Control of Tuberculosis: An Agent Carter & Captain America Size Task

The popular culture infectious diseases references continue.

On last night's premiere of ABC's new 1940s-era show, Marvel's Agent Carter a character who sneezes exclaims that she likely has tuberculosis. (For those of who might not know, in the Marvel universe, Agent Carter was an associate of Captain America.) 

In the 1940s tuberculosis was a serious fear in the US and pre-streptomycin (1944) there was no effective treatment available. Despite this, deaths had been declining due to improving socioeconomic and health conditions in the US. However, in 1945 the incidence rate was still was at an alarming 87 per 100,000. For comparison, it was 3 per 100,000 in 2013--a 96% reduction.

Though, as I've written before, there are vulnerabilities in our control of tuberculosis including drug resistance and the fact that the bulk of tuberculosis cases in the US occur in foreign-born individuals, who may present special challenges with respect to case identification, contact tracing, and treatment. 

With those caveats, a 96% reduction in tuberculosis cases in 70 years, in the absence of a vaccine program, was a Captain America seized feat.

 

Consumption: A Disease For All Seasons, not Just a Winter's Tale

We often talk colloquially about a disease consuming an individual. Examples include AIDS, cancer, or, quite literally flesh-eating bacteria. However, there is one disease that actually has the original claim to that moniker: tuberculosis. 

Consumption was the name of the condition that eventually became known as tuberculosis and its first mentions reach back to the times of Hippocrates and Herodotus. Indeed the Hippocratic corpus distinctively describes consumption (phthisis in Greek) as being nearly always fatal and consisting of symptoms recognizable to a physician practicing over 2000 years later. The disease, in an era without antibiotics and proper nutrition, could be a death sentence and as the infection progress patients would literally waste away as the disease consumed them.

In the developed world, tuberculosis has faded from the mind of the general public and in the US we are now at an all time low with cases falling below 10,000 with 65% of cases occurring in those born outside the US--a statistic often misused by anti-immigration advocates. Because certain types of tuberculosis are transmitted from person-to-person through the air it is one of the instances in which legitimate quarantine orders are issued in the US for non-compliant patients.

A recent movie--in which I had to suspend disbelief about a flying horse, cessation of aging, and Lucifer--reminded me that anti-immigration sentiment over tuberculosis is nothing new. In the supernatural film Winter's Tale a couple arriving in late 19th century America is summarily deported when a "pulmonary" problem is detected on their screening immigration physical examination and later in the film a character dies of it. The pulmonary problem was tuberculosis.

If one reads historical accounts of how immigration and infectious diseases interacted--such as Howard Markel's When Germs Travel--you will learn that fear of tuberculosis led to a very unscientific process of looking for and excluding those with a physical appearance thought to be conducive to tuberculosis infection--ignoring the fact that the disease had stricken many individuals including the famous and the beautiful.

Tuberculosis was, for a time, the reigning king of infectious disease killers before being replaced by HIV and it has not lost its appetite for blood. Now armed with drug resistance genes, tuberculosis control will remain an important task for the foreseeable future.

To Be or Not To Be...Quarantined for TB

With all the talk of quarantine being used with the Ebola outbreak in West Africa--and now a separate Ebola outbreak in the DRC--an actual quarantine order was issued in Santa Barbara. It wasn't for Ebola though and it wasn't for an entire region--decisions that are really not evidence-based nor effective.

This order was issued for an individual with drug-resistant tuberculosis who is apparently communicable (i.e. smear positive) who represents a contagion risk to others. According to news reports, he has refused treatment and cannot be located. 

Quarantines and isolation orders are difficult topics with many legal nuances however, in my view, they should be used exclusively when solid criteria for contagion with a non-trivial pathogen--not the common cold--are met for individuals (vs. geographic locales) who possess  an actual risk of spreading disease. Smear-positive cases of tuberculosis, in which an individual's cough has been shown to harbor the bacteria, can represent such a contagion risk. 

Diseases spread through the airborne route, like tuberculosis, necessitate a higher degree of intervention than diseases spread  through blood and bodily fluids which are much harder to contract. 

