Tuberculosis Infection In Children Research Articles

Occurence and risk factors of tuberculosis infection in orphanage children in Bali

Background Tuberculosis (TB) is an infectious disease that is still a common threat worldwide, especially in pediatric populations. TB transmission occurs particularly when the transmitter has no obvious manifestation of the disease. There is a higher incidence of TB infection in children than in the general population, especially in high risk populations such as children in orphanages. However, the incidence of TB infection in orphaned children in Indonesia, including Bali, is unknown. Objective To describe the incidence and risk factors for TB infection in children in orphanages in Bali. Methods This case-control study was conducted in 12 orphanages in Bali. Subjects were divided into a case group comprised of children with TB infection, and a control group comprised of those without TB infection. TB infection was diagnosed by positive tuberculin test without clinically confirmed TB. Results A total of 175 children were recruited as subjects. There were 49 (28.0%) children with TB infection. Bivariate analysis revealed significant associations between density, humidity, ventilation/room area ratio, and area of ??origin with TB infection. Multivariate analysis showed that ventilation/room area ratio and room humidity of ?73% were independently positive correlated with TB infection. Natural lighting and BCG scar were not significantly different between groups. Conclusion The occurence of TB infection in children residing in orphanages in Bali is high (28%). The risk factors identified independently are lower ventilation and higher room humidity.

Assessment of specificity of immunologic tests for detection of tuberculosis infection in children with juvenile idiopathic arthritis

Introduction. The use of genetic engineering biological agents (GEBA) in the treatment of rheumatic diseases over the past decades has led to a significant improvement in the prognosis in this group of patients. However, against the background of anti-tumor necrosis factor α therapy (anti TNF-α), the risk of developing tuberculosis increases tenfold.Aim. To evaluate the specificity and safety of Mantoux test, recombinant tuberculosis allergen (RTA) test, IGRA tests: TB-Feron IGRA, T-SPOT.TB, QuantiFERON-TB GIT in patients from 5 to 18 years of age, who are at risk for the development of tuberculosis, due to the use of immunosuppressive therapy, including GEBP.Materials and methods. This clinical trial is a prospective single-center open-label study with 120 patients under observation. Girls predominated among the patients – 71 (59.2%), the average age was 12 years (95% CI [5.2–17.4]). As part of the treatment of the underlying disease, patients in the vast majority of cases (78.3%) received iFNO-α drugs: etanercept (67 people), adalimumab (25 people), golimumab (2 people).Results and discussion. According to the results of a comprehensive medical examination, including CT scan of the chest organs, the presence of active tuberculosis was not established in any of the patients. A positive result of the RTA sample was registered in 0.8% of the subjects, Mantoux test in 46.6%, T-SPOT.TB – 1.7%, TB-Feron IGRA and QuantiFERON-TB GIT – 0.8% each. During the safety assessment, it was noted that within 28 days after the study, none of the 120 patients had any adverse events. Patients need appropriate screening before starting treatment and regular follow-up examinations.Conclusions. The Mantoux test with 2 TE has low specificity (0.49), and the sample with RTA (0.99), TB-Feron IGRA (0.99), T-SPOT.TB (0.98) and QuantiFERON-TB GIT (0.99) are highly specific and safe as tests for detecting tuberculosis infection in children with juvenile idiopathic arthritis.

QuantiFERON Gold-In-Tube for the diagnosis of mycobacterial tuberculosis infection in children under 5 years of age: A systematic review and meta-analysis.

Previous meta-analysis regarding the performance of QuantiFERON Gold-In-Tube in children have yielded contrasting results. Emerging data in children younger than 5 years of age necessitates a new analysis. Systematic searches were conducted of MedLINE, EMBASE and Cochrane databases between 1998-2023. Pooled estimates of sensitivities and specificities of QFT-GIT compared to tuberculin skin test (TST) were calculated. The Kappa (k) coefficient was calculated for each study to determine the degree of congruence between TST and QFT-GIT results. Studies including patients co-infected with HIV or other immune compromising conditions or those treated with anti-tubercular treatment were excluded. Seventeen studies (4335 patients) were included in quantitative analysis. All studies were conducted in middle to high income countries. They were conducted across 14 countries and 4 studies in countries with high TB incidence. The pooled sensitivity, specificity and DOR were 0.45 (0.42-0.48), 0.96 (0.96-0.97) and 18.84 (7.33-48.41) respectively. The ability of QFT-GIT to discriminate with disease and no disease was "good" as demonstrated by a summary receiver operating characteristic curve with area under curve of 0.7812. The average Kappa (k) co-efficient was 0.501 with a wide variety of values between studies (0.167 to 0.800). The findings of this meta-analysis support the judicious use of QFT-GIT in children 5 years and under, with caution as a sole test to exclude Tuberculosis in this age group. The heterogeneity and methodological quality of diagnostic studies limits the generalisability of results.

