Table 2.
Advantages and limitations of some of the newest TB diagnostic strategies
| TB diagnostic strategya | Sample type | Advantages | Limitations | References |
|---|---|---|---|---|
| Loop-mediated isothermal amplification or LAMPb (NAAT) | Sputum |
• No need for a thermocycler • High amplification efficiency • High sensitivity and specificity • Low cost; commercial kits available • Easy visualization of results • Simple and rapid, potential POC test |
• Needs extraction of nucleic acids • Specificity relies on good primer design • In some cases, enrichment methods before PCR amplification are needed |
Sahoo et al. [50]; WHO et al. [51] |
| Lateral-flow urine LAM test (LF-LAM) and relatedb | Urine |
• Appropriate when sputum sample is difficult to obtain or in extrapulmonary TB (such as in PLWH) • Fast, POC test • Needs very little amount of sample |
• Low sensitivity • Requires confirmation by other methods • Needs previous clinical suspicion of TB to perform the test • Only detected in people with active TB |
Singhroy et al. [52]; WHO et al. [53] |
| Host-response-based diagnostics: transcriptomics and/or proteomics signature | Blood |
• Prognostic value: prevent TB disease progression, allowing for targeted treatment and/or case investigation • Fast • Potential to be used as POC test |
• Host responses influenced by other TB co-morbidities and host genetic background: one transcriptomic/proteomic signature does not fit all • Needs standardization • Sensitivity and specificity differ among cohorts and between different proposed signatures |
Warsinske et al. [54]; Penn-Nicholson et al. [55••] |
| Whole-genome sequencing (WGS) | Sputum |
• Whole bacterial genome information • Highly accurate • No need for culture, advances in the detection of M.tb directly from clinical samples • Short turnaround time • Multiple applications: diagnostics, epidemiology, DR profiling, M.tb evolution • Identification of new DR mutations • Identification of mixed infections • Portable platforms (e.g. MinION) |
• Need for high sequencing depth to detect mutations (increased cost) • Difficult to implement in low income countries with few resources • Need of well-defined genotypic-phenotypic associations • Complex data analysis: requires bioinformatics expertise |
Soundararajan et al. [56]; Cohen et al. [57] |
aThere are other strategies and related tests such as the Lionex test and the new FujiLAM test not mentioned in the table but included in the main text
bEndorsed by the World Health Organization (WHO)