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Pathogens
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Responding to the Challenge of Drug-Resistant Tuberculosis
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Responding to the Challenge of Drug-Resistant Tuberculosis

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Bacterial Pathogens".

Deadline for manuscript submissions: 31 August 2024 | Viewed by 6793

Special Issue Editors

Dr. Marian Loveday

E-Mail Website
Guest Editor
1. South African Medical Research Council, Durban, South Africa
2. CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, South African Medical Research Council, Durban, South Africa
3. Centre for Health Systems Research & Development, University of the Free State, Bloemfontein, South Africa
Interests: tuberculosis; drug-resistant tuberculosis; HIV; health systems; person-centered care
Dr. Helen Cox

E-Mail Website
Guest Editor
1. Division of Medical Microbiology, Department of Pathology, University of Cape Town, Cape Town, South Africa
2. Institute of Infectious Disease and Molecular Medicine and Wellcome Centre for Infectious Disease Research, University of Cape Town, Cape Town, South Africa
Interests: tuberculosis; drug-resistance; prevention; treatment; person-centred care

Special Issue Information

Dear Colleagues,

Drug-resistant tuberculosis (DR-TB) remains a global crisis with an increasing incidence that threatens TB control. In the last decade, there have been several major scientific breakthroughs leading to the development and implementation of diagnostic tools which can detect resistant forms of TB within hours and new and repurposed drugs together with shorter, injectable-free treatment regimens. However, these advances are being undermined by emerging resistance to new and repurposed drugs, limited access to detecting this resistance, and an inadequate public health approach with absent or insufficient patient support. In addition, most individuals infected with DR-TB are from low- and middle-income countries where the disease burden is high, health systems are fragile, and country resources are limited. These individuals live in densely populated settings where the burden of TB and risk of DR-TB transmission is high. Trapped in a cycle of poverty and disease, household and individual resources are limited and their resilience to withstand the months of treatment with repeated visits to a health facility and the toxic treatment with a high pill-burden is limited. This Special Issue aims to present the latest research into DR-TB together with the challenges that need to be overcome in responding to the challenge of DR-TB.

Dr. Marian Loveday
Dr. Helen Cox
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Pathogens 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 2700 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

  • tuberculosis
  • drug resistance
  • drug-resistant tuberculosis
  • prevention
  • diagnosis
  • treatment
  • socioeconomic

Published Papers (5 papers)

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Research

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13 pages, 964 KiB  
Article
Assessment of Comorbidity in Patients with Drug-Resistant Tuberculosis
by Anna Starshinova, Michail Nazarenko, Ekaterina Belyaeva, Alexander Chuzhov, Nikolay Osipov and Dmitry Kudlay
Pathogens 2023, 12(12), 1394; https://doi.org/10.3390/pathogens12121394 - 27 Nov 2023
Viewed by 1017
Abstract
A wide range of comorbidities, especially in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients, markedly complicates selecting effective treatment of tuberculosis (TB) and preventing the development of adverse events. At present, it is impossible to assess the severity of comorbid pathologies [...] Read more.
A wide range of comorbidities, especially in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients, markedly complicates selecting effective treatment of tuberculosis (TB) and preventing the development of adverse events. At present, it is impossible to assess the severity of comorbid pathologies and develop indications for the administration of accompanying therapy in TB patients. The aim of this study was to identify the difference in the range of comorbidities between patients with MDR-TB and XDR-TB and assess the impact of comorbidities on TB treatment. Materials and Methods: A retrospective, prospective study was conducted where 307 patients with MDR-TB and XDR-TB pulmonary tuberculosis aged 18 to 75 years who received eTB treatment from 2016 to 2021 in St. Petersburg hospitals were analyzed. The analysis showed that the comorbidity level in MDR-TB and XDR-TB patients with TB treatment success and treatment failure was comparable with the use of the Charlson Comorbidity Index (CCI). The CCI demonstrated declining data in terms of TB treatment outcome period in both groups. A slight predominance of CCI score (3 to 4 points) in XDR-TB (22.7%) vs. MDR-TB (15.4%) patients was found. In the case of an TB treatment failure, the CCI level in MDR-TB vs. XDR-TB patients was characterized by a significantly higher rate of low magnitude (ranging from 1 to 2 points) in 21.1% vs. 4.5% (p < 0.05), which was higher in XDR-TB patients (ranging from 4 to 5 points, in 10.0% vs. 0, χ2 = 33.7 (p < 0.01)). Chronic viral hepatitis B and C infection, cardiovascular pathology, chronic obstructive pulmonary disease, and chronic alcoholism were found to be significant comorbidity factors that influenced the TB treatment success. Conclusions: It is evident that XDR-TB patients comprise a cohort with the most severe disease course due to comorbidities impacting TB treatment efficacy. The obtained data pointed to the need to determine comorbidity severity in patients with drug-resistant Mbt prior to administering TB treatment schemes. Full article
(This article belongs to the Special Issue Responding to the Challenge of Drug-Resistant Tuberculosis)
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Review

