The Coming Plague (96 page)

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Authors: Laurie Garrett

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The New Mexico State Health Commissioner soon requested federal assistance in handling public response to the outbreak, asking that the CDC send out an expert in media relations to handle local panic and the press. Again, an unprecedented step was taken, and CDC information officer Bob Howard flew out to New Mexico on June 5 to coordinate all press operations.
By then the field team included more than a hundred scientists, physicians, animal trappers, and paraprofessionals who were scouring the Four Corners area. Among them were the CDC's Chapman, Breimen, Childs, Butler, McDade, and dozens more.
And by then they knew what was causing the illnesses and deaths.
C. J. Peters's lab group struck pay dirt during the predawn hours of Thursday, June 3, when antibodies against a family of viruses called hantaviruses cross-reacted in test tubes with blood from the patients. Furthermore, patient blood carefully injected into mice housed in the P4 laboratory showed even stronger antibody reaction to hantavirus reagents. That proved that the agent was infectious and that the virus could reproduce and multiply inside mice.
“That raised some serious eyebrows,” Peters recalled. “As soon as we knew where to focus, we got the molecular biologists into the act.”
Peters's old Fort Detrick comrade Tom Ksiazek, also a DOD budget cuts refugee recently arrived at the CDC, helped coordinate what would turn out to be the fastest new viral identification ever carried out during an epidemic. In just seven days Ksiazek's laboratory team had serologically narrowed their clues down to hantaviruses; now they needed to determine which specific virus strain was causing the Four Corners epidemic.
Identifying the exact strain of hantavirus responsible for the outbreak required infected wild animals—the microbes' reservoirs. Only in the animal reservoirs would virus levels be sufficient to make isolation and identification possible, Peters knew. So at a CDC staff meeting that day Peters told McDade, Breimen, Chapman, and other scientists who were about to head out to Four Corners that the culprit was probably a hantavirus, and he wanted them to send back plenty of wild rodent samples. Applause and disbelief followed. While the staff praised the lab's speedy solution of the cause of the epidemic, some were dubious. Breimen noted that all known hantaviruses caused kidney problems, none produced respiratory distress.
“It doesn't match,” he said, garnering support from most of the physicians in the room. Those in the meeting who were familiar with hantavirus history were skeptical that the virus—first noted in Korea—could have found its way to a landlocked, remote region of North America.
Peters told the group that his molecular biology team was working on a
detailed genetic analysis of the Four Corners virus, and he suspected it might turn out to be something new.
“Look, we know there are different types of hantas out there [in the world],” he said. “So let's not rule things out, or in. Finding antibodies isn't enough. We know that.”
 
