Leprosy of the Past and Today

Despite enhanced disease control efforts, leprosy remains an important cause of disability in several countries. Being based on case detection, the exact prevalence of the disease is not easily estimated. Currently around 600,000 new cases are treated annually. Advances in immunology and molecular biology have led to a greater understanding of the disease and to hopes for improved diagnostic tests and vaccination strategies. The major advance, though, is the development of highly effective combination drug regimens which, provided all doses are taken, rarely fails to cure. The challenge to leprosy control services is to overcome the stigma associated with the disease so that patients present with minimal lesions and before disabilities have developed. Although it is hoped that leprosy as a serious public health problem will be eliminated within a few years, continuing care for those suffering from deformity and rejection by society will be required for several decades.

KEYWORDS

Leprosy - Mycobacterium leprae - hypersensitivity reactions - multi-drug therapy - vaccination - stigma

REFERENCES

• 1 Grange J M. Lupus and lepros.  Int J Lepr Other Mycobact Dis. 1988;  56 111-112
• 2 Robertson J O. International Leprosy Association global project on the history of leprosy. Editorial.  Lepr Rev. 2003;  74 103-111
• 3 World Health Organization .Global Strategy for the Elimination of Leprosy as a Public Health Problem. Geneva; World Health Organization 1999
• 4 World Health Organization .Chemotherapy of Leprosy for Control Programmes. Report of a WHO Study Group, TRS 675. Geneva; World Health Organization 1982
• 5 Cole S T, Eiglmeier K, Parkhill J et al.. Massive gene decay in the leprosy bacillus.  Nature. 2001;  409 1007-1011
• 6 Young D, Robertson B. Genomics: leprosy: a degenerative disease of the genome.  Curr Biol. 2001;  11 R381-R383
• 7 Brennan P J, Vissa V D. Genomic evidence for the retention of the essential mycobacterial cell wall in the otherwise defective Mycobacterium leprae .  Lepr Rev. 2001;  72 415-428
• 8 Sassetti C M, Boyd D H, Rubin E J. Genes required for mycobacterial growth defined by high density mutagenesis.  Mol Microbiol. 2003;  48 77-84
• 9 Stanford J L, Rook G AW, Convit J et al.. Preliminary taxonomic studies on the leprosy bacillus.  Br J Exp Pathol. 1975;  56 579-585
• 10 Chakrabarty A N, Dastidar S G. Is soil an alternative source of leprosy infection?.  Acta Leprol. 2001-2002;  12 79-84
• 11 Grange J M, Dewar C A, Rowbotham T J. Microbe-dependence of Mycobacterium leprae: a possible intracellular relationship with protozoa.  Int J Lepr Other Mycobact Dis. 1987;  55 565
• 12 Kazda J, Irgens L M, Muller K. Isolation of noncultivable acid-fast bacilli in sphagnum moss vegetation by footpad technique in mice.  Int J Lepr Other Mycobact Dis. 1980;  48 1-6
• 13 Mendum T A, Chilima B Z, Hirsch P R. The PCR amplification of nontuberculous mycobacterial 16S rRNA sequences from soil.  FEMS Microbiol Lett. 2000;  185 189-192
• 14 Valverde C R, Canfield D, Tarara R, Esteves M I, Gormus B J. Spontaneous leprosy in a wild-caught cynomolgus macaque.  Int J Lepr Other Mycobact Dis. 1998;  66 140-148
• 15 Paige C F, Scholl D T, Truman R W. Prevalence and incidence density of Mycobacterium leprae and Trypanosoma cruzi infections within a population of wild nine-banded armadillos.  Am J Trop Med Hyg. 2002;  67 528-532
• 16 Lumpkin L R, Cox G F, Wolf J E. Leprosy in five armadillo handlers.  J Am Acad Dermatol. 1983;  9 899-903
• 17 Davey T F, Rees R JW. The nasal discharge in leprosy: clinical and bacteriological aspects.  Lepr Rev. 1974;  45 121-134
• 18 Sehgal V N. Leprosy following mechanical trauma.  Lepr Rev. 1986;  57 74-76
• 19 Blake L A, West B C, Lary C H, Todd IV J R. Environmental nonhuman sources of leprosy.  Rev Infect Dis. 1987;  9 562-577
• 20 World Health Organization . Leprosy: global situation.  Wkly Epidemiol Rec. 2000;  75 226-231
• 21 World Health Organization .Leprosy. Fact Sheet No. 101. Revised January 2003 Geneva; World Health Organization 2003
• 22 Leprosy Group, WHO .Leprosy. In: Cook GC, Zumla A Manson's Tropical Diseases. 21st ed. Edinburgh; Saunders (Elsevier) 2003: 1065-1084
• 23 Lockwood D NJ. Leprosy (Hansen's disease). In: Warrell DA, Cox TM, Firth JD, Benz EJ Oxford Textbook of Medicine. 4th ed. Oxford; Oxford University Press 2003: 575-584
