C.I.D.: Revisting The Parotitis Clusters During The 2014-15 Flu Season

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The 2014-15 flu season was remarkable both not only for its unusually severe, and recently mutated H3N2 virus (see CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus) - but also for a multi-state cluster of non-mumps parotitis,  ostensibly linked to influenza infection. 

The classic cause of parotitis is the mumps virus, but other viruses (EBV & HIV), along with acute bacterial parotitis or Extrapulmonary Tuberculosis can cause inflammation of these glands, as well as some autoimmune diseases.

In early January of 2015, the Chicago Department of Public Health issued an alert to local doctors to test for both influenza, and mumps, when diagnosing parotitis, as several unusual influenza-related cases had surfaced (see Unusual Presentation Of Parotitis With Seasonal Influenza).

The following month, the CDC published an overview of the 2014-15 flu season, with the following comment on these parotitis cases. 

What You Should Know for the 2014-2015 Influenza Season

(excerpt)
 
Is there any unusual disease activity going on this season?

Since December 2014, multiple states have notified CDC of laboratory-confirmed influenza infections in persons who have swelling of their salivary glands (a condition called ‘parotitis’). Of the cases of influenza infection with parotitis that have been reported to CDC, the majority have occurred in children with influenza A (H3) infection, and have resulted in mild illness. No deaths have been reported. CDC is currently investigating the situation in order to understand the characteristics of patients and the occurrence of parotitis.

Aside from a 2016 Eurosurveillance: Parotitis Associated With A Drifted A/H3N2 Infection report which looked at a small number of similar cases in the UK, we've not heard much about this event (or seen a recurrence) over the past 3 years. 

That is - until yesterday - when Clinical Infectious Diseases published two studies - led by the CDC's EID (Epidemic Intelligence Service) - and an editorial comment on their findings.

Fair warning: these studies are both lengthy and fairly technical, and you'll probably need to devote an hour or more to read them in their entirety. 

The studies are:

Non-mumps Viral Parotitis During the 2014–2015 Influenza Season in the United States

Lina I Elbadawi Pamela Talley Melissa A Rolfes Alexander J Millman Erik Reisdorf Natalie A Kramer John R Barnes Lenee Blanton Jaime Christensen Stefanie Cole

Clinical Infectious Diseases, ciy137, https://doi.org/10.1093/cid/ciy137
Published: 30 March 2018

Abstract

Background

During the 2014–2015 US influenza season, 320 cases of non-mumps parotitis (NMP) among residents of 21 states were reported to the Centers for Disease Control and Prevention (CDC). We conducted an epidemiologic and laboratory investigation to determine viral etiologies and clinical features of NMP during this unusually large occurrence.

Methods

NMP was defined as acute parotitis or other salivary gland swelling of >2 days duration in a person with a mumps- negative laboratory result. Using a standardized questionnaire, we collected demographic and clinical information. Buccal samples were tested at the CDC for selected viruses, including mumps, influenza, human parainfluenza viruses (HPIVs) 1–4, adenoviruses, cytomegalovirus, Epstein-Barr virus (EBV), herpes simplex viruses (HSVs) 1 and 2, and human herpes viruses (HHVs) 6A and 6B.

Results

Among the 320 patients, 65% were male, median age was 14.5 years (range, 0–90), and 67% reported unilateral parotitis. Commonly reported symptoms included sore throat (55%) and fever (48%). Viruses were detected in 210 (71%) of 294 NMP patients with adequate samples for testing, ≥2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2. Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses.

Conclusions

Our findings suggest that, in addition to mumps, clinicians should consider respiratory viral (influenza) and herpes viral etiologies for parotitis, particularly among patients without epidemiologic links to mumps cases or outbreaks.

(Continue . . . .) 

Influenza-Associated Parotitis During the 2014–2015 Influenza Season in the United States

Melissa A Rolfes Alexander J Millman Pamela Talley Lina I Elbadawi Natalie A Kramer John R Barnes Lenee Blanton Jeffrey P Davis Stefanie Cole John J Dreisig ...

Clinical Infectious Diseases, ciy136, https://doi.org/10.1093/cid/ciy136
Published: 30 March 2018
Abstract

Background

During the 2014–2015 influenza season in the United States, 256 cases of influenza-associated parotitis were reported from 27 states. We conducted a case-control study and laboratory investigation to further describe this rare clinical manifestation of influenza.

Methods

During February 2015–April 2015, we interviewed 50 cases (with parotitis) and 124 ill controls (without parotitis) with laboratory-confirmed influenza; participants resided in 11 states and were matched by age, state, hospital admission status, and specimen collection date. Influenza viruses were characterized using real-time polymerase chain reaction and next-generation sequencing. We compared cases and controls using conditional logistic regression. Specimens from additional reported cases were also analyzed.
Results

Cases, 73% of whom were aged < 20 years, experienced painful (86%), unilateral (68%) parotitis a median of 4 (range, 0–16) days after onset of systemic or respiratory symptoms. Cases were more likely than controls to be male (76% vs 51%; P = .005). We detected influenza A(H3N2) viruses, genetic group 3C.2a, in 100% (32/32) of case and 92% (105/108) of control specimens sequenced (P = .22). Influenza B and A(H3N2) 3C.3 and 3C.3b genetic group virus infections were detected in specimens from additional cases.

Conclusions

Influenza-associated parotitis, as reported here and in prior sporadic case reports, seems to occur primarily with influenza A(H3N2) virus infection. Because of the different clinical and infection control considerations for mumps and influenza virus infections, we recommend clinicians consider influenza in the differential diagnoses among patients with acute parotitis during the influenza season.

