HISTORY OF

LEPROSY
Presented by Chandana.M
 The history of leprosy was traced to its origins by an international team of 22 geneticists using comparative
genomics of the worldwide distribution of Mycobacterium leprae. Monot et al. (2005) determined that leprosy
originated in East Africa or the Near East and traveled with humans along their migration routes, including those
of trade in goods and slaves.
The four strains of M. leprae are based in specific geographic regions where each predominantly occurs:
Strain 1 – East Africa, Asia, and the Pacific region
Strain 2 – Ethiopia, Malawi, Nepal/North India, and New Caledonia
Strain 3 – Europe, North Africa, and the Americas; and
Strain 4 – West Africa and the Caribbean.

They created a map of the dissemination of leprosy in the world. This confirmed the spread of the disease along
the migration, colonisation, and slave trade routes taken from East Africa to India, West Africa to the New World,
and from Africa into Europe and vice versa.
 In 1873 G.H. Armauer Hansen in Norway discovered the causative agent of leprosy,
Mycobacterium leprae. This was the first bacterium to be identified as causing disease in
humans.From the 19th century, European nations adopted some practices of India and China,
administering naturally occurring oils.
They were given by injection and orally, and were believed to cure some people, but results
were often disputed. It was not until the 1940s that the first effective treatment, promin,
became available.The search for additional anti-leprosy drugs led to the use of clofazimine
and rifampicin in the 1960s and 1970s.
Later, Indian scientist Shantaram Yawalkar and his colleagues formulated a combined
therapy using rifampicin and dapsone, intended to mitigate bacterial resistance.Multi-drug
therapy (MDT) combining all three drugs was first recommended by the World Health
Organization (WHO) of the United Nations in 1981. These three anti-leprosy drugs are still
used in the standard MDT regimens.
 ETYMOLOGY
The word leprosy comes from ancient Greek Λέπρα [léprā], "a disease that makes the
skin scaly", in turn, a nominal derivation of the verb Λέπω [lépō], "to peel, scale off".
Throughout history, individuals with leprosy have been known as lepers. In the 21st
century, this term is falling into disuse as a result of the diminishing number of leprosy
patients. Because of the stigma to patients, some prefer not to use the word 'leprosy',
preferring 'Hansen's disease'. The term 'leprosy' is still used by the U.S. Centers for
Disease Control and Prevention and the World Health Organization.
 ANCIENT
The ability to use historical records to trace the spread and treatment of leprosy in
antiquity is greatly limited by confusion over which skin diseases were being
discussed.[8] Famously, the "leprosy" of most translations of the Bible as far back as
the Septuagint represents a multilayered historical process of confusion. The state of
ritual impurity known to the Hebrews as tzara'ath (‫ָצַרַעת‬, "struck")[9] seems to have
been a conflation of various skin disorders, owing to the undeveloped state of medical
science at that period. The Greek term employed to translate the Hebrew was lépra
(λέπρα, "scaly"), which possessed an entirely separate diagnostic history which dealt
with psoriasis and dandruff, only being applied to leprosy in a later period.[10] A
tumorous skin disease described in the Ebers Papyrus dating to c.1550 bc has found
some identification as leprosy, however, given that the text presents surgical excision
of the tumors as an effective treatment, the implicated disorder likely refers to a skin
condition such as epidermoid cysts.
 Debatably, the oldest known records of genuine Hansen's disease are the Indian vedas, whose
kuṣṭha (कु ष्ठ, "eating away") is clearly focused on leprosy by the time of Suśruta's Compendium,
which prescribes chaulmoogra oil as the remedy;[11] unfortunately, its usual dating to 600 bc is
wrong and the present text may be as recent as ad 600.[12] Similarly, the "Great Chronicle" of
Sri Lanka describes royal ancestors of Gautama Buddha who contract leprosy, flee to the
wilderness, and cure themelves using herbal medicine sometime before 700 bc but the present
text dates to the 5th century or later. The Vendidad of the Zoroastrian Avesta, surviving only in
texts after ad 1300 but presumably recording practices nearly as old as the Vedas, discusses
leprosy as paēsa (Avestan: 𐬀𐬯𐬉𐬀𐬞) and prescribes direct application of cow's urine as a cure.
[13] Writing in the 5th century bc, Herodotus mentions the Persian practice of shunning native
lepers and deporting foreign ones as part of a discussion of that area's peculiar habits; he
reported that they considered the condition to have been caused by offense against the sun god.
[14][15] The ancient Greek and Roman doctors considered that "elephantitis" had been
introduced to their areas by the armies of Alexander and Pompey, respectively. It is discussed in
particular by the authors Aulus Cornelius Celsus (25 bc – ad 37) and Pliny the Elder (ad 23–
79).
The "Models for Sealing and Investigating" ( 封診式 , Fēngzhěnshì), written
between 266 and 246 bc in the State of Qin during the Warring States period,
is the earliest known Chinese text which describes the symptoms of leprosy,
termed under the generic word li ( 癘 ) used for various skin disorders.[16]
This text mentioned the destruction of the nasal septum in those with leprosy,
an observation that would not be made outside of China until the writings of
Avicenna in the 11th century; according to Katrina McLeod and Robin Yates
it also stated lepers had "swelling of the eyebrows, loss of hair, absorption of
nasal cartilage, affliction of knees difficult and hoarse respiration, as well as
anaesthesia."
 MODERN

