Generic selectors
Exact matches only
Search in title
Search in content
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obervation Letter
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Studies
Study Letter
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Tables
Technology
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF
Letter to the Editor
2013:79:4;527-529
doi: 10.4103/0378-6323.113096
PMID: 23760326

Primary dapsone resistant Mycobacterium leprae in a non endemic country

Adawiyah Jamil1 , Noorlaily M Noor2 , Amrish S Osman3 , Mazlin M Baseri1 , Leelavathi Muthupalaniappen4
1 Department of Medicine, University Kebangsaan Malaysia Medical Center, Bandar Tun Razak, Cheras, Malaysia
2 Department of Dermatology, Hospital Kuala Lumpur, Jalan Pahang, Kuala Lumpur, Malaysia
3 Leprosy Unit, National Public Health Laboratory Sungai Buloh, Selangor, Malaysia
4 Department of Family Medicine, University Kebangsaan Malaysia Medical Center, Bandar Tun Razak, Cheras, Malaysia

Correspondence Address:
Adawiyah Jamil
Department of Medicine, University Kebangsaan Malaysia Medical Center, Bandar Tun Razak, Cheras- 56000 Kuala Lumpur
Malaysia
How to cite this article:
Jamil A, Noor NM, Osman AS, Baseri MM, Muthupalaniappen L. Primary dapsone resistant Mycobacterium leprae in a non endemic country. Indian J Dermatol Venereol Leprol 2013;79:527-529
Copyright: (C)2013 Indian Journal of Dermatology, Venereology, and Leprology

Sir,

Dapsone monotherapy in leprosy resulted in high resistance rates since the 1960s. After introduction of multidrug therapy (MDT), the rate declined but dapsone resistant Mycobacterium leprae has not been eradicated. [1],[2],[3],[4],[5] Leprosy is not endemic in Malaysia, however, surveillance of drug resistance was continued to guide therapy to prevent the spread of resistant strains. We report a 12 years surveillance of primary dapsone resistance using the mouse foot pad (MFP) technique.

Skin biopsy samples of multibacillary leprosy patients throughout the country were sent to the National Public Health Laboratory, Sungai Buloh. The MFP cultivation technique: Saline albumin is added to grounded

4 mm × 12 mm skin specimen containing lesion to produce a 10 4 bacilli/0.03 ml suspension. The suspension is inoculated into mice foot pads. The mice were given feeds mixed with dapsone concentrations of 0.01% or 0.001% or 0.0001%. Six mice were fed with each concentration. A control group of six mice was not treated. Reassessment of the inoculated M. leprae was performed by harvesting the footpad of one mouse from each group after six months, the rest of the mice were assessed after 12 months incubation. Results are expressed as low level (resistance to dapsone concentration 0.0001%), intermediate (resistance to concentration 0.001%) or high level resistance (resistance to concentration 0.01%). Results from 1997 to 2008 were retrospectively reviewed.

A total of 457 cases were referred to the laboratory, 362 were newly diagnosed multibacillary leprosy patients. Ninety five were patients with relapsed disease or treatment problems. The median age was 37(6-85) years, 290(80.1%) were males and 72(19.9%) were females. There were 217(59.9%) Malaysians, 125(34.5%) Indonesians, 5(1.4%) Myanmarese, 5(1.4%) Nepalese, and 2(0.6%) Bangladeshis. Specimens from 271(74.9%) patients were successfully cultured and tested. Overall, 60(22.1%) were identified to have intermediate and high level resistance. Low level resistance was observed in 83(31%) cases. The prevalence of resistance is illustrated in [Table - 1].

Table 1: Results of MFP showing primary dapsone resistance

Intermediate and high-level resistances account to about 10-20%; however, in 2000, 2003 and 2007, the prevalence was higher than 30%. The highest clinically significant resistance recorded was 44.8% in 2007, of which 6.9% was of high level. In cases with intermediate or high resistance, the majority of patients are Malaysians (66%), followed by Indonesians (27%), Myanmarese (3.4%), and Nepalese (1.7%). Low level resistance was not observed in the Indonesians, 63.6% had intermediate or high level resistance.

