Combining TBDx with Other New Detection Technologies

In recent years the rapid advancement of new diagnostic technology has aided greatly in the fight against the spread of tuberculosis.    Molecular diagnostics and line probe assay technologies detect Mycobacterium by exploring the DNA present in sputa.  While more sensitive than smear microscopy, their most significant benefits are improved diagnostic speed and the ability to determine drug resistance to rifampicin (a first-line drug used to treat TB), which often indicates multi-drug resistant TB.

Although these technologies are a leap forward in TB detection they have significant deployment drawbacks. These tools require a sophisticated, state-of-the-art clinical environment replete with power source redundancy. Their operation requires highly trained professionals. Each technology requires expensive equipment and an ongoing commitment to test-specific consumables.  For example, detecting TB in a molecular diagnostic test will cost approximately $20.00 per cartridge. Currently this price is subsidized.  Though this molecular test is accurate, it represents a major economic commitment for developing nations.  The cost of sputum smear microscopy is approximately $2.40 to $5.00 per test.

Can a developing country, economically burdened with multiple societal needs (i.e. telecommunications, energy, housing, clean water, food, etc.), afford to pay an additional $17.50 per test to detect more TB cases?

Providers of these new technologies have materially subsidized the required equipment and the consumables to make them more affordable. However, no subsidy is inexhaustible.  Pricing, at some point, must reflect the true cost of the materials.  Moving forward, under the existing financial constraints, many international TB experts believe the best solution may be to deploy the best combination of technologies that provide the most accurate diagnoses, detecting the greatest number of TB positive cases, at the lowest cost-per-positive test.

Can TBDx, if combined with other technologies, provide higher sensitivity rates (detection), acceptable specificity rates (false positive), and a cost-per-positive case detection that places a lower cost burden on government agencies? Will these combinations find more TB positive cases, at a cost that includes testing for drug susceptibility, similar to costs in place today?  Our current testing and analysis are helping us to answer these questions. Let’s begin by reviewing the performance characteristics of each diagnostic approach

Diagnostic Approach Detection Rate Per Test Cost
Sputum Microscopy 50.00% ~$2.40
Molecular Tests 87.50% ~$20.00
TBDx 86.50% ~$2.50

For our analysis we used 181 slides provided by the National Health Laboratory Services of South Africa. The slide set included 104 negative and 74 positive cases, which were confirmed by culture. The results of this relatively small study provide some encouraging numbers. Analytical Assumptions:

  1. All positive cases detected must be tested for drug susceptibility.  In the example below, if sputum microscopy identified 37 cases (50% of 74; costing approximately $2.40 per test), these same 37 cases require drug susceptibility testing (costing approximately $20.00 per test).
  2. Total Cost to Process = 181 cases processed in three configurations: (i) smear microscopy + molecular testing, (ii) molecular testing only, or, (iii) TBDx + molecular testing.
  3. Cost-Per-Positive Case = Total Cost to Process divided by the total number of positive cases detected and confirmed.
Diagnostic Approach Positive/False Positive Cases Total Cost to Process Cost Per Positive Test
Sputum Microscopy

37/0

$1,174.40

$32.00

Molecular / DNA

65/0

$3,620.00

$56.00

TBDx

64/32

$2,046.70

$32.00

By combining technologies, first using TBDx to screen slides for the most probable positive cases, and then using molecular testing to confirm these candidates and assess drug susceptibility, 27 more positive cases were found at a cost per positive case that is the same as routine sputum smear microscopy.

Increasing the size of the analytical database and the accumulation of a larger set of statistics is needed before the medical and scientific community will be satisfied with the conclusions. We are very encouraged to see that TBDx, when combined with another diagnostic technology, can deliver on the promise of greater detection at a lower cost per positive case.

We had an opportunity to discuss these results in South Africa with the Director of the Center for Tuberculosis, a Senior Program Officer with the Bill & Melinda Gates Foundation, and the Deputy-CEO of The Aurum Institute.   The next blog posting will report on our activities while in South Africa, outcomes of our meetings and demonstrations, and next steps as we move towards the deployment of TBDx in South Africa.

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