Paediatric TB care riddled with uncertainty, study says

Uncertainty weighs heavily on managing tuberculosis (TB) infection in children, with multi-level factors influencing the decision-making regarding testing and treatment.

When it comes to screening for TB, the provider, health system, and diagnostic test come into play, according to the results of an umbrella analysis that included 24 systematic reviews. [ESPID 2023, abstract PV0732]

Poor provider TB knowledge, as well as the lack of diagnostic, infrastructural, and administrative resources are the major barriers, said one of the authors of the umbrella analysis Dr Francesca Wanda Basile, a paediatrician specializing in infectious diseases and a postdoctoral fellow at the University of Oxford, UK, who spoke at ESPID 2023.

Additionally, some healthcare workers harbour a fear of acquiring TB through respiratory sampling. It also does not help that certain specimen collection techniques, such as gastric aspirate, are complex and invasive. All these can prevent children from getting tested, according to Basile.

Meanwhile, uncertainties about treatment have been attributed to previous TB infection, unknown TB exposure, the healthcare providers’ high confidence in negative test results (irrespective of true negative predictive value), and fear of TB drugs’ side effects.

“Provider and health system factors, in addition to patient and diagnostic test factors, should be addressed to optimize testing and treatment decision-making,” according to Basile.

An advanced professional qualification and confidence in tests can facilitate testing for paediatric TB, she said. Important diagnostic test characteristics such as automation, nonsputum-based assays, and quick turnaround times have been also found to increase testing uptake.

On the other hand, young age, severe sickness, and test inaccessibility have been reported to aid decisions regarding initiation of empiric TB treatment.

“Pragmatic trials at the point-of-care are needed to ensure that provider characteristics and the operating context are considered early during the development of diagnostic tests and decision algorithms,” Basile said.

Unfavourable outcomes despite TB vaccine

Underreporting, underdiagnosis, and inadequate treatment of TB in children can be an important contributor to the burden of childhood TB, as reported in a separate study.

In countries that practice universal Bacille Calmette-Guérin (BCG) vaccination, unfavourable outcomes including death persist among younger children with TB and those with HIV coinfection, according to lead investigator Dr Joana Valente Dias from Hospital Beatriz Ângelo in Loures, Portugal.

Epidemiological data from 35 studies conducted across 24 countries showed that among children with TB, 19.52 percent (95 percent confidence interval [CI], 14.44–25.84) experienced unfavourable outcomes, with a pooled case fatality ratio of 6.06 percent (95 percent CI, 4.34–8.40). Notably, younger children (0–4 years) were more likely to die than their older peers (6.56 percent, 95 percent CI, 4.91–8.71 and 4.61 percent, 95 percent CI, 3.06–6.90). [ESPID 2023, abstract PD0049]

Mortality was even higher for children with HIV coinfection (pooled prevalence, 21.30 percent (95 percent CI, 11.89–35.17), Dias noted.

The case fatality ratio for TB was 15.09 percent (95 percent CI, 7.86–27.02) among HIV-positive children as opposed to 4.16 percent (95 percent CI, 2.00–8.44) among those who were HIV-negative.

Finally, the overall proportion of multidrug-resistant TB was 8.14 percent (95 percent CI, 4.64–13.90).

“Although limited by heterogeneity, our findings [highlight the need for] global efforts to close remaining gaps, such as underreporting, underdiagnosis and, inadequate treatment … if we aim to effectively tackle the burden of childhood TB,” Dias concluded.