• 24 Narayan N P, Ramu G, Desikan K V, Vallishayee R S. Correlation of clinical, histological and immunological features across the leprosy spectrum.  Indian J Lepr. 2001;  73 329-342
• 25 Brennan P J. Skin test development in leprosy: progress with first-generation skin test antigens, and an approach to the second generation.  Lepr Rev. 2000;  71(suppl) S50-S54
• 26 Torres P, Camarena J J, Gomez J R et al.. 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. 2003;  74 18-30
• 27 Kang T J, Kim S K, Lee S B, Chae G T, Kim J P. Comparison of two different PCR amplification products (the 18-kDa protein gene vs. RLEP repetitive sequence) in the diagnosis of Mycobacterium leprae .  Clin Exp Dermatol. 2003;  28 420-424
• 28 Chae G T, Kim M J, Kang T J et al.. 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. 2002;  51 417-422
• 29 Ridley D S, Jopling W H. Classification of leprosy according to immunity: a five-group system.  Int J Lepr Other Mycobact Dis. 1966;  34 255-273
• 30 Godal M B, Myrvang B, Stanford J L, Samuel D R. Recent advances in the immunology of leprosy with special reference to new approaches in immunoprophylaxis.  Bull Inst Pasteur. 1974;  72 273-310
• 31 Waters M F, Stanford J L. Giant reactions to tuberculin in lepromatous leprosy patients.  Int J Lepr Other Mycobact Dis. 1985;  53 546-553
• 32 Sampaio E P, Duppre N C, Nery J A, Moreira A L, Sarno E N. Development of giant reaction in response to PPD skin test in lepromatous leprosy patients.  Int J Lepr Other Mycobact Dis. 1993;  61 205-213
• 33 Bloom B R, Salgame P, Diamond B. Revisiting and revising suppressor T cells.  Immunol Today. 1992;  13 131-136
• 34 Hashimoto K, Maeda Y, Kimura H et al.. Mycobacterium leprae infection in monocyte-derived dendritic cells and its influence on antigen-presenting function.  Infect Immun. 2002;  70 5167-5176
• 35 Bloom B R. Learning from leprosy: a perspective on immunology and the third world (American Association of Immunologists Presidential Address).  J Immunol. 1986;  137 i-x
• 36 Modlin R L, Hofman F M, Taylor C R, Rea T H. T-lymphocyte subsets in the skin lesions of patients with leprosy.  J Am Acad Dermatol. 1983;  8 182-189
• 37 Yamamura M, Uyemura K, Deans R J et al.. Defining protective responses to pathogens: cytokine profiles in leprosy patients.  Science. 1991;  254 277-279
• 38 Rook G AW, Zumla A. Advances in the immunopathogenesis of pulmonary tuberculosis.  Curr Opin Pulm Med. 2001;  7 116-123
• 39 Stanford J L, Stanford C A, Grange J M. Environmental echoes.  Sci Prog. 2001;  84(pt 2) 105-124
• 40 Muzur A, Skrobonja A, Rotschild V, Skrobonja Jr A. Saints protectors from leprosy: historical hints of suggestive therapy?.  Int J Lepr Other Mycobact Dis. 2002;  70 269-273
• 41 Stanford J L. The history and future of vaccination and immunotherapy for leprosy.  Trop Geogr Med. 1994;  46 93-107
• 42 Samuel N M, Grange J M, Samuel S et al.. A study of the effects of intradermal administration of recombinant gamma interferon in lepromatous leprosy patients.  Lepr Rev. 1987;  58 389-400
• 43 Nath I, Vemuri N, Reddi A L et al.. The effect of antigen presenting cells on the cytokine profiles of stable and reactional lepromatous leprosy patients.  Immunol Lett. 2000;  75 69-76
• 44 Filley E, Andreoli A, Steele J et al.. A transient rise in agalactosyl IgG correlating with free interleukin-2 receptors during episodes of erythema nodosum leprosum.  Clin Exp Immunol. 1989;  76 343-347
• 45 Spierings E, de Boer T, Wieles B et al.. Mycobacterium leprae-specific, HLA Class II-restricted killing of human schwann cells by CD4+ Th1 cells: a novel immunopathogenic mechanism of nerve damage in leprosy.  J Immunol. 2001;  166 5883-5888
• 46 Oliveira R B, Ochoa M T, Sieling P A et al.. Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy.  Infect Immun. 2003;  71 1427-1433
• 47 Kang T J, Chae G T. Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients.  FEMS Immunol Med Microbiol. 2001;  31 53-58
• 48 Abbot N C, Beck J S, Samson P D, Butlin C R, Bennett P J, Grange J M. Cold fingers in leprosy.  Int J Lepr Other Mycobact Dis. 1992;  60 580-586
• 49 Abbot N C, Beck J S, Samson P D et al.. Impairment of fingertip vasomotor reflexes in leprosy patients and apparently healthy contacts.  Int J Lepr Other Mycobact Dis. 1991;  59 537-547
