Leprosy: Difference between revisions
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'''Leprosy''' (from the [[Greek language|Greek]] ''lepi'', meaning scales on a fish), or '''Hansen's disease (HD)''', is a [[Chronic (medical)|chronic]] disease caused by the [[bacteria]] ''[[Mycobacterium leprae]]'' and ''[[Mycobacterium lepromatosis]]''.<ref name=Sasaki_2001>{{cite journal |author=Sasaki S, Takeshita F, Okuda K, Ishii N |title=Mycobacterium leprae and leprosy: a compendium |journal=Microbiol Immunol |volume=45 |issue=11 |pages=729–36 |year=2001 |url = http://www.jstage.jst.go.jp/article/mandi/45/11/729/_pdf |pmid=11791665}}</ref><ref name = new>[http://www.sciencedaily.com/releases/2008/11/081124141047.htm New Leprosy Bacterium: Scientists xxxx Use Genetic Fingerprint To Nail 'Killing Organism'<!-- Bot generated title -->]</ref> Leprosy is primarily a [[granuloma]]tous disease of the [[Peripheral nervous system|peripheral nerves]] and [[Mucous membrane|mucosa]] of the [[upper respiratory tract]]; skin lesions are the primary external symptom.<ref name=Sherris>{{cite book | editor = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | pages = 451–3 | publisher = McGraw Hill | year = 2004 | isbn = 0838585299 | author = Kenneth J. Ryan, C. George Ray, editors. | oclc = 52358530 61405904}}</ref> Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes. Leprosy does not directly cause body parts to fall off on their own accord;<ref>{{cite journal |author= |title=Lifting the stigma of leprosy: a new vaccine offers hope against an ancient disease |journal=Time |volume=119 |issue=19 |pages=87 |year=1982 |month=May |pmid=10255067 |doi= |url=http://www.time.com/time/magazine/article/0,9171,925377,00.html}}</ref> instead they become disfigured or amputated as a result of disease symptoms.<ref>{{cite book | title = Textbook of Orthopedics and Trauma | edition = 2 | page = 779 | publisher = Jaypee Brothers Publishers | year = 2008 | isbn = 8184482426, 9788184482423 | author = G S Kulkarni }}</ref> |
'''Leprosy''' (from the [[Greek language|Greek]] ''lepi'', meaning scales on a fish), or '''Hansen's disease (HD)''', is a [[Chronic (medical)|chronic]] disease caused by the [[bacteria]] ''[[Mycobacterium leprae]]'' and ''[[Mycobacterium lepromatosis]]''.<ref name=Sasaki_2001>{{cite journal |author=Sasaki S, Takeshita F, Okuda K, Ishii N |title=Mycobacterium leprae and leprosy: a compendium |journal=Microbiol Immunol |volume=45 |issue=11 |pages=729–36 |year=2001 |url = http://www.jstage.jst.go.jp/article/mandi/45/11/729/_pdf |pmid=11791665}}</ref><ref name = new>[http://www.sciencedaily.com/releases/2008/11/081124141047.htm New Leprosy Bacterium: Scientists xxxx Use Genetic Fingerprint To Nail 'Killing Organism'<!-- Bot generated title -->]</ref> Leprosy is primarily a [[granuloma]]tous disease of the [[Peripheral nervous system|peripheral nerves]] and [[Mucous membrane|mucosa]] of the [[upper respiratory tract]]; skin lesions are the primary external symptom.<ref name=Sherris>{{cite book | editor = Ryan KJ, Ray CG | title = Sherris Medical Microbiology | edition = 4th | pages = 451–3 | publisher = McGraw Hill | year = 2004 | isbn = 0838585299 | author = Kenneth J. Ryan, C. George Ray, editors. | oclc = 52358530 61405904}}</ref> Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes. Leprosy does not directly cause body parts to fall off on their own accord;<ref>{{cite journal |author= |title=Lifting the stigma of leprosy: a new vaccine offers hope against an ancient disease |journal=Time |volume=119 |issue=19 |pages=87 |year=1982 |month=May |pmid=10255067 |doi= |url=http://www.time.com/time/magazine/article/0,9171,925377,00.html}}</ref> instead they become disfigured or amputated as a result of disease symptoms.<ref>{{cite book | title = Textbook of Orthopedics and Trauma | edition = 2 | page = 779 | publisher = Jaypee Brothers Publishers | year = 2008 | isbn = 8184482426, 9788184482423 | author = G S Kulkarni }}</ref> |
