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Pathogens on a plane: The XDR-TB case in the age of bioterror
Those incubating disease are the real sleeper cells
Questions regarding homeland security, bioterrorism, and containment of emerging infectious diseases have been raised in the aftermath of the recent, highly publicized case of the airline traveler with extensively drug-resistant tuberculosis (XDR-TB). The fact that the Atlanta man successfully eluded federal quarantine efforts and managed to cross the Canadian border despite orders to detain him has opened the federal agencies involved to criticism in congressional hearings.
"We dodged a bullet," said Rep. Bennie Thompson (D-MS), chairman of the Homeland Security Committee. Noting that the 9/11 Commission had found "a failure of imagination" among intelligence officials and Hurricane Katrina postmortems saw "a failure of initiative," Thompson said officials in this case "should have connected more dots." Officials testifying in the aftermath of the case outlined an array of failures that several members of Congress called "a wake-up call for a serious bioterrorism incident," according to press reports.1
Counterterrorism planners such as Jason D. Söderblom, an analyst for the Terrorism Intelligence Centre in Canberra, Australia, have researched scenarios in which terrorists intentionally infect themselves with diseases including plague or smallpox and try to start an outbreak before succumbing to the illness. Indeed, Söderblom outlines a chilling "piggyback" scenario — using both smallpox and pneumonic plague — that has infected terrorists going to crowded clinics and waiting rooms in hospitals and physician offices while suffering from "flu-like" symptoms to mask their true disease and purpose.2
He points out in a paper on the subject that biological warfare in the ancient world included use of "smallpox martyrs" and "poison maidens" as weapons against enemies. "Biological ruses using contaminated humans to counter strong military powers have an ancient and terrifying pedigree in both legend and fact," he wrote. " . . . Democracies, even in the broad definition of the term, are poorly organized to prevent a suicide bioterrorist from entering a public space, such as an airport, stadium, school, or shopping mall, and spreading a biological weapon before the symptoms become apparent."
Catch me if you can
But what of our more recent international incident, the elusive travels of the man with XDR-TB? While there appears to be considerable confusion about who said what to whom, the man was allegedly advised not to travel before doing so, setting off a one-man test of the international infectious disease warning and containment system in a series of plane rides and border crossings that played out like the sequel to Catch Me If You Can. Unfortunately, passengers on the flights in question became unwitting test subjects in a real-life clinical trial that asks the question: Can XDR-TB be transmitted from an apparently asymptomatic but potentially infectious patient to those seated nearby? The Centers for Disease Control and Prevention (CDC) notified all U.S. passengers on the international flights in question and advised them to seek TB testing. Previous investigations indicate that air travel passengers with symptomatic TB (e.g., coughing) can transmit the disease during prolonged flights.3,4
In this case, the answer will not be known for weeks and months as follow-up and testing continues through TB's potentially prolonged incubation period. However, it is doubtful transmission occurred in the absence of symptoms. Another encouraging finding is that none of the passenger's friends or family have been found to be infected. The man is undergoing treatment at the National Jewish Medical and Research Center in Denver. He originally was considered infectious based on three respiratory tract specimens that were reported culture positive for XDR-TB, the CDC reported. However, subsequent news reports had the hospital listing him as "relatively noncontagious," based on sputum tests taken since his return to the states.
"While he may not have been highly infectious, he certainly was potentially capable of transmitting this infection to someone else," Julie Gerberding, MD, CDC director, said at a recent press conference. " . . . We really had to be assertive as a public health agency in protecting people in this case because of the nature of the bacteria." Indeed, the CDC had to pull out all the stops because XDR-TB is an absolutely unforgiving and virtually untreatable infection. By the current definition, XDR-TB is resistant to at least isoniazid and rifampin among the first-line anti-TB drugs and among second-line drugs is resistant to any fluoroquinolone and at least one of three injectable drugs. The staggering mortality rates among the HIV-infected in Africa are only part of the XDR-TB story. Unpublished CDC data indicate that the chances for survival — even in a person without HIV — are worse than 50/50 within four years of acquiring XDR-TB. A cancer diagnosis carries better odds — 55% survival rate within five years.
