Mycobacterium tuberculosis Complex: Diagnosis, Drug-Resistance, Genetic Diversity and Transmission

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (1 September 2023) | Viewed by 5139

Special Issue Editor


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Guest Editor
Division of Bioresources, Hokkaido University International Institute for Zoonosis Control, Sapporo 001-0020, Japan
Interests: Mycobacterium tuberculosis complex; multi-drug resistance tuberculosis; drug-resistance acquisition mechanism; molecular epidemiology; host-pathogen interaction; Chlamydia trachomatis molecular dynamics

Special Issue Information

Dear Colleagues,

Despite sincere efforts to control tuberculosis (TB), which is caused by Mycobacterium tuberculosis, it has remained a constant threat to public health worldwide, with an estimated 5.8 million new cases and 1.5 million deaths in 2020. This bacterium has learned to survive, transmit, and cause disease by adapting into a drug-resistant form. Other members of the M. tuberculosis complex are also increasingly recognized to cause TB in humans and animals. In addition to proper diagnosis and treatment, understanding the drug resistance and transmission dynamics of these pathogens is critical for controlling TB.

For this Special Issue, we are seeking manuscript submissions that cover, but are not limited to, the following topics:

  • Genetic diversity and transmission dynamics of tuberculosis complex;
  • Drug-resistant TB;
  • Drug-resistant acquisition mechanism of TB;
  • Development of diagnostic methods for TB;
  • Diagnosis and treatment of TB.

Dr. Jeewan Thapa
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Mycobacterium tuberculosis
  • tuberculosis
  • drug resistance
  • diagnostics
  • Mycobacterium tuberculosis complex
  • genetic diversity and transmission

Published Papers (3 papers)

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16 pages, 1869 KiB  
Article
Genomic Analysis of Mycobacterium tuberculosis Strains Resistant to Second-Line Anti-Tuberculosis Drugs in Lusaka, Zambia
by Joseph Yamweka Chizimu, Eddie Samuneti Solo, Precious Bwalya, Thoko Flav Kapalamula, Kaemba Kunkuta Mwale, David Squarre, Misheck Shawa, Patrick Lungu, David Atomanyi Barnes, Kaunda Yamba, Tiza Mufune, Herman Chambaro, Harvey Kamboyi, Musso Munyeme, Bernard Mudenda Hang’ombe, Nathan Kapata, Victor Mukonka, Roma Chilengi, Jeewan Thapa, Chie Nakajima and Yasuhiko Suzukiadd Show full author list remove Hide full author list
Antibiotics 2023, 12(7), 1126; https://doi.org/10.3390/antibiotics12071126 - 29 Jun 2023
Cited by 4 | Viewed by 1787
Abstract
The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, [...] Read more.
The emergence of pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is a threat to TB control programs in developing countries such as Zambia. Studies in Zambia have applied molecular techniques to understand drug-resistance-associated mutations, circulating lineages and transmission patterns of multi-drug-resistant (MDR) Mycobacterium tuberculosis. However, none has reported genotypes and mutations associated with pre-XDR TB. This study characterized 63 drug-resistant M. tuberculosis strains from the University Teaching Hospital between 2018 and 2019 using targeted gene sequencing and conveniently selected 50 strains for whole genome sequencing. Sixty strains had resistance mutations associated to MDR, one polyresistant, and two rifampicin resistant. Among MDR strains, seven percent (4/60) had mutations associated with pre-XDR-TB. While four, one and nine strains had mutations associated with ethionamide, para-amino-salicylic acid and streptomycin resistances, respectively. All 50 strains belonged to lineage 4 with the predominant sub-lineage 4.3.4.2.1 (38%). Three of four pre-XDR strains belonged to sub-lineage 4.3.4.2.1. Sub-lineage 4.3.4.2.1 strains were less clustered when compared to sub-lineages L4.9.1 and L4.3.4.1 based on single nucleotide polymorphism differences. The finding that resistances to second-line drugs have emerged among MDR-TB is a threat to TB control. Hence, the study recommends a strengthened routine drug susceptibility testing for second-line TB drugs to stop the progression of pre-XDR to XDR-TB and improve patient treatment outcomes. Full article
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9 pages, 244 KiB  
Article
Treatment Outcomes of Childhood TB Patients in Four TB High Burden States of Malaysia: Results from a Multicenter Retrospective Cohort Study
by Rabbiya Ahmad, Syed Azhar Syed Sulaiman, Abdul Razak Muttalif, Nafees Ahmad, Aseel Rezeq Ali Yaghi, Khang Wen Goh, Long Chiau Ming, Nehad Jaser Ahmed and Amer Hayat Khan
Antibiotics 2022, 11(11), 1639; https://doi.org/10.3390/antibiotics11111639 - 16 Nov 2022
Cited by 2 | Viewed by 1814
Abstract
Data regarding treatment outcomes among childhood TB patients are lacking in Malaysia. The present study aimed to evaluate the treatment outcomes and predictors of unsuccessful treatment outcomes among childhood TB patients in four TB high-burden states of Malaysia. This was a retrospective cohort [...] Read more.
Data regarding treatment outcomes among childhood TB patients are lacking in Malaysia. The present study aimed to evaluate the treatment outcomes and predictors of unsuccessful treatment outcomes among childhood TB patients in four TB high-burden states of Malaysia. This was a retrospective cohort study conducted at 13 healthcare centers in four states of Malaysia, namely, Sabah, Sarawak, Selangor, and Penang. During the study period, a total of 8932 TB patients were enrolled for treatment at the study sites, of whom 206 (2.31%) were children. The majority of the childhood TB patients were female (52.9%) and belonged to the age group of 6–10 years (42.7%). Pulmonary TB accounted for 70.9% of childhood TB. Among childhood PTB patients, 50% were sputum smear negative. One hundred and seventy-eight patients (86.4%) were successfully treated (87 were cured and 91 completed treatment). Among 28 (13.6%) patients with unsuccessful treatment outcomes, 13 (6.3%) died, 3 (1.5%) failed treatment, 9 (4.4%) defaulted, and 3 (1.5%) were transferred out. Multivariate analysis revealed that patients’ age (5–14 years) (OR = 0.279, p-value = 0.006) and male gender (OR = 0.390, p-value = 0.046) had a statistically significant negative association with unsuccessful treatment outcomes. The prevalence of childhood TB in the current study was comparable to the recently published national estimates. The study sites reached the WHO target of treatment success. Special attention to patients with identified risk factors can improve treatment outcomes. Full article

