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Journal of the American Academy of... Dec 2023Tuberculosis is an ancient disease that continues to affect an estimated 10 million people per year and is responsible for 1.4 million deaths per year. Additionally, the... (Review)
Review
Tuberculosis is an ancient disease that continues to affect an estimated 10 million people per year and is responsible for 1.4 million deaths per year. Additionally, the HIV epidemic and multidrug resistance present challenges to disease control. Cutaneous tuberculosis is an uncommon, often indolent, manifestation of mycobacterial infection that has a varied presentation. Its diagnosis is challenging, as lesions mimic other, more common conditions and microbiological confirmation is often not possible. Cutaneous tuberculosis can be broadly categorized into multibacillary and paucibacillary forms. Approximately one-third of skin tuberculosis is associated with systemic involvement. By recognizing cutaneous tuberculosis early, dermatologists can play an important role in disease control. The first article in this 2-part continuing medical education series describes the latest epidemiology, microbiology, and pathogenesis of tuberculosis. Furthermore, we review the classification, clinical manifestations, common clinical differentials, and systemic involvement that occur in cutaneous tuberculosis.
Topics: Humans; Tuberculosis, Cutaneous; Diagnosis, Differential
PubMed: 35149149
DOI: 10.1016/j.jaad.2021.12.063 -
Clinics in Chest Medicine Dec 2023Nontuberculous mycobacterial (NTM) isolation and pulmonary disease (NTM-PD) have continued to increase in most regions of the world, driven mainly by Mycobacterium... (Review)
Review
Nontuberculous mycobacterial (NTM) isolation and pulmonary disease (NTM-PD) have continued to increase in most regions of the world, driven mainly by Mycobacterium avium. Single-center studies also support increasing trends as well as a persistent burden of undiagnosed NTM among persons suspected of having tuberculosis (TB), in countries with moderate-to-high TB prevalence. Cumulative exposure to water and soil presents an increased risk to susceptible hosts, and trace metals in water supply are recently recognized risk factors. Establishing standard case definitions for subnational and national surveillance systems with mandatory notification of NTM-PD are needed to allow comparisons within and across countries and regions.
Topics: Humans; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Lung; Lung Diseases; Tuberculosis
PubMed: 37890910
DOI: 10.1016/j.ccm.2023.08.012 -
Nature Reviews. Disease Primers Mar 2024Tuberculosis (TB) remains the foremost cause of death by an infectious disease globally. Multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB; resistance to... (Review)
Review
Tuberculosis (TB) remains the foremost cause of death by an infectious disease globally. Multidrug-resistant or rifampicin-resistant TB (MDR/RR-TB; resistance to rifampicin and isoniazid, or rifampicin alone) is a burgeoning public health challenge in several parts of the world, and especially Eastern Europe, Russia, Asia and sub-Saharan Africa. Pre-extensively drug-resistant TB (pre-XDR-TB) refers to MDR/RR-TB that is also resistant to a fluoroquinolone, and extensively drug-resistant TB (XDR-TB) isolates are additionally resistant to other key drugs such as bedaquiline and/or linezolid. Collectively, these subgroups are referred to as drug-resistant TB (DR-TB). All forms of DR-TB can be as transmissible as rifampicin-susceptible TB; however, it is more difficult to diagnose, is associated with higher mortality and morbidity, and higher rates of post-TB lung damage. The various forms of DR-TB often consume >50% of national TB budgets despite comprising <5-10% of the total TB case-load. The past decade has seen a dramatic change in the DR-TB treatment landscape with the introduction of new diagnostics and therapeutic agents. However, there is limited guidance on understanding and managing various aspects of this complex entity, including the pathogenesis, transmission, diagnosis, management and prevention of MDR-TB and XDR-TB, especially at the primary care physician level.
Topics: Humans; Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; Rifampin; Tuberculosis, Multidrug-Resistant; Isoniazid
PubMed: 38523140
DOI: 10.1038/s41572-024-00504-2 -
Lancet (London, England) Oct 2023
Review
Topics: Humans; Tuberculosis; Global Health
PubMed: 37716363
DOI: 10.1016/S0140-6736(23)01379-X -
Deutsche Medizinische Wochenschrift... Sep 2023Extrapulmonary tuberculosis (TB) presents unique diagnostic and therapeutic challenges. The site of involvement can vary widely, with common sites including the lymph...
