Rapid PCR rules as labs ready flu arsenal

Compared with drugs, which are easy to transport and require little space, “Detection technologies are a little trickier because they’re bulkier and using them is more complicated than giving someone a pill.” Nevertheless, he says, companies that are developing diagnostic hardware that is more portable, more user friendly (through battery power, for example), and more useful in remote areas are more likely to be competitive in worldwide markets.

The core microbiology laboratory at Henry Ford Health System in Detroit is a busy one. It receives microbiology samples 24/7 from the system’s six hospitals and 30 associated medical centers. But two years ago, the laboratory decided to decentralize influenza testing to nine of the system’s stat labs, says Linoj Samuel, PhD, division head of clinical microbiology. “We have EDs all over southeast Michigan and all these urgent care centers, and they need timely results for things like influenza.”

During the decentralization process, the rapid antigen tests at almost all these locations were replaced with 20 to 25 Roche rapid PCR Liat instruments, and the laboratory knew this switch would require careful groundwork. “We put a lot of work into educating clinicians about the new technology. We made sure to convey to the emergency department physicians the advantages of having the new technology operating closer to them. And that it was on them, first, to order testing only in patients where it was required because the molecular test was more expensive, and, second, to only order the test in patients for whom we knew it would make a difference in management.”

“Before we even went live with the new rapid PCR installation,” Dr. Samuel says, “the ER clinicians told the laboratory the Liats would have a dramatic impact in terms of better antiviral usage, better antibiotic usage, and potentially reduced admissions.” Dr. Samuel’s team reported at the American Society for Microbiology Microbe meeting, after extensive data collection, that between the 2015–2016 season (running the antigen test) and 2016–2017 season (running the rapid PCR test), there were 40 percent fewer tests due to the impact of clinician education, but a 25 percent increase in the number of flu cases detected.

“We also had data showing that patients who were tested with PCR and shown to be positive were actually less likely to be admitted using these molecular tests.” A separate study the team presented at the Infectious Diseases Society of America IDWeek showed that in the ED setting, “We reduced antibiotic usage from about 14 percent in the base group of patients getting antigen testing to eight percent in patients tested by PCR. We also reduced our 30-day revisit rate for patients with respiratory symptoms from 10 percent to four percent.

“So this is one of the few cases where you predict what will happen with new technology and the prediction actually works out in the manner you expected,” Dr. Samuel says.

One of the early challenges of transitioning from rapid antigen tests to molecular testing, his laboratory discovered, was that there are more bottlenecks because the instruments run only one test at a time. “With the Liats, the limiting factor is the number of machines at each location. So early on, we had to increase the number of machines,” and that drove up the laboratory’s capital expenditures.

Another challenge came from early instrument problems that took a little time for the company to fix. This required an adjustment by the clinicians, who were not used to relying on a machine. “Unlike with the influenza antigen, which was a manual test, with PCR when the machine went down your testing was not happening. So we had a lot of frustrated clinicians at the time. But we worked through it and the instrumentation issues were solved. The second season we were live with the machines and we did not see that problem at all.”

In a heavy flu season like 2017–2018, the benefit of using stat PCR was seen at Henry Ford: It freed up isolation rooms faster than when traditional PCR was performed once or twice a day. “The availability of a stat influenza PCR 24/7 that can rule out influenza definitely allows you to take patients out of isolation and free up the rooms,” Dr. Samuel says.

“Over time, in addition to that, we have shown that we have reduced the length of stay in patients by bringing in the stat PCR tests available 24/7. At our main campus, we reduced length of stay by one day of incubation. If you factor that in, at a cost of $750 per room per day, that adds up to a lot of money, and it goes quite a way toward compensating the cost of bringing in this testing.”
Rapid PCR flu testing doesn’t offer any improvement in turnaround time compared with rapid antigen. “In some cases, it might be a little slower, especially if you have a high volume of samples and only so many instruments to run them on. But I think those delays are offset by having a much more reliable result.”

