A brief review on hansen’s disease
Corresponding Author(s) : V. Srividhya
srividhyaveeramuthu1995@gmail.com
International Journal of Allied Medical Sciences and Clinical Research,
Vol. 9 No. 2 (2021): 2021 Volume - 9 Issue - 2
Abstract
Hansen disease is also known as Leprosy. Leprosy is caused by Mycobacterium leprae and has been known since biblical times. The mechanism of transmission of leprosy consists of prolonged close contact between susceptible and genetically predisposed individuals and untreated multibacillary patients. Transmission occurs through inhalation of bacilli present in upper airway secretion. The nasal mucosa is the main entry or exit route of M. leprae. The deeper understanding of the structural and biological characteristics of M. leprae, the sequencing of its genome, along with the advances in understanding the mechanisms of host immune response against the bacilli, dependent on genetic susceptibility, have contributed to the understanding of the pathogenesis, variations in the clinical characteristics, and progression of the disease. This article aims update on epidemiological, clinical, and etiopathogenic leprosy aspects.
Keywords
Classification
Clinical diagnosis
Disease transmission
Epidemiology
Leprosy
Mycobacterium leprae
1.
Dr. R. Manivannan, Dr. S. Kameshwaran, V. Srividhya, S. Divyadarshini, M Uma bharathi. A brief review on hansen’s disease. Int. J. of Allied Med. Sci. and Clin. Res. [Internet]. 2021 Apr. 3 [cited 2026 Jan. 23];9(2):120-3. Available from: https://ijamscr.com/ijamscr/article/view/983
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References
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1. Eidt LM. Breve história da hanseníase: sua expansão do mundo para as Américas, o Brasil e o Rio Grande do Sul e sua trajetória na saúde pública brasileira. Saúde Soc. 2004;13:76–88. [Google Scholar] [Ref list]
2. Cavaliere IAL, Costa SG. Isolamento social, sociabilidades e redes sociais de cuidados. Physis. 2011;21:491–516. [Google Scholar] [Ref list]
3. Opromolla PA, Martelli ACC. Terminology related to Hansen's disease. An Bras Dermatol. 2005;80:293–294. [Google Scholar] [Ref list]
4. Global leprosy situation, 2012.Wkly Epidemiol Rec. 2012 Aug 24; 87(34):317-28.[PubMed] [Ref list]
5. Talhari S, Grossi MA, Oliveira ML, Gontijo B, Talhari C, Penna GO
6. Mem Inst Oswaldo Cruz. 2012 Dec; 107 Suppl 1():13-6. [PubMed] [Ref list]
7. Barbieri CL, Marques HH. Leprosy in children and adolescents: bibliographical review and current situation in Brazil. Pediatria (São Paulo) Pediatria (São Paulo) 2009;31:281–290. [Google Scholar] [Ref list]
8. Ignotti E, Rodrigues AM, Andrade VLG, Valente JG. Aplicação de métodos de estimativa da prevalência de hanseníase no Estado de Mato Grosso. Rev Bras Epidemiol. 2004;7:155–166. [Google Scholar] [Ref list]
9. Paho.org. World Health Organization . Elimination of leprosy as a public health problem. Leprosy Resolution WHA 44.9, 44th World Health Assembly. Geneva: 1991. [cited 2012 oct 19]. [homepage on the internet] Available from: http://www.paho.org/English/AD/DPC/CD/lep-wha-1991.htm. [Google Scholar] [Ref list]
10. Rees RJW, Young DB. The microbiology of leprosy. In: Hastings RC, editor. Leprosy. 2nd ed. New York: Churchill Livingstone; 1994. pp. 49–83. [Google Scholar] [Ref list]
