Palavras-chave
hanseníase multibacilar
poliquimioterapia
clofazimina
dapsona
minociclina
ofloxacina
rifampicina
poliquimioterapia
clofazimina
dapsona
minociclina
ofloxacina
rifampicina
Como Citar
1.
Ura S, Diório SM, Carreira BG, Lauris JR, Fleury RN, Barraviera B. Estudo terapêutico comparando a associação de rifampicina, ofloxacina e minociclina com a associação rifampicina, clofazimina e dapsona em pacientes com hanseníase multibacila. Hansen. Int. [Internet]. 30º de junho de 2007 [citado 24º de novembro de 2024];32(1):57-65. Disponível em: https://periodicos.saude.sp.gov.br/hansenologia/article/view/35194
Resumo
Foram comparados dois esquemas terapêuticos em pacientes com hanseníase multibacilar. O grupo controle com 14 pacientes recebeu o tratamento convencional. O grupo teste com 12 pacientes recebeu a associação de rifampicina 600 mg, ofloxacina 400 mg, e minociclina 100 mg, uma vez por mês, durante dois anos. Na avaliação inicial foram realizados exames clínicos, baciloscópicos e histológicos. A baciloscopia e a biópsia foram repetidas no final do primeiro e segundo ano de tratamento. As avaliações clínicas realizadas mensalmente. Todos pacientes apresentavam lesões cutâneas, que os caracterizavam como virchovianos ou peri-virchovianos. No grupo controle, o índice baciloscópico antes do tratamento variou de 2 a 4,8 e no grupo teste de 1,6 a 4,8. Histologicamente apresentavam quadro de hanseníase virchoviana ativa, exceto um paciente do grupo teste. Ao final do primeiro ano de tratamento estavam todos clinicamente melhorados, o índice baciloscópico diminuído e quadro histológico regressivo. Essa tendência se mantinha e ao final do segundo ano todos estavam clinicamente, baciloscopicamente e histologicamente ainda melhores. Análise estatística mostrou não haver diferença significante entre os grupos, sendo os esquemas equivalentes. No grupo controle todos apresentaram pigmentação cutânea devido a clofazimina. Os resultados deste estudo demonstraram que o esquema com rifampicina, ofloxacina e minociclina, teve eficácia e segurança equivalente a poliquimioterapia convencional para multibacilar. Além disso, não causa pigmentação cutânea, pode ser totalmente supervisionado, podendo ser utilizado como esquema alternativo.
Referências
1 Faget GH et al. The promin treatment of leprosy: a progress report. Int j lepr other mycobact dis 1966; 34(3):298-310.
2 Opromolla DVA. Contribuição ao estudo da terapêutica da lepra (hanseníase)[tese]. Bauru: Universidade de São Paulo, Faculdade de Odontologia de Bauru; 1972.
3 Souza Lima L. Histórico e importância da Sulfonoterapia. In: Brasil. Ministério da Educação e Saúde. Departamento Nacional de Saúde. Serviço Nacional de Lepra. Estado atual da terapêutica da lepra. São Paulo: Imprensa Oficial; 1953. p.23-9.
4 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.
5 Jacobson RR. Treatment. In: Hastings RC. Leprosy. Edimburg: Churchill Livingstone; 1985. p. 193-222.
6 Shepard CSC. Multiplication of “Mycobacterium leprae” in the foot-pad of the mouse. Int j lepr 1962; 30: 291-3.
7 Rees JRW, Valentine RC. The appearence of dead leprosy bacilli by light and electron microscopy. Int j lepr. 1962; 30:1-9.
8 Ridley DS, Hilson GR. A logarithimic index of bacilli in biopsies. I. Method. Int j lepr other mycobact dis 1967; 35(2):184-6.
9 Waters, M.F, Rees, R.J. Changes in morphology of Mycobacterium leprae in patients under treatment. Int j lepr 1962; 30:266-77.
10 Browne SG, Hogerzeil LM. “B- 663” in the treatment of leprosy: preliminary report of a pilot trial. Lepr rev 1962; 33:6-10.
