Nice Work if You Can Get It: Paid Stool Donors

A long-time friend of mine yesterday said that, unlike many, he hasn't gained any weight since high school: a span of two decades in which weight gain is the norm for many people. I immediately replied that he must have a good conglomeration of bacteria in his intestines that are partly responsible for his feat through their metabolism of what he eats. In fact, he eats so much with little effect on his weight that his nickname was "Worm" because a tapeworm was thought to be responsible for his physiological feat.

The conversation yesterday ultimately devolved into how his stool will be highly sought after once fecal transplantation and microbiome alteration for obesity and weight management are more fully developed. 

The microbiome will be the key to understanding many diseases -- infectious and non-infectious alike -- and fine-tuning the microbiome will be a full-fledged medical speciality. With respect obesity, more and more evidence is accumulating that the microbiomes of obese patients are distinct from the non-obese. Animal studies have shown that antibiotic treatment, which by definition alters the microbiome, can cause test animals to gain weight. Transferring of the stool from obese to non-obese animals can also induce obesity. In short, multiple strains of converging evidence all provide ample evidence supporting the hypothesis that the microbiome and obesity are strongly connected. 

Fecal transplantation is the current crude mechanism for altering the microbiome and is being used for refractory or recurrent C.diff (Clostridium difficile) infection. Right now the FDA is exercising "discretionary enforcement" allowing the innovative treatment to flourish (I hope they continue to exercise such discretion forever).  Results have been stellar and there are efforts underway to capture the magic of the stool transplant and bottle it in a pill.

Until pills become the means of microbiome alteration, fecal transplantation will be the major mechanism for microbiome improvement. This scenario leads to the need for stool donors. These donors must have their stool screened for potential pathogens and themselves must not be obese (a fecal transplant from an overweight donor can induce obesity in the recipient).  

All this discussion leads to my suggestion that my friend become a paid stool donor -- which he took as a means of saving the world (with his stool). He is eager to get to work and looks forward to being in his "office".

Burkholderia Exploits the Desire for Soft Stool

One of the tell-tale smells of the hospital is the aroma of poop. The smell of poop abounds in all its varieties: infected and non-infected, formed or liquid, and any other variety you could imagine. Part of the reason for this fragrance has to do with what happens to one in the hospital: the food, the antibiotics, the infections (e.g. C.diff), and the "bowel regimens". 

Bowel regimens involve a cocktail of various medications that promote softening of the stool, act as a laxative, or both. These medications are often prescribed for ordinary constipation but also to counteract the actions of painkillers like morphine which predictably constipate patients.

An alert from the CDC issued this week, however, warns of a possible infection risk that is associated with a widely used product: the stool softener liquid docusate. The bacteria possibly associated with this product, Burkholderia cepacia complex, is one that is well-known to infectious disease physicians as a major cause of lung infections in those with cystic fibrosis. However in these cases, which appear to be confined to a single state, the patients involved do not have cystic fibrosis but are mostly critically ill ICU patients on mechanical ventilators. Because these patients are critically ill and this bacteria is difficult to treat, I suspect the mortality rate may be high.

This warning includes the recommendation that liquid docusate products not be used in critically ill patients or the immunosuppressed (other formulations of the drug are unaffected and can be used).

This outbreak underscores the well-established fact that hospitals aren't always the safest places to be. Product contamination-related outbreaks can have major consequences and be difficult to contain as products can be distributed widely and, if medical products are involved, are administered to sick patients. 

I don't think the bowel regimen will be going anywhere soon so the faster this outbreak is dissected and controlled the better.

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.