Physicians in India publicized the first cases of totally drug-resistant tuberculosis there in a December Clinical Infectious Diseases paper, making theirs the third country in which the disease has reportedly emerged this decade, following Iran and Italy.
Meanwhile, India's Ministry of Health and Family Welfare has disputed the physicians' claims to have seen patients with this completely resistant form of TB, known as TDR-TB, saying instead that the patients were likely affected by an extensively drug resistant form, or XDR-TB. Discussions over the possibility of such a disease arising speak to how little researchers know about the mechanisms underlying drug resistance in tuberculosis.
That is where the Special Program for Research and Training in Tropical Diseases' TB Strain Bank comes in. The program, sponsored in part by the World Health Organization, set out to "establish a bank that could allow researchers to develop and evaluate tools for drug-susceptibility testing of tuberculosis," says Leen Rigouts at the Institute of Tropical Medicine in Antwerp, Belgium. "The second aim, linked to that, was to make these strains available ... among the worldwide network of laboratories performing surveillance of drug-susceptible and drug-resistant TB."
The newly launched TDR TB Strain Bank consists of 229 clinical Mycobacterium tuberculosis isolates collected from around the world, plus five reference strains. Rigouts and her colleagues phenotyped each strain extensively, estimating minimum inhibitory concentrations for both first- and second-line drugs, and genotyped each using DNA fingerprinting techniques. Further, the team sequenced target genes involved in anti-TB drug interaction in each strain.
The team found it important "to include strains from all over the world because there are different genotypes prevailing, and different genotypes might act in different ways phenotypically," Rigouts says. She adds that information gleaned from these strains "can help [researchers] to develop proper tools, because if you have knowledge of the genetic background of the resistance, it's easier to develop rapid [screening] tools."
Indeed, among the requests for samples her group has fielded thus far have been several from companies working to develop and validate tools to rapidly detect drug-resistant TB strains.
Now, to take their analysis of TB drug susceptibility a step further, Rigouts and her collaborators at the London School of Hygiene and Tropical Medicine, King Abdullah University of Science and Technology in Saudi Arabia, and elsewhere intend to produce whole-genome sequences for each strain in the bank. "The availability, now, of whole-genome sequences will be important to gain insights into drug-resistance mechanisms that have not been discovered yet," Rigouts says, adding that she expects the genome sequences will be available by year's end.