A cheaper, indigenously developed molecular diagnostic test for drug-sensitive and rifampicin-resistant TB is entering the final leg of performance validation and operational feasibility testing by the Indian Council of Medical Research (ICMR).
ICMR plans to take the test to Public Health Centres, which currently use smear samples to test for TB, with a sensitivity level of only 50%, which is roughly half of what the newer method has achieved.
The diagnostic tool, Truenat MTB, which uses sputum samples for diagnosing TB is being tested in the field in 100 designated microscopy centres in 50 districts in 10 States. The one-month study will look at nearly 18,000 samples and the results are expected next month. The diagnostic tool has already been installed in 80% of designated microscopy centres for testing.
Encouraging results
Validation carried by ICMR at four sites in India tested nearly 5,000 samples from 2,500 patients. The samples were also tested for resistance to the drug rifampicin and the results have been encouraging.
Based on the results of a preliminary test carried out on 191 patient samples in 2013 , the sensitivity (ability of a test to correctly identify those with the disease) of Truenat MTB was found to be over 91% and the specificity (ability of the test to correctly identify those without the disease) was 100%. The results of the study were published in January 2013 in the journal PLOS ONE .
The battery-operated, hand-held machine takes about 25 minutes for DNA extraction and another 35 minutes for diagnosing TB. It takes an additional one hour for testing rifampicin resistance. Compared with a one ml of sample needed when GeneXpert, a molecular test developed in the U.S., is used, only about 0.5 ml is required for a test with Truenat MTB.
Operational feasibility
“Besides validating the performance, the focus is on operational feasibility in field settings. We want to see if the machine performs to our satisfaction in hot and humid conditions and whether the machine can work even in the absence of power, and lab technicians with minimum training can operate the machine,” says Dr. N.S. Gomathi at Chennai’s National Institute for Research in Tuberculosis (NIRT), who is coordinating the feasibility study.
According to Dr. Gomathi, the main advantage of Truenat MTB over GeneXpert is that only when samples are tested positive for TB will tests for rifampicin resistance be carried out. “That way the use of reagents may be reduced and will help make the testing cheaper,” she says.
“Diagnosing TB using Truenat MTB may be about 50% cheaper than GeneXpert,” says Dr. Soumya Swaminathan, Director-General of ICMR.
“The technology is chip-based and not cartilage-based like GeneXpert. So it will be more environment-friendly,” she says.
According to Dr. Gomathi, independent validation of Truenat MTB is being taken up by ICMR for paediatric and extra-pulmonary TB, where the amount of TB bacilli in a sample is low.
Open system
While GeneXpert is a closed cartilage system, Truenat MTB is an open system — the DNA is first extracted and the testing is carried out using a portion of that DNA.
“If we are not able to determine the results based on one test we can always retest the sample using the remaining DNA. The remaining DNA can be used for any other molecular confirmatory test or for testing rifampicin resistance if the test result is positive for TB,” Dr. Gomathi says. GeneXpert requires additional sample if the test has to be repeated.
“We can avoid drop-outs [patients not returning to provide second sample] since Truenat MTB does not need two samples,” she says.
“We are not going to replace GeneXpert. We are planning to take Truenat MTB to the primary health centre level, which cannot be done using GeneXpert since it needs uninterrupted power supply and air conditioning,” says Dr. Swaminathan.
