and the disability it causes. there is no recommended test to diagnose latent leprosy in people without symptoms. few people with latent leprosy test positive for anti pgl-1. the presence of m. leprae bacterial dna can be identified using a polymerase chain reaction (pcr)-based technique. this molecular test alone is not sufficient to diagnose a person, but this approach may be used to identify someone who is at high risk of developing or transmitting leprosy such as those with few lesions or an atypical clinical presentation. classification several different approaches for classifying leprosy exist. there are similarities between the classification approaches. the world health organization system distinguishes "paucibacillary" and "multibacillary" based upon the proliferation of bacteria. ("pauci-" refers to a low quantity.) the ridley-jopling scale provides five gradations. the icd-10, though developed by the who, uses ridley-jopling and not the who system. it also adds an indeterminate ("i") entry. in mesh, three groupings are used. who ridley-jopling icd-10 mesh description lepromin test paucibacillary tuberculoid ("tt"),borderlinetuberculoid ("bt") a30.1, a30.2 tuberculoid it is characterized by one or more hypopigmented skin macules and patches where skin sensations are lost because of damaged peripheral nerves that have been attacked by the human host's immune cells. tt is characterized by the formation of epithelioid cell granulomas with a large number of epithelioid cells. in this form of leprosy mycobacterium leprae are either absent from the lesion or occur in very small numbers. this type of leprosy is most benign. positive multibacillary midborderlineorborderline ("bb") a30.3 borderline borderline leprosy is of intermediate severity and is the most common form. skin lesions resemble tuberculoid leprosy, but are more numerous and irregular; large patches may affect a whole limb, and peripheral nerve involvement with weakness and loss of sensation is common. this type is unstable and may become more like lepromatous leprosy or may undergo a reversal reaction, becoming more like the tuberculoid form. negative multibacillary borderline lepromatous ("bl"),and lepromatous ("ll") a30.4, a30.5 lepromatous it is associated with symmetric skin lesions, nodules, plaques, thickened dermis, and frequent involvement of the nasal mucosa resulting in nasal congestion and nose bleeds, but, typically, detectable nerve damage is late. loss of eyebrows and lashes can be seen in advanced disease. ll is characterized by the absence of epithelioid cells in the lesions. in this form of leprosy, mycobacteria leprae are found in lesions in large numbers. this is the most unfavorable clinical variant of leprosy, which occurs with a generalized lesion of the skin, mucous membranes, eyes, peripheral nerves, lymph nodes, and internal organs. negative leprosy may also occur with only neural involvement, without skin lesions. complications leprosy may cause the victim to lose limbs and digits but not directly. m. leprae attacks nerve endings and destroys the body’s ability to feel pain and injury. without feeling pain, people injure themselves on fire, thorns, rocks, and even hot coffee cups. injuries become infected and result in tissue loss. fingers, toes, and limbs become shortened and deformed as the tissue is absorbed into the body. prevention early detection of the disease is important, since physical and neurological damage may be irreversible even if cured. medications can decrease the risk of those living with people who have leprosy from acquiring the disease and likely those with whom people with leprosy come into contact outside the home. the who recommends that preventive medicine be given to people who are in close contact with someone who has leprosy. the suggested preventive treatment is a single dose of rifampicin (sdr) in adults and children over 2 years old who do not already have leprosy or tuberculosis. preventive treatment is associated with a 57% reduction in infections within 2 years and a 30% reduction in infections within 6 years. the bacillus calmette–guérin (bcg) vaccine offers a variable amount of protection against leprosy in addition to its closely related target of tuberculosis. it appears to be 26% to 41% effective (based on controlled trials) and about 60% effective based on observational studies with two doses possibly working better than one. the who concluded in 2018 that the bcg vaccine at birth reduces leprosy risk and is recommended in countries with high incidence of tb and people who have leprosy. people living in the same home as a person with leprosy are suggested to take a bcg booster which may improve their immunity by 56%. development of a more effective vaccine is ongoing. a novel vaccine called lepvax entered clinical trials in 2017 with the first encouraging results reported on 24 participants published in 2020. if successful, this would be the first leprosy-specific vaccine available. treatment mdt antileprosy drugs: standard regimens from 2010 anti-leprosy medication a number of leprostatic agents are available for treatment. a three-drug regimen of rifampicin, dapsone and clofazimine is recommended for all people with leprosy, for six months for paucibacillary leprosy and 12 months for multibacillary leprosy. multidrug therapy (mdt) remains highly effective, and people are no longer infectious after the first monthly dose. it is safe and easy to use under field conditions because of its presentation in calendar blister packs. post-treatment relapse rates remain low. resistance has been reported in several countries, although the number of cases is small. people with rifampicin-resistant leprosy may be treated with second line drugs such as fluoroquinolones, minocycline, or clarithromycin, but the treatment duration is 24 months because of their lower