01 - Is Leprosy A Historical Disease?

Leprosy is one of the oldest diseases known to affect mankind. The disease is known by various names across the countries. The term 'leprosy' or the disease carries fear, stigma, and discrimination in most countries still reporting the condition. 

The article 'Is Leprosy A Historical Disease?' collates the historical aspects documented across different literature and how the causative bacteria evolved over time. This is an evolving article and is subject to change in the future. 

 
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Is Leprosy A Historical Disease?

Leprosy is a chronic infectious disease caused by a bacteria - Mycobacterium leprae. The leprosy bacteria are known to survive and disseminate in humans. The armadillos are known to be the natural reservoir of the disease. However, a recent study suggests humans infected armadillos first and now are giving them back.  

It is one of the oldest known diseases documented since Vedic times. The disease has affected millions of people across the world in modern times. The condition is well known to result in visible deformities if not treated or due to delayed treatment. 

 
The term lepros means scaly in Greek. Leprosy is known by different names across different countries:
 
India - Kushtha or Raktpit or Kodh
Japan - Raibyo
China - Mafung
Arabic - Judham
Russia - Prokaza
Germany - Aussatz 
France - Lepre
Spain - Lepra

 

Historical insights

Leprosy is one of the ancient diseases. The earliest record that mentions measures to prevent leprosy are Vedas which date back to 2000 BC (1). An Indian surgeon 'Sushruta' described using Chaulmoogra oil to treat leprosy in his book 'Sushruta Samhita' in 600 BC (2). 

A human skeleton excavated in 2009 in India dates back to 2000 BC and has evidence of lepromatous leprosy (3). References to leprosy are found in Egyptian Ebers papyrus as early as 1500 BC (4)

 

One of the earliest Chinese medical scripture Nei Jing in 400 BC, described the clinical features of leprosy under the name 'Da Feng'. The Egyptian mummies dating back to 2 BC are found to have bone involvement due to leprosy.

 

The leprosy infection probably reached Mediterranian from India through Alexander's army 327-326 BC after their military campaign on India, from the Mediterranean or Africa to Europe and America. The leprosy infection may have spread to China and from there to Korea, and further to Japan. 

The Old and the New Testaments of the Bible mention the disease (5). Al-Bukhari's Muslim Hadith (volume 1, 2.443) documented Prophet Mohammed's apparent dread of leprosy in his statement: “Escape from the leprous the way you escape from a lion” (2). Between 1000 to 1400 Current Era, Europe had almost 19,000 leprosy hospitals. 

 

The available literature suggests varied information about the geographic origin of the disease. Comparative genomics and DNA analysis suggest the original source of leprosy is probably in East Africa. From Africa, the infection reached India and other Asian countries, the middle east, and Europe, and from Europe and Asia to the Americas through travellers (6).

In 1874 Dr Gerhard A Hansen, a Norwegian physician, discovered the causative microorganism of leprosy disease - Mycobacterium leprae (7). Leprosy is also known as Hansen's disease, named after its discoverer. 

 

Evolution of Leprosy - Few Insights

The causative organism has evolved with human evolution. Genome-scale analysis indicates the ancestors' of tuberculosis and leprosy bacteria probably separated about 36 million years ago (8). 

The leprosy bacteria, during reductive evolution, retained the ESX-3 gene cluster involved in iron and zinc uptake. However, myobactin (mbt) gene cluster essential for in-vivo growth (9) and virulence seen in M. tuberculosis is missing in leprosy bacteria. 

The first Homo sapiens appeared about 200,000 years ago (10). Probably the last Neanderthals and the first Homo sapiens were exposed to leprosy and tuberculosis-causative organisms.

 

Bayesian dating analysis revealed M. leprae diverged from its Most Recent Common Ancestor (MRCA) about 13.9 million years ago, and the other strain, M. lepromatosis remained closer to its MRCA. Instead, M leprae has undergone reductive evolution (11, 12). 

 

Both strains cause leprosy disease and may cause visible disability in the modern era. Leprosy bacteria reprograms its preferred host niche, the de-differentiated adult Schwann cells, to progenitor stem cells-like cells (pSLC), which may facilitate bacterial spread in the body (13).   

 

M. lepromatosis, like M. leprae, cannot be cultured in any culture media. It was first described by Han et al. in 2008 (14). It is associated with Diffuse Lepromatous Leprosy and the reaction state Lucio phenomenon. M. lepromatosis is rare and isolated from a few Mexican leprosy patients. 

Though deaths are rare due to leprosy, Diffuse Lepromatous Leprosy caused by M. lepromatosis and the associated Lucio phenomenon is reported to have high mortality (15). Death may occur due to necrotising severe cutaneous reaction, blood dyscrasia or sepsis in such patients (16). M. lepromatosis differs from M. leprae in its ability to infiltrate the endothelium of the blood vessels. 

