Neglected Mycobacterial Diseases

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

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 3954

Special Issue Editors


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Guest Editor
Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil
Interests: mycobacterial diseases; cell death; host-pathogen interaction; diagnosis; treatment

E-Mail Website
Guest Editor
Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
Interests: leprosy; lipid metabolism; purinergic signaling; BCG; treatment

Special Issue Information

Dear Colleagues, 

Mycobacterium is one of the most sequenced bacterial genera. Species of mycobacteria can cause diseases that represent major public health problems, such as tuberculosis, leprosy, and Buruli ulcer, and emerging diseases caused by Nontuberculous mycobacteria species (NTM).       

In developing countries where tuberculosis is still a health challenge, the prevalence of nontuberculous mycobacterial diseases is expected to rise as medical conditions that compromise the immune system become more widespread. NTM refer to all the species in the family of mycobacteria that may cause human disease but do not cause tuberculosis or leprosy. Recent epidemiological studies have shown the emergence of NTM species in causing lung diseases in humans. Although more than 170 NTM species are present in various environmental niches, only M. avium complex and M. abscessus have been implicated in pulmonary disease. NTM species display significant heterogeneity in their susceptibility to anti-TB drugs, and new studies focusing on more effective strategies are required.

Mycobacterium leprae is the organism that causes leprosy. Although an ancient disease, leprosy remains endemic and continues to be a major public health problem, and aspects related to the development of more effective strategies of diagnosis and treatment are needed. In this Special Issue, we aim to advance communication between microbiologists, immunologists, biochemical and molecular biologists and, as a result, knowledge at the interface of interactions between mycobacteria and the host immune system, which can help in new strategies to control mycobacterial infection. This Special Issue will focus on the pathogenesis of leprosy and pulmonary diseases caused by NTM. Both original and review articles are welcomed.

Prof. Dr. Roberta Olmo Pinheiro
Dr. Marcia Berrêdo-Pinho
Guest Editors

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Keywords

  • leprosy
  • NTM
  • host–pathogen interaction
  • diagnosis
  • treatment

Published Papers (3 papers)

