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WSLH Featured in APHL Minute Article on Pandemic Preparedness

The following article is from the Association of Public Health Laboratories (APHL) news publication, The APHL Minute for January & February 2006, pages 4-8.

Expected Increase in Federal Funding to Bolster Preparedness for Pandemic Flu

“How should they have given a thought to anything like plague, which rules out any future, cancels journeys, silences the exchange of views. They fancied themselves free, and no one will ever be free so long as there are pestilences.”
  -- Albert Camus, The Plague

Even in Camus’ fictional world of Oran, laboratory data were used to confirm the identity of the plague bacillus. New Hampshire’s public health laboratory director, Christine Bean, points out that today laboratory data is as crucial as ever to identify microbes: “The #1 way to stop the spread of [infectious] disease is containment. And without the laboratory, containment is not possible.”

This is an important message for policymakers as they formulate plans and proposals for pandemic influenza preparedness—a topic that has finally made its way onto the agendas of leaders on both ends of Pennsylvania Avenue. This past October the White House invited members of Congress to an unusual top-secret briefing on the subject, which galvanized legislative activity—including the adoption of two
amendments in the Senate to increase federal spending on pandemic preparedness by anywhere from $4 to $8 billion. And in November the Department of Health and Human Services unveiled a national pandemic influenza plan.

In late December, Congress approved at least an additional $350 million for state and local public health systems to prepare for worst-case scenarios. Although this sum is far short of the $1.03 billion  recommended by the Association of State and Territorial Health Officials (excluding the cost of anti-viral drugs), the good news is that the legislative language makes it likely that an appropriate amount of this new funding will be allocated for public health laboratory improvements. Indeed, the funding vehicle—the Department of Defense appropriations bill (HR 2863)—makes frequent reference to the importance of laboratory diagnostics in the joint explanatory statement from the
House and Senate conferees.

Once enacted, the bill will also provide an additional $50 million for CDC
laboratory capacity improvements and an additional $150 million for CDC’s global and domestic surveillance activities. It would also require the Health and Human Services’ secretary to report to Congress next spring during hearings on fiscal year 2007 appropriations, on a plan for using diagnostics during the early stage clinical response to a pandemic. “All told,” said Peter Kyriacopoulos, APHL’s public policy director, “this is a welcome recognition of a critical aspect of pandemic preparedness that received scant attention previously.”

Squeezing Every Last Penny
While politicians finalize the numbers, public health laboratories are doing their best to plan with the limited resources on hand. Jane Getchell, APHL president-elect and director of the Delaware public health laboratory, said her facility is “not yet ready” for an influenza
pandemic. The CDC, she said, recommends real-time polymerase chain reaction (PCR) testing as the gold standard for virus detection. “We can’t afford to buy those reagents,” she said. “They’re expensive, so we’re sticking with the culture as our gold standard test. Of course that takes longer [at least 2-3 days compared to 2-4 hours] and probably
doesn’t have the sensitivity of the PCR, which will detect even dead virus.”

"The CDC recommends real-time polymerase chain reaction (PCR) testing as the gold standard for virus detection. ... We can't afford to buy those reagents."

Pete Shult, an influenza expert who oversees communicable disease testing at the Wisconsin State Laboratory of Hygiene, said, “I have no doubt with the first emergence of a pandemic influenza strain—particularly if it happens to be H5N1—there will be a panic.” Yet he said, “If I could maintain the staffing I have right now, with cost-of-living increases, I could hold the fort. We don’t have room to lose any staff. . . If I had to take a cut and lose 10 to 20 percent of my staff—which has happened once in my tenure here—we would lose much of my emergency response capacity.”

This past November, the New Hampshire public health laboratory participated in an avian influenza drill. Bean, said, “We actually did a lot of work in preparation for this drill to see what we wanted to test and what were our objectives for the laboratory. How will we know that we have the capacity that we need?”

The exercise is still being evaluated by outside consultants, but several needs were immediately apparent: greater courier capacity to assure that specimens reach the laboratory without delay, additional
employees to process specimens in the laboratory’s central receiving area and at least one additional $50,000 high-throughput thermocycler to test specimens. Bean said, “. . . our limitation was in our instrumentation. Once they’re put on the instrument for testing, it takes at least two hours for samples to run; that gave us some downtime.”
Bean noted that, like virtually all public health laboratories, her facility does not charge on a per test basis for surveillance and emergency response services. “We are supported in doing this work by grants. A lot of federal funds are used to fund positions and reagents and
supplies. Federal grant money is mandatory for all of these efforts to continue.”

