Wednesday, April 25, 2018

Illinois Reports 4th Death Related to Synthetic Cannabinoids


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***

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

Tuesday, April 24, 2018

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

Credit NIAID


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;  
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 
The Journal of Infectious Diseases, jiy217,
Published: 24 April 2018   OPEN ACCESS PDF


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


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.

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.

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


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:
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


This COCA Clinical Action updates the message sent on April 5, 2018:

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

ECDC: C. Auris Rapid Risk Assessment For Healthcare Settings - Europe

Credit ECDC


On Saturday, in CDC Update: Candida Auris - April 2018, we looked at the CDC's latest monthly update on this difficult to diagnose, hard to treat (anti-fungal resistant), and often deadly fungal infection.  
In some slightly more encouraging news, last night CIDRAP News reported the FDA approves rapid diagnostic test for Candida auris. While still a laboratory test (not point of care), this should improve accuracy and turn-around times for lab results. 
As previously mentioned, this isn't just a United States' problem, but a global health threat.  This fungal infection, which was first detected in Japan in 2009, has now turned up on multiple continents, and in 2016 we looked at its impact in the UK (see PHE On The Emergence Of Candida auris In The UK).

Yesterday the ECDC published a Rapid Risk Assessment (RRA) on C. auris in Europe, where at least 620 cases of infection or colonization have now been identified in 7 EU nations.
Credit ECDC

Due to its length, I'll only provide a link to the document and their summary.  Follow the link to read the full RRA.

Candida auris in healthcare settings – Europe
First update, 23 April 2018
Main conclusions and options for response

Candida auris poses a risk for patients in healthcare facilities across Europe due to its propensity to cause outbreaks and its antifungal resistance. Difficulties with laboratory identification and lack of awareness of this Candida species may delay early detection increasing the potential for horizontal transmission. C. auris was first identified in 2009 and within a few years has emerged as a cause of healthcare-associated infections.
Outbreaks have been reported in countries in five continents. The number of reported C. auris cases in European countries has increased significantly since the last ECDC rapid risk assessment on C. auris in December 2016. There continues to be a need to raise awareness of C. auris in European healthcare facilities, so that they may adapt their laboratory testing strategies and implement enhanced infection prevention and control measures where necessary.
       (Continue . . . .)

Monday, April 23, 2018

San Diego: 6 Cases Of Wound Botulism Among Injection Drug Users

Credit CDC


According to the CDC, about 20 people each year (in the U.S.) contract wound botulism, mostly from subcutaneous injection of black tar heroin.

A pretty low number, which makes the following headline from San Diego's Office of Communications all the more remarkable.

Three More Wound Botulism Cases Reported in County

Three more cases of wound botulism in people who injected black tar heroin have been reported in San Diego County, bringing the total to six in the past month, the San Diego County Health and Human Services Agency announced today.

Five of the cases are men and have been confirmed with botulism by the California Department of Public Health. The latest case is a 25-year-old woman who is being tested for confirmation. Although all were hospitalized and treated with anti-toxin obtained from CDPH, one of the previously reported cases, a 67-year-old man, has died.

Two of the six cases are connected, but the others appear to be unrelated and the sources of the black tar heroin are unknown. Investigation is continuing and additional cases may occur.

“This is the largest group of wound botulism cases ever reported in San Diego County,” said Wilma Wooten, M.D., M.P.H., County public health officer. “Black tar heroin users can suffer from overdose, skin infections, endocarditis, botulism, and other serious illnesses that can be life-threatening. We urge anyone who uses this substance to seek treament.”

Symptoms of wound botulism occur within days or weeks of injecting contaminated drug and may be mistaken for drug overdose. Symptoms can include weak or drooping eyelids, blurred or double vision, dry mouth, sore throat, slurred speech, trouble swallowing, difficulty breathing, and a progressive symmetric paralysis that begins at the face and head and travels down the body.

If left untreated, symptoms may lead to paralysis of the respiratory muscles, arms, legs and trunk, and can cause death. Prompt diagnosis and treatment are critical to decreasing the severity and duration of illness.

(Continue . . . .)

