WHO Sets New Targets for Next-Generation TB Screening Tests
The World Health Organization has released updated Target Product Profiles to guide manufacturers in developing faster, more affordable, and accurate tuberculosis screening tools.
Since 2014, the World Health Organization (WHO) has regularly published Target Product Profiles (TPP) for tuberculosis (TB) screening tests. Aimed at manufacturers of TB tests and equipment, they are akin to a wish list for addressing global TB screening needs. The WHO recently published updated TPPs.
The WHO indicates that in 2023, a total of 1.25 million deaths occurred from TB globally. In that year, about 10.8 million people were estimated to have TB, with official diagnoses of about 8.2 million and another 2.6 million believed to have gone undetected. Of the 10.8 million, 1.3 million were children.
TB is an airborne infectious disease caused by the bacterium Mycobacterium tuberculosis. Primarily affecting the lungs, it can impact the entire body. It is typically diagnosed via tuberculin skin tests, blood tests, chest X-rays, and sputum analysis.
TB has recently been moved to the top of the list—over COVID-19—as the leading cause of death in the world from a single infectious agent. TB is also the top killer of people with HIV. About two out of five TB deaths are related to antibiotic-resistant strains of TB.
The WHO stated in the TPPs that, “If TB screening is to be implemented at the levels needed to significantly reduce the global TB burden, there is an urgent need for new tools for TB screening that can be readily and rapidly deployed and brought to scale.”
Tereza Kasaeva, MD, PhD, Director of the WHO Department for HIV, Tuberculosis, Hepatitis, and Sexually Transmitted Infections, stated in a press announcement on the new Target Product Profiles, “The global community needs tools to screen and detect TB which are better and more accessible in hard-to-reach settings.”
Tereza Kasaeva, MD, PhD, Director of the WHO Department for HIV, noted “The new WHO TPPs will inform manufacturers about the features that these new tests should have if they are to address the needs of the TB community and achieve the ambitious global commitments for TB detection and reduction of TB incidence and deaths.”
There have been many recent advancements, including mobile and portable digital radiographic equipment, as well as artificial intelligence (AI) in computer-aided detection software. Yet, the WHO notes, there are still challenges to scaling technology to close “the case detection gap.” Some of those challenges include availability, low cost, and high accuracy.
The TPP defined three distinct types of screening tools:
- High-sensitivity, high-specificity screening test using a single screening step before referral for diagnostic testing or ruling out TB.
- High-sensitivity screening as part of a two-step screening process before referral for diagnostic testing.
- A moderate-sensitivity screening test with high specificity that can be used in settings that have limited access to health systems and can’t be reached via existing screening technology.
Current screening methods have accuracy limitations and difficulty in screening asymptomatic TB. The WHO TPPs noted that, “CXR (chest X-ray) can be used to screen most populations and has the best demonstrated sensitivity of available screening tools. CAD software for automated interpretation of CXR imaging can be used along CXR for screening all adults aged 15 years and older.”
The WHO also recommends rapid molecular diagnostic tests for screening all adults, and C-reactive protein (CRP) to screen adults living with HIV.
The latest TPP emphasizes effective community-based screening on a larger scale in settings with lower TB prevalence. This is a challenge to TB assay developers, especially in finding cost-effective methods with high accuracy. Ideally, they would have a small per-test cost and very little or no equipment or capital investments. If they do require centralized equipment for processing, they should have low per-test costs and implementation requirements.
For each category of testing, the TPP sets pricing goals. For high-accuracy one-step tests, the minimum is ≤ US$3; for high-sensitivity two-step tests, the minimum is ≤ US$2 with an optimal of ≤ US$1; and for a high-specificity test, the minimum is ≤ US$2.
The TPP states, “Ideally, a new test should be priced according to the cost of goods and estimated volumes, and should include a reasonable profit margin. Ensuring access to tests while maintaining business interests can be achieved through fair pricing, which requires transparency about the cost of goods and estimated volumes, and a reasonable profit margin.”
The expert panel that created the TPP understands the challenges, noting that “manufacturers may have to consider trade-offs, whereby a novel test has some clear advantages that may offset other downsides.”
Ultimately, the WHO states that the TPPs were issued to “guide and encourage product development for new screening tools in these settings.”
—Mark Terry
