Emergence and Transmission of Drug-/Multidrug-resistant Mycobacterium Leprae in a Former Leprosy Colony in the Brazilian Amazon

Overview

Journal Clin Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2019 Jul 2

PMID 31260522

Citations 13

Authors

Patricia S Rosa

Helena R S DEspindula

Ana C L Melo

Amanda N B Fontes

Amanda J Finardi

Andrea F F Belone

Beatriz G C Sartori

Carla A A Pires

Cleverson T Soares

Flavio B Marques

Francisco J D Branco

Ida M F D Baptista

Lazara M Trino

Luciana R V Fachin

Marilia B Xavier

Marcos C Floriano

Somei Ura

Suzana M Diorio

Wladimir F B Delanina

Milton O Moraes

Marcos C L Virmond

Philip N Suffys

Marcelo T Mira

Affiliations

Soon will be listed here.

Abstract

Background: Leprosy has been treated with multidrug therapy, which has been distributed for free across the globe and regarded as highly efficient. However, the impossibility of growing Mycobacterium leprae in axenic media has historically impaired assessments of M. leprae resistance, a parameter only recently detectable through molecular methods.

Methods: A systematic, population-based search for M. leprae resistance in suspected leprosy relapse cases and contacts was performed in Prata Village, an isolated, hyperendemic, former leprosy colony located in the Brazilian Amazon. Results led to an extended active search involving the entire Prata population. Confirmed leprosy cases were investigated for bacterial resistance using a combination of in vivo testing and direct sequencing of resistance genes folP1, rpoB, and gyrA. A molecular epidemiology analysis was performed using data from 17 variable number tandem repeats (VNTR).

Results: Mycobacterium leprae was obtained from biopsies of 37 leprosy cases (18 relapses and 19 new cases): 16 (43.24%) displayed drug-resistance variants. Multidrug resistance to rifampicin and dapsone was observed in 8 relapses and 4 new cases. Single resistance to rifampicin was detected in 1 new case. Resistance to dapsone was present in 2 relapses and 1 new case. Combined molecular resistance and VNTR data revealed evidence of intra-familial primary transmission of resistant M. leprae.

Conclusions: A comprehensive, population-based systematic approach to investigate M. leprae resistance in a unique population revealed an alarming scenario of the emergence and transmission of resistant strains. These findings may be used for the development of new strategies for surveillance of drug resistance in other populations.

Citing Articles

Insights into leprosy epidemiology from an isolated population located in the Brazilian Amazon.

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Computational investigation of the global prevalence of multidrug resistant : A systematic review and meta-analysis.

Zivarifar H, Ahrari F, Karbalaei M J Clin Tuberc Other Mycobact Dis. 2025; 37:100495.

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Grijsen M, Nguyen T, Pinheiro R, Singh P, Lambert S, Walker S Nat Rev Dis Primers. 2024; 10(1):90.

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Role of histopathological, serological and molecular findings for the early diagnosis of treatment failure in leprosy.

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Specialized active leprosy search strategies in an endemic area of the Brazilian Amazon identifies a hypermutated strain causing primary drug resistance.

Bouth R, Gobbo A, Barreto J, do Carmo Pinto P, Bittencourt M, Cipriani Frade M Front Med (Lausanne). 2023; 10:1243571.

PMID: 37780551 PMC: 10534026. DOI: 10.3389/fmed.2023.1243571.

References

Matsuoka M . Drug resistance in leprosy. Jpn J Infect Dis. 2010; 63(1):1-7. View

Cambau E, Saunderson P, Matsuoka M, Cole S, Kai M, Suffys P . Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009-15. Clin Microbiol Infect. 2018; 24(12):1305-1310. PMC: 6286419. DOI: 10.1016/j.cmi.2018.02.022. View

Jacobson R, Hastings R . Rifampin-resistant leprosy. Lancet. 1976; 2(7998):1304-5. DOI: 10.1016/s0140-6736(76)92071-7. View

Salgado C, Barreto J, da Silva M, Goulart I, Barreto J, de Medeiros Junior N . Are leprosy case numbers reliable?. Lancet Infect Dis. 2018; 18(2):135-137. DOI: 10.1016/S1473-3099(18)30012-4. View