Interferon-gamma release assay for screening of tuberculosis infection in children

BackgroundInterferon-gamma release assay (IGRA) is the main tool for the diagnosis of latent tuberculosis (TB) infection (LTBI). However, the indeterminate results were more frequent in children, and the underlying reasons were largely speculative. We aimed to compare QuantiFERON-TB Gold In-Tube (QFT-GIT) with X.DOT-TB (XDOT) for diagnosing LTBI, and to identify the risk factors associated with indeterminate results in children.MethodsA retrospective study for children<18 years old, at risk for LTBI or progression to TB disease, received either QFT-GIT or X.DOT-TB tests was performed at Beijing Children’s Hospital from August 2019 to August 2022.ResultsA total of 33,662 children were recruited, including 15,129 (44.9%) tested with X.DOT-TB and 18,533 (55.1%) with QFT-GIT. Proportion of positive and indeterminate results in children with respiratory disease was significantly higher than did that with other diseases, respectively (P < 0.001). The indeterminate rate of X.DOT-TB and QFT-GIT results decreased with increasing age (P < 0.001). Proportion of QFT-GIT indeterminate results was higher than that of X.DOT-TB across age groups. Male, age and disease classification all presented a statistically significant association with indeterminate IGRA results.ConclusionsThe positive rates of X.DOT-TB and QFT-GIT in children were 3.1% and 1.8%, respectively. The X.DOT-TB assay performed better than QFT-GIT in children, and male, age and underlying diseases were associated with an increased risk of indeterminate IGRA results.

Utility of interferon-gamma releasing assay for the diagnosis of active tuberculosis in children: A systematic review and meta-analysis

IntroductionThe accurate diagnosis of tuberculosis (TB) in children is essential for its effective management and control. Reliable diagnostic tools that are currently available for identifying TB infection include the in vivo tuberculosis skin test (TST) and ex vivo interferon-gamma release assays (IGRAs). This systematic review and meta-analysis aimed to evaluate the diagnostic accuracy of IGRAs in children. MethodsOf the 768 screened studies, 47 met the eligibility criteria. Data from 9065 patients, including 1086 (12.0 %) with confirmed TB, were included in the analysis. The overall quality of the included studies, assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, was unclear. ResultsThe calculated pooled sensitivity and specificity of IGRAs in children were 0.85 (95 % confidence interval [CI]: 0.79–0.89) and 0.94 (95 % CI: 0.88–0.97), respectively. Subpopulation analysis revealed that the sensitivities and specificities were as follows: QuantiFERON tests: 0.83 (95 % CI: 0.74–0.89) and 0.93 (95 % CI: 0.87–0.96), T-SPOT: 0.87 (95 % CI: 0.79–0.91) and 0.99 (95 % CI: 0.85–1.00), IGRAs in children under 15 years: 0.77 (95 % CI: 0.43–0.94) and 0.96 (95 % CI: 0.84–0.97), and IGRAs in children under 5 years: 0.85 (95 % CI: 0.52–0.97) and 0.94 (95 % CI: 0.90–0.99), respectively. ConclusionsThis study demonstrated that the sensitivity and specificity of the IGRAs in children were moderate and high, respectively. Therefore, the IGRAs may be useful for detecting TB infection in children. Clinical trial registrationThe review protocol was prospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000046737).

