Updates in Pediatric Tuberculosis in International Settings

https://doi.org/10.1016/j.pcl.2021.09.004Get rights and content

Section snippets

Key points

  • •

    Poor surveillance in international settings, especially resource-poor high-burden settings, due largely to health system barriers, variations in case definitions and difficulty in diagnosis, and standardization and reporting, lead to an underdetected epidemic of childhood tuberculosis (TB).

  • •

    Considerable progress has been made in consolidated guidelines on appropriate dosing and safe and effective regimens for treating childhood TB. However, gaps in implementing treatment completion in

Epidemiology of pediatric tuberculosis in international settings

TB continues to afflict several populations across the globe in different socioeconomic settings. The highest burden of disease is typically seen in countries with weakened health systems,3,4 which characteristically also marginalize vulnerable pediatric populations. Prevention of spread and control as well as adequate individual management of TB therefore requires political will and a strategic system approach, with ambitious targets and rigorous monitoring and evaluation framework.

Updates in pediatric tuberculosis case detection and diagnosis

Diagnosis of pediatric TB may be made based on bacteriologic testing, clinical criteria, or a combination of supportive evidence provided by biomarkers and radiological imaging. Despite advances in each of these, diagnosis of pediatric TB remains difficult in clinical settings.

Treatment of Drug-Susceptible Tuberculosis in Children

TB disease in children has traditionally been treated with the agents used to treat adult disease. First-line regimens for drug-susceptible TB across the world still contain isoniazid, rifampin, ethambutol, and pyrazinamide. Dosages have recently been increased by WHO41,42 with 2 months of rifampicin (R) (10–20 mg/kg, maximum [max] dose 600 mg/d), pyrazinamide (Z) (30–40 mg/kg), isoniazid (H) (10–15 mg/kg, max dose 300 mg/d), and sometimes ethambutol (E) (15–25 mg/kg, in areas of high HIV or

Human Immunodeficiency Virus and Tuberculosis

HIV-infected children are at high risk of acquiring and developing TB after exposure. These children require immediate preventive therapy after exclusion of active disease, irrespective of age and immune status. Although preventive therapy should be provided at each TB exposure, continuous isoniazid prophylaxis is not recommended.

For all patients with HIV and drug-susceptible TB, antiretrovirals should be started regardless of their CD4 cell count; however, TB treatment should be initiated

Preventive Therapy

Contact investigation is not routinely implemented in most HBCs. Case finding is passive at best with very little community engagement or empowerment of first-line health professionals108; this leads indirectly to poor coverage rates of preventive treatment to children. In 2017, preventive therapy was not accessed by more than 75% of 1.3 million eligible household contacts younger than 5 years of age. There is a need to address persistent policy-practice gaps in screening children for TB

Clinics care points

  • •

    When biopsying tissue for histopathological diagnosis of suspected exptrapulmonary TB (EPTB) in LMICs, it should be ensured that tissue (lymph node, bone marrow, skin lesions refractory to standard treatment, lumps/masses) is sent for Xpert and/or AFB culture to avoid missing nontuberculous mycobacterial infections, fungal infection, and lymphoma (TB mimics).

  • •

    TB should be part of most chronic presentations by default because it can have atypical presentations in endemic HBCs such as isolated

Disclosure

The authors have nothing to disclose.

First page preview

First page preview
Click to open first page preview
View PDF

References (119)

  • S.K. Jain et al.

    Advanced imaging tools for childhood tuberculosis: potential applications and research needs

    Lancet Infect Dis

    (2020)
  • A.T. Cruz et al.

    Clinical manifestations of tuberculosis in children

    Paediatr Respir Rev

    (2007)
  • S.G. David et al.

    A comparison of tuberculosis diagnostic systems in a retrospective cohort of HIV-infected children in Rio de Janeiro, Brazil

    Int J Infect Dis

    (2017)
  • M. Holm et al.

    New optimism to the use of clinical scoring systems for the diagnosis of child tuberculosis–even among HIV co-infected

    Int J Infect Dis

    (2017)
  • J. Ranjalkar et al.

    Isoniazid and rifampicin concentrations in children with tuberculosis with either a daily or intermittent regimen: implications for the revised RNTCP 2012 doses in India

    Int J Antimicrob Agents

    (2018)
  • G. Sotgiu et al.

    Applicability of the shorter ‘Bangladesh regimen’ in high multidrug-resistant tuberculosis settings

    Int J Infect Dis

    (2017)
  • F. Fregonese et al.

    Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis

    Lancet Respir Med

    (2018)
  • K. Golka et al.

    NAT2 Genotype and isoniazid medication in children

    EBioMedicine

    (2016)
  • P.R. Donald et al.

    Old and new drugs for the treatment of tuberculosis in children

    Paediatr Respir Rev

    (2007)
  • D. Ettehad et al.

    Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis

    Lancet Infect Dis

    (2012)
  • J.A. Seddon et al.

    Paediatric use of second-line anti-tuberculosis agents: a review

    Tuberculosis

    (2012)

  • Global tuberculosis report 2020

    (2020)
  • J. Kim et al.

    Health systems performance in managing tuberculosis: analysis of tuberculosis care cascades among high-burden and non-high-burden countries

    J Glob Health

    (2019)
  • M. Osman et al.

    Health system determinants of tuberculosis mortality in South Africa: a causal loop model

    BMC Health Serv Res

    (2021)
  • E.P. Harausz et al.

    Treatment and outcomes in children with multidrug-resistant tuberculosis: a systematic review and individual patient data meta-analysis

    PLoS Med

    (2018)
  • S.E. Smith et al.

    Epidemiology of pediatric multidrug-resistant tuberculosis in the United States, 1993–2014

    Clin Infect Dis

    (2017)
  • J.-Y. Wang et al.

    Disseminated tuberculosis: a 10-year experience in a medical center

    Medicine

    (2007)
  • K. Snow et al.

    Tuberculosis in pregnant women and neonates: A meta-review of current evidence

    Paediatr Respir Rev

    (2020)

  • HIV estimates with uncertainty bounds 1990-2019

  • UNAIDS. Global HIV & AIDS statistics — Fact sheet

  • HIV and Children: fact sheet

  • Chiang C-Y, Bam TS. Should tobacco control intervention be implemented into tuberculosis control program? In: Taylor &...
  • B. Abdelmoez et al.

    Prevalence of tuberculosis among children who had type 1 diabetes and were admitted to Elminia University Hospital

    Pediatrics

    (2008)
  • T.N. Jakaza et al.

    Emerging dynamics of substance abuse among street children in Zimbabwe. A case of Harare Central Business District

    Afr J Soc Work

    (2018)
  • L.A. Martyn

    Health knowledge, attitudes, and practices among street children in LMICs

    (2016)
  • E. Chiappini et al.

    Recommendations for the diagnosis of pediatric tuberculosis

    Eur J Clin Microbiol Infect Dis

    (2016)
  • K.S. Wong et al.

    Validity of symptoms and radiographic features in predicting positive AFB smears in adolescents with tuberculosis

    Int J Tuberc Lung Dis

    (2010)
  • S.M. Graham et al.

    Clinical case definitions for classification of intrathoracic tuberculosis in children: an update

    Clin Infect Dis

    (2015)
  • Organization WH. Molecular assays intended as initial tests for the diagnosis of pulmonary and extrapulmonary TB and...
  • D. Cazabon et al.

    Market penetration of Xpert MTB/RIF in high tuberculosis burden countries: a trend analysis from 2014-2016

    Gates Open Res

    (2018)
  • S. Shakoor et al.

    Common alternative diagnoses among a pediatric hospital-based cohort evaluated for tuberculosis in Karachi, Pakistan: The need for facilitated referral in tuberculosis clinics

    Int J Mycobacteriol

    (2019)

  • Lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis of active tuberculosis in people living with HIV: policy update 2019

    (2019)
  • T.O. Togun et al.

    Biomarkers for diagnosis of childhood tuberculosis: A systematic review

    PLoS One

    (2018)
  • J. Maertzdorf et al.

    Toward a unified biosignature for tuberculosis

    Cold Spring Harb Perspect Med

    (2015)
  • B.M. Bergamini et al.

    Performance of commercial blood tests for the diagnosis of latent tuberculosis infection in children and adolescents

    Pediatrics

    (2009)
  • E.C. Pearce et al.

    A systematic review of clinical diagnostic systems used in the diagnosis of tuberculosis in children

    AIDS Res Treat

    (2012)
  • J. Das et al.

    In urban and rural India, a standardized patient study showed low levels of provider training and huge quality gaps

    Health Aff (Millwood)

    (2012)
  • Organization WH. Guidelines for treatment of drug-susceptible tuberculosis and patient care....

  • Guidance for national tuberculosis programmes on the management of tuberculosis in children

    (2014)
  • A. Mukherjee et al.

    Pharmacokinetics of isoniazid, rifampicin, pyrazinamide and ethambutol in HIV-infected Indian children

    Int J Tuberc Lung Dis

    (2016)

    • Cited by (3)

    • Magnitude of tuberculosis and its associated factors among under-five children admitted with severe acute malnutrition to public hospitals in the city of Dire Dawa, Eastern Ethiopia, 2021: multi-center cross-sectional study

      2022, IJID Regions

    • Importance of next-generation diagnostics in control of tuberculosis in LMICs

      2021, eBioMedicine

    • Pulmonary Tuberculosis in Children: A Forgotten Disease?

      2023, Microorganisms
    View full text
    © 2021 Elsevier Inc. All rights reserved.