NEW YORK (360Dx) – The New York State Department of Health is planning to stop conducting drug susceptibility testing for tuberculosis isolates that are determined to be pan-susceptible through whole-genome sequencing.
The move, which NYSDOH says it is able to do because of the accuracy and the comprehensiveness of its whole-genome sequencing data, is expected to save time and money, and free staff to explore other areas of tuberculosis testing that have not been as thoroughly investigated, according to lab officials.
"It's only because we are looking at the whole genome, and all of the different drugs that are being used, and all of the literature – being able to have this comprehensive assessment is what is really different in this case rather than just having a couple of different assays and looking at a couple of different mutations," said Kim Musser, chief of bacterial diseases at the New York State Department of Health's Wadsworth Center.
Of the 806 cases of tuberculosis in New York State last year, just 46 were drug resistant, and an even smaller number of those were multi-drug resistant or extensively drug resistant, according to data presented by Vincent Escuyer, director of the NYSDOH Wadsworth Center microbiology laboratory, at the American Society for Clinical Lab Science annual meeting in Chicago earlier this month.
That percentage is fairly typical, according to Musser.
"Ninety to 95 percent of the isolates that get sent to us turn out to be fully treatable with the normal drug regimen for TB. So, that is a lot of work on isolates that are predominantly drug susceptible," Musser said.
While the Wadsworth Center conducts susceptibility testing on a primary specimen, such as sputum, as well as isolates, the move away from drug susceptibility testing is only for isolates, Musser noted. Protocols may differ among labs, but many labs sent isolates to the NYSDOH after a positive acid-fast bacilli (AFB) culture, a common test for tuberculosis, she noted.
NYSDOH is taking a very conservative stance in determining which isolates are pan-susceptible, Musser said, noting that isolates for which there is not yet enough data available will continue to be tested until the lab is confident that it has amassed sufficient data. To make the move, NYSDOH used protocols similar to those that have been used in other disease areas.
"We are very used to doing that sort of evaluation and making a decision based on the data," Musser said.
Musser did not provide a precise date for when the susceptibility testing on pan-susceptible isolates would stop, but the center has begun the process to make the transition.
Currently, all isolates that come to the NYSDOH Wadsworth Center undergo a PCR-based test to confirm the mycobacterium tuberculosis present. Whole-genome sequencing is then conducted to create a resistance profile, according to Musser.
The lab uses an Ion Torrent from Thermo Fisher Scientific and a MiSeq from Illumina for WGS, and has been conducting whole-genome sequencing for over two years. On average, whole-genome sequencing results are released in 12 days for isolates, nine days before the first isolates drug susceptibility test results, Escuyer said in his conference presentation. Additional WGS time savings could be achieved if they further optimize batch testing, but that has not yet been emphasized, he noted.
The drug susceptibility testing is conducted using a Bactec mycobacteria growth indicator tube (MGIT) 960 from Becton, Dickinson, Musser said. It is this process, which can be lengthy because it takes time for bacteria to grow, that will no longer be conducted on pan-susceptible isolates.
"We only have a certain amount of budget we can use to do all the testing we do," said Musser, who did not quantify the cost savings from moving away from susceptibility testing for pan-susceptible isolates.
"If we can use this whole-genome sequencing that we are very comfortable with, and which provides so much valuable data, and then drop something like doing months of susceptibility testing on a strain we know from experience is not going to be resistant to any drug, we can put time and resources of our staff into the next type of testing," she said.
As a result of reducing the amount of susceptibility testing it performs, the Wadsworth Center might be able to increase direct specimen testing, she noted. "We have been doing some testing on [primary specimens] for a couple of years, but there is a lot to be done to bring that to the same level as isolate testing," Musser said.
In addition, the center would like to devote additional resources to minimum inhibitory concentration (MIC) testing, which would enable the lab team to look more closely at different concentration levels of a drug for a subset of bacteria. There are also new tuberculosis drugs the center would like to study more fully in terms of susceptibility, and the center would like to conduct more testing of nontuberculous mycobacteria, which would be specimens that test positive for acid-fast bacilli, but do not cause tuberculosis, Musser said.
The data on whole-genome sequencing for tuberculosis has become extensive enough that other countries that have invested in in WGS testing have reached similar conclusions about moving away from drug susceptibility testing for pan-susceptible isolates, Musser said. As a result, the NYSDOH's change to testing procedures will be loosely coordinated with similar efforts in the UK and the Netherlands, Musser said.
"It wasn't really a planned coordination per se, but as we are scientists and we are working on important public health issues, we have been doing work and publishing on our testing. It has led us to come to similar conclusions with some of these other groups that have been testing large subsets of either their data or large consortium sets of data," Musser said.
NYSDOH representatives have participated in conference calls with representatives of Public Health England, who are planning a similar time table to move away from susceptibility testing for pan-susceptible isolates. Public health officials from the Netherlands who have been coordinating with Public Health England have been on the call as well.
Significantly, the UK and Dutch public health officials are in agreement with NYSDOH as to which isolates are pan-susceptible and do not need to be tested for drug resistance.
"The true backbone to understanding what the genome predictions for pan-susceptible isolates provide is very agreed upon. The gene targets, the types of mutations, all of that is very much agreed upon among the different groups," Musser said.
Thus far, the representatives of the different countries have mostly shared where they are in the process of making the testing change. NYSDOH, for example, had to involve the Centers for Disease Control and Prevention in the process, and the UK and Netherlands groups had similar approval steps to take.
Moving forward, the three organizations plan to share details of what they learn as they change processes.
"I think we have agreed through discussions that we will let each other know the date that we move forward, and we will have a meeting at a certain point in time, maybe three or six months after we start, just to talk about how it's going and anything we have learned," she said. "We may talk about any exceptions or challenges to making this step, but I think it would be more on a scientific level, learning from each other about logistics in different areas."