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Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''
Mycobacterium leprae ''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus) is one of the two species of bacteria that cause Hansen's disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and ta ...
'' or ''
Mycobacterium lepromatosis ''Mycobacterium lepromatosis'' is an aerobic, Acid-fastness, acid-fast bacillus (AFB), and the second known causative agent of Hansen's disease (leprosy). It was discovered in 2008. Analysis of the 16S ribosomal RNA, 16S rRNA gene confirms that th ...
''. Infection can lead to damage of the
nerves A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called ...
,
respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respirato ...
, skin, and eyes. This nerve damage may result in a lack of ability to feel pain, which can lead to the loss of parts of a person's extremities from repeated injuries or infection through unnoticed wounds. An infected person may also experience muscle weakness and poor eyesight. Leprosy symptoms may begin within one year, but for some people symptoms may take 20 years or more to occur. Leprosy is spread between people, although extensive contact is necessary. Leprosy has a low
pathogenicity In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ. The term ...
, and 95% of people who contract or who are exposed to ''M. leprae'' do not develop the disease. Spread is likely through a cough or contact with fluid from the nose of a person infected by leprosy. Genetic factors and immune function play a role in how easily a person catches the disease. Leprosy does not spread during pregnancy to the unborn child or through sexual contact. Leprosy occurs more commonly among people living in poverty. There are two main types of the disease – paucibacillary and multibacillary, which differ in the number of bacteria present. A person with paucibacillary disease has five or fewer poorly pigmented, numb skin patches, while a person with multibacillary disease has more than five skin patches. The diagnosis is confirmed by finding
acid-fast Acid-fastness is a physical property of certain bacterial and eukaryotic cells, as well as some sub-cellular structures, specifically their resistance to decolorization by acids during laboratory staining procedures. Once stained as part of a sa ...
bacilli in a biopsy of the skin. Leprosy is curable with multidrug therapy. Treatment of paucibacillary leprosy is with the medications
dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment an ...
,
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...
, and
clofazimine Clofazimine, sold under the brand name Lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. It is specifically used for multibacillary (MB) leprosy and erythema nodosum leprosum, and its discovery greatly impro ...
for six months. Treatment for multibacillary leprosy uses the same medications for 12 months. Several other antibiotics may also be used. These treatments are provided free of charge by the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
. Leprosy is not highly contagious. People with leprosy can live with their families and go to school and work. In the 1980s, there were 5.2 million cases globally, but by 2020 this decreased to fewer than 200,000. Most new cases occur in one of 14 countries, with India accounting for more than half of all new cases. In the 20 years from 1994 to 2014, 16 million people worldwide were cured of leprosy. About 200 cases per year are reported in the United States. Central Florida accounted for 81% of cases in Florida and nearly 1 out of 5 leprosy cases nationwide. Separating people affected by leprosy by placing them in
leper colonies A leper colony, also known by many other names, is an isolated community for the quarantining and treatment of lepers, people suffering from leprosy. '' M. leprae'', the bacterium responsible for leprosy, is believed to have spread from East ...
is not supported by evidence but still occurs in some areas of India, China, Japan, Africa, and Thailand. Leprosy has affected humanity for thousands of years. The disease takes its name from the
Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...
word (), from (; 'scale'), while the term "Hansen's disease" is named after the Norwegian physician
Gerhard Armauer Hansen Gerhard Henrik Armauer Hansen (; 29 July 1841 – 12 February 1912) was a Norwegians, Norwegian physician, remembered for his identification of the Bacteria, bacterium ''Mycobacterium leprae'' in 1873 as the causative agent of leprosy. His dis ...
. Leprosy has historically been associated with
social stigma Stigma, originally referring to the visible marking of people considered inferior, has evolved to mean a negative perception or sense of disapproval that a society places on a group or individual based on certain characteristics such as their ...
, which continues to be a barrier to self-reporting and early treatment. Leprosy is classified as a
neglected tropical disease Neglected tropical diseases (NTDs) are a diverse group of tropical infections that are common in low-income populations in developing regions of Africa, Asia, and the Americas. They are caused by a variety of pathogens, such as viruses, bacteri ...
. World Leprosy Day was started in 1954 to draw awareness to those affected by leprosy. The study of leprosy and its treatment is known as leprology.


Signs and symptoms

Common symptoms present in the different types of leprosy include a runny nose; dry
scalp The scalp is the area of the head where head hair grows. It is made up of skin, layers of connective and fibrous tissues, and the membrane of the skull. Anatomically, the scalp is part of the epicranium, a collection of structures covering th ...
; eye problems; skin
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals. Types There is no de ...
s; muscle weakness; reddish skin; smooth, shiny, diffuse thickening of facial skin, ear, and hand; loss of sensation in fingers and toes; thickening of
peripheral nerves The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain a ...
; a flat nose from the destruction of
nasal cartilage The nasal cartilages are structures within the nose that provide form and support to the nasal cavity. The nasal cartilages are made up of a flexible material called hyaline cartilage (packed collagen) in the distal portion of the nose. There are f ...
s; and changes in
phonation The term phonation has slightly different meanings depending on the subfield of phonetics. Among some phoneticians, ''phonation'' is the process by which the vocal folds produce certain sounds through quasi-periodic vibration. This is the defi ...
and other aspects of speech production. In addition,
atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), malnutrition, poor nourishment, poor circulatory system, circulation, loss of hormone, ...
of the testes and
impotence Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...
may occur. Leprosy can affect people in different ways. The average
incubation period Incubation period (also known as the latent period or latency period) is the time elapsed between exposure to a pathogenic organism, a chemical, or ionizing radiation, radiation, and when symptoms and signs are first apparent. In a typical infect ...
is five years. People may begin to notice symptoms within the first year or up to 20 years after infection. The first noticeable sign of leprosy is often the development of pale or pink coloured patches of skin that may be insensitive to temperature or pain. Patches of discolored skin are sometimes accompanied or preceded by nerve problems including numbness or tenderness in the hands or feet.
Secondary infection infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s (additional bacterial or viral infections) can result in tissue loss, causing fingers and toes to become shortened and deformed, as cartilage is absorbed into the body. A person's immune response differs depending on the form of leprosy. Approximately 30% of people affected with leprosy experience nerve damage. The nerve damage sustained is reversible when treated early but becomes permanent when appropriate treatment is delayed by several months. Damage to nerves may cause loss of muscle function, leading to paralysis. It may also lead to sensation abnormalities or
numbness Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to Sensory receptor, sensory stimuli. In everyday speech this is generally r ...
, which may lead to additional infections, ulcerations, and joint deformities. File:Tuberous Leprosy Wellcome L0032810.jpg, Face severely deformed by leprosy File:Leprosy deformities hands.jpg, Hands deformed by leprosy File:Fox Plate XL.jpg, Face mildly deformed by leprosy


Cause


''M. leprae'' and ''M. lepromatosis''

