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MORE THAN SEVEN YEARS HAVE PASSED since anthrax mailings killed four people, injured 17, and forced the government to spend hundreds of millions to clean up contaminated facilities. Since then, the specter of biological threats has not diminished. Asked about what potentially “unstoppable” threat keeps him awake at night, then Homeland Security Secretary Michael Chertoff said, “particularly a biological threat.… A biological threat can’t be necessarily detected. It can be carried in a very small vial.”

Chertoff went on to say, “You could theoretically infect somebody and send an infected person into the country and create a biological weapon that way.”

Chertoff also noted that the Department of Homeland Security (DHS) has “concluded that aerosolized anthrax...is our number one bioterrorism concern.”

Col. Randall Larsen, U.S. Air Force (Ret.), national security advisor to the Center for Biosecurity at the University of Pittsburgh Medical Center (UPMC), agrees that anthrax is the major biological threat, noting that once released, most biological agents that don’t infect hosts die off within hours, “except anthrax, which is why we worry about it so much.”

Larsen points to Gruinard Island in the Scottish Hebrides, where the British tested anthrax for possible use in an attack on Germany in World War II. The idea was scrapped after scientists determined that target areas would be uninhabitable for decades. In fact, Gruinard Island itself was quarantined for 48 years until the British government decontaminated the site.

Yet Larsen says the greatest—or at least most probable—biological risks, even after 9-11, do not come from terrorists. “We know for a fact that there are going to be biological attacks from Mother Nature,” he says. “There’s supposed to be a flu pandemic every 30 years. We’re overdue now. Will it be as bad as 1918 or similar to 1968? We don’t know.”

Since 9-11 and the anthrax attacks, the federal government has spent more than $41 billion to defend against bioterrorism and the prospect of pandemic disease for activities ranging from planning and information sharing to vaccines and advanced pharmaceutical research. It’s clear, however, that more needs to be done to improve the nation’s disease detection and response capabilities.

Early Detection

While much of the public attention directed at the biological terror threat—and to a greater degree the threat of a pandemic—is focused on response, the best hope for mitigating the impact of an event is early detection. With that goal in mind, federal officials launched project BioWatch within two years after 2001’s anthrax attacks.

As one part of that project, DHS installed additional filters in existing U.S. Environmental Protection

Agency (EPA) air quality testing filters, primarily around major U.S. cities. The existing filters, however, were not located where DHS saw the highest risk for attack. Thus the program incorporated mission specific “sniffer” units, which are now placed at strategic locations in roughly 30 cities, says Dr. B. Tillman Jolly, DHS’s assistant chief medical officer for medical readiness.

The agency does not discuss the units’ capabilities in detail, but Jolly indicated they contain passive filters that catch objects—like anthrax spores—for either scheduled testing or immediate evaluation in the event of a suspected or known release.

While chemical and radiological sensors can provide positive alerts in real time, biological sensors cannot. Due to the inherent complexity of cells and spores, samples must either be grown in labs to determine the presence of biological agents or subjected to DNA polymerase chain reaction (PCR) testing.

Prototype briefcase-size PCR testing units exist, but biological testing requires that DHS, in collaboration with local health departments, pull BioWatch filters, such as in the event of a suspected release, and send the filters to labs for tests. Those lab tests currently take up to 24 hours. Research is underway, however, to create a way to have units that can detect biological threats autonomously without the need to send filters to a lab.

“While it’s not as good as the one-to-three hours we’d like to get to, it’s better than waiting several days until victims start arriving at hospitals and are diagnosed,” Jolly says.

Those tests all concern air quality. Testing of the nation’s water supply remains, as it was prior to 9-11, the responsibility of state public health authorities, based on a list of 90 contaminants issued and updated by the EPA. Along with harmful industrial by-products like benzene and dioxin, the EPA mandates zero-tolerance standards for radioactivity, viruses, and commonly known disease-causing bacteria.

Testing frequency is often elevated for larger water supplies, says DHS spokeswoman Amy Kudwa. If they feel that threat assessments warrant additional testing, individual states can set standards exceeding the EPA’s.

Disease reporting.