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Historically, leprosy has affected mankind since at least 4,000 years ago,<ref>[http://sciencenow.sciencemag.org/cgi/content/full/2009/527/1 Skeleton Pushes Back Leprosy's Origins - Holden 2009 (527): 1 - ScienceNOW<!-- Bot generated title -->]</ref> and was well-recognized in the civilizations of [[History of China|ancient China]], [[ancient Egypt|Egypt]], and [[History of India|India]],<ref name=WHO_Factsheet>{{cite web | title = Leprosy | work = WHO | url = http://www.who.int/mediacentre/factsheets/fs101/en/ | accessdate = 2007-08-22}}</ref> but it is unknown if it is the same [[Tzaraath|disease]] mentioned in the [[Hebrew Bible]].<ref>Burnam, Tom, ''The Dictionary of Misinformation'', Crowell, 1975.</ref> In 1995, the [[World Health Organization]] (WHO) estimated that between 2 and 3 million people were permanently disabled because of leprosy.<ref name="WHO_1995">{{cite journal |author=WHO|title=Leprosy disabilities: magnitude of the problem |journal=Weekly Epidemiological Record |volume=70 |issue=38 |pages=269–75 |year=1995 |pmid=7577430}}</ref> In the past 20 years, 15 million people worldwide have been cured of leprosy.<ref name=Leprosy>[http://news.bbc.co.uk/2/hi/programmes/from_our_own_correspondent/6510503.stm The hidden suffering of India's lepers]. BBC News. March 31, 2007.</ref> Although the forced [[quarantine]] or segregation of patients is unnecessary in places where adequate treatments are available—and can be considered [[ethics|unethical]]—many [[leper colony|leper colonies]] still remain around the world, in countries such as [[India]] (where there are still more than 1,000 leper colonies),<ref name=Leprosy/> [[People's Republic of China|China]],<ref>[http://www.iol.co.za/index.php?set_id=1&click_id=117&art_id=qw1158139440409B243 'Ignorance breeds leper colonies in China']. Independent News & Media. September 13, 2006.</ref> [[Romania]],<ref>[http://news.bbc.co.uk/2/hi/europe/1639335.stm Europe's last leper colony lives on]. BBC News. November 6, 2001.</ref> [[Egypt]], [[Nepal]], [[Somalia]], [[Liberia]], [[Vietnam]],<ref>[http://english.vovnews.vn/Home/Making-Peace-With-Vietnam-to-be-screened-at-Beijing-film-festival/20092/101642.vov “Making Peace With Vietnam” to be screened at Beijing film festival]. VOVNEWS.VN. 02/08/2009</ref> and [[National Hansen's Disease Museum (Japan)|Japan]].<ref>Japan repealed its "Leprosy Prevention Laws" in 1996 but former patients still reside in sanatoriums. See [http://news.bbc.co.uk/2/hi/asia-pacific/1350630.stm Koizumi apologises for leper colonies. BBC News. May 25, 2001] and [http://search.japantimes.co.jp/cgi-bin/nn20070607f2.html Ex-Hansen's disease patients still struggling with prejudice Japan Times June 7, 2007]. </ref> Leprosy was once believed to be highly contagious, sexually transmitted and was treated with [[Mercury (element)|mercury]]—all 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.<ref>[http://www.britannica.com/EBchecked/topic/578770/syphilis/253277/Syphilis-through-history#ref252973 Syphilis through history] [[Encyclopædia Britannica]]</ref> Leprosy is in fact neither sexually transmitted nor is it highly infectious after treatment, as approximately 95% of people are naturally immune<ref> |
Historically, leprosy has affected mankind since at least 4,000 years ago,<ref>[http://sciencenow.sciencemag.org/cgi/content/full/2009/527/1 Skeleton Pushes Back Leprosy's Origins - Holden 2009 (527): 1 - ScienceNOW<!-- Bot generated title -->]</ref> and was well-recognized in the civilizations of [[History of China|ancient China]], [[ancient Egypt|Egypt]], and [[History of India|India]],<ref name=WHO_Factsheet>{{cite web | title = Leprosy | work = WHO | url = http://www.who.int/mediacentre/factsheets/fs101/en/ | accessdate = 2007-08-22}}</ref> but it is unknown if it is the same [[Tzaraath|disease]] mentioned in the [[Hebrew Bible]].<ref>Burnam, Tom, ''The Dictionary of Misinformation'', Crowell, 1975.