter, red-crested Pochard, Pink-footed Goose, Greylag Goose, Swan Goose, Egyptian Goose, Bean Goose, White-fronted Goose, White-fronted Goose, Teal , Shelduck
    Ardeidae: Grey Heron, Egret beef, Great Egret
    Ciconiidés : Cigogne blanche
    Colombidae: wood pigeon, collared dove
    Corvidae: Hooded Crow, Carrion Crow, Raven, Magpie
    Dromaiidés: Emus
    Falcon: Common Kestrel, Peregrine Falcon, Saker
    Gulls: Herring Gull, Black-backed Gull, Mew Gull, Yellow-legged Gull, Gull, Black-headed Gull
    Pelecanidés : Pélican blanc
    Phalacrocoracidés  : Cormoran pygmée, Grand cormoran,
    Podicipedidae: Little Grebe, Great Crested Grebe
    Psittacidés : Perroquet jaco
    Rallidae: Crested Coot, Eurasian Coot, Common Moorhen
    Scolopacidae  : Green Sandpiper, Curlew spp.
    Owls  : Eagle Owl, Ural Owl
    Thrushes  : Blackbird, Fieldfare, Song Thrush

 

Saudi MOH Announces 3 MERS Cases

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Reports of MERS-CoV infections in Saudi Arabia continue at a fairly slow rate, with only 17 cases (including today's) reported thus far in the month of February.   

Cases remain widely scattered, and this month, more than half  (n=10) are described as `Primary' cases with recent contact with camels.

Despite constant warnings, camel to human transmission remains fairly common. It has been theorized that young camels - usually born during the winter or early spring - are immunologically naive, and are therefore more likely to acquire the virus and transmit it to humans this time of year.

HK CHP Avian Influenza Report Week 8

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Hong Kong's CHP has published their latest weekly avian influenza report - which includes an increase of 32 H7N9 cases from the Mainland over last week's tally.  While still a substantial weekly number, this represents a sharp decrease over the what has been reported in recent weeks.

They now report 454 Mainland cases since November of 2016 (plus 4 in Hong Kong, 2 in Macao & 1 in Taiwan), nearly quadrupling last year's 12 month tally in only 90 days.

Whether this week's drop is due to recent poultry market closures, a post-peak winding down of cases, or delays in reporting due to the upcoming `Two Sessions' (annual meetings of the National People’s Congress (NPC) and the National Committee of the People’s Political Consultative Congress (CPPCC)) - or some other reason entirely - isn't clear.

Once again (for cases where data is provided), males outnumber females by more than 3:1, and the skewing towards older cases continues, with only 3 (of 32) cases under the age of 30.  Both have been consistent trends with this virus.

Six of 32 cases are listed as having died, 17 are listed as having `Severe Pneumonia', while one case is listed as `Mild' ; a 4 y.o. female from Fujian Province.   Mild cases - while only rarely hospitalized - have been most common in children.


The full report (which runs 10 pages) is well worth downloading and reading, as it contains updates not only on avian flu activity in Mainland China, but around the world.

Avian Influenza Report

Avian Influenza Report is a weekly report produced by the Respiratory Disease Office, Centre for Health Protection of the Department of Health. This report highlights global avian influenza activity in humans and birds.

VOLUME 13, NUMBER 08

Reporting period: February 19, 2017 – February 25, 2017 (Week 08)
(Published on February 28, 2017)

Summary

1. Since the previous issue of Avian Influenza Report (AIR), there were 32 new human cases of avian influenza A(H7N9) reported by Mainland China health authorities in Anhui (5 cases), Guangdong (5 cases), Jiangsu (4 cases), Zhejiang (4 cases), Henan (3 cases), Hunan (2 cases), Jiangxi (2 cases), Sichuan (2 cases), Fujian (1 case), Guangxi (1 case), Guizhou (1 case), Hubei (1 case) and Shandong (1 case). Since March 2013 (as of February 27, 2017), there were a total of 1259 human cases of avian influenza A(H7N9) reported globally. Since November 2016 (as of February 27, 2017), 454 cases have been recorded in Mainland China.

2. Since the previous issue of AIR, there were no new human cases of avian influenza A(H5N6). Since 2014 (as of February 25, 2017), 16 human cases of avian influenza A(H5N6) were reported globally and all occurred in Mainland China. The latest case was reported on December 1, 2016.

3. There were no new human cases of avian influenza A(H5N1) reported by the World Health Organization (WHO) in 2017. From 2011 to 2015, 32 to 145 confirmed human cases of avian influenza A(H5N1) were reported to WHO annually (according to onset date). In 2016, there have been 10 cases in Egypt.*

* Since November 21, 2012, WHO only publishes information on human cases with avian influenza A(H5N1) infection in “Influenza at human - animal interface: Monthly Risk Assessment Summary”. Only cases of human infection with H5N1 involved in events that are unusual or associated with potential increased risks will be reported in Disease Outbreak News. The latest report was published in February, 2017.
 

             

Taiwan Reports Imported H7N9 Patient Has Died

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A little over 3 weeks ago, in Taiwan CDC Announces An Imported H7N9 Case, we learned of a 69 year old businessman who fell ill while visiting Guangdong Province in late January.  After first seeking medical attention on the Mainland, he returned to Taiwan where he was hospitalized, and eventually (on Feb. 4th) was diagnosed with H7N9.

This story took a major twist  8 days ago when it was revealed this patient - who was in critical condition - carried a similar HPAI mutation to the one announced discovered in two Guangdong patients 9 days ago (see WHO Report).

All three known cases of HPAI H7N9 infection are also reported as having genetic changes associated with neuraminidase inhibitor antiviral drug resistance.

There appears to be some question over whether these viruses carried these changes when they were acquired - or if these patients developed resistance after receiving antiviral treatment (aka a `spontaneous mutation').  

Of these three patients, the first (a 43-year-old woman who fell ill in late December) has recovered, the second (a 57-year-old male who fell ill in early January) remains in critical condition, and the third we learn, died overnight. 

First the media report, then I'll return with a bit more.

Taiwanese man dies of H7N9 avian flu

2017/02/28 15:23:01

Taipei, Feb. 28 (CNA) A 69-year-old man who contracted the H7N9 avian flu virus in China last month has died, becoming the first Taiwanese victim of that virus strain, the Centers for Disease Control (CDC) said Tuesday.

The businessman died late Monday, said Lo Yi-chun (羅一鈞), deputy director-general of the CDC. The patient had been in hospital in Kaohsiung for 27 days after falling ill in China and returning to Taiwan on Jan. 25 to seek medical help.

