Clinical trial NCT06239337: Evaluation of Xpert MTB/RIF Ultra in Stools and Urine to Improve Tuberculosis Diagnosis in Children
Official title: Evaluation of Xpert MTB/RIF Ultra in Stools and Urine to Improve Tuberculosis Diagnosis in Children
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Pediatric Infectious Disease
Keywords: Pediatric TB
Xpert MTB/RIF Ultra
Stools
Urine
Lead sponsor: Medecins Sans Frontieres, Spain
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Guinea-Bissau
name: Ministry of Health, South Sudan
name: Institute of Tropical Medicine, University of Tuebingen
First posted: 2024-02-02
Enrollment: 563
Sex: ALL
Minimum age (years): 6
Maximum age (years): 15
Standard ages: CHILD
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The research population are children with presumptive TB at Malakal hospitals (South Sudan) at Simão Mendes National Hospital (Guinea-Bissau).

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Through study completion, up to 60 months
Secondary outcomes:
measure: 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.
timeFrame: Through study completion, up to 60 months
measure: To determine the added diagnostic yield of Xpert MTB/RIF Ultra in stool and urine samples when gold standard is negative
timeFrame: Through study completion, up to 60 months
Other outcomes:
Locations:
city: Bissau
country: Guinea-Bissau
facility: Simao Mendes hospital
city: Malakal
country: South Sudan
facility: Malakal hospital
state: Upper Nile
Study officials:
affiliation: MSF OCBA
name: Laura Moretó Planas, MD
role: PRINCIPAL_INVESTIGATOR
References:
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