The tuberculin skin test has significant limitations for use in individuals vaccinated with BCG. The presence in the genome of
of the RDI region, which is absent in the genome of Mycobacterium bovis ...BCG and most non-tuberculous mycobacteria, made it possible to develop new skin tests, which include a skin test with a recombinant tuberculosis allergen RTA (Diaskintest®, JSC Generium, Russia). Diaskintest has shown high diagnostic performance in clinical trials and in conditions of high prevalence of tuberculosis infection. In 2021, the Russia was excluded from the WHO list of high TB burden countries, which makes relevant an assessment of the specificity of the RTA test under conditions of low epidemiologic risk for tuberculosis to confirm the high specificity of the test.
To assess the specificity of Diaskintest in the regions of the Russian Federation with low epidemiologic risk for tuberculosis.
A multicenter, open-label, prospective study was conducted, which included 150 healthy volunteers aged 18-30 years old, vaccinated with BCG, who were not at risk of tuberculosis, from regions with low epidemiologic risk (Oryol region, Ryazan region, and Arkhangelsk region). During the study, 4 visits were scheduled for each participant: Visit 0 (screening), Visit 1, Visit 2 (in 72 h) and Visit 3 (in 28 days). All participants, who excluded active and latent tuberculosis infection, underwent a test with RTA. To assess the safety of RTA tests, all systemic and local adverse events that occurred during 28 days were recorded. The trial was filed in the NIH clinical trials database ClinicalTrials.gov (NCT05203068).
In individuals with a negative T-SPOT.TB test, the specificity of the RTA test was 97% (95% CI: 92-99%) with a cut-off of >0 mm. The study findings confirm data 2009: 100.00 (95% CI: 94-100). When evaluating the safety of the RTA test during 28 days of follow-up, the participants did not report local and systemic adverse reactions that had a causal relationship with the RTA test.
Diaskintest is highly specific and safe, therefore it is a valuable tool as a screening test for early detection of tuberculosis.
In a prospective study involving 5340 individuals, humoral and cellular responses revealed magnitude-dependent protection from COVID-19. Antibodies alone significantly decreased infection rates; ...isolated cellular response provided an intermediate level of protection. The lowest COVID-19 incidence was in the double-positive group.
Abstract
Background
During the ongoing coronavirus disease 2019 (COVID-19) pandemic, many individuals were infected with and have cleared the virus, developing virus-specific antibodies and effector/memory T cells. An important unanswered question is what levels of T-cell and antibody responses are sufficient to protect from the infection.
Methods
In 5340 Moscow residents, we evaluated anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin M (IgM)/immunoglobulin G (IgG) titers and frequencies of the T cells specific to the membrane, nucleocapsid, and spike proteins of SARS-CoV-2, using interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay. Additionally, we evaluated the fractions of virus-specific CD4+ and CD8+ T cells using intracellular staining of IFN-γ and interleukin 2 followed by flow cytometry. We analyzed the COVID-19 rates as a function of the assessed antibody and T-cell responses, using the Kaplan–Meier estimator method, for up to 300 days postinclusion.
Results
We showed that T-cell and antibody responses are closely interconnected and are commonly induced concurrently. Magnitudes of both responses inversely correlated with infection probability. Individuals positive for both responses demonstrated the highest levels of protectivity against the SARS-CoV-2 infection. A comparable level of protection was found in individuals with antibody response only, whereas the T-cell response by itself granted only intermediate protection.
Conclusions
We found that the contribution of the virus-specific antibodies to protection against SARS-CoV-2 infection is more pronounced than that of the T cells. The data on the virus-specific IgG titers may be instructive for making decisions in personalized healthcare and public anti–COVID-19 policies.
Clinical Trials Registration. NCT04898140.
During the ongoing coronavirus disease COVID-19 pandemic, many individuals were infected with and have cleared the virus, developing virus-specific antibodies and effector/memory T cells. An ...important unanswered question is what levels of T cell and antibody responses are sufficient to protect from the infection.
In 5340 Moscow residents, we evaluated anti-SARS-CoV-2 IgM/IgG titers and frequencies of the T cells specific to the membrane, nucleocapsid, and spike proteins of SARS-CoV-2, using IFNγ ELISpot assay. Additionally, we evaluated the fractions of virus-specific CD4+ and CD8+ T cells using intracellular staining of IFNγ and IL2 followed by flow cytometry. We analyzed the COVID-19 rates as a function of the assessed antibody and T cell responses, using the Kaplan-Meyer estimator method, for up to 300 days post-inclusion.
