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Tiny tech to make big changes in testing for tuberculosis

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Postdoctoral Research Associate in the i-sense McKendry group at UCL, Dr Harriet Gliddon, recently travelled to South Africa with the support of a UCL Global Engagement Grant. The visit helped Dr Gliddon plan for a study looking at new sequencing technology to diagnose drug-resistant tuberculosis.



The current landscape

“Tuberculosis continues to elude control efforts, with an estimated 10.4 million new infections occurring in 2015,” says Dr Gliddon.

The same year saw 580,000 new cases of rifampicin-resistant tuberculosis or multidrug-resistant tuberculosis.

South Africa bears one of the highest tuberculosis burdens in the world and is one of the 27 high multidrug-resistant tuberculosis burden countries. Treatment at an early stage of infection can prevent people with tuberculosis from becoming more unwell and reduce the spread of infection, however knowing exactly what antibiotics a particular person should be treated with currently takes several weeks.



Engaging globally

i-sense has strong links with the Africa Health Research Institute, or AHRI, based in KwaZulu-Natal, South Africa and has expertise in diagnostics for antibiotic-resistant infections, rapid diagnostic tests, and online systems for rapid disease reporting and monitoring.

“Working at i-sense meant that I have been able to leverage off unique partnerships and expertise from across different disciplines in order to broaden my research,” explains Dr Gliddon

“I applied for and was awarded the UCL Global Engagement Grant with the aim of visiting AHRI to learn more about the problem of drug-resistant tuberculosis and understand how i-sense could make a difference.”

The objectives of Dr Gliddon’s visit were:

  • To understand the pathway of diagnosis for multidrug-resistant tuberculosis in South Africa, and to consider how genome sequencing could hasten it.
  • To meet and form collaborations researchers at the AHRI, and build new partnerships in tuberculosis research.
  • To commence planning of a preliminary study using the small, portable MinION sequencer for tuberculosis drug-resistance genotyping, and explore future funding opportunities.

Diagnosing drug-resistant tuberculosis in South Africa

“The MinION sequencer is portable, easy to use, has long sequencing reads, and can interoperate data easily,” says Dr Gliddon.

Currently in South Africa, patients with suspected tuberculosis provide a sputum sample, which is used for a Gene Xpert test. If found to have rifampicin-resistant tuberculosis, they are referred for phenotypic drug susceptibility testing, which can take weeks to yield results.

Whole genome sequencing has been shown to accurately diagnose tuberculosis and predict drug susceptibility. However, most platforms for performing whole genome sequencing rely on large, costly machines and highly trained personnel.

“With only 10 minutes required for DNA library preparation prior to sequencing, the MinION platform represents an extremely promising opportunity for sequencing in the field.”



Visit to Africa Health Research Institute (AHRI)

AHRI was established in 2016 through the merger of two existing research organisations: the Africa Centre for Population Health, and the KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH). As a consequence, AHRI now has bases in two sites, Durban and Somkhele, which are located 230 km apart.

“In the first week of my visit, I was given a tour of AHRI’s state-of-the-art laboratories, based in the K-RITH Tower Building in Durban, where a number of sequencing machines and biosafety level 3 laboratories are available,” says Dr Gliddon.

Visiting local clinics, such as Kwadabeka Community Clinic demonstrated the challenge of a lack of laboratory personnel and resources for tuberculosis diagnosis.

“My visit to Don McKenzie Hospital, which specialises in the care of patients with multidrug-resistant tuberculosis care, demonstrated the scale of the burden of the disease from the health system to individuals.”

In the second week, Dr Gliddon visited AHRI’s Somkhele site, which hosts 16 years of detailed population data from over 100,000 people. She also visited the nearby Hlabisa Hospita that is often used as a site of recruitment for AHRI’s studies, and was given a tour of their onsite laboratory, which is run by the National Health Laboratory Service.

“Over the course of this visit I was able to meet a number of clinicians and researchers that were extremely useful in refining our aims for this work,” explains Dr Gliddon.

“The visit has already informed our research and will aid the planning of future studies.”

Acknowledgements

I would like thank Dr Alex Pym for hosting this visit, and the following individuals who gave their time to me in South Africa: Vanisha Munsamy, Dr Kobus Herbst, Dr Richard Lessells, Prof. Tulio de Oliveira, Dr Eleanor Quicke, Dr Siva Danaviah and Theresa Smit. I would also like to extend my thanks to the support staff at AHRI for their help in arranging meetings and visits, and the UCL Global Engagement Office for their financial support.