Dataset Information

Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results.

ABSTRACT: Drug resistance to tuberculosis remains a major public health threat. Here, we report two cases of extended-spectrum extensively drug-resistant (XXDR) tuberculosis showing resistance to most first- and second-line agents. The results of a correlation of whole-genome sequencing (WGS) and phenotypic testing were discordant, suggesting that overreliance on WGS may miss clinically relevant resistance in extensively drug-resistant disease.

SUBMITTER: Li H

PROVIDER: S-EPMC4508398 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Publications

Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results.

Li Hao H Kayani Masood ur Rehman Mu Gu Yunting Y Wang Xiaobo X Zhu Ting T Duan Hongfei H Ma Yifeng Y Huang Hairong H Javid Babak B

Journal of clinical microbiology 20150610 8

Drug resistance to tuberculosis remains a major public health threat. Here, we report two cases of extended-spectrum extensively drug-resistant (XXDR) tuberculosis showing resistance to most first- and second-line agents. The results of a correlation of whole-genome sequencing (WGS) and phenotypic testing were discordant, suggesting that overreliance on WGS may miss clinically relevant resistance in extensively drug-resistant disease. ...[more]

PMID: 26063862

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Project description:Introducción. La tuberculosis extremadamente resistente a los medicamentos (TB-XDR) es el resultado de deficiencias en la administración del tratamiento y en la prevención de la transmisión de la enfermedad; además, es un reto para los programas nacionales de control de la tuberculosis. Objetivo. Describir las características clínicas y epidemiológicas de los casos de TB-XDR diagnosticados en Colombia. Materiales y métodos. Se trata de un estudio de serie de casos, de pacientes con diagnóstico de TB-XDR, de 2006 a 2016 en Colombia. Las fuentes de información fueron el formato único de vigilancia y la base de datos del Laboratorio Nacional de Referencia. Se analizaron las variables: entidad territorial de procedencia, sexo, edad, régimen de afiliación, forma de tuberculosis, coinfección tuberculosis-HIV, patrón de sensibilidad a los fármacos de segunda línea y resultado (vivo o muerto). Resultados. En el período de estudio, se diagnosticaron 51 casos de TB-XDR, 28 hombres y 23 mujeres, con un promedio anual de cinco casos. En los departamentos de Antioquia, Valle del Cauca y Atlántico, se presentaron 46 (90 %) de los casos. El rango de edad fue de 5 a 81 años y, la mediana, de 40 años. De los 51 pacientes, 32 (63 %) estaban afiliados al régimen subsidiado de salud y 46 (90 %) presentaron tuberculosis pulmonar; de los 22 a quienes se les practicó la prueba para HIV, en tres (13,6 %) había coinfección con HIV, y 29 (57 %) murieron. Los fármacos a los cuales hubo mayor resistencia, fueron ofloxacina en 45 (88 %) casos y amikacina en 43 (84 %). Conclusión. La TB-XDR se presentó principalmente en formas pulmonares, lo cual aumenta la probabilidad de transmisión en la comunidad y se refleja en la aparición de tuberculosis resistente en menores de 15 años. La población más afectada es la económicamente activa, con una gran mortalidad. El Programa Nacional de Prevención y Control de la Tuberculosis debe generar estrategias para evitar la propagación de cepas resistentes.

Project description:Improved molecular diagnostic methods for detection drug resistance in Mycobacterium tuberculosis (MTB) strains are required. Resistance to first- and second- line anti-tuberculous drugs has been associated with single nucleotide polymorphisms (SNPs) in particular genes. However, these SNPs can vary between MTB lineages therefore local data is required to describe different strain populations. We used whole genome sequencing (WGS) to characterize 37 extensively drug-resistant (XDR) MTB isolates from Pakistan and investigated 40 genes associated with drug resistance. Rifampicin resistance was attributable to SNPs in the rpoB hot-spot region. Isoniazid resistance was most commonly associated with the katG codon 315 (92%) mutation followed by inhA S94A (8%) however, one strain did not have SNPs in katG, inhA or oxyR-ahpC. All strains were pyrazimamide resistant but only 43% had pncA SNPs. Ethambutol resistant strains predominantly had embB codon 306 (62%) mutations, but additional SNPs at embB codons 406, 378 and 328 were also present. Fluoroquinolone resistance was associated with gyrA 91-94 codons in 81% of strains; four strains had only gyrB mutations, while others did not have SNPs in either gyrA or gyrB. Streptomycin resistant strains had mutations in ribosomal RNA genes; rpsL codon 43 (42%); rrs 500 region (16%), and gidB (34%) while six strains did not have mutations in any of these genes. Amikacin/kanamycin/capreomycin resistance was associated with SNPs in rrs at nt1401 (78%) and nt1484 (3%), except in seven (19%) strains. We estimate that if only the common hot-spot region targets of current commercial assays were used, the concordance between phenotypic and genotypic testing for these XDR strains would vary between rifampicin (100%), isoniazid (92%), flouroquinolones (81%), aminoglycoside (78%) and ethambutol (62%); while pncA sequencing would provide genotypic resistance in less than half the isolates. This work highlights the importance of expanded targets for drug resistance detection in MTB isolates.

Dataset Information

Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results.

Publications

Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results.

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