China's Nervous Neighbors

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Eastern China has long had the reputation of being the `cradle of influenza' (see Viral Reassortants: Rocking The Cradle Of Influenza), being the birthplace of H5N1 in the mid 1990s, SARS (admittedly a coronavirus, not influenza) in the early 2000's, and the strong suspicion that 2 of the 3 major influenza pandemics of the last century (1957's Asian Flu, 1968's Hong Kong Flu) originated from that region.

In recent years, the number of novel flu viruses coming out of China has only accelerated, with H7N9 emerging in 2013 - followed by H10N8 - both of which have infected and killed humans.  In 2014, two more avian flu viruses - H5N6 and H5N8 - emerged, and both can be traced back to China.

Each of these subtypes has spun off multiple clades, strains, or lineages - and these are just the major players.  China's poultry, and wild bird populations are hosts to dozens of other influenza A subtypes (H9N2, H6N1, H6N6, H4N1, etc.) providing abundant genetic building blocks for generating new subtypes.

When you add human and swine influenza viruses to the mix, live markets with many different types of birds grouped together, and ample opportunities for humans and livestock to interact - you've got the essential ingredients for brewing zoonotic diseases.

Just two weeks before we first learned about the newly emerging H7N9 virus in the spring of 2013  a study (see EID Journal: Predicting Hotspots for Influenza Virus Reassortment)  identified 6 key geographic regions where reassortments are likely to emerge.

And high on that list (you guessed it), was Eastern mainland China.

Between this winter's unprecedented H7N9 epidemic and the jump of H5N6 from China to Korea, Japan, and Taiwan, there's little wonder that China's neighbors are worried that they may be next.


Two weeks ago, in FAO: Reinforcing Control Efforts Against H7N9 In China, in response to both the increased rate of infection, and the emergence of an HPAI H7N9 strain, the FAO warned:

Neighbouring countries remain at high risk, and all those that have poultry trade connections - either formal or informal - to China. A further concern is the possibility that changes seen in the H7N9 virus may affect wild bird population, posing risks to their health or turn them into migratory carriers of the virus, expanding the risk of the virus spreading further as has been seen with other avian influenza strains in faraway Europe, Africa or the Americas.

Over the past month we've seen repeated dire warnings from the Vietnamese government over that country's vulnerability to H7N9 (see Vietnam Girds Against H7N9).  

Today, it seems to be Russia's turn to fret, with media warnings that avian H5N6 may be winging its way out of China and into Russian territory with this spring's migration.

The headline `России грозит опасный для человека птичий грипп'  - `Russia is in danger to human bird flu' - or variants thereof, have appeared on dozens of Russian websites in the past few hours. 

Typical of these reports is the following from dp.ru, which contains a statement from Nikolai Vlasov, the Deputy Head of Rosselkhoznadzor  Russia's Federal Service for Veterinary and Phytosanitary Surveillance.

The authorities have warned of the possibility of visiting Russia for the deadly bird flu human

In Russia, you may receive the avian flu, which is very dangerous to humans. It originated in Southeast Asia, several people have died from it.

Deputy Head of Rosselkhoznadzor Nikolai Vlasov said that Russia may appear dangerous to the human strain of bird flu. First of all at-risk group includes areas of the Far East, he said, reports RBC .

Vlasov also said that the virus originated in Southeast Asia, several people have died from it. "This bird flu virus was born in Southeast Asia, and already have the first fatalities from the virus it threatens our Far Eastern District, if the drift of influenza virus will be, it is not predetermined, but highly probable.", - said Vlasov.

The official stressed that due to the current threat is necessary to be extremely careful.

As explained in the press-service agency, we are talking about the danger of getting H5N6 strain. According to Vlasov, now operates three avian influenza virus in the world.

As Vlasov points out, while the export of H5N6 into Russia isn't guaranteed, a look at the migratory flyways of East and Central Asia  (see below) provide plenty of reasons for concern.

And while H5N6's recent incursions in to Japan, South Korea, and Taiwan suggest it may be the more mobile of the two, the recent emergence (and spread) of HPAI H7N9 has to be on their minds as well.

As southbound migrations have historically sparked more avian flu outbreaks than northbound, perhaps the bigger concern is; what comes back next fall after these novel, and highly promiscuous, viruses have spent the summer in the world's high latitude nesting areas?

While it's not actually a Chinese curse, we do seem to live in `interesting times'.

