By Dylan Powell, Research Analyst, Deloitte Centre for Health Solutions

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Thursday the 24th of March is World Tuberculosis (TB) Day, an important day in the World Health Organisation (WHO) calendar as it provides an opportunity to raise public awareness about the devastating health, social and economic consequences of the world’s oldest and most deadly infectious disease, after COVID-19.  The main preventative treatment, the TB vaccine Bacille Calmette-Guérin (BCG), has been used all over the world for over 100 years.1 Nevertheless, TB still claimed the lives of 1.5 million people in 2020 predominantly in low-and middle-income countries. While access to the vaccine remains very uneven, simply improving access won’t be enough to eradicate TB. Increased global awareness and investment, and a shared purpose is also needed.2 This week’s blog is our testament to World TB Day and explores achievements to date and what more can and should be done to end the global TB epidemic.

What is known about TB today?

Inline1

The evolving burden and epidemiology of TB

50 years ago, many industrial areas of the UK, such as South Wales where much of my family lived and worked in the 19th and 20th centuries, were plagued by TB.3 Crowded living and working conditions, and a reliance on industries such as coal mining, created optimum environments for infectious diseases to spread rapidly. Often undiagnosed and latent for many years, TB accounted for over one quarter of all UK deaths in the 19th century.4 Thankfully vaccinations, improvements in diagnostics and antimicrobials have almost eradicated TB in the UK, with only 161,200 cases over the past 20 years, and most of these cases were associated with foreign travel.5

In 2014 and 2015, all Member States of WHO and the UN adopted the UN Sustainable Development Goals (SDGs) and WHO’s End TB Strategy. The SDGs and End TB Strategy both include targets and milestones for a 90 per cent reduction in TB deaths and an 80 per cent reduction in the TB incidence rate by 2030, compared to the 2015 baseline. It also aims to increase investment and reduce deaths and costs faced by TB patients and their households. Today, most of the people who are ill with this preventable and curable disease live in low- and middle-income countries and every day over 4,100 people die and around 28,000 people fall ill with TB. The top eight countries in terms of incidence, account for two thirds of the total cases (see Figure 1).6

Inline 2

While global efforts to combat TB have saved an estimated 66 million lives since the year 2000 and TB incidence fell by 11 per cent between 2015 and 2020, this was just over half-way to the End TB Strategy milestone of 20 per cent reduction between 2015 and 2020. Globally, the reduction in the number of TB deaths between 2015 and 2020 was only 9.2 per cent - about one quarter of the way to the 2020 milestone of 35 per cent.7

The COVID-19 pandemic, with lockdowns and disruption of essential health services, is considered to have reversed years of global progress in tackling TB. There has been a large global drop in the number of people newly diagnosed with TB and reported, falling from 7.1 million in 2019 to 5.8 million in 2020. Reduced access to TB diagnosis and treatment resulted in an increase in TB deaths to 1.5 million in 2020. Furthermore, reductions in the number of people treated for multi drug-resistant TB (MDR-TB) and TB preventive treatment (decreasing from 3.6 million to 2.8 million people treated), and a fall in global spending on TB diagnostic, treatment and prevention services (from US$ 5.8 billion to US$ 5.3 billion, less than half of what is needed).8

So, can TB be fully eradicated?

Global eradication of any infectious disease is a daunting task requiring concerted and coordinated social, political, and economic efforts. Well-orchestrated vaccination programmes have been shown to prevent many infections, as has improving the early detection of TB, including recent innovation in rapid molecular diagnostics, in regions of the world with coordinated disease surveillance and mass vaccination campaigns. In countries without such campaigns, and with limited access to healthcare, people rarely seek immediate care or obtain a diagnosis; passing the infection on unknowingly to others.  There has also been very little investment in the development of new vaccines over the past century.9

The epidemiology of TB is also becoming increasingly more complex due to modern conflicts and frequent natural disasters, which have provided the ideal conditions for TB to spread. For example, the Philippines experienced large increases in TB cases after the 2013 Bohol earthquake and typhoon.10 MDR-TB remains a public health crisis and health security threat with only one in three people with MDR-TB accessing treatment in 2020.

What innovative solutions could prove useful?

Research breakthroughs to develop innovative TB vaccines is urgently needed. Even if children are vaccinated, in high incidence countries immunity usually wanes in adolescence, with immunity in adults highly variable, ranging from zero to 80 per cent depending on the country and environment. The ‘WHO strategy to end TB’ has identified research priorities including a vaccine to lower the risk of infection, a vaccine or new drug treatment to cut the risk of TB disease in people already infected, rapid diagnostics for use at the point of care, and simpler, shorter treatments for TB disease.11

Harness mRNA technology to develop more effective and tailored vaccines

Can the development and roll out of RNA vaccines against TB have an impact comparable to that against COVID-19? Research from academia would appear to support this. As far back as 2004 there was proof of concept for the protective effect of RNA vaccination against tuberculosis in mice.12 The BCG vaccine has conflicting reports of efficacy and more recently there has been considerable focus on the opportunities afforded by mRNA vaccines which include building libraries of gene-based constructs encoding various antigens for more targeted and much faster technologies to produce a vaccine.13 Some are already in clinical trials, however more late stage research and investment is required for tangible impacts.