The other side to early detection is to be on the look out for evidence of symptoms among the population. In the event of a bioterror attack or the emergence of a natural epidemic in humans, society’s best hope for early warning lies in rapid public reporting of illnesses to government authorities. Simple as it sounds, it’s a complicated process only as strong as its weakest link.

An emergency room physician or family practitioner observing the symptoms of a disease like smallpox—eradicated globally in 1978 and existing now only in heavily guarded government laboratories—would know to report it to the authorities. Any contemporary case would pose an imminent threat to public health and would most likely be the result of biological warfare or terrorism.

Other, more common, biological threats would not announce themselves as clearly. A new, virulent strain of influenza might present itself in healthy adults like traditional flu, while potential bioterror threats like plague and inhalation anthrax are likely to initially present only flu-like symptoms in many cases.

Given that challenge, the first link in effective disease detection is the astute clinician. An astute clinician could be a physician who considers the unlikely causes of vague symptoms or a lab technician who alerts a supervisor after spotting an unusual pattern in a week’s worth of patient samples.

In either case, state protocols require that medical professionals contact public health authorities usually local or state officials in some areas—about detection of reportable diseases. Once state public health and epidemiology officials collect reportable disease data, the information is passed along to the U.S. Centers for Disease Control and Prevention (CDC) for analysis and tracking at the national level.

But more than seven years after 9-11 and the anthrax mailings, state officials say data sharing between city and state public health officials remains disjointed, for the same reasons first responders still struggle to communicate across jurisdictions: technical interoperability and culture.

To address the problem, the CDC originally established the National Electronic Disease Surveillance System (NEDSS), a national Web-based data exchange for public health information. All but a handful of states are interoperable with NEDSS, according to an annual analysis by the Trust for America’s Health. But use of the system both at the state and city level remains anemic, says Dr. Steven Hinrichs, director of the Nebraska Public Health Laboratory and chair of pathology and microbiology at the University of Nebraska Medical Center.

The reason for resistance among those stakeholders is that NEDSS was handed down by CDC without their input and, thus, never received their full buy-in, says Hinrichs, who is also a member of the Association of Public Health Laboratories’ National Biosurveillance Advisory Subcommittee. State public health officials around the country, therefore, report disease information to CDC through various means, from NEDSS to phone, fax, and e-mail, he says.

In an attempt to build a better alternative with their own input from the ground up, state health-department officials from Nebraska and six other states are working on the Public Health Laboratory

Interoperability Project (PHLIP). CDC is funding this effort as well.

PHLIP is essentially message-based middleware built to interact with standard database languages, from standard XML to healthcare-specific protocols, effectively translating data from different systems, allowing users to send data messages seamlessly. As envisioned, PHLIP will serve not only as a hub-and spoke architecture for communication between CDC and states but as an all-channels medium among states, critical in regional outbreaks when states must share information and resources across borders. PHLIP, which the CDC is financing through the national Association of Public Health Laboratories, is expected to go online within two years with as many as 20 states expected to use the system initially, Hinrichs says.

Challenges to developing a system of shared medical information go beyond the technical issues, however. For example, different states not only use different tests for, say, influenza, but they also use different terminology for the results, such as “detected” versus “positive.” They may also indicate a positive result with the name of the strain found.

Tracking Indicators

Public health agencies around the country, from New York City to the state of Iowa to the CDC itself, have pursued a novel approach to detecting the emergence of disease, regardless of cause, through a process called syndromic surveillance. Rather than tracking diagnoses, the method relies upon tracking and mapping reports of symptoms that might indicate disease outbreaks.

The simplest form of syndromic surveillance is practiced in Iowa and many other states, where school districts are required to report school absence rates if they rise beyond a designated level. More sophisticated projects track surveyed metrics, such as emergency room visits or symptoms reported during the visits. Other experts have proposed tracking sales of prescription or over-the-counter drugs to spot health trends. Most recently, Google established (working with the CDC) a public health initiative it calls Google Flu Trends, which looks at the popularity of flu-related search terms to determine where flu outbreaks may be occurring. It does not track results on an individual user basis, however.

Most of the work to date does not produce results fast enough to be of value in spotting a bioterror attack or emerging pandemic, says Michael Mair, an associate at the UPMC’s Center for Biosecurity, who calls syndromic surveillance “a work in progress.”

