Thursday, March 30, 2017

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

Pigs as `Flu Factories'















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Due to their unusual virulence in humans, H5 and H7 avian influenza viruses rightfully garner much of the attention of pandemic planners. We can take some solace, however, from the knowledge that - at least over 100 years we can identify pandemic strains - all have come from the H1, H2, and H3 subtypes (Are Influenza Pandemic Viruses Members Of An Exclusive Club?).

While recent history doesn't preclude our seeing an avian flu pandemic, swine - which are susceptible to a wide variety of H1, H2, and H3 influenza viruses, and are physiologically much closer to humans (if that bothers you, think how the pig feels) - may be a much more likely source of pandemic flu viruses. 

Which is precisely the host the 2009 H1N1 pandemic virus - a triple-reassortment of swine, human, and avian flu viruses - used during its lengthy evolutionary trek towards gaining its ability transmit readily among humans. 

Pigs are viewed as potential `mixing vessels' for  influenza viruses, due to having both mammalian α2,6 receptor cells and avian-like α2,6 receptor cells, and having frequent contact with humans and birds.   

The 2009 H1N1 pandemic virus, which leapt from pigs to humans in Mexico, subsequently turned up in pig herds around the world, undoubtedly carried to them by infected humans. This evolutionary feedback loop (reverse zoonosis) has enabled many new swine flu combinations to emerge. 
 
Over the past 10 years we've seen roughly 400 human infections with swine variant viruses reported in the United States, with the H3N2v strain the most common (94%).

Last August, over a period of several weeks 18 people - all fair attendees - were diagnosed with swine-variant H3N2v in two states; Michigan and Ohio. In October the 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 testing for swine-origin viruses in humans is only rarely done, over the winter we've seen two high profile cases in Europe:
Eurosurveillance: Swine Origin H1N1 Infection Leading To Severe Illness - Italy, 2016

Eurosurveillance: Severe acute respiratory infection caused by swine influenza virus in a child).
 
Which brings us to a new, open-access report - in the journal Influenza and Other Respiratory Viruses - of the establishment of a new H3 triple reassortant influenza A virus in Danish pigs. 

Particularly intriguing is the `reappearance' of an H3 gene that hadn't been seen in any host for nearly a decade.  

But perhaps of greater importance is that this novel reassortant virus is of 7/8ths human origin (contributions from the seasonal H3 and H1N109 viruses), and includes the A(H1N1)pdm09 matrix gene, which the CDC has previously speculated:`. . .  may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’ CDC HAN 2012
 
The full report is well worth reading, and underscores how much viral evolution goes on in swine herds around the world, mostly without our knowledge.

Triple-reassortant influenza A virus with H3 of human seasonal origin, NA of swine origin, and internal A(H1N1) pandemic 2009 genes is established in Danish pigs

First published: 21 March 2017
DOI: 10.1111/irv.12451  


Abstract

This report describes a triple-reassortant influenza A virus with a HA that resembles H3 of human seasonal influenza from 2004 to 2005, N2 from influenza A virus already established in swine, and the internal gene cassette from A(H1N1)pdm09 has spread in Danish pig herds. The virus has been detected in several Danish pig herds during the last 2-3 years and may possess a challenge for human as well as animal health.

(SNIP) 
3 Conclusions
We report here the detection of a new triple-reassortant H3N2 influenza virus in swine with H3 gene of seasonal human influenza virus origin, internal genes from A(H1N1)pdm09-like viruses, and NA from contemporary N2 swine viruses. Its genetic makeup is distinct from previously known European swine H3N2 viruses, and the virus was retrospectively detected in a sample from 2013.

It is now apparent that the subtype has become established in the Danish pig population. The reservoir of this virus during the period from 2004 to 2005 human influenza season until 2013 can only be speculated, as it has been reported neither in the human nor in any animal populations during that period. Therefore, further molecular clock analysis is needed on more isolates to elucidate when this virus emerged, and to confirm that the parent virus is indeed from the 2004 to 2005 human influenza season. The reassortment events leading to this virus also remain speculative.

If the H3 gene indeed originated from the human seasonal influenza strains circulating in 2004/2005, this H3 gene have circulated undetected in swine or another host for more than 10 years, and until the emergence of A(H1N1)pdm09, this must have been without the internal genes derived thereof. In our view, a likely scenario is that the H3 gene reassorted with a swine influenza strain with an HXN2-avian-like backbone creating a virus that did not cause severe clinical signs. 