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25 pages, 344 KiB  
Review
Rapid Diagnosis of Drug-Resistant Tuberculosis–Opportunities and Challenges
by Kogieleum Naidoo, Rubeshan Perumal, Senamile L. Ngema, Letitia Shunmugam and Anou M. Somboro
Pathogens 2024, 13(1), 27; https://doi.org/10.3390/pathogens13010027 - 27 Dec 2023
Viewed by 1550
Abstract
Global tuberculosis (TB) eradication is undermined by increasing prevalence of emerging resistance to available drugs, fuelling ongoing demand for more complex diagnostic and treatment strategies. Early detection of TB drug resistance coupled with therapeutic decision making guided by rapid characterisation of pre-treatment and [...] Read more.
Global tuberculosis (TB) eradication is undermined by increasing prevalence of emerging resistance to available drugs, fuelling ongoing demand for more complex diagnostic and treatment strategies. Early detection of TB drug resistance coupled with therapeutic decision making guided by rapid characterisation of pre-treatment and treatment emergent resistance remains the most effective strategy for averting Drug-Resistant TB (DR-TB) transmission, reducing DR-TB associated mortality, and improving patient outcomes. Solid- and liquid-based mycobacterial culture methods remain the gold standard for Mycobacterium tuberculosis (MTB) detection and drug susceptibility testing (DST). Unfortunately, delays to result return, and associated technical challenges from requirements for specialised resource and capacity, have limited DST use and availability in many high TB burden resource-limited countries. There is increasing availability of a variety of rapid nucleic acid-based diagnostic assays with adequate sensitivity and specificity to detect gene mutations associated with resistance to one or more drugs. While a few of these assays produce comprehensive calls for resistance to several first- and second-line drugs, there is still no endorsed genotypic drug susceptibility test assay for bedaquiline, pretomanid, and delamanid. The global implementation of regimens comprising these novel drugs in the absence of rapid phenotypic drug resistance profiling has generated a new set of diagnostic challenges and heralded a return to culture-based phenotypic DST. In this review, we describe the available tools for rapid diagnosis of drug-resistant tuberculosis and discuss the associated opportunities and challenges. Full article
(This article belongs to the Special Issue Responding to the Challenge of Drug-Resistant Tuberculosis)
12 pages, 290 KiB  
Review
Pharmacokinetics and Safety of Group A and B Anti-Tuberculosis Drugs Used in Treatment of Rifampicin-Resistant Tuberculosis during Pregnancy and Post-Partum: A Narrative Review
by Jennifer Hughes
Pathogens 2023, 12(12), 1385; https://doi.org/10.3390/pathogens12121385 - 24 Nov 2023
Viewed by 987
Abstract
Recommendations for treatment of rifampicin-resistant tuberculosis (RR-TB) during pregnancy and post-partum now include Group A and B antituberculosis drugs. While pharmacokinetic data for most of these drugs among adults receiving treatment for RR-TB are limited, the data from pregnant patients and their infants [...] Read more.
Recommendations for treatment of rifampicin-resistant tuberculosis (RR-TB) during pregnancy and post-partum now include Group A and B antituberculosis drugs. While pharmacokinetic data for most of these drugs among adults receiving treatment for RR-TB are limited, the data from pregnant patients and their infants are extremely scarce. Existing data suggest that fluoroquinolones, bedaquiline, clofazimine and terizidone may be used safely in pregnancy. Pharmacokinetic exposures, particularly between trimesters, are potentially sub-optimal; however, there is currently no evidence to support dose adjustment during pregnancy. Linezolid poses a potentially serious toxicity risk, particularly as exposures appear to be high in the later stages of pregnancy and post-partum following extended use, but this should be considered alongside the benefits of this extremely effective drug in the treatment of this life-threatening disease. While plenty of questions remain regarding the exposure to Group A and B antituberculosis drugs through breastmilk, existing literature suggests minimal harm to the breastfed infant. Pregnant patients and their infants should be included in therapeutic trials and pharmacokinetic studies of effective antituberculosis drugs. Full article