Utilise Artificial Intelligence (AI) to speed up diagnosis and combat MDR-TB

Imaging techniques such as X-rays are commonly used for screening patients especially in countries with high case rates.14 The main caveat and limiting factor are often cost and availability of equipment and medical professionals including radiographers, which can be as low as 1 per 100,000 in countries such as India.15 A recent study found that effective AI-powered screening could save up to 80 per cent of the cost per positive TB case detected, when considering cost of staff.16 Therefore, the use of AI to automate screening of X-rays and triaging those at higher risk, could provide an important first step in improving diagnosis throughput and early intervention.  

To combat MDR-TB, advancements in natural language processing, which can interpret patient notes, and compare digital information on dosages and success rates may aid in stratifying high-risk populations and subsequently evaluating the most optimal dose response for antimicrobials in TB. Machine Learning techniques have been used extensively in computational biology and bioinformatics such as RNA binding protein sites.17 This is already expanding and being applied to TB, with potential for evaluating tuberculosis drug resistance status from genome sequencing data, yielding more targeted use of anti-microbials.18

How to invigorate the implementation of WHO’s Strategy to end TB

The strategy to end TB by 2030 requires a unified response incorporating several principles.

  1. Raising awareness of TB and taking ownership – this requires leadership and political commitment engagement of communities, public and private care providers, and regulatory frameworks for case notification, quality and rational use of medicines and infection control.
  2. Urgent investment of resources - the WHO estimates an extra $7.7 billion is required each year to properly address TB. This is critical in the context of the COVID-19 pandemic that has drawn huge attention and resources away from other infectious diseases such as TB.
  3. Integrated patient-centred care and prevention – the WHO reiterated in 2015 the need for implementing universal health coverage, social protection, and strengthened regulatory frameworks. Longer term improvements include addressing the social determinants of TB which can include people living with HIV, migrants, refugees, and prisoners.19
Conclusion

The theme of World TB Day 2022 - ‘Invest to End TB. Save Lives’ aims to raise awareness of the investment and the urgent need to invest the resources required to ramp up the fight against TB. This is particularly important in the context of the COVID-19 pandemic as people struggled to access services and most countries attention and resources were diverted to tackling the pandemic, putting the End TB progress at risk.20  Although TB isn’t considered a burden to many developed countries, perhaps the most important lesson learnt from the pandemic is that unless we are all safe, no-one is safe and eradicating this treatable and preventable disease is a task for today not tomorrow.

LSHC blog 7 Jan 2022 author

Dylan Powell, Research Analyst, UK Centre for Health Solutions

Dylan is a Research Analyst at the Centre for Health Solutions. He is excited by the value of technology, data and innovation in healthcare and life sciences to optimise care and wellbeing for patients and society. Prior to joining the centre, Dylan’s professional background as a Physiotherapist has spanned the NHS, professional sport, and the armed forces. His doctoral work in Computer Science explores the use of wearables in remote monitoring & objective healthcare assessment with collaborators across the USA and Australia. Dylan holds a Bachelor of Science degree in Human Biosciences (University of Exeter) and a Master of Science degree in Physiotherapy.

Email | LinkedIn

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1 https://science.thewire.in/health/preventing-tuberculosis-relied-bcg-vaccine-100-years-innovation/

2 https://theconversation.com/vaccines-alone-arent-enough-to-eradicate-a-virus-lessons-from-history-152734

3 https://www.familyhistory.co.uk/the-tuberculosis-epidemic/

4 https://www.theguardian.com/commentisfree/2013/dec/01/fight-against-tb-killer-is-back?msclkid=154eb5c6aa0011ec9aab7018c647b67c

5 https://www.who.int/teams/global-tuberculosis-programme/data#csv_files

6 https://www.who.int/teams/global-tuberculosis-programme/data#csv_files

7 https://www.who.int/news/item/14-10-2021-tuberculosis-deaths-rise-for-the-first-time-in-more-than-a-decade-due-to-the-covid-19-pandemic?msclkid=340849f2ab7e11ecb4a37e91ec317a89

8 https://www.who.int/teams/global-tuberculosis-programme/tb-reports

9 https://science.thewire.in/health/preventing-tuberculosis-relied-bcg-vaccine-100-years-innovation/

10 https://wwwnc.cdc.gov/eid/article/25/10/19-0619_article

11 https://www.who.int/teams/global-tuberculosis-programme/tb-reports

12 https://pubmed.ncbi.nlm.nih.gov/34036874/

13 https://pubmed.ncbi.nlm.nih.gov/16826312/

14 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592106/

15 https://medium.com/deeptek/how-ai-is-helping-us-fight-the-war-against-tb-c937cec8343c

16 https://blog.google/technology/health/tuberculosis-screening-ai-io-2021/

17 https://www.biorxiv.org/content/10.1101/275628v2.full.pdf

18 Deep learning predicts tuberculosis drug resistance status from genome sequencing data (biorxiv.org)

19 https://www.who.int/news-room/fact-sheets/detail/tuberculosis

20 https://www.who.int/news/item/14-10-2021-tuberculosis-deaths-rise-for-the-first-time-in-more-than-a-decade-due-to-the-covid-19-pandemic

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