HK CHP Notified Of 17 New H7N9 Cases From The Mainland

H7N9 Waves - Credit FAO - March 29th Update

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Hong Kong's CHP has announced their notification of an additional 17 H7N9 cases from the mainland, one less than they reported last week.  Of particular note, this is the second week in a row the Mainland is reporting no new cases from Hong Kong's closest neighbor; Guangdong Province.

This welcomed March slowdown is likely due to the temporary closure of live poultry markets in affected regions ordered 6 weeks ago (see  Beijing Orders Closure Of Live Bird Markets To Control H7N9).

Despite these market closures, the (roughly) 80 cases reported (so far) this March exceeds the combined March totals for 2014, 2015, and 2016. Their epidemic dampening effect this year hasn't seemed nearly as immediate or dramatic as in years past (see The Lancet: Poultry Market Closure Effect On H7N9 Transmission).

Whether this indicates a change in the virus, continued illicit trade in poultry, or some other confounding factor is unknown.

In case you missed it, yesterday's Eurosurveillance: Preliminary Epidemiology & Analysis Of Jiangsu's 5th H7N9 Wave, suggested several behavior changes may be occurring in the virus this year, including increase virulence resulting in `accelerated disease progression', and possibly increased tolerance to higher ambient temperatures.

While both are concerning, any change in the virus that would extend the traditional `cold weather' season of H7N9  into the warmer summer months would pose significant challenges.

Concerns we discussed last summer in Hong Kong's Bird Flu Dilemma and China: An Unusual June Surge In H7N9 cases. Right now, all we have are the barest hints of a trend, but we'll be watching this summer's H7N9 activity with particular interest.

Beyond that, the skewing of age and gender continues this week, with the youngest patient listed as 35, and 82% of the cases male. Onsets are said to range from March 6th to the 24th.

As always, the big unknown is how many cases are going undetected.  H7N9 can produce a wild range of illness, ranging from asymptomatic or mild, to severe and life threatening. Only the `sickest of the sick' are likely to hospitalized and tested, so the true number of cases could be substantially higher than reported (see Beneath The H7N9 Pyramid).



This from Hong Kong's CHP.

CHP notified of human cases of avian influenza A(H7N9) in Mainland

 

     The Centre for Health Protection (CHP) of the Department of Health today (March 31) received notification from the National Health and Family Planning Commission that 17 additional human cases of avian influenza A(H7N9), including three deaths, were recorded from March 24 to 30. The CHP strongly urges the public to maintain strict personal, food and environmental hygiene both locally and during travel.
 
     The 14 male and three female patients, aged from 35 to 81, had their onset from March 6 to 24. The cases were six cases from Hunan, three cases each in Jiangsu and Guangxi, two cases each from Fujian and Guizhou, and one case in Zhejiang. Among them, 16 were known to have exposure to poultry or poultry markets.
 
     Travellers to the Mainland or other affected areas must avoid visiting wet markets, live poultry markets or farms. They should be alert to the presence of backyard poultry when visiting relatives and friends. They should also avoid the purchase of live or freshly slaughtered poultry, and avoid touching poultry/birds or their droppings. They should strictly observe personal and hand hygiene when visiting any place with live poultry.
 
     Travellers returning from affected areas should consult a doctor promptly if symptoms develop, and inform the doctor of their travel history for prompt diagnosis and treatment of potential diseases. It is essential to tell the doctor if they have seen any live poultry during travel, which may imply possible exposure to contaminated environments. This will enable the doctor to assess the possibility of avian influenza and arrange necessary investigations and appropriate treatment in a timely manner.
 
     While local surveillance, prevention and control measures are in place, the CHP will remain vigilant and work closely with the World Health Organization and relevant health authorities to monitor the latest developments.
 
     The CHP's Port Health Office conducts health surveillance measures at all boundary control points. Thermal imaging systems are in place for body temperature checks on inbound travellers. Suspected cases will be immediately referred to public hospitals for follow-up.
 
     The display of posters and broadcasting of health messages in departure and arrival halls as health education for travellers is under way. The travel industry and other stakeholders are regularly updated on the latest information.
 