Extrapulmonary tuberculosis (TB) presents unique diagnostic and therapeutic challenges. The site of involvement can vary widely, with common sites including the lymph nodes, pleura, skin, ear, nose and throat, genitourinary system, pericardium, gastrointestinal tract, bones and joints, and central nervous system. Clinical manifestations of extrapulmonary TB are diverse and often non-specific. Diagnosis is based on a combination of clinical suspicion, imaging, histopathology, and microbiology. Treatment of extrapulmonary TB generally follows similar principles to pulmonary TB, but the duration of treatment depends on the site of involvement and the extent of the disease. Increased awareness among healthcare providers is essential for the timely recognition and effective management of extrapulmonary TB cases.
Topics: Humans; Tuberculosis; Tuberculosis, Extrapulmonary; Tuberculosis, Pulmonary; Diagnostic Imaging; Lymph Nodes
PubMed: 37793616
DOI: 10.1055/a-1937-8186 -
Lancet (London, England) Aug 2023In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the... (Randomized Controlled Trial)
Randomized Controlled Trial
Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial.
BACKGROUND
In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis.
METHODS
In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs). This study is registered with CTRI-India, CTRI/2019/08/020490.
FINDINGS
Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities (eg, Santhals, Ho, Munda, Oraon, and Bhumij) and 34% (3543 of 10 345) had undernutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2-3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4-2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43-0·85; aHR 0·59 [0·42-0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35-0·79]; 0·51 [0·34-0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis.
INTERPRETATION
To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39-48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and undernutrition syndemic.
FUNDING
Indian Council of Medical Research-India TB Research Consortium.
Topics: Adult; Humans; Incidence; India; Tuberculosis; Tuberculosis, Pulmonary; Dietary Supplements
PubMed: 37567200
DOI: 10.1016/S0140-6736(23)01231-X -
Emerging Infectious Diseases Aug 2023Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to... (Review)
Review
Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001-2020. During 2010-2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.
Topics: Adult; Humans; Diphtheria; Japan; Corynebacterium; Corynebacterium Infections; Corynebacterium diphtheriae; Diphtheria Toxin; Diphtheria Toxoid
PubMed: 37486266
DOI: 10.3201/eid2908.220058 -
The New England Journal of Medicine Oct 2023
Topics: Humans; Antitubercular Agents; Tuberculosis, Meningeal; Tuberculosis, Multidrug-Resistant
PubMed: 37819958
DOI: 10.1056/NEJMe2310262 -
Emerging Microbes & Infections Dec 2023Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune...
Mycobacterium tuberculosis (Mtb) infection, including active tuberculosis (TB) and latent Mtb infection (LTBI), leads to diverse outcomes owing to different host immune responses. However, the immune mechanisms that govern the progression from LTBI to TB remain poorly defined in humans. Here, we profiled the lung immune cell populations within the bronchoalveolar lavage fluid (BALF) from patients with LTBI or TB using single-cell RNA sequencing (scRNA-seq). We found that Mtb infection substantially changed the immune cell compartments in the BALF, especially for the three subsets of macrophages, monocyte macrophage (MM)-CCL23, MM-FCN1, and MM-SPP1, which were found to be associated with the disease status of TB infection. Notably, MM-CCL23 cells derived from monocytes after stimulation with Mtb were characterized by high levels of chemokine ( and ) production and might serve as a marker for Mtb infection. The MM-CCL23 population mainly recruited CD8-CCR6 T cells through CCL20/CCR6, which was a prominent feature associated with protection immunity in LTBI. This study improves our understanding of the lung immune landscape during Mtb infection, which may inform future vaccine design for protective immunity.
Topics: Humans; Latent Tuberculosis; Bronchoalveolar Lavage Fluid; Mycobacterium tuberculosis; Tuberculosis; CD8-Positive T-Lymphocytes; Macrophages
PubMed: 37470432
DOI: 10.1080/22221751.2023.2239940 -
CMAJ : Canadian Medical Association... Nov 2023
Topics: Humans; Rifampin; Tuberculosis; Latent Tuberculosis; Patients; Shock
PubMed: 37931950
DOI: 10.1503/cmaj.230317-f