Beyond the everyday hazards of overdosing, Hepatitis C, Hepatitis B, HIV, Staphylococcus aureus, and even tetanus, there are exotic risks including wound botulism and wound anthrax (see Eurosurveillance: Anthrax Encounters Of The 4th Kind).
Black tar heroin is cheap, and therefore popular, but it is crudely refined and can be cut (or more properly adulterated) with a variety of substances, including (reportedly) ground up paper, shoe polish, and whatever floor sweepings might be available.  
This creates a thick, sticky substance which is difficult to inject intravenously, making skin popping or muscle popping the preferred route, which can often lead to tissue necrosis and abscesses under the skin. 

According to the CDC's Wound Botulism page:
We don’t know how black tar heroin gets contaminated with the germ that causes botulism. Because the germ lives in soil, it might get into heroin when the drug is produced or transported, when it is cut or mixed with other substances, when it is prepared for use, or through some other way. Drug-use equipment (“works”) used to prepare or inject contaminated drugs might also spread the botulism germs to anyone who uses it.
Key facts:
  • You cannot see the germ that causes botulism. Contaminated drugs do not look different from non-contaminated drugs. Lab testing is the only way to tell if your drugs are contaminated with the germ that causes botulism.
  • Heating (“cooking”) heroin will not kill the botulism germ. It takes special conditions to kill this germ.
  • You cannot get botulism from another person. It is not contagious. But if you share contaminated heroin or equipment (“works”) with another person, both of you might get botulism.
Between the nation's mounting opioid epidemic, the recent outbreak of severe internal bleeding due to rat poison laced Spice/K2, and now this latest cluster of wound botulism in San Diego, the societal and personal costs of drug abuse continue to climb.


PAHO Epidemiological Update: Diphtheria In The Americas


According to the noted anthropologist and researcher George Armelagos (May 22, 1936 - May 15, 2014) of Emory University - in his work The Changing Disease-Scape in the Third Epidemiological Transition-  in the mid-1970s we entered the age of newly emerging infectious diseases, re-emerging diseases and a rise in antimicrobial resistant pathogens.

While emerging pathogens - like novel flu, hemorrhagic fevers, SARS and other exotic pathogens are a major concern -  antimicrobial resistance continues to rise to alarming levels around the world, and we are seeing the resurgence of old, nearly forgotten infectious diseases like measles, mumps, scarlet fever, and diphtheria. 
Pretty much as predicted 32 years ago by Dr. Armelagos.  For a more detailed review of his work, and the reasons behind his conclusions, you may wish to revisit my 2016 blog  The Third Epidemiological Transition.
A couple of weeks ago, in UK: `Exceptional' Scarlet Fever Season Continue, we looked at the (still) unexplained return of Scarlet fever around the world. 

A month ago, in ECDC RRA On Measles In EU & Harvard Study On Mumps Vaccine, we looked at two more infectious diseases - once nearly vanquished in Europe and the United States - which are on the rise again. 

And perhaps most surprisingly, we been following the come back of diphtheria around the globe.  A few recent blogs include:
WHO Update & Risk Assessment: Diphtheria At Cox's Bazar, Bangladesh
WHO: Diphtheria Spreading Rapidly In Cox’s Bazar, Bangladesh
Vietnam MOH Warns Of Diphtheria’s Spread From Laos
Over the past 50 years diphtheria has become so well controlled by vaccines in Western countries that many doctors can now go their entire career without ever seeing a case.  
But that success story may be in danger, as over the past few years we've seen more and more outbreaks around the globe. 
Last week PAHO (the Pan American Health Organization) released an epidemiological update on Diphtheria in the Americas, citing four countries (Brazil, Colombia, Haiti & Venezuela) that have reported cases in the past year.

Hardest hit, with more than 1600 confirmed or suspected cases since 2016, has been Venezuela (see last summer's Venezuela: Reports Of A Growing Diphtheria Outbreak).

