Tuberculous Infection In Children Research Articles

Impact of Active Case Finding on Clinical Structure and Severity of Tuberculosis in School-Aged Children (7-15 Years Old)

The objective: to evaluate the impact of active case finding in children 7-15 years old on the clinical structure of tuberculosis and epidemic risk of detected patients.Subjects and Methods: 1,679 children aged 7-15 ill with tuberculosis.Result. The following has been observed in active case finding of tuberculosis versus tuberculosis detection when the patient is seeking medical care: A 9-fold reduction in the risk of disseminated and generalized tuberculosis; a 4.5-fold reduction in the risk of epidemically dangerous cases of tuberculosis; a 6-fold reduction in the risk of destructive forms of pulmonary tuberculosis. Cases of extrapulmonary tuberculosis were more frequently detected when patients were seeking medical care.Thus, the strategy adopted in Russia for active tuberculosis detection in children leads to significant results: preventing the spread of tuberculous infection in children's communities and reducing the proportion of severe forms of tuberculosis that create the risk of disability and death from tuberculosis.

Utility of Tuberculin Testing in Children Under 5 Years of Age

The usefulness of the tuberculin sensitivity in children as an index of tuberculosis was evaluated in terms of the conversion index. Out of 62 children, 27 had abnormal X-rays. Family surveys lead to picking up of nine children who had radiological evidence of the disease. Lymph node biopsy in one of the subjects showed tuberculous lymphadenitis. How relevant this index of tuberculin conversion is as an indicator of tuberculous disease in childhood is clear from the present study. It is an important procedure for screening and can considerably reduce the work load and increase case yield. It also gives us a good idea about the prevalence and epidemiology of tuberculous infection in children.

ПРОЯВЛЕНИЯ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ У ДЕТЕЙ ПРИ ПОЛОЖИТЕЛЬНОЙ ПРОБЕ С АЛЛЕРГЕНОМ ТУБЕРКУЛЕЗНЫМ РЕКОМБИНАНТНЫМ

The objective : to study manifestations of tuberculous infection in children with a positive result of the test with TRA and determine the tactics for their follow-up. Subjects and methods . In 217 children with a positive result of the test with tuberculosis recombinant allergen (TRA) followed up in a TB dispensary, the results of clinical and radiological (multispiral computed tomography MSCT) examinations were studied and the response to the test with TRA during monitoring (within 3 years) was evaluated to justify terms of dispensary follow-up. Results . It was found that the test with TRA and MSCT allows diagnosing both latent tuberculous infection and detecting minimal post-tuberculous changes (calcifications). Monitoring was performed in 2 groups: Group 1 (n = 112) included patients with newly detected calcifications in the lungs and chest lymph nodes, Group 2 (n = 105) consisted of patients without detected changes in the lungs and chest lymph nodes. The frequency of hyperergic reactions to the test with TRA recorded in patients of both groups was the same (46.7 ± 4.4 and 48.2 ± 4.7%). Results of the test with TRA in children without radiological changes stabilized two years, and in case of calcifications - in three years of follow-up, which allowed predicting the terms of follow-up for such children as belonging to tuberculosis risk group.

АНАЛИЗ ПРИМЕНЕНИЯ КОЖНОЙ ПРОБЫ С ПРЕПАРАТОМ АЛЛЕРГЕНОМ ТУБЕРКУЛЕЗНЫМ РЕКОМБИНАНТНЫМ КАК СКРИНИНГОВОГО МЕТОДА ОБСЛЕДОВАНИЯ НА ТУБЕРКУЛЕЗНУЮ ИНФЕКЦИЮ У ДЕТЕЙ СТАРШЕ 7 ЛЕТ В ПЕНЗЕНСКОЙ ОБЛАСТИ В 2014-2016 гг.

