140 years later: Do our COVID-19 successes highlight our TB response failures?
Worldwide, an estimated 1.7 billion people are currently infected with tuberculosis (TB). In the US alone, ~13 million people are living with TB infection. By comparison, roughly 500 million people have had COVID-19. Considerable progress has been made against the COVID pandemic over the past two years, particularly with the rapid development and deployment of effective vaccines in countries with limited infrastructure. Along with better diagnostic tools, the case fatality rates had decreased significantly.
March 24th marks 140 years since Robert Koch announced the identification of the bacterium which causes TB. Since then, medicine has advanced in quantum leaps, and some infectious diseases have been eradicated.
However, TB remains the leading infectious disease killer in the world annually, with 95% of all TB deaths occurring in developing regions. In addition to being the leading cause of death in resource-limited settings, TB causes significant associated morbidities and co-morbidities, as well as large financial and resource strains on challenged healthcare systems. According to a 2015 Lancet study “Unless control efforts are stepped up, tuberculosis will kill 28 million people between 2015 and 2030, and cost the global economy almost US$1 trillion.” And almost a third of the cost will be borne on Africa alone. The challenges in identifying and treating TB cases are compounded by the fact that TB is transmitted through exhaled particles. In many of the settings with the highest TB prevalence, population-wide resource challenges are prevalent and many live in densely populated and crowded environments. Thus facilitating TB transmission, and continuing the disease cycle.
Therefore, as we approach another World TB Day anniversary, we should reflect on how we must do better to reduce TB cases and deaths, particularly among marginalised populations.
Firstly, let's begin with the actual identification of TB cases — which remains a challenge. Currently, there is no single, easy-to-access, cost-effective, and accurate point of care (POC) test available. The current options include rapid molecular testing, X-Rays, new rapid technologies, and experimental acoustic signature related screening tools. The first of these has major cost and access limitations. X-rays, on the other hand, are limited in terms of both their access and accuracy, whilst new rapid test technologies may be more accessible but still limited in terms of their accuracy. Lastly, experimental acoustic signature-related screening tools have shown potential, but are at an early stage of research and development. In short, we still battle to identify TB cases which is the entry into the care and treatment pathway.
Once cases are identified, we need to treat the infection — which also remains a challenge. Effective TB treatment depends on the anatomical location and infective strain of TB. A variety of tailored treatment algorithms exist, however for most patients living with TB, the best case scenario remains a daily medication for at least four months. The four-month course is a challenge for those with limited access to healthcare services due, for instance, to long distances to health facilities, as well as low overall household income, especially in high-burden settings. Medical adherence, as a result, is inconsistent and contributes to the increasing cases of drug resistant and multi-drug resistant TB. These cases are of growing concern as treatment outcomes are inconsistent and can be unsuccessful. TB vaccines are available, but while vaccinations show effectiveness in limiting disease burden in paediatric populations, it yields far less success and efficacy as people age.
The obstacles in identifying and treating TB are numerous and complex, delaying our success in overcoming this killer, but we could be doing better in addressing them. The successes from the COVID pandemic might highlight areas for intervention and improvements.
The massive investment in COVID-19 testing during the pandemic, which ultimately led to the decrease in deaths and hospitalisations, shows an opportunity to do more screen tests for the identification of TB cases. Over the past two years, the global spend on COVID-19 has been unprecedented. In 2020 alone, the annual Financing Global Health report, produced by the Institute for Health Metrics and Evaluation (IHME) at the University of Washington School of Medicine, found that $13.7 billion in development assistance for health (DAH) went to COVID-19. Whilst in the same year, 2020, fiscal support for TB was $5.3 billion. This is despite the fact that in 2020 the reported death toll from COVID-19 was ~1.8 million and the reported number of TB deaths was ~1.6 million. This brings the total number of TB deaths back to 2015 levels, given the 25% reduction in TB detection in the first three months of the COVID pandemic. Estimates show that this led to an additional ~200k TB deaths that year.
This is a pattern often seen in global health — prioritisation of global disease is often vertical in nature. Global health donors and experts are often grounded and siloed by disease focus and area, which have specific targets and indicators. This makes it challenging for decision makers, program leaders, and implementers to plan integrated services that target improving the health care system. The focus on COVID-19 in the past two years, to the detriment of other continuing global health challenges, once again highlighted this unfortunate and limiting global health phenomenon.
How many people with respiratory system symptoms were tested for COVID-19? How many negative test results were there, and how often were these negative cases further explored to identify the cause of symptoms? One wonders how many TB cases we missed and — with a little more effort, investment, and focus — could have been identified and treated. Integrating more TB testing to complement COVID-19 testing was a significant missed opportunity for global impact.
Towards the latter part of the pandemic, however, there has been more attention placed on the idea and objective of integrated multipurpose/multiplex testing algorithms, platforms, products, and treatment pathways. The ultimate goal being that a patient can find out their diagnosis faster and easier. The notion is that a patient, ideally with the guidance of a well-designed digital health tool, could collect a simple test sample (via a nose, mouth, or tongue swab) and access an affordable and easy to use testing option or platform. The testing option or platform would cover a panel of the most relevant and dangerous conditions associated with the system affected (e.g. the respiratory system) — not only providing a result for one target condition (in recent times this would have been COVID-19), but also a result for other key conditions such as influenza, TB, or other respiratory pathogens. Imagine the impact of being able to effectively screen, test, and link patients to appropriate treatment in a more holistic and integrated approach.
As we once again pause and reflect on TB and its significant impact in the world over the past 140 years — when we consider what we have achieved and accomplished in so many other disease areas in a relatively short amount of time — it does make one wonder and reflect on the drivers of global health investment and focus. Why does the developing world always pay such a high human price? Having shown how well we could do in the face of the COVID pandemic, it's time to take a tough and honest look at where we are with TB. Increased TB investment and progress can be better integrated, accelerated, and reprioritised across diagnostics, treatment, and vaccine development pathways. Undoubtedly, there are opportunities to do better and make greater progress against TB.
