Archives of Dermatological Research

, Volume 300, Issue 6, pp 269–290

Leprosy: diagnostic and control challenges for a worldwide disease

  • Isabela Maria Bernardes Goulart
  • Luiz Ricardo Goulart
Review Article

Abstract

Leprosy is a curable disease with well-defined etiology, but lacks better diagnostic tools, preventive and therapeutic strategies. The continued application of the Ridley–Jopling clinical classification that recognizes the natural diversity of the immune response has provided the basis for understanding leprosy, and this review proposes its implementation in all Reference Centers in order to standardize the diagnostic resources, aiming at the improvement of the disease control. Due to the broad bioepidemiological aspects of infection its eradication is difficult, and proper diagnosis of the disease and the correct clinical classification are required to ensure proper treatment. Tools and markers for diagnosis and prognosis, and the novel use of nanotechnology, as well as strategies for disease control and monitoring populations at higher risk are still continuous challenges, which will be specifically reviewed with additional insights. The use of the current diagnostic tools, such as ELISA and PCR has a very limited approach for leprosy that has been considered as a marginal disease; therefore, the current diagnostic tools must be applied extensively in the routine to accumulate clinical experience in order to improve their precise application, like what has been done in many other infectious diseases. Since a vaccine for leprosy presents an unpredictable future, the proposed chemoprophylaxis of contacts (healthy carriers and/or with subclinical infection) must also be employed in referral centers of endemic countries not only to evaluate its efficacy, but also because of the favorable cost–benefit ratio, given that there is no other available approach, besides the multi-drug therapy of patients. This strategy should readily be applied as a public health policy, and may lead to a substantial breakage of the transmission chain aiming a world without leprosy.

Keywords

Leprosy Molecular epidemiology Diagnostic tools Monitoring strategies Clinical classification Serological assays PCR tests 

References

  1. 1.
    Adams E, Britton W, Morgan A, Sergeantson S, Basten A (1994) Individuals from different populations identify multiple and diverse determinants of mycobacterial HSP70. Scand J Immunol 39:588–596PubMedGoogle Scholar
  2. 2.
    Afonso AS, Goulart LR, Moura M, Goulart IMB, Madurro JM, Brito-Madurro AG (2007) Detection of Mycobacterium leprae DNA onto graphite for leprosy diagnostics. In: International congress of nanotechnology 2007, San Francisco, CA, USA, pp 1–2Google Scholar
  3. 3.
    Agger EM, Brock I, Okkels LM, Arend SM, Aagaard CS, Weldingh KN, Andersen P (2003) Human T cell responses to the RDl-encoded protein TB27.4 (Rv3878) from Mycobacterium tuberculosis. Immunology 110:507–512PubMedGoogle Scholar
  4. 4.
    Andersen P, Munk ME, Pollock JM, Doherty TM (2000) Specific immune-based diagnosis of tuberculosis. Lancet 356:1099–1104PubMedGoogle Scholar
  5. 5.
    Anderson DC, Van Schooten WCA, Barry ME, Janson AAM, Buchanan TM, De Vries RRP (1988) A Mycobacterium leprae-specific human T cell epitope cross reactive with an HLA-DR2 peptide. Science 242:259–261PubMedGoogle Scholar
  6. 6.
    Aráoz R, Honore N, Cho S, Kim JP, Cho SN, Monot M, Demangel C, Brennan PJ, Cole ST (2006) Antigen discovery: a postgenomic approach to leprosy diagnosis. Infect Immun 74:175–182PubMedGoogle Scholar
  7. 7.
    Aráoz R, Honoré N, Banu S, Demangel C, Cissoko Y, Arama C, Uddin MK, Hadi SK, Monot M, Cho SN, Ji B, Brennan PJ, Sow S, Cole ST (2006) Towards an immunodiagnostic test for leprosy. Microbes Infect 8:2270–2276PubMedGoogle Scholar
  8. 8.
    Araújo S, Goulart IMB, Cardoso AM, Marangoni K, Nunes MM, Santos FAA, Goulart LR (2006) Detecção por PCR de infecção pelo Mycobacterium leprae em amostras de sangue de pacientes com hanseníase e seus contatos em Uberlândia MG. In: Resumos do 12º Congresso de La Associación Latinoamericana de Genética e do 52º Congresso Brasileiro de Genética, Foz do Iguaçu, PR. Sociedade Brasileira de Genética, Ribeirão Preto, SP, Brazil, p 635Google Scholar
  9. 9.
    Arend SM, Andersen P, van Meijgaarden KE, Skjot RL, Subronto YW, van Dissel JT, Ottenhoff THM (2000) Detection of active tuberculosis infection by T cell responses to earlysecreted antigenic target 6-kDa protein and culture filtrate protein 10. J Infect Dis 181:1850–1854PubMedGoogle Scholar
  10. 10.
    Bakker MI, Hatta M, Kwenang A, Faber WR, Van Beers SM, Klatser PR, Oskam L (2004) Population survey to determine risk factors for Mycobacterium leprae transmission and infection. Int J Epidemiol 33:1329–1336PubMedGoogle Scholar
  11. 11.
    Bathia AS, Katoch K, Narayanan RB, Ramu G, Mukherjee A, Lavania RK (1993) Clinical and histopathological correlation in the classification of leprosy. Int J Lepr Other Mycobact Dis 61:433–438Google Scholar
  12. 12.
    Baumgart KW, Britton WJ, Mullins RJ, Basten A, Barnetson RS (1993) Subclinical infection with Mycobacterium leprae—a problem for leprosy control strategies. Trans R Soc Trop Med Hyg 87:412–415PubMedGoogle Scholar
  13. 13.
    Beneditti PF, Anderson MW, Masseli R, Rogero GW (1994) Hypertrophic peripheral neuropathy due to leprosy. J Comput Assist Tomogr 18:995–996CrossRefGoogle Scholar
  14. 14.
    Bezerra Da Cunha FM, Werneck MC, Scola RH, Werneck LC (2006) Pure neural leprosy: diagnostic value of the polymerase chain reaction. Muscle Nerve 33:409–414PubMedGoogle Scholar
  15. 15.
    Brahmbhatt S, Hussain R, Zafar S, Dawood G, Ottenhoff TH, Drijfhout JW, Bothamley G, Smith S, Lopez FV, Dockrell HM (2002) Human T cell responses to peptides of the Mycobacterium leprae 45-kD serine-rich antigen. Clin Exp Immunol 128:140–148PubMedGoogle Scholar
  16. 16.
    Brasil-Neto JP (1992) Electrophysiologic studies in leprosy. Arq Neuropsiquiatr 50:313–318PubMedGoogle Scholar
  17. 17.
    Brenan P (2000) Skin test development in leprosy: progress with first-generation skin test antigens, and an approach to the second generation. Lepr Rev 71:S50–S54Google Scholar
  18. 18.
    Brito-Madurro AG, Franco L, Nunes S, Ariza RG, Goulart Filho LR, Madurro JM (2006) Immobilization of purine bases on a poly-4-aminophenol matrix. J Mater Sci 42:3238–3243Google Scholar
  19. 19.
    Brock L, Weldingh K, Leyten EM, Arend SM, Ravn P, Andersen P (2004) Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection. J Clin Microbiol 42:2379–2387PubMedGoogle Scholar
  20. 20.
    Buhrer S, Smits HL, Gussenhoven GC, Van Ingen CW, Klatser PR (1998) A simple dipstick for the detection of antibodies to phenolic glycolipid-1 of Mycobacterium leprae. Int J Trop Med Hyg 58:133–136Google Scholar
  21. 21.