(Continue . . . )

A mutated H7N9 virus displaying signs of antiviral resistance is obviously a serious concern.  But we are still dealing with a fairly small sample size (n=3) out of 52 cases reported this year from Guangdong Province.  The first two patients were infected roughly 60 days ago, and the third in mid to late January, and China has not announced any more recent cases.

While there may well be more cases like these, China will have to disclose a lot more surveillance data (human & poultry) before we can know if this new strain has `legs'.  

And while worrisome, these are far from the first antiviral resistant H7N9 strains we've seen.

A small number of oseltamivir (Tamiflu ®) resistant strains were detected during the first wave in 2013 (see The Lancet: Antiviral Resistance In Two H7N9 Patients), including Taiwan's very first imported case (see The Taiwan H7N9 Patient & Antiviral Resistance), who developed resistance while receiving treatment. 

For a more detailed look at the mechanisms and drivers of antiviral resistance you may wish to revisit mBio: Antiviral Resistance In H7N9.

Whether this particular HPAI H7N9 stain is biologically `fit' enough to compete with all the other wild types in circulation - or turns out to be an evolutionary flash in the pan - remains to be seen.

But successful or not, with literally dozens of genotypes already in circulation - and their continual intermixing with other influenza A viruses - this won't be the last time we see this virus reinvent itself. 

While most of these incarnations will carry no significant evolutionary advantage, it only has to get it `right' once for us to find ourselves facing another global public health crisis.

Egypt: FAO Reports Two Human H5N1 Cases

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Getting avian flu news out of Egypt is often tougher than it is from China, but on Saturday - in Egypt: Conflicting Media Reports Of An Avian Flu Fatality In Fayoum - we saw an Arabic media report about what was supposedly their first H5N1 case of the year.

Today the FAO is reporting on a fatal case in Fayoum (presumably the same one), and another case -  apparently from almost a month ago - in Menia. 

Both show a `reporting' date of the 27th, but the Menia case's `Observation Date' is listed as 01/02/2017, while the Fayoum case is listed as  01/05/2017.   There doesn't appear to be any mention of either of these cases on the Egyptian MOH website. 


The two FAO reports follow:

 I should also note that FluTrackers has picked up a media report suggesting the Fayoum case may be part of a family cluster (see ​Egypt - FAO confirms H5N1 bird flu death - Fayoum governorate - February 25, 2017 - Possible family cluster).

For more on the (murky) bird flu situation in Egypt, you may want to revisit my blog of three weeks ago called H5N8 & H5N1: Murmurs From The Middle East.
 

WHO H7N9 Update On Three Human Cases With HPAI Mutation

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Eight days ago we learned of the first detection of an HPAI strain of H7N9 in two patients in Guangdong Province (see Two H7N9 `Variants' Isolated From Human Cases), followed 24 hours later by an announcement from the Taiwan CDC: January's Imported H7N9 Case Carried HPAI Mutation.

Over the past few days we've also learned that all three infections were oseltamivr (Tamiflu (c)) resistant - although it isn't clear whether these viruses were resistant in the wild, or if the resistance formed while these patients were receiving antiviral treatment.

Details on these cases, beyond that, have been scant.  While there is still much we don't know about the future impact of these genetic changes, today we have fairly detailed report from the World Health Organization on these three cases, and China's immediate response.

Human infection with avian influenza A(H7N9) virus – China

Disease outbreak news
27 February 2017

On 18 February 2017, the National Health and Family Planning Commission of China (NHFPC) reported to WHO the results of genetic sequencing on virus isolates from two previously reported cases of human infection with avian influenza A(H7N9) virus from Guangdong province. Changes at the cleavage site of the HA gene suggestive of being highly pathogenic to poultry was confirmed by the Chinese National Influenza Centre of the Chinese Centre for Disease Control and Prevention (China CDC).

Details of the cases
The two cases were reported through International Health Regulations (IHR) notification on 19 January 2017.

    A 43-year-old female with symptom onset on 29 December 2016. The case recovered. She had poultry exposure but also cared for her sister who was hospitalized with avian influenza A(H7N9). This was reported as a family cluster.
    A 57-year-old male with symptom onset on 5 January 2017. The case is still hospitalized and in critical condition as of 22 February 2017. He was reported to have had poultry exposure.

Investigation revealed exposure to sick and dead poultry. None of the 105 close contacts of these two cases developed symptoms during the two weeks of medical observation. To date, there is no evidence of changes in pathogenicity to and transmissibility among humans.

Public health response

Considering the new developments in H7N9 genetic sequence, the Chinese government is implementing additional measures in Guangdong province on top of current existing measures:

    Closure of markets for cleaning.
    Emergency monitoring of poultry markets and flocks.
    Culling of flocks if the strain is confirmed in them.

WHO risk assessment

This is the first report of avian influenza A(H7N9) virus, since its emergence in 2013, having genetic sequences that are suggestive of evolving from a low pathogenic into a highly pathogenic avian virus. Similar changes at the cleavage site of the HA gene were also found in genetic sequence data uploaded in Global Initiative on Sharing Avian Influenza Data (GISAID) of a virus from a recent human case reported by Taiwan, China earlier to WHO on 4 February 2017 with travel history to Guangdong. In addition the Ministry of Agriculture China reported to World Organisation for Animal Health (OIE) on 21 February 2017 that genetic sequences of virus samples from live poultry markets in Guangdong also showed changes consistent with highly pathogenic avian influenza viruses. So far the above genetic changes have been found in viruses from human, poultry and environmental samples from Guangdong or with travel history to Guangdong province.

In addition the genetic sequences from the two human cases from Guangdong and the case reported by Taiwan, China showed amino acid substitutions associated with neuraminidase inhibitor antiviral drug resistance. It was reported that the three patients received antiviral treatment before samples were taken.

So far there is no evidence of change of epidemiological patterns of avian influenza A(H7N9) infection in humans. There is no evidence that a change in the virus from low pathogenic to high pathogenic avian influenza virus has an impact on the pathogenicity or transmissibility in humans.

Overall the likelihood of further community level spread remains low.

WHO is closely monitoring the impact of these viruses on public health through its Global Influenza Surveillance and Research System (GISRS) network, and its effect on animal health through collaboration with Food and Agriculture Organization of the United Nations (FAO) and OIE, and will update public health risk assessment accordingly.

