Cyanide in White House Mail & The Need for Eternal Vigilance

I come from Pittsburgh so I am particularly attuned to mentions of cyanide in the press since we've recently had one prominent researcher murder his physician wife using the substance as well as another researcher use it to commit suicide.

News that The White House received a cyanide-laden piece of mail should not, however, lead to widespread panic as cyanide, like ricin (which has also been concealed in recent mailings to several government officials), is better thought of as a poisoner's tool rather than a mass casualty inducing substance (though it was used in gas form in Germany's WWII concentration camps). I often describe such substances as weapons of mass hysteria rather than mass destruction. In the context of mail, the intended mode of exposure would be via the skin which is less effective than via inhalation or ingestion. It appears that this attack originated from someone known to government officials.

Cyanide is a simple substance that is relatively easy to obtain and is a well-known component of house fire smoke as it is formed from the burning of carpet. Cyanide's deadly characteristics come from its ability to block the ability of cell's to utilize oxygen to make energy. This property essentially halts all cellular activity and ultimately leads to death. There are antidotes to this poison, but they must be administered quite rapidly to have any effect. 

An interesting aspect of the nefarious use of cyanide is the past effort (which thankfully never came to fruition) by Al Qaeda to develop a device to disperse the cyanide gas in a manner capable of causing mass casualty in the New York City Subway. Finding this device, named the "mubtakkar", and uncovering the plot to use it became a major priority for the Bush Administration. 

Anytime a biologically active substance is used in the initiation of force it is a major cause for concern and should reinforce in the minds of all how easy it is use these substances as weapons. While 14 years have passed since the anthrax attacks, cyanide and ricin biocrimes have been occurring with increased frequency, highlighting the low barrier to their acquisition. Preparing for such events by heightening awareness, improving diagnostic capability, and developing effective countermeasures must remain a priority. 

Could Infectious Disease Physicians Replace Psychiatrists?

Infectious disease physicians always like to imagine that every type of pathology is due to an infection. Cancer-causing viruses and ulcer-inducing bacteria are cases that illustrate the ubiquity of microbes as etiologic agents for conditions long thought to be non-infectious. Psychiatric illnesses have, thus far, not demonstrated a definitive link to infection. A growing body of fascinating new research, however, is beginning to change that.

Many science and evolutionary biology enthusiasts are familiar with the parasitic infection toxoplasmosis, an organism that often has pregnant woman avoiding kitty litter boxes. It is well established that toxoplasmosis infections in the brain of rodents change their behavior by attracting them to a substance they naturally avoid, cat urine. Such a behavior change renders them much more likely to be devoured by a feline allowing the Toxoplasma parasite to reach its beloved primary host.

Could this infection also influence human behaviors?

Perhaps it is behind the plague of humans who display a zombie-like obsession with endlessly watching cat videos on the internet? 

About a quarter of humans are infected with toxoplasmosis and it is generally considered to not be a major problem except for in certain circumstances such as pregnancy, HIV, or transplantation. What really is striking is the fact that those with certain mental conditions are harbor the organism at a higher rate than the general public. For example, schizophrenics are 2.7 times more likely to be antibody positive than members of the general public. Associations have also been noted for generalized anxiety disorder and bipolar disorders.

Correlation is not causation and an infection cannot override the volitional nature of human consciousness. However many questions remain to be answered such as: is toxoplasmosis a surrogate marker for something else that lies behind these conditions, if the organism plays a causative role is it the infection or the post-infection immune response that is operative, would treatment change the course of illness? 

It is also important to remember that not every case shows this association and multifactorial explanations for psychiatric illnesses are the norm. 

Nevertheless that an infectious disease may play a partial role in some of these illnesses would represent an important breakthrough that could lead to new means of both prevention and treatment.

Measles & Making a Quick $100,000+

When someone offers to pay over $100,000 to someone for proving something that is already incontrovertible, it makes me wonder. 