11. Desikan KV Lepr Rev. 1977 Dec; 48(4):231-5.[PubMed] [Ref list]
12. Hirata T Int J Lepr Other Mycobact Dis. 1985 Sep; 53(3):433-40. [PubMed] [Ref list]
13. Vissa VD, Brennan PJ Genome Biol. 2001; 2(8):REVIEWS1023.[PubMed] [Ref list]
14. Bona SH, Fonseca APM, Silva ACL, Costa RJ. Bacilos álcool-ácido resistentes no Culex fatigans. An Bras Dermatol. 1985;60:163–170. [Google Scholar] [Ref list]
15. Job CK. Nasal mucosa and abraded skin are the two routes of entry of Mycobacterium leprae. Star. 1990;49:1. [Google Scholar] [Ref list]
16. Pedley JC Lepr Rev. 1967 Oct; 38(4):239-42. [PubMed] [Ref list]
17. Cree IA, Smith WC Lepr Rev. 1998 Jun; 69(2):112-21. [PubMed] [Ref list]
18. Moet FJ, Meima A, Oskam L, Richardus JH Lepr Rev. 2004 Dec; 75(4):310-26. [PubMed] [Ref list]
19. Prevedello FC, Mira MT. Leprosy: a genetic disease? An Bras Dermatol. 2007;82:451–459. [Google Scholar] [Ref list]
20. Alcais A, Alter A, Antoni G, Orlova M, Nguyen VT, Singh M, et al. Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. Nat Genet. 2007;39:517–522. [PubMed] [Google Scholar] [Ref list]
21. Roy S, McGuire W, Mascie-Taylor CG, Saha B, Hazra SK, Hill AV, et al. Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy. J Infect Dis. 1997;176:530–532. [PubMed] [Google Scholar] [Ref list]
22. Sarno EN, Santos AR, Jardim MR, Suffys PN, Almeida AS, Nery JA, et al. Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNF? Lepr Rev. 2000;71:S154–S158. [PubMed] [Google Scholar] [Ref list]
23. Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, et al. Genomewide association study of leprosy. N Engl J Med. 2009;361:2609–2618. [PubMed] [Google Scholar] [Ref list]
24. Roy S, Frodsham A, Saha B, Hazra SK, Mascie-Taylor CG, Hill AV. Association of vitamin D receptor genotype with leprosy type. J Infect Dis. 1999;179:187–191. [PubMed] [Google Scholar] [Ref list]
25. Bochud PY, Hawn TR, Siddiqui MR, Saunderson P, Britton S, Abraham I, et al. Tolllike receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. J Infect Dis. 2008;197:253–261. [PMC free article] [PubMed] [Google Scholar] [Ref list]
26. Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing challenges of leprosy. Clin Microbiol Rev. 2006;19:338–381. [PMC free article] [PubMed] [Google Scholar] [Ref list]
27. Mendonça VA, Costa RD, Melo GEBA, Antunes CM, Teixeira AL. Immunology of leprosy. An Bras Dermatol. 2008;83:343–350. [Google Scholar] [Ref list]
28. Oliveira MLW, Cavaliére FAM, Maceira JMP, Bührer-Sékula S. The use of serology as an additional tool to support diagnosis of difficult multibacillary leprosy cases: lessons from clinical care. Rev Soc Bras Med Trop. 2008;41:27–33. [PubMed] [Google Scholar] [Ref list]
29. Modlin RL, Melancon-Kaplan J, Young SM, Pirmez C, Kino H, Convit J, et al. Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A. 1988;85:1213–1217. [PMC free article] [PubMed] [Google Scholar] [Ref list]
30. Sieling PA, Abrams JS, Yamamura M, Salgame P, Bloom BR, Rea TH, et al. Immunosuppressive roles for IL-10 and IL-4 in human infection: In vitro modulation of T cell responses in leprosy. J Immunol. 1993;150:5501–5510. [PubMed] [Google Scholar] [Ref list]
31. Silva CL, Foss NT. Tumor necrosis factor in leprosy patients. J Infect Dis. 1989;159:787–790. [PubMed] [Google Scholar] [Ref list]