In New York, Kirsten St. George, who oversees the state laboratory’s clinical virology and virus reference and surveillance programs, said she is “very comfortable” with the level of expertise among her staff. But equipment is another matter. “My wish list,” she said, “would include more automated equipment to cope with that [pandemic] surge. And I think that is probably the case for most, if not all, the public health
laboratories. The equipment situation could definitely be improved.” St.
George figures it will cost several hundred thousand dollars to purchase
the instruments on her wish list.

PHL Testing Fills Important Niche
Without adequate public health laboratory capacity, all of the scientists interviewed for this article agreed that routine and emergency influenza-related activities would be compromised. There is simply no other facility with the ability or the mission to carry out the functions performed by public health laboratories. Wisconsin’s Shult, who has
weathered SARS, monkeypox, pertussis and anthrax crises, said, “The state public health laboratory is the only lab with the culture and the mentality of emergency response. There is an expectation that we follow incident command structure, that we have continuity-of operations plans. . .We’re emergency responders from the lab perspective.”

While public health laboratories would play an important role throughout an influenza outbreak, their work is especially critical at the onset of an outbreak—to figure out what’s going on—and again at the end—to sound the ‘all clear,’ and gauge what is likely to emerge as the dominant virus strain in the next season.

Rapid Test Sites Aid Surveillance
Shult explained that most state and large local public health laboratories conduct laboratory-based surveillance to monitor influenza activity early in the flu season. Such surveillance requires a network of
frontline hospital clinical laboratories, sentinel clinicians and rapid test sites scattered throughout the community. In Wisconsin this network includes about 30 sentinel clinicians that routinely submit specimens, 10 virology laboratories and over 100 rapid test sites in small clinics, emergency rooms, longterm care facilities and other locations. Plus, the public health lab works with the state veterinary diagnostic laboratory
to keep abreast of animal influenza outbreaks that might have implications for human surveillance.

Rapid test sites, in particular, have the potential to expand the scope of
influenza surveillance. Last year, Shult said, the rapid test sites known to the state performed over 50,000 influenza tests throughout Wisconsin. “That means that 50,000 ill individuals went in for these tests,” he said. “That greatly expands the sensitivity of our surveillance.
We have identified our first influenza in the state each year for the
last four years from specimens that were submitted from these rapid testing sites. And over those four years, the identification was up to three weeks earlier than would have been the case relying on
sentinel submitters alone.”

Rapid test sites and other network members report the number and type of specimens they receive and the number of positive test results. They also send selected patient specimens or isolates— including the first few specimens that test positive for influenza—to the public health laboratory for specialized testing that is beyond the scope of routine lab work.

"Federal grant money is mandatory for all of these efforts to continue."

The public health laboratory is then able to:

• Determine whether positive screening results are true positives.
• Identify the types and subtypes of influenza circulating.
• Monitor laboratory-confirmed influenza activity across the state.
• Send information back to the sentinel laboratories to help them
  optimize the use of their screening tests.
• Send selected viral samples to the CDC and to the World Health
  Organization to contribute to national and global influenza surveillance and vaccine development.

All these activities are of vital importance.

Confirmatory Testing is Vital
First of all, without definitive laboratory data, health officials can’t be sure that a flu-like illness is actually flu. And the key word here is definitive. There are more than a dozen influenza screening test kits available commercially, of varying quality. In general these screening tests tend to have high positive predictive value—that is, to render a high probability that a person actually has influenza given a positive test result— only when there is a high prevalence of influenza among those being tested. When the prevalence of influenza is low—as it always is at the very beginning and the tail end of flu season— many rapid tests are prone to false-positive results.

On the other hand, screening tests can also miss true positives. Shult said some screening tests are reported to have a sensitivity as low as 60-70%, meaning that as many as 4 out of 10 true positive specimens might be reported as negatives.

Obviously, an incorrect test result can lead to misdiagnosis and mistreatment or possibly lack of treatment and prolonged infectiousness. Hence the importance of definitive, confirmatory testing by the public health lab. Shult said, “If [sentinel laboratories] get a positive result in October and we know we have no influenza in Wisconsin, that’s probably a false-positive. We would encourage them to send that specimen to us for confirmatory testing.”