'' Mycobacterioum leprae'' and ''
Mycobacterium lepromatosis ''Mycobacterium lepromatosis'' is an aerobic, Acid-fastness, acid-fast bacillus (AFB), and the second known causative agent of Hansen's disease (leprosy). It was discovered in 2008. Analysis of the 16S ribosomal RNA, 16S rRNA gene confirms that th ...
'' are the
mycobacteria ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') a ...
that cause leprosy. ''M. lepromatosis'' is a relatively newly identified mycobacterium isolated from a fatal case of diffuse lepromatous leprosy in 2008. ''M. lepromatosis'' is indistinguishable clinically from ''M. leprae''. ''M. leprae'' is an
aerobic Aerobic means "requiring air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Aerobic respiration, the aerobic process of cellu ...
, rod-shaped, acid-fast
bacterium Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...
with a waxy
cell envelope The cell envelope comprises the inner cell membrane and the cell wall of a bacterium. In Gram-negative bacteria an bacterial outer membrane, outer membrane is also included. This envelope is not present in the Mollicutes where the cell wall is abse ...
characteristic of the genus ''
Mycobacterium ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis (''Mycobacterium tuberculo ...
''. ''M. leprae'' and ''M. lepromatosis'' are obligate intracellular pathogens and cannot grow or be cultured outside of host tissues. However, they can be grown using research animals such as mice and
armadillo Armadillos () are New World placental mammals in the order (biology), order Cingulata. They form part of the superorder Xenarthra, along with the anteaters and sloths. 21 extant species of armadillo have been described, some of which are dis ...
s. Naturally occurring infections have been reported in nonhuman primates (including the African
chimpanzee The chimpanzee (; ''Pan troglodytes''), also simply known as the chimp, is a species of Hominidae, great ape native to the forests and savannahs of tropical Africa. It has four confirmed subspecies and a fifth proposed one. When its close rel ...
, the
sooty mangabey The sooty mangabey (''Cercocebus atys'') is an Old World monkey found in forests from Senegal in a margin along the coast down to the Ivory Coast. Habitat and ecology The sooty mangabey is native to tropical West Africa, being found in Guinea, G ...
, and the
cynomolgus The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque or cynomolgus macaque, is a cercopithecine primate native to Southeast Asia. As a synanthropic species, the crab-eating macaque thrives near human settleme ...
macaque), armadillos, and
red squirrel The red squirrel (''Sciurus vulgaris''), also called Eurasian red squirrel, is a species of tree squirrel in the genus ''Sciurus''. It is an arboreal and primarily herbivorous rodent and common throughout Eurasia. Taxonomy There have been ...
s.
Multilocus sequence typing Multilocus sequence typing (MLST) is a technique in molecular biology for the typing of multiple loci, using DNA sequences of internal fragments of multiple housekeeping genes to characterize isolates of microbial species. The first MLST scheme ...
of the armadillo ''M. leprae'' strains suggests that they were of human origin for at most a few hundred years. Thus, it is suspected that armadillos first acquired the organism incidentally from early European explorers of the Americas. This incidental transmission was sustained in the armadillo population, and it may be transmitted back to humans, making leprosy a zoonotic disease (spread between humans and animals). Red squirrels (''Sciurus vulgaris''), a threatened species in Great Britain, were found to carry leprosy in November 2016. It has been suggested that the trade in red squirrel fur, highly prized in the medieval period and intensively traded, may have been responsible for the leprosy epidemic in medieval Europe. A pre-
Norman Norman or Normans may refer to: Ethnic and cultural identity * The Normans, a people partly descended from Norse Vikings who settled in the territory of Normandy in France in the 9th and 10th centuries ** People or things connected with the Norma ...
era skull excavated in Hoxne, Suffolk, in 2017 was found to carry DNA from a strain of ''M. leprae'' which closely matched the strain carried by modern red squirrels on
Brownsea Island Brownsea Island is the largest of the islands in Poole Harbour in the county of Dorset, England. The island is owned by the National Trust for Places of Historic Interest or Natural Beauty, National Trust with the northern half managed by the Do ...
.


Risk factors

The greatest risk factor for developing leprosy is contact with another person infected by leprosy. People who are exposed to a person who has leprosy are 5–8 times more likely to develop leprosy than members of the general population. Leprosy occurs more commonly among those living in poverty. Not all people who are infected with ''M. leprae'' develop symptoms. Conditions that reduce immune function, such as malnutrition, other illnesses, or genetic mutations, may increase the risk of developing leprosy. Infection with
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...
does not appear to increase the risk of developing leprosy. Certain genetic factors in the person exposed have been associated with developing lepromatous or tuberculoid leprosy.


Transmission

Transmission of leprosy occurs during close contact with those who are infected. Transmission of leprosy is through the upper
respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respirato ...
. Older research suggested the skin as the main route of transmission, but research has increasingly favored the respiratory route. Transmission occurs through inhalation of bacilli present in upper airway secretion. Leprosy is not sexually transmitted and is not spread through pregnancy to the unborn child. The majority (95%) of people who are exposed to ''M. leprae'' do not develop leprosy; casual contact such as shaking hands and sitting next to someone with leprosy does not lead to transmission. People are considered non-infectious 72 hours after starting appropriate multi-drug therapy. Two exit routes of ''M. leprae'' from the human body that are 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 The dermis or corium is a layer of skin between the epidermis (skin), epidermis (with which it makes up the cutis (anatomy), cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from s ...
, but whether they reach the skin surface in sufficient numbers is doubtful. Humans can acquire a leprosy infection from armadillos by handling them or consuming armadillo meat. The mechanism is not fully understood.


Genetics

Not all people infected or exposed to ''M. leprae'' develop leprosy, and genetic factors are suspected to play a role in susceptibility to an infection. Cases of leprosy often cluster in families, and several genetic variants have been identified. In many who are exposed, the immune system can eliminate the leprosy bacteria during the early infection stage before severe symptoms develop. A genetic defect in cell-mediated immunity may cause a person to be susceptible to develop leprosy symptoms after exposure to the bacteria. The region of
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
responsible for this variability is also involved in
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...
, giving rise to current speculation that the two disorders may be linked at the biochemical level.


Mechanism

Most leprosy complications are the result of nerve damage. The nerve damage occurs from direct invasion by the ''M. leprae'' bacteria and a person's immune response resulting in inflammation. The molecular mechanism underlying how ''M. leprae'' produces the symptoms of leprosy is not clear, but ''M. leprae'' has been shown to bind to
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include Satellite glial cell, satellite ...
s, which may lead to nerve injury including
demyelination A demyelinating disease refers to any disease affecting the nervous system where the myelin sheath surrounding neurons is damaged. This damage disrupts the transmission of signals through the affected nerves, resulting in a decrease in their con ...
and a loss of nerve function (specifically a loss of
axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...
al conductance). Numerous molecular mechanisms have been associated with this nerve damage including the presence of a
laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...
-binding protein and the glycoconjugate (PGL-1) on the surface of ''M. leprae'' that can bind to laminin on
peripheral nerves The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain a ...
. As part of the human immune response,
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
-derived
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s may engulf ''M. leprae'' by
phagocytosis Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
. In the initial stages, small sensory and autonomic nerve fibers in the skin of a person with leprosy are damaged. This damage usually results in hair loss to the area, a loss of the ability to sweat, and numbness (decreased ability to detect sensations such as temperature and touch). Further peripheral nerve damage may result in skin dryness, more numbness, and muscle weaknesses or paralysis in the area affected. The skin can crack and if the skin injuries are not carefully cared for, there is a risk for a secondary infection that can lead to more severe damage.


Diagnosis

In countries where people are frequently infected, a person is considered to have leprosy if they have one of the following two signs: * Skin lesion consistent with leprosy and with definite sensory loss. * Positive skin smears. Skin lesions can be single or many, and usually hypopigmented, although occasionally reddish or copper-colored. The lesions may be flat (
macule A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sys ...
s), raised (
papule A papule is a small, well-defined bump in the skin lesion, skin. It may have a rounded, pointed or flat top, and may have a umbilication, dip. It can appear with a Peduncle (anatomy), stalk, be thread-like or look warty. It can be soft or firm a ...
s), or solid elevated areas ( nodular). Experiencing sensory loss at the skin lesion is a feature that can help determine if the lesion is caused by leprosy or by another disorder such as
tinea versicolor Tinea versicolor (also pityriasis versicolor) is a condition characterized by a skin eruption on the trunk and proximal extremities. The majority of tinea versicolor is caused by the fungus '' Malassezia globosa'', although '' Malassezia furfur' ...
. Thickened nerves are associated with leprosy and can be accompanied by loss of sensation or muscle weakness, but muscle weakness without the characteristic skin lesion and sensory loss is not considered a reliable sign of leprosy. In some cases, the presence of
acid-fast Acid-fastness is a physical property of certain bacterial and eukaryotic cells, as well as some sub-cellular structures, specifically their resistance to decolorization by acids during laboratory staining procedures. Once stained as part of a sa ...
leprosy
bacilli Bacilli is a Taxonomy (biology), taxonomic Class (biology), class of bacteria that includes two orders, Bacillales and Lactobacillales, which contain several well-known pathogens such as ''Bacillus anthracis'' (the cause of anthrax). ''Bacilli'' ...
in skin smears is considered diagnostic; however, the diagnosis is typically made without laboratory tests, based on symptoms. If a person has a new leprosy diagnosis and already has a visible disability caused by leprosy, the diagnosis is considered late. In countries or areas where leprosy is uncommon, such as the United States, diagnosis of leprosy is often delayed because healthcare providers are unaware of leprosy and its symptoms. Early diagnosis and treatment prevent nerve involvement, the hallmark of leprosy, and the disability it causes.U.S. Department of Health and Human Services, Health Resources and Services Administration. (n.d.). National Hansen's disease (leprosy) program Retrieved from There is no recommended test to diagnose latent leprosy in people without symptoms. Few people with latent leprosy test positive for anti PGL-1. The presence of ''M. leprae'' bacterial
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
can be identified using a
polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to make millions to billions of copies of a specific DNA sample rapidly, allowing scientists to amplify a very small sample of DNA (or a part of it) sufficiently to enable detailed st ...
(PCR)-based technique. This molecular test alone is not sufficient to diagnose a person, but this approach may be used to identify someone who is at high risk of developing or transmitting leprosy such as those with few lesions or an atypical clinical presentation. New approaches propose tools to diagnose leprosy through artificial intelligence.


