Medical Management in Tuberculosis: Current Updates and Perspectives

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (31 July 2022) | Viewed by 7465

Special Issue Editor


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Guest Editor
Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA
Interests: Tuberculosis, Emerging Infectious Diseases, Global Health, health equity

Special Issue Information

Dear Colleagues,

The past decade has seen major advances in the medical management of tuberculosis. After a long period in which no new therapies for TB had been developed, several new agents for the treatment of multidrug-resistant TB have been approved and widely deployed, and recent clinical trials demonstrate that shorter regimens for drug-sensitive tuberculosis are effective. Similarly, studies show that latent TB can be effectively treated with short regimens of combination chemotherapy, thereby opening the door to more effective use of this strategy in preventing TB disease. At the same time, there is growing evidence that comorbidities such as diabetes mellitus, undernutrition, HIV infection, and alcohol and substance use disorders contribute to poor TB treatment outcomes, and studies are needed to define how best to manage these patients. Similarly, we need to identify optimal management strategies for unique populations, including children, adolescents, patients on immunosuppressant drugs, incarcerated individuals, and those with concurrent COVID-19 infection. Other recent work has focused on the long-term sequelae of TB disease following successful treatment and has emphasized the increased mortality and morbidity following TB treatment.

In this issue on the medical management of tuberculosis, we encourage submissions on any of these topics. We are specifically interested in studies that address the optimal use of new drugs and/or treatment regimens, host-directed therapies, and/or the unique treatment needs of the special populations listed above. Studies can include those that report on original unpublished research or systematic reviews. We aim to provide a topical update on recent advances in the medical management of TB and to highlight research that addresses outcomes among populations at especially high risk for poor responses to therapy.

Prof. Dr. Megan B. Murray
Guest Editor

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Keywords

  • Tuberculosis
  • Drug resistance
  • Comorbidities
  • Diabetes mellitus
  • HIV
  • COVID-19
  • Substance use disorders
  • Host-directed therapies
  • Children
  • Adolescents

Published Papers (3 papers)

