Indiana Reports H3N2v Infection In Fairgoer

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As we discussed almost a month ago, The `Other' Novel Flu Threat We'll Be Watching This Summer, the summer and fall are typically the times of the year when we see scattered reports of human swine variant flu infection, which  are often linked to visiting animal exhibits at state or country fairs.   

The CDC describes Swine Variant viruses in their Key Facts FAQ.

What is a variant influenza virus?

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a “variant influenza virus.” For example, if a swine origin influenza A H3N2 virus is detected in a person, that virus will be called an “H3N2 variant” virus or “H3N2v” virus.

Most (but not all) swine variant infections are mild or moderate, and are clinically indistinguishable from regular seasonal influenza. Which is why it is believed many swine variant infections go undetected (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).

Overnight numerous Indiana media outlets have carried reports of that state's first swine variant case since 2013, when 4 cases were reported.  The previous year, 2012, Indiana saw the largest outbreak on record (n=138). 

These reports, as you'll see, carry very little specific information.  While we are told the exposure was linked to attendance at a county fair, we aren't told when or in what county that exposure occurred.

This from Tribune-Star.

Officials warn of flu; 1 Hoosier confirmed case after exposure to pigs
Tribune-Star staff report

The state department said its seen one recent, confirmed case of a resident developing influenza after exposure to pigs.

This is the first human case of H3N2 variant influenza reported in Indiana since 2013 and the first human case in the U.S. this year, according to the Centers for Disease Control and Prevention, which confirmed the test results Friday.

H3N2 variant influenza is most commonly associated with contact with pigs. The Indiana resident became ill after being exposed to pigs during a county fair that has since ended. The resident is recovering.

The affected county health department has been notified and is collaborating on the investigation. No additional details about the patient or the fair will be released at this time in order to maintain the patient’s privacy, the state agencies said in a news release.

        (Continue . . . )


The decision not to release the name of the county fair where exposure occurred is a bit unusual, and could prove problematic, should more cases turn up.

Despite concerns over `patient privacy', other states have released basic information, like the location and likely time frame of the exposure (see Maryland DOH: 20 Presumptive Positive & Confirmed H3N2v Cases), to help facilitate surveillance and reporting.

While I suspect it's not what the organizers of agricultural exhibits want to hear, last August's  EID Journal: Transmission Of Swine H3N2 To Humans At Agricultural Exhibits - Michigan & Ohio 2016 examined the risks of novel flu transmission at these types of venues, including from healthy-looking pigs. 

Of particular interest, while widespread illness in pigs was only rarely reported, surveillance revealed an average prevalence of influenza A in fair pigs of 77.5%. The authors cautioned that this suggests `that subclinical influenza A infections in pigs remain a threat to public health (3).'

Despite the current low risk of infection, there are some things you should consider doing to reduce your chances of getting sick, particularly if you are at `high risk' of flu complications.  This from the CDC.

CDC Recommendations For People At High Risk:

• If you are at high risk of serious flu complications and are going to a fair where pigs will be present, avoid pigs and swine barns at the fair. This includes children younger than 5 years, people 65 years and older, pregnant women, and people with certain long-term health conditions (like asthma, diabetes, heart disease, weakened immune systems, and neurological or neurodevelopmental conditions).

If you are not at high risk, take these precautions:

• Don’t take food or drink into pig areas; don’t eat, drink or put anything in your mouth in pig areas.
• Don’t take toys, pacifiers, cups, baby bottles, strollers, or similar items into pig areas.
• Wash your hands often with soap and running water before and after exposure to pigs. If soap and water are not available, use an alcohol-based hand rub.
• Avoid close contact with pigs that look or act ill.
• Take protective measures if you must come in contact with pigs that are known or suspected to be sick. This includes wearing personal protective equipment like protective clothing, gloves and masks that cover your mouth and nose when contact is required.
• To further reduce the risk of infection, minimize contact with pigs in the pig barn and arenas.

 
That said, swine variant flu infection remains a relatively minor public health threat in the United States. But flu viruses are constantly changing, and so that could change. The CDC's Risk Assessment on H3N2v and other swine variant viruses reads:

CDC Assessment

Sporadic infections and even localized outbreaks among people with variant influenza viruses may occur. All influenza viruses have the capacity to change and it's possible that variant viruses may change such that they infect people easily and spread easily from person-to-person. The Centers for Disease Control and Prevention (CDC) continues to monitor closely for variant influenza virus infections and will report cases of H3N2v and other variant influenza viruses weekly in FluView and on the case count tables on this website

H3N2 Variant:[A/Indiana/08/11] is among the 16 novel viruses currently being  tracked by the CDC's IRAT (Influenza Risk Assessment Tool) Rankings.

The summary average risk score for the virus to achieve sustained human-to-human transmission was in the moderate risk category (less than 6). The summary average risk score for the virus to significantly impact public health if it were to achieve sustained human-to-human transmission was in the low-moderate risk category (less than 5).

For more information on swine variant viruses, and how to protect yourself when in contact with farm animals, the CDC provides the following guides.

