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==Overview==
==Overview==
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==Historical Perspective==
==Historical Perspective==
''[[Mycobacterium leprae]]'', the causative agent of leprosy, was discovered by [[Gerhard Armauer Hansen|G. H. Armauer Hansen]] in Norway in 1873, making it the first [[bacterium]] to be identified as causing [[disease]] in man.<ref name=Hansen_1874>{{cite journal | author = Hansen GHA | title = Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy) | journal = Norsk Mag. Laegervidenskaben | year = 1874 | volume = 4| pages = pp. 1–88 | language = Norwegian }}</ref><ref name=Irgens_2002>{{cite journal |author=Irgens L |title=The discovery of the leprosy bacillus |journal=Tidsskr Nor Laegeforen |volume=122 |issue=7 |pages=708-9 |year=2002 |pmid=11998735}}</ref> The importance of the [[nasal mucosa]] was recognized as early as 1898 by Schäffer, particularly that of the [[Ulcer|ulcerated]] [[mucosa]].  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 people and agencies working in the field of Hansen's disease is 'people affected by Hansen's disease.
''[[Mycobacterium leprae]]'', the causative agent of leprosy, was discovered by [[Gerhard Armauer Hansen|G. H. Armauer Hansen]] in Norway in 1873, making it the first [[bacterium]] to be identified as causing [[disease]] in man.<ref name=Hansen_1874>{{cite journal | author = Hansen GHA | title = Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy) | journal = Norsk Mag. Laegervidenskaben | year = 1874 | volume = 4| pages = pp. 1–88 | language = Norwegian }}</ref><ref name=Irgens_2002>{{cite journal |author=Irgens L |title=The discovery of the leprosy bacillus |journal=Tidsskr Nor Laegeforen |volume=122 |issue=7 |pages=708-9 |year=2002 |pmid=11998735}}</ref> Historically, individuals with leprosy have been known as ''lepers'', however, this term is falling into disuse due the pejorative connotation of the term.


==Classification==
==Classification==
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==Pathophysiology==
==Pathophysiology==
Leprosy is a [[chronic disease]], whose clinical features depend on the [[immune response]] of the host towards the [[infection]]. Once the [[bacterial]] [[cells]] penetrate and multiply within host cells, predominately [[skin]] and [[peripheral nerve]] cells, the [[immune system]] develops a responses against those [[infected]] [[cells]], thereby justifying some of the [[symptoms]]. There have identified several [[gene]] [[SNPs]] related to susceptibility to the [[disease]], which has microscopic and gross manifestations.
The clinical manifestations of leprosy largely reflect the [[immune response]] of the host towards the [[infection]]. Once the [[bacterial]] [[cells]] penetrate and multiply within the hosts [[skin]] and [[peripheral nerve]] cells, the [[immune system]] mounts a response toward the [[infected]] [[cells]], which results in clinical [[symptoms]]. Several [[single-nucleotide polymorphism]]s such as [[TNF-α]], [[IL-10]], [[IFN-γ]], [[TLR 1]]  have been associated with a greater susceptibility to leprosy as have other genetic markers.