"While public health laboratories would play an important role throughout an influenza outbreak, their work is especially critical at the onset of an outbreak — to figure out what's going on — and again at the end — to sound the 'all clear,' and gauge what is likely to emerge as the dominant virus strain in the next season."

In Wisconsin, as in many states, the laboratory makes recommendations about the appropriate use and interpretation
of these tests, but it also shares data about the local prevalence of
influenza and teaches both laboratorians and clinicians how to use surveillance data to interpret screening results. Carol Kirk, who coordinates the laboratory network for the state of Wisconsin, noted that some laboratories are now putting qualifiers on their test reports,
indicating that early positives should be confirmed.

Typing the Strain Helps Vaccine Development
But public health laboratories not only have the ability to differentiate between influenza and no influenza, they can also discern exactly what kind of influenza it is. Is it familiar and relatively benign? Or is it a potentially pandemic mutant?

There are three types of influenza virus: Type A (which infects birds, humans and other mammals), Type B (which infects only humans) and Type C (which is rarely identified and usually of little clinical concern). The laboratory can distinguish among these and also identify subtypes of influenza A based on differences in two major glycoprotein molecules found on the virus’ outer surface or envelope: hemagglutinin and
neuraminidase. (There are 16 hemagglutinin and 9 neuraminidase subtypes that have been identified in wild waterfowl, the natural hosts for influenza A viruses.) And, peering ever more closely, some laboratories can perform what is called strain analysis by mapping out the actual genetic sequences that code for the hemagglutinin and neuraminidase molecules.

This level of detail is extremely valuable. St. George, who runs one of the most sophisticated influenza diagnostic laboratories in the country, pointed out that for vaccine development “subtype alone is grossly insufficient.” She said, “Knowing exactly what’s circulating helps CDC and WHO determine what to put into the vaccine in the following
year and to assure that what’s in the current vaccine is protective.”

St. George also explained that most influenza pandemics have been caused by novel subtypes of influenza A virus that tend to have major changes in the hemagglutinin gene; changes that can be documented and monitored with the appropriate technology. Outside of public health laboratories, though, extremely few laboratories can perform such advanced analyses. “Most [private clinical laboratories] do not do
subtyping,” said St. George, “and I don’t think any of them do strain analysis.” Bean mentioned that in New Hampshire the state public health laboratory is the only laboratory capable of performing virus subtyping. She said, “We are using methodology from the CDC. The
methodology is not approved by the FDA for just any clinical or private laboratory to do.”

As part of their responsibility to provide this expertise, public health labs must acquire and maintain costly instruments and complex skillsets. St. George said that she and her staff “keep a close watch” on scientific communications to continually assess and investigate new
testing platforms and analytical techniques. They also monitor national and global surveillance data from various sources to assure that the New York state virology laboratory has the appropriate oligonucleotide sequences used in molecular assays to detect the viruses known to be circulating even beyond New York state. As the 2003 SARS scare
demonstrated, microbes can cross political boundaries with no advance warning.

Using the Data to Protect the Public

Collectively, the detailed data provided by public health laboratories across the country enables health officials to know when, where and which influenza viruses are circulating within states and nationally.
This information, in turn, enables health officials to make the best use of existing pharmaceutical stockpiles and—if need be—to make informed
decisions about the use of more extreme measures, such as quarantine.

“If [public health laboratories] were not able to carry out our functions for testing, really no disease or case investigations could take place,” said Bean. “What that would mean is that it would be quite difficult to limit the spread of disease from person to person. Disease control [authorities] would not be able to make the decision about whether
someone could go back to work or not or go back to school or not. Really, without the results from the laboratory, then no more work can be done to try to stop the spread of disease.”

Surveillance Networks Require Constant Maintenance
The whole chain of surveillance, however, depends upon the clinical specimens or isolates that are forwarded to public health laboratories by their carefully nurtured networks of frontline laboratories and rapid testing sites. And those specimens are forwarded on a purely voluntary basis. Said Shult, “We’re really at the mercy of these surveillance participants.”