• Key Facts for People Exhibiting Pigs at Fairs[545 KB, 2 pages]
• Take Action to Prevent the Spread of Flu Between People and Pigs[1.3 MB, 2 pages]
• Educational Posters[389 KB, 1 page]
• Compendium of Measures to Prevent Disease Associated with Animals in Public Settings, 2013.
• Reduce Your Risk (English)[22 KB, 1 page] | (Spanish)[22 KB, 1 page]
• Measures to Minimize Influenza Transmission at Swine Exhibitions, 2016 – NASAHO and NASPHV[97 KB, 8 pages]

Why No News Isn't Necessarily Good News

 
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As economic, societal, and political winds shift around the world - the willingness of many countries to publicly (and apparently, even privately) acknowledge infectious disease outbreaks tends to change - sometimes dramatically. 

A positive example, five years ago, we saw a remarkable (and highly praised) shift in reporting of avian flu details out of China following  the emergence of H7N9 in 2013.  

After the debacle of trying to hide the SARS epidemic burning through Chinese hospitals in 2002-2003, and a 10-year history of minimizing H5N1 cases, we were suddenly flooded with detailed epidemiological information on this new novel flu threat.

That openness ended early in the spring of 2015, when China's MOH went strangely silent on H7N9 (see H7N9: No News Is . . . . Curious), and the level of patient detail reported to the WHO dropped dramatically.

This subdued reporting continued until January 2017 - when faced with a sudden avalanche of human H7N9 cases - the MOH belatedly announced a batch of cases from the previous month (see HK CHP: China Reports An Additional 83 H7N9 Cases For December).

While reporting improved somewhat - at least temporarily - it has never returned to the level of detail we were enjoying in 2013 and 2014. 

At roughly the same time Egypt - which had seen a record setting outbreak of human H5N1 infections beginning in November of 2014 - stopped nearly all reporting of cases on their MOH website (see Revisiting Egypt’s Murky H5N1 Battle) in late January of 2015 - and began issuing denials of new cases to the local media.

For the past three years, avian flu news out of Egypt - whether it be from the MOH, MOA, or their local media (ranked 161st in press freedom) - has been eerily subdued.

More recently, 45 days ago the Saudi MOH stopped reporting on MERS-CoV cases, and removed months worth of accrued data from their surveillance website.

The site is supposedly `under construction', but will hopefully come back online at some point. For now, however, our visibility of MERS cases in KSA - just 6 weeks before the start of the Hajj - is pretty much absent. 

Since the Saudi press (ranked 169th in press freedom) is even more tightly controlled than is Egypt's, there is little help to be found there.

It is now nearly the end of June, and the last MERS case publicly revealed was part of a household cluster which began in May, where the latest (June 10th) WHO EMRO report stated:

The index case had a date of onset of symptoms on 17 May 2018 and by 31 May, seven symptomatic secondary cases were reported from this cluster. More cases are expected to be reported from this cluster as the close contacts are being followed up and the laboratory test result of some of the close contacts are awaiting.

Saudi Arabia appeared to reach their peak in MERS-CoV openness between the fall of 2015 and the middle of 2016, with the publication of a Weekly MERS Monitor report from their CCC (Command & Control Centre).

Not only was this excellent weekly report discontinued in August of 2016, the repository of old reports now only returns a 404 error. 

Granted, the list of countries that try to keep disease outbreak information close to the vest extends far beyond just China, Egypt, and Saudi Arabia.  But these three countries have a recent history of novel virus outbreaks, and are therefore of greatest concern. 

While these pullbacks are both disappointing and worrisome, sovereign nations are under no legal obligation to publicly acknowledge disease outbreaks to their public - or for that matter - to provide us with detailed epidemiological data.

But under the terms of the 2005 IHR (International Health Regulations) - WHO member countries have agreed to develop mandated surveillance and testing systems - and to report certain disease outbreaks and public health events to WHO in a timely manner. 

Thirteen years after it was approved, however, fewer than half the countries of the world self-report having met the core requirements of the IHR. 

But even among those who have - timely reporting continues to be problematic. While public chastisement is uncommon in diplomatic circles, in recent years we've seen signs of growing frustration over the lack of progress on the IHR, including:

• In January of 2017, amid initial reports of a surge in H7N9 cases in China (see WHO DIrector-General Chan On H7N9 In China), the D-G once again urged that all countries promptly report cases under the IHR 2005 agreement.
• In 2015, the World Health Organization issued a particularly strong rebuke (without singling out the Saudis) on the reporting of MERS-CoV and the handling of asymptomatic cases in their WHO Statement On The 10th Meeting Of the IHR Emergency Committee On MERS.
• Also in 2015, in the wake of the slow international response to the West African Ebola Epidemic, we looked at proposals to add some `teeth' to the IHR (see Adding Accountability To The IHR).

It is one thing to try to overcome the limited resources preventing some countries from conducting adequate surveillance and reporting their findings to the WHO, while it is quite another if some countries are deliberately slow walking disease outbreak information for political or economic reasons.  

