Evaluation of Xpert MTB/RIF Ultra in Stools and Urine to Improve Tuberculosis Diagnosis in Children

Completed

• Conditions: Tuberculosis; Pediatric Infectious Disease

• Registration Number: NCT06239337
• Lead Sponsor: Medecins Sans Frontieres, Spain

Brief Summary

Tuberculosis (TB) diagnosis in children is challenging in low and middle-income countries where access to TB culture and X-ray is limited. More than half cases of childhood TB remain undiagnosed every year. A delay in TB diagnosis can lead to an increase in preventable morbidity and mortality.

This study aims to provide evidence on the diagnostic accuracy of Xpert MTB/RIF Ultra in stools and urine for TB diagnosis in children.

Detailed Description

This multicentric cross-sectional study took place at Malakal hospitals from November 2019 to December 2023, and at Simão Mendes National Hospital between July 2019 and April 2020. Children with presumptive TB underwent clinical and laboratory evaluation.

Study Population, Clinical, and Laboratory procedures Children 6 months to 15 years were considered presumptive TB cases if they showed persistent cough for more than 2 weeks, unexplained fever for more than 1 week or signs of extrapulmonary TB such as: gibbous deformity of the spine, lymphadenopathy, subacute meningitis, distended abdomen with ascites, diarrhoea for more than two weeks, painless enlarged joints, or pleural effusion.

Presumptive TB cases were also identified after a week of inpatient admission, characterized by low weight gain despite nutritional treatment, persistent pneumonia or cough despite adequate antibiotic therapy, persistent fever (\>38ºC), and persistent or aggravated fatigue. Patients were screened for TB based on their medical history and clinical presentation, including TB contacts, past TB treatment or known HIV infection; physical examination was conducted in all patients and included relevant anthropometrics (Mid-Upper-Arm Circumference (MUAC), Weight-for-height z scores (WHZ) and/or body mass index (BMI) for age z scores). All patients with unknown HIV status were tested for HIV and were tested for at least one pulmonary or extrapulmonary sample (considered as gold standard), and one stool and one urine samples.

All patients underwent a diagnostic evaluation and were included in three different categories: Confirmed TB (patients who had an Xpert MTB/RIF Ultra positive in one of the samples); Unconfirmed TB (clinical TB diagnosis without microbiological confirmation); Unlikely TB (alternative diagnosis with adequate response to alternative treatments, and TB treatment not started).

Respiratory samples included naso-pharyngeal aspirate, gastric lavage, or spontaneous sputum; extrapulmonary samples included lymph node puncture, pus aspirate, and ascetic, pleural, or cerebrospinal fluids. Stools and urine were collected from all patients as well. All specimens were kept between 2 and 8ºC until processed, which was done within 24 hours. Xpert MTB/RIF Ultra was performed in all collected sample.

In Malakal, MSF supported the TB program in collaboration with the Ministry of Health (MoH) all along the study. In Bissau, all results were communicated to MoH who were responsible for treatment initiation.

Study Timeline

• Study Start: 2019-06-26
• Primary Completion: 2023-06-01
• Study Completion: 2023-12-15
• Status Verified: 2024-01
• Study First Submitted: 2024-01-15
• Study First Submitted QC: 2024-01-25
• Last Update Submitted: 2024-01-25
• Study First Posted: 2024-02-02
• Last Update Posted: 2024-02-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 563

Inclusion Criteria

• Any child from 6 months of life to 15 years old
• TB suspected according to diagnostic criteria
• Informed consent provided by legal responsible or companion

Exclusion Criteria

• Patients who have received TB treatment for > 1 day in the last 3 months
• Patients not producing stools or urine during period of admission and prior to starting TB drugs

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in presumptive TB pediatric cases in comparison to Xpert MTB/RIF Ultra in respiratory/extrapulmonary sample	Through study completion, up to 60 months	To determine the sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in presumptive TB pediatric cases in comparison to Xpert MTB/RIF Ultra in respiratory/extrapulmonary sample

Secondary Outcome Measures

Name	Time	Method
To determine sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in subpopulations: HIV/not HIV, SAM/no SAM, <5 years old vs. 5 or more years old.	Through study completion, up to 60 months	To determine sensitivity and specificity of Xpert MTB/RIF Ultra in stool and urine samples in subpopulations: HIV/not HIV, SAM/no SAM, \<5 years old vs. 5 or more years old.
To determine the added diagnostic yield of Xpert MTB/RIF Ultra in stool and urine samples when gold standard is negative	Through study completion, up to 60 months	To determine the added diagnostic yield of Xpert MTB/RIF Ultra in stool and urine samples when gold standard is negative

Trial Locations

Locations (2)

Simao Mendes hospital; 🇬🇼 Bissau, Guinea-Bissau

Malakal hospital; 🇸🇸 Malakal, Upper Nile, South Sudan