In 2010 or later, this virus reassorted with A(H1N1)pdm09 creating the H3hu05N2 virus which apparently is capable of inducing severe clinical signs in pigs. Denmark is annually exporting more than 10 million living pigs. As pigs are not routinely tested for IAV in relation to export, it is likely that this virus will spread to other European countries, emphasizing the need of joint European surveillance initiatives such as the former European Union funded ESNIP programs.[1, 8

As there was no link between the two independent production systems, the introductions either happened independently from a third source or by transmission between the production systems by other horizontal routes, for example, airborne transmission.

The human-like swine H3N2 virus is distinct from the strains included in all available swine vaccines in Europe and, furthermore, the prevalence of viruses in swine with an H3 gene is very low in pigs in most European countries including Denmark.[8] Thus, the establishment of this new H3N2 virus in pigs could have a significant impact on the swine industry due to lack of population immunity. Indeed, the respiratory disease in pigs and reproductive failures in sows reported from some of the herds in this study were quite severe despite vaccination of the sows.

According to the practitioners we have had contact with, the clinical sigs seen in the herds are comparable to or even more severe than the clinical signs normally encountered during acute outbreak of influenza in Danish swine, so this virus seems to be as virulent or even more virulent than the enzootic circulating strains. Further controlled studies are needed to address this further.

The identification of this new virus with seven of eight genes of human origin including an A(H1N1)pdm09 matrix gene also raises severe concern on the impact on human health. In the United States, swine-adapted H3N2 viruses which also have acquired the A(H1N1)pdm09 matrix gene[13] have been shown to be able to infect humans, albeit with limited human-to-human transmission.
The new virus reported here has in addition to the A(H1N1)pdm09 matrix gene also a human-adapted HA gene which may lead to an improved risk of human-to-human transmission if introduced into humans. Studies are ongoing to investigate these further using ferrets as infection models.
         (Continue . . . )


For more on swine variant viruses, both in the United States and around the world, you may wish to revisit:

CDC On Protecting Against Swine Variant Viruses

Front. Microbiol.: A Novel H1N2 Reassorted Influenza Virus In Chinese Pigs
PNAS: The Pandemic Potential Of Eurasian Avian-like H1N1 (EAH1N1) Swine Influenza
Sci Rpts: Transmission & Pathogenicity Of Novel Swine Flu Reassortant Viruses
 

Wednesday, March 29, 2017

Emerg. Microbes & Infect.: Novel Coronaviruses In Least Horseshoe Bats In Southwestern China





















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While bats have been long been known to carry rabies, its only been in the past couple of decades have other bat-hosted viruses really gained our attention. 
  • Among the first, were the Hendra and Nipah viruses, which were first recognized in the 1990s (see Update: Hendra In Queensland, Nipah In Bangladesh).
  • In 2003 the SARS-Cov (coronavirus) epidemic emerged - and while it was originally linked to civets, later research suggested civets were (at best) intermediate hosts. SARS-like viruses have been found in bats around the world (see EID Journal: Novel Bat Coronaviruses, Brazil and Mexico).
  • In addition to Ebola and Marburg, bats are also suspected to be part of the ecology of MERS-CoV (camels, like civets, may be secondary hosts).  
  • And in the past four years, bats have even been found to harbor several unique influenza viruses (see CDC: Bat Flu Q&A).
Given all that, the past 25 years have been a pretty good time to be a Chiropterist. 
When Steven Soderbergh made his pandemic thriller `Contagion’ a few years ago, technical adviser Professor Ian Lipkin created fictional MEV-1 virus based on a mutated Nipah virus (see The Scientific Plausibility of `Contagion’) simply because of the potential of someday seeing a bat-borne pandemic virus.
 .
The list of potentially zoonotic viruses that bats carry grows every year. Just over a year ago, in Study: Hotspots For Bat To Human Disease Transmission, we looked at a study that attempted to quantify the risks of zoonotic transmission of a wide variety of bat viruses to humans.

In March of 2016 a paper (PNAS SARS-like WIV1-CoV poised for human emergence) from researchers at UNC Chapel Hill highlighted a coronavirus isolated from Chinese horseshoe bats, that already seems to have much of the `right stuff' needed to infect, and replicate, in humans.

