Leprosy
Overview
Leprosy or Hansen's disease (HD) is a chronic
Chronic
Chronic may refer to:* Chronic , a disease that is long-lasting and reoccurring.* Chronic toxicity, a substance with toxic effects after continuous or repeated exposure* The Chronic, a 1992 album by Dr. Dre...

 disease caused by the bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 Mycobacterium leprae
Mycobacterium leprae
Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...

and Mycobacterium lepromatosis
Mycobacterium lepromatosis
Mycobacterium lepromatosis is a bacterium that, along with Mycobacterium leprae, causes leprosy . It was only recently discovered, in 2008. Analysis of its 16S rRNA gene confirms that the species is distinct from Mycobacterium leprae.M.lepromatosis is an Acid Fast Bacilli which causes diffuse...

. Named after physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...

 Gerhard Armauer Hansen
Gerhard Armauer Hansen
Gerhard Henrik Armauer Hansen was a Norwegian physician, remembered for his identification of the bacterium Mycobacterium leprae in 1873 as the causative agent of leprosy....

, leprosy is primarily a granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...

tous disease of the peripheral nerves
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...

 and mucosa
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

 of the upper respiratory tract
Upper respiratory tract
The upper respiratory tract or upper airway primarily refers to the parts of the respiratory system lying outside of the thorax or above the sternal angle. Another definition commomly used in medicine is the airway above the glottis or vocal cords...

; skin lesions are the primary external sign. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes. Contrary to folklore, leprosy does not cause body parts to fall off, although they can become numb or diseased as a result of secondary infections; these occur as a result of the body's defences being compromised by the primary disease.
Encyclopedia
Leprosy or Hansen's disease (HD) is a chronic
Chronic
Chronic may refer to:* Chronic , a disease that is long-lasting and reoccurring.* Chronic toxicity, a substance with toxic effects after continuous or repeated exposure* The Chronic, a 1992 album by Dr. Dre...

 disease caused by the bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 Mycobacterium leprae
Mycobacterium leprae
Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...

and Mycobacterium lepromatosis
Mycobacterium lepromatosis
Mycobacterium lepromatosis is a bacterium that, along with Mycobacterium leprae, causes leprosy . It was only recently discovered, in 2008. Analysis of its 16S rRNA gene confirms that the species is distinct from Mycobacterium leprae.M.lepromatosis is an Acid Fast Bacilli which causes diffuse...

. Named after physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...

 Gerhard Armauer Hansen
Gerhard Armauer Hansen
Gerhard Henrik Armauer Hansen was a Norwegian physician, remembered for his identification of the bacterium Mycobacterium leprae in 1873 as the causative agent of leprosy....

, leprosy is primarily a granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...

tous disease of the peripheral nerves
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...

 and mucosa
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

 of the upper respiratory tract
Upper respiratory tract
The upper respiratory tract or upper airway primarily refers to the parts of the respiratory system lying outside of the thorax or above the sternal angle. Another definition commomly used in medicine is the airway above the glottis or vocal cords...

; skin lesions are the primary external sign. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes. Contrary to folklore, leprosy does not cause body parts to fall off, although they can become numb or diseased as a result of secondary infections; these occur as a result of the body's defences being compromised by the primary disease. Secondary infections, in turn, can result in tissue loss causing fingers and toes to become shortened and deformed, as cartilage is absorbed into the body.

Although the mode of transmission of Hansen's disease remains uncertain, most investigators think that M. leprae is usually spread from person to person in respiratory droplets. Studies have shown that leprosy can be transmitted to humans by armadillos. Leprosy is now known to be neither sexually transmitted nor highly infectious after treatment. Approximately 95% of people are naturally immune and sufferers are no longer infectious after as little as 2 weeks of treatment.

The minimum incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

 reported is as short as a few weeks, based on the very occasional occurrence of leprosy among young infants. The maximum incubation period reported is as long as 30 years, or over, as observed among war veterans known to have been exposed for short periods in endemic areas but otherwise living in non-endemic areas. It is generally agreed that the average incubation period is between three and five years.

Leprosy has affected humanity for over 4,000 years, and was well-recognized in the civilizations of ancient China
History of China
Chinese civilization originated in various regional centers along both the Yellow River and the Yangtze River valleys in the Neolithic era, but the Yellow River is said to be the Cradle of Chinese Civilization. With thousands of years of continuous history, China is one of the world's oldest...

, Egypt
Ancient Egypt
Ancient Egypt was an ancient civilization of Northeastern Africa, concentrated along the lower reaches of the Nile River in what is now the modern country of Egypt. Egyptian civilization coalesced around 3150 BC with the political unification of Upper and Lower Egypt under the first pharaoh...

, and India
History of India
The history of India begins with evidence of human activity of Homo sapiens as long as 75,000 years ago, or with earlier hominids including Homo erectus from about 500,000 years ago. The Indus Valley Civilization, which spread and flourished in the northwestern part of the Indian subcontinent from...

. In 1995, the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO) estimated that between 2 and 3 million people were permanently disabled because of leprosy at that time. In the past 20 years, 15 million people worldwide have been cured of leprosy. Although the forced quarantine
Quarantine
Quarantine is compulsory isolation, typically to contain the spread of something considered dangerous, often but not always disease. The word comes from the Italian quarantena, meaning forty-day period....

 or segregation of patients is unnecessary in places where adequate treatments are available, many leper colonies
Leper colony
A leper colony, leprosarium, or lazar house is a place to quarantine leprous people.-History:Leper colonies or houses became widespread in the Middle Ages, particularly in Europe and India, and often run by monastic orders...

 still remain around the world in countries such as India (where there are still more than 1,000 leper colonies), China, Romania
Romania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...

, Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

, Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...

, Somalia
Somalia
Somalia , officially the Somali Republic and formerly known as the Somali Democratic Republic under Socialist rule, is a country located in the Horn of Africa. Since the outbreak of the Somali Civil War in 1991 there has been no central government control over most of the country's territory...

, Liberia
Liberia
Liberia , officially the Republic of Liberia, is a country in West Africa. It is bordered by Sierra Leone on the west, Guinea on the north and Côte d'Ivoire on the east. Liberia's coastline is composed of mostly mangrove forests while the more sparsely populated inland consists of forests that open...

, Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...

, and Japan
National Hansen's Disease Museum (Japan)
The ' is a museum in Higashimurayama, Tokyo, Japan that is dedicated to education about Hansen's disease and to eliminate discriminatory practices against its sufferers...

. Leprosy was once believed to be highly contagious and was treated with mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...

 — all of which applied to syphilis
Syphilis
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis...

, which was first described in 1530. It is now thought that many early cases of leprosy could have been syphilis.

The age-old social stigma
Leprosy stigma
Leprosy stigma is a kind of social stigma, a strong feeling that a leprosy patient is shameful and is not accepted normally in society. Also called leprosy related stigma, leprostigma and stigma of leprosy.-Stigma:...

 associated with the advanced form of leprosy lingers in many areas, and remains a major obstacle to self-reporting and early treatment. Effective treatment for leprosy appeared in the late 1930s with the introduction of dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...

 and its derivatives. Leprosy bacilli
Bacillus (shape)
The word bacillus may be used to describe any rod-shaped bacterium, and such bacilli are found in many different taxonomic groups of bacteria. However, the name Bacillus, capitalized and italicized, refers to a specific genus of bacteria...

 resistant to dapsone soon evolved
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 and, due to overuse of dapsone, became widespread. It was not until the introduction of multidrug therapy (MDT) in the early 1980s that the disease could be diagnosed and treated successfully within the community.

MDT for multibacillary leprosy consists of rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...

, dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...

, and clofazimine
Clofazimine
Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients and...

 taken over 12 months. Dosages adjusted appropriately for children and adults are available in all primary health centre
Primary Health Centre
The Primary Health Centre is the basic structural and functional unit of the public health services in developing countries. PHCs were established to provide accessible, affordable and available primary health care to people, in accordance with the Alma Ata Declaration of 1978 by the member...

s in the form of blister packages. Single dose MDT for single lesion leprosy consists of rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...

, ofloxacin
Ofloxacin
Ofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class considered to be a second-generation fluoroquinolone. The original brand, Floxin, has been discontinued by the manufacturer in the United States on 18 June 2009, though generic equivalents continue to be...

, and minocycline
Minocycline
Minocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type...

. The move toward single-dose treatment strategies has reduced the prevalence of disease in some regions, since prevalence is dependent on duration of treatment.

World Leprosy Day was created to draw awareness to leprosy and its sufferers.

Classification

There are several different approaches for classifying leprosy; however, parallels exist.
  • The World Health Organization
    World Health Organization
    The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

     system distinguishes "paucibacillary" and "multibacillary" based upon the proliferation of bacteria ("pauci-" refers to a low quantity.)
  • The SHAY scale provides five gradations.
  • The ICD-10
    ICD-10
    The International Statistical Classification of Diseases and Related Health Problems, 10th Revision is a medical classification list for the coding of diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases, as maintained by the...

    , though developed by the WHO, uses Ridley-Jopling and not the WHO system. It also adds an indeterminate ("I") entry.
  • In MeSH
    Medical Subject Headings
    Medical Subject Headings is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences; it can also serve as a thesaurus that facilitates searching...

    , three groupings are used.