    Buhrer-Sekula S, Smits HL, Gussenhoven GC, van Leeuwen J, Amador S, Fujiwara T, Klatser PR, Oskam L (2003) Simple and fast lateral flow test for classification of leprosy patients and identification of contacts with high risk of developing leprosy. J Clin Microbiol 41:1991–1995PubMedGoogle Scholar
  22. 22.
    Butlin CR, Soares D, Neupane KD, Failbus SS, Roche PW (1997) IgM anti-phenolic glycolipid-1 antibody measurements from skin-smear sites: correlation with venous antibody levels and bacterial index. Int J Lepr Other Mycobact Dis 65:465–468PubMedGoogle Scholar
  23. 23.
    Cabalier MED, Pérez HJ (1995) 22 años de lepra: histopatología. Rev Fac Cienc Med 53:17–21Google Scholar
  24. 24.
    Cambau E, Sougakoff W, Besson M, Truffot-Pernot C, Grosset J, Jarlier V (1994) Selection of a gyrA mutant of Mycobacterium tuberculosis resistant to fluoroquinolones during treatment with ofloxacin. J Infect Dis 170:479–483PubMedGoogle Scholar
  25. 25.
    Cambau E, Jarlier V (1996) Resistance to quinolones in mycobacteria. Res Microbiol 147:52–59PubMedGoogle Scholar
  26. 26.
    Cambau E, Perani E, Guillemin I, Jamet P, Ji B (1997) Multidrug resistance to dapsone, rifampicin and ofloxacin in Mycobacterium leprae. Lancet 349:103–104PubMedGoogle Scholar
  27. 27.
    Caparo AC (1989) Aspectos histológicos de la lepra en diferentes regiones del Peru. OPS, p 22Google Scholar
  28. 28.
    Capparelli FE, Oliveira JDD, Marangoni K, Goulart IMB, Goulart LR (2005) Desenvolvimento de mimetopos protéicos de PGL-1 imunorreativos contra soro de pacientes com hanseníase. Hansenol Int 30:120Google Scholar
  29. 29.
    Cellona RV, Walsh GP, Fajardo TT, Abalos RM, de la Cruz EC, Guido-Villahermosa L, Felicio-Balagon MV, Steenbergen GJ, Douglas JT (1993) Cross-sectional assessment of ELISA-reactivity in leprosy patients, contacts and normal population using the semisynthetic antigen natural disaccharide octyl bovine serum albumin (ND-O-BSA) in Cebu, The Philippines. Int J Lepr Other Mycobact Dis 61:192–198PubMedGoogle Scholar
  30. 30.
    Chae GT, Kim MJ, Kang TJ, Lee SB, Shin HK, Kim JP, Ko YH, Kim SH, Kim NH (2002) DNA-PCR and RT-PCR for the 18-kDa gene of Mycobacterium leprae to assess the efficacy of multi-drug therapy for leprosy. J Med Microbiol 51:417–422PubMedGoogle Scholar
  31. 31.
    Chaturvedi V, Girdhar BK, Sengupta U, Sinha S (2007) Semi-quantitative detection of Mycobacterium leprae antigens in skin scrapings: suitability as a laboratory aid for field diagnosis of leprosy. Trans R Soc Trop Med Hyg 101:699–706PubMedGoogle Scholar
  32. 32.
    Chaudhuri S, Hajra SK, Mukherjee A, Saha B, Mazumder B, Chattapadhya D, Saha K (1998) Why relapse occurs in PB leprosy patients after adequate MDT despite they are Mitsuda reactive: lessons form Convit’s experiment on bacteria-clearing capacity of lepromin-induced granuloma. Int J Lepr Other Mycobact Dis 66:182–189PubMedGoogle Scholar
  33. 33.
    Chimelli L, Freitas M, Nascimento O (1997) Value of nerve biopsy in the diagnosis and follow-up of leprosy: the role of vascular lesions and usefulness of studies in the detection of persistent bacilli. J Neurol 244:318–323PubMedGoogle Scholar
  34. 34.
    Chedore P, Broukhanski G, Shainhouse Z, Jamieson F (2006) False-positive amplified Mycobacterium Tuberculosis Direct Test results for samples containing Mycobacterium leprae. J Clin Microbiol 44:612–613PubMedGoogle Scholar
  35. 35.
    Chemouilli P, Woods S, Said G, Cole ST (1996) Detection of Mycobacterium leprae in nerve lesions by the polymerase chain reaction. Int J Lepr Other Mycobact Dis 64:1–5PubMedGoogle Scholar
  36. 36.
    Cho SN, Shin JS, Choi IH, Kim SH, Kim DI, Kim JD (1988) Detection of phenolic glycolipid I of Mycobacterium leprae and antibodies to the antigen in sera from leprosy patients and their contacts. Yonsei Med J 29:219–224PubMedGoogle Scholar
  37. 37.
    Cho SN, Kim SH, Cellona RV, Chan JP, Fajardo TT, Walsh GP, Kim JD (1992) Prevalence of IgM antibodies to phenolic glycolipid I among household contacts and controls in Korea and the Philippines. Lepr Rev 63:12–20PubMedGoogle Scholar
  38. 38.
    Cho SN, Cellona RV, Villahermosa LG, Fajardo TT, Balagon MV Jr, Abalos RM, Tan EV, Walsh GP, Kim JD, Brennan PJ (2001) Detection of phenolic glycolipid I of Mycobacterium leprae in sera from leprosy patients before and after start of multidrug therapy. Clin Diagn Lab Immunol 8:138–142PubMedGoogle Scholar
  39. 39.
    Cree IA, Smith CS (1998) Leprosy transmission and mucosal immunity: towards eradication? Lepr Rev 69:112–121PubMedGoogle Scholar
  40. 40.
    Cree IA, Srinivasan T, Krishnan SA, Gardiner CA, Mehta J, Fisher CA, Beck JS (1988) Reproducibility of histology in leprosy lesions. Int J Lepr Other Mycobact Dis 56:296–301PubMedGoogle Scholar
  41. 41.
    Collings AF, Caruso F (1997) Biosensors: recent advances. Rep Prog Phys 60:1397–1145Google Scholar
  42. 42.
    Convit J, Sampson C, Zuniga M, Smith PG, Plata J, Silva J, Molina J, Pinardi ME, Bloom BR, Salgado A (1992) Immunoprophylactic trial with combined Mycobacterium leprae/BCG vaccine against leprosy: preliminary results. Lancet 339:446–450PubMedGoogle Scholar
  43. 43.
    Convit J, Smiths PG, Zuniga M, Sampson C, Ulrich M, Plata JA, Silva J, Molina J, Salgado A (1993) BCG vaccination protects against leprosy in Venezuela: a case-control study. Int J Lepr Other Mycobact Dis 62:185–191Google Scholar
  44. 44.
    Cunanan A, Chan GP, Douglas JT (1998) Risk of development of leprosy among Culion contacts. Int J Lepr Other Mycobact Dis 66:78AGoogle Scholar
  45. 45.
    Cunha FMB (1990) Forma neural pura na hanseníase. Arq Neuropsiquiatr 48(Suppl):134Google Scholar
  46. 46.
    Dayal R, Singh SP, Mathur PP, Katoch VM, Katoch K, Natrajan M (2005) Diagnostic value of in situ polymerase chain reaction in leprosy. Indian J Pediatr 72:1043–1046PubMedGoogle Scholar
  47. 47.
    de Wit MYL, Faber WR, Krieg SR, Douglas JT, Lucas SB, Montreewasuwat N, Pattyn SR, Hussain R, Ponnighaus JM, Hartskeerl RA, Klatser PR (1991) Application of the polymerase chain reaction for the detection of Mycobacterium leprae in skin tissues. J Clin Microbiol 29:906–910PubMedGoogle Scholar
  48. 48.
    de Wit MYL, Douglas JT, McFadden J, Klatser PR (1993) Polymerase chain reaction for detection of Mycobacterium leprae in nasal swab specimes. J Clin Microbiol 31:502–506PubMedGoogle Scholar
  49. 49.
