Table 1.
Status of the available AlereLAM, FujiLAM, and sputum-based tuberculosis (TB) diagnosis vs. biomarker target product profile (TPP) [4]. WHO: World Health Organization; PLHIV: people living with HIV; TPP: Target product profile; CRS: Composite reference standard; IVD: in vitro diagnostic; “✓” indicates that the TPP minimal criteria is met; “x” indicates that the TPP minimal criteria is not met; “?” indicates that it is currently unclear whether the TPP criteria is met.
| WHO Target Product Profiles (TPPs) Minimal Criteria: “Biomarker Test” | Abbott Determine TB LAM Ag (AlereLAM) |
Fujifilm SILVAMP TB LAM Assay (FujiLAM) | Sputum-Based TB Diagnosis (Smear Microscopy; Xpert MTB/RIF; Xpert MTB/RIF Ultra) |
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|---|---|---|---|---|---|---|---|
| Price per test (ex-works) | <US$6.00 | ✓ | US$3.00–3.50 [17] (likely cost-effective among hospitalized HIV-postive patients) |
? | Fujifilm has not yet released information on the price (initial cost-effectiveness modelling data presented [18]) | x | Xpert MTB/RIF US$9.98 [19] |
| Regulatory requirements and availability | Registered for in vitro diagnostic (IVD) use | ✓ | CE-IVD marked IVD WHO recommendation (Table 2) On the market |
? | CE-IVD marked IVD WHO evaluation expected Q4/2020 Market entry expected Q1/2021 [20] |
✓ | CE-IVD marked IVD Several WHO recommendations On the market |
| Equipment | Ideally instrument free and small, portable, or handheld, <1 kg, <US$500 instrument acceptable | ✓ | Instrument free | ✓ | Instrument free | x | US$17,500.00 [19] (GeneXpert platform plus laptop) |
| Sensitivity in HIV positive patients (independent of CD4 count) | ≥65% (not specifically defined for HIV-positives in the TPP) |
x | 42% [21] | ✓ | 70.7% [22] | ✓ | 90% (Xpert MTB/RIF Ultra) [23] 77% (Xpert MTB/RIF) [23] 47% (Microscopy) [24] |
| Sensitivity in HIV negative patients | ≥65% | x | 18% [25] | ? | No information published. Studies ongoing. | ✓ | 91% (Xpert MTB/RIF Ultra) [23] 90% (Xpert MTB/RIF) [23] |
| Specificity | ≥98% | ? | 96–98% against CRS [26] (likely meeting the target as specificity might be underestimated due to limitations of the reference standard) |
? | 95.7% against CRS [27] (likely meeting the target as specificity might be underestimated due to limitations of the reference standard) |
✓ | 96% (Xpert MTB/RIF Ultra) [23] 98% (Xpert MTB/RIF) [23] 98% (Microscopy) [24] |
| Day 1 diagnostic yield in HIV-positive inpatients (TB patients diagnosed on the first day they present) | No target defined in TPP | 43.3% [27] | 64.5% [27] | 26.2% (Xpert MTB/RIF) [27] 19.1% (Microscopy) [27] |
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|
Outcome/ /
mortality impact |
No target defined in TPP | Mortality impact shown in hospitalized PLHIV but not in more general populations. A positive result is associated with increased risk of mortality [28,29,30] | No impact studies available. A positive result is associated with increased risk of mortality [31,32] | Unclear | |||
| Sample type | Non-sputum | ✓ | Urine | ✓ | Urine | x | Sputum |
| Time-to-result | <60 min | ✓ | 25 min | ✓ | 50–60 min | x | 100 min (Xpert MTB/RIF and Xpert MTB/RIF Ultra) |
| Number of steps | Limited number of steps, no precise measuring | ✓ | 2 steps | ✓ | 5 steps | x | Xpert MTB/RIF and Xpert MTB/RIF Ultra: 11 steps Microscopy: >10 steps |
| Setting and infrastructure needs | Primary health-care clinics with lab or microscopy center or higher levels | ✓ | Simple to use lateral flow assay | ✓ | Simple to use lateral flow assay | x | Laboratory required Electricity required Equipment susceptible to dust and shock |