While the causative organisms have to date been impossible to culture ''in vitro'', it has been possible to grow them in animals such as mice
A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...
and armadillos.
Naturally occurring infection has been reported in nonhuman primates (including the African
chimpanzee, the
sooty mangabey, and the
cynomolgus
The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque and referred to as the cynomolgus monkey in laboratories, is a cercopithecine primate native to Southeast Asia. A species of macaque, the crab-eating macaque ...
macaque), armadillos, and
red squirrels.
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 American explorers.
This incidental transmission was sustained in the armadillo population, and it may be transmitted back to humans, making leprosy a
zoonotic disease
A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human ...
(spread between humans and animals).
Red squirrels (''Sciurus vulgaris''), a threatened species in
Great Britain
Great Britain is an island in the North Atlantic Ocean off the northwest coast of continental Europe. With an area of , it is the largest of the British Isles, the largest European island and the ninth-largest island in the world. It is ...
, 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-era skull excavated in
Hoxne, Suffolk, in 2017 was found to carry DNA from a strain of ''Mycobacterium 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 with the northern half managed by the Dorset Wildlife Trust. Much of the island is open to the public and ...
, UK.
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 also 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 immune ...
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.
Older research suggested the skin as the main route of transmission, but recent research has increasingly favored the respiratory route.
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 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, but whether they reach the skin surface in sufficient numbers is doubtful.
Leprosy may also be transmitted to humans by
armadillos, although the mechanism is not fully understood.
Genetics
Not all people who are 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 people who are exposed, the immune system is able to eliminate the leprosy bacteria during the early infection stage before severe symptoms develop. A genetic defect in
cell-mediated immunity
Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
may cause a person to be susceptible to develop leprosy symptoms after exposure to the bacteria.
The region of
DNA responsible for this variability is also involved in
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
, 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 cells, olfactory ens ...
s, which may lead to nerve injury including demyelination
A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency i ...
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 spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action p ...
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 components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...
-binding protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
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 an ...
.
As part of the human immune response, white blood cell-derived macrophages may engulf ''M. leprae'' by phagocytosis
Phagocytosis () is the process by which a 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 phagocytosis is ...
.
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.["Diagnosis of Leprosy." WHO. from accessed on 14 July 2014.]
* 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 s ...
s), raised (papule
A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
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, 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 sam ...
leprosy bacilli
Bacilli is a taxonomic 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'' are almost exclusively gram-positi ...
in skin smears are 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 can be identified using a polymerase chain reaction
The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) ...
(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.
Classification
Several different approaches for classifying leprosy exist. There are similarities between the classification approaches.
* The World Health Organization system distinguishes "paucibacillary" and "multibacillary" based upon the proliferation of bacteria. (" pauci-" refers to a low quantity.)
* The Ridley-Jopling scale provides five gradations.
* The ICD-10, 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 Nov. 2010. .]
* In MeSH
A mesh is a barrier made of connected strands of metal, fiber, or other flexible or ductile materials. A mesh is similar to a web or a net in that it has many attached or woven strands.
Types
* A plastic mesh may be extruded, oriented, exp ...
, three groupings are used.
Leprosy may also occur with only neural involvement, without skin lesions.
Prevention
Early detection of the disease 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 (SDR) 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) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
. 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
Anti-leprosy medication
A number of leprostatic agents are available for treatment. A three-drug regimen of rifampicin, dapsone 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. Evidence is insufficient to sup ...
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. It is safe and easy to use under field conditions because of its presentation in calendar blister packs. Post-treatment relapse rates remain low. Resistance has been reported in several countries, although the number of cases is small. People with rifampicin-resistant leprosy may be treated with second line drugs such as fluoroquinolones
A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as we ...
, 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 pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also ...
, 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. Clarith ...
, but the treatment duration is 24 months because of their lower bactericidal activity. Evidence on the potential benefits and harms of alternative regimens for drug-resistant leprosy is not yet available.