The follow-up and after-action analysis of this case at the CDC and among its international partners will be critical as XDR-TB continues to emerge globally, pandemic flu threatens to emerge, and the scenario of intentional infection continues to be discussed in bioterrorism circles. One obvious question is whether — had he been symptomatic — would the infected traveler been detected and barred from travel by public health, customs, and airport officials? "This is one case, but there are actually many, many cases where we have been successful," Gerberding said. "Obviously this [case] has been very visible, but what's not visible to you are the many patients [with] tuberculosis where health officials have been notified, patients have complied voluntarily with the recommendations and advice, and there has not been a risk to other people in the community."
Gaps in the quarantine system
Still, in 2004, a man suffering from fever, chills, severe sore throat, and diarrhea flew from Sierra Leone to Newark, NJ. He died from Lassa fever less than a week after arrival, having exposed 188 people to the disease. That case was cited by the Institute of Medicine (IOM) in a 2005 report on the need for improving the current quarantine system.5 Indeed, the XDR-TB case actually may speed along ongoing improvements in the quarantine system and strengthen international partnerships, pushing ahead an effort that earlier was redoubled after the IOM report. Noting that some 120 million people travel into or out of the country through the nation's 474 airports, seaports, and land-border crossings every year, the IOM warned that the system of using CDC quarantine stations no longer is sufficient to protect the population against microbial threats of public health significance that originate abroad. The current list of federally authorized quarantinable communicable diseases includes cholera, diphtheria, infectious tuberculosis, plague, smallpox, yellow fever, viral hemorrhagic fevers (Lassa, Marburg, Ebola, etc.), severe acute respiratory syndrome (SARS), and flu strains that have the potential to cause a pandemic.
One significant gap in the current quarantine system is the difficulty involved in quickly locating airline passengers who may have been exposed to a high-risk infectious agent such as the SARS virus during a flight, the IOM reported. Often, travelers have to be found days after the flight is over. The IOM report supported the targeted use of passenger locator cards as an interim solution. The cards — which would be distributed on flights to and from countries where a disease outbreak is occurring or when a passenger or crew member becomes ill during a flight — would record passenger contact information and seat numbers in a scannable format so that the data could be retrieved and transmitted easily. In addition, in a conclusion that seems prescient regarding the XDR-TB fiasco, which involved travel of an asymptomatic passenger, the IOM report concludes: "infected individuals and animals do not necessarily develop signs of disease while in transit or by the time of arrival, and available noninvasive diagnostics cannot always identify infected travelers with reasonable sensitivity, specificity, and speed."
Indeed, much of the hue and cry over the XDR-TB case has overshadowed a more insidious reality in daily global air travel: A passenger in the incubation stages of some emerging infectious disease could be headed to any given U.S. community and there is very little that anyone can do about it. Such infected passengers may be traveling from one of the 17 countries that have reported XDR-TB. Air travel connecting any two points in the world can certainly be accomplished well within the prolonged incubation period for TB and for the vast majority of other infectious diseases as well. The 2003 emergence of SARS in Hong Kong was fueled by rapid global spread via air travel. While airline passengers were at risk of SARS transmission, the real outbreak occurred in various nations after those incubating and infected had deplaned. In that regard, much of the coverage and discussion of the XDR-TB case has missed the point, says Eric Toner, MD, senior associate at the Center for Biosecurity at the University of Pittsburgh Medical Center. While a passenger infecting others on a plane would be a public health incident, the asymptomatic passenger whose infection will appear later is the real threat of a major biological event, he notes.
"The issue with infectious diseases and travel is not that someone contagious would get on an airplane, but rather that people who are incubating can travel around the world, as happened with SARS," he says. "For the most part, they didn't transmit the disease on the airplane but within the country they were traveling to once they got there. And there is no way through regulations and technology to identify people with incubating disease. That's the real issue."