(This article belongs to the Special Issue Responding to the Challenge of Drug-Resistant Tuberculosis)
12 pages, 597 KiB  
Review
Current Perspectives and Challenges of MAIT Cell-Directed Therapy for Tuberculosis Infection
by Melissa D. Chengalroyen
Pathogens 2023, 12(11), 1343; https://doi.org/10.3390/pathogens12111343 - 12 Nov 2023
Viewed by 1262
Abstract
Mucosal-associated invariant T (MAIT) cells are a distinct population of non-conventional T cells that have been preserved through evolution and possess properties of both innate and adaptive immune cells. They are activated through the recognition of antigens presented by non-polymorphic MR1 proteins or, [...] Read more.
Mucosal-associated invariant T (MAIT) cells are a distinct population of non-conventional T cells that have been preserved through evolution and possess properties of both innate and adaptive immune cells. They are activated through the recognition of antigens presented by non-polymorphic MR1 proteins or, alternately, can be stimulated by specific cytokines. These cells are multifaceted and exert robust antimicrobial activity against bacterial and viral infections, direct the immune response through the modulation of other immune cells, and exhibit a specialized tissue homeostasis and repair function. These distinct characteristics have instigated interest in MAIT cell biology for immunotherapy and vaccine development. This review describes the current understanding of MAIT cell activation, their role in infections and diseases with an emphasis on tuberculosis (TB) infection, and perspectives on the future use of MAIT cells in immune-mediated therapy. Full article
(This article belongs to the Special Issue Responding to the Challenge of Drug-Resistant Tuberculosis)
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9 pages, 705 KiB  
Review
Treatment of Infection as a Core Strategy to Prevent Rifampicin-Resistant/Multidrug-Resistant Tuberculosis
by Anja Reuter and Jennifer Furin
Pathogens 2023, 12(5), 728; https://doi.org/10.3390/pathogens12050728 - 17 May 2023
Viewed by 1269
Abstract
An estimated 19 million people are infected with rifampicin-resistant/multidrug-resistant strains of tuberculosis worldwide. There is little done to prevent these individuals from becoming sick with RR/MDR-TB, a disease that is associated with high rates of morbidity, mortality, and suffering. There are multiple phase [...] Read more.
An estimated 19 million people are infected with rifampicin-resistant/multidrug-resistant strains of tuberculosis worldwide. There is little done to prevent these individuals from becoming sick with RR/MDR-TB, a disease that is associated with high rates of morbidity, mortality, and suffering. There are multiple phase III trials currently being conducted to assess the effectiveness of treatment of infection (i.e., “preventive therapy”) for RR/MDR-TB, but their results are likely years away. In the meantime, there is sufficient evidence to support a more comprehensive management of people who have been exposed to RR/MDR-TB so that they can maintain their health. We present a patient scenario and share our experience in implementing a systematic post-exposure management program in South Africa with the goal of inspiring similar programs in other high-burden RR/MDR-TB settings. Full article
(This article belongs to the Special Issue Responding to the Challenge of Drug-Resistant Tuberculosis)
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