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Rationale: Although World Health Organization guidelines emphasize contact investigation for tuberculosis (TB)-exposed children, data that support chest radiography as a useful tool are lacking. Objectives: We evaluated the diagnostic and prognostic information of chest radiography in children exposed to TB and measured the efficacy of isoniazid preventive therapy (IPT) in those with relevant radiographic abnormalities. Methods: Between September 2009 and August 2012, we enrolled 4,468 TB-exposed children who were screened by tuberculin skin testing, symptom assessment, and chest radiography. Those negative for TB disease were followed for 1 year for the occurrence of new TB diagnoses. We assessed the protective efficacy of IPT in children with and without abnormal chest radiographs. Measurements and Main Results: Compared with asymptomatic children with normal chest films, asymptomatic children with abnormal radiographs were 25.1-fold more likely to have coprevalent TB (95% confidence interval [CI], 1.02-613.76) and 26.7-fold more likely to be diagnosed with incident TB disease during follow-up (95% CI, 10.44-68.30). Among the 29 symptom-negative and CXR-abnormal child contacts, 20% (3/15) of the isoniazid recipients developed incident TB, compared with 57% (8/14) of those who did not receive IPT (82% IPT efficacy). Conclusions: Our results strongly support the use of chest radiography as a routine screening tool for the evaluation of child TB contacts, which is readily available. Radiographic abnormalities not usually considered suggestive of TB may indicate incipient or subclinical disease, although TB preventive treatment is adequate in most cases.

Background: Tuberculosis (TB) is a leading cause of illness and death in children globally. Improved bacteriologic and clinical diagnostic approaches in children are urgently needed., Methods: In a prospective cohort study, a consecutive series of young (<5 years) children presenting with symptoms suggestive of TB and parenchymal abnormality on chest radiograph in inpatient and outpatient settings in Kisumu County, Kenya from October 2013 to August 2015 were evaluated at baseline and over 6 months. Up to 14 specimens per child were tested for the Mycobacterium tuberculosis complex by fluorescence microscopy, Xpert MTB/RIF and mycobacterial culture. Using detailed clinical characterization, cases were retrospectively classified according to standardized research case definitions and the sensitivity and specificity of microbiological tests on different specimen types were determined., Results: Among 300 young children enrolled, 266 had sufficient information to be classified according to the research clinical case definition. Of these, 36% (96/266) had TB disease; 32% (31/96) with bacteriologically confirmed intrathoracic TB. Compared to culture, the sensitivity of a single Xpert test ranged from 60 to 67% and specificity from 97.5 to 100% for different specimen types., Conclusions: Despite extensive specimen collection and laboratory testing, TB could not be bacteriologically confirmed in almost two-thirds of children with intrathoracic TB classified by research clinical case definitions. Improved diagnostic tests are needed to identify children with TB and to exclude other potential causes of illness., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: To discuss the recommendations pertaining to infants, children, and adolescents in new and updated tuberculosis (TB) guidelines that have been published since 2010 - with emphasis on those from supranational organizations., Recent Findings: The main developments in the guidelines covered in this article are related to: novel diagnostics for TB infection, disease, and drug resistance; updated treatment regimens for childhood and drug-resistant TB (DR-TB); and primary and secondary prevention of TB disease in HIV-infected children and adolescents., Summary: These new guidelines have significant implications for improving pediatric TB care. Regarding diagnosis, current interferon-gamma release assays should not replace tuberculin skin testing, but may be complementary; a polymerase chain reaction assay has been validated for detecting Mycobacterium tuberculosis and rifampicin resistance in microscopy-negative samples, especially in HIV-infected and DR-TB suspects; and a molecular line probe assay has been validated for detecting DR-TB in microscopy-positive samples and culture isolates in DR-TB suspects. With respect to treatment, there have been certain changes in the recent World Health Organization recommendations for certain clinical syndromes, for multidrug-resistant TB disease, and for HIV/TB disease. Concerning prevention, there are new screening algorithms for case finding, and new recommendations for treating HIV-infected children with presumed TB infection and with TB disease with treatment completed (i.e., secondary prophylaxis).