     The public should maintain strict personal, hand, food and environmental hygiene and take heed of the advice below while handling poultry:
 
•    Avoid touching poultry, birds, animals or their droppings;
•    When buying live chickens, do not touch them and their droppings. Do not blow at their bottoms. Wash eggs with detergent if soiled with faecal matter and cook and consume them immediately. Always wash hands thoroughly with soap and water after handling chickens and eggs;
•    Eggs should be cooked well until the white and yolk become firm. Do not eat raw eggs or dip cooked food into any sauce with raw eggs. Poultry should be cooked thoroughly. If there is pinkish juice running from the cooked poultry or the middle part of its bone is still red, the poultry should be cooked again until fully done;
•    Wash hands frequently, especially before touching the mouth, nose or eyes, before handling food or eating, and after going to the toilet, touching public installations or equipment such as escalator handrails, elevator control panels or door knobs, or when hands are dirtied by respiratory secretions after coughing or sneezing; and
•    Wear a mask if fever or respiratory symptoms develop, when going to a hospital or clinic, or while taking care of patients with fever or respiratory symptoms.
 
     The public may visit the CHP's pages for more information: the avian influenza page, the weekly Avian Influenza Report, global statistics and affected areas of avian influenza, the Facebook Page and the YouTube Channel.

 

Ends/Friday, March 31, 2017

Issued at HKT 15:55

Eurosurveillance: Preliminary Epidemiology & Analysis Of Jiangsu's 5th H7N9 Wave

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Although China's 5th winter epidemic of H7N9 has been remarkable across the board, nowhere has this year's epidemic hit harder than in Jiangsu province, which in the last update had reported 133 new cases since October.

While we've been able to follow the number of cases being reported from China, they are usually provided with very little context.   

Recently, we have learned that a new lineage of H7N9 (Yangtze River Delta) has emerged - along with an HPAI version  (see MMWR:Increase in Human Infections with Avian Influenza A(H7N9) In China's 5th Wave) - but epidemiological details have been lacking. 


Today via the ECDC's journal Eurosurveillance, we get our first detailed look at the epidemiology of cases in Jiangsu Province, and we learn that the H7N9 continues to evolve - both genetically, and in terms of behavior.

While I urge you to read the entire report, a few highlights you'll encounter along the way include:

• Despite better medical treatment for patients, the mortality rate remains high (30%+), and the authors report an`accelerated disease progression of H7N9 patients', which they note  `suggests that the viral pathogenicity might have become stronger'.
• The authors also note ` . . .  increased detection rate of H7N9 in environmental samples suggests that the virus might become more resistant to high ambient temperature.' - which you may recall was a concern raised last summer (see HK CHP: Additional Details On China's July H7N9 Cases) when we saw a dozen `out of season H7N9 cases'. 
• At least one co-infection (H7N9 & Seasonal H3N2) was observed, a fairly rare event that opens the door for potential viral reassortment (see EID Journal: Human Co-Infection with Avian and Seasonal Influenza Viruses, China for a more complete discussion). 
• Viral analysis showed that while the virus `shared the same ancestor as earlier viruses from 2013 to 2015, but clustered in an independent clade (Figure 3), which suggested that H7N9 virus is continuously evolving.'

There's a lot to read and absorb here, so allot some time to review this paper.

Eurosurveillance, Volume 22, Issue 13, 30 March 2017
Research article

Significantly elevated number of human infections with H7N9 virus in Jiangsu in eastern China, October 2016 to January 2017

X Huo 1 2 , L Chen 2 3 , X Qi 1 2 , H Huang 1 , Q Dai 1 , H Yu 1 , Y Xia 3 , W Liu 1 , K Xu 1 , W Ma 4 , J Zhang 3 , C Bao 1

+ Author affiliations

Correspondence: Chang-jun Bao (bao2000_cn@163.com)

Citation style for this article: Huo X, Chen L, Qi X, Huang H, Dai Q, Yu H, Xia Y, Liu W, Xu K, Ma W, Zhang J, Bao C. Significantly elevated number of human infections with H7N9 virus in Jiangsu in eastern China, October 2016 to January 2017. Euro Surveill. 2017;22(13):pii=30496. DOI: http://dx.doi.org/10.2807/1560-7917.ES.2017.22.13.30496

Received:14 February 2017; Accepted:08 March 2017

Since first identified in 2013, the H7N9 virus has caused several waves of human infections in China, with a current wave including a number of patients with very severe disease. Jiangsu is one of the most impacted provinces, whereby as of 31 January 2017, the number of human infections (n = 109) in the ongoing fifth H7N9 wave has exceeded the sum of those in the four preceding ones. Ten of 13 cities in Jiangsu have been affected, and clustered infections as well as one co-infection with seasonal influenza have been observed. 