</ref> In 1995, the [[World Health Organization]] (WHO) estimated that between 2 and 3 million people were permanently disabled because of leprosy.<ref name="WHO_1995">{{cite journal |author=WHO|title=Leprosy disabilities: magnitude of the problem |journal=Weekly Epidemiological Record |volume=70 |issue=38 |pages=269–75 |year=1995 |pmid=7577430}}</ref> In the past 20 years, 15 million people worldwide have been cured of leprosy.<ref name=Leprosy>[http://news.bbc.co.uk/2/hi/programmes/from_our_own_correspondent/6510503.stm The hidden suffering of India's lepers]. BBC News. March 31, 2007.</ref> Although the forced [[quarantine]] or segregation of patients is unnecessary in places where adequate treatments are available—and can be considered [[ethics|unethical]]—many [[leper colony|leper colonies]] still remain around the world, in countries such as [[India]] (where there are still more than 1,000 leper colonies),<ref name=Leprosy/> [[People's Republic of China|China]],<ref>[http://www.iol.co.za/index.php?set_id=1&click_id=117&art_id=qw1158139440409B243 'Ignorance breeds leper colonies in China']. Independent News & Media. September 13, 2006.</ref> [[Romania]],<ref>[http://news.bbc.co.uk/2/hi/europe/1639335.stm Europe's last leper colony lives on]. BBC News. November 6, 2001.</ref> [[Egypt]], [[Nepal]], [[Somalia]], [[Liberia]], [[Vietnam]],<ref>[http://english.vovnews.vn/Home/Making-Peace-With-Vietnam-to-be-screened-at-Beijing-film-festival/20092/101642.vov “Making Peace With Vietnam” to be screened at Beijing film festival]. VOVNEWS.VN. 02/08/2009</ref> and [[National Hansen's Disease Museum (Japan)|Japan]].<ref>Japan repealed its "Leprosy Prevention Laws" in 1996 but former patients still reside in sanatoriums. See [http://news.bbc.co.uk/2/hi/asia-pacific/1350630.stm Koizumi apologises for leper colonies. BBC News. May 25, 2001] and [http://search.japantimes.co.jp/cgi-bin/nn20070607f2.html Ex-Hansen's disease patients still struggling with prejudice Japan Times June 7, 2007]. </ref> Leprosy was once believed to be highly contagious, sexually transmitted and was treated with [[Mercury (element)|mercury]]—all 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.<ref>[http://www.britannica.com/EBchecked/topic/578770/syphilis/253277/Syphilis-through-history#ref252973 Syphilis through history] [[Encyclopædia Britannica]]</ref> Leprosy is in fact neither sexually transmitted nor is it highly infectious after treatment, as approximately 95% of people are naturally immune<ref>{{cite web |title=about leprosy: frequently asked questions |url=http://www.leprosy.org/getinformed/aboutleprosy/leprosyfaq.php |publisher=American Leprosy Missions, Inc |accessdate=September 19, 2009}}</ref> and sufferers are no longer infectious after as little as 2 weeks of treatment. However, before treatment was developed, leprosy was certainly contagious.<ref>{{cite web |title=about leprosy: statistics |url=http://www.leprosy.org/getinformed/aboutleprosy/statistics.php |publisher=American Leprosy Missions, Inc |accessdate=September 19, 2009}}</ref><ref>{{cite web |title=about leprosy: the basics |url=http://www.leprosy.org/getinformed/aboutleprosy/basics.php |publisher=American Leprosy Missions, Inc |accessdate=September 19, 2009}}</ref> |
||
The age-old [[social stigma]] 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. However, leprosy [[bacilli]] resistant to dapsone soon [[Antibiotic resistance|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.<ref name="WHOleprosyFAQ">{{cite web |
The age-old [[social stigma]] 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. However, leprosy [[bacilli]] resistant to dapsone soon [[Antibiotic resistance|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.<ref name="WHOleprosyFAQ">{{cite web |
Revision as of 05:22, 19 September 2009
- For the Hebrew Bible term and its varied meanings, see Tzaraath. For other uses, see Leprosy (disambiguation).