Classification

Several different approaches for classifying leprosy exist. There are similarities between the classification approaches. * The World Health Organization (WHO) system distinguishes patients with 5 or fewer skin lesions and no bacilli in a skin smear as "paucibacillary" (" pauci-" refers to a small quantity) from patients with more lesions or detected bacilli as "multibacillary". * The Ridley-Jopling scale provides five gradations. * The
ICD-10 ICD-10 is the 10th revision of the International Classification of Diseases (ICD), a medical classification list by the World Health Organization (WHO). It contains codes for diseases, signs and symptoms, abnormal findings, complaints, social cir ...
, though developed by the WHO, uses Ridley-Jopling and not the WHO system. It also adds an indeterminate ("I") entry."What Is Leprosy?", from News-Medical.Net – Latest Medical News and Research from Around the World. Web. 20 November 2010. . * In
MeSH Medical Subject Headings (MeSH) is a comprehensive controlled vocabulary for the purpose of indexing journal articles and books in the life sciences. It serves as a thesaurus of index terms that facilitates searching. Created and updated by th ...
, three groupings are used. Leprosy may also occur with only neural involvement, without skin lesions.


Complications

Leprosy may cause the victim to lose limbs and digits but not directly. ''M. leprae'' attacks nerve endings and destroys the body's ability to feel pain and injury. Without feeling pain, people with leprosy have an increased risk of injuring themselves. Injuries become infected and result in tissue loss. Fingers, toes, and limbs become shortened and deformed as the tissue is absorbed into the body.


Prevention

Early disease detection is important, since physical and neurological damage may be irreversible even if cured. Medications can decrease the risk of those living with people who have leprosy from acquiring the disease and likely those with whom people with leprosy come into contact outside the home. The WHO recommends that preventive medicine be given to people who are in close contact with someone who has leprosy. The suggested preventive treatment is a single dose of
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...
in adults and children over 2 years old who do not already have leprosy or tuberculosis. Preventive treatment is associated with a 57% reduction in infections within 2 years and a 30% reduction in infections within 6 years. The Bacillus Calmette–Guérin ( BCG) vaccine offers a variable amount of protection against leprosy in addition to its closely related target of
tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
. It appears to be 26% to 41% effective (based on controlled trials) and about 60% effective based on observational studies with two doses possibly working better than one. The WHO concluded in 2018 that the BCG vaccine at birth reduces leprosy risk and is recommended in countries with high incidence of TB and people who have leprosy. People living in the same home as a person with leprosy are suggested to take a BCG booster which may improve their immunity by 56%. Development of a more effective vaccine is ongoing. A novel vaccine called LepVax entered clinical trials in 2017 with the first encouraging results reported on 24 participants published in 2020. If successful, this would be the first leprosy-specific vaccine available.


Treatment

Several
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 * rifamp ...
s are available for treatment. A three-drug regimen of
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...
,
dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment an ...
, and
clofazimine Clofazimine, sold under the brand name Lamprene, is a medication used together with rifampicin and dapsone to treat leprosy. It is specifically used for multibacillary (MB) leprosy and erythema nodosum leprosum, and its discovery greatly impro ...
is recommended for all people with leprosy, for six months for paucibacillary leprosy and 12 months for multibacillary leprosy. Multidrug therapy (MDT) remains highly effective, and people are no longer infectious after the first monthly dose. MDT is safe and easy to use under field conditions because it is available in calendar-labelled blister packs. The treatment does pose compliance challenges for young children who find swallowing multiple solid pills difficult. Post-treatment relapse rates remain low. The combination treatment accelerates treatment and decreases the chance of creating drug-resistant bacteria. All three drugs in the three-drug regimen are antibacterial, with rifampicin being the most potent. Rifampicin is scheduled monthly since it interferes with dapsone by inducing its increased metabolism. Resistance to the three-drug regimen has been reported in several countries, although the number of cases is small. People with rifampicin-resistant leprosy may be treated with second-line medications such as
fluoroquinolones Quinolone antibiotics constitute a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ve ...
,
minocycline Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as some occurring in certain forms of pneumonia. It is generally (but not always) less pre ...
, or
clarithromycin Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, '' H. pylori'' infection, and Lyme disease, among others. Clari ...
, but the treatment duration is 24 months because of their lower
bactericidal A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their p ...
activity. Evidence on the potential benefits and harms of alternative regimens for drug-resistant leprosy is not available. For people with nerve damage, protective footwear may help prevent ulcers and secondary infection. Canvas shoes may be better than PVC boots. There may be no difference between double rocker shoes and below-knee plaster. Topical
ketanserin Ketanserin, sold under the brand name Sufrexal, is an antihypertensive agent which is used to treat arterial hypertension and vasospasm, vasospastic disorders. It is also used in scientific research as an antiserotonergic medication, agent in th ...
seems to have a better effect on ulcer healing than clioquinol cream or zinc paste, but the evidence for this is weak.
Phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anticonvulsant, anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence se ...
applied to the skin improves skin changes to a greater degree when compared to saline dressings.


Outcomes

Although leprosy has been curable since the mid-20th century, left untreated it can cause permanent physical impairments and damage to a person's nerves, skin, eyes, and limbs. Despite leprosy not being very infectious and having a low pathogenicity, there is still significant stigma and prejudice associated with the disease. Because of this stigma, leprosy can affect a person's participation in social activities and may also affect the lives of their family and friends. People with leprosy are also at a higher risk for problems with their mental well-being. The social stigma may contribute to problems obtaining employment, financial difficulties, and social isolation. Efforts to reduce discrimination and reduce the stigma surrounding leprosy may help improve outcomes for people with leprosy.


Epidemiology

In 2018, there were 208,619 new cases of leprosy recorded, a slight decrease from 2017. In 2015, 94% of the new leprosy cases were confined to 14 countries. India reported the greatest number of new cases (60% of reported cases), followed by Brazil (13%) and
Indonesia Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania, between the Indian Ocean, Indian and Pacific Ocean, Pacific oceans. Comprising over List of islands of Indonesia, 17,000 islands, including Sumatra, ...
(8%). Although the number of cases worldwide continues to fall, there are parts of the world where leprosy is more common, including Brazil, South Asia (India, Nepal, Bhutan), some parts of Africa (Tanzania, Madagascar, Mozambique), and the western Pacific. About 150 to 250 cases are diagnosed in the United States each year. In the 1960s, there were tens of millions of leprosy cases recorded when the bacteria started to develop resistance to
dapsone Dapsone, also known as 4,4'-sulfonyldianiline (SDA) or diaminodiphenyl sulfone (DDS), is an antibiotic commonly used in combination with rifampicin and clofazimine for the treatment of leprosy. It is a second-line medication for the treatment an ...
, the most common treatment option at the time. International (e.g., the
WHO The World Health Organization (WHO) is a specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Geneva, Switzerland, and has 6 regional offices and 15 ...
's "Global Strategy for Reducing Disease Burden Due to Leprosy" and the International Federation of Anti-Leprosy Associations) and national initiatives have reduced the total number and the number of new cases of the disease. The number of new leprosy cases is difficult to measure and monitor because of leprosy's long incubation period, delays in diagnosis after the onset of the disease, and lack of medical care in affected areas. The registered
prevalence In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
of the disease is used to determine
disease burden Disease burden is the impact of a health problem as measured by financial cost, mortality, morbidity, or other indicators. It is often quantified in terms of quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs). Both ...
. 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.


