Active tuberculosis can be sniffed out from TB-like diseases in just 30 minutes, thanks to this test

Over a million people die from active tuberculosis every year and the test aims to address this issue.


                            Active tuberculosis can be sniffed out from TB-like diseases in just 30 minutes, thanks to this test

Over 10 million people around the world have active tuberculosis (ATB), and every year more than a million die from it, mostly in low-resource countries. To address this problem, scientists have developed a highly sensitive test that can distinguish active cases of tuberculosis (TB) from similar diseases in adults in less than an hour - helping to meet an elusive goal for global health authorities. 

The setup used in the study can be configured into an easy-to-use, point-of-care diagnostic test that costs only about $2 for spotting TB cases, which often go undiagnosed in vulnerable patients such as those with HIV. It can give results within 30 minutes, says the research team from Wyss Institute for Biologically Inspired Engineering, The Broad Institute of MIT and Harvard, Brigham and Women's Hospital (BWH), and several other collaborating institutions. 

"Our test demonstrated 86% sensitivity and 69% specificity, which are very close to the World Health Organization or WHO's minimum requirements of 90% sensitivity and 70% specificity for an effective TB triage test," says first author Dr Rushdy Ahmad, a former research scientist at the Broad Institute, who is now president of True North Bio.

The test can be used by local providers in local settings to determine which patients need to be taken to a clinic for the evaluation and definitive TB diagnosis.

First author Rushdy Ahmad trains local  staff in processing blood samples at the Department of Parasitology and Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. (Rushdy Ahmad)

The researchers say the test also performed very well on patients with samples across three different continents. This, explains the team, implies that the TB test is effective in all types of TB strains. It was also effective on HIV positive and HIV negative samples, making it widely applicable to most active TB patients. According to the researchers, this is particularly important in resource-poor settings, where a lot of patients who get HIV also get TB.

"It also effectively identified the ATB signature in patient samples from three different continents, meaning it can detect many strains of the pathogen, and in both HIV-positive and HIV-negative samples, making it widely applicable to most ATB patients," says Dr Ahmad.

Why is the study important?

The prevention and control of TB depend on having an effective, accessible test to detect cases and identify people who are at risk of infection. However, diagnosing cases of active TB can be difficult because there are many other diseases that cause TB-like symptoms. This challenge, on top of obstacles such as drug resistance and a high burden in the HIV-positive population, has thwarted efforts to bring the disease in check, especially in developing countries.

Diagnosing cases of active TB can be difficult because there are many other diseases that cause TB-like symptoms. (Getty Images)

"There is an urgent need for improved diagnostics to detect, treat, and thereby reduce the tremendous global health burden of active tuberculosis (ATB). The Global Burden of Disease collaborators estimate that in 2015, total new and relapsed TB incident cases reached 10.2 million, with 10.1 million prevalent cases and 1.3 million deaths," says the study published in Science Translational Medicine.

It further says, "Most recently, the WHO reported similar TB mortality numbers for 2017, where they estimated that 1.3 million deaths were caused by TB among HIV-negative people with an additional 300,000 deaths from TB among HIV-positive people." 

The researchers say the historic standards of taking a sputum sample and culturing it is slow and often not sensitive enough to correctly identify TB, which means that there are many patients whose disease needs treatment are not identified until it is too late.

The majority of patients live in low-resource countries where diagnosing ATB is especially challenging. The researchers explain while there are newer, sensitive methods that are of good quality, but they require expensive lab equipment and infrastructure that are not available in local communities where it is needed. 

To help ill patients at highest risk for having active TB get the care they need, the WHO has called for the creation of a triage test that is blood-based rather than sputum-based - to minimize the infrastructure required to deploy it - that can identify high-risk patients who should be given a diagnostic test. Several commercial blood tests have sought to fill this gap, but the WHO has strongly recommended against their use based on evidence that these tests are too inaccurate.

How does the new test work?

The new diagnostic test analyzes the levels of four proteins and an anti-TB antibody in blood to distinguish patients who have ATB from those who look like they have TB, but have other respiratory diseases.

The researchers studied three cohorts of patients with chronic cough (406 total) using machine learning techniques and identified four blood proteins that could distinguish active cases of TB from TB-like diseases. The team then created an ultra-sensitive immunoassay that screens for these proteins in blood samples. The team’s panel could pick out TB infections in 317 samples from patients with persistent cough from Africa, Asia, and South America, and performed well in patients regardless of their HIV infection status.

The research team says it will continue to refine and improve their triage test by adding more diagnostic biomarkers.

The research team worked with staff at the Public Health Laboratory-Ivo de Carneri on the Tanzanian island of Pemba to obtain blood samples from patients with suspected tuberculosis for the study. (Rushdy Ahmad)

"The fast, ultrasensitive, multiplexed blood-based TB triage test analyzes a 'signature' of the combined levels of four proteins and an anti-TB antibody in blood samples to identify patients who are likely to have ATB and require advanced diagnostics and treatment. It can be configured into a point-of-care test that costs only $2 and gives results in about 30 minutes, lowering the barrier to care in low-resource settings and potentially saving millions of lives," the findings state.

The setup used in the study costs about $10 per test but could be configured into a $2 version using less expensive materials.

"Not only is this method one of the fastest and most accurate ATB triage tests available, it is also much more amenable to deployment in low-resource communities than other existing approaches, it works on patients with different strains of TB, and its results are not complicated by HIV infection status," says co-corresponding author Michael Gillette, a research scientist and senior group leader of the proteomics and biomarker discovery program at the Broad Institute.

Gillette — who is also a pulmonary/critical care physician at Massachusetts General Hospital — adds, "These qualities give it the potential to be a lifesaver by identifying patients who need a diagnostic TB test right away, which would reduce both deaths from undiagnosed ATB and overuse of antibiotics and expensive diagnostics on non-ATB patients."

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