Learning about Tuberculosis at the Opera (Again)

I had one more tuberculosis-related opera on my list and just had the opportunity to experience it. Again, the disclaimer — I am not a regular opera consumer but am someone who has an interest in consumption. Verdi’s La Traviata which predates La Boheme, is based on a novel and play that recounts the life and demise of a famous courtesan from tuberculosis. Since it was written several decades before La Boheme it is not surprising that tuberculosis is a fatal disease.

One of the elements of this tuberculosis portrayal is that the main character, VIoletta, is a well-accepted, highly sought-after person of interest despite her sickness. Today, tuberculosis is known as a contagious infectious disease and those with pulmonary tuberculosis (who are smear positive and not on therapy) are not the people who should be interacting all that much with the general public until their disease is under control.

Robert Koch discovered Mycobacterium tuberculosis as the cause of tuberculosis in 1882 — decades after La Traviata — dispelling mistaken notions regarding the cause of tuberculosis, including heredity or a disposition/temperament. In La Traviata, there is a line about how a person lives confers susceptibility (which is not entirely untrue) but in the opera it appears to matter-of-factly be more about continual parties and being a courtesan than any moral judgment.

Perhaps the lack of fear of contagion explains why tuberculosis wasn’t stigmatized at that time and it was only with Koch’s discoveries and the acceptance of the germ theory of disease, that tuberculosis exposure was re-conceptualized as something to be avoided. When tuberculosis modern descendant (in terms of widespread infection, targeted demographic, etc) appeared that type of view of disease

Going to the Opera to Learn About Tuberculosis

Last month, on March 24, it was “World Tuberculosis Day” and it likely came and went without notice. Though tuberculosis is something that often doesn’t make headlines much, it is #1 infectious disease killer of humans. It killed 1.3 million people in 2017—more than flu, HIV, malaria, and measles. It has infected about one-quarter of the world’s population. Though the US tuberculosis burden has fallen to record lows (9105 cases in 2017), it nonetheless remains an important public health threat.

A disease that leaves such a mark on humanity is bound to leave its mark on culture as well. Probably one of the most famous cultural monuments to tuberculosis is the Puccini opera La Boheme, which I finally was able to see earlier this month. To modern audiences, La Boheme is probably more noted for being the inspiration behind Jonathan Larsen’s Rent rather than in its own right.

I am not an opera aficionado by any standard and don’t really know how to evaluate operas, but I am an infectious disease nerd and that’s why I wanted to see La Boheme. La Boheme, just like Rent, is centered around a group of artistic, financially challenged friends one of whom has an advanced case of tuberculosis (Mimi). The plot revolves around the friends daily trials with romance, career, and (not surprisingly) rent.

La Boheme was written in 1896 nearly half a century before streptomycin — the first anti-tuberculosis antibiotic was discovered — and about three decades before the BCG vaccine was developed. At that time, tuberculosis was incurable so it is not surprising how La Boheme ends. Interestingly, during that era, TB was thought by many to be an inspiration to the artist as well as a manifestation of beauty (this was part of the “illness as metaphor” work of Susan Sontag). Today, I don’t think that impression persists as tuberculosis patients are often stigmatized for various reasons and no one is claiming tuberculosis is “romantic.”

Seeing infectious diseases portrayed in great works of art importantly concretizes how impactful they can be and for that reason, I thought La Boheme is an important part of understanding the cascading effects of infectious diseases that spread much farther and deeper than many other medical conditions.

Rediscovering TB: A Review of Discovering Tuberculosis

The single microbe that kills the most humans in 2016 is not Ebola, not Zika, not brain-eating amoebas. It is not an infection that continually grabs headlines. It is Mycobacterium tuberculosis, a profligate killer that has menaced humans since our appearance on the planet. In 2014, tuberculosis felled 1.5 million humans.

There are many books about very aspects of tuberculosis that I have read but none of them have really attempted, in my recollection, to tell the story of tuberculosis with an aim to make the history of our species' battles with disease relevant to the present. That lack of present-centrism is no more with UVA History professor Christian McMillen's Discovering Tuberculosis: A Global History 1900 to the Present.

Discovering Tuberculosis is a scholarly work that takes the reader through several important phases in the control of tuberculosis with attention to the principles at play in each of them. From efforts to control TB on Native American reservations to the global fight against HIV/TB coinfection, McMillen skillfully makes the past not just come alive but completely inform how we presently face this infection.

Some important highlights of the book include the failure of the BCG vaccine and how this vaccine may have stymied vaccine development more generally; the early harbingers of the threat of drug resistant TB in 1960s Kenya; the vicissitudes of the approach to HIV/TB coinfection, and the not often mentioned negative effects of directly observed therapy.

One of the most important aspects of this book is that it relies on Professor McMillen's extensive review of the actual communications between programmatic leaders and health agencies. Such a level of granularity grounds his analysis in the actual medical debates that were occurring, allowing almost direct application to current efforts.

Discovering Tuberculosis allowed me to gain a better understanding of today's global anti-tuberculosis effort and grasp how difficult it will be to rid our race of its most astute infectious disease killer. I highly recommend it.

Dissecting Tuberculosis in the US

Today the CDC released the latest numbers on tuberculosis in the US and it is all good news with a couple of caveats.

Overall, there's been a 2.2% decline in tuberculosis in the US with just 9412 cases reported in 2014. This translates to a rate of 3 cases per 100,000 people which is extremely low but not yet at the goal of 1 case per 1,000,000. Indeed, recent news stories have shown that the risk of tuberculosis still exists with an active case diagnosed in a Pittsburgh school; a similar incident in Kansas caused 27 students becoming skin test positive, indicating they contracted latent TB.

When one dissects the rate of 3 cases per 100,000 there are several important and ominous findings: 

• The rate of tuberculosis is 13.4 times higher in those foreign born when compared to those born in the US; 66.5% of cases are in this group
• Asians are the ethnic group with the highest burden of cases in the US
• Hawaii is the state with the highest rate of tuberculosis in the US
• California, Florida, New York, and Texas account for 50.9% of all US cases in 2014
• 6.3% are HIV-positive
• Just 1.3% of cases (in 2013) were multi-drug resistant

Interpreting these numbers, it becomes clear that tuberculosis is a waning problem in the US when looked at in aggregate. However, looking at the data in all its granularity it becomes clear that the final push for tuberculosis control will be in finding foreign-borne individuals with latent tuberculosis--immigrants are screened for active tuberculosis via culture and chest x-ray in their home country--and placing them on treatment to prevent reactivation. Such an effort is daunting as many of the individuals in these communities are not readily available to public health and medical officials, but placing them on treatment is the means to eliminate tuberculosis from the US. 

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.