(Continue . . . )

While influenza H3N2 was the most commonly identified virus among 210 patients with adequate samples for testing, it was far from alone.  According to the first study:

. . . ≥ 2 viruses were detected in 37 samples, and 248 total virus detections were made among all samples. These included 156 influenza A(H3N2), 42 HHV6B, 32 EBV, 8 HPIV2, 2 HPIV3, 3 adenovirus, 4 HSV-1, and 1 HSV-2.

Influenza A(H3N2), HHV6B, and EBV were the most frequently codetected viruses.

The accompanying editorial Is Parotitis One More Complication of Influenza? The Ongoing Challenge of Determining Causal Associations  by Andrew T Pavia briefly summarizes both studies, examines the sometimes inconsistent findings, and reminds us of how high the bar is purposefully set (i.e. The Bradford Hill criteria) to establish causation.

Pavia concludes by writing:

In the absence of experimental data or the demonstration that influenza virus replicates in salivary glands, it will be hard to prove to a high degree of scientific certainty that influenza causes parotitis. There are potential weaknesses in both of the current studies [5, 6], including case finding strategies leading to an increased prevalence of influenza cases in the sample, selection bias, the use of buccal swab specimens alone, and the limited ability to completely exclude mumps or bacterial infection.

However, the contributions of Elbadawi, Rolfes, and colleagues strongly suggest that parotitis can be added to the long list of syndromes caused by influenza.

While not definitive, this is another reminder that influenza can surprise us and  present in unusual ways, and it is more than just a respiratory virus.

Illinois: IDPH Update On Cluster Of Hemorrhage Linked To Spice/K2 Use

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Following up on yesterday's report, where the Illinois Department of Public Health announced 22 recent cases of severe internal bleeding linked to synthetic cannabinoid use, we have today's update which adds 10 more cases to the list.

For background on Spice/K2 you'll want to revisit yesterday's blog.

First today's update, then I'll return with a bit more.

Synthetic Cannabinoids

As of March 30, 2018, IDPH has received reports of 32 cases linked to an outbreak, since March 7, 2018; cases report using synthetic cannabinoid products before suffering from severe bleeding. 

***Numbers are provisional and subject to change; IDPH will update the website every day at 1:30pm, for the duration of the outbreak***
 

While many of the cases report acquiring the synthetic cannabinoid products in the Chicagoland area, contaminated products could be in counties across the state.  Individuals reported obtaining synthetic cannabinoid products (i.e., K2, spice, synthetic marijuana, and legal weed) from convenience stores, dealers, and friends.   

If you have purchased any of this product in the past month, do not use it.  If you have used any of these products, and start experiencing severe, unexplained bleeding or bruising, please have someone take you to the hospital immediately or call 911. Do not walk or drive yourself. Tell your health care providers about the possible link between your symptoms and synthetic cannabinoid use.

Since this side effect doesn't appear to have been reported before, something about the chemical witches' brew which is used to make this drug has apparently been changed. 

But whatever they are using hasn't been identified yet. 

A reader yesterday left a link to a 2014 study called Spice/K2 drugs – more than innocent substitutes for marijuana, which raises one possibility. According to the authors:

In addition, Spice products are supposed to contain up to 15 different vegetal compounds, which gives rise to a wide variety of drug combinations (Dresen et al., 2010; Zuba et al., 2011). Moreover, they have been found to contain large amounts of vitamin E, added to hamper the analysis of the active cannabinoids (Dresen et al., 2010; Zuba et al., 2011).

Vitamin E, at least in very large doses, can have a significant anti-coagulating effect - but it is usually only a concern for those who have a bleeding disorder or are taking other Rx blood thinners.

It would take a very large dose of Vitamin E on its own to provoke the kind of bleeding being reported in these patients.  The wild card is that Vitamin E is rarely absorbed through the lungs.

So while plausible, we'll simply have to wait to see if Vitamin E is the culprit, or if something else is going on here. 

FluView Week 12: Influenza Continues To Decrease Across The Nation

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Despite some overly hyperbolic headlines this week warning of a `second wave' of Influenza B (which has now become the dominant strain reported across the U.S.), the overall level of influenza-like-illness activity across the country has dropped almost to the seasonal baseline level.

Among the flu that remains circulating, roughly 60% are influenza B. While the threat of catching the flu lessens with each passing week, it still makes sense to maintain good flu hygiene (stay home if you are sick, cover coughs, wash / sanitize hands, etc.).


Some highlights from today's FluView Summary include:

2017-2018 Influenza Season Week 12 ending March 24, 2018

All data are preliminary and may change as more reports are received.

Synopsis:

During week 12 (March 18-24, 2018), influenza activity decreased in the United States.

• Viral Surveillance: Overall, influenza A(H3) viruses have predominated this season. However, in recent weeks the proportion of influenza A viruses has declined, and during week 12, influenza B viruses were more frequently reported than influenza A viruses. The percentage of respiratory specimens testing positive for influenza in clinical laboratories decreased.
• Pneumonia and Influenza Mortality: The proportion of deaths attributed to pneumonia and influenza (P&I) was above the system-specific epidemic threshold in the National Center for Health Statistics (NCHS) Mortality Surveillance System.
• Influenza-associated Pediatric Deaths: Four influenza-associated pediatric deaths were reported.
• Influenza-associated Hospitalizations: A cumulative rate of 96.1 laboratory-confirmed influenza-associated hospitalizations per 100,000 population was reported.
• Outpatient Illness Surveillance: The proportion of outpatient visits for influenza-like illness (ILI) was 2.5%, which is above the national baseline of 2.2%. Nine of 10 regions reported ILI at or above region-specific baseline levels. Four states experienced high ILI activity; eight states experienced moderate ILI activity; New York City, Puerto Rico, the District of Columbia, and 14 states experienced low ILI activity; and 24 states experienced minimal ILI activity.
• Geographic Spread of Influenza: The geographic spread of influenza in Puerto Rico and 16 states was reported as widespread; 22 states reported regional activity; the District of Columbia, Guam and eight states reported local activity; four states reported sporadic activity; and the U.S. Virgin Islands reported no influenza activity.

