03095nas a2200409 4500000000100000008004100001260001300042653001600055653001900071653003100090653001100121653001400132653002300146653001200169653001300181653002500194653001600219653003000235653001500265100001500280700001500295700001100310700001100321700001100332700001600343700001300359700001700372700001500389700001600404245016800420856005100588300001100639490000700650050003200657520198200689022001402671 2007 d c2007 Dec10aDNA Primers10aDNA, Bacterial10aDrug Resistance, Bacterial10aHumans10aIndonesia10aLeprostatic Agents10aleprosy10aMutation10aMycobacterium leprae10aPhilippines10apolymerase chain reaction10aRecurrence1 aMatsuoka M1 aBudiawan T1 aAye KS1 aKyaw K1 aTan EV1 aDela Cruz E1 aGelber R1 aSaunderson P1 aBalagon VF1 aPannikar VK00aThe frequency of drug resistance mutations in Mycobacterium leprae isolates in untreated and relapsed leprosy patients from Myanmar, Indonesia and the Philippines. uhttps://leprosyreview.org/article/78/4/34-3352 a343-520 v78 aInfolep Library - available3 a

INTRODUCTION: The magnitude of drug resistance in Mycobacterium leprae to dapsone, rifampicin, and ofloxacin was studied in three Southeast Asian countries with a high prevalence of leprosy.

METHODS: M. leprae from the skin of leprosy patients was collected in North Maluku and North Sulawesi in Indonesia, Yangon in Myanmar, and Cebu in the Philippines. Mutations in the drug resistance determining regions in the folP1, rpoB, and gyrA genes, which have been proven to confer resistance, were analysed. In addition, samples from 51 newly diagnosed cases and 13 patients with leprosy relapse in Cebu were submitted for susceptibility testing in the mouse footpad.

RESULTS: Of 252 isolates obtained from new cases, 3% were dapsone resistant and 2% were rifampicin resistant. In samples taken from patients with relapsed leprosy (n = 53), significantly more resistance mutations were detected: 15% had dapsone resistance mutations, and 8% had rifampicin resistance mutations. Two patients with relapsed leprosy had mutations for both dapsone and rifampicin resistance. No mutations conferring quinolone resistance were detected. No mutations were detected in the folP1 gene of M. leprae isolates with a low degree of resistance to dapsone.

DISCUSSION: Detection of drug-resistant cases by mutation detection in the drug resistance determining region of the genome is a practical method for monitoring resistance. A comparison of the results obtained in this study with previous data obtained prior to the use of multidrug therapy (MDT), does not indicate clearly whether the magnitude of drug resistance has changed. Larger studies of resistance mutations in M. leprae isolated from patients with relapsed leprosy are needed to confirm our results.

CONCLUSION: We recommend monitoring the magnitude of drug resistance globally, by testing M. leprae DNA from relapse cases and a representative sample of new cases.

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