This World Tuberculosis (TB) Day, we are losing ground in the fight against TB.
While substantial progress has been made over the past two decades in treating and controlling the disease, the last few years have seen a concerning backslide. If we compare 2021 with 2020:
100,000 more people lost their lives to TB – a total of 1.6 million people
4.5 per cent more people fell ill with TB – over 10.6 million cases
An estimated 3.1 per cent more people developed multi-drug-resistant or rifampicin-resistant TB (the first-line treatment for the disease)
Yet despite the recent trend, we can make 2023 a turning point in our global fight to eradicate this deadly disease by harnessing the power of new technologies, alongside effective government leadership and a doubling of TB funding. Innovations in TB surveillance and diagnostics (such as genomic-sequencing and bioinformatic technologies), as well as new treatments and therapeutic decision-making tools, have the potential to transform this battle – and put an end to one of humanity’s oldest diseases.
Chapter 1
TB is one of the leading causes of global disease burden, resulting in premature mortality and reduced quality of life. One in every four people have been infected with TB, with many unaware because they don’t exhibit symptoms, known as “latent TB”. TB disproportionally affects those in low- and middle-income countries (LMICs); 24 of the 30 highest-burden countries are LMICs. These 30 countries account for 87 per cent of new cases, with just eight countries accounting for more than two-thirds of the global disease burden.
TB prevention and treatment was a casualty of the pandemic; resources were redirected towards the Covid-19 response, leading to a reduction in access to care.
However, problems with global eradication efforts go far beyond recent pandemic disruption. They are rooted in long-term underinvestment and an outdated approach to detection, prevention and treatment that fails to capitalise on the power of new technologies.
The first high-level TB meeting, held during the September 2018 UN General Assembly, led to the establishment of an annual $13 billion global-funding target to provide universal access to quality TB prevention, diagnosis, treatment and care. Yet in 2021 global spending was just 42 per cent of this target. This has reduced peoples access to free TB services, including prevention and effective treatment, and is being felt most keenly by those who are the poorest and most at risk from ill health. These socioeconomic determinants of health – like extreme poverty and malnutrition – have worsened during the pandemic, further exacerbating the impact of underinvestment. Collectively, this has had catastrophic ramifications for patients’ access to care and continuity of treatment, which undermines recovery, worsens outcomes and increases the opportunities for TB to spread.
Meanwhile, resource-constrained settings continue to overly rely on inexpensive-but-insensitive sputum smears as their primary diagnostic method. Unfortunately, these tests cannot identify drug resistance or differentiate Mycobacterium tuberculosis (the bacteria that causes TB) from Nontuberculous mycobacteria (NTM). These legacy methods rely on developing bacteria cultures and drug-susceptibility testing (DST) to identify the pathogen and drug-resistance patterns – processes that take weeks. Furthermore, DST is not easily accessible in many countries with high TB burden, often resulting in inappropriate therapeutic management. This is especially the case in areas where there are high rates of drug resistance.
As a result of these inefficiencies, most TB patients and suspected cases wait too long for diagnosis and treatment, creating more opportunities for the disease to spread unimpeded. Delayed diagnosis, coupled with limited DST, also results in over-prescription of antibiotics, further feeding the global rise in antimicrobial resistance (AMR) and placing us all at risk.
In recent years, rapid molecular diagnostic tests have become available. They are more sensitive, easier to use and allow detection of drug resistance, enabling health professionals to provide appropriate therapies and accurately monitor patients’ responsiveness to treatment in real time. However, in 2021 only around 25 per cent of TB diagnostic sites had access to rapid diagnostic tests recommended by the World Health Organisation (WHO). Across the 30 countries with the highest TB burden only seven reported that more than half of sites had access. Cost reductions and improved access to devices and reagents are needed to expand the adoption of these rapid molecular diagnostic tests.
Chapter 2
The advent of new genomic-sequencing and bioinformatic technologies have the potential to further transform the way TB is diagnosed, monitored and treated, providing governments with the ability to identify and respond to emerging threats rapidly and effectively. As a result, WHO now recommends the use of next-generation sequencing for TB surveillance to ensure public-health agencies can effectively monitor emerging pathogens and resistance patterns.
The Global Pathogen Analysis Service (GPAS) will soon launch an innovative tool for Mycobacterium tuberculosis that will facilitate a global understanding of the scale and spread of different TB lineages, and allow for early identification of new outbreaks by understanding how cases relate to each other. This will enable public-health officials to track and trace an outbreak in real time, significantly bolstering surveillance-system capabilities. The GPAS tool will also detect whether samples contain any NTM species that also cause pulmonary diseases that resemble TB, for example M bovis.
We strongly support WHO's evaluation of targeted sequencing for the detection of drug-resistance among people diagnosed with TB for use in clinical care and treatment. Should this become a WHO recommendation, we anticipate that it will become standard practice to use genomic sequencing alongside rapid diagnostic tests to quickly identify variants and drug resistance. Genomic sequencing will become an important component in the design of diagnostic and treatment services as well as in monitoring the effectiveness of TB programmes and interventions.
In its future applications, and subject to regulatory approval, GPAS’s tool will be able to support individual-patient care, aiding prescription decisions. This would improve the likelihood of treatment success and prevent the inappropriate use of medicines, helping to contain the threat of AMR.
Chapter 3
To harness the true potential of innovative TB technologies, we need to see governments, multilateral organisations, industry and the international donor community step up. Government leadership is critical to directing where efforts will be most effective locally and to addressing the shortfall in global funding to meet existing international commitments. We therefore call on all governments to:
Rebuild, strengthen and accelerate existing TB programmes
Enhance universal access to diagnostics and treatments
Stand up a multi-ministerial, multi-sectoral taskforce to erode the impact of socioeconomic factors on health outcomes – for example through focus on financial deprivation and malnutrition
Work with industry to provide the evidence base and incentives to rapidly identify, trial and manufacture new vaccines and therapeutics for TB
Strengthen lab capacity through digital technologies, such as genomic sequencing and foundational digital infrastructure, which together will transform the surveillance, diagnosis and treatment of TB
The advent of promising innovations across drugs, vaccines and particularly genomic-sequencing and bioinformatic technologies, like GPAS, means that the dream of ending TB is now within reach. As the pressures of the pandemic begin to fade and demand for TB services returns to normal, we must renew our focus and harness the power of these new technologies to finally eradicate one of the world’s oldest infectious-disease threats.