bactericidal activity. evidence on the potential benefits and harms of alternative regimens for drug-resistant leprosy is not available. skin changes for people with nerve damage, protective footwear may help prevent ulcers and secondary infection. canvas shoes may be better than pvc boots. there may be no difference between double rocker shoes and below-knee plaster. topical ketanserin 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. outcomes although leprosy has been curable since the mid-20th century, left untreated it can cause permanent physical impairments and damage to a person's nerves, skin, eyes, and limbs. despite leprosy not being very infectious and having a low pathogenicity, there is still significant stigma and prejudice associated with the disease. because of this stigma, leprosy can affect a person's participation in social activities and may also affect the lives of their family and friends. people with leprosy are also at a higher risk for problems with their mental well-being. the social stigma may contribute to problems obtaining employment, financial difficulties, and social isolation. efforts to reduce discrimination and reduce the stigma surrounding leprosy may help improve outcomes for people with leprosy. epidemiology main article: epidemiology of leprosy new cases of leprosy in 2016. disability-adjusted life year for leprosy per 100,000 inhabitants in 2004 no data < 1.5 1.5–3 3–4.5 4.5–6 6–7.5 7.5–9 9–10.5 10.5–12 12–13.5 13.5–15 15–20 > 20 in 2018, there were 208,619 new cases of leprosy recorded, a slight decrease from 2017. in 2015, 94% of the new leprosy cases were confined to 14 countries. india reported the greatest number of new cases (60% of reported cases), followed by brazil (13%) and indonesia (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 have reduced the total number and the number of new cases of the disease. disease burden the number of new leprosy cases is difficult to measure and monitor because of leprosy's long incubation period, delays in diagnosis after onset of the disease, and lack of medical care in affected areas. the registered prevalence 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. year 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 no. of new cases 296,479 258,980 252,541 249,018 244,797 228,488 224,344 232,847 215,636 213,861 211,945 217,927 210,973 208,613 202,166 127,506 history g. h. a. hansen, discoverer of m. leprae historical distribution using comparative genomics, in 2005, geneticists traced the origins and worldwide distribution of leprosy from east africa or the near east along human migration routes. they found four strains of m. leprae with specific regional locations: monot et al. (2005) determined that leprosy originated in east africa or the near east and traveled with humans along their migration routes, including those of trade in goods and slaves. the four strains of m. leprae are based in specific geographic regions where each predominantly occurs: strain 1 in asia, the pacific region, and east africa; strain 2 in ethiopia, malawi, nepal, north india, and new caledonia; strain 3 in europe, north africa, and the americas; strain 4 in west africa and the caribbean. this confirms the spread of the disease along the migration, colonisation, and slave trade routes taken from east africa to india, west africa to the new world, and from africa into europe and vice versa. skeletal remains discovered in 2009 represent the oldest documented evidence for leprosy, dating to the 2nd millennium bc. located at balathal, rajasthan, in northwest india, the discoverers suggest that, if the disease did migrate from africa to india during the 3rd millennium bc "at a time when there was substantial interaction among the indus civilization, mesopotamia, and egypt, there needs to be additional skeletal and molecular evidence of leprosy in india and africa to confirm the african origin of the disease." a proven human case was verified by dna taken from the shrouded remains of a man discovered by researchers from the hebrew university of jerusalem in a tomb next to the old city of jerusalem, israel, dated by radiocarbon methods to the first half of the 1st century. the oldest strains of leprosy known from europe are from great chesterford in southeast england and dating back to ad 415–545. these findings suggest a different path for the spread of leprosy, meaning it may have originated in western eurasia. this study also indicates that there were more strains in europe at the time than previously determined. discovery and scientific progress literary attestation of leprosy is unclear because of the ambiguity of many early sources, including the indian atharvaveda and kausika sutra, the egyptian ebers papyrus, and the hebrew bible's various sections regarding signs of impurity (tzaraath). clearly leprotic symptoms are attested in the indian doctor sushruta's compendium, originally dating to c. 600 bc but only surviving in emended texts no earlier than the 5th century. they were separately described by hippocrates in 460 bc. however, hansen's disease probably did not exist in greece or the middle east before the common era. in 1846, francis adams produced the seven books of paulus aegineta which included a commentary on all medical and surgical knowledge and descriptions and remedies to do with leprosy from the romans, greeks, and arabs. leprosy did not exist in the americas before colonization by modern europeans nor did it exist in polynesia until the middle of the 19th century. distribution of leprosy around the world in 1891 the causative agent of leprosy, m. leprae, was discovered by gerhard armauer hansen in norway in 1873, making it the first bacterium to be identified as causing disease in humans. treatment the first effective treatment (promin) 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