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19 pages, 1503 KiB  
Article
Extrapulmonary and Drug-Resistant Childhood Tuberculosis: Unveiling the Disease to Adopt the Optimal Treatment Strategy
by Domenico Pace, Francesca Corvaglia, Catiuscia Lisi, Luisa Galli and Elena Chiappini
Pathogens 2023, 12(12), 1439; https://doi.org/10.3390/pathogens12121439 - 12 Dec 2023
Cited by 1 | Viewed by 1103
Abstract
Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) [...] Read more.
Paediatric tuberculosis (TB) is a substantial threat among infectious diseases, particularly considering the high risk of extrapulmonary tuberculosis (EPTB), severe forms of the disease, and the spreading of drug-resistant strains. Describing the characteristics of children with EPTB and those with drug-resistant tuberculosis (DR-TB) and analysing the role of second-line drugs could facilitate the management of these cases. This retrospective study was conducted on 271 children diagnosed with active TB disease (44 EPTB cases, 9 DR-TB cases), originating from diverse geographic areas, who were referred to the infectious disease unit at Meyer Children’s Hospital, Florence, Italy, from 2006 to 2022. In most patients, the management of therapies was complicated by the impossibility to obtain drug susceptibility testing (DST) results, which improved over the years: 17/154 (11.04%) children had DST results between 2006 and 2013, and 50/117 (42.73%, p < 0.001) between 2014 and 2022. Second-line drugs were not exclusively administered to DR-TB cases, but also to EPTB cases (20/44, 45.45%). Drugs were generally well tolerated; adverse events occurred in 13 children (13/271, 4.80%) and were generally mild and reversable. Therapies were successful in 267 children (98.52%) considered cured, while 4 (1.48%) presented sequelae. Both univariate and multivariate logistic regression analyses were conducted to investigate factors associated with EPTB, DR-TB, and second-line drugs administration. Originating from Asia emerged as a risk factor associated with both EPTB and DR-TB (p = 0.013 and p = 0.045, respectively). The introduction of GeneXpert tests has significantly improved TB diagnosis and the obtaining of DST results. The administration of second-line therapies should be limited primarily to DR-TB cases, but it is possible that these drugs may also be beneficial in selected EPTB cases. Full article
(This article belongs to the Special Issue Neglected Mycobacterial Diseases)
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14 pages, 2484 KiB  
Article
Immunohistochemical Characterization of M1, M2, and M4 Macrophages in Leprosy Skin Lesions
by Tatiane Costa Quaresma, Lívia de Aguiar Valentim, Jorge Rodrigues de Sousa, Tinara Leila de Souza Aarão, Hellen Thais Fuzii, Maria Irma Seixas Duarte, Juarez de Souza and Juarez Antônio Simões Quaresma
Pathogens 2023, 12(10), 1225; https://doi.org/10.3390/pathogens12101225 - 09 Oct 2023
Cited by 1 | Viewed by 935
Abstract
Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of [...] Read more.
Mycobacterium leprae is the etiological agent of leprosy. Macrophages (Mφs) are key players involved in the pathogenesis of leprosy. In this study, immunohistochemical analysis was performed to examine the phenotype of Mφ subpopulations, namely M1, M2, and M4, in the skin lesions of patients diagnosed with leprosy. Based on the database of treatment-naïve patients treated between 2015 and 2019 at the Department of Dermatology of the University of the State of Pará, Belém, routine clinical screening samples were identified. The monolabeling protocol was used for M1 macrophages (iNOS, IL-6, TNF-α) and M2 macrophages (IL-10, IL-13, CD163, Arginase 1, TGF-β, FGFb), and the double-labeling protocol was used for M4 macrophages (IL-6, MMP7, MRP8, TNF-α e CD68). To confirm the M4 macrophage lineage, double labeling of the monoclonal antibodies CD68 and MRP8 was also performed. Our results demonstrated a statistically significant difference for the M1 phenotype among the Virchowian (VV) (4.5 ± 1.3, p < 0.0001), Borderline (1.6 ± 0.4, p < 0.0001), and tuberculoid (TT) (12.5 ± 1.8, p < 0.0001) clinical forms of leprosy. Additionally, the M2 phenotype showed a statistically significant difference among the VV (12.5 ± 2.3, p < 0.0001), Borderline (1.3 ± 0.2, p < 0.0001), and TT (3.2 ± 0.7, p < 0.0001) forms. For the M4 phenotype, a statistically significant difference was observed in the VV (9.8 ± 1.7, p < 0.0001), Borderline (1.2 ± 0.2, p < 0.0001), and TT (2.6 ± 0.7, p < 0.0001) forms. A significant correlation was observed between the VV M1 and M4 (r = 0.8712; p = 0.0000) and between the VV M2 × TT M1 (r = 0.834; p = 0.0002) phenotypes. The M1 Mφs constituted the predominant Mφ subpopulation in the TT and Borderline forms of leprosy, whereas the M2 Mφs showed increased immunoexpression and M4 was the predominant Mφ phenotype in VV leprosy. These results confirm the relationship of the Mφ profile with chronic pathological processes of the inflammatory response in leprosy. Full article
(This article belongs to the Special Issue Neglected Mycobacterial Diseases)
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Systematic Review
Xenophagy as a Strategy for Mycobacterium leprae Elimination during Type 1 or Type 2 Leprosy Reactions: A Systematic Review
by Débora Dantas Nucci Cerqueira, Ana Letícia Silva Pereira, Ana Elisa Coelho da Costa, Tarcísio Joaquim de Souza, Matheus Santos de Sousa Fernandes, Fabrício Oliveira Souto and Patrícia d’Emery Alves Santos
Pathogens 2023, 12(12), 1455; https://doi.org/10.3390/pathogens12121455 - 15 Dec 2023
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Abstract
Background: Mycobacterium leprae is an intracellular bacillus that causes leprosy, a neglected disease that affects macrophages and Schwann cells. Leprosy reactions are acute inflammatory responses to mycobacterial antigens, classified as type1 (T1R), a predominant cellular immune response, or type2 (T2R), a humoral phenomenon, [...] Read more.
Background: Mycobacterium leprae is an intracellular bacillus that causes leprosy, a neglected disease that affects macrophages and Schwann cells. Leprosy reactions are acute inflammatory responses to mycobacterial antigens, classified as type1 (T1R), a predominant cellular immune response, or type2 (T2R), a humoral phenomenon, leading to a high number of bacilli in infected cells and nerve structures. Xenophagy is a type of selective autophagy that targets intracellular bacteria for lysosomal degradation; however, its immune mechanisms during leprosy reactions are still unclear. This review summarizes the relationship between the autophagic process and M. leprae elimination during leprosy reactions. Methods: Three databases, PubMed/Medline (n = 91), Scopus (n = 73), and ScienceDirect (n = 124), were searched. After applying the eligibility criteria, articles were selected for independent peer reviewers in August 2023. Results: From a total of 288 studies retrieved, eight were included. In multibacillary (MB) patients who progressed to T1R, xenophagy blockade and increased inflammasome activation were observed, with IL-1β secretion before the reactional episode occurrence. On the other hand, recent data actually observed increased IL-15 levels before the reaction began, as well as IFN-γ production and xenophagy induction. Conclusion: Our search results showed a dichotomy in the T1R development and their relationship with xenophagy. No T2R studies were found. Full article
(This article belongs to the Special Issue Neglected Mycobacterial Diseases)
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