“To date, syndromic surveillance hasn’t proven that it gives us any lead time over what an astute clinician would give us,” Mair says. “Not even two days.”

Hinrichs further notes that syndromic surveillance data generally provides no information about who is actually sick. “The next question is, ‘So what?’ What can you do with the information? And my thought is that if you can’t use data, then what’s the point of collecting it?” he says.

Dr. Alan Zelicoff, a former researcher at Sandia National Laboratories and author of 2005’s Microbe: Are We Ready for the Next Plague?, agrees that most syndromic surveillance is useless because it is passive analysis of old information, essentially data mining.

While at Sandia, Zelicoff developed an active, provider-driven syndromic surveillance tool called the Rapid Syndromic Validation Project, or RSVP, which is now licensed commercially by Albuquerque, New Mexico’s ARES Corp. as the Syndrome Reporting Information System (SYRIS).

A simple Web-based interface currently used in roughly 45 west Texas counties, SYRIS allows clinicians from school nurses to emergency medical technicians and doctors to upload sign and symptom data about unnamed patients into the program’s mapping application.

SYRIS requests data on six different syndromes: flu-like symptoms, jaundice, respiratory distress, skin outbreak, central nervous system disorders, and diarrhea. Some of the syndromes may be minor, but if they are widespread in a region, or if many minor symptoms are combined in the same patient—such as skin rash and flu symptoms—that becomes significant, because in groups, these symptoms usually indicate “something awful,” Zelicoff says.

SYRIS offers parallel applications for the medical and veterinary sciences, a reflection, Zelicoff says, of his belief that zoonotic diseases, which are carried by, but often harmless to, animals, pose the greatest threat of epidemic or pandemic should they cross to human hosts and spread rapidly.

When a practitioner or public health professional logs into SYRIS and queries an area at the local, county, or state level, areas are shaded based on the user’s search criteria for specific syndromes, with horizontal stripes representing human syndromes and vertical stripes representing animals. Local public health alerts appear on the screen, while custom-graphing functions can report syndrome cases over time.

The system eliminates the problems of passive syndromic surveillance, because it provides data in real time and gives providers the ability to contact and treat the patients they reported on should public health authorities determine that there is a major disease outbreak.

Lubbock, Texas, area public health authorities used SYRIS following the September 2005 evacuation of roughly 800 Hurricane Katrina victims to the former Reese Air Force Base.

More than two dozen New Orleans-area residents arrived at Reese suffering from diarrhea, skin rash, fever, and disorders of the central nervous system.

The victims were diagnosed with vibrio vulnificus, a bacterial cousin of cholera contracted from walking through sewage- laced floodwaters. All were treated with antibiotics and recovered. SYRIS’s syndrome charts showed an outbreak of relevant syndromes in the region from September 8 to 12, 2005, but none thereafter, demonstrating that the region did not face a communicable disease outbreak, Zelicoff says. That knowledge helped the area avoid any waste of medical or public health resources.

ARES licenses SYRIS to government public health agencies for between 10 and 15 cents per resident of the region, or $10,000 to $15,000 annually for an agency representing a population of 100,000, Zelicoff says.

Response Preparedness

Anyone who has contracted the flu despite receiving a seasonal flu shot will appreciate the limitations of such medical efforts. Stockpiling vaccines in advance of a pandemic can only achieve so much because pandemics are, by definition, caused by a novel, virulent strain that is partially, if not completely, impervious to existing vaccines.

Experts anticipate that a major pandemic would spread across the globe in waves and afflict victims for at least six months and as long as a year. Once the pandemic strain is isolated, it would take an estimated six months to develop and begin delivering a vaccine.

Despite that, the World Health Organization (WHO) has begun stockpiling vaccines for the highly virulent H5N1 “bird flu” that, as of September, had infected at least 387 people in Asia and Africa, killing at least 245. WHO says manufacturers can produce 1 billion doses by 2010; HHS announced last year that the agency had purchased 13 million doses.

Should the United States confront a large-scale biological attack or the emergence of pandemic influenza, the government is likely to tap its storehouse of hundreds of millions of doses of disease vaccines and treatments, called the Strategic National Stockpile (SNS), administered by the CDC and its parent, the Department of Health and Human Services (HHS).