Epidemiological Update
16 April 2018

Diphtheria in the Americas - Summary of the situation
In 2017, four countries in the Region of the Americas—Brazil, the Dominican Republic, Haiti, and the Bolivarian Republic of Venezuela—reported confirmed diphtheria cases. In 2018 as of epidemiological week (EW) 14 of 2018, four countries in the Region—Brazil, Colombia, Haiti, and Venezuela—have reported suspected and confirmed diphtheria cases.
The following is a summary of the situation in each country with reported suspected and confirmed cases in 2018.
In Brazil in 2017, there were 42 suspected cases reported in 14 states. Of the reported cases, 5 were confirmed in four states: Acre (1), Minas Gerais (2), Roraima (1 fatal case, imported from Venezuela), and São Paulo (1). The remaining 37 cases were ruled out. Three of the 5 confirmed cases (2 in Minas Gerais and 1 in São Paulo) had received the full vaccination scheme. The confirmed cases range from 4 to 66 years of age (median 19 years), and four are male and one is female. Additionally, in EW 14 of 2018, 6 suspected cases were reported in 6 states; one reported in the state of Roraima (imported from Venezuela) is currently under investigation. As of EW 14, none were confirmed.
In Colombia in EW 7 of 2018, a fatal confirmed case of diphtheria imported from Venezuela was reported in La Guajira Department. The case is a 3-year-old Venezuela national with an unknown vaccination history. Onset of symptoms was on 2 January 2018 and the case died on 8 January. The case was laboratory-confirmed based on clinical, epidemiological, and laboratory criteria (Gram-positive bacilli and RT-PCR positive for Corynebacterium diphtheriae with no identification of biotype or positive toxin).
In Haiti, since the beginning of the outbreak at the end of 2014 up to EW 6 of 2018, there have been 410 probable cases of diphtheria reported, including 75 deaths. 1 Reported case-fatality rates were 22.3% in 2015, 27% in 2016 and 10.7% in 2017 and 2018. During the first four epidemiological weeks of 2018, 2 to 5 probable cases per EW were reported similar to that observed during the last four weeks of 2017.
Females accounted for 57% of the total probable cases in 2015, 50% in 2016, 60% in 2017, and 47% in 2018 (up to EW 6). With respect to vaccination coverage, between 2015 and 2018 the unvaccinated cases accounted for 17% (2018) to 38% (2015) of the total cases. Children less than 10 years of age accounted for 64% of the probable cases reported between 2017 to EW 4 of 2018.
Per the Haiti Ministry of Public Health and Population, a probable case is defined as any person, of any age, that presents laryngitis, pharyngitis or tonsillitis with false adherent membranes in the tonsils, pharynx and / or nasal pits, associated with edema of the neck.
Since the beginning of the outbreak the departments reporting the highest number of probable cases are Artibonite, Centre, and Ouest.
In Venezuela, the diphtheria outbreak that began in July 2016 remains active (Figure 1). Since the start of the outbreak until EW 10 of 2018, a total of 1,602 suspected diphtheria cases were reported (324 cases in 2016, 1,040 in 2017, and 238 in 2018), of which 976 were confirmed by laboratory (314) or epidemiological-link (662), and 142 died (17 in 2016, 103 in 2017, and 22 in 2018). The cumulative case fatality rate is 14.5%
In 2016, cases were reported in five states (Anzoátegui, Bolívar, Delta Amacuro, Monagas, and Sucre), while in 2017, 22 states and the Capital District reported confirmed cases. In 2018, 9 federal entities have reported confirmed cases. Cases have been reported among all age groups; however, the majority of cases occurred among the 1-49 year age group while the highest incidence rate occurred among the 5-19 year age group.
Health authorities are intensifying epidemiological surveillance, investigations, medical care, and vaccinations. In addition, they are maintaining continuous training of healthcare workers (based on the updated manual of standards, guidelines, and procedures for the management of the disease) as well as health education.

(Continue . . . )

Although the diphtheria vaccine is highly protective against the disease, vaccinated individuals can still can be asymptomatic carriers of toxigenic C. diphtheriae. 

And the vaccines' protection doesn't last forever, booster shots - even for adults - are required to maintain immunity (see WHO report below).
Diphtheria vaccine
Review of evidence on vaccine effectiveness and immunogenicity to assess the duration of protection ≥10 years after the last booster dose.
April 2017
So it doesn't take very long into the collapse of a nation's public health system before unvaccinated children and adults whose immunity has waned to start coming down with this highly contagious disease.
Diphtheria antitoxin (DAT) has been in short supply for several years, even in the EU (see ECDC RRA A case of diphtheria in Spain), complicating treatment.
A grim reminder of just how thin the veneer of modern civilization really is, and how easily an economic collapse, or some other major calamity (war, natural disaster, pandemic, etc.) can erode and disrupt those things we currently take for granted.