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Evolution of Tuberculosis Treatments: Hope Is on the Horizon

March 21, 2025

Like many medical providers, I am often frustrated by tuberculosis. It can be hard to treat, with long courses of unpalatable therapy, ever-present concerns of resistance and non-compliance, and it taxes already limited and strained public health resources. However, it may be helpful to put our concerns in context, as medical providers throughout history have also struggled to manage this devastating disease. 

The Ebers papyrus, an early Egyptian medical text (estimated 1550 BC),1 may describe one of the earliest treatments for tuberculous adenopathy, namely a complex concoction which included, among other ingredients, salt, mangoes, honey, and bird blood.2,3 Not to be outdone, Hippocrates recommended affected patients consume wolf’s liver and drink elephant urine, compliance with which (and procurement of) may have proved even more dangerous than the disease itself.4 By the 18th century, it comes as no surprise that bloodletting and leeches were advanced as potentially curative as well.5

Treatments evolved in the 20th century with the advent of the sanatorium movement, which treated the disease through isolation, open air, and rest.3 By 1953, there were an estimated 839 such facilities in the country. It was during this period that surgical treatments for cavitary tuberculosis also took hold in the US, attempting to compress the lung and thus close cavitary lesions. These surgeries included therapeutic pneumothoraces, thoracoplasty/rib resection, and phrenicectomy (ligation of the phrenic nerve to paralyze the diaphragm).6

Much to the relief of physicians and their patients, anti-infective therapy against Mycobacterium tuberculosis appeared in 1944, when the first patients were treated with streptomycin and para-aminosalicylic acid. This was followed by the discovery of isoniazid in 1951, and a growing appreciation of the need for combination therapy.3 

As is often the case in the history of infectious diseases, it may have been tempting at that time to conclude that, with effective antimycobacterial agents, the battle against tuberculosis would soon be won. Sadly, this was not the case. In 2023, almost 80 years after the discovery of streptomycin, tuberculosis was the leading cause of death from a single infectious agent in the world.7 Nearly 11 million people worldwide developed the disease, with 1.25 million dying.7 Indeed, many modern physicians may be tempted to adopt a fatalistic outlook on the disease, particularly as many of our first-line tuberculosis drugs were developed over 60 years ago.

In the March issue of Pediatrics in Review, Drs. Alvarez and Rathore do a fine job of shattering the idea that there is no hope on the horizon for the management of tuberculosis. Following a thorough overview of the disease, they provide a detailed, current, and comprehensive description of many new and exciting developments. These include advances in therapy, such as shorter courses for treatment of tuberculosis infection (as brief as 3 months, even in younger children), new anti-mycobacterial agents for use in treating drug resistant tuberculosis (including the drugs bedaquiline, delamanid, and pretomanid), and new information on diagnostic testing, such as updated recommendations for the use of interferon gamma release assays in young children and updates on molecular testing. 

One can only hope that in the not-so-distant future, such exciting and groundbreaking advances will lead to an ability to better control this pervasive and deadly disease. Perhaps someday, therapeutic advancements will become so effective that future providers will look back on drugs such as bedaquiline, delamanid, and pretomanid with the same incredulity I did upon learning of Hippocrates’s use of wolf’s liver and elephant urine.  We have reason for hope. 

References

  1. World Archaeology.  Available at: https://www.world-archaeology.com/features/egyptian-medicine/#:~:text='Magic%20is%20effective%20together%20with,1500%20BC. Accessed January 14, 2025.
  2. University of Leipzig. Available at: https://papyrusebers.de/en/?fbclid=IwAR1UCeQ_JjhWWKJPYJQRldqae1vsmzyUkdK-XDLqbInNR9Q3WbPkQkEsVqw. Accessed January 14, 2016.
  3. Murray JF, Schraufnagel DE, Hopewell PC, et al. Treatment of tuberculosis: A historical perspective. Ann Am Thorac Soc.  2015;12(12):1749-1759.
  4. Rosenblatt, MB. Pulmonary tuberculosis: evolution of modern therapy. Bull NY Acad Med. 1973;49(3):163-197.
  5. Riva, MA. From milk to rifampicin and back again: history of failures and successes in the treatment for tuberculosis. J Antibiotics. 2014;67:661-665.
  6. Firth J. History of tuberculosis. Part 1---Phthisis, consumption and the white plague. J Military and Veteran’s Health. 2014;22(2):29-36.
  7. World Health Organization. Available at: Tuberculosis. Accessed January 16, 2025.
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