Mycobacterium tuberculosis infection among children under fifteen years of age: A population-based study in Indonesia

Objective: To assess the prevalence of Mycobacterium (M.) tuberculosis infection and its associated risks in children under fifteen years of age. Methods: Based on secondary data from the 2018 Indonesian Basic Health Survey (RISKESDAS 2018), this cross-sectional study employed M. tuberculosis infection in children as a dependent variable and age level, sex, region, location, family case positive, and smoking as independent variables. Geospatial analysis was applied to show the prevalence of M. tuberculosis infection and multivariate regression was performed to analyze the risk factors of getting the infection among children under 15 years of age. Results: Prevalence ranges of M. tuberculosis infection among children aged 0-14 years, babies (age &lt;12 months), toddlers (age 12-59 months), and children aged between 5 and 14 years were 0.03% to 0.57%, 0% to 0.64%, 0% to 0.78%, and 0.01% to 0.53%, respectively in Indonesia. A high prevalence of M. tuberculosis infection among children under 15 years of age was found in Papua and other provinces, such as Kalimantan and Java. Contacting with tuberculosis family members was positively associated with M. tuberculosis infection in children as shown by multivariate logistic regression (OR 8.94; 95% CI 5.4-14.6, P&lt;0.05). Conclusions: Contacting with family member who has tuberculosis is related with M. tuberculosis infection among children in Indonesia. Therefore, screening the household for contact with tuberculosis patients is a preventive treatment for children.

Area-Based Sociodemographic Factors Associated with Latent Tuberculosis Infection in a Low-Prevalence Setting.

Area-based sociodemographic markers, such as census tract foreign-born population, have been used to identify individuals and communities with a high risk for tuberculosis (TB) infection in the United States. However, these markers have not been evaluated as independent risk factors for TB infection in children. We evaluated associations between census tract poverty, crowding, foreign-born population, and the CDC's Social Vulnerability Index (CDC-SVI) ranking and TB infection in a population of children tested for TB infection in Boston, Massachusetts. After adjustment for age, crowding, and foreign-born percentage, increasing census tract poverty was associated with increased odds of TB infection (adjusted odds ratio [aOR] per 10% increase in population proportion living in poverty: 1.20 [95% CI, 1.04-1.40]; P = 0.01), although this association was attenuated after further adjustment for preferred language. In separate models, increasing CDC-SVI ranking was associated with increased odds of TB infection, including after adjustment for age and language preference (aOR per 10-point increase in CDC-SVI rank: 1.08 [95% CI, 1.02-1.15]; P = 0.01). Our findings suggest area-based sociodemographic factors may be valuable for characterizing TB infection risk and defining the social ecology of pediatric TB infection in low-burden settings.

Clinical case of diagnosis of generalized tuberculosis in a child with a positive result of an intradermal test

At present day, generalized forms are rarely found in the structure of tuberculosis in children. A significant risk factor for the development of generalized lesions is prolonged contact with a tuberculosis patient. The diagnosis of a specific etiology is often complicated by the absence of pathognomonic symptoms. Immunodiagnostics, microbiological and molecular genetic research play an important role in the diagnosis of tuberculosis infection in children. The purpose of this study was to analyze the case of the development and diagnosis of generalized tuberculosis in a child of primary school age (7 years and 11 months) with lesions of the lungs, larynx, middle ear. The examination methods included immunological intradermal tests (Mantoux test, RTA test), in vitro test (QuantiFERON-TB), multispiral computed tomography, bronchoscopy and laboratory methods of examination. The manifestation of the disease occurred gradually with the occurrence of hypochromic anemia with a further increase in symptoms of intoxication. A comprehensive examination established a disseminated process in the lungs, larynx and middle ear lesions. Family tuberculosis contact was established when the disease was detected in a child. During the examination, the evaluation result of the Mantoux test showed an increase in sensitivity to tuberculin. The hyperergic result of the RTA test indicated the activity of MBT in the body. At the same time, the irregular conduct of immunodiagnostics using the Mantoux test, the monotony of the test did not allow timely measures to be taken in relation to the in-depth examination of the child for tuberculosis. The specific etiology of the disease was reliably confirmed by cultural and molecular genetic research methods. The child was diagnosed with generalized tuberculosis, disseminated pulmonary tuberculosis in the infiltration phase, MBT (+) with drug resistance to isoniazid, streptomycin, paraaminosalicylic acid, tuberculosis of the larynx and vocal apparatus, PCR (+) with drug resistance to isoniazid, tuberculous right-sided otitis media, MBT (+) with drug resistance to isoniazid, streptomycin, paraaminosalicylic acid. The presented clinical case indicates the need for timely detection of tuberculosis contacts, regular immunodiagnostics, and compliance with phthisiological alertness of doctors of all specialties in relation to children with long-lasting symptoms of various diseases. The complete physical examination using an intradermal RTA test (Diaskintest), microbiological and molecular genetic research methods allows to establish the tuberculous etiology of the lesion.

