Method for diagnosing immunocompromise in workers exposed to mixed aerosols containing crystalline silicon dioxide from 10 to 70% and metals in solid phase

Abstract

FIELD: occupational medicine.SUBSTANCE: used to diagnose immunocompromise in workers exposed to mixed aerosols containing crystalline silicon dioxide from 10 to 70% and metals in the solid phase. Samples of venous blood and smears from the mucous membrane of the pharynx are taken. In the presence of Streptococcus pneumoniae DNA in scrapings from the mucous membrane of the pharynx and with the level of immunoglobulin M in the blood serum≤ 1.7 g / l is used to diagnose immunocompromise in workers exposed to mixed aerosols containing crystalline silicon dioxide from 10 to 70% and metals in the solid phase.EFFECT: method provides the possibility of selecting immunocompromised workers exposed to industrial mixed aerosols for priority vaccination against pneumococcal infection at the stage of periodic medical examination, by determining the level of immunoglobulin M in the blood serum and Streptococcus pneumoniae DNA in swabs from the mucous membrane of the pharynx.1 cl, 1 tbl, 1 ex

Description

[0001] The invention relates to occupational medicine, in particular to the prevention of respiratory diseases, and can be used as an indication for priority vaccination against pneumococcal infection of immunocompromised workers exposed to mixed aerosols, the solid phase of which includes crystalline silicon dioxide in a content of 10 to 70% and metals.

[0002] It is proposed to use the detection of Streptococcus pneumoniae DNA in a scraping from the mucous membrane of the pharynx and one of the parameters of cellular or humoral immunity as criterion indicators, since the effect of mixed aerosols on the immune system and the properties of Streptococcus pneumoniae increase the risk of developing diseases of the bronchopulmonary system of pneumococcal etiology.

[0003] Colonization of the mucous membranes of the upper respiratory tract by Streptococcus pneumoniae is usually asymptomatic, being the initial stage of the development of pneumococcal pneumonia (Carriage of Streptococcus pneumoniae in adults hospitalized with community-acquired pneumonia / Louise Lansbury, Tricia M. McKeever, Hannah Lawrence, [et al.] / / Journal of Infection.-2024.- 89 (5). 106277). Immunodeficiency is a risk factor for community-acquired pneumonia in adult patients carrying Streptococcus pneumoniae (High nasopharyngeal pneumococcal density, increased by viral coinfection, is associated with invasive pneumococcal pneumonia / N. Wolter, S. Tempia, C. Cohen, SA, [et al.] / / J Infect Dis.-2014.- 210 (10). P. 1649-1657). Exposure to industrial aerosols containing inorganic dust and metals increases the risk of developing pneumococcal infection due to the effect on the mucous membrane of the respiratory tract, the properties of the pathogen and the immune status of the worker (Beentjes D. et al.Mechanistic insights into the impact of air pollution on pneumococcal pathogenesis and transmission / / American Journal of Respiratory and Critical Care Medicine. - 2022. - Vol. 206. - No. 9. - Pp. 1070-1080; Torén K. et al. Occupational exposure to dust and fumes, work as a welder and invasive pneumococcal disease risk / / Occupational and environmental medicine. - 2020. - Vol. 77. - No. 2. - Pp. 57-63). Specific vaccination is effective protection against pneumococcal pneumonia (Kobayashi M. Pneumococcal vaccine for adults aged ≥ 19 years: recommendations of the Advisory Committee on Immunization Practices, United States, 2023 / / MMWR. Recommendations and Reports. - 2023. - Vol. 72).Detection of Streptococcus pneumoniae DNA and altered immune system parameters in workers exposed to mixed aerosols to form a priority group for Streptococcus pneumoniae vaccination is a promising direction for improving the effectiveness of specific respiratory disease prevention.

[0004] A method is known for diagnosing cellular immunity disorders in workers in chemical industries exposed to formaldehyde, based on the calculation of an integral criterion equal to the ratio of the established percentage of CD3 + CD95 + - lymphocytes to CD4 percentage + CD25 + CD127 - - lymphocytes. If this integral indicator is equal to or greater than 40, a cellular immune disorder is diagnosed in chemical industry workers exposed to formaldehyde (Russian Federation Patent RU 2 539 391 C1).

[0005] The disadvantage of this method is that the proposed criterion characterizes an immune response that develops according to the autoimmune type and is not associated with the development of an anti-infectious immune response.

[0006] For the prototype of the proposed method for diagnosing immunocompromise in workers exposed to industrial mixed aerosols containing metals and crystalline silicon dioxide in the solid phase at a content of 10 to 70%, a method for the prevention and correction of immune disorders caused by toxic substances was selected, including the introduction of an immunostimulant at certain immune indicators, cycloferon is administered as an immunostimulant, before the introduction, the individual reaction to cycloferon is determined by incubating mononuclear cells isolated from the patient's peripheral blood with cycloferon in vitro (patent of the Russian Federation RU 2 364 396 C2).