Hantaviruses first came to world attention during the Korean War.
4
Between 1951 and 1954, more than 2,500 GIs and an unknown number of Korean soldiers fell ill to a mysterious disease that caused fevers, weakness, fatigue, and kidney failure: 121 GIs died of the ailment.
5
U.S. Army researchers fairly quickly figured out that the disease was caused by a virus that was normally carried by field mice.
But it took over twenty years for scientists to successfully isolate the virus—dubbed Korean Hantaan—from the lungs of infected
Apodemus agrarius
mice. Dr. Karl Johnson, then with the U.S. Army Medical Research Institute of Infectious Disease (USAMRIID) at Fort Detrick, collaborated with Dr. Ho Wang Lee of Korea University Medical School in Seoul to discover the virus, using electron microscopes to spot the round microbes that were neatly stacked in rows along the epithelial lining of
Apodemus
lungs.
6
The natural territory of
A
.
agrarius
included large parts of Japan, Korea, northeastern China, and southeastern and central Russia. In South Korea between 1955 and 1977, over 9,000 cases of Hantaan were documented; 6.5 percent were fatal. Far more cases were suspected, but were thought to have escaped diagnosis because of their similarity to milder, common ailments, such as influenza.
During the 1970s eleven other forms of hantaviruses were discovered in Eastern Europe and Asia, all linked to usually mild kidney diseases with fatality rates ranging from 10 down to 0.1 percent of all infected people. The viruses were always carried by some type of wild rodent, and people came in contact with the microbes through skin exposure or inhalation of infected animal feces or urine.
In 1977 Belgian researcher Guido van der Gröen, having maintained his interest in hemorrhagic viruses since the Ebola investigation in Zaire, discovered in his laboratory at the Institute of Tropical Diseases in Antwerp hantavirus-induced mild cases of muscle pain, hypertension, and kidney dysfunction among residents of his city. The apparently urban viral strain was very similar to one previously discovered in Sweden,
7
called Puumala virus, carried by voles (
Clethrionomys glareolus
) that inhabited riverbanks. Between 1977 and 1986 van der Gröen identified seventy-six cases of Antwerp-type hantaviral disease in Belgium and France, and tried to warn local physicians that many hanta cases were undoubtedly going undiagnosed because they were confused with occupational back problems, flu, and other minor ailments.
8
Johnson and Lee, intrigued by van der Gröen's urban hanta findings,
tested rats in downtown Seoul, finding that the two most common species in the world—
Rattus rattus
and
Rattus norvegicus
—carried a form of virus only slightly different from the Korean Hantaan strain. They were convinced that the rat infections were relatively recent, having occurred sometime around the Korean War when aerial bombing campaigns drove the A.
agrarius
field mice out of their natural habitats into urban areas, where they got into turf battles with the rats and probably passed the virus on to the larger rodents in biting and clawing fights.
Since Korea was rapidly becoming one of America's biggest trading partners, Johnson wondered whether infected Seoul rats might have found their way into the cargo holds of Korean ships and then escaped into U.S. harbor cities. In 1982, at Johnson's urging, Fort Detrick and CDC scientists combed the harbor areas of Baltimore, Houston, Philadelphia, San Pedro, and New Orleans looking for rats. Everywhere the Army scientists looked, Seoul virus turned up in both black
R. rattus
and their brown cousins,
R. norvegicus.
That year, 1982, Lee teamed up with NIH Nobel laureate Carleton Gajdusek to test common North American voles for hantaviruses. They scoured Gajdusek's property in Frederick, Maryland, capturing local rodents. And the scientists found a new strain of hantavirus—dubbed Prospect Hill virus after the site of its discovery—and showed that it was carried by two vole species,
Microtus pennsylvanicus
and
M. californicus
. Between them, these voles spanned territory encompassing most of North America.
One of the U.S. Army scientists most intrigued by evidence of hantaviruses in North American rodents was a tall, lean microbiologist named James LeDuc. During the early 1980s LeDuc reasoned that somebody in the United States must suffer Hantaan illness if the virus was infecting domestic rats, so he teamed up with other Army scientists and Jamie Childs, then at Johns Hopkins Medical School, to search for evidence of hanta disease in Baltimore. First, they carefully tested the local rats, discovering to their amazement that virtually every rat over two years of age was infected with a hanta virus. The team then tested 1,788 adults admitted either to Johns Hopkins or a Baltimore sexually transmitted disease clinic in 1986; four were infected with the Korean Hantaan virus. Because the individuals hadn't traveled outside the United States, LeDuc and Childs concluded that they had acquired their infections from local rats.
9
That led LeDuc and Childs to consider focusing their research on people who suffered symptoms that could be produced by hantaviruses. They knew that the viruses could cause chronic kidney disease in Korea and parts of Europe, so they tested the blood of 1,766 people who were undergoing proteinuria blood chemistry analysis at Johns Hopkins, as well as 254 kidney dialysis patients. They discovered that 6.5 percent of the dialysis patients who were suffering hypertensive kidney disease had serum that reacted with Seoul hantavirus antibodies, indicating that they had been infected.
10
LeDuc and Childs also found that common Baltimore house mice—
Mus musculus
—carried the Seoul virus.
In August 1986 a Mexican immigrant working in the town of Leakey, Texas, died of internal hemorrhaging and kidney failure. Scientists from the NIH suspected a hantavirus was responsible, and trapped rodents found in areas known to have been frequented by the deceased individual. They discovered that local house mice—again
M. musculus
—were infected with another type of hantavirus, which they designated Leakey virus.
11
By 1992, LeDuc was convinced that hantaviruses of various types were prevalent in rodents throughout North America, and strongly believed that they were responsible for the higher rates of hypertension and kidney disease seen among America's inner-city poor, particularly African-Americans.
12
Furthermore, he feared that the problems might be worsening, as rat infestation of American inner-city areas increased. Between 1989 and 1991, for example, citizen complaints about rat infestation increased 33 percent in Baltimore and rodent control staff over the same period declined by 50 percent. All the lost staff had been funded under a federal program which was severely slashed by the Bush administration. Similarly, New York City took significant cuts in rodent control funds between 1989 and 1994, during which federal and local funding plummeted from $10.3 million to $5.2 million. Federal funding completely evaporated by 1992, prompting the New York City Health Commissioner, Dr. Margaret Hamburg, to formally express grave concern to the CDC that hantaviruses and other rodent-borne disease agents might get out of control in America's largest metropolis. Despite the commissioner's warnings, the newly elected mayor of New York City, Rudolph Giuliani, slashed the city's rodent control budget by a further 50 percent in early 1994.
Budget cuts in 1991–92 at the U.S. Department of Defense forced closure of most Army medical research programs; Childs, Peters, and Ksiazek went to the CDC and LeDuc ended up working at the World Health Organization headquarters in Geneva. Army hantavirus research slowed radically, leaving only the fortunately prolific molecular biology labs of Dr. Connie Schmaljohn and Peter Jahrling at Fort Detrick to carry the load.
 