Leprosy | |
---|---|
Specialty | Infectious diseases ![]() |
Frequency | 0.002413966% (world) |
Leprosy (from the Greek lepi, meaning scales on a fish), or Hansen's disease (HD), is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis.[1][2] Leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary external symptom.[3] Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs and eyes. Leprosy does not directly cause body parts to fall off on their own accord;[4] instead they become disfigured or amputated as a result of disease symptoms.[5]
Historically, leprosy has affected mankind since at least 4,000 years ago,[6] and was well-recognized in the civilizations of ancient China, Egypt, and India,[7] but it is unknown if it is the same disease mentioned in the Hebrew Bible.[8] In 1995, the World Health Organization (WHO) estimated that between 2 and 3 million people were permanently disabled because of leprosy.[9] In the past 20 years, 15 million people worldwide have been cured of leprosy.[10] Although the forced quarantine or segregation of patients is unnecessary in places where adequate treatments are available—and can be considered unethical—many leper colonies still remain around the world, in countries such as India (where there are still more than 1,000 leper colonies),[10] China,[11] Romania,[12] Egypt, Nepal, Somalia, Liberia, Vietnam,[13] and Japan.[14] Leprosy was once believed to be highly contagious, sexually transmitted and was treated with mercury—all 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.[15] Leprosy is in fact neither sexually transmitted nor is it highly infectious after treatment, as approximately 95% of people are naturally immune[16] and sufferers are no longer infectious after as little as 2 weeks of treatment. However, before treatment was developed, leprosy was certainly contagious.[17][18]
The age-old social stigma 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. However, 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.[19]
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.[19] 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.
International Leprosy Day was created to draw awareness to leprosy and its sufferers.
Classification
There are several different approaches for classifying leprosy, but parallels exist.
- The World Health Organization system distinguishes "paucibacillary" and "multibacillary" based upon the proliferation of bacteria[20] ("pauci-" refers to a low quantity.)
- The Ridley-Jopling scale provides five gradations.[21][22]
- 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 | Immune target |
---|---|---|---|---|---|---|
Paucibacillary | tuberculoid ("TT"), borderline tuberculoid ("BT") | A30.1, A30.2 | Tuberculoid | It is characterized by one or more hypopigmented skin 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. | Positive | bacillus (Th1) |
Multibacillary | midborderline or borderline ("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. | ||
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 epistaxis (nose bleeds) but typically detectable nerve damage is late. | Negative | plasmid inside bacillus (Th2) |
There is a difference in immune response to the tuberculoid and lepromatous forms.[23][24]
Hansen's disease may also be divided into the following types:[25]: 344–346
- Early and indeterminate leprosy
- Tuberculoid leprosy
- Borderline tuberculoid leprosy
- Borderline leprosy
- Borderline lepromatous leprosy
- Lepromatous leprosy
- Histoid leprosy
Genetics
Several genes have been associated with a susceptibility to leprosy:
Name | Locus | OMIM | Gene |
---|---|---|---|
LPRS1 | 10p13 | Template:OMIM2 | |
LPRS2 | 6q25 | Template:OMIM2 | PARK2, PACRG |
LPRS3 | 4q32 | Template:OMIM2 | TLR2 |
LPRS4 | 6p21.3 | Template:OMIM2 | LTA |
Cause
![](http://upload.wikimedia.org/wikipedia/commons/thumb/7/7e/M_leprae_ziehl_nielsen2.jpg/220px-M_leprae_ziehl_nielsen2.jpg)
Mycobacterium leprae and Mycobacterium lepromatosis are the causative agents of leprosy. M. lepromatosis is only the causative agent in diffuse lepromatous leprosy, which can be lethal.[2][3]
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.[26]
Due to extensive loss of genes necessary for independent growth, M. leprae and M. lepromatosis are unculturable in the laboratory, a factor which leads to difficulty in definitively identifying the organism under a strict interpretation of Koch's postulates.[2][27] The use of non-culture-based techniques such as molecular genetics has allowed for alternative establishment of causation.