However, both leprosy bacteria respond to Multi-Drug Therapy (MDT).

References:
1. Bloomfield M. Hymns of the Atharva Veda. Whitefish, MT: Kessinger Publishing; 2004.
2. Dogra S, Narang T, Kumar B. Leprosy--evolution of the path to eradication. Indian J Med Res. 2013 Jan;137(1):15-35. Retraction in: Indian J Med Res. 2013 Dec;138(6):1038. PMID: 23481049; PMCID: PMC3657879.
3. Robbins G, Tripathy VM, Misra VN, Mohanty RK, Shinde VS, Gray KM, Schug MD. Ancient skeletal evidence for leprosy in India (2000 B.C.). PLoS One. 2009 May 27;4(5):e5669. doi: 10.1371/journal.pone.0005669. PMID: 19479078; PMCID: PMC2682583.
4. Hulse EV. Leprosy and Ancient Egypt. Lancet. 1972;2:1024.
5. Roberts C, Manchester K. The Archaeology of Disease. Ithaca: Cornell University Press; 2005.
6. Mark S. Early Human Migrations (ca. 13,000 Years Ago) or Postcontact Europeans for the Earliest Spread of Mycobacterium leprae and Mycobacterium lepromatosis to the Americas. Interdiscip Perspect Infect Dis. 2017;2017:6491606. doi: 10.1155/2017/6491606. Epub 2017 Nov 9. PMID: 29250112; PMCID: PMC5700473. 
7. Irgens, Lorentz. (2002). The discovery of the leprosy bacillus. Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række. 122. 708-9. 
8. Djelouadji Z, Raoult D, Drancourt M. Palaeogenomics of Mycobacterium tuberculosis: epidemic bursts with a degrading genome. Lancet Infect Dis. 2011 Aug;11(8):641-50. doi: 10.1016/S1473-3099(11)70093-7. Epub 2011 Jun 13. PMID: 21672667.
9.  Reddy PV, et al. (2013) Disruption of mycobactin biosynthesis leads to attenuation of Mycobacterium tuberculosis for growth and virulence. J Infect Dis 208(8):1255–1265.
10. Stringer C. The origin and evolution of Homo sapiens. Philos Trans R Soc Lond B Biol Sci. 2016 Jul 5;371(1698):20150237. doi: 10.1098/rstb.2015.0237. PMID: 27298468; PMCID: PMC4920294.
11. Singh P, Benjak A, Schuenemann VJ, Herbig A, Avanzi C, Busso P, Nieselt K, Krause J, Vera-Cabrera L, Cole ST. Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4459-64. doi: 10.1073/pnas.1421504112. Epub 2015 Mar 23. PMID: 25831531; PMCID: PMC4394283.
12. Cole, S. T., Eiglmeier, K., Parkhill, J., James, K. D., Thomson, N. R., Wheeler, P. R., Honore, N., Garnier, T., Churcher, C., Harris, D., Mungall, K., Basham, D., Brown, D., Chillingworth, T., Connor, R., Davies, R. M., Devlin, K., Duthoy, S., Feltwell, T., ...Barrell, B. G. (2001). Massive gene decay in the leprosy bacillus. Nature, 409(6823), 1007+. https://link.gale.com/apps/doc/A188007439/HRCA?u=anon~6ff0dc30&sid=googleScholar&xid=debfec2d
13. Masaki T, McGlinchey A, Tomlinson SR, Qu J, Rambukkana A. Reprogramming diminishes retention of Mycobacterium leprae in Schwann cells and elevates bacterial transfer property to fibroblasts. F1000research. 2013 ;2:198. DOI: 10.12688/f1000research.2-198.v3. PMID: 24358891; PMCID: PMC3829123.
14. Han XY, Seo YH, Sizer KC, Schoberle T, May GS, Spencer JS, Li W, Nair RG. A new Mycobacterium species causing diffuse lepromatous leprosy. Am J Clin Pathol. 2008 Dec;130(6):856-64. doi: 10.1309/AJCPP72FJZZRRVMM. PMID: 19019760.
15. Frade MAC, Coltro PS, Filho FB, Horácio GS, Neto AA, da Silva VZ, Westin AT, Guimarães FR, Innocentini LMAR, Motta ACF, Farina JA Junior. Lucio's phenomenon: A systematic literature review of definition, clinical features, histopathogenesis and management. Indian J Dermatol Venereol Leprol. 2022 May-Jun;88(4):464-477. doi: 10.25259/IJDVL_909_19. PMID: 34672479.
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