Mycobacterium Tuberculosis (Tuberculosis)

2021 ◽  
Author(s):  
Stefan HE Kaufmann
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Viral Vectors ◽  
Age Groups ◽  
Bacterial Pathogen ◽  
Disease Manifestation ◽  
Latently Infected ◽  
Childhood Tb ◽  
Maturation Stages ◽  
Pathogen Entry ◽  
The Individual

Tuberculosis (TB) is a major health threat caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). Globally, 10 million individuals fell ill of TB and 1.4 million died in 2019. The COVID-19 pandemic has severely impacted on TB notifications in 2020, thereby markedly increasing morbidity and mortality caused by TB. The lung is the most frequent site of disease manifestation, the site of pathogen entry and the source of dissemination. In the infected lung, granulomas are formed at the site of Mtb persistence which primarily consist of macrophages of different maturation stages and T lymphocytes. Solid granulomas contain Mtb, thus preventing outbreak of active disease. The individual is now latently infected. Once Mtb evades immune control, granulomas become necrotic and later caseous. Active TB disease has started. Diagnosis of TB is done by chest X-ray, microscopy, bacterial culture, molecular test, and immunologic test. TB can be cured by a combination of 3-4 specific drugs given over a period of 6-9 months. Increasing incidences of multi-drug and extensively drug-resistant Mtb render therapy difficult to impossible. The current vaccine, Bacille Calmette-Guérin (BCG) prevents extrapulmonary childhood TB but fails to protect against pulmonary TB in all age groups. New vaccines against TB are urgently needed. New candidates that have entered clinical trials are killed whole cell vaccines, recombinant live vaccines, Mtb antigen-adjuvant formulations or viral vectors expressing Mtb antigens.

scholarly journals Preclinical Progress of Subunit and Live Attenuated Mycobacterium tuberculosis Vaccines: A Review following the First in Human Efficacy Trial

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 848
Author(s):  
Jacqueline Watt ◽  
Jun Liu
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Viral Vectors ◽  
Infectious Agent ◽  
Efficacy Trial ◽  
Bacille Calmette Guerin ◽  
Antigen Discovery ◽  
Latently Infected ◽  
Delivery Strategies ◽  
Recombinant Bcg ◽  
Selection Of

Tuberculosis (TB) is the global leading cause of death from an infectious agent with approximately 10 million new cases of TB and 1.45 million deaths in 2018. Bacille Calmette-Guérin (BCG) remains the only approved vaccine for Mycobacterium tuberculosis (M. tb, causative agent of TB), however clinical studies have shown BCG has variable effectiveness ranging from 0–80% in adults. With 1.7 billion people latently infected, it is becoming clear that vaccine regimens aimed at both post-exposure and pre-exposure to M. tb will be crucial to end the TB epidemic. The two main strategies to improve or replace BCG are subunit and live attenuated vaccines. However, following the failure of the MVA85A phase IIb trial in 2013, more varied and innovative approaches are being developed. These include recombinant BCG strains, genetically attenuated M. tb and naturally attenuated mycobacteria strains, novel methods of immunogenic antigen discovery including for hypervirulent M. tb strains, improved antigen recognition and delivery strategies, and broader selection of viral vectors. This article reviews preclinical vaccine work in the last 5 years with focus on those tested against M. tb challenge in relevant animal models.

Kinase Targets for Mycolic Acid Biosynthesis in Mycobacterium tuberculosis

2019 ◽  
Vol 12 (1) ◽  
pp. 27-49 ◽  
Author(s):  
Shahinda S.R. Alsayed ◽  
Chau C. Beh ◽  
Neil R. Foster ◽  
Alan D. Payne ◽  
Yu Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Enzymatic Activity ◽  
Bacterial Pathogen ◽  
Building Blocks ◽  
Mycolic Acid ◽  
Adaptive Responses ◽  
Mycolic Acids ◽  
Hydroxylated Fatty Acids