             (Continue . . . )

Russia's Late Season Flu Surge Continues - More Resistant H1N1pdm In Moscow

Cumulative Flu Subtypes This Season

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Russia saw an unusually late start to their influenza season this winter, passing their epidemic threshold for the first time in mid-February (week 6), only to fall below that threshold four weeks later (week 10). 

That drop (possibly due to a lack of reporting) was short-lived, as the rate of flu jumped markedly the following week and continues to rise with this week's report.

All of this is a bit out of character, as we saw reported last January in Eurosurveillance: Changes In Timing Of Influenza Epidemics - WHO European Region 1996-2016, over the past 2 decades Russia's flu seasons have tended to peak earlier with each passing year.

Due to its 6,000 mile wide expanse and varied climate, Russia often sees a very complex flu season, with many areas experiencing different mixes of flu subtypes, and much different epidemic onset dates (see map above).

While still highly variable by region, over the past couple of months we've seen the dominant flu strain in Russia shift from A(H3N2) to A(H1N1)pdm, with Influenza B making a late season surge. 

Also of note, this week Russia National Influenza Centre (RII NIC) is reporting on two more Moscow isolates found to be resistant to NAI (Neuraminidase Inhibiting) antiviral drugs. 

Five weeks ago, in Russia : A Late Season Flu Surge & 3 NAI Resistant H1N1 Viruses, we saw the initial report on resistant viruses carrying the H275Y mutation in Moscow.

This week's report only references a total of 19 isolates (8 H1N1pdm, 4 H3N2, and 7 Influenza B) having been tested for resistance this winter, with 5 of 8 H1N1 isolates (62%) - all from Moscow - showing significant resistance to NAI antivirals.

By contrast, the CDC has tested more than 700 H1N1pdm viruses this winter, and has found only 9 (1.3%) showing signs of  NAI resistance - a percentage that has been fairly steady since the virus emerged in 2009.

On the face of it, today's report makes it look as if 100% of the H1N1pdm  viruses tested from Moscow this winter have shown resistance - and that would be concerning - but what we don't know is their criteria for testing viruses for resistance (or if they really only tested 5 isolates from Moscow).

If they are doing targeted testing - say of patients receiving antivirals who are not responding to treatment - then a high rate of resistance would be expected.

If these are random tests, then 5 out of 5 H1N1pdm viruses turning up NAI resistant (assuming that is the correct ratio) from Moscow is a pretty big deal. Pending the receipt of more solid information,  or similar reports from outside of Russia, I'm filing this under `curious' and something to definitely keep an eye on.

Although a late arriving Russian flu season is far from unheard of, given the atypical flu epidemics we've been seeing the past 12 months around the globe (summer H3N2 outbreaks in Hong Kong & China, followed by Influenza B this winter, and back-to-back H3N2 seasons in the Northern Hemisphere), the current flu situation in Russia is worth following.

Some excerpts from this week's Russian Influenza Epidemiological Report (Week 12) follow:

Conclusion

Influenza and ARI morbidity data.  Increase of influenza and other ARI activity was registered during week 12.2018 in Russia. The ILI & ARI incidence rate (96.3 per 10 000 of population) was above by 32.7% the nationalwide baseline.

Etiology of ILI & ARI morbidity. The overall percent of respiratory samples positive for influenza was estimated as 29.1%. Proportion of influenza A(H1N1)pdm09, A(H3N2), type A and type B viruses was estimated as 38.6%, 22.9%, 5.5% and 33.0%, respectively.

Antigenic characterization. 255 influenza viruses were characterized antigenically in Moscow and Saint-Petersburg NICs, including 69 influenza A(H1N1)pdm09 viruses, 54 influenza A(H3N2) strains and 132 influenza type B strains. 

All influenza A(H1N1)pdm09 strains were related to influenza A/Michigan/45/2015, influenza A(H3N2) strains to A/Hong Kong/4801/2014 viruses. 126 influenza type B strains belonged to Yamagata lineage and were like B/Phuket/3073/2013 reference virus, 6 influenza type B strains belonged to Victoria lineage and were antigenically related to B/Brisbain/60/2008 strain.

Genetic characterization. Full-genome NGS of 58 influenza positive samples and viruses from 6 cities was conducted. 16 influenza A(H1N1)pdm09  viruses belonged to phylogenetic group 6B.1 with amino acid substitutions in HA S84N, S162N and I216T. 

According to phylogenetic analisis of HA 18 of 22 tested influenza A(H3N2) viruses belonged to clade 3C.2a carring aa substitutions L3I, N144S, F159Y, K160T, N225D and Q311H in HA1. Four influenza A(H3N2) viruses belonged to genetic subgroup 3C.2a1 and carried aa substitutions K92R, N121K, T135K and H311Q.

2 influenza B viruses of Victoria-lineage belonged to genetic subgroup 1A (B/Brisbane/60/2008-like). All 18 influenza B viruses of Yamagata-lineage belonged to clade 3 (B/Phuket/3073/2013-like) and had substitution L172Q and M251V in HA1.

Susceptibility to antivirals. Most viruses were susceptible to NA inhibitors excluding 5 influenza A(H1N1)pdm09 strains isolated in Moscow which had H275Y amino acid substitution in NA responsible for highly reduced susceptibility to oseltamivir and zanamivir.

14 influenza strains tested in MUNANA-assay for antiviral resistance to NA inhibitors in RII NIC, including 3 A(H1N1)pdm09 strains isolated in St.Petersburg, 4 A(H3N2), two B Victoria strains and 5 B Yamagata viruses were susceptible to oseltamivir and zanamivir. All influenza A strains tested were resistant to rimantadine.