WHO Ridley-Jopling ICD-10
ICD-10
The International Statistical Classification of Diseases and Related Health Problems, 10th Revision is a medical classification list for the coding of diseases, signs and symptoms, abnormal findings, complaints, social circumstances, and external causes of injury or diseases, as maintained by the...

MeSH
Medical Subject Headings
Medical Subject Headings is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences; it can also serve as a thesaurus that facilitates searching...

Description Lepromin
Lepromin
The lepromin skin test is used to determine what type of leprosy a person has. It involves the injection of a standardized extract of the inactivated "leprosy bacillus", under the skin...

 test
Immune target
Paucibacillary tuberculoid ("TT"), borderline tuberculoid ("BT") A30.1, A30.2 Tuberculoid It is characterized by one or more hypopigmented
Hypopigmentation
Hypopigmentation is the loss of skin color. It is caused by melanocyte or melanin depletion, or a decrease in the amino acid tyrosine, which is used by melanocytes to make melanin.-Treatments:...

 skin macules and anaesthetic patches, where skin sensations are lost because of damaged peripheral nerves that have been attacked by the human host's immune cells.
Positive bacillus (Th1)
Multibacillary midborderline or borderline ("BB") A30.3 Borderline Borderline leprosy is of intermediate severity and is the most common form. Skin lesions resemble tuberculoid leprosy but are more numerous and irregular; large patches may affect a whole limb, and peripheral nerve involvement with weakness and loss of sensation is common. This type is unstable and may become more like lepromatous leprosy or may undergo a reversal reaction, becoming more like the tuberculoid form.
Multibacillary borderline lepromatous ("BL"), and lepromatous ("LL") A30.4, A30.5 Lepromatous It is associated with symmetric skin lesion
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...

s, nodules
Nodule (medicine)
For use of the term nodule in dermatology, see Nodule In medicine, a nodule refers to a relatively hard, roughly spherical abnormal structure....

, plaques, thickened dermis, and frequent involvement of the nasal mucosa resulting in nasal congestion and epistaxis (nose bleeds), but, typically, detectable nerve damage is late.
Negative plasmid inside bacillus (Th2)


There is a difference in immune response to the tuberculoid and lepromatous forms.

Hansen's disease may also be divided into the following types:
  • Early and indeterminate leprosy
  • Tuberculoid leprosy
    Tuberculoid leprosy
    Tuberculoid leprosy is a skin condition characterized by solitary skin lesions that are asymmetrically distributed....

  • Borderline tuberculoid leprosy
    Borderline tuberculoid leprosy
    Borderline tuberculoid leprosy is a cutaneous condition similar to tuberculoid leprosy except the skin lesions are smaller and more numerous....

  • Borderline leprosy
    Borderline leprosy
    Borderline leprosy is a cutaneous skin condition with numerous skin lesions that are red irregularly shaped plaques....

  • Borderline lepromatous leprosy
    Borderline lepromatous leprosy
    Borderline lepromatous leprosy is a skin condition with numerous, symmetrical skin lesions....

  • Lepromatous leprosy
    Lepromatous leprosy
    Lepromatous leprosy is a skin condition consisting of pale macules.It results from the failure of Th1 cell activation which is necessary to eradicate the parasite....

  • Histoid leprosy
  • Diffuse leprosy of Lucio and Latapí
    Diffuse leprosy of Lucio and Latapí
    The diffuse leprosy of Lucio and Lapatí, also known as diffuse lepromatous leprosy or "pretty leprosy" is a clinical variety of lepromatous leprosy. It was first described by Lucio and Alvarado in 1852 and re-identified by Latapí in 1936...



This disease may also occur with only neural involvement, without skin lesions. This disease is also known as Hansen's Disease.

Signs and symptoms

Skin lesions are the primary external sign. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs, and eyes.

Diagnosis

Diagnosis in the U.S. is often delayed because healthcare providers are unaware of leprosy and its symptoms. Early diagnosis and treatment prevents nerve involvement, the hallmark of leprosy, and the disability it causes.

There are many kinds of leprosy but there are common symptoms. These include runny nose, dry scalp, eye problems, skin lesions, and muscle weakness.

Mycobacterium leprae

Mycobacterium leprae and Mycobacterium lepromatosis
Mycobacterium lepromatosis
Mycobacterium lepromatosis is a bacterium that, along with Mycobacterium leprae, causes leprosy . It was only recently discovered, in 2008. Analysis of its 16S rRNA gene confirms that the species is distinct from Mycobacterium leprae.M.lepromatosis is an Acid Fast Bacilli which causes diffuse...

are the causative agents of leprosy. M. lepromatosis is a relatively newly identified mycobacterium isolated from a fatal case of diffuse lepromatous leprosy in 2008.

An intracellular, acid-fast
Acid-fast
Acid-fastness is a physical property of certain bacteria, specifically their resistance to decolorization by acids during staining procedures.Acid-fast organisms are difficult to characterize using standard microbiological techniques Acid-fastness is a physical property of certain bacteria,...

 bacterium
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

, M. leprae is aerobic
Aerobic organism
An aerobic organism or aerobe is an organism that can survive and grow in an oxygenated environment.Faculitative anaerobes grow and survive in an oxygenated environment and so do aerotolerant anaerobes.-Glucose:...

 and rod-shaped, and is surrounded by the waxy cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...

 coating characteristic of Mycobacterium
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...

species.

Due to extensive loss of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s necessary for independent growth, M. leprae and M. lepromatosis are obligate pathogens, and unculturable
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...

 in the laboratory, a factor that leads to difficulty in definitively identifying the organism under a strict interpretation of Koch's postulates
Koch's postulates
Koch's postulates are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and refined and published by Koch in 1890...

. The use of non-culture-based techniques such as molecular genetics
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...

 has allowed for alternative establishment of causation.

While the causative organisms have to date been impossible to culture in vitro, it has been possible to grow them in animals. Charles Shepard, chairman of the United States Leprosy Panel, successfully grew the organisms in the footpads of mice in 1960. This method was improved with the use of congenitally athymic mice (nude mice
Nude mouse
A nude mouse is a laboratory mouse from a strain with a genetic mutation that causes a deteriorated or absent thymus, resulting in an inhibited immune system due to a greatly reduced number of T cells. The phenotype, or main outward appearance of the mouse is a lack of body hair, which gives it...

) in 1970 by Joseph Colson and Richard Hilson at St George's Hospital, London.

A second animal model was developed by Eleanor Storrs at the Gulf South Research Institute. Dr Storrs had worked on the nine-banded armadillo
Nine-banded Armadillo
The nine-banded armadillo , or the nine-banded, long-nosed armadillo, is a species of armadillo found in North, Central, and South America, making it the most widespread of the armadillos...

 for her PhD, because this animal had a lower body temperature than humans and might therefore be a suitable animal model. The work started in 1968 with material provided by Waldemar Kirchheimer at the United States Public Health Leprosarium in Carville, Louisiana
Louisiana
Louisiana is a state located in the southern region of the United States of America. Its capital is Baton Rouge and largest city is New Orleans. Louisiana is the only state in the U.S. with political subdivisions termed parishes, which are local governments equivalent to counties...

. These experiments proved unsuccessful, but additional work in 1970 with material provided by Chapman Binford, medical director of the Leonard's Wood Memorial, was successful. The papers describing this model led to a dispute of priority. Further controversy was generated when it was discovered that wild armadillos in Louisiana were naturally infected with leprosy.

Naturally occurring infection also has been reported in non-human primates including the African chimpanzee, sooty mangabey, and cynomolgus macaque.

Genetics

Several genes have been associated with a susceptibility to leprosy.
Name Locus
Locus (genetics)
In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...

OMIM Gene
LPRS1 10p13
LPRS2 6q25 PARK2, PACRG
PACRG
Parkin coregulated gene protein is a protein that in humans is encoded by the PACRG gene.-Further reading:...

LPRS3 4q32 TLR2
LPRS4 6p21.3 LTA
Lymphotoxin alpha
Lymphotoxin-alpha is a protein that in humans is encoded by the LTA gene.- Function :Lymphotoxin alpha, a member of the tumor necrosis factor family, is a cytokine produced by lymphocytes. LTA is highly inducible, secreted, and exists as homotrimeric molecule. LTA forms heterotrimers with...

LPRS5 4p14 TLR1
LPRS6 13q14.11

Risk factors

At highest risk are those living in endemic areas with poor conditions such as inadequate bedding, contaminated water, and insufficient diet, or other diseases that compromise immune function. However, though hard evidence is limited, and fringe publications have made passionate claims to the contrary, professional studies show little evidence that HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

 is an important factor in increasing the risk of leprosy infection. It is presumed that this might be because of differences between the modes of immunity involved. However, it is plain that the two infections and their signs and progressions need not be fully independent, so the matter should be regarded with reserve.
For example, a Medscape
Medscape
Medscape is a web resource for physicians and other health professionals. It features peer-reviewed original medical journal articles, CME , a customized version of the National Library of Medicine's MEDLINE database, daily medical news, major conference coverage, and drug information—including a...

 clinical presentation reports that HIV infection neither is a risk factor for acquisition nor for increased virulence of leprosy, but that latent cases of leprosy may emerge after starting HAART
Antiretroviral drug
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART...

