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Tuberculosis, Drug and Diagnostics Development

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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 (30 November 2020) | Viewed by 19002

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Dr. Byung Woo Jhun

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Guest Editor

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Interests: pulmonary; tuberculosis; diagnosis; resistance; treatment; nontuberculous mycobacteria
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Special Issue Information

Dear Colleagues,

Despite the availability of anti-tuberculosis (TB) chemotherapy, TB remains a threat to public health and is the leading cause of death by a single infectious agent worldwide. Approximately 10 million people develop TB annually, and 1.6 million die from the disease. TB is a highly infectious disease; about 30% of persons in close contact with an infected individual become infected themselves, of whom about 5%–15% develop TB in their lifetime. The management of drug-resistant TB is also important; in this respect, disease outcomes are still unsatisfactory compared with those of drug-susceptible TB. Systematic meta-analyses have shown that resistance to first-line drugs reduces the probability of treatment success and increases the risk of acquiring resistance to other important drugs (multidrug-resistant TB). Drug-resistant TB generally requires a longer treatment course than drug-susceptible TB, which increases the disease burden. Therefore, early detection of TB is critically important. The worldwide prevalence and incidence of nontuberculous mycobacterial (NTM) infections are also increasing. It is important to further explore the distribution of this disease. NTM disease is radiographically very similar to TB, and early differentiation is very important. The purpose of this Special Issue is to update our knowledge of TB and NTM diagnosis and treatment. Researchers in the field are encouraged to submit original articles or reviews.

Dr. Byung Woo Jhun
Guest Editor

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Keywords

tuberculosis
diagnosis
resistance
treatment
nontuberculous mycobacteria

Published Papers (7 papers)

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Research

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9 pages, 732 KiB

Open AccessArticle

High-Resolution CT Findings as Predictive Factors for Recurrent Nontuberculous Mycobacterial Pulmonary Disease after Successful Treatment

by Hyewon Choi, Min Jae Cha, Yang Soo Kim and Jae Chol Choi

J. Clin. Med. 2021, 10(2), 172; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020172 - 06 Jan 2021

Cited by 1 | Viewed by 1806

Abstract

Despite long-term treatment for nontuberculous mycobacterial pulmonary disease (NTM-PD), recurrence is common. We aim to identify computed tomography (CT) findings that predict recurrence after successful treatment of NTM-PD. This retrospective study included 44 patients (12 men, 60 ± 11.2 years) successfully treated for NTM-PD between March 2009 and September 2016. Recurrence developed in 18 patients (40.9%) during follow-up (median, 852 days). CT scores for bronchiectasis, bronchiolitis, consolidation, cavities, and nodules at the initiation and termination of treatment were evaluated, then determined association with recurrence. We also assessed the diagnostic performance and reproducibility of CT scores. Patients with recurrent NTM-PD showed higher CT scores for bronchiectasis (p = 0.008), nodules (p = 0.006), consolidation (p = 0.033), and total CT scores (p = 0.017) at the time of treatment termination. On the contrary, only nodule score differed among the initial CT scores (p = 0.014). Regression analysis showed that the scores for bronchiectasis (odds ratio (OR) = 1.638, 95% confidence interval (CI) = 1.049–2.558, p = 0.030) and nodules (OR = 5.246, 95% CI = 1.370–20.087, p = 0.016) at treatment termination were significant predictors. The AUC of the regression model was 0.814 (95% CI = 0.689–0.939, p = 0.005). The interreader agreement for the total CT score was excellent (intraclass correlation coefficient = 0.841, p < 0.001). CT scores at the time of treatment termination can predict disease recurrence with good reproducibility. Full article

(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)

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10 pages, 4452 KiB

Open AccessArticle

Changes in Nutritional Status in Pulmonary Tuberculosis: Longitudinal Changes in BMI According to Acid-Fast Bacilli Smear Positivity

by Yousang Ko, Changwhan Kim, Yong Bum Park, Eun-Kyung Mo and Jin-Wook Moon

J. Clin. Med. 2020, 9(12), 4082; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9124082 - 17 Dec 2020

Cited by 8 | Viewed by 1871

Abstract

Malnutrition is closely associated with pulmonary tuberculosis (PTB). However, changes before and after treatment remain unclear. We aimed to investigate the longitudinal changes in nutritional status from treatment to follow-up of TB in 215 PTB cases in South Korea. First, we evaluated the trend in body mass index (BMI) from the time of diagnosis to a 2-year follow-up. Second, we compared the BMIs of our cases with 5694 controls who participated in a Korean national survey after treatment. During the treatment period, the BMI of the smear-positive group (n = 72) significantly increased compared with that of the smear-negative group (n = 143) (+1.9 kg/m² vs. +0.4 kg/m², p = 0.001). Almost all the changes occurred in the early phase, with unremarkable differences in the rest of the treatment period and up to the 2-year follow-up period. When compared with controls, the smear-positive PTB group also had a lower BMI than the smear-negative PTB group, which, however, was lower than that of the general population, though all the participants regained their BMIs during treatment. These results clarify the nutritional aspects of PTB and enable better strategies to support patients with PTB. Full article