Percent of positive ARI cases of non-influenza etiology (PIV, adeno- and RSV) was estimated as 21.4% of investigated patients by IFA and 6.0% by PCR. Last weeks RSV dominated among ARI agents.

In sentinel surveillance system clinical samples from 127 SARI and ILI/ARI patients were investigated by rRT-PCR. 27 (47.4%) influenza cases were detected among SARI patients, including 6 influenza A(H1N1)pdm09 cases, 11 influenza A(H3N2) cases and 10 influenza B cases. Among ILI/ARI patients 27 (38.6%) influenza cases were detected, including 9 influenza A(H1N1)pdm09, 13 influenza A(H3N2) and 5 influenza B cases.
 

Illinois Dept Public Health: Cluster of Severe Bleeding Linked to Recreational Spice Use

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Playing on people’s perception that marijuana is relatively harmless (and indeed, legal in some states) - synthetic cannabinoids - have gained increasing popularity as a street drug - particularly by teenagers.

Cheap, and often sold as "herbal incense" or sometimes as "herbal smoking blends" - with names like `Spice’, `K2’, or `Aroma’ – these synthetics have a growing reputation among ER doctors, and mental health professionals as extremely dangerous drugs.

• In 2013 we looked at an MMWR report of these Synthetic Cannabinoids Associated With Severe Illness, Stroke & Psychosis, and a study from USF linking their use to ischemic stroke.
• A year later we saw the Governor of New Hampshire declare a 21-day state of Emergency after 40 `serious overdoses' were reported in his state over just 72 hours (see NH Governor Declares State Of Emergency Over `Spice’ Overdoses).
• And again in the summer of 2015, in MMWR: Adverse Health Effects Related to Synthetic Cannabinoid Use, we looked at a Notes from the Field that looked at a recent surge in monthly calls to poison centers related to cannabinoid ingestion.

As if all that weren't enough of a deterrent, over the past few days reports have been coming out of Illinois of a growing cluster of severe internal bleeding associated with spice use.

Indiana State Department of Health warns of ‘spice’ dangers after cases of bleeding reported

State health officials warn about heavy bleeding after use of spice, other synthetic cannabinoids

Today the IDPH posted the following update on their website:

Synthetic Cannabinoids

As of March 29, 2017, IDPH has received reports of 22 cases linked to an outbreak, since March 7, 2018; cases report using synthetic cannabinoid products before suffering from severe bleeding. 

***Numbers are provisional and subject to change; IDPH will update the website every day at 1:30pm, for the duration of the outbreak***

While many of the cases report acquiring the synthetic cannabinoid products in the Chicagoland area, contaminated products could be in counties across the state.  Individuals reported obtaining synthetic cannabinoid products (i.e., K2, spice, synthetic marijuana, and legal weed) from convenience stores, dealers, and friends.   

If you have purchased any of this product in the past month, do not use it.  If you have used any of these products, and start experiencing severe, unexplained bleeding or bruising, please have someone take you to the hospital immediately or call 911. Do not walk or drive yourself. Tell your health care providers about the possible link between your symptoms and synthetic cannabinoid use.
_______________________________________________

Synthetic cannabinoids are human-made, mind-altering chemicals that are either sprayed on dried, shredded plant material so they can be smoked or sold as liquids to be vaporized and inhaled in e-cigarettes and other devices. They are sold for recreational drug use with claims they will provide the user the effects of cannabis. These products are also known as herbal or liquid incense and have brand names such as K2, Spice, Black Mamba, Bombay Blue, Genie, and Zohai, but may be packaged under other brand names also.

These chemicals are called cannabinoids because they are similar to chemicals found in the marijuana plant. Because of this similarity, synthetic cannabinoids are sometimes misleadingly called "synthetic marijuana" (or "fake weed"), and they are often marketed as safe, legal alternatives to that drug. In fact, they are not safe and may affect the brain much more powerfully than marijuana; their actual effects can be unpredictable and, in some cases, more dangerous or even life-threatening.

Synthetic cannabinoids are part of a group of drugs called new psychoactive substances (NPS). NPS are unregulated mind-altering substances that have become newly available on the market and are intended to produce the same effects as illegal drugs. Some of these substances may have been around for years but have reentered the market in altered chemical forms, or due to renewed popularity.

 

In 2016 the CDC held a COCA Call on Synthetic Cannabinoids: Information and Guidance for Clinicians, which is archived and may be viewed at the link below:

Title:  Synthetic Cannabinoids: Information and Guidance for Clinicians

Date: Thursday, March 31, 2016

Speaker(s):Amelia M. Kasper, MD, MHS
Epidemic Intelligence Service Office
Division of Environmental Hazards and Health Effects
National Center for Environmental Health
Centers for Disease Control and Prevention

Speaker(s):Robert Galli, MD
Professor
Department of Emergency Medicine
University of Mississippi School of Medicine
Executive Director
TelEmergency

Speaker(s):Justin K. Arnold, DO, MPH
Assistant Professor
Department of Emergency Medicine
University of Alabama at Birmingham

 

CDC Statement & Risk Assessment On Reassorted H1N2 Virus Reported By The Netherlands

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Last Friday, in Netherlands Reports A Reassorted H1N2 Flu Virus, we looked at a NIVEL (Dutch Institute For Health Services Research) report on the discovery of a reassorted seasonal H1N2 virus and looked back at other H1N2 detections in the past.

Seasonal H1N2 was reported briefly by China in 1988-1989 (see Human influenza A (H1N2) viruses isolated from China), and was reported again in the Northern Hemisphere between 2000 and 2003 (see A Historical Perspective of Influenza A(H1N2) Virus). 

Later that day the World Health Organization released their own assessment  on this newly reassorted H1N2 Virus. Today it is the CDC's turn, as they've posted the following statement on their Flu News & Spotlights page.

