7. TB research and innovation

Tuberculosis (TB) research and innovation is essential to achieve the global TB targets of the United Nations (UN) Sustainable Development Goals (SDGs) and the World Health Organization (WHO) End TB Strategy. The SDG target is to “end the epidemic” by 2030; more specific targets for 2030 set in the End TB Strategy are a 90% reduction in TB deaths and an 80% reduction in TB incidence compared with 2015 levels, with targets for further reductions (95% and 90%, respectively) by 2035. Reaching these targets requires major technological breakthroughs by 2025, such as a TB vaccine that is effective both before and after exposure, so that the rate at which TB incidence falls can be dramatically accelerated compared with historic levels (2% per year globally in recent years, with the fastest national declines of around 10% per year achieved in the 1950s and 1960s), to an average of 17% per year between 2025 and 2035.

“Intensified research and innovation” is the third pillar of the End TB Strategy. This includes research and development of affordable and accessible rapid point-of-care tests for TB infection and TB disease; shorter, safer and more effective treatments for TB infection, drug-susceptible TB and drug-resistant TB (DR-TB); a TB vaccine that is effective before and after exposure; and innovative strategies to address broader determinants of TB, such as poverty, undernutrition, HIV infection, smoking and diabetes. Target 3b of the SDGs includes supporting research and development related to vaccines and medicines for “communicable and non-communicable diseases that primarily affect developing countries”.

The political declaration at the first UN high-level meeting on TB, held in 2018, included the first global funding target for TB research to be agreed by all UN Member States. The target is to mobilize US$ 2 billion per year in the period 2018–2022. Although funding has been slowly increasing (Fig. 7.1), the latest published data show that only US$ 901 million was available in 2019 (1). This was a decrease from US$ 906 million in 2018 and was less than half of the global target.

WHO continues to promote and monitor progress in the development of new TB vaccines, diagnostics and medicines.

The diagnostic pipeline remains robust in terms of the number of tests, products or methods in development (Table 7.1). These include newer skin tests for TB infection based on recombinant early secretory antigen target (ESAT)-6 and culture filtrate protein (CFP)-10 antigens, with better performance than tuberculin skin tests, particularly in terms of specificity; next-generation lateral-flow lipoarabinomannan (LF-LAM) assays that perform better than currently marketed assays, particularly in terms of sensitivity; amplification-based targeted next-generation sequencing (NGS) assays for detecting DR-TB directly from sputum specimens; broth microdilution methods for drug-susceptibility testing (DST); an expanding pipeline of new interferon gamma release assays (IGRAs) to test for TB infection; and several computer-aided detection (CAD) software products employing artificial intelligence to screen for TB on digital chest radiographs. A growing number of nucleic-acid amplification test (NAAT) products are available; these products are automated, are of low to moderate complexity, and can detect both TB and resistance to various anti-TB drugs (e.g. rifampicin, isoniazid and fluoroquinolones). Six new technologies for the molecular detection of TB and resistance to anti-TB drugs were endorsed by WHO in 2021. These are: FluoroType MTB and MTBDR, Hain Lifescience, Germany; Abbott RealTime MTB and MTB RIF/INH on m2000sp and m2000rt systems, Abbott, USA; BD Max MDR-TB, Becton Dickinson, USA; Roche cobas® MTB and MTB-RIF/INH on Cobas 6800/880 systems, Roche Diagnostics, Switzerland; Genoscholar PZA TB II, Nipro, Japan; and Xpert MTB/XDR cartridge, Cepheid, USA. 

In August 2021, there were 25 drugs for the treatment of drug-susceptible TB, multidrug-resistant TB (MDR-TB) or TB infection in Phase I, Phase II or Phase III trials (Table 7.2,  Table 7.3). These drugs comprise 16 new chemical entities, two drugs that have received accelerated regulatory approval, one drug that was recently approved by the United States (US) Food and Drug Administration under the limited population pathway for antibacterial and antifungal drugs, and six repurposed drugs. Various combination regimens with new or repurposed drugs, as well as host-directed therapies, are in Phase II or Phase III trials.

There are 14 vaccine candidates in clinical trials: two in Phase I, eight in Phase II and four in Phase III (Table 7.4). They include candidates to prevent TB infection and TB disease, and candidates to help improve the outcomes of treatment for TB disease.

Further details about the products in clinical trials can be found by clicking on the links in Table 7.2, Table 7.3, and Table 7.4.

A Global Strategy for TB Research and Innovation was adopted by the World Health Assembly in August 2020 (2). It provides strategic guidance for how to accelerate research and innovation efforts that are aligned to the needs of Member States. The strategy calls for an enabling environment for research; mobilization of increased domestic and international investments in TB research; leveraging of the potential of data sharing; and global collective action to improve equitable access to the benefits of research and innovation. In 2021, WHO launched a situational assessment checklist (3) to help countries to contextualize the implementation of the global strategy through changes in policies, programmes and interventions. To promote research driven by country needs that is aligned to the recommendations of the global strategy, WHO is providing support to the secretariat of a TB research network that comprises Brazil, Russian Federation, India, China and South Africa (BRICS) (4). In 2020, WHO’s Global TB Programme co-hosted and facilitated three meetings of this BRICS TB research network, covering a range of TB research projects.

WHO will complete a health and economic impact assessment of the full value of new TB vaccines in 2021. The assessment is intended to guide investments in late-stage research as well as the introduction and implementation of new TB vaccines (6). WHO is also developing a research agenda on TB social protection, to build the high-quality evidence required to guide efforts to address the social and economic determinants and consequences of TB.

In 2021, WHO convened a multistakeholder consultation to discuss the emerging needs of Member States for policy guidance, evidence gaps for policy-making, translation of research evidence into policy and strategies to enhance the implementation of global TB policy guidance (7).

Technologies endorsed by WHO

Table 7.2 The global clinical development pipeline for new anti-TB drugs and drug regimens to treat TB disease, August 2021

Table 7.3 The global clinical development pipeline for new drugs and drug regimens to treat TB infection, August 2021

Table 7.4 The global clinical development pipeline for new TB vaccines, August 2021^a