Medical texts from the medieval period have loose and seemingly incorrect depictions
of leprosy, leading some historians to suspect that doctors of the era were not able to
distinguish leprosy from other ailments such as syphilis. Nevertheless, analysis of
human remains in leper colony graveyards shows that the vast majority were affected
by advanced forms of the disease considered as leprosy by modern doctors, so it is
possible that medical practitioners of the era were better at distinguishing the disease
than the scholars who wrote the manuscripts that survived to modern times.
 In 1846, Francis Adams compiled The Seven Books of Paulus Aegineta, which
included a commentary on all medical and surgical knowledge and descriptions and
remedies from the Romans, Greeks, and Arabs. Descriptions of what is believed to be
leprosy are included.[18][19] A proven ancient human case was verified by DNA taken
from the shrouded remains of a man discovered in a tomb next to the Old City of
Jerusalem; it was dated by radiocarbon methods to ad 1–50.[20]

Skin infections causing symptoms similar to leprosy were likely common in the
ancient world. In particular, tinea capitis (fungal scalp infection) and related infections
on other body parts caused by the dermatophyte fungus Trichophyton violaceum are
abundant in the late 20th century throughout North Africa and the Middle East. They
may also have been common in biblical times. Likewise, the disfiguring skin disease
favus is caused by Trichophyton schoenleinii, which appears to have been common
throughout Africa and Eurasia before the advent of modern medicine.
As late as the 17th century in Europe, persons with severe favus and similar
fungal diseases (and potentially also with severe psoriasis and other diseases
not caused by microorganisms) tended to be classified as having leprosy.The
painting The Regents of the Leper Hospital in Haarlem 1667 by Jan de Bray
(Frans Hals Museum, Haarlem, the Netherlands) shows a young Dutchman
with a vivid scalp infection. It may have been caused by a fungus, but he is
being cared for by three officials of a charitable home intended for people
with leprosy. The use of the word "leprosy" before the mid-19th century,
when microscopic examination of skin for medical diagnosis was first
developed, can seldom be correlated reliably with leprosy as it is understood
today.
 GENETIC ANALYSIS
DNA analysis has been applied to the origins and history of leprosy. Geneticists in
2005 used comparative genomics to study these aspects, including the paths of how the
disease was spread throughout the world. The researchers determined that leprosy
originated in East Africa or the Near East and traveled with humans along their
migration routes, including those of trade in goods and slaves. The four strains of M.
leprae are based in specific geographic regions where each predominantly occurs:[1]