With a median age of 58 years and 74.3% (81/109) of patients being male, the characteristics of cases are similar to those in previous waves, however patients with H7N9 seem to have an accelerated disease progression. Preliminary case fatality remains above 30%. No significant viral mutations have been found in key functional loci.

Environmental H7N9 detection rate and number of days with high risk ambient temperatures were both significantly elevated during the month of December 2016 when most human infections were reported. A number of municipal governments in Jiangsu have implemented live poultry market closures to impede viral transmission to humans. A detectable decline in human infections has been observed in these municipalities and the entire province since January 2017.

 Discussion

Jiangsu province is now experiencing the fifth wave of human infections with H7N9, with a significantly elevated number of cases. Visiting live poultry markets is the main risk factor for H7N9 infection for the public, due to poultry contact in this setting or environmental contamination [15,16]. The high H7N9 virus detection rate in these sites may directly contribute to the elevated human H7N9 infections. Therefore, live poultry market closures have been suggested as an effective method to control such infections [17,18]. Accordingly, several municipal governments in Jiangsu province, including Suzhou, Wuxi and Changzhou, have implemented temporary comprehensive live poultry market closures since December 2016. Subsequently, a significant decline in human infections has been observed in these cities/municipalities, as well as province-wide since January 2017 (Figure 1). The decrease was even more evident in February (data not shown).

Many meteorological factors, such as temperature, relative humidity [7,19], specific humidity [20] and solar radiation [21], have been reported to influence influenza activity. As for H7N9, both daily minimum and daily maximum temperatures have been reported to contribute significantly to human infection, but not relative humidity [22]. Other meteorological factors have not been reported. The overall impact of ambient temperature on human infection rates with H7N9 may nevertheless also depend on the underlying level of environmental H7N9 virus contamination, as exemplified by the results in November 2016, when although temperatures appeared to be permissive to human infection, low rates were observed, coinciding with low rates of environmental contamination.

The environmental H7N9 contamination rate could be influenced by multiple factors, such as H7N9 virus infection rate of poultry for sale, and the hygiene level of the live poultry market. The interaction and correlation between temperature and other factors and their impact on human infections need to be investigated further in future studies.

Antivirals such as oseltamivir were administrated to almost all of the H7N9 patients in recent years in Jiangsu province. Furthermore, the time interval from onset of disease to antiviral administration is becoming shorter due to promoted sensitivity of clinicians. Clinicians also gained experiences in treatment, such as the rational use of ventilators and extracorporeal membrane oxygenation (ECMO). All of these measures are beneficial for the patients’ clinical outcome.

Nevertheless, an accelerated disease progression of H7N9 patients during latest waves was still observed, which suggests that the viral pathogenicity might have become stronger. In addition, the increased detection rate of H7N9 in environmental samples suggests that the virus might become more resistant to high ambient temperature.

Although no significant mutations were observed in key functional loci of the isolates from the current wave in our preliminary analyses, further work still needs to be conducted in detail. For instance, changes in the length of the neuraminidase stalk region might impact virulence [23] and residues 41V and/or 210D in the nucleoprotein (NP) protein could enhance polymerase activities and potential replication at low temperature [24].

The pandemic potential of the H7N9 virus needs to be closely watched. In humans, co-infection of this virus with seasonal influenza might provide reassortment opportunities for the emergence of a new pandemic virus. In addition, the continuous mutation and reassortment of H7N9 with other avian influenza viruses lately resulted in the identification of H7N9 isolates with characteristics of high pathogenicity to poultry, which was concerning for the poultry industry [25]. There is also a risk that H7N9 might acquire better ability of spreading from poultry to ducks and wild birds, and thus be disseminated worldwide, threatening humans in a much wider geographical range [26-28]. Therefore, it is critical to control the transmission of H7N9 virus in poultry to lower these risks.

To avoid the possibility of further adaption to human of this virus, early identification of human infections with H7N9 and early administration of neuraminidase inhibitors are critically needed. At present, the median time intervals from onset of disease to first medical consultation and from onset of disease to administration of neuraminidase inhibitors are two and six days, respectively. Efforts implementing effective rapid diagnostic kits in primary medical facilities, such as community clinics, could further promote the timeliness of diagnosis and antiviral therapy, as nearly half of the H7N9 patients first seek medical services in these facilities.

Until now, older males still account for most of the H7N9 patients. An overwhelming majority of the reported patients were severely infected and the overall case fatality remained above 30%. Live bird markets are the most common sites for the public to contact birds or bird materials which might carry H7N9 virus. With the continuous closures of live bird markets, the case number is expected to keep decreasing. In addition, the upcoming warmer weather would also deter the transmission of H7N9.