.
Lewis, F. S. et al. ; Dermatologic Manifestations of Leprosy Clinical Presentation

Recent research suggests that there is a defect in cell-mediated immunity that causes susceptibility to Hansen's disease. Less than ten percent of the world's population is capable of acquiring the disease. The region of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 responsible for this variability is also involved in Parkinson disease, giving rise to current speculation that the two disorders may be linked in some way at the biochemical
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...

 level. In early 2003, an international team of scientists conducted a genome scan in Vietnamese multiplex leprosy families and found that susceptibility to leprosy was significantly linked to region q25 on the long arm of chromosome 6. Further confirmation of the chromosome 6 locus was provided by high-resolution linkage mapping in simplex leprosy families. Now, in a continuation of these findings, the team has pinpointed the chromosome 6 susceptibility locus to the 5' regulatory promoter region shared by both the Parkinson's disease gene PARK2 and its co-regulated gene PACRG. According to The Leprosy Mission Canada, most people-–about 95% of the population-–are naturally immune to the disease.

Pathophysiology

The mechanism of transmission of leprosy is prolonged close contact and transmission by nasal droplet. In addition to humans, leprosy has been observed in nine-banded armadillo
Nine-banded Armadillo
The nine-banded armadillo , or the nine-banded, long-nosed armadillo, is a species of armadillo found in North, Central, and South America, making it the most widespread of the armadillos...

, (which, it has recently been confirmed, are among the primary sources of new cases of leprosy in Americans
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

), and three species of primates. The bacterium can also be grown in the laboratory by injection into the footpads of mice. There is evidence that not all people who are infected with M. leprae develop leprosy, and genetic factors have long been thought to play a role, due to the observation of clustering of leprosy around certain families, and the failure to understand why certain individuals develop lepromatous leprosy while others develop other types of leprosy. It is estimated that due to genetic factors, only 5% of the population is susceptible to leprosy. This is mostly because the body is naturally immune to the bacteria, and those persons that do become infected are experiencing a severe allergic reaction to the disease. However, the role of genetic factors is not entirely clear in determining this clinical expression. In addition, malnutrition and prolonged exposure to infected persons may play a role in development of the overt disease.

The most widely held belief is that the disease is transmitted by contact between infected persons and healthy persons. In general, closeness of contact is related to the dose of infection, which in turn is related to the occurrence of disease. Of the various situations that promote close contact, contact within the household is the only one that is easily identified, although the incidence among contacts and the relative risk for them appear to vary considerably in different studies. In incidence studies
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

, infection rates for contacts of lepromatous leprosy have varied from 6.2 per 1000 per year in Cebu
Cebu
Cebu is a province in the Philippines, consisting of Cebu Island and 167 surrounding islands. It is located to the east of Negros, to the west of Leyte and Bohol islands...

, Philippines
Philippines
The Philippines , officially known as the Republic of the Philippines , is a country in Southeast Asia in the western Pacific Ocean. To its north across the Luzon Strait lies Taiwan. West across the South China Sea sits Vietnam...

 to 53 per 1000 per year in part of Western India to 55.8 per 1000 per year in a part of Southern India.

Two exit routes of M. leprae from the human body often described are the skin and the nasal mucosa, although their relative importance is not clear. Lepromatous cases show large numbers of organisms deep in the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...

, but whether they reach the skin surface in sufficient numbers is doubtful. Although there are reports of acid-fast bacilli being found in the desquamating epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 (sloughing of superficial layer of skin) of the skin, Weddell et al. had reported in 1963 that they could not find any acid-fast bacilli in the epidermis, even after examining a very large number of specimens from patients and contacts. In a recent study, Job et al. found fairly large numbers of M. leprae in the superficial keratin
Keratin
Keratin refers to a family of fibrous structural proteins. Keratin is the key of structural material making up the outer layer of human skin. It is also the key structural component of hair and nails...

 layer of the skin of lepromatous leprosy patients, suggesting that the organism could exit along with the sebaceous
Sebaceous gland
The sebaceous glands are microscopic glands in the skin that secrete an oily/waxy matter, called sebum, to lubricate and waterproof the skin and hair of mammals...

 secretions.

The importance of the nasal mucosa was recognized as early as 1898 by Schäffer, in particular that of the ulcerated mucosa. The quantity of bacilli from nasal mucosal lesions in lepromatous leprosy was demonstrated by Shepard as large, with counts ranging from 10,000 to 10,000,000. Pedley reported that the majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through blowing the nose. Davey and Rees indicated that nasal secretions from lepromatous patients could yield as much as 10 million viable organisms per day.

The entry route of M. leprae into the human body is also not definitively known: The skin and the upper respiratory tract are most likely. While older research dealt with the skin route, recent research has increasingly favored the respiratory route. Rees and McDougall succeeded in the experimental transmission of leprosy through aerosols containing M. leprae in immune-suppressed mice, suggesting a similar possibility in humans. Successful results have also been reported on experiments with nude mice
Nude mouse
A nude mouse is a laboratory mouse from a strain with a genetic mutation that causes a deteriorated or absent thymus, resulting in an inhibited immune system due to a greatly reduced number of T cells. The phenotype, or main outward appearance of the mouse is a lack of body hair, which gives it...

 when M. leprae were introduced into the nasal cavity by topical application. In summary, entry through the respiratory route appears the most probable route, although other routes, particularly broken skin, cannot be ruled out. The CDC notes the following assertion about the transmission of the disease: "Although the mode of transmission of Hansen's disease remains uncertain, most investigators think that M. leprae is usually spread from person to person in respiratory droplets."

In leprosy, both the reference points for measuring the incubation period and the times of infection and onset of disease are difficult to define, the former because of the lack of adequate immunological tools and the latter because of the disease's slow onset. Even so, several investigators have attempted to measure the incubation period for leprosy. The minimum incubation period reported is as short as a few weeks and this is based on the very occasional occurrence of leprosy among young infants. The maximum incubation period reported is as long as 30 years, or over, as observed among war veterans known to have been exposed for short periods in endemic areas but otherwise living in non-endemic areas. It is generally agreed that the average incubation period is between three and five years.

Prevention

In a recent trial, a single dose of rifampicin reduced the rate at which contacts acquired leprosy in the two years after contact by 57%; 265 treatments with rifampicin prevented one case
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...

 of leprosy in this period. A non-randomized study found that rifampicin reduced the number of new cases of leprosy by 75% after three years.

BCG
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...

 offers a variable amount of protection against leprosy as well as against tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

.

Efforts to overcome persistent obstacles to the elimination of the disease include improving detection, educating patients and the population about its cause, and fighting social taboos about a disease that has caused its patients throughout history to be considered "unclean" or "cursed by God" as outcasts. Leprosy is not a hereditary disease. Where taboos are strong, patients may be forced to hide their condition (and avoid seeking treatment) to avoid discrimination. The lack of awareness about Hansen's disease can lead people to believe (falsely) that the disease is highly contagious and incurable.

The ALERT
ALERT (medical facility, Ethiopia)
ALERT is a medical facility on the edge of Addis Ababa, specializing in Hansen’s disease, also known as “leprosy”. It was originally the All Africa Leprosy Rehabilitation and Training Center , but the official name is now expanded to include tuberculosis: All Africa Leprosy, Tuberculosis and...

 hospital and research facility in Ethiopia provides training to medical personnel from around the world in the treatment of leprosy, as well as treating many local patients. Surgical techniques, such as for the restoration of control of movement of thumbs, have been developed.

Treatment

Enough synthetic pharmaceuticals that are effective against leprosy
Leprostatic agent
A Leprostatic agent is a drug that interferes with proliferation of the bacterium that causes leprosy.The following agents are leprostatic agents:* acedapsone* clofazimine* dapsone* desoxyfructo-serotonin* diucifon* ethionamide* rifampin* rifapentine...

 have by now been identified, and support a flexible choice of treatments. The WHO Study Group's report on the Chemotherapy of Leprosy in 1993 recommended two types of standard MDT regimen be adopted. The first was a 24-month treatment for multibacillary (MB or lepromatous) cases using rifampicin, clofazimine, and dapsone. The second was a six-month treatment for paucibacillary (PB or tuberculoid) cases, using rifampicin and dapsone. At the First International Conference on the Elimination of Leprosy as a Public Health Problem, held in Hanoi the next year, the global strategy was endorsed and funds provided to WHO for the procurement and supply of MDT to all endemic countries.
Between 1995 and 1999, WHO, with the aid of the Nippon Foundation
Nippon Foundation
is a private, non-profit grant-making organization. It was established in 1962 by Ryoichi Sasakawa, the late statesman and businessman who, following World War II, was accused, albeit not convicted, of class A war crimes...

 (Chairman Yōhei Sasakawa
Yohei Sasakawa
is chairman of The Nippon Foundation, the World Health Organization Goodwill Ambassador for Leprosy Elimination, and Japan's Ambassador for the Human Rights of People Affected by leprosy. As chairman of The Nippon Foundation, Japan's largest charitable foundation, he is seen as a pioneer in guiding...

, World Health Organization Goodwill Ambassador for Leprosy Elimination), supplied all endemic countries with free MDT in blister packs, channelled through Ministries of Health. This free provision was extended in 2000 and again in 2005 with donations by the MDT manufacturer Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...

 through WHO. In the latest agreement signed between the company and WHO in October 2010, the provision of free MDT by WHO to all endemic countries will now run until at least the end of 2015. At the national level, non-government organizations
Non-governmental organization
A non-governmental organization is a legally constituted organization created by natural or legal persons that operates independently from any government. The term originated from the United Nations , and is normally used to refer to organizations that do not form part of the government and are...