The article presents the analysis of efficiency of skin test with tuberculous recombinant allergen (TRA, diaskintest), as a screening method for tuberculous infection in children and adolescents above 8 years old using Penza Region as an example. In 2016, 112,808 persons were screened with TRA test, 97.5% of children were covered with this test. TRA test proved to be effective for detection of tuberculosis in children and adolescents. When TRA test is used, less than 1% respond positively to it among those screened on a regular basis (in 2015 – 0.97% and in 2016 – 0.86%). The differential approach to the prescription of preventive treatment in risk groups significantly increases the motivation of 92.0% of parents to have it. With a positive result of TRA test, the screening for tuberculosis with this test and multispiral computer tomography of the chest significantly improve the structure of clinical forms of tuberculosis in children and adolescents due to an increase of the number of limited lesions with minimal manifestations.

РЕЗУЛЬТАТЫ ПРИМЕНЕНИЯ ИММУНОЛОГИЧЕСКИХ ТЕСТОВ НОВОГО ПОКОЛЕНИЯ У ДЕТЕЙ В УСЛОВИЯХ МАССОВОЙ ВАКЦИНАЦИИ ПРОТИВ ТУБЕРКУЛЕЗА

Development of new methods of immune diagnostics of tuberculous infection and their introduction into tuberculosis control practice have changed approaches to diagnostics of tuberculosis in Russia. Along with world recognized IGRA-tests the test with tuberculous recombinant allergen (TRA) developed by Russian researchers is also widely used. High diagnostic value of each of the methods is proved by multiple national and international trials however there is no research comparing results of these methods in the diagnostics of tuberculous infection in children, including those with concurrent conditions. During the study data of testing in 654 children in the age from 0 to 14 years old with positive sensitivity to tuberculin as per Mantoux test with 2 TU were analyzed. All patients had modern immunological tests done: TRA and IGRA-tests (QuantifeRON® Gold ELISA (QFT) and T-SPOT.TB). The study confirmed the low value of Mantoux test with 2 TU as a method of early tuberculosis detection in children; it detected underdiagnosis (10-50%) and overdiagnosis (78%) of latent tuberculous infection in the children with different sensitivity level as per data of Mantoux test with 2 TU. Comparing the results of TRA and IGRA tests it is possible to state that they are compatible for 76-81% of cases. The group of children was detected who had allergic and endocrine disorders (obesity), for whom IGRA tests were recommended to exclude chances of false-positive results of TRA tests.

EVALUATION OF SPECIFIC ANTIGENS AT THE EARLY STAGE OF TUBERCULOUS INFECTION IN CHILDREN

More specific antigens are still being searched for in order to increase informativeness of techniques for early diagnostics of tuberculous infection. Aimed at the investigation of proteins of tuberculous mycobacteria (PPD-L, ESAT 6, 85, hybrid of ЕSAT 6 CFP 10, CFP32B, Rv2660c) the study was conducted including testing of induced IFN-γ in the children ill with tuberculosis in the early period of primary tuberculous infection and also those not infected with tuberculous mycobacteria – 130 children in the age from 6.0 ± 0.4 years old. It was found out that tuberculin remained to be valuable for evaluation of the intensity of anti-tuberculosis immunity. Antigens of ESAT 6, 85, CFP32B, Rv2660c were identified as proteins of the early stage of tuberculous infection. The presence of response when stimulating by the above antigens was typical of the favorable course of tuberculosis. Antigens of ESAT 6 and Rv2660c were valuable for assessment of latent tuberculous infections and the hybrid of ЕSAT 6 CFP 10 – for diagnostics of tuberculosis. Therefore introduction of immunological tests (in vitro) into the set of diagnostic tools allows optimizing the early diagnostics of tuberculous infection in children and forecasting the course of the disease when tuberculosis has developed.

СКРИНИНГ ЛАТЕНТНОЙ ТУБЕРКУЛЕЗНОЙ ИНФЕКЦИИ С ПРИМЕНЕНИЕМ АЛЛЕРГЕНА ТУБЕРКУЛЕЗНОГО РЕКОМБИНАНТНОГО

In recent years the significant deterioration of health has been observed in schoolchildren. As per official data only 20% of children graduating from school are considered to be completely healthy, and 60% suffer from chronic diseases, i.e. belong to health groups III, IV and V, among which there are many children belonging to tuberculosis risk groups and suffering from undetected latent tuberculous infection. The efficiency of the new technique aimed to detect active tuberculous infection in children and adolescents of health groups III, IV and V has been evaluated. Screening proved the reduction in the number of patients in need of TB doctor advising by 8.4 fold compared to traditional mass diagnostics with tuberculin. Hyperergic reactions to diaskintest are 6 fold less common compared to Mantoux test. And 99.2% of children referred to TB doctor were registered to the dispensary follow-up versus 23.4% of children referred to TB doctor as per mass tuberculin testing results. (p < 0.001). Thus the validity of referral to TB doctor increased 4.2 fold. The detection rate of active forms of tuberculosis made 0.4 per 1000 examinations versus 0.1 in case of mass screening with tuberculin testing.