Today we've another paper - again on Coronaviruses isolated from horseshoe bats in China - that finds that the least horseshoe bat  (R.pusillus) is (quote):

. . . . a prominent natural reservoir or mixer of genetically diverse Alphacoronavirus and Betacoronavirus species and plays a pivotal role in the evolution and dissemination of these viruses.

Other bat species in the region tested negative for these viruses.  The range of the R. pusillus is shown below.



Below you'll find the abstract and an excerpt from the discussion of a much longer (and at times pretty technical) open access study.

Discovery and genetic analysis of novel coronaviruses in least horseshoe bats in southwestern China
Open

Lihua Wang1,2, Shihong Fu1,2, Yuxi Cao1,2, Hailin Zhang3, Yun Feng3, Weihong Yang3, Kai Nie1,2, Xuejun Ma1,2 and Guodong Liang1,2

Received 23 August 2016; Revised 21 December 2016; Accepted 27 December 2016

ABSTRACT

To investigate bat coronaviruses (CoVs), we collected 132 rectal swabs and urine samples from five bat species in three countries in southwestern China. Seven CoVs belonging to distinct groups of severe acute respiratory syndrome (SARS)-like CoVs and α-CoVs were detected in samples from least horseshoe bats.
Samples from other bat species were negative for these viruses, indicating that the least horseshoe bat represents one of the natural reservoirs and mixers for strains of CoVs and has a pivotal role in the evolution and dissemination of these viruses. The genetic and evolutionary characteristics of these strains were described.
Whole-genome sequencing of a new isolate (F46) from a rectal swab from a least horseshoe bat showed that it contained 29 699 nucleotides, excluding the poly (A) tail, with 13 open reading frames (ORFs). Phylogenetic and recombination analyses of F46 provided evidence of natural recombination between bat SARS-like CoVs (Rs3367 and LYRa11) or SARS-CoV (BJ01), suggesting that F46 could be a new recombinant virus from SARS-like CoVs or SARS-CoVs.


 (SNIP)
In conclusion, horseshoe bats carry genetically diverse SARS-like CoVs. Owing to the high likelihood of recombination among bat CoVs, additional bat SARS-like CoVs are likely to be identified in the future. To better predict and prevent the next emergence of disease caused by CoVs of bat origin, it is necessary to maintain long-term surveillance of bat CoVs.


Bats are the most abundant and geographically dispersed vertebrates on earth. Their ability to carry and vector dangerous diseases without ill-effect (i.e. Rabies, Nipah, Hendra, etc.) is increasingly viewed as a potential public health threat.

None of this is meant to demonize bats, as they are an important part of our environment (they even eat mosquitoes). Still, the CDC offers some sage advice when it comes to avoid coming in contact with bats.

 Take Caution When Bats Are Near


And for some other bat-related posts you may wish to revisit:


Bat Flu Reassortment Possibilities : Revisited
Tiết Canh - An Incredibly Bat Idea
Virology Journal: Ebola Virus In Chinese Bats
FAO: Animal Health `Weak link’ In Preventing Human Diseases

Saudi MOH Announces 1 MERS Case




















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With only 15 cases reported this month - and most of those stemming from a household/nosocomial cluster in Wadi Al Dawasir - MERS continues to pop up at a steady, if unspectacular, rate during the first three months of the year.

Today the Saudi MOH announces 1 primary case in Buraidah (Primary - camel contact) and 1 recovery from the Wadi Al Dawsir cluster.




This leaves 9 cases currently under treatment in KSA.

The pattern with MERS over the past four years has been a  slow, sporadic, trickle of primary cases - punctuated by large (usually hospital driven) clusters (see graph below).



The most recent hospital cluster notwithstanding, KSA has done a much better job over the past year preventing and/or containing hospital outbreaks. 

As long as they are successful doing that - and assuming the virus doesn't evolve into a more transmissible form - we are likely to remain entwined in this uneasy status quo with the MERS virus.




Tuesday, March 28, 2017

WHO Avian Flu Risk Assessment - March 2017


















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The World Health Organization has released an updated Influenza at the human-animal interface report - one that reflects H7N9 cases officially notified to WHO by the Chinese government through March 16th of this year, along with two H5N1 cases reported by Egypt in February.
Since this report is dated March 16th, and China doesn't always notify WHO immediately of cases, today's report is running about 40 behind Hong Kong's most recent tally. 