(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)

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9 pages, 518 KiB

Open AccessArticle

BCG Vaccine Protection against TB Infection among Children Older than 5 Years in Close Contact with an Infectious Adult TB Case

by Angeliki Syggelou, Nikolaos Spyridis, Kyriaki Benetatou, Eleni Kourkouni, Georgia Kourlaba, Maria Tsagaraki, Despoina Maritsi, Irini Eleftheriou and Maria Tsolia

J. Clin. Med. 2020, 9(10), 3224; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9103224 - 08 Oct 2020

Cited by 7 | Viewed by 3048

Abstract

The Bacille Calmette–Guérin (BCG) vaccine has been shown to provide considerable protection against miliary or meningeal tuberculosis (TB), but whether it prevents other forms of disease remains controversial. Recent evidence has shown that the BCG vaccine also provides protection against latent TB infection (LTBI). The aim of the current study was to examine whether BCG has a protective role against LTBI among children in close contact with an adult index case in a low TB endemicity setting with the use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT). A cross-sectional study was conducted over a 10-year period among children referred to our outpatient TB clinic with a history of close contact with an adult with pulmonary TB. All subjects had a QFT-GIT performed. In total, 207 children > 5 to 16 years of age with known recent exposure were enrolled. BCG-vaccinated subjects had a 59% lower risk of presenting with LTBI after close contact with an adult index case compared with unvaccinated subjects (OR = 0.41, 95% CI: 0.23–0.73, p = 0.002). After adjustment for possible confounders, the protective effect of prior BCG immunization was estimated at 68% (OR = 0.32, 95% CI: 0.15–0.66, p = 0.002). Other risk factors for LTBI included a history of migration (OR = 2.27, 95% CI: 1.13–4.53, p = 0.021) and transmission of infection to other exposed child contacts (OR = 4.62, 95% CI: 2.27–9.39, p = 0.001). We were able to determine a strong protective role of BCG vaccination among children older than 5 years, immunized at school entry, who had close contact with an adult infectious TB case. Full article

(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)

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12 pages, 755 KiB

Open AccessArticle

Treatment of Bone and Joint Tuberculosis in France: A Multicentre Retrospective Study

by Aurélie Guillouzouic, Claire Andrejak, Olivia Peuchant, Geneviève Hery-Arnaud, Farida Hamdad, Philippe Lanotte, Benjamin Gaborit, Louis Bernard and Pascale Bémer

J. Clin. Med. 2020, 9(8), 2529; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082529 - 05 Aug 2020

Cited by 8 | Viewed by 2641

Abstract

Background: Nine percent of all cases of tuberculosis are bone and joint tuberculosis (BJTB). BJTB occurs in two main forms: spinal (STB) and extraspinal (ESTB). The aim of this study was to compare STB with ESTB in terms of diagnosis, treatment and outcomes. Methods: We collected demographic, clinical, microbiological, treatment duration and outcome data for patients with BJTB in a retrospective multicentre study over a 17-year period. Results: Of the 116 patients included in the study, 69 (59.5%) had STB and 47 (40.5%) had ESTB. The median age was higher in the ESTB group. There were significantly more foreign-born patients in the STB group. The median time for diagnosis was longer for ESTB (6 months) than STB (4 months) (p = 0.017). Magnetic resonance imaging was highly reliable for the diagnosis. Direct examination and histology allowed the diagnosis to be made in more than 80% of cases. The median treatment duration of 12 months, regardless of the type of BJTB, was longer than recommended. A favourable outcome was achieved in 91.9% of cases. Conclusion: The management of BJTB remains challenging. An earlier diagnosis should be more effective, reducing the total duration of treatment and leading to better tolerance. Full article

(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)

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15 pages, 586 KiB

Open AccessArticle

Course of Adverse Events during Short Treatment Regimen in Patients with Rifampicin-Resistant Tuberculosis in Burundi

by François Ciza, Tinne Gils, Michel Sawadogo, Tom Decroo, Alberto Roggi, Alberto Piubello and Nimer Ortuño-Gutiérrez