Strain 1 – East Africa, Asia, and the Pacific region

Strain 2 – Ethiopia, Malawi, Nepal/North India, and New Caledonia
Strain 3 – Europe, North Africa, and the Americas; and
Strain 4 – West Africa and the Caribbean.
The researchers created a map showing the dissemination of leprosy by these strains.
The disease clearly accompanied humans along their migration, colonisation, and slave
trade routes taken since ancient times. Some peoples traveled from East Africa to
India, millions were taken in the slave trade from West Africa to the New World, and
others traveled from Africa into Europe and vice versa.
 In 2009 skeletal remains from the second millennium BCE were discovered at
Balathal, in Rajasthan, northwest India. Study and analysis of these remains were
documented as the oldest skeletal evidence for leprosy. The scholars who studied these
remains suggest that, if the disease did migrate from Africa to India during the third
millennium BCE, "at a time when there was substantial interaction among the Indus
Civilization, Mesopotamia, and Egypt, there needs to be additional skeletal and
molecular evidence of leprosy in India and Africa so as to confirm the African origin
of the disease."[22] Evidence for the disease was later confirmed in the human skeletal
remains from the archaeological site of Harappa, in Pakistan.[23] The disease was thus
present in the urban centers of the Indus civilization before 2000 BCE, further
supporting the hypothesis it migrated here as part of the "third millennium BCE
interaction sphere" – an exchange network that spanned the Arabian Sea.
 Discovery of bacterium
After the end of the 17th century, Norway, Iceland, and England were the countries in
Western Europe where leprosy was a significant problem. Norway appointed a medical
superintendent for leprosy in 1854 and established a national register for people with leprosy
in 1856. This was the first national patient register in the world.[24]

Mycobacterium leprae, the causative agent of leprosy, was discovered by G. H. Armauer

Hansen in Norway in 1873, making it the first bacterium to be identified as causing disease
in humans.[2][25] Hansen observed a number of nonrefractile small rods in unstained tissue
sections. The rods were not soluble in potassium lye, and they were acid- and alcohol-fast.
In 1879, he stained these organisms with Ziehl's method and noted the similarities with
Koch's bacillus (Mycobacterium tuberculosis). There were three significant differences
between these organisms:

(1) the rods in the leprosy lesions were extremely numerous,

(2) they formed characteristic intracellular collections (globii), and
(3) the rods had a variety of shapes with branching and swelling.
These differences suggested that leprosy was caused by an organism related to but distinct
from Mycobacterium tuberculosis. Hansen worked at St. Jørgens Hospital in Bergen,
founded early in the fifteenth century. St. Jørgens is now preserved as Lepramuseet – a
museum related to the history and research of leprosy.
 Hansen's finding was opposed principally by his father-in-law, Daniel Cornelius
Danielssen, who considered it a hereditary disease. He had described it as such in his
book, Traité de la Spedalskhed ou Elephantiasis des Grecs – the standard reference
book on leprosy from 1848 until the death of Danielssen in 1895.[27] While
Danielssen's book was a highly used source and provided a solid foundation for
worldwide leprosy understanding, it was soon surpassed. In 1867 Dr. Gavin Milroy
finished the Royal College of Physicians' report on leprosy. His work, which compiled
data from all corners of the British Empire, agreed with Danielssen that leprosy was a
hereditary disease. In addition, he said that leprosy was also a constitutional disease
that could be mitigated by improvements to a patient's health, diet, and living
conditions
 Historical treatments
The disease was known in Ancient Greece as elephantiasis (elephantiasis graecorum).
At various times blood was considered to be a treatment either as a beverage or as a
bath; sometimes the blood of children or virgins was required, suggesting associations
of ritual purity.[29] Europeans associated this practice with the Ancient Egyptians, but
it appears to have been developed independently in China. This practice was used
until at least 1790, when the use of dog blood was mentioned in De Secretis Naturae.
Paracelsus recommended the use of lamb's blood, and blood from dead bodies was
sometimes used.

Snakes were also used, according to Pliny, Aretaeus of Cappadocia, and Theodorus.
Gaucher recommended treatment with cobra venom. Boinet, in 1913, tried increasing
doses of bee stings (up to 4000). Scorpions and frogs were used occasionally instead
of snakes. The excreta of Anabas (the climbing fish) was also tried.

