Elsevier

The Lancet

Volume 394, Issue 10202, 14–20 September 2019, Pages 967-978
The Lancet

Series
Challenges and controversies in childhood tuberculosis

https://doi.org/10.1016/S0140-6736(19)32045-8Get rights and content

Summary

Children bear a substantial burden of suffering when it comes to tuberculosis. Ironically, they are often left out of the scientific and public health advances that have led to important improvements in tuberculosis diagnosis, treatment, and prevention over the past decade. This Series paper describes some of the challenges and controversies in paediatric tuberculosis, including the epidemiology and treatment of tuberculosis in children. Two areas in which substantial challenges and controversies exist (ie, diagnosis and prevention) are explored in more detail. This Series paper also offers possible solutions for including children in all efforts to end tuberculosis, with a focus on ensuring that the proper financial and human resources are in place to best serve children exposed to, infected with, and sick from all forms of tuberculosis.

Introduction

An estimated 1 million children become sick with tuberculosis each year and most of these children are never diagnosed or treated for their disease.1 With appropriate and timely treatment the prognosis for children with tuberculosis is excellent. However, because of gaps in diagnosis and linkage to care, mortality from tuberculosis in children is high.2 As shown in the figure, modelling estimates suggest that as many as one in four children sick from tuberculosis will die from this disease.3 Striking gaps in the diagnosis and treatment cascade are also apparent when considering rifampicin-resistant and multidrug-resistant forms of tuberculosis, in which fewer than 5% of the estimated 25 000–32 000 children who become sick each year4 ever receive treatment.5 Children are considered a vulnerable population and should be considered a priority in global approaches to improve diagnosis, treatment, and prevention of tuberculosis.6 Since the 1970s, however, the public health approach focusing only on sputum smear-positive individuals led to children being excluded from larger tuberculosis control efforts.7 This Series paper will explore some of the key challenges and controversies in approaches to paediatric tuberculosis and suggest some ways in which children can be prioritised in the era of WHO's EndTB strategy to end tuberculosis. An in-depth discussion of challenges and controversies in tuberculosis diagnosis in children is presented in panel 1 and in tuberculosis prevention in children in panel 2. Other relevant challenges in paediatric tuberculosis epidemiology and treatment are discussed briefly and summarised in panel 3; research priorities for paediatric tuberculosis are summarised in panel 4.

Section snippets

Challenges and controversies in diagnosis of paediatric tuberculosis

For both drug-susceptible and drug-resistant forms of tuberculosis, screening for and diagnosis of disease in children is a challenge, especially in the younger age groups (≤5 years).8 Children might have extrapulmonary or paucibacillary tuberculosis and although many do present with typical findings of pulmonary tuberculosis,9 others are missed with diagnostic and screening strategies that were developed for adults.10 Furthermore, many children with tuberculosis might be missed when they

Sample acquisition and testing

Although children can be diagnosed with possible or probable tuberculosis on the basis of history, symptoms, and physical examination,26 NTPs and clinical providers also seek bacteriological confirmation of tuberculosis disease. This confirmation requires obtaining samples to test and deciding what types of tests will be done on these samples. Older children (>5 years) are more likely to have pulmonary disease than younger children and can usually produce a respiratory specimen, but for younger

Vaccination and treatment of infection

Vaccination with BCG is an important way to prevent disseminated tuberculosis and tuberculosis meningitis, especially in children younger than 2 years; however, its wider role has yet to be realised.48 Revaccination with BCG might be a way to improve its efficacy, and to overcome registration and cost barriers that might be associated with new vaccines, as seen in a randomised trial in HIV-negative children who had a negative QuantiFERON test (Qiagen, Hilden, Germany).49 New vaccines are being

Definitions, epidemiology, and treatment

One key challenge in paediatric tuberculosis is scarcity of robust prevalence data. The term paediatric itself can be controversial, with various stakeholders defining the paediatric population as those under 18 years,88 those under 15 years,89 and those under 24 years.90 Variable interpretation of the terms children, youth, and adolescents makes standardised reporting difficult. Because of the scarcity of definitive microbiological confirmation of tuberculosis disease, children under 14 years

Conclusions

A reason for optimism exists in the field of childhood tuberculosis, because most children who are promptly diagnosed and started on effective therapy thrive when they are treated for their disease. In spite of this, the diagnosis and management of children with tuberculosis can be difficult, and challenges abound, especially in diagnosis and prevention of tuberculosis. However, one thing is clear: if we as a global community are serious about ending tuberculosis and reducing

Search strategy and selection criteria

References for this Series paper were identified by searching the following databases: PubMed, OVID, and MEDLINE. Articles published in English, French, or Spanish between Jan 1, 2015, and April 1, 2019, were identified if they contained the following terms: “child/ren”, “pediatric”, “childhood”, OR “adolescent” AND “tuberculosis”, “drug-resistant”, “diagnosis”, “treatment”, “prevention” and “clinical trials”. With this strategy, more than 3000 articles were identified, and the abstracts of

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