A change in the virus from low pathogenicity to highly pathogenicity in poultry may have implications on surveillance and control strategies at the animal sector.
WHO advice

WHO advises that travellers to countries with known outbreaks of avian influenza should avoid, if possible, poultry farms, contact with animals in live poultry markets, entering areas where poultry may be slaughtered, or contact with any surfaces that appear to be contaminated with faeces from poultry or other animals. Travellers should also wash their hands often with soap and water, and follow good food safety and good food hygiene practices.

WHO does not advise special screening at points of entry with regard to this event, nor does it currently recommend any travel or trade restrictions. As always, a diagnosis of infection with an avian influenza virus should be considered in individuals who develop severe acute respiratory symptoms while travelling in or soon after returning from an area where avian influenza is a concern.

WHO encourages countries to continue strengthening influenza surveillance, including surveillance for severe acute respiratory infections (SARI) and influenza-like illness (ILI) and to carefully review any unusual patterns, ensure reporting of human infections under the IHR 2005, and continue national health preparedness actions.

WHO WPRO Update On H7N9 In China

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Although it doesn't add a lot to what we've already seen reported, over the weekend the WHO's WPRO (Western Pacific Region) published an update on China's record breaking 5th winter H7N9 epidemic  - one which also confirms their notification of the recent HPAI mutations reported from Gaungdong province.

While the WHO is continuing to investigate this new finding, along with the general behavior and spread of this year's epidemic, for now they state - `Overall, the public health risk from avian influenza A(H7N9) viruses has not changed.'

For more on the emergence of an HPAI strain of H7N8, you  may wish to revisit Saturday's ECDC Comment On HPAI Mutation Of H7N9,  and yesterday's interview with Zhong Nanshan On China's Mutated H7N9 Virus.

Human Infection with Avian Influenza A(H7N9)
 
24 February 2017

From 17 to 23 February 2017, 305 cases of human infection with avian influenza A(H7N9) virus were published in Disease Outbreak News. The last case of human infection with avian influenza A(H7N9) virus in the Western Pacific Region published through Disease Outbreak News was notified to WHO 22 February 2017. (Source: http://www.who.int/csr/don/22-february-2017-ah7n9-china/en/). A total of 1,223 laboratory-confirmed human infections with avian influenza A(H7N9) virus were reported to WHO between early 2013 and 22 February 2017.

WHO is continuing to assess the epidemiological situation and will conduct further risk assessments with new information. Overall, the public health risk from avian influenza A(H7N9) viruses has not changed.

Further sporadic human cases of avian influenza A(H7N9) virus infection are expected in affected and possibly neighbouring areas. Should human cases from affected areas travel internationally, their infection may be detected in another country during or after arrival. If this were to occur, community level spread is considered unlikely as the virus does not have the ability to transmit easily among humans.

On 18 February 2017, the National Health and Family Planning Commission of China (NHFPC) reported to WHO the results of genetic sequencing on virus isolates from 2 previously reported cases of human infection with A(H7N9) virus from Guangdong province. Insertions at the cleavage site of the HA gene suggestive of being highly pathogenic to poultry was confirmed by the Chinese National Influenza Centre of the Chinese Centre for Disease Control and Prevention (China CDC).

To date, there has been no evidence of sustained human-to-human transmission of avian influenza A(H7N9) virus. Human infections with the A (H7N9) virus are unusual and need to be monitored closely in order to identify changes in the virus and/or its transmission behaviour to humans as it may have a serious public health impact.

For more information on human infection with avian influenza A (H7N9) virus reported to WHO:

http://www.who.int/influenza/human_animal_interface/influenza_h7n9/en/

For more information on risk assessment for avian influenza A(H7N9) virus:
http://www.who.int/influenza/human_animal_interface/influenza_h7n9/RiskAssessment_H7N9_23Feb20115.pdf

Zhong Nanshan On China's Mutated H7N9 Virus

H7N9 Waves - Credit WHO

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Fourteen years ago, when SARS was burning its way through parts of China - and the Chinese government actively hid that information from its people, its doctors, and the rest of the world - one man boldly went before the TV cameras and told the truth.

His name : Dr. Zhong Nanshan.

In 2003 he was the director of Guangzhou's Institute of Respiratory Diseases, a member of China’s Academy of Sciences, and pioneered some of the earliest (and most successful) treatments for SARS patients.

Zhong also did something that normally isn't conducive to good health and long life in China . . .  he publicly challenged official government statements on the epidemic. 

But in doing so, Zhong Nanshan not only helped to break the back of an epidemic, he became a much respected and revered household name in China - and the rest of the world. 

So, when Zhong Nanshan (now 80, and Editor-in-Chief of  The Journal of Thoracic Disease) speaks, we listen.

The following (translated) interview with Zhong Nanshan - where he discusses recent changes in the H7N9 virus,  and warns people to avoid contact with live poultry - has been making the rounds in the Chinese media overnight.

In it he confirms some degree of oseltamivir resistance in the two Guangdong patients (something previously announced in the Taiwan case), although he is quick to point out that most H7N9 infections are not anti-viral resistant.  

There are, however, many unknowns, including how widespread this new mutation will become in the months ahead.

I normally dislike using large excerpts from a media report, but seeing as I've not (yet) found a detailed English language version I can link to, and given the importance of the information provided, I've elected to use most of the report below.

Zhong Nanshan: H7N9 viruses resistant mutants public not to touch live poultry

2017-02-26 06:47 

 

Since the beginning of winter, the number of cases of human infection with the H7N9 virus of bird flu surge. 25, the Chinese Academy of Engineering academician Zhong Nanshan, in an interview with reporters said the two virus variants recently discovered in the highly pathogenic avian exhibit, and appears resistant to Tamiflu (oseltamivir phosphate). He called on members of the public do not contact with live birds, once the fever and other flu symptoms, to timely medical treatment.

Fatality rate more than 40%? "not necessarily"

(SNIP)

Statistics show that this year's H7N9 epidemic mortality rate of over 40%, disease control experts believe that this is about to miss the best treatment time. However, this figure, Zhong Nanshan that "play a big question mark," "because the current total number of sick people not statistics, confirmed cases are generally severe, not necessarily have such a high mortality rate."

"A considerable part of the virus is not mutation"

February 19, the Chinese Center for Disease Control and Prevention of Guangdong provincial CDC sent from two cases of human infection with the H7N9 virus isolated cases have been reviewed, verified discovery of H7N9 virus variants from human infections.

Zhong Nanshan pointed out that the two cases of H7N9 virus variants recently discovered there are two characteristics: First, the mutant virus to become highly pathogenic in poultry. "In the past H7N9 virus in poultry is not the disease, pathogenic in humans, but the virus can also cause mutation of avian disease, it is also attach great importance to the agricultural sector."