 (NGOs) affiliated to the national programme will continue to be provided with an appropriate free supply of this WHO supplied MDT by the government.

MDT remains highly effective, and patients are no longer infectious after the first monthly dose. It is safe and easy to use under field conditions due to its presentation in calendar blister packs. Relapse
Relapse
Relapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...

 rates remain low, and there is no known resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 to the combined drugs. The Seventh WHO Expert Committee on Leprosy, reporting in 1997, concluded that the MB duration of treatment — then standing at 24 months — could safely be shortened to 12 months "without significantly compromising its efficacy."

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
Bathing
Bathing is the washing or cleansing of the body in a fluid, usually water or an aqueous solution. It may be practised for personal hygiene, religious ritual or therapeutic purposes or as a recreational activity....

. That of virgins or children was considered to be especially potent. This practice seems to have originated with the Ancient Egyptians but was also known in China, where people were murdered for their blood. This practice persisted until at least 1790, when the use of dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...

 blood was mentioned in De Secretis Naturae. Paracelsus
Paracelsus
Paracelsus was a German-Swiss Renaissance physician, botanist, alchemist, astrologer, and general occultist....

 recommended the use of lamb
Domestic sheep
Sheep are quadrupedal, ruminant mammals typically kept as livestock. Like all ruminants, sheep are members of the order Artiodactyla, the even-toed ungulates. Although the name "sheep" applies to many species in the genus Ovis, in everyday usage it almost always refers to Ovis aries...

's blood and even blood from dead bodies was used.

Snakes were also used, according to Pliny
Pliny the Elder
Gaius Plinius Secundus , better known as Pliny the Elder, was a Roman author, naturalist, and natural philosopher, as well as naval and army commander of the early Roman Empire, and personal friend of the emperor Vespasian...

, Aretaeus of Cappadocia
Aretaeus of Cappadocia
Aretaeus , is one of the most celebrated of the ancient Greek physicians, of whose life, however, few particulars are known. There is some uncertainty regarding both his age and country, but it seems probable that he practised in the 1st century CE, during the reign of Nero or Vespasian...

, and Theodorus
Theodorus Priscianus
Theodorus Priscianus was a physician at Constantinople during the 4th century, and the author of the Latin work Rerum Medicarum Libri Quatuor.-Career:...

. Gaucher recommended treatment with cobra
Cobra
Cobra is a venomous snake belonging to the family Elapidae. However, not all snakes commonly referred to as cobras are of the same genus, or even of the same family. The name is short for cobra capo or capa Snake, which is Portuguese for "snake with hood", or "hood-snake"...

 venom. Boinet, in 1913, tried increasing doses of bee
Bee
Bees are flying insects closely related to wasps and ants, and are known for their role in pollination and for producing honey and beeswax. Bees are a monophyletic lineage within the superfamily Apoidea, presently classified by the unranked taxon name Anthophila...

 stings (up to 4000). Scorpion
Scorpion
Scorpions are predatory arthropod animals of the order Scorpiones within the class Arachnida. They have eight legs and are easily recognized by the pair of grasping claws and the narrow, segmented tail, often carried in a characteristic forward curve over the back, ending with a venomous stinger...

s and frog
Frog
Frogs are amphibians in the order Anura , formerly referred to as Salientia . Most frogs are characterized by a short body, webbed digits , protruding eyes and the absence of a tail...

s were used occasionally instead of snakes. The excreta of Anabas
Anabas
Anabas also called climbing perch or Ikan Puyu is a genus of the bone fishes from familia from perciform fish.-Description:Fresh-water fishes have the length up to 20 cm. Anabas reside in both brackish and fresh water....

(the climbing fish) was also tried.

Alternative treatments included scarification with or without the addition of irritants including arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...

 and hellebore
Hellebore
Commonly known as hellebores, members of the genus Helleborus comprise approximately 20 species of herbaceous perennial flowering plants in the family Ranunculaceae, within which it gave its name to the tribe of Helleboreae...

. Castration
Castration
Castration is any action, surgical, chemical, or otherwise, by which a male loses the functions of the testicles or a female loses the functions of the ovaries.-Humans:...

 was also practiced in the Middle Ages.

Chaulmoogra oil

A common pre-modern treatment of leprosy was chaulmoogra oil
Hydnocarpus wightiana
Hydnocarpus wightiana or Chaulmoogra is a tree in the Achariaceae family. The oil from its seeds has been widely used in Indian medicine and Chinese traditional medicine for the treatment of leprosy. It entered early Western medicine in the ninteenth century before the era of sulfones and...

. One Indian legend relates that Rama
Rama
Rama or full name Ramachandra is considered to be the seventh avatar of Vishnu in Hinduism, and a king of Ayodhya in ancient Indian...

 acquired leprosy and was cured by eating the fruit of the Kalaw (a species of the genus Hydnocarpus
Hydnocarpus
Hydnocarpus is a genus of medium to large trees of Indonesia, Malaysia and the Philippines, having alternate leaves, small dioecious racemose flowers, and capsular fruits of which several are sources of chaulmoogra oil and hydnocarpus oil....

) tree. He went on to cure the princess Piya with the same fruit and the pair returned to Benares to spread the word of their discovery.

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, and 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.

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
William Roxburgh
William Roxburgh was a Scottish surgeon and botanist. He has been called the Father of Indian Botany.-Early life:Roxburgh was born at Underwood in the parish of Craigie, Ayrshire. He studied medicine in Edinburgh...

, a surgeon and naturalist, while he was cataloging the plants in the East India Company
East India Company
The East India Company was an early English joint-stock company that was formed initially for pursuing trade with the East Indies, but that ended up trading mainly with the Indian subcontinent and China...

’s botanical garden in Calcutta. This tree is also known as Gynocardia odorata
Gynocardia odorata
Gynocardia odorata is a species of evergreen tree belonging to the Achariaceae family. The trees grow up to 30 m tall. The species is found in moist forests of mountain valleys in South Asia - India, South-east Xizang and Yunnan in China, Bangladesh, Nepal and Myanmar.The seeds of this plant have...

. For the rest of the 19th century, this tree was thought to be the source of the oil. In 1901, Sir David Prain
David Prain
Sir David Prain FRS was a Scottish botanist.-Biography:Prain was born to a saddler in Fettercairn, Kincardineshire, Scotland and studied at the local Parish Schhool and the University of Aberdeen. He taught for two years at Ramsgate College and then returned to Scotland to enter the University of...

 identified the true chaulmoogra seeds of the Calcutta bazaar
Bazaar
A bazaar , Cypriot Greek: pantopoula) is a permanent merchandising area, marketplace, or street of shops where goods and services are exchanged or sold. The term is sometimes also used to refer to the "network of merchants, bankers and craftsmen" who work that area...

 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 from the tree Hydnocarpus wightiana
Hydnocarpus wightiana
Hydnocarpus wightiana or Chaulmoogra is a tree in the Achariaceae family. The oil from its seeds has been widely used in Indian medicine and Chinese traditional medicine for the treatment of leprosy. It entered early Western medicine in the ninteenth century before the era of sulfones and...

, known as Tuvakara in Sanskrit
Sanskrit
Sanskrit , is a historical Indo-Aryan language and the primary liturgical language of Hinduism, Jainism and Buddhism.Buddhism: besides Pali, see Buddhist Hybrid Sanskrit Today, it is listed as one of the 22 scheduled languages of India and is an official language of the state of Uttarakhand...

 and chaulmugra in Hindi
Hindi
Standard Hindi, or more precisely Modern Standard Hindi, also known as Manak Hindi , High Hindi, Nagari Hindi, and Literary Hindi, is a standardized and sanskritized register of the Hindustani language derived from the Khariboli dialect of Delhi...

 and Persian
Persian language
Persian is an Iranian language within the Indo-Iranian branch of the Indo-European languages. It is primarily spoken in Iran, Afghanistan, Tajikistan and countries which historically came under Persian influence...

.

The first parenteral administration was given by the Egyptian doctor Tortoulis Bey, personal physician to the Sultan Hussein Kamel
Hussein Kamel
Hussein Kamel Hassan al-Majid was the son-in-law and second cousin of Iraqi leader Saddam Hussein. He defected to Jordan and assisted United Nations Special Commission and International Atomic Energy Agency inspection teams assigned to look for weapons of mass destruction in...

. He had been using subcutaneous injections of creosote
Creosote
Creosote is the portion of chemical products obtained by the distillation of a tar that remains heavier than water, notably useful for its anti-septic and preservative properties...

 for tuberculosis and in 1894 administered subcutaneous injection of chaulmoogra oil in a 36-year-old Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

ian Copt
Copt
The Copts are the native Egyptian Christians , a major ethnoreligious group in Egypt....

 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 anthelmintica and Hydnocarpus wightiana
Hydnocarpus wightiana
Hydnocarpus wightiana or Chaulmoogra is a tree in the Achariaceae family. The oil from its seeds has been widely used in Indian medicine and Chinese traditional medicine for the treatment of leprosy. It entered early Western medicine in the ninteenth century before the era of sulfones and...

. From these two 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
Hydnocarpus kurzii
Hydnocarpus kurzii is a species of plant in the Achariaceae family. It is found in India and Myanmar.-Sources:* CAMP Workshops on Medicinal Plants, India 1998. . Downloaded on 22 August 2007....

) also produced chaulmoogric acid.