Skin changes
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 ( INN, USAN, BAN) (brand name Sufrexal; former developmental code name R41468) is a drug used clinically as an antihypertensive agent and in scientific research to study the serotonin system; specifically, the 5-HT2 receptor family. I ...
seems to have a better effect on ulcer healing than clioquinol
Clioquinol (iodochlorhydroxyquin) is an antifungal drug and antiprotozoal drug. It is neurotoxic in large doses. It is a member of a family of drugs called hydroxyquinolines which inhibit certain enzymes related to DNA replication. The drugs h ...
cream or zinc paste, but the evidence for this is weak. Phenytoin
Phenytoin (PHT), sold under the brand name Dilantin among others, is an 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 seizures. The in ...
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
Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
(13%) and Indonesia
Indonesia, officially the Republic of Indonesia, is a country in Southeast Asia and Oceania between the Indian and Pacific oceans. It consists of over 17,000 islands, including Sumatra, Java, Sulawesi, and parts of Borneo and New Guine ...
(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, the most common treatment option at the time. International (e.g., the WHO
Who or WHO may refer to:
* Who (pronoun), an interrogative or relative pronoun
* Who?, one of the Five Ws in journalism
* World Health Organization
Arts and entertainment Fictional characters
* Who, a creature in the Dr. Seuss book '' Horton He ...
's "Global Strategy for Reducing Disease Burden Due to Leprosy") and national (e.g., the International Federation of Anti-Leprosy Associations) initiatives have reduced the total number and the number of new cases of the disease.
Disease burden
The number of new leprosy cases is difficult to measure and monitor because of leprosy's long incubation period, delays in diagnosis after 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). Bot ...
. 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, 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. Strain 1 occurs predominantly in Asia, the Pacific region, and East Africa; strain 4, in West Africa and the Caribbean; strain 3 in Europe, North Africa, and the Americas; and strain 2 only in Ethiopia, Malawi
Malawi (; or aláwi Tumbuka: ''Malaŵi''), officially the Republic of Malawi, is a landlocked country in Southeastern Africa that was formerly known as Nyasaland. It is bordered by Zambia to the west, Tanzania to the north and northeas ...
, Nepal, north India, and New Caledonia
)
, anthem = ""
, image_map = New Caledonia on the globe (small islands magnified) (Polynesia centered).svg
, map_alt = Location of New Caledonia
, map_caption = Location of New Caledonia
, mapsize = 290px
, subdivision_type = Sovereign st ...
.
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 into 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
Balathal is an archaeological site located in Vallabhnagar tehsil of Udaipur district of Rajasthan state in western India. It is one of the ninety Ahar-Banas culture sites located in the Basins of the Banas river and its tributaries.
Excavatio ...
, Rajasthan
Rajasthan (; lit. 'Land of Kings') is a state in northern India. It covers or 10.4 per cent of India's total geographical area. It is the largest Indian state by area and the seventh largest by population. It is on India's northwestern s ...
, in northwest India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
, 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 in a tomb next to the Old City of Jerusalem
Jerusalem (; he, יְרוּשָׁלַיִם ; ar, القُدس ) (combining the Biblical and common usage Arabic names); grc, Ἱερουσαλήμ/Ἰεροσόλυμα, Hierousalḗm/Hierosóluma; hy, Երուսաղեմ, Erusałēm. i ...
, Palestine, dated by radiocarbon methods to the first half of the 1st century.
The oldest strains of leprosy known from Europe are from Great Chesterford
Great Chesterford is a village and civil parish in the Uttlesford district of Essex, England. The village is north from Bishop's Stortford, south from Cambridge and about northwest from the city and Essex county town of Chelmsford.
The Ickn ...
in southeast England and dating 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 India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
n Atharvaveda and Kausika Sutra, the Egyptian
Egyptian describes something of, from, or related to Egypt.
Egyptian or Egyptians may refer to:
Nations and ethnic groups
* Egyptians, a national group in North Africa
** Egyptian culture, a complex and stable culture with thousands of years of ...
Ebers papyrus, and the Hebrew
Hebrew (; ; ) is a Northwest Semitic language of the Afroasiatic language family. Historically, it is one of the spoken languages of the Israelites and their longest-surviving descendants, the Jews and Samaritans. It was largely preserved ...
Bible
The Bible (from Koine Greek , , 'the books') is a collection of religious texts or scriptures that are held to be sacred in Christianity, Judaism, Samaritanism, and many other religions. The Bible is an anthologya compilation of texts of a ...
