Leprosy: From Leviticus to Novartis

What disease can we relate to Jesus, armadillos, Parkinson's Disease, and vaccination with BCG (Bacillus Calmette–Guérin). Hint: Dr. Hansen of Norway became the first to show that a bacterium could cause human disease.

Prior to Dr. Hansen’s discovery that leprosy is the exemplar of the ‘germ theory’ of disease, it was thought to be either hereditary or ‘miasmatic’ in origin. Miasma (due to ‘bad air’) was a prevailing explanation for other contagions such as cholera and plague. As a pathogen, the causative agent, Mycobacterium leprae, has been a fellow traveler with humans for millennia. It has transitioned from a disfiguring incurable disease, leading to ostracization, to one that is curable (for free) and ever-diminishing in prevalence. But it left it’s stigma on millions.

Selected reading...

Dr. Hansen

Before we explore the ancient history and paleopathology of leprosy, lets complete the story of Dr. Hansen. In 1873 he isolated ‘something’ from the tissues of lepers which appeared with such strong association that it was regarded as causative. However, leprosy is hard to grow, and to use as an inoculum, and with which to satisfy Koch’s postulates for causation, (a tenant of germ theory research). That didn’t stop him from trying though, and he lost his hospital post having been sued for inoculating a women—without consent. Within a few years Robert Koch discovered another ‘acid-fast’ bacillus, leprosy’s cousin—tuberculosis. This Koch could grow and work with. But Leprosy he tried to, but failed, as did Hansen.

 Doctor Hansen

Doctor Hansen

 A Leper

A Leper

However, it was Hansen’s understanding of the epidemiology of the disease that sustained his career, which ended honorably as Norway enjoyed a marked decline in the disease due to public health measures which he supervised. 

The history of the histologic investigations of the disease is no less intriguing. Before Hansen, Danielssen and Boeck described pathognomonic brown granules (1847) and Virchow noted the presence of foamy histiocytes (1864), and so lumped it in with other ‘granulomatous’ diseases such as lupus and syphilis, the later of which Dr. Hansen had as a chronic condition. Five years after Hansen made his discovery, Dr. Neisser showed up in his lab with a box of synthetic dyes. With these he was able to clearly identify Mycobacterium leprae. (Yes, that Neisser, the one who discovered Neisseria gonorrhoeae)Before long, an academic cat fight broke out in the journals. 

 mycobacteria on acid-fast stain

mycobacteria on acid-fast stain

Fellow Traveler

Comparative genomics puts the origin of leprosy in East Africa or the Near East, with migration along trades routes, eventually with four different strains assuming specific geographies.

 Leprosy distribution WHO 2003. Red is highest rate.

Leprosy distribution WHO 2003. Red is highest rate.

The earliest known cases, based on characteristic skeletal lesions, were discovered in northwest India and are from the second millennium BC. The earliest based on DNA evidence is from Jerusalem c.1-50 AD. Most of us are aware of the antiquity of leprosy from Bible references. However, ‘leprosy’ as discussed In the Bible may not be leprosy as caused by the mycobacterium.

Leviticus

In the Gospel of Luke (17:11-19) we are told that Jesus performed a roadside miracle by healing ten lepers. Leprosy in the Bible was likely conflated with any number of skin lesions, but these were taken very seriously, as discussed in the Old Testament. Leviticus chapters 14 and 15 outline the Law of Tzaraath. In the broadest the term includes blemishes of skin, of garments or even on walls. The derivation of the Hebrew ‘Tzaraath’ from ‘smiting’ implied a punishment for sin. Greek interpretations of the Bible used the term lepra, which use in Greek was restricted to a skin blemish. Some scholars glean from the descriptions of ‘leprosy’ in the Bible that the lesions were non-contagious, associated with patches of white hair and with rapid growth. This suggests that vitiligo was more likely the skin condition that stigmatized individuals. Isolation was in fact based on sinful character, not fear of contagion.

The Pilgrim and the King

In 1200AD the cemetery of the church of St. Mary Magdalen in Winchester, UK was the final resting place of a number of people whose skeletal remains has the hallmarks of leprosy. A team of archeologists and other scientists took special interest in one that had been interred with a scallop shell. The analysis of the shell showed it be a type (Pectus maximus) indigent to a region of Spain where stood on of the great shrines of the Middle Ages. They were dealing with a pilgrim. 

They brought all the sophisticated tools of paleopathology to the project and published the results as an open source document on PLOS (Public Library of Science). Isotope analysis of carbon, nitrogen, strontium and oxygen made bone, collagen and teeth give up the historic age of this young adult male. PCR and gene sequencing of DNA allowed them to find and genotype M.lepra. They were surprised to find a particular strain, 2F, that suggested the person was from central Asia or the Middle East, and his cranial morphology suggested he was not indigenous to the burial region.

 Pilgrim leper, c1200AD

Pilgrim leper, c1200AD

Around the time that our pilgrim was buried, and apparently not shunned, as in Biblical times, there was another leper who enjoyed even higher status—King Baldwin IV, the “Leper King of Jerusalem” (1161—1185). His leprosy was apparent as a young teen, complete with skin lesions and sensory deficit. He lived to age 24 but managed to defeat Saladin in battle and secure his throne for his family. He is depicted in the feature film Kingdom of Heaven.

 King Baldwin's leprosy discovered

King Baldwin's leprosy discovered

Novartis

Leprosy is more than a chronic skin disease. And, no, the flesh does not fall off. But it can be a devastating disease. The sensory deficit leads to injuries and infection. Cartilage gets absorbed, resulting in deformed digits, nasal deformity (leprous facies). Upper respiratory tract and eyes can be injured. There are a number of clinical staging systems for extent of disease, a common one being pauci(few) vs multi(many) –bacillary forms, referring to the number of skin lesions. It can be lethal, especially that caused by a newly identified speciesM.lepromatosis, which leads to diffuse lepromatous leprosy, known as Lucio’s phenomenon.

 leprous hands

leprous hands

 leprous nasal cavitation

leprous nasal cavitation

With awareness of the contagious factors, nasal droplets but not sex apparently, and prompt treatment the incidence has declined dramatically. BCG vaccination is effective about half the time. And leprosy can be cured. And the cure has been free since 1995 via a program of the WHO, aided at first by the Nippon Foundation, then since 2000 subsidized by free drug from Novartis. Novartis just got FDA approval for a novel gene-based therapy for leukemia. And it has renewed its commitment to “go the last mile in effort to eliminate leprosy,” committing $40M over five years to reach 1.3 million patients world wide. See there related articles (free) in Lancet this month (on multidrig therapy (dapsone, clofazimine, rifampicin) and controlling transimission).

What is on the horizon? A better understanding of the molecular etiology of M.leprae. It has been known for centuries that some people are more susceptible to getting it than others. The reason may be related to variants on the PARK2 and PACRG genes, which are associated with increased risk of leprosy. PARK2, as it turns out, is the cuase of early onset Parkinson’s Disease. 

[Armadillos? I thought you'd never ask. Armadilos, and red squirrels, are susceptible to infection by leprosy.] 

Reading...

Images of Leprosy: Disease, Religion, and Politics in European Art. Christine M Boeckl.

This interdisciplinary art-historical survey on lepra and its visualization in sculpture, murals, stained glass, and other media provides new information on the history of art, medicine, religion, and European society.

Leprosy in Medieval England. Carole Rawcliffe.

One of the most important publications for many years in the fields of medical, religious and social history. Rawcliffe's book completely overhauls our understanding of leprosy...