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From: Association of Public Health Laboratories; http://www.aphl.org/articles/Pages/APublicHealthBalancingAct.aspx

A Public Health Balancing Act;
More Diseases, Fewer Dollars

by Nancy Maddox, writer

For a brief, hopeful moment in the mid-twentieth century, spurred by the widespread availability of the first antibiotic "wonder drugs" and a growing array of vaccines, it was possible to believe that infectious pathogens were on the run. Today, despite laudable infection control achievements, such a notion seems hopelessly naïve.
Not only are centuries-old pathogens re-emerging in new and improved forms, but, according to the World Health Organization's (WHO) latest annual report, new diseases have been identified at the "unprecedented rate" of at least one per year since the 1970s. Humankind today faces at least 39 diseases that were unknown a generation ago, with more certain to appear "sooner or later."
The stark reality, the WHO reports, is that "the battle to keep up with microbial evolution and adaptation will never be won."
For the public health laboratory, this reality has been playing out for years. New fronts in the microbial wars open at a steady rate, requiring the ability to test for an ever-growing slate of disease organisms. Yet scientists can safely abandon few, if any, traditional fronts.
Even smallpox, the only infectious disease believed to be globally eradicated, is of renewed relevance because of the threat of bioterrorism. Consequently, public health laboratories have had to reestablish the one testing program that had been universally retired in state and local laboratories.
Recent outbreaks of measles in Indiana, mumps in Iowa and pertussis (whooping cough) across the upper US underscore the need for vigilance against familiar disease organisms even as laboratories ramp up to respond to the latest threats, including SARS, West Nile virus and avian influenza.
Ron Limberger, director of the division of infectious disease at the Wadsworth Center, the New York state public health laboratory, said, "Right now, except for Level 4 agents, we test for just about anything that's known to man."

"A Funding Nightmare"
The Wadsworth Center and other public health laboratories have been able to keep pace with a rash of new testing demands largely because of an influx of federal funding in the wake of the 2001 anthrax attacks. Federal Emerging Infectious Disease, Epidemiology and Laboratory Capacity (ELC), Public Health Emergency Preparedness (PHEP) and bioterrorism grants have enabled many labs to hire and train additional scientists, improve communication systems and upgrade testing technology.
In particular, state and large local public health laboratories have been able to add molecular methods to their repertoire of diagnostic techniques for some diseases.
Molecular methods offer distinct advantages—including high speed, specificity and sensitivity—that enable laboratorians to deliver accurate information more quickly. But they are enormously more expensive than classic laboratory techniques, and the stability of federal dollars needed to employ and train support scientists and maintain real-time PCR thermal cyclers and other instrumentation is slipping away.
In written testimony on behalf of APHL to the US House of Representatives' Committee on Homeland Security this past September, Pete Shult, director of the communicable disease division at the Wisconsin State Laboratory of Hygiene, noted: "In Wisconsin and in many other states, substantial laboratory emergency response capability, capacity and infrastructure have been developed. But this is only the beginning of addressing laboratory needs; what has been built needs to be sustained and this is where the greatest problem may lie. Maintenance of what has been built in terms of emergency laboratory response capability much less continuous future improvements in diagnostic technology, information and data sharing, etc. now may be in jeopardy."
Shult pointed out that the Wisconsin public health aboratory's PHEP funding was cut by nearly 60 percent n fiscal year (FY) 2007, and this cut will be carried over o FY 2008.
Total ELC grant funding peaked in FY 2002 at $78 million and was down to $56 million by FY 2006. President Bush has proposed an additional $17 million cut for FY 2008.
Other major public health laboratory grant programs, such as those supporting emerging disease and TB testing, have been flat for years.
From his perspective in New York, Limberger said, "I can see (federal funding) continuing to drop off 10 to 20 percent or more per year for some programs."
Susie Zanto, who oversees microbiology and molecular testing for the Montana Laboratory Services Bureau, noted, "The best tests are the more expensive tests. And to find a way to be able to offer the best tests to our clients is always a funding nightmare."
Both the Wadsworth Center and the Montana Laboratory Services Bureau have looked for creative ways to live within their shrinking federal budgets without compromising their public health missions. The challenge has been to cut costs and yet preserve—or enhance—routine disease surveillance and emergency preparedness. As pathogens proliferate and gain new drug resistance, this balancing act becomes more and more formidable.
In fact, there are few services or staff positions that public health laboratories can prudently forgo.

