Keywords
drug resistance
dapsone
rifampin
How to Cite
Abstract
In 1981, reports of resistance to dapsone and rifampin led WHO to recommend multidrugtherapy in leprosy treatment. One of its main goals is preventing the selection of drug-resistant strains of mutant bactéria. Dapsone was the first drug which was experimentally proved to induce resistance; thisbecame possible only after the mouse foot pad inoculation technique was standardized, in 1960. There are some important criteria to suspect the existence of resistance, such as: relapses in multibacillary patients already treated or undergoing treatment or unsatisfactory clinicai response. Our study aimed at detection of dapsone and rifampin resistam strains among 40 treated patients with clinicai signs of relapse, from different cities of São Paulo State and its capital, employing the mouse footpad inoculation. We detected dapsone resistam bacilli in 11 cases. Among them, 5 showed total resistance, 1 intermediary resistance and 5 partial resistance. Rifampin resistant bacilli were detected in only two cases. We did not detect any case of multiple resistance. The high levei of resistance to dapsone is probably a consequence of many years of sulfone and sulfone derivative monotherapy. As for the rifampin, the drug was probably irregularly used in monotherapy; or the patient may have used it previously to treat another disease. The detection of resistant bacilli in patients who do not show any clinicai improvement, or relapse after treatment, is an important matter to be considered in the future prevention of new cases of resistance. The emergence of resistant strains, especially to rifampin, as well as its dissemination, may cause difficulties to the patients's treatment and jeopardize the leprosy control programs.
References
Report Series. Geneva, 675).
2 World Health Organization. [homepage on the internet]: EHmination of Leprosy as a Public Health Problem [updated 2005 March], Disponível em: http://www.who.int/lep/
3 Ji B. Drug resistence in leprosy - a review. Lepr rev 1985; 56: 265-78.
4 Floch H. La sulfono-résistance du Bacille de Hansen. Archlves de LvInstitui Pasteur de la Cuyane Française et de L'lnini 1957; 18: 1-9, pub licação nc429.
5 Shepard CC. The experimental disease that follows the injection of human leprosy bacilli into foot pads of mice. j exp med 1960; 112: 445-57.
6 Pettit jHS, Rees RJW. Sulfone resistance tn leprosy. An experimental and clinicai study. Lancet 1964; 2: 673-4.
7 Guinto RS, Cellona RV, Fajardo, TT, Cruz EC. Primary dapsone-resistant leprosy in Cebu, Philippines. Int j lepr other mycobact dis 1981; 49(4): 427-30.
8 Matsuoka M, Kashiwabara Y, Namisato M. A Mycobacterium leprae isolate resistant to dapsone, rifampin, ofloxacin and sparfloxacin. Int j lepr other mycobact dis 2000; 68 (4): 452-55.
9 Cillis TP, Williams DL. Dapsone resistance in Mycobacterium leprae. Lepr rev, Workshop Proceedings 2000; 71(1), Suppl S91-5.
10 Cambau E, Bonnafous P, Perani E, Sougakoff W, Ji B, Jarlier V. Molecular detection of rifampin and ofloxacin resistance for patients who experience relapse of multibacillary leprosy. Clin infect dis 2002; 34: 39-45.
11 Sekar B et a/. Drug susceptibility of Mycobacterium leprae: a retrospective analysis of mouse foot pad inoculation results from 1983 to 1997. Lepr rev 2002; 73: 239-44.
12 Shetty VP, Wakade AV, Ghate S, Pai W, Ganapati R, Antia NH. Viability and drug susceptibility test ing of Mycobacterium leprae using mouse foot pad in 37 relapse cases of leprosy. Int j lepr other mycobact dis 2002; 71 (3): 210-17.
13 Costa HC, Opromolla DVA, Madeira S, Marques FB, Martel li ACC, Ura S. Prevalência de sulfono resistência em pacientes hansenianos do município de Bauru, Estado de São Paulo. Hansen int 1993; 18(1/2): 5-10.
14 World Health Organization - Dapsone-resistant leprosy - The THELEP Approach. Int j lepr other mycobact dis 1981; 49(4): 421 -25.
15 World Health Organization. Laboratory Techniques for Leprosy. Geneya; WHO; 1987.
16 |i B. Drug susceptibility testing of Mycobacterium leprae. Int j lepr other mycobact dis 1987; 55(4) Suppl 830-35.
17 Opromolla DVA, Costa HC, Oliveira PRD. Resistência medicamentosa múltipla secundária na hanseníase. Hansen int 1993; 18(1/2): 11-6.
18 Dallas WS, et al. Cloning, sequencing and enhanced expression of the dihydropteroate syn thase gene of Escherichia coli MC 4100. j bacteri ol 1992; 174(18): 5961-70.
19 Fermer C, Swedberg G. Adaptation to sulfonamide resistance in Neisseria meningitidis may have required compensatory changes to retain enzyme function: kinetíc analysis of Dihydropteroate synthase from Neisseria meningitidis expressed in aknockout mutant of Escherichia coli. J bacteriol 1997; 179(3): 831-37.
20 Lopez P, Espinosa M, Greenberg B, Sacks, S A. Sulfonamide resistance in Streptococcus pneumo niae: DNA sequence of the gene encoding dihy dropteroate synthase and characterization of the enzyme. ) bacteriol 1987; 169(9): 4320-26.
21 Jacobson RR, Hastings RC. Rifampin resistant leprosy. (Letter) Lancet 1976; ii:l 304-5.
22 Jacobson RR. Final report of the WHO regional working group on drug policy and operational research in the leprosy programme; Manila, Philippines; 1981; 10.
23 Guelpa-Lauras CC, Crosset JH, Constant- Deportes M, Brucker G. Nine cases of rifampicin resistant leprosy. Int j lepr other
mycobactdis 1984; 52:101-2.
24 Grosset JH et al. Study of 39 documented relapses of multi bacillary leprosy after treatment with rifampin. Int j lepr other mycobact dis 1989; 57: 607-14.
25 Honoré N, Cole ST. Molecular basis of rifampin resistance in Mycobacterium leprae. Antimicrob agents chemother 1993; 37: 414-18.
26 Levy L. Multiplication of Mycobacterium leprae in normal mice. Int J lepr other mycobact dis 1987; 55(4)Suppl 814-18.
27 Gupta UD, Katoch K, Singh HB. Assessment of via bility by normal MFP and bacillary ATP biolumi nescenceassay in multi bacillary cases treated with an MDT using conventional as well as newer drugs like minocycline and ofloxacin. Indian j lepr 2000; 72: 437- 42.
28 Subcommittee on clinicai trials of the chemotherapy of leprosy (THELEP). Scientific working group of the UNDP/World Bank/WHO special programme for research and training in tropical disease. The THELEP controlled clinicai drug trials. Int j lepr other mycobact dis 1987; 55: 864-71.
29 Almeida JG, Chacko CJC, Christian M. The significance of dapsone (DDS)- resistant Mycobacterium leprae in untreated patients. Int j lepr othermycobact dis 1983; 51: 374-77.
30 Gupta UD, Katoch VM. Understanding the phnomenon of persistence in mycobacterial infections. Indian j lepr 1997; 69(4):385-93.
31 Levy L. Treatment failures in leprosy. Int j lepr other mycobact dis 1976; 44:177-82
This journal is licensed under a Creative Commons Attribution 4.0 International License.
Downloads