History


Historical distribution

Using
comparative genomics Comparative genomics is a branch of biological research that examines genome sequences across a spectrum of species, spanning from humans and mice to a diverse array of organisms from bacteria to chimpanzees. This large-scale holistic approach c ...
, in 2005, geneticists traced the origins and worldwide distribution of leprosy from East Africa or the Near East along human migration routes. They found four strains of ''M. leprae'' with specific regional locations: Monot ''et al.'' (2005) determined that leprosy originated in East Africa or the Near East and traveled with humans along their migration routes, including those of trade in goods and slaves. The four strains of ''M. leprae'' are based in specific geographic regions where each predominantly occurs: * strain 1 in Asia, the Pacific region, and East Africa; * strain 2 in Ethiopia,
Malawi Malawi, officially the Republic of Malawi, is a landlocked country in Southeastern Africa. It is bordered by Zambia to the west, Tanzania to the north and northeast, and Mozambique to the east, south, and southwest. Malawi spans over and ...
, Nepal, north India, and
New Caledonia New Caledonia ( ; ) is a group of islands in the southwest Pacific Ocean, southwest of Vanuatu and east of Australia. Located from Metropolitan France, it forms a Overseas France#Sui generis collectivity, ''sui generis'' collectivity of t ...
; * strain 3 in Europe, North Africa, and the Americas; * strain 4 in West Africa and the Caribbean. This confirms the spread of the disease along the migration, colonisation, and slave trade routes taken from East Africa to India, West Africa to the New World, and from Africa to Europe and vice versa. Skeletal remains discovered in 2009 represent the oldest documented evidence for leprosy, dating to the 2nd millennium BC. Located at Balathal, Rajasthan, in northwest India, the discoverers suggest that if the disease did migrate from Africa to India during the 3rd millennium BC "at a time when there was substantial interaction among the Indus Civilization, Mesopotamia, and Egypt, there needs to be additional skeletal and molecular evidence of leprosy in India and Africa to confirm the African origin of the disease". A proven human case was verified by DNA taken from the shrouded remains of a man discovered by researchers from the
Hebrew University of Jerusalem The Hebrew University of Jerusalem (HUJI; ) is an Israeli public university, public research university based in Jerusalem. Co-founded by Albert Einstein and Chaim Weizmann in July 1918, the public university officially opened on 1 April 1925. ...
in a tomb in
Akeldama Akeldama (Aramaic: חקל דמא or 𐡇𐡒𐡋 𐡃𐡌𐡀 ''Ḥaqel D'ma'', "field of blood"; Hebrew: חקל דמא; Arabic: حقل الدم, ''Ḥaqel Ad-dam'') is the Aramaic name for a place in Jerusalem associated with Judas Iscariot, o ...
, next to the
Old City of Jerusalem The Old City of Jerusalem (; ) is a walled area in Jerusalem. In a tradition that may have begun with an 1840s British map of the city, the Old City is divided into four uneven quarters: the Muslim Quarter, the Christian Quarter, the Arm ...
dated by radiocarbon methods to the first half of the 1st century. The oldest strains of leprosy known from Europe are from Great Chesterford in southeast England and date back to AD 415–545. These findings suggest a different path for the spread of leprosy, meaning it may have originated in western Eurasia. This study also indicates that there were more strains in Europe at the time than previously determined.


Discovery and scientific progress

Literary attestation of leprosy is unclear because of the ambiguity of many early sources, including the Indian
Atharvaveda The Atharvaveda or Atharva Veda (, , from ''wikt:अथर्वन्, अथर्वन्'', "priest" and ''wikt:वेद, वेद'', "knowledge") or is the "knowledge storehouse of ''wikt:अथर्वन्, atharvans'', the proced ...
and Kausika Sutra, the Egyptian
Ebers Papyrus The Ebers Papyrus, also known as Papyrus Ebers, is an Egyptian medical papyrus of herbal knowledge dating to (the late Second Intermediate Period or early New Kingdom). Among the oldest and most important medical papyri of Ancient Egypt, it ...
, and the
Hebrew Bible The Hebrew Bible or Tanakh (;"Tanach"
. '' tzaraath ''Tzaraath'' (Hebrew language, Hebrew: ''ṣāraʿaṯ''), #Name, variously transcribed into English and frequently translated as leprosy (though it is not Hansen's disease, the disease known as "leprosy" in modern times), is a term used in the ...
''). Leprotic symptoms are attested in the Indian doctor
Sushruta Suśruta (, ) is the listed author of the '' Suśruta Saṃhiāa'' (''Suśruta's Compendium''), considered to be one of the most important surviving ancient treatises on medicine. It is also considered a foundational text of Ayurveda. The treat ...
's ''Compendium'', originally dating to c. 600 BC but only surviving in emended texts no earlier than the 5th century BC. Symptoms consistent with leprosy were possibly described by
Hippocrates Hippocrates of Kos (; ; ), also known as Hippocrates II, was a Greek physician and philosopher of the Classical Greece, classical period who is considered one of the most outstanding figures in the history of medicine. He is traditionally referr ...
in 460 BC. However, Hansen's disease probably did not exist in Greece or the Middle East before the
Common Era Common Era (CE) and Before the Common Era (BCE) are year notations for the Gregorian calendar (and its predecessor, the Julian calendar), the world's most widely used calendar era. Common Era and Before the Common Era are alternatives to the ...
. In 1846, Francis Adams produced ''The Seven Books of Paulus Aegineta'' which included a commentary on all medical and surgical knowledge and descriptions and remedies to do with leprosy from the Romans, Greeks, and Arabs. Leprosy did not exist in the Americas before
colonization 475px, Map of the year each country achieved List of sovereign states by date of formation, independence. Colonization (British English: colonisation) is a process of establishing occupation of or control over foreign territories or peoples f ...
by modern Europeans nor did it exist in
Polynesia Polynesia ( , ) is a subregion of Oceania, made up of more than 1,000 islands scattered over the central and southern Pacific Ocean. The indigenous people who inhabit the islands of Polynesia are called Polynesians. They have many things in ...
until the middle of the 19th century. The causative agent of leprosy, ''M. leprae'', was discovered by
Gerhard Armauer Hansen Gerhard Henrik Armauer Hansen (; 29 July 1841 – 12 February 1912) was a Norwegians, Norwegian physician, remembered for his identification of the Bacteria, bacterium ''Mycobacterium leprae'' in 1873 as the causative agent of leprosy. His dis ...
in
Norway Norway, officially the Kingdom of Norway, is a Nordic countries, Nordic country located on the Scandinavian Peninsula in Northern Europe. The remote Arctic island of Jan Mayen and the archipelago of Svalbard also form part of the Kingdom of ...
in 1873, making it one of the first species of pathogenic bacteria identified.