Alternative treatments included scarification with or without the addition of irritants

including arsenic and hellebore. Castration was also practiced in the Middle Ages.
 A common pre-modern treatment of leprosy was chaulmoogra oil. The oil has long
been used in India as an Ayurvedic medicine for the treatment of leprosy and various
skin conditions. It has also been used in China and Burma. It was introduced to the
West by Frederic John Mouat, a professor at Bengal Medical College. He tried the oil
as an oral and topical agent in two cases of leprosy and reported significant
improvements in an 1854 paper.[31]

This paper caused some confusion. Mouat indicated that the oil was the product of a
tree Chaulmoogra odorata, which had been described in 1815 by William Roxburgh, a
surgeon and naturalist, while he was cataloging the plants in the East India Company's
botanical garden in Calcutta. This tree is also known as Gynocardia odorata. For the
rest of the 19th century, this tree was thought to be the source of the oil. In 1901, Sir
David Prain identified the chaulmoogra seeds of the Calcutta bazaar and of the Paris
and London apothecaries as coming from Taraktogenos kurzii, which is found in
Burma and Northeast India. The oil mentioned in the Ayurvedic texts was determined
to be from the tree Hydnocarpus wightiana, known as Tuvakara in Sanskrit and
chaulmugra in Hindi and Persian.
 The first parenteral administration was given by the Egyptian doctor Tortoulis Bey,
personal physician to the Sultan Hussein Kamel of Egypt. He had been using
subcutaneous injections of creosote for tuberculosis. In 1894 he administered
subcutaneous injection of chaulmoogra oil to a 36-year-old Egyptian Copt who had
been unable to tolerate oral treatment. After 6 years and 584 injections, the patient was
declared cured.

An early scientific analysis of the oil was carried out by Frederick B. Power in
London in 1904. He and his colleagues isolated a new unsaturated fatty acid from the
seeds, which they named 'chaulmoogric acid'. They also investigated two closely
related species: Hydnocarpus wightiana and Hydnocarpus anthelmintica. By
comparing material from the trees, they isolated both chaulmoogric acid and a closely
related compound, 'hydnocarpus acid'. They also investigated Gynocardia odorata and
found that it produced neither of these acids. Later investigation showed that
'taraktogenos' (Hydnocarpus kurzii) also produced chaulmoogric acid.
Administration of the oil was difficult. Taken orally it is extremely nauseating. Given
by enema may cause peri-anal ulcers and fissures. Given by injection the drug caused
fever and other local reactions. The first successful leprosy treatment was developed
in 1916 by African-American Chemist Alice Ball, who came up with the pioneering
injectable oil treatment at the University of Hawaii. Tragically, Ball died in a lab
accident shortly after inventing the treatment. She was just 24 years old.

Despite these difficulties, a series of 170 patients were studied in 1916 by Ralph
Hopkins, the attending physician at the Louisiana Leper Home in Carville, Louisiana.
He divided the patients into two groups – 'incipient' and 'advanced'. He reported that in
the advanced cases, 25% (at most) showed any improvement or arrest of their
condition; in the incipient cases, 45% showed an improvement or stabilization of the
disease (mortality rates were 4% and 8%, respectively). The remainder absconded
from the Home, apparently in improved condition
Given the apparent usefulness of this agent, a search began for improved formulations.
Victor Heiser the Chief Quarantine Officer and Director of Health for Manila, and
Elidoro Mercado the house physician at the San Lazaro Hospital for lepers in Manila,
decided to add camphor to a prescription of chaulmoogra and resorcin, which was
typically given orally. This was at the suggestion of Merck and Company in Germany
to whom Heiser had written. They found that patients could tolerate this new
compound without the nausea that had accompanied the earlier preparations.