Federal agencies including CDC and DHS, which would take the lead in a national-level incident, do not fully disclose the composition of the SNS because it directly reflects DHS’s assessment of risk relative to biological events. Yet several major elements of the SNS have been disclosed publicly, such as the component of 300 million doses of smallpox vaccine, enough for every person in the United States.

Mair explains that stockpiling vaccine for a known strain is a reasonable hedge given the chance that it might boost resistance to a similar mutated strain. This would, in turn, reduce the severity of infection.

The federal government has also invested in research that may reduce the time and resources required to produce flu vaccine in large volumes. Currently, flu vaccine is manufactured from virus grown in chicken eggs. Growing viruses in culture cells, rather than eggs, could provide a faster, more scalable manufacturing process, while averting a supply crisis if insufficient numbers of eggs are available during a pandemic.

European scientists, meanwhile, are pursuing a universal flu vaccine, focusing on the chemicals inside the flu virus, as opposed to the proteins on its exterior, which are targeted by today’s vaccines. Those outside proteins provide the flu entry into healthy cells, but they are also the portion of the virus that mutates, producing dynamic strains. Researchers say a universal flu vaccine remains at least five to 10 years away.

HHS has also purchased close to 40 million doses of antiviral drugs Tamiflu and Relenza. The drugs are intended for both treatment of flu after onset and as a preventative to infection. Scientists, however, find that more recent incidences of H5N1 are increasingly resistant to the two antivirals.

Plans to respond to man-made biological threats, such as an anthrax attack, are also ongoing. As many will recall from the 2001 anthrax mailings, the primary treatment for exposure to anthrax is a long cycle of oral antibiotics like Bayer AG’s ciprofloxacin. Such antibiotics are included in the SNS.

Separately, the SNS includes the culture- grown anthrax vaccine BioThrax. But the vaccine requires a cycle of six shots delivered over the course of roughly 18 months. This prolonged treatment time raises the question of its efficacy in response to a sudden attack.

The U.S. military’s mandatory administration of BioThrax, also called Anthrax Vaccine Absorbed, stoked controversy first in the late 1990s and again in the run-up to the Iraq invasion, due to doubts about the vaccine’s effectiveness against inhalation anthrax and the possibility of severe side effects. In 2001, a group of service members sued the Department of Defense to stop mandatory vaccinations, winning the case two years later.

In the wake of an attack, the vaccine may be administered to first responders and others at high risk of exposure as well as to victims at risk of secondary exposure, says Jolly. He and other medical practitioners note that individuals already exposed to anthrax may only require a three-shot cycle to become resistant to the bacteria.

In September, HHS selected PharmAthene of Annapolis, Maryland, to develop the long-awaited next-generation recombinant Protective Antigen (rPA) anthrax vaccine, a genetically modified, purer serum that holds the promise of immunization with only three inoculations.

In 2007, HHS aborted its first attempt to procure rPA vaccine from the South San Francisco, California based firm Vax-Gen, canceling a 2004 contract worth $877.5 million. The deal for 75 million doses, enough to vaccinate 25 million people, was cancelled amid missed clinical trial deadlines and doubts about the vaccine’s stability. An investigation by the U.S. Government Accountability Office later faulted both HHS, for overly aggressive procurement, and VaxGen, for overestimating its own ability to satisfy the contract.

BioThrax manufacturer Emergent BioSolutions, meanwhile, which was already contracted to produce more than 33 million individual doses of BioThrax—enough to vaccinate at least 6.5 million people—won funding to test administration of the drug along with an immunity-boosting complement drug that could reduce its required shot cycle from six to two shots.

Drug dissemination. The medicines in the SNS cost billions of dollars, but they are worthless if they sit on pallets in highly secured government warehouses. If a bioterror attack occurs or a pandemic threatens, the next question is “how to get pills into people’s mouths quickly,” says Jolly. The government’s ability to do that effectively remains unclear, especially when it comes to delivering limited amounts of some drugs to the people who need them most.

In a crisis, delivery of SNS drugs would primarily be the responsibility of state public health authorities. Palletized supplies would be quickly shipped to individual states in need, then the states themselves would deliver the medicines to predetermined points of distribution (PODs) for their citizens.