A reminder that `No news isn't necessarily good news', and that the current lull in infectious disease outbreaks around the globe may be - at least partly - illusory, and at the very best, temporary.  

All reasons why pandemic planning needs to be an ongoing priority, and not just ramped up based on the most recent 24-hour news cycle.

ECDC: Avian Influenza Overview, February – May 2018

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Because LPAI and HPAI avian flu reports come in from all over the globe, often belatedly or with varying levels of detail, it isn't always easy to maintain an accurate sense of bird flu's progress and evolution.  

While `breaking news' is important, so is looking back, and analyzing what has transpired over the past few months.  And you'd be hard pressed to find any entity that does surveillance reviews better than the ECDC. 

Today we have a quarterly review - covering the time period from mid-February to mid-May 2018 - which looks not only at the avian flu situation in Europe, but also around the globe.

This 50-page PDF (which I've already saved to my desktop for future reference), is chock full of charts, graphs, maps, and analysis.

Below you'll find  the Executive Summary, and a couple of snippets from the report, but you'll want to download the full report ( Avian influenza overview, February – May 2018 - EN - [PDF-2.31 MB]), and read it in its entirety.  
 

Executive summary

Between 16 February and 15 May 2018, three highly pathogenic avian influenza (HPAI) A(H5N6) and 11 HPAI A(H5N8) outbreaks in poultry holdings, one HPAI A(H5N6) and one HPAI A(H5N8) outbreak in captive birds, and 55 HPAI A(H5N6) wild bird events were reported in Europe. There is no evidence to date that HPAI A(H5N6) viruses circulating in Europe are associated with clades infecting humans. 

Fewer HPAI wild bird cases have been detected than during the same period of previous year. Most of mortality events among wild birds involved single birds and species listed in the revised list of target species for passive surveillance. Raptor species constitute 74% of the HPAI-infected wild birds found dead. Those raptor species probably became infected by hunting or scavenging HPAI virus-positive birds, and so raptor cases may predominate later in the course of an HPAI epidemic. 

Despite the important HPAI virus incursion via wild birds there have been few associated HPAI A(H5N6) outbreaks in poultry. Fifteen low pathogenic avian influenza (LPAI) outbreaks were reported in three Member States. The risk of zoonotic transmission to the general public in Europe is considered to be very low. 

The situation in Africa and the Middle East should be closely monitored with regards to HPAI A(H5N1) and A(H5N8). Uncontrolled spread of the virus and subsequent further genetic evolution in regions geographically connected to Europe may increase uncertainty and the risk for further dissemination of virus. 

Long-distance migrating wild birds from southern Africa, e.g. the common tern ( Sterna hirundo ), may be included in targeted active surveillance schemes at a few priority locations in Europe in order to detect HPAI A(H5)-infected migrating birds early. However, the risk of HPAI introduction from non-EU countries via migratory wild birds to Europe is still considered to be much lower for wild birds crossing the southern borders than for those crossing the north-eastern borders.

(Excerpt)

Conclusions

• The risk of zoonotic transmission of avian influenza (AI) viruses to the general public in the EU/EEA countries is considered to be very low.
• HPAI A(H5N6) wild bird cases were detected from east to west Europe, as far as Ireland, through the north European regions, suggesting that there were multiple primary introductions of HPAIV into the EU via migrating wild birds.
• Fewer HPAI wild bird cases have been detected this year than during the same reporting period in 2017. Even if there is uncertainty around conclusive reasons to explain this observed difference, it may be the result of a lower AI virus prevalence in wild birds, a smaller susceptible wild bird population (due to an existing population immunity given the antigenic similarity of HPAIV A(H5N8) circulating in 2017 to HPAIV A(H5N6) in 2018) or a later onset of winter.
• As seen in previous years, raptors probably become infected with HPAIV by hunting or scavenging HPAIV-positive birds, and so raptor cases may predominate later in the course of an HPAIV epidemic.
• In this reporting period, the high proportion of raptor and scavenger cases reported may be biased by the heterogeneous implementation of the passive surveillance across years and Member States (e.g. increased proportion of raptor and scavenger species tested compared with previous years; the cut-off value for wild bird mortality events applied to test birds found dead for AI, differing by Member States and wild bird species within Member States).
• Relative to the number of wild bird events there have been few associated HPAI outbreaks in poultry.

While the slowdown in avian flu reports this past winter in Europe, the Middle East, and China are quite welcome - particularly after the record setting 2016-2017 bird flu season - the history has been that very active `bird flu years' are often followed by one or more less active seasons.  
 

ESA Epidemiological Update: Global Circulation Of Avian Flu

The above chart shows outbreaks of avian flu reported to the OIE from 2005 to the start of 2018, and highlights the initial surge associated with the emergence of HPAI H5N1 early in the last decade and its sudden westward expansion to Europe, Africa and the Middle East - followed by a slow decline starting in 2009 - to a resurgence in 2015 propelled by the emergence and global spread of HPAI H5 Clade 2.3.4.4.

