Efsane

Por fim, podemos concluir que o esquema alternativo proposto no presente estudo para pacientes com intolerância à sulfona e principalmente para pacientes que se recusam a tomar a clofazimina devido a pigmentação cutânea, trata-se de uma alternativa importante e segura.

Novos estudos devem ser realizados, com um número maior de pacientes, para confirmação destas observações.

7-RESUMO

O presente trabalho comparou dois esquemas terapêuticos em pacientes com hanseníase multibacilar. O grupo 1, que recebeu o tratamento convencional (PQT-MB), foi denominado grupo controle. O grupo 2, denominado de grupo teste, recebeu a associação de rifampicina 600 mg, mais ofloxacina 400 mg, mais minociclina 100 mg (ROM), administrado sob supervisão, uma vez por mês. A duração total do tratamento nos dois grupos foi de dois anos. Na avaliação inicial foram realizados: exame clínico, baciloscópico e histológico. A baciloscopia e a biópsia foram repetidas no final do primeiro ano e novamente no final do segundo ano de tratamento. A avaliação clínica foi realizada mensalmente por ocasião da administração da dose supervisionada.

No grupo 1 foram avaliados 14 pacientes. O índice baciloscópico (IB) antes do tratamento variou de 2 a 4,8. No grupo 2 foram estudados 12 pacientes. O IB antes do tratamento nesse grupo variou de 1,6 a 4,8. Ambos os grupos apresentavam lesões cutâneas que os caracterizavam como pertencentes ao pólo virchoviano. Histologicamente apresentavam quadro de hanseníase virchoviana ativa, exceto um paciente do grupo 2.

Ao final do primeiro ano de tratamento estavam todos clinicamente melhorados, o índice baciloscópico diminuído e com quadro histológico em regressão. Essa tendência de melhora se mantinha e na avaliação do final do segundo ano todos estavam clinicamente, baciloscopicamente e histologicamente ainda melhores.

A análise estatística dos parâmetros, baciloscópico e histológico, mostrou que não houve diferença estatisticamente significativa entre os grupos estudados, sendo, portanto os dois esquemas equivalentes. A ocorrência de reação tipo 2 (eritema nodoso hansênico - ENH) foi igual nos dois grupos. No grupo 1, todos apresentaram pigmentação cutânea devido a clofazimina. Os resultados, portanto, demonstraram que o esquema com administração mensal de rifampicina, mais ofloxacina, mais minociclina tem eficácia e segurança equivalente ao esquema convencional. Além disso, tem a vantagem de não acarretar pigmentação cutânea, ser totalmente supervisionado, podendo ser utilizado como esquema alternativo.

8-ABSTRACT

The present study compared two therapeutic schemes in multibacillary leprosy patients. Group 1 was the control group that received the conventional (MDT-MB) treatment. Group 2 was the test group that received the association of rifampin 600 mg, ofloxacin 400 mg and minocyclin 100 mg (ROM), administrated once a month under supervision. Both groups were treated for two years. Initial evaluation of patients included: clinical examination, bacilloscopy and histology. Bacilloscopy and skin biopsy were repeated at the end of the first and second years of treatment. Clinical evaluation was performed monthly concomitant to administration of drugs.

Fourteen patients were evaluated in group 1. Bacilloscopic index (BI) before treatment varied from 2 to 4.8. Twelve patients were evaluated in group 2. The BI before treatment in this group varied from 1.6 to 4.8. Both groups presented cutaneous lesions characteristic of the lepromatous type. The histological picture resembled active lepromatous leprosy, except for one patient of group 2.

At the end of the first year of treatment all patients showed clinical improvement, the BI decreased and they presented regressive histological picture. This tendency to improvement was maintained and at the final evaluation in the second year all patient showed even better clinical, bacilloscopic and histological improvement.

