Saudi MOH Reports 1 MERS Case

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For the past 3 months daily reporting of MERS cases from the Saudi MOH has become increasingly erratic, with batches of days posted - often every 5 to 7 days - frequently omitting days entirely.

So far in April, the MOH has reported on just 18 of 26 days, skipping the 3rd, 5th, 11th, 19th, 21st, 23nd, 24rd and 25th. 

While it is likely many of these dates had no MERS activity, on many days where reports are posted, they likewise report no activity.  So the reasons behind these gaps are unknown.

This mornings batch update covers 7 days, but only provides 3 daily reports. Only one - the 22nd - shows activity; a new case in Al Qunfudhah, and a recovery in Najran.

Two days ago Crof carried a media report Saudi Arabia: A MERS case in critical condition of a new case, but obviously not the one reported, as it was of a 60 y.o. from Al Ahsa.

Today marks exactly 3 months since the last WHO DON (with a line listing of cases) was published on Saudi MERS cases, which is the longest gap I've seen in years.

We have seen monthly WHO EMRO summary Reports (see here and here), but their case counts have differed sharply from the Saudi MOH reports.

As concerning as this gap in reporting is  - the good news is -  we've still seen no signs of any sustained or efficient transmission of the MERS virus outside of health care facilities.

But with the holy month of Ramadan now less than 3 weeks away (May 16th) - which will bring with it a surge in international religious pilgrims second only to the Hajj - some better reporting from the MOH would be welcome. 

South Korea Lowers Bird Flu Alert Status To `Caution'

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As in Europe, Japan and South Korea saw the arrival of a reassorted HPAI H5N6 virus in place of the HPAI H5N8 virus which had dominated the previous three winters.  And like Europe, they saw a much less intense bird flu season than the the winter of 2016-17.

Part of this success - at least in South Korea - was likely due to the enhanced biosecurity put in place last fall in order to prevent outbreaks during their hosting of the XXIII Olympic Winter Games last February. 

But part of it seems due to HPAI H5N6 not being quite as robust of a threat as was H5N8.  That could change over time, of course. 

After a month without an outbreak in commercial poultry, we learn from this Yonhap report that MAFRA has lowered the alert level from `Serious' to `Caution'.

S. Korea lowers bird flu alert status

By Yonhap

Published : Apr 26, 2018 - 11:20

South Korea has downgraded its bird flu alert status and lifted a movement ban on local poultry farms as no additional cases have been reported in over a month, the agriculture ministry said Thursday.

The Ministry of Agriculture, Food and Rural Affairs said it lowered the avian influenza alert status from "serious" to "caution" and released a standstill order on farms in 20 regions.

South Korea strengthened bird flu quarantine measures to prevent further spread of the animal disease since the first outbreak at a duck farm in North Jeolla Province in November. Since then, a total of 22 cases broke out up until March 17 and 6.54 million poultry were culled, according to the ministry.

Given that there were roughly 300 outbreaks reported over the winter of 2016-17, this has been a much milder year. 

In year's past, South Korea assumed that avian flu was only a fall/winter threat, and stopped - or at least greatly curtailed - their monitoring programs for the summer.   

After persistent outbreaks in June of last year, South Korea announced their Move To Year-Round AI Prevention, and so while reduced, the threat of further outbreaks is not eliminated.

As we've seen in the past, often very big `bird flu years' are followed by one or more less severe seasons.  Sometimes this happens globally (see chart below), and sometimes it is a regional phenomenon.

All of which means, while this year's slowdown in avian flu activity around the world has been welcome, it isn't guaranteed to last.

Sweden & Finland Report HPAI H5N6 In Wild Birds

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The reassorted HPAI H5N6 virus, which arrived in Northern Europe for the first time in December of last year, continues to turn up sporadically in wild birds, with the bulk of reports coming from the UK, Netherlands, Finland and Sweden. 

While nowhere near as prevalent as was HPAI H5N8 during the epizootic of 2016-17, it has nonetheless make a bigger showing than did H5N8 during its inaugural visit to Europe in 2014-15. 

With migratory birds heading to northern latitudes for their summer roosting, the risks of seeing avian flu outbreaks in poultry or wild birds along their migratory routes is elevated.