    DeFaria CR, Silva IM (1990) Electromyographic diagnosis of leprosy. Arq Neuropsiquiatr 48:403–413PubMedGoogle Scholar
  50. 50.
    Dockrell HM, Stoker NG, Lee SP, Jackson M, Grant KA, Jouy NF, Lucas SB, Hasan R, Hussain R, McAdam KPWJ (1989) T-cell recognition of the 18-kilodalton antigen of Mycobacterium leprae. Infect Immun 57:1979–1983PubMedGoogle Scholar
  51. 51.
    Dockrell HM, Brahmbhatt S, Robertson BD, Britton S, Fruth U, Gebre N, Hunegnaw M, Hussain R, Manandhar R, Murillo RL, Pessolani MCV, Roche P, Salgado JL, Sampaio EP, Shahid F, Thole JER, Young DB (2000) A postgenomic approach to identification of Mycobacterium leprae-specific peptides as T-cell reagents. Infect Immun 68:5846–5855PubMedGoogle Scholar
  52. 52.
    Donoghue HD, Holton J, Spigelman M (2001) PCR primers that can detect low levels of Mycobacterium leprae DNA. J Med Microbiol 50:177–182PubMedGoogle Scholar
  53. 53.
    Douglas JT, Cellona RV, Abalos RM, Madarang MG, Fajardo T (1987) Serological reactivity and early detection of leprosy among contacts of lepromatous patients in Cebu, the Philippines. Int J Lepr Other Mycobact Dis 55:718–721PubMedGoogle Scholar
  54. 54.
    Douglas JT, Cellona RV, Fajardo TT Jr, Abalos RM, Balagon MVF, Klatser PR (2004) Prospective study of serological conversion as a risk factor for development of leprosy among household contacts. Clin Diagn Lab Immunol 11:897–900PubMedGoogle Scholar
  55. 55.
    Dubey GK, Joglekar VK, Grover S, Chaubey BS (1981) Correlation of clinical and histopathological studies in classification leprosy. Lepr India 53:562–565PubMedGoogle Scholar
  56. 56.
    Ebenezer GJ, Suneetha S, Mohandas R, Arunthathi S (1996) Multibacillary nerve histology in clinical diagnosed borderline tuberculoid leprosy patients. Int J Lepr Other Mycobact Dis 64:311–315PubMedGoogle Scholar
  57. 57.
    Ferreira FR, Goulart LR, Silva HD, Goulart IMB (2004) Susceptibility to leprosy may be conditioned by an interaction between the NRAMP1 promoter polymorphisms and the lepromin response. Int J Leprosy Other Mycobact Dis 72:457–467Google Scholar
  58. 58.
    Fiallo P, Williams DL, Chan JP, Gillis TP (1992) Effects of fixation on polymerase chain reaction detection of Mycobacterium leprae. J Clin Microbiol 30:3095–3098PubMedGoogle Scholar
  59. 59.
    Fine PE, Job CK, Lucas SB, Meyers WM, Pönnighaus JM, Sterne JA (1993) Extent, origin, and implications of observer variation in the histopathological diagnosis of suspected leprosy. Int J Lepr Other Mycobact Dis 61:270–282PubMedGoogle Scholar
  60. 60.
    Fine PE, Sterne JA, Ponninghaus JM, Bliss L, Saul J, Chihana A, Munthali M, Warndorff DK (1997) Household and dwelling contact as risk factors for leprosy in northern Malawi. Am J Epidemiol 146:91–102PubMedGoogle Scholar
  61. 61.
    Freitas RG, Nascimento O, Drago MJ, Freitas AR, Hahn MD (1998) Paralisia de nervo ulnar na lepra sem alterações cutâneas: biópsia do ramo superficial do nervo ulnar na mão. Arq Neuropsiquiatr 56:585–594PubMedGoogle Scholar
  62. 62.
    Freitas MRG, Nascimento OJM, Quaglino EAM, Oliveira A, Hahn MD (2003) Small-fiber polyneuropathy in leprosy without skin changes. Study of 17 cases. Arq Neuropsiquiatr 61:542–546PubMedGoogle Scholar
  63. 63.
    Freitas MRG, Nascimento OJM, Freitas MR, Hahn MD (2004) Isolated superficial peroneal nerve lesion in pure neural leprosy. Case report. Arq Neuropsiquiatr 62:535–539PubMedGoogle Scholar
  64. 64.
    Geluk A, van Meijgaarden KE, Franken KLMC, Subronto YW, Wieles B, Arend SM, Sampaio EP, De Boer T, Faber WR, Naafs B, Ottenhoff THM (2002) Identification and characterization of the ESAT-6 homologue of Mycobacterium leprae and T cell cross reactivity with Mycobacterium tuberculosis. Infect Immun 70:2544–2548PubMedGoogle Scholar
  65. 65.
    Geluk A, van Meijgaarden KE, Franken KLMC, Wieles B, Arend SM, Faber WR, Naafs B, Ottenhoff THM (2004) Immunological cross reactivity of the Mycobacterium leprae CFP-10 with its homologue in Mycobacterium tuberculosis. Scand J Immunol 59:66–70PubMedGoogle Scholar
  66. 66.
    Geluk A, Klein MR, Franken KLMC, van Meijgaarden KE, Wieles B, Pereira KC, Buhrer-Sekula S, Klatser PR, Brennan PJ, Spencer JS, Williams DL, Pessolani MCV, Sampaio EP, Ottenhoff THM (2005) A postgenomic approach to identify novel antigens of Mycobacterium leprae for improved immunodiagnosis of M. leprae infection. Infect Immun 73:5636–5644PubMedGoogle Scholar
  67. 67.
    Geluk A, van der Ploeg J, Teles ROB, Franken KLMC, Prins C, Drijfhout JW, Sarno EN, Sampaio EP, Ottenhoff THM (2008) Rational combination of peptides derived from different Mycobacterium leprae proteins improves sensitivity for immunodiagnosis of M. leprae infection. Clin Vaccine Immunol 15:522–533PubMedGoogle Scholar
  68. 68.
    Girdhar BK (1996) Neuritic leprosy. Indian J Lepr 68:35–42PubMedGoogle Scholar
  69. 69.
    Gonzalez-Abreu E, Mora N, Perez M, Pereira M, Perez J, Gonzalez AB (1990) Serodiagnosis of leprosy in patients’ contacts by enzyme linked immunosorbent assay. Lepr Rev 61:145–150PubMedGoogle Scholar
  70. 70.
    Gonzalez-Martinez MA, Puchades R, Maquieira A (1999) On-line immunoanalysis for environmental pollutants: from batch assay to automated sensors. Trends Analyt Chem 18:204–218Google Scholar
  71. 71.
    Goulart IMB, Figueiredo F, Coimbra T, Foss NT (1996) Detection of transforming growth factor-beta 1 in dermal lesions of different clinical forms of leprosy. Am J Pathol 148:911–917PubMedGoogle Scholar
  72. 72.
    Goulart IMB, Ferreira FR, Goulart LR, Pinheiro CA, Borges DS, Cunha G (2001) Detection of Mycobacterium leprae by PCR in nasal and buccal mucosae in leprosy patients and household contacts. Int J Leprosy Other Mycobact Dis 69:S230Google Scholar
  73. 73.