Interferon gamma inducible protein-10 in the diagnosis of paediatric tuberculosis infection in a low TB incidence country.

To assess interferon-gamma inducible protein 10 (IP-10) as a diagnostic marker for tuberculous infection in children, particularly in relation to its differential diagnostic performance in young children. A case-control study was conducted among 161 children and adolescents (mean age 6.3 years ± standard deviation 1.7; males n = 79, 49%). Fifty-four (33.5%) had active TB, 53 (33%) had latent tuberculous infection (LTBI), and 54 (33.5%) were non-LTBI controls. Unstimulated IP-10 levels did not differ between groups (P > 0.05 for all comparisons). TB-specific antigen stimulated IP-10 levels were more profoundly increased in infected groups than in controls (P < 0.001 for all comparisons). None of the IP-10-based diagnostic indexes demonstrated the ability to discriminate active disease from LTBI. A value of IP-10 ⩾ 1222 pg/ml had 83.3% sensitivity, 79.6% specificity, 80.4% positive predictive value and 82.7% negative predictive value for the diagnosis of LTBI. IP-10 based indexes demonstrated a trend towards better performance in the population group aged <5 years. The IP-10 assay could be useful in improving the diagnosis of LTBI in patients aged <5 years in combination with existing interferon-gamma release assays.

Safety and completion of a 4-month course of rifampicin for latent tuberculous infection in children

Children's Tuberculosis Clinic, Houston, Texas. To describe adherence to and tolerability of 4 months of rifampicin (4RMP) compared to 9 months of isoniazid (9INH) in children with latent tuberculous infection (LTBI). Retrospective descriptive case series of children treated for LTBI from 2010 to 2013 by self-administered therapy or directly observed preventive therapy (DOPT) administered by the local health department. Four hundred and four children were treated, 324 (80%) with 9INH and 80 with 4RMP: the mean age was 7.3 years, and 47% were girls. Of these, 37% were identified during contact investigations. DOPT was used in 51% and self-administered therapy in 49%; 81% completed therapy. Completion of self-administered 4RMP therapy was not significantly different from completion rates for children receiving 9INH administered as DOPT (93% vs. 88%, OR 0.6, 95%CI 0.2-1.7), but was significantly higher than in the 9INH self-administration group (OR 7.9, 95%CI 2.7-23.2). Adverse events were rare: 20 (6%) in the 9INH group and 2 (3%) in the 4RMP group, and none was serious. Completion rates for 4RMP surpassed those of 9INH for all methods of delivery, except for DOPT, where completion rates were similar. 4RMP was well tolerated. The increased cost of 4RMP over 9INH may be offset by increased effectiveness, as gauged by completion rates.

Treatment of latent tuberculous infection in children and adolescent

Tuberculosis continues to cause an unacceptably high toll of disease and death among children worldwide. Whereas intense scientific and clinical research efforts into novel diagnostic, therapeutic, and preventive interventions have focused on tuberculosis in adults, childhood tuberculosis has been relatively neglected. However, children are particularly vulnerable to severe disease and death following infection, and those with latent infection become the reservoir for future transmission following disease reactivation in adulthood, fuelling future epidemics. Therefore, it is very important to understand the significance, diagnosis and treatment of latent tuberculous infection to decrease a future disease burden of tuberculosis. Unfortunately, these concept still have not fully implicated in Korean National Tuberculosis Control Program, it should be engaged and enforced as soon as possible.

Mycobacterium tuberculosis infection after travel to or contact with visitors from countries with a high prevalence of tuberculosis.

