During the modern era of antibiotic treatment, we have gained unprecedented control over diseases that have plagued humans for centuries. Among the pathogens that the average American never encounters is Mycobacterium leprae, the causative agent of leprosy. This is also known as Hansen’s Disease, named after G.H. Armauer Hansen, who first isolated and described the bacterium in 1873. Thankfully though, while many of us have heard of this now-exotic disease, very few Americans will ever see someone with this condition.
So what is so interesting about leprosy and the bacterium that is responsible for this disease? Read on to find out.
Mycobacterium leprae is actually distantly related to Mycobacterium tuberculosis, the causative agent of the disease tuberculosis. However, leprosy is a very different condition from tuberculosis, largelydue t o differences in the genomes of these two bacteria. The genome of M. leprae is roughly 30% smaller than M. tuberculosis, and much of the remaining genetic code is non-functional pseudogenes (over 1000 genes in total). These pseudogenes are fully functional in M. tuberculosis, indicating that over eons of evolution from a common ancestor M. leprae lost these gene functions.
From the standpoint of trying to work with Leprosy, it is a strange and frustrating organism. Among one of the difficulties in working with M. leprae is simply growing enough to study. It cannot be cultured in broth like more common bacteria such as E. coli. So, if you’re going to grow M. leprae in the lab for studies, it has to be grown the footpads of mice. To make things more difficult, M. leprae has a doubling time of 14 days, meaning that even basic experiments take large amounts of time to complete. With the invention of molecular diagnostics such as PCR is has become fairly simple to diagnose patients rapidly, but much about M. leprae pathogenesis still remains unknown.
There is only one known natural reservoir for M. leprae: the nine banded armadillo. This oddly cute creature lives in the American southwest and is responsible for zoonotic transmission of the bacteria to humans. Because of this, there are still cases of leprosy in the American south where nine banded armadillos and humans intersect. Fortunately, roughly 95% of humans are naturally immune to M. leprae, which means you probably don’t need to run in fear if you ever see a nine banded armadillo. For the same reason, contact with infected persons is not a dangerous as one would imagine, and the reason why some people were historically able to treat lepers without contracting the disease themselves.
In humans, leprosy is primarily a skin-based condition that can involve the nerves and eyes. While the primary mode of transmission hasn’t been confirmed, some research indicates the M. leprae can spread by infecting the lungs like tuberculosis, or through touch by contact of the microbe with broken skin. After the initial infection event it can take anywhere from months to decades to develop overt symptoms of the disease. This is the phase of leprosy that has been reported for centuries, with notable appearances in historical literature, such as the parable of Jesus curing the leper in the New Testament.
There is a reason that this disease was recorded in our history, and that is directly due to it’s pathology. To have untreated, advanced leprosy is to feel your skin slowly lose sensation and pigment. The most common forms of the disease (and there are 5 accepted forms) manifest as thickened skin lesions, coarsening of the facial features as the skin thickens, asymmetric enlargement of peripheral nerves and their eventual damage and loss. This last element is part of why it was so common for advanced untreated cases to lose fingers, toes, and even entire limbs to the disease. All of these features combined make for a terrifying appearance for those unprepared to deal with infected individuals, leading to their historical isolation from the community and lowered social status.
Thankfully, leprosy is a now treatable disease that responds to common antibiotics, which means we no longer have reason to isolate those infected with the disease. For centuries, it could be argued that one of the most damaging aspects of leprosy was the attendant social isolation that occurred with visible disease. This social stigma gave rise to leper colonies, also known as (my new favorite word of the day) leprosariums. Among these was the Kalaupapa leper colony in Hawaii, pictured below.
The last leprosarium in the US was located in Carville, Lousiana; and closed in 1999. Leper colonies still exist in other parts of the world where infected individuals can come for treatment, such as the image of a woman at a leper colony in Afghanistan shown at the top of this article. Endemic pockets of leprosy can still be found in places such as Angola, Brazil, India, Madagascar, and elsewhere and treatment has managed to eliminate the disease in many other regions. Due to the efficacy of modern antibiotics against M. leprae, those treated at these colonies have a hope for cure as long as the infection is treated as soon as possible after symptoms emerge.
It is quite possible that with continued surveillance, care, and treatment the levels of endemic leprosy could be eliminated as a public health concern (barring zoonotic infections from armadillos) and relegate leprosy to the realm of Smallpox: an ancient foe eliminated by careful planning, social engagement, and modern scientific advances.
Reference: Legendre, D. P., Muzny, C. A. & Swiatlo, E. Hansen’s disease (Leprosy): current and future pharmacotherapy and treatment of disease-related immunologic reactions. Pharmacotherapy 32, 27–37 (2012).