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Leprosy

Leprosy
For the Hebrew Bible term and its varied meanings, see Tzaraath. For other uses, see Leprosy (disambiguation).

Leprosy (Hansen's disease)


Classification and external resources

A 24-year-old man infected with leprosy. ICD-10 ICD-9 OMIM DiseasesDB A 30. 030
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246300 8478

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MedlinePlus 001347 [5] eMedicine MeSH med/1281


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derm/223

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neuro/187
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C01.252.410.040.552.386

Leprosy or Hansen's disease (HD), is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis.[10] [11] Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary external sign.[12] Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes. Contrary to folklore, leprosy does not cause body parts to fall off, although they can become numb and/or diseased as a result of infection.[13] [14] Although the mode of transmission of Hansen's disease remains uncertain, most investigators think that M. leprae is usually spread from person to person in respiratory droplets.[15] The minimum incubation period reported is as short as a few weeks and this is based on the very occasional occurrence of leprosy among young infants. The maximum incubation period reported is as long as 30 years, or over, as observed among war veterans known to have been exposed for short periods in endemic areas but otherwise living in non-endemic areas. It is generally agreed that the average incubation period is between three and five years. Leprosy is now known to be neither sexually transmitted nor highly infectious after treatment. Approximately 95% of people are naturally immune[16] and sufferers are no

Leprosy longer infectious after as little as 2 weeks of treatment. Leprosy has affected humanity for over 4,000 years,[17] and was well-recognized in the civilizations of ancient China, Egypt, and India.[18] DNA taken from the shrouded remains of a man discovered in a tomb next to the Old City of Jerusalem shows him to be the earliest human proven to have suffered from leprosy.[19] In 1995, the World Health Organization (WHO) estimated that between 2 and 3 million people were permanently disabled because of leprosy at that time.[20] In the past 20 years, 15 million people worldwide have been cured of leprosy.[21] Although the forced quarantine or segregation of patients is unnecessary in places where adequate treatments are available, many leper colonies still remain around the world in countries such as India (where there are still more than 1,000 leper colonies),[21] China,[22] Romania,[23] Egypt, Nepal, Somalia, Liberia, Vietnam,[24] and Japan.[25] Leprosy was once believed to be highly contagious and sexually transmitted, and was treated with mercuryall of which applied to syphilis which was first described in 1530. It is now thought that many early cases of leprosy could have been syphilis.[26] The age-old social stigma, in other words, leprosy stigma[27] associated with the advanced form of leprosy lingers in many areas, and remains a major obstacle to self-reporting and early treatment. Effective treatment for leprosy appeared in the late 1930s with the introduction of dapsone and its derivatives. Leprosy bacilli resistant to dapsone soon evolved and, due to overuse of dapsone, became widespread. It was not until the introduction of multidrug therapy (MDT) in the early 1980s that the disease could be diagnosed and treated successfully within the community.[28] MDT for multibacillary leprosy consists of rifampicin, dapsone, and clofazimine taken over 12 months. Dosages adjusted appropriately for children and adults are available in all Primary Health Centres in the form of blister packages.[28] Single dose MDT for single lesion leprosy consists of rifampicin, ofloxacin, and minocycline. The move towards single dose treatment strategies has reduced the prevalence of disease in some regions since prevalence is dependent on duration of treatment. World Leprosy Day was created to draw awareness to leprosy and its sufferers.

Classification
There are several different approaches for classifying leprosy, however, parallels exist. The World Health Organization system distinguishes "paucibacillary" and "multibacillary" based upon the proliferation of bacteria[29] ("pauci- [30]" refers to a low quantity.) The SHAY scale provides five gradations.[31] [32] The ICD-10, though developed by the WHO, uses Ridley-Jopling and not the WHO system. It also adds an indeterminate ("I") entry.[33] In MeSH, three groupings are used.
WHO Ridley-Jopling ICD-10 MeSH Description Lepromin test Immune target bacillus (Th1)

Paucibacillary tuberculoid ("TT"), A30.1, borderline A30.2 tuberculoid ("BT")

Tuberculoid

It is characterized by one or more hypopigmented skin Positive macules and anaesthetic patches, where skin sensations are lost because of damaged peripheral nerves that have been attacked by the human host's immune cells. Borderline leprosy is of intermediate severity and is the most common form. Skin lesions resemble tuberculoid leprosy but are more numerous and irregular; large patches may affect a whole limb, and peripheral nerve involvement with weakness and loss of sensation is common. This type is unstable and may become more like lepromatous leprosy or may undergo a reversal reaction, becoming more like the tuberculoid form.

Multibacillary midborderline or borderline ("BB")

A30.3

Borderline

Leprosy

3
Lepromatous It is associated with symmetric skin lesions, nodules, plaques, thickened dermis, and frequent involvement of the nasal mucosa resulting in nasal congestion and epistaxis (nose bleeds) but typically detectable nerve damage is late. Negative plasmid inside bacillus (Th2)

Multibacillary borderline A30.4, lepromatous A30.5 ("BL"), and lepromatous ("LL")

There is a difference in immune response to the tuberculoid and lepromatous forms.[34] Hansen's disease may also be divided into the following types:[35] :344-346 Early and indeterminate leprosy Tuberculoid leprosy Borderline tuberculoid leprosy Borderline leprosy Borderline lepromatous leprosy Lepromatous leprosy Histoid leprosy Diffuse leprosy of Lucio and Latap

This disease may also occur with only neural involvement, without skin lesions.[18] [36] [37] [38] [39] [40] This disease is also known as Hansen's Disease.

Signs and symptoms


Skin lesions are the primary external sign.[12] Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes. Contrary to folklore, leprosy does not cause body parts to fall off but they can become numb and/or diseased as a result of the disease.[13] [41]

Diagnosis
Diagnosis in the U.S. is often delayed because health care providers are unaware of Hansen's disease (leprosy) and its symptoms. Early diagnosis and treatment prevents nerve involvement, the hallmark of Hansen's disease (leprosy), and the disability it causes.[42] There are many kinds of leprosy but there are common symptoms. These include runny nose, dry scalp, eye problems, and muscle weakness.

Cause
Mycobacterium leprae
Mycobacterium leprae and Mycobacterium lepromatosis are the causative agents of leprosy. M. lepromatosis is a relatively newly identified mycobacterium which was isolated from a fatal case of diffuse lepromatous leprosy in 2008.[11] [12] An intracellular, acid-fast bacterium, M. leprae is aerobic and rod-shaped, and is surrounded by the waxy cell membrane coating characteristic of Mycobacterium species.[43] Due to extensive loss of genes necessary for independent growth, M. leprae and M. lepromatosis are unculturable in the laboratory, a factor
Mycobacterium leprae, one of the causative agents of leprosy. As acid-fast bacteria, M. leprae appear red when a Ziehl-Neelsen stain is used.

Leprosy which leads to difficulty in definitively identifying the organism under a strict interpretation of Koch's postulates.[11] [44] The use of non-culture-based techniques such as molecular genetics has allowed for alternative establishment of causation. While the causative organisms have to date been impossible to culture in vitro it has been possible to grow them in animals. Charles Shepard, chairman of the United States Leprosy Panel, successfully grew the organisms in the footpads of mice in 1960. This method was improved with the use of congenitally athymic mice ('nude mice') in 1970 by Joseph Colson and Richard Hilson at St George's Hospital, London. A second animal model was developed by Eleanor Storrs at the Gulf South Research Institute. Dr Storrs had worked on the nine-banded armadillo for her PhD, because this animal had a lower body temperature than humans and might therefore be a suitable animal model. The work started in 1968 with material provided by Waldemar Kirchheimer at the United States Public Health Leprosarium in Carville, Louisiana. These experiments proved unsuccessful but additional work in 1970 with material provided by Chapman Binford, medical director of the Leonard's Wood Memorial, was successful. The papers describing this model led to a dispute of priority. Further controversy was generated when it was discovered that wild armadillos in Louisiana were naturally infected with leprosy. Naturally occurring infection also has been reported in non-human primates including the African chimpanzee, sooty mangabey, and cynomolgus macaque.