Treatment

Chaulmoogra ''Hydnocarpus pentandrus'' (previously ''Hydnocarpus wightianus'') or chaulmoogra is a medium-sized tree in the family Achariaceae. This dioecious tree grows up to 10m height, in moist deciduous forests of Western Ghats in India. ''Hydnocarpu ...
tree oil was used topically to manage Hansen's disease for centuries. Chaulmoogra oil could not be taken orally without causing nausea or injected without forming an abscess. Leprosy was once believed to be highly contagious and was treated with mercury, as was
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...
, which was first described in 1530. Many early cases thought to be leprosy could actually have been syphilis. In 1915, Alice Ball, the first black woman to graduate from the University of Hawai'i with a masters in chemistry, discovered how to make the oil water soluble. This technique led to marked improvements in patients with Hansen's disease who were treated in Hawai'i. The first effective drug ( promin) became available in the 1940s. In the 1950s, dapsone was introduced. The search for further effective antileprosy drugs led to the use of clofazimine and rifampicin in the 1960s and 1970s. Later, Indian scientist Shantaram Yawalkar and his colleagues formulated a combined therapy using rifampicin and dapsone, intended to mitigate bacterial resistance. Combining all three drugs was first recommended by the WHO in 1981. These three drugs are still used in the standard MDT regimens. Resistance has developed to initial treatment. Until the introduction of MDT in the early 1980s, leprosy could not be diagnosed and treated successfully within the community. The importance of the nasal mucosa in the transmission of ''M. leprae'' was recognized as early as 1898 by Schäffer, in particular, that of the ulcerated mucosa.''Arch Dermato Syphilis'' 1898; 44:159–174 The mechanism of plantar ulceration in leprosy and its treatment was first described by Ernest W. Price.


Etymology

The word "leprosy" comes from the Greek word "λέπος (lépos) – skin" and "λεπερός (leperós) – scaly man".


Society and culture


Treatment cost

Between 1995 and 1999 the WHO, with the aid of the
Nippon Foundation of Tokyo, Japan, is a private, non-profit grant-making organization. It was established in 1962 by Ryōichi Sasakawa. The foundation's mission is to direct Japanese motorboat racing revenue into philanthropic activities, it uses this money t ...
, supplied all endemic countries with free MDT in blister packs, channeled through ministries of health. This free provision was extended in 2000 and again in 2005, 2010, and 2015 with donations by the MDT manufacturer
Novartis Novartis AG is a Swiss multinational corporation, multinational pharmaceutical company, pharmaceutical corporation based in Basel, Switzerland. Novartis is one of the largest pharmaceutical companies in the world and was the eighth largest by re ...
through the WHO. At the national level,
non-governmental organizations A non-governmental organization (NGO) is an independent, typically nonprofit organization that operates outside government control, though it may get a significant percentage of its funding from government or corporate sources. NGOs often focus ...
(NGOs) affiliated with the national program will continue to be provided with an appropriate free supply.


Historical texts

Written accounts of leprosy date back thousands of years. Various skin diseases translated as leprosy appear in the ancient Indian text, the '' Atharava Veda'', by 600 BC. Another Indian text, the ''
Manusmriti The ''Manusmṛti'' (), also known as the ''Mānava-Dharmaśāstra'' or the Laws of Manu, is one of the many legal texts and constitutions among the many ' of Hinduism. Over fifty manuscripts of the ''Manusmriti'' are now known, but the earli ...
'' (200 BC),  prohibit contact with those infected with the disease and make marriage to a person infected with leprosy punishable. The Hebraic root tsara or tsaraath (צָרַע, – tsaw-rah' – to be struck with leprosy, to be leprous) and the Greek (λεπρός – lepros), are of broader classification than the more narrow use of the term related to Hansen's Disease. Any progressive skin disease (a whitening or splotchy bleaching of the skin, raised manifestations of scales, scabs, infections, rashes, etc.) — as well as generalized molds and surface discoloration of any clothing, leather, or discoloration on walls or surfaces throughout homes — all came under the "law of leprosy" ( Leviticus 14:54–57). Ancient sources such as the
Talmud The Talmud (; ) is the central text of Rabbinic Judaism and the primary source of Jewish religious law (''halakha'') and Jewish theology. Until the advent of Haskalah#Effects, modernity, in nearly all Jewish communities, the Talmud was the cen ...
(Sifra 63) make clear that'' tzaraath'' refers to various types of lesions or stains associated with
ritual impurity Ritual purification is a ritual prescribed by a religion through which a person is considered to be freed of ''uncleanliness'', especially prior to the worship of a deity, and ritual purity is a state of ritual cleanliness. Ritual purification ...
and occurring on cloth, leather, or houses, as well as skin. Traditional
Judaism Judaism () is an Abrahamic religions, Abrahamic, Monotheism, monotheistic, ethnic religion that comprises the collective spiritual, cultural, and legal traditions of the Jews, Jewish people. Religious Jews regard Judaism as their means of o ...
and Jewish rabbinical authorities, both historical and modern, emphasize that the ''tsaraath'' of Leviticus is a spiritual ailment with no direct relationship to Hansen's disease or physical contagions. The relation of ''tsaraath'' to "leprosy" comes from translations of Hebrew Biblical texts into Greek and ensuing misconceptions. All three
Synoptic Gospels The gospels of Gospel of Matthew, Matthew, Gospel of Mark, Mark, and Gospel of Luke, Luke are referred to as the synoptic Gospels because they include many of the same stories, often in a similar sequence and in similar or sometimes identical ...
of the
New Testament The New Testament (NT) is the second division of the Christian biblical canon. It discusses the teachings and person of Jesus in Christianity, Jesus, as well as events relating to Christianity in the 1st century, first-century Christianit ...
describe instances of
Jesus Jesus (AD 30 or 33), also referred to as Jesus Christ, Jesus of Nazareth, and many Names and titles of Jesus in the New Testament, other names and titles, was a 1st-century Jewish preacher and religious leader. He is the Jesus in Chris ...
healing people with leprosy
Matthew 8:1–4Mark 1:40–45
an
Luke 5:12–16
. The Bible's description of leprosy is congruous (if lacking detail) with the symptoms of modern leprosy, but the relationship between this disease, ''tzaraath'', and Hansen's disease has been disputed. The biblical perception that people with leprosy were unclean can be found in a passage fro
Leviticus 13:44–46
While this text defines the leper as impure, it does not explicitly make a moral judgement on those with leprosy. Some
early Christians Early Christianity, otherwise called the Early Church or Paleo-Christianity, describes the historical era of the Christian religion up to the First Council of Nicaea in 325. Christianity spread from the Levant, across the Roman Empire, and bey ...
believed that those affected by leprosy were being punished by God for sinful behavior. Moral associations have persisted throughout history. In the 6th century Pope
Gregory the Great Pope Gregory I (; ; – 12 March 604), commonly known as Saint Gregory the Great (; ), was the 64th Bishop of Rome from 3 September 590 until his death on 12 March 604. He is known for instituting the first recorded large-scale mission from Rom ...
and
Isidore of Seville Isidore of Seville (; 4 April 636) was a Spania, Hispano-Roman scholar, theologian and Roman Catholic Archdiocese of Seville, archbishop of Seville. He is widely regarded, in the words of the 19th-century historian Charles Forbes René de Montal ...
considered people with the disease to be heretics.