32. Warwick-Davies J, Lowrie DB, Cole PJ. Selective deactivation of human monocyte functions by TGF-beta. J Immunol. 1995;155:3186–3193. [PubMed] [Google Scholar] [Ref list]
33. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of Th1 CD4+ T-cells through IL-12 produced by Listeria-induced macrophages. Science. 1993;260:547–549. [PubMed] [Google Scholar] [Ref list]
34. Sieling PA, Modlin RL. Cytokine patterns at the site of mycobacterial infection. Immunobiology. 1994;191:378–387. [PubMed] [Google Scholar]
35. Foss NT. Aspectos imunológicos da hanseníase. Medicina (Ribeirão Preto) 1997;30:335–339. [Google Scholar] [Ref list]
36. Rabello FE., Júnior Uma classificação clínico-epidemiológica das formas de lepra. Rev Bras Leprol. 1936:375–410. [Google Scholar] [Ref list]
37. Ridley DS, Jopling WH. Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 1966;34:255–273. [PubMed] [Google Scholar] [Ref list]
38. Chemotherapy of leprosy for control programmes. World Health Organ Tech Rep Ser. 1982;675:1–33. [PubMed] [Google Scholar] [Ref list]
39. WHO Expert Committee on Leprosy World Health Organ Tech Rep. Ser. 1988;768:1–51. [PubMed] [Google Scholar] [Ref list]
40. Contin LA, Alves CJM, Fogagnolo L, Nassif PW, Barreto JA, Lauris JRP L, et al. Use of the ML-Flow test as a tool in classifying and treating leprosy. An Bras Dermatol. 2011;86:91–95. [PubMed] [Google Scholar] [Ref list]
41. Douglas JT, Cellona RV, Fajardo TT, Jr, Abalos RM, Balagon MV, Klatser PR. Prospective study of serological conversion as a risk factor for development of leprosy among household contacts. Clin Diagn Lab Immunol. 2004;11:897–900. [PMC free article] [PubMed] [Google Scholar] [Ref list]
42. Kahawita IP, Walker SL, Lockwood DNJ. Leprosy type 1 reactions and erythema nodosum leprosum. An Bras Dermatol. 2008;83:75–82. [Google Scholar] [Ref list]
43. Nery JAC, Sales AM, Illarramendi X, Duppre NC, Jardim MR, Machado AM. Contribuição ao diagnóstico e manejo dos estados reacionais: Uma abordagem prática. An bras dermatol. 2006;81(4):367–375. [Google Scholar] [Ref list]
44. Garbino JA. O paciente com suspeita de hanseníase primariamente neural / The patient with suspicion of primarily neural leprosy. Hansen Int. 2007;32:203–206. [Google Scholar] [Ref list]
45. Lewallen S, Tungpakorn NC, Kim SH, Courtright P. Progression of eye disease in "cured" leprosy patients: implications for understanding the pathophysiology of ocular disease and for addressing eyecare needs. Br J Ophthalmol. 2000;84:817–821. [PMC free article] [PubMed] [Google Scholar] [Ref list]
46. Meneses S, Cirelli NM, Aranzazu N, Rondon Lugo AJ. Lepra visceral: presentacion de dos casos y revision de la literatura. Dermatol Venez. 1988;26:79–84. [Google Scholar] [Ref list]
47. Klioze AM, Ramos-Caro FA. Visceral leprosy. Int J Dermatol. 2000;39:641–658. [PubMed] [Google Scholar] [Ref list]
References
1. Eidt LM. Breve história da hanseníase: sua expansão do mundo para as Américas, o Brasil e o Rio Grande do Sul e sua trajetória na saúde pública brasileira. Saúde Soc. 2004;13:76–88. [Google Scholar] [Ref list]
2. Cavaliere IAL, Costa SG. Isolamento social, sociabilidades e redes sociais de cuidados. Physis. 2011;21:491–516. [Google Scholar] [Ref list]
3. Opromolla PA, Martelli ACC. Terminology related to Hansen's disease. An Bras Dermatol. 2005;80:293–294. [Google Scholar] [Ref list]