==Causes==
==Causes==
''[[Mycobacterium leprae]]'' is a [[gram-positive]] [[Obligate intracellular parasite|obligate intracellular]], [[acid-fast bacillus]], responsible for the development of leprosy, or Hansen's disease. This [[organism]] has a very slow growth and affects particularly colder parts of the [[body]], such as the [[skin]], superficial [[nerves]] and [[upper respiratory tract|upper respiratory]] [[mucous membranes]]. Although a route of [[transmission]] has not been absolutely defined yet, studies are pointing to a colonization of the [[dermis]] and [[respiratory]] [[mucosa]] of the [[infected]] patients, with the [[respiratory system]] also as the entry port. It is an uncommon [[bacteria]], since it has only been noticed to [[infect]] and grown in some [[species]] of primates and in the nine-banded armadillo.<ref name="BhatPrakash2012">{{cite journal|last1=Bhat|first1=Ramesh Marne|last2=Prakash|first2=Chaitra|title=Leprosy: An Overview of Pathophysiology|journal=Interdisciplinary Perspectives on Infectious Diseases|volume=2012|year=2012|pages=1–6|issn=1687-708X|doi=10.1155/2012/181089}}</ref>
''[[Mycobacterium leprae]]'' is a [[gram-positive]] [[Obligate intracellular parasite|obligate intracellular]], [[acid-fast bacillus]], responsible for the development of leprosy, or Hansen's disease. This [[organism]] has a very slow growth and has a predilection to affect colder parts of the [[body]], such as the [[skin]], superficial [[nerves]] and [[upper respiratory tract|upper respiratory]] [[mucous membranes]]. Although a route of [[transmission]] has not been absolutely defined yet, studies are pointing to a colonization of the [[dermis]] and [[respiratory]] [[mucosa]] of the [[infected]] patients. It is an uncommon [[bacteria]], since it has only been noticed to [[infect]] and grow in some [[species]] of primates and in the nine-banded armadillo.<ref name="BhatPrakash2012">{{cite journal|last1=Bhat|first1=Ramesh Marne|last2=Prakash|first2=Chaitra|title=Leprosy: An Overview of Pathophysiology|journal=Interdisciplinary Perspectives on Infectious Diseases|volume=2012|year=2012|pages=1–6|issn=1687-708X|doi=10.1155/2012/181089}}</ref>


==Differential Diagnosis==
==Differential Diagnosis==
Due to clinical manifestations such as [[skin lesions]], [[nodules]], [[plaques]]  [[paresthesias]] and [[nerve pain]], leprosy should be distinguished from conditions with similar presentations, such as [[autoimmune diseases]], [[SLE]], [[parasitic infections]], [[vitiligo]] or [[tuberculosis|cutaneous tuberculosis]].
Leprosy must be differentiated from other diseases that cause [[skin lesions]], [[nodules]], [[plaques]]  [[paresthesias]] and [[nerve pain]], such as [[autoimmune diseases]], [[SLE]], [[parasitic infections]], [[vitiligo]] or [[tuberculosis|cutaneous tuberculosis]].


==Epidemiology and Demographics==
==Epidemiology and Demographics==
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==Risk Factors==
==Risk Factors==
Close contacts of patients with untreated, active [[bacilli|multibacillary]] disease are at highest [[Risk factor|risk]] of acquiring leprosy. Children are more susceptible than adults to contracting the [[disease]].
Risk factors for contracting leprosy include close contact with an untreated, active [[bacilli|multibacillary]] disease patient with the subtype of lepromatous leprosy, living in an endemic region (Angola, Brazil, Central African Republic, Democratic Republic of Congo, Federated States of Micronesia, India, Kiribati, Madagascar, Mozambique, Nepal, Republic of Marshall Islands, United Republic of Tanzania), age between 5 and 15 as well as over 30, Armadillo contact, tattoos, and genetic variants of the [[NOD2]]-mediated signaling pathway.


==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==
Leprosy, when not [[diagnosis|diagnosed]] early and [[therapy|treated]] appropriately may lead to severe [[complications]], such as severe [[nerve damage]], [[blindness]], [[contractures]] and Lucio phenomenon. The [[prognosis]] will depend on how early the [[diagnosis]] is reached and how soon the multidrug therapy is started.
Leprosy may lead to severe [[complications]] if not [[diagnosis|diagnosed]] and treated early, which will affect the [[prognosis]].


==Diagnosis==
==Diagnosis==
===Diagnostic Criteria===
===Diagnostic Criteria===
Leprosy is a [[disease]] with very different clinical presentations, depending on the [[immune response]] provided by the host. Therefore it is important to consider the different conditions that may mimic leprosy's presentation, particularly since the [[diagnosis]] of leprosy has a very serious [[psychological]] and social impact in someone's life. To minimize the risk of reaching an erroneous [[diagnosis]] and inflicting [[stress]] and concern in the [[patient]], criteria were developed to guide the [[diagnosis]], which should only be communicated to the patient when a reasonable degree of certainty is present.
The [[diagnosis]] of leprosy requires at least 1 of 3 criteria to be present: 1) [[loss of sensation]] of a [[Hypopigmentation|hipopigmented]] [[skin]] patch, 2) a thickened [[peripheral nerve]] concomitantly with [[weakness]] or [[loss of sensation]] of the area, and/or 3) confirmation of [[mycobacterium leprae]] in a [[skin]] smear.