Our results showed a high prevalence of low level resistance, however, this is not associated with clinical therapy failure as the dose used in the MFP is equivalent to treating a patient with dapsone 1mg daily, compared to the standard dose of 100 mg daily. [1],[2] Intermediate and high level resistances are clinically significant.

There are a few reported prevalence of primary dapsone resistant M. leprae from this region. Kai et al.,[3] in Vietnam found 6.1% folP1 mutation 33 new cases of leprosy and 6.4% in recently diagnosed cases between 2004 and 2009. In Yangoon, Myanmar between 2003 and 2005, there were 7.3% folP1 mutation in 54 new/recent cases. [2] In Cebu Philippines (2001-2006), 2.6% folP1 mutation was seen in 77 new/recent cases. [2] Between 2000-2005, 0.8% folP1 mutation was reported in Indonesia (North Maluku, North Sulawesi). [2] Cambau et al.,[1] in 1987-2000, found 14.3% folP1 mutation and equal number of resistance using the MFP in 21 new/recent cases in patients from the West Indies, Africa, Asia, and the Pacifics. In the 1980s, de la Cruz et al.,[4] detected 21% dapsone resistance using the MFP in 38 new cases in Cebu, Philippines.

Our figures within the same period are higher compared to other countries. Although, in general, the prevalence is much lower compared to pre-MDT, dapsone resistance persisted. Current dapsone resistant M. leprae in Malaysia is likely acquired from patients with resistant strains in the pre-MDT era. Transmission of dapsone resistant M. leprae among close contacts has been demonstrated by Li et al.,[5] in a molecular epidemiological study. Irregular therapy, inadequate coverage, and delay in diagnosis or treatment are other reasons why resistance continues.

M. leprae cultivation using MFP is currently the standard in drug susceptibility testing. However, the MFP is time consuming, labor intensive, and insensitive. Detection of mutation in the folP1 gene identifies dapsone resistance more rapidly, but compared to DNA methods, MFP differentiates viable and non-viable M. leprae and it reflects clinical efficacy. [1]

Primary dapsone-resistance in Malaysia may increase further. Early identification of resistance using rapid methods of detection will help maintain the effectiveness of the MDT and prevent spread of resistant cases. M. leprae cultivation using MFP may be used in adjunct to molecular techniques.

References
1.
Cambau E, Carthagena L, Chauffour A, Ji B, Jarlier V. Dihydropteroate synthase mutations in the folP1 gene predictdapsone resistance in relapsed cases of leprosy. Clin Infect Dis 2006;42:238-41.
[Google Scholar]
2.
Matsuoka M, Budiawan T, Aye KS, Kyaw K, Tan EV, Cruz E, et al. The frequency of drug resistance mutations in Mycobacterium lepraeisolates in untreated and relapsed leprosy patients from Myanmar, Indonesia and the Philippines. Lepr Rev 2007;78:343-52.
[Google Scholar]
3.
Kai M, NguyenPhuc NH, Nguyen HA, Pham TH, Nguyen KH,Miyamoto Y, et al.Analysis of drug-resistant strains of Mycobacterium leprae in an endemic area of Vietnam. Clin Infect Dis 2011;52:e127-32.
[Google Scholar]
4.
de la Cruz E, Cellona RV, Balagon MV, Villahermosa LG, Fajardo TT Jr., Abalos RM,et al. Primary dapsone resistance in Cebu, The Philippines; cause for concern. Int J Lepr Other Mycobact Dis 1996;64:253.
[Google Scholar]
5.
Li W, Sakamuri RM, Lyons DE, Orcullos FM, Shinde V, de la Pena EL, et al. Transmission of dapsone-resistant leprosy detected by molecular epidemiological approaches. Antimicrob Agents Chemother 2011;55:5384-7.
[Google Scholar]

Fulltext Views
178

PDF downloads
85
Show Sections