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Tuberculosis (Edinburgh, Scotland) Mar 2020Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria... (Review)
Review
Mycobacteria are important causes of disease in human and animal hosts. Diseases caused by mycobacteria include leprosy, tuberculosis (TB), nontuberculous mycobacteria (NTM) infections and Buruli Ulcer. To better understand and treat mycobacterial disease, clinicians, veterinarians and scientists use a range of discipline-specific approaches to conduct basic and applied research, including conducting epidemiological surveys, patient studies, wildlife sampling, animal models, genetic studies and computational simulations. To foster the exchange of knowledge and collaboration across disciplines, the Many Hosts of Mycobacteria (MHM) conference series brings together clinical, veterinary and basic scientists who are dedicated to advancing mycobacterial disease research. Started in 2007, the MHM series recently held its 8th conference at the Albert Einstein College of Medicine (Bronx, NY). Here, we review the diseases discussed at MHM8 and summarize the presentations on research advances in leprosy, NTM and Buruli Ulcer, human and animal TB, mycobacterial disease comorbidities, mycobacterial genetics and 'omics, and animal models. A mouse models workshop, which was held immediately after MHM8, is also summarized. In addition to being a resource for those who were unable to attend MHM8, we anticipate this review will provide a benchmark to gauge the progress of future research concerning mycobacteria and their many hosts.
Topics: Animals; Bacteriology; Biomedical Research; Congresses as Topic; Diffusion of Innovation; Disease Models, Animal; Host-Pathogen Interactions; Humans; Infectious Disease Medicine; Mycobacterium; Mycobacterium Infections, Nontuberculous; Tuberculosis
PubMed: 32279870
DOI: 10.1016/j.tube.2020.101914 -
International Journal of Infectious... Aug 2020A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In...
OBJECTIVES
A standard treatment regimen against Mycobacteroides abscessus complex (MABC) infections has not yet been established, making MABC difficult to treat successfully. In this study, we sought to develop an active ingredient for the clinical treatment of MABC infections.
METHODS
We screened 102 MABC strains isolated from clinical specimens using DNA sequence analysis with the housekeeping genes hsp65 and rpoB. Drug susceptibility testing was performed against two subspecies-Mycobacteroides abscessus subsp. abscessus (M. abscessus) and Mycobacteroides abscessus subsp. massiliense (M. massiliense)-using eight antimicrobial agents (clarithromycin, amikacin, doxycycline, imipenem, linezolid, moxifloxacin, faropenem, and rifampicin). The combined efficacy of the antimicrobial agents was investigated using a checkerboard method.
RESULTS
We identified 51 isolates as M. abscessus, 46 as M. massiliense, and five as others. Most of the M. abscessus isolates (83.0 %) exhibited inducible resistance to clarithromycin via the expression of the erm(41) gene. Combinations of imipenem with linezolid, moxifloxacin, and rifampicin exhibited additive effects against 81.0 %, 40.7 %, and 26.9 % of M. abscessus, respectively, and against 54.5 %, 69.2 %, and 30.8 % of M. massiliense, respectively.
CONCLUSIONS
These results demonstrated the potential efficacy of a regimen containing imipenem against M. abscessus and M. massiliense infections.
Topics: Actinomycetales Infections; Amikacin; Anti-Bacterial Agents; Clarithromycin; Doxycycline; Humans; Imipenem; Linezolid; Microbial Sensitivity Tests; Moxifloxacin; Mycobacteriaceae; Sequence Analysis, DNA; beta-Lactams
PubMed: 32526389
DOI: 10.1016/j.ijid.2020.06.007 -
Respiratory Research Jan 2024Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any...
BACKGROUND
Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional.
METHODS
A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method.
RESULTS
In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found.
CONCLUSION
Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.
Topics: Humans; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Genome-Wide Association Study; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 38178098
DOI: 10.1186/s12931-023-02652-7 -
Frontiers in Immunology 2021
Topics: Cytokines; Immunotherapy; Mycobacterium Infections; Tuberculosis, Pulmonary
PubMed: 33968090
DOI: 10.3389/fimmu.2021.684200 -
The European Respiratory Journal Jul 2022
Topics: China; Clinical Protocols; Follow-Up Studies; Humans; Latent Tuberculosis; Tuberculosis
PubMed: 35798372
DOI: 10.1183/13993003.00540-2022 -
The Lancet. Child & Adolescent Health May 2023Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres.
METHODS
For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings.
FINDINGS
Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms.
INTERPRETATION
We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance.
FUNDING
WHO, US National Institutes of Health.
Topics: United States; Adolescent; Humans; Child; Retrospective Studies; Tuberculosis, Pulmonary; Tuberculosis; Triage; Algorithms
PubMed: 36924781
DOI: 10.1016/S2352-4642(23)00004-4 -
The International Journal of... Dec 2021There is a dearth of economic analysis required to support increased investment in TB in India. This study estimates the costs of TB services from a health systems´... (Review)
Review
There is a dearth of economic analysis required to support increased investment in TB in India. This study estimates the costs of TB services from a health systems´ perspective to facilitate the efficient allocation of resources by India´s National Tuberculosis Elimination Programme. Data were collected from a multi-stage, stratified random sample of 20 facilities delivering TB services in two purposively selected states in India as per Global Health Cost Consortium standards and using Value TB Data Collection Tool. Unit costs were estimated using the top-down (TD) and bottom-up (BU) methodology and are reported in 2018 US dollars. Cost of delivering 50 types of TB services and four interventions varied according to costing method. Key services included sputum smear microscopy, Xpert MTB/RIF and X-ray with an average BU costs of respectively US$2.45, US$17.36 and US$2.85. Average BU cost for bacille Calmette-Guérin vaccination, passive case-finding, TB prevention in children under 5 years using isoniazid and first-line drug treatment in new pulmonary and extrapulmonary TB cases was respectively US$0.76, US$1.62, US$2.41, US$103 and US$98. The unit cost of TB services and outputs are now available to support investment decisions, as diagnosis algorithms are reviewed and prevention or treatment for TB are expanded or updated in India.