's various sections regarding signs of impurity (''tzaraath
''Tzaraath'' (Hebrew צָרַעַת ''ṣāraʿaṯ''), variously transcribed into English and frequently mistranslated as leprosy, describes various ritually unclean disfigurative conditions of the skin, hair of the beard and head, clothing mad ...
''). Clearly leprotic symptoms are attested in the Indian doctor Sushruta's ''Compendium'', originally dating to c. 600 BC but only surviving in emended texts no earlier than the 5th century. They were separately described by Hippocrates
Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the classical period who is considered one of the most outstanding figures in the history o ...
in 460 BC. However, Hansen's disease probably did not exist in Greece or the Middle East
The Middle East ( ar, الشرق الأوسط, ISO 233: ) is a geopolitical region commonly encompassing Arabia (including the Arabian Peninsula and Bahrain), Asia Minor (Asian part of Turkey except Hatay Province), East Thrace (Europ ...
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 o ...
. 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 by modern Europeans nor did it exist in Polynesia
Polynesia () "many" and νῆσος () "island"), to, Polinisia; mi, Porinihia; haw, Polenekia; fj, Polinisia; sm, Polenisia; rar, Porinetia; ty, Pōrīnetia; tvl, Polenisia; tkl, Polenihia (, ) is a subregion of Oceania, made up of ...
until the middle of the 19th century.
The causative agent of leprosy, ''M. leprae'', was discovered by G. H. Armauer Hansen in Norway in 1873, making it the first bacterium to be identified as causing disease in humans.
Treatment
The first effective treatment (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
The first synthesis of Promin is some ...
) became available in the 1940s. In the 1950s, dapsone was introduced. The search for further effective antileprosy drugs led to the use of 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. Evidence is insufficient to sup ...
and rifampicin in the 1960s and 1970s. Later, Indian scientist Shantaram Yawalkar and his colleagues formulated a combined therapy using rifampicin and dapsone, intended to mitigate bacterial resistance. Multi-drug therapy (MDT) combining all three drugs was first recommended by the WHO
Who or WHO may refer to:
* Who (pronoun), an interrogative or relative pronoun
* Who?, one of the Five Ws in journalism
* World Health Organization
Arts and entertainment Fictional characters
* Who, a creature in the Dr. Seuss book '' Horton He ...
in 1981. These three antileprosy drugs are still used in the standard MDT regimens.
Leprosy was once believed to be highly contagious and was treated with mercury, as was syphilis, which was first described in 1530. Many early cases thought to be leprosy could actually have been syphilis.
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.
Japan
Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...
still has sanatoriums (although Japan's sanatoriums no longer have active leprosy cases, nor are survivors held in them by law).
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; 44:159–74] The mechanism of plantar ulceration in leprosy and its treatment was first described by Dr Ernest W Price
Dr Ernest Woodward Price MD, FRCSE, DTM&H, OBE (20 July 1907 31 January 1990) was a missionary doctor, orthopaedic surgeon, leprosy specialist and the discoverer of podoconiosis, one of the neglected tropical diseases. A list of his publicati ...
.
Etymology
The word "leprosy" comes from the Greek word "λέπος (lépos) – skin" and "λεπερός (leperós) – scaly man".
Society and culture
India
British India
The provinces of India, earlier presidencies of British India and still earlier, presidency towns, were the administrative divisions of British governance on the Indian subcontinent. Collectively, they have been called British India. In one ...
enacted the Leprosy Act of 1898 which institutionalized those affected and segregated them by sex to prevent reproduction. The act was difficult to enforce but was repealed in 1983 only after multidrug therapy had become widely available. 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, one could justify a petition for divorce with the spouse's diagnosis of leprosy.
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 Ryoichi Sasakawa. The foundation's mission is to direct Japanese motorboat racing revenue into philanthropic activities, it uses this money ...
, supplied all endemic countries with free multidrug therapy 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 multidrug therapy manufacturer Novartis
Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and
Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...
through the WHO. In the latest agreement signed between the company and the WHO in October 2015, the provision of free multidrug therapy by the WHO to all endemic countries will run until the end of 2025. At the national level, nongovernment organizations affiliated with the national program will continue to be provided with an appropriate free supply of multidrug therapy by the WHO.
