New Tool Shows Promise for Diagnosing TB in HIV-Infected Children

By Marilynn Larkin

August 29, 2019

NEW YORK (Reuters Health) - A score based on the Xpert MTB/RIF assay and easy-to-collect clinical and imaging features could enable early treatment decisions for many HIV-infected children with tuberculosis (TB), researchers say.

"Despite their potential diagnostic value, the numerous scores and classifications developed to help standardize diagnosis of tuberculosis in children are not currently recommended in the World Health Organization childhood tuberculosis guidance because of their heterogeneity, lack of validation, and poor performance in children infected with HIV," write Dr. Olivier Marcy of the University of Bordeaux and colleagues in Pediatrics, online August 27.

Dr. Marcy told Reuters Health by email, "Although no individual test - be it clinical, radiological, biological - has by itself the diagnostic performance enabling its use as a standalone test..., these can be combined in a score with a good performance."

To develop the score, the team enrolled HIV-infected children ages 13 and younger with suspected TB based on at least one of the following criteria: (1) persistent cough; (2) fever lasting more than two weeks; (3) failure to thrive, defined as recent deviation in the growth curve or a weight-for-age z score; (4) failure of antibiotics for a pulmonary infection; or (5) a suggestive chest radiograph. Children were enrolled in Burkina Faso, Cambodia, Cameroon and Vietnam.

At the end of the study, participants were retrospectively classified as having confirmed, unconfirmed, or unlikely TB.

Of the 438 enrolled children (median age, 7.3 years; about half boys), 251 (57.3%) had TB, including 12.6% with culture- or Xpert-confirmed TB.

Based on 355 children with data on all predictors, the features/imaging included in model development were Xpert; fever lasting more than two weeks; unremitting cough, hemoptysis and weight loss in the past four weeks; contact with a patient with smear-positive tuberculosis; tachycardia; miliary tuberculosis; alveolar opacities and lymph nodes on the chest radiograph; plus, abdominal lymph nodes on ultrasound and Quantiferon Gold In-Tube (QFT).

The final TB diagnostic models were: (1) all predictors included; (2) QFT excluded; (3) ultrasonography excluded; and (4) QFT and ultrasonography excluded.

The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score was developed on model 2, which had a sensitivity of 88.6% and a specificity of 61.2% for a TB diagnosis.

"Overall, our score did not perform as well as clinicians from study tertiary healthcare facilities who treated 92% of children with tuberculosis and only 6% of those without," the authors acknowledge. "However, we expect that it will contribute to faster treatment decisions at lower levels of care, especially when used with feasible and sensitive specimens for Xpert, such as nasopharyngeal aspirates and stools."

Dr. Marcy said, "As part of the TB-Speed project led by the University of Bordeaux (, we are implementing (the tool) in a new validation cohort study." The study will enroll children with presumptive TB in Côte d'Ivoire, Mozambique, Uganda, and Zambia. The goals are to externally validate the proposed algorithm in different epidemiological and clinical settings; assess its feasibility; check its transferability and scalability; and strengthen practical recommendations for its wide-scale implementation.

Five hundred and fifty children will be enrolled in the study, which began recruiting patients in August, according to Dr. Marcy. Results should be available by early 2021.

Dr. Vanessa Raabe, a pediatric infectious disease specialist at Hassenfeld Children's Hospital at NYU Langone in New York City, told Reuters Health, "This appears to be a promising tool for front-line healthcare providers for guiding decision-making on starting anti-TB therapy in HIV- infected children, even in settings where access to TB diagnostics and imaging may be limited."

"The step-wise approach makes it user friendly, allowing healthcare providers to start the treatment decision-making process using information that can easily be obtained from the patient's family and only escalating to laboratory and imaging tests when needed," she said by email.

"It would be useful in future studies to see if using this tool helps improve clinical addition to diagnostic outcomes," she said. "It may not be as useful in specialized hospitals, (where) the tool may be a useful diagnostic adjunct, but it shouldn't be a substitute for clinical judgement."

Dr. Dwight Yin, an infectious diseases specialist at Children's Mercy Kansas City, commented by email, "Although this treatment-decision score has reasonable performance characteristics, the tool still struggles with accuracy problems."

"Based on calculations of the tool's accuracy, a positive score should increase the odds of TB by 2.3 times, whereas a negative score should decrease the odds by 1.9 times," he said by email. "These changes in odds should be helpful but are still imperfect."

"The authors note that the purpose of the tool is not to be exactly accurate in the diagnosis of TB in children living with HIV, but to improve initiation of antituberculous therapy in this population," he added. "This tool should help accomplish that goal."


Pediatrics 2019.