The statistical analysis of bacilloscopic and histological parameters showed there weren’t significant differences between the groups studied, therefore, treatments were equally efficacious. Occurrence of type 2 (erythema leprosum nodosum –ENL) reactional episodes was similar in both groups. In group 1 all patients presented skin pigmentation due to clofazimine. These results demonstrate that monthly administration of rifampin, plus ofloxacin plus minocyclin are as efficacious and secure as the conventional scheme. Besides, it presents the advantage of not provoking skin pigmentation, it is given under supervision and can be used as an alternative treatment scheme.

9-REFERÊNCIAS *

1. Cochrane RG. The history of leprosy and its spread throughout the world. In: Leprosy in theory and practice. 2nd ed London: Jhon Wrigt & Sons; 1964. p.1-12.

2. Skinsnes OK. Notes from the history of leprosy. I. Interpretative chronology of leprosy Concept and Practice. Int J Lepr Other Mycobact Dis. 1973; 41:220-33.

3. Skinsnes OK, Chang PH. Understanding of leprosy in ancient China. Int J Lepr Other Mycobact Dis. 1985; 53:298-307.

4. Opromolla, D.V.A. História. In: Noções de Hansenologia. 2o ed. Bauru: Centro de estudos “Dr. Reinaldo Quagliatto”. Instituto Lauro de Souza Lima; 2000. p.1-5.

5. Browne SG. The history of leprosy. In: Hastings RC. Leprosy. Edinburg: Churchill Livingstone; 1985. p. 1-14.

6. Ell, SR. Leprosy in history. In: Hastings RC. Leprosy.2nd ed. Edinburg: Churchill Livingstone; 2 ed.1994. p. 3-10.

7. Fliess, E. La lepra en la historia. II: El desarollo de la endemia em América. Rev Hosp Nac Baldonero Sommer, 1999; 2: 8-20.

8. Rees JRW. The microbiology of leprosy. In: Hastings RC. Leprosy. Edinburg: Churchill Livingstone; 1985. p.31-52.

9. Trautman JR. The history of leprosy. In: Hastings R.C. Leprosy. 2nd ed. Edinburg: Churchill Livingstone;, 1994. p.11-25.

10. Maurano F. História da lepra em São Paulo. São Paulo: Empresa Gráfica da Revista dos Tribunais; 1939. v. 1- 2.

11. WhiteC. Carville and Curupaiti: experiences of confinement and community. Hist Cienc Saúde Manguinhos. 2003; 10 supl 1: 123-41.

____________________________

* International Committee of Medical Journal Editors. Uniform Requirements for Manuscripts Submitted to Biomedical Journals: sample references.[homepage on the Internet]. Bethesda:U.S. National Library of Medicine; 2003[last update 2003 July 09; cited 2005 Jun 01]. Avaliable from:http://www.nlm.nih.gov/bsd/uniform_requirements.html National Library of Medicine. List of journals indexed in Index Medicus. Washington, 2003.

12. Obregón D. The anti-leprosy campaign in Colômbia: the retoric of hygiene and science, 1920-1940. Hist Cienc Saúde Manguinhos, 2003; 10 supl 1:197-207.

13. Faget GH, Pogge RC, Johansen FA, Dinan JF, Prejean BM, Eccles CG. The promin treatment of leprosy: a progress report. Int J Lepr Other Mycobact Dis.1966; 34:298-310.

14. Opromolla DVA. Contribuição ao estudo da terapêutica da lepra (hanseníase)[tese]. Bauru: Universidade de São Paulo, Faculdade de Odontologia de Bauru; 1972.

15. Souza Lima L. Histórico e importância da Sulfonoterapia. In: Estado atual da terapêutica da lepra. São Paulo: Serviço Nacional de Lepra; 1953.

16. Jacobson RR, Trautman JA. The treatment of leprosy with sulphones: the original Faget´s 22 patients: a follow up of thirty years under sulphonetherapy. Int J Lepr Other Mycobact Dis. 1971; 39:71-8.