Influenza A (H1N2) Reassortant Infection in the Netherlands

Background:

On Thursday, March 22, 2018, the Netherlands reported a human infection with an influenza A(H1N2) virus. The virus likely resulted from a reassortment event between circulating human seasonal influenza A(H1N1)pdm09 and influenza A(H3N2) viruses. The infected person experienced mild illness and has since recovered. No further spread of this virus has been detected. Surveillance in the area has been enhanced. The World Health Organization (WHO) first reported the case in its International Health Regulations (IHR) report.

Influenza Virus Reassortment:

Reassortment happens when two or more influenza viruses infect a single host and swap genetic material. While this can sometimes result in the emergence of new influenza viruses, genetic sequencing shows that the A(H1N2) virus in the Netherlands is a reassortant of human seasonal flu viruses  containing the same hemagglutinin “H1” gene as circulating seasonal A(H1N1)pdm09 viruses and the same neuraminidase “N2” gene as circulating seasonal A(H3N2) viruses.

Human infections with reassortant A(H1N2) viruses have occurred rarely in the past, but these were reassortants with the A(H1N1) virus that circulating prior to emergence of the 2009 A(H1N1)pdm09 virus that triggered a pandemic. This is the first reassortant of seasonal 2009 A(H1N1)pdm09 and seasonal A(H3N2) viruses. Previous laboratory experiments with past A(H1N1) reassortants has suggested that these have limited capacity for transmission.

Risk Assessment:

This A(H1N2) reassortant virus is thought to pose a health risk similar to other seasonal influenza viruses. The virus has not been detected beyond this one person and current seasonal flu vaccines would likely offer protection against this virus. Additionally, this virus does not have markers associated with resistance to the neuraminidase inhibitor class of antiviral drugs, and thus should be susceptible to treatment with currently licensed and available flu antiviral medications, such as oseltamivir, zanamivir and peramivir.

Disaster Planning For Major Events

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Whether we like to think about it or not, we live in increasingly perilous times.  And while there have always been threats from natural disasters, pandemics, and wars, our growing dependence on technology has added another layer of risk - one that if seriously compromised, could easily overshadow the rest. 

Once only available to a handful of nations, technology is also making it increasingly easier - and cheaper - for non-state bad actors to modify or create biological, chemical, cyber, and even radiological weapons. 

Add in changing, and often destructive, weather patterns,  a growing population of over 7 billion people, and an increasingly brittle environment .  .  . and you have a recipe for any number of disasters.

Most are local; floods, hurricanes, wild fires, earthquakes, volcanic eruptions or tsunamis . . .  and they have the distinct advantage that help can come from the outside.

A very few will impact an entire nation or large region, such as the economic collapse in Venezuela, the West African Ebola epidemic of 2014, or the war in Yemen.  

Here, for a variety of political and logistic reasons, outside help may sometimes be either slow in coming or practically non-existent.

But at the very top of the list are the hemispheric or even global disasters, and here many nations will have to fend for themselves.

This list includes severe pandemics, a major war (with or without nuclear weapons), and the dreaded long-term `grid down' scenario which can be caused by cyber attack, an earth directed CME (solar flare), or an EMP weapon. 

While least common, these are the ones that induce nightmares in emergency planners.  Partially because of their enormous impact and scope, and partially because they appear to be more likely to occur today than they were a decade or two ago.

And while these may seem far-fetched or fanciful scenarios, these are threats that FEMA, the CDC, the U.S. military, and governments around the world take seriously and actively prepare for.

Few people realize we barely escaped a grid down disaster six years ago (see NASA: The Solar Super Storm Of 2012). Last September, another major X-flare erupted just after it had passed around the limb of the sun, missing earth by only a few days (see USGS: Preparing The Nation For Severe Space Weather).

In 2014 a study was published suggesting the odds of earth being struck by one of these solar super storms is actually a lot higher than we’ve previously thought.  From a NASA article:

In February 2014, physicist Pete Riley of Predictive Science Inc. published a paper in Space Weather entitled "On the probability of occurrence of extreme space weather events."  In it, he analyzed records of solar storms going back 50+ years.  By extrapolating the frequency of ordinary storms to the extreme, he calculated the odds that a Carrington-class storm would hit Earth in the next ten years.

The answer: 12%.

The grid can also be taken down by other, more nefarious means, a topic explored by well known journalist Ted Koppel in his 2015 book called Lights Out: A Cyberattack, A Nation Unprepared, Surviving the Aftermath.  

There are hours of interviews with Ted Koppel about his book on YouTube, including with PBS, Charlie Rose, and the following hour long discussion with the National Press Foundation. 

This is a topic we've looked at before (see The Lloyd’s Business Blackout Scenario) - and despite congressional committees and national GridEx preparedness drills - a new Congressional Research Service report
warns that the US power grid remains vulnerable to attack. 

Last August, in DHS: NIAC Cyber Threat Report - August 2017, we looked at a 45 page report addressing urgent cyber threats to our critical infrastructure that called for `bold, decisive actions'.

Equally worrisome, every four years the ASCE (American Society of Civil Engineers) releases a report card on America’s infrastructure, and their most recent report (2017) warns that our cumulative GPA for infrastructure sits at only a D+, and two of our most vulnerable infrastructures are drinking water and the electrical grid (see When Our Modern Infrastructure Fails).

Without electrical power, water, gasoline, and sewage lift stations don't pump, elevators, air conditioners, lights and computers don’t run, ATM machines and banks close, grocery stores can’t take debit or credit cards, food spoils, and everything from cooking, to flushing toilets, becomes a major challenge.  

Like seeing a another pandemic, a major interruption in the power grid for some major urban area is probably more of a matter of when, not if.

The U.S. isn't alone in these concerns.  Every couple of years the UK reassesses their threat landscape, and releases an updated CIVIL RISKS REGISTER.  