• 50 Abbot N C, Beck J S, Feval F et al.. Immunotherapy with Mycobacterium vaccae and peripheral blood flow in long-treated leprosy patients, a randomised, placebo-controlled trial.  Eur J Vasc Endovasc Surg. 2002;  24 202-208
• 51 Courtright P, Daniel E, Sundarrao et al.. Eye disease in multibacillary leprosy patients at the time of their leprosy diagnosis: findings from the Longitudinal Study of Ocular Leprosy (LOSOL) in India, the Philippines and Ethiopia.  Lepr Rev. 2002;  73 225-238
• 52 Ridley D S. Pathogenesis of Leprosy and Related Diseases. London; Wright 1988: 89
• 53 Nakayama E E, Ura S, Fleury R N, Soares V. Renal lesions in leprosy: a retrospective study of 199 autopsies.  Am J Kidney Dis. 2001;  38 26-30
• 54 Eastwood J B, Dilley S A, Grange J M. Tuberculosis, leprosy and other mycobacterial diseases. In: Cattel W Infections of the Kidney and Urinary Tract. Oxford; Oxford University Press 1996: 291-318
• 55 Saporta L, Yuksel A. Androgenic status in patients with lepromatous leprosy.  Br J Urol. 1994;  74 221-224
• 56 Ishikawa S, Mizushima M, Furuta M, Ishikawa A, Kawamura K. Leydig cell hyperplasia and the maintenance of bone volume: bone histomorphometry and testicular histopathology in 29 male leprosy autopsy cases.  Int J Lepr Other Mycobact Dis. 2000;  68 258-266
• 57 Neena K, Ammini A C, Singh M, Pandhi R K. Ovarian function in female patients with multibacillary leprosy.  Int J Lepr Other Mycobact Dis. 2003;  71 101-105
• 58 Lienhardt C, Kamate B, Jamet P et al.. Effect of HIV infection on leprosy: a three-year survey in Bamako, Mali.  Int J Lepr Other Mycobact Dis. 1996;  64 383-391
• 59 Lucas S. Human immunodeficiency virus and leprosy.  Lepr Rev. 1993;  64 97-103
• 60 Lawn S D, Wood C, Lockwood D N. Borderline tuberculoid leprosy: an immune reconstitution phenomenon in a human immunodeficiency virus-infected person.  Clin Infect Dis. 2003;  36 e5-e6
• 61 Brown J AK, Stone M M, Sutherland I. BCG vaccination of children against leprosy in Uganda: first results.  BMJ. 1966;  1 7-14
• 62 Gupte M D. Vaccine trials in leprosy: Venezuela, Malawi and India.  Int J Lepr Other Mycobact Dis. 1999;  67(suppl 4) S32-S37
• 63 Gupte M D, Vallishayee R S, Anantharaman D S et al.. Comparative leprosy vaccine trial in south India.  Indian J Lepr. 1998;  70 369-388
• 64 Azuly R D. Antileprosy vaccinations.  An Bras Dermatol. 2002;  77 489-494
• 65 Ramu G, Grange J M, Stanford J L. Evaluation of adjunct immunotherapy with killed Mycobacterium vaccae in the treatment of multibacillary leprosy and erythema nodosum leprosum. In: Casal M Clinical Mycobacteriology. Barcelona; Prous Science 1998: 393-402
• 66 World Health Organization .Expert Committee on Leprosy. WHO Technical Report series, No. 874. Geneva; World Health Organization 1998
• 67 World Health Organization .7th WHO Expert Committee on leprosy June 1997. Geneva; World Health Organization 1997
• 68 Lockwood D, Marlowe S. Leprosy. In: Finch RG, Greenwood D, Norrby SR, Whitley RJ Antibiotic and Chemotherapy. 8th ed. Edinburgh; Churchill Livingstone 2003: 808-816
• 69 Withington S G, Joha S, Baird D, Brink M, Brink J. Assessing socioeconomic factors in relation to stigmatisation, impairment status, and selection for socioeconomic rehabilitation: a 1-year cohort of new leprosy cases in north Bangladesh.  Lepr Rev. 2003;  74 120-123
• 70 de Stigter D H, de Geus L, Heynders M L. Leprosy: between acceptance and segregation: community behavior towards persons affected by leprosy in eastern Nepal.  Lepr Rev. 200;  71 492-498
• 71 Rao S, Garole V, Walawalkar S et al.. Gender differences in the social impact of leprosy.  Lepr Rev. 1996;  67 190-199
• 72 Peters E S, Eshiet A L. Male-female (sex) differences in leprosy patients in south eastern Nigeria: females present late for diagnosis and treatment and have higher rates of deformity.  Lepr Rev. 2002;  73 262-267
• 73 Arole S, Premkumar R, Arole R, Maury M, Saunderson P. Social stigma: a comparative qualitative study of integrated and vertical care approaches to leprosy.  Lepr Rev. 2002;  73 186-196
• 74 Van Dijk M, Visschedijk J, Van Der Kwaak A. “Client satisfaction”: guidelines for assessing the quality of leprosy services from the clients' perspective.  Lepr Rev. 2003;  74 112-119
• 75 Reichman L B. The U-shaped curve of concern.  Am Rev Respir Dis. 1991;  144 741-742