Stool Processing Kit (SPK) Evaluation for Paediatric TB
Study Details
Study Description
Brief Summary
This is a prospective, multicentre cohort study in which the accuracy and the diagnostic yield of the Stool Processing Kit (SPK) in combination with Xpert Ultra MTB/RIF (Ultra) on stool samples will be assessed using a microbiological reference standard and a composite reference standard among children with signs and symptoms of pulmonary tuberculosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
FIND and partners have developed a simple Stool Processing Kit (SPK) that will enable processing of large numbers of stool samples, removal of PCR inhibitors which can be used at level 1 health facilities in low and middle income countries.
The SPK is not a diagnostic kit as such but rather a sample processing method. This study aims to determine the sensitivity and specificity of Xpert Ultra MTB/RIF (Ultra) combined with SPK for TB detection using microbiological confirmation on respiratory specimens (defined as: sputum, nasopharyngeal aspirate, and/or gastric aspirate) as the reference standard. We will further evaluate operational characteristics, including implementation considerations that will be needed for the potential roll out of the SPK.
Additionally, a comparison of the performance of the SPK with up to two other cnetrifuge-free stool processing methods will be done on the same stool samples. The first is a method developed by researchers at the KNCV Tuberculosis Foundation (Single One Step Stool) which does not require any additional reagents other than the Ultra Sample Reagent. The second is a method developed by the Paediatric Asian African Network for Tuberculosis and HIV Research (PAANTHER) group, the Optimized Sucrose Flotation method. Another diagnostic candidate, the urine Fujifilm SILVAMP TB LAM (FujiLAM) test will be assessed during the study.
Therefore, if the sensitivity of any of these tests is shown to be promising this may support further research and provide other alternatives to respiratory samples.
Study Design
Outcome Measures
Primary Outcome Measures
- Sensitivity and specificity of a single Ultra/SPK using microbiological confirmation on respiratory specimens as reference standard [2 months]
Point estimates of sensitivity and specificity with 95% confidence intervals, using microbiological confirmation including two cultures and two Xpert MTB/RIF Ultra in respiratory samples
Secondary Outcome Measures
- Diagnostic accuracy of a single Ultra/SPK using the NIH classification as reference standard [2 months]
Point estimates of sensitivity and specificity with 95% confidence intervals, using the Revised Classification NIH classification for diagnostic evaluation studies in children (S. Graham et al.; CID)
- Diagnostic accuracy of a single Ultra/SPK for RIF resistance detection [2 months]
Point estimates of sensitivity and specificity with 95% confidence intervals, with phenotypic MGIT DST on respiratory specimens as reference standard
- Additional yield (increase in sensitivity) of a 2nd Ultra/SPK [2 months]
Sensitivity of a 2nd sampling on the same stool with Ultra/SPK for TB and RIF resistance detection using the different reference standards (Outcome 1 & 2)
- Diagnostic accuracy of a single Ultra/SPK for TB detection per subgroup [2 months]
Sensitivity and specificity of Ultra/SPK by sample, by site, by smear grade, by HIV status, by TB history, by stool consistency, and by age using the different reference standards (Outcome 1 & 2)
- Diagnostic accuracy of additional interventions: Simple One Step (SOS), Optimized Sucrose Flotation (OSF) and Fujifilm SILVAMP TB LAM [2 months]
Sensitivity and specificity, by intervention using the different reference standards (Outcome 1 & 2) and by subgroup (Outcome 5)
- Feasibility and user appraisal of the different stool processing methods [6 months]
Assessment of user appraisal on ease of use and potential implementation of stool processing methods using a standardized questionnaire
Eligibility Criteria
Criteria
Inclusion Criteria:
Children of 14 years of age or younger + written parent/guardian consent + child assent based on age and national ethical guidelines + willingness to have a study follow-up visit
- [clinical suspicion of active pulmonary TB* (irrespective of extra-pulmonary disease) OR microbiological confirmation of active TB disease referred from non-study health facilities].
*CXR suggestive of TB, or weight loss or failure to thrive within 3 months not solely due to inadequate feeding, or another non-TB cause, or any cough with loss of weight, or cough alone >=14 days, or persistent (>1 week) and unexplained fever
Exclusion Criteria:
Anti-TB treatment for >5 days or any antibiotic with anti-mycobacterial activity within 60 days prior to enrolment including children on IPT, OR (confirmed) extrapulmonary TB only
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | All India Institute of Medical Sciences | New Delhi | India | ||
| 2 | KEM Hospital Research Centre | Pune | India | ||
| 3 | University of Cape Town Lung Institute | Cape Town | South Africa | ||
| 4 | Mulago Hospital | Kampala | Uganda |
Sponsors and Collaborators
- Foundation for Innovative New Diagnostics, Switzerland
- Mulago Hospital, Uganda
- University of Cape Town Lung Institute
- University of California, San Francisco
- All India Institute of Medical Sciences, New Delhi
- KEM Hospital Research Centre
Investigators
- Study Director: Morten Ruhwald, MD, Find
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 7210-07-2/1