We looked at their previous plan a little over 2 years ago in UK: 2015 Civil Risks Register, where they placed a severe Pandemic and a catastrophic terrorist attack at the very top of their worry list. 

Last fall they published an new update, putting a pandemic, followed by major `grid down' event at the top of their list of greatest concerns (see below). 

Yesterday the UK released an updated National Security Capability Review (NSCR) which (among other things) emphasized the greatest  threats facing the UK over the next 5 years. 

Diseases and natural hazards affecting the UK.

One or more major hazards can be expected to materialise in the UK in every five year period. The most serious are pandemic influenza, national blackout and severe flooding. We published the latest edition of the National Risk Register of Civil Emergencies in September 2017. It provides an assessment of the likelihood and potential impact of a range of different civil emergency risks that may directly affect the UK over the next five years.

While there are admittedly limits to what individuals can do to prepare for these sorts of major disaster scenarios, the reality is some preparedness is a heck of a lot better than none.

Particularly since it could take days or even weeks (think: Puerto Rico) before substantial help arrives.

Living in Florida, I prepare with hurricanes in mind, although I strive for `all threats' preparedness wherever I can.  If you live in earthquake, flood, wildfire, or tornado country, those should be covered specifically in your plan

But some scenarios, like power outages - can occur with almost any disaster. And you and your loved ones will need food, water, first aid kit, a plan, and other essential supplies.

As many residents of Florida learned the hard way last September - you need to be prepared before a threat appears imminent - as there wasn't a flashlight, candle, or battery left on the shelves a full four days before the arrival of hurricane Irma.

So, if the power were to unexpectedly go out in your city, state, or country for the next couple of weeks, do you already have:

• A battery operated NWS Emergency Radio to find out what was going on, and to get vital instructions from emergency officials
• A decent first-aid kit, so that you can treat injuries
• Enough non-perishable food and water on hand to feed and hydrate your family (including pets) for the duration
• A way to provide light when the grid is down.
• A way to cook safely without electricity
• A way to purify or filter water
• A way to stay cool (fans) or warm when the power is out.
• A small supply of cash to use in case credit/debit machines are not working 
• An emergency plan, including meeting places, emergency out-of-state contact numbers, a disaster buddy,  and in case you must evacuate, a bug-out bag
• Spare supply of essential prescription medicines that you or your family may need
• A way to entertain yourself, or your kids, during a prolonged blackout

If your answer is `no’, you have some work to do.  A good place to get started is by visiting Ready.gov.

Preparedness may seem like a lot of work, it really isn’t.

While it might be nice to have an underground bunker or a mountain retreat with 2 years worth of dehydrated food, a well, and a garden -  what you really need to focus on are the basics to carry on without outside help for a couple of weeks, and a workable family, business, or neighborhood emergency/ disaster plan.

For more information on how to prepare, I would invite you  to visit:

FEMA http://www.fema.gov/index.shtm
READY.GOV http://www.ready.gov/
AMERICAN RED CROSS http://www.redcross.org/

And for some of my other preparedness blogs, you may wish to revisit:

Preparedness: Some Holiday Gift Items Worth Considering

When 72 Hours Isn’t Enough

The Challenge Of Promoting Pandemic Preparedness

World Bank: World Ill-Prepared For A Pandemic

FAO: Slovakia Reports HPAI H5N6 In Gulls

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Although it has yet to appear in the OIE listings, overnight the Slovakian SVPS (State Veterinary and Food Administration) has posted an announcement, and the FAO has filed a brief report, on HPAI H5N6 discovered in dead wild birds recovered from the water reservoir in the Kráľová district.

First a screen shot of the FAO report, followed by the SVPS announcement. After which, I'll return with a bit more.

Current information on the occurrence of avian influenza subtype H5 in Slovakia

On 28.03.2018 was the result of laboratory reference laboratory VU Elected confirmation of avian influenza subtype H5 in wild birds. Outbreaks confirmed the water reservoir Kráľová district. Galanta the headed Gull ( Chroicocephalus ridibundus ). It is a high - pathogenic type H5N6 confirmed in one of the 5 found dead seagulls.

Based on genetic analyzes of relatedness in terms of virus isolates originating from Japan and Taiwan, which circulated in the years 2016/2017. In 2017 spread to Europe circulation was recorded in Greece, followed by UK, NL, DE, SE, DK.

Regional Veterinary and Food Administration in Galante, in this context ordered the respective hunting associations steps of setting a monitoring area with a radius of 3 km from the place of finding and also increased surveillance of wild bird populations, in particular water fowl, and further monitoring for dead or sick birds, cooperation with ornithological organizations and reporting obligation to DVFA Galanta. He was further ordered a ban on hunting of wild birds as well as a ban on otherwise taking them from the wild unless it is authorized by the competent authority for specific purposes and that discharges of game birds from captivity into the wild.

In the place of judgment / confirmation of there are no poultry holdings (a place on the waterfront tank Králové). Within a radius of 3 km it falls part of one community (Kajal), where in addition to a listing of all breeds of poultry, pigeons and other birds kept in captivity prescribes measures to prevent the introduction of disease in herds, including preventing direct and indirect contact farmed birds with wild birds and informing the public about the measures ordered.

In connection with the above, it is necessary to be very careful with regard to the risk of spreading infection in the Slovak Republic. Defense against the outbreak in farms is prevention. As a precautionary measure (many are still part of the current extraordinary emergency measures) pointed out:

        (Continue . . . )


While it may be a limitation of the machine translation, the above report appears to link this HPAI H5N6 discovery to both the HPAI H5N6 virus that circulated in Japan and Taiwan in 2016/2017 and to the HPAI H5N6 that emerged in Greece, followed by UK, NL, DE, SE, DK in 2017.

Those are, in fact, two different lineages of H5N6.