4. Global leprosy situation, 2012.Wkly Epidemiol Rec. 2012 Aug 24; 87(34):317-28.[PubMed] [Ref list]
5. Talhari S, Grossi MA, Oliveira ML, Gontijo B, Talhari C, Penna GO
6. Mem Inst Oswaldo Cruz. 2012 Dec; 107 Suppl 1():13-6. [PubMed] [Ref list]
7. Barbieri CL, Marques HH. Leprosy in children and adolescents: bibliographical review and current situation in Brazil. Pediatria (São Paulo) Pediatria (São Paulo) 2009;31:281–290. [Google Scholar] [Ref list]
8. Ignotti E, Rodrigues AM, Andrade VLG, Valente JG. Aplicação de métodos de estimativa da prevalência de hanseníase no Estado de Mato Grosso. Rev Bras Epidemiol. 2004;7:155–166. [Google Scholar] [Ref list]
9. Paho.org. World Health Organization . Elimination of leprosy as a public health problem. Leprosy Resolution WHA 44.9, 44th World Health Assembly. Geneva: 1991. [cited 2012 oct 19]. [homepage on the internet] Available from: http://www.paho.org/English/AD/DPC/CD/lep-wha-1991.htm. [Google Scholar] [Ref list]
10. Rees RJW, Young DB. The microbiology of leprosy. In: Hastings RC, editor. Leprosy. 2nd ed. New York: Churchill Livingstone; 1994. pp. 49–83. [Google Scholar] [Ref list]
11. Desikan KV Lepr Rev. 1977 Dec; 48(4):231-5.[PubMed] [Ref list]
12. Hirata T Int J Lepr Other Mycobact Dis. 1985 Sep; 53(3):433-40. [PubMed] [Ref list]
13. Vissa VD, Brennan PJ Genome Biol. 2001; 2(8):REVIEWS1023.[PubMed] [Ref list]
14. Bona SH, Fonseca APM, Silva ACL, Costa RJ. Bacilos álcool-ácido resistentes no Culex fatigans. An Bras Dermatol. 1985;60:163–170. [Google Scholar] [Ref list]
15. Job CK. Nasal mucosa and abraded skin are the two routes of entry of Mycobacterium leprae. Star. 1990;49:1. [Google Scholar] [Ref list]
16. Pedley JC Lepr Rev. 1967 Oct; 38(4):239-42. [PubMed] [Ref list]
17. Cree IA, Smith WC Lepr Rev. 1998 Jun; 69(2):112-21. [PubMed] [Ref list]
18. Moet FJ, Meima A, Oskam L, Richardus JH Lepr Rev. 2004 Dec; 75(4):310-26. [PubMed] [Ref list]
19. Prevedello FC, Mira MT. Leprosy: a genetic disease? An Bras Dermatol. 2007;82:451–459. [Google Scholar] [Ref list]
20. Alcais A, Alter A, Antoni G, Orlova M, Nguyen VT, Singh M, et al. Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. Nat Genet. 2007;39:517–522. [PubMed] [Google Scholar] [Ref list]
21. Roy S, McGuire W, Mascie-Taylor CG, Saha B, Hazra SK, Hill AV, et al. Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy. J Infect Dis. 1997;176:530–532. [PubMed] [Google Scholar] [Ref list]
22. Sarno EN, Santos AR, Jardim MR, Suffys PN, Almeida AS, Nery JA, et al. Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNF? Lepr Rev. 2000;71:S154–S158. [PubMed] [Google Scholar] [Ref list]
23. Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, et al. Genomewide association study of leprosy. N Engl J Med. 2009;361:2609–2618. [PubMed] [Google Scholar] [Ref list]
24. Roy S, Frodsham A, Saha B, Hazra SK, Mascie-Taylor CG, Hill AV. Association of vitamin D receptor genotype with leprosy type. J Infect Dis. 1999;179:187–191. [PubMed] [Google Scholar] [Ref list]
25. Bochud PY, Hawn TR, Siddiqui MR, Saunderson P, Britton S, Abraham I, et al. Tolllike receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. J Infect Dis. 2008;197:253–261. [PMC free article] [PubMed] [Google Scholar] [Ref list]
26. Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing challenges of leprosy. Clin Microbiol Rev. 2006;19:338–381. [PMC free article] [PubMed] [Google Scholar] [Ref list]
27. Mendonça VA, Costa RD, Melo GEBA, Antunes CM, Teixeira AL. Immunology of leprosy. An Bras Dermatol. 2008;83:343–350. [Google Scholar] [Ref list]
28. Oliveira MLW, Cavaliére FAM, Maceira JMP, Bührer-Sékula S. The use of serology as an additional tool to support diagnosis of difficult multibacillary leprosy cases: lessons from clinical care. Rev Soc Bras Med Trop. 2008;41:27–33. [PubMed] [Google Scholar] [Ref list]
29. Modlin RL, Melancon-Kaplan J, Young SM, Pirmez C, Kino H, Convit J, et al. Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A. 1988;85:1213–1217. [PMC free article] [PubMed] [Google Scholar] [Ref list]
30. Sieling PA, Abrams JS, Yamamura M, Salgame P, Bloom BR, Rea TH, et al. Immunosuppressive roles for IL-10 and IL-4 in human infection: In vitro modulation of T cell responses in leprosy. J Immunol. 1993;150:5501–5510. [PubMed] [Google Scholar] [Ref list]
31. Silva CL, Foss NT. Tumor necrosis factor in leprosy patients. J Infect Dis. 1989;159:787–790. [PubMed] [Google Scholar] [Ref list]
32. Warwick-Davies J, Lowrie DB, Cole PJ. Selective deactivation of human monocyte functions by TGF-beta. J Immunol. 1995;155:3186–3193. [PubMed] [Google Scholar] [Ref list]
33. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of Th1 CD4+ T-cells through IL-12 produced by Listeria-induced macrophages. Science. 1993;260:547–549. [PubMed] [Google Scholar] [Ref list]
34. Sieling PA, Modlin RL. Cytokine patterns at the site of mycobacterial infection. Immunobiology. 1994;191:378–387. [PubMed] [Google Scholar]
35. Foss NT. Aspectos imunológicos da hanseníase. Medicina (Ribeirão Preto) 1997;30:335–339. [Google Scholar] [Ref list]
36. Rabello FE., Júnior Uma classificação clínico-epidemiológica das formas de lepra. Rev Bras Leprol. 1936:375–410. [Google Scholar] [Ref list]
37. Ridley DS, Jopling WH. Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 1966;34:255–273. [PubMed] [Google Scholar] [Ref list]
38. Chemotherapy of leprosy for control programmes. World Health Organ Tech Rep Ser. 1982;675:1–33. [PubMed] [Google Scholar] [Ref list]
39. WHO Expert Committee on Leprosy World Health Organ Tech Rep. Ser. 1988;768:1–51. [PubMed] [Google Scholar] [Ref list]
40. Contin LA, Alves CJM, Fogagnolo L, Nassif PW, Barreto JA, Lauris JRP L, et al. Use of the ML-Flow test as a tool in classifying and treating leprosy. An Bras Dermatol. 2011;86:91–95. [PubMed] [Google Scholar] [Ref list]
41. Douglas JT, Cellona RV, Fajardo TT, Jr, Abalos RM, Balagon MV, Klatser PR. Prospective study of serological conversion as a risk factor for development of leprosy among household contacts. Clin Diagn Lab Immunol. 2004;11:897–900. [PMC free article] [PubMed] [Google Scholar] [Ref list]
42. Kahawita IP, Walker SL, Lockwood DNJ. Leprosy type 1 reactions and erythema nodosum leprosum. An Bras Dermatol. 2008;83:75–82. [Google Scholar] [Ref list]
43. Nery JAC, Sales AM, Illarramendi X, Duppre NC, Jardim MR, Machado AM. Contribuição ao diagnóstico e manejo dos estados reacionais: Uma abordagem prática. An bras dermatol. 2006;81(4):367–375. [Google Scholar] [Ref list]