17. Jacobson RR. Treatment. In: Hastings RC. Leprosy. Edimburg: Churchill Livingstone; 1985. p. 193-222.

18. Shepard CSC. Multiplication of “Mycobacterium leprae” in the foot-pad of the mouse. Int J Lepr. 1962; 30: 291-3.

19. Rees JRW, Valentine RC. The appearence of dead leprosy bacilli by light and electron microscopy. Int J Lepr. 1962; 30:1-9.

20. Ridley DS, Hilson GR. A logarithimic index of bacilli in biopsies. I. Method. Int J Lepr Other Mycobact Dis. 1967; 35: 184-6.

21. Waters MF, Rees RJ. Changes in morphology of Mycobacterium leprae in patients under treatment. Int J Lepr. 1962; 30:266-77.

22. Browne SG, Hogerzeil LM. “B- 663” in the treatment of leprosy: preliminary report of a pilot trial. Lepr Rev. 1962; 33:6-10.

23. Opromolla DVA. Primeiros resultados com a “Rifamicina SV” na lepra lepromatosa. In: Anais do VIII Congresso Internacional de Leprologia; Rio de Janeiro: Serviço Nacional de de lepra; 1963. v. 2, p.346-55.

24. Belda W, Margarido LC, Marlet JL. Martinez EALW, Kliemann TJA, Lombardi C, et al. Estudo comparativo das médias movéis dos índices baciloscópico e morfológico em pacientes de hanseníase virchoviana

tratados pela Rifampicina e pela Diamino-Difenil Sulfona. Rev Saúde Pública. 1979; 13:80-91.

25. Rees JRW. Experimental and clinical studies on rifampicin in the treatment of leprosy. Br Med J.1970; 1:89-92.

26. Shepard CC, Levy L, Fasal P. Rapid bactericidal effect of Rifamycin on the experimental infection by M. leprae. Am J Trop Med Hyg 1972; 21:446-9.

27. Waters MFR, Rees RJW, Pearson JMH, Laig ABG, Helmy HS, Gelber RH. Rifampicin for lepromatous leprosy: nine years experience. Br Med J. 1978; 1(6106):133-6.

28. Opromolla DV, Tonello CJ, McDougall AC, Yawalkar SJ. Acontroled trial to compare the therapeutics effects of dapsone in combination with daily or once-monthly rifampin in patients with lepromatous leprosy. Int J Lepr Other Mycobact Dis. 1981; 49:393-7.

29. Ministério da Saúde. Secretaria Nacional de Programas Especiais de Saúde. Divisão Nacional de Dermatologia Sanitária. Normas Técnicas e Procedimentos para Utilização dos Esquemas de Poliquimioterapia no Tratamento da Hanseníase. Brasília; 1989.

30. WHO Study Group. Chemotherapy of leprosy for control programmes. Geneva: World Health Organization; 1982. Tech Rep Ser, 675.

31. Ministério da Saúde. Fundação Nacional de Saúde. Guia de controle da Hanseníase. Brasília; 1994.

32. WHO Study Group. Chemotherapy of leprosy for control programmes. Geneva: World Health Organization; 1993. Tech Rep Ser, 847.

33. Penna GO. Treatment of leprosy with WHO´s standard fixed duration chemotherapy. Rev Soc Bras Med Trop. 1995; 28:167-8.

34. Grosset JH. Progress in the Chemotherapy of leprosy. Int J Lepr Other Mycobact Dis.1994; 62:268-77.

35. Shaw IN, Cristian M, Jesudasan K, Kurian N, Rao GS. Effectiveness of multidrug therapy in multibacillary leprosy: a long term follow-up of 34 multibacillary leprosy patients treated with multidrug regimes til skin

37. Ji B, Perani EG, Petinom C, Grosset JH. Bactericidal Activities of Combinations of New Drugs against Mycobactrium leprae in Nude Mice. Antimicrob Agents Chemother. 1996; 40:393-9.