Maintaining a Full Range of Testing Capability
Molecular assays, for example, are superior to older test methods in many critical regards, but cannot entirely replace them. Public health systems still need the ability to grow, or "culture," microbes to detect and identify unknown organisms and to generate sufficient quantities of organisms for conventional drug susceptibility tests, genotyping and other specialized analyses to support epidemiology and outbreak investigations.
Similarly, they need the ability to run serology tests to detect antibodies to disease organisms when the organisms themselves are no longer detectable (either having moved into human tissues that cannot be safely sampled, as West Nile virus does, or having been killed by the immune system or by antibiotics).
As private clinical laboratories turn increasingly to molecular methods, public health laboratories are becoming scarce repositories for these older techniques.
In North Dakota, for instance, the state lab is the only facility capable of culturing M. tuberculosis for drug susceptibility testing.
Thus, public health laboratories are in the position of adopting—and often developing—the new molecular workhorses of laboratory testing, while also striving to maintain basic skill sets in classic, time-intensive techniques.
Sometimes funding will not support both.
"We haven't taken any agents off our (testing) menu," said Limberger, "but we have taken some of the methods away when shown side-by-side that one is better in particular cases. We're at a critical point. If (federal funding) starts to go down more, really tough choices have to be made."

Maximizing, Straining Staff Resources
To save money, many public health laboratories are making do with fewer staff members and asking others to do double duty. The Wadsworth Center has chosen not to fill some vacant, federally-funded positions since the funding stream has become so insecure. Just after the anthrax attacks, the Center created a biodefense "SWAT" team, comprised of working bench scientists with expertise in bacteriology and virology. Team members are the first on-call for surge testing, although it means that their routine work is then delayed.
In Montana, there is a strong emphasis on crosstraining. Said Zanto, "We don't allow (scientists) to just work in one area; we expect them to be experts in at least three areas of the laboratory. We have somebody who works in TB and food microbiology and parasitology."
Such creative arrangements will help public health laboratories make the best use of staff during a disease outbreak, but may not compensate for overall reduced workforce levels during a major event, particularly if partner laboratories in neighboring states are also working to capacity.
In his congressional testimony, Shult noted that inadequate laboratory staffing "is a particularly bad outcome" should surge capacity be needed for an influenza pandemic when "perhaps 30 percent or more of the workforce may be incapacitated at various points during the pandemic."

Mumps Outbreak Sounds A Cautionary Note
A mumps outbreak that spread outward from Iowa last year demonstrates the necessity of a strong public health laboratory system, as well as the strain that even a mid-size outbreak can impose.
For a decade prior to 2006, the University of Iowa Hygienic Laboratory (UHL), the state public health laboratory, confirmed just five cases of mumps per year, on average. So when the laboratory received a few serologically positive specimens over a short period in December 2005, scientists were wary.
Mike Pentella, associate director of the UHL disease control division, said, "We decided to do a culture... and by growing it we were able to send it to CDC for genotyping." Results in both cases were positive.
In January the laboratory tallied 13 more cases of mumps, 48 in February, 273 in March and 1,033 in the peak month of April. Altogether, between January and October 2006 the UHL tested more 6,000 patient specimens and confirmed 1,957 cases. But the process required considerable problem-solving and "a tremendous outpouring of help throughout the laboratory."
Early on, scientists realized that their supply of testing reagents and supplies would be quickly depleted and that outside sources would not be able to fill the gap. They switched from rhesus monkey kidney tissue culture to a Vero cell culture to grow the mumps virus. This solution worked as a stopgap measure. It soon became apparent, said Pentella, that "we couldn't continue on with culture. It was too time-consuming. It took too long to get results out."
Since there are no commercially-available molecular assays for low-incidence diseases like mumps, UHL scientists teamed up with colleagues at the CDC to develop and validate one. This process consumed thousands of man hours over a period of eight weeks between February and April, but resulted in a real-time PCR assay that reduced test turn-around-times from 10 days to less than 24 hours.
"It made a huge difference," said Pentella.
Even with the molecular test, though, UHL employees were stretched to their limit. Scientists worked hundreds of extra hours over weekends and into evenings. Many staff members were re-assigned from their usual duties to take on new scientific and administrative tasks, including answering an emergency hotline. Retired UHL scientists were called in to help. "We didn't have any excess capacity for any other emergency at that time," said Pentella.
Fortunately, by May the number of new cases, although still in the hundreds, began to subside. By June the case rate was down considerably.
The precise source of the infection—which spread to more than half a dozen states and as far afield as Virginia—remains unknown, although the first patients were associated with college campuses in northeast Iowa. Authorities speculate that the disease originated in the United Kingdom, where more than 72,000 people contracted mumps in a nationwide epidemic during 2004-2005, and was brought to Iowa by a college student.
A combination of factors—including an intensive vaccination campaign, the close of the academic year and the onset of spring (when disease rates traditionally drop)—ultimately contained it.
An unsettling facet of the outbreak was that most of the ill (7 percent) had been exposed to the disease.
In fact, a substantial majority of those with known vaccination status had received the recommended two doses of measles-mumps-rubella (MMR) vaccine.
Said Pentella, "We've seen a good example here with mumps of a disease that we don't normally think about, in the category of vaccine-preventable, making a comeback. I think we should expect the re-emergence of other diseases."
A CDC report of the mumps outbreak states that the recommended vaccine dosage is "not 100 percent effective in preventing disease, and accumulation of susceptible persons who were not successfully immunized might be sufficient to sustain transmission in certain settings."
The same cautionary note applies to other vaccine-preventable diseases that have been relegated to the past.

