CEO SUMMARY: Discovery of the A/H1N1 strain of influenza made it imperative that public health laboratories in the United States, Mexico, Canada, and other countries have more molecular testing capacity and capabilities in support of efforts to track and control the outbreak. Applied Biosystems, a division of Life Technologies Corporation, stepped into the breach, upgrading existing public health lab instrument systems while installing 40 more instruments in the United States and 60 additional instruments in countries across the globe.
WITH AN URGENT NEED TO IDENTIFY the A/H1N1 influenza virus quickly and accurately, officials from the federal Centers for Disease Control and Prevention (CDC) placed a call to Brian Plew, Director of Biosecurity Solutions for Applied Biosystems, a division of Life Technologies Corporation of Carlsbad, California.
It was Thursday, April 23. The world was not yet familiar with the novel A/H1N1 strain of influenza virus that was already spreading from Mexico to the United States, to Canada, and to other countries worldwide.
At the time, Plew and a team of Applied Biosystems professionals were already collaborating with the CDC to roll out the company’s 7500 Fast Dx Real-Time PCR Instrument for use by public health labs in the United States. The 7500 Fast Dx is the only machine cleared by the FDA for molecular testing of influenza.
Prior to the A/H1N1 flu outbreak in April, Applied Biosystems had already installed about 105 of these systems across the country. Following an FDA 510(k) clearance issued to Applied Biosystems on September 30, 2008, the firm started to recalibrate these systems in the field from research-use only to diagnostic capability.
Installing New Systems
The upgrade process had proceeded at a measured pace. But that changed immediately after the outbreak of A/H1N1 flu in Mexico in late April. The need for additional instruments meant that Plew and more than 100 of Applied Biosystems’ lab professionals and consultants would work almost nonstop to install 40 of the 7500 Fast Dx machines in the United States and another 60 systems in public health labs worldwide. The pace of installations was—and continues to be—frenetic.
“From the moment when the CDC called us on April 23, any step we took with respect to public health labs in the United States was coordinated among us, The CDC, and the Association of Public Health Laboratories (APHL),” Plew said last week in an interview with THE DARK REPORT. “Absolutely, the CDC helped set the priorities in the United States. Following that initial call on April 23, we set up a task force the next day, which was Friday, April 24. Then calls starting coming in from around the world. By Sunday, we had a global task force up and running.
“On Monday, April 27, Mexico was the absolute top priority for us,” recalled Plew. “That country had very little testing capability. A CDC team was traveling there and asked us to support health authorities in Mexico as well.
“In recent years, we have worked with the CDC on influenza, but at a measured pace,” recounted Plew. “Applied Biosystems was upgrading certain instruments in the field to give them the diagnostic capability for influenza. As part of its plan for influenza surveillance, the CDC was also training state health laboratories in how to operate the instrument as a diagnostic tool. However, that measured pace changed overnight into a crash program to help boost molecular testing capability and capacity for the CDC, for public health labs in the United States, and for public health programs in countries across the globe.
Fastest Detection Methods
“The reason the CDC wanted the 7500 Fast Dx is that it has two capabilities,” observed Plew. “First, it can detect H1N1. Second, it is a 96-well instrument, providing public health laboratories with the throughput required to support outbreaks.
“Epidemiologists know the limitations of many flu tests,” he continued. “Antibody tests can identify that the virus is influenza A or B. But these tests can’t tell you if it’s swine influenza A/H1N1. Nor can they confirm any influenza subtype.
“Also, antibody tests might offer a faster turnaround time to result—but antibody assays deliver less specificity and less sensitivity,” Plew stated. “Studies show some of those assays typically run at about 50% to 60% sensitivity, which is close to the odds on a coin toss.”
To cope with the flood of influenza specimens generated by the outbreak, public health laboratories needed the higher capabilities provided by more sophisticated molecular technologies. Thus, Applied Biosystems worked non-stop to meet the urgent demand for instrument systems. “In New York City, for example, we upgraded five instruments over a single weekend by shipping the machines overnight and having multiple technicians running each upgrade in parallel,” he said. “The same was true for machines we installed in many states, such as Texas, which was hit hard by H1N1.