Pathophysiology
![](http://upload.wikimedia.org/wikipedia/commons/thumb/6/61/Bundesarchiv_Bild_105-DOA0199%2C_Deutsch-Ostafrika%2C_Leprakranke.jpg/300px-Bundesarchiv_Bild_105-DOA0199%2C_Deutsch-Ostafrika%2C_Leprakranke.jpg)
The exact mechanism of transmission of leprosy is unknown: prolonged close contact and transmission by nasal droplet have both been proposed, and, while the latter fits the pattern of disease, both remain unproven.[28] The only animal other than humans that is known to contract leprosy is the armadillo.[29] The bacterium can also be grown in the laboratory by injection into the footpads of mice.[30] 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 other types of leprosy.[31] It is estimated that due to genetic factors, only 5% of the population is susceptible to leprosy.[32] 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 incubation period for the bacteria can last anywhere from two to ten years.
The most widely held belief is that the disease is transmitted by contact between infected persons and healthy persons.[33] 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 actual 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[34] to 55.8 per 1000 per year in a part of Southern India.[35]
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. It is true that lepromatous cases show large numbers of organisms deep down in the dermis. However, whether they reach the skin surface in sufficient numbers is doubtful. 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.[36] 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.[37]
The importance of the nasal mucosa was recognized as early as 1898 by Schäffer, particularly that of the ulcerated mucosa.[38] 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.[39] Pedley reported that the majority of lepromatous patients showed leprosy bacilli in their nasal secretions as collected through blowing the nose.[40] Davey and Rees indicated that nasal secretions from lepromatous patients could yield as much as 10 million viable organisms per day.[41]
The entry route of M. leprae into the human body is also not definitely known. The two seriously considered are the skin and the upper respiratory tract. 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 containing M. leprae in immune-suppressed mice, suggesting a similar possibility in humans.[42] Successful results have also been reported on experiments with nude mice when M. leprae were introduced into the nasal cavity by topical application.[43] 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."[44]
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.[45] 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.
Treatment
![](http://upload.wikimedia.org/wikipedia/commons/0/00/Multidrug_therapy_%28MDT%29_for_the_treatment_of_leprosy.jpg)
Until the development of dapsone in the 1940s, there was no effective treatment for leprosy. However, dapsone is only weakly bactericidal against M. leprae and it was considered necessary for patients to take the drug indefinitely. Moreover, when dapsone was used alone, the M. leprae population 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 than dapsone led to the use of clofazimine and rifampicin in the 1960s and 1970s.[46] Later, Indian scientist Shantaram Yawalkar and his colleagues formulated a combined therapy using rifampicin and dapsone, intended to mitigate bacterial resistance.[47] Multidrug therapy (MDT) and 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 are used alone because of the risk of developing resistance.
Because this treatment was quite expensive, it 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 2000—defined as reducing the global prevalence of the disease to less than 1 case per 100,000. 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.
The WHO Study Group's report on the Chemotherapy of Leprosy in 1993 recommended two types of standard MDT regimen be adopted.[48] 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.