Second, the emergence of resistant strains variation of Tamiflu. Zhong Nanshan said the two patients in Guangdong blood and the upper and lower respiratory tract were found in this variant virus, the treatment of preliminary findings are resistant to Tamiflu. However, Zhong Nanshan also pointed out that the majority of patients with Tamiflu treatment is effective, "explained the mutated virus strains did not become widely prevalent epidemic strains, that a considerable part of (virus) no variation."

(SNIP)

Enhanced ability to communicate mutation has not yet appeared

H7N9 epidemic trends this year will be how? Zhong Nanshan believes that there are still many unknowns. For example, resistant strains of the virus mutation will become the predominant strains of a wide range of spread is unclear; or resistant mutant virus strains will make human morbidity, higher mortality was not sure.

The Chinese Center for Disease Control and Prevention earlier analysis, based on sequence analysis of the virus, the virus mutation occurs in human infectivity, virulence and transmissibility among humans enhanced mutation has not yet appeared.

After the emergence of resistant mutant virus strains, will make adjustments to the treatment plan? Zhong Nanshan explained, the mutated virus strains found just shortly (adjustment programs) too early. Currently there are methods of combination therapy, and treatment of the most critical H7N9 virus is supportive therapy. "From our experience, patients with lung damage largest, patients with severe avian influenza virus will harden the lungs, and finally respiratory failure, while the heart, kidneys also have different degrees of damage, so we antiviral therapy At the same time to take on these important organ support therapy, if these vital organs to support live, we will be able to passed the critical stage. "

● Nanfang all media reporter Yan Huifang Xu Jiang Ou

To date we've only been notified of three human infections with this HPAI H7N9 variant.  We don't yet know how representative these cases are, how well it spreads in birds, how easily it jumps from birds to humans, or if it has in any way become more virulent or transmissible in humans.

While we await more details, it is worth noting that there are literally dozens of other H7N9 genotypes spreading across China - along with a bevy of HPAI H5 viruses - each is on its own evolutionary path.

Which means that this new HPAI variant, while appearing to up the ante, isn't the only one with pandemic potential we need to keep our eyes on.

ECDC Comment On HPAI Mutation Of H7N9

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It's been less than a week since we were first notified that the LPAI (up until now) H7N9 virus in China had mutated - at least in a few locations in Guangdong Province - into an HPAI (high path) virus (see Guangdong CDC: Two H7N9 `Variants' Isolated From Human Cases).


There are two broad categories of avian influenza; LPAI (Low Pathogenic Avian Influenza) and HPAI (Highly Pathogenic Avian Influenza).  

• LPAI viruses are quite common in wild birds, cause little illness, and only rarely death.  They are generally not considered a serious threat to human health (H7N9 being the exception), but are of concern since H5 & H7 strains have the potential to mutate into HPAI strains.
• HPAI viruses are more dangerous, can produce high morbidity and mortality in wild birds and poultry, and can sometimes infect humans with serious result.  The number of HPAI viruses that scientists have been tracking has increased markedly over the past 3 years, and now includes H5N1, H5N2, H5N6, H5N8,H10N8, and others.

Since it was first detected in the spring of 2013, H7N9 has always been an LPAI virus. We've always known there was a possibility that it might mutate into an HPAI virus - since we've seen that occur with other LPAI H7 viruses (see Genome Announcements: LPAI-to-HPAI Mutation Cited in January's H7N8 Outbreak).


Over the past 6 days there's been a scramble to try to understand the significance of this change, a task that has been complicated by the slow release of information out of China.  We are aware of two human cases in Guangdong, and a `similar' exported case (ex Guangdong) in Taiwan (see Taiwan CDC: January's Imported H7N9 Case Carried HPAI Mutation).

Taiwan's case remains in critical condition after nearly a month, and is reportedly infected with an antiviral `resistant' strain of the virus,  although we don't know whether he was infected by a resistant virus, or the virus acquired resistance during his treatment. 
   
The most immediate effect of H7N9 becoming an HPAI virus is its impact on birds. 

As an LPAI virus, it could spread stealthily among birds, without alerting poultry owners.  Now, this mutated strain is expected to cause morbidity and some degree of mortality among some bird species. Although more costly to poultry producers, this is actually a good thing,  as it may help in the identification and eradication of diseased birds.

While we know this HPAI version can infect humans, we haven't seen any evidence that the virus is any more virulent, or any more transmissible, in people.  Nor do we know how transmissible it is in birds.

The main caveats being, there's obviously a lot we don't yet know about how this new virus works, and that H7N9 (both LPAI and HPAI versions) will continue to diversify and evolve (see Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission).


 Yesterday the ECDC published a summary of events, and a comment, which you'll find below.

Mutation of avian influenza A(H7N9): now highly pathogenic for poultry but risk of human-to-human transmission remains low

24 Feb 2017

On 22 February 2017, WHO published the updated cumulative number of human cases of avian influenza A(H7N9) infection, which has now reached 1 223 since the first case in 2013. Nearly one-third of cases have occurred since October 2016 [1]. WHO’s risk assessment states that despite the identification of two small potential clusters of human cases, there is no evidence of sustained A(H7N9) transmission among humans [2]. The likelihood of person-to-person community level spread is therefore considered low.

On 19 February 2017, China’s Center for Disease Control and Prevention reported two human infections with a mutant strain of avian influenza A(H7N9) virus in Guangdong. The gene sequencing analysis found insertion mutations in the haemagglutinin gene. One case has recovered, the other case is still undergoing treatment [3].

The Veterinary Bureau of the China Animal Disease Control Center notified the World Organisation for Animal Health (OIE) on 18 February 2017 about the detection of a highly pathogenic avian influenza virus A(H7N9) in birds sampled on 10 January 2017 at live bird markets in Guangdong [4].

This follows the information shared by the Food and Agriculture Organization of the United Nations (FAO) on 20 February 2017 in an A(H7N9) ‘special edition’ of the FAO EMPRES Situation Update sent by email that ‘the H7N9 virus in China has converted into the highly pathogenic form (HPAI). This strain… shows a mutation leading to multiple basic amino acids at the cleavage site - a sign for high pathogenicity in poultry. The virus was isolated both from live bird market samples and two human cases in Guangdong Province. Following these findings, the MoA [Ministry of Agriculture] China published an emergency notice to strengthen national H7N9 prevention and control’ [5].

