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Differential Diagnostics: What do PCR reactions and cell phones have in common?


Hello again from Hyderabad! Last time we talked about the purchasing power of patients in low income countries and what this meant for drug prices. With this edition of the blog I’d like to take one step back from treatment and discuss diagnosis. During a few of our recent stops in Hyderabad we’ve seen the utility and the need for genetic based testing. Two prime examples have been:

  1. Diagnosis and resistance patterns of tuberculosis
  2. Monitoring of viral loads in HIV.

Each of these tests are simple PCR reactions that can be highly sensitive and specific.  In most cases TB detection depends on prepared slides with examination under a microscope followed by the gold standard, bacterial cultures. Despite being the gold standard culturing for TB takes six weeks to result. The slides are faster but do take significant training. So what is the promise of genetic based testing? Yesterday I watched a technician take a potential TB sputum sample, place it in a tube of buffer solution and then transfer this liquid to a cartridge containing all the other reagents needed for the reaction. In 90 minutes we knew the patient had multi-drug resistant TB. For those not familiar with molecular techniques the steps involved were not much beyond preparing a cup of tea. Unlike the variability in steeping your morning chai this method has been shown to be quite sensitive and specific for both the diagnosis of TB and also the detection of multi-drug resistant TB (1). Due to cost this test is only used in cases of suspected resistance, but given the data I could envision this being a primary diagnostic approach.

In the case of patients with HIV measuring the viral load (the amount of HIV present) is critical to disease monitoring. This is because as the disease progresses or becomes resistant to treatment the viral load will increase weeks ahead of a drop in CD4 count. Yet cost has again gotten in the way. At one of our stops today the patient would have to pay a bill of 600 rupees ~$9 for CD4 testing alone. CD4 testing with viral load is 3000 rupees or $45. Recent price analyses have shown that with high volume use and new techniques for collection this price point can and should drop (2). Further, getting patients on the right treatment sooner or conversely switching patient’s regimen unnecessarily can have a big impact on the use of second line agents and ultimately treatment costs (3).

Genotyping has me particularly excited because it has a much wider potential. Low resources settings have continued to struggle for a lack of of qualified pathologists and those that they do have are often under resourced in regards to sub-specialty training, equipment and adoption of new markers of disease. Consider cancer which are now sub-classified based upon mutations of specific genes rather than simply the structural patterns of the biopsied tissue. If we can detect gene changes in tuberculosis why not cancer cells? This would allow for a much more targeted approach to cancer therapy (i.e. small molecule inhibitors, immunotherapy) that go after the specific mutation change. This would subsequently save the patient the ravages of chemotherapy. If one thinks that the side effects of chemotherapy are bad in U.S. think what it is like in low resource settings, which often lack the capacity to support side effects. The jump to genetic testing in place of advanced pathology could be what the cell phone was to land lines in the same settings. Despite my optimism I do fear that as these technologies develop their value and licensing could lead to continued cost limitations. Therefore, given genetic testing’s great promise in low resource settings, we must ensure that as these technologies develop they are developed to be accessible and functional where they are needed the most.


Eddie Briercheck is a PGY-2 at Boston Medical Center and a member of the Global Health Pathway.You can follow him on twitter @eddiebriercheck or search #BMCglobalhealth to learn how the rest of the team is doing. And please tweet us your thoughts, questions and culinary suggestions.




(1) Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid Molecular Detection of Tuberculosis and Rifampin Resistance. N Engl J Med. 2010;363:1005–15.


(3) Rewari BB et al. Evaluating patients for second-line antiretroviral therapy in India: the role of targeted viral load testing. Journal of Acquired Immune Deficiency Syndromes, advance online publication, October 6, 2010

This entry was posted in BMC.
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