Middle Ages

The social perception of leprosy in the general population was mixed. On one hand, people feared getting infected with the disease and thought of people suspected of leprosy to be unclean, untrustworthy, and occasionally morally corrupt. On the other hand, Jesus' interaction with lepers, the writing of church leaders, and the Christian focus on charitable works led to viewing the lepers as "chosen by God" or seeing the disease as a means of obtaining access to heaven. Early medieval understanding of leprosy was influenced by early Christian writers such as
Gregory of Nazianzus Gregory of Nazianzus (; ''Liturgy of the Hours'' Volume I, Proper of Saints, 2 January. – 25 January 390), also known as Gregory the Theologian or Gregory Nazianzen, was an early Roman Christian theologian and prelate who served as Archbi ...
and
John Chrysostom John Chrysostom (; ; – 14 September 407) was an important Church Father who served as archbishop of Constantinople. He is known for his preaching and public speaking, his denunciation of abuse of authority by both ecclesiastical and p ...
, whose writings were later embraced by Byzantine and Latin writers. Gregory, for example, composed sermons urging Christians to assist victims of the disease, and he condemned pagans or Christians who justified rejecting lepers on the allegation that God had sent them the disease to punish them. As cases of leprosy increased in the
Eastern Roman Empire The Byzantine Empire, also known as the Eastern Roman Empire, was the continuation of the Roman Empire centred on Constantinople during late antiquity and the Middle Ages. Having survived the events that caused the fall of the Western Roman E ...
, becoming a major health issue, the ecclesiastic leaders discussed how to assist those affected as well as how to change the attitude of society towards them. They also tried this by using the name "holy disease" instead of the commonly used "elephant's disease" (elephantiasis), implying that God did not create this disease to punish people but to purify them for heaven. Although not always successful in persuading the public and a cure was never found by Greek medicians, they created an environment where victims could get
palliative care Palliative care (from Latin root "to cloak") is an interdisciplinary medical care-giving approach aimed at optimizing quality of life and mitigating or reducing suffering among people with serious, complex, and often terminal illnesses. Man ...
and were never expressly banned from society, as sometimes happened in western Europe. Theodore Balsamon, a 12th-century jurist in
Constantinople Constantinople (#Names of Constantinople, see other names) was a historical city located on the Bosporus that served as the capital of the Roman Empire, Roman, Byzantine Empire, Byzantine, Latin Empire, Latin, and Ottoman Empire, Ottoman empire ...
, noted that lepers were allowed to enter the same churches, cities, and assemblies that healthy people attended. As the disease became more prevalent in western Europe in the 5th century, efforts began to set up permanent institutions to house and feed lepers. These efforts were, inclusively, the work of bishops in France at the end of the sixth century, such as in
Chalon-sur-Saône Chalon-sur-Saône (, literally ''Chalon on Saône'') is a city in the Saône-et-Loire Departments of France, department in the Regions of France, region of Bourgogne-Franche-Comté in eastern France. It is a Subprefectures in France, sub-prefectu ...
. The increase in hospitals or leprosaria (sing. leprosarium) that treated people with leprosy in the 12th and 13th century seems to indicate a rise in cases, possibly in connection with the increase in urbanisation as well as returning crusaders from the Middle East. France alone had nearly 2,000 leprosaria during this period. Additionally to the new leprosia, further steps were taken by secular and religious leaders to prevent further spread of the disease. The
third Lateran Council The Third Council of the Lateran met in Rome in March 1179. Pope Alexander III presided and 302 bishops attended. The Catholic Church regards it as the eleventh ecumenical council. By agreement reached at the Peace of Venice in 1177 the bitter ...
of 1179 required lepers to have their own priests and churches and a 1346 edict by
King Edward King Edward may refer to: Monarchs of England and the United Kingdom * Edward the Elder (–924) * Edward the Martyr (–978) * Edward the Confessor (–1066) * Edward I of England (1239–1307) * Edward II of England (1284–1327) * Edward III o ...
expelled lepers from city limits. Segregation from mainstream society became common, and people with leprosy were often required to wear clothing that identified them as such or carry a bell announcing their presence. As in the East, it was the
Church Church may refer to: Religion * Church (building), a place/building for Christian religious activities and praying * Church (congregation), a local congregation of a Christian denomination * Church service, a formalized period of Christian comm ...
who took care of the lepers due to the persisting moral stigma and who ran the leprosaria. Although the leprosaria in Western Europe removed the sick from society, they were never a place to quarantine them or from which they could not leave: lepers would go beg for alms for the upkeep of the leprosaria or meet with their families. Multiple groups in Western Europe from the Middle Ages faced social ostracization and discrimination that was justified, in part, due to claims that they were the descendants of lepers. These groups included the
Cagot The ''Cagots'' () were a persecuted minority who lived in the west of France and northern Spain: the Navarrese Pyrenees, Basque provinces, Béarn, Aragón, Gascony and Brittany. Evidence of the group exists as far back as 1000 CE. The name th ...
s and the Caquins.


19th century

Norway was the location of a progressive stance on leprosy tracking and treatment and played an influential role in European understanding of the disease. In 1832, Dr. JJ Hjort conducted the first leprosy survey, thus establishing a basis for epidemiological surveys. Subsequent surveys resulted in the establishment of a national leprosy registry to study the causes of leprosy and to track the rate of infection. Early leprosy research throughout Europe was conducted by Norwegian scientists Daniel Cornelius Danielssen and Carl Wilhelm Boeck. Their work resulted in the establishment of the National Leprosy Research and Treatment Center. Danielssen and Boeck believed the cause of leprosy transmission was hereditary. This stance was influential in advocating for the isolation of those infected by sex to prevent reproduction. Though leprosy rates were on the decline in the
Western world The Western world, also known as the West, primarily refers to various nations and state (polity), states in Western Europe, Northern America, and Australasia; with some debate as to whether those in Eastern Europe and Latin America also const ...
by the 1860s, authorities frequently embraced isolation treatment due to a combination of reasons, including fears of the disease spreading from the
Global South Global North and Global South are terms that denote a method of grouping countries based on their defining characteristics with regard to socioeconomics and politics. According to UN Trade and Development (UNCTAD), the Global South broadly com ...
, efforts by Christian missionaries and a lack of understanding concerning
bacteriology Bacteriology is the branch and specialty of biology that studies the Morphology (biology), morphology, ecology, genetics and biochemistry of bacteria as well as many other aspects related to them. This subdivision of microbiology involves the iden ...
,
medical diagnosis Medical diagnosis (abbreviated Dx, Dx, or Ds) is the process of determining which disease or condition explains a person's symptoms and signs. It is most often referred to as a diagnosis with the medical context being implicit. The information ...
and how contagious the disease was. The rapid expansion of Western imperialism during the
Victorian era In the history of the United Kingdom and the British Empire, the Victorian era was the reign of Queen Victoria, from 20 June 1837 until her death on 22 January 1901. Slightly different definitions are sometimes used. The era followed the ...
resulted in westerners coming into increasing contact with regions where the disease was endemic, including British India. English surgeon
Henry Vandyke Carter Henry Vandyke Carter (born 22 May 1831 – 4 May 1897) was an English anatomist, surgeon, and anatomical artist most notable for his illustrations of the book ''Gray's Anatomy''. Childhood Henry Vandyke Carter was born on 22 May 1831 in Kingsto ...
observed isolation treatment for leprosy patients first-hand while visiting Norway, applying these methods in British India with the financial and logistical assistance of Protestant missionaries. Colonialist and religious viewpoints of the disease continued to be a major factor in the treatment and public perception of the disease in the Global South until
decolonization Decolonization is the undoing of colonialism, the latter being the process whereby Imperialism, imperial nations establish and dominate foreign territories, often overseas. The meanings and applications of the term are disputed. Some scholar ...
in the mid-20th century.


20th and 21st century

In 1898, the colonial government in
British India The provinces of India, earlier presidencies of British India and still earlier, presidency towns, were the administrative divisions of British governance in South Asia. Collectively, they have been called British India. In one form or another ...
enacted the Leprosy Act of 1898, which mandated the compulsory segregation of people with leprosy by authorities in newly established leper asylums, where they were segregated by sex to prevent sexual activity. The act, which proved difficult to enforce, was repealed in 1983 by the
Indian government The Government of India (ISO: Bhārata Sarakāra, legally the Union Government or Union of India or the Central Government) is the national authority of the Republic of India, located in South Asia, consisting of 36 states and union territor ...
after MDT had become widely available in India. In 1983, the National Leprosy Elimination Programme, previously the National Leprosy Control Programme, changed its methods from surveillance to the treatment of people with leprosy. India still accounts for over half of the global disease burden. According to WHO, new cases in India during 2019 diminished to 114,451 patients (57% of the world's total new cases). Until 2019, Indians could justify a petition for divorce with their spouse's diagnosis of leprosy. The National Leprosarium at
Carville, Louisiana Carville is a neighborhood of St. Gabriel, located in Iberville Parish in southern Louisiana, sixteen miles south of Baton Rouge, on the Mississippi River. Best known as the childhood hometown of famed political consultant James Carville, i ...
, known in 1955 as the Louisiana Leper Home, was the only leprosy hospital in the mainland United States. Leprosy patients from all over the United States were sent to Carville to be kept in isolation away from the public, as not much about leprosy transmission was known at the time and stigma against those with leprosy was high. The Carville leprosarium was known for its innovations in reconstructive surgery for those with leprosy. In 1941, 22 patients at Carville underwent trials for a new drug called promin. The results were described as miraculous, and soon after the success of promin came dapsone, a medicine even more effective in the fight against leprosy. Leprosy incidence peaked in the United States in 1983, followed by a steep decline. However, case numbers have been slowly rising again since 2000. In 2020, 159 cases were reported in the country.


