Wednesday, March 21, 2018

Germany: Schleswig-Holstein Ag Minister Confirms H5N6 On Hallig Suederoog


Although Germany reported the new H5N6 virus for the first time in a wild duck during the first week of January (see OIE Report), it hadn't - until today - reported this recent reassortment in poultry. 

The following announcement from the Schleswig-Holstein Government website, and describes an outbreak on the small island of Hallig Suederoog (pop. 2) off the northwest coast of Germany.

Avian Influenza on Hallig Süderoog

datum 03.21.2018
In a poultry farm with 57 chickens, turkeys, ducks and geese the avian influenza virus of subtype H5N6 has been detected.
Approximately one year after the last detection of avian influenza in Schleswig-Holstein has come again to an outbreak of notifiable animal disease. In a small animal husbandry on the holm Süderoog in the district of North Friesland experts from the Friedrich Loeffler Institute had detected the pathogen subtype H5N6. The 57 chickens, turkeys, ducks and geese must now be killed.
Restricted zones established

On the holm a restricted area was established after the outbreak. A complementary observation area includes the island of Pellworm. In these zones, strict security measures such as an obligation to keep poultry apply. In addition, the transport of live birds in the area is prohibited.
Strict security measures

The Environment Ministry urged all poultry farmers to comply with the prescribed safety regulations and for example, to feed their animals where wild birds do not have access. Feed, bedding and other items with which the poultry can come into contact should be kept away from wild birds. If it comes in a stable to increased animal deaths must be called a veterinarian to determine the cause. Dead wild birds such as ducks, geese, gulls and raptors should be reported to the veterinary or town clerk's office.

new subtype

The now proven pathogen subtype H5N6 is very similar to the subtype H5N8, which infected many animals in Europe in winter 2016/2017. H5N6 has so far been detected in Switzerland, the United Kingdom, Ireland, Sweden and Denmark. In January, the pathogen first appeared in a wild duck in Bavaria. It is not known that the virus can be transmitted to humans.

With migratory birds now headed north for the spring, countries along the flyways will need to stay alert for additional outbreaks.

J. Virology: Analysis Of A Swine Variant H1N1 Virus Associated With A Fatal Outcome


Novel flu viruses (like H5N1, H5N6, H7N9, and H10N8), are particularly worrisome because - while they haven't yet figured out how to spread efficiently among humans  - when they do jump to humans they tend to have a very high mortality rate. 
But going back 130 years, we've only seen human influenza pandemics (and seasonal flu epidemics) sparked by H1, H2, and H3 viruses (see  Are Influenza Pandemic Viruses Members Of An Exclusive Club?).
Granted, we've no clue what influenza subtypes might have circulated in humans before 1890, and there is some guesswork surrounding those prior to 1918.  But based on a relatively limited sample size - H1, H2, and H3 viruses are the most likely to produce a human pandemic.
Which is why, even though they tend to produce far lower mortality than novel flu, we keep a close eye on human, avian, and swine-origin H1, H2, and H3 viruses. 
Between 2005 and the end of 2010, the CDC  documented 19 human infections by swine origin influenza viruses (SOIV) across the United States, 12 of which were trH1N1 viruses, 6 were trH3N2, and 1 was trH1N2.
During the summer of 2011 a new strain of swine influenza  - originally dubbed trH3N2 but renamed H3N2v (swine variant influenza) – was discovered to have evolved in pigs. 
What made this virus different from the earlier trH3N2 novel strains was that it was a reassortant swine H3N2 which had acquired the matrix (M) gene from the 2009 H1N1 pandemic virus. The CDC has speculated that:
`This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.CDC HAN 2012
The CDC’s MMWR  in November of 2011 detailed the Iowa cases in a dispatch called Limited Human-to-Human Transmission of Novel Influenza A (H3N2) Virus — Iowa, November 2011.
By then  it was pretty apparent that this swine H3N2 virus had a greater affinity to human hosts than most of the other SOIVs we’d seen in the past (excluding the 2009 H1N1pdm virus).
A few more scattered cases occurred in Minnesota and West Virginia by year's end, and the virus was given a new name WHO/FAO/OIE: Call It A(H3N2)v, which raised the total for 2011 to a dozen cases reported around the country.
This was, in all likelihood, a substantial undercount with at least one estimate putting the number 200 times greater (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).
The following summer (2012) the floodgates opened - and while still likely badly under counted - over a little more than two months more than 300 human swine variant infections were reported across 10 states.
Again, nearly all had direct contact with pigs at state and local fairs (see CID Journal: H3N2v Outbreaks In United States – 2012).
Although the number of reported swine variant infections dropped back to single digits for each of the next three years (2013, 2014, 2015) in 2016 we saw a renewed surge of cases (20+), and last year (2017) 67 cases were reported (see FluView Wk 49: Influenza Increasing - 1 Novel H3N2v Report From Iowa).