We showed that T cell and antibody responses are closely interconnected and are commonly induced concurrently. Magnitudes of both responses inversely correlated with infection probability. Individuals positive for both responses demonstrated the highest levels of protectivity against the SARS-CoV-2 infection. A comparable level of protection was found in individuals with antibody response only, while the T cell response by itself granted only intermediate protection.
We found that the contribution of the virus-specific antibodies to protection against the SARS-CoV-2 infection is more pronounced than that of the T cells. The data on the virus-specific IgG titers may be instructive for making decisions in personalized health care and public anti-COVID-19 policies.
The review addresses publications on genetic polymorphisms that potentially impact the effectiveness of therapy with hypoglycemic drugs of the dipeptidyl peptidase-4 inhibitor group. The literature ...was searched in the PubMed database from 2017 to 2023. Polymorphisms of several genes (GLP1R, TCF7L2, DPP-4, KCNQ1, KCNJ11, PNPLA3, PRKD1) are associated with the pharmacokinetic values and efficacy of dipeptidyl peptidase-4 inhibitors, which may be promising for personalizing the treatment of patients with type 2 diabetes mellitus.
Type 2 diabetes mellitus (DM) remains the most common type of DM and is associat-ed with disabling complications, reduced quality of life and reduced life expectancy. Satisfactory control of ...carbohydrate metabolism remains the key way to manage them.
To perform a retrospective analysis of carbohydrate metabolism (in terms of glycated hemoglobin - HbA
), the prevalence of complications, and features of hypoglycemic and concomitant therapy in patients with type 2 DM.
The analysis of sex and age characteristics, achieved level of HbA
, diabetes complications, sugar-reducing and concomitant therapy according to the data of outpatient records of the patients who are on dispensary registration with an endocrinologist in the Endocrinology Department of the Consultative and Diagnostic Polyclinic of the Tomsk Regional Clinical Hospital in Tomsk was carried out.
546 outpatient medical records of patients with type 2 DM were analysed, among which there were 39.6% men (
=216) with a history of type 2 DM 8.0 years 3.0; 13.0 , median age 64.0 years 54.5; 71.0 and 60.4% women (
=330), history of type 2 DM 10.0 years 5.0; 15.0, median age 70.0 years 63.0; 75.0. The achieved HbA
level in men was 7.6% 6.3; 9.0 and in women 7.4% 6.4; 9.1. 19.4% of men and 13.6% of women had an aggravated history of type 2 DM. According to the history, 6.5% of men (
=14) and 3% of women (
=10) with type 2 DM had a history of stroke, and myocardial infarction 12% (
=26) and 1.5% (
=5), respectively. Among the analysed outpatient records of type 2 DM patients, 18.5% of men (
=40) and 12.4% of women (
=41) were found to have diabetic nephropathy. Diabetic retinopathy was reported in 9.3% (
=20) of men and 4.2% (
=14) of women. Diabetic macroangiopathies were detected in 29.6% (
=64) of males and 9.7% (
=32) of females. Among other chronic complications of DM, diabetic neuroosteoarthropathy was recorded in 1% (
=2) of males and 3% (
=10) of females, diabetic polyneuropathy in 25% (
=54) and 21.5% (
=71), respectively. Diabetic foot was diagnosed in 1.9% (
=4) of men and 1.8% (
=6) of women. Among comorbid pathology, obesity was diagnosed in 45.4% (
=88) of men and 69.1% (
=228) of women, dyslipidaemia in 10.2% (
=22) and 10.6% (
=35) respectively, hypertension in 39.8% (
=86) and 32.6% (
=108) of cases. The diagnosis of non-alcoholic fatty liver disease was verified in 3.7% of men (
=7) and 1.8% of women (
=6), chronic heart failure in 7.4% of men (
=16) and 2.4% of women (
=8) registered for type 2 DM. According to the analysed outpatient records, 4.1% (
=23) of patients received diet therapy, 48.3% (
=263) received monotherapy and 47.6% (
=260) received combination therapy for type 2 DM. Metformin was the most commonly used monotherapy for type 2 DM 36.1% (
=197), followed by insulin 6.9% (
=38), sulfonylurea derivatives - 2.7% (
=15). Combination of metformin and dipeptidyl peptidase-4 inhibitors (13.9%) was the most commonly used combination therapy.
Analysis of the current situation in the diabetology service will help to identify weaknesses and strengths, which is necessary to optimise existing therapeutic approaches in accordance with current clinical recommendations.