38. Ji B, Perani EG, Grosset JH. Bactericidal activities of single or multiple dose of various combinations of new anti-leprosy drugs and/or Rifampicin against M. leprae in mice. Int J Lepr Other Mycobact Dis. 1992; 60:556-61.

39. Opromolla DVA. Novos rumos na terapêutica da hanseníase. An Bras Dermatol. 1990; 65:86-90.

40. Grosset JH, Guelpas-Lauras CC, Perani EG, Beoletto C. Activity of Ofloxacin against M. leprae in the mouse. Int J Lepr Other Mycobact Dis. 1988; 56:259-64.

41. Grosset JH, Ji B, Guelpas-Lauras CC, Perani EG, N´Deli LN. Clinical trial of Pefloxacin and Ofloxacin in the treatment of lepromatous leprosy. Int J Lepr Other Mycobact Dis. 1985; 58:581-6.

42. Guelpas-Lauras C.C, Perani EG, Giroir AM, Grosset JH. Activities of Pefloxacin and Ciprofloxacin against M. leprae in the mouse. Int J Lepr Other Mycobact Dis. 1987; 55:70-7.

43. Monk JP, Campoli-Richards DM. Ofloxacin: a review of its antibacterial activity, pharmacokinetic and therapeutic use. Drugs. 1987; 33:346-91. 44. Wolfson JS, Hooper D. The fluorquinolones: structures, mechanism of

action and resistence and stpectra of activity in vitro. Antimicrob Agents Chemother.1985; 28:581-6.

45. N´Deli L, Guelpas-Lauras CC, Perani EG, Grosset JH. Effectiveness of Pefloxacin in the treatment of lepromatous leprosy. Int J Lepr Other Mycobact Dis. 1990; 58:12-8.

46. Ji B, Jamet P, Perani EG, Sow S, Lienhardt C, Petinon C, et al. Bactericidal Activity of single dose of Clarthromicin plus Minocycline, with or without Ofloxacin, against Mycobacterium leprae in patients. Antimicrob Agents Chemother. 1996; 40:2137-41.

47. Gelber RH. Activity of minocycline in M.leprae infected mice. J Infect Dis. 1987; 156:236-9.

48. Gelber RH, Siu P, Tsang M, Alley P, Murray LP. Effect of low-level and intermittent minocycline therapy on the growth of M. leprae in mice. Antimicrob Agents Chemother. 1991; 35:992-4.

49. Gelber RH, Siu P, Tsang M, Murray LP. The minimal bactericidal dietary concentration of minocycline for M. leprae infected mice is very low and similar to its minimal inhibitory dietary concentration. Int J Lepr Other Mycobact Dis.1992; 60:276-7.

50. Gelber RH, Fukuda K, Byrd S, Murray LP, Tsang M, Rea TH. A clinical trial of minocycline in lepromatous leprosy. Br Med J. 1992; 304 (6819):91-2.

51. Ridley DS, Jopling WH. Classification of leprosy accordind to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 1966; 34:255-73. 52. Ridley DS. Bacterial indices. In: Cochrane R, Davey TF. Leprosy in

theory and practice. 2nd ed. Bristol: John Wright; 1964. p.620-2.

53. Ridley DS, Job CK. The pathology of leprosy. In: Hastings RC. Leprosy. Edinburg: Churchill Livingstone; 1985. p 100-33.

54. Girling DJ. Adverse reactions to Rifampicin in antituberculosis rgimes. J Antimicrob Chemother. 1977; 3:115-32.

55. Viana FR, Avelleira JCR, Marques AB. Síndrome pseudogripal. Relato de um caso. An Bras Dermatol. 1991; 66:127-8.

56. Fanning WL, Gump DW, Sofferman RA. Side effects of Minocycline: A Double-Blind Study. Antimicrob Agents Chemother. 1977; 11:712-7. 57. Zar JH. Biostatistical analysis. 3rd ed. New Jersey: Prentice Hall; 1996. 58. Opromolla DVA. Manifestações clínicas e reações. In: Noções de

Hansenologia. 2o ed. Bauru: Centro de Estudos “Dr. Reinaldo Quagliatto”. Instituto Lauro de Souza Lima; 2000. p.51-8.

