Over the past 18 months hearing someone cough has probably made you wince and withdraw, while holding your breath, from what might well be a virus-laden cloud of aerosols. A cough has come to mean more than just a cold. It is the telltale sign of the highly contagious viral infection of the lungs, COVID-19.
In some parts of the world, however, a cough has never been just a cough.
At the start of the 19th century, tuberculosis (TB) had killed one in seven of all people who ever lived. Today, despite being curable and preventable, TB remains deadly. It kills approximately one person every 22 seconds, about 1.4 million people in 2019 alone. This makes it one of the top 10 causes of death worldwide and the leading cause of death from a single infectious agent according to the World Health Organization.
However, the care you receive when expressing symptoms depends on where you live.
In a high income country, a cough that could be symptomatic of TB would result in a test where you receive a small injection of an expensive protein extract, tuberculin. If you develop a bump of a certain diameter at the injection site you are diagnosed with TB and administered antibiotics. If that antibiotic doesn’t work, a test identifies the resistance of the infection and a more effective antibiotic will be prescribed. In such cases, TB is diagnosed and treated within a few days.
A similar cough in a medium to low income country may result in a sputum smear test which can take 8 weeks to diagnose TB. Once diagnosed, you will be administered antibiotics. If the antibiotic doesn’t work, it will take four weeks to do another drug susceptibility culture growth which tests for the effectiveness of antibiotics against the strain of TB that you have. However this is very time consuming and in India, one of the highest TB burdened countries, the total diagnostic delay from perception of symptoms to time of diagnosis is as long as 55 days.
An almost two month delay in diagnostic can be detrimental to the survival of the patient.
In South Africa, 10 million people developed TB in 2019 and 1.4 million people (14%) with TB died. One study found, of those in this category that died, around 70% of the deaths occurred within 30 days of diagnosis. This is why we need rapid diagnostics.
In many countries, socio-economic barriers put constraints on healthcare restricting access to diagnosis and treatment. Thus TB remains undiagnosed and spreads in communities causing death.
Many diseases across the globe are considered by those in wealthier nations as “diseases of the past”, but often they are rather diseases of the poor – still affecting millions of people every day. Researchers claim what is known as the 10/90 gap: only 10% of global health research is devoted to conditions that account for 90% of the global disease burden. In populations with no access to proper diagnostic technologies, these diseases are detrimental and cause easily preventable deaths. While some rapid diagnostic TB tests are being designed, the most common ones have suboptimal sensitivity and a high rate of false positivity.
This lack of an efficient and affordable diagnostic test fuels TB epidemic, which is where my work comes in.
For my PhD at the University of Cambridge Cavendish Laboratory, I am developing a technological platform that targets diseases affecting low-income countries the hardest. The platform is a small portable sensor which rapidly diagnoses the infection and identifies the genes encoding the antibiotic resistance and posing a therapeutic challenge. I do this using nanopore sensing combined with gene editing technologies.
As its name suggests, a nanopore is a nanometer-sized hole (a human hair is about 100,000 nanometers in comparison). The pore, typically 10-15 nanometers, is comparable to the size of single molecules including TB bacterial DNA which is 3 nanometers. We make a nanopore by using laser to heat, pull and shoot a straw-like glass capillary to create a nanosized opening, thus changing the straw into what looks more like a sharp-tipped pencil.
Through this nanosized opening in glass, salt is ushered using forces induced by electric fields which causes a stable current to develop, called “baseline current”. When molecules such as DNA from a patient sample are added and they go through the nanopore, because of their different sizes they cause blockages or changes from the baseline current. This change in the current allows us to directly observe the DNA passing through (see figure).
In infected patients, TB bacterial DNA and other useful TB biomarkers can be found in their sample. By using proteins and DNA nanotechnology, specifically CRISPR-dCa9 proteins, we can create a panel of specific barcodes that can be read by a nanopore sensor, allowing us to identify both the presence of TB and the resistance of the patient to different antibiotic treatments. You can see these proteins as spheres attached to the DNA in the figure.
Through planned field visits and industry support, I hope that my dream of creating an efficient and affordable diagnostic TB test becomes a reality.
Jamy-Lee Bam, Data Scientist, Cape Town
Paarmita Pandey, Physics Masters student, India
Nesibe Feyza Dogan, Highschool student, Netherlands
Una, writer and educator
Radu Toma, Romania
Financier and CEO, USA
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