To assess whether there is increased risk of tuberculous infection in children who traveled to or had a household visitor from a country having a high prevalence of tuberculosis, we conducted a case-control study. Children younger than 6 yr of age who had a tuberculin skin test read at public health clinics in areas of California that have a high prevalence of tuberculosis were enrolled. Of the 953 children who had a skin test read, 72 (7.6%) had a positive reaction. By multiple logistic regression analysis, children who had traveled in the 12 mo before the skin test were 3.9 times more likely to have a positive skin test than were children who had not traveled (95% confidence interval [CI], 1.9 to 7.9). Among children born in the United States, those who had traveled were 4.7 times more likely to have a positive skin test (95% CI, 2.0 to 11.2). Children who had a household visitor from a country having a high prevalence of tuberculosis were 2.4 times more likely to have a positive skin test than were those who did not have a visitor (95% CI, 1.0 to 5.5). These data indicate that travel to a country that has a high prevalence of tuberculosis or having a visitor from such countries increase the risk of tuberculous infection among young children. Physicians and tuberculosis control programs should incorporate questions about travel and visitors into their evaluations, and children with a history of extended travel should have a tuberculin skin test.

Contribution of the polymerase chain reaction to the diagnosis of tuberculous infections in children.

The purpose of the study was to evaluate the contribution of polymerase chain reaction (PCR) to the diagnosis of tuberculous infection in children. Two different PCR techniques were compared to the standard bacteriological methods for the detection of Mycobacterium tuberculosis in 157 specimens obtained from the respiratory system of 51 children. Patients were classified in three groups: 12 patients with active disease (57 specimens), 12 patients with silent tuberculous infection (23 specimens) and 27 patients without tuberculosis (77 specimens). One PCR method (PCR/Ag85) used amplification of a fragment of the genes coding for the mycobacterial antigen 85 followed by hybridization of a probe specific for M. tuberculosis on the Southern blot of amplified DNA. The other PCR technique was a nested PCR (NPCR) using double amplification of a fragment of the insertion element IS6110 only present in the M. tuberculosis genome. The sensitivities of the different techniques, compared to the clinical diagnosis, were 7.0% for acid fast staining, 22.8% for culture, 24.6% for PCR/Ag85 and 44.9% for NPCR in active disease, 4.3% for culture, 8.7% for PCR/Ag85 and 28.6% for NPCR in silent tuberculous infection. The specificities were 100% for culture, 94.8% for PCR/Ag85 and 87.9% for NPCR. Among the 12 children clinically considered as having active tuberculosis, 1 had smear positive samples, 4 had at least one positive culture, 7 at least one positive PCR/Ag85 and 9 at least one NPCR positive sample. Among the 12 children having silent tuberculous infection, none had positive smears, 1 had one positive culture, 2 had at least one positive PCR/Ag85 and 5 at least one NPCR positive sample. Our study suggests that both PCR techniques, and especially NPCR, are able to detect M. tuberculosis DNA in specimens containing few micro-organisms. PCR methods are more sensitive than culture and the results are available more quickly. Testing multiple samples from the same individual increased the sensitivity. In view of occasional false-positive results, cultures remain the gold standard to establish definitive diagnosis of primary tuberculous infection in children.

Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination.

BCG vaccination alters the response to tuberculin testing and influences the potential validity of the Heaf test in the diagnosis of tuberculosis. This study used a purified protein derivative 1 tuberculin unit (TU) Mantoux test with a cut off of 5 mm induration as an indicator of tuberculous infection in high risk children to determine whether this would distinguish infection from previous neonatal BCG vaccination. Children at high risk of tuberculosis on chest radiography, Heaf test, or contact history who had been screened in the contact tracing clinic and referred for further assessment were included in the study. After clinical examination, chest radiography, and Mantoux testing they were assigned to three groups (tuberculous disease, chemoprophylaxis, or no treatment) and followed up for 6-24 months in the outpatient clinic and subsequently by postal questionnaire. Comparison of the Heaf and Mantoux tests showed a difference in the results with 82% of cases positive by the Heaf test and 59% positive by the Mantoux test. Using the Mantoux test result in combination with clinical and radiographic findings 194 children were allocated to the three groups as follows: primary tuberculosis (5), chemoprophylaxis (101), no treatment (88). During follow up for a mean (range) time of 46 (11-102) months four additional cases received treatment for primary tuberculosis, two in the chemoprophylaxis group and two in the untreated group. The use of the 1 TU Mantoux test after neonatal BCG vaccination reduced the number of children receiving treatment from 129 to 93-that is, by 36%. Although the numbers are small, there was no increase in the later development of tuberculosis.