44. Garbino JA. O paciente com suspeita de hanseníase primariamente neural / The patient with suspicion of primarily neural leprosy. Hansen Int. 2007;32:203–206. [Google Scholar] [Ref list]
45. Lewallen S, Tungpakorn NC, Kim SH, Courtright P. Progression of eye disease in "cured" leprosy patients: implications for understanding the pathophysiology of ocular disease and for addressing eyecare needs. Br J Ophthalmol. 2000;84:817–821. [PMC free article] [PubMed] [Google Scholar] [Ref list]
46. Meneses S, Cirelli NM, Aranzazu N, Rondon Lugo AJ. Lepra visceral: presentacion de dos casos y revision de la literatura. Dermatol Venez. 1988;26:79–84. [Google Scholar] [Ref list]
47. Klioze AM, Ramos-Caro FA. Visceral leprosy. Int J Dermatol. 2000;39:641–658. [PubMed] [Google Scholar] [Ref list]
2. Cavaliere IAL, Costa SG. Isolamento social, sociabilidades e redes sociais de cuidados. Physis. 2011;21:491–516. [Google Scholar] [Ref list]
3. Opromolla PA, Martelli ACC. Terminology related to Hansen's disease. An Bras Dermatol. 2005;80:293–294. [Google Scholar] [Ref list]
4. Global leprosy situation, 2012.Wkly Epidemiol Rec. 2012 Aug 24; 87(34):317-28.[PubMed] [Ref list]
5. Talhari S, Grossi MA, Oliveira ML, Gontijo B, Talhari C, Penna GO
6. Mem Inst Oswaldo Cruz. 2012 Dec; 107 Suppl 1():13-6. [PubMed] [Ref list]
7. Barbieri CL, Marques HH. Leprosy in children and adolescents: bibliographical review and current situation in Brazil. Pediatria (São Paulo) Pediatria (São Paulo) 2009;31:281–290. [Google Scholar] [Ref list]
8. Ignotti E, Rodrigues AM, Andrade VLG, Valente JG. Aplicação de métodos de estimativa da prevalência de hanseníase no Estado de Mato Grosso. Rev Bras Epidemiol. 2004;7:155–166. [Google Scholar] [Ref list]
9. Paho.org. World Health Organization . Elimination of leprosy as a public health problem. Leprosy Resolution WHA 44.9, 44th World Health Assembly. Geneva: 1991. [cited 2012 oct 19]. [homepage on the internet] Available from: http://www.paho.org/English/AD/DPC/CD/lep-wha-1991.htm. [Google Scholar] [Ref list]
10. Rees RJW, Young DB. The microbiology of leprosy. In: Hastings RC, editor. Leprosy. 2nd ed. New York: Churchill Livingstone; 1994. pp. 49–83. [Google Scholar] [Ref list]
11. Desikan KV Lepr Rev. 1977 Dec; 48(4):231-5.[PubMed] [Ref list]
12. Hirata T Int J Lepr Other Mycobact Dis. 1985 Sep; 53(3):433-40. [PubMed] [Ref list]
13. Vissa VD, Brennan PJ Genome Biol. 2001; 2(8):REVIEWS1023.[PubMed] [Ref list]
14. Bona SH, Fonseca APM, Silva ACL, Costa RJ. Bacilos álcool-ácido resistentes no Culex fatigans. An Bras Dermatol. 1985;60:163–170. [Google Scholar] [Ref list]
15. Job CK. Nasal mucosa and abraded skin are the two routes of entry of Mycobacterium leprae. Star. 1990;49:1. [Google Scholar] [Ref list]
16. Pedley JC Lepr Rev. 1967 Oct; 38(4):239-42. [PubMed] [Ref list]
17. Cree IA, Smith WC Lepr Rev. 1998 Jun; 69(2):112-21. [PubMed] [Ref list]
18. Moet FJ, Meima A, Oskam L, Richardus JH Lepr Rev. 2004 Dec; 75(4):310-26. [PubMed] [Ref list]
19. Prevedello FC, Mira MT. Leprosy: a genetic disease? An Bras Dermatol. 2007;82:451–459. [Google Scholar] [Ref list]
20. Alcais A, Alter A, Antoni G, Orlova M, Nguyen VT, Singh M, et al. Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy. Nat Genet. 2007;39:517–522. [PubMed] [Google Scholar] [Ref list]