===History and Symptoms===
===History and Symptoms===
Despite the considerable decrease in the [[incidence]] of leprosy in recent years, after the [[prevention|preventive]] and [[Therapy|treatment]] measures applied by the [[WHO]], there are still [[endemic]] areas of this [[disease]], particularly in developing countries. Accordingly, the [[diagnostic]] procedures and the time to reach a correct [[diagnosis]] will depend on the area of the world it occurs. The [[diagnosis]] of leprosy should be considered when there is history of [[skin lesions]] that do not respond to [[Therapy|treatment]] for more common conditions or when in presence of [[sensory loss]] with concomitant [[trauma]] lesions or [[burns]]. Elements such as travel history, social contacts and concomitant clinical manifestations are also essential in reaching a correct [[diagnosis]], which contributes to a decrease of [[morbidity]] of this condition.
Common [[symptoms]] of leprosy include [[hypopigmentation|hypopigmented]], [[anesthetic]], red [[skin lesions]], that are hard to heal, [[nodular]] growths on the [[skin]], [[muscle weakness]] and [[paresthesia]] of the extremities and [[eye]] problems. If left untreated [[blindness]] and [[paralysis]] may occur.


===Physical Examination===
===Physical Examination===
Leprosy is a disease that may present with different clinical manifestations throughout its course, and among different patients, depending on the response of the [[immune system]]. Therefore, physical findings will depend on the class of leprosy on that particular patient. Common physical findings include [[Hypopigmentation|hypopigmented]] [[skin lesions]], usually [[macular]] or [[papules|papular]], thickened [[dermis]], [[loss of sensation]] and [[peripheral nerve]] thickening, with common evolvement of the [[nasal mucosa]].
Although the findings on [[physical examination]] may vary depending upon the subytpe of leprosy, common findings include [[Hypopigmentation|hypopigmented]] [[skin lesions]], thickened [[dermis]], and [[loss of sensation]].


===Laboratory Findings===
===Laboratory Findings===
No laboratory tests are available for the [[diagnosis]] of leprosy.
There are no laboratory tests that diagnose leprosy.


===X Ray===
===X Ray===
[[Osteoporosis]] is a common finding in leprosy patients, which along with the decreased [[sensitivity]] and [[pain]] experienced by these individuals, make evidence of [[fractures]] on the [[X-ray]], a common finding.
[[Osteoporosis]] is a common finding in leprosy patients which along with the [[loss of sensation]] may lead to [[fractures]].


===Other Imaging Findings===
===Other Imaging Findings===
No other imaging studies are indicated for the [[diagnosis]] of leprosy.
There are no other imaging studies that diagnose leprosy.


===Other Diagnostic Studies===
===Other Diagnostic Studies===
Although there are no laboratory studies to help in the [[diagnosis]] of leprosy, other studies such as [[biopsy]] of [[skin lesions]] and [[skin]] smear tests have an important contribution for the [[diagnosis]] of leprosy in patients, whose [[diagnosis]] is suspected from the clinical presentation.
[[Biopsy]] of [[skin lesions]] and [[skin]] smear tests are important for the [[diagnosis]] of leprosy in patients whose clinical examination is suspicious of the disease.


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
The [[medical treatment]] of leprosy is made with a multiple [[drug]] regimen, that must be followed rigorously during a long period of time, 6 to 12 months, depending on the class of [[disease]]. This [[drug]] regimen includes 2 to 3 different drugs, in order to minimize the risk of [[resistance]] by the [[bacillus]], and its administration should be monitored closely by health care personnel to insure adherence to the [[therapy|treatment]].
The [[medical treatment]] of leprosy is made with a multiple [[drug]] regimen, for 6 to 12 months. This [[drug]] regimen may include 2 or 3 drugs: [[rifampicin]], [[dapsone]] and [[clofazimine]], or [[rifampicin]] and [[dapsone]], depending on the class of the disease.