The 2016 H5N6 virus in Japan and Taiwan was related to the China's H5N6 virus - which has infected more than a dozen humans - while the 2017 European H5N6 is a reassortant of the 2016/2017 H5N8 virus which to date, is not known to have infected humans.

Based on reporting from other European countries this winter, this report is almost certainly related to the European reassorted lineage.

While it hasn't sparked the kind of large scale avian epizootic we saw last year with H5N8 - both HPAI H5N8 and HPAI H5N6 have shown remarkable persistence, and an expanded host range - in wild birds.

And that is a fairly recent change.

In 2015 we looked at a study (see PNAS: The Enigma Of Disappearing HPAI H5 In North American Migratory Waterfowl) which concluded that while migratory waterfowl can briefly carry HPAI H5, they were not a good long-term reservoir for highly pathogenic avian flu viruses.

HPAI viruses appeared to burn out fairly quickly in aquatic waterfowl populations - likely due to their immunity to LPAI viruses - and would therefore have to be reintroduced periodically.

That changed in the fall of 2016 when H5N8 returned to Europe and brought with it a number of genetic and behavioral changes attributed to a reassortment event that likely took place sometime in the spring of 2016 (see EID Journal: Reassorted HPAI H5N8 Clade 2.3.4.4. - Germany 2016).

A newer study, published in 2016 (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1), suggests that waterfowl pick up new HPAI viruses in the spring (likely from poultry or terrestrial birds) on their way to their summer breeding, spots and then redistribute them on their southbound journey the following fall. 

With migratory birds headed now north to their summer roosting areas, the concern is that these newly persistent HPAI H5 viruses could hitch a ride and spend their summer vacation in the high latitudes - perhaps reassorting with other viruses - and producing new avian subtypes which could return next fall. 

EID J. & Virology Reports On Emerging Coxsackievirus A6

Vesicular eruptions in A) hand, B) foot, and C) mouth
 of a 6.5-year-old boy from Turku, Finland, with 
coxsackievirus (CV) A6 infection.  Credit - CDC EID Journal

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Non-polio Enteroviruses (NPEV's) - of which there are dozens - typically spread in the summer and early fall, and generally produce mild or even asymptomatic infections, mostly in children under the age of 10.

Symptomatic cases can range from a mild fever or a runny nose - to HFMD (Hand Foot Mouth Disease) - a generally mild childhood disease characterized by blisters on the hand, feet, and mouth.

For several decades - particularly in Asian and Western Pacific nations - we've monitored yearly NPEV epidemics of a much more serious nature, with the most severe illness linked to Human Enterovirus 71 (EV-71), which can cause a polio-like paralysis, and sometimes even death.

• In 2009 China reported 1,155,525 HFMD cases, including 13,810 severe cases and 353 deaths. Among laboratory confirmed cases, EV71 was responsible for 41% of cases, 82% of severe cases, and 93% of the deaths (cite WHO HFMD Guide Pg.6).
• In 2012, we saw an outbreak of EV-71 in Cambodia that claimed the lives of dozens of children (see Updating The Cambodian EV71 Story).
• In 2013 in Australia: Acute Flaccid Paralysis & EV71, we looked at a report that described 5 cases of acute flaccid paralysis (AFP) in children who tested positive for the EV71 virus.

In 2014 a nationwide outbreak of EV-D68 was linked to a concurrent spike in AFP (Acute Flaccid Paralysis) cases across the United States, and since then we've seen a number of EV-D68 outbreaks around the world (see here, here & here).

While a causal link between EV-D68 and AFM hasn't been fully established, last January's Eurosurveillance Review: Association Between Acute Flaccid Myelitis (AFM) & Enterovirus D68 (EV-D68), presented a pretty good argument for causation. 

Less well known, but rapidly coming up in the ranks, is Coxsackievirus A6, which was only first described about a decade ago.

In 2008, the CDC’s EID Journal carried a dispatch regarding an outbreak of HFMD in Finland due to an unusual, and apparently emerging, viral cause; the Coxsackie A6 virus. 

Dispatch

Coxsackievirus A6 and Hand, Foot, and Mouth Disease, Finland

Riikka Österback, Tytti Vuorinen, Mervi Linna, Petri Susi, Timo Hyypiä, and Matti Waris

Abstract

During fall 2008, an outbreak of hand, foot, and mouth disease (HFMD) with onychomadesis (nail shedding) as a common feature occurred in Finland. We identified an unusual enterovirus type, coxsackievirus A6 (CVA6), as the causative agent. CVA6 infections may be emerging as a new and major cause of epidemic HFMD.

Since then, we’ve seen a growing number of reports of HFMD outbreaks around the world attributed to this emerging coxsackievirus, including outbreaks in Europe, Asia and North America (see Nevada: HFMD Coxsackievirus A6 Outbreak).

In 2012, in EID Journal: HFMD Cluster Due To CVA6 we looked at a report on cluster of 8 patients who were treated CVA6 HFMD at Boston Children’s Hospital.

The authors cautioned:

Given the numerous CVA6 outbreaks in multiple countries in 2008 and a US population that may be relatively naïve to this serotype, CVA6 is likely to spread throughout North America.

Which brings us to two recent reports on CVA6.

First from Virology, a report that CVA6 has overtaken both EV71 and CV-A16 as the primary cause of HFMD in China, and that it continues to evolve.

An emerging and expanding clade accounts for the persistent outbreak of Coxsackievirus A6-associated hand, foot, and mouth disease in China since 2013

Shuizhen Hea, 1, ,Mengyuan Chenb, c, d, 1, ,Wenhui Wub, c, d, ,Qiang Yanc, ,Zhihao Zhuob, c, ,Xiaosong Sub, c, d, ,Shiyin Zhangb, c, d, , ,Shengxiang Geb, c, d, , ,Ningshao Xiab, c, d,

https://doi.org/10.1016/j.virol.2018.03.012Get rights and content

Highlights

• CV-A6 became the primary pathogen in China in 2013 and 2015.
• D5.4 Lineage strains were responsible for CV-A6 epidemics since 2013 in China.
• Eight VP1 candidate substitutions were identified between different CV-A6 lineage strains.
  