J. Clin. Med. 2020, 9(6), 1873; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9061873 - 16 Jun 2020

Cited by 7 | Viewed by 2358

Abstract

The introduction of the nine-month short-treatment regimen (STR) has drastically improved outcomes of rifampicin-resistant tuberculosis (RR-TB) treatment. Adverse events (AE) commonly occur, including injectable-induced hearing loss. In Burundi we retrospectively assessed the frequency of adverse events and treatment modifications in all patients who initiated the STR between 2013–2017. Among 225 included patients, 93% were successfully treated without relapse, 5% died, 1% was lost-to-follow-up, 0.4% had treatment failure and 0.4% relapsed after completion. AE were reported in 53%, with grade 3 or 4 AE in 4% of patients. AE occurred after a median of two months. Hepatotoxicity (31%), gastro-intestinal toxicity (22%) and ototoxicity (10%) were most commonly reported. One patient suffered severe hearing loss. Following AE, 7% of patients had a dose reduction and 1% a drug interruption. Kanamycin-induced ototoxicity led to 94% of modifications. All 18 patients with a modified regimen were cured relapse-free. In this exhaustive national RR-TB cohort, RR-TB was treated successfully with the STR. Adverse events were infrequent. To replace the present STR, all-oral regimens should be at least as effective and also less toxic. During and after transition, monitoring, management, and documentation of AE will remain essential. Full article

(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)

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13 pages, 2210 KiB

Open AccessArticle

Characteristics of Circulating CD4⁺ T Cell Subsets in Patients with Mycobacterium avium Complex Pulmonary Disease

by Sun Ae Han, Yousang Ko, Sung Jae Shin and Byung Woo Jhun

J. Clin. Med. 2020, 9(5), 1331; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9051331 - 03 May 2020

Cited by 11 | Viewed by 2446

Abstract

Although prevalence of Mycobacterium avium complex pulmonary disease (MAC-PD) is increasing, limited data are available regarding vulnerability to Mycobacterium avium complex (MAC) infections. To understand the pathobiology of interaction between MAC and host-immunity, it is important to understand the characteristics for circulating T cells in terms of the immunological phenotype and functional correlates in MAC-PD. We aimed to characterize immunophenotype, cytokine profile, and immune inhibitory receptors of circulating CD4⁺ T cells in MAC-PD patients. We enrolled 71 MAC-PD and 20 control individuals. Flow cytometric analysis was performed to determine T cell subsets and immune checkpoint markers. Ex vivo cytokine productions in response to MAC were determined using enzyme-linked immunosorbent assay. The frequencies of CD4⁺ T cells and CD4⁺IL-17⁺ T cells decreased, while CD4⁺IL-4⁺ T cells and CD4⁺CD25⁺Foxp3⁺ T cells increased in peripheral blood mononuclear cells (PBMCs) of MAC-PD individuals upon MAC stimulation compared with those cells in healthy donor-PBMCs. Additionally, we found increased PD-1, CTLA-4, and TIM-3-expressing T cells in MAC- PD individuals in response to MAC-stimulation, indicating that suppressed T cell-mediated response is associated with the susceptibility to MAC infection. These results may help to explain impaired T cell-mediated responses and pave the way for better strategies to achieve protective immunity against MAC infection. Full article

(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)

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Review

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18 pages, 1192 KiB

Open AccessReview

Composition and Clinical Significance of Exosomes in Tuberculosis: A Systematic Literature Review

by Fantahun Biadglegne, Brigitte König, Arne C. Rodloff, Anca Dorhoi and Ulrich Sack

J. Clin. Med. 2021, 10(1), 145; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10010145 - 04 Jan 2021

Cited by 11 | Viewed by 4208

Abstract

Tuberculosis (TB) remains a major health issue worldwide. In order to contain TB infections, improved vaccines as well as accurate and reliable diagnostic tools are desirable. Exosomes are employed for the diagnosis of various diseases. At present, research on exosomes in TB is still at the preliminary stage. Recent studies have described isolation and characterization of Mycobacterium tuberculosis (Mtb) derived exosomes in vivo and in vitro. Mtb-derived exosomes (Mtbexo) may be critical for TB pathogenesis by delivering mycobacterial-derived components to the recipient cells. Proteomic and transcriptomic analysis of Mtbexo have revealed a variety of proteins and miRNA, which are utilized by the TB bacteria for pathogenesis. Exosomes have been isolated in body fluids, are amenable for fast detection, and could contribute as diagnostic or prognostic biomarker to disease control. Extraction of exosomes from biological fluids is essential for the exosome research and requires careful standardization for TB. In this review, we summarized the different studies on Mtbexo molecules, including protein and miRNA and the methods used to detect exosomes in biological fluids and cell culture supernatants. Thus, the detection of Mtbexo molecules in biological fluids may have a potential to expedite the diagnosis of TB infection. Moreover, the analysis of Mtbexo may generate new aspects in vaccine development. Full article

(This article belongs to the Special Issue Tuberculosis, Drug and Diagnostics Development)

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