Another difficulty with the use of this oil was administration. 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. Despite these difficulties, a series of 170 patients were reported in 1916 by Ralph Hopkins, the attending physician at the Louisiana
Louisiana
Louisiana is a state located in the southern region of the United States of America. Its capital is Baton Rouge and largest city is New Orleans. Louisiana is the only state in the U.S. with political subdivisions termed parishes, which are local governments equivalent to counties...

 Leper Home in Carville, Louisiana. He divided the patients into two groups - 'incipient' and 'advanced'. In the advanced cases, 25% (at most) showed any improvement or arrest of their condition; in the incipient cases, 45% reported 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
Manila
Manila is the capital of the Philippines. It is one of the sixteen cities forming Metro Manila.Manila is located on the eastern shores of Manila Bay and is bordered by Navotas and Caloocan to the north, Quezon City to the northeast, San Juan and Mandaluyong to the east, Makati on the southeast,...

 and Elidoro Mercadothe house physician at the San Lazaro Hospital for lepers in Manila decided to add camphor
Camphor
Camphor is a waxy, white or transparent solid with a strong, aromatic odor. It is a terpenoid with the chemical formula C10H16O. It is found in wood of the camphor laurel , a large evergreen tree found in Asia and also of Dryobalanops aromatica, a giant of the Bornean forests...

 to a prescription of chaulmoogra and resorcin, which was typically given orally at the suggestion of Merck and Company
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...

 in Germany to whom Heiser had written. They found that this new compound was readily absorbed without the nausea that had plagued the earlier preparations.

Heiser and Mercado in 1913 then administered the oil by injection to two patients who were cured of the disease. Since this treatment was administered in conjunction with other materials, the results were not clear. A further two patients were treated with the oil by injection without other treatments and again appeared to be cured of the disease. The following year, Heiser reported a further 12 patients but the results were mixed.

Less toxic injectable forms of this oil were then sought. Between 1920 and 1922, a series of papers were published describing the esters of these oils. These may have been based on the work of Alice Ball - the record is not clear on this point and Ms Ball died in 1916. Trials of these esters were carried out in 1921 and appeared to give useful results.

These attempts had been preceded by others. Merck of Darmstadt
Darmstadt
Darmstadt is a city in the Bundesland of Hesse in Germany, located in the southern part of the Rhine Main Area.The sandy soils in the Darmstadt area, ill-suited for agriculture in times before industrial fertilisation, prevented any larger settlement from developing, until the city became the seat...

 had 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
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...

 in 1908 marketed a commercial version of the esters under the name 'Antileprol'.

To ensure a supply of this agent Joseph Rock
Joseph Rock
Joseph Francis Charles Rock was an Austrian-American explorer, geographer, linguist and botanist.-Life:He was born in Vienna, Austria, but emigrated to the United States in 1905 and moved to Honolulu, Hawaii in 1907, where he eventually became an authority on the flora there...

, Professor of Systematic Botany at the College of Hawaii, traveled to Burma. The local villagers located a grove of trees in seed, which he used to establish a plantation in 2,980 trees on the island of Oahu
Oahu
Oahu or Oahu , known as "The Gathering Place", is the third largest of the Hawaiian Islands and most populous of the islands in the U.S. state of Hawaii. The state capital Honolulu is located on the southeast coast...

, Hawaii between 1921 and 1922.

The oil remained a popular treatment despite the common side effects until the introduction of sulfone
Sulfone
A sulfone is a chemical compound containing a sulfonyl functional group attached to two carbon atoms. The central hexavalent sulfur atom is double bonded to each of two oxygen atoms and has a single bond to each of two carbon atoms, usually in two separate hydrocarbon substituents.-IUPAC name and...

s in the 1940s. Debate about its efficacy continued until it was discontinued.

Modern drug treatment
It has been said that Promin
Promin
Promin, or sodium glucosulfone is a sulfone drug that was investigated for the treatment of malaria, tuberculosis and leprosy. It is broken down in the body to dapsone, which is the therapeutic form.-History:...

 was first synthesised in 1940 by Feldman of Parke-Davis
Parke-Davis
Parke-Davis is a subsidiary of the pharmaceutical company Pfizer. Although no longer an independent corporation, it was once America's oldest and largest drug maker, and played an important role in medical history.- History :...

 and company. Although Parke-Davis did in fact synthesise the compound, it seems certain that they were not the first; in cooperation with J. Wittmann, Emil Fromm synthesised both dapsone and some of its derivatives, including promin, in 1908. He was however a chemist and not a medical worker, nor did anyone investigate its medical value till some decades afterwards.

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
Guy Henry Faget
Guy Henry Faget was an American doctor who revolutionalized the treatment of leprosy by demonstrating the efficacy of promin, in a paper reported in 1943. Promin is a sulfone compound synthesized by Feldman and his co-workers in 1940 as an agent against tuberculosis effective in experimental animals...

 and his co-workers in 1943 at Carville, Louisiana. In the 1950s dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...

 was introduced to Carville by Dr. R.G. Cochrane. It is only weakly bactericidal against M. leprae
Mycobacterium leprae
Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...

and it was considered necessary for patients to take the drug indefinitely. When dapsone was used alone, the M. leprae population quickly evolved
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

 antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

; by the 1960s, the world's only known anti-leprosy drug became virtually useless.

The search for more effective anti-leprosy drugs led to the use of clofazimine
Clofazimine
Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients and...

 and rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...

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. The first trials of combined treatment were carried out in Malta
Malta
Malta , officially known as the Republic of Malta , is a Southern European country consisting of an archipelago situated in the centre of the Mediterranean, south of Sicily, east of Tunisia and north of Libya, with Gibraltar to the west and Alexandria to the east.Malta covers just over in...

 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.

This treatment was quite expensive, and was not quickly adopted in most endemic countries. 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
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

 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, based on increasing the geographical coverage of MDT and patients’ accessibility to the treatment.

Epidemiology

Worldwide, two to three million people are estimated to be permanently disabled because of leprosy. India has the greatest number of cases, with Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

 second and Burma third.

In 1999, the world incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 of Hansen's disease was estimated to be 640,000. In 2000, 738,284 cases were identified. In 2000, the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO) listed 91 countries in which Hansen's disease is endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

. India, Burma, and Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...

 contained 70% of cases. India reports over 50% of the world's leprosy cases. In 2002, 763,917 new cases were detected worldwide, and in that year the WHO listed Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

, Madagascar
Madagascar
The Republic of Madagascar is an island country located in the Indian Ocean off the southeastern coast of Africa...

, Mozambique
Mozambique
Mozambique, officially the Republic of Mozambique , is a country in southeastern Africa bordered by the Indian Ocean to the east, Tanzania to the north, Malawi and Zambia to the northwest, Zimbabwe to the west and Swaziland and South Africa to the southwest...

, Tanzania
Tanzania
The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...

, and Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...

 as having 90% of Hansen's disease cases.

According to recent figures from the WHO, new cases detected worldwide have decreased by approximately 107,000 cases (or 21%) from 2003 to 2004. This decreasing trend has been consistent for the past three years. In addition, the global registered prevalence of HD was 286,063 cases; 407,791 new cases were detected during 2004.

In the United States, the disease is tracked by the Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

 (CDC), with a total of 166 new cases reported in the U.S. in 2005. Most (100 or 60%) of these new cases were reported in the following states; California, Louisiana, Massachusetts, New York, and Texas.
Although the number of cases worldwide continues to fall, pockets of high prevalence continue in certain areas such as Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

, South Asia
South Asia
South Asia, also known as Southern Asia, is the southern region of the Asian continent, which comprises the sub-Himalayan countries and, for some authorities , also includes the adjoining countries to the west and the east...

 (India, Nepal
Nepal
Nepal , officially the Federal Democratic Republic of Nepal, is a landlocked sovereign state located in South Asia. It is located in the Himalayas and bordered to the north by the People's Republic of China, and to the south, east, and west by the Republic of India...

), some parts of Africa (Tanzania
Tanzania
The United Republic of Tanzania is a country in East Africa bordered by Kenya and Uganda to the north, Rwanda, Burundi, and the Democratic Republic of the Congo to the west, and Zambia, Malawi, and Mozambique to the south. The country's eastern borders lie on the Indian Ocean.Tanzania is a state...

, Madagascar
Madagascar
The Republic of Madagascar is an island country located in the Indian Ocean off the southeastern coast of Africa...

, Mozambique
Mozambique
Mozambique, officially the Republic of Mozambique , is a country in southeastern Africa bordered by the Indian Ocean to the east, Tanzania to the north, Malawi and Zambia to the northwest, Zimbabwe to the west and Swaziland and South Africa to the southwest...

), and the western Pacific.

Disease burden

Although annual incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 — the number of new leprosy cases occurring each year — is important as a measure of transmission, it is difficult to measure in leprosy due to its long incubation period, delays in diagnosis after onset of the disease, and the lack of laboratory tools to detect leprosy in its very early stages. Instead, the registered prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

 is used. Registered prevalence is a useful proxy indicator of the disease burden, as it reflects the number of active leprosy cases diagnosed with the disease and receiving treatment with MDT at a given point in time. The prevalence rate is defined as the number of cases registered for MDT treatment among the population in which the cases have occurred, again at a given point in time.

New case detection is another indicator of the disease that is usually reported by countries on an annual basis. It includes cases diagnosed with onset of disease in the year in question (true incidence) and a large proportion of cases with onset in previous years (termed a backlog prevalence of undetected cases).