Genetics
Several genes have been associated with a susceptibility to leprosy.
Name LPRS1 LPRS2 LPRS3 LPRS4 LPRS5 LPRS6 Locus 10p13 6q25 4q32 6p21.3 4p14 13q14.11 OMIM 609888 607572 246300 610988 613223 613407 Gene

[45] [46] PARK2, PACRG [3]


TLR2

[47] LTA [48] TLR1 [49]

Risk factors
At highest risk are those living in endemic areas with poor conditions such as inadequate bedding, contaminated water and insufficient diet, or other diseases (such as HIV) that compromise immune function. Recent research suggests that there is a defect in cell-mediated immunity that causes susceptibility to the disease. Less than ten percent of the world's population is actually capable of acquiring the disease.[50] The region of DNA responsible for this variability is also involved in Parkinson disease, giving rise to current speculation that the two disorders may be linked in some way at the biochemical level. In early 2003, an international team of scientists conducted a genome scan in Vietnamese multiplex leprosy families and found that susceptibility to leprosy was significantly linked to region q25 on the long arm of chromosome 6. Further confirmation of the chromosome 6 locus was provided by high-resolution linkage mapping in simplex leprosy families. Now, in a continuation of these findings, the team has pinpointed the chromosome 6 susceptibility locus to the 5' regulatory promoter region shared by both the Parkinson's disease gene PARK2 and its co-regulated gene PACRG.[51] According to The Leprosy Mission Canada, most people-about 95% of the population-are naturally immune to the disease.[50]

Leprosy

Pathophysiology
The mechanism of transmission of leprosy is prolonged close contact and transmission by nasal droplet.[18] In addition to humans, leprosy has been observed in nine-banded armadillo, and three species of primates.[52] The bacterium can also be grown in the laboratory by injection into the footpads of mice.[53] There is evidence that not all people who are infected with M. leprae develop leprosy, and genetic factors have long been thought to play a role, due to the observation of clustering of leprosy around certain families, and the failure to understand why certain individuals develop lepromatous leprosy while others develop Leprosy sufferers home in Bagamoyo in German East Africa. other types of leprosy.[54] It is estimated that due to genetic factors, only 5% of the population is susceptible to leprosy.[55] This is mostly because the body is naturally immune to the bacteria, and those persons who do become infected are experiencing a severe allergic reaction to the disease. However, the role of genetic factors is not entirely clear in determining this clinical expression. In addition, malnutrition and prolonged exposure to infected persons may play a role in development of the overt disease. The most widely held belief is that the disease is transmitted by contact between infected persons and healthy persons.[56] In general, closeness of contact is related to the dose of infection, which in turn is related to the occurrence of disease. Of the various situations that promote close contact, contact within the household is the only one that is easily identified, although the incidence among contacts and the relative risk for them appear to vary considerably in different studies. In incidence studies, infection rates for contacts of lepromatous leprosy have varied from 6.2 per 1000 per year in Cebu, Philippines[57] to 55.8 per 1000 per year in a part of Southern India.[58] 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.[59] Although there are reports of acid-fast bacilli being found in the desquamating epithelium (sloughing of superficial layer of skin) of the skin, Weddell et al. had reported in 1963 that they could not find any acid-fast bacilli in the epidermis, even after examining a very large number of specimens from patients and contacts.[60] In a recent study, Job et al. found fairly large numbers of M. leprae in the superficial keratin layer of the skin of lepromatous leprosy patients, suggesting that the organism could exit along with the sebaceous secretions.[61] The importance of the nasal mucosa was recognized as early as 1898 by Schffer, particularly that of the ulcerated mucosa.[62] The quantity of bacilli from nasal mucosal lesions in lepromatous leprosy was demonstrated by Shepard as large, with counts ranging from 10,000 to 10,000,000.[63] Pedley reported that the majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through blowing the nose.[64] Davey and Rees indicated that nasal secretions from lepromatous patients could yield as much as 10 million viable organisms per day.[65] The entry route of M. leprae into the human body is also not definitively known: the skin and the upper respiratory tract are most likely. While older research dealt with the skin route, recent research has increasingly favored the respiratory route. Rees and McDougall succeeded in the experimental transmission of leprosy through aerosols

Leprosy containing M. leprae in immune-suppressed mice, suggesting a similar possibility in humans.[66] Successful results have also been reported on experiments with nude mice when M. leprae were introduced into the nasal cavity by topical application.[67] In summary, entry through the respiratory route appears the most probable route, although other routes, particularly broken skin, cannot be ruled out. The CDC notes the following assertion about the transmission of the disease: "Although the mode of transmission of Hansen's disease remains uncertain, most investigators think that M. leprae is usually spread from person to person in respiratory droplets."[68] In leprosy both the reference points for measuring the incubation period and the times of infection and onset of disease are difficult to define; the former because of the lack of adequate immunological tools and the latter because of the disease's slow onset. Even so, several investigators have attempted to measure the incubation period for leprosy. The minimum incubation period reported is as short as a few weeks and this is based on the very occasional occurrence of leprosy among young infants.[69] The maximum incubation period reported is as long as 30 years, or over, as observed among war veterans known to have been exposed for short periods in endemic areas but otherwise living in non-endemic areas. It is generally agreed that the average incubation period is between three and five years.

Prevention
Venezuelan Dr. Jacinto Convit synthesized a vaccine from the tuberculosis vaccine and the Mycobacterium leprae, a feat that earned him a nomination for the Nobel prize in medicine in the late 1990s. In a recent trial, a single dose of rifampicin reduced the rate at which contacts acquired leprosy in the two years after contact by 57%; 265 treatments with rifampicin prevented one case of leprosy in this period.[70] A non-randomized study found that rifampicin reduced the number of new cases of leprosy by 75% after three years.[71] BCG offers a variable amount of protection against leprosy as well as against tuberculosis.[72] [73] Efforts to overcome persistent obstacles to the elimination of the disease include improving detection, educating patients and the population about its cause, and fighting social taboos about a disease that has caused its patients historically to be considered "unclean" or "cursed by God" as outcasts. Leprosy is not a hereditary disease. Where taboos are strong, patients may be forced to hide their condition (and avoid seeking treatment) to avoid discrimination. The lack of awareness about Hansen's disease can lead people to believe (falsely) that the disease is highly contagious and incurable. The ALERT hospital and research facility in Ethiopia provides training to medical personnel from around the world in the treatment of leprosy, as well as treating many local patients. Surgical techniques, such as for the restoration of control of movement of thumbs, have been developed.

Treatment
The WHO Study Group's report on the Chemotherapy of Leprosy in 1993 recommended two types of standard MDT regimen be adopted.[74] The first was a 24-month treatment for multibacillary (MB or lepromatous) cases using rifampicin, clofazimine, and dapsone. The second was a six-month treatment for paucibacillary (PB or tuberculoid) cases, using rifampicin and dapsone. At the First International Conference on the Elimination of Leprosy as a Public Health Problem, held in Hanoi the next year, the global strategy was endorsed and funds provided to WHO for the procurement and supply of MDT to all endemic countries.

MDT anti-leprosy drugs: standard regimens

Between 1995 and 1999, WHO, with the aid of the Nippon Foundation (Chairman Yhei Sasakawa, World Health Organization Goodwill Ambassador for Leprosy Elimination), supplied all endemic countries with free MDT in blister packs, channelled through Ministries of Health. This free provision was extended in 2000 with a donation by

Leprosy the MDT manufacturer Novartis, which will run until at least the end of 2010. At the national level, non-government organizations (NGOs) affiliated to the national programme will continue to be provided with an appropriate free supply of this WHO supplied MDT by the government. MDT remains highly effective, and patients are no longer infectious after the first monthly dose.[18] It is safe and easy to use under field conditions due to its presentation in calendar blister packs.[18] Relapse rates remain low, and there is no known resistance to the combined drugs.[18] The Seventh WHO Expert Committee on Leprosy,[75] reporting in 1997, concluded that the MB duration of treatmentthen standing at 24 monthscould safely be shortened to 12 months "without significantly compromising its efficacy."

