The March of Antibiotic Resistance Leads to Another CRE Outbreak

Today there was much attention devoted to the "superbug" outbreak involving a California hospital. The basic facts surrounding this event are that duodenoscopes, a telescopic medical device used during ERCP procedures, were found to be contaminated with carbapenem-resistant Enterobacteriaceae (CRE). An ERCP is a procedure employed to evaluate the pancreas and bile ducts and is an essential part of modern medical diagnosis treatment for myriad conditions. Thus far, 7 people were infected with 2 succumbing to their infections; 179 were exposed from October 2014 through January 2015.

A couple of important points regarding these events:

• Expect more CRE outbreaks as the march of antibiotic resistance continues
• This type of hospital-acquired (nosocomial) infection is exactly what is meant by antibiotic resistance threatening modern medicine (i.e. can procedures be performed safely when the risk of contracting an untreatable infection is considerable)
• Anytime one has a breach of an immune defense, there is risk for infection. Sticking an intricate and flexible telescope through the mouth into the small intestine is most definitely a breach (albeit one that is necessary to treat and diagnose certain conditions)
• Scope related infections are nothing new and this outbreak reinforces the need for device sterilization to be performed meticulously and without fail (at my institution gas sterilization using ethylene oxide has been employed with great success since an 18 person outbreak was uncovered)

CRE are labeled an urgent threat by the CDC because they are near impossible to treat and have a high attributable mortality.  As this outbreak remains in the headlines I believe it is an important opportunity to reiterate to the public that this is the end result of injudicious antibiotic use and there is a desperate need for new approaches to combat bacterial infections (monoclonal antibodies, vaccines, bacteriophages, lysins, antimicrobial peptides, virulence disruptors).

The often unwarranted demand for antibiotics--and physician acquiescence--must stop or else the antibiotic age, which dawned in the first half of the 20th Century, will become a mere memory.

A Simple Tool Illustrating the Protective Shield of Vaccines

A screen shot showing the Pittsburgh area with simulated measles cases at 95% and 80% vaccination rates

When discussing the topic of highly contagious infectious diseases such as measles that require a the population to maintain a high vaccination rate to be kept at bay I invoke concepts like herd protection. Herd protection, sometimes also described as herd immunity, refers to the ability of an unvaccinated or vaccine non-responding individual to rely on the fact that others are adequately immunized so the contagion's ability to reach them is severely restricted. 

When I was an infectious disease fellow one of my attending physicians would illustrate this point with a graphic of a herd of cows with various degrees of vaccination within the ranks of their herd. 

The point he was concretizing is that the more contagious a microbe is the higher the vaccination rate must be. In mathematical and epidemiological terms the level of vaccination must be 1 - (1/Ro). Ro represents the contagiousness of the disease and you can see just by plugging in an approximate number of say 20 for measles, how high the vaccination rate must be (95%).

If that all seems too abstract and the cow example seems too simplistic, I have a solution.

The Graduate School of Public Health (GSPH) at the University of Pittsburgh has a fun tool to help illustrate these points. Affectionately known as FRED, this epidemic stimulator allows one to see a measles outbreak unfold in various locales with disparate vaccination coverage rates. One can see how a measles outbreak is stopped when vaccination rates are at the 95% threshold and how the spread when below. 

Such a tool, coupled with the data and graphics of another of GSPH's great projects, is a welcome addition to the armamentarium when trying to educate the public and policymakers (some of who defend vaccines like PA State Rep. Corbin and US Reps. Dent and Marino) of just how important the measles vaccination has been in eliminating this disease from the US--a status that is now severely threatened. 

Will Science One Day Prove There's No Time to Die? A Review of Kira Peikoff's Latest Novel

Imagine being on the cusp of a scientific breakthrough about to change the entire nature of everything we know about life. We’ve all been taught that living organisms are born, they develop, they age, and they die.  But what if aging—thought to be an axiomatic part of living—is really a pathological process that should be attacked with the same vigor reserved for influenza, Ebola, and other infectious diseases. After all, it was once a “normal” fact of life that people succumbed to infectious diseases. That is before antibiotics, vaccines, and antivirals were developed. Now imagine such a discovery was not welcomed (as it should be), but forbidden because it would bankrupt the social welfare programs that are premised on specific limited life spans as well as disrupt the “natural order” of things. What do the scientists and physicians relentlessly pursuing the quest for knowledge and understanding in this realm do?  Theirs is not an endeavor detached from life because they seek, not just to understand how to halt aging, but to use it to improve human life. Such is the premise behind Kira Peikoff’s second novel No Time to Die which I highly recommend.

