Sunday, February 26, 2017

Zhong Nanshan On China's Mutated H7N9 Virus

H7N9 Waves - Credit WHO


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"

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."
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.

Saturday, February 25, 2017

ECDC Comment On HPAI Mutation Of H7N9


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


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

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

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


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 (, 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.

Friday, February 24, 2017

France: MOA Announces 38 Additional H5N8 Farm Outbreaks


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


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.