Did the Microbe Make Me Do It? A Review of Infectious Madness

In recent years there has been a growing accumulation of evidence of the role infectious diseases may have in the development of neuropsychiatric illness. A new book, Infectious Madness: The Surprising Science of How We "Catch" Mental Illness by Harriet Washington, provides an extensive overview of the evidence behind this linkage.

While I don't agree with everything suggested in the book, it is indisputable that several converging lines of evidence exist in this realm. The role of the enteric nervous system, its interaction with the microbiome, and attributes of specific pathogens (e.g. influenza, Toxoplasma, and group A streptococcus) are all fascinating and illustrate the potential role specific infections can have on mental functioning. 

For anyone who has taken care of a person sick with an infection, it is clear that mentation and cognitive ability are adversely effected in a global manner. Also, infections such as rabies and viral encephalitis are obvious examples familiar to all. However, Washington moves beyond these canonical examples by providing an overview of infections that possibly provoke specific mental disorders such as schizophrenia and anorexia. Toxoplasmosis is probably the most interesting pathogen that is known to alter behavior in rodents and, intriguingly, possibly behind the attraction to cat pee flavored wine.

While I am (and remain) a staunch defender of free will and do not believe that a microbe can determine behavior, Washington provides ample evidence of microbe-induced alterations in neural circuitry, brain neurochemistry, and hormonal balance and mental illness that can no longer be dismissed as mere coincidence. Perhaps many mental illnesses are varieties of encephalitis?

The Value (and disvalue) of Conducting Secret Science: A Review of the Book

In my field there are certain locations that are spoken of in the same tone one might spike of Camelot. Fort Detrick, the CDC, Plum Island, and the NIH are some US-based locations that have reached this rarified air. In England, Porton Down has that status. 

This military establishment in the English countryside is the site in which much of the British work on biological and chemical weapons -- offensive and defensive -- took place for decades. A recent book I read, Secret Science: A Century of Poison Warfare and Human Experiments by University of Kent professor Ulf Schmidt, is a notable history of the famous (or infamous depending on your context) installation that I strongly recommend.

Professor Schmidt's primary purpose in this book is to explore the medical ethics and biosafety procedures at Porton Down in an attempt to understand how they evolved over time as the field of bioethics emerged from the Nuremberg Code and the Declaration of Helsinki. To that end, Professor Schmidt meticulously catalogs internal deliberations that occurred on informed consent, risk-benefit analysis, public disclosure requirements, and reactions to the death of a volunteer serviceman in a sarin exposure experiment.

The fascinating insight into how military science is similar and dissimilar to civilian science is one of the biggest values of the book and would be a useful guide for those engaged with these same issues in the modern era. However, as an infectious disease physician exquisitely interested in thinking around biological weapons the book provides a unique glimpse of how, before the Biological Weapons Convention, nation-states evaluated biological weapons and where they were placed in the armamentarium.

Some fascinating facts I learned included the unfortunate excursion of the trawler Carella into a cloud of plague during Operation Cauldron, the horrific and vividly described effects of the chemical incapacitant BZ, the "doubtful predictability" of biological weapons, and many other important anecdotes.

Reading the book with all its details, I was tempted to forget Professor Schmidt's goals of highlighting how volunteer soldiers were experimental test subjects  who were placed at risk of death and disability without proper consent being obtained--a fact that cannot be ignored--in the name of "national security".

I (and presumably Professor Schmidt) do not believe that national security can ever be used as an excuse to abrogate individual rights for they are the very reasons governments are instituted. 

Silent Spray of C.diff

Hospitals aren't always the safest places to be. This statement was true hundreds of years ago and is still true today. Among the many hazards that a patient faces when hospitalized is the omnipresent threat of a hospital-acquired infection (HAI). Among the literal cornucopia of HAIs, Clostridium difficile (C.diff) is one that merits special attention. This infection, the result of a disrupted intestinal microbiome, causes a spectrum of illness that  can range from mild diarrhea to life threatening dilation of the colon. Antibiotics are a major risk factor for disrupted one's microbiome allowing the bacteria to take hold. 

Patients with C.diff literally spray the room with the organism -- a fact that requires special infection control measures to be put in place (e.g., isolation, soap/water hand-washing). However, even with strict adherence to those measures C.diff transmission still occurs.

Why? 

There is a silent majority of asymptomatic C.diff shedders that abound in the hospital surreptitiously spreading the infection. A new study conducted in Quebec shows how this reservoir of contagion leads to potentially preventable cases of C.diff. In this study, approximately 5% of hospitalized patients were found to harbor C.diff without symptoms. The study not only quantified the burden of asymptomatic C.diff but then implemented some infection control measures (but not full C.diff infection control). By doing so, they prevented over 60% of the cases of C.diff they "expected" to occur based on historical pre-intervention rates. 

