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Gut Microbes 2022Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that...
Nontuberculous mycobacterial pulmonary diseases (NTM-PDs) are emerging as global health threats with issues of antibiotic resistance. Accumulating evidence suggests that the gut-lung axis may provide novel candidates for host-directed therapeutics against various infectious diseases. However, little is known about the gut-lung axis in the context of host protective immunity to identify new therapeutics for NTM-PDs. This study was performed to identify gut microbes and metabolites capable of conferring pulmonary immunity to NTM-PDs. Using metabolomics analysis of sera from NTM-PD patients and mouse models, we showed that the levels of l-arginine were decreased in sera from NTM-PD patients and NTM-infected mice. Oral administration of l-arginine significantly enhanced pulmonary antimicrobial activities with the expansion of IFN-γ-producing effector T cells and a shift to microbicidal (M1) macrophages in the lungs of NTM-PD model mice. Mice that received fecal microbiota transplants from l-arginine-treated mice showed increased protective host defense in the lungs against NTM-PD, whereas l-arginine-induced pulmonary host defense was attenuated in mice treated with antibiotics. Using 16S rRNA sequencing, we further showed that l-arginine administration resulted in enrichment of the gut microbiota composition with species. Notably, oral treatment with either or inosine enhanced antimicrobial pulmonary immune defense against NTM infection, even with multidrug-resistant clinical NTM strains. Our findings indicate that l-arginine-induced gut microbiota remodeling with enrichment of boosts pulmonary immune defense against NTM infection by driving the protective gut-lung axis .
Topics: Animals; Anti-Bacterial Agents; Arginine; Gastrointestinal Microbiome; Humans; Lung; Mice; Mycobacterium Infections, Nontuberculous; RNA, Ribosomal, 16S
PubMed: 35579969
DOI: 10.1080/19490976.2022.2073132 -
Current Opinion in Infectious Diseases Apr 2022The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021. (Review)
Review
PURPOSE OF REVIEW
The aim of this article is to review the most recent evidences concerning mycobacterial skin infections, limiting the period of literature research to 2020--2021.
RECENT FINDINGS
Mycobacterial skin infections include a heterogeneous group of cutaneous diseases.Cutaneous tuberculosis is usually the result of hematogenous dissemination or spread from underlying foci and it must be distinguished from tuberculids, resulting from the immunological reaction to Mycobacterium tuberculosis antigens. Leprosy prevalence was drastically reduced after introduction of multidrug therapy in the 1980 s, but cases are still reported due to underdiagnosis, and animal and environmental reservoirs. Recent advances concentrate in the diagnostic field. Specific guidelines for the treatment of nontuberculous mycobacteria skin infections are missing and surgical procedures may be required. Prognosis is better as compared to nontuberculous mycobacteria lung disease. Rapid laboratory-confirmed diagnosis of Buruli ulcer may be achieved by the IS2404 PCR. Among new drugs, telacebec is promising in terms of potency, shorter duration and tolerability in animal studies. A clinical trial in humans is planned.
SUMMARY
Mycobacterial cutaneous lesions are nonpathognomonic and clinical suspicion must be confirmed by culture or molecular detection. Long-course multidrug treatment is required based on susceptibility tests. Surgical intervention may also be required. Rehabilitation and psychosocial support reduce long-term physical and mental consequences mostly in Buruli ulcer and leprosy.
Topics: Animals; Buruli Ulcer; Drug Therapy, Combination; Humans; Leprostatic Agents; Mycobacterium; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous
PubMed: 35067521
DOI: 10.1097/QCO.0000000000000820 -
International Journal of Molecular... Jan 2022Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of... (Review)
Review
Cytokine receptors are critical regulators of the antimycobacterial immune response, playing a key role in initiating and coordinating the recruitment and activation of immune cells during infection. They recognize and bind specific cytokines and are involved in inducing intracellular signal transduction pathways that regulate a diverse range of biological functions, including proliferation, differentiation, metabolism and cell growth. Due to mutations in cytokine receptor genes, defective signaling may contribute to increased susceptibility to mycobacteria, allowing the pathogens to avoid killing and immune surveillance. This paper provides an overview of cytokine receptors important for the innate and adaptive immune responses against mycobacteria and discusses the implications of receptor gene defects for the course of mycobacterial infection.
Topics: Adaptive Immunity; Animals; Cytokines; Humans; Immunity, Innate; Mutation; Mycobacterium Infections; Receptors, Cytokine; Signal Transduction
PubMed: 35163035
DOI: 10.3390/ijms23031112 -
BMJ Case Reports Mar 2022SummaryHabitual cough suppression leading to non-tuberculous mycobacteria infections and bronchiectasis has been reported. We present a case of a 55-year-old woman with...