Background:Mycolic acids (MAs) are the characteristic, integral building blocks for the mycomembrane belonging to the insidious bacterial pathogen Mycobacterium tuberculosis (M.tb). These C60-C90 long α-alkyl-β-hydroxylated fatty acids provide protection to the tubercle bacilli against the outside threats, thus allowing its survival, virulence and resistance to the current antibacterial agents. In the post-genomic era, progress has been made towards understanding the crucial enzymatic machineries involved in the biosynthesis of MAs in M.tb. However, gaps still remain in the exact role of the phosphorylation and dephosphorylation of regulatory mechanisms within these systems. To date, a total of 11 serine-threonine protein kinases (STPKs) are found in M.tb. Most enzymes implicated in the MAs synthesis were found to be phosphorylated in vitro and/or in vivo. For instance, phosphorylation of KasA, KasB, mtFabH, InhA, MabA, and FadD32 downregulated their enzymatic activity, while phosphorylation of VirS increased its enzymatic activity. These observations suggest that the kinases and phosphatases system could play a role in M.tb adaptive responses and survival mechanisms in the human host. As the mycobacterial STPKs do not share a high sequence homology to the human’s, there have been some early drug discovery efforts towards developing potent and selective inhibitors.Objective:Recent updates to the kinases and phosphatases involved in the regulation of MAs biosynthesis will be presented in this mini-review, including their known small molecule inhibitors.Conclusion:Mycobacterial kinases and phosphatases involved in the MAs regulation may serve as a useful avenue for antitubercular therapy.

scholarly journals Validity of the Gender Dysphoria diagnosis and incidence trends in Sweden: a nationwide register study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Malin Indremo ◽  
Richard White ◽  
Thomas Frisell ◽  
Sven Cnattingius ◽  
Alkistis Skalkidou ◽  
...  
Keyword(s):  
Gender Dysphoria ◽  
Age Groups ◽  
Medical Intervention ◽  
Future Research ◽  
Advantages And Disadvantages ◽  
Incidence Trends ◽  
Interaction Terms ◽  
Definition Of ◽  
The Individual ◽  
Nationwide Register Study

AbstractThe aim of this study was to examine the validity of the Gender Dysphoria (GD) diagnoses in the Swedish National Patient Register (NPR), to discuss different register-based definitions of GD and to investigate incidence trends. We collected data on all individuals with registered GD diagnoses between 2001 and 2016 as well as data on the coverage in the NPR. We regarded gender confirming medical intervention (GCMI) as one proxy for a clinically valid diagnosis and calculated the positive predictive value (PPV) for receiving GCMI for increasing number of registered GD diagnoses. We assessed crude and coverage-adjusted time trends of GD during 2004–2015 with a Poisson regression, using assigned sex and age as interaction terms. The PPV for receiving GCMI was 68% for ≥ 1 and 79% for ≥ 4 GD-diagnoses. The incidence of GD was on average 35% higher with the definition of ≥ 1 compared to the definition of ≥ 4 diagnoses. The incidence of GD, defined as ≥ 4 diagnoses increased significantly during the study period and mostly in the age categories 10–17 and 18–30 years, even after adjusting for register coverage. We concluded that the validity of a single ICD code denoting clinical GD in the Swedish NPR can be questioned. For future research, we propose to carefully weight the advantages and disadvantages of different register-based definitions according to the individual study’s needs, the time periods involved and the age-groups under study.

Evaluation of the sensitivity of faecal sampling for detection of monophasic Salmonella Typhimurium and other Salmonella in cattle and pigs

2014 ◽  
Vol 143 (8) ◽  
pp. 1681-1691 ◽  
Author(s):  
M. E. ARNOLD ◽  
R. J. GOSLING ◽  
F. MARTELLI ◽  
D. MUELLER-DOBLIES ◽  
R. H. DAVIES
Keyword(s):  
Faecal Sample ◽  
Management Practices ◽  
Age Groups ◽  
Farm Animals ◽  
Infection Prevalence ◽  
Sample Type ◽  
Sample Data ◽  
Using Data ◽  
The Individual ◽  
Positive Groups