Stigma

Despite now effective treatment and education efforts, leprosy stigma continues to be problematic in developing countries where the disease is common. Leprosy is most common amongst impoverished populations where social stigma is likely to be compounded by poverty. Fears of ostracism, loss of employment, or expulsion from family and society may contribute to a delayed diagnosis and treatment. Folk beliefs, lack of education, and religious connotations of the disease continue to influence social perceptions of those affected in many parts of the world. In Brazil, for example, folklore holds that leprosy is a disease transmitted by dogs, or that it is associated with sexual promiscuity, or that it is a punishment for sins or moral transgressions (distinct from other diseases and misfortunes, which are in general thought of as being according to the will of God). Socioeconomic factors also have a direct impact. Lower-class domestic workers who are often employed by those in a higher socioeconomic class may find their employment in jeopardy as physical manifestations of the disease become apparent. Skin discoloration and darker pigmentation resulting from the disease also have social repercussions. In extreme cases in northern India, leprosy is equated with an "untouchable" status that "often persists long after individuals with leprosy have been cured of the disease, creating lifelong prospects of divorce, eviction, loss of employment, and ostracism from family and social networks."


Public policy

The World Health Organization maintains an Expert Committee on Leprosy since 1954, and a goal of the WHO is to "eliminate leprosy." In 2016 the organization launched "Global Leprosy Strategy 2016–2020: Accelerating towards a leprosy-free world". Elimination of leprosy is defined as "reducing the proportion of (people with) leprosy in the community to very low levels, specifically to below one case per 10,000 population". Diagnosis and treatment with multidrug therapy are effective, and a 45% decline in disease burden has occurred since MDT has become more widely available. The organization emphasizes the importance of fully integrating leprosy treatment into public health services, effective diagnosis and treatment, and access to information. The approach includes supporting an increase in health care professionals who understand the disease, and a coordinated and renewed political commitment that includes coordination between countries and improvements in the methodology for collecting and analysing data. Interventions include: * Early detection of cases focusing on children to reduce transmission and disabilities. * Enhanced healthcare services and improved access for people who may be marginalized. * For countries where leprosy is endemic, further interventions include an improved screening of close contacts, improved treatment regimens, and interventions to reduce stigma and discrimination against people who have leprosy. In some instances in India, community-based rehabilitation is embraced by local governments and NGOs alike. Often, the identity cultivated by a community environment is preferable to reintegration, and models of self-management and collective agency independent of NGOs and government support have been desirable and successful.


Notable cases

* Josephine Cafrine of
Seychelles Seychelles (, ; ), officially the Republic of Seychelles (; Seychellois Creole: ), is an island country and archipelagic state consisting of 155 islands (as per the Constitution) in the Indian Ocean. Its capital and largest city, Victoria, ...
(1877–1907) had leprosy from age 12 and kept a journal that documented her struggles and suffering. It was published as an autobiography in 1923. * Saint Damien De Veuster (1840–1889), a Catholic priest from Belgium, contracted leprosy and ministered to lepers who had been placed under a government-sanctioned medical quarantine on
Molokai Molokai or Molokai ( or ; Molokaʻi dialect: Morotaʻi ) is the fifth most populated of the eight major islands that make up the Hawaiian Islands archipelago in the middle of the Pacific Ocean. It is 38 by 10 miles (61 by 16 km) at its g ...
in the
Kingdom of Hawaii The Hawaiian Kingdom, also known as the Kingdom of Hawaiʻi (Hawaiian language, Hawaiian: ɛ ɐwˈpuni həˈvɐjʔi, was an Archipelagic state, archipelagic country from 1795 to 1893, which eventually encompassed all of the inhabited Hawaii ...
. *
Baldwin IV of Jerusalem Baldwin IV (1161–1185), known as the Leper King, was the king of Jerusalem from 1174 until his death in 1185. He was admired by historians and his contemporaries for his dedication to the Kingdom of Jerusalem in the face of his debilitating ...
(1161–1185), Catholic king of Latin Jerusalem, had leprosy. *
Ingeborg Grytten Ingeborg Andersdatter Grytten ( – after 1705) was a Norwegian poet and hymn writer. Grytten and Dorothe Engelbretsdatter were the only known Norwegian poets in the 17th-century. Her life was defined by the onset of leprosy from an early age. ...
( – after 1705), Norwegian writer whose leprosy is thought to have influenced her poetry, which is characterized by a strong religious faith in God's salvation. * Josefina Guerrero (1917–1996), Filipino
World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...
spy who used the Japanese fear of her leprosy to listen to their battle plans and deliver the information to the American forces under
Douglas MacArthur Douglas MacArthur (26 January 18805 April 1964) was an American general who served as a top commander during World War II and the Korean War, achieving the rank of General of the Army (United States), General of the Army. He served with dis ...
. * King
Henry IV of England Henry IV ( – 20 March 1413), also known as Henry Bolingbroke, was King of England from 1399 to 1413. Henry was the son of John of Gaunt, Duke of Lancaster (a son of King Edward III), and Blanche of Lancaster. Henry was involved in the 1388 ...
() possibly had leprosy. * Vietnamese poet
Hàn Mặc Tử Francis Nguyễn Trọng Trí, penname Hàn Mặc Tử (September 22, 1912 – November 11, 1940), was a Vietnamese poet. He was the most celebrated Vietnamese Catholic literary figure during the colonial era. He was born Nguyễn Trọng Trí, ...
(1912–1940) *
Ōtani Yoshitsugu was a Japanese samurai of the Sengoku period through the Azuchi-Momoyama Period. He was also known by his court title ''Junior Assistant Minister of Justice'' or . He was born in 1558 to a father who was said to be a retainer of either Ōtom ...
(1558 or 1565–1600), a Japanese ''
daimyō were powerful Japanese magnates, feudal lords who, from the 10th century to the early Meiji era, Meiji period in the middle 19th century, ruled most of Japan from their vast hereditary land holdings. They were subordinate to the shogun and no ...
'' (feudal lord). * British writer
Peter Greave Peter Greave (29 October 1910 – 1 November 1977) was an English writer. Personal life Peter Greave was born Gerald Peter Wilkinson on 29 October 1910 in Calcutta. His father, Herbert Reginald Wilkinson, was a former British Army soldier worki ...
(1910–1977). * Popular Indian actress
Dimple Kapadia Dimple Kapadia (born 8 June 1957) is an Indian actress predominantly appearing in Hindi films. Born and raised in Mumbai by wealthy parents, she aspired to become an actress from a young age and received her first opportunity through her fathe ...
(1957–present) was diagnosed with leprosy a few months before the shoot of the 1973 musical romance film,
Bobby (1973 film) ''Bobby'' is a 1973 Indian Hindi-language musical romance film, produced and directed by Raj Kapoor, and written by Khwaja Ahmad Abbas. The film stars Raj Kapoor's son, Rishi Kapoor, in his first leading role, opposite Dimple Kapadia in her ...
. She later recovered completely and went on to have a successful acting career.


