Back to basics. TB screening

Clinical Brief – September 1st

The Brief

TB (or tuberculosis) is a potentially lethal infection which is particularly serious for patients living with HIV.

To circumvent the high cost of genetic tests used to screen for active TB, a new study showed that a simple finger-prick test for CRP may do the job at less than a fifth the cost.

What’s the deal with TB?

TB is the leading infectious cause of death around the world, and it’s devastating for people with HIV.

According to the WHO, TB killed 400k people with HIV in 2015, accounting for a third of all HIV-related deaths that year.

Why don’t we screen for TB?

We do. In fact, the WHO’s target for an effective screen calls for a test that’s at least 90% sensitive and 70% specific.

High sensitivity means that the risk of a false negative is low. The relatively high specificity means that a positive test is likely not a false positive and wouldn’t need a second confirmation test for most patients.

For people with HIV, no test or algorithm meets these targets. Purely screening by looking for symptoms of active TB is highly sensitive, but has sub par specificity. To deal with the false positives, a genetic test called Genexpert is needed.

Genexpert can take up to 2 hours and cost ~$10 USD per test. Multiplied by a factor of hundreds of thousands, the financial and time constraints can be prohibitive for countries with limited resources. I won’t bother counting the costs of owning the $17k USD machine that runs these tests.

This was why an international group of researchers led by Dr Christina Yoon of San Francisco, US, ran this study to look for a better test.

Does the CRP test work?

Dr Yoon’s group honed in on a simple biomarker, CRP (short for C-reactive protein). It’s a commonly used marker for inflammation. And while it’s not unique to TB, it has “consistently shown higher sensitivity for active TB vs other inflammatory markers”, writes Dr Yoon and colleagues.

Plus, CRP is inexpensive and easy to measure using blood from a finger prick. Apparently, it takes only 3 minutes and costs less than $2 USD per test.

For their study, Dr Yoon’s group recruited over 1,200 people with HIV from two Uganda clinics just as they started their HIV treatments. They tested everyone for TB using the CRP test, and also collected sputum samples for bacterial culture for use as a control.

They showed that the CRP test was 89% sensitive and 72% specific for TB. When compared to the WHO symptom-based screening, it was 7% less sensitive but 58% more specific.

In other words, the test might miss a few more patients by throwing out false negatives, but more patients can be screened because much fewer patients would need the expensive genetic confirmation test.

Bottom line

If the CRP test can be proven to be reliable after being rolled out in large scale public health projects, it can significantly help more communities screen for TB and provide treatment or prevention as needed.

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