Pertussis Is Still a Danger
Just as mumps was making a return debut in Iowa, several northern US states were still recovering from a pertussis resurgence. The number of cases associated with that outbreak peaked in 2004 when states reported more than 25,000 cases to the CDC, the highest number reported since 1959.
New York health authorities alone documented more than 1,900 probable or confirmed cases. Cindy Schulte, with the New York State Department of Health Immunization Program, said "We continue to be challenged with continued incidence and with outbreaks."
Overall, said Schulte, pertussis rates have been trending upward for years due to a growing pool of susceptibles. Having the disease confers no immunity. And the pertussis component of the pediatric diphtheria-tetanusacellular pertussis (DTaP) vaccine confers only 70 to 80 percent immunity, which wanes over time. (The FDA licensed the first pertussis vaccines for older children and adults in 2005, but it is too soon to gauge their effectiveness.)
Before the availability of molecular tests, the highly contagious disease was prone to misdiagnosis for a couple of reasons. First, adults and adolescents don' always exhibit the classic "whooping" sound associated with pertussis, and other symptoms are easily attributed to other respiratory ailments. Second, Bordetella pertussis is a slow-growing bacterium that dies off rapidly in transit, requires specialized growth media and is liable to be overgrown by any other organism present in patient specimens.
To improve diagnosis, the Wadsworth Center developed and now uses its own PCR assay, which is able to differentiate B. pertussis from the closely related B. holmesii and B. parapertussis. However, New York's Limberger said, "It is important for labs to maintain both culture and molecular testing capabilities... to readily confirm the authenticity of an outbreak rather than a potential PCR contamination issue." The Wadsworth Center provides its customers with culture transport tubes that enable scientists to perform PCR and culture, if needed, from the same patient specimen.

What's Next?
If public health authorities have learned anything from recent disease scares, it is that the next big outbreak is just as likely to involve a re-emerging pathogen as a new one.
"An organism that can replicate itself a million times within a day clearly has an evolutionary advantage, with chance and surprise on its side," notes the WHO.
In its annual report, the WHO presents a lengthy list of circumstances that have abetted a global microbial renaissance. Most aren't likely to go away anytime soon: a warming climate, changing land use patterns, lax disease surveillance, antibiotic misuse, inadequate immunization of at-risk populations, ill-advised animal husbandry practices, increased international travel and trade, poverty, war and forced migration.
Perhaps the most feared and closely monitored disease in the world today is avian influenza. Based on data from past pandemics, some experts predict an influenza pandemic would affect about a quarter of the world's population or more than 1.5 billion people. Health authorities are petitioning governments for the resources to heighten influenza preparedness and hopefully avert the worst-case scenarios.
But other diseases cannot be dismissed. Montana, which four years ago had zero cases of endemic syphilis, is now experiencing pockets of the disease. Drug resistant gonorrhea—a significant problem in many states—has also made an appearance in historically low-incidence Montana.
In New York, drug-resistant Staphylococcus aureus has been a serious emerging issue. A staph outbreak was reported recently among more than two dozen Maryland high school students, including several with Methicillin-resistant infection.
Two diseases that are not yet established in the US, but are of growing concern, are dengue and chikungunya virus.