[0007] The disadvantages of this method include the use of an immunomodulator, which has a nonspecific immunomodulatory effect and is not involved in the formation of specific antibodies against Streptococcus pneumoniae. The labor-intensive nature of the method limits its use in mass screening during periodic medical examinations.

[0008] The objective of the proposed invention is to select immunocompromised workers exposed to industrial mixed aerosols for priority vaccination against pneumococcal infection at the stage of periodic medical examination.

[0009] The technical result, which the claimed invention is aimed at achieving, is to ensure the possibility of selecting immunocompromised workers exposed to industrial mixed aerosols for priority vaccination against pneumococcal infection at the stage of periodic medical examination.

[0010] The claimed technical result is achieved in that the method for diagnosing immunocompromise in workers exposed to mixed aerosols containing crystalline silicon dioxide in the solid phase from 10 to 70% and metals includes collecting a sample of venous blood, smears from the mucous membrane of the pharynx, measuring the level of immunoglobulin M in the blood serum, determining the DNA of Streptococcus pneumoniae in smears, where, if there is DNA of Streptococcus pneumoniae in scrapings from the mucous membrane of the pharynx and if the level of immunoglobulin M in the blood serum is ≤1.7 g / l, immunocompromise is diagnosed in workers exposed to mixed aerosols containing crystalline silicon dioxide in the solid phase from 10 to 70% and metals.

[0011] The proposed method is implemented as follows.

[0012] 1. A sample is collected by taking a scraping (smear) from the mucous membrane of the tonsils, uvula, palatine arches, and posterior pharyngeal wall using a sterile disposable swab on an empty stomach or 2 hours after eating or drinking water. The sample is immersed in transport medium and stored at -56°C for no more than 14 days prior to Streptococcus pneumoniae DNA extraction, which is performed using polymerase chain reaction with real-time fluorescence hybridization detection of PCR products. The efficiency of DNA extraction from the samples was determined by the simultaneous preliminary addition of an internal control sample. Results were recorded in strict accordance with the kit instructions.

[0013] 2. Venous blood is collected in the morning on an empty stomach into sterile vacuum tubes with a blood coagulation activator (to determine immunoglobulin M).

[0014] 3. Immunoglobulin M is determined by enzyme immunoassay using ready-made test systems.

[0015] The methods used are generally accepted, the ready-made test systems have control samples and calibration solutions, which allows you to obtain correct and accurate results.

[0016] To validate the selected immunocompromise criteria, 48 workers exposed to mixed aerosols were examined. Diagnostic sensitivity, diagnostic specificity, and diagnostic efficacy were calculated for the group. Immune compromise criteria were calculated based on the type of aerosol exposed using ROC analysis (a binary classification model).

[0017] Characteristics of ROC curves obtained for cellular and humoral immunity parameters in workers exposed to mixed aerosols

[0018] Indicator Area under the curve (AUC) Root mean square error CI, 95% Level of significance immunoglobulin A, g / l 0,55 0,061 0,441 – 0,654 0,42 immunoglobulin M, g / l 0,69 0,056 0,582 – 0,782 0,0007 immunoglobulin G, g / l 0,56 0,061 0,455 – 0,688 0,31

[0019] Immunoglobulin M in serum is a sensitive immunological marker in Streptococcus pneumoniae carriers exposed to mixed aerosols (0.69, 95% CI 0.582–0.782). A level ≤ 1.7 g / L corresponds to a diagnostic efficiency of 65.1% (95% CI 74.8–95.3) with a sensitivity of 85.7% (95% CI 74.8–95.3) and a specificity of 42.86 (95% CI 27.7–59.0).

[0020] The combination of carriage of Streptococcus pneumoniae and the level of immunoglobulin M ≤ 1.7 g / L in the blood serum is a sign of immunocompromise when exposed to mixed aerosols.

[0021] Example. Male A., 47, an anode smelter at a copper smelting plant. The content of crystalline silicon dioxide in the industrial aerosol fluctuated between 2 and 10% or higher (up to 70%), with average shift aerosol concentrations periodically exceeding the corresponding MACs by up to 1.8 times. The aerosol also contained compounds of copper, lead, zinc, nickel, cadmium, and arsenic. Concentrations of these substances were below or at the level of the corresponding MACs, with the exception of lead and arsenic, the latter of which exceeded their MACs by up to 2 times.

[0022] Cellular and humoral immunity indicators: leukocytes - 6.9x109 / l; CD3 - 1385 cells per μl; CD4 - 889; CD8 - 347 cells per μl; CD19 - 219 cells per μl; secretory immunoglobulin A - 457.1 μg / ml; immunoglobulin A - 3.4 g / l; immunoglobulin M - 0.75 g / l; immunoglobulin G - 10.4 g / l.

[0023] Thus, the claimed invention makes it possible to identify individuals who require priority vaccination against pneumococcal pneumonia at the stage of periodic medical examination.