Two reports.  First  a translated report from Finland's EVIRA.

Eat bird H5N6 avian influenza in Sauvon

04/25/2018

Southwest Finland has repeatedly found bird flu from birdwatch. H5N6-type avian influenza causing high pathogenic or high mortality to birds was now detected in the sea-bird found dead in Sauvos. To prevent infections, poultry and domestic birds must be kept inside or protected from contact with wild birds until the end of May.

The eel was found in the Savo region last Wednesday (18 April). The bird flu virus diagnosis in Kotka was confirmed by the Finnish Food Safety Authority's Evia study.

Due to the spring migration of birds, the risk of infection with avian influenza is particularly high. At the end of March, H5N6 avian influenza was found in the eel seen from Parainen, Southwest Finland. During the first part of the year, high pathogenic H5N6 bird flu virus has been found in wild birds and poultry farms, Sweden, Germany, Denmark, the Netherlands and the United Kingdom. All the birds have had to stop the infected farms.

Avian influenza viruses are poorly infected with humans, and infection usually requires close contact with diseased wild birds, poultry or their secretions. Europe's H5N6-type avian influenza found in Europe is never known to be infected with humans.

And from neighboring Sweden, we get this translated report from the Swedish Board of Agriculture (Jordbruksverket).

New cases of bird flu - still important with good poultry care routines
 
Press Release • Apr 26, 2018 10:04 CEST

Three new cases of H5N6 bird flu have been identified after analysis at the National Veterinary Office (SVA). It is about a sea eagle, a pigeon hut and a buzzard found in the areas surrounding Mörrum and Bromölla in southern Sweden. This virus has not been found to present a risk to humans, unlike the H5N6 virus that circulates in Asia.

"In order to avoid spreading to poultry, it is important that poultry producers and hobby farmer owners have good contingency routines," said Karin Åhl, chairman of the unit for horse, poultry and game at the Swedish Agriculture Agency.

- The H5N6 is still circulating in wild bird populations in the country and we do not know how extensive the spread is. It is likely that new cases of wild birds will be detected, and there is still a risk of infestation of the bird of birds. Therefore, we would like to remind you that it is always important to protect your domestic birds from direct and indirect contact with wild birds, "says Karl Ståhl, Deputy State Psychologist at SVA.

The virus is closely related to H5N8, which circulated among wild birds in Sweden in 2016 and 2017, and also caused outbreaks in poultry. While the H5N8 has been massive in large parts of Europe, the H5N6 has not been reported to the same extent, nor has it been associated with the same mortality.

Available naturally among wild birds

In February 2018, a H5N6 bird flu was detected at a sea eagle and a snake on the Blekinge coast. Thereafter, additional cases have been found in a hobby crew in Uppsala County and two sea ears in Blekinge.

Bird flu exists in many varieties and is highly contagious between birds. Milder variants of the virus are found naturally among wild birds, especially in marine birds. Protection level 1 applies in Sweden, which means that poultry may go out, but feed and water should be given under roof or under outdoor protection.

It is important to have good care routines and to prevent direct and indirect contact with wild birds as far as possible. Animal owners should pay attention and contact the vet if poultry show increased mortality, changes in feed and water consumption, egg production reduction or impaired general condition.

General hygiene rules

• Ensure that only those who care for the domestic birds have access to the zoos.
• Keep clean around houses and enclosures.
• Be sure to observe the routines at the hygiene limits.
• Wash hands after contact with birds.
• After a foreign visit, you should not be in contact with domestic birds until after 48 hours.

More information

The Swedish Agricultural Agency's information on bird flu

On preventive measures for those who keep poultry and birds in captivity

SVA's information on bird flu

Public Health Information on bird flu 

Although Europe has gotten off pretty easy this winter - like its predecessor H5N8,  H5N6 has shown considerable persistence in wild birds - and it now in the process of returning the northern breeding grounds for the summer, possibly to further evolve or reassort with other viruses. 

Last summer, the $64 question was whether H5N8 would return in the fall, or something else.  In the end, we got something new; a reassorted HPAI H5N6 virus.  

Once again this summer, we'll be waiting to see what returns in the fall.

