This is the first post in a three-part blog series on smear microscopy – it’s continuing role in TB diagnostics, how it can be improved, and how it can be combined with GeneXpert and other molecular diagnostic technologies to increase case findings, while effectively managing ever-tightening laboratory budgets.
Smear Microscopy: It’s Near Future
Smear microscopy has been an essential laboratory diagnostic tool for more than 130 years. Will it maintain this status into the future? In an ever-increasing digital world, where technologies get faster, smaller, cheaper and more distributed, it is hard to imagine smear microscopy will be unaffected. Evidence abounds in the growth of molecular diagnostics and the funding of new technologies and research initiatives exploring how to develop point-of-care technologies using iPhone cameras, CMOS sensors, and biomarkers. An exciting glimpse of the future can be seen at Matternet. Though this may be a transportation system for drug delivery, could it not be used to deliver sputum specimens to TB laboratories, too? So, it is a fair question to ask how a 130 year-old smear microscopy technology remains relevant in this evolving digital world. Our answer is that it will remain relevant by embracing the digital world.
We are often asked “Why would you apply your digital analysis technology to microscopy when it appears that molecular diagnostics is the future?” Our viewpoint continues to be that smear microscopy holds multiple advantages and is a perfect fit for our Signature Mapping™ digital analysis technology. Costs are relatively low. There is an extensive body of scientific evidence surrounding it. The laboratory infrastructure is in place; it is used for other applications, not just tuberculosis. Human resources are available that can be quickly trained to be productive and efficient laboratory technicians. The primary initiative should not be to abandon the technology, rather it should be to leverage these existing advantages and identify how this increasing digital world can improve its’ performance.
We are not alone in this opinion. In an article appearing in the most recent edition of Public Health Action, entitled “For Better or Worse, Smear Microscopy is Here to Stay,” an editorial makes the same case. Commenting on a recent Pakistani project studying the effectiveness of GeneXpert in diagnosing TB, Dr. Richard Lumb, Chief Medical Scientist with the Australia National TB Reference Lab and member of the GLI Supranational TB Reference Laboratory notes that:
Although this much maligned diagnostic tool may miss nearly half of all cases, an optimized and quality assured smear microscopy network can approach ‘point-of-care testing’ for all TB suspects…..National TB programmes in high burden settings need both smear microscopy and Xpert MTB/RIF.
Something similar can be gleaned from the research article, “Comparison of Laboratory Costs of Rapid Molecular Tests and Conventional Diagnostics for Detection of Tuberculosis and Drug-Resistant Tuberculosis in South Africa.” In an excellent study of cost comparisons between molecular and conventional diagnostics the authors present clear evidence that costs are becoming more comparable. Molecular tests are especially efficient in high HIV settings. In the concluding remarks it is noted:
Overall, laboratories and TB programs must balance costs with performance characteristics and the need for rapid results. Intensive implementation of molecular assays as an addition to conventional automated liquid culture and DST may lead to significant laboratory cost increases; selective implementation of molecular assays could be considered for some settings.
Supporting our opinions and those noted by TB experts, that smear microscopy will remain a diagnostic alternative, are the barriers that exist to the full deployment of molecular tests in peripheral laboratories. In a recent edition of the European Respiratory Journal a research article was published entitled, “Are Peripheral Microscopy Centres Ready for Next Generation Molecular Tuberculosis Diagnostics,” that presents a compelling graphic charting the characteristics of peripheral microscopy centers in 22 high-burdened countries. The study explored the environmental conditions necessary to deploy the latest molecular tests. The authors concluded:
When asked about the biggest challenges for implementing molecular assays in these peripheral microscopy centers the three most commonly cited responses were lack of a stable water supply, harsh weather conditions and lack of skilled labor. Unless upgraded and better staffed, existing microscopy centers will find it challenging to implement Xpert MTB/RIF as well as newer NAATs, especially since they require manual sputum processing and DNA extraction.
Each of these three research studies illustrate that the pace of diagnostic change in laboratories may be slower than first thought, though it is inevitable that better diagnostic technologies will find its way to the point-of-care. Until then smear microscopy will continue to perform a valuable diagnostic service. In the meantime, how can it be improved?
We will explore that question in our second post later this week.