Keeping an eye on H7N9, and learning from the past

The H7N9 influenza virus is the latest in a string of potentially pandemic viruses that have shaped the relationship between public and private laboratories in the United States. “The molecular testing community has come an enormous way since the SARS outbreak in Hong Kong in 2002,” says David Hillyard, MD, medical director for molecular infectious disease testing at ARUP Laboratories. During the SARS outbreak, three labs quickly produced and shared genomic sequences, paving the way for laboratories to develop their own tests and distribute inactivated calibration proficiency materials. “We learned that people could discover efficiently, that they could get complete viral genomic sequences quickly, and that testing could be brought to bear very rapidly,” Dr. Hillyard recalls.

Things became more complicated with the avian threat of 2006, he says, when China’s nonrelease of sequences crystalized the importance of open-access information. With limited sequence data, the laboratory community found it much more challenging to mount a widespread response of the scale used to monitor and diagnose SARS.

In 2009, the H1N1 pandemic changed the landscape again. Within a short time—as the virus moved from Mexico to North America and beyond—viral sequences were released from several labs, and the CDC began distributing diagnostic reagents to state laboratories.

“So we find ourselves now with an influenza strain that has a very high case mortality rate, and we’re just learning about its source and how it is transmitted to humans,” Dr. Hillyard says. “There’s nothing to indicate we’ll have a widespread human pandemic, but fortunately there is a much improved infrastructure in place compared to previous threats. And the most important thing is how government, reference, and local laboratories have learned to better work together.”

The collaborative spirit lives on: In May, Nancy Cox, PhD, director of the CDC’s Influenza Division, spoke by teleconference to attendees at the Pan American Society for Clinical Virology annual meeting in Daytona, Fla. She provided a clinical and epidemiologic update on the state of the H7N9 outbreak and monitoring and containment efforts, as well as a description of the CDC’s current testing capabilities. Beyond meetings and updates, the CDC and WHO maintain excellent H7N9 Web pages that include information for laboratory testing, Dr. Hillyard notes. “Communication and cooperation between state laboratories and hospital, reference, and other non-government testing entities also seems to have improved,” he says.

“Our plan, based on early access to H7N9 sequences, and probably the plan of many other laboratories like ours, is to have H7N9 test reagents on hand now, not knowing what’s going to happen with this current threat,” Dr. Hillyard says. “We’ll perform initial preliminary validation testing in order to have an independent test’s capability in the eventuality of a need for spillover testing.”

One thing that hasn’t changed much since the early 2000s is the technology used to detect novel viruses like SARS or H7N9. Real-time PCR has remained the tool of choice, with a few modifications and enhancements over the years. “What has progressed are the databases we have for the design of real-time PCR tests,” Dr. Hillyard explains. “And what’s really progressed are the logistic relationships and algorithms for determining who to test, when to test, and when to forward specimens.”

In 2009, the first H1N1 assay to complete the full regulatory approval process was the Simplexa test, developed by Focus Diagnostics for the 3M Integrated Cycler system. Since the news broke in spring about H7N9, Focus, a business of Quest Diagnostics, has been building the capability to unveil an H7-specific test should the need arise.

“Our flu A detection is very robust, but right now we don’t have a multiplex test to differentiate H7,” explains Michelle Tabb, PhD, vice president of research and development at Focus Diagnostics. “Basically, it would involve dropping [H7] into a different channel on an existing test.” The new test would detect influenza A in one channel and H7 in another channel, and combine those results to generate a positive result for H7N9. In May, Quest received viral stock from the CDC and began producing contrived samples to confirm that its new test can detect H7 in human patients.

“We want to make sure we have the detection system worked out and that we have a predetermined sensitivity, so we can launch this right away if needed,” says Rick Pesano, MD, PhD, medical director for infectious disease at Quest Diagnostics. “Because in the case of H7N9 and similar viruses, it’s imperative that the physician has the information as rapidly as possible. If you’re standing in front of someone with a communicable disease that has the ability to spread, it’s important to get sensitive, rapid answers in order to intervene and provide supportive care.”

Numerous laboratories, public and private, have also begun to reverse-engineer the viral genes and produce seed viruses for use in vaccine development. Several vaccines have been designed, providing the U.S. with a reasonably strong arsenal to ward off H7N9 in the event it crosses the Pacific.

Meanwhile, clinicians remain watchful. “You want reasoned and thoughtful preparedness,” says Gary Procop, MD, chairman of the Department of Molecular Pathology and medical director of the molecular microbiology, mycology, and parasitology laboratories at the Cleveland Clinic. “The medical community is always trying to prepare for the next outbreak. We never know how bad next year’s flu will be, so we tend to plan for the worst without becoming too frantic over it.”

Novel influenza viruses receive a lot of press, notes Dr. Procop. “But it’s also important to circle back and recall that there are many preventable deaths every year from the seasonal influenza.” The H7N9 virus is definitely worth watching, he says, but routine preparedness and vaccination for the regular influenza virus will save lives in the here and now. And for the time being, that’s what America needs most.

Ann Griswold is a writer in Annapolis, Md.