These swine variant viruses have also continued to evolve. Eighteen months ago an MMWR: Investigation Into H3N2v Outbreak In Ohio & Michigan - Summer 2016 revealed that 16 of the 18 cases analyzed belonged to a new genotype not previously detected in humans.

While most human infections have been either mild or moderate, a couple of deaths have been reported, including a fatal case in Ohio in 2015 (see FluView Week 17: Fatal Swine Variant (H1N1v) Case In Ohio).
Often the severity and outcome of an influenza infection is based on a person's preexisting conditions, or even host genetics (see  A Genetic Predisposition To Severe Flu Infection), but sometimes a severe outcome can be due to subtle changes in the virus. 
All of which brings us to a study by researchers at the Influenza Division, National Center for Immunization and Respiratory Diseases, CDC -  published this week in the Journal of Virology - that looks at the genetics and infectivity and transmissibility (in ferrets) of the swine origin virus that caused the death of the patient in Ohio in 2015.

Antigenically diverse swine-origin H1N1 variant influenza viruses exhibit differential ferret pathogenesis and transmission phenotypes

Joanna A. Pulit-Penaloza1, Joyce Jones1, Xiangjie Sun1, Yunho Jang1, Sharmi Thor1, Jessica A. Belser1, Natosha Zanders1, Hannah M. Creager1, Callie Ridenour1, Li Wang1, Thomas J. Stark1, Rebecca Garten1, Li-Mei Chen1, John Barnes1, Terrence M. Tumpey1, David E. Wentworth1, Taronna R. Maines1# and C. Todd Davis1#


Influenza A(H1) viruses circulating in swine represent an emerging virus threat as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. 

To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed. 

Antigenic analysis of the virus isolated from the fatal case, A/Ohio/09/2015, demonstrated significant antigenic drift away from classical swine H1N1 variant viruses and H1N1 pandemic 2009 viruses. A substitution in the H1 hemagglutinin (G155E) was identified that likely impacted antigenicity, and reverse genetics was employed to understand the molecular mechanism of antibody escape. 

Reversion of the substitution to 155G, in a reverse genetics A/Ohio/09/2015 virus, showed that this residue was central to the loss of hemagglutination inhibition by ferret antisera raised against a prototypical H1N1 pandemic 2009 virus (A/California/07/2009), as well as gamma lineage classical swine H1N1 viruses, demonstrating the importance of this residue for antibody recognition of this H1 lineage. 

When analyzed in the ferret model, A/Ohio/09/2015 and another H1N1v virus (A/Iowa/39/2015), as well as A/California/07/2009, replicated efficiently in the respiratory tract of ferrets.
The two H1N1v viruses transmitted efficiently among cohoused ferrets, but respiratory droplet transmission studies showed that A/California/07/2009 transmitted through the air more efficiently. Pre-existing immunity to A/California/07/2009 did not fully protect ferrets from challenge with A/Ohio/09/2015.

Human infections with classical swine influenza A(H1N1) viruses that circulate in pigs continue to occur in the United States following exposure to swine.
To understand the genetic and virologic characteristics of a virus (A/Ohio/09/2015) associated with a fatal infection and a virus associated with a non-fatal infection (A/Iowa/39/2015), we performed genome sequence analysis, antigenic testing, and pathogenicity and transmission studies in a ferret model. 