Current recommendations
Pauci-bacillary leprosy (1-5 skin lesions) Treat with rifampicin and dapsone for 6 months Multi-bacillary leprosy (>5 skin lesions) Treat with rifampicin, clofazimine and dapsone for 12 months

Historical treatments
The disease was known in Ancient Greece as elephantiasis (elephantiasis graecorum). Saint Giles, Saint Martin, Saint Maxillian and Saint Roman were associated with this practice. Several monarchs were also associated with this practice: among these were Elizabeth I , Henry III of England and Charlemagne. At various times blood was considered to be a treatment either as a beverage or as a bath. That of virgins or children was considered to be especially potent. This practice seems to have originated with the Ancient Egyptians but was also known in China where people were murdered for their blood. This practice persisted until at least 1790 when the use of dog blood was mentioned in De Secretis Naturae. Paracelsus recommended the use of lamb's blood and even blood from dead bodies was used. Snakes were also used, according to Pliny, Aretaeus of Cappadocia and Theodorus. Gaucher recommended treatment with cobra venom. Boinet, in 1913, tried increasing doses of bee stings (up to 4000). Scorpions and frogs were used occasionally instead of snakes. The excreta of Anabas (the climbing fish) was also tried. Alternative treatments included scarification with or without the addition of irritants including arsenic and hellebore. Castration was also practiced in the Middle Ages. Chaulmoogra oil A common pre-modern treatment of leprosy was chaulmoogra oil. One Indian legend relates that Rama acquired leprosy and was cured by eating the fruit of the Kalaw (a species of the genus Hydnocarpus) tree. He went on to cure the princess Piya with the same fruit and the pair returned to Benares to spread the word of their discovery. The oil has long been used in India as an Ayurvedic medicine for the treatment of leprosy and various skin conditions. It has also been used in China and Burma, and was introduced to the West by Frederic John Mouat, a professor at Bengal Medical College. He tried the oil as an oral and topical agent in two cases of leprosy and reported significant improvements in an 1854 paper.[76] This paper caused some confusion. Mouat indicated that the oil was the product of a tree Chaulmoogra odorata which had been described in 1815 by William Roxburgh, a surgeon and naturalist, while he was cataloging the plants in the East India Companys botanical garden in Calcutta. This tree is also known as Gynocardia odorata. For the rest of the 19th century this tree was thought to be the source of the oil. In 1901 Sir David Prain identified the true chaulmoogra seeds of the Calcutta bazaar and of the Paris and London apothecaries as coming from Taraktogenos kurzii which is found in Burma and Northeast India. The oil mentioned in the Ayurvedic texts was from the tree Hydnocarpus wightiana known as Tuvakara in Sanskrit and chaulmugra in Hindi and Persian. The first parenteral administration was given by the Egyptian doctor Tortoulis Bey, personal physician to the Sultan Hussein Kamel. He had been using subcutaneous injections of creosite for tuberculosis and in 1894 administered subcutaneous injection of chaulmoogra oil in a 36-year old Egyptian Copt who had been unable to tolerate oral

Leprosy treatment. After 6 years and 584 injections the patient was declared cured. An early scientific analysis of the oil was carried out by Frederick B. Power in London in 1904. He and his colleagues isolated a new unsaturated fatty acid from the seeds which they named 'chaulmoogric acid'. They also investigated two closely related species: Hydnocarpus anthelmintica and Hydnocarpus wightiana. From these two trees they isolated both chaulmoogric acid and a closely related compound, 'hydnocarpus acid'. They also investigated Gynocardia odorata and found that it produced neither of these acids. Later investigation showed that 'taraktogenos' (Hydnocarpus kurzii) also produced chaulmoogric acid. Another difficulty with the use of this oil was administration. Taken orally it is extremely nauseating. Given by enema may cause peri-anal ulcers and fissures. Given by injection the drug caused fever and other local reactions. Despite these difficulties, a series of 170 patients were reported in 1916 by Ralph Hopkins, the attending physician at the Louisiana Leper Home in Carville, Louisiana. He divided the patients into two groups - 'incipient' and 'advanced'. In the advanced cases, 25% (at most) showed any improvement or arrest of their condition; in the incipient cases, 45% reported an improvement or stabilization of the disease (mortality rates were 4% and 8%, respectively). The remainder absconded from the Home apparently in improved condition. Given the apparent usefulness of this agent, a search began for improved formulations. Victor Heiser the Chief Quarantine Officer and Director of Health for Manila and Elidoro Mercadothe house physician at the San Lazaro Hospital for lepers in Manila decided to add camphor to a prescription of chaulmoogra and resorcin which was typically given orally at the suggestion of Merck and Company in Germany to whom Heiser had written. They found that this new compound was readily absorbed without the nausea that had plagued the earlier preparations. Heiser and Mercado in 1913 then administered the oil by injection to two patients who were apparently cured of the disease. Since this treatment was administered in conjunction with other materials the results were not clear. A further two patients were treated with the oil by injection without other treatments and again appeared to be cured of the disease. The following year Heiser reported a further 12 patients but the results were mixed. Less toxic injectable forms of this oil were then sought. Between 1920 and 1922 a series of papers were published describing the esters of these oils. These may have been based on the work of Alice Ball - the record is not clear on this point and Ms Ball died in 1916. Trials of these esters were carried out in 1921 and appeared to give useful results. These attempts had been preceded by others. Merck of Darmstadt had produced a version of the sodium salts in 1891. They named this sodium gynocardate in the mistaken belief that the origin of the oil was Gynocardia odorata. Bayer in 1908 marketed a commercial version of the esters under the name 'Antileprol'. To ensure a supply of this agent Joseph Rock, Professor of Systematic Botany at the College of Hawaii, traveled to Burma. The local villagers located a grove of trees in seed which he used to establish a plantation in 2,980 trees on the island of Oahu, Hawaii between 1921 and 1922. The oil remained a popular treatment despite the common side effects until the introduction of sulfones in the 1940s. Debate about its efficacy continued until it was discontinued. Promin was first synthesised in 1908 by Emil Fromm, professor of chemistry at Albert-Ludwig University in Freiburg im Breisgau, Germany. Its anti strepococcal activity was investigated by Gladstone Buttle at Burroughs Wellcome and Ernest Fourneau (French) at the Institut Pasteur. Until the development of promin in the 1940s, there was no effective treatment for leprosy. The efficacy of promin was first discovered by Guy Henry Faget and his co-workers in 1943 at Carville, Louisiana. In

MDT patient packs and blisters

Leprosy the 1950s dapsone was introduced to Carville by Dr. R.G. Cochrane. It is only weakly bactericidal against M. leprae and it was considered necessary for patients to take the drug indefinitely. When dapsone was used alone, the M. lepraepopulation quickly evolved antibiotic resistance; by the 1960s, the world's only known anti-leprosy drug became virtually useless. The search for more effective anti-leprosy drugs led to the use of clofazimine and rifampicinin the 1960s and 1970s.[77] Later, Indian scientist Shantaram Yawalkar and his colleagues formulated a combined therapy using rifampicin and dapsone, intended to mitigate bacterial resistance.[78] The first trials of combined treatment were carried out in Malta in the 1970s. Multidrug therapy (MDT) combining all three drugs was first recommended by a WHO Expert Committee in 1981. These three anti-leprosy drugs are still used in the standard MDT regimens. None of them is used alone because of the risk of developing resistance. This treatment was quite expensive, and was not quickly adopted in most endemic countries. In 1985 leprosy was still considered a public health problem in 122 countries. The 44th World Health Assembly (WHA), held in Geneva in 1991, passed a resolution to eliminate leprosy as a public-health problem by the year 2000defined as reducing the global prevalence of the disease to less than 1 case per 10,000. At the Assembly, the World Health Organization (WHO) was given the mandate to develop an elimination strategy by its member states, based on increasing the geographical coverage of MDT and patients accessibility to the treatment.

Epidemiology
Worldwide, two to three million people are estimated to be permanently disabled because of leprosy.[20] India has the greatest number of cases, with Brazil second and Burma third. In 1999, the world incidence of Hansen's disease was estimated to be 640,000. In 2000, 738,284 cases were identified.[80] In 2000, the World Health Organization (WHO) listed 91 countries in which Hansen's disease is endemic. India, Myanmar and Nepal contained 70% of cases. India reports over 50% of the world's leprosy cases.[81] In 2002, 763,917 new cases were detected worldwide, and in that year the WHO listed Brazil, Madagascar, Mozambique, Tanzania and Nepal as having 90% of Hansen's disease cases.
World distribution of leprosy, 2003.