Joining H5Nx, we've also seen the emergence and spread of LPAI and HPAI H7N9, H10N8, and an array of lesser LPAI and HPAI viruses. 

Since we've seen one-year lulls and multi-year lulls, we don't know how long this latest respite will last. 

But considering the growing number of novel subtypes in circulation, HPAI's recent expansion into the Southern Hemisphere, and reports of fresh HPAI H5 activity in Russia, we need to be using this lull to learn as much as we can about the current avian flu threats, and to prepare for whatever comes next.

Because, whether it's a change in a virus we know - like H5Nx, or H7N9, or something new or unexpected coming out of left field - something always seems to come next.
 

A Snapshot From Last Winter's Severe Flu Season - Texas

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It is not exactly  news that last winter's (2017-18) seasonal flu season was the worst non-pandemic flu season in recent memory, but the final tally of hospitalizations and deaths has yet to published.  

Two weeks ago, we saw the CDC report Flu Deaths in Children Exceeds Seasonal High since reporting became mandatory in 2004, and the latest FluView report hospitalization chart (below) showed a 40% increase over the previous influenza season. 

 
There is a lot of data to sift through, and while an exact count will never be known, all of the metrics to date seem to validate our perception of the severity of last winter's H3N2 flu season.

The State of Texas, which has roughly 28 million residents (a little less than 9% of the nation's total), has published their weekly influenza surveillance report (week 24), and it provides some insight into just how severe their flu really was.

Since influenza doesn't necessarily hit evenly or equally across the country, we can't just take the Texas numbers and multiply them by 11 to get a national average. But as more data from individual states become available, we should get a better idea of the national impact. 

The full report (link below), is well worth reading, but we'll be looking at one particular chart of interest; P&I (pneumonia & Influenza) mortality by age.

Texas Influenza Surveillance Summer Report

2017–2018 Season/2018 MMWR Week 24

(June 10, 2018 – June 16, 2018)

Report produced on 6/22/2018

P&I deaths - while a useful metric - are still unlikely to capture the full burden of influenza-related fatalities, because so many people die due to complications of influenza and are never tested for the virus. 

As we've discussed previously, heart attacks and strokes are linked to recent flu infections (see Eur. Resp.J.: Influenza & Pneumonia Infections Increase Risk Of Heart Attack and Stroke) and many of those deaths are attributed to cardiovascular - not viral - causes.

To be picked up by the P&I surveillance system, influenza or pneumonia has to be cited on the death certificate as being a contributing factor to a patient's death.

If the patient had cancer, or heart problems, was of advanced age, or had any other significant co-morbidity - that - not influenza or pneumonia, is usually listed as the primary cause of death.

But we can only work with the numbers we have, and while the following is unlikely to be an exact count, it does provide a pretty good data point to compare to other flu seasons.

Texas reported 62 pediatric P&I deaths - while the CDC has (so far) documented 174 flu-related deaths. The CDC uses a fairly strict criteria (see below), and it isn't clear whether all of these Texas P&I pediatric cases would be included on that list.

That said, it is likely that pediatric flu-related cases are under counted every year, even with mandatory reporting. In the aftermath of the H1N1 pandemic of 2009, the CDC estimated that the likely number of pediatric deaths in the United States ranged from 910 to 1880, or anywhere from 3 to 6 times higher than reported.

Last January, in a CDC press conference, Dr. Dan Jernigan once again addressed the problem of getting a handle on the number of flu fatalities (underlining mine).

DAN JERNIGAN:
(excerpt) 

So with pediatric deaths, these that are in the graphs and the ones we report again, probably also are an underestimation of the actual deaths that are out there. There may even be as much as twice than the number we have.

Among adults, those over 65 were hardest hit (7275 deaths), but more than 2,000 adults in Texas- ages 18-65 - also succumbed, bringing the the total for that one state to to almost 9,500 P&I deaths. 

And that may well turn out to be a significant undercount. 

Last January, in Why Flu Fatality Numbers Are So Hard To Determine,
we looked at some of the statistical methodology used by the CDC, and by individual states, to come up with an estimate of the burden of influenza each winter. 

Although the CDC has an `expected range' of seasonal influenza hospitalizations and deaths (see chart below), even without a novel virus, it is possible to see an unusually severe `outlier' season.  

 
While the full accounting has yet to be published, it seems likely - based on the numbers we've seen so far - that the 2017-18 flu season will end up being an outlier, and that its final tally will exceed the upper range of deaths and hospitalizations in the above chart.

A reminder that seasonal flu can be quite deadly, and that we take it lightly at considerable personal risk.

EID Journal: Isolation of VEEV Genome from Human Swab Specimen, Peru

Credit EID Journal

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Conventional wisdom - particularly when it comes to infectious diseases - isn't what it used to be. The more knowledge we glean, the more unexpected findings, and `exceptions to the rule', that end up in the scientific literature.

A few recent examples include:

Five years ago, it was generally accepted that Ebola was simply too debilitating, and too lethal, to have `legs’ . . . to spread beyond a limited geographic area.  Those infected were believed `too sick to travel’, and therefore small outbreaks would inevitably `burn themselves out’  in relatively short order. 