Reverse genetics was employed to identify a single antigenic site substitution (HA G155E) responsible for antigenic variation of A/Ohio/09/2015 compared to related classical swine influenza A(H1N1) viruses. Ferrets with pre-existing immunity to the pandemic A(H1N1) virus were challenged with A/Ohio/09/2015 demonstrating decreased protection. 

This data illustrates the potential for currently circulating swine influenza viruses to infect and cause illness in humans with pre-existing immunity to H1N1 pandemic 2009 viruses and a need for ongoing risk assessment and development of candidate vaccine viruses for improved pandemic preparedness.

Although swine-variant infections have been reported year-round, the prime `season' appears to be from early summer and into the fall, when millions of people visit state fairs and agricultural exhibits across the country.  
While most human infections are reported in the United States, that is likely due to our relatively high level of surveillance and testing, and not due to a paucity of porcine influenza around the globe. 
For more on swine-origin influenza, and the public health risks they pose, you may wish to revisit:
oonosis & PH: Survey Of Animal Exhibitor's KAP During Swine Variant Outbreak

EID Journal: Transmission Of Swine H3N2 To Humans At Agricultural Exhibits - Michigan & Ohio 2016
J. Virol: Novel Reassortant Human-like H3N2 & H3N1 Influenza A Viruses In Pigs
J. Virology: A Single Amino Acid Change Alters Transmissability Of EAH1N1 In Guinea Pigs

I&ORV: Triple-Reassortant Novel H3 Virus of Human/Swine Origin Established In Danish Pigs

Taiwan's Counterfeit AI Vaccine Trade


Taiwan - which  lies under the East-Asian Migratory Flyway - has been plagued with (mostly LPAI H5N2) outbreaks for years. But in 2015 Taiwan saw the arrival of at least 3 new HPAI strains of H5 - all apparently related to the H5N8 virus which first erupted in South Korea 12 months earlier.
Unlike Mainland China - which is the world's largest consumer of poultry AI vaccines - Taiwan prefers instead to use the OIE recommended methods of strict quarantine and culling.
That hasn't stopped desperate poultry farmers from circumventing the law - something we looked at a little over two years ago in Taiwan COA Warns Against Importation & Use Of AI Vaccines.

Last summer Taiwanese police arrested 9 people accused of making and selling - or buying - counterfeit pig vaccines At least 7,800 vials of this fake porcine  vaccine had been sold to 32 farmers, and nearly 400,000 pigs had  been injected.
Not only were these vaccines diluted to the point of being useless to prevent porcine circovirus (PCV), they were also contaminated with bacteria, and many of the vaccinated pigs died.
This report from Focus Taiwan.
Nine people charged in fake pig vaccine case 
2017/06/06 18:32:01
Taipei, June 6 (CNA) Nine people have been charged in a case involving the supply of fake vaccines to pig farmers, the Yunlin District Prosecutors' Office said Tuesday.

The nine individuals were indicted on June 2 on charges of fraud, making and selling counterfeit veterinary drugs, and forging or altering documents - offenses that violate the Veterinary Drugs Control Act and the Criminal Code, according to the prosecutors.

The investigation was launched following the sudden death of a number of piglets in Yunlin and Changhua and after prosecutors received a tipoff in March that dubious pig vaccines were being sold to farmers.

During the investigation, prosecutors found that two men had been purchasing genuine vaccines at a cost of NT$3,750 (US$124) per vial, diluting them with distilled water, and repackaging them.
(Continue . . . )

Aside from the bacterial contamination issue and the lack of protection afforded these `vaccinated' pigs, diluted vaccines pose an incredible risk of allowing viruses to replicate and evolve away from the vaccine strain, putting the entire pig population at risk.
But the story gets even worse today.
Based on Chinese language media reports overnight, last summer's arrests lead to an even larger investigation into counterfeit poultry vaccines, and this week additional arrests have been made.

According to multiple reports (see here, here, and here), the scheme involved the illicit collection of blood from (supposedly) previously infected and recovered poultry at a slaughterhouse.
The harvested blood was reportedly `centrifuged', and the serum collected - and after adding antibiotics and `other drugs' - injected as a vaccine.
It isn't clear how many birds already received this fake vaccine, but enough of this witch's brew vaccinate 500,000 birds was recovered by authorities.