Illinois Reports 4th Death Related to Synthetic Cannabinoids

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Despite weeks of media coverage and warnings from public health officials we continue to see new cases of severe bleeding - and sometimes death - from the recreational use of adulterated Spice/K2.  

While most of the cases have been in Illinois, yesterday we learned that cases have been reported from 8 other states.

In addition to updating their case count, yesterday Illinois's Department of Public Health (IDPH) announced the fourth death related to this cluster of poisonings.  First the latest tally, then the announcement:

Synthetic Cannabinoids

As of April 24, 2018, IDPH has received reports of 153 cases, including four deaths, 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 everyday at 1:30pm, for the duration of the outbreak***

Fourth Death Related to Synthetic Cannabinoids

24th Apr, 2018

 

SPRINGFIELD – The Illinois Department of Public Health (IDPH) is reporting the fourth death connected to synthetic cannabinoid use.  The most recent death was a woman in her 30s in central Illinois.  Two men, one in his 20s and another in his 40s, have also died in central Illinois.  A Chicago-area man in his 20s also passed away.  More than 150 people in Illinois in 13 counties have been sickened by synthetic cannabinoids laced with rat poison.

“We continue to see new cases of individuals experiencing severe bleeding after using synthetic cannabinoids,” said IDPH Director Nirav D. Shah, M.D., J.D.  “Like so many other drugs, synthetic cannabinoids are addictive and people are not able to give them up.  Alternatively, they think that it won’t happen to them because they know their dealer or trust wherever they purchased the drugs.  If you know someone who uses synthetic cannabinoids, tell them these are deadly products and try to help them get treatment.”

Individuals who have been sickened by the synthetic cannabinoids have reported coughing up blood, blood in the urine, severe bloody nose, bleeding gums, and/or internal bleeding.  A chemical found in rat poison, brodifacoum, prevents blood from clotting, resulting in severe bleeding.  High doses of vitamin K, up to 30 tablets a day for up to six months, can help restore the blood’s ability to clot.

Because of the large amount of vitamin K needed, the long duration of treatment, and costs up to thousands of dollars per patient, IDPH started discussions with key stakeholders to find a solution with no financial burden on patients.  IDPH recently received a massive donation of nearly 800,000 tablets of vitamin K from the Bausch Foundation and Valeant Pharmaceuticals.  This donation will allow every individual who has experienced severe bleeding to receive lifesaving treatment free of charge.

Synthetic cannabinoids are human-made, mind-altering chemicals that are sprayed on to dried plant material.  These chemicals are called cannabinoids because they act on the same brain cell receptors as the main active ingredient in marijuana.  The health effects from using synthetic cannabinoids can be unpredictable, harmful, and deadly.

People should not use synthetic cannabinoids, but if they have used these drugs and have severe, unexplained bleeding or bruising, call 911 or take them to the emergency department.

More information is available at http://dph.illinois.gov/topics-services/prevention-wellness/medical-cannabis/synthetic-cannabinoids.

As mentioned previously, we've seen a heavy toll from these synthetic cannabinoids in the past. A few blogs include.

• Synthetic Cannabinoids Associated With Severe Illness, Stroke & Psychosis
• NH Governor Declares State Of Emergency Over `Spice’ Overdoses.
• MMWR: Adverse Health Effects Related to Synthetic Cannabinoid Use

On Monday, in San Diego: 6 Cases Of Wound Botulism Among Injection Drug Users, we looked at another spike in bad outcomes from the use of a different adulterated drug; black tar heroin. 

While just last month, in CDC COCA Webinar: Public Health Responses to Opioid Overdoses Treated in Emergency Departments, we looked at data from emergency departments around the country showing that the U.S. opioid overdose epidemic continues to worsen.

In the 1970s, when I was a young paramedic, drug overdoses and related deaths were very common.  We saw them almost daily.

Sadly, it appears that very little has changed in the past 40 years.

J.I.D.: Dynamic Variation & Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection

Credit NIAID

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Like all organisms, flu viruses must constantly adapt in order to survive in new surroundings.  While well adapted to avian hosts, bird flu viruses (like H7N9, H5N1, H5N6) can occasionally jump to humans (and other mammals), whose physiology can present barriers to its spread and survival.