As of mid-November, “sporadic” was the adjective the microbiology laboratory and New York State public health officials have been using to label this flu season, says William Jerome, MLT, point-of-care coordinator for St. Peter’s Health Partners in Albany, a large multihospital system with many owned medical practices in upstate New York.

Jerome is happy with the performance of the benchtop Quidel Sofia fluorescent immunoassay instruments that St. Peter’s 60 physician offices have been operating since March 2017. In some cases the offices have multiple instruments running the Influenza A+B assay.

In October 2017, the practice’s 60 physician office labs performed 130 flu tests with 10.7 percent positive. In October 2018, “we did 350 flu tests at the 60 sites and our percent positives were only 3.9 percent. It seems the doctors are testing a lot more than they should be, considering the percent positives so far we are seeing this year,” Jerome says. He speculates the increase is due to apprehension about a repeat of last year’s spike in influenza infections. As a benchmark, in all of New York for the week ending Nov. 10, there were seven patients who tested positive for influenza A and one for influenza B.

User error with the rapid antigen test is small, he says. The instrument is “almost foolproof,” and his laboratory has found that false-negatives are not an issue. The core laboratory at St. Peter’s Hospital uses the Cepheid GeneXpert Infinity System PCR assay for confirmation testing with a turnaround time of 24 hours. For strep testing, following testing on the Sofia, a second swab is sent to the microbiology lab for culture. However, the lab is considering discontinuing that practice because it rarely turns up a positive.

At Jacobi Medical Center in the Bronx, one of 11 New York City hospitals, the priority in the run-up to flu season has been readiness, says Stephen Apfelroth, MD, PhD, director of clinical laboratories and assistant professor, Department of Pathology, Albert Einstein College of Medicine. “So far this season is very slow, but we went to a lot of effort to get prepared after the big season we had last year.” Among the problems: not having capacity or money to do PCR testing on everybody. “In the beginning where we were triaging, only patients to be admitted would be tested by PCR, and patients who weren’t sick enough and were going to get sent home would be done by rapid antigen testing.”

“But once we got comfortable with the PCR testing, doctors wanted the right answer on everybody.” So this year the laboratory has already increased the capacity of its Cepheid GeneXpert from four modules to eight. “On a busy day in the ER, you can easily get 10 to 15 people coming in within an hour or two. With four modules it was a struggle. We did manage, but with eight modules it is a lot more comfortable.”

Jacobi Medical Center’s patients are particularly susceptible to flu. “We have more patients with comorbidities and a big proportion of our admitted patients are nursing home patients. The Bronx is one of the counties with the highest incidence of diabetes, and that also makes patients with the flu more likely to be hospitalized,” Dr. Apfelroth says.

Cepheid is also marketing its point-of-care PCR for influenza, but Jacobi Medical Center is not using it. “The volume is enough that they can send their samples to the main laboratory,” he says. Antigen testing is still available but largely phased out. “You know everyone in the ED knows they want PCR. When we were doing rapid antigen, a positive on either test would lead the clinician to initiate antivirals, but they would also treat some of the negatives if they still had a strong suspicion of flu. Now they are satisfied with the predictive value of the negative with the PCR, so they are only treating the ones that come out positive.”

In general, the budgets of health care systems for flu testing have to increase significantly because PCR costs more, Dr. Apfelroth says, but in terms of patient management and sometimes discharging patients who don’t have the flu, “molecular testing definitely pays for itself.”

Facing a flu season of unknown intensity, “We’re in a better position than we have ever been,” Dr. Samuel says of clinical laboratories. When he first started training 10 or 15 years ago, influenza culture performed by centralized facilities required seven days. Later, rapid culture made that a two-day process. “We then transitioned to core lab molecular testing, which was a much better test but still centralized. And now we’ve pushed this complex, highly sensitive test out to point of care.” It’s only a matter of time, he says, before CVS, Walgreens, and Walmart are offering these tests. “But in the past, when patients would be sent home and treated empirically, people were getting antibiotics they didn’t need or not getting the Tamiflu they did need. Now, with these rapid tests, the patient can wait at the ED, get the appropriate drug, and then be sent home.”

Anne Paxton is a writer and attorney in Seattle.