    Goulart IMB, Cardoso AM, Santos MS, Gonçalves MA, Pereira JE, Goulart LR (2007) Detection of Mycobacterium leprae DNA in skin lesions of leprosy patients by PCR may be affected by amplicon size. Arch Dermatol Res 299:267–271PubMedGoogle Scholar
  74. 74.
    Goulart IMB, Bernardes Souza DO, Marques CR, Pimenta VL, Gonçalves MA, Goulart LR (2008) Risk and protective factors for leprosy development in an epidemiological surveillance of household contacts. Clin Vaccine Immunol 15:101–105PubMedGoogle Scholar
  75. 75.
    Groathouse NA, Amin A, Marques MAM, Spencer JS, Gelber R, Knudson DL, Belisle JT, Brennan PJ, Slayden RA (2006) Use of protein microarrays to define the humoral immune response in leprosy patients and identification of disease-state specific antigenic profiles. Infect Immun 74:6458–6466PubMedGoogle Scholar
  76. 76.
    Groathouse NA, Brown SE, Knudson DL, Brennan PJ, Slayden RA (2006) Isothermal amplification and molecular typing of the obligate intracellular pathogen Mycobacterium leprae isolated from tissues of unknown origin. J Clin Microbiol 44:1502–1508PubMedGoogle Scholar
  77. 77.
    Haile Y, Ryon JJ (2004) Colorimetric microtitre plate hybridization assay for the detection of Mycobacterium leprae 16S rRNA in clinical specimens. Lepr Rev 75:40–49PubMedGoogle Scholar
  78. 78.
    Harboe M (1985) The immunology of leprosy. In: Hastings RC (ed) Leprosy. Churchill Livingstone, Edinburgh, pp 53–87Google Scholar
  79. 79.
    Hardas U, Lele V (1981) Evaluation of fluorescent microscopy for detection of Mycobacterium leprae. Lepr India 53:273–277PubMedGoogle Scholar
  80. 80.
    Hari S, Subramanian S, Sharma R (2007) Magnetic resonance imaging of ulnar nerve abscess in leprosy: a case report. Lepr Rev 78:155–159PubMedGoogle Scholar
  81. 81.
    Hatta M, van Beers SM, Madjid B, Djumadi A, de Wit MY, Klatser PR (1995) Distribution and persistence of Mycobacterium leprae nasal carriage among a population in which leprosy is endemic in Indonesia. Trans R Soc Trop Med Hyg 89:381–385PubMedGoogle Scholar
  82. 82.
    Hong JC, Yi HC, See YC, Jin BL, Chang CY (2003) Peripheral nerve lesions: role of high-resolution US. Radiographics 23:e15Google Scholar
  83. 83.
    Honoré N, Perrani E, Telenti A, Grosset J, Cole ST (1993) A simple and rapid technique for the detection of rifampin resistance in Mycobacterium leprae. Int J Lepr 61:600–604Google Scholar
  84. 84.
    Hunter SW, Rivoire B, Mehra V, Bloom BR, Brennan PJ (1990) The major native proteins of the leprosy bacillus. J Biol Chem 265:14065–14068PubMedGoogle Scholar
  85. 85.
    Hussain R, Shahid F, Zafar S, Dojki M, Dockrell HM (2004) Immune profiling of leprosy and tuberculosis patients to 15-mer peptides of Mycobacterium leprae and M. tuberculosis GroES in a BCG vaccinated area: implications for development of vaccine and diagnostic reagents. Immunology 111:462–471PubMedGoogle Scholar
  86. 86.
    Innis MA, Gelfand DH, Sninsky JJ, White TJ (1990) PCR: a guide to methods and applications. I. Optimization of PCRs. In: Innis MA, Gelfand DH, Sninsky JJ, White TJ (eds) Academic Press, San Diego, pp 3–12Google Scholar
  87. 87.
    International Leprosy Association Technical Forum (2002) Report of the International Leprosy Association Technical Forum. The diagnosis and classification of leprosy. Int J Lepr Other Mycobact Dis 70:S23–S31Google Scholar
  88. 88.
    Izumi S, Budiawan T, Saeki K, Matsuoka M, Kawatsu K (1999) An epidemiological study on Mycobacterium leprae infection and prevalence of leprosy in endemic villages by molecular biological technique. Indian J Lepr 71:37–43PubMedGoogle Scholar
  89. 89.
    Jacobson RR, Hastings RC (1976) Rifampin-resistant leprosy. Lancet 2:1304–1305PubMedGoogle Scholar
  90. 90.
    Jain KK (2003) Nanodiagnostics: application of nanotechnology in molecular diagnostics. Expert Rev Mol Diagn 3:153–161PubMedGoogle Scholar
  91. 91.
    Jain KK (2005) Nanotechnology in clinical laboratory diagnostics. Clin Chim Acta 358:37–54PubMedGoogle Scholar
  92. 92.
    Jamal MA, Maeda S, Nakata N, Kai M, Fukuchi K, Kashiwabara Y (2000) Molecular basis of clarithromycin-resistance in Mycobacterium avium–intracellulare complex. Tuber Lung Dis 80:1–4PubMedGoogle Scholar
  93. 93.
    Jardim MR, Antunes SL, Simons B, Wildenbeest JG, Nery JA, Illarramendi X, Moraes MO, Martinez AN, Oskam L, Faber WR, Sarno EN, Sampaio EP, Bührer-Sékula S (2005) Role of PGL-I antibody detection in the diagnosis of pure neural leprosy. Lepr Rev 76:232–240PubMedGoogle Scholar
  94. 94.
    Jardim MR, Chimelli L, Faria SCR, Fernandes PV, Néri JAC, Sales AM, Sarno EM, Antunes SLG (2004) Clinical, electroneuromyographic and morfological studies of pure neural leprosy in a Brazilian referral centre. Lepr Rev 75:242–253PubMedGoogle Scholar
  95. 95.
    Jebaraj I, Rao A, Shyamkumar NK, Vidyasagar NK (2005) Imaging of tender neuropathy in leprosy. Ind J Lepr 77:51–54Google Scholar
  96. 96.
    Jerath VP, Desai SR (1982) Diversities in clinical and histopathological classification of leprosy. Lepr India 54:130–134PubMedGoogle Scholar
  97. 97.
    Ji B, Perani EG, Petinom C, Grosset JH (1996) Bactericidal activities of combinations of new drugs against Mycobacterium leprae in nude mice. Antimicrob Agents Chemother 40:393–399PubMedGoogle Scholar
  98. 98.
    Job CK, Baskaran B, Jayakumar J, Aschoff M (1997) Histopathologic evidence to show that indeterminate leprosy may be a primary lesion of the disease. Int J Lepr Other Mycobact Dis 65:443–449PubMedGoogle Scholar
  99. 99.
    Job CK, Jayakumar J, Williams DL, Gillis TP (1997) Role of polymerase chain reaction in the diagnosis of early leprosy. Int J Lepr Other Mycobact Dis 65:461–464PubMedGoogle Scholar
  100. 100.
    Job CK, Jayakumar J, Kearney M, Gillis TP (2008) Transmission of leprosy: a study of skin and nasal secretions of household contacts of leprosy patients using PCR. Am J Trop Med Hyg 78:518–521PubMedGoogle Scholar
  101. 101.
    Julião OF (1963) As manifestações neurológicas da lepra. Rev Med 47:63–71Google Scholar
  102. 102.
    Kai M., Matsuoka M, Nakata N, Maeda S, Gidoh M, Maeda Y, Hashimoto K, Kobayashi K, Kashiwabara Y (1999) Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene. FEMS Microbiol Lett 177:231–235PubMedGoogle Scholar
  103. 103.