Abstract

Enterovirus (EV)-A71 and Coxsackievirus (CV)-A16 have historically been the major pathogens of hand, foot, and mouth disease (HMFD) in China; however, CV-A6， which had previously received little attention, became the predominant pathogen in 2013, and has remained one of the common pathogens since then.

In this work, we conducted a molecular epidemiology study of CV-A6-associated HFMD in Xiamen from 2009 to 2015. The data showed CV-A6 pandemics had a certain periodicity rather than occurring randomly. Evolution analysis based on near-complete VP1 nucleotide sequences showed subgenotype D5 lineage 4 strains account for the persistent outbreak of CV-A6-associated HFMD in China since 2013.

Alignment analysis revealed eight candidate amino acid substitutions in VP1, which may provide useful information for the research of CV-A6 virulence enhancement. This study contributed to elucidating the circulation patterns and genetic characteristics of CV-A6 in China; however, further surveillance and intervention in CV-A6 epidemics is recommended.

And from the EID Journal, this cautionary report from Vietnam warning of the ongoing evolution and pandemic potential of CVA6.

Volume 24, Number 4—April 2018
Research

Emerging Coxsackievirus A6 Causing Hand, Foot and Mouth Disease, Vietnam

Nguyen To Anh, Le Nguyen Truc Nhu, Hoang Minh Tu Van, Nguyen Thi Thu Hong, Tran Tan Thanh, Vu Thi Ty Hang, Nguyen Thi Han Ny, Lam Anh Nguyet, Tran Thi Lan Phuong, Le Nguyen Thanh Nhan, Nguyen Thanh Hung, Truong Huu Khanh, Ha Manh Tuan, Ho Lu Viet, Nguyen Tran Nam, Do Chau Viet, Phan Tu Qui, Bridget Wills, Sarawathy Sabanathan, Nguyen Van Vinh Chau, Louise Thwaites, H. Rogier van Doorn, Guy Thwaites, Maia A. Rabaa, and Le Van Tan

Abstract

Hand, foot and mouth disease (HFMD) is a major public health issue in Asia and has global pandemic potential. Coxsackievirus A6 (CV-A6) was detected in 514/2,230 (23%) of HFMD patients admitted to 3 major hospitals in southern Vietnam during 2011–2015.

Of these patients, 93 (18%) had severe HFMD.

Phylogenetic analysis of 98 genome sequences revealed they belonged to cluster A and had been circulating in Vietnam for 2 years before emergence. CV-A6 movement among localities within Vietnam occurred frequently, whereas viral movement across international borders appeared rare.

Skyline plots identified fluctuations in the relative genetic diversity of CV-A6 corresponding to large CV-A6–associated HFMD outbreaks worldwide. These data show that CV-A6 is an emerging pathogen and emphasize the necessity of active surveillance and understanding the mechanisms that shape the pathogen evolution and emergence, which is essential for development and implementation of intervention strategies.

Hand, foot and mouth disease (HFMD) is an emerging infection that has overwhelmed countries in the Asia–Pacific region over the past 2 decades. The outbreak in Sarawak, Malaysia, in 1997 caused 2,628 reported cases and 29 deaths and marked the start of explosive regional HFMD outbreaks in subsequent years.

On average, >1 million cases have been recorded in China annually since 2008 (1). In Vietnam, the average annual incidence is ≈80,000 cases; an epidemic peak occurred during 2011–2012, resulting in >200,000 cases and >200 deaths (2).

HFMD is caused by enterovirus A (genus Enterovirus, family Picornaviridae), but the epidemic patterns until now have been punctuated by the frequent replacement of dominant pathogens between enterovirus serotypes over time.

Enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) have been regarded as the major causes of HFMD (3). CV-A6 was isolated in the United States in 1949 (4) and has steadily become one of the main viruses causing HFMD outbreaks in Europe, America, and Asia, including China, Japan, Taiwan, and Thailand (3,5–10).

Unlike EV-A71, for which the (sub)genogroup designation has been well established (11), but similar to other coxsackieviruses (CV-A16 and CV-A10), CV-A6 is arbitrarily divided into several phylogenetic clusters or lineages, from cluster A to F (12) or lineage A to E (E1 and E2) (3). Cluster A/lineage E2 is distributed worldwide and has frequently been detected in recent outbreaks. We use the term cluster in this article.

Despite the public health burden of HFMD, no antiviral drug has been clinically proven effective. A vaccine for EV-A71 has recently been licensed in China only (13), and CV-A16 vaccines (either monovalent or EV-A71/CV-A16 bivalent forms) are under development (14,15).

The emergence of CV-A6 has further challenged the development of intervention strategies, including vaccines, to reduce the burden of HFMD (13). It also emphasizes the need to better understand the molecular evolution of this emerging pathogen, which is essential for development of an effective CV-A6 vaccine in the future (16).

(Continue . . . )

Just as we see with influenza, these non-polio enteroviruses continue to evolve - and while not as deadly as flu - they are capable of causing large epidemics or potentially even pandemics (referring to spread, not severity). 
 
Some of my earlier blogs NPEVs include:

MMWR: Cluster of Acute Flaccid Myelitis in Five Pediatric Patients - Arizona, 2016

CDC Acute Flaccid Myelitis Update - January 2017

EID Journal Upsurge In EV-D68 In The Netherlands, 2016

ECDC: Rapid Risk Assessment On Recent Enterovirus Outbreaks In Europe

EID Journal: New Introductions Of EV-71 Subtype C4 To France – 2012