11 Opromolla D.V.A. Primeiros resultados com a “Rifamicina SV” na lepra lepromatosa. In: Congresso Internacional de Leprologia, 8, Rio de Janeiro, 1963 Anais. Rio de Janeiro: Serviço Nacional de de lepra, 1963; 2:346-55.
12 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 pel Diamino-Difenil Sulfona. Rev. saúde pública 1979; 13:80-91.
13 Rees JRW. Experimental and clinical studies on rifampicin in the treatment of leprosy. Br med j 1970; 1:89-92.
14 Shepard, C.C.; 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.
15 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.
16 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
17 Ministério da Saúde (BR). 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: Ministério da Saúde; 1989
18 Who Study Group. Chemotherapy of leprosy for control programmes. Geneva: World Halth Organization, 1982. Tech Rep Ser 675.
19 Ministério da Saúde (BR). Fundação Nacional de Saúde. Guia de controle da Hanseníase. Brasília: Ministério da Saúde; 1994.
20 World Health Organization.Global leprosy situation. Wkl Epidemiol Rec 2007; 82(25):225-32.
21 Penna GO. Treatment of leprosy with WHO´s standard fixed duration chemotherapy. Rev soc bras med trop 1995; 28(3):167-8.
22 Grosset JH. Progress in the Chemotherapy of leprosy. Int j lepr other mycobact dis 1994; 62(2):268-77.
23 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 smear negativity. Lepr rev 2003; 74:141-7.
24 World Health Organization.Global leprosy situation. Wkl epidemiol rec 2005; 80(34):289-95.
25 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(2):393-9.
26 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 (4):556-61.
27 Opromolla, D.V.A. Novos rumos na terapêutica da hanseníase. An bras dermatol 1990; 65(2): 86-90.
28 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.
29 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.
30 Guelpas-Lauras CC, 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.
31 Monk JP, Campoli-Richards DM. Ofloxacin: a review of its antibacterial activity, pharmacokinetic and therapeutic use. Drugs 1987; 33:346-91.
32 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.
33 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.
34 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(9):2137-41.
35 Gelber R.H. Activity of minocycline in M.leprae infected mice. J infect dis 1987; 156:236-9.
36 Gelber RH, Siu P, Tsang M, Alley P, Murray LP. Effect of lowlevel and intermittent minocycline therapy on the growth of M. leprae in mice. Antimicrob agents chemother 1991; 35(5):992-4.
37 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.
38 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.
39 Ridley DS, Jopling WH. Classification of leprosy accordind to immunity. A five-group system. Int j lepr other mycobact dis 1966; 34(3):255-73.
40 Ridley DS. Bacterial indices. In: Cochrane R & Davey TF. Leprosy in theory and practice. 2 ed., Bristol: John Wright; 1964. p.620-22.
41 Ridley DS, Job CK. The pathology of leprosy. In: Hastings RC. Leprosy. Edinburg: Churchill Livingstone; 1985. p. 100-33.
42 Zar JH. Biostatistical analysis. 3 ed. New Jersey: Prentice Hall; 1996.43 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(2):182-6.
44 Mane I, Cartel JL, Grosset JH. Field trial on efficacy of supervised monthly dose of 600mg rifampin, 400mg ofloxacin and 100mg minocycline for the treatment of leprosy; first results. Int j lepr other mycobact dis 1997; 65:224-9.
45 Villahermosa LG, Fajardo TF, Abalos RM, Cellona RV, Balgon MV, Dela Cruz EC. Walsh GP and Walsh DS. 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(2):197-200.
46 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(1):53-4.
47 Kishore BN, Shetty JN. Bacterial clearance with WHO – recommended multidrug regimen for multibacillary leprosy. Indian j lepr 1995; 67(3):301-8.
48 Li Huan-Yng, Yu Xio-Lu, Zhang Mao-Sheng. Short term MDT in MB leprosy- Review of 80 cases of two provinces of China. Int j lepr other mycobact dis 1989; 57:622-7.
