19. Ending tuberculosis through low-cost and effective detection

Lena Fiebig

APOPO is a global non-profit organisation that researches and deploys detection rat technology to address global social issues, namely to detect landmines and tuberculosis. https://www.apopo.org/en.

Barriers to accessing healthcare leave many cases of tuberculosis undiagnosed

Tuberculosis (TB), although preventable and treatable, remains the world's deadliest infectious disease with approximately 1.6 million TB-related deaths in 2017. The World Health Organization (WHO) further estimated that 10 million people contracted TB that year and, among them, 3.6 million were either missed by healthcare systems, left undiagnosed or untreated, or were unreported. Many of these “missed” patients will die, while others will remain ill and are likely to pass the pathogen on to others. The reasons why so many TB cases are missed include existing barriers to accessing healthcare and the limitations of existing diagnostic tools. An ideal test, which is simple, cheap, fast, reliable, accurate across patients irrespective of age and HIV status, and can be used without a stable power source, has yet to be developed. Ending TB is one of the targets of the United Nations Sustainable Development Goal (SDG) 3 on health and well-being. The need for intensified research and innovation towards new tools, interventions and strategies is reflected in the WHO’s End TB strategy.

Training rats to diagnose tuberculosis at low cost

APOPO is a global non-profit organisation founded in Belgium in 1997 that researches and deploys scent detection rat technology to address global issues, namely to detect landmines and TB.

Under a collaboration agreement with the Sokoine University of Agriculture, APOPO established its operational headquarters and training and research facilities in Morogoro, United Republic of Tanzania (“Tanzania”). Our response to the TB case detection gap is special in that:

  • We are developing an entirely new diagnostic tool - we make use of African giant pouched rats and their remarkable sense of smell; and

  • We strive to already make a difference even while our technology is under continued research and development.

For APOPO’s research, human sputum samples are being collected from more than 100 partner clinics in Tanzania, Mozambique and Ethiopia (under research agreements with the respective health authorities). The clinics have already tested the samples for TB using locally available sputum smear microscopy, which has a limited sensitivity. All samples are transported to one of APOPO’s centralised facilities, where they are heat-inactivated (made safe), sorted and placed in batches of ten in a specialised chamber to allow sequential rat inspection. When a rat suspects TB, it “indicates” this to handlers by holding its nose over the sample for three seconds. Suspect samples are then rechecked using WHO-endorsed confirmation tests such as LED fluorescence microscopy or molecular tests. Confirmed TB-positive results are conveyed back to the clinics, which then orchestrate patient treatment. Collaboration with community health workers from patient organisations ensures that more newly diagnosed TB patients are linked to standard TB care at the clinics and no one is left behind.

Combining high-quality research with low-cost solutions as a key to success

Since its inception, APOPO’s TB detection programme has evaluated 517 325 sputum samples from 270 567 patients with presumptive TB, resulting in the detection of 14 086 additional TB cases. APOPO’s research raises partner clinic detection rates by about 40%.

One driver of success is our ambition to tackle global problems holistically, that is, to combine our TB scent detection research using African giant pouched rats - a low-cost and virtually unlimited natural resource - with service models including motorbike sample referral networks, 24-hour result delivery and patient tracking to ensure that newly diagnosed patients begin their anti-TB treatment.1 A further component is capacity building among our staff, partners and young researchers, the majority of whom are natives of the countries where we work, which have a high TB burden to tackle.

Additionally, maintaining strong scientific records is key in diagnostic test development, in particular our study of the test principle - what the rats actually smell (patterns of volatile organic compounds specific to the TB-causing bacteria) - and of rat odour discrimination, learning and performance.2

We have learned that diagnostic tool development, with the ambition to meet international standards, requires perseverance and partnership. A non-profit organisation, such as APOPO, can create innovation for comparatively low budgets; however, we are fully aware of the importance of our academic and collaborating partners, and our committed support network.3

What next?

Despite our continued accomplishments in detecting additional TB cases, we believe that our technology can and should be further improved upon. We have a strong ambition to conduct additional research and development into a refined TB detection technology (e.g. using non-invasive sample materials, like urine), and to make our innovation accessible to more people - first and foremost children, people living with HIV and other vulnerable groups. Our research has great potential for transfer to other medical (animal) scent detection applications and may inform the development or refinement of highly cost-effective and scalable synthetic devices, such as e-noses.

In its aspiration to inspire positive social change, APOPO continually explores other exciting and impactful areas of animal detection research, such as the detection of illegal wildlife products.

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