Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria Mycobacterium leprae or Mycobacterium lepromatosis. Initially, a person who is infected does not have symptoms and typically remains this way for 5 to 20 years. Infection can lead to damage of the nerves, respiratory tract, 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 due to unnoticed wounds. An infected person may also experience weakness and poor eyesight.
Leprosy is spread between people, although extensive contact is necessary. About 95% of people who contact M. leprae do not develop the disease. Spread is thought to occur through a cough or contact with fluid from the nose of a person infected by leprosy. Leprosy is not spread during pregnancy to the unborn children or through sexual contact. Leprosy occurs more commonly among people living in poverty. Genetic factors and immune function play a role in how easily a person catches the disease. The two main types of disease – paucibacillary and multibacillary – 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. The diagnosis is confirmed by finding acid-fast bacilli in a biopsy of the skin or by detecting the bacteria's DNA using polymerase chain reaction.
Leprosy is curable with multidrug therapy. Treatment of paucibacillary leprosy is with the medications dapsone, rifampicin, and clofazimine for six months. Treatment for multibacillary leprosy uses the same medications for 12 months. A number of other antibiotics may also be used. These treatments are provided free of charge by the World Health Organization. People with leprosy can live with their families and go to school and work. At the end of 2016, there were 173,000 leprosy cases globally, down from 5.2 million in the 1980s. The number of new cases in 2016 was 216,000. Most new cases occur in 14 countries, with India accounting for more than half. In the past 20 years, 16 million people worldwide have been cured of leprosy. About 200 cases per year are reported in the United States.
Leprosy has affected humanity for thousands of years. The disease takes its name from the Greek word λέπρᾱ (léprā), from λεπῐ́ς (lepís; "scale"), while the term "Hansen's disease" is named after the Norwegian physician Gerhard Armauer Hansen. Leprosy has historically been associated with social stigma, which continues to be a barrier to self-reporting and early treatment. Separating people affected by leprosy by placing them in leper colonies still occurs in some areas of India, China, and Africa. However, most colonies have closed, since leprosy is not very contagious. Some consider the word "leper" offensive, preferring the phrase "person affected with leprosy". Leprosy is classified as a neglected tropical disease. World Leprosy Day was started in 1954 to draw awareness to those affected by leprosy.
Leprosy can affect people in different ways. 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 infections (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.
Approximately 30% of people affected with leprosy experience nerve damage. The nerve damage sustained is irreversible, even with treatment of the infection. Damage to nerves may cause sensation abnormalities or numbness, which may lead to additional infections, ulcerations, and joint deformities.
M. leprae and M. lepromatosis are the mycobacterium 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.
Genetically, M. leprae and M. lepromatosis lack the genes that are necessary for independent growth. M. leprae and M. lepromatosis are obligate intracellular pathogens, and can not be grown (cultured) in the laboratory. The inability to culture M. leprae and M. lepromatosis has resulted in a difficulty definitively identifying the bacterial organism under a strict interpretation of Koch's postulates.
Naturally occurring infection has been reported in nonhuman primates (including the African chimpanzee, the sooty mangabey, and the cynomolgus macaque), armadillos, and red squirrels. Multilocus sequence typing 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 (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-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, UK.
The greatest risk factor for developing leprosy is contact with another person infected by leprosy. People who are exposed (in contact) with 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 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 of leprosy occurs during close contact with those who are infected. Transmission of leprosy is not well understood, but the upper respiratory tract is thought to be the most likely entry route. 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 multidrug 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.
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 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, giving rise to current speculation that the two disorders may be linked at the biochemical level.
There is limited evidence to determine the mechanism underlying how M. leprae produces the symptoms of leprosy.
M. leprae has been shown to bind to schwann cells, which may lead to nerve injury including demylination and a loss of nerve function (specifically a loss of axonal conductance). Numerous molecular mechanisms have been associated with this nerve damage including the presence of a laminin-binding protein and the glycoconjugate (PGL-1) on the surface of M. leprae that can bind to laminin on peripheral nerves.
In countries where people are frequently infected, a person is considered to have leprosy if they have one of the following two signs:
Skin lesions can be single or many, and usually hypopigmented, although occasionally reddish or copper-colored. The lesions may be flat (macules), raised (papules), 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 if the lesion is caused by another disorder such as tinea versicolor. Thickened nerves are associated with leprosy and can be accompanied by loss of sensation or muscle weakness, however, without the characteristic skin lesion and sensory loss, muscle weakness is not considered a reliable sign of leprosy.
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.
Common symptoms present in the different types of leprosy include a runny nose; dry scalp; eye problems; skin lesions; 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; a flat nose due to destruction of nasal cartilage; phonation and resonation of sound during speech. In addition, atrophy of the testes and impotence may occur. A person's immune response differs depending on the form of leprosy.
Several different approaches for classifying leprosy exist. There are similarities between the classification approaches.
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 with leprosy from acquiring the disease and likely those with whom people with leprosy come into contact outside the home. The WHO recommends that preventative medicine is given to people who are in close contact with someone who has leprosy. The suggested preventative treatment is a single dose of rifampicin (SDR) in adults and children over 2 years old who do not already have leprosy or tuberculosis. Preventative 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 target of tuberculosis. 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 leprosy. Development of a more effective vaccine is ongoing.