And then, defying all expectations, we saw the first urban epidemic of Ebola spreading across three West African nations in 2014, resulting in more than 28,600 cases and causing at least 11,325 deaths (cite).

Additionally, from this epidemic we learned that the Ebola virus can persist in a `recovered' patient for months (see Virus Evolution: Rapid Sequencing Reveals Rare Ebola Transmission Via Breast milk And Semen), adding new, and unexpected ways to reintroduce the virus back into the community.

For forty years - since it famously sparked an infamous pneumonia outbreak at Philadelphia’s Bellevue Stratford Hotel during an American Legion convention in 1976 - Legionella pneumonia has been considered strictly an environmental illness. 

It was not believed transmissible from human-to-human (cite).  

And while that conventional wisdom is still probably true 99.99% of the time, in 2016's NEJM: Probable Person-to-Person Transmission Of Legionnaires’ Disease, we saw evidence presented that person-to-person transmission of Legionnaires Disease may have occurred in 2014 during an outbreak in Portugal.

In 2015, an obscure vector borne arbovirus - Zika - was suddenly implicated in hundreds of severe birth defects in South America (see NEJM: CDC Concludes Zika Causes Microcephaly & Other Birth Defects) - an impact never before attributed to a mosquito borne virus.

But Zika wasn't done confounding conventional wisdom, as we also learned in early 2016 that a Zika infection could be transmitted sexually.  Something that had not been previously considered a serious public health risk (see WHO: Updated Interim Guidance On Prevention Of Sexual Transmission Of Zika Virus).

The list of recent viral `surprises' is both lengthy and growing. 

Some of these events are extreme outliers - like H-2-H Legionella transmission - and probably don't have a great amount of real world implications - while others, like the surprises delivered by the Zika and Ebola viruses, do.

Today via the CDC's EID Journal, we get yet another surprise finding, with a virus showing up in an unexpected part of a human host.

While its real world significance is unknown right now, it involves a fascinating bit of scientific detective work based on the testing of a nasopharyngeal swab of a 16 year-old boy from Peru suffering from unexplained `flu-like' symptoms.

A link and some excerpts follow, but you'll want to click the link to read it in its entirety.

 Volume 24, Number 8—August 2018
Research Letter 

Isolation of Complete Equine Encephalitis Virus Genome from Human Swab Specimen, Peru
  
Diana Juarez, Carolina Guevara, Michael Wiley, Armando Torre, Gustavo Palacios, Eric S. Halsey, Sonia Ampuero, and Mariana Leguia

Abstract

While studying respiratory infections in Peru, we identified Venezuelan equine encephalitis virus (VEEV) in a nasopharyngeal swab, indicating that this alphavirus can be present in human respiratory secretions. Because VEEV may be infectious when aerosolized, our finding is relevant for the management of VEEV-infected patients and for VEEV transmission studies.

Venezuelan equine encephalitis virus (VEEV) is one of many alphaviruses transmitted through the bite of infected mosquitoes (1,2). VEEV primarily infects equine species, causing severe encephalitis and death. VEEV may also infect humans, causing fever and influenza-like symptoms that include headache, chills, myalgia, nausea, and vomiting. In severe cases, human VEEV infection may result in neurologic complications that lead to fatalities. Acute VEEV infection is usually confirmed by PCR, sequencing from blood (3), or both, or in the case of encephalitis, from spinal fluid. Nasopharyngeal swabs are rarely tested for alphaviruses like VEEV because they are considered nontraditional sample types for these kinds of pathogens.

(SNIP)

In 2013, in Iquitos, Peru, we identified a 16-year-old boy who reported a variety of undifferentiated illness symptoms, including fever, chills, general malaise, myalgia, headache, rhinorrhea, sore throat, nausea, vomiting, abdominal pain, retroorbital pain, rash, and photophobia. A field-administered rapid test for influenza on a nasopharyngeal swab specimen was negative. More thorough laboratory tests, including a highly multiplexed MassTag PCR assay that can detect >20 viral and bacterial pathogens (4), were also negative (Figure, panel A). 

The sample entered a pathogen discovery pipeline routinely used to amplify and identify unknown etiologies (5). In brief, we cultured 200 μL of the original nasopharyngeal sample in Vero-E6, LLCMK2, and MDCK cells. Cytopathic effect appeared by day 4 in Vero-E6 and LLCKM2 cells and by day 19 in MDCK cells. We used culture supernatant from day 4 LLCMK2 cells as starting material for NGS MiSeq libraries, which we prepared, sequenced, and processed as described (5). Sequencing generated 704,444 raw reads, from which 28,555 were de novo assembled into a single 11,412-nt contig (Figure, panel B). When blasted, the contig matched the complete genome of a VEEV-ID strain isolated in Peru from 1994 (GenBank accession no. KC344526.1) with 99% identity.