To keep the specimens coming, the Wisconsin public health laboratory pays for the specimen collection kits as well as a private specimen courier system. It also pays Kirk to coordinate outreach, training and information-sharing activities to maintain the proficiency and the
goodwill of these frontline laboratories. All of these public health activities are ultimately funded in whole or in part through federal grants for bioterrorism (BT) preparedness or epidemiology and
laboratory capacity building.

The money is well spent. Shult noted that the network infrastructure will be “instrumental” in tracking flu activity if a pandemic strain emerges. “People are used to working with us and understand the importance of being part of the network and that they would play an
important role.” He also noted that the network is set up to contribute to surveillance for any infectious disease of public health significance. “We’ve tried not to make the distinction between BT and influenza,” he said. “It is a multi-use network. And I’ll say unashamedly that
we feel our network is one of the better networks out there.”

And yet, even in Wisconsin, Shult stressed, “That is a very, very fragile
network. If we keep on top of it and continue to foster it, we’ll be fine. But if we skip a beat—if we didn’t provide them the free shipping, if we didn’t continue to give them training that they need, if we didn’t give them summary reports—that network will come apart pretty quick. My worst nightmare is that something will happen to Carol.”

In Delaware the statewide laboratory network is already showing signs of strain. For the past five years, the state’s physicians had become accustomed to same-day turn-around for rapid influenza testing performed by the Delaware public health laboratory. But no more.

“We don’t have the funds to buy the reagents for that this year,” said
Getchell. An immediate consequence as been a drop in the number of influenza specimens coming in. “Physicians just liked the quick turn-around,” Getchell said, and now are less motivated to go to the trouble of sending specimens, even though all of laboratory’s flu testing is
performed free-of-charge.

This is an alarming development in a state with more chickens than people, a state that is a potential paradise for avian influenza and strategically located on the high-traffic corridor between DC and
New York. Should a pandemic occur, Getchell said, “As long as we can identify the early cases, that’s really the critical part. That’s why capturing a large number of people in our surveillance program is really important and why all the submissions from our docs out there is something we’ll sorely miss.”

The situation in Delaware highlights the importance of adequate public health laboratory funding. Shult said, “I don’t see any one else taking up the banner if we don’t do it. We’re the only one [charged] by mission to do this.” Quite simply, said Kirk, “If funding collapsed and state public health laboratory surveillance were not done, you won’t have national data either. Nobody will know what types or subtypes of influenza are circulating. You wouldn’t even know for sure that it is influenza.”

Find a Place at the Table: Pandemic Influenza Planning

All states and several federal agencies are now involved in pandemic influenza planning. Jane Getchell, APHL president-elect and chair of the association’s Infectious Diseases Committee, noted that an APHL
policy statement outlining the public health laboratory role in pandemic influenza preparedness and response was expedited by her committee
precisely “to emphasize why the laboratory needs to be included in these plans.”

In South Dakota, inclusion has not been a problem. “We tend to be all-inclusive,” said Mike Smith, director of the state public health laboratory. Smith said the South Dakota pandemic plan was begun “as soon as the word pandemic began to be used.” The plan is still being tweaked. A core group of state officials meets every two weeks to review new
information coming from the federal government and to adapt it to fit state circumstances. Smith has served on the committee since its inception. Moreover, his microbiology section supervisor and bioterrorism coordinator provide much needed input and attend meetings when their expertise is needed.

Without public health laboratory involvement, said Smith, the pandemic plan “would miss almost that entire [laboratory] universe.” He pointed out that the lab not only contributes to the content of the plan— explaining, for example, its ability to do PCR testing and to train local laboratorians—but also plays a critical role communicating the plan to clinical laboratories throughout the state. “If you’re talking to med
techs out there, you have to speak their language,” said Smith. “We can do that education to our colleagues in hospitals and clinics so that they’re aware that the state of South Dakota has a plan and this is
[their] part; this is what we expect.”

The laboratory component of pandemic influenza response, said Smith, is “huge.” He advises his colleagues, “If the laboratory has not been invited to the table, just walk into that room and sit down.”

To access the US pandemic influenza plan, visit www.pandemicflu.gov. For a copy of the APHL policy statement, “The Role of the Public
Health Laboratory in Pandemic Influenza: Preparedness and Response,” visit www.aphl.org.

To learn more about the public health lab role in an influenza pandemic, visit www.aphl.org/docs/influenza_q_a.pdf.

Posted By: Jessica D. Burda, WSLH Public Affairs