A number of leprostatic agents are available for treatment. A 3-drug regimen of rifampicin, dapsone and clofazimine is recommended for all people with leprosy, for 6 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 due to 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, minocycline, or clarithromycin, but the treatment duration is 24 months due to their lower bactericidal activity. Evidence on the potential benefits and harms of alternative regimens for drug-resistant leprosy is not yet 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 seems to have a better effect on ulcer healing than clioquinol cream or zinc paste, but the evidence for this is weak. Phenytoin applied to the skin improves skin changes to a greater degree when compared to saline dressings.
In 2016, there were 216,108 new cases of leprosy registered, corresponding to a global detection rate of 0.29 per 10,000 people. 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 (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's "Global Strategy for Reducing Disease Burden Due to Leprosy") and national (e.g., the International Federation of Anti-Leprosy Associations) initiatives and 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 due to leprosy's long incubation period, delays in diagnosis after onset of the disease, and lack of medical care in affected areas. The registered prevalence of the disease is used to determine disease burden. 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.
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, Nepal/north India, and New Caledonia.
On the basis of this, they offer a map of the dissemination of leprosy in the world. 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.
Although retrospectively identifying descriptions of leprosy-like symptoms is difficult, what appears to be leprosy was discussed by Hippocrates in 460 BC. 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.
Interpretations of the presence of leprosy have been made on the basis of descriptions in ancient Indian (Atharva Veda and Kausika Sutra), Greek, and Middle Eastern documentary sources that describe skin afflictions.
Leprosy probably did not exist in Greece or the Middle East before Common Era. It did not exist in the Americas before colonization by modern Europeans. It did not exist in Polynesia until the middle of the 19th century.
Skeletal remains from the second millennium BC, discovered in 2009, represent the oldest documented evidence for leprosy. Located at Balathal, in Rajasthan, northwest India, the discoverers suggest that if the disease did migrate from Africa to India, during the third 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 so as 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 dated by radiocarbon methods to 1–50 AD.
However, a study published in 2018 found the oldest strains of leprosy in remains from Europe, the oldest strain being from Great Chesterford and dating back to 415 to 545 AD. 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.
The first effective treatment (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. Multi-drug therapy (MDT) combining all three drugs was first recommended by the WHO 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.
The word "leprosy" comes from the Greek word "λέπος (lépos) – skin" and "λεπερός (leperós) – scaly man.
British India 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 MDT 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.
Between 1995 and 1999, the WHO, with the aid of the Nippon Foundation, 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 through the WHO. In the latest agreement signed between the company and the WHO in October 2015, the provision of free MDT by the WHO to all endemic countries will run until the end of 2020. At the national level, nongovernment organizations affiliated with the national program will continue to be provided with an appropriate free supply of MDT by the WHO.
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 (1500 BC), prohibited contact with those infected with the disease and made marriage to a person infected with leprosy punishable.
Biblically speaking, 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 skin, raised manifestations of scales, scabs, infections, rashes, etc....) as well as generalized molds and surface discoloration of any clothing, leather, and/or discoloration on walls surfaces throughout homes all came under the "law of leprosy" (Leviticus 14:54–57). Ancient sources also such as the Talmud (Sifra 63) make clear that tzaraath refers to various types of lesions or stains associated with ritual impurity and occurring on cloth, leather, or houses, as well as skin. The New Testament describes instances of Jesus healing people with leprosy in Luke 17:11, although the relationship between this disease, tzaraath, and Hansen's disease is not established.
The biblical perception that people with leprosy were unclean may be connected to a passage from Leviticus 13: 44–46, which indicated that leprosy was of moral consequence. 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.
It is believed that a rise in leprosy in Europe occurred in the Middle Ages based on the increased number of hospitals created to treat people with leprosy in the 12th and 13th centuries. France alone had nearly 2,000 leprosariums during this period.
The social perception of leprosy in medieval communities was generally one of fear, and people infected with the disease were thought to be unclean, untrustworthy, and morally corrupt. Segregation from mainstream society was common, and people with leprosy were often required to wear clothing that identified them as such or carry a bell announcing their presence. The third Lateran Council of 1179 and a 1346 edict by King Edward expelled lepers from city limits. Because of the moral stigma of the disease, methods of treatment were both physical and spiritual, and leprosariums were established under the purview of the church.
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 of 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 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 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 resulted in a Western presence in countries where leprosy was endemic, namely the 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. 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.
Despite 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 or marginalized populations where social stigma is likely to be compounded by other social inequities. 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 afflicted in many parts of the world. In Brazil, for example, folklore holds that leprosy is transmitted by dogs, it is a disease associated with sexual promiscuity, and is sometimes thought to be punishment for sins or moral transgressions. 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."
The WHO states that diagnosis and treatment with MDT are easy and 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.
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.
Wild nine-banded armadillos (Dayspus novemcinctus) in south central United States often carry Mycobacterium leprae. This is believed to be because armadillos have such 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 did not persist at the site of entry in animals, M. leprae multiplied in macrophages at the site of inoculation and lymph nodes.