SummaryHabitual cough suppression leading to non-tuberculous mycobacteria infections and bronchiectasis has been reported. We present a case of a 55-year-old woman with a chronic history of cough with mild expectoration and frequent lower respiratory tract infections, remitting with antibiotic therapy and other supportive measures. She also reported habitual cough suppression for several years. She was eventually diagnosed with Mycobacterium avium complex (MAC) positive right middle lobe bronchiectasis-Lady Windermere syndrome and obstructive sleep apnoea (OSA), causing disabling symptoms limiting her daily activities. We aim to highlight two key issues-diagnosing MAC infections in a tuberculosis endemic country, and OSA and its long-term clinical implications.
Topics: Bronchiectasis; Cough; Female; Humans; Middle Aged; Mycobacterium Infections, Nontuberculous; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Nontuberculous Mycobacteria
PubMed: 35256362
DOI: 10.1136/bcr-2021-246285 -
Hand (New York, N.Y.) Jul 2022Hand infections caused by mycobacteria are relatively uncommon compared to infections caused by other pathogens; therefore, much of the available literature consists of... (Review)
Review
BACKGROUND
Hand infections caused by mycobacteria are relatively uncommon compared to infections caused by other pathogens; therefore, much of the available literature consists of case reports and limited case series. Broadly categorized into tuberculous and nontuberculous mycobacterial (NTM) infections, both tuberculous and NTM infections are typically insidious with long incubation periods and with the ability to remain dormant for prolonged periods.
METHODS
We reviewed the most current literature on the epidemiology, presentations, treatment methods, and resistance patterns of mycobacterial infections of the hand focusing on the indications and outcomes of nonoperative as well as operative interventions.
RESULTS
The worldwide burden of tuberculosis remains high and while the overall rate of new diagnosis drug resistant tuberculosis has been on the decline some regions of the world have demonstrated staggeringly high resistance rates to first-line tuberculosis therapies. Signs and symptoms of mycobacterial hand infection are typically inconsistent, and highly dependent on the specific structures of the hand that are affected; therefore, these infections may mimic other infections of the hand like tenosynovitis, joint space infections, and cutaneous infections. The main stay of treatment remains antimycobacterial therapies including but not limited to rifampin, isoniazid, pyrazinamide, and ethambutol.
CONCLUSIONS
The complications associated with mycobacterial hand infections can be significant. Prompt evaluation, including a thorough history to evaluate for potential exposures to infectious sources, followed by appropriate antibiotic choice and duration, with surgical management as needed, is key to reducing the chance that patients experience lasting effects of the infection.
Topics: Anti-Bacterial Agents; Hand; Humans; Mycobacterium Infections, Nontuberculous; Tenosynovitis; Tuberculosis
PubMed: 32940064
DOI: 10.1177/1558944720940064 -
CMAJ : Canadian Medical Association... Oct 2023
Topics: Female; Humans; Adolescent; Mycobacterium bovis; Mycobacterium Infections, Nontuberculous; Lymphadenitis
PubMed: 37903520
DOI: 10.1503/cmaj.230700-f -
Ethiopian Journal of Health Sciences Sep 2023Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar... (Review)
Review
BACKGROUND
Non-tuberculous mycobacteria (NTM) have been reported to cause pulmonary and extrapulmonary infections. These NTMs are often misdiagnosed as MTB due to their similar clinical presentations to tuberculosis, leading to inappropriate treatment and increased morbidity and mortality rates. This literature review aims to provide an overview of the prevalence, clinical manifestations, diagnosis, and management of NTM infections in Africa.
METHODS
A systematic search was performed using various electronic databases including PubMed, Scopus, and Web of Science. The search was limited to studies published in the English language from 2000 to 2021. The following keywords were used: "non-tuberculous mycobacteria", "NTM", "Africa", and "prevalence". Studies that focused solely on the Mycobacterium tuberculosis complex or those that did not report prevalence rates were excluded. Data extraction was performed on eligible studies. Overall, a total of 32 studies met the inclusion criteria and were included in this review.
RESULTS
In our literature review, we identified a total of 32 studies that reported non-tuberculosis mycobacteria (NTM) in Africa. The majority of these studies were conducted in South Africa, followed by Ethiopia and Nigeria. The most commonly isolated NTM species were Mycobacterium avium complex (MAC), Mycobacterium fortuitum, and Mycobacterium abscessus. Many of the studies reported a high prevalence of NTM infections among HIV-positive individuals. Other risk factors for NTM infection included advanced age, chronic lung disease, and previous tuberculosis infection.
