Antimicrobial resistance in leprosy: results of the first prospective open survey conducted by a WHO surveillance network for the period 2009–15

Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resis...

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Published in:	Clinical microbiology and infection Vol. 24; no. 12; pp. 1305 - 1310
Main Authors:	Saunderson, P., Kai, M., Suffys, P., Rosa, P.S., Williams, D., Gupta, U.D., Lavania, M., Cardona-Castro, N., Miyamoto, Y., Vissa, V., Johnson, R.C., Cauchoix, B., Cooreman, E.A.W.D., Pemmaraju, V.R.R., Gillini, L., Al-Samie, Abdul Rahim, Issoufou, Ahamed, Tiendrebeogo, Alexandre, Kingalu, AmriMiraju, Randrianantoandro, Andriamira, Kumar, Anil, Chauffour, Aurelie, Win, Aye Aye, Pandey, Basudev, Agrawal, C.M., Widaningrum, Christiana, Sema, Cynthia, Vidanagama, D.S., Scollard, David M., Beyene, Demmissew, Morelo, Eliane Faria, Kassa, Elizabeth Dizaneh, Claco, Eric, Villalon, Ernesto ES, Sidibe, Famoussa, Sakho, Fatoumata, Abdoulaye, Fomba, Guilengue, Francisco F., Babu, Gadde Rajan, Thakur, Garib Das, Cabanos, Gemma, Clugston, Greame, Zaidy, Hany, Watanabe, Haruo, Kawuma, Herman Joseph, Mallari, Irene Balenton, Goulart, Isabella Maria Bernandes, Ahamed, Issoufou, Subbanna, J., Luengu, Jean Norbert Mputu, Bertolli, Jeanne, Lloyd-Owen, Jonathan, Matheu, Jorge, Brunelli, José Pereira, Osuga, Katsunori, Yamaguchi, Kazuko, Azam, Khalid, Momoudu, Kodia, Doanh, Le Huu, My, Ley Huyen, Shah, Mahesh, Sidibe, Mamadou, Ebenezer, Mannam, Grossi, Maria Aparecida de Faria, Balagon, Marivic F., Canlonon, Marlience, Ahmed, Md Jamsheed, Roferos, Florenda Orcullo, Krismawati, Hana, Htoon, Myo Thet, Van, NguyenThi Hai, Hai, Ngyuen Phuc Nhu, Ishii, Norisha, Soe, Oke, Amiel, Olga, Tossou, Omar, Joshi, P.L., Ranganadha Rao, P.V., Krishnamurthy, Padebettu, Brennan, Patrick J., Busso, Phillipe, Rakoto Andrianarivelo, Mala, Ramdas, D.R., Chabi, Raoul, Gusmao, Renato, DjupuriIzwardy, Rita, Soares, Rosa Castalia Franca Riberio, Buhrer, Samira, Cho, Sang-Nae Ray, Lzumi, Shinzo, Barua, Sumana, Chaitanya, Sundeep, Khang, Tan Hau, Vijayalakshmi, V., Kamara, Vedastus Deusdedit, Wei, Wang, Smith, W.Cairn S., Li, Wei, Lew, Woojin, Al-Qubati, Yasin
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-12-2018 Elsevier for the European Society of Clinical Microbiology and Infectious Diseases Elsevier
Subjects:	Anti-Bacterial Agents - adverse effects Anti-Bacterial Agents - therapeutic use Antibiotic Bacterial Proteins - genetics Bacteriology Biopsy, Needle Brazil - epidemiology Colombia - epidemiology Dapsone Dapsone - therapeutic use DNA Gyrase - genetics Drug Resistance, Bacterial - genetics Endemic Diseases - statistics & numerical data Epidemiological Monitoring Global Health Humans India - epidemiology Leprosy - diagnosis Leprosy - drug therapy Leprosy - epidemiology Leprosy - microbiology Life Sciences Microbial Sensitivity Tests Microbiology and Parasitology Mutation Mycobacterium leprae Mycobacterium leprae - drug effects Mycobacterium leprae - genetics Ofloxacin Ofloxacin - therapeutic use Polymerase Chain Reaction Prospective Studies Recurrence Resistance Rifampicin Rifampin - therapeutic use Sentinel Surveillance Skin - microbiology Skin - pathology Surveys and Questionnaires World Health Organization Brazil Colombia India Resistance Dapsone Antibiotic Mycobacterium leprae Rifampicin Ofloxacin
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Summary:	Antimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. From 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. This is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy. [Display omitted]
Bibliography:	PMCID: PMC6286419 Other members of the WHO surveillance network of antimicrobial resistance in leprosy are listed as collaborators in the Acknowledgements section.
ISSN:	1198-743X 1469-0691
DOI:	10.1016/j.cmi.2018.02.022