Skip to main content
SearchLoginLogin or Signup

Review 1: "External Validation of a Treatment Decision Algorithm for Tuberculosis in Children Living with HIV - A Diagnostic Cohort Study"

The study is recognized as important work that could inform global and national policies, emphasizing the need for external validation of TDAs in different contexts.

Published onJan 21, 2025
Review 1: "External Validation of a Treatment Decision Algorithm for Tuberculosis in Children Living with HIV - A Diagnostic Cohort Study"
1 of 2
key-enterThis Pub is a Review of
External validation of a treatment decision algorithm for tuberculosis in children living with HIV - a diagnostic cohort study
External validation of a treatment decision algorithm for tuberculosis in children living with HIV - a diagnostic cohort study
Description

ABSTRACT Introduction Tuberculosis (TB) is the leading cause of death in children living with HIV (CLHIV) and is challenging to confirm the diagnosis. The PAANTHER treatment decision algorithm (TDA) was developed to improve the diagnosis of TB in CLHIV. We aimed to externally validate the PAANTHER TDA in CLHIV with presumptive TB.Methods We conducted a prospective diagnostic cohort study in seven tertiary hospitals across Côte d’Ivoire, Mozambique, Uganda, and Zambia, implementing the PAANTHER TDA in CLHIV aged between 1 month and 14 years with presumptive TB. TDA assessments included Xpert MTB/RIF Ultra (Ultra) on respiratory and stool samples, history of contact, symptoms (fever >2 weeks, unremitting cough, haemoptysis and/or weight loss in previous 4 weeks, tachycardia), chest radiography and abdominal ultrasound. A positive score (>100) prompted TB treatment initiation. Children were followed-up for 6 months, and retrospectively classified as having confirmed, unconfirmed or unlikely TB. The primary outcome was the proportion of missed TB cases (false negative) among children with negative scores; secondary outcomes included TDA diagnostic accuracy, feasibility, and time to treatment initiation. The TDA was considered validated if the negative predictive value (NPV, 1 - rate of false negative) was superior to a 75% pre-established confidence interval lower limit.Findings From 2 October 2019 to 31 December 2021, we enrolled 277 CLHIV, including 175 (63·2%) who were on antiretroviral therapy at inclusion. 272 (98·2%) children had a complete TDA evaluation; 215 (75.8%) scored >100, including 24 (8·7%) with positive Ultra. 182 (86·7%) children who scored ≥100, and 12 children who scored negative, initiated TB treatment at a median of 1 (IQR: 0-3) and 27 [8·2; 64] days after inclusion, respectively. 62/215 children (28·8%) who scored ≥100 were classified as having unlikely TB and 4/12 (33·3%) who scored negative were initiated on treatment and were classified as having unconfirmed TB. The proportion of children with TB (confirmed and unconfirmed) was 155/273 (56·8%; 95% CI: 50·9; 62·5). The NPV was 55/67 (93·3%; 95% CI: 84·1; 97·4), reaching protocol-defined validation. The TDA sensitivity was 97·4% (95% CI: 93·6; 90·0) with specificity of 47·5 (95% CI: 38·7; 56·4).Interpretation The PAANTHER TDA was validated in CLHIV. Its high sensitivity, excellent feasibility, and short turnaround time to treatment initiation, should allow rapid treatment decision-making and could reduce morbidity and mortality in CLHIV.Funding UNITAID

RR\ID Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

***************************************

Review: This prospective study was performed to validate a previously developed PAANTHER TDA assessment in CLHIV with presumptive TB in 4 countries in Africa. Their aim was to assess its diagnostic performance, feasibility and impact on treatment decisions in diverse clinical, geographic and epidemiological settings in low and middle income countries.

This study has a clear primary and secondary outcome and is well-structured and executed. The methodology used is appropriate to the primary question and it has been performed satisfactorily. Limitations are adequately addressed as they detail the challenges of adopting PAANTHER TDA in routine clinical condition. Results have been interpreted correctly and the conclusions are appropriate to the data presented

There are few comments regarding the write up:

  1. There are few spelling mistakes and grammatical errors that need to be corrected

    Eg: CLHIVHIV has been mentioned in few places

    Discussion:

    • 3rd paragraph – the last sentence “TDA A” and the sentence need to modified and split into 2 sentences to convey the message in

    • Introduction – 3rd paragraph – 3rd sentence-“ part due” to is mentioned thrice

  2. In the Introduction there is repetition of the same sentences in the 2nd (last 2 sentences) and 3rd ( 4th and 5th sentences ) paragraphs

    • “ Hospital – based studies report.... HIV negative children”

  3. Few sentences are incomplete:

    • Methodology – 2nd paragraph last sentence

    • Results- 2nd paragraph 1st sentence

  4. As the sensitivity of PAANTHER TDA is high and specificity is low, they should discuss how this TDA can be modified or used in the clinical setting to improve the specificity .

Comments
0
comment
No comments here
Why not start the discussion?