Review identifies ways to detect undiagnosed TB in children

Key takeaways:

• Currently, WHO recommends TB screening in children only under certain conditions.
• A systematic review identified more opportunities to detect undiagnosed cases.

There has been a rebound in cases of tuberculosis in the United States, according to the CDC, with the largest increase occurring among children aged 4 years or younger.

Newly reported findings from a systematic review indicate that the most efficient ways to detect undiagnosed cases of TB among children may be to screen them in outpatient settings — including HIV clinics — and to screen children younger than age 5 years in both community and health care settings, according to results published in Pediatrics.

TB “is a large but underrecognized cause of morbidity and mortality among children,” with more than 1 million cases and an estimated 226,000 deaths occurring among children aged younger than 15 years in 2020, the authors of the study wrote.

“Treatment success for children initiated on anti-TB treatment is high (88%) and reduces pediatric mortality, but TB case detection is unacceptably poor in this age group, with an estimated 65% of pediatric cases going undiagnosed,” they wrote. “The majority of children with TB are therefore not linked to care.”

WHO recommends TB screening for children with HIV and children who are close contacts of an individual with active TB disease. Optimal strategies for active case finding in children are otherwise unclear, the researchers said.

They conducted a systematic review “to estimate the number of individuals needed to screen to detect a single case of active TB among children using different screening approaches and across different settings,” they wrote.

They reviewed 27,221 titles and abstracts and ultimately included 31 studies of active case findings conducted among children aged younger than 15 years old. They used the studies to estimate the number of children who needed to be screened (NNS) to detect one case of active TB.

Symptom-based screening was the most common screening modality, with a weighted mean NNS of 257. The weighted mean NNS was lower in both inpatient (216) and outpatient (67) settings compared with community (1,117) and school (464) settings. It was even lower (24) for screening children aged younger than 5 years not known to have HIV, suggesting that screening this group “may be particularly efficient,” the authors wrote.

They advocated screening patients for TB whenever they are in contact with the health care system “for other reasons.”

“Improving case detection for children with TB, with appropriate linkage to TB treatment or TB-preventive treatment, is critical to improving outcomes among children in high-burden TB settings,” they wrote.

In an accompanying editorial, Helen E. Jenkins, PhD, associate professor of biostatistics at the Boston University School of Public Health, and Jeffrey Starke, MD, Healio Pediatrics Peer Perspective Board Member and professor of pediatric infectious diseases at Baylor College of Medicine, noted that the two groups with the lowest NNS to detect a case of TB — children younger than age 5 years and children with HIV — “are also precisely the groups of children who are less likely to have microbiological confirmation ... and because of the fact that they are at the highest risk of poor outcomes and mortality, they will likely be overdiagnosed as a precaution to avoid these poor outcomes.”

“This raises the specter of the burden of false positives, because it is unlikely that all of the children diagnosed with TB actually had TB,” they wrote. “Although some degree of

overtreatment has been deemed acceptable, the importance of more studies that are sufficiently powered to identify and stratify by presence and absence of specific clinical findings and microbiological diagnosis would help us minimize both over- and underdiagnosis.”

Jenkins and Starke said TB “has only recently been officially recognized” as one of the top 10 causes of death among children aged younger than 5 years, and that most children who die of TB each year are never diagnosed with the disease.

“Identifying additional and alternative case-finding strategies and appropriate settings to use them would inform policy to identify more children with TB and ultimately save lives,” they wrote. “However, without sufficient data from high-quality studies to inform these policies, children with TB will continue to suffer and be neglected.”

References:

Jenkins HE, et al. Pediatrics. 2023;doi:10.1542/peds.2022-059849.

Robsky KO, et al. Pediatrics. 2023;doi:10.1542/peds.2022-059189.