Based on the video of the premises (see below), this operation was conducted under absolutely squalid and primitive conditions, and the resultant `vaccine' appears to have undergone absolutely no testing for purity, contents, or strength.

Frankly, if you wanted to spark a new  epizootic (or worse, a pandemic), it would be hard to come up with a better scheme.  One wonders how much this operation has contributed to the ongoing AI epizootic on the island.

Some (translated) excerpts from one the media reports follow:
Taiwan's unscrupulous peddlers made fake tens of millions of yuan worth of fake poultry flu
March 21, 2018 16:05 Taiwan , China

Unscrupulous traders sold fake black bird flu fake drugs, and the group "injection team" peddled them to the poultry industry and profited tens of millions of yuan. (Source: Taiwan "China Times")

China Taiwan Network March 21st According to Taiwan’s “China Times” report, Yunlin DPA seized two groups of illegal elements in Yunlin, Taoyuan, and Changhua. They made black heart avian influenza counterfeit drugs and formed “injection teams” everywhere. Selling to poultry farms will earn millions of dollars (NT, the same below). The whole case continued to expand in investigations.

The report said that when the prosecutor of the Yunlin Land Prosecutor's Office investigated the black heart pig vaccine case in 2017, he discovered that there were unscrupulous people who formed an "injection team" to sell black duck avian influenza animal counterfeit medicines to duck raisers and immediately reported to the Attorney General Cheng Mingqian, Zheng Mingqian. Instruct immediately to initiate investigation.

After prosecutor He Jinsheng directed the case handlers to conduct long-term cabling and search, on March 15 this year, the owner of Wu Xing, Dongzhi Township, Yunlin County was found to have collected bird blood from poultry farms that had survived the bird flu since 2015. The use of centrifuges to separate serum from blood and blood clots, and then add antibiotics and other unknown drugs to make bird flu known to prevent bird flu virus counterfeit animal drugs.

The prosecutor stated that a total of 544 fake drugs for black-hearted bird flu animals have been detained and estimated to be injectable with 1,000 birds per bottle. The quantity of counterfeit drugs could allow 540,000 birds to become poison-protected animals with viruses. Virus-infected animals that do not have the disease on their face, if found in the market, will cause more serious bird flu outbreaks. (China Taiwan Net Juanzi)

This investigation is reportedly ongoing, and more arrests appear likely.  Hopefully laboratory testing will provide additional information on virological legacy of this illicit operation. 

Tuesday, March 20, 2018

South Africa: Media Reports Of Another Penguin Colony Hit By H5N8


Almost a month ago, in South Africa: Endangered African Penguins Hit By H5N8, we saw reports of H5N8 activity in six penguin colonies - producing both morbidity and mortality among the endangered birds - along the shores of the Western Cape.
Although outbreaks in commercial flocks have dropped dramatically since November of last year, reports of H5N8 in wild birds - particularly shore birds - has continued throughout their summer.
Today local media is reporting of a fresh outbreak at the Table Mountain National Park in Simon's Town, just south of Cape Town.   So far, South Africa's Department of Agriculture (DAFF) hasn't posted anything on their website. 

What we do have is this representative report from IOL

Avian Flu outbreak confirmed at Cape Town's Boulders penguin colony

20 March 2018, 3:08pm / Staff Reporter

Cape Town - The Table Mountain National Park has confirmed there is an outbreak of avian flu (bird flu) at the Boulders penguin colony in Simons Town.

"Table Mountain management would like to alert the public that several cases of bird flu in the penguin colony at Boulders have been confirmed by state veterinary services," TMNP spokesperson Merle Collins said.

"It is reiterated that this virus is a very low risk to humans, but is a real threat to domestic poultry. This strain of avian influenza virus (H5N8 strain) has been detected in a range of wild seabirds e.g. swift, sandwich and common terns, African penguins and gannets.

