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Emily MacLean, McGill University, works on tuberculosis (TB) in a global health context. She mostly focuses on diagnostics, specifically biomarker-based tests for TB, interested in understanding how accurate tests are, as well as their implementation in health systems.

In this blog, Emily discusses the TB landscape and the barriers to the adoption of diagnostic tests for TB. She talks about her and fellow researchers’ recent study, published on Gates Open Research, a partner platform with F1000. About finding a gap between country-level policy and real-world use of the Alere-LAM lateral flow urine test, shining a spotlight on the critical need for cheap and reliable diagnostic tests for population health.

Is an ideal diagnostic test soon within our reach?

An ideal diagnostic test is accurate, fast, and cheap, but all available TB diagnostic tests come up short with respect to at least one of these criteria. Still, the landscape is better now than 10-20 years ago. Besides traditional tools like smear microscopy, bacterial culture, and chest x-ray, we now have molecular tests that are helping to quickly diagnose TB and identify drug resistance. We also have the lateral flow Alere-LAM assay, the focus of our paper. Each of these tests have been taken up to various degrees by different countries.

Emerging technologies include next generation sequencing and centralized high-throughput assays for identifying resistance to a range of TB drugs (e.g. Abbott RealTime MTB, BD Max MDR-TB), and TB tests that are being designed, manufactured, and rolled-out in high TB burden countries (e.g. MolBio Truenat MTB in India, UStar Biotechnologies EasyNAT in China). Many more tests are in the developmental pipeline, so maybe soon we’ll have an accurate, fast, and cheap TB assay.

What are the barriers to diagnosing and treating TB?

Some barriers are test-related and some are more systemic. Certain tests, like smear microscopy, are not very accurate and tend to miss cases, so some sick people will test negative and won’t be properly treated. Others, like culture, are accurate but take weeks to produce results, so often patients are lost to follow-up by the healthcare system and won’t receive treatment.

Some molecular tests give accurate, rapid results, but are too expensive for many people to afford so they never get tested or treated. Most tests require lab infrastructure, so they are not available in non-centralized clinics where many people first present for TB care. Additionally, almost all TB tests perform less well in people living with HIV (PLHIV),  so it’s particularly difficult to give them proper diagnoses.

How was the lateral-flow urine LAM test supposed to assist with this?

The Alere-LAM lateral flow urine test has several characteristics that help with diagnosing TB in PLHIV. This is a distinct sub-group of people with TB who are at very high risk of severe disease and mortality. Alere-LAM uses a urine sample, which is advantageous because it is hard for PLHIV to produce a respiratory sample (the typical sample for other TB tests).

Its diagnostic accuracy improves with decreasing CD4 count (a measure of the number of white blood T-cells in the blood), so it can diagnose TB in PLHIV who otherwise would be especially difficult to classify. As well, it can be run at the point of care and produces results in less than an hour, which is crucial since severely ill PLHIV with TB need to be treated immediately to prevent them from dying. It is also cheaper than most other TB tests, at 3.50 USD.

What did you find from your study?

Unfortunately, despite its advantages, Alere-LAM uptake by most high TB burden countries was low. Less than half of WHO-defined high TB burden countries had policies in place for TB testing with Alere-LAM. Additionally, of the 24 countries who responded to our survey, only five reported actual on-the-ground use of Alere-LAM. This is despite WHO recommending the Alere-LAM assay for TB testing in severely ill PLHIV of all ages. On a more hopeful note, 15 of the countries had plans to implement Alere-LAM testing in the near future.

What do you think can be done to improve TB diagnosis?

To really improve diagnostics for TB, I think we need to take a larger view of diagnostics generally. Diagnostics is kind of the poor cousin of treatment – informing people that they have an illness is not as satisfying as curing them of it, and diagnosis on its own does not translate into saved lives. Improving diagnostics will require a reconsideration of the value of testing for TB. Some (although not all) of the study’s co-authors and I were surprised that the most frequently stated barrier to implementation of Alere-LAM, a 3.50 USD test, was budget concerns.

To me, this demonstrates that countries or funders or other relevant stakeholders are not prioritizing testing enough. For a test that leads to faster treatment initiation and decreased mortality when properly deployed, that seems like a good price tag. As a field researcher, I guess we need to get better at communicating to countries and donors how important it is to quickly and accurately identify people with TB. Ensuring their proper care starts with testing. One thing that the COVID-19 pandemic has very clearly illustrated is that testing for disease is critical to population health, so maybe that is a silver lining of this whole thing.

As a researcher, what does open research mean to you? How does the accessibility of the research help researchers working on TB and towards ending the TB epidemic?

In terms of availability of published information, open research seems more fair than traditional models of scientific publishing. This is particularly important for research of diseases, such as TB, that primarily occur in low- and middle-income countries, since institutions in these  countries may lack resources to subscribe to many relevant journals/publishers, where the research is behind a paywall.

Obviously publishing good quality material costs money, but it just seems wrong that many researchers of “diseases of poverty”, including TB, cannot access research that is most pertinent to them. Regardless of where they are located, people working on TB need reliable, peer-reviewed information. This is critical in terms of building on the existing evidence base, designing new studies and interventions, and advancing the field towards ending the TB epidemic.