    Kalla G, Salodkar A, Kachhawa D (2000) Clinical and histopathological correlation in leprosy. Int J Lepr Other Mycobact Dis 68:184–185PubMedGoogle Scholar
  104. 104.
    Kampirapap K, Singtham N, Klaster P, Wirivawipart S (1998) DNA amplification for detection of leprosy and assessment of efficacy of leprosy chemotherapy. Int J Lepr Other Mycobact Dis 66:16–21PubMedGoogle Scholar
  105. 105.
    Kang TJ, Kim SK, Lee SB, Chae GT, Kim JP (2003) Comparison of two different amplification products (the 18-kDa protein gene vs. RLEP repetitive sequence) in the diagnosis of Mycobacterium leprae. Clin Exp Dermatol 28:420–424PubMedGoogle Scholar
  106. 106.
    Kaur G, Girdhar B, Girdhar A, Malaviya GN, Mukherjee A, Sengupta U, Desikan KV (1991) A clinical, immunological and histological study of neuritic leprosy patients. Int J Lepr Other Mycobact Dis 59:385–391PubMedGoogle Scholar
  107. 107.
    Kaur S, Sharma VK, Basak P, Kaur I, Radotra BD (1993) Concurrent skin and nerve histology in leprosy and its role in the classification of leprosy. Lepr Rev 64:110–116PubMedGoogle Scholar
  108. 108.
    Kent L, McHugh TD, Billigton O, Dale JW, Gillespie SH (1995) Demonstration of homology between IS6110 of Mycobacterium tuberculosis and DNAs or other Mycobacterium spp. J Clin Microbiol 33:2290–2293PubMedGoogle Scholar
  109. 109.
    Kim SK, Lee SB, Kang TJ, Chae GT (2003) Detection of gene mutations related with drug resistance in Mycobacterium leprae from leprosy patients using Touch-Down (TD) PCR. FEMS Immun Med Microbiol 36:27–32Google Scholar
  110. 110.
    Klatser PR, van Beers S, Madjid B, Day R, de Wit MY (1993) Detection of Mycobacterium leprae nasal carriers in populations for which leprosy is endemic. J Clin Microbiol 31:2947–2951PubMedGoogle Scholar
  111. 111.
    Koga T, Wand-Wurttenberger A, DeBruyn J, Munk ME, Schoel B, Kaufmann SH (1989) T cells against a bacterial heat shock protein recognize stressed macrophages. Science 245:1112–1115PubMedGoogle Scholar
  112. 112.
    Kramme S, Bretzel G, Panning M, Kawuma J, Drosten C (2004) Detection and quantification of Mycobacterium leprae in tissue samples by real-time PCR. Med Microbiol Immunol 193:189–193PubMedGoogle Scholar
  113. 113.
    Kumar SK, Rebby BS, Ratnakar C (1996) Correlation of skin and nerve histopathology in leprosy. Lepr Rev 67:119–125PubMedGoogle Scholar
  114. 114.
    Kurabachew M, Wondimu A, Ryon JJ (1998) Reverse transcription-PCR detection of Mycobacterium leprae in clinical specimens. J Clin Microbiol 36:1352–1356PubMedGoogle Scholar
  115. 115.
    Lal H, Jain VK, Mittal RA, Chaudhary SD, Saini V (1993) Detection of antibodies to phenolic glycolipid by ELISA in leprosy patients. Indian J Lepr 65:95–99PubMedGoogle Scholar
  116. 116.
    Launius BK, Brown PA, Cush E, Mancini C (2004) A case study in hansen’s disease acquired after heart transplant. Crit Care Nurs Q 27:87–91PubMedGoogle Scholar
  117. 117.
    Liu XQ, Dosanjh D, Varia H, Ewer K, Cockle P, Pasvol G, Lalvani A (2004) Evaluation of T-cell responses to novel RDl- and RD2-encoded Mycobacterium tuberculosis gene products for specific detection of human tuberculosis infection. Infect Immun 72:2574–2581PubMedGoogle Scholar
  118. 118.
    Lockwood DN, Suneetha S (2005) Leprosy: too complex a disease for a simple elimination paradigm. Bull World Health Organ 83:230–235PubMedGoogle Scholar
  119. 119.
    Lombardi C, Suárez REG (1997) Epidemiologia da Hanseníase. In: Talhari S, Neves RG (eds) Hanseníase. Gráfica Tropical, Manaus, Brazil, pp 127–136Google Scholar
  120. 120.
    Mackay M (2004) Real-time PCR in the microbiology laboratory. Clin Microbiol Infect 10:190–212PubMedGoogle Scholar
  121. 121.
    Maeda S, Matsuoka M, Nakata N, Kai M, Maeda Y, Hashimoto K, Kimura H, Kobayashi K, Kashiwabara Y (2001) Multidrug resistant Mycobacterium leprae from patients with leprosy. Antimicrob Agents Chemother 45:3635–3639PubMedGoogle Scholar
  122. 122.
    Maeda Y, Mukai T, Spencer J, Makino M. (2005) Identification of an immunomodulating agent from Mycobacterium leprae. Infect Immun 73:2744–2750PubMedGoogle Scholar
  123. 123.
    Mahajan PM, Jogaikar DG, Mehta JM (1996) A study of pure neuritic leprosy: clinical experience. Indian J Lepr 68:137–141PubMedGoogle Scholar
  124. 124.
    Marques Junior W, Foss NT, Arruda APM, Barreira AA (2003) Near nerve potential in lepromatous leprosy. Muscle Nerve 28:460–463Google Scholar
  125. 125.
    Marques MA, Espinosa BJ, Xavier da Silveira EK, Pessolani MC, Chapeaurouge A, Perales J, Dobos KM, Belisle JT, Spencer JS, Brennan PJ (2004) Continued proteomic analysis of Mycobacterium leprae subcellular fractions. Proteomics 4:2942–2953PubMedGoogle Scholar
  126. 126.
    Martinez AN, Britto CFPC, Nery JAC, Sampaio EP, Jardim MR, Sarno EN, Moraes MO (2006) Evaluation of real-time and conventional PCR targeting complex 85 genes for detection of Mycobacterium leprae DNA in skin biopsy samples from patients diagnosed with leprosy. J Clin Microbiol 44:3154–3159PubMedGoogle Scholar
  127. 127.
    Martinoli C, Derchi LE, Bertolotto M, Gandolfo N, Bianchi S, Fiallo P, Nunzi E (2000) US and MR imaging of peripheral nerves in leprosy. Skeletal Radiol 29:142–150PubMedGoogle Scholar
  128. 128.
    Martinoli C, Bianchi S, Dahmane M, Pugliese F, Bianchi-Zamorani M, Valle M (2004) Ultrasound of tendons and nerves. Eur Radiol 12:44–55Google Scholar
  129. 129.
    McDougall AC, Ponnighaus JM, Fine PE (1987) Histopathological examination of skin biopsies from an epidemiological study of leprosy in northern Malawi. Int J Lepr Other Mycobact Dis 55:88–98PubMedGoogle Scholar
  130. 130.
    McHugh TD, Newport LE, Gillespie SH (1997) IS6110 homologs are present in multiple copies in Mycobacteria other than tuberculosis-causing mycobacteria. J Clin Microbiol 35:1769–1771PubMedGoogle Scholar
  131. 131.
    Mehra V, Bloom BR, Bajardi AC, Grisso CL, Sieling PA, Alland D, Convit J, Fan XD, Hunter SW, Brennan PJ, Rea TH, Modlin RL (1992) A major T cell antigen of Mycobacterium leprae is a 10-kD heat-shock cognate protein. J Exp Med 175:275–284PubMedGoogle Scholar
  132. 132.
