TB meningitis is a major cause of death in Southern Africa. Early diagnosis is the key to improving the health outcomes of this disease, but the current diagnostic tests are not as quick or as sensitive as they need to be. That is changing thanks to researchers at Antrum Biotech and the University of Cape Town.
Antrum Biotech and the University of Cape Town have developed a new rapid test able to diagnose tuberculosis (TB) meningitis within two hours. The test is currently undergoing validation to enter the market.
Two percent of TB cases, which are caused by Mycobacterium tuberculosis, develop into an infection of the membranes around the central nervous system (meninges). TB meningitis can cause death or disability, especially in children, but is easily treatable if diagnosed early.
“The accurate diagnosis of TB meningitis is therefore a critical unmet need in public health, with problems of undetected TB meningitis and misdiagnosis affecting health outcomes,” says Khilona Radia, chief executive officer of UCT spin-off company Antrum Biotech.
“The greatest need for the test is in populations with a high burden of TB and HIV; particularly in sub-Saharan Africa where the test will be evaluated and launched,” she says. “The long-term goal of this project is to reduce global TB meningitis deaths.”
The new Antrum Biotech test will compete against TB meningitis tests that either take too long to detect Mycobacterium, or are not sensitive enough to find it when it is there. The test surpasses smear microscopy and the WHO-recommended GeneXpert diagnostic in sensitivity, and since it takes a few hours to yield results, it is much more rapid than growing a culture in a lab.
“Detection under the microscope only works 5% of the time. Smear microscopy is a very poor test,” says Professor Keertan Dheda, the director of the Centre for Lung Infection and Immunity at UCT and principal investigator of the clinical evaluation studies.
“Another existing test for TB meningitis involves growing the bug in the lab in a culture, and there are problems with that too,” he says. This culture-based test has a sensitivity of only 60-70%, and it can take four to eight weeks to give a result. “By then most people would have died, or they would have developed severe disabilities,” says Dheda.
The GeneXpert DNA detection test for TB is widely used in South Africa, but studies show that it has limited sensitivity. “Although it is rapid in getting the answer on the same day, the problem is that it detects TB meningitis in only 50-60% of cases; we have a major unmet need for a more sensitive test,” says Dheda. “Preliminary results from our studies show a vast improvement in sensitivity when compared to GeneXpert.”
Funding from the Finnish – Southern African Partnership Programme BioFISA II has allowed the researchers to develop the test further, and it is now undergoing a series of validation studies in southern African populations to pin down its sensitivity more accurately. This will include comparative sensitivity to GeneXpert.
“The Southern Africa Network for Biosciences (NEPAD SANBio) funded collaboration between the University of Malawi College of Medicine, the Biomedical Research Training Institute in Zimbabwe, and Antrum Biotech was a first; this has solidified our partnerships for future research, development and capacity building across African countries,” says Radia.
Antrum Biotech and its partners plan to continue with validation studies in other forms of extra-pulmonary TB even after the test goes on sale in the near future.
“There will be ongoing studies by different groups of people in different parts of the world to confirm the results that we find in southern Africa,” Dheda says.