The Coming Plague (97 page)
Authors: Laurie Garrett
By June 7 the CDC had confirmed twenty-four cases of the strange sickness, twelve lethal, all occurring in the Four Corners area.
The most important clue the investigators had was the CDC lab's hints of hantaviruses, which, based on the history of such viruses, pointed to rodent disease carriers. Childs, Chapman, and CDC ecologist John Krebs were among the three dozen investigators who, teamed with Navajo trappers and health workers, went out to every site where people had become ill and set hundreds of rodent traps. They had two types of spring-action traps; one, a heavy steel case, could handle animals as large as raccoons and skunks, while the smaller aluminum traps were designed for mice, prairie dogs, and the like.
The crews had to be careful, avoiding exposure not only to the mystery virus but also to bubonic plague. Despite a temperature of over 100 degrees, they wore respirator masks, goggles, paper body suits, double-layered latex gloves, and disposable booties over their shoes. These precautions might protect them against airborne bits of hanta-contaminated dust, but Chapman was much more worried about getting bitten by a plague-carrying flea that might crawl under her protective garments to reach her vulnerable skin. She slathered generous layers of insect repellent on her skin as well,
knowing that she wouldn't be able to swat pests when she was wearing the gloves and body suit.
knowing that she wouldn't be able to swat pests when she was wearing the gloves and body suit.
When an inhabited trap was opened, scientists always stood upwind of the animal and carefully placed a plastic bag containing anesthetic over the door of the trap. As the animal fell into the bag, it quickly went unconscious. Later the scientists would withdraw blood and tissue samples, place them on dry ice, and ship the materials back to Peters's P3/P4 laboratory for analysis.
It seemed that the Navajo elders and Robert Parmenter's scientific team were both right about the huge piñon harvest and a very large rodent population. After five years of severe drought, the Four Corners area had record snowfalls during the 1992â93 winter season, followed by an extraordinarily moist spring. Even in June the scientists could still see greenery in the desert and piñon trees standing flush with nutted cones.
With the abundant vegetation came apparently unprecedented rodent populations.
Nearly half the traps contained all sorts of creatures, from mice and prairie dogs to fat rats and smelly skunks, but by far the most common were
Peromyscus maniculatus
, a brown, big-eared mouse with white belly and tail and huge, black eyes sunk into the skull. Because of its brownand-white coloring,
P. maniculatus
was called a deer mouse.
Peromyscus maniculatus
, a brown, big-eared mouse with white belly and tail and huge, black eyes sunk into the skull. Because of its brownand-white coloring,
P. maniculatus
was called a deer mouse.
In initial blood antibody tests the CDC investigators found evidence of hanta infection in the deer mice, as well as two other
Peromyscus
species, two types of chipmunks, common house mice, and
Neotoma albigula
pack rats.
Peromyscus
species, two types of chipmunks, common house mice, and
Neotoma albigula
pack rats.
In the lab, however, where CDC scientists had just perfected the use of PCR techniques for diagnosing these infections, only the deer mice were found to be commonly carrying the virus. With time the CDC lab would confirm by PCR the presence of the virus in a third of the first 770 P.
maniculatus
caught in the Four Corners area, as well as in 19.7 percent of
P. truei
(of 314 tested) and 6.9 percent of
P. boylii
mice (of 59 tested).
maniculatus
caught in the Four Corners area, as well as in 19.7 percent of
P. truei
(of 314 tested) and 6.9 percent of
P. boylii
mice (of 59 tested).
The
P. maniculatus
were not mice restricted to habitats in Four Corners; on the contrary, these deer mice could be found all over Canada, as far north as the Arctic Circle, and, to the south, throughout the United States and northern Mexico. Only the Deep South states of the United States seemed to be excluded from the deer mouse's natural territory.
P
.
maniculatus
were, in other words, ubiquitous North American field rodents.
P. maniculatus
were not mice restricted to habitats in Four Corners; on the contrary, these deer mice could be found all over Canada, as far north as the Arctic Circle, and, to the south, throughout the United States and northern Mexico. Only the Deep South states of the United States seemed to be excluded from the deer mouse's natural territory.
P
.
maniculatus
were, in other words, ubiquitous North American field rodents.
Knowing that, Breimen and McDade wondered how long it might be before mysterious ARDS cases turned up in other states.
By the end of the first week in June, Peters's lab already had suspicions, based on PCR analysis, that the virus infecting both people and
Peromyscus
in Four Corners was yet another newly discovered hanta strain. By mid-June they were sure: the Four Corners virus was, as they wrote in the CDC weekly publication, “a previously unrecognized hantavirus.”