59. McNair NA, Revankar CR, Ganapati R. Clinical, bacteriological and histopathological assessment of multibacillary leprosy cases after 1 and 2 years multidrug therapy. Preliminary communication. Lepr Rev. 1987; 58:182-6.

61. Villahermosa LG, Fajardo TF, Abalos RM, Cellona RV, Balgon MV, Dela Cruz EC, et al. Parallel assessment of 24 monthly doses of Rifampin, Ofloxacin, and Minocycline versus two years of World Health Organization Multi-Drug Therapy for Multi-Bacillary Leprosy. Am J Trop Med Hyg. 2004; 70:197-200.

62. Suneetha S, Reddy R. Histological resolution and bacterial clearance with pulse ROM therapy in borderline lepromatous leprosy. . Int J Lepr Other Mycobact Dis. 2001; 69:53-4.

63. Kishore BN, Shetty JN. Bacterial clearance with WHO – recommended multidrug regimen for multibacillary leprosy. Indian J Lepr. 1995; 67:301- 8.

64. Li HY. Yu XL, Zhang MS, Duan CX, Huang WB, Zhang SB, et al. Short term MDT in MB leprosy- Review of 80 cases of two provinces of China (1983-1988). Int J Lepr Other Mycobact Dis. 1989; 57:622-7.

65. Katoch K, Ramu G, Ramanathan U, Sengupta U, Sreevatsa.. Folow-up of BL/LL patients on a slightly modified WHO regimen of MDT. Indian J Lepr. 1987; 59:36-43.

66. Ramesh V, Misra RS, Saxena U. Multidrug therapy in multibacillary leprosy; experience in a urban leprosy center. Int J Lepr Other Mycobact Dis.1992; 60:13-7.

67. Naik SS, Bhanage ND, Sawant KV, Ganapati R. A bacteriological assessment of multibacillary cases in leprosy colonies after 4 1/2 years of

MDT. Indian J Lepr. 1988; 60:393-9.

68. Ganapati R, Pai VV, Shrof HJ, Gandelwar K. Rate of decline in bacterial index in leprosy; observations after three different chemotherapeutic interventions. Int J Lepr Other Mycobact Dis. 1997; 65:364-6.

69. Sheela GR, Gopa AK, Gandelwar KL. Multidrug therapy in multibacillary leprosy cases in a urban context- a study in Bombay. Indian J Lepr. 1989; 61:190-5.

70. Vijayakumaran P, Jesudasan K, Manimozhi N. Fixed-duration therapy (FDT) in multibacillary leprosy; efficacy and complications. Int J Lepr Other Mycobact Dis. 1996; 64:123-7.

71. Amenu A, Saunderson P, Desta K, Byass P. The patern of decline in bacillary index after 2 years of WHO recommended multiple drug therapy: the AMFES cohort. Lepr Rev. 2000; 71:332-7.

72. Kumar A, Girdhar A, Girdhar BK. Pattern of bacillary clearance in multibacillary leprosy patients with multidrug therapy. Acta Leprol. 2003;12:123-8.

73. Wabistsch KR, Meyers WM. Histopathologic observations on persistence of Mycobacterium leprae in the skin of multibacillary leprosy patients under chemotherapy. Lepr Rev, 1988; 59:341-6.

74. Sharma A, Sharma VK, Rajwashi A, Das A, Kaur I, Kumar B. Presence of M. leprae in tissues in slit skin smear negative multibacillary (MB) pacients after WHO- MBR. Lepr Rev. 1999; 70:281-6.

75. Cree IA, Coghill G, Subedi AMC, Abbot NC, Butlin SR, Samson PD, et al. Effects of treatment on the histopathology of leprosy. J Clin Pathol. 1995; 48:304-7.