 First the summary, then some excerpts from the report:


 
Summary and assessment, 14 February to 16 March 2017

  • New infections1: Since the previous update, new human infections with influenza A(H5N1) and A(H7N9) viruses were reported.
  • Risk assessment: The overall public health risk from currently known influenza viruses at the human-animal interface has not changed, and the likelihood of sustained human-to-human transmission of these viruses remains low. Further human infections with viruses of animal origin 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 and non-circulating seasonal influenza viruses. Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.

As the chart at the top of this blow shows, after a record-breaking winter/spring of human cases in 2014-15, case reports dropped dramatically. We still hear of `possible' cases in the Egyptian media (see Egypt: Peering Down The Rabbit Hole), but so far in 2017 Egypt has only confirmed two cases:

The report continues:

Avian influenza A(H5) viruses
Current situation:


Since the last update, two new laboratory-confirmed human cases of influenza A(H5N1) virus infection were reported to WHO. A 4-year-old male resident of Menia Governorate, Egypt, had onset of illness on 2 February 2017, was hospitalized on 10 February and treated with antivirals for pneumonia. A sample collected on admission tested positive for influenza A(H5N1). The patient recovered and was discharged on 20 February. Prior to his illness, the case had contact with domestic birds in his household.


In addition, a 48-year-old man from Fayoum Governorate had onset of illness on 10 February 2017, was hospitalized on 15 February and treated with antivirals for pneumonia. A sample collected on admission tested positive for influenza A(H5N1). The patient developed severe disease and passed away on 24 February. Prior to his illness, the case had contact with sick and dead backyard poultry.


Investigation and follow up of contacts of the two cases took place for 14 days with no further cases reported. Avian influenza A(H5N1) viruses are enzootic in poultry in Egypt.
Since 2003, a total of 858 laboratory-confirmed cases of human infection with avian influenza A(H5N1) virus, including 453 deaths, have been reported to WHO from 16 countries (see Figure 1).
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, and influenza A(H5N5) in wild birds in Europe. 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.
 (SNIP)




Avian influenza A(H7N9) viruses

Current situation:


During this reporting period, 84 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, public health interventions, and the recently detected influenza A(H7N9) viruses with genetic changes consistent with highly pathogenic avian influenza, 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.


As of 16 March 2017, a total of 1307 laboratory-confirmed cases of human infection with avian influenza A(H7N9) viruses, including at least 489 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.

         (Continue . . . )

 
While the risk assessments for these two viruses remains unchanged - and the virus has not demonstrated the ability to transmit efficiently from human to human -  it is fair to say that  recent developments with H7N9 have raised concerns world wide.
  1. This year's surge in human cases not only ends a two year decline in the number of  human infections, it appears likely to double the size of biggest previous epidemic (winter 2013-14).  
  2. H7N9 has recently split into two major lineages - Pearl River Delta and Yangtze River Delta - (see MMWR:Increase in Human Infections with Avian Influenza A(H7N9) In China's 5th Wave) This new lineage will require a new vaccine - meanwhile the virus continues to evolve at an impressive rate.
  3. Previously only an LPAI virus, a new virulent (in birds) HPAI version of H7N9 emerged in Guangdong province this winter, and has demonstrated the ability to infect humans. 
  4. And just last week we learned that this HPAI H7N9 virus is mobile, and `fit' enough to have turned up in a different province, several hundred miles away from it first appeared (see China MOA: High Mortality In Poultry Infected With H7N9 In Hunan Province). 

 Download the PDF File to read the entire report.



CDC Update On Candida Auris - March 2017


















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Last summer the CDC issued a Clinical Alert to U.S. Healthcare facilities about the Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris.

C. auris - an emerging fungal pathogen  - was first isolated about 8 years ago in Japan, found in the discharge from the patient's external ear (hence the name `auris') - although retrospective analysis has traced this fungal infection back over 20 years.

A week later we saw a release from the UK's PHE On The Emergence Of Candida auris In The UK, where they detailed a large (and ongoing since April 2015) nosocomial outbreak at an adult critical care unit in England.