Disability-adjusted life year for leprosy per 100,000inhabitants in 2002. "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002. .no dataless than 1.51.5-33-4.54.5-66-7.57.5-99-10.510.5-1212-13.513.5-1515-20more than 20

According to recent figures from the WHO, new cases detected worldwide have decreased by approximately 107,000 cases (or 21%) from 2003 to 2004. This decreasing trend has been consistent for the past three years. In addition, the global registered prevalence of HD was 286,063 cases; 407,791 new cases were detected during 2004. In the United States, Hansen's disease is tracked by the Centers for Disease Control and Prevention (CDC), with a total of 166 new cases reported in the U.S. in 2005. Most (100 or 60%) of these new cases were reported in the following states; California, Louisiana, Massachusetts, New York, and Texas.[42] Although the number of cases worldwide continues to fall, pockets of high prevalence continue in certain areas such as Brazil, South Asia (India, Nepal), some parts of Africa (Tanzania, Madagascar, Mozambique) and the western Pacific.

Leprosy

10

Disease burden
Although annual incidencethe number of new leprosy cases occurring each yearis important as a measure of transmission, it is difficult to measure in leprosy due to its long incubation period, delays in diagnosis after onset of the disease and the lack of laboratory tools to detect leprosy in its very early stages. Instead, the registered prevalence is used. Registered prevalence is a useful proxy indicator of the disease burden as it reflects the number of active leprosy cases diagnosed with the disease and receiving treatment with MDT at a given point in time. The prevalence rate is defined as the number of cases registered for MDT treatment among the population in which the cases have occurred, again at a given point in time.[82] New case detection is another indicator of the disease that is usually reported by countries on an annual basis. It includes cases diagnosed with onset of disease in the year in question (true incidence) and a large proportion of cases with onset in previous years (termed a backlog prevalence of undetected cases). Endemic countries also report the number of new cases with established disabilities at the time of detection, as an indicator of the backlog prevalence. Determination of the time of onset of the disease is generally unreliable, is very labor-intensive and is seldom done in recording these statistics.

Global situation Table 1: Prevalence at beginning of 2006, and trends in new case detection 2001-2005, excluding Europe
Region Registered prevalence (rate/10,000 pop.) Start of 2006 Africa Americas South-East Asia Eastern Mediterranean Western Pacific Totals 40,830 (0.56) 32,904 (0.39) 133,422 (0.81) 4,024 (0.09) 8,646 (0.05) 219,826 New case detection during the year

2001 39,612 42,830

2002 48,248 39,939

2003 47,006 52,435

2004 46,918 52,662

2005 42,814 41,780

668,658 520,632 405,147 298,603 201,635 4,758 7,404 4,665 7,154 3,940 6,190 3,392 6,216 3,133 7,137

763,262 620,638 514,718 407,791 296,499

Table 2: Prevalence and detection, countries still to reach elimination


Countries Registered prevalence (rate/10,000 pop.) Start of 2004 Brazil 79,908 (4.6) Start of 2005 30,693 (1.7) 4,692 (2.4) 4,699 (1.8) 4,777 (1.3) NA Start of 2006 27,313 (1.5) 4,889 (2.5) 4,921 (1.8) 4,190 (1.1) NA New case detection (rate/100,000 pop.) During 2003 49,206 (28.6) 5,907 (29.4) 8,046 (32.9) 5,279 (15.4) NA During 2004 49,384 (26.9) 4,266 (22.0) 6,958 (26.2) 5,190 (13.8) NA During 2005 38,410 (20.6) 5,371 (27.1) 6,150 (22.7) 4,237 (11.1) NA

Mozambique 6,810 (3.4) Nepal Tanzania Totals 7,549 (3.1) 5,420 (1.6) NA

As reported to WHO by 115 countries and territories in 2006, and published in the Weekly Epidemiological Record the global registered prevalence of leprosy at the beginning of the year was 219,826 cases.[83] New case detection during the previous year (2005 - the last year for which full country information is available) was 296,499. The

Leprosy reason for the annual detection being higher than the prevalence at the end of the year can be explained by the fact that a proportion of new cases complete their treatment within the year and therefore no longer remain on the registers. The global detection of new cases continues to show a sharp decline, falling by 110,000 cases (27%) during 2005 compared with the previous year. Table 1 shows that global annual detection has been declining since 2001. The African region reported an 8.7% decline in the number of new cases compared with 2004. The comparable figure for the Americas was 20.1%, for South-East Asia 32% and for the Eastern Mediterranean it was 7.6%. The Western Pacific area, however, showed a 14.8% increase during the same period. Table 2 shows the leprosy situation in the four major countries which have yet to achieve the goal of elimination at the national level. It should be noted that: a) Elimination is defined as a prevalence of less than 1 case per 10,000 population; b) Madagascar reached elimination at the national level in September 2006; c) Nepal detection reported from mid-November 2004 to mid-November 2005; and d) D.R. Congo officially reported to WHO in 2008 that it had reached elimination by the end of 2007, at the national level.

11

History
After the end of the 17th century, Norway and Iceland were the only countries in Western Europe where leprosy was a significant problem. During the 1830s, the number of lepers in Norway rose rapidly, causing an increase in medical research into the condition, and the disease became a political issue. Norway appointed a medical superintendent for leprosy in 1854 and established a national register for lepers in 1856, the first national patient register in the world.[84] Mycobacterium leprae, the causative agent of leprosy, was discovered by G. H. Armauer Hansen in Norway in 1873, making it the first bacterium to be identified as causing disease in humans.[85] [86] Hansen observed a number of non refractile small rods in unstained tissue sections. The rods were not soluble in potassium lye and they were acid and alcohol fast. In 1879 he was able to stain these organisms with Ziehl's method and the similarities with Koch's bacillus (Mycobacterium tuberculosis) were noted. There were three significant differences between these organisms: (1) the rods in the leprosy lesions G. H. A. Hansen, discoverer of M. leprae were extremely numerous (2) they formed characteristic intracellular collections (globii) and (3) the rods had a variety of shapes with branching and swelling. These differences suggested that leprosy was caused by an organism related to but distinct from Mycobacterium tuberculosis. He worked at St. Jrgens Hospital in Bergen, founded early in the fifteenth century. St. Jrgens is today a museum, Lepramuseet, probably the best preserved leprosy hospital in Northern Europe.[87]

Etymology
The word leprosy comes from ancient Greek [lpr], "a disease which makes the skin scaly", in turn a nominal derivation of the verb [lp], "to peel, scale off". (Lepos) in ancient Greek means peel, or scale, so from we have ( = who has peels - scales) --> and then (=leprous)[88] . The word came into the English language via Latin and old French. The first attested English use is in the Ancrene Wisse, a 13th-century manual for nuns ("Moyseses hond..bisemde o e spitel uuel & uhte lepruse." The Middle English Dictionary, s.v., "leprous"). A roughly contemporaneous use is attested in the Anglo-Norman Dialogues of Saint

Leprosy Gregory, "Esmondez i sont li lieprous" (Anglo-Norman Dictionary, s.v., "leprus"). Historically, individuals with Hansen's disease have been known as lepers; however, this term is falling into disuse as a result of the diminishing number of leprosy patients. Because of the stigma to patients, some prefer not to use the word "leprosy," though the term is used by the U.S. Centers for Disease Control and Prevention and the World Health Organization.[89] Historically, the term Tzaraath from the Hebrew Bible was, erroneously, commonly translated as leprosy, although the symptoms of Tzaraath were not entirely consistent with leprosy and rather referred to a variety of disorders other than Hansen's disease.[90] The first mention of leprosy recorded is found in Leviticus 13:2 - "When a man shall have in the skin of his flesh a rising, a scab, or bright spot, and it be in the skin of his flesh like the plague of leprosy; then he shall be brought unto Aaron the priest, or unto one of his sons the priests." There is also the well known Bible story of the Syrian Naaman, "captain of the host of the king of Syria" (2 Kings 5:1), who suffered from this severe and savage skin disease. In particular, tinea capitis (fungal scalp infection) and related infections on other body parts caused by the dermatophyte fungus Trichophyton violaceum are abundant throughout the Middle East and North Africa today and might also have been common in biblical times. Similarly, the related agent of the disfiguring skin disease favus, Trichophyton schoenleinii, appears to have been common throughout Eurasia and Africa before the advent of modern medicine. Persons with severe favus and similar fungal diseases (and potentially also with severe psoriasis and other diseases not caused by microorganisms) tended to be classed as having leprosy as late as the 17th century in Europe.[91] This is clearly shown in the painting The Regents of the Leper Hospital in Haarlem 1667 by Jan de Bray (Frans Hals Museum, Haarlem, the Netherlands), where a young Dutchman with a vivid scalp infection, almost certainly caused by a fungus, is shown being cared for by three officials of a charitable home intended for leprosy sufferers. The use of the word "leprosy" before the mid-19th century, when microscopic examination of skin for medical diagnosis was first developed, can seldom be correlated reliably with Hansen's disease as we understand it today.