These facts should be kept in mind when using government force with respect to contagious infectious diseases. 

Sherlock Holmes: Proto-Infectious Disease Physician

"I love the detective work."

That's the answer I give when people ask me how I chose infectious diseases as my subspecialty. Detective work in infectious disease involves reasoning from the perceptual level, according to the laws of logic, to arrive at a diagnosis and formulate a treatment plan. This method, which has both deductive and inductive aspects, is not exclusively applicable to medicine, but all of life. One realm, however, where it is employed in a striking manner is in forensic science and the practitioner par excellence is the fictional Sherlock Holmes who, fittingly, was the creation of the physician Sir Arthur Conan Doyle

Not surprisingly, when I came across the book The Remedy: Robert Koch, Arthur Conan Doyle & the Quest to Cure Tuberculosis, I had to read it immediately. This excellent  book was written by former Wired executive editor Thomas Goetz, now CEO of the innovative health data concern Iodine. The book is focused on two seemingly disparate topics that Goetz expertly weaves together into a cohesive and illuminating whole: the evolution of the germ theory of disease and its intersection with Sir Arthur Conan Doyle.

Tuberculosis can scarcely be mentioned without thinking of Robert Koch, the Nobel Prize-winning physician. Koch definitively proved that the dread disease was caused by an invading pathogen, Mycobacterium tuberculosis. Such a discovery provided further evidence of the veracity of the germ theory of disease, which was catapulted from fringe hypothesis status by Louis Pasteur. Koch's contributions to the study of tuberculosis, anthrax, cholera, and other infectious diseases--in my view and in Goetz's--pale before the enormous feat he performed in developing and articulating his eponymous postulates. The postulates form the basis for proving a pathogen is the cause of a disease in question. This achievement, as Goetz recognizes, cannot be understated.

The other strand of the story told is that of Sir Arthur Conan Doyle, a physician in practice who longed to be a writer. Goetz writes of how Doyle employed his medical worldview, which consisted of meticulous observation coupled with deductive reasoning, to create the character of Sherlock Holmes, who first appeared in two early novels. However, Holmes ascended as a celebrity in his own right after a fascinating incident: Koch's mistaken claim regarding tuberculin. What Koch claimed was that tuberculin, a glycerin extract of M.tuberculosis now in common use in tuberculosis skin testing, was a remedy for tuberculosis. Doyle, dispatched to Germany as physician correspondent for an English paper, was unconvinced of the data behind this claim and his subsequent article helped to publicize the errors behind what came to be a scandal over tuberculin. Doyle soon fully committed to writing and left medicine; Sherlock Holmes soared to the point that he even eclipsed his creator. 

The book also contains many historical gems, provides a thorough treatment of how the germ theory increasingly gained acceptance one mind at a time, and concretizes how medicine (and detective fiction) was revolutionized. 

I highly recommend it.

TB: Treating Humans as Matter

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The biopic of brilliant Nobel Prize winning physicist Richard FeynmanInfinity, not only portrays the awesome power of his genius, but also the struggles he faced dealing with the fatal illness of his wife.

In the 1930s and 40s, the diagnosis and treatment of infectious diseases was very rudimentary--in some ways, it still is--and Arline Feynman's illness was sequentially labeled typhoid fever and Hodgkin's Disease, before the final diagnosis of tuberculosis was made.


It was not until 1946 that the first trials in humans of streptomycin--the discovery of which generated much controversy (see Experiment Eleven)--took place.  In the pre-antibiotic era in which the events of the movie take place, tuberculosis was a major killer that literally consumed the bodies of its victims, hence its alias "consumption". In the absence of treatment, or with highly resistant forms of the illness, it can still kill in its original manner. 

I can't imagine how someone of Feynman's ability and intelligence must have felt watching this simple microbe kill his wife. 

Speaking of the power of the atomic bomb in the movie, Feynman quotes fellow physicist Isidor Rabi as saying the bomb treated humans like matter--a description equally fitting for tuberculosis.