Health authorities in Taiwan also reported a possible new A(H7N9) genotype in a recent imported case which was ‘slightly different [from the current strain], denoting a possible new genotype, with a highly pathogenic trait in birds.’ It was noted that this virus contains a mutation in the neuraminidase (NA) protein relevant for antiviral resistance against oseltamivir and zanamivir. It is unclear as yet whether this antiviral resistance was acquired during treatment of the patient [6,7].

ECDC comment:

The upsurge of human cases in China during the winter 2016-2017 due to A(H7N9) gives cause for concern. On 26 January 2017, ECDC published a rapid risk assessment to remind the EU/EEA Member States of the possibility of travellers infected with A(H7N9) arriving from China [8].

The higher number of infected birds and the observed contamination of the environment in China are considered to have led to greater exposure to A(H7N9) and the increase in human cases.

So far A(H7N9) has had low pathogenicity in poultry, causing no mortality or signs of illness and making it difficult to identify infected birds for any intervention strategy. The evolution of this virus from having low pathogenicity to becoming highly pathogenic offers the opportunity to identify infected animals more readily and to implement the control measures established for all HPAI viruses.

The significant number of cases in both poultry and humans in China represents a risk for the spread of the virus beyond China to Central Asia and Europe. Sequences and viruses containing these new mutations need to be shared internationally (for example, to the Global Initiative on Sharing All Influenza Data (GISAID) and WHO Collaborating Centres) to improve diagnostics and the development of candidate vaccines [9].

Although no virulence factors for increased pathogenicity related to animal-to-human or human-to-human transmission have been described, each human case needs to be carefully assessed so as not to miss further evolution of the virus. Moreover, the above-mentioned antiviral resistance needs to be monitored as only limited treatment measures are available. Vaccines against A(H7N9) have been developed in the US, but their availability is limited [10]. In addition, it is unclear how well the A(H7N9) viruses currently circulating – evolved from the 2013 clade – antigenically match the candidate vaccine strain. Other vaccines against the A(H7N9) strain have been approved for clinical trials by the China Food and Drug Administration (CFDA) [11].

The ECDC risk assessment and the options for response have not changed since the last rapid risk assessment in January 2017. However, these new developments need to be monitored and assessed. ECDC will continue to follow the epidemiological and scientific developments related to avian influenza A(H7N9) virus and will continue to work with public health and veterinary experts in the EU/EEA Member States, WHO and other international partners.

               

Egypt: Conflicting Media Reports Of An Avian Flu Fatality In Fayoum

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Since official confirmation of avian flu infections from Egypt's Ministry of Health are often delayed (sometimes for weeks), we are forced to use local media reports to try to monitor the situation there.  

The MOH's website, which has been badly neglected (and often offline) over the past few years, has been recently revamped - but a site search for avian flu `(انفلونزا الطيور)  this morning returns no results.

They may be still adding content, so hopefully that will change.

After a record-setting 2015, where Egypt reported 136 H5N1 cases (39 deaths), 2016 saw only 10 cases (and 3 deaths) reported.  The reasons behind this welcomed drop are not clear, but it should be noted that several studies have suggested that the majority of avian flu cases are never identified and reported (see EID Journal: H5N1 In Egypt).


Today we have several Arabic media reports today of a supposedly fatal case of avian flu (subtype not provided, but probably H5N1) in Fayoum, and at least one report from the Fayoum health department stating they had not received an official report.


Two reports then, the first from Youm7.com.

Governor of Fayoum: Veterinary Medicine called for an urgent report on the death of a patient with bird flu
 
Saturday, February 25, 2017 14:36

Governor of Fayoum: Veterinary Medicine called for an urgent report on the death of a patient with bird flu Dr. Jamal Sami governor of Fayoum

Dr. Jamal Sami governor of Fayoum, said in a special statement for the "seventh day," he demanded of Veterinary Medicine and the Department of Health to maintain an urgent report on the incident and the death of infected citizens of bird flu on Saturday, and procedures that have been followed for Immunization and eliminate the epicenter of the disease.


The Undersecretary of the Ministry of Health in Fayoum, Dr. Hisham El Shenawy, announced the death of the first cases of bird flu in 2017, hospital diets to someone named Ocharf.a.m (48 years - factor) from the village of "compromise" Senoras Center, pointing out that he was booked Status General Hospital suffering from symptoms of a cold and high temperature, and was transferred to a hospital in Fayoum chest and took samples from him and sent to labs central Cairo, which has proven results bird flu, was transferred to the Abbasid Fever, where he died.

The second story, comes from VetoGate.com

Fayoum Health»: We have not received a report on the death of a patient bird flu

Saturday 25 / February / 2017 - 13:57
File photo File photo Taha al - Banna

Dr. Hisham Shenawi, Undersecretary of the Ministry of Health in Fayoum, said he had not yet received a report on the death of «Ashraf Abdul Baki Mukhaimar» (48 years old) , who died of his injuries bird flu, according to the statements of Veterinary Medicine Department in the governorate.

The victim was hit by a rise in temperature and shortness of breath, and went to the Chest Hospital and was detained by three days, pulling him to the doctors a sample was sent to the analysis of the Ministry of Health which confirmed a positive case coefficient, was transferred to the Abbasid Hospital and pronounced dead there.

His body was flown to his home village on Friday night, and sent the Veterinary Medicine Department of the Committee for the sterilization of the area around the poultry farm , which was dealing with.
 

While this sounds like a probable case, hopefully they will get this sorted out and reported to the WHO in short order.

 

Iran: Media Reports Of H5N8's Spread

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In their most recent  OIE filing (Feb 13th), Iran reported 30 outbreaks of HPAI H5N8 since it first appeared last November, resulting in the loss of just over a million birds.  According to the accompanying map, outbreaks were spread across 11 provinces in the northern half of the country.

A week earlier, however - (see H5N8 & H5N1: Murmurs From The Middle East)  - we were seeing state media (IRNA) reports that the real losses were closer to 6 million birds.

As with China, getting reliable outbreak information from the Middle East can be difficult, although Iran has been a bit more forthcoming than some of its neighbors.  The official silence from Egypt - which has been the biggest hotbed of avian flu in the Mid East for a decade - is deafening (note: since H5N1 was declared endemic in 2008, they are no longer required to file weekly OIE reports).

Overnight the Iranian and Persian Language press have been filled with reports of H5N8 avian flu spreading - depending on the source - to either 15 or 21 provinces. 

While stressing that no human infections have been reported, warnings are going out to the public to avoid contact with wild birds or migratory birds (living or dead), to stop using local poultry products “until further notice.”, and to only consume chickens and eggs that have certification from the Iran Veterinary Organization or the Ministry of Agriculture.

