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

NCT ID: NCT06239337

Last Updated: 2024-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

563 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-06-26

Study Completion Date

2023-12-15

Brief Summary

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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

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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.

Conditions

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Tuberculosis Pediatric Infectious Disease

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Interventions

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Xpert MTB/RIF Ultra in stools and urine

All children with presumptive TB had at least 1 sample collected of respiratory or extrapulmonary specimen (considered as gold standard) and 1 sample of stools and 1 sample of urine. All of them were analyzed with Xpert MTB/RIF Ultra.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

6 Months

Maximum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, Guinea-Bissau

UNKNOWN

Sponsor Role collaborator

Ministry of Health, South Sudan

UNKNOWN

Sponsor Role collaborator

Institute of Tropical Medicine, University of Tuebingen

OTHER

Sponsor Role collaborator

Medecins Sans Frontieres, Spain

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laura Moretó Planas, MD

Role: PRINCIPAL_INVESTIGATOR

MSF OCBA

Locations

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Simao Mendes hospital

Bissau, , Guinea-Bissau

Site Status

Malakal hospital

Malakal, Upper Nile, South Sudan

Site Status

Countries

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Guinea-Bissau South Sudan

References

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Jenkins HE, Yuen CM, Rodriguez CA, Nathavitharana RR, McLaughlin MM, Donald P, Marais BJ, Becerra MC. Mortality in children diagnosed with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis. 2017 Mar;17(3):285-295. doi: 10.1016/S1473-3099(16)30474-1. Epub 2016 Dec 8.

Reference Type BACKGROUND
PMID: 27964822 (View on PubMed)

POSEE Info Note_Pediatric TB diagnosis_Final_17.6.2021.pdf. Taskforce PTOaSEEP. Summary guidance for Microbiological and Clinical Diagnosis of pulmonary tuberculosis among Children: Pediatric TB Operational and Sustainability Expertise Exchange (POSEE) Taskforce, 2021.

Reference Type BACKGROUND

Dodd PJ, Prendergast AJ, Beecroft C, Kampmann B, Seddon JA. The impact of HIV and antiretroviral therapy on TB risk in children: a systematic review and meta-analysis. Thorax. 2017 Jun;72(6):559-575. doi: 10.1136/thoraxjnl-2016-209421. Epub 2017 Jan 23.

Reference Type BACKGROUND
PMID: 28115682 (View on PubMed)

WHO consolidated guidelines on tuberculosis: Module 5: Management of tuberculosis in children and adolescents [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK579387/

Reference Type BACKGROUND
PMID: 35404556 (View on PubMed)

Kay AW, Ness T, Verkuijl SE, Viney K, Brands A, Masini T, Gonzalez Fernandez L, Eisenhut M, Detjen AK, Mandalakas AM, Steingart KR, Takwoingi Y. Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children. Cochrane Database Syst Rev. 2022 Sep 6;9(9):CD013359. doi: 10.1002/14651858.CD013359.pub3.

Reference Type BACKGROUND
PMID: 36065889 (View on PubMed)

Atherton RR, Cresswell FV, Ellis J, Kitaka SB, Boulware DR. Xpert MTB/RIF Ultra for Tuberculosis Testing in Children: A Mini-Review and Commentary. Front Pediatr. 2019 Feb 28;7:34. doi: 10.3389/fped.2019.00034. eCollection 2019.

Reference Type BACKGROUND
PMID: 30873392 (View on PubMed)

Vessiere A, Font H, Gabillard D, Adonis-Koffi L, Borand L, Chabala C, Khosa C, Mavale S, Moh R, Mulenga V, Mwanga-Amumpere J, Taguebue JV, Eang MT, Delacourt C, Seddon JA, Lounnas M, Godreuil S, Wobudeya E, Bonnet M, Marcy O. Impact of systematic early tuberculosis detection using Xpert MTB/RIF Ultra in children with severe pneumonia in high tuberculosis burden countries (TB-Speed pneumonia): a stepped wedge cluster randomized trial. BMC Pediatr. 2021 Mar 20;21(1):136. doi: 10.1186/s12887-021-02576-5.

Reference Type BACKGROUND
PMID: 33743621 (View on PubMed)

Kabir S, Rahman SMM, Ahmed S, Islam MS, Banu RS, Shewade HD, Thekkur P, Anwar S, Banu NA, Nasrin R, Uddin MKM, Choudhury S, Ahmed S, Paul KK, Khatun R, Chisti MJ, Banu S. Xpert Ultra Assay on Stool to Diagnose Pulmonary Tuberculosis in Children. Clin Infect Dis. 2021 Jul 15;73(2):226-234. doi: 10.1093/cid/ciaa583.

Reference Type BACKGROUND
PMID: 32421765 (View on PubMed)

Sun L, Liu Y, Fang M, Chen Y, Zhu Y, Xia C, Jia J, Quan S, Wang Y, Tian X, Shi Y, Duan L, Shi X, Liao Q, Wan C, Shen A. Use of Xpert MTB/RIF Ultra assay on stool and gastric aspirate samples to diagnose pulmonary tuberculosis in children in a high-tuberculosis-burden but resource-limited area of China. Int J Infect Dis. 2022 Jan;114:236-243. doi: 10.1016/j.ijid.2021.11.012. Epub 2021 Nov 10.

Reference Type BACKGROUND
PMID: 34774781 (View on PubMed)

Moreto-Planas L, Mahajan R, Fidelle Nyikayo L, Ajack YBP, Tut Chol B, Osman E, Sangma M, Tobi A, Gallo J, Biague E, Goncalves R, Rocaspana M, Medina C, Camara M, Flevaud L, Ruby LC, Belard S, Sagrado MJ, Molina I, Llosa AE. Xpert-Ultra Assay in Stool and Urine Samples to Improve Tuberculosis Diagnosis in Children: The Medecins Sans Frontieres Experience in Guinea-Bissau and South Sudan. Open Forum Infect Dis. 2024 May 2;11(5):ofae221. doi: 10.1093/ofid/ofae221. eCollection 2024 May.

Reference Type DERIVED
PMID: 38798893 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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MSF18115

Identifier Type: -

Identifier Source: org_study_id

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