Potential Limitations of the World Health Organization Criteria for Nonsevere Tuberculosis in Children in a Low Prevalence, High-resource Setting

BACKGROUND: In 2022, the World Health Organization (WHO) adapted its pediatric tuberculosis disease (TBD) treatment guidelines, recommending a shortened 4-month treatment regimen for nonsevere TB, based on a single study in high TB prevalence, low-resource settings. This study investigated to what extent the recommendations apply to a high-resource setting. METHODS: Retrospective cohort study of patients with TBD <16 years of age treated at the Austrian Reference Centre for Paediatric TB from 2010 to 2023. RESULTS: One hundred fifty-nine patients were included in the final analysis. Based on the WHO guidelines, 104 (65.4%) met the criteria for nonsevere TBD. Compared with children with severe TBD (n = 55; 34.6%), children with nonsevere TBD were significantly more commonly asymptomatic (26.0% vs. 83.6%; P ≤ 0.0001), more commonly detected by TB screening (14.6% vs. 74.0%; P ≤ 0.0001) and less commonly microbiologically-confirmed (36.5% vs. 85.5%; P ≤ 0.0001). Eight children categorized as nonsevere had evidence of severe disease on chest computed tomography; 9 had evidence of severe disease on bronchoscopy. Nineteen children in the nonsevere group had positive polymerase chain reaction results for Mycobacterium tuberculosis complex. Taking computed tomography, bronchoscopy and polymerase chain reaction results into account, 28 (26.9%) of the 104 cases initially classified as nonsevere would have to be reclassified as severe (equating to a 50.9% increase in the severe group). Consequently, only 76 (47.8%) patients would ultimately qualify as nonsevere TBD, while 83 (52.2%) had severe TBD. CONCLUSIONS: Our results suggest there is a substantial risk of underestimating disease severity when using the WHO criteria in isolation. Incorrect classification of disease severity may result in insufficient treatment and potentially treatment failure.