![](http://upload.wikimedia.org/wikipedia/commons/thumb/7/71/MDTRegimens.jpg/400px-MDTRegimens.jpg)
Between 1995 and 1999, WHO, with the aid of the Nippon Foundation (Chairman Yōhei 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 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.[7] It is safe and easy to use under field conditions due to its presentation in calendar blister packs.[7] Relapse rates remain low, and there is no known resistance to the combined drugs.[7] The Seventh WHO Expert Committee on Leprosy,[49] reporting in 1997, concluded that the MB duration of treatment—then standing at 24 months—could safely be shortened to 12 months "without significantly compromising its efficacy."
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 whose patients have historically been considered "unclean" or "cursed by God" as outcasts. 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 falsely believe 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.
Prevention
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.[50] A non-randomized study found that rifampicin reduced the number of new cases of leprosy by 75% after three years.[51]
BCG offers a variable amount of protection against leprosy as well as against tuberculosis.[52][53]
Epidemiology
![](http://upload.wikimedia.org/wikipedia/commons/thumb/9/91/Lepra_2003.png/350px-Lepra_2003.png)
Worldwide, two to three million people are estimated to be permanently disabled because of leprosy.[9] 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.[54] In 1999, 108 cases occurred in the United States. 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.[55] 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.
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 92 cases being reported in 2002.[56] 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.
Risk groups
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.[citation needed] The region of DNA responsible for this variability is also involved in Parkinson disease,[citation needed] giving rise to current speculation that the two disorders may be linked in some way at the biochemical level. In addition, men are twice as likely to contract leprosy as women.[citation needed] According to The Leprosy Mission Canada, most people – about 95% of the population – are naturally immune.[57]
Disease burden
Although annual incidence—the number of new leprosy cases occurring each year—is 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.[58]
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). The new case detection rate (NCDR) is defined by the number of newly detected cases, previously untreated, during a year divided by the population in which the cases have occurred.
Endemic countries also report the number of new cases with established disabilities at the time of detection, as an indicator of the backlog prevalence. However, 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
Region | Registered prevalence (rate/1,000,000 pop.) |
New case detection during the year | ||||
---|---|---|---|---|---|---|
Start of 2006 | 2001 | 2002 | 2003 | 2004 | 2005 | |
Africa | 40,830 (0.56) | 39,612 | 48,248 | 47,006 | 46,918 | 42,814 |
Americas | 32,904 (0.39) | 42,830 | 39,939 | 52,435 | 52,662 | 41,780 |
South-East Asia | 133,422 (0.81) | 668,658 | 520,632 | 405,147 | 298,603 | 201,635 |
Eastern Mediterranean | 4,024 (0.09) | 4,758 | 4,665 | 3,940 | 3,392 | 3,133 |
Western Pacific | 8,646 (0.05) | 7,404 | 7,154 | 6,190 | 6,216 | 7,137 |
Totals | 219,826 | 763,262 | 620,638 | 514,718 | 407,791 | 296,499 |
Countries | Registered prevalence (rate/10,000 pop.) |
New case detection (rate/100,000 pop.) | ||||
---|---|---|---|---|---|---|
Start of 2004 | Start of 2005 | Start of 2006 | During 2003 | During 2004 | During 2005 | |
![]() |
79,908 (4.6) | 30,693 (1.7) | 27,313 (1.5) | 49,206 (28.6) | 49,384 (26.9) | 38,410 (20.6) |
![]() |
6,810 (3.4) | 4,692 (2.4) | 4,889 (2.5) | 5,907 (29.4) | 4,266 (22.0) | 5,371 (27.1) |
![]() |
7,549 (3.1) | 4,699 (1.8) | 4,921 (1.8) | 8,046 (32.9) | 6,958 (26.2) | 6,150 (22.7) |
![]() |
5,420 (1.6) | 4,777 (1.3) | 4,190 (1.1) | 5,279 (15.4) | 5,190 (13.8) | 4,237 (11.1) |
Totals | NA | NA | NA | NA | NA | 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.[59] New case detection during the previous year (2005 - the last year for which full country information is available) was 296,499. The 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.