12

Rome
In the West, the earliest known description of leprosy there was made by the Roman encyclopedist Aulus Cornelius Celsus (25 BC 37 AD) in his De Medicina; he called leprosy "elephantiasis".[92] The Roman author Pliny the Elder (2379 AD) mentioned the same disease.[92] Although "sara't" of Leviticus (Old Testament) is translated as "lepra" in the 5th century AD Vulgate, the original term sara't found in Leviticus was not the elephantiasis described by Celsus and Pliny; in fact, sara't was used to describe a disease which could affect houses and clothing.[92] Katrina C. D. McLeod and Robin D. S. Yates state that sara't "denotes a condition of ritual impurity or a temporary form of skin disease."[92]

Leprosy

13

Persia (Iran)
The Persian polymath Avicenna (c. 9801037) was the first outside of China to describe the destruction of the nasal septum in those suffering from leprosy.[92]

Middle Ages
Numerous leprosaria, or leper hospitals, sprang up in the Middle Ages; Matthew Paris, a Benedictine Monk, estimated that in the early thirteenth century there were 19,000 across Europe.[93] The first recorded Leper colony was in Harbledown. These institutions were run along monastic lines and, while lepers were encouraged to live in these monastic-type establishments, this was for their own health as well as quarantine. Indeed, some medieval sources indicate belief that those suffering from leprosy were considered to be going through Purgatory on Earth, and for this reason their suffering was considered holier than the ordinary person's. More frequently, lepers were seen to exist in a place between life and death: they were still alive, yet many chose or were forced to ritually separate themselves from mundane existence.[94] The Order of Saint Lazarus was a hospitaller and military order of monks that began as a leper hospital outside Jerusalem in the twelfth century and remained associated with leprosy throughout its history. The first monks in this order were leper knights and they originally had leper grand masters, although these aspects of the order changed over the centuries.

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

Engraving "The leprose" by Albrecht Durer. Created in 1513.

India
The Oxford Illustrated Companion to Medicine holds that the mention of leprosy, as well as cures for it, were already described in the Hindu religious book Atharva-veda.[95] Writing in the Encyclopedia Britannica 2008, Kearns & Nash state that the first mention of leprosy is in the Indian medical treatise Sushruta Samhita (6th century BC).[96] The Cambridge Encyclopedia of Human Paleopathology (1998) holds that: "The Sushruta Samhita from India describes the condition quite well and even offers therapeutic suggestions as early as about 600BC"[97] The surgeon Sushruta lived in the Indian city of Kashi by the 6th centuryBC,[98] and the medical treatise Sushruta Samhitaattributed to himmade its appearance during the 1st millenniumBC.[96] The earliest surviving excavated written material which contains the works of Sushruta is the Bower Manuscriptdated to the 4th centuryAD, almost a millennium after the original work.[99] Despite the existence of these earlier works the first generally considered accurate description of the disease was that of Galen of Pergamum in 150 AD. In 2009, a 4,000-year-old skeleton was uncovered in India that was shown to contain traces of leprosy.[100] The discovery was made at a site called Balathal, which is today part of Rajasthan, and is believed to be the oldest case of the disease ever found.[101] This pre-dated the previous earliest recognized case, dating back to 6th-century Egypt, by 1,500 years.[102] It is believed that the excavated skeleton belonged to a male, who was in his late 30s and belonged to the Ahar Chalcolithic culture.[102] [103] Archaeologists have stated that not only does the skeleton represent the

Leprosy oldest case of leprosy ever found, but is also the first such example that dates back to prehistoric India.[104] This finding supports one of the theories regarding the origin of the disease, which is believed to have originated in either India or Africa, before being subsequently spread to Europe by the armies of Alexander the Great.[101] In 1881, around 120,000 leprosy patients existed in India. The central government passed the Lepers Act of 1898, which provided legal provision for forcible confinement of leprosy sufferers in India.[105]

14

China
Regarding ancient China, Katrina C. D. McLeod and Robin D. S. Yates identify the State of Qin's Feng zhen shi (Models for sealing and investigating), dated 266-246 BC, as offering the earliest known unambiguous description of the symptoms of low-resistance leprosy, even though it was termed then under li , a general Chinese word for skin disorder.[92] This 3rd century BC Chinese text on bamboo slip, found in an excavation of 1975 at Shuihudi, Yunmeng, Hubei province, not only described the destruction of the "pillar of the nose", but also the "swelling of the eyebrows, loss of hair, absorption of nasal cartilage, affliction of knees and elbows, difficult and hoarse respiration, as well as anesthesia."[92]

Japan
Japan has had a unique history of segregation of patients into sanatoriums based on leprosy prevention laws of 1907, 1931 and 1953, and hence, it intensified leprosy stigma. The 1953 law was abrogated in 1996. There are still 2717 ex-patients in 13 national sanatoriums and 2 private hospitals as of 2008. In a document written in 833, leprosy was described as "caused by a parasite which eats five organs of the body. The eyebrows and eyelashes come off, and the nose is deformed. The disease brings hoarseness, and necessitates amputations of the fingers and toes. Do not sleep with the patients, as the disease is transmittable to those nearby." This was the first document concerning infectivity.[106]

Society and culture


Notable cases
Saint Damien of Molokai, a Roman Catholic Priest from Belgium who ministered to the people with leprosy, who had been placed under a government-sanctioned medical quarantine on the island of Molokai in the Kingdom of Hawaii.[107] Baldwin IV, who was a king of Latin Jerusalem and was portrayed as a character in the film Kingdom of Heaven[108] Vietnamese poet Han Mac Tu[109] Probably not Robert the Bruce although one English source said that he did.[110] In the 1995 Mel Gibson film Braveheart, Robert the Bruce's father - Robert de Brus, 6th Lord of Annandale - is depicted as having leprosy. Otani Yoshitsugu, a Japanese daimyo[111] Biblical writings have a number of references such as Moses's sister,[112] Moses,[113] commander of the army of Syria Naaman the Syrian and later the prophet Elisha's servant Gehazi,[114] and several people Jesus healed,[115] [116] though the aflicted mentioned and symptoms described are now thought not to be, or not exclusively to be, the result of Hansen's Disease (see discussion at 'Tzaraath').