"The park is monitoring the situation closely and has now implemented the following precautions:

  • With the exception of visitors on Boulders Beach boardwalk, nobody may access the main breeding colony.
  • In instances where staff need to go off boardwalks to collect injured birds or hats, camera lens, caps etc dropped by visitors they will limit their access to essential work and then sterilise their boots afterwards - gum boots have been issued and are easier to clean than the normal boot.
  • Monitoring routes used for moult/nest counts have been reviewed to ensure that staff and Penguin monitors do not walk through the main breeding colony.
          (Continue . . . )

While penguins are are flightless birds and not long-distance vectors of avian flu -  other seabirds in the area are not - and could potentially spread the virus both locally, and globally via migratory flyways (see map below).

HPAI H5N8 arrived in South Africa for the first time last June, and rapidly spread to dozens of poultry farms, forcing the culling of millions of birds.  With fall's arrival in the Southern Hemisphere concerns over a repeat this winter are very real.

WHO Reports 3 H9N2 Cases In China (2017-2018)


Although avian flu reports have been in unusually short supply this winter from China - with only 1 H5N6 human infection, and 3 H7N9 cases - we learn from the latest (March 2nd)  WHO Influenza at the human - animal interface report of 3 new H9N2 infections between late December and the middle of February.

All three cases were described as `mild', and 2 of the 3 had recent exposure to poultry.  In 2017, China reported 5 cases, while the year before, China reported 7 cases and Egypt reported 1 (see FluTrackers Global Cumulative H9N2 Partial Case List 1998-2017).
Over the past 2 decades just over 3 dozen human H9N2 infections have been recorded in 3 countries (China, Egypt & Bangladesh). That number is undoubtedly both under diagnosed and underreported as the virus is endemic in poultry across Asia, the Middle East, and has recently moved into Africa.
A 2014 seroprevalence study, found antibodies against H9N2 ranged from 5.9% to 7.5% among poultry exposed individuals in Egypt, suggesting human infection is far more common than the official tallys would suggest.
On the positive side, H9N2 infection in humans has generally been mild, and no human-to-human spread has been detected.  
H9N2 is viewed as having some pandemic potential (see CDC IRAT SCORE), and so several candidate vaccines have been developed over the years.

The avian H9N2 virus occupies a special spot in our bird flu coverage because - while (until recently) only seen as an LPAI (low pathogenic) virus in poultry - its internal genes routinely make up the backbone of many of the HPAI viruses that pose the greatest risks to both poultry, and human health.

In the past, we’ve looked at this propensity of the H9N2 virus to reassort with other avian flu viruses (see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses & PNAS: Reassortment Potential Of Avian H9N2) which have shown the H9N2 capable of producing `biologically fit’ and highly pathogenic reassortant viruses.
Nearly 4 years ago, in PLoS Path: Genetics, Receptor Binding, and Transmissibility Of Avian H9N2 researchers found evidence of Chinese H9N2 viruses binding preferentially to alpha 2,6 receptor cells -  the type commonly found in the human upper respiratory tract - rather than to alpha 2,3 receptor cells.
Five weeks ago, in A Curious OIE Notification From Ghana: HPAI H9N2?, we saw what appears to have been the first detection of an HPAI (Highly Pathogenic) H9N2 virus in West Africa.

While we are still awaiting clarification and detailed analysis of this HPAI strain, this is a reminder that avian flu viruses are perfectly capable of changing on a dime, and are quite capable of throwing us curve balls.

mBio: The Gathering Storm: Is Untreatable Typhoid Fever on the Way?


Roughly three weeks ago a team of British and Pakistani researchers published a study in the American Society For Microbiology Journal mBio - which detailed the first large outbreak of extensively drug-resistant (XDR) typhoid - which emerged in the Sindh region of Pakistan (includes Karachi & Hyderbad) in late  2016.

You can read the full paper at the link below, or read CIDRAP's excellent summary of Feb 20th (see Study: XDR typhoid in Pakistan carries added resistance genes).

Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins 
Elizabeth J. Klemma, Sadia Shakoorb, Andrew J. Pagea, Farah Naz Qamarb, Kim Judgea, Dania K. Saeedb, Vanessa K. Wongc, Timothy J. Dallmand, Satheesh Naird, Stephen Bakere,f,g, Ghazala Shaheenb, Shahida Qureshib, Mohammad Tahir Yousafzaib, Muhammad Khalid Saleemb, Zahra Hasanb, Gordon Dougana,c, Rumina Hasanb
(Continue . . . )

Although XDR, this particular strain of Typhoid is not yet completely resistant; it remains susceptible to oral azithromycin.  Other strains in Southeast Asia have already shown resistance to azithromycin, leading to concerns that susceptibility to this last oral antibiotic may eventually fall.