In media

* — the short story collection ''Life's Handicap'' by
Rudyard Kipling Joseph Rudyard Kipling ( ; 30 December 1865 – 18 January 1936)''The Times'', (London) 18 January 1936, p. 12. was an English journalist, novelist, poet, and short-story writer. He was born in British Raj, British India, which inspired much ...
has a story "The Mark of the Beast" in which a traveller on horseback literally stumbles into a leper colony in India. * — Jack London published "Koolau the Leper" in his ''Tales of Hawai'i'' about Molokai and people consigned to it circa 1893. * —
James Michener James Albert Michener ( or ; February 3, 1907 – October 16, 1997) was an American writer. He wrote more than 40 books, most of which were long, fictional family sagas covering the lives of many generations, set in particular geographic locales ...
's novel ''
Hawaii Hawaii ( ; ) is an island U.S. state, state of the United States, in the Pacific Ocean about southwest of the U.S. mainland. One of the two Non-contiguous United States, non-contiguous U.S. states (along with Alaska), it is the only sta ...
'' dramatizes Molokai's leper settlement, including Father Damien. * — ''Ben-Hur'' depicts the title character's mother, Miriam, and younger sister, Tirzah, are imprisoned by the Roman Empire. When they are freed years later, they have leprosy and leave town for the Valley of the Lepers, rather than stay and reunite with Ben-Hur. They leave the colony, and when Jesus dies on the cross, they are miraculously cured. * — English author Graham Greene's novel ''
A Burnt-Out Case ''A Burnt-Out Case'' (1960) is a novel by English author Graham Greene, set in a leper colony on the upper reaches of a tributary of the Congo River in Africa. Plot summary Querry, a famous architect who is fed up with his celebrity, no longe ...
'' is set in a leper colony in Belgian Congo. The story is also predominantly about a disillusioned architect working with a doctor on devising new cures and amenities for mutilated victims of lepers; the title, too, refers to the condition of mutilation and disfigurement in the disease. * —
Forugh Farrokhzad Forugh Farrokhzad (; 28 December 1934 – 14 February 1967) was an influential Iranian poet and film director. She was a controversial modernist poet and an iconoclastic,* feminist author. Farrokhzad died in a car accident at the age of 32. Ear ...
made a 22-minute documentary about a leprosy colony in
Iran Iran, officially the Islamic Republic of Iran (IRI) and also known as Persia, is a country in West Asia. It borders Iraq to the west, Turkey, Azerbaijan, and Armenia to the northwest, the Caspian Sea to the north, Turkmenistan to the nort ...
titled '' The House Is Black''. The film humanizes the people affected and opens by saying that "there is no shortage of ugliness in the world, but by closing our eyes on ugliness, we will intensify it." * — The lead character in ''
The Chronicles of Thomas Covenant ''The Chronicles of Thomas Covenant'' is a series of ten high fantasy novels written by American author Stephen R. Donaldson. The series began as a trilogy, entitled ''The Chronicles of Thomas Covenant the Unbeliever''. This was followed by ano ...
'' by Stephen R. Donaldson suffers from leprosy. His condition seems to be cured by the magic of the fantasy land he finds himself in, but he resists believing in its reality, for example, by continuing to perform a regular visual surveillance of extremities as a safety check. Donaldson gained experience with the disease as a young man in India, where his father worked in a missionary for people with leprosy. * — ''Moloka'i'' is a novel by
Alan Brennert Alan Brennert (born May 30, 1954) is an American author, television producer, and screenwriter. Brennert has lived in Southern California since 1973 and completed graduate work in screenwriting at the University of California, Los Angeles. Care ...
about a leper colony in Hawaii. This novel follows the story of a seven-year-old girl taken from her family and put on Molokai's leper settlement. * — ''Squint: My Journey with Leprosy'' is a memoir by Jose P. Ramirez.


Infection of animals

Between 15 and 20% of nine-banded armadillos (''Dasypus novemcinctus'') in the south-central United States carry ''M. leprae''.Liang, Jiayu (10/16/2023). "Leprosy in Florida: medical experts monitoring unusual, new cases of Hansen's disease". ''University of Florida Emerging Pathogens Institute''
https://epi.ufl.edu/2023/10/16/leprosy-in-florida-medical-experts-monitoring-unusual-new-cases-of-hansens-disease/#:~:text=A%20major%20hint%20that%20someone,leprae%20bacteria.
/ref> As a result of their low body temperature their tissues commonly contain massive numbers of organisms which help in the dissemination of the infection. Armadillos were first demonstrated in 1971 to develop leprosy after inoculation with ''M. leprae''.Adams L. B. (2021). Susceptibility and resistance in leprosy: Studies in the mouse model. ''Immunological reviews'', ''301''(1), 157–174. https://doi.org/10.1111/imr.12960 Because of armadillos' armor, skin lesions are difficult to ascertain. Abrasions around the eyes, nose, and feet are the most common signs. Infected armadillos make up a large reservoir of ''M. leprae'' and may be a source of infection for some humans in the United States or other locations in the armadillos' home range. In armadillo leprosy, lesions do not persist at the site of entry in animals; ''M. leprae'' multiply in
macrophage Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...
s at the site of
inoculation Inoculation is the act of implanting a pathogen or other microbe or virus into a person or other organism. It is a method of artificially inducing immunity against various infectious diseases. The term "inoculation" is also used more generally ...
and lymph nodes. Armadillos have been used in immunological research to fight leprosy. Some notable reagents include recombinant interleukin-2 and recombinant interferon-gamma reagents. Additionally, they have been key and have been useful models of leprosy for studies regarding neuropathy.Truman, R. W., Ebenezer, G. J., Pena, M. T., Sharma, R., Balamayooran, G., Gillingwater, T. H., Scollard, D. M., McArthur, J. C., & Rambukkana, A. (2014). The armadillo as a model for peripheral neuropathy in leprosy. ''ILAR journal'', ''54''(3), 304–314. https://doi.org/10.1093/ilar/ilt050 In clinical procedures such as electrophysiological nerve conduction tests Armadillo's nerve function has been properly assessed. Despite the studies mentioned regarding Armadillo's relationship to neuropathy and other effects of leprosy, there is still a lack of proper study on armadillos, and in conducting more armadillo-specific regents our understanding of leprosy’s effects on armadillos and possible humans can be found. Armadillos are a key component of modern-day research on leprosy. There is a stigma surrounding armadillos and the carrying of leprosy. Because many people do not understand armadillos very well it is common for people to think of them as being dangerous to society and as a result valuing their lives less than other animals. It has become more common in parts of America for people to eat raw or undercooked armadillo, making the chances high that if not properly handled with care, one may become infected. An outbreak in chimpanzees in West Africa is showing that the bacteria can infect another species and also possibly have additional rodent hosts. Studies have demonstrated that the disease is endemic in the UK red Eurasian squirrel population, with ''M. leprae'' and ''M. lepromatosis'' appearing in different populations. The ''M. leprae'' strain discovered on
Brownsea Island Brownsea Island is the largest of the islands in Poole Harbour in the county of Dorset, England. The island is owned by the National Trust for Places of Historic Interest or Natural Beauty, National Trust with the northern half managed by the Do ...
is equated to one thought to have died out in the human population in mediaeval times. Despite this, and speculation regarding past transmission through trade in squirrel furs, there does not seem to be a high risk of squirrel to human transmission from the wild population. Although leprosy continues to be diagnosed in immigrants to the UK, the last known human case of leprosy arising in the UK was recorded over 200 years ago. It has been shown that leprosy can reprogram cells in mouse and armadillo models, similar to how
induced pluripotent stem cell Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka and Kazutoshi Takahashi in Kyoto, Jap ...
s are generated by the
transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...
Myc ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes r ...
, Oct3/4, Sox2, and Klf4. A notable study conducted by Charles Shepard used mice to find how leprosy, an infection that has a preference for cooler areas of the body, would work in a warm-blooded animal. This mice study helped further the understanding of how leprosy works in humans. This was called "The Mouse Model." The main findings were that even in mice whose immune systems were severely impaired and at a perceived high risk of developing leprosy, the body was still in most cases able to fight off leprosy. The findings suggest that in mice, the body will use their body's energy to fight leprosy. Using The Mouse Model Shepard was able to conduct new research regarding leprosy. This model can now be used as a tool to further study ''M. leprae''. The Mouse Model takes a more easily accessible animal model to better understand this complex disease. There are a few other up-and-coming models for ''M. leprae'' including the use of other animals including but not limited to mammals, birds, and cold-blooded animals. These animals do not tend to give as great results as armadillos and mice as different animals have different levels of disease resistance.


References


Further reading

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External links

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