    Miranda RN, Pereira LC, Tarlé SF, Nascimento RA, Mello SL, Mesquita LAF, Dechandt IT (2005) Development of a Mitsuda-like antigen and its evaluation in multibacillary, Mitsuda-negative leprosy patients. An Bras Dermatol 80:355–362Google Scholar
  133. 133.
    Misra N, Ramesh V, Misra RS, Narayan NPS, Colston MJ, Nath I (1995) Clinical utility of LSR/A15 gene for Mycobacterium leprae detection in leprosy tissues using the polymerase chain reaction. Int J Lepr Other Mycobact Dis 63:35–41PubMedGoogle Scholar
  134. 134.
    Mitsuda K (1919) On the value of a skin reaction to a suspension of leprosy nodules. Jpn J Dermatol Urol 19:697–708Google Scholar
  135. 135.
    Modi K, Mancini M, Joyce MP (2003) Lepromatous leprosy in a heart transplant recipient. Am J Transpl 3:1600–1603Google Scholar
  136. 136.
    Moet FJ, Meima A, Oskam L, Richardus JH (2004) Risk factors for the development of clinical leprosy among contacts, and their relevance for targeted interventions. Lepr Rev 75:310–326PubMedGoogle Scholar
  137. 137.
    Monot M, Honore N, Garnier T, Araoz R, Coppee JY, Lacroix C, Sow S, Spencer JS, Truman RW, Williams DL, Gelber R, Virmond M, Flageul B, Cho SN, Ji B, Paniz-Mondolfi A, Convit J, Young S, Fine PE, Rasolofo V, Brennan PJ, Cole ST (2005) On the origin of leprosy. Science 308:1040–1042PubMedGoogle Scholar
  138. 138.
    Moorthy BN, Kumar P, Chatura KR, Chandrasekhar HR, Basavaraja PK (2001) Histopathological correlation of skin biopsies in leprosy. Indian J Dermatol Venereol Leprol 67:299–301PubMedGoogle Scholar
  139. 139.
    Muliyil J, Nelson KE, Diamond EL (1991) Effect of BCG on the risk of leprosy in an endemic area: a case-control study. Int J Lepr Other Mycobact Dis 59:229–236PubMedGoogle Scholar
  140. 140.
    Musser JM (1995) Antimicrobial agent resistance in mycobacteria: molecular insights. Clin Mol Microbiol Rev 8:496–514Google Scholar
  141. 141.
    NJIL (National JALMA Institute of Leprosy, Other Mycobacterial Diseases) (2007) Informal consultation on rifampicin resistance in leprosy. Lepr Rev 78:295–305Google Scholar
  142. 142.
    Nordeen SK (1972) Epidemiology of (poly) neuritic type of leprosy. Lepr India 44:90–96Google Scholar
  143. 143.
    Oskam L, Bakker MI (2007) A report of the workshop on the use of chemoprophylaxis in the control of leprosy held in Amsterdam, the Netherlands, on 14 December 2006. Lepr Rev 78:173–185PubMedGoogle Scholar
  144. 144.
    Patel PD (2002) (Bio) sensors for measurement of analytes implicated in food safety: a review. Trends Anal Chem 21:96–115Google Scholar
  145. 145.
    Patrocínio LG, Goulart IMB, Goulart LR, Patrocínio JA, Ferreira FR, Fleury RN (2005) Detection of Mycobacterium leprae in nasal mucosa biopsies by the polymerase chain reaction. FEMS Immunol Med Microbiol 44:311–316PubMedGoogle Scholar
  146. 146.
    Pattyn SR, Ursi D, Ieven M, Grillone S, Raes V (1993) Detection of Mycobacterium leprae by the polymerase chain reaction in nasal swabs of leprosy patients and their contacts. Int J Lepr Other Mycobact Dis 61:389–393PubMedGoogle Scholar
  147. 147.
    Pattyn SR, Ursi D, Ieven M, Raes V, Jamet P (1992) Polymerase chain reaction amplifying DNA coding for species-specific rRNA of Mycobacterium leprae. Int J Lepr Other Mycobact Dis 60:234–243PubMedGoogle Scholar
  148. 148.
    Pereira JH, Palande DD, Gschmeissner SE (1991) Mycobacteria in nerve trunks of long-term treated leprosy patients. Lepr Rev 64:134–142Google Scholar
  149. 149.
    Pereira HLA, Ribeiro SLE, Ciconelli RM, Fernandes ARC (2006) Imaging methods evaluation in osteoarticular and peripheral nerves involvement in leprosy. Rev Bras Reumatol 46(Suppl 1):30–35Google Scholar
  150. 150.
    Pettit JHS, Rees RJW (1964) Sulphone resistance in leprosy. An experimental and clinical study. Lancet 2:673–674PubMedGoogle Scholar
  151. 151.
    Pfaltzgraff RE, Bryceson A (1985) Clinical leprosy. In: Hastings RC (ed) Leprosy—(medicine in the tropics series). Churchill Livinstone, New York, pp 134–176Google Scholar
  152. 152.
    Phetsuksiri B, Rudeeaneksin J, Supapkul P, Wachapong S, Mahotarn K, Brennan PJ (2006) A simplified reverse transcriptase PCR for rapid detection of Mycobacterium leprae in skin specimens. FEMS Immunol Med Microbiol 48:319–328PubMedGoogle Scholar
  153. 153.
    Plikaytis BB, Gelber RH, Shinnick TM (1990) Rapid and sensitive detection of Mycobacterium leprae using a nested-primer gene amplification assay. J Clin Microbiol 28:1913–1917PubMedGoogle Scholar
  154. 154.
    Ponnighaus JM (1996) Diagnosis and management of single lesions in leprosy. Lepr Rev 97:89–94Google Scholar
  155. 155.
    Rafi A, Donoghue HD, Stanford JL (1994) Application of polymerase chain reaction for the detection of Mycobacterium leprae DNA in specimens from treated leprosy patients. Int J Lepr Other Mycobact Dis 63:42–47Google Scholar
  156. 156.
    Ramaprasad P, Fernando A, Madhale S, Rao JR, Edward VK, Samson PD, Klatser PR, de Wit MY, Smith WC, Cree IA (1997) Transmission and protection in leprosy: indications of the role of mucosal immunity. Lepr Rev 68:301–315PubMedGoogle Scholar
  157. 157.
    Ramasoota P, Sampunachot P, Sampunachot P (2000) Multiple mutations in the rpoB gene of Mycobacterium leprae strains from leprosy patients in Thailand. Southeast Asian J Trop Med Pub Health 31:493–497Google Scholar
  158. 158.
    Ramaswamy S, Musser JM (1998) Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis. Tuber Lung Dis 79:3–29PubMedGoogle Scholar
  159. 159.
    Rambukkana A (2000) How does Mycobacterium leprae target the peripheral nervous system? Trends Microbiol 8:23–28PubMedGoogle Scholar
  160. 160.
    Ranque B, Alcais A, Van Thuc N, Woynard S, Thai VH, Huong NT, Ba NN, Khoa PX, Schurr E, Abel L (2005) A recessive major gene controls the Mitsuda reaction in a region endemic for leprosy. J Infect Dis Oct 192:1475–1482Google Scholar
  161. 161.
    Reece ST, Ireton G, Mohamath R, Guderian J, Goto W, Gelber R, Groathouse N, Spencer J, Brennan P, Reed SG (2006) ML0405 and ML2331 are antigens of Mycobacterium leprae with potential for diagnosis of leprosy. Clin Vaccine Immunol 13:333–340PubMedGoogle Scholar
  162. 162.