15
Peromyscus
in Four Corners was yet another newly discovered hanta strain. By mid-June they were sure: the Four Corners virus was, as they wrote in the CDC weekly publication, “a previously unrecognized hantavirus.”
15
If the virus was genetically different from previously identified hantas,
its ability to produce acute respiratory symptoms, as opposed to the kidney problems caused by all other hantaviruses, became less questionable. The CDC lab spent the rest of June, July, and August comparing bits of the genetic sequences of the Four Corners virus with the eleven other known hantaviruses, discovering to their amazement that the new virus cross-reacted most strongly with Prospect Hill, the strain found in Maryland voles that had never been associated with human disease.
its ability to produce acute respiratory symptoms, as opposed to the kidney problems caused by all other hantaviruses, became less questionable. The CDC lab spent the rest of June, July, and August comparing bits of the genetic sequences of the Four Corners virus with the eleven other known hantaviruses, discovering to their amazement that the new virus cross-reacted most strongly with Prospect Hill, the strain found in Maryland voles that had never been associated with human disease.
“That surprised us,” Ksiazek said, “because here you had human mortality rates of seventy or eighty percent in Four Corners, and no disease of any kind with Prospect Hill.”
The PCR analysis eventually revealed some significant differences in the genetic sequences of the two viral strains, yet Prospect Hill remained Four Corners' closest known relative.
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By mid-July the CDC lab had received over 10,000 animal and human samples for analysis; by late August that number was approaching 20,000. In addition to the tremendous burden of simply storing and labeling all those samples, Peters and Ksiazek felt they should pull out of their Atlanta freezers archived rodent samples collected during previous years around Four Corners for plague studies. They wanted to use the archive material to answer two key questions: (1) Is there an epidemic of the virus this year among the rodents or are the animals always carrying the virus at about the same frequency of infection? (2) Has this sudden apparent set of infections been the result of the virus's mutating recently from a benign Prospect Hill-like form to a new type capable of causing ARDS?
The latter question had some purely circumstantial evidence behind it. Hantaviruses were of a class of viruses whose genetic material was stored in the form of three discrete pieces of RNA. Other segmented RNA viruses, such as influenza, were known to mutate frequently because during viral replication the copying of these big pieces of RNA was often a sloppy business. One RNA piece might cross over another, mixing up their genes. Extraneous bits of RNA in the cell the virus infected might get picked up and incorporated into the virus's genetic blueprint. The result for many segmented RNA viruses was a sort of natural crapshoot, with each viral replication event carrying some odds of mutation.
But by August the CDC lab was far too overwhelmed to consider an immediate foray through the archives. The questions would have to remain unanswered for the time being.
Meanwhile, a woman seemed to have died of the mysterious ARDS a thousand miles away from Four Corners, in East Texas. The epidemic had expanded. In a matter of hours, Dr. Ali Khan, having just completed two years of postmedical training as a CDC Epidemic Intelligence Officer, was wandering around the East Texas town of Lufkin, working with state investigators to ensure that all clues at the death site were properly collected and none was overlooked.
The victim, a youthful grandmother, had lived in a fairly elegant, neat
house located in a rural area not far from the Louisiana border. No rodents were in or around her house, but Khan discovered telltale mouse feces in a back shed the woman used for putting up fruits and vegetables. Her husband said that she spent hours out there, canning all sorts of produce.
house located in a rural area not far from the Louisiana border. No rodents were in or around her house, but Khan discovered telltale mouse feces in a back shed the woman used for putting up fruits and vegetables. Her husband said that she spent hours out there, canning all sorts of produce.
The autopsy revealed that she had suffered a classic case of ARDS of unknown etiology, and Khan had her tissue and blood samples sent to C. J. Peters's lab, where Four Corners virus infection was confirmed by PCR.
Over the next four weeks Khan was constantly on airplanes, flying into suspected ARDS-hanta outbreaks in California, Nevada, Oregon, Louisiana, Arizona, Utah, and Idaho. His second case involved a fifty-one-year-old woman who “lived in smack-of-the-middle-of-nowhere Nevada,” as Khan later described it. She survived acute ARDS, thanks to what Khan insisted was “brilliant medical care by her rural doctors.” According to the woman, all spring and summer her pet cat kept dragging rodents into the house. Her area of Nevada had unusual rainfall, and most of the locals felt the rodent population was just about out of control.