But flu viruses have a secret weapon.  

As they replicate in a host, they generate millions of copies in a few short hours. Since flu viruses are notoriously sloppy replicators, they make numerous mistakes. Most of these faulty copies are evolutionary failures and fall by the wayside, but occasionally a new mutation will appear that is better suited to the new host. 

Host adapted viruses are more likely to replicate and survive, and over time, can become dominant and even `fixed' in the virus.

As long as humans remain a dead end host (i.e. they don't transmit efficiently to other humans) for avian flu, the biggest danger is to the health of the infected individual.  But should these viruses gain the ability to transmit efficiently, then the real problems begin. 

While we often see reports of `mammalian adaptations' in H7N9, or mutations that favor anti-viral resistance, our understanding of exactly when (and where) these mutations are spawned is still lacking.

Adding to our knowledge today, we've a new, open access study, published in the Journal of Infectious Diseases, which looks at the evolution of H7N9 in 11 subjects during the course of  their infection.

Today's report focuses on 3 mutations we've seen often in the past;  

• NA R292K which can provide resistance not only to oseltamivir, but to zanamivir and peramivir as well (see EID Journal: R292K Substitution & Antiviral Resistance)
• PB2 E627K which enables an influenza virus to replicate at the lower temperatures (roughly 33C) normally found in the upper human respiratory tract (see Eurosurveillance: Genetic Analysis Of Novel H7N9 Virus)
• and PB2 D701N (see Dual E627K and D701N mutations in the PB2 protein of A(H7N9) influenza virus increased its virulence in mammalian models)

Due to it length and complexity, I'll simply post the abstract.  So you'll want to follow the link to read it in its entirety. 

Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection 

 

Xiaohui Zou Qiang Guo Wei Zhang Hui Chen Wei Bai Binghuai Lu Wang Zhang Yanyan Fan Chao Liu Yeming Wang ... Show more

 

The Journal of Infectious Diseases, jiy217, https://doi.org/10.1093/infdis/jiy217

Published: 24 April 2018   OPEN ACCESS PDF

Abstract

Background

Signature amino acids of H7N9 influenza virus play critical roles in human adaption and pathogenesis, but their dynamic variation is unknown during disease development.

Methods

We sequentially collected respiratory samples from H7N9 patients at different timepoints and applied next-generation sequencing (NGS) to the whole genome of the H7N9 virus to investigate the variation at signature sites.

Results

A total of 11 patients were involved and from whom 29 samples were successfully sequenced, including samples from multiple timepoints in 9 patients. NA R292K, PB2 E627K, and D701N were the three most dynamic mutations. The oseltamivir resistance-related NA R292K mutation was present in 9 samples from 5 patients, including one sample obtained before antiviral therapy.

In all patients with the NA 292K mutation, the oseltamivir-sensitive 292R genotype persisted and was not eliminated by antiviral treatment. The PB2 E627K substitution was present in 18 samples from 8 patients, among which 12 samples demonstrated a mixture of E/K and the 627K frequency exhibited dynamic variation. Dual D701N and E627K mutations emerged but failed to achieve predominance in any of the samples.

Conclusions

Signature amino acids in PB2 and NA demonstrated high polymorphism and dynamic variation within individual patients during H7N9 virus infection.

CDC COCA Outbreak Alert Update: Coagulopathy Associated With Synthetic Cannabinoids Use

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The cluster of severe bleeding linked to synthetic cannabinoid use (K2/Spice/etc.) which we've been following for more than a month (see last update) has spread from Illinois (still the epicenter) to at least 8 additional states (Florida, Indiana, Kentucky, Maryland, Missouri, Pennsylvania, Virginia, and Wisconsin). 

Due to its relatively low cost, easy availability, and murky legal status, Spice or `synthetic weed', has become a popular option to get high.

Unfortunately, even before this latest cluster of severe coagulopathy (due to adulteration with rat poison), K2/Spice had a dismal reputation, which we've examined in the past. A few past blogs include:

• Synthetic Cannabinoids Associated With Severe Illness, Stroke & Psychosis
• NH Governor Declares State Of Emergency Over `Spice’ Overdoses.
• MMWR: Adverse Health Effects Related to Synthetic Cannabinoid Use

Yesterday afternoon the CDC updated their initial COCA Outbreak Alert of April 5th, which adds 4 new states (Florida, Kentucky, Pennsylvania & Virgina) to the list, and provides additional clinical information for health care providers.