Mosquito-borne Viruses Are a Real Threat
Dengue, a mosquito-borne flavivirus causing flu-like symptoms, has been around for hundreds of years, and for much of that time was considered a disease of the tropics.
The dengue vector, Aedes aegypti, was nearly eliminated in the New World thanks to intensive mosquito control efforts meant to eradicate yellow fever (also spread by Ae. aegypti). Those efforts were abandoned in the 1960s and 1970s, and mosquito populations rebounded. Ae. aegypti, a day-biting mosquito that readily feeds on humans, is now prevalent throughout the southern US, particularly along the Gulf Coast.
Still, in 1970, only one of four dengue serotypes,DEN-2, had a significant presence in the Americas. By the mid-1990s, all four known serotypes—plus new, apparently more virulent strains of DEN-2 and DEN- 3—were endemic in parts of Latin America.
Dengue has gained attention recently because one of the worst outbreaks in decades is spreading across Latin America and the Caribbean, affecting hundreds of thousands of people. During dengue epidemics, attack rates among susceptibles are often 40 to 50 percent, but may reach 80 to 90 percent.
There is no vaccine to prevent dengue, and patients infected with one serotype develop immunity only to this single type. Subsequent infection with a different serotype places them at increased risk for dengue hemorrhagic fever (DHF), a severe and potentially fatal form of the disease.
From 1977 to 2004, just fewer than 4,000 suspected cases of imported dengue were reported in the US, with many more probably unreported. Of concern, the first case of locally acquired DHF in a US native was documented in a resident of Brownsville, TX, in 2005.
Liz Delamater, director of microbiological sciences for the Texas state public health laboratory said, "If we have a lot of activity across the (US-Mexico) border, which we do, it would be very possible to have a major outbreak here." Of all the vector-borne diseases circulating in the world today, however, Lyle Petersen, director of the CDC Division of Vector-borne Infectious Diseases, said, "I think the greatest risk to the US right now is from chikungunya virus."
Chikungunya is a Makonde word meaning "that which bends up," a reference to the stooped posture resulting from the crippling arthritis that accompanies viral infection and that often lasts several months. The illness was first described in 1952 in connection with an outbreak along the Mozambique border.
Chikungunya virus, an alphavirus, is spread by both Aedes aegypti and the Asian tiger mosquito, Aedes albopictus.
Said Petersen, "So far we've been lucky that this virus hasn't established yet in the Americas. But if it does, I think it's going to spread like wildfire. We definitely have the right mosquitoes for it." The virus has caused explosive outbreaks in urban settings in East Africa, Asia and the islands of the Indian Ocean, collectively involving millions of cases. An outbreak in Italy's Ravenna province in August-September 2007 marks the first recorded incidence of transmission in Europe.
"Definitely we should be worried," said Petersen. "What happened with West Nile virus was a real wakeup call that we can get an exotic vector-borne pathogen and it can spread all the way across the country and it may not behave the same way it does in its original endemic zone."
In the face of such threats, the CDC is working to increase its capacity to diagnose known pathogens with new molecular tools, such as DNA micro-arrays and consensus PCR primers. "We're developing assays that can pick up every single alphavirus or every single flavivirus," said Petersen. "We can sort it out in a matter of hours at this point."
As with West Nile virus, the first cases of a novel microbe will almost certainly be referred to the CDC for diagnosis, with later cases referred to state and large, local public health laboratories once the CDC disseminates the testing technology. "The lesson to be learned here," said Petersen, "is that importation of exotic vector-borne disease is only going to continue, and we need to keep our vigilance and be prepared, and the public health laboratories are really our frontline."
Given the multitude of new and re-surging infectious disease threats, federal cutbacks for public health services come at a particularly bad time.
"You won't know a disease is emerging or re-emerging if you don't test for it," said New York's Limberger.
For every federal dollar that disappears, Limberger said, "either the state has to pick it up or we can't continue. With a modest cut, we would reduce the volume of our surveillance testing. We have cut back on our volume... It would be a very dark day if we had to reduce the breadth of our testing..."

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A Public Health Balancing Act; More Diseases, Fewer Dollars

A Public Health Balancing Act;
More Diseases, Fewer Dollars