(SNIP)

Febrile surveillance studies have shown that VEEV is prevalent in many countries throughout Latin America (3,6). Although respiratory symptoms have been reported in association with VEEV infection (7), and there is >1 report of VEEV in throat swabs (8), human respiratory secretions are seldom tested for alphaviruses. In fact, the presence of VEEV in respiratory secretions, as well as its implications for health and biosafety, are rarely discussed. 

Although person-to-person transmission of VEEV has not been documented, VEEV can be infectious through aerosolized particles (9,10), so the potential for an alternate transmission route exists. This possibility should be considered both during individual management of VEEV-infected patients and in studies considering VEEV transmission dynamics or prevention strategies.

Ms. Juarez has worked as a researcher at US Naval Medical Research Unit No. 6, in Lima, Peru. She is now with the Genomics Laboratory at Pontificia Universidad Católica del Perú. Her work focuses on the characterization of emerging and novel pathogens.

While this may end up being little more than a fascinating footnote in the VEEV literature, from tiny clues like these, bigger discoveries are often forged.  Hopefully in the next year or two, we'll see some follow up studies.

History has shown that the better scientists get at looking for things, the more strangeness they will find.

Which is why - when it comes to predicting how infectious diseases will behave now - or in the future - it is probably prudent to never say `never'.

Denmark: LPAI H5 Avian Flu Reported In Vordingbord

Credit Wikipedia

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Although the summer months are generally a slow season for HPAI avian flu - at least in the more temperate regions of the globe - it isn't terribly unusual to see reports of `mild', LPAI viruses any time of the year.

In early May, in DVFA orders 20,000 Ducks Culled Due To LPAI H5, we looked at a report out of Denmark of an outbreak in ducks near Holstebro, which was discovered due to routine surveillance.

LPAI (low path avian influenza) viruses are often carried by wild birds and can occasionally find their way into poultry flocks. They (generally) pose little direct threat to poultry or humans.

But LPAI H5 and H7 viruses are a concern because they have a habit of mutating into far more dangerous HPAI (high path) viruses when they are allowed to spread unchecked in poultry (see chart below).

While most of our focus has been on abrupt reassortment events, over the past few years we've seen an increasing number of these spontaneous H5 and H7 LPAI-to-HPAI mutations.

• In Europe (see here, here, and here) 
• Two years ago in the H7N8 outbreaks in Indiana (see Genome Announcements: LPAI-to-HPAI Mutation Cited in January's H7N8 Outbreak) 
• And last year with H7N9 in Tennessee (see EID Journal: Mammalian Pathogenesis & Transmission of Avian H7N9 Viruses - Tennessee 2017).

These HPAI viruses - once generated in a commercial flock - can be carried to other farms via personnel, poultry products, or equipment or be picked up by migratory birds and spread into the environment (possibly sparking new reassortments along the way).

Although spontaneous mutation from LPAI-to-HPAI doesn't happen all that often, the risk is considered great enough that all LPAI H5 and H7 outbreaks must be reported to the OIE, and immediate steps must be taken to contain and eradicate the virus.

Which brings us to another report from Denmark's DVFA (The Danish Veterinary and Food Administration) ordering the depopulation of about 3,500 ducks in Vordingbord after routine surveillance detected LPAI H5.

Bird flu - current situation

On 26 June, low pathogenic avian influenza has been found in a gray duck seal in Vordingborg Municipality

domestic poultry

Outbreaks of low pathogenic avian influenza in gråandebesætning

A gråandebesætning near Faksinge in Vordingborg was June 26 found infected with low pathogenic avian influenza H5. The samples were taken during the control of avian influenza in poultry farms and have been examined at the National Veterinary Institute. The crew of about 3,500 ducks will be culled to prevent the virus from developing into a more serious influenza (highly pathogenic avian influenza).

Food Administration has set up a 1km restricted zone around the infected herd. Within the restricted zone are special rules for particular the movement and transport of poultry.

Where is the restricted zone?

See map of the restricted zone here

Notice the restricted zone

Sci. Reports: Efficacy Of AI Vaccines Against The H5N8 Virus in Egypt

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While we may not be getting all of the data out of China, the remarkable drop in reported outbreaks of H7N9 avian influenza since last fall (see chart below) - which closely follows last summer's nationwide deployment of a newly developed H7+H5 poultry vaccine - has to be viewed as a very encouraging sign. 

Credit FAO

How long this lull will last remains to be seen, as antigenic changes in the circulating viruses - or the emergence of a new subtype - may eventually derail  the vaccine's success.  

But for now, China's MOA appears to have hit a home run. 

The use of AI vaccines is not without controversy, and while China, Egypt, Indonesia, Vietnam and Hong Kong have embraced them, most countries around the world eschew their use.

Aside from complicated international trade issues, the biggest concern is that most AI poultry vaccines are only able to suppress avian flu viruses to reduce morbidity and mortality in poultry, but they don't necessarily eliminate them.    

And as avian viruses evolve, over time existing poultry vaccines become increasingly less effective. Poor vaccine matches can then allow AI viruses to spread silently among flocks, to continue to reassort and evolve, and potentially lead to the emergence new subtypes of avian flu.

A few earlier blogs on those concerns include:

Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China).

