Analysis of Drug-Resistant Strains of Mycobacterium leprae in an Endemic Area of Vietnam

• Published in: Clinical infectious diseases Vol. 52; no. 5; pp. e127 - e132
• Main Authors: Kai, Masanori, Nguyen Phuc, Nhu Ha, Nguyen, Hoang An, Pham, Thi Hoang Bich Diu, Nguyen, Khanh Hoa, Miyamoto, Yuji, Maeda, Yumi, Fukutomi, Yasuo, Nakata, Noboru, Matsuoka, Masanori, Makino, Masahiko, Nguyen, Thanh Tan
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.03.2011
• Subjects: Bacterial Proteins - genetics; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; Drug Resistance, Bacterial; Endemic Diseases; Genotype; Humans; Leprostatic Agents - pharmacology; Leprosy - epidemiology; Leprosy - microbiology; Mycobacterium leprae - drug effects; Mycobacterium leprae - genetics; Mycobacterium leprae - isolation & purification; Recurrence; Sequence Analysis, DNA; Vietnam - epidemiology; Vietnam
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciq217

Though, multi-drug therapy (MDT) has effectively reduced the number of leprosy cases, the rate of reduction has slowed. We show high rates of dapsone resistance in relapse patients in our study. Therefore, early detection of early detection of Mycobacterium leprae and epidemiological study of relapse is relevant in attempts to eliminate the disease. (See brief report by Ramien and Wong, e133-e135.) Background.  Multidrug therapy has effectively reduced the number of leprosy cases in the world. However, the rate of reduction has decelerated over the years, giving early detection of Mycobacterium leprae and epidemiological study of relapse renewed relevance in attempts to eliminate the disease. Methods.  A molecular epidemiological survey for drug-resistant M. leprae was conducted in the central and highland regions of Vietnam. A total of 423 samples taken from patients, including 83 patients with new cases, 321 patients receiving treatment, and 19 patients with relapse, were studied for detection of M. leprae with mutations relating to drug resistance by sequencing the drug resistance determining region of the folP1, rpoB, and gyrA genes, which are responsible for dapsone, rifampicin, and ofloxacin resistance, respectively. Results.  Nineteen mutations were found in the folP1 gene samples, and no mutations relating to drug resistance were found in either the rpoB or gyrA genes. Samples from patients with relapse showed folP1 mutation rates as high as 57%, and the mutation rates in samples from new and recent cases were <10%. Patients with relapse who had histories of treatment with dapsone monotherapy showed high mutation rates (78%), compared with patients with relapse who had previously only received multidrug therapy (33%). Conclusions.  Our study indicated high rates of dapsone resistance in patients with relapse, compared with patients with new and recent cases of leprosy. Moreover, it was observed that many of the patients with relapse who had dapsone-resistant mutations had histories of treatment with dapsone monotherapy.