CONCLUSION
In conclusion, this literature review highlights the significant burden of non-tuberculosis mycobacteria infections in Africa. The prevalence of these infections is high, and they are often misdiagnosed due to their similarity to tuberculosis. The lack of awareness and diagnostic tools for non-tuberculosis mycobacteria infections in Africa is a major concern that needs to be addressed urgently. It is crucial to improve laboratory capacity and develop appropriate diagnostic algorithms for these infections.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Africa; Prevalence
PubMed: 38784502
DOI: 10.4314/ejhs.v33i5.21 -
Frontiers in Immunology 2021The mycobacterium genus contains a broad range of species, including the human pathogens and . These bacteria are best known for their residence inside host cells.... (Review)
Review
The mycobacterium genus contains a broad range of species, including the human pathogens and . These bacteria are best known for their residence inside host cells. Neutrophils are frequently observed at sites of mycobacterial infection, but their role in clearance is not well understood. In this review, we discuss how neutrophils attempt to control mycobacterial infections, either through the ingestion of bacteria into intracellular phagosomes, or the release of neutrophil extracellular traps (NETs). Despite their powerful antimicrobial activity, including the production of reactive oxidants such as hypochlorous acid, neutrophils appear ineffective in killing pathogenic mycobacteria. We explore mycobacterial resistance mechanisms, and how thwarting neutrophil action exacerbates disease pathology. A better understanding of how mycobacteria protect themselves from neutrophils will aid the development of novel strategies that facilitate bacterial clearance and limit host tissue damage.
Topics: Animals; Biomarkers; Cytotoxicity, Immunologic; Disease Susceptibility; Extracellular Traps; Host-Pathogen Interactions; Humans; Immunity, Innate; Mycobacterium; Mycobacterium Infections; Neutrophil Activation; Neutrophils; Oxidants; Oxidative Stress; Phagocytosis; Phagosomes
PubMed: 35003097
DOI: 10.3389/fimmu.2021.782495 -
Journal of the Formosan Medical... Jun 2020Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant... (Review)
Review
Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant pathogens capable of a wide spectrum of infections, with 50% of infections involving the lungs. The decision to commence treatment is determined according to the severity of the disease, risk of progressive disease, presence of comorbidities, and goals of treatment. MABC is resistant to standard antituberculous agents and has variable drug susceptibility across different geographical locations, therefore, antibiotic susceptibility testing of all clinically significant isolates is crucial for selecting a treatment strategy. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. Despite the introduction of new drugs for treatment, treatment outcomes remain unsatisfactory. The combination of surgical resection of limited lung disease regions with a multidrug, macrolide-based therapy offers the optimal chance of achieving clinical cure of the disease. This review focuses on medical treatment of MABC-lung disease and the efficacy of new agents, such as clofazimine, amikacin inhalation therapy, tigecycline and linezolid, for treating MABC-lung disease.
Topics: Anti-Bacterial Agents; Humans; Lung Diseases; Microbial Sensitivity Tests; Mycobacterium Infections, Nontuberculous; Mycobacterium abscessus
PubMed: 32527504
DOI: 10.1016/j.jfma.2020.05.028 -
Epidemiology and Infection Dec 2022A cross-sectional and retrospective study of patients with spp. in a Portuguese tertiary hospital, in 2009 and 2019, was performed to understand better the rise in...
A cross-sectional and retrospective study of patients with spp. in a Portuguese tertiary hospital, in 2009 and 2019, was performed to understand better the rise in isolations of nontuberculous mycobacteria (NTM). The number of patients with positive samples for spp. grew from 56 in 2009 to 83 in 2019. The proportion of NTM rose from 39.3% to 49.4% ( = 0.240), with being more frequent in 2009 and in 2019, and decreased from 60.7% to 50.6%. Higher age was associated with NTM in both years, and pulmonary disease and immunosuppression were associated with NTM in 2019 ( < 0.05), with weak to moderate correlation ( = 0.231-0.343). The overall rise of NTM, allied to their known capacity to resist antimicrobial therapy, alerts clinicians to the importance of recognising potential risk factors for infection and improving future prevention strategies.
Topics: Humans; Nontuberculous Mycobacteria; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Cross-Sectional Studies; Mycobacterium avium Complex; Mycobacterium
PubMed: 36503567
DOI: 10.1017/S0950268822000899