Study: Recombinant H5N2 Avian Influenza Virus Strains In Vaccinated Chickens

EID Journal: Subclinical HPAI In Vaccinated Poultry – China

There are, however, some strong advocates for using AI poultry vaccines, who see their proper use as being the only reasonable course of action for countries where these viruses are firmly entrenched.

Earlier this month I received a comment from Les Sims, who outlines his reasons in the following hour-long FAO webinar. 

Admittedly, the apparent success with China's recent vaccination program suggests that modern vaccines, when properly and consistently applied, can have a positive effect. 

But far too often, we've seen badly outdated, illegally obtained, and sometimes even home brewed vaccines used in the field (see Taiwan's Counterfeit AI Vaccine Trade). Vaccination coverage in many  places has been spotty and intermittent, and the results have been less than satisfactory. 

In 2012’s Egypt: A Paltry Poultry Vaccine, we saw a study conducted by the Virology department at St. Jude Children’s Research Hospital that looked at the effectiveness of six commercially available H5 poultry vaccines then deployed in Egypt, and found only one (based on a locally acquired H5N1 seed virus) actually appeared to offer protection.

Five months ago, in PLoS One: Effectiveness of HPAI H5N1 Vaccination in Poultry - Indonesia, we saw another study that painted a less than impressive picture of poultry vaccination effectiveness in Indonesia.

The authors cited frequent low HI titres in poultry even after three rounds of vaccines, vaccination failures, and warned of silent infections and the generation of new H5N1 antigenic variants.  

Fast forward to today, and we have a new study published in Nature's Scientific Reports on the efficacy of Egyptian poultry vaccines in light of the arrival (in late 2016) of the clade 2.3.4.4. HPAI H5N8 virus.   

Many of the authors contributed to the 2012 paper mentioned above, and the results are eerily similar to what was reported nearly 6 years ago.

Efficacy of commercial vaccines against newly emerging avian influenza H5N8 virus in Egypt
Ahmed Kandeil, Jamal S. M. Sabir, Ahmed Abdelaal, Ehab H. Mattar, Ahmed N. El-Taweel, Mumdooh J. Sabir, Ahmed Aly Khalil, Richard Webby,  Ghazi Kayali & Mohamed A. Ali

Scientific Reports volume 8, Article number: 9697 (2018 )

Abstract

The newly emerging, highly pathogenic avian influenza (HPAI) H5N8 virus of clade 2.3.4.4 was recently detected in wild birds and domestic poultry in Egypt in the 2016/2017 winter season. Vaccination based on commercial H5 vaccines is used as an essential control strategy in Egyptian poultry.

Here, we studied the efficacy of the eight most common commercial H5 poultry vaccines in the Egyptian market and compared them with an experimental vaccine based on the Egyptian LPAI H5N8 virus that was prepared by using reverse genetics.

The experimental vaccine and Re-5 commercial vaccine were able to completely protect chickens and significantly reduce virus shedding.

Our results indicate that most of the commercial poultry H5 vaccines used in the present study were ineffective because the seed viruses in these vaccines are genetically distinct from the H5N8 viruses currently circulating in Egypt.

Although some of the commercial vaccines protected chickens from mortality, they failed to prevent chickens from shedding the virus. Accordingly, we recommend updating and reinforcing the H5N8 prevention and control strategies in Egypt. The vaccination strategy should be reconsidered based on currently circulating viruses.

        (SNIP) 

The experimental homologous H5N8 vaccine provided the best protection against a challenge with the clade 2.3.4.4 virus. The sera of chickens vaccinated with the Re-5 Merial, Zoetis, EgyFlu, CEVac Flukem and Volvac (B.E.S.T.) vaccines showed reduced cross-reactivity against the Egyptian H5N8 virus and provided ≥ 80% protection, while the Nobilis, ME Flu VAC, and SERA-VAC vaccines did not reach the protection limit recommended by the OIE. 

The Re-5 Merial (based on a clade 2.3.4 H5N1 virus) vaccine protected the chickens from mortality and reduced virus shedding. Most of the commercial vaccines protected chickens from mortality but did not reduce or prevent virus shedding. This suggests that the circulating H5N8 viruses may evade vaccine protection.

The genetic dissimilarity and poor reactivity between the H5 commercial vaccines used in Egypt and the currently circulating H5N8 viruses proves that the vaccines might not be effective in the field or may introduce only partial protection and thus could lead to vaccine-induced escape mutant strains.

        (Continue . . .)

In many developing countries, poultry and eggs are not only prime sources of badly needed and relatively inexpensive protein, they are often a measure of an individual's wealth. The wholesale culling of poultry, whether commercial or backyard , can have dramatic economic and societal effects (see Iran: Bird Flu, Food Insecurity & Civil Unrest).

No government is more aware of this fact than China, and so when HPAI H7N9 emerged in early 2017, the decision to go on the offensive with an experimental H5+H7 vaccine was viewed as a matter of national security.

