R Gordon | February 8th, 2022

Leprosy is an infectious disease that has been stigmatized to the point that being a “leper” is a noun for being shunned from society. The causative agent, Mycobacterium leprae, has caused fear and ostracism of the patients with the disease are big reasons why scientists began studying this organism. Between the unique biology and terrifying history, M. leprae still exists as a neglected tropical disease that isn’t going away soon (Figure 1). 

Figure 1. Woman with leprosy in Northern India. Photo credit: Wan-Yan King via Flickr.

Usually the bacteria we hear about on the news or from a health-focused institution are not neglected. Governments and regulators want to ensure that food and other consumables are free of pathogens, so guidelines are issued to make the public aware. For instance, the FDA website says that Salmonella “can survive several weeks in dry environments and several months in wet environments.” This informs the public about what makes Salmonella such a good pathogen⁠—it survives and sticks around waiting for the next host [1].

But what about pathogens that need a host? Some bacteria require a host for basic survival because that host provides all of their nutrients, and being without a host leads to certain death. A great example of this type of pathogen is the bacteria M. leprae, the causative agent of Hansen’s Disease (HD), also known as leprosy. 

M. leprae is an old pathogen⁠—genome analysis tells us it evolved around 100,000 years ago into the species that still exists today. Since that time, some of its genes have become non-functional and the “ghost” of these genes can be found in the DNA sequence. These ghostly remains of genes are called pseudogenes. The gene functions “lost” were ones that M. leprae didn’t need if it was going to be entirely dependent on its host. This includes losing the ability to break down complex nutrients like fats, eliminating the utilization of different sugars, and being unable to produce energy in oxygenless environments. All of these factors combined have likely contributed to its extremely slow growth; a single bacteria only divides once every 14 days! In comparison, E. coli doubles every 20-30 minutes and the closely-related species Mycobacterium tuberculosis doubles every 24 hours. 

This concept of decreasing the number of functional genes down to a minimum is called reductive evolution. M. leprae’s functional genome is down to 60% [2]. Other bacteria have also pursued reductive evolution as a means to being a more host-dependent pathogen, including Yersinia pestis (the plague), Bordetella pertussis (whooping cough), Mycobacterium ulcerans (Buruli ulcer)[3], and chlamydia trachomatis (chlamydia)[4], amongst many others. 

Given that the genome has been reduced, one would think that transmission of the bacteria from person to person would be reduced as well. So, how does a minimalist pathogen like M. leprae spread?  They are hypothesized to spread by aerosolization through sneezing or coughing, since the bacteria have been found in the mucus membrane [5]. This aerosolization route is the same method of spreading as the common cold and tuberculosis, but disseminating the disease is not the same thing as being infected by it. Catching M. leprae is much more difficult than the common cold or tuberculosis. A year-long study conducted in Bangladesh looked at 250 households that had at least 1 member with an active case of leprosy. During the study, only 4 other household members contracted leprosy, demonstrating the limited ability of M. leprae to spread from one person to another [6]. 

For those that contract leprosy, the disease progression is slow. It begins with skin discoloration, painless lumps, stiff and scaly skin, and loss of eyebrows. The lack of pain is due to M. leprae targeting the nerve cells of the fingers, toes, and limbs. This exacerbates the problem of not feeling injuries, resulting in deformity from accidents like not feeling the heat from a fire or stove. Additionally, the affected areas may experience muscle weakness/paralysis and perhaps blindness if the optic nerves are infected. Advanced leprosy can cripple the hands and feet, create burning sensations, cause nose disfigurement, and shorten the fingers and toes, amongst other deformities [7].

From such deformities, across time and location there has been stigma and fear surrounding people afflicted with M. leprae. Leprosy has been documented as far back as 1400 BCE in India and across East Asia. It likely entered the Middle East and eastern Europe with Alexander the Great and was given the name “elephantiasis Graecorum” by the Greeks [8]. The Roman invasions, and subsequent Crusades, spread M. leprae further around Europe. In the Middle Ages, religious orders and communities created special houses for people with leprosy to  separate them from where other people lived, thus perpetuating the idea that leprosy is spread by touch. Additionally, the severe disfigurement that occurs with advanced leprosy created an atmosphere of stigma and fear of those afflicted [9]. People’s revulsion to those with leprosy lasted well into the 20th century with the rise of institutional (and legally mandated) residences away from their friends, family, and community. These locations were called leprosaria. The most famous one in the USA is in Carville, Louisiana: it was there that  antibiotics for treating leprosy were developed and optimized in the 1940s [10]. Further work was done to reduce stigma about leprosy by encouraging doctors to not use the term “lepers” anymore, and to be replaced with “patients suffering from leprosy” [11].

Figure 2. A sample from the pamphlet, “Leprosy News and Notes”, from the 1948 Fifth International Leprosy Conference.

208,619 new cases of leprosy were reported in 2018, but with leprosy’s slow disease progression, many new cases are missed every year. Areas persist in poor, developing countries where leprosy is still common, even though it can be cured with antibiotics. This adds leprosy to the list of Neglected Tropical Diseases, because leprosy is all but ignored by major healthcare initiatives in the world [12]. 

[1] Salmonella (Salmonellosis). Food and Drug Administration (2019).

[2] Cole, S. T., K. Eiglmeier, J. Parkhill, K. D. James, N. R. Thomson, P. R. Wheeler, N. Honore et al. “Massive gene decay in the leprosy bacillus.” Nature 409, no. 6823 (2001): 1007-1011.

[3] Demangel, Caroline, Timothy P. Stinear, and Stewart T. Cole. “Buruli ulcer: reductive evolution enhances pathogenicity of Mycobacterium ulcerans.” Nature Reviews Microbiology 7, no. 1 (2009): 50-60.

[4] Giles, Teresa N., Derek J. Fisher, and David E. Graham. “Independent inactivation of arginine decarboxylase genes by nonsense and missense mutations led to pseudogene formation in Chlamydia trachomatis serovar L2 and D strains.” BMC Evolutionary Biology 9, no. 1 (2009): 1-13.

[5] Araujo, Sergio, Larissa Oliveira Freitas, Luiz Ricardo Goulart, and Isabela Maria Bernardes Goulart. “Molecular Evidence for the Aerial Route of Infection of Mycobacterium leprae and the Role of Asymptomatic Carriers in the Persistence of Leprosy.” Clinical Infectious Diseases 63, no. 11 (2016): 1412-1420.

[6] Tió-Coma, Maria, Charlotte Avanzi, Els M. Verhard, Louise Pierneef, Anouk Van Hooij, Andrej Benjak, Johan Chandra Roy et al. “Genomic Characterization of Mycobacterium leprae to Explore Transmission Patterns Identifies New Subtype in Bangladesh.” Frontiers in Microbiology (2020): 1220.

[7] Signs and Symptoms | Hansen’s Disease (Leprosy). Centers for Disease Control and Prevention (2017).

[8] “Etymologia: Leprosy.” Emerging Infectious Diseases vol. 21,12 (2015): 2134. 

[9] Bennett, Brian H., David L. Parker, and Mark Robson. “Leprosy: steps along the journey of eradication.” Public Health Reports 123, no. 2 (2008): 198-205.

[10] Han, Xiang Y., and Francisco J. Silva. “On the age of leprosy.” PLoS Neglected Tropical Diseases 8, no. 2 (2014): e2544.

[11] History of Leprosy: The United States of America. International Leprosy Association. Accessed Feb 9 2022.

[12] World Leprosy Day: Bust the Myths, Learn the Facts | Hansen’s Disease (Leprosy). Centers for Disease Control and Prevention (2021).