Clinical standards for drug-susceptible TB in children and adolescents.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Epidemiology and clinical characteristics of childhood TB identified using active and passive case finding.

BACKGROUND: Childhood TB cases can be found using passive case finding (PCF), i.e., by diagnosing children presenting with symptoms, or using active case finding (ACF), i.e., by identifying children with TB through contact tracing. Our study determined epidemiologic, clinical, and radiographic differences between these groups.DESIGN/METHODS: Retrospective cohort study of children aged 0-19 years diagnosed with TB from January 1, 2012 to December 31, 2019 at a U.S. TB clinic, comparing clinical, radiographic, microbiologic, and epidemiological characteristics of children identified using PCF and ACF.RESULTS: Of 178 eligible patients, 99 (55.6%) were diagnosed using PCF. Children identified using PCF were older (mean 8.9 vs. 6.1 years, P = 0.003), more often non-US-born (OR 2.29, 95% CI 1.12-4.67), had more extrapulmonary disease (44.4% vs. 3.8%, OR 20.27, 95% CI 5.98-68.64) and severe intrathoracic findings (39.4% vs. 10.1%, OR 5.77, 95% CI 2.50-13.29). Children identified using ACF were often asymptomatic, had isolated hilar/mediastinal adenopathy, but had more availability of drug susceptibility data from a link to a source case.CONCLUSION: Children identified using PCF had more severe manifestations, while those identified using ACF had greater availability of drug susceptibility data. Clinicians should be aware that clinical and radiographic presentations in children identified using PCF and those identified using ACF differ, and that the latter may be eligible for shorter treatment regimens.

Controversies in tuberculous infection among pediatric infectious disease specialists in North America.

OBJECTIVE: To evaluate the extent to which advancements in the diagnosis and treatment of latent tuberculous infection (LTBI) have been integrated into practice by pediatric infectious disease (PID) specialists. DESIGN: We conducted an online survey of the Infectious Diseases Society of America's Emerging Infections Network (EIN) membership. RESULTS: Of the 323 members, 197 (61%) responded: 7% cared for ⩾5 children with TB disease and 34% for ⩾5 children with LTBI annually. We identified substantial variations in the use of interferon-gamma release assays (IGRAs) based upon age, immune status, and TB risk factors. In addition, tuberculin skin test (TST) use was three times more common in younger children. Variations existed in managing children with discordant TST and IGRA results. Less variation existed in LTBI treatment, with 86% preferring a 9-month course of isoniazid; few other, newer regimens were used routinely. CONCLUSION: Substantial variations exist in LTBI management; uptake of newer diagnostic tools and treatment regimens has been slow. Variations in practice and the lag time to integrating new data into practice may indicate the relative infrequency with which providers encounter LTBI. Our findings reflect the need for increased visibility of existing TB guidelines and resources for expert consultation for scenarios not covered by guidelines.

Childhood tuberculosis in the United States: shifting the focus to prevention.

In the last century, the United States has transitioned from a high to a low tuberculosis (TB) incidence country. A major factor in this decline has been the emphasis on identification and treatment of patients with tuberculous infection. While identification, testing, and preventive therapy pose challenges, recent developments in childhood TB offer more options for effective strategies that are acceptable to both children and their families. These include screening and testing in non-traditional settings, use of more specific assays (interferon-gamma release assays) for testing, and implementation of shorter-course preventive regimens.

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

SETTING: Children's Tuberculosis Clinic, Houston, Texas. OBJECTIVE: 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). DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Twice-weekly therapy for children with tuberculosis infection or exposure.

SETTING: Children's tuberculosis clinic, Houston, TX, United States. OBJECTIVE: To determine the safety, adherence and efficacy of intermittent directly observed preventive therapy (DOPT). DESIGN: Retrospective cohort of children receiving intermittent DOPT for exposure to tuberculosis (TB) or latent TB infection (LTBI) seen from 1989 to 2011 at one clinic. RESULTS: A total of 1383 children were treated for either TB exposure for 2-3 months (n = 935, 68%) or LTBI for 9 months (n = 448, 32%) with isoniazid 20-30 mg/kg/dose or rifampin 10-15 mg/kg/dose biweekly. All children with exposure and 411 (92%) with LTBI were identified via contact investigations. Twelve (1.3%) children with exposure experienced adverse effects (5 abdominal pain, 4 vomiting, 3 rash); 8 had transaminases evaluated and only 1 had elevated levels. Thirty (6.7%) children with LTBI experienced adverse effects (16 abdominal pain, 6 rash, 3 vomiting, 3 headache and 2 abdominal pain/vomiting); 19 had transaminases obtained and 2 had elevated transaminases. All transaminases normalized after the discontinuation of medication. Over 99% of exposed and 95.8% of infected children completed treatment. One child, who had sickle cell anemia, was treated for LTBI and later developed TB disease. When compared to rates of disease progression by age, the efficacy of intermittent DOPT was 98%. CONCLUSION: Intermittent DOPT in childhood TB is safe, effective and offers high adherence rates.