Leprosy

15

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March 22, 2003. [81] Surgery grants for leprosy sufferers in India (http:/ / southasia. oneworld. net/ todaysheadlines/ surgery-grants-for-leprosy-sufferers-in-india). Times of India. February 2, 2009. [82] World Health Organization. (1985). "Epidemiology of leprosy in relation to control. Report of a WHO Study Group". World Health Organ Tech Rep Ser (Geneva: World Health Organization) 716: 160. ISBN9241207167. OCLC12095109. PMID3925646. [83] "Global leprosy situation, 2006" (http:/ / www. who. int/ lep/ resources/ wer8132. pdf) (PDF). Weekly Epidemiological Record 81 (32): 30916. August 2006. PMID16903018. . [84] "The Leprosy Archives in Bergen, Norway" (http:/ / digitalarkivet. uib. no/ lepra-eng/ intro. htm). . Retrieved 2009-05-30. [85] Hansen GHA (1874). "Undersgelser Angende Spedalskhedens rsager (Investigations concerning the etiology of leprosy)" (in Norwegian). Norsk Mag. Laegervidenskaben 4: 188. [86] Irgens L (2002). "The discovery of the leprosy bacillus". Tidsskr nor Laegeforen 122 (7): 7089. PMID11998735. [87] "Bymuseet i Bergen" (http:/ / www. bymuseet. no/ ?vis=80). Bymuseet.no. . Retrieved 2010-09-10. [88] Greek Dictionary Tegopoulos-Fytrakis, Athens, 1999 [89] "What Is Leprosy?" THE MEDICAL NEWS | from News-Medical.Net - Latest Medical News and Research from Around the World. Web. 20 Nov. 2010. <http://www.news-medical.net/health/What-is-Leprosy.aspx>. [90] Artscroll Tanakh, 6 [91] Kane J, Summerbell RC, Sigler L, Krajden S, Land G (1997). Laboratory Handbook of Dermatophytes: A clinical guide and laboratory manual of dermatophytes and other filamentous fungi from skin, hair and nails. Star Publishers (Belmont, CA). ISBN0898631572. OCLC37116438. [92] McLeod, Katrina C. D. and Robin D. S. Yates (June 1981). "Forms of Ch'in Law: An Annotated Translation of The Feng-chen shih" (http:/ / jstor. org/ stable/ 2719003). Harvard Journal of Asiatic Studies 41 (1): 11163. Pages 1523 & footnote 147. doi:10.2307/2719003. . Angela Leung's Leprosy in China: A History (New York: Columbia University Press, 2009) is the authoritative source on leprosy in China. [93] "Leprosy". Catholic Encyclopedia. New York: Robert Appleton Company. 1913. [94] Brody, Saul Nathaniel (1974). The Disease of the Soul: Leprosy in Medieval Literature. Ithaca: Cornell Press. [95] Lock et al; p. 420 [96] Kearns & Nash (2008) [97] Aufderheide, A. C.; Rodriguez-Martin, C. & Langsjoen, O. (1998) The Cambridge Encyclopedia of Human Paleopathology. Cambridge University Press ISBN 0-521-55203-6; p. 148. [98] Dwivedi & Dwivedi (2007) [99] Kutumbian, P. (2005) Ancient Indian Medicine. Orient Longman ISBN 81-250-1521-3; pp. XXXII-XXXIII [100] Robbins G, Tripathy VM, Misra VN, Mohanty RK, Shinde VS, et al. (2009). Ancient Skeletal Evidence for Leprosy in India (2000 B.C.) (http:/ / www. plosone. org/ article/ info:doi/ 10. 1371/ journal. pone. 0005669) PLoS ONE 4(5): e5669. doi:10.1371/journal.pone.0005669 [101] "Skeleton shows earliest evidence of leprosy" (http:/ / www. google. com/ hostednews/ ap/ article/ ALeqM5idNIe5ytThacobusirf-k5Bfwl_gD98E87F80). Associated Press. 2009-05-27. . Retrieved 2009-05-29. [102] "Skeleton Pushes Back Leprosy's Origins" (http:/ / sciencenow. sciencemag. org/ cgi/ content/ full/ 2009/ 527/ 1?rss=1). Science Now. 2009-05-27. . Retrieved 2009-05-29. [103] Shinde, Swati (2009-05-29). "Leprosy belonged to Ahar Chalcolithic era: Expert" (http:/ / timesofindia. indiatimes. com/ Pune/ Leprosy-belonged-to-Ahar-Chalcolithic-era-Expert/ articleshow/ 4590778. cms). The Times of India. . Retrieved 2009-05-29. [104] "Oldest evidence of leprosy found in India" (http:/ / timesofindia. indiatimes. com/ Health--Science/ Oldest-proof-of-leprosy-found-in-India/ articleshow/ 4585654. cms). The Times of India. 2009-05-27. . Retrieved 2009-05-29.

17

Leprosy
[105] Leprosy Medical History of British India (http:/ / www. nls. uk/ indiapapers/ leprosy. html), National Library of Scotland [106] Hansen's disease in Japan: a brief history Kikuchi I Int J Dermatol 1997:36:629-633. [107] Tayman, John (2007). The Colony: The Harrowing True Story of the Exiles of Molokai (http:/ / books. google. com/ books?id=rKUaLE6s1lgC& dq). New York: Simon and Schuster. ISBN9780743233019. . [108] Hamilton, Bernard (2000). The leper king and his heirs: Baldwin IV and the Crusader Kingdom of Jerusalem. Cambridge, UK: Cambridge University Press. ISBN0-521-64187-X. [109] Cung giu Nguyn (1955). "Contemporary Vietnamese Writing" (http:/ / www. jstor. org/ stable/ 40093803). Books Abroad (University of Oklahoma) 29 (1): 1925. doi:10.2307/40093803. . Retrieved 2010-02-28. [110] Kaufman MH, MacLennan WJ (2001-04-01). "Robert the Bruce and Leprosy" (http:/ / www. rcpsg. ac. uk/ hdrg/ April015. htm). History of Dentistry Research Newsletter. . Retrieved 2010-02-28. [111] Bryant A (1995). Sekigahara 1600: The Final Struggle for Power (Campaign Series, 40) (http:/ / books. google. com/ ?id=UzhzhxfmncsC& pg=PA24& dq=Otani+ Yoshitsugu+ leprosy& q=Otani Yoshitsugu leprosy). Osprey Publishing (UK). ISBN1-85532-395-8. . Retrieved 2010-02-28. [112] "Numbers 12:9-16; - Passage Lookup - American Standard Version" (http:/ / www. biblegateway. com/ passage/ ?search=Numbers 12:9-16;& version=8;). BibleGateway.com. . Retrieved 2010-09-10. [113] "Exodus 4:6; - Passage Lookup - American Standard Version" (http:/ / www. biblegateway. com/ passage/ ?search=Exodus 4:6;& version=8;). BibleGateway.com. . Retrieved 2010-09-10. [114] "2 Kings; - Passage Lookup - American Standard Version" (http:/ / www. biblegateway. com/ passage/ ?search=2 Kings%;& version=8;). BibleGateway.com. . Retrieved 2010-09-10. [115] "Luke; - Passage Lookup - American Standard Version" (http:/ / www. biblegateway. com/ passage/ ?search=Luke%;& version=8;). BibleGateway.com. . Retrieved 2010-09-10. [116] "Luke 17:11-19; - Passage Lookup - American Standard Version" (http:/ / www. biblegateway. com/ passage/ ?search=Luke 17:11-19;& version=8;). BibleGateway.com. . Retrieved 2010-09-10.

18

Further reading
1877: Lewis, T. R.; D. D. Cunningham (1877). Leprosy In India (http://books.google.com/ ?id=wHMIAAAAQAAJ). Calcutta: Office Of The Superintendent Of Government Printing. Retrieved 2009-08-07. 1895: Ashmead, Albert S. (1895). Pre-Columbian Leprosy (http://books.google.com/?id=imSHLN5DvgYC). Chicago: American Medical Association Press. Retrieved 2009-08-07. 1895: Prize Essays On Leprosy (http://books.google.com/?id=qUEJAAAAIAAJ). London: The New Sydenham Society. 1895. Retrieved 2009-08-07. 1896: Impey, S. P. (1896). A Handbook On Leprosy (http://books.google.com/?id=wHMIAAAAQAAJ). Philadelphia: P. Blakiston, Son & Co.. Retrieved 2009-08-07. 1916: "Fighting Leprosy In The Philippines" (http://books.google.com/?id=09_Sr9emceQC&pg=PA310). The World's Work: A History of Our Time XXXI: 310320. January 1916. Retrieved 2009-08-04. 1991:William Jopling. Leprosy stigma. Lepr Rev 1991, 62, 1-12.