The moment Peters and his CDC laboratory staff had hints of hantaviruses in the Four Corners outbreak, Childs and LeDuc were excited and intrigued. LeDuc was in daily telephone communication with his former Army colleagues, providing insight and gathering information to pass on to interested WHO scientists.
Childs and LeDuc were the first scientists to apply polymerase chain reactions, or PCR, to the diagnosis and study of hantaviruses. LeDuc and Childs developed PCR techniques for hantaviral searches in 1991,
13
and Peters's Special Pathogens Laboratory would benefit enormously from that legacy in 1993. As the second wave of CDC field investigators, led by Breimen and McDade, headed out to Four Corners over the first June
weekend, Peters, Ksiazek, and PCR expert Stuart Nichol eagerly anticipated receipt of rodent samples, upon which they intended to perform PCR analysis to identify which species of hantavirus was causing the Southwest outbreak.
Breimen was skeptical of the hanta connection, though he did note that all earlier animal studies of various hantaviruses found high concentrations of the viruses in rodent lungs. One LeDuc/Childs study even indicated that lung tissue was the only site from which viruses could easily be extracted over the full course of a mouse infection.
During their first forty-eight hours in Albuquerque, Breimen and Chapman hammered out a standard description of the disease, setting out the criteria for designating a suspected ARDS case as a possible hantavirus infection. And they created the questionnaires to be used by Navajo and CDC field investigators making door-to-door surveys on the outbreak.
No sooner had Chapman completed those tasks, sleeping no more than four hours in two days, than she was asked to assess the utility of ribavirin as a treatment for the mystery disease. LeDuc and his colleagues had tested the antiviral drug on Hantaan patients in China in 1987, finding that it decreased the likelihood of dying if ribavirin was taken within the first three days of the disease. After that time, it wasn't clear whether or not the drug was beneficial.
14
For physicians in the Four Corners area it was a desperate matter to find something—even a drug of dubious value—to give their ailing patients. Short of ribavirin, all the doctors could offer was good hospital management and TLC. And the mortality rate from the virus was very high, appearing to exceed 70 percent.

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