Current Situation in China
As the case with much of the rest of the world, China also has many leprosy recovered patients who have been isolated from the rest of society. In the '50s the Chinese government created "Recovered Villages" in rural remote mountaintops for the recovered patients. Although leprosy is now curable with the advent of the multi-drug treatment, the villagers remain because they have been stigmatized by the outside world. Fortunately, health NGO such as Joy in Action have arisen in China to especially focus on improving the conditions of "Recovered Villages".
History
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.[60] Writing in the Encyclopedia Britannica 2008, Kearns & Nash state that the first mention of leprosy is described in the Indian medical treatise Sushruta Samhita (6th century BC).[61] 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 600 BC"[62] The surgeon Sushruta flourished in the Indian city of Kashi by the 6th century BC,[63] and the medical treatise Sushruta Samhita—attributed to him—made its appearance during the 1st millennium BC.[61] The earliest surviving excavated written material which contains the works of Sushruta is the Bower Manuscript—dated to the 4th century AD, almost a millennium after the original work.[64] 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.[65] In 2009, a 4,000-year-old skeleton was uncovered in India that was shown to contain traces of leprosy.[66] 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.[67] This pre-dated the previous earliest recognised case, dating back to 6th-century Egypt, by 1,500 years.[68] It is believed that the excavated skeleton belonged to a male, who was in his late 30s and belonged to the Ahar Chalcolithic culture.[68][69] Archaeologists have stated that not only does the skeleton represent the oldest case of leprosy ever found, but is also the first such example that dates back to prehistoric India.[70] 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.[67]
China
With regards to ancient China, Katrina C. D. McLeod and Robin D. S. Yates identify the State of Qin's Feng zhen shi 封診式 (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 癘, a general Chinese word for skin disorder.[71] 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."[71]
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".[71] The Roman author Pliny the Elder (23–79 AD) mentioned the same disease.[71] 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.[71] 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."[71]
Muslim world
In the Muslim world, the Persian polymath Avicenna (c. 980–1037) was the first outside of China to describe the destruction of the nasal septum in those suffering from leprosy.[71]
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.[72] 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.[73] 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.
Modern
![](http://upload.wikimedia.org/wikipedia/commons/thumb/5/53/Gerhard_Armauer_Hansen.jpg/220px-Gerhard_Armauer_Hansen.jpg)
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.[74]
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.[75][76] He worked at St. Jørgens Hospital in Bergen, founded early in the fifteenth century. St. Jørgens is today a museum, Lepramuseet, probably the best preserved leprosy hospital in Northern Europe.[77]
Etymology
The word leprosy derives from the ancient Greek words lepros, a scale, and lepein, to peel.[78] 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 þe spitel uuel & þuhte lepruse." The Middle English Dictionary, s.v., "leprous"). A roughly contemporaneous use is attested in the Anglo-Norman Dialogues of Saint 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 and the pejorative connotations of the term. The term most widely accepted among professionals is "people affected by Hansen's disease."
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.[79]
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.[80] 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.[citation needed] 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.[citation needed]
Famous lepers
- Blessed Damien of Molokaʻi was a Roman Catholic missionary-priest who contracted leprosy while serving the leper colony at Molokaʻi. He continued to serve the lepers until he died from the effects of the disease. He is scheduled to be canonized on October 11, 2009 at a Vatican ceremony presided over by Pope Benedict XVI.[81]
- King Baldwin IV of Jerusalem, who was portrayed as a character in the film Kingdom of Heaven.
- Possibly Robert the Bruce, King of Scots.
- Vietnamese poet Han Mac Tu.
- Otani Yoshitsugu, a Japanese daimyo.
Lepers in the Bible
- The Bible has a number of references such as Moses's sister ([1]), Moses ([2]), Syrian army chief Naaman and later the prophet Elisha's servant Gehazi ([3]), and several people Jesus healed ([4], [5]).
Fictional lepers
- The protagonist of The Chronicles of Thomas Covenant, the Unbeliever contracts leprosy, the central point of the entire series.
- In Shakespeare's play, the ghost of old king Hamlet, prince Hamlet's father, claimed to have been poisoned by a 'leprous distillment', as he contracted several symptoms similar to those of leprosy such as pustulating boils.