Endemic countries also report the number of new cases with established disabilities at the time of detection, as an indicator of the backlog prevalence. Determination of the time of onset of the disease is, in general, unreliable, is very labor-intensive, and is seldom done in recording these statistics.

Global situation

Table 1: Prevalence at beginning of 2006, and trends in new case detection 2001-2005, excluding Europe [registered prevalence is the national total of chronic cases]
Region Registered prevalence
(cases per 10,000 pop.)
New case detection during the year
Start of 2006 2001 2002 2003 2004 2005
Africa 40,830 (0.56) 39,612 48,248 47,006 46,918 42,814
Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...

32,904 (0.39) 42,830 39,939 52,435 52,662 41,780
South-East Asia 133,422 (0.81) 668,658 520,632 405,147 298,603 201,635
Eastern Mediterranean 4,024 (0.09) 4,758 4,665 3,940 3,392 3,133
Western Pacific 8,646 (0.05) 7,404 7,154 6,190 6,216 7,137
Totals 219,826 763,262 620,638 514,718 407,791 296,499

Table 2: Prevalence and detection, countries still to reach elimination. [registered prevalence is the national total of chronic cases]
Countries Registered prevalence
(cases per 10,000 pop.)
New case detection
(rate/100,000 pop.)
Start of 2004 Start of 2005 Start of 2006 During 2003 During 2004 During 2005
79,908 (4.6) 30,693 (1.7) 27,313 (1.5) 49,206 (28.6) 49,384 (26.9) 38,410 (20.6)
6,810 (3.4) 4,692 (2.4) 4,889 (2.5) 5,907 (29.4) 4,266 (22.0) 5,371 (27.1)
7,549 (3.1) 4,699 (1.8) 4,921 (1.8) 8,046 (32.9) 6,958 (26.2) 6,150 (22.7)
5,420 (1.6) 4,777 (1.3) 4,190 (1.1) 5,279 (15.4) 5,190 (13.8) 4,237 (11.1)
Totals NA NA NA NA NA NA


As reported to WHO
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 by 115 countries and territories in 2006, and published in the Weekly Epidemiological Record, the global registered prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

 of leprosy at the beginning of the year was 219,826 cases. New-case detection during the previous year (2005 - the last year for which full country information is available) was 296,499. The reason for the annual detection's being higher than the prevalence at the end of the year can be explained by the fact that a proportion of new cases complete their treatment within the year and, therefore, no longer remain on the registers. The global detection of new cases continues to show a sharp decline, falling by 110,000 cases (27%) during 2005 compared with the previous year.

Table 1 shows that global annual detection has been declining since 2001. The African region reported an 8.7% decline in the number of new cases compared with 2004. The comparable figure for the Americas was 20.1%, for South-East Asia 32%, and for the Eastern Mediterranean 7.6%. The Western Pacific area, however, showed a 14.8% increase during the same period.

Table 2 shows the leprosy situation in the four major countries that have yet to achieve the goal of elimination at the national level. It should be noted that: a) Elimination is defined as a prevalence of less than 1 case per 10,000 population; b) Madagascar reached elimination at the national level in September 2006; c) Nepal detection reported from mid-November 2004 to mid-November 2005; and d) D.R. Congo officially reported to WHO in 2008 that it had reached elimination by the end of 2007, at the national level.

History

DNA taken from the shrouded remains of a man discovered in a tomb next to the Old City of Jerusalem shows him to be the earliest human proven to have suffered from leprosy. The remains were dated by radiocarbon methods to 1-50 C.E.

After the end of the 17th century, Norway
Norway
Norway , officially the Kingdom of Norway, is a Nordic unitary constitutional monarchy whose territory comprises the western portion of the Scandinavian Peninsula, Jan Mayen, and the Arctic archipelago of Svalbard and Bouvet Island. Norway has a total area of and a population of about 4.9 million...

, Iceland
Iceland
Iceland , described as the Republic of Iceland, is a Nordic and European island country in the North Atlantic Ocean, on the Mid-Atlantic Ridge. Iceland also refers to the main island of the country, which contains almost all the population and almost all the land area. The country has a population...

 and England
England
England is a country that is part of the United Kingdom. It shares land borders with Scotland to the north and Wales to the west; the Irish Sea is to the north west, the Celtic Sea to the south west, with the North Sea to the east and the English Channel to the south separating it from continental...

 were the countries in Western Europe where leprosy was a significant problem. During the 1830s, the number of lepers in Norway, Iceland and England rose rapidly, believed to be caused by frequent visits of sailors who visited Western India, causing an increase in medical research into the condition, and the disease became a political issue. Norway appointed a medical superintendent for leprosy in 1854 and established a national register for lepers in 1856, the first national patient register in the world.

Mycobacterium leprae
Mycobacterium leprae
Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...

, the causative agent of leprosy, was discovered by G. H. Armauer Hansen
Gerhard Armauer Hansen
Gerhard Henrik Armauer Hansen was a Norwegian physician, remembered for his identification of the bacterium Mycobacterium leprae in 1873 as the causative agent of leprosy....

 in Norway in 1873, making it the first bacterium to be identified as causing disease in humans. The principal opposition to Hansen's view that leprosy was an infectious disease came from his father-in-law, Daniel Cornelius Danielssen who considered it a hereditary disease and had stated this 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.

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 was able to stain these organisms with Ziehl's method and the similarities with Koch's bacillus (Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

) were noted. 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.

He worked at St. Jørgens Hospital in Bergen
Bergen
Bergen is the second largest city in Norway with a population of as of , . Bergen is the administrative centre of Hordaland county. Greater Bergen or Bergen Metropolitan Area as defined by Statistics Norway, has a population of as of , ....

, founded early in the fifteenth century. St. Jørgens is today a museum, Lepramuseet, it can be argued the best-preserved leprosy hospital in Northern Europe.

Etymology

The word leprosy comes from ancient Greek
Ancient Greek
Ancient Greek is the stage of the Greek language in the periods spanning the times c. 9th–6th centuries BC, , c. 5th–4th centuries BC , and the c. 3rd century BC – 6th century AD of ancient Greece and the ancient world; being predated in the 2nd millennium BC by Mycenaean Greek...

 Λέπρα [léprā], "a disease that makes the skin scaly", in turn, a nominal derivation of the verb Λέπω [lépō], "to peel, scale off". Λέπος (Lepos) in ancient Greek means peel, or scale, so from Λέπος we have Λεπερός (Λεπερός = who has peels - scales) --> and then Λεπρός (=leprous). The word came into the English language via Latin and old French. The first attested English use is in the Ancrene Wisse, a 13th-century manual for nuns ("Moyseses hond..bisemde o þe spitel uuel & þuhte lepruse." The Middle English Dictionary, s.v., "leprous"). A roughly contemporaneous use is attested in the Anglo-Norman Dialogues of Saint Gregory, "Esmondez i sont li lieprous" (Anglo-Norman Dictionary, s.v., "leprus").

Throughout history, individuals with Hansen's disease have been known as lepers; however, 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," though the term is used by the U.S. Centers for Disease Control and Prevention and the World Health Organization. Historically, the term Tzaraath
Tzaraath
The Hebrew noun tzaraath describes a disfigurative condition mainly referred to in chapters 13-14 of Leviticus, as well as conditions equivalent to be "mildew" on clothes and houses.Tzaraath affects both animate...

from the Hebrew Bible
Hebrew Bible
The Hebrew Bible is a term used by biblical scholars outside of Judaism to refer to the Tanakh , a canonical collection of Jewish texts, and the common textual antecedent of the several canonical editions of the Christian Old Testament...

 was, erroneously, commonly translated as leprosy, although the symptoms of Tzaraath were not entirely consistent with leprosy and, rather, referred to a variety of disorders other than Hansen's disease. The first mention of leprosy recorded is found in Leviticus 13:2 - "When a man shall have in the skin of his flesh a rising, a scab, or bright spot, and it be in the skin of his flesh like the plague of leprosy; then he shall be brought unto Aaron the priest, or unto one of his sons the priests." There is also the well-known Bible story of the Syrian Naaman, "captain of the host of the king of Syria" (2 Kings 5:1), who suffered from this severe and savage skin disease.

In particular, tinea capitis
Tinea capitis
Tinea capitis is a superficial fungal infection of the scalp. The disease is primarily caused by dermatophytes in the Trichophyton and Microsporum genera that invade the hair shaft...

 (fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 scalp infection) and related infections on other body parts caused by the dermatophyte
Dermatophyte
Dermatophytes are a common label for a group of three types of fungus that commonly causes skin disease in animals and humans. These anamorphic genera are: Microsporum, Epidermophyton and Trichophyton. There are about 40 species in these three genera...

 fungus Trichophyton violaceum are abundant throughout the Middle East and North Africa today and might also have been common in biblical times. Likewise, the related agent of the disfiguring skin disease favus
Favus
Favus is a disease usually affecting the scalp, but occurring occasionally on any part of the skin, and even at times on mucous membranes.-Presentation:...

 Trichophyton schoenleinii appears to have been common throughout Eurasia and Africa before the advent of modern medicine. Persons with severe favus and similar fungal diseases (and potentially also with severe psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

 and other diseases not caused by microorganisms) tended to be classed as having leprosy as late as the 17th century in Europe. This is clearly shown in the painting The Regents of the Leper Hospital in Haarlem 1667 by Jan de Bray
Jan de Bray
Jan de Bray , was a Dutch Golden Age painter.-Biography:Jan de Bray was born in Haarlem. According to Houbraken he was the most famous pupil of his father, the architect and poet Salomon de Bray. Houbraken called Jan the "pearl in Haarlem's crown"...