    Richardus JH, Finlay KM, Croft RP, Smith WCS (1996) Nerve function impairment in leprosy at diagnosis and at completion of MDT: a retrospective chort study of 786 patients in Bangladesh. Lepr Rev 67:297–305PubMedGoogle Scholar
  163. 163.
    Ridley DS (1990) Skin biopsy in leprosy, 3rd edn edn. CIBA-GEIGY Ltd, Basle, p 63Google Scholar
  164. 164.
    Ridley DS, Job CK (1985) The pathology of leprosy. In: Hastings RC (ed) Leprosy—(medicine in the tropics series). Churchill Livinstone, New York, pp 100–133Google Scholar
  165. 165.
    Ridley DS, Jopling WH (1966) Classification of leprosy according to immunity: a five-group system. Int J Lepr Other Mycobact Dis 34:255–273PubMedGoogle Scholar
  166. 166.
    Roche PW, Britton WJ, Failbus SS, Williams D, Pradhan HM, Theuvenet WJ (1990) Operational value of serological measurements in multibacillary leprosy patients: clinical and bacteriological correlates of antibody responses. Int J Lepr Other Mycobact Dis 58:480–490PubMedGoogle Scholar
  167. 167.
    Robert JW, Leonard JZ, Michel AB, Eustace SJ (1999) Case 4: tuberculoid leprosy. In: Musculoskeletal case of the day. Am J Roentgenol 173:803Google Scholar
  168. 168.
    Rodriguez-Mozaz S, Marco MP, Alda MJL, Barceló D (2004) Biosensors for environmental applications: future development trends. Pure Appl Chem 76:723–752Google Scholar
  169. 169.
    Said G (1999) Indications and value of nerve biopsy. Muscle Nerve 22:1617–1619PubMedGoogle Scholar
  170. 170.
    Santos MS, Burgos Junior FR, Gonçalves MA, Pereira JE, Goulart LR, Goulart IMB (2006) Diagnostic value of polymerase chain reaction and quantitative competitive polymerase chain reaction in pure neuritic leprosy. In: Anais do XXII Congresso Brasileiro de Neurologia/VI Encontro Luso-Brasileiro de Neurologia/II Congresso da Federação Latino-Americana de Neurologia, NEUROSUR, Recife-BrasilGoogle Scholar
  171. 171.
    Sapkota BR, Ranjit C, Macdonald M (2006) Reverse line probe assay for the rapid detection of rifampicin resistance in Mycobacterium leprae. Nepal Med Coll J 8:122–127PubMedGoogle Scholar
  172. 172.
    Scollard MD (2000) Endothelial cells and the pathogenesis of lepromatous neuritis: insights from the armadillo model. Microbe Infect 2:1835–1843Google Scholar
  173. 173.
    Scollard MD, Adams LB, Gillis TP, Krahembuhl JL, Truman RW, Williams DL (2006) The continuing challenges of leprosy. Clin Microbiol Rev 19:166–168Google Scholar
  174. 174.
    Scollard MD (2004) Classification of leprosy: a full color spectrum, or black and white? Int J Lepr Other Mycobact Dis 72:166–168PubMedGoogle Scholar
  175. 175.
    Sehgal VN, Rege VL, Reys M (1977) Correlation between clinical and histopathological classification in leprosy. Int J Lepr Other Mycobact Dis 40:278–280Google Scholar
  176. 176.
    Sena PG (1976) Eletromyographic and neurological aspects of leprosy: study of 100 cases. Arq Neuropsiquiatr 34:1–17PubMedGoogle Scholar
  177. 177.
    Sethna KB, Birdi TJ, Antia NH (1997) Adherence of Mycobacterium leprae to the nasal mucosa is influenced by surface integrity and viability. J Biosci 22:575–583Google Scholar
  178. 178.
    Shepard CC (1967) A kinetic method for the study of drugs against Mycobacterium leprae in mice. Int J Lepr Other Mycobact Dis 35:429–435Google Scholar
  179. 179.
    Shi L, Yajima M, Kawatsu K, Matsuoka M, Kashiwabara Y (2000) Comparison of polymerase chain reaction, immunohistochemistry and conventional histopathology in the diagnosis of early leprosy in Sichuan Province of China. Jpn J Lepr 69:147–155Google Scholar
  180. 180.
    Singh PA, Agarwal R, Misra V, Gupta SC, Bajaj AK (2000) Clinico-histopathological concordance in leprosy. Trop Doct 30:228–231PubMedGoogle Scholar
  181. 181.
    Skacel M, Antunes SLG, Rodrigues MAJ, Nery JAC, Valentim VC, Morais RPB, Sarno EN (2000) The diagnosis of leprosy among patients with symptoms of peripheral neuropathy without cutaneo lesions—a follow-up study. Arq Neuropsiquiatr 58:800–807PubMedGoogle Scholar
  182. 182.
    Skjøt RLV, Oettinger T, Rosenkrands I, Ravn P, Brock I, Jacobsen S, Andersen P (2000) Comparative evaluation of low-molecular-mass proteins from Mycobacterium tuberculosis identifies members of the ESAT-6 family as immunodominant T-cell antigens. Infect Immun 68:214–220PubMedCrossRefGoogle Scholar
  183. 183.
    Spencer JS, Marques MAM, Lima MCBS, Junqueira-Kipnis AP, Gregory BC, Truman RW, Brennan PJ (2002) Antigenic specificity of the Mycobacterium leprae homologue of ESAT-6. Infect Immun 70:1010–1013PubMedGoogle Scholar
  184. 184.
    Spencer JS, Kim HJ, Marques MAM, Gonzalez-Juarerro M, Lima MC, Vissa VD, Truman RW, Gennaro ML, Cho SN, Cole ST, Brennan PJ (2004) Comparative analysis of B- and T-cell epitopes of Mycobacterium leprae and Mycobacterium tuberculosis culture filtrate protein 10. Infect Immun 72:3161–3170PubMedGoogle Scholar
  185. 185.
    Spencer JS, Dockrell HM, Kim HJ, Marques MAM, Williams DL, Martins MVSB, Martins MLF, Lima MCBS, Sarno EN, Pereira GMB, Matos H, Fonseca LS, Sampaio EP, Ottenhoff TH, Geluk A, Cho S, Stoker NG, Cole ST, Brennan PJ, Pessolani MCV (2005) Identification of specific proteins and peptides in Mycobacterium leprae suitable for the selective diagnosis of leprosy. J Immunol 175:7930–7938PubMedGoogle Scholar
  186. 186.
    Sugita Y (2001) PCR in leprosy. Jpn J Lepr 70:3–13Google Scholar
  187. 187.
    Suneetha S, Arunthathi S, Chandi S, Kurian N, Chacko CJG (1998) Histological studies in primary neuritic leprosy: changes in apparently normal skin. Lepr Rev 69:351–357PubMedGoogle Scholar
  188. 188.
    Suzuki Y, Matsuoka M (2006) DNA microarray based rapid drug susceptibility test for Mycobacterium leprae. Jpn J Lepr 75:271–277Google Scholar
  189. 189.
    Teixeira AC, Cruvinel DL, Roma FR., Luppino LF, Resende LHP, Sousa T, Goulart IMB (2005) Avaliação da concordância entre exames clínicos e laboratoriais no diagnóstico da hanseníase. Hansenol Int 30:89Google Scholar
  190. 190.
    Torres P, Camarena JJ, Gomez JR, Nogueira JM, Gimeno V, Navarro JC, Olmos A (2003) Comparison of PCR mediated amplification of DNA and the classical methods for detection of Mycobacterium leprae in different types of clinical samples in leprosy patients and contacts. Lepr Rev 74:18–30PubMedGoogle Scholar
  191. 191.