Factors influencing the risk of tuberculous infection in children up to seven years of age

Factors influencing the risk of tuberculous infection in children up to seven years of age

Occult tuberculous infection in children

Three hundred and fifty New Zealand children with occult tuberculous infection are reviewed. Ninety four had received BCG vaccine previously. Three hundred and forty were admitted to hospital and 3 gastric aspirations were obtained from each child and cultured for tubercle bacilli. Mycobacterium tuberculosis was isolated from 1 or more aspirates in 29 (8.5 %) of the children. Excluding those who had received BCG the isolation rate was 10.9 %. Mycobacterium bovis was not cultured from any child. X-rays of the chest which were initially normal showed calcification after 2 to 5 years in 73 (20.8 %) cases. The 350 children were treated with 2 drugs, during the early years isoniazid and PAS and in the past 3 years isoniazid and rifampicin in standard dosage for either 12 or 18 months. The reasons for treating these children are discussed.

Tuberculosis in White and Negro Children, Volume I: The Roentgenologic Aspects of the Harriet Lane Study

These two volumes constitute the long-awaited report on the Harriet Lane Study of tuberculosis in children. Over 1000 children were entered in this long term study between 1928 and 1944; the patients were followed until the study terminated in 1950. The first volume is essentially an atlas of roentgenograms demonstrating very well many forms of tuberculosis seen in children, with the addition of films illustrating differential diagnosis of tuberculosis and other pulmonary conditions. The natural course of tuberculosis is shown by serial roentgenograms sometimes supplemented by bronchoscopic findings or illustrations from material obtained postmortem. The captions contain relatively little clinical information. There is a useful section on anatomy of the lung in relation to interpretation of chest x-rays and a chapter on bronchoscopy and bronchography. The second volume consists of an analysis of the records of the Harriet Lane Study, mainly concerned with the prognosis of primary tuberculous infection in children and with the risk to the survivors of later developing “reinfection”-type pulmonary tuberculosis.

Tuberculosis Pulmonar Infantil

This profusely and very beautifully illustrated textbook should be a welcome addition to the libraries of our Spanish-reading colleagues. Particularly good chapters on segmental anatomy of the lungs and on roentgenographic findings in the chest in tuberculous children are followed by chapters on the evolution of the primary complex; on endobronchial tuberculosis and obstructive lesions; pleurisy and pericarditis; progressive primary lesions with cavitation; hematogenous dissemination; chronic pulmonary tuberculosis of "reinfection" type in children and adolescents. Shorter chapters are devoted to such special problems as primary infection during puberty, primary infection in adults, congenital tuberculosis and the chronology of tuberculous infection in children.

THE HUMAN SOURCE OF TUBERCULOUS INFECTION IN CHILDREN

THE HUMAN SOURCE OF TUBERCULOUS INFECTION IN CHILDREN

EXTENT AND NATURE OF THE DECLINE OF TUBERCULOUS INFECTION IN CHILDREN

Workers interested in tuberculous infection in children are aware that its incidence, measured either by clinical signs or by the presence of a positive reaction to tuberculin, has been decreasing. It has been my impression that this decline has been felt in Rochester and that the severity of the infection itself has been decreasing. This analysis was undertaken to determine the annual incidence of tuberculous infection here and the annual percentage of children with positive reactions to tuberculin who show clinical or roentgenologic evidence of the disease. Any change may in a manner determine whether the virulence of the organism has altered. GENERAL CONSIDERATIONS Since 1926, when the Strong Memorial Hospital and the Rochester Municipal Hospital first admitted patients, a tuberculin test of all children admitted to the pediatric division has been a routine. The children referred to in this study are from this group. In determining the annual distribution

Massive generalized tuberculous infection in children, with recovery

Massive generalized tuberculous infection in children, with recovery