Heiser and Mercado in 1913 administered the oil by injection to two patients, with the
result that they were cured of the disease. Since the doctors had been using the oil in
conjunction with other materials, the results were not clear. Two additional patients
were treated by injections of oil alone and appeared to be cured of the disease. The
following year, Heiser reported on an additional 12 patients, but the results were
mixed.
 Researchers worked to develop less toxic injectable forms of this oil. Merck of
Darmstadt had already produced a version of the sodium salts in 1891. They named
this sodium gynocardate in the mistaken belief that the origin of the oil was
Gynocardia odorata. Bayer in 1908 marketed a commercial version of the esters under
the name 'Antileprol'. At the University of Hawaii, the young chemist Alice Ball
developed a chemical process that made the oil less hydrophobic and therefore more
readily absorbed by the body. She died before she could see the results of her work:
After being treated with the modified oil, 78 patients were able to return home from
leper colonies in 1920. Despite the common side effects and continuing debates about
its efficacy, chaulmoogra oil remained the best available treatment for leprosy into the
1940s.

To ensure a supply of this agent, Joseph Rock, Professor of Systematic Botany at the
College of Hawaii, traveled to Burma to procure seeds of the trees. The local villagers
located a grove of trees in seed, which he used to establish a plantation of 2,980 trees
on the island of Oahu, Hawaii between 1921 and 1922. There continued to be
numerous leprosy patients in the islands.
 MODERN TREATMENT
Promin was synthesised in 1940 by Feldman of Parke-Davis and company.[43]
Although Parke-Davis synthesised the compound, it seems certain that they
were not the first. In the same year that Gelmo described sulphanilamide
(1908), Emil Fromm, professor of chemistry in the medical faculty of the
University of Freiburg im Breisgau, in Germany, described another compound
related to the sulphonamides: this was diaminodiphenylsulphone or dapsone
(DDS). No one recognised the potential of this compound until Buttle and his
colleagues at the Wellcome laboratories and Fourneau and the researchers at
the Institut Pasteur simultaneously found in 1937 that dapsone was ten times as
potent against streptococcal infection in mice and about a hundred times as
toxic as sulphanilamide.
 Until the introduction of treatment with promin in the 1940s, there was no effective
treatment for leprosy. The efficacy of promin was first discovered by Guy Henry Faget
and his co-workers in 1943 at Carville, Louisiana. Robert Cochrane was the first to
use DDS, the active component of promin, at the Lady Willingdon Leprosy
Settlement, in Chingleput, near Madras, India. John Lowe was the first to successfully
administer DDS orally at Uzuakoli Leper Settlement, in Nigeria, in spite of indications
that the drug was highly toxic. Both innovations made it possible to produce a
treatment that was cheap, seemingly effective, and could be distributed on a large
scale.

Scientists eventually realised that DDS was only weakly bactericidal against M.
leprae, and it was considered necessary for patients to take the drug indefinitely. When
dapsone was used alone, the M. leprae population quickly evolved antibiotic
resistance. By the 1960s, the world's only known anti-leprosy drug became ineffective
against resistant bacteria.
 The search for more effective anti-leprosy drugs led to the use of clofazimine and
rifampicin in the 1960s and 1970s.[4] Later, Indian scientist Shantaram Yawalkar and
his colleagues formulated a combined therapy using rifampicin and dapsone, intended
to mitigate bacterial resistance.[5] The first trials of combined treatment were carried
out in Malta in the 1970s.

Multidrug therapy (MDT) combining all three drugs was first recommended by a
WHO Expert Committee in 1981. These three anti-leprosy drugs are still used in the
standard MDT regimens. None of them is used alone because of the risk of developing
resistance.

As this treatment was quite expensive, it was not quickly adopted in most countries
where the disease is endemic. In 1985, leprosy was still considered a public health
problem in 122 countries. The 44th World Health Assembly (WHA), held in Geneva in
1991, passed a resolution to eliminate leprosy as a public-health problem by the year
2000 – defined as reducing the global prevalence of the disease to less than 1 case per
10,000. At the Assembly, the World Health Organization (WHO) was given the
mandate to develop an elimination strategy by its member states. This was based on
increasing the geographical coverage of MDT and patients' accessibility to the
treatment. Novartis produces this medication for free.
T ha nk
y o u !