Few children with drug-resistant (DR) tuberculosis (TB) are identified, diagnosed, and given an appropriate treatment. The few studies that have described this vulnerable population have used inconsistent definitions. The World Health Organization (WHO) definitions used for adults with DR-TB and for children with drug-susceptible TB are not always appropriate for children with DR-TB. The Sentinel Project on Pediatric Drug-Resistant Tuberculosis was formed in 2011 as a network of experts and stakeholders in childhood DR-TB. An early priority was to establish standardized definitions for key parameters in order to facilitate study comparisons and the development of an evidence base to guide future clinical management. This consensus statement proposes standardized definitions to be used in research. In particular, it suggests consistent terminology, as well as definitions for measures of exposure, drug resistance testing, previous episodes and treatment, certainty of diagnosis, site and severity of disease, adverse events, and treatment outcome. [ABSTRACT FROM PUBLISHER]

Children suffer a huge and often underappreciated burden of disease in tuberculosis (TB) endemic countries. Major hurdles include limited awareness among health care workers, poor integration of TB into maternal and child health approaches, diagnostic difficulties and a lack of child-friendly treatment options. Accurate disease diagnosis is particularly difficult in young and vulnerable children who tend to develop paucibacillary disease and are unable to produce an expectorated sputum sample. In addition, access to chest radiography is problematic in resource-limited settings. Differentiating between TB exposure and M. tuberculosis infection, and especially between M. tuberculosis infection and TB disease is crucial to guide clinical management. TB represents a dynamic continuum from well-contained "latent" infection to incipient and ultimately severe disease. The clinical spectrum of disease in children is broad and can be confused with a myriad of common infections. We provide a pragmatic 4-step approach to diagnose intra-thoracic TB in children and demonstrate how classifying clinical, radiological and laboratory findings into recognised clinical syndromes may provide a more refined diagnostic approach, even in resource-limited settings. [ABSTRACT FROM AUTHOR]

For microbiological confirmation of pediatric pulmonary tuberculosis (PTB), gastric aspirates (GA) are often operationally unfeasible without hospitalization, and the encapsulated orogastric string test is not easily swallowed in young children. The Combined-NasoGastric-Tube-and-String-Test (CNGTST) enables dual collection of GA and string specimens. In a prospective cohort study in Kenya, we examined its feasibility in children under five with presumptive PTB and compared the bacteriological yield of string to GA. Paired GA and string samples were successfully collected in 95.6 % (281/294) of children. Mycobacterium tuberculosis was isolated from 7.0 % (38/541) of GA and 4.3 % (23/541) of string samples, diagnosing 8.2 % (23/281) of children using GA and 5.3 % (15/281) using string. The CNGTST was feasible in nearly all children. Yield from string was two-thirds that of GA despite a half-hour median dwelling time. In settings where the feasibility of hospitalisation for GA is uncertain, the string component can be used to confirm PTB. [ABSTRACT FROM AUTHOR]

Tuberculosis is the leading cause of death globally that is due to a single pathogen, and up to a fifth of patients with tuberculosis in high-incidence countries are children younger than 16 years. Unfortunately, the diagnosis of childhood tuberculosis is challenging because the disease is often paucibacillary and it is difficult to obtain suitable specimens, causing poor sensitivity of currently available pathogen-based tests. Chest radiography is important for diagnostic evaluations because it detects abnormalities consistent with childhood tuberculosis, but several limitations exist in the interpretation of such results. Therefore, other imaging methods need to be systematically evaluated in children with tuberculosis, although current data suggest that when available, cross-sectional imaging, such as CT, should be considered in the diagnostic evaluation for tuberculosis in a symptomatic child. Additionally, much of the understanding of childhood tuberculosis stems from clinical specimens that might not accurately represent the lesional biology at infection sites. By providing non-invasive measures of lesional biology, advanced imaging tools could enhance the understanding of basic biology and improve on the poor sensitivity of current pathogen detection systems. Finally, there are key knowledge gaps regarding the use of imaging tools for childhood tuberculosis that we outlined in this Personal View, in conjunction with a proposed roadmap for future research. [ABSTRACT FROM AUTHOR]