Identification of cuproptosis-related molecular subtypes as a biomarker for differentiating active from latent tuberculosis in children

BackgroundCell death plays a crucial role in the progression of active tuberculosis (ATB) from latent infection (LTBI). Cuproptosis, a novel programmed cell death, has been reported to be associated with the pathology of various diseases. We aimed to identify cuproptosis-related molecular subtypes as biomarkers for distinguishing ATB from LTBI in pediatric patients.MethodThe expression profiles of cuproptosis regulators and immune characteristics in pediatric patients with ATB and LTBI were analyzed based on GSE39939 downloaded from the Gene Expression Omnibus. From the 52 ATB samples, we investigated the molecular subtypes based on differentially expressed cuproptosis-related genes (DE-CRGs) via consensus clustering and related immune cell infiltration. Subtype-specific differentially expressed genes (DEGs) were found using the weighted gene co-expression network analysis. The optimum machine model was then determined by comparing the performance of the eXtreme Gradient Boost (XGB), the random forest model (RF), the general linear model (GLM), and the support vector machine model (SVM). Nomogram and test datasets (GSE39940) were used to verify the prediction accuracy.ResultsNine DE-CRGs (NFE2L2, NLRP3, FDX1, LIPT1, PDHB, MTF1, GLS, DBT, and DLST) associated with active immune responses were ascertained between ATB and LTBI patients. Two cuproptosis-related molecular subtypes were defined in ATB pediatrics. Single sample gene set enrichment analysis suggested that compared with Subtype 2, Subtype 1 was characterized by decreased lymphocytes and increased inflammatory activation. Gene set variation analysis showed that cluster-specific DEGs in Subtype 1 were closely associated with immune and inflammation responses and energy and amino acids metabolism. The SVM model exhibited the best discriminative performance with a higher area under the curve (AUC = 0.983) and relatively lower root mean square and residual error. A final 5-gene-based (MAN1C1, DKFZP434N035, SIRT4, BPGM, and APBA2) SVM model was created, demonstrating satisfactory performance in the test datasets (AUC = 0.905). The decision curve analysis and nomogram calibration curve also revealed the accuracy of differentiating ATB from LTBI in children.ConclusionOur study suggested that cuproptosis might be associated with the immunopathology of Mycobacterium tuberculosis infection in children. Additionally, we built a satisfactory prediction model to assess the cuproptosis subtype risk in ATB, which can be used as a reliable biomarker for the distinguishment between pediatric ATB and LTBI.

Features of detection of latent tuberculosis infection and tuberculosis in children from household contacts within a household (clinical case)

Aim: to demonstrate the features of detection and diagnosis of latent tuberculosis infection and pulmonary tuberculosis in children from household contacts based on own clinical observation.&#x0D; Materials and methods. A clinical case of own observation of pulmonary tuberculosis and latent tuberculosis infection in children from household contacts who were treated in the paediatric department of the clinical base of the Phthysiatry and Pulmonology Department of Zaporizhzhia State Medical and Pharmaceutical University on Public Non-Profit Enterprise of the “Zaporizhzhia Regional Clinical and Diagnostic Center of Phthysiatry and Pulmonology” of Zaporizhzhia Regional Council.&#x0D; Results. Children from household contacts were examined at ages: 8 months, 2, 3, 5 and 7 years, after their mother was diagnosed with tuberculosis (TB). All children showed an increase in tuberculin skin test, at the X-ray of the thoracic cavity organs (TCO) no changes were detected in any child. Taking into account the age of the children and their constant residence with the index patient, a decision was made to conduct an additional examination using CT scan of the TCO. Thus, three children were diagnosed with pulmonary tuberculosis – primary tuberculosis complex, and two were infected. After receiving the results of the culture test in the gastric lavage, the youngest child was found MBT, which was resistant to first-line drugs, namely isoniazid and rifampicin, which required a treatment regimen adjustment. It should be noted that the youngest girl, who was not vaccinated, had the most widespread process in the lungs compared to other children.&#x0D; Conclusions. Monitoring and screening of children who have been in contact with the index patient within the household maximises the detection of additional cases of latent tuberculosis infection and pulmonary TB. The most at-risk groups are those who not vaccinated with BCG vaccine and children under 5 years of age. Early detection and timely prescription of anti-TB therapy is the key not only to effective treatment, but also to preventing the transmission of TB infection.