49 Katoch K, Ramu G, Ramanathan U. Folow-up of BL/LL patients on a slightly modified WHO regimen of MDT. Indian j lepr 1987; 59:36-43.
50 Ramesh V, Misra RS, Saxena U. Multidrug therapy in multibacillary leprosy; experience in a urban leprosy center. Int j
lepr other mycobact dis 1992 March; 60(1):13-7.
51 Naik SS, Bhanage ND, Sawant K. A bacteriological assessment of multibacillary cases in leprosy colonies after 4 1/2 years of MDT. Indian j lepr 1988; 60:393-9.
52 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(2):364-6.
53 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(2):190-5.
54 Vijayakumaran P, Jesudasan K, Manimozhi N. Fixed-duration therapy (FDT) in multibacillary leprosy; efficacy and complications. Int j lepr other mycobact dis 1996; 64(2):123-7.
55 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(3):332-7.
56 Kumar A, Girdhar A, Girdhar BK. Pattern of bacillary clearance in multibacillary leprosy patients with multidrug therapy. Acta leprol 2003;12(3):123-8.
57 Wabistsch KR, Meyers WM. Histopathologic observations on persistence of Mycobacterium leprae in the skin of multibacillary leprosy patients under chemotherapy. Lepr rev 1988; 59(4): 341-6.
58 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(3):281-6.
59 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
2 Opromolla DVA. Contribuição ao estudo da terapêutica da lepra (hanseníase)[tese]. Bauru: Universidade de São Paulo, Faculdade de Odontologia de Bauru; 1972.
3 Souza Lima L. Histórico e importância da Sulfonoterapia. In: Brasil. Ministério da Educação e Saúde. Departamento Nacional de Saúde. Serviço Nacional de Lepra. Estado atual da terapêutica da lepra. São Paulo: Imprensa Oficial; 1953. p.23-9.
4 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.
5 Jacobson RR. Treatment. In: Hastings RC. Leprosy. Edimburg: Churchill Livingstone; 1985. p. 193-222.
6 Shepard CSC. Multiplication of “Mycobacterium leprae” in the foot-pad of the mouse. Int j lepr 1962; 30: 291-3.
7 Rees JRW, Valentine RC. The appearence of dead leprosy bacilli by light and electron microscopy. Int j lepr. 1962; 30:1-9.
8 Ridley DS, Hilson GR. A logarithimic index of bacilli in biopsies. I. Method. Int j lepr other mycobact dis 1967; 35(2):184-6.
9 Waters, M.F, Rees, R.J. Changes in morphology of Mycobacterium leprae in patients under treatment. Int j lepr 1962; 30:266-77.
10 Browne SG, Hogerzeil LM. “B- 663” in the treatment of leprosy: preliminary report of a pilot trial. Lepr rev 1962; 33:6-10.
11 Opromolla D.V.A. Primeiros resultados com a “Rifamicina SV” na lepra lepromatosa. In: Congresso Internacional de Leprologia, 8, Rio de Janeiro, 1963 Anais. Rio de Janeiro: Serviço Nacional de de lepra, 1963; 2:346-55.
12 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 pel Diamino-Difenil Sulfona. Rev. saúde pública 1979; 13:80-91.
13 Rees JRW. Experimental and clinical studies on rifampicin in the treatment of leprosy. Br med j 1970; 1:89-92.
14 Shepard, C.C.; 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.
15 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.
16 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
17 Ministério da Saúde (BR). 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: Ministério da Saúde; 1989
18 Who Study Group. Chemotherapy of leprosy for control programmes. Geneva: World Halth Organization, 1982. Tech Rep Ser 675.
19 Ministério da Saúde (BR). Fundação Nacional de Saúde. Guia de controle da Hanseníase. Brasília: Ministério da Saúde; 1994.
20 World Health Organization.Global leprosy situation. Wkl Epidemiol Rec 2007; 82(25):225-32.
21 Penna GO. Treatment of leprosy with WHO´s standard fixed duration chemotherapy. Rev soc bras med trop 1995; 28(3):167-8.