21. Roy S, McGuire W, Mascie-Taylor CG, Saha B, Hazra SK, Hill AV, et al. Tumor necrosis factor promoter polymorphism and susceptibility to lepromatous leprosy. J Infect Dis. 1997;176:530–532. [PubMed] [Google Scholar] [Ref list]
22. Sarno EN, Santos AR, Jardim MR, Suffys PN, Almeida AS, Nery JA, et al. Pathogenesis of nerve damage in leprosy: genetic polymorphism regulates the production of TNF? Lepr Rev. 2000;71:S154–S158. [PubMed] [Google Scholar] [Ref list]
23. Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, et al. Genomewide association study of leprosy. N Engl J Med. 2009;361:2609–2618. [PubMed] [Google Scholar] [Ref list]
24. Roy S, Frodsham A, Saha B, Hazra SK, Mascie-Taylor CG, Hill AV. Association of vitamin D receptor genotype with leprosy type. J Infect Dis. 1999;179:187–191. [PubMed] [Google Scholar] [Ref list]
25. Bochud PY, Hawn TR, Siddiqui MR, Saunderson P, Britton S, Abraham I, et al. Tolllike receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. J Infect Dis. 2008;197:253–261. [PMC free article] [PubMed] [Google Scholar] [Ref list]
26. Scollard DM, Adams LB, Gillis TP, Krahenbuhl JL, Truman RW, Williams DL. The continuing challenges of leprosy. Clin Microbiol Rev. 2006;19:338–381. [PMC free article] [PubMed] [Google Scholar] [Ref list]
27. Mendonça VA, Costa RD, Melo GEBA, Antunes CM, Teixeira AL. Immunology of leprosy. An Bras Dermatol. 2008;83:343–350. [Google Scholar] [Ref list]
28. Oliveira MLW, Cavaliére FAM, Maceira JMP, Bührer-Sékula S. The use of serology as an additional tool to support diagnosis of difficult multibacillary leprosy cases: lessons from clinical care. Rev Soc Bras Med Trop. 2008;41:27–33. [PubMed] [Google Scholar] [Ref list]
29. Modlin RL, Melancon-Kaplan J, Young SM, Pirmez C, Kino H, Convit J, et al. Learning from lesions: patterns of tissue inflammation in leprosy. Proc Natl Acad Sci U S A. 1988;85:1213–1217. [PMC free article] [PubMed] [Google Scholar] [Ref list]
30. Sieling PA, Abrams JS, Yamamura M, Salgame P, Bloom BR, Rea TH, et al. Immunosuppressive roles for IL-10 and IL-4 in human infection: In vitro modulation of T cell responses in leprosy. J Immunol. 1993;150:5501–5510. [PubMed] [Google Scholar] [Ref list]
31. Silva CL, Foss NT. Tumor necrosis factor in leprosy patients. J Infect Dis. 1989;159:787–790. [PubMed] [Google Scholar] [Ref list]
32. Warwick-Davies J, Lowrie DB, Cole PJ. Selective deactivation of human monocyte functions by TGF-beta. J Immunol. 1995;155:3186–3193. [PubMed] [Google Scholar] [Ref list]
33. Hsieh CS, Macatonia SE, Tripp CS, Wolf SF, O'Garra A, Murphy KM. Development of Th1 CD4+ T-cells through IL-12 produced by Listeria-induced macrophages. Science. 1993;260:547–549. [PubMed] [Google Scholar] [Ref list]
34. Sieling PA, Modlin RL. Cytokine patterns at the site of mycobacterial infection. Immunobiology. 1994;191:378–387. [PubMed] [Google Scholar]
35. Foss NT. Aspectos imunológicos da hanseníase. Medicina (Ribeirão Preto) 1997;30:335–339. [Google Scholar] [Ref list]
36. Rabello FE., Júnior Uma classificação clínico-epidemiológica das formas de lepra. Rev Bras Leprol. 1936:375–410. [Google Scholar] [Ref list]
37. Ridley DS, Jopling WH. Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 1966;34:255–273. [PubMed] [Google Scholar] [Ref list]
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