Williams D, Gillis T . Drug-resistant leprosy: monitoring and current status. Lepr Rev. 2013; 83(3):269-81. View

Benjak A, Avanzi C, Singh P, Loiseau C, Girma S, Busso P . Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium leprae. Nat Commun. 2018; 9(1):352. PMC: 5783932. DOI: 10.1038/s41467-017-02576-z. View

Singh P, Benjak A, Carat S, Kai M, Busso P, Avanzi C . Genome-wide re-sequencing of multidrug-resistant Mycobacterium leprae Airaku-3. Clin Microbiol Infect. 2014; 20(10):O619-22. DOI: 10.1111/1469-0691.12609. View

Smith C, Aerts A, Saunderson P, Kawuma J, Kita E, Virmond M . Multidrug therapy for leprosy: a game changer on the path to elimination. Lancet Infect Dis. 2017; 17(9):e293-e297. DOI: 10.1016/S1473-3099(17)30418-8. View

Mejia M, Porto Dos Santos M, Silva G, da Motta Passos I, Naveca F, Souza Cunha M . Identification of primary drug resistance to rifampin in Mycobacterium leprae strains from leprosy patients in Amazonas State, Brazil. J Clin Microbiol. 2014; 52(12):4359-60. PMC: 4313315. DOI: 10.1128/JCM.01688-14. View

10.

Shetty V, Uplekar M, Antia N . Primary resistance to single and multiple drugs in leprosy--a mouse footpad study. Lepr Rev. 1996; 67(4):280-6. DOI: 10.5935/0305-7518.19960028. View

11.

Rocha A, Cunha M, Diniz L, Salgado C, Aires M, Nery J . Drug and multidrug resistance among Mycobacterium leprae isolates from Brazilian relapsed leprosy patients. J Clin Microbiol. 2012; 50(6):1912-7. PMC: 3372169. DOI: 10.1128/JCM.06561-11. View

12.

Avanzi C, Del-Pozo J, Benjak A, Stevenson K, Simpson V, Busso P . Red squirrels in the British Isles are infected with leprosy bacilli. Science. 2016; 354(6313):744-747. DOI: 10.1126/science.aah3783. View

13.

Yew W, Liang D, Chan D, Shi W, Zhang Y . Molecular mechanisms of clofazimine resistance in Mycobacterium tuberculosis. J Antimicrob Chemother. 2017; 72(10):2943-2944. DOI: 10.1093/jac/dkx227. View

14.

Lavania M, Singh I, Turankar R, Ahuja M, Pathak V, Sengupta U . Molecular detection of multidrug-resistant Mycobacterium leprae from Indian leprosy patients. J Glob Antimicrob Resist. 2017; 12:214-219. DOI: 10.1016/j.jgar.2017.10.010. View

15.

Fontes A, Lima L, Mota R, Almeida R, Pontes M, Goncalves H . Genotyping of Mycobacterium leprae for better understanding of leprosy transmission in Fortaleza, Northeastern Brazil. PLoS Negl Trop Dis. 2017; 11(12):e0006117. PMC: 5747459. DOI: 10.1371/journal.pntd.0006117. View

16.

. Chemotherapy of leprosy for control programmes. World Health Organ Tech Rep Ser. 1982; 675:1-33. View

17.

Pettit J, Rees R . SULPHONE RESISTANCE IN LEPROSY. AN EXPERIMENTAL AND CLINICAL STUDY. Lancet. 1964; 2(7361):673-4. DOI: 10.1016/s0140-6736(64)92482-1. View

18.

Cambau E, Perani E, Guillemin I, Jamet P, Ji B . Multidrug-resistance to dapsone, rifampicin, and ofloxacin in Mycobacterium leprae. Lancet. 1997; 349(9045):103-4. DOI: 10.1016/S0140-6736(05)60888-4. View

19.

Pearson J, Haile G, Rees R . Primary dapsone-resistant leprosy. Lepr Rev. 1977; 48(2):129-32. DOI: 10.5935/0305-7518.19770016. View

20.

Machado D, Lecorche E, Mougari F, Cambau E, Viveiros M . Insights on Efflux Pumps and Their Implications in Drug Resistance and Virulence. Front Microbiol. 2019; 9:3072. PMC: 6300501. DOI: 10.3389/fmicb.2018.03072. View