However, we should be alert that H7N9 cases might occur in areas where live bird market closures are not implemented, also because live poultry from places affected by H7N9 and with market closures, may be transferred to these areas. A full investigation of the current wave of human infections with H7N9 virus is still ongoing. This study presents timely preliminary results, including possible causes, which could help researchers in further detailed analyses.

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

 

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.

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:

Influenza at the human-animal interface

 
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.

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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:

Candida auris 

What's New?

• March 16, 2017: case count update
• March 16, 2017: Updated recommendation for when C. auris should be suspected

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.*

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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).

Georgia Dept Of Agriculture Confirms Avian H7 (Presumptive LPAI) in Chattooga County

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While hardly unexpected given the report earlier today (see HK Suspends Poultry Imports From Chattooga County, Georgia), Georgia's Department of Agriculture has confirmed that lab testing of a commercial flock in the far northwestern part of the state has come back positive for avian H7.

Over the past three weeks we've seen more than a half dozen other detections - all a newly reassortant North American H7N9 virus - centered in southern Tennessee and North Alabama.

Georgia Department of Agriculture
Gary W. Black, Commissioner
19 Martin Luther King Jr. Dr. SW
Atlanta, GA 30334
www.agr.georgia.gov

Press Release
FOR IMMEDIATE RELEASE
Monday, March 27, 2017
Office of Communications
404-656-3689

Confirmed H7, Presumptive Low Pathogenic Avian Influenza in a Commercial Flock in Georgia

A flock of chickens at a commercial poultry breeding operation located in Chattooga County has tested positive for H7, presumptive low pathogenic avian influenza (LPAI). This is the first confirmation of avian influenza in domestic poultry in Georgia. Avian influenza does not pose a risk to the food supply, and no affected animals entered the food chain. The risk of human infection with avian influenza during poultry outbreaks is very low.

The virus was identified during routine pre-sale screening for the commercial facility and was confirmed as H7 avian influenza by the USDA National Veterinary Services Laboratory (NVSL) in Ames, Iowa. As a precaution the affected flock has been depopulated. Officials are testing and monitoring other flocks within the surveillance area and no other flocks have tested positive or experienced any clinical signs.

The announcement follows similar confirmations from Alabama, Kentucky and Tennessee in recent weeks. The Georgia case is considered a presumptive low pathogenic avian influenza because the flock did not show any signs of illness. While LPAI is different from HPAI, control measures are under way as a precautionary measure. Wild birds are the source of the virus. Avian influenza virus strains often occur naturally in wild birds, and can infect wild migratory birds without causing illness.

“Poultry is the top sector of our number one industry, agriculture, and we are committed to protecting the livelihoods of the many farm families that are dependent on it,” said Georgia Commissioner of Agriculture Gary W. Black. “In order to successfully do that, it is imperative that we continue our efforts of extensive biosecurity.”

The official order prohibiting poultry exhibitions and the assembling of poultry to be sold issued by the state veterinarian’s office on March 16, 2017, remains in effect. The order prohibits all poultry exhibitions, sales at regional and county fairs, festivals, swap meets, live bird markets, flea markets, and auctions. The order also prohibits the concentration, collection or assembly of poultry of all types, including wild waterfowl from one or more premises for purposes of sale. Shipments of eggs or baby chicks from National Poultry Improvement Plan (NPIP), Avian Influenza Clean, approved facilities are not affected by this order.

Owners of poultry flocks are encouraged to closely observe their birds and report a sudden increase in the number of sick birds or bird deaths to the state veterinarian’s office at (855) 491-1432. For more updates and information regarding biosecurity tips visit www.ga-ai.org or www.allinallgone.com.

ECDC: Rapid Risk Assessment On Multi-Country Cluster Of MDR-TB In Migrants

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Whether it is a tourist returning from Carnival in Rio, a businessman traveling from the Arabian Peninsula to Asia, or a migrant making their way from North Africa into Europe - they all have one thing in common.

They all have the ability to be exposed to - and then inadvertently carry - exotic infectious diseases (like Zika, MERS, Dengue, Yellow Fever, Avian Flu, TB, etc.) from one part of the world to another.

Last December the ECDC reported on a cluster of MDR-TB among a group of 16 migrants who had recently entered the EU during the first six months of 2016 (see Multidrug-resistant tuberculosis in migrants, multi-country cluster, first update 19 Dec 2016).