External links
Documentary film about leprosy (http://www.netflix.com/Movie/ Triumph_at_Carville_A_Tale_of_Leprosy_in_America/70092906) Netflix Leprosy (http://www.dmoz.org/Health/Conditions_and_Diseases/Infectious_Diseases/Mycobacterial/ Hansen's_Disease//) at the Open Directory Project

Article Sources and Contributors

19

Article Sources and Contributors


Leprosy Source: http://en.wikipedia.org/w/index.php?oldid=408787862 Contributors: -b, 16@r, 1exec1, 21655, 25or6to4, 5 albert square, A.C. Norman, A8UDI, ABF, Aardark, Aaron Brenneman, Abce2, Abhask, Academic Challenger, Acalamari, Accurizer, Adam murgittroyd, Adambro, AdultSwim, Aericanwizard, Ahlahaie, Ahoerstemeier, AirBa, Airballrad, Aitias, Ajraddatz, Akriasas, Alan Liefting, Alansohn, Alex.tan, Alexpasternak, Alfred Centauri, Alisfos, AlphaEta, Alphachimp, Altairisfar, Altarr, Amberrock, AmiDaniel, Amybeam, AnakngAraw, Andre Engels, Angelaf, Animum, Anna Lincoln, AnotherNitPicker, Anpersonalaccount, Anrkist, Ansonman1, Anthony Ivanoff, Anthonyhcole, Antonio Lopez, Anty, Arcadian, Arch dude, Arjun01, Arjun122889, Art LaPella, Arthurian Legend, Aslankard, AssegaiAli, Atticmouse, Autocracy, Axl, Aznfury363, B. Meijlink, BAxelrod, BD2412, BOARshevik, Baa, Barkeep, BarretBonden, Bart Versieck, Bart133, Beland, Belgianpride07, Bellpepper, Bemoeial, Benandorsqueaks, Betacommand, Big Bird, Bikeable, Binksternet, Binky, Bissinger, Blackangel25, Blah00&*rz, BlakFlak, Blehfu, Blood Red Sandman, Bloodyawful, Bluerondo, Bnwwf91, Bobblewik, Bobo192, Bogey97, Boing! said Zebedee, Bonjedward, BorgQueen, Bovineone, Boyisty, Branddobbe, Brandonshelley, Brendan Moody, Brian1979, Brianhe, Bryanmackinnon, Bushcarrot, Busybutterflybeezwax, C.Fred, CBHA, CL, Cabinet of Art and Medicine, Cactus.man, Caesura, Caiaffa, Calmer Waters, Caltas, Camw, Can't sleep, clown will eat me, Capecodeph, Captdoc, Carlosguitar, Catbar, Catquach2341, Causa sui, CavinSays, Cerberus63, Chachilongbow, Chairboy, Chanting Fox, Charles Matthews, Chcknwnm, Chikalin, Chock9, Cholmes75, Chorrol07, Choster, Chrislk02, Chrysaor, Cinik, Citicat, Civ200202, Clemwang, Cliftonshipway, Cman, Coelacan, Colonies Chris, Cometstyles, Comicretard, Commander Keane, CommonsDelinker, Complainer, Constantine, Corevette789, CormorantEnt, Craynor, CrimsQn, CryptoDerk, Cthompson, Curtbash, Cxz111, Cybercobra, Cyferx, D.c.camero, DBaba, DJPhazer, DMacks, DNewhall, DRosenbach, DWaterson, DaisukeVulgar, Dale Arnett, DancingPenguin, Danierrr, Danny Bierek, DaveGorman, David Edgar, DavidOaks, Davidfrankel, Davidruben, Daviessimo, Dawn Bard, Dbarnes99, Dbtfz, DebateLord, Debresser, Decltype, Deli nk, Der Falke, DerHexer, Dfoofnik, Dialectric, Dillan and Jen, Dlynes, Dmadeo, Dnickers, Doc sameer, DocWatson42, Dolson45, Donfbreed, Dono, Donreed, DopefishJustin, DougRWms, Dougz1, Dpeters11, DrM!KEY, DrMacrophage, DrMicro, DrSamba, Dspradau, Dtgriscom, Ductapeman94, Dwight666, DyingIce, EJF, EJS814, Ebyabe, Ed Poor, Edivorce, Eje211, Ejosse1, Ekuhaupt, Elassint, Eleassar, Eleassar777, Elemesh, Elias007, Elm-39, EnochHenderson, Enviroboy, EoGuy, Epbr123, Epidem, Epimorph, Eprengam, Equazcion, Eric-Wester, EricWesBrown, Esperant, Esrob, Eubulides, Everyking, EvilOverlordX, Ewlyahoocom, Excirial, Extransit, Eyesurgeon, FCStaehle, FaerieInGrey, Faijo33, Fama Clamosa, FangedFaerie, Farhat58, Fatuglyhor, Favonian, Fconaway, Felix Folio Secundus, Fightingpenguins, Finavon, Finlay McWalter, Firsfron, Flamerule, Flapdragon, FlipmodePlaya, Florentino floro, Flowerpotman, Fluffernutter, Fluri, FlyingToaster, Foochar, Foofbun, Foozao, Frank, FrankMJohnson, Freak in the bunnysuit, Freedomlinux, FreplySpang, Frotz, Frozen4322, Fubar Obfusco, Fueled, Funandtrvl, Fuzzbox, Fuzzysun, Gabbe, Gaius Cornelius, Gak, Galanskov, Garik, Garrondo, Gbinal, Gblaz, GeeJo, Gekritzl, Geoff B, Gilliam, Gizelle Rocks, Glen, Globalhelper, Gmelli, Gnowor, Goatboy, Gogo Dodo, Gonzalo Diethelm, Gorrin, Goustien, Grafen, Graham87, Grandpafootsoldier, Graymornings, GregorB, Grubel, Gurchzilla, Gus, Gutza, Guyaka, Gwandoya, Gwernol, Hadal, Hansen2010, Hapster11, Harrygouvas, Hebrides, Heran et Sang'gres, HexaChord, Hiperpinguino, Hires an editor, Hirpex, Hitokirishinji, Hiyazmin09, Hobofuzz, Hordaland, Hut 8.5, IAMTHEEGGMAN, Icairns, Icarus3, Ichiro Kikuchi, Iclbmc1, Ida Shaw, Idleguy, Immunize, InfoSaw, Insanity Incarnate, Insomniac By Choice, Inter, Inthend9, InvisibleK, Iosef, Irishguy, Isopropyl, Itaintnecessarily, Ixfd64, J.delanoy, J04n, JASpencer, JForget, JNW, JRawle, JSR, Ja 62, Jahiegel, JamesAM, Janus Shadowsong, Javert, JayFBee, JayWhitney, Jaymac407, Jclemens, Jcvajoolz, Jdforrester, Jdlh, Jediwashuu, Jeffq, Jeffrey Mall, Jengod, Jeremy Sheffel, Jerome Charles Potts, Jerry teps, Jfdwolff, Jia.volunteers, Jim keller, Jmh649, JoanneB, John, John Bahrain, John Cardinal, Johnrdee, Johnwilen, Jon Harald Sby, Jonathunder, Josechavez, Joseph Solis in Australia, Jossi, Jsonitsac, Jstiteler, Jujubean55, JuniperisCommunis, KAVEBEAR, KC Panchal, Kageskull, Kaihsu, Kalogeropoulos, Kandar, Katieh5584, Kay Dekker, Kayag, Kazvorpal, Kbh3rd, Keegan, Keimzelle, Keinstein, KeithH, Kelovy, Kenshinflyer, Kenyon, Kesac, Khetem, Killy mcgee, Kilo-Lima, Kim Dent-Brown, King Bee, Kinneyboy90, Kinu, Kmcarter, Kmccoy, Koavf, Kookysong, Korin, Kravdraa Ulb, Krawunsel, Krithin, Krun, Kungfuadam, KuroiShiroi, Kuzaar, Kwedin, L Kensington, Ladybird Sauce, Lainagier, Lancethex, LarRan, Lawrencegold, LearningKnight, LeaveSleaves, Leontes, Lesgles, LilHelpa, Lilaac, Lisieux, LittleHow, LizardJr8, Lomaprieta, LtNOWIS, Lucyrjones, Luk, Lukegabello, Lulzhansolo, Lupin, MER-C, MRtiz, Madhero88, Madhuperiasamy, Madmagic, Makemewannascreamm, Malick78, Malleus Fatuorum, Marc Kupper, Marcejose, MarcoTolo, Mark Foskey, Marluxia.Kyoshu, MaryNeedsSleep, Mattbr, Matuszek, MaxSem, Maxbwrs, Mblaze, Mcorazao, Mdagre, Meaghan, Medievalkarl, Melesse, Mensch, Mentifisto, Mercy11, Mgcsinc, Michael Daly, Michael Hardy, Michaelas10, Michaelbarreto, Mickey912, Mieciu K, Migp, Mike Garcia, Mike Rosoft, Mimihitam, Minimac's Clone, Miwolverine94, Mlpearc, Modify, Mr Stephen, Mr pand, Mr. Lefty, MrNoblet, Ms2ger, Mschlindwein, Msh210, Mtbab, Murgh, Mwanner, Mx3, Mxstirner, My Core Competency is Competency, Myanw, Nakon, Naniwako, Nasubabanasu, Natalie Erin, Nate1481, Natl1, NawlinWiki, Ndyguy, Neale Monks, Necris, Necrothesp, Neilc, Neilclerkin, Neurolysis, Nick Number, NickW557, Nickdc, Nicolas M. Perrault, Nightmaj, Nimakha, Nolte, Notinasnaid, NrDg, Nsaa, Nuujinn, Nyttend, Oda Mari, Offensiveandconfusing, Ohnoitsjamie, Olivier, Olorin28, Onceler, Onorem, Ostrovitch, Otisjimmy1, OwenX, PJM, PainMan, Pakaran, Panchhee, Parsecboy, Paul August, Paul Barlow, Pearle, Pengo, PericlesofAthens, Peruvianllama, Pete unseth, Peter McGinley, Petersam, Pharaoh of the Wizards, Phil Bridger, Philip Trueman, Piledhigheranddeeper, Pill, Pinethicket, Pingswept, Plattler01, PonyPrincess12, Portillo, Possum, Postdlf, PowerWill500, Prestonmcconkie, Pschemp, PseudoSudo, PureRED, Pyrospirit, QmunkE, Quebec99, QuiteUnusual, Qwerty 699, Qwerty Binary, R'n'B, RDBrown, RFerreira, RadiantRay, Radonir, Rajah, RazorICE, Razorflame, Rbethune, Reconsider the static, Red marquis, Reedy, Regger270, Remiel, Rentachimp, Retiono Virginian, Rhobite, Rich Farmbrough, Richard D. LeCour, Richard Keatinge, Richard-of-Earth, Richprentice, Ridemate, Rjfost, Rjwilmsi, Robartin, Robert K S, Rocxror, RodC, Rogersface, Ronhjones, RossMM, Rousse, Rror, Rsabbatini, Rune.welsh, Ryanbrunnerpingas, SJP, ST47, Saihung, SakotGrimshine, Sam Korn, Sam ware, Samsara, San Fernando Valley, Saranghae honey, Sauerlemon33, SchnitzelMannGreek, Scott Sanchez, Scoty6776, Sdurrant, SeanMack, Seb az86556, Seddon, Sega381, Seglea, SelfQ, Seminole Sam, Seraphim, Seth Ilys, Shadow1, Shanes, ShelfSkewed, Sherurcij, Shinkolobwe, Shinobi defran, Shoeofdeath, SiberioS, Sidonuke, SilentGuy, Simetrical, Simoes, Sir Vicious, SkerHawx, SlamDiego, Slambo, Sleepy2222, SmartOneK, Smcarter95, Solace098, Soledad 99, Solipsist, Someguy1221, Sonicology, Sottolacqua, Soundcomm, Spanglej, Spasemunki, Spearhead, Spellcast, Spock of Vulcan, SpunkyLepton, Squeezeweasel, St.daniel, Stalkerlees, Stefanshipman, SteinbDJ, Stephenb, SteveChervitzTrutane, Stevenfruitsmaak, Stevenmitchell, Stevertigo, Stui, Stuttermullet1, Sudoku424, Summerbell, Superbeecat, Superjoo, Suramik, SvenAERTS, Sw.my, Symon, Szquirrel, THEN WHO WAS PHONE?, TJRC, TTGL, Tabletop, Tad Lincoln, Tangotango, Tannin, Tasc, Tataryn77, Tb81, Tebynum, Techelf, TestPilot, Teukros, Tgwizard, ThF, The Anome, The High Commander, The Letter J, The Thing That Should Not Be, The wub, TheChosen1420, TheQuestionGuy, TheTrojanHought, Thedeadlyparadox, Theseeker4, Theshitmonster, Thingg, Thirdeyeopen33, Thomas Paine1776, Tide rolls, Tim Keighley, Tim1988, Tom Lougheed, Tpbradbury, Trent Arms, Treybien, Trimp, Tt39966, Twaz, Twinsday, UBeR, Ufwuct, Ulric1313, Umalee, Uncle Dick, UnitedStatesian, Unyounyo, Unyoyega, Urbane Legend, Useight, Utcursch, Valentinejoesmith, Vapour, Vector Potential, Veddharta, Vicenarian, Vicki Rosenzweig, Vignaux, Violetriga, Viriditas, VolatileChemical, W33v1l, WAS 4.250, WHO Leprosy, WLRoss, WadeSimMiser, Wahrhaft, Wansanchez, Wassup123456789, Watsimous, Wayward, Wccaccamise, Weeeii90, Whistlesgowhoo, Why Not A Duck, Wiki alf, WikiFiend64, William Avery, William charles caccamise sr, md, Wimt, Wizzy, Wmahan, Woody77, Woohookitty, Wootten23, Wouterstomp, WriterHound, Wsiegmund, Wtmitchell, Wysprgr2005, Xanthippas, Xcountry99, Xdcdx, Xenophon777, Xeren, Xiner, Xtopherous, Xymmax, YangYouRen, Youaresome, Zingus, Zonath, Zvn, , , , 1835 anonymous edits

