Poor treatment compliance leads to a higher mutation for rifampicin resistance in multibacillary leprosy patients
AbstractBackground: Multidrug therapy (MDT) is a safe and effective drug combination for leprosy treatment that can prevent drug resistance. Mycobacterium leprae resistance, especially to rifampicin, is a serious problem as it potentially thwarts the worldwide leprosy-elimination program by the World Health Organization (WHO). One of the suspected causes of rifampicin resistance is poor treatment compliance. It was necessary to assess the association between the treatment compliance and the occurrence of mutation rifampicin resistance in multibacillary (MB) leprosy patients.
Methods: A comparative, analytical, cross-sectional study was performed in MB leprosy patients who had completed treatment at the Dermatovenereology Outpatient Clinic in Cipto Mangunkusumo Hospital and the Sitanala Center for Leprosy Hospital from October 2012 to April 2013. Based on treatment regularity and history of drug discontinuation, the subjects were classified as either having good or poor compliance. Skin smear from a slit skin smear (SSS) examination was further analyzed by using the polymerase chain reaction (PCR) sequencing technique to detect rifampicin resistance.
Results: Fifty-seven study subjects were enrolled in this study. In the good treatment compliance group (29 subjects), only 1 case of mutation for rifampicin resistance was found. Meanwhile, in the poor drug compliance group (28 subjects), 8 cases of mutation for resistance (29%) were found. This difference in mutation rate was statistically significant (OR=11.2; 95% CI=1.296–96.787; p=0.012).
Conclusion: This study revealed that the risk of occurrence of M. leprae resistance to rifampicin in patients with poor drug compliance was significantly higher than in those with good drug compliance.
Amirudin MD, Hakim Z, Darwis E. Diagnosis Penyakit Kusta. In: Sjamsoe-Daili ES, Menaldi SL, Ismiarto SP, Nilasari H, editors. Kusta. 1. 2 ed. Jakarta: Balai Penerbit FKUI; 2003. p. 12–32.
Shepard CC, Rees RJ, Levy L, Pattyn SR, Baohong J, Dela Cruz EC. Susceptibility of strains of Mycobacterium leprae isolated prior to 1977 from patients with previously untreated lepromatous leprosy. Int J Lepr Other Mycobact Dis. 1986;54(1):11–5.
World Health Organization. WHO global strategy for further reducing the leprosy burden and sustaining leprosy control activities (Plan period: 2006-2010). Indian J Lepr. 2006;78(1):7–31.
Guinto RS, Cellona RV, Fajardo TT, de la Cruz EC. Primary dapsone-resistant leprosy in Cebu, Philippines. Int J Lepr Other Mycobact Dis. 1981;49(4):427–30.
Saonere JA. Leprosy: an overview. J Infect Dis Immun. 2011;3(14):233–43. https://doi.org/10.5897/JIDI11.038
Chemotherapy of leprosy. Report of a WHO Study Group. World Health Organ Tech Rep Ser. 1994;847:1–24.
Drug resistance in leprosy: reports from selected endemic countries. Wkly Epidemiol Rec. 2009;84(26):264–7.
Girdhar BK. Chemotherapy: Drugs Used in Leprosy Including Newer Drugs. In: Kar HK, Kumar B, editors. IAL Textbook of Leprosy. 1. 1 ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd; 2010. p. 335–52.
Ericsson CD, Steffen R, Ooi WW, Moschella SL. Update on leprosy in immigrants in the United States: status in the year 2000. Clin Infect Dis. 2001;32(6):930–7. https://doi.org/10.1086/319357
Honore N, Cole ST. Molecular basis of rifampin resistance in Mycobacterium leprae. Antimicrob Agents Chemother. 1993;37(3):414–8. https://doi.org/10.1128/AAC.37.3.414
Matsuoka M. Drug resistance in leprosy. Jpn J Infect Dis. 2010;63(1):1–7.
Williams DL, Gillis TP. Molecular detection of drug resistance in Mycobacterium leprae. Lepr Rev. 2004;75(2):118–30.
Saxena VM. In vitro methods for rapid monitoring of drug therapy and drug resistance in leprosy. Icmr Bull. 2001;31(8):1–6.
Maeda S, Matsuoka M, Nakata N, Kai M, Maeda Y, Hashimoto K, et al. Multidrug resistant Mycobacterium leprae from patients with leprosy. Antimicrob Agents Chemother. 2001;45(12):3635–9.
Matsuoka M, Budiawan T, Aye KS, Kyaw K, Tan EV, Cruz ED, et al. The frequency of drug resistance mutations in Mycobacterium leprae isolates in untreated and relapsed leprosy patients from Myanmar, Indonesia and the Philippines. Lepr Rev. 2007;78(4):343–52.
Kar S, Pal R, Bharati DR. Understanding non-compliance with WHO-multidrug therapy among leprosy patients in Assam, India. J Neurosci Rural Pract. 2010;1(1):9–13. https://doi.org/10.4103/0976-3147.63093
Guidelines for global surveillance of drug resistance in leprosy. New Delhi: World Health Organization, Regional Office for South-East Asia, 2009.
Williams DL, Waguespack C, Eisenach K, Crawford JT, Portaels F, Salfinger M, et al. Characterization of rifampin-resistance in pathogenic mycobacteria. Antimicrob Agents Chemother. 1994;38(10):2380–6. https://doi.org/10.1128/AAC.38.10.2380
Motta AC, Pereira KJ, Tarquínio DC, Vieira MB, Miyake K, Foss NT. Leprosy reactions: coinfections as a possible risk factor. Clinics (Sao Paulo). 2012;67(10):1145–8. https://doi.org/10.6061/clinics/2012(10)05
Laporan data kunjungan pasien poliklinik Morbus Hansen rekapitulasi bulan Januari-Desember 2012. Jakarta: Departemen Ilmu Kesehatan Kulit dan Kelamin FKUI-RSCM, 2013. Indonesian.
Brown TA. Mutation, repair, and recombination. Genomes. 1. 2 ed. Oxford: Wiley-Liss; 2002. p. 418–57.
Wahyuni R, Adriaty D, Iswahyudi, Prakoeswa CR, Agusni I, Izumi S. Profile of mutation on drug resistance Mycobacterium leprae isolates in Indonesia collected during 2003–2011. Microbiol Indones. 2012;6(3):135–8. https://doi.org/10.5454/mi.6.3.7
Honoré N, Roche PW, Grosset JH, Cole ST. A method for rapid detection of rifampicin-resistant isolates of Mycobacterium leprae. Lepr Rev. 2001;72(4):441–8. https://doi.org/10.5935/0305-7518.20010052
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(1):39–45. https://doi.org/10.1086/324623
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