Faster, more accurate tuberculosis test developed

December 2006

Researchers have developed a more sensitive, faster and cheaper rapid tuberculosis test than current culture-based tests called microscopic-observation drug-susceptibility, or MODS, according to a study in The New England Journal of Medicine.

“In the fight to stop the spread of TB, new diagnostic tools are urgently needed to detect TB and multidrug-resistant TB. MODS is just such a tool,” said researcher Robert H. Gilman, MD, professor in the Johns Hopkins University Bloomberg School of Public Health’s department of international health. “It will change the practice of TB testing in developing countries.”

MODS is a simple, rapid test that the researchers expect will have a major effect in developing countries where resources are limited, according to a release. Globally, more than 5,000 people die of TB every day and the poor are disproportionately affected, according to researcher David A. J. Moore, MD, senior lecturer in infectious diseases and tropical medicine at Imperial College in London.

“This is a curable illness. MODS was developed for developing countries in developing countries,” he said.

Moore added that testing with MODS is beneficial because it is performed on the clinical sample. “Drug susceptibility testing in the MODS assay is direct, or primary, rather than indirect, or secondary,” he said. “That is to say that it is performed directly on the clinical sample and not on a TB strain subcultured from the original. Thus, test results are much faster and the test is much safer than conventional tests because culture manipulation is not needed. As a further safety measure the plate is kept inside a polythene bag after sample inoculation.”

MODS TB test

Between April 2003 and July 2004, researchers from the Bloomberg School of Public Health, Imperial College London, the Universidad Peruana Cayetano Heredia in Peru, and other institutions collected 3,760 sputum-saliva samples mixed with respiratory discharge to complete sensitivity and susceptibility studies of the MODS test. They evaluated culture and drug-susceptibility tests in three target groups of patients: unselected patients with suspected TB, prescreened patients at high risk for TB or multidrug-resistant TB and unselected hospitalized HIV patients.

The researchers decontaminated all samples and then used for parallel MODS testing, as well as for two current gold standard TB tests, the Lowenstein-Jensen culture and automated mycobacterial culture (using the MBBacT system).

In order to test the samples using MODS, they observed the cultures under an inverted light microscope for 40 days. The sensitivity of detecting TB was 97.8% for MODS culture, compared with 89% for automated mycobacterial culture and 84% for Lowenstein-Jensen culture. The median time for detection of TB was seven days for MODS culture, 13 days for automated mycobacterial culture and 26 days for Lowenstein-Jensen culture.

The researchers also introduced isoniazid, rifampin, ethambutol and streptomycin-TB antibiotics-to the cultures in order to detect drug-resistant TB. Compared with standard culture reference methods, drug-resistant susceptibility agreement for MODS was 100% for rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined for multi-drug resistance), 95% for ethambutol and 92% for streptomycin. MODS results were available, on average, in seven days, making them clinically relevant. Standard antimicrobial tests can take up to several months.

“A single MODS culture of a sputum sample offers more rapid and sensitive detection of tuberculosis and multidrug-resistant tuberculosis than the existing gold-standard methods used,” the researchers concluded.

The MODS test relies on three principles:

1. Mycobacterium tuberculosis grows faster in liquid medium than in solid medium;
2. TB grows in characteristic tangles or coils and these characteristic cord formations can be seen microscopically in liquid medium;
3. The ability to incorporate drugs permits rapid and direct drug-susceptibility testing at the same time as the detection of bacterial growth.

The researchers acknowledged that MODS testing requires a trained technician and a biosecure environment in which to perform the test. However, they noted that the 10-day training period is comparable to testing currently done to read malaria smears.

For more information:

• Moore DAJ, Evans CAW, Gilman, RH, et al. Microscopic-observation drug-susceptibility assay for the diagnosis of TB. N Eng J Med. 2006;355:1539-1550.