At least, that’s the plan. Experts remain unconvinced that the country can effectively execute it, however. Dr. Jeffrey Levi, executive director of the Trust for America’s Health, faults federal stakeholders, such as HHS and DHS, for not setting clear expectations for distribution capabilities. “There’s still not a systemic set of core capabilities that we would expect every state to have met and tested,” Levi says.

Those criteria need to be established and tested. Then, HHS and its partners should share the results of those exercises with the public, Levi says.

He cites a model: “The Nuclear Regulatory Commission has exercises for facilities every couple of years, and it posts performance results on the Web site. If we can learn about nuclear protection programs, we should be able to learn about what states are doing to prepare for a pandemic or anthrax attack.”

The government, meanwhile, is exploring options other than relying on states as middlemen. Late last year, HHS announced a pilot project in Minnesota to test the use of U.S. Postal Service letter carriers to deliver drugs directly to residents during a biological response.

Larsen was among many experts who had advocated that approach. Levi says that he, too, welcomes the idea. “These are people who have to move things for a living, and I think it’s time we tapped that resource,” he says. “I think the question is, have we been creating this capability fast enough.”

Jolly says direct drug delivery might mitigate problems inherent in using PODs, such as the prospect of lines—or worse—forming outside and the difficulty of ensuring that everyone knows where to go to get the vaccine. He acknowledges, however, that postal service delivery is not without its own clear security concerns, and thus, will require heavy participation by local law enforcement.

Resources. Through its Hospital Preparedness Program, HHS has set priority actions for state public health officials and healthcare sector stakeholders to prepare for large-scale emergencies, whether they are local incidents like terror attacks that draw on regional resources or a global event such as a pandemic. Of the 5,640 hospitals that states have reported to HHS, 4,934, or roughly 87 percent, are participating in the program, according to agency spokeswoman Gretchen Michael.

The first critical metric is hospital bed surge capacity, as measured in extra beds per million residents of a given state. These extra “beds” may be outpatient examining room tables, cots, or even waiting room furniture that could be used for critical patients during a response. A recent U.S. Government Accountability Office (GAO) analysis of HHS data found that at least 37 states had met the minimum HHS recommendation of 500 potential critical-care beds for each 1 million in-state population. Overall, states have reported a total of 716 surge beds for every 1 million Americans, according to HHS.

Another issue is hospital personnel. The 2002-2003 outbreak of severe acute respiratory syndrome (SARS), primarily in east Asia and Canada, demonstrated that if the relatives of emergency medical personnel fall ill with a dangerous communicable disease, those healthcare providers will often stay home to care for loved ones at the expense of their jobs.

Heeding that lesson, HHS has assigned critical-care providers’ immediate families an equally high priority for treatment with stockpiled vaccines and medicines. Yet GAO found that only 26 states had enough medicine stockpiled to treat both hospital personnel and their families.

A third issue is how to allocate limited hospital resources in a surge. HHS has directed states to establish electronic cataloging and tracking for beds and care givers. In its own survey of 20 states, GAO found that 15 of them had instituted electronic, pre-event registration of volunteer medical professionals willing to provide care in a mass casualty event or pandemic. Meanwhile, 42 states have instituted bed tracking systems that are interoperable with HHS’s Hospital Available Beds for Emergencies and Disasters, or HAvBED, program, a system of systems HHS has developed for tracking and mapping available healthcare assets during a major emergency.

Triage. The nation’s emergency healthcare sector has taken the unpleasant—but, experts say, necessary—step of issuing peer-reviewed guidelines for who would and would not receive critical medical care in a flu pandemic, which the government calls “altered standards of care.” (see “Hard Questions in Emergency Critical Care,” Security Management, August 2008).

Earlier last year, HHS issued guidelines providing protocols for tiered administration of available pandemic influenza vaccines and antivirals. The guidelines categorize the population into four groups: those responsible for national and homeland security, healthcare providers, operators of critical infrastructure, and everyone else.

Each group is further tiered based on priority, with “Tier 1” drug recipients from the respective groups including mission critical federal personnel, physicians and public health personnel, first responders and drug manufacturers, and pregnant women and infants. The entire Tier 1 group is estimated to consist of 24 million people.