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
The Atharva Veda (, ' from ' and ''veda'', meaning "knowledge") is the "knowledge storehouse of ''atharvāṇas'', the procedures for everyday life".Laurie Patton (2004), Veda and Upanishad, in ''The Hindu World'' (Editors: Sushil Mittal and G ...
'', by 600 BC. Another Indian text, the ''Manusmriti
The ''Manusmṛiti'' ( sa, मनुस्मृति), also known as the ''Mānava-Dharmaśāstra'' or Laws of Manu, is one of the many legal texts and constitution among the many ' of Hinduism. In ancient India, the sages often wrote thei ...
'' (200 BC), prohibited contact with those infected with the disease and made marriage to a person infected with leprosy punishable.
The Hebraic root tsara or tsaraath
''Tzaraath'' (Hebrew language, Hebrew צָרַעַת ''ṣāraʿaṯ''), #Name, variously transcribed into English and frequently mistranslated as leprosy, describes various ritual impurity, ritually unclean disfigurative conditions of the skin, ...
(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 (; he, , Talmūḏ) is the central text of Rabbinic Judaism and the primary source of Jewish religious law (''halakha'') and Jewish theology. Until the advent of modernity, in nearly all Jewish communities, the Talmud was the cente ...
(Sifra 63) make clear that'' tzaraath'' refers to various types of lesions or stains associated with ritual impurity
Ritual purification is the ritual prescribed by a religion by which a person is considered to be free of ''uncleanliness'', especially prior to the worship of a deity, and ritual purity is a state of ritual cleanliness. Ritual purification may ...
and occurring on cloth, leather, or houses, as well as skin. Traditional Judaism 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 of the New Testament
The New Testament grc, Ἡ Καινὴ Διαθήκη, transl. ; la, Novum Testamentum. (NT) is the second division of the Christian biblical canon. It discusses the teachings and person of Jesus, as well as events in first-century Chri ...
describe instances of Jesus healing people with leprosy
Matthew 8:1–4
Mark 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 from Leviticus 13: 44–46. While this text defines the leper as Tumah and taharah, impure, it did not explicitly make a moral judgement on those with leprosy. Some Early Christianity, Early Christians believed that those affected by leprosy were being punished by God for sinful behavior. Moral associations have persisted throughout history. Pope Gregory the Great (540–604) and Isidor of Seville (560–636) considered people with the disease to be heretics.
Middle Ages
The social perception of leprosy in the general population was in general 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 of John Chrysostom whose writing were later embraced
by Byzantine and Latin writers. Gregory for example did not only compose sermons urging Christians to assist victims of the disease but also 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 during these years in the Eastern Roman Empire, becoming a major health issue, the ecclesiastic leaders of the time discussed how to assist those affected as well as 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 and were never expressly banned from society, as sometimes happened in Western Europe. Theodore Balsamon, a 12th century jurist in Constantinople 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 fifth century, first efforts to set up permanent institutions to house and feed lepers were made for instance by bishops in France at the end of the sixth century, such as in Chalon-sur-Saône. 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 urbanification 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 of 1179 required lepers to have their own priests and churches and a 1346 edict by Edward III of England, King Edward 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 Catholic Church, Church who took care of the lepers due to the still 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.
19th century
Norway
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 for tracking 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.
Colonialism and imperialism
Though leprosy in Europe was again on the decline by the 1860s, Western countries embraced isolation treatment out of fear of the spread of disease from Developing country, developing countries, minimal understanding of bacteriology, lack of diagnostic ability or knowledge of how contagious the disease was, and missionary activity. Growing imperialism and pressures of the Industrial Revolution, industrial revolution resulted in a Western presence in countries where leprosy was endemic, namely the British Raj, British presence in India. Isolation treatment methods were observed by Surgeon-Mayor Henry Vandyke Carter of the British Colony in India while visiting Norway, and these methods were applied in India with the financial and logistical assistance of religious missionaries. Colonialism, Colonial and religious influence and associated stigma continued to be a major factor in the treatment and public perception of leprosy in endemic developing countries until the mid-twentieth century.