SUMMARYThere has been a rapid rise in the prevalence of cases of monophasic Salmonella Typhimurium (mST) in both humans and farm animals, and it has been found in pigs, cattle and poultry. It is therefore vital to have a good understanding of how to efficiently detect infected farms. The objective of this project was to determine sample type sensitivity in the detection of Salmonella to detect infected groups of animals on both pig (breeder, grower and finisher sites) and cattle (beef and dairy) farms, using data collected from a study investigating farms that were positive for mST, and to explore any variation between different age groups and management practices. A Bayesian approach in the absence of a gold standard was adopted to analyse the individual and pooled faecal sample data collected from each epidemiological group on each of the farms. The sensitivity of pooled sampling depended on the prevalence of infection in the group being sampled, with a higher prevalence leading to higher sensitivity. Pooled sampling was found to be more efficient at detecting positive groups of animals than individual sampling, with the probability of a random sample from a group of animals with 5% prevalence testing positive being equal to 15·5% for immature pigs (3·6% for an individual faecal sample, taking into account the sensitivity and infection prevalence), 7·1% for adult pigs (1·2% for individual sampling), 30% for outdoor cattle (2% for individual sampling) and 34% for indoor cattle (1% for individual sampling). The mean prevalence of each epidemiological group was higher in outdoor farms than indoor for both pigs and cattle (mean within-farm prevalence of 29·4% and 38·7% for outdoor pigs and cattle, respectively, compared to 19·8% and 22·1% for indoor pigs and cattle)

Inequality in active ageing: evidence from a new individual-level index for European countries

2017 ◽  
Vol 39 (3) ◽  
pp. 541-567 ◽  
Author(s):  
MIKKEL BARSLUND ◽  
MARTEN VON WERDER ◽  
ASGHAR ZAIDI
Keyword(s):  
Age Groups ◽  
Positive Association ◽  
European Countries ◽  
Active Ageing ◽  
Unequal Distribution ◽  
Individual Level ◽  
Country Level ◽  
Challenges And Opportunities ◽  
Share Data ◽  
The Individual

ABSTRACTIn the context of emerging challenges and opportunities associated with population ageing, the study of inequality in active-ageing outcomes is critical to the design of appropriate and effective social policies. While there is much discussion about active ageing at the aggregate country level, little is known about inequality in active-ageing experiences within countries. Based on the existing literature on active ageing, this paper proposes an individual-level composite active ageing index based on Survey of Health, Ageing and Retirement in Europe (SHARE) data. The individual-level nature of the index allows us to analyse inequality in experiences of active ageing within selected European countries. One important motivation behind measuring active ageing at the individual level is that it allows for a better understanding of unequal experiences of ageing, which may otherwise be masked in aggregate-level measures of active ageing. Results show large differences in the distribution of individual-level active ageing across the 13 European countries covered and across age groups. Furthermore, there is a positive association between the country-level active ageing index and the equality of its distribution within a country. Hence, countries with the lowest average active ageing index tend to have the most unequal distribution in active-ageing experiences. For nine European countries, where temporal data are also available, we find that inequality in active-ageing outcomes decreased in the period 2004 to 2013.

scholarly journals Preclinical Evidence of Nanomedicine Formulation to Target Mycobacterium tuberculosis at Its Bone Marrow Niche

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 372 ◽  
Author(s):  
Jaishree Garhyan ◽  
Surender Mohan ◽  
Vinoth Rajendran ◽  
Rakesh Bhatnagar
Keyword(s):  
Bone Marrow ◽  
Mycobacterium Tuberculosis ◽  
In Vitro Release ◽  
Bone Marrow Niche ◽  
Mice Model ◽  
Latently Infected ◽  
Marrow Mesenchymal Stem Cells