- In Braveheart, Robert the Bruce's father, Robert de Brus, 6th Lord of Annandale is portrayed with leprosy.
- In The Simpsons episode Little Big Mom, Bart and Homer are tricked into thinking they have leprosy.
- In Ben Hur, the family of the protagonist contract leprosy while in prison.
- In Monk, episode 10 of season 5, Adrian Monk deals with a client who has leprosy.
- Rachel Kalama in the novel Molokai is sent away from Honolulu to live on the leper colony in Molokai.
- In the young adult novel Healing Water by Joyce Moyer Hostetter, a Hawaiian teenager struggles to survive the leper colony of Molokai in the 1860s.
- The Island is a historical fiction novel written by Victoria Hislop, much of which is set in a leper colony on island of Spinalonga, off the coast of Crete.
- In Samurai X: Reflection, Kenshin Himura exhibited leprosy-like symptoms. His eventual wife Kaoru Kamiya contracted the disease out of love.
- Caius Merlyn Brittanicus from The Camulod Chronicles contracts Leprosy while trying to save a bleeding Leper from freezing to death.
- The protagonist of the book The Leper by Steve Thayer is an American soldier who is infected during World War I and contracts the disease
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- ^ a b "Skeleton Pushes Back Leprosy's Origins". Science Now. 2009-05-27. Retrieved 2009-05-29.
- ^ "Leprosy belonged to Ahar Chalcolithic era: Expert". The Times of India. 2009-05-29. Retrieved 2009-05-29.
- ^ "'Oldest evidence of leprosy found in India'". The Times of India. 2009-05-27. Retrieved 2009-05-29.
- ^ a b c d e f g McLeod, Katrina C. D. and Robin D. S. Yates (1981). "Forms of Ch'in Law: An Annotated Translation of The Feng-chen shih". Harvard Journal of Asiatic Studies. 41 (1): 111–63. Pages 152–3 & footnote 147. doi:10.2307/2719003.
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ignored (help) - ^ Herbermann, Charles, ed. (1913). Catholic Encyclopedia. New York: Robert Appleton Company. .
- ^ Brody, Saul Nathaniel (1974). The Disease of the Soul: Leprosy in Medieval Literature. Ithaca: Cornell Press.
- ^ "The Leprosy Archives in Bergen, Norway". Retrieved 2009-05-30.
- ^ Hansen GHA (1874). "Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy)". Norsk Mag. Laegervidenskaben (in Norwegian). 4: 1–88.
- ^ Irgens L (2002). "The discovery of the leprosy bacillus". Tidsskr nor Laegeforen. 122 (7): 708–9. PMID 11998735.
- ^ Bymuseet i Bergen
- ^ Barnhart RK (1995). Barnhart Concise Dictionary of Etymology. New York: Harper Collins. ISBN 0062700847. OCLC 221898877 223496345 231655185 30399281.
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value (help) - ^ Artscroll Tanakh, 6
- ^ 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). ISBN 0898631572. OCLC 37116438.
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: CS1 maint: multiple names: authors list (link) - ^ Priest who aided lepers in Hawaii to become saint - http://news.yahoo.com/s/ap/20090221/ap_on_re_eu/eu_vatican_saint
Further reading
- 1877: Lewis, T. R. (1877). Leprosy In India. Calcutta: Office Of The Superintendent Of Government Printing. Retrieved 2009-08-07.
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suggested) (help) - 1895: Ashmead, Albert S. (1895). Pre-Columbian Leprosy. Chicago: American Medical Association Press. Retrieved 2009-08-07.
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(help) - 1895: Prize Essays On Leprosy. London: The New Sydenham Society. 1895. Retrieved 2009-08-07.
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(help) - 1896: Impey, S. P. (1896). A Handbook On Leprosy. Philadelphia: P. Blakiston, Son & Co. Retrieved 2009-08-07.
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(help) - 1916: "Fighting Leprosy In The Philippines". The World's Work: A History of Our Time. XXXI: 310–320. 1916. Retrieved 2009-08-04.
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External links
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