While still rare, we've seen an increasing number of cases (and hospital clusters) reported internationally, generally involving bloodstream infections, wound infections or otitis.

Unlike most systemic Candida infections, which usually arise when a previously colonized person is weakened from illness or infirmity, this strain appears to have a propensity for nosocomial transmission.
When you add in that:
  1. C. auris infections have a high fatality rate
  2. The strain appears to be resistant to multiple classes of anti-fungals 
  3. And it can be difficult for labs to differentiate between Candida strains 
It is little wonder that the CDC is placing a high priority on improved testing, surveillance, and reporting. Last August, in MMWR: Investigation of the First Seven Reported Cases of Candida auris In the United States, we looked at - what was then - only a handful of known US cases.

In the eight months since that report the CDC has recorded an additional 46 cases - mostly from New York State - and all in patients with underlying medical problems staying in health care facilities.  
While this jump may indicate increased incidence of the infection, it may also be the product of improved surveillance and reporting. 

The CDC update for March Follows:
What's New?
Candida auris is an emerging fungus that presents a serious global health threat. Healthcare facilities in several countries have reported that C. auris has caused severe illness in hospitalized patients. Some strains of Candida auris are resistant to all three major classes of antifungal drugs. This type of multidrug resistance has not been seen before in other species of Candida.

Also of concern, C. auris can persist on surfaces in healthcare environments and spread between patients in healthcare facilities, unlike most other Candida species. CDC has developed Interim Recommendations to help prevent the spread of C. auris.

C. auris is difficult to identify with standard laboratory methods and can be misidentified in labs without specific technology. CDC encourages all U.S. laboratory staff who identify C. auris strains to notify their state or local public health authorities and CDC at candidaauris@cdc.gov

Find answers to frequently asked questions about C. auris on our questions and answers page and in the Candida auris: Interim Recommendations.


CDC is working with state and local health departments to identify and investigate cases of C. auris. The following map displays where C. auris cases have been identified in the United States as of March 16, 2017. This map will be updated monthly.




For a bit more on this emerging health threat, you may wish to revisit mSphere: Comparative Pathogenicity of UK Isolates of the Emerging Candida auris.


HK CHP Avian Influenza Report Week 12












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Hong Kong's CHP has published their latest weekly avian influenza report, which adds 18 H7N9 cases from the Mainland -  all of which were reported last Friday by the NHFPC (see Hong Kong CHP Notified By Mainland Of 18 Additional H7N9 Case). 

While still elevated, weekly case counts continue to decline (down almost 20% over last week) - a sign perhaps that the closing of live bird markets in areas reporting cases is having its desired effect. 

Since the start of this 5th epidemic season last October, just shy of 550 H7N9 infections have been reported - 541 on the Mainland - plus 8 exported cases (5 in Hong Kong, 2 in Macao & 1 in Taiwan).

Since only those those ill enough to be hospitalized are generally tested, and H7N9 can produce a wide spectrum of illness - ranging from asymptomatic to severe - the actual number of infections is unknown (see Beneath The H7N9 Pyramid).  


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 12


Reporting period: March 19, 2017 – March 25, 2017 (Week 12)



(Published on March 28, 2017)


Summary


1. Since the previous issue of Avian Influenza Report (AIR), there were 18 new human cases of avian influenza A(H7N9) reported by Mainland China health authorities in Guangxi (5 cases), Hunan (4 cases), Hubei (2 cases), Zhejiang (2 cases), Anhui (1 case), Fujian (1 case), Henan (1 case), Jiangxi (1 case) and Guizhou (1 case). Since March 2013 (as of March 25, 2017), there were a total of 1347 human cases of avian influenza A(H7N9) reported globally. Since October 2016 (as of March 25, 2017), 541 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 March 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.*




        (Continue . . .)



The full report (which runs 9 pages) is well worth downloading and reading, as it contains updates not only on avian flu activity in Mainland China, but around the world. 

While it still doesn't reflect it, we are aware of at least 2 H5N1 cases (1 fatal) in Egypt this year.

After two years of declining epidemic numbers, this winter's surge in H7N9 cases - along with its continual evolution (see MMWR:Increase in Human Infections with Avian Influenza A(H7N9) In China's 5th Wave) - keep H7N9 firmly atop the growing list of novel flu viruses with pandemic potential (see IRAT: Revisited).