Image Sources, Licenses and Contributors


File:Leprosy.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Leprosy.jpg License: unknown Contributors: Akira Kouchiyama, Buchanan-Hermit, Cabinet of Art and Medicine, Dirk Hnniger, Ida Shaw, Jusjih, Kevin Payravi, Nagy, Pismire, Sam, StMH, 25 anonymous edits Image:M leprae ziehl nielsen2.jpg Source: http://en.wikipedia.org/w/index.php?title=File:M_leprae_ziehl_nielsen2.jpg License: Public Domain Contributors: Balthazaar, Kookaburra, Muriel Gottrop, 3 anonymous edits File:Bundesarchiv Bild 105-DOA0199, Deutsch-Ostafrika, Leprakranke.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Bundesarchiv_Bild_105-DOA0199,_Deutsch-Ostafrika,_Leprakranke.jpg License: Public Domain Contributors: Martin H. Image:MDTRegimens.jpg Source: http://en.wikipedia.org/w/index.php?title=File:MDTRegimens.jpg License: Public Domain Contributors: Psychonaut, WHO Leprosy Image:Blisters01.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Blisters01.jpg License: Public Domain Contributors: Benjah-bmm27, Mogelzahn, WHO Leprosy Image:Lepra 2003.png Source: http://en.wikipedia.org/w/index.php?title=File:Lepra_2003.png License: Free Art License Contributors: DO11.10, Katpatuka, PaweS, 3 anonymous edits Image:Leprosy world map - DALY - WHO2002.svg Source: http://en.wikipedia.org/w/index.php?title=File:Leprosy_world_map_-_DALY_-_WHO2002.svg License: Creative Commons Attribution-Sharealike 2.5 Contributors: User:Lokal_Profil File:Flag of Brazil.svg Source: http://en.wikipedia.org/w/index.php?title=File:Flag_of_Brazil.svg License: Public Domain Contributors: Brazilian Government File:Flag of Mozambique.svg Source: http://en.wikipedia.org/w/index.php?title=File:Flag_of_Mozambique.svg License: Public Domain Contributors: User:Nightstallion File:Flag of Nepal.svg Source: http://en.wikipedia.org/w/index.php?title=File:Flag_of_Nepal.svg License: Public Domain Contributors: User:SKopp File:Flag of Tanzania.svg Source: http://en.wikipedia.org/w/index.php?title=File:Flag_of_Tanzania.svg License: unknown Contributors: User:SKopp Image:Gerhard Armauer Hansen.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Gerhard_Armauer_Hansen.jpg License: Public Domain Contributors: Original uploader was Rsabbatini at en.wikipedia File:The leprose-Albrecht Durer.jpg Source: http://en.wikipedia.org/w/index.php?title=File:The_leprose-Albrecht_Durer.jpg License: Public Domain Contributors: Albrecht Durer

License

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License
Creative Commons Attribution-Share Alike 3.0 Unported http:/ / creativecommons. org/ licenses/ by-sa/ 3. 0/

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