Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The infection occurs most often in the lungs (so-called pulmonary TB) but can also infect almost any other part of the body. The disease is typically transmitted when patients with active pulmonary TB cough, expelling bacteria into the air which others inhale.
An estimated 2-3 billion people in the world have latent TB, meaning they have been infected with the TB bacterium at some point in the past, but are asymptomatic because their immune systems are able to cope with the infection by ‘walling-off’ the bacteria. Nonetheless, these 2-3 billion people are at risk for developing active TB. Those that develop active pulmonary TB have symptoms ranging from a deep cough with sputum and blood, to chest pains, night fevers, weight loss, and weakness.
In 2014, some 9.6 million people developed active pulmonary TB and 1.5 million died as a result, making it equivalent to HIV as the most deadly infection in the world. It is particularly lethal for people who are living with HIV, who are 30 times more likely to develop active pulmonary TB. About 12% of all TB patients are also HIV-positive.
TB is readily curable with appropriate treatment. Standard TB care requires a six-month regimen of first-line drugs. The inappropriate use of TB drugs—in large part due to prescriptions based on presumptive diagnosis rather than confirmed testing for TB and drug susceptibility—has led to an increase in drug-resistant strains of the disease.
Multidrug-resistant TB (MDR-TB) does not respond to at least two of the four first-line drugs and therefore must be treated more aggressively for approximately 20 months with second-line medications—drugs that are more expensive, much more toxic and less effective. A rarer form of TB, extensively drug-resistant TB (XDR-TB), does not respond to first- or second-line treatments, meaning treatment options are limited and have low success rates.
Simpler, more robust and easy-to-use TB tests are urgently needed, especially for use in decentralized health facilities and other places with limited laboratory infrastructure, including tests that don’t require sputum samples (especially to more easily diagnose children) and tests that can assess drug susceptibility.
New TB drugs are also needed to make TB treatment shorter and more effective, and new strategies are needed to halt TB transmission, such as vaccines. There are currently TB vaccines in Phase 1 and Phase 2 trials.
The diagnostic landscape
Rapid and accurate detection of TB and drug resistance is the essential first step in guiding treatment that can cure patients and prevent the ongoing spread of drug resistance. Diagnosis also enables disease monitoring and better targeting of interventions, which are essential in controlling TB transmission in populations.
It is estimated that approximately 3 million TB patients are ‘missing’, meaning they have not been diagnosed or received appropriate TB treatment. This is partly due to the lack of ready access to reliable and affordable TB diagnosis outside of major population centres. It is also partly due to the difficulty of diagnosing TB in some populations, such as children and people living with HIV, and the lack of TB drug susceptibility tests to guide appropriate treatment for patients whose TB is resistant to standard drugs.
TB diagnosis using older diagnostic techniques, such as microscopy, is still common, but the landscape is gradually changing. Since 2010, FIND and partners have worked to introduce and scale up the use of a WHO-recommended rapid molecular testing platform, the Gene Xpert, in clinical reference testing laboratories. The tool uses a simple cartridge system to diagnose TB as well as to detect specific mutations that are associated with resistance to rifampicin, a first-line TB drug. Rifampicin resistance generally indicates TB that is also resistant to at least one other TB drug and is a sign that second-line treatment will be needed because the usual first-line drugs won’t work.
More than 16 million Gene Xpert MTB/RIF cartridges have been procured since 2010 by 116 low- and middle-income countries at FIND-negotiated discount prices. As well, FIND works with national TB control programmes to provide implementation support and laboratory capacity building.
Still, even simpler, more robust, easy-to-use and more affordable tests are urgently needed, especially for use in decentralized health facilities and other places with limited laboratory infrastructure. Priority tests include: tests that can support more widespread diagnosis and triaging , tests that can detect when latent TB infections are becoming active, tests to rapidly determine drug susceptibility, and tests to simplify the diagnosis of TB in patients who are difficult to diagnose, including children and people living with HIV.
There are currently several test technologies in the TB diagnostics development pipeline; however, the pipeline is dominated by molecular tests and the search is ongoing for other biomarkers to meet some of the needs for better fit-for-purpose tests. Furthermore, product development companies face large funding hurdles: securing the financing to bring product manufacturing to scale and to conduct extensive clinical studies are common challenges.
FIND’s strategic approach
Since 2003, FIND has promoted improvements in TB diagnostics and accelerated access to new diagnostic tools by working directly with health ministries to develop locally appropriate solutions based on international best practices.
FIND’s strategic approach for TB from 2015-2020 builds on this work and is guided by a vision of the future in which all people affected by TB have access to fit-for-purpose diagnostics and are linked to treatment. In pursuit of this vision, FIND’s activities are focused around four key objectives:
- Cutting transmission through early detection
- Providing correct treatment through early drug susceptibility testing (DST), preventing antimicrobial resistance and decreased morbidity and mortality
- Maximizing the impact of available TB diagnostics through comprehensive, country-specific solutions
- Demonstrating the vital role of diagnostics in controlling TB
These activities are conducted with a wide range of partners from companies, academic and research institutions, international organizations, health ministries and civil society organizations.