One-third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (Mtb). Recently, we found that dormant Mtb hides in bone marrow mesenchymal stem cells (BM-MSCs) post-chemotherapy in mice model and in clinical subjects. It is known that residual Mtb post-chemotherapy may be responsible for increased relapse rates. However, strategies for Mtb clearance post-chemotherapy are lacking. In this study, we engineered and formulated novel bone-homing PEGylated liposome nanoparticles (BTL-NPs) which actively targeted the bone microenvironment leading to Mtb clearance. Targeting of BM-resident Mtb was carried out through bone-homing liposomes tagged with alendronate (Ald). BTL characterization using TEM and DLS showed that the size of bone-homing isoniazid (INH) and rifampicin (RIF) BTLs were 100 ± 16.3 nm and 84 ± 18.4 nm, respectively, with the encapsulation efficiency of 69.5% ± 4.2% and 70.6% ± 4.7%. Further characterization of BTLs, displayed by sustained in vitro release patterns, increased in vivo tissue uptake and enhanced internalization of BTLs in RAW cells and CD271+BM-MSCs. The efficacy of isoniazid (INH)- and rifampicin (RIF)-loaded BTLs were shown using a mice model where the relapse rate of the tuberculosis was decreased significantly in targeted versus non-targeted groups. Our findings suggest that BTLs may play an important role in developing a clinical strategy for the clearance of dormant Mtb post-chemotherapy in BM cells.

scholarly journals THE ANDRONOVO AGE WOMEN’S COSTUME, BASED ON FINDS FROM MAYTAN, CENTRAL KAZAKHSTAN

2018 ◽  
Vol 46 (2) ◽  
pp. 35-42
Author(s):  
A. A. Tkachev ◽  
N. A. Tkacheva
Keyword(s):  
Bronze Age ◽  
Age Groups ◽  
Cultural Tradition ◽  
Adult Women ◽  
Middle Bronze Age ◽  
The Individual ◽  
Hands And Feet ◽  
Head Neck ◽  
Age Category ◽  
Two Age Groups

This article describes burials of women at a Middle Bronze Age cemetery of Maytan—the only completely excavated Andronovo burial ground in the steppes of central Kazakhstan. On the basis of the location of ornaments in burials, an attempt is made to reconstruct details of costume with regard to age groups. The composition and arrangement of the individual elements of the costume indicate several decoration areas such as head; neck and chest; hands and feet. Exceptional areas are accessories (bags and boxes), belt, and lap of dress. Most ornaments mark the age category of women. There are two age groups: girls and adult women. Though many graves have been looted, a tentative reconstruction of the costume with regard to these groups is possible. Such a reconstruction is relevant to cultural tradition, ideas of beauty, and social status.

scholarly journals CAN STATURE, ABDOMINAL PERIMETER AND BMI INDEX PREDICT POSSIBLE CARDIOMETABOLIC RISKS IN FUTURE OBESITY?

2020 ◽  
Vol 33 (2) ◽  
Author(s):  
Ricardo Wallace das Chagas LUCAS ◽  
Paulo Afonso Nunes NASSIF ◽  
Fernando Issamu TABUSHI ◽  
Denise Serpa Bopp NASSIF ◽  
Bruno Luiz ARIEDE ◽  
...  
Keyword(s):  
Age Groups ◽  
Abdominal Circumference ◽  
Fat Percentage ◽  
Height Measurement ◽  
Men And Women ◽  
Functional Changes ◽  
Abdominal Perimeter ◽  
Cardiometabolic Risks ◽  
The Aesthetic ◽  
The Individual

ABSTRACT Background: Obesity changes the anatomy of the patient. In addition to the aesthetic change, the high percentage of fat determines evident functional changes. Anthropometric normality in measuring abdominal circumference and height can serve as a basis for measuring cardiometabolic risks of obesity. Aim: To verify if it is possible to determine parameters of normality between waist and height in people with normal BMI and fat percentages, to serve as a basis for assessing risks for obesity comorbidities. Methods: A sample of 454 individuals with BMI and percentages of fat considered within the normal range was extracted. It was divided into age groups for both men and women between 18 and 25; 26 to 35; 36 to 45; 46 to 55; 56 to 65. A total of 249 men and 205 women were included. Results: Regarding the percentage of height as a measure of the abdominal perimeter, the total female sample had an average of 44.2±1.1% and the male 45.3%+1.5. For women, this percentage determined the equation of the waist-height ratio represented by X=(age+217) / 5.875, and for men X=(age+190.89) / 5.2222. “X” represents the percentage of the height measurement so that the individual falls into the category of adequate percentage of fat and BMI. Conclusion: Between the stature of adult men and women with normal fat percentage and BMI, there is a common numerical relationship, with is on average 44% for women and 45% for men.

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