This English language report from Iran's PRESSTV.    

Birds infected with flu seen in 15 Iranian provinces: Health Ministry official

Sat Feb 25, 2017 8:54AM

Iran’s Ministry of Health has detected flu in birds in 15 Iranian provinces and has prohibited the use of local poultry products nationwide.

Mahmood Soroush, the head of the ministry’s Center for Communicable Disease Control, told Iran’s IRNA news agency on Saturday that the avian flu, most common form of which is the H5N8 strain, had infected birds in more than 15 Iranian provinces.

Soroush said it had already been detected in many countries, especially in the region spanning between Siberia and the Horn of Africa.
A view of the building of Iran’s Ministry of Health, Treatment and Medical Education in the capital, Tehran

He said the ministry had issued three statements warning about contamination even close to urban areas, particularly near lagoons, and demanding people to avoid touching any kind of birds.

“We seriously urge people to avoid touching dead birds or even living migratory ones,” the official said.

The Iranian Health Ministry is taking different measures concerning education, vaccination, and the distribution of medication in affected areas, Soroush added.

He stressed that people should use only chickens and eggs that have certification from the Iran Veterinary Organization or the Ministry of Agriculture and avoid using local poultry products “until further notice.”

‘No human cases of bird flu’

Those who have fever following physical contact with birds should promptly refer to medical centers, the official pointed out. He said, however, that no cases of human infection had been detected in Iran.

“So far, we haven’t had even a single case of human infection with bird flu or anything like it, but preventative measures such as vaccination, distribution of medication, and sampling from at-risk individuals continue,” he added.

The H5N8 strain of bird flu is deadly for poultry, but has not been detected in humans. The virus has spread across Europe and the Middle East since late last year and led to the culling of hundreds of thousands of poultry.

I was unable to find any official statement on the Iranian MOH website (http://behdasht.gov.ir/), but I'll continue to check.

Other Persian language media reports (see Influenza is still going / 21 provinces were involved) put the number of affected provinces considerably higher, and indicate the price of eggs has risen sharply in recent weeks. 

The OIE's WAHIS mapping tool shows where outbreaks have been reported around the world  - and despite media reports suggesting widespread activity - notifications from the Middle East (and points east, for that matter) since January 1st are few and far between.

While a lack of reports can be comforting - as with China, parts of South East Asia, and much of Africa - no avian flu news isn't necessarily good avian flu news.

France: MOA Announces 38 Additional H5N8 Farm Outbreaks

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The number of farms affected by the HPAI H5N8 virus continues to rise rapidly in France, with 38 new outbreaks and 13 new detections in wild birds reported since last Tuesday. This is an increase of 141 cases over the past 21 days (see Feb 3rd's 200th H5N8 Outbreak In Poultry Farms Over Past 60 Days).
 

Earlier this week officials announced plans to completely cull the duck population in Landes, the hardest hit region of southern France (France Expands Preemptive Culling As H5N8 Outbreaks Exceed 300), in an attempt to halt the spread of the virus. 

According to the latest report by France's ESA (Epidemiosurveillance Santé Animale) - dated Februrary 21st - the tallys so far this fall's HPAI H5Nx epizootic across Europe:

The total number of outbreaks and cases of HPAI reported continues to increase and is now to 1779 including 965 in wild birds (72 species affected), 777 livestock and 37 in the avifauna captive.

Based on those numbers, France accounts for roughly 40% of the farm-related outbreaks in Europe this winter.  The latest update from the French MOA follows:

H5N8 avian influenza: monitoring the spread of the virus in farms and wildlife

24/02/2017 avian influenza
© Pascal Xicluna / Min.Agri.Fr

In France
 
Situation at February 24, 2017: 341 H5N8 outbreaks in farms and 41 cases in wildlife confirmed and communicated.

Learn more about the epidemiological surveillance Animal Health platform .
List of homes in the departments

• Country: 183
• Tarn : 8
• Gers : 94
• Lot-et-Garonne: 9
• Hautes-Pyrénées: 25
• Pyrénées-Atlantiques: 16
• Aveyron : 2
• Deux-Sèvres: 3
• Lot: 1

 List of cases in wildlife

• Pas-de-Calais: 1
• Haute-Savoie: 2
• Tarn : 2
• Manche: 1
• Ain : 17
• Lot-et-Garonne: 2
• Country: 3
• Gers : 7
• Loire-Atlantique: 1
• Pyrénées-Atlantiques: 3
• Vosges: 2

 

China: NHFPC Announces 35 New H7N9 Cases Over Past 11 Days

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With the ever present caveat that we are pretty much dependent upon whatever information the Chinese government chooses to divulge, today their NHFPC (National Health & Family Planning Commission) has announced an apparent slowdown in the number of H7N9 cases over the past 11 days.

This comes after three days of very high profile meetings with the Chinese Premier, the MOA, and the NHFPC (see here, here, and here), all vowing to contain the epidemic.

The dissident press, located outside of Mainland China, continues to insist that cases are being concealed, and that the outbreak is far from under control. Claims that are almost impossible to verify.

They cite the upcoming `two sessions' - the very high profile annual meetings of the National People’s Congress (NPC) and the National Committee of the People’s Political Consultative Congress (CPPCC) which are held in early March - as reasons for slow-rolling the numbers. 

Slowdown or not, 35 cases in 11 days is still an elevated number.  And once poultry markets re-open, those numbers could easily spike again.  Cases generally peak during January-February, but usually continue into April and May, so a lull now is no guarantee the epidemic is waning.


This from the NHFPC.

Do a good job to further strengthen joint prevention and control of H7N9 epidemic prevention and control measures implemented to stabilize
 
Published: 2017-02-24

　　February 22, Comrade Premier Li Keqiang chaired a State Council executive meeting of the deployment H7N9 epidemic prevention and control work. The meeting pointed out that this year China H7N9 outbreak came earlier compared with previous years, the number of cases increases. Local and relevant departments in accordance with the State Council deployed effectively conduct joint prevention and control. The meeting urged all localities and departments concerned to continue to do H7N9 epidemic joint prevention and control, open and transparent timely release of authoritative information on the epidemic, strengthen epidemic source control, do the monitoring and early warning and treatment of cases, the implementation of "large-scale farming, centralized slaughtering, cold chain transport, ice listed fresh "new model, and effectively protect people's health and safety.