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12 pages, 996 KiB  
Article
Tobacco Smoking and Second-Hand Smoke Exposure Impact on Tuberculosis in Children
by Neus Altet, Irene Latorre, María Ángeles Jiménez-Fuentes, Antoni Soriano-Arandes, Raquel Villar-Hernández, Celia Milà, Pablo Rodríguez-Fernández, Beatriz Muriel-Moreno, Patricia Comella-del-Barrio, Pere Godoy, Joan-Pau Millet, Maria Luiza de Souza-Galvão, Carlos A. Jiménez-Ruiz, Jose Domínguez and on behalf of PII Smoking SEPAR Working Group
J. Clin. Med. 2022, 11(7), 2000; https://doi.org/10.3390/jcm11072000 - 02 Apr 2022
Cited by 2 | Viewed by 2428
Abstract
Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays’ (IGRAs) performance and cytokine immune responses. A total [...] Read more.
Little is known about whether second-hand smoke (SHS) exposure affects tuberculosis (TB). Here, we investigate the association of cigarette smoke exposure with active TB and latent TB infection (LTBI) in children, analyzing Interferon-Gamma Release Assays’ (IGRAs) performance and cytokine immune responses. A total of 616 children from contact-tracing studies were included and classified regarding their smoking habits [unexposed, SHS, or smokers]. Risk factors for positive IGRAs, LTBI, and active TB were defined. GM-CSF, IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-22, IL-17, TNF-α, IL-1RA and IP-10 cytokines were detected in a subgroup of patients. Being SHS exposed was associated with a positive IGRA [aOR (95% CI): 8.7 (5.9–12.8)] and was a main factor related with LTBI [aOR (95% CI): 7.57 (4.79–11.94)] and active TB [aOR (95% CI): 3.40 (1.45–7.98)]. Moreover, IGRAs’ sensitivity was reduced in active TB patients exposed to tobacco. IL-22, GM-CSF, IL-5, TNF-α, IP-10, and IL-13 were less secreted in LTBI children exposed to SHS. In conclusion, SHS is associated with LTBI and active TB in children. In addition, false-negative IGRAs obtained on active TB patients exposed to SHS, together with the decrease of specific cytokines released, suggest that tobacco may alter the immune response. Full article
(This article belongs to the Special Issue Medical Management in Tuberculosis: Current Updates and Perspectives)
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15 pages, 1168 KiB  
Article
Characterization of Drug-Resistant Lipid-Dependent Differentially Detectable Mycobacterium tuberculosis
by Annelies W. Mesman, Seung-Hun Baek, Chuan-Chin Huang, Young-Mi Kim, Sang-Nae Cho, Thomas R. Ioerger, Nadia N. Barreda, Roger Calderon, Christopher M. Sassetti and Megan B. Murray
J. Clin. Med. 2021, 10(15), 3249; https://doi.org/10.3390/jcm10153249 - 23 Jul 2021
Cited by 6 | Viewed by 2104
Abstract
An estimated 15–20% of patients who are treated for pulmonary tuberculosis (TB) are culture-negative at the time of diagnosis. Recent work has focused on the existence of differentially detectable Mycobacterium tuberculosis (Mtb) bacilli that do not grow under routine solid culture [...] Read more.
An estimated 15–20% of patients who are treated for pulmonary tuberculosis (TB) are culture-negative at the time of diagnosis. Recent work has focused on the existence of differentially detectable Mycobacterium tuberculosis (Mtb) bacilli that do not grow under routine solid culture conditions without the addition of supplementary stimuli. We identified a cohort of TB patients in Lima, Peru, in whom acid-fast bacilli could be detected by sputum smear microscopy, but from whom Mtb could not be grown in standard solid culture media. When we attempted to re-grow Mtb from the frozen sputum samples of these patients, we found that 10 out of 15 could be grown in a glycerol-poor/lipid-rich medium. These fell into the following two groups: a subset that could be regrown in glycerol after “lipid-resuscitation”, and a group that displayed a heritable glycerol-sensitive phenotype that were unable to grow in the presence of this carbon source. Notably, all of the glycerol-sensitive strains were found to be multidrug resistant. Although whole-genome sequencing of the lipid-resuscitated strains identified 20 unique mutations compared to closely related strains, no single genetic lesion could be associated with this phenotype. In summary, we found that lipid-based media effectively fostered the growth of Mtb from a series of sputum smear-positive samples that were not culturable in glycerol-based Lowenstein–Jensen or 7H9 media, which is consistent with Mtb’s known preference for non-glycolytic sources during infection. Analysis of the recovered strains demonstrated that both genetic and non-genetic mechanisms contribute to the observed differential capturability, and suggested that this phenotype may be associated with drug resistance. Full article
(This article belongs to the Special Issue Medical Management in Tuberculosis: Current Updates and Perspectives)
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19 pages, 637 KiB  
Systematic Review
Clinical Outcomes of Individuals with COVID-19 and Tuberculosis during the Pre-Vaccination Period of the Pandemic: A Systematic Review
by Tulip A. Jhaveri, Celia Fung, Allison N. LaHood, Andrew Lindeborg, Chengbo Zeng, Rifat Rahman, Paul A. Bain, Gustavo E. Velásquez and Carole D. Mitnick
J. Clin. Med. 2022, 11(19), 5656; https://doi.org/10.3390/jcm11195656 - 26 Sep 2022
Cited by 4 | Viewed by 2199
Abstract
Background: Tuberculosis, like COVID-19, is most often a pulmonary disease. The COVID-19 pandemic has severely disrupted tuberculosis services in myriad ways: health facility closures, lockdowns, travel bans, overwhelmed healthcare systems, restricted export of antituberculous drugs, etc. The effects of the shared risk on [...] Read more.
Background: Tuberculosis, like COVID-19, is most often a pulmonary disease. The COVID-19 pandemic has severely disrupted tuberculosis services in myriad ways: health facility closures, lockdowns, travel bans, overwhelmed healthcare systems, restricted export of antituberculous drugs, etc. The effects of the shared risk on outcomes of the two diseases is not known, particularly for the first year of the pandemic, during the period before COVID-19 vaccines became widely available. Objective: We embarked on a systematic review to elucidate the consequences of tuberculosis on COVID-19 outcomes and of COVID-19 on tuberculosis outcomes during the pre-vaccination period of the pandemic. Methods: The systematic review protocol is registered in PROSPERO. We conducted an initial search of PubMed, Embase, Web of Science, WHO coronavirus database, medRxiv, bioRxiv, preprints.org, and Google Scholar using terms relating to COVID-19 and tuberculosis. We selected cohort and case–control studies for extraction and assessed quality with the Newcastle-Ottawa scale. Results and Conclusion: We identified 2108 unique abstracts published between December 2019 and January 2021. We extracted data from 18 studies from 8 countries. A total of 650,317 persons had a diagnosis of COVID-19, and 4179 had a diagnosis of current or prior tuberculosis. We explored links between tuberculosis and COVID-19 incidence, mortality, and other adverse outcomes. Nine studies reported on mortality and 13 on other adverse outcomes; results on the association between tuberculosis and COVID-19 mortality/adverse outcomes were heterogenous. Tuberculosis outcomes were not fully available in any studies, due to short follow-up (maximum of 3 months after COVID-19 diagnosis), so the effects of COVID-19 on tuberculosis outcomes could not be assessed. Much of the rapid influx of literature on tuberculosis and COVID-19 during this period was published on preprint servers, and therefore not peer-reviewed. It offered limited examination of the effect of tuberculosis on COVID-19 outcomes and even less on the effect of COVID-19 on tuberculosis treatment outcomes. Full article
(This article belongs to the Special Issue Medical Management in Tuberculosis: Current Updates and Perspectives)
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