At the other end of the spectrum, healthy adults between the ages of 19 and 64 are not even recommended for treatment from the SNS unless those drugs are available in sufficient quantity to have all the other groups taken care of. Healthy adults may also receive drugs when the situation merits, such as a Category 5 pandemic, like the 1918 Spanish flu, which killed 2 percent or more of the infected. Extrapolated to 2006 U.S. population figures, HHS projected the mortality rate of a Category 5 pandemic at 1.8 million people.

Mair of UPMC anticipates that problems could arise with the risk-based drug allocation, whether in a pandemic or terrorist attack, because it may not be clear who is in which category. “I do have concerns about it, because we’ve got so many people in so many different groups, how do you determine who’s who,” says Mair.

Mair expressed further concerns about making sure recipients are administered the drug properly and for the full regimen. He notes that drugs like post-exposure antibiotics may require weeks or months of treatment and carry mild but unpleasant side effects. “People will not want to take them for 60 days,” he says, noting that they don’t want to take regular antibiotics for the 10 days that they are typically prescribed.

Incomplete antibiotic treatment elevates the risk that bacteria will mutate into drug-resistant strains.

The Human Factor

Concern about proper drug use is just one aspect of the greatest unknown amid a bioterror attack or disease pandemic: the public’s response. Experts believe that reaction will depend largely on how well the government handles communication throughout the crisis.

Some decisions, such as whether to impose international travel restrictions, will fall to federal authorities. Most issues, however, will be left to state and local agencies, which will also be responsible for communicating them to the public. The measures might include “social distancing,” which might require the cancellation of mass-gathering events, including suspension of public education in some areas.

Public health officials may ask anyone who knows or suspects that they have been exposed to a pathogen to voluntarily impose a self-quarantine. Similarly, healthy people with weak immune systems or other health conditions may be urged to stay home and “reverse quarantine” to prevent exposure.

In the case of the 2003 SARS outbreak, as many as 30,000 Canadians who were potentially exposed to the virus self-quarantined. That illustrates the willingness of an informed public to do what’s recommended for the greater good, says Mario Possamai, CFE, CAMS, managing director of Forensic Financial Research and Consulting, Inc., in Toronto, who served as an advisor to the SARS Commission, which investigated Ontario’s handling of the SARS outbreak that killed more than 700 people, 43 of them in that city.

Possamai also notes, however, that one exposed individual went to his factory job and infected a coworker who died. The factory then had to shut down until the epidemic passed, leaving roughly 1,500 people out of work.

“[I]f there’s an outbreak, one of our greatest challenges is going to be working together,” Possamai says.

Will Americans follow direction? Larsen looks to this year’s Gulf Coast hurricanes Gustav and Ike. Given the documented history of a serious storm’s capacity to devastate the region, first in Galveston in 1900 and then in 2005, most residents on barrier islands honored mandatory evacuation orders, but not all. And that was a short-term situation with a clear and present danger.

Funding

Possamai emphasizes that local public health departments require adequate financial resources to be effective. “If they’re not adequately resourced and able to communicate, there could be some real problems there,” he says.

Jack Herrmann, senior advisor on public health preparedness for the U.S. National Association of City and County Health Officials, says financial resources, which flowed down to local agencies after the massive 2005 federal expenditures to address the pandemic, have effectively been shut off.

According to an analysis of federal biodefense spending by Crystal Franco of UPMC’s Center for Biosecurity, published in the center’s journal, Biosecurity and Bioterrorism, federal agencies have spent a total of $42 billion on biodefense since 2001, with expenditures peaking in fiscal year 2005, with the appearance of avian flu in humans, at $8.2 billion. From 2006 through 2008, federal biodefense funding held steady at close to $5.5 billion, with roughly $4 billion expected in 2009, according to Michael of HHS.

Federal grant funding to state and local public health agencies, which totaled more than $5 billion through 2008, has stopped flowing, Herrmann says. Given the current economic crisis, funding is likely to remain scarce.

Levi of the Trust for America’s Health worries about “pandemic fatigue” among the public, as the world approaches four years since the first major alarms sounded over the prospect of H5N1 moving from birds to humans. When another biological attack or pandemic does finally arrive, Larson cites a critical need for candor from government officials. “What’s most important is that the government establish credibility with the public,” Larsen says. “Because if you lose it early on, you never get it back.”

Joseph Straw is an assistant editor at Security Management.