　　Deal with H7N9 joint prevention and control mechanism to conscientiously implement the State Council executive meeting, to further strengthen the H7N9 outbreak in accordance with joint prevention and control video conference agreed that matters, since February 23, the National Health and Family Planning Commission, the Ministry of Agriculture, SAIC, food and drug regulation Administration, FDA joint Steering group composed of seven, focusing on epidemic prevention and control of provinces to carry out supervision, to further promote the implementation of the measures. Recently, the National Health and Family Planning Commission, the Ministry of Agriculture, Industry and Commerce Administration, Food and Drug Administration of the four departments will jointly issued a circular calling for the spirit of the State Council meeting to further strengthen and transporting live poultry farms supervision, strict implementation of live poultry markets were closed, disinfection and quarantine system, or detection of pathogen detection of cases of cities and counties to close the live bird markets as soon as possible to take measures such as culling according to regulations. At the same time, severely crack down on illegal transport, management, slaughter and other acts. 

At present, all related to epidemic prevention and control work is solid and orderly progress, the early momentum of rapid increase epidemic has been effectively curbed. February 13, 2017 - 2 23, the Mainland of China reported a total of 11 days cases of 35 cases of H7N9, which killed seven people, the epidemic has stabilized.

　　Experts believe that the current H7N9 outbreak in a highly circulated, H7N9 virus transmission is still by birds to humans, contact with infected birds or exposure to live poultry market is an important risk factor for human infection. Experts predict that the most recent period, it is possible to continue our sporadic cases occur H7N9. Experts suggest that the public in their daily lives should avoid contact with dead birds, avoid direct contact with live poultry category; quarantine certificates should be purchased fresh, live and frozen poultry and poultry-related products; attention to food hygiene, food processing to do Health cooked separately; improve self-protection awareness, found that fever and respiratory symptoms should wear a mask, doctor as soon as possible.

Eurosurveillance: Emergence Of A Novel Subclade Of Seasonal A/H3N2 - London

Credit NIAID

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Twice each year (February & September) influenza experts from around the world meet (often electronically) to discuss recent developments in human and animal influenza viruses, and to decide on the composition of the next influenza season’s flu vaccine.  Vaccine strains must be selected for two A strains (H1N1 & H3N2) and two B strains (Victoria & Yamagata Lineage)

NIAID has a terrific 3-minute video that shows how influenza viruses drift over time, and why the flu shot must be frequently updated, which you can view at this link.

Due to the time it takes to manufacture and distribute a vaccine, these decisions must be made six months in advance, so the composition of next fall's flu vaccine is expected soon.

While we talk about 2 primary influenza A subtypes (H1N1 & H3N2) - in truth there are multiple variations of each subtype in circulation at any given time. Usually, one of these versions is dominant, but these evolving strains are constantly playing a viral game of `king of the mountain’, and the balance of power can shift quickly.

In the fall of 2014, a late arriving `drifted' H3N2 virus practically negated that year's flu vaccine's effectiveness (see CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus).

Since 2009 seven distinct genetic groups have been defined for H3N2.  While all belong to clade 3C, they are divided into three subdivisions; 3C.1 , 3C.2, and 3C.3, with last November's ECDC Influenza Virus Characterization Report stating:

In 2014 three new subclades emerged, one in subdivision 3C.2, 3C.2a, and two in 3C.3, 3C.3a and 3C.3b , with subclade 3C.2a viruses dominating in recent months.

Yesterday's edition of  the Journal Eurosurveillance adds yet another layer of complexity to this already diverse field of H3N2 viruses. A new subclade of H3N2 - proposed as 3C.2a2 - has recently appeared in London. 

While more studies are needed - and the future spread or dominance of subclade 3C.2a2 is far from assured  - there are concerns that the current H3N2 vaccine may offer sub-optimal protection against this new strain.

Eurosurveillance, Volume 22, Issue 8, 23 February 2017
Rapid communication
Emergence of a novel subclade of influenza A(H3N2) virus in London, December 2016 to January 2017

H Harvala 1 2 , D Frampton 2 , P Grant 1 , J Raffle 2 , RB Ferns 2 3 , Z Kozlakidis 2 , P Kellam 4 , D Pillay 2 , A Hayward 5 , E Nastouli 1 3 6 , For the ICONIC Consortium 7


Correspondence: Eleni Nastouli (e.nastouli@ucl.ac.uk), Heli Harvala (heli.harvala@uclh.nhs.uk)

Citation style for this article: Harvala H, Frampton D, Grant P, Raffle J, Ferns RB, Kozlakidis Z, Kellam P, Pillay D, Hayward A, Nastouli E, For the ICONIC Consortium. Emergence of a novel subclade of influenza A(H3N2) virus in London, December 2016 to January 2017. Euro Surveill. 2017;22(8):pii=30466. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.8.30466
Received:13 February 2017; Accepted:23 February 2017

We report the molecular investigations of a large influenza A(H3N2) outbreak, in a season characterised by sharp increase in influenza admissions since December 2016. Analysis of haemagglutinin (HA) sequences demonstrated co-circulation of multiple clades (3C.3a, 3C.2a and 3C.2a1). Most variants fell into a novel subclade (proposed as 3C.2a2); they possessed four unique amino acid substitutions in the HA protein and loss of a potential glycosylation site. These changes potentially modify the H3N2 strain antigenicity.

The ongoing influenza season started early in eleven European Union countries, including England, on week 46 of 2016 [1]. The majority of reported infections have been caused by clade 3C.2a or 3C.2a1 influenza A(H3N2) viruses. The clade 3C.2a contains the current vaccine strain A/Hong Kong/4801/2014, and the first few viruses within the more recently emerged subclade 3C.2a1 were earlier shown to be antigenically matched with the vaccine component [2]. However, evidence for suboptimal vaccine effectiveness (VE) against laboratory-confirmed influenza A infection in people over 65 years-old was obtained in the first studies from Finland [3] and Sweden [4].

An outbreak of influenza A(H3N2) was first notified in our London centre on 30 December 2016. The outbreak coincided with unusually high ongoing circulation of respiratory syncytial virus (RSV) (Figure 1), and affected both patients and staff in the acute medical unit (AMU).

While infection control precautions were intensified, it resulted in multiple bay closures. We suspected that the sharp increase in the number of influenza A(H3N2) infections may have been caused by the emergence of a new genetic variant of H3N2, a hypothesis investigated through next generation sequencing (NGS) of influenza A(H3N2) strains.