This, to me and many others, seems like a clear path forward to reducing the burden of C.diff infection which kills about 30,000 people annually in the US. But, there is clearly an aversion by some hospital quality management executives to quantifying--or even studying--this phenomenon. It appears to me they prefer to not know so as to avoid the need for more private isolation rooms and/or opening up another avenue of medical-legal risk. However, asymptomatic shedders transmit C.diff whether one acknowledges it or not and until hospitals address this fact C.diff will prowl the hospitals cloaked in a robe of invisibility.

 

While You Were Watching Zika, Chikungunya came to Texas

Though chikungunya, last year's infectious disease fashion, slipped from headlines it is nonetheless a significant virus that is in the midst of its first ever foray into the Western Hemisphere. Spread by the now all too familiar, Aedes mosquitoes this virus has the penchant for causing severe disease characterized by debilitating arthritis. There is no vaccine and no treatment for chikungunya. 

There have been millions of cases since this outbreak began in the Caribbean and even about a dozen cases of local spread in Florida -- a hotspot for Aedes transmitted diseases.

Yesterday, however, local spread was reported in Cameron County, Texas. Cameron County is a Mexico-bordering county and is an area that is a national leader when it comes to another Aedes-related infection: dengue. The close proximity to Mexico confers a continual dengue-risk. When my colleagues and I conducted a research project on dengue response in the US, Cameron County public health authorities were near the top of those we wanted to speak with. 

It will be interesting to see how Texas ramps up anti-Aedes activities which are already enhanced due to the threat of Zika. Perhaps this is another area in which GMO mosquitoes should be considered? I suspect that the local populace, more attuned to the risk of dengue, would be more receptive to the idea than other locales.

It is unfortunate that chikungunya has slipped from the headlines because local spread in Texas is a significant event that merits more attention -- maybe we need another celebrity to become infected.

Dissecting the Latest Super Bug

The report of a highly resistant E.coli bacterium isolated from a urinary tract infection that occurred in a 49 year old Pennsylvania woman (in April of 2016) has temporarily stolen the headlines from Zika. This colistin-resistant E.coli was uncovered via a Department of Defense program in which bacteria that meet certain criteria are automatically forwarded on for further study. While there has been much written about this event and its implications, there are a lot of misconceptions in the headlines.

A few facts about this phenomenon:

1. Plasmid-mediated colistin resistance is a very bad development.

Colistin resistance has existed before, but usually is conferred through changes in the genes of the bacterial chromosome delimiting spread to other bacteria. Indeed, I've seen many colistin resistant bacteria. When resistance is present on a plasmid, which is a mobile piece of genetic information, it can more easily disseminate to neighboring bacteria. The mcr-1 plasmid is such a mechanism for transmission of resistance. Colistin, a drug well known to infectious disease physicians, was a drug put on the shelf decades ago because of toxicity concerns. Today, it is often a drug of last resort and taken off the shelf in special situations in which resistance makes its use necsessary. Losing it through the dissemination of plasmid-resistance, first described in China, would be very problematic. Of note, the woman, who recovered from her infection, had no travel in the 5 months prior to the infection and it will be important to investigate her close contacts (animal and human) to attempt to pinpoint how the strain was acquired.

2. This E.coli isolate was, thankfully not totally drug resistant.

Though this bacterium deserves the "superbug" moniker, given it was both colistin-resistant and harbored an extended-spectrum beta-lactamase (ESBL), it was not resistant to all antibiotics known to man -- something I have battled against twice (Klebsiella pneumonia, Pseudomonas aeruginosa) not too successfully. Cabapenem (it's not a CRE), aminoglycoside, and nitrofurantoin (!) susceptibility was present in the strain leaving the patient with options. 

3. The isolation of an E.coli bearing the mcr-1 plasmid in a pig intestine sample is highly significant.

The aspect of the story -- which hasn't garnered as much attention with the notable exception  Maryn McKenna, one of the best infectious disease journalists -- is a puzzling development as colistin is not an antibiotic used in agriculture. Tracing the origin of the pig intestine to the farm in which the pig it belonged to resided will be important as will sampling other animals -- and humans -- on the farm.

Antibiotic resistance is the norm--it is what bacteria do naturally to survive. The discovery of this strain in the US is not surprising in the least. This event, however, should serve to underscore the need to treat antibiotics as the precious resources they are and not squander them through injudicious use whether in the hospital, the pediatrician's office, or the urgent care center. Additionally, infectious disease medicine must meet these challenges with less reliance on broad-spectrum non-specific antimicrobials and more with targeted therapies such as monoclonal antibodies, bacteriophages, lysins, and virulence factor disruptors and sophisticated and fast companion diagnostics.