Changes of abdominal organs in children with tuberculosis infection detected by ultrasound diagnostics

BACKGROUND: Ultrasound diagnostics of abdominal organs is an early method of detecting functional and structural changes in tuberculosis infection before the manifestation of clinical manifestations. Currently, there are no uniform criteria for interpreting the sonographic pathology of parenchymal organs in tuberculosis infection in children, which requires its analysis.&#x0D; AIM: The aim is to determine the frequency and nature of sonographic changes in abdominal organs in children with tuberculosis infection, as well as their dynamics against the background of chemotherapy.&#x0D; MATERIALS AND METHODS: 192 patients aged 6 months 14 years of tuberculosis department of City Childrens Infectious Hospital No. 3 for the period 20192021 were examined. 3 groups of patients were identified: group 1 92 children with active tuberculosis of the respiratory organs; group 2 52 children with residual post-tuberculosis changes; group 3 48 children with latent tuberculosis infection from tuberculosis risk groups. Comprehensive examination of patients included evaluation of the results of immunodiagnostics (Mantoux test with 2TE and test with recombinant tuberculosis allergen), multispiral computed tomography of the chest, laboratory tests. Ultrasound examination of the abdominal organs was prescribed to children in the diagnosis of tuberculosis infection and on the background of anti-tuberculosis therapy after 3 and 6 months.&#x0D; RESULTS: Sonographic changes of the liver (reactive and/or intrahepatic cholestasis and/or hepatomegaly) were observed in children with active tuberculosis in 40.2 5.1% of cases, in children of group 3 in 35.4 6.9% of cases and less often in children of group 2 in 17.3 5.3% of cases (p 0.05). Changes of the gallbladder (violations of bile outflow and/or shape changes) in children with active tuberculosis were visualized in 73.9 4.6% of cases, in children of group 3 (60.4 7.1%), less often in children of group 2 (55.8 6.7%, p 0.05 for group 1). Changes of the pancreas were reactive and were more often observed in children of group 1 (in 14.1 3.5%) than in children of group 2 (5.8 3.2%, p 0.05) and group 3 (4.2 2.9%). Changes of the spleen were more often detected in children with active tuberculosis (in 17.4 4.0%) than in children of group 2 (5.8 3.2%, p 0.05) and group 3 (2.1 2.1%, p 0.05). During chemotherapy, there was an increase in the number of sonographic changes of the liver and gallbladder by 23 months, which was due to the undesirable effects of anti-tuberculosis drugs.&#x0D; CONCLUSIONS: Ultrasound diagnostics of the abdominal organs allows the most timely diagnosis of changes in the abdominal organs in children with tuberculosis infection, which allows individualizing pathogenetic therapy, if necessary, tuberculosis chemotherapy regimen.

Modern immunological tests for early detection of tuberculosis infection in children in the Yaroslavl Oblast