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17 pages, 4484 KiB  
Brief Report
Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan
by Dana Auganova, Sabina Atavliyeva, Asylulan Amirgazin, Akmaral Akisheva, Anna Tsepke and Pavel Tarlykov
Antibiotics 2023, 12(10), 1523; https://doi.org/10.3390/antibiotics12101523 - 10 Oct 2023
Cited by 1 | Viewed by 1068
Abstract
Kazakhstan ranks among the countries with the highest number of MDR-TB patients per 100,000 population worldwide. The successful transmission of local MDR strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to disease control. In this study, we employed whole-genome sequencing to examine [...] Read more.
Kazakhstan ranks among the countries with the highest number of MDR-TB patients per 100,000 population worldwide. The successful transmission of local MDR strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to disease control. In this study, we employed whole-genome sequencing to examine drug resistance, compensatory mutations, population structure, and transmission patterns in a sample of 24 clinical isolates of L2/Beijing Mtb collected in Astana, Kazakhstan between 2021 and 2022. The genotypic prediction of Mtb susceptibility to anti-TB agents was consistent with the phenotypic susceptibility, except for bedaquiline. An analysis of resistance-associated genes characterized most of the isolates as pre-extensively drug-resistant tuberculosis (pre-XDR-TB) (n = 15; 62.5%). The phylogenetic analysis grouped the isolates into four transmission clusters; the dominant cluster was assigned to the “aggressive” Central Asia outbreak (CAO) clade of L2/Beijing (n = 15; 62.5%). Thirteen mutations with putative compensatory effects were observed exclusively in Mtb isolates containing the rpoB S450L mutation. The putative compensatory mutations had a stabilizing effect on RpoABC protein stability and dynamics. The high prevalence of the CAO clade in the population structure of Mtb may explain the rapid spread of MDR-TB in Kazakhstan. Full article
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