“The CDC also had us working in Mexico, where we probably had our greatest positive impact,” Plew said. “Since the beginning of the flu outbreak, we have installed about 30 instruments in Mexico, and helped establish perhaps 10 new laboratories.
“We continue to maintain technicians in Mexico to support those labs and the CDC’s team in that country,” he stated. “Around the world, Applied Biosystems had an installed base of 100 instruments in public health laboratories. About 60 more instruments have been delivered and made operational globally since the beginning of the flu outbreak.”
“Now that we have these systems in place in U.S. public health labs, all states have the capability to identify the spread of the H1N1 virus, which is something many states didn’t have at the beginning of the outbreak,” noted Plew. “Currently state health officials can evaluate flu specimens with specificity using the CDC’s influenza test panel and our instrument.
Used Only For Epidemiology
“Of course, this system is currently used for epidemiology only, and not for patient care,” Plew added. “It speeds up the identification of the virus at the state public health level, but it does not improve conditions at the clinical level. Doctors treating patients do not have access to this science and technology.
“Someday it may be available for clinical laboratories, but the challenge with an influenza virus like H1N1 is that it is highly susceptible to mutation,” he explained. “Thus, the more specific you make the assay, the more likely the mutation will drift off your design. This in turn requires closer monitoring of performance and the ability to rapidly implement subtyping assays.”
Plew points out that molecular diagnostics is a game changer in public health. “This latest influenza outbreak demonstrate the immense value of molecular testing. Twenty years ago, there was no way for public health officials to recognize this type of disease outbreak as it happened. The off-season flu cases would be recorded as a flu outbreak. Then, later in the fall, the same flu strain might come back and be a big killer.
Ready For Next Flu Season
“In fact, that is now the big question: will the U.S. public health system be ready for influenza season in the fall?” he asked. “Absolutely! The public health establishment now has the capability to monitor an outbreak from an epidemiological stand-point and to manage surveillance.
“What worries some is the fact that this molecular flu testing capability doesn’t yet translate into patient care,” observed Plew. “If H1N1 turns more deadly, and people start demanding a flu test to know if they have H1N1, those demands could over-whelm the public health system—in locations where the doors might be opened to permit that type of testing. After all, demand for access to more accurate influenza testing by a worried public would be difficult for health officials to ignore.”
THE DARK REPORT observes that the A/H1N1 outbreak is probably the first major global disease outbreak where molecular testing played a front line role. Further, ongoing improvements in molecular technologies and laboratory testing systems guarantee that a growing number of public health laboratories and clinical laboratories will have more sophisticated assays for influenza and other types of infectious disease.
100+ Instruments Installed
This speed of technology change and its introduction into use is well-illustrated by Applied Biosystems’ response to the A/H1N1 flu outbreak. In only a few weeks, it was able to manufacture, install, and bring up more than 100 new, sophisticated testing systems. That’s an impressive reaction to a national and global need.
Instrument Runs 24 Specimens With Three-Hour Time to Result
IT’S NOT A BIG INSTRUMENT SYSTEM. The 7500 Fast Dx Real-Time PCR Instrument manufactured by Applied Biosystems “looks like two desktop computers side by side with a cover on them, and it’s connected to a lap-top,” said Brian Plew, Director of Biosecurity Solutions at Applied Biosystems, a division of Life Technologies Corporation.
“The instrument processes 96 reactions in a single run, which takes about an hour for the detection component,” explained Plew. “This comes after the steps to extract the nucleic acid and prepare the sample for analysis on our instrument.
“The entire process takes about three hours, from specimen prep to result,” he added. “Running 96 tests in three hours is considered high throughput for this particular molecular technology.
“These 96 tests represent 24 samples because each sample receives the four tests that are part of the CDC’s swine flu panel,” noted Plew. “The CDC’s Human Influenza Virus Real-time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) has:
- a) a matrix test for influenza A;
- b) an updated matrix for the new novel strain of influenza A (meaning A/H1N1);
- c) a subtype for H1; and,
- d) a control (which is a human gene).”