An international whole genome sequencing cluster involving 16 cases of multidrug-resistant tuberculosis (MDR TB) in asylum seekers has been detected. The first seven cases were identified in Switzerland between February and August 2016. Their countries of origin are Somalia (5 cases), Eritrea (1) and Ethiopia (1). Whole genome sequencing (WGS) showed no difference among isolates in four cases and differences of one allele in the three others. Based on the WGS results, the strains belong to a single molecular cluster. The same genetic clone with the same and so far unknown drug resistance profile was detected in nine additional cases from Somalia, six of them diagnosed in Germany, two in Austria, and one in Sweden.

Fast forward a little more than 3 months and the ECDC has published an updated RRA, which has now identified 25 cases.  Follow the link to read the full 4-page report.

Conclusions and options for response 

A multi-country cluster of multidrug-resistant tuberculosis (MDR TB) involving 25 migrants has been delineated by whole genome sequencing (WGS). All cases have a recent history of migration from Somalia (22 cases), Eritrea (2 cases) and Ethiopia (1 case). Cases have been reported by Germany (13 cases), Switzerland (8 cases), Austria (2 cases), Finland and Sweden (1 case each). 

A WGS analysis of the 25 cluster isolates supports the hypothesis that the cases are part of a chain of recent transmission likely to have taken place either in the country of origin or in a place along the migration route to the country of destination. Based on the currently available information, it is not possible as of yet to rule out that transmission occurred in an EU/EFTA country. 

It therefore remains important to rapidly investigate exposure risk factors, including the travel history and itineraries of patients and their contacts, and share this information to determine whether transmission may have taken place in the EU/EFTA, during migration, or in the country of origin. Depending on the results of the investigation, appropriate prevention and control measures should be taken. 

Although the number of cases detected so far suggests that there is only a limited risk of this cluster becoming a widespread event in Europe, more cases may yet be identified in association with this cluster. Early case finding of active TB and drug susceptibility testing, especially in newly arriving migrants from the Horn of Africa, is important in order to identify and treat active cases and to provide preventive treatment or monitoring for those diagnosed with latent tuberculosis infection.

Saudi MOH Announces 1 New MERS-CoV case

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After a lull of 7 days without reporting a new MERS case, the Saudi MOH today has announced a primary (Direct Camel Contact) case in Al Kharj, in a 54 y.o. male who is listed in stable condition.

There are a total of 10 active cases receiving treatment in Saudi Hospitals.  We've not heard of any new cases in the Wadi Al Dawasir Cluster - which produced at least 10 cases earlier in the month - in nearly two weeks. 

HK Suspends Poultry Imports From Chattooga County, Georgia

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Over the weekend we've been watching media reports of poultry testing for avian flu in Northwestern Chattooga county Georgia (see Test Results on Possible Bird Flu Near Menlo Expected Today), adjacent to the Alabama border. 

While there's no official announcement (yet) from state agricultural officials, Hong Kong's CFS (Centre for Food Safety) has apparently already been notified, as evidenced by the following statement issued this morning.

Hong Kong bans import of poultry meat and products from Pickens County, Alabama and Chattooga County, Georgia in US (27.3.2017)

The Centre for Food Safety (CFS) of the Food and Environmental Hygiene Department announced today (March 27) that in view of a notification from the World Organisation for Animal Health (OIE) about an outbreak of low pathogenic H7N9 avian influenza in Pickens County, Alabama in the United States (US), and a notification from the US authorities about an outbreak of low pathogenic H7 avian influenza in Chattooga County, Georgia, the CFS has banned the import of poultry meat and products (including poultry eggs) from the two areas with immediate effect to protect public health in Hong Kong.

Assuming this is confirmed by the USDA and state agricultural officials later today, Georgia will become the 4th state to report this new LPAI H7N9 virus.  

While it shares the same subtype name as China's H7N9 virus - this North American Lineage virus is genetically distinct from its Asian counterpart - and is not currently expected to pose a serious human health threat.

H7 viruses, however - even LPAI strains - have caused minor illnesses in humans in the past (see A Brief History Of H7 Avian Flu Infections and  NYC Health Dept Statement On Human H7N2 Infection), and viruses can change their behavior and virulence over time 

Since it appears that LPAI H7N9 continues to spread in the wild bird population, and may spark additional outbreaks in backyard and commercial poultry this spring, those in contact with live birds should heed the CDC's advice on avoiding infection.