While we've been watching the inroads made by a growing array of antibiotic resistant organisms around the globe for years, for the most part, human infections have been sporadic, and thus far, very few `pan-resistant' infections have emerged.

The past couple of years, however, we've seen an increase in the number and variety of resistant organisms, many exhibiting even broader resistance than before.  A few recent blogs include:

Global AMR Threat: Centrally Approved & Unapproved Antibiotic Formulations Sold In India
WHO: First Global Antimicrobial Surveillance System (GLASS) Report
MMWR: Fatal Pan-Drug Resistant CRE - Nevada 2016
mBio: 1st Colistin & Carbapenem Resistant E. Coli Infection In A U.S. Patient
And last fall CIDRAP reported on a Hypervirulent, highly resistant Klebsiella identified in China, one which a week later was described as New Klebsiella strains 'worst-case scenario,' experts say.
Of particular concern, the enzymes that convey antibiotic resistance can be carried by a plasmid – a snippet of portable DNA  - that can be horizontally transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species). 
This provides bacteria with a great advantage, as resistance need not develop independently in individual pathogens; it can be shared and passed along to other organisms.
If we're in a war against antibiotic resistance, then the news from the front isn't good.
Salmonella Typhi, the causative agent of Typhoid Fever, is a bacterium that has no known natural reservoir outside of humans. It is usually acquired via the fecal-oral route, often by consuming food or drink that has been handled by someone who is shedding the Salmonella Typhi bacteria.

While still common in some developing countries, Typhoid fever is rarely seen anymore in the United States. The CDC’s Typhoid Fever FAQ states the U.S. sees only about 400 cases of Typhoid each year, of which 3/4ths are brought into this country via international travel.   
Today mBio carries a commentary on last month's study, which the authors describe as `momentous'.  I've only included the abstract, so you'll want to follow the link and read it in its entirety.
When you return, I'll have a postscript.
The Gathering Storm: Is Untreatable Typhoid Fever on the Way?
Myron M. Levinea, Raphael Simona


Klemm et al. (mBio 9:e00105-18, 2018, present comprehensive antibiotic sensitivity patterns and genomic sequence data on Salmonella enterica serovar Typhi blood culture isolates from typhoid fever cases during an epidemic in Pakistan. Microbiologic and genomic data pinpoint the identities and locations of the antimicrobial resistance genes and the outbreak strain’s lineage.
They propose that Salmonella enterica serovar Typhi be added to the list of bacterial pathogens of public health importance that have become extensively drug resistant (XDR). This paper portends possible dire scenarios for typhoid fever control if XDR strains disseminate globally. Since the outbreak strain is of the H58 haplotype, known for its ability to spread worldwide and displace endemic S. Typhi, this concern is well-founded. 
The report of Klemm et al. forewarns the global community to address control of typhoid fever more aggressively through prevention, should therapeutic options disappear. This Commentary frames the Klemm et al. findings within a historic perspective.
     (Continue . . . .) 

Once a major scourge around the world, deaths from Typhoid Fever have declined greatly since the chlorination of water supplies in industrialized nations began early in the last century, along with the development of effective antibiotic treatments. 

While modern sanitation methods - at least in industrialized nations - may limit the impact of AMR (antimicrobial resistant) Typhoid, the reality is this is just one of a growing array of AMR threats in the wings.
Short of a 1918-style (or worse) pandemic, the rise of antibiotic (and anti-fungal) resistant organisms is likely the greatest public health threat we will face in the next couple of decades.
While I cover AMR topics from time to time, I can heartily recommend CIDRAP's Antimicrobial Stewardship Project as the best place to learn about this looming global threat of AMR.

You'll also want to check out the CIDRAP-ASP Youtube Channel, which has more than 20 hours of lectures and webinars on Antimicrobial stewardship.