Objective. To evaluate the efficacy of immunological tests for early detection of tuberculosis infection in children in the Yaroslavl Oblast (Russia).Material and methods. Medical records of 354 children and adolescents examined by ELISPOT (Enzyme-Linked ImmunoSpot) assay (T-SPOT.TB) in the Yaroslavl Oblast in 2020–2022 were studied. Four groups of children were distinguished: group 1 included children with active tuberculosis (n = 3); group 2 included children under 7 with altered tuberculin sensitivity (conversion of the tuberculin test) or children over 8 first-time tested positive for RTA, who were under the supervision of a phthisiatrician in the VI A group of dispensary registration (n = 52); group 3 included children with medical exemptions from screening immunodiagnostics (n = 49); and group 4 included children with refusals of their parents or legal representatives from skin tests (n = 250).Results. The sensitivity of both RTA and T-SPOT.TB tests achieved 100%, with the concordance level of 100%. When assessing discordant results (positive result for RTA and negative for T-SPOT.TB) in the VI A dispensary registration group, the majority of children were found to have an aggravated allergic anamnesis and somatic pathology. The maximum number of children examined by the laboratory method included those whose parents or legal representatives refused from skin test administration (70.6%).Conclusions. T-SPOT.TB is an optimal method for early detection of latent TB infection and TB in children at risk, including those with medical contraindications for skin tests or whose parents refused from screening immunodiagnostics.

A screening study of latent tuberculosis infection in children in a metropolis city

Objective. To carry out a screening study among children and adolescents for tuberculosis infection in the city of Moscow using modern immunodiagnostic methods.Materials and methods. The results of a mass screening study for tuberculosis prevalence in the pediatric population of a metropolis city were analyzed. The study was conducted during 2019–2021 in Moscow using the Mantoux skin test with 2 TE PPD-L and a skin test with a recombinant tuberculosis allergen (RTA), as well as the indicators of tuberculosis incidence in children.Results. The introduction of mass screening for tuberculosis based on RTA among the pediatric population and subsequent work with the identified risk groups contributed to a decrease in the number of newly-diagnosed cases. In 2019–2021, the incidence of tuberculosis among children in Moscow did not exceed 3.8 per 100 thousand children aged 0–17 years, with this number varying from 1.2 to 2.1 among permanent residents. The risk indicators of primary infection among children aged 1–7 according to the Mantoux test (0.37% in 2019, 0.47%, in 2020, and 0.35% in 2021) and the prevalence of latent tuberculosis according to the results of screening based on RTA among children aged 8–17 in 2019–2021 (no more than 0.3%) indicate a stable epidemiological situation as regards tuberculosis infection in the city.Conclusions. The development of an effective monitoring system for preventive tuberculosis screening among urban pediatric populations contributed to the detection of latent tuberculosis cases prior to the development of its local forms. The subsequent implementation of preventive measures in risk groups allowed the incidence of tuberculosis among children to be reduced.

ЗНАЧЕНИЕ ТЕРРИТОРИАЛЬНЫХ И СОЦИАЛЬНЫХ ОБЪЕКТОВ ПРИ ФОРМИРОВАНИИ РЕЗЕРВУАРОВ ТУБЕРКУЛЁЗНОЙ ИНФЕКЦИИ В МЕГАПОЛИСЕ

Significance. One of the key areas of TB prevention is work with household contacts, including epidemic monitoring and territorial assessment. However, approaches to dividing and defining the borders of the studied territories, assessing the impact of territorial objects on the risk of developing tuberculosis are undeveloped. It is important for analyzing dynamic changes in the epidemiology of tuberculosis within a particular territory and drawing up a plan of preventive measures. The purpose of the study was to analyze the relationship and impact of territorial objects within the borders of microterritories of a metropolis on TB spread in population of these territories. Material and methods: In 2021-2022, a longitudinal (retrospective-prospective) continuous spatial-epidemiological study of the epidemic situation of tuberculosis and latent tuberculosis infection was conducted. Results: The most significant parameters in the spread of tuberculosis infection are building density (p&lt;0.0001) and population density, territorial objects as shops, educational facilities, medical organizations, recreation areas. MDR-TB in patients does not have a significant effect on the spread. However, the incidence of tuberculosis and territorial facilities in the catchment area of a phthisiological unit affect the spread of latent tuberculosis infection in children. Conclusion: The hypothesis about the relationship and influence of territorial objects on the spread of tuberculosis infection among the population of microterritories was confirmed. Epidemiological assessment and monitoring of the supervised territories should be carried out using boundaries established according to the principles of the geographical field. Scope of application. The results obtained should be taken into account when assessing the epidemiological situation and determining the workload of the phthisiological service in megacities, which is directly related to financial planning and individualization of approaches to evaluate performance of the district service, optimize interdepartmental and intradepartmental interaction and develop principles of interaction with the general medical network and population of microterritories.