 (Frans Hals Museum
Frans Hals Museum
The Frans Hals Museum is a hofje and municipal museum in Haarlem, Netherlands. The museum was founded in 1862 in the newly renovated former cloister located in the back of the Haarlem city hall known as the Prinsenhof...

, Haarlem
Haarlem
Haarlem is a municipality and a city in the Netherlands. It is the capital of the province of North Holland, the northern half of Holland, which at one time was the most powerful of the seven provinces of the Dutch Republic...

, the Netherlands), where a young Dutchman with a vivid scalp infection, it is presumed caused by a fungus, is shown being cared for by three officials of a charitable home intended for leprosy sufferers. 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 Hansen's disease as we understand it today.

Ancient Rome

In the West
Western world
The Western world, also known as the West and the Occident , is a term referring to the countries of Western Europe , the countries of the Americas, as well all countries of Northern and Central Europe, Australia and New Zealand...

, the earliest known description of leprosy there was made by the Roman
Ancient Rome
Ancient Rome was a thriving civilization that grew on the Italian Peninsula as early as the 8th century BC. Located along the Mediterranean Sea and centered on the city of Rome, it expanded to one of the largest empires in the ancient world....

 encyclopedist Aulus Cornelius Celsus
Aulus Cornelius Celsus
Aulus Cornelius Celsus was a Roman encyclopedist, known for his extant medical work, De Medicina, which is believed to be the only surviving section of a much larger encyclopedia. The De Medicina is a primary source on diet, pharmacy, surgery and related fields, and it is one of the best sources...

 (25 BC – 37 AD) in his De Medicina
De Medicina
De Medicina is a 1st-century medical treatise by Aulus Cornelius Celsus, a Roman encyclopedist and possibly a practicing physician. It is the only surviving section of a much larger encyclopedia; only small parts still survive from sections on agriculture, military science, oratory, jurisprudence...

; he called leprosy "elephantiasis". The Roman author Pliny the Elder
Pliny the Elder
Gaius Plinius Secundus , better known as Pliny the Elder, was a Roman author, naturalist, and natural philosopher, as well as naval and army commander of the early Roman Empire, and personal friend of the emperor Vespasian...

 (23–79 AD) mentioned the same disease. Although "sara't" of Leviticus
Leviticus
The Book of Leviticus is the third book of the Hebrew Bible, and the third of five books of the Torah ....

 (Old Testament
Old Testament
The Old Testament, of which Christians hold different views, is a Christian term for the religious writings of ancient Israel held sacred and inspired by Christians which overlaps with the 24-book canon of the Masoretic Text of Judaism...

) is translated as "lepra" in the 5th century AD Vulgate
Vulgate
The Vulgate is a late 4th-century Latin translation of the Bible. It was largely the work of St. Jerome, who was commissioned by Pope Damasus I in 382 to make a revision of the old Latin translations...

, the original term sara't found in Leviticus was not the elephantiasis described by Celsus and Pliny; in fact, sara't was used to describe a disease that could affect houses and clothing. Katrina C. D. McLeod and Robin D. S. Yates state that sara't "denotes a condition of ritual impurity or a temporary form of skin disease."

Persia (Iran)

The Persian
Persian people
The Persian people are part of the Iranian peoples who speak the modern Persian language and closely akin Iranian dialects and languages. The origin of the ethnic Iranian/Persian peoples are traced to the Ancient Iranian peoples, who were part of the ancient Indo-Iranians and themselves part of...

 polymath
Polymath
A polymath is a person whose expertise spans a significant number of different subject areas. In less formal terms, a polymath may simply be someone who is very knowledgeable...

 Avicenna
Avicenna
Abū ʿAlī al-Ḥusayn ibn ʿAbd Allāh ibn Sīnā , commonly known as Ibn Sīnā or by his Latinized name Avicenna, was a Persian polymath, who wrote almost 450 treatises on a wide range of subjects, of which around 240 have survived...

 (c. 980–1037) was the first outside of China to describe the destruction of the nasal septum
Nasal septum
The nasal septum separates the left and right airways in the nose, dividing the two nostrils.It is depressed by the Depressor septi nasi muscle.-Composition:The fleshy external end of the nasal septum is sometimes also called columella....

 in those suffering from leprosy.

Middle Ages

Numerous leprosaria, or leper hospitals, sprang up in the Middle Ages; Matthew Paris
Matthew Paris
Matthew Paris was a Benedictine monk, English chronicler, artist in illuminated manuscripts and cartographer, based at St Albans Abbey in Hertfordshire...

, a Benedictine Monk
Benedictine
Benedictine refers to the spirituality and consecrated life in accordance with the Rule of St Benedict, written by Benedict of Nursia in the sixth century for the cenobitic communities he founded in central Italy. The most notable of these is Monte Cassino, the first monastery founded by Benedict...

, estimated that in the early thirteenth century there were 19,000 across Europe. The first recorded Leper colony was in Harbledown
Harbledown
Harbledown is a village to the west of Canterbury, Kent in England, now contiguous with the city, although still a separate village. It forms part of the civil parish of Harbledown and Rough Common. The High Street is a conservation area with many fascinating colloquial buildings either side of a...

. These institutions were run along monastic lines and, while lepers were encouraged to live in these monastic-type establishments, this was for their own health as well as quarantine. Indeed, some medieval sources indicate belief that those suffering from leprosy were considered to be going through Purgatory
Purgatory
Purgatory is the condition or process of purification or temporary punishment in which, it is believed, the souls of those who die in a state of grace are made ready for Heaven...

 on Earth, and for this reason their suffering was considered holier than the ordinary person's. More frequently, lepers were seen to exist in a place between life and death: They were still alive, yet many chose or were forced to ritually separate themselves
Separatio Leprosorum
The Separatio Leprosorum was a ceremony performed during the Middle Ages whenever a person was declared a leper by their community. The individual was ritually buried by the community and exiled to the edge of the settlement. The term also applies to the subsequent shunning of the individuals...

 from mundane existence. The Order of Saint Lazarus
Order of Saint Lazarus
This article concerns the order of knighthood named after Saint Lazarus. For other uses of the name Lazarus, see Lazarus .The Military and Hospitaller Order of Saint Lazarus of Jerusalem is an order of chivalry which originated in a leper hospital founded by the Knights Hospitaller in 1098 by the...

 was a hospitaller and military order of monks that began as a leper hospital outside Jerusalem in the twelfth century and remained associated with leprosy throughout its history. The first monks in this order were leper knights, and they originally had leper grand masters, although these aspects of the order changed over the centuries.

Radegund
Radegund
Radegund was a 6th century Frankish princess, who founded the monastery of the Holy Cross at Poitiers. Canonized in the 9th century, she is the patron saint of several English churches and of Jesus College, Cambridge.-Life history:Radegund was born about 520 to Bertachar, one of the three kings...

 was noted for washing the feet of lepers. Orderic Vitalis
Orderic Vitalis
Orderic Vitalis was an English chronicler of Norman ancestry who wrote one of the great contemporary chronicles of 11th and 12th century Normandy and Anglo-Norman England. The modern biographer of Henry I of England, C...

 writes of a monk, Ralf, who was so overcome by the plight of lepers that he prayed to catch leprosy himself (which he eventually did). The leper would carry a clapper and bell to warn of his approach, and this was as much to attract attention for charity as to warn people that a diseased person was near.

India

The Oxford Illustrated Companion to Medicine holds that the mention of leprosy, as well as cures for it, were already described in the Hindu religious book Atharva-veda. Writing in the Encyclopedia Britannica 2008, Kearns & Nash state that the first mention of leprosy is in the Indian medical treatise Sushruta Samhita
Sushruta Samhita
The Sushruta Samhita is a Sanskrit text, attributed to one Sushruta, foundational to Ayurvedic medicine , with innovative chapters on surgery....

(6th century BC). The Cambridge Encyclopedia of Human Paleopathology (1998) holds that: "The Sushruta Samhita from India describes the condition quite well and even offers therapeutic suggestions as early as about 600 BC" The surgeon Sushruta lived in the Indian city of Kashi
Varanasi
-Etymology:The name Varanasi has its origin possibly from the names of the two rivers Varuna and Assi, for the old city lies in the north shores of the Ganga bounded by its two tributaries, the Varuna and the Asi, with the Ganges being to its south...

 by the 6th century BC, and the medical treatise Sushruta Samhita — attributed to him — made its appearance during the 1st millennium BC. The earliest surviving excavated written material that contains the works of Sushruta is the Bower Manuscript
Bower Manuscript
The Bower Manuscript is a medical manuscript written predominantly in the Sanskrit language,made up of 51 birch-bark leaves, written in an early Indian script.It is today preserved as part of the collections of the Bodleian Library in Oxford...

—dated to the 4th century AD, almost a millennium after the original work. Despite the existence of these earlier works the first generally considered accurate description of the disease was that of Galen
Galen
Aelius Galenus or Claudius Galenus , better known as Galen of Pergamon , was a prominent Roman physician, surgeon and philosopher...

 of Pergamum in 150 AD.