22 Grosset JH. Progress in the Chemotherapy of leprosy. Int j lepr other mycobact dis 1994; 62(2):268-77.
23 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 smear negativity. Lepr rev 2003; 74:141-7.
24 World Health Organization.Global leprosy situation. Wkl epidemiol rec 2005; 80(34):289-95.
25 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(2):393-9.
26 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 (4):556-61.
27 Opromolla, D.V.A. Novos rumos na terapêutica da hanseníase. An bras dermatol 1990; 65(2): 86-90.
28 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.
29 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.
30 Guelpas-Lauras CC, 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.
31 Monk JP, Campoli-Richards DM. Ofloxacin: a review of its antibacterial activity, pharmacokinetic and therapeutic use. Drugs 1987; 33:346-91.
32 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.
33 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.
34 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(9):2137-41.
35 Gelber R.H. Activity of minocycline in M.leprae infected mice. J infect dis 1987; 156:236-9.
36 Gelber RH, Siu P, Tsang M, Alley P, Murray LP. Effect of lowlevel and intermittent minocycline therapy on the growth of M. leprae in mice. Antimicrob agents chemother 1991; 35(5):992-4.
37 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.
38 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.
39 Ridley DS, Jopling WH. Classification of leprosy accordind to immunity. A five-group system. Int j lepr other mycobact dis 1966; 34(3):255-73.
40 Ridley DS. Bacterial indices. In: Cochrane R & Davey TF. Leprosy in theory and practice. 2 ed., Bristol: John Wright; 1964. p.620-22.
41 Ridley DS, Job CK. The pathology of leprosy. In: Hastings RC. Leprosy. Edinburg: Churchill Livingstone; 1985. p. 100-33.
42 Zar JH. Biostatistical analysis. 3 ed. New Jersey: Prentice Hall; 1996.43 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(2):182-6.
44 Mane I, Cartel JL, Grosset JH. Field trial on efficacy of supervised monthly dose of 600mg rifampin, 400mg ofloxacin and 100mg minocycline for the treatment of leprosy; first results. Int j lepr other mycobact dis 1997; 65:224-9.
45 Villahermosa LG, Fajardo TF, Abalos RM, Cellona RV, Balgon MV, Dela Cruz EC. Walsh GP and Walsh DS. 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(2):197-200.
46 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(1):53-4.
47 Kishore BN, Shetty JN. Bacterial clearance with WHO – recommended multidrug regimen for multibacillary leprosy. Indian j lepr 1995; 67(3):301-8.
48 Li Huan-Yng, Yu Xio-Lu, Zhang Mao-Sheng. Short term MDT in MB leprosy- Review of 80 cases of two provinces of China. Int j lepr other mycobact dis 1989; 57:622-7.
49 Katoch K, Ramu G, Ramanathan U. Folow-up of BL/LL patients on a slightly modified WHO regimen of MDT. Indian j lepr 1987; 59:36-43.
50 Ramesh V, Misra RS, Saxena U. Multidrug therapy in multibacillary leprosy; experience in a urban leprosy center. Int j
lepr other mycobact dis 1992 March; 60(1):13-7.
51 Naik SS, Bhanage ND, Sawant K. A bacteriological assessment of multibacillary cases in leprosy colonies after 4 1/2 years of MDT. Indian j lepr 1988; 60:393-9.
52 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(2):364-6.
53 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(2):190-5.
54 Vijayakumaran P, Jesudasan K, Manimozhi N. Fixed-duration therapy (FDT) in multibacillary leprosy; efficacy and complications. Int j lepr other mycobact dis 1996; 64(2):123-7.
55 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(3):332-7.
56 Kumar A, Girdhar A, Girdhar BK. Pattern of bacillary clearance in multibacillary leprosy patients with multidrug therapy. Acta leprol 2003;12(3):123-8.
57 Wabistsch KR, Meyers WM. Histopathologic observations on persistence of Mycobacterium leprae in the skin of multibacillary leprosy patients under chemotherapy. Lepr rev 1988; 59(4): 341-6.
58 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(3):281-6.
59 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
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