Chest X-ray aids in early diagnosis of children exposed to TB

In children exposed to tuberculosis, chest radiography helped in detecting asymptomatic coprevalent TB and predicting incident TB after baseline, according to a study in American Journal of Respiratory and Critical Care Medicine.

Further, isoniazid preventive therapy (IPT) was 82% effective in preventing a future diagnosis of incident TB in asymptomatic children with abnormal chest radiographs, according to researchers.

“The clinical management of TB-exposed children involves two different decision points,” Chuan-Chin Huang, ScD, professor in the department of global health and social medicine at Harvard Medical School, and colleagues wrote. “First, making a definitive diagnosis of TB disease in children is challenging because they are much less likely than adults to have microbiologically confirmed disease, and it is, therefore, necessary to rely on ‘clinical diagnosis’ using a combination of findings from history, physical exam, radiologic imaging, and TB immune-based testing (eg, tuberculin skin test [TST] and interferon-g release assays), all of which have their limitations.

“Second, clinicians are often reluctant to initiate [TB preventive therapy] for TB infection in children with clinical or radiologic abnormalities compatible with intrathoracic TB (but for which they have low suspicion that TB is indeed the etiology) because of the concern that a child with undetected TB disease who is inadvertently treated with preventive monotherapy might develop drug resistance,” Huang and colleagues added.

In a longitudinal cohort study, Huang and colleagues evaluated 4,452 children from September 2009 to August 2012 in Lima, Peru who were exposed to TB through household contacts to observe the diagnostic and prognostic characteristics of chest radiography in this patient population.

Researchers additionally sought to understand the protective efficacy of IPT in children who had abnormal chest radiographs. Clinicians screened the children by TST, symptom assessment and chest radiography.

The study’s primary outcomes included coprevalent TB, or TB that presented at the beginning of the study, and incident TB, or TB diagnosed within a 1-year follow-up period among children without initial coprevalent TB.

Of the 4,448 children screened for TB symptoms, 908 (20%) had positive results. Further, 1,124 of the 4,280 children (25%) screened by TST were positive.

Additionally, 1,012 (23%) children underwent chest radiography, of which 79 (2%) came back abnormal, and 2,320 (54%) children received IPT.

Overall, 95 children were diagnosed with coprevalent TB.

Researchers observed that those with TB symptoms had a 4.71 (95% CI, 2.93-7.59) higher likelihood to be diagnosed with coprevalent TB than asymptomatic children.

Coprevalent TB also appeared more likely in symptomatic vs. asymptomatic children with normal chest radiographs (adjusted RR = 4.21; 95% CI, 1.28-13.86), according to researchers.

Among those with abnormal radiographs, researchers found that coprevalent TB was 25.06 (95% CI, 1.02-613.76) times more likely among asymptomatic children and 34.23 (95% CI, 7.58-154.68) times more likely among symptomatic children.

In terms of incident TB, 95 children were diagnosed during 1-year follow-up.

Incident TB diagnosis appeared more common among children who had abnormal chest radiographs and who were asymptomatic (adjusted HR = 26.71; 95% CI, 10.44-68.3), as well as symptomatic (aHR = 25.94; 95% CI, 4.1-164.28), compared with children with normal chest X-rays and no symptoms.

IPT showed 82% efficacy in the children who were asymptomatic and had an abnormal chest radiography (aHR = 0.18; 95% CI, 0.04-0.95).

Among children with TB symptoms and normal chest radiography, researchers found that two of the five (40%) children not given IPT developed incident TB compared with none of the seven children given IPT.

Additionally, of the 35 children who had a positive TST and abnormal chest radiography, researchers found that 28 of their radiography results did not suggest TB. IPT was found to be 93% effective in this subgroup, as eight out of 14 children not receiving IPT developed incident TB compared with only one child of 14 who received IPT.

Overall, of 46 asymptomatic children who had an abnormal chest X-ray at enrollment, 28 were diagnosed with coprevalent or incident TB.

“Our study suggests that the addition of radiography for child TB contacts may not only allow for TB diagnosis earlier than would be accomplished through symptom screening alone but may also identify a subgroup of child contacts at high risk of later TB progression,” Huang and colleagues wrote. “We also show that nonspecific [chest radiography] findings in child TB contacts may indicate incipient or subclinical TB disease that requires formal treatment. However, access to tuberculosis preventive therapy should not be constrained because it remains highly effective in asymptomatic contacts, even in those with [chest radiography] abnormalities.”

This study by Huang and colleagues adds to the literature indicating the importance of child TB prevention and the need for solid evidence in older children/adolescents who are diagnosed with TB, according to an accompanying editorial by Ben J. Marais, MD, PhD, professor at The University of Sydney Children’s Hospital at Westmead Clinical School, and Stephen M. Graham, MD, PhD, professor of international child health at the University of Melbourne.

“Closing persistent gaps in child TB prevention and detection is essential to meet targets formulated at the United Nations high-level meeting on the fight against TB,” Marais and Graham wrote. “In the end, [TB preventive treatment] implementation and scale-up will only be achieved if it is perceived as a priority by TB programs and major donors, as demonstrated by the high [TB prevention treatment] coverage in HIV programs. This will require practical implementation plans, reliable drug supply and effective monitoring and evaluation systems.”

Reference:

Marais BJ, et al. Am J Respir Crit Care Med. 2022; doi:10.1164/rccm.202205-1023ED.