In 2009, a 4,000-year-old skeleton was uncovered in India that was shown to contain traces of leprosy. The discovery was made at a site called Balathal, which is today part of Rajasthan
Rajasthan
Rājasthān the land of Rajasthanis, , is the largest state of the Republic of India by area. It is located in the northwest of India. It encompasses most of the area of the large, inhospitable Great Indian Desert , which has an edge paralleling the Sutlej-Indus river valley along its border with...

, and is believed to be the oldest case of the disease ever found. This pre-dated the previous earliest recognized case, dating back to 6th-century Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

, by 1,500 years. It is believed that the excavated skeleton belonged to a male, who was in his late 30s and belonged to the Ahar Chalcolithic culture. Archaeologists have stated that not only does the skeleton represent the oldest case of leprosy ever found, but is also the first such example that dates back to prehistoric India. This finding supports one of the theories regarding the origin of the disease, which is believed to have originated in either India or Africa, before being subsequently spread to Europe by the armies of Alexander the Great.

In 1881, around 120,000 leprosy patients existed in India. The central government passed the Lepers Act of 1898, which provided legal provision for forcible confinement of leprosy sufferers in India.

China

Regarding ancient China
History of China
Chinese civilization originated in various regional centers along both the Yellow River and the Yangtze River valleys in the Neolithic era, but the Yellow River is said to be the Cradle of Chinese Civilization. With thousands of years of continuous history, China is one of the world's oldest...

, Katrina C. D. McLeod and Robin D. S. Yates identify the State of Qin's
Qin (state)
The State of Qin was a Chinese feudal state that existed during the Spring and Autumn and Warring States Periods of Chinese history...

 Feng zhen shi 封診式 (Models for sealing and investigating), dated 266-246 BC, as offering the earliest known unambiguous description of the symptoms of low-resistance leprosy, even though it was termed then under li 癘, a general Chinese word for skin disorder. This 3rd-century BC Chinese text on bamboo slip
Shuihudi Qin bamboo texts
The Shuihudi Qin bamboo texts are early Chinese texts written on bamboo slips, and are also sometimes called the Yúnmèng Qin bamboo texts. They were excavated in December 1975 from Tomb #11 at Chéngguān Shuìhǔdì , Yunmeng County, Hubei Province, China. The tomb belonged to a Qin administrator....

, found in an excavation of 1975 at Shuihudi, Yunmeng
Yunmeng County
Yunmeng County is a county in Hubei Province, People's Republic of China administered by Xiaogan City.-History:...

, Hubei
Hubei
' Hupeh) is a province in Central China. The name of the province means "north of the lake", referring to its position north of Lake Dongting...

 province, described not only the destruction of the "pillar of the nose" but also the "swelling of the eyebrows, loss of hair, absorption of nasal cartilage, affliction of knees and elbows, difficult and hoarse respiration, as well as anesthesia."

Indonesia

Across Indonesia the rate of prevalence is slightly under one new case per 10,000 people, with approximately 20,000 new cases detected each year. However, the rate is considerably higher in particular regions, particularly South Sulawesi (with more than 3 new cases per 10,000 people) and North Maluku (with more than 5 new cases per ten thousand people). MDT is provided free of charge to patients who require it in Indonesia and there are a number of hospitals in major population centers specifically intended to deal with the medical needs of those affected by the disease. While the early detection and treatment of leprosy has certainly improved over the years, approximately ten percent of patients in Indonesia have already suffered significant nerve or other damage prior to the identification and treatment of their disease, largely due to lack of awareness and to a pervasive stigma that discourages those with the disease from coming forward to seek treatment.

PERMATA (Perhimpunan Mandiri Kusta) Indonesia was established in 2007 with the specific vision of fighting the stigma associated with leprosy and eliminating the discrimination against those identified as suffering from the disease. The organization was founded by a small group of individuals who had all personally been treated for leprosy. The founders worked to establish links with key figures amongst those suffering from the disease in communities in South Sulawesi, East Java and NTT, the three provinces where the rate of incidence of the disease is probably amongst the highest in Indonesia.

Japan

Japan has had a unique history of segregation of patients into sanatoriums based on leprosy prevention laws of 1907, 1931, and 1953, and, hence, it intensified leprosy stigma
Leprosy stigma
Leprosy stigma is a kind of social stigma, a strong feeling that a leprosy patient is shameful and is not accepted normally in society. Also called leprosy related stigma, leprostigma and stigma of leprosy.-Stigma:...

. The 1953 law was abrogated in 1996. There are still 2717 ex-patients in 13 national sanatoriums and 2 private hospitals as of 2008. In a document written in 833, leprosy was described as "caused by a parasite that eats five organs of the body. The eyebrows and eyelashes come off, and the nose is deformed. The disease brings hoarseness, and necessitates amputations of the fingers and toes. Do not sleep with the patients, as the disease is transmittable to those nearby." This was the first document concerning infectivity.

Notable cases

  • Saint Damien of Molokai
    Father Damien
    Father Damien or Saint Damien of Molokai, SS.CC. , born Jozef De Veuster, was a Roman Catholic priest from Belgium and member of the Congregation of the Sacred Hearts of Jesus and Mary, a missionary religious order...

    , a Roman Catholic Priest from Belgium who ministered to the people with leprosy, who had been placed under a government-sanctioned medical quarantine on the island of Molokai
    Molokai
    Molokai or Molokai is an island in the Hawaiian archipelago. It is 38 by 10 miles in size with a land area of , making it the fifth largest of the main Hawaiian Islands and the 27th largest island in the United States. It lies east of Oahu across the 25-mile wide Kaiwi Channel and north of...

     in the Kingdom of Hawaii
    Kingdom of Hawaii
    The Kingdom of Hawaii was established during the years 1795 to 1810 with the subjugation of the smaller independent chiefdoms of Oahu, Maui, Molokai, Lānai, Kauai and Niihau by the chiefdom of Hawaii into one unified government...

    .
  • Baldwin IV, who was a king of Latin Jerusalem and was portrayed as a character in the film Kingdom of Heaven
    Kingdom of Heaven (film)
    Kingdom of Heaven is a 2005 epic action film directed by Ridley Scott and written by William Monahan. It stars Orlando Bloom, Eva Green, Jeremy Irons, David Thewlis, Marton Csokas, Brendan Gleeson, Kevin McKidd, Alexander Siddig, Ghassan Massoud, Edward Norton, Jon Finch, Michael Sheen and Liam...

  • Vietnamese poet Han Mac Tu
    Han Mac Tu
    Hàn Mặc Tử was a Vietnamese poet. He was born Nguyễn Trọng Trí, at Lệ Mỹ Village, Đồng Hới District, Quảng Bình Province. His pen names included: Minh Duệ, Phong Trần, Lệ Thanh, and finally Hàn Mặc Tử, by which name is known today. He grew up in a poor family, his father having died when he was...

  • Otani Yoshitsugu
    Otani Yoshitsugu
    was a Japanese samurai of the Sengoku period though Azuchi-Momoyama Period. He was also known by his court title, . He was born in 1559 to a father who was said to be a retainer of either Ōtomo Sōrin or of Rokkaku Yoshikata. He become one of Toyotomi Hideyoshi's followers...

    , a Japanese daimyo
    Daimyo
    is a generic term referring to the powerful territorial lords in pre-modern Japan who ruled most of the country from their vast, hereditary land holdings...

  • Biblical writings have a number of references such as Moses's sister, Miriam, Moses
    Moses
    Moses was, according to the Hebrew Bible and Qur'an, a religious leader, lawgiver and prophet, to whom the authorship of the Torah is traditionally attributed...

    , commander of the army of Syria Naaman the Syrian
    Naaman
    Naaman was a commander of the armies of Ben-Hadad II in the time of Joram, king of Israel. He is mentioned in of the Tanakh. According to the narrative, he was afflicted with tzaraath...

     and later the prophet Elisha
    Elisha
    Elisha is a prophet mentioned in the Hebrew Bible and the Qur'an. His name is commonly transliterated into English as Elisha via Hebrew, Eliseus via Greek and Latin, or Alyasa via Arabic.-Biblical biography:...

    's servant Gehazi
    Gehazi
    Gehazi, Geichazi, or Giezi is a figure found in the Tanakh Books of Kings. He was Elisha's servant. He appears in connection with the history of the Shunammite and of Naaman the Syrian...

    , and several people Jesus
    Jesus
    Jesus of Nazareth , commonly referred to as Jesus Christ or simply as Jesus or Christ, is the central figure of Christianity...

     healed, though the afflicted mentioned and symptoms described are now thought not to be, or not exclusively to be, the result of Hansen's Disease (see discussion at 'Tzaraath
    Tzaraath
    The Hebrew noun tzaraath describes a disfigurative condition mainly referred to in chapters 13-14 of Leviticus, as well as conditions equivalent to be "mildew" on clothes and houses.Tzaraath affects both animate...

    ').

Further reading

  • 1877:
  • 1895:
  • 1895:
  • 1896:
  • 1916:
  • 1991:William Jopling
    William Jopling
    William Jopling was a leprologist who together with Ridley D.S. proposed the Ridley-Jopling classification of leprosy , and wrote the widely read textbook of "Handbook of Leprosy" which had a fifth edition...

    . Leprosy stigma
    Leprosy stigma
    Leprosy stigma is a kind of social stigma, a strong feeling that a leprosy patient is shameful and is not accepted normally in society. Also called leprosy related stigma, leprostigma and stigma of leprosy.-Stigma:...

    . Lepr Rev 1991, 62, 1-12.

External links

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