===Surgery===
===Surgery===
Although [[surgery]] is not indicated in the [[Therapy|treatment]] of leprosy, it may treat, or decrease the impact, of some of the [[complications]] that may arise from the [[disease]].
[[Surgery]] is not indicated in the [[Therapy|treatment]] of leprosy, yet it may treat or decrease the impact of some of the [[complications]] that may arise from the [[disease]].


===Primary prevention===
===Primary prevention===
Unfortunately there are still [[endemic]] regions in the world, where people are deeply affected by leprosy, and that due to international travels, threaten to be be a source of the [[bacteria]] for the entire world. Although an effective [[Therapy|treatment]] regimen is available, [[primary prevention]] measures play a dominant role in minimizing the impact of the [[disease]].  [[Immunoprophylaxis |Immuno]] and [[chemoprophylaxis]] of leprosy and other [[infectious diseases]] are fundamental measures to prevent [[infection]] by the ''[[Mycobacterium leprae]]'', however, adequate education of the populations also has a great impact in minimizing this [[Risk factor|risk]].
[[Primary prevention]] of leprosy includes [[immunoprophylaxis]], [[chemoprophylaxis]] and education of the populations to prevent [[infection]] by the ''[[Mycobacterium leprae]]''.


===Secondary Prevention===
===Secondary Prevention===
Unfortunately today it is not available a test to identify if a person was [[infected]] by [Mycobacterium leprae]] until the first [[symptoms]] start to appear. However, [[primary prevention|primary]] and [[tertiary prevention]] are two ways of [[prevention|preventing]] being [[infected]] with the [[disease]], as well as minimizing damage caused in patients with this condition.
There is no [[secondary prevention]] of leprosy available because it is not possible to know if contact with leprosy will lead to the development of the disease, until first [[symptoms]] appear.


===Tertiary prevention===
===Tertiary prevention===
After leprosy has been [[diagnosis|diagnosed]] and [[Therapy|treatment]] has been initiated, other measures may be taken, in order to minimize further damage to the patient. These include: education of the patient and family members to monitor and treat [[skin]] [[ulcers]] and other lesions, primary care facilities to provide help to the populations and to direct patients to a specialist, whenever needed.<ref name=WHO>{{cite web | title = Enhanced global strategy for further reducing the disease burden due to leprosy (2011-2015) | url = http://www.searo.who.int/entity/global_leprosy_programme/documents/enhanced_global_strategy_2011_2015_operational_guidelines.pdf }}</ref>
After [[Therapy|treatment]] has been initiated, other measures to minimize further damage to the patient include: education of the individual and family members to monitor and treat [[skin]] [[ulcers]] and other lesions, primary care facilities to provide help to the populations and to direct patients to a specialist, whenever necessary.<ref name=WHO>{{cite web | title = Enhanced global strategy for further reducing the disease burden due to leprosy (2011-2015) | url = http://www.searo.who.int/entity/global_leprosy_programme/documents/enhanced_global_strategy_2011_2015_operational_guidelines.pdf }}</ref>


