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Better diagnostic tools are needed in the fight against tuberculosis
Rapid diagnosis and treatment are crucial. However, today's testing methods are not good enough. Tests based on blood biomarkers may be the solution.
Many of us believe that tuberculosis has been eradicated, but this is not the case. In large parts of the world, tuberculosis is the infectious disease that takes most lives.
Every year, 1.5 million people die from tuberculosis, according to the World Health Organization (WHO).
South Africa is one of the countries that is most affected.
What is tuberculosis?
Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis bacterium. The infection can occur in various organs of the body, such as the lungs, brain, lymph nodes, and the skeleton.
The immune system plays a key role in the development of tuberculosis. Individuals who become ill have usually been infected with the tuberculosis bacterium at some point earlier in life. Those who live in areas with high tuberculosis prevalence are often infected during childhood.
However, most people do not become ill but develop a condition called latent tuberculosis. This means that there are small remnants of the tuberculosis bacterium in the body. The immune system keeps the infection under control. If the immune system becomes weakened, for example due to illness or as a person gets older, the immune cells may not always be able to containt the tuberculosis infection. It is only then that the person becomes ill.
During the Covid-19 pandemic, the situation became even worse. More people became ill and died from tuberculosis due to lockdowns and poorer access to healthcare.
Urgent need for rapid diagnosis and treatment
Similar to Covid-19, early and rapid testing and treatment are important both for those who are ill and to prevent the spread of the disease to others.
“With the increase in the number of cases and deaths during the Covid-19 pandemic, we cannot stress the need for early, fast, and accurate diagnosis enough,” Bih Hycenta Chendi says.
She is a researcher at Stellenbosch University in South Africa where she works with Professor Novel Chegou. They collaborate with Professor Anne Ma Dyrhol-Riise at the Institute of Clinical Medicine at the University of Oslo.
Several challenges with current tuberculosis tests
Tuberculosis is caused by a bacterium called Mycobacterium tuberculosis. The most common testing method today involves bacterial cultures. Healthcare personnel take samples of the patient's sputum to find out if it contains the bacteria.
“There are several challenges with today's tests. One of them is that it takes a long time to get the result. In addition, they are not that sensitive or accurate,” Chendi explains. “Especially in areas with poor infrastructure, such as several areas in South Africa, there is a great need for new ways of detecting tuberculosis."
Have found a new way to test for tuberculosis
In a new study, Chendi and colleagues have found that some substances in the blood can show whether a person has tuberculosis.
Such substances are called biomarkers.
The biomarkers refer to any measurable biological component in the blood that reflects ongoing immune processes in the body at a particular state.
“We now know more about how the immune system reacts to a tuberculosis infection. This is the reason that some researchers have suggested that these biomarkers may be used to diagnose tuberculosis,” Chendi explains.
Could detect tuberculosis using a blood sample
The researchers analysed blood samples to see if the various biomarkers that had already been identified could be used to diagnose tuberculosis in a setting like Norway, where the prevalence of tuberculosis is low.
“Most of the biomarkers that we looked at could detect with good accuracy whether a person had tuberculosis,” Chendi says.
She explains that this is consistent with what other researchers have found in previous studies.
Additionally, Chendi and her colleagues looked at combinations of different biomarkers.
“Compared to a single biomarker, the combinations of different biomarkers performed even better,” she says.
The tests can be used to monitor treatment response
Patients with tuberculosis are often seriously ill and hospitalised. The treatment involves a prolonged course of antibiotics aimed at eliminating the infection.
In the study, the researchers also investigated whether the biomarkers could be used to monitor the effect of the treatment.
“We saw that the concentration of some of the biomarkers in the blood changed from the time of treatment initiation and when evaluated at week two, month two and month six of treatment, highlighting their usefulness in monitoring treatment response,” Chendi explains.
New tests could reduce the number of unknown cases
The researchers believe it may be possible to develop new and improved tests for tuberculosis based on the biomarkers they examined in the study.
“The results from our study are promising. They show that the biomarkers we investigated have good diagnostic value for tuberculosis,” Chendi says.
Especially in areas heavily affected by the disease and with poor infrastructure, such new tests may be of great importance.
“Such a tool will ensure that we can make the diagnosis quickly and easily. It can also help reduce the number of undiagnosed cases and those affected can receive faster treatment. In particular, the gains will be large in African environments with few resources,” the researcher says.
Examined blood samples from individuals in South Africa and Norway
The study is a collaboration between researchers from the Immunology Research Group at Stellenbosch University and the Chronic Infectious Diseases research group at the University of Oslo (UiO) and Oslo University Hospital (OUS).
The researchers examined blood samples from 107 individuals with tuberculosis, 78 individuals with other lung infections, and 150 individuals without tuberculosis in both South Africa and Norway.
“The comparison between patients in South Africa and Norway made it possible to examine blood samples from people with different backgrounds and who are infected by the Mycobacterium tuberculosis in different parts of the world,” Chendi explains.
She adds that this is useful because it gave them the opportunity to investigate the diagnostic value of these biomarkers in a heterogeneous group with diverse biological and cultural characteristics.
The researchers used various statistical methods to investigate the selected biomarkers in the blood related to immune response.
Chendi et al. Utility of a three-gene transcriptomic signature in the diagnosis of tuberculosis in a low-endemic hospital setting, Infectious Diseases, 2022. DOI: 10.1080/23744235.2022.2129779
About the study:
The study was part of Bih Hycenta Chendi’s doctoral work. She received a scholarship from UiO and worked in the research group at UiO and OUS in 2019. She defended her thesis at UiO in 2022.
“The collaboration contributed enormously to the capacity development I achieved throughout my PhD and to the quality of my research. It made it possible to contribute to the field of tuberculosis research with important new knowledge that can have large implications for tackling this major global health challenge,” Chendi says.
The researchers in Stellenbosch and Oslo will continue collaborating.
The researchers at UiO and OUS are furthermore partners in an EU Horizon 2020 project on personalised treatment for tuberculosis patients.
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