Impact of Systematic Early Tuberculosis Detection Using Xpert MTB/RIF Ultra in Children With Severe Pneumonia in High Tuberculosis Burden Countries (TB-Speed Pneumonia)

Summary

Despite progress in reducing tuberculosis (TB) incidence and mortality in the past 20 years, TB is a top ten cause of death in children under 5 years worldwide. However, childhood TB remains massively underreported and undiagnosed, mostly because of the challenges in confirming its diagnosis due to the paucibacillary nature of the disease and the difficulty in obtaining expectorated sputum in children.

Pneumonia is the leading cause of death in children under the age of 5 years worldwide. There is growing evidence that, in high TB burden settings, TB is common in children with pneumonia, with up to 23% of those admitted to hospital with an initial diagnosis of pneumonia later being diagnosed as TB. However, the current World Health Organization (WHO) standard of care (SOC) for young children with pneumonia considers a diagnosis of TB only if the child has a history of prolonged symptoms or fails to respond to antibiotic treatments. Hence, TB is often under-diagnosed or diagnosed late in children presenting with pneumonia.

In this context, the investigators are proposing to assess the impact on mortality of adding the systematic early detection of TB using Xpert MTB/RIF Ultra, performed on NPAs and stool samples, to the WHO SOC for children with severe pneumonia, followed by immediate initiation of anti-TB treatment in children testing positive on any of the samples.

TB-Speed Pneumonia is a multicentric, stepped wedge diagnostic trial conducted in six countries with high TB incidence: Cote d'Ivoire, Cameroon, Uganda, Mozambique, Zambia and Cambodia.

The sub-study on Covid-19 will assess the prevalence and impact of the Covid-19 in young children hospitalized with severe pneumonia. The sub-study findings are expected to guide policy makers and clinicians on potential specific screening and management measures for these vulnerable groups of children. They are also key to analysing TB-Speed Pneumonia results on mortality in a context of the Covid-19 outbreak and to take into consideration SARS-CoV-2 infection status in the main study analysis.

Conditions

• Tuberculosis
• Severe Pneumonia
• Covid19

Interventions

DIAGNOSTIC_TEST

Xpert MTB/RIF Ultra (Ultra)

The intervention will consist of the WHO standard of care for children with severe pneumonia plus the study intervention consisting in rapid detection of TB on the day of hospital admission using the Ultra assay performed on 1 NPA and 1 stool sample. The sample flow will be organised to reduce time-to-results to 3 hours. Ultra will be performed at the hospital laboratory using a standard GeneXpert device, or implemented directly inward using a one-module, battery-operated GeneXpert device (G1 Edge). Drugs will be available at the inpatient level to enable immediate initiation of TB treatment, as soon as a positive Ultra result is available.

Sponsors & Collaborators

• UNITAID

  collaborator OTHER

• Institut National de la Santé Et de la Recherche Médicale, France

  lead OTHER_GOV

Principal Investigators

• Olivier Marcy, MD, PhD · University of Bordeaux, France

• Maryline Bonnet, MD, PhD · Institut de Recherche pour le Développemnt (IRD) Montpellier, France

• Eric Wobudeya, MD, PhD · MU-JHU Care Ltd, Kampala, Uganda

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

2 Months

Max Age

59 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-03-20

Primary Completion

2021-06-30

Completion

2021-06-30

Countries

• Cambodia
• Cameroon
• Côte d’Ivoire
• Mozambique
• Uganda
• Zambia

Study Locations