While modern AI poultry vaccines hold a lot of promise - and would likely better the lives of millions of people in low resource countries dealing with endemic avian flu - they have to be frequently updated and correctly applied, if they are to be effective.

But all too often we see exactly the opposite in the field. 

Until that changes, and we see more success stories like what we've seen this past year out of China, the global reluctance to embrace AI vaccines will likely remain unchanged.

Rosselkhoznadzor Statement On Outbreaks Of Avian Flu In Western Russia

#13,384


Although we've reports of avian flu outbreaks in 5 different regions of Russia over the past 10 days (see here, here, and here) the following (translated)  statement from Russia Federal Service for Veterinary and Phytosanitary Surveillance (Rosselkhoznadzor) only cites the first 3 affected regions.
 

Outbreaks of bird flu in the country predictable and are due to seasonality

June 25, 2018

© Central body

 

The situation with the spread of the avian influenza virus is predictable and is due to seasonality. To date, outbreaks of disease registered in three regions of the country.

It should be emphasized that registered in the country bird flu virus does not pose a threat to human life. Disease is subject exclusively ptitsepogolove.

Foci localized and carried all the measures to prevent the spread of the virus.

"Just an hour ago we had a meeting with the Chairman of veterinary control and supervision of the Committee of the Ministry of the Republic of Kazakhstan Mr. Utegulovym. We discussed, including the issue of the spread of animal diseases, both in Russia and in the territory of the Republic of Kazakhstan. In particular, it agreed to hold next Friday in technical consultations on mutual withdrawal restrictions. We hope that the measures imposed by Kazakhstan on the supply of products of Russian poultry farms will be adjusted as early as next week "- said the head of the Rosselkhoznadzor Sergey Dankvert.

Sergey Dankvert added that Rosselkhoznadzor received instructions from the Deputy Prime Minister Alexei Gordeyev to conduct unscheduled inspections of public veterinary services subektovyh Penza, Kursk and Saratov regions. During the test, the Federal Service for Veterinary and Phytosanitary Supervision will evaluate the effectiveness of these bodies to take measures on the prevention of the introduction and spread of animal diseases.

While officially trying to minimize the situation - possibly because the 2018 World Cup is being held in Russia this month and next -  the local media continues to report heavily on outbreaks, and concerns over contaminated poultry products making it into the food chain. 

Reminiscent of last year's scramble to remove H5N8 tainted food products from store shelves (see Rosselkhoznador: HPAI Contaminated Poultry Shipped To At Least 9 Regions Of Russia), we have the following (translated) report from Inter-fax.

25.06.18 08:37

Bird flu discovered in Bashkortostan in Penza imported from turkey

June 25. Interfax-Russia.ru - The bird flu virus is detected on the territory of Bashkortostan in Penza production enterprises, said Veterinary Department press service of Bashkiria.

"In the course of activities carried out under the verification information from the Rosselkhoznadzor and the Russian Ministry of Agriculture, outbreaks of highly pathogenic avian influenza type A, subtype H5 bird in the Penza region at the two production sites LLC" PenzaMolInvest "and JSC" Poultry Farm "Vasilyevskaya", revealed the facts receipt of poultry products of these enterprises on the territory of Bashkortostan ", - said in a statement.

The study collected samples of products in the Bashkir research and production of veterinary laboratories detected avian influenza virus type A. In order to confirm the results of the study materials sent to the laboratory in the city of Vladimir.

       (Continue . . . )


The assumption right now is that Russia is dealing with a relatively low-risk (to humans) H5N8 virus, but the OIE has only identified it as HPAI H5.   None of the official reports I've seen specify the exact subtype.

Last summer, in Appl Environ Microbiol: Survival of HPAI H5N1 In Infected Poultry Tissues, we looked at several studies on the long-term viability of HPAI H5N1 - arguably a much more dangerous virus - in frozen and fresh poultry.

Appl Environ Microbiol. 2017 Jun 16. pii: AEM.00604-17. doi: 10.1128/AEM.00604-17. [Epub ahead of print]

Survival of H5N1 Highly Pathogenic Avian Influenza Virus in Tissues Derived from Experimentally Infected Chickens.

Yamamoto Y1, Nakamura K2, Mase M2.

Abstract

         (Excerpt)

The tissues were stored at +4°C or +20°C and viral isolation was performed at different times for 360 days. The maximum period for viral survival was observed in samples stored at +4°C in all tissue types, i.e., 240 days in feather tissues, 160 days in muscle, and 20 days in liver. 

The viral infectivity at +20°C was maintained for a maximum of 30 days in the feather tissues, 20 days in muscle, and 3 days in liver. 

(Continue . . . )

Good reasons why - even if it doesn't pose a direct threat to human health - that all contaminated products need to be disposed of in a way that prevents further spread of the virus to wild birds, scavengers, or poultry.

`Seasonal and predictable' or not, the sudden spread of avian flu across multiple oblasts - and making its way (again) into the food chain -  is a bigger problem than the Rosselkhoznador's statement would suggest

And with the world's eyes firmly fixed on Russia and the World Cup for the next few weeks, it is coming at a very bad time as well.