Fast, accurate and easy TB test developed, but concerns about its safety raised

An international team of researchers has developed a new test for tuberculosis (TB) that is faster and more accurate than the current “gold standard" tests. A study conducted in Lima, Peru, found that a microscopic-observation drug-susceptibility (MODS) test on sputum samples not only detected the presence of TB more accurately and faster than the two tests in standard use, but was also able to determine, with a high degree of sensitivity, if a patient was infected with drug-resistant TB. The study is published in the October 12^th edition of the New England Journal of Medicine.

However, although an editorial in the same issue of the journal notes the advantages of the MODS assay, it raises concerns about the biosafety of MODS.

TB is a completely curable disease, but there are approximately 1.7 million TB deaths a year around the world, mainly in poorer countries. Current sputum-smear diagnosis misses half of all new TB cases at first presentation, so there is an urgent need for new diagnostic tools that are cheap and easy to use.

Proof-of-concept studies have already shown that the MODS assay is able to distinguish between patients with TB and healthy controls. In the current study, an international team of investigators collected over 3,750 sputum samples from patients in Lima to further examine the utility of the MODS assay. The study was conducted between 2003 and 2004.

The patients recruited to the study came from three groups: individuals presenting with suspected TB at ten government clinics in Lima; patients who were at high-risk of TB, including multi-drug resistant TB, who were seen at one of five specialist TB clinics in east Lima; and, HIV-positive patients who were receiving treatment as in-patients at two Lima hospitals.

Sputum samples were collected from the patients and tested for TB using the MODS assay and the two current gold standard diagnostic tests – the Lowenstein-Jensen culture and the automated mycobacterial culture.

The researchers also exposed the sputum cultures to four anti-TB drugs – isoniazid, rifampicin, ethambutol and streptomycin, to see how accurately and quickly the three different testing assays could detect drug-resistant TB.

A total of 401 (11%) sputum samples yielded positive TB cultures. The MODS culture had a sensitivity of 98% compared to 89% for the automated mycobacterial culture and 84% for the Lowenstein-Jensen culture. The difference between the sensitivity of the MODS assay and the two current gold standard tests was statistically significant (p < 0.001).

Then the researchers looked at how rapidly the three methods of testing yielded results. They found that the median time for the detection of TB was seven days using the MODS assay, compared to 13 days for the automated mycobacterial culture and 26 days for the Lowenstein-Jensen assay. Once again, these differences were statistically significant (p < 0.001).

Furthermore, the investigators found that the MODS test could determine if TB was drug-sensitive or drug-resistant quicker than the other two methods of testing and with a high degree of accuracy. Results were available using the MODS assay after a median of seven days, compared to 22 days using the automated mycobacterial culture and the 68 days for the Lowenstein-Jensen culture. These differences were described by the investigators as “clinically relevant.”

“MODS was developed for developing countries in developing countries,” commented the lead author of the study, Dr DAJ Moore of London’s Imperial College.

Although MODS testing requires trained technicians, and a biosecure environment, the investigators note that the duration of training is ten days, comparable to that provided to laboratory staff for the reading of malaria smears.

The investigators are hopeful that the MODS test will have a major impact on the detection of TB and facilitate its appropriate treatment in resource limited settings.

The authors of an accompanying editorial write "his report...provide(s) support for an affordable, rapid method of culture-based diagnosis and detection of drug resistance in countries with limited resources." However, they have reservations about the MODS assay, adding, "we believe that, in its current form, the MODS assay will require further improvement and standardization before it can be recommended for broad application in such countries." Their principal concern regards the biosafety of MODS testing, and they emphasise that its safe use will require a "basic tuberculosis laboratory."