    Triccas JA, Winter N, Roche PW, Gilpin A, Kendrick KE, Britton WJ (1998) Specific serological diagnosis of leprosy with a recombinant Mycobacterium leprae protein purified from a rapidly growing mycobacterial host. J Clin Microbiol 36:2363–2665PubMedGoogle Scholar
  192. 192.
    Turner APF (2000) Biosensors—sense and sensitivity. Science 290:1315–1317PubMedGoogle Scholar
  193. 193.
    Van Beers SM, Izumi S, Madrid B, Maeda Y, Day R, Klatser PR (1994) An epidemiological study of leprosy infection by serology and polymerase chain reaction. Int J Lepr Other Mycobact Dis 62:1–9PubMedGoogle Scholar
  194. 194.
    Van Beers SM, de Wit MYL, Klatser PR (1996) The epidemiology of Mycobacterium leprae: recent insight. FEMS Microbiol Lett 136:221–230PubMedGoogle Scholar
  195. 195.
    Van Beers S, Hatta M, Klatser PR (1999) Seroprevalence rates of antibodies to phenolic glycolipid I among school children as an indicator of leprosy endemicity. Int J Lepr Other Mycobact Dis 67:243–249PubMedGoogle Scholar
  196. 196.
    Van Beers S, Hatta M, Klatser PR (1999) Patient contact is the major determinant in incident leprosy: implications for future control. Int J Lepr Other Mycobact Dis 67:119–128PubMedGoogle Scholar
  197. 197.
    Van der Vliet GM, Cho SN, Kampirapap K, van Leeuwen J, Schukkink RA, van Gemen B, Das PK, Faber WR, Walsh GP, Klatser PR (1996) Use of NASBA RNA amplification for detection of Mycobacterium leprae in skin biopsies from untreated and treated leprosy patients. Int J Lepr Other Mycobact Dis 64:396–403PubMedGoogle Scholar
  198. 198.
    Vargas-Ocampo F (2004) Analysis of 6000 skin biopsies of the national leprosy control program in Mexico. Int J Lepr Other Mycobact Dis 72:427–436PubMedGoogle Scholar
  199. 199.
    Veen J (1992) Microepidemics of tuberculosis: the stone-in-the-pond principle. Tuber Lung Dis 73:73–76PubMedGoogle Scholar
  200. 200.
    Vega-Lopez F, Brooks LA, Dockrell HM, De Smeet KAL, Thompson JK, Hussain R, Stoker NG (1993) Sequence and immunological characterization of a serine-rich antigen from Mycobacterium leprae. Infect Immun 61:2145–2153PubMedGoogle Scholar
  201. 201.
    Weir RE, Brennan PJ, Butlin CR, Dockrell HM (1999) Use of whole blood assay to evaluate in vitro T cell responses to new leprosy skin test antigens in leprosy patients and healthy subjects. Clin Exp Immunol 116:263–269PubMedGoogle Scholar
  202. 202.
    WHO (1988) Expert committee on leprosy sixth report. World Health Organization, Technical Report Series, p 768Google Scholar
  203. 203.
    WHO (2000) Expert committee on leprosy guide to eliminate leprosy as a public health problem, vol 1st edn. WHO, GenevaGoogle Scholar
  204. 204.
    WHO (2006) Report of the global forum on elimination of leprosy as a public health problem. WHO, GenevaGoogle Scholar
  205. 205.
    Wichtwechkarn J, Karnjan S, Shuntawuttisettee S, Sorjprasit C, Kampirapap K, Peerapakorn S (1995) Detection of Mycobacterium leprae infection by PCR. J Clin Microbiol 33:45–49Google Scholar
  206. 206.
    Wilder-Smith E, Wilder-Smith A, Egger M (1997) Peripheral autonomic nerve disfunction in asymptomatic leprosy contacts. J Neurol Sci 150:33–38PubMedGoogle Scholar
  207. 207.
    Wilkinson RJ, Wilkinson KA, Jurcevic S, Hills A, Sinha S, Sengupta U, Lockwood DNJ, Katoch K, Altman D, Ivanyi J (1999) Specificity and function of immunogenic peptides from the 35-kilodalton protein of Mycobacterium leprae. Infect Immun 67:1501–1504PubMedGoogle Scholar
  208. 208.
    Williams D, Waguespack C, Eisenach K, Crawford JT, Portaels F, Salfinger M, Nolan CM, Abe C, Sticht-Groh V, Gillis TP (1994) Characterization of rifampin resistance in pathogenic mycobacteria. Antimicrob Agents Chemother 38:2380–2386PubMedGoogle Scholar
  209. 209.
    Williams DL, Spring L, Harris E, Roche P, Gillis TP (2000) Dihydropteroate synthase of Mycobacterium leprae and dapsone resistance. Antimicrob Agents Chemother 44:1530–1537PubMedGoogle Scholar
  210. 210.
    Williams DL, Pittman TL, Gillis TP, Matsuoka M, Kashiwabara Y (2001) Simultaneous detection of Mycobacterium leprae and its susceptibility to dapsone using DNA heteroduplex analysis. J Clin Microbiol 39:2083–2088PubMedGoogle Scholar
  211. 211.
    Williams DL, Scollard DM, Gillis TP (2003) PCR-based diagnosis of leprosy in the United States. Clin Microbiol Newslett 25:57–61Google Scholar
  212. 212.
    Winter N, Triccas JA, Rivoire B, Pessolani MC, Eiglmeier K, Lim EM, Hunter SW, Brennan PJ, Britton WJ (1995) Characterization of the gene encoding the immunodominant 35 kDa protein of Mycobacterium leprae. Mol Microbiol 16:865–876PubMedGoogle Scholar
  213. 213.
    Woods SA, Cole ST (1989) A rapid method for the detection of Mycobacterium leprae in human biopsies: a novel application of PCR. FEMS Microbiol Lett 65:305–310Google Scholar
  214. 214.
    Yamamura M, Uyemura K, Dens RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL (1991) Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 254:277–279PubMedGoogle Scholar
  215. 215.
    Yoon KH, Cho SN, Lee MK, Abalos MR, Cellona RV, Fajardo JR, Guido LS, Dela Cruz EC, Waijh GP, Kim JD (1993) Evaluation of polymerase chain reaction amplification of Mycobacterium leprae-specific repetitive sequence in biopsy specimens from leprosy patients. J Clin Microbiol 31:895–899PubMedGoogle Scholar
  216. 216.
    You E, Kang T, Kim S, Lee S, Chae G (2005) Mutations in genes related to drug resistance in Mycobacterium leprae isolates from leprosy patients in Korea. J Infect 50:6–11PubMedGoogle Scholar
  217. 217.
    Young SK, Taylor GM, Jain S, Suneetha LM, Suneetha S, Lockwood DN, Young DB (2004) Microsatellite mapping of Mycobacterium leprae populations in infected humans. J Clin Microbiol 42:4931–4936PubMedGoogle Scholar
  218. 218.
    Zhang L, Budiawan T, Matsuoka M (2005) Diversity of potential short tandem repeats in Mycobacterium leprae and application for molecular typing. J Clin Microbiol 43:5221–5229PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Isabela Maria Bernardes Goulart
    • 1
    • 3
  • Luiz Ricardo Goulart
    • 1
    • 2
  1. 1.Leprosy National Reference Center, Clinics’ Hospital, School of MedicineFederal University of Uberlândia (UFU)UberlândiaBrazil
  2. 2.Institute of Genetics and BiochemistryFederal University of Uberlândia (UFU)UberlândiaBrazil
  3. 3.Departamento de Clínica Médica, Faculdade de MedicinaFederal University of Uberlândia (UFU)UberlândiaBrazil

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