20th century
United States
The National Leprosarium at Carville, Louisiana, known in 1955 as the Louisiana Leper Home, was the only leprosy hospital on the mainland United States. Leprosy patients from all over the United States were sent to Carville in order 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 (see Leprosy stigma). 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
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
The first synthesis of Promin is some ...
. 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.
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
Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
, 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."
File:Three Tahitians suffering from leprosy, Tahiti, approximately 1895.jpg, Leprosy in Tahiti,
File:A 26 year old woman with leprous lesions Wellcome L0074857.jpg, A 26-year-old woman with leprous lesions
File:13 year old boy with severe leprosy Wellcome L0074842.jpg, A 13-year-old boy with severe leprosy
Public policy
A goal of the World Health Organization is to "eliminate leprosy" and 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 leprosy patients 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 multidrug therapy 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 in the "Global Leprosy Strategy 2016–2020: Accelerating towards a leprosy-free world":
* 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.
Community-based interventions
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 had leprosy from the age of 12 and kept a personal journal that documented her struggles and suffering. It was published as an autobiography in 1923.
* Father Damien, Saint Damien De Veuster, a Roman Catholic priest from Belgium, himself eventually contracting leprosy, ministered to lepers who had been placed under a government-sanctioned medical quarantine on the island of Molokai in the Kingdom of Hawaii.
* Baldwin IV of Jerusalem was a Christian king of Latin Jerusalem who had leprosy.
*Josefina Guerrero was a Filipino spy during World War II, 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.
* King Henry IV of England (reigned 1399 to 1413) possibly had leprosy.
* Vietnamese poet Hàn Mặc Tử
* Ōtani Yoshitsugu, a Japanese ''daimyō''
Leprosy in the media
* English author Graham Greene's novel ''A Burnt-Out Case'' 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 cure and amenities for mutilated victims of lepers; the title, too, refers to the condition of mutilation and disfigurement in the disease.
* Forugh Farrokhzad made a 22-minute documentary about a leprosy colony in Iran in 1962 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."
*Moloka'i is a novel by Alan Brennert about a leper colony in Hawaii. This novel follows the story of a seven-year-old girl taken from her family and put on the small Hawaiian island of Molokai's leper settlement. Even though this is a fiction novel it is based upon some very true and revealing incidents which occurred at this Leprosy settlement.
*Jack London in 1909 published Jack London#Race, Koolau the Leper in his ''Tales of Hawai'i'' about Molokai and people consigned to it circa 1893.
* The lead character in The Chronicles of Thomas Covenant 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.
* In George R. R. Martin's ''Fire & Blood (novel), Fire and Blood'' and its TV adaptation ''House of the Dragon'', King Viserys I Targaryen suffered a debilitating disease where parts of his body developed lesions and slowly rotted away over time. In the lore of the books, this was partly attributed to the Iron Throne (A Song of Ice and Fire), Iron Throne, the physical and metaphorical seat of the ruler, rejecting monarchs unworthy of bearing the crown. However, the actor playing the role of Viserys in the TV series, Paddy Considine, explained on a podcast with Entertainment Weekly that Viserys actually suffered from "a form of leprosy".
Infection of animals
Wild nine-banded armadillos (''Dasypus novemcinctus'') in south central United States often carry ''Mycobacterium leprae''. This is believed to be because armadillos have a low body temperature. Leprosy lesions appear mainly in cooler body regions such as the skin and mucous membranes of the upper respiratory tract. Because of armadillos' armor, skin lesions are hard to see. 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 macrophages at the site of inoculation and lymph nodes.
A recent outbreak in chimpanzees in West Africa is showing that the bacteria can infect another species and also possibly have additional rodent hosts.
Recent studies have demonstrated that the disease is endemic in the UK red Eurasian squirrel population, with ''Mycobacterium leprae'' and ''Mycobacterium lepromatosis'' appearing in different populations. The Mycobacteria 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 with the northern half managed by the Dorset Wildlife Trust. Much of the island is open to the public and ...
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 armadillos models similarly as how Induced pluripotent stem cells are generated by the transcription factors Myc, Oct-4, Oct3/4, Sox2 and Klf4.
See also
* Leper Colony
* Alice Ball
* Maurice Born
* Kate Marsden
References
Further reading
*
External links
*
Links and resources
to information about leprosy selected by the World Health Organization
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