===Cost-effectiveness of Therapy===
===Cost-effectiveness of Therapy===
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===Future or Investigational Therapies===
===Future or Investigational Therapies===
In the last few years the [[WHO]] has implemented measures and [[Therapy|treatment]] approaches that were able to considerably decrease the [[incidence]] of leprosy on a worldwide level. However, there are still [[endemic]] areas that need to see these and further measures implemented, in order to minimize the impact of this [[disease]]. For this to be accomplished, new [[research]] studies are required to help improve the current concepts of [[diagnosis]] and [[therapy]] of leprosy, bringing the same level of [[Therapy|treatment]] to every area in the world, particularly [[endemic]] regions in developing countries.
Ongoing [[research]] focuses on the the mechanism of leprosy transmission as well as the identification of patients at high risk of infection in order to improve disease prevention and to treat infected individuals earlier. <ref name=WHO>{{cite web | title = Enhanced Global Strategy for Further Reducing the Disease Burden due to Leprosy | url = http://www.searo.who.int/entity/global_leprosy_programme/documents/enhanced_global_strategy_2011_2015_operational_guidelines.pdf }}</ref>  Identification of alternatives to existing [[drugs]], such as [[rifampicin]] is also critical in so far as these agents may be [[contraindicated]] either because of [[toxicity]] or [[resistance]]. <ref name=WHO>{{cite web | title = Enhanced Global Strategy for Further Reducing the Disease Burden due to Leprosy | url = http://www.searo.who.int/entity/global_leprosy_programme/documents/enhanced_global_strategy_2011_2015_operational_guidelines.pdf }}</ref>
 
==References==
==References==
{{reflist|2}}
{{reflist|2}}
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Dermatology]]
[[Category:Dermatology]]
[[Category:Infectious disease]]
 
[[Category:Tropical disease]]
[[Category:Tropical disease]]
[[Category:Leprosy]]
[[Category:Leprosy]]

Latest revision as of 18:10, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Leprosy is a chronic infectious disease caused by the bacterium Mycobacterium leprae.[1] Leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions are the primary external symptom. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs, and eyes.

Historical Perspective

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 man.[2][3] Historically, individuals with leprosy have been known as lepers, however, this term is falling into disuse due the pejorative connotation of the term.

Classification

The Ridley Jopling classification and the WHO classification are the two most widely used systems to classify Leprosy. These classification systems are based on clinical, microbiologic and histopathological features, and are used to determine the patient's prognosis and the treatment regimen.[4][5][6]

Pathophysiology

The clinical manifestations of leprosy largely reflect the immune response of the host towards the infection. Once the bacterial cells penetrate and multiply within the hosts skin and peripheral nerve cells, the immune system mounts a response toward the infected cells, which results in clinical symptoms. Several single-nucleotide polymorphisms such as TNF-α, IL-10, IFN-γ, TLR 1 have been associated with a greater susceptibility to leprosy as have other genetic markers.

Causes

Mycobacterium leprae is a gram-positive obligate intracellular, acid-fast bacillus, responsible for the development of leprosy, or Hansen's disease. This organism has a very slow growth and has a predilection to affect colder parts of the body, such as the skin, superficial nerves and upper respiratory mucous membranes. Although a route of transmission has not been absolutely defined yet, studies are pointing to a colonization of the dermis and respiratory mucosa of the infected patients. It is an uncommon bacteria, since it has only been noticed to infect and grow in some species of primates and in the nine-banded armadillo.[6]

Differential Diagnosis

Leprosy must be differentiated from other diseases that cause skin lesions, nodules, plaques paresthesias and nerve pain, such as autoimmune diseases, SLE, parasitic infections, vitiligo or cutaneous tuberculosis.

Epidemiology and Demographics

Current prevalence rate of leprosy per 100,000 is 3.7. The disease is more prevalent in endemic areas, which represent a potential source of spread of the disease to the rest of the world.

Risk Factors

Risk factors for contracting leprosy include close contact with an untreated, active multibacillary disease patient with the subtype of lepromatous leprosy, living in an endemic region (Angola, Brazil, Central African Republic, Democratic Republic of Congo, Federated States of Micronesia, India, Kiribati, Madagascar, Mozambique, Nepal, Republic of Marshall Islands, United Republic of Tanzania), age between 5 and 15 as well as over 30, Armadillo contact, tattoos, and genetic variants of the NOD2-mediated signaling pathway.

Natural History, Complications and Prognosis

Leprosy may lead to severe complications if not diagnosed and treated early, which will affect the prognosis.

Diagnosis

Diagnostic Criteria

The diagnosis of leprosy requires at least 1 of 3 criteria to be present: 1) loss of sensation of a hipopigmented skin patch, 2) a thickened peripheral nerve concomitantly with weakness or loss of sensation of the area, and/or 3) confirmation of mycobacterium leprae in a skin smear.

