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Towards Accurate Point-of-Care Tests for Tuberculosis in Children
Nina Vaezipour1,2, Nora Fritschi1, Noé Brasier3,4
1Mycobacterial and Migrant Health Research Group, University Children's Hospital Basel, Department for Clinical Research, University of Basel, 4056 Basel, Switzerland.
Insights
Accurate point-of-care tests (POCTs) are crucial for diagnosing childhood tuberculosis (TB), a disease often missed in young children. Advances in molecular diagnostics and imaging offer new hope for early detection and improved outcomes.
Area of Science:
- * Pediatric infectious diseases
- * Diagnostic technology development
- * Global health
Background:
- * Childhood tuberculosis (TB) has a significant case detection gap, with an estimated 69% of cases missed in children under five.
- * This gap is attributed to the paucibacillary nature of pediatric TB and challenges in obtaining sputum samples from children.
- * There is a critical need for accurate and accessible point-of-care tests (POCTs) to reduce TB-related morbidity and mortality in children.
Purpose of the Study:
- * To review the current landscape and future directions of point-of-care tests (POCTs) for diagnosing childhood tuberculosis (TB).
- * To highlight advancements in molecular diagnostics, imaging, and emerging technologies for TB detection in children.
- * To identify challenges in the development and implementation of TB POCTs.
Main Methods:
- * Review of recent advancements in TB POCTs, including molecular amplification techniques (LAMP, PCR-based GeneXpert), biomarker detection (urine LAM), and imaging modalities (POCUS).
- * Discussion of emerging technologies such as AI-integrated imaging interpretation, portable radiography, robotics-assisted ultrasound, and omics-based blood tests.
- * Analysis of implementation challenges, including sample accessibility, differentiation of infection from disease, and user acceptance.
Main Results:
- * Several POCTs are available or in development, including molecular tests for respiratory/gastric samples, urine LAM tests, and POCUS.
- * AI is enhancing interpretation of imaging, with portable radiography and robotics-supported ultrasound in trials.
- * Omics-based blood tests show future potential but are distant from POCT format.
Conclusions:
- * Significant progress has been made in developing diverse POCTs for childhood TB, addressing limitations of traditional methods.
- * Key challenges remain in standardizing sample access, distinguishing TB infection from active disease, and ensuring acceptance of new strategies.
- * Continued innovation and strategic implementation are essential to bridge the diagnostic gap and improve outcomes for children with TB.
Abstract:
In childhood tuberculosis (TB), with an estimated 69% of missed cases in children under 5 years of age, the case detection gap is larger than in other age groups, mainly due to its paucibacillary nature and children's difficulties in delivering sputum specimens. Accurate and accessible point-of-care tests (POCTs) are needed to detect TB disease in children and, in turn, reduce TB-related morbidity and mortality in this vulnerable population. In recent years, several POCTs for TB have been developed. These include new tools to improve the detection of TB in respiratory and gastric samples, such as molecular detection of Mycobacterium tuberculosis using loop-mediated isothermal amplification (LAMP) and portable polymerase chain reaction (PCR)-based GeneXpert. In addition, the urine-based detection of lipoarabinomannan (LAM), as well as imaging modalities through point-of-care ultrasonography (POCUS), are currently the POCTs in use. Further to this, artificial intelligence-based interpretation of ultrasound imaging and radiography is now integrated into computer-aided detection products. In the future, portable radiography may become more widely available, and robotics-supported ultrasound imaging is currently being trialed. Finally, novel blood-based tests evaluating the immune response using "omic-"techniques are underway. This approach, including transcriptomics, metabolomic, proteomics, lipidomics and genomics, is still distant from being translated into POCT formats, but the digital development may rapidly enhance innovation in this field. Despite these significant advances, TB-POCT development and implementation remains challenged by the lack of standard ways to access non-sputum-based samples, the need to differentiate TB infection from disease and to gain acceptance for novel testing strategies specific to the conditions and settings of use.
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