The Role of Interferon-Gamma Release Assays in Diagnosis of Latent Tuberculosis Infection in Children

The Role of Interferon-Gamma Release Assays in Diagnosis of Latent Tuberculosis Infection in Children

TREC И KREC – ПЕРСПЕКТИВНЫЕ МАРКЕРЫ АКТИВНОСТИ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ

Scientists around the Globe are making deliberate attempts to develop the new methods for predicting and diagnosing tuberculosis, but these measures are not enough to end its epidemic. The purpose of the study was to evaluate the excisional rings of the T-cell receptor (TREC) and K-deletion element of B-cells (KREC) in infants and preschool children at high risk of tuberculosis as a promising prognostic marker for tuberculosis infection activity. A cross-sectional study was conducted in Jan. - Sept. 2022. The observation group consisted of 87 children aged 1 to 7 [6 (5‒7)] y/o, of which 13 (14.9%) aged 1 to 3 y/o and 74 aged 4 to 7 y/o; 53 (60.9%) boys/34 (39.1%) girls. The three groups were formed: G1 (n=27) with an established diagnosis of tuberculosis (TB), G2 (n=34) with TB infection diagnosis made based on the results of tuberculin diagnosis and without signs of a local specific process, and [control] G3 (n=26) without signs of TB infection according to the results of specific skin tests and without signs of TB, i.e., conditionally healthy. All children, in addition to methods to confirm or exclude TB and methods of specific immunodiagnostics, have undergone a molecular genetic study: DNA extraction from a dry blood spot and quantitative determination of TREC and KREC by real-time PCR in values of TREC and KREC copies per 105 cells. In order to build the reference values of TREC and KREC quantitative indicators in dry blood spots, the results obtained in G3 were analyzed as well. Results: the reference values of TREC and KREC were established for children of early and preschool ages when extracting DNA from a dry blood spot. When assessing tuberculosis infection in children of early and preschool ages, statistically significant criteria were determined, such as: anti-tuberculosis therapy (F=42.001; p&lt;0.001), positive or negative reaction to the recombinant tuberculosis allergen during an intradermal test (F=39.394; p&lt;0.001), high blood TREC level (F=12.707; p&lt;0.001), tuberculin reaction (F=10.625; p&lt;0.001), and KREC level (F=3.182; p=0.039). Conclusion: high level of TREC can be considered as a marker for the activity or a personalized predictor for the risk of progression of TB infection in children of early and preschool ages with high risk of TB.

Screening for tuberculosis infection in children and adolescents by two intracutaneous tests: with tuberculin and tuberculosis recombinant allergen (ESAT-6/CFP-10) in Moscow in 2021

The objective: to evaluate effectiveness of mass screening for tuberculosis infection in children and adolescents in Moscow using two different options according to age; to determine impact of the COVID-19 pandemic on effectiveness of screening campaign judging by incidence rates in children and adolescents.Subjects and Methods. In 2021, 758,634 children aged 0-7 years, or 99.2% of those to be screened, were screened using the Mantoux test. Should the reaction increase compared to the previous year, an additional test with the tuberculosis recombinant allergen (TRA) was performed. Children of 8-17 years old were screened only with TRA test. 1,070,961 people were examined, or 97.9% of those to be examined.Results. It has been demonstrated that the test with TRA can be used as a screening tool and effectively identify patients with a high risk of tuberculosis development. The preventive therapy received by those positively responding to TRA test resulted in almost no disease in them. The predominance of new cases with post-tuberculosis changes over new cases of active tuberculosis while the number of both is decreasing indicates the ability of the methods (TRA together with computed tomography) to detect minor forms of the active disease and post-tuberculous changes. In 2021 versus 2020, the number of children diagnosed with tuberculosis did not statistically significantly increase because of those who failed to be detected in 2020 due to incomplete coverage with screening related to spread of COVID-19. However, in 2021 the rates were lower than in 2019 which confirmed their positive change.Conclusion: Screening with TRA test is effective, easy to perform and can be used in primary health care.

Tuberculosis Infection in Children and Adolescents.