History and Symptoms

Common symptoms of leprosy include hypopigmented, anesthetic, red skin lesions, that are hard to heal, nodular growths on the skin, muscle weakness and paresthesia of the extremities and eye problems. If left untreated blindness and paralysis may occur.

Physical Examination

Although the findings on physical examination may vary depending upon the subytpe of leprosy, common findings include hypopigmented skin lesions, thickened dermis, and loss of sensation.

Laboratory Findings

There are no laboratory tests that diagnose leprosy.

X Ray

Osteoporosis is a common finding in leprosy patients which along with the loss of sensation may lead to fractures.

Other Imaging Findings

There are no other imaging studies that diagnose leprosy.

Other Diagnostic Studies

Biopsy of skin lesions and skin smear tests are important for the diagnosis of leprosy in patients whose clinical examination is suspicious of the disease.

Treatment

Medical Therapy

The medical treatment of leprosy is made with a multiple drug regimen, for 6 to 12 months. This drug regimen may include 2 or 3 drugs: rifampicin, dapsone and clofazimine, or rifampicin and dapsone, depending on the class of the disease.

Surgery

Surgery is not indicated in the treatment of leprosy, yet it may treat or decrease the impact of some of the complications that may arise from the disease.

Primary prevention

Primary prevention of leprosy includes immunoprophylaxis, chemoprophylaxis and education of the populations to prevent infection by the Mycobacterium leprae.

Secondary Prevention

There is no secondary prevention of leprosy available because it is not possible to know if contact with leprosy will lead to the development of the disease, until first symptoms appear.

Tertiary prevention

After treatment has been initiated, other measures to minimize further damage to the patient include: education of the individual and family members to monitor and treat skin ulcers and other lesions, primary care facilities to provide help to the populations and to direct patients to a specialist, whenever necessary.[7]

Cost-effectiveness of Therapy

After the results of the campaign of the WHO to eradicate leprosy, the treatment of this disease may be considered cost-effective.

Future or Investigational Therapies

Ongoing research focuses on the the mechanism of leprosy transmission as well as the identification of patients at high risk of infection in order to improve disease prevention and to treat infected individuals earlier. [7] Identification of alternatives to existing drugs, such as rifampicin is also critical in so far as these agents may be contraindicated either because of toxicity or resistance. [7]

References

  1. Sasaki S, Takeshita F, Okuda K, Ishii N (2001). "Mycobacterium leprae and leprosy: a compendium". Microbiol Immunol. 45 (11): 729–36. PMID 11791665.
  2. Hansen GHA (1874). "Undersøgelser Angående Spedalskhedens Årsager (Investigations concerning the etiology of leprosy)". Norsk Mag. Laegervidenskaben (in Norwegian). 4: pp. 1–88.
  3. Irgens L (2002). "The discovery of the leprosy bacillus". Tidsskr Nor Laegeforen. 122 (7): 708–9. PMID 11998735.
  4. Walker, Stephen L.; Lockwood, Dina N.J. (2007). "Leprosy". Clinics in Dermatology. 25 (2): 165–172. doi:10.1016/j.clindermatol.2006.05.012. ISSN 0738-081X.
  5. Eichelmann, K.; González González, S.E.; Salas-Alanis, J.C.; Ocampo-Candiani, J. (2013). "Leprosy. An Update: Definition, Pathogenesis, Classification, Diagnosis, and Treatment". Actas Dermo-Sifiliográficas (English Edition). 104 (7): 554–563. doi:10.1016/j.adengl.2012.03.028. ISSN 1578-2190.
  6. 6.0 6.1 Bhat, Ramesh Marne; Prakash, Chaitra (2012). "Leprosy: An Overview of Pathophysiology". Interdisciplinary Perspectives on Infectious Diseases. 2012: 1–6. doi:10.1155/2012/181089. ISSN 1687-708X.
  7. 7.0 7.1 7.2 "Enhanced global strategy for further reducing the disease burden due to leprosy (2011-2015)" (PDF).


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