In this case, a "biologist" in Germany  offered a cash prize, not for proving a fancy mathematical conjecture, but for proving that measles is an infectious disease versus a disease of social separation (!). This scenario is odd for numerous reasons that include:

• Rhazes, before the year 1000, counseled people to avoid the disease lest it become an epidemic.
• The virus that causes the disease was isolated in the 1950s.
• Instead of social separation being a cause, as conjectured by this biologist, it is social interaction that abets the virus as a susceptible population of a certain size is required for the virus to sustain transmission.

That, in the 21st century, we are faced with a debate over a fact of reality long established is more than just a curious novelty--it is evidence of an erosion of the intellect and a true return to the primitive in which nebulous causes for diseases held sway and humans lived in a demon-haunted world.

Adding Layers to my Understanding of Tuberculosis

When I teach medical students a concept my technique often involves reducing the concept down to the level of simple observation or unsophisticated laboratory or radiographic tests. This approach allows the medical student to not get lost in complexity and lose track of what's actually going on, namely a patient with certain signs or symptoms. 

As an avid attender of myriad infectious disease lectures I, myself, also tend to prefer this type of teaching approach. At a recent meeting of the Baltimore Tropical Medicine Dinner Club, on whose board I serve, I was treated to an exceptional employment of this very technique by an icon in the field of tuberculosis pathology: Johns Hopkins University's Dr. Arthur Dannenberg. 

What Dr. Dannenberg did in this lecture is reduce all the esoteric jargon of tuberculous pathology to literally entities visible to the naked eye (i.e. lesions on rabbit lungs). This lecture deepened my understanding of tuberculosis immensely because it provided me with a new framework to think about tuberculosis, namely as balancing act between two types of T-cell response. One type of response kills infected macrophages, the other activates macrophages to kill the bacteria. 

Using this paradigm it becomes much easier to understand why 90% of people are resistant to tuberculosis and never develop the disease after exposure. The infecting bacilli that survive the initial onslaught by alveolar macrophages are kept in check by a response which kills the cells that harbor them, creating a solid foci of necrosis surrounded by macrophage sentries poised to act. Most human's immune systems are able to keep this foci which, as it liquefies may leech out bacilli, in check (latent TB) but in those whose are unable, macrophages must release firepower on the area, causing the classic destructive lesions of tuberculosis. Aging and immunosuppression are two factor that can lead to loss of control and symptomatology. Similarly the poor population results of the BCG vaccine might be related to the fact that only a small proportion of the population actually needs it.

Such an understanding of tuberculosis provides a green light to think of therapy and vaccines differently. Primarily, tuberculosis therapy involves the prolonged use of antimicrobial therapy to kill bacilli in both the active and the latent stages. Therapies to keep the initial foci of necrosis from liquifying could modify therapy for latent TB. Additionally, immune modulation to dampen inflammation could also play a role (steroids are currently a part of the regimen used in tuberculous meningitis).

A proper conceptualization of a disease is really the only true means to understanding and conquering it.

Preparing Minds for Bioterrorism

I often give interviews to the press on various infectious disease topics and a few months ago I was talking to a journalist and referenced the anthrax attacks of 2001. The journalist replied, “Oh yeah, the anthrax 'scare' back then.” I replied, “it wasn’t a ‘scare’ it was an attack in which 22 people were infected and 5 murdered via spores being sent through the US Postal System.”

That 14 years have now passed since the Amerithrax attacks means that those horrific times have faded from people’s memory and that’s not a good thing because the threat remains.

With that context in mind, my colleagues and I wrote a clinical review paper with the aim of refreshing clinician’s minds with new information on these important infectious diseases (anthrax, plague, botulism, tularemia, and smallpox). We were ecstatic when the most prestigious medical journal in the world, The New England Journal of Medicine, accepted it for publication.

The subtext of the entire update is that it is vitally important for clinicians—the front-line defense against these pathogens—is armed with the knowledge necessary to recognize and treat these diseases as well as know when to sound the alarm.

As my hero Louis Pasteur famously said, “chance favors the prepared mind” and our hope is that our paper will prepared the minds of those crucial to protecting this nation from another bioattack.