The burden of tuberculosis (TB) in children and adolescents remains very significant. Several million children and adolescents are infected with TB each year worldwide following exposure to an infectious TB case and the risk of progression from TB infection to tuberculosis disease is higher in this group compared to adults. This review describes the risk factors for TB infection in children and adolescents. Following TB exposure, the risk of TB infection is determined by a combination of index case characteristics, contact features, and environmental determinants. We also present the recently recommended approaches to diagnose and treat TB infection as well as novel tests for infection. The tests for TB infection have limitations and diagnosis still relies on an indirect immunological assessment of cellular immune response to Mycobacterium tuberculosis antigens using immunodiagnostic testing. It is recommended that TB exposed children and adolescents and those living with HIV receive TB preventive treatment (TPT) to reduce the risk of progression to TB disease. Several TPT regimens of similar effectiveness and safety are now available and recommended by the World Health Organisation.

Interferon Gamma Release Assay Results and Testing Trends Among Patients Younger Than 2 Years Old at Two US Health Centers.

Interferon-gamma release assays (IGRAs) are approved for children ≥2 years old to aid in diagnosis of Mycobacterium tuberculosis (TB) infection and disease. Tuberculin skin tests (TSTs) continue to be the recommended method for diagnosis of TB infection in children <2 years, in part due to limited data and concern for high rates of uninterpretable results. We performed a retrospective cohort study of IGRA use in patients <2 years old in 2 large Boston healthcare systems. The primary outcome was the proportion of valid versus invalid/indeterminate IGRA results. Secondary outcomes included concordance of IGRAs with paired TSTs and trends in IGRA usage over time. A total of 321 IGRA results were analyzed; 308 tests (96%) were valid and 13 (4%) were invalid/indeterminate. Thirty-seven IGRAs were obtained in immunocompromised patients; the proportion of invalid/indeterminate results was significantly higher among immunocompromised (27%) compared with immunocompetent (1%) patients ( P < 0.001). Paired IGRAs and TSTs had a concordance rate of 64%, with most discordant results in bacille Calmette-Guérin-vaccinated patients. The proportion of total TB tests that were IGRAs increased over the study period (Pearson correlation coefficient 0.85, P < 0.001). The high proportion of valid IGRA test results in patients <2 years of age in a low TB prevalence setting in combination with the known logistical and interpretation challenges associated with TSTs support the adoption of IGRAs for this age group in certain clinical scenarios. Interpretation of IGRAs, particularly in immunocompromised patients, should involve consideration of the broader clinical context.

Aberrant expression of long non-coding RNAs in peripheral blood mononuclear cells response to tuberculosis in children.

We aimed to identify long non-coding RNAs (lncRNAs) aberrantly expressed in peripheral blood mononuclear cells (PBMCs) triggered by active tuberculosis (ATB), latent tuberculosis infection (LTBI), and healthy controls (HC). We examined lncRNAs expression in PBMCs isolated from children with ATB and LTBI, and from HC using RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the biological processes and signaling pathways of aberrantly expressed mRNAs. A total of 348 and 205 lncRNAs were differentially expressed in the ATB and LTBI groups, respectively, compared to the HC group. Compared to the LTBI group, 125 lncRNAs were differentially expressed in the ATB group. Compared to the HC group, 2317 mRNAs were differentially expressed in the ATB group, and 1093 mRNAs were differentially expressed in the LTBI group. Compared to the LTBI group, 2328 mRNAs were differentially expressed in the ATB group. The upregulated mRNAs were mainly enriched in neutrophil activation, neutrophil-mediated biological processes, and positive regulation of immune response in tuberculosis (TB), whereas the downregulated mRNAs were enriched in signaling pathways and structural processes, such as the Wnt signaling pathway and rDNA heterochromatin assembly. This is the first study on the differential expression of lncRNAs in PBMCs of children with TB. We identified significant differences in the expression profiles of lncRNAs and mRNAs in the PBMCs of children with ATB, LTBI, and HC, which has important implications for exploring lncRNAs as novel biomarkers for the diagnosis of TB. In addition, further experimental identification and validation of lncRNA roles could help elucidate the underlying mechanisms of Mycobacterium tuberculosis infection in children.