Ms. Peikoff masterfully integrates cutting-edge science with her plot in a manner that made me eager to learn just how close we are to the discoveries that drive of the plot of the novel. Like she demonstrated in her first novel, Living Proof, Ms. Peikoff has developed a rare ability to credibly (and ominously) project a society of the near future in which those that oppose the advance of scientific and medical discovery—for religious or other reasons—have been granted the ability to arbitrate over what is allowed and what is forbidden. Such a world is not far-fetched; just peruse the debates regarding embryonic stem cell research, speculation about rapamycin's anti-aging properties, genetically modified organisms (GMOs),  gain-of-function virologic experiments, and the desire by some to die at age 75 to understand that this trend already exists in the non-fictional world of today.  The modern backlash against life-enhancing vaccines, which literally catapulted human lifespans, is also a case in point. 

If I were to attempt to identify the theme of this remarkable book, I would identify its abstract meaning to be the promise of science, a product of human reason, to illuminate the world, transforming what once was a terrifying mystery into a benevolent place in which humans can flourish.

A novel with such a theme is well worth immersing oneself in. 

Scabies vs. Measles: What Is Unseen is Worse Than What is Seen

It's often said that when you see healthcare workers practicing meticulous infection control the diagnosis of the patient being cared for is one of two things: lice or scabies. For some reason, ectoparasites (macro) visible to the naked eye strike fear in the hearts of the world. While an invisible potentially lethal virus like, for instance, measles is something to have a party for and wish on partygoers. 

Another ectoparasite that also merits this misplaced terror are bed bugs, which are really are incapable of transmitting disease to humans (with the possible exception of Chagas Disease in certain contexts). Case in point: a local community college in the Pittsburgh area cancelled classes  because a student had bed bugs in his home! 

Why? 

The action was taken "out of an abundance of caution" -- the familiar phrase used to justify serious threat misperceptions and excuse the performance of response actions for which there is no evidence.

Similarly, a recent episode of a television program mentioned scabies as a "complication" of promiscuity when much more dangers pathogens such as syphilis, gonorrhea, and chlamydia (not to mention HIV, hepatitis B, and HPV) shows how widespread this phenomenon of prioritizing macro ectoparasites reaches.

What accounts for this threat misperception?

My own speculation is that it is the same thing that stalled the development of the germ theory until more powerful microscopes were developed: people are much more accepting of what they can see vs. what they have to imagine, infer, or abstract. In other words, the more concrete an entity (like a scabies mite) seems the more it can be evaluated and judged; conversely, the more abstract an entity is (like a virus) the more distant and unreal it seems. This cognitive bias can be harmful because what isn't seen, in the case of infectious diseases, can be deadly.

Who Made Who? Enterovirus & Paralysis

Since enterovirus-D68  (EV-D68) emerged on the scene there has been increased attention focused on cases of acute flaccid myelitis (AFM)—the limb weakness that was once the hallmark of the almost eradicated poliovirus. 

The focus on AFM-associated EV-D68 stems from the fact that that polio itself is an enterovirus and viruses within the same family often produce similar symptoms. Thus far 112 cases have been found with many patients experiencing antecedent illnesses compatible with EV-D68 and only one recovering. There have now been several reports and at least one major paper linking EV-D68 to cases of paralysis but all have fallen short of definitively proving causation. This is not surprising since microbiological causation can be hard to definitively establish with a fleeting infection and when the paralysis could be caused by immunologic phenomenon rather than direct viral infection, explaining the inability to recover EV-D68 RNA from the CSF of paralyzed individuals. 

It may be some time before EV-D68’s role in the pathophysiology of paralysis is definitely determined but I believe, ultimately, EV-D68 and possibly some related enteroviruses will be found to be behind these cases, even if only as an immunologic trigger, for several reasons that include:

·      Antecedent upper respiratory infections, some of which were due to EV-D68

·      The emergence of EV-D68 and its widespread dissemination throughout the population

·      The ability of enteroviruses to cause flaccid paralysis

·       The seasonality of paralysis matching that of enteroviruses

However, I wouldn't exactly label these cases with the ominous-sounding adjective “mysterious," as some have done, despite the lack of finding EV-D68 in the spinal fluid of paralyzed cases, and invoke memories of fear-inducing polio, which--through direct viral effects--paralyzes at a rate of 0.5% and is easily demonstrable in spinal fluid, just yet. What remains to be done is to look at cases of AFM and compare them with non-cases in a case-control study that may point clues to the etiology. Also, since the genetic signature of EV-D68 was note found, are antibodies present in cases? Scouring the country for more AFM cases, which isn't nationally reportable, will also be needed to understand the baseline and account for increased case finding in the wake of widespread awareness of EV-D68.

It will be interesting to see how EV-D68, now the dominant enterovirus, behaves during this year's enteroviral season because the 1100+ confirmed cases with 14 deaths did not represent the full reach of this virus.