Topics: Child; Child, Preschool; Cost-Benefit Analysis; Humans; India; Mycobacterium tuberculosis; Sensitivity and Specificity; Sputum; Tuberculosis; Tuberculosis, Pulmonary
PubMed: 34886932
DOI: 10.5588/ijtld.21.0105 -
Journal of Infection and Public Health Aug 2020Hospital-acquired tuberculosis infection among healthcare workers is a global concern due to the increased attributable risk of tuberculosis infection among this group....
Hospital-acquired tuberculosis infection among healthcare workers is a global concern due to the increased attributable risk of tuberculosis infection among this group. To reduce healthcare workers' exposure to airborne Mycobacterium tuberculosis, various policies and guidelines have been developed and updated by the World Health Organisation (WHO) since 1999. In March 2019, the WHO published the updated tuberculosis infection control guidelines. It had previously been suggested that the existence of multiple guidelines and the changes in the contents across versions may confuse end-users and challenge the implementation. With this issue in mind, we examined the updated WHO 2019 TB infection control guidelines. The WHO 2019 updated guideline is a shorter and more focused document that includes more of the evidence from published systematic reviews for TB infection prevention and control. The guidelines focus on implementing TB infection control as an integrated infection control and prevention 'package'. However, a few key elements have been omitted or integrated with other WHO policies that were previously included in the guidelines, many of which are also still present in other international and in many national level TB infection control guidelines. In this commentary, we highlighted the inconsistencies in the different versions of the guidelines, the challenges that the high TB burden and low-income countries may face while implementing the guidelines and some factors that may be considered in the future guidelines. The arguments we made have important implications for tuberculosis infection control strategy development and implementation in low-income and high TB burden countries.
Topics: Guidelines as Topic; Humans; Infection Control; Latent Tuberculosis; Tuberculosis; World Health Organization
PubMed: 32241724
DOI: 10.1016/j.jiph.2020.02.039 -
Wounds : a Compendium of Clinical... Dec 2022LP is an uncommon reaction characterized by outbreaks of erythematous, painful, slightly infiltrated macules and hemorrhagic bullae that progress to ulceration that...
INTRODUCTION
LP is an uncommon reaction characterized by outbreaks of erythematous, painful, slightly infiltrated macules and hemorrhagic bullae that progress to ulceration that occurs in patients with Lucio leprosy and lepromatous leprosy; it can be considered a variant of type 2 or 3 reaction. Death can occur because of blood dyscrasia or sepsis. Precipitating factors include infections, drugs, and pregnancy.
CASE REPORT
A 17-year-old female presented with fever, tachycardia, adynamia, extensive hyperchromic and purplish macular lesions, erythematous plaques, multiple blisters with serohematic content, and necrotic exulcerations and ulcers on the lower and upper limbs, ears, nose, palms, and soles. Past medical history included leprosy and a first trimester miscarriage. The patient was diagnosed with borderline lepromatous leprosy in reactional state (ie, LP) and MDT was restarted in association with systemic corticosteroid and pentoxifylline. Local therapy was performed with cleansing solution (0.9% sodium chloride), dressing with silver sulfadiazine ointment, and surgical debridement of the necrotic lesions.
CONCLUSION
LP is a rare manifestation that may be fatal because of considerable inflammatory activity and the extent and severity of dermatologic lesions. Pregnancy is strongly associated with exacerbation of symptoms. Debridement is required to excise nonviable tissue and promote wound healing.
Topics: Humans; Female; Adolescent; Leprosy, Lepromatous; Leprosy, Multibacillary; Leprosy; Erythema
PubMed: 36645661
DOI: 10.25270/wnds/21095 -
The International Journal of... May 2023Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for... (Review)
Review
Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for further research in this population, it is important to recognize that much can be done to improve the services they currently receive. Following a systematic review of the literature and the input of a global team of health professionals, a series of best practices for the diagnosis, prevention and treatment of TB during pregnancy were developed. Best practices were developed for each of the following areas: 1) screening and diagnosis; 2) reproductive health services and family planning; 3) treatment of drug-susceptible TB; 4) treatment of rifampicin-resistant/multidrug-resistant TB; 5) compassionate infection control practices; 6) feeding considerations; 7) counseling and support; 8) treatment of TB infection/TB preventive therapy; and 9) research considerations. Effective strategies for the care of pregnant people across the TB spectrum are readily achievable and will greatly improve the lives and health of this under-served population.
Topics: Pregnancy; Female; Humans; Tuberculosis; Rifampin; Counseling; Delivery of Health Care; Tuberculosis, Multidrug-Resistant
PubMed: 37143222
DOI: 10.5588/ijtld.23.0031