(SNIP)

Discussion

In our centre in London, the early start and higher intensity of the 2016/17 influenza A(H3N2) virus epidemic mirrored that of the season 2014/15 where the subtype H3N2 also predominated. During the 2014/15 season, most influenza A(H3N2) infections in Europe were shown to be caused by antigenically drifted virus variants within the new genetic subgroup 3C.2a [8]. Our genetic analysis of London A(H3N2) viruses demonstrates ongoing co-circulation of drifted variants from multiple subclades (3C.3a, 3C.2a1 and proposed 3C.2a2). 

Four or more substitutions in two or more antibody binding sites are predicted to give an antigenically different virus [9] as in our case. Although we did not observe mutations in the seven positions suggested as being responsible for major transition clusters [10], position 144 is at the flank of the RBS, and additionally recognised as antigenic [11].

Although not necessarily determining major antigenic drift, the alterations of N-linked glycosylation sites are likely to contribute to more complex conformational changes in the HA due to gain or loss of glycosylation and can thus facilitate immune escape [12]. Furthermore, any amino acid changes in the 140–146 region of HA have been shown to be characteristic for antigenically distinct viruses of epidemic significance [9,13,14]. The amino acid substitution S144K in the emerging subclade 3C.2a2 viruses together with the loss of an N-linked glycosylation site (N122D) shows potential for antigenic drift that warrants further monitoring during this ongoing season. A limitation of our study was the lack of detailed vaccination data.

Our findings in London of the rapid emergence of genetically drifted influenza A(H3N2) viruses underscore the potential for such strains to spread rapidly in hospital environments among patients and staff. Characterising emerging strains of influenza by next generation sequencing adds to the local and national monitoring of influenza trends. Further studies are needed to investigate the antigenic effects of substitutions occurring within the newly described subclade.

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WHO H7N9 Risk Assessment - Feb 2017

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Yesterday the World Health Organization released a new Influenza at the human-animal interface report - one that reflects information provided by the Chinese government through February 14th of this year.  As new cases continue to be announced - and others are presumably in the `pipeline' - case totals increase almost daily.

As the chart above illustrates, H7N9 cases this winter have already exceeded anything we've seen to date, and China's winter epidemic season typically has a couple of more months to run.

The cases reported reflect the `sickest of the sick' - those ill enough to require hospitalization - and so we really don't have a good handle on how many mild or moderate cases there may be.  The assumption is that number is substantial (see Beneath The H7N9 Pyramid).


Despite this abrupt increase in cases, we've seen no evidence of sustained or efficient human-to-human transmission of the virus.  Clusters have been small, and infrequently reported.  For cases where information is known, the vast majority appear to have had recent close contact with live poultry. 

Today's report does not address the recent HPAI variant viruses detected in both Taiwan and Guangdong Province (see Two H7N9 `Variants' Isolated From Human Cases) in January, as this report was compiled prior to those announcements.  So far, we've not seen any indication that these genetic changes increase the health risk to humans.

Today's report also details two swine origin H1N1 infections in Europe, and contains a line listing of H7N9 cases.   Follow the link to read the full report.

Influenza at the human-animal interface
Summary and assessment, 17 January to 14 February 2017

• New infections1: Since the previous update, new human infections with influenza A(H7N9) andA(H1N1)v viruses were reported.
• Risk assessment: The overall public health risk from currently known influenza viruses at thehuman-animal interface has not changed, and the likelihood of sustained human-to-humantransmission of these viruses remains low. Further human infections with viruses of animalorigin are expected.
• IHR compliance: All human infections caused by a new influenza subtype are required to be reported under the International Health Regulations (IHR, 2005).2 This includes any animal andnon-circulating seasonal influenza viruses. Information from these notifications is critical toinform risk assessments for influenza at the human-animal interface.

Avian Influenza Viruses

Avian influenza A(H5) viruses

Current situation:

Since the last update, no new laboratory-confirmed human cases of influenza A(H5) virus infection were reported to WHO. Influenza A(H5) subtype viruses have the potential to cause disease in humans and thus far, no human cases, other than those with influenza A(H5N1) and A(H5N6) viruses, have been reported to WHO. According to reports received by the World Organisation for Animal Health (OIE), various influenza A(H5) subtypes continue to be detected in birds in West Africa, Europe and Asia. There have also been numerous detections of influenza A(H5N8) viruses in wild birds and domestic poultry in several countries in Africa, Asia and Europe since June 2016. For more information on the background and public health risk of these viruses, please see the WHO assessment of risk associated with influenza A(H5N8) virus here.

Avian influenza A(H7N9) viruses

Current situation:

During this reporting period, 305 laboratory-confirmed human cases of influenza A(H7N9) virus infection were reported to WHO from China. Case details are presented in the table in the Annex of this document. For additional details on these cases and public health interventions, see the Disease Outbreak News, and for analysis of recent scientific information on the A(H7N9) influenza virus, please see a recent WHO publication here.

1 For epidemiological and virological features of human infections with animal influenza viruses not reported in this assessment, see the yearly report on human cases of influenza at the human-animal interface published in the Weekly Epidemiological Record. www.who.int/wer/en/
2 World Health Organization. Case definitions for the four diseases requiring notification in all
circumstances under the International Health Regulations (2005). www.who.int/ihr/Case_Definitions.pdf

As of 14 February 2017, a total of 1223 laboratory-confirmed cases of human infection with avian influenza A(H7N9) viruses, including at least 380 deaths3, have been reported to WHO (Figure 2). According to reports received by the Food and Agriculture Organization (FAO) on surveillance activities for avian influenza A(H7N9) viruses in China4, positives among virological samples continue to be detected mainly from live bird markets, vendors and some commercial or breeding farms.

Risk Assessment:

1. What is the likelihood that additional human cases of infection with avian influenza A(H7N9) viruses will occur? Most human cases are exposed to the A(H7N9) virus through contact with infected poultry or contaminated environments, including live poultry markets. Since the virus continues to be detected in animals and environments, further human cases can be expected. Additional sporadic human cases of influenza A(H7N9) in other provinces in China that have not
yet reported human cases are also expected.

2. What is the likelihood of human-to-human transmission of avian influenza A(H7N9) viruses? Even though small clusters of cases have been reported, including those involving healthcare workers, current epidemiological and virological evidence suggests that this virus has not acquired the ability of sustained transmission among humans, thus the likelihood is low.

3 Total number of fatal cases is published on a monthly basis by China National Health and Family Planning Commission.
4 Food and Agriculture Organization. H7N9 situation update.
www.fao.org/ag/againfo/programmes/en/empres/H7N9/situation_update.html

3. What is the risk of international spread of avian influenza A(H7N9) virus by travellers? Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this were to occur, further community level spread is considered unlikely as this virus has not acquired the ability to transmit easily among humans.

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