OutbreakAlert Update: Potential Life-Threatening Vitamin K-Dependent Antagonist Coagulopathy AssociatedWith Synthetic Cannabinoids Use

Summary

This COCA Clinical Action updates the message sent on April 5, 2018: https://content.govdelivery.com/accounts/USCDC/bulletins/1e6dac3

Since the index case was identified on March 8, 2018 in Illinois, at least 160 people have presented to Healthcare facilities with serious unexplained bleeding. The preponderant number of patient presentations were in Illinois with other cases being reported from Florida, Indiana, Kentucky, Maryland, Missouri, Pennsylvania, Virginia, and Wisconsin. Laboratory investigation confirms brodifacoum exposure in at least 60 patients. There are at least 3 fatalities. At least 7 synthetic cannabinoids product samples related to this outbreak have tested positive for brodifacoum. At least one synthetic cannabinoids product has tested positive for both synthetic cannabinoid AB-FUBINACA and brodifacoum.
Lessons Learned:

Patients with a history of synthetic cannabinoids (e.g., K2, Spice, and AK47) use may:

• Present with complaints unrelated to bleeding (e.g., appendicitis) and have numerical coagulopathy.
• Be asymptomatic and ignorant of their numerical coagulopathy.

The issue with vitamin K treatment is cost, not availability. The cost of oral vitamin K for two weeks treatment can be $8,000 and treatment may be for months. Options are being explored to address these issues.

What are the Clinical Signs of Coagulopathy?
Clinical signs of coagulopathy include bruising, nosebleeds, bleeding gums, bleeding disproportionate to injury, vomiting blood, coughing up blood, blood in urine or stool, excessively heavy menstrual bleeding, back or flank pain, altered mental status, feeling faint or fainting, loss of consciousness, and collapse.

What Do Health Care Providers Need To Do?

Healthcare providers should maintain a high index of suspicion for vitamin K-dependent antagonist coagulopathy in patients with a history of synthetic cannabinoids (e.g., K2, Spice, and AK47) use: 

• Presenting with clinical signs of coagulopathy, bleeding unrelated to an injury, or bleeding without another explanation; some patients may not divulge use of synthetic cannabinoids.
• Presenting with complaints unrelated to bleeding (e.g., appendicitis).

Healthcare providers should be aware that patients with vitamin K-dependent antagonist coagulopathy associated with synthetic cannabinoids use may have friends or associates who have used the same synthetic cannabinoids product but are asymptomatic and ignorant of their numerical coagulopathy.

All patients should be asked about history of illicit drug use. All “high-risk” patients (e.g., synthetic cannabinoids users), regardless of their presentation, should be screened for vitamin K-dependent antagonist coagulopathy by checking their coagulation profile (e.g., international normalized ratio (INR) and prothrombin time (PT)).

Proceduralists (e.g., trauma/general/orthopedic/oral/OB-GYN/cosmetic surgeons, dentists, interventional cardiologists/radiologists, and nephrologists) should be aware that patients with a history of synthetic cannabinoids (e.g., K2, Spice, and AK47) use may be anti-coagulated without clinical signs of coagulopathy. These patients should be screened for vitamin K-dependent anti-coagulant coagulopathy prior to their procedure. 

Contact your local Poison Information Center (1-800-222-1222) for questions on diagnostic testing and management of these patients. 

Promptly report suspected cases to your local health department or your state health department, if your local health department is unavailable. In addition, report any similar cases encountered since 01 February 2018 to your local health department.

In an effort to better understand the scope of this outbreak, ask your Medical Examiners’ office to report suspected cases, especially those without an alternative diagnosis. If individuals are identified after death or at autopsy showing signs of suspicious bleeding as described above, coroners are encouraged to report the cases to their local health department.

For updated information about the Illinois outbreak—connect with the Illinois Department of Health http://www.dph.illinois.gov/topics-services/prevention-wellness/medical-cannabis/synthetic-cannabinoids