Khan's third hantavirus victim wasn't as lucky; a resident of a remote area straddling the California-Nevada border, she died of hanta-ARDS. Khan's team found infected mice around her property.
The fourth Khan case involved a twenty-nine-year-old ranch hand who worked the range along the northern California coast. He, too, died of acute ARDS.
An Oregon physician alerted the CDC to the possibility that one of his patients, a sixteen-year-old boy, had died mysteriously of ARDS a year earlier and might have been a hantavirus victim. By the end of August the CDC's lab had confirmed that hantaviruses were in the dead boy's body.
A particularly emotional case for Khan involved a fellow scientist: a promising twenty-seven-year-old female graduate student, Jeanne Messier, who was conducting ecology research in an isolated part of the California Sierras. Ailing, Messier made her way down to a small medical clinic in Mammoth Lake, California, on July 31, and was immediately airlifted to a hospital in Reno. She died shortly after arrival. Scientists found her Sierras cabin overrun by mice.
The U.S. Congress took notice of these events, and the eight senators representing the Four Corners states pushed through legislation during the dog days of July that allocated $6 million in emergency funds to assist the state and federal investigation; $2.6 million went to the CDC. Some members of Congress remarked that such an allocation might not have been necessary if DOD budget cutters hadn't gutted the Army's hanta program two years earlier.
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In August, New Mexico authorities requested additional laboratory assistance from USAMRIID scientists, and Peter Jahrling and Connie Schmaljohn began separate efforts to isolate the strange new hantaviruses that
were seemingly cropping up all over the United States. Soon the Army researchers were in a competitionâlater a rivalryâwith their CDC colleagues. They discovered the virus in the body of an eight-year-old Mississippi girl who died of an ailment whose symptoms didn't match the CDC definition of hanta-ARDS that Breimen and Chapman had written three months earlier. The CDC refused to add the Mississippi case to its growing list of Four Corners virus victims.
were seemingly cropping up all over the United States. Soon the Army researchers were in a competitionâlater a rivalryâwith their CDC colleagues. They discovered the virus in the body of an eight-year-old Mississippi girl who died of an ailment whose symptoms didn't match the CDC definition of hanta-ARDS that Breimen and Chapman had written three months earlier. The CDC refused to add the Mississippi case to its growing list of Four Corners virus victims.
“The CDC is claiming it did not meet their case criteria,” Jahrling would later say with some bitterness. “They cannot refute, however, our evidence that we have a replicating hantavirus from that case, in cell culture.”
In early June, another alert rural physician spotted what would prove to be one of the most puzzling hanta cases, this one occurring in Louisiana. A fifty-eight-year-old bridge inspector had died of sudden ARDS, and rural physicians called Khan in late July. While the Louisiana doctors frankly doubted the case could be another example of Four Corners disease, they had read the CDC's bulletins and thought Khan should know that the symptoms matched.
Khan was dubious. The
Peromyscus
mouse didn't inhabit Louisiana, and the area was over 200 miles away from the East Texas site of Khan's first investigation. All doubt vanished, however, when Khan saw the patient's medical records and Peters's lab group confirmed that the blood samples were antibody-positive for hanta infection. The victim's farmhouse was neat as a pinâno signs of rodent infestation. But the victim's co-workers told Khan that they ran into rats and mice every day as they crawled around culverts and ditches to inspect western Louisiana's bridges.
Peromyscus
mouse didn't inhabit Louisiana, and the area was over 200 miles away from the East Texas site of Khan's first investigation. All doubt vanished, however, when Khan saw the patient's medical records and Peters's lab group confirmed that the blood samples were antibody-positive for hanta infection. The victim's farmhouse was neat as a pinâno signs of rodent infestation. But the victim's co-workers told Khan that they ran into rats and mice every day as they crawled around culverts and ditches to inspect western Louisiana's bridges.
When the lab did PCR analysis on the Louisiana man's virus, the mystery deepened: it didn't match with the Four Corners strain or any other known hantavirus. Fellow bridge workers hadn't seen the distinctive white-bellied deer mice around their work site, but they had encountered plenty of the big brown
Rattus norvegicus
âthe same rat species LeDuc discovered years earlier carrying Seoul-strain hanta in Baltimore.
Rattus norvegicus
âthe same rat species LeDuc discovered years earlier carrying Seoul-strain hanta in Baltimore.
Ksiazek was one of the few CDC scientists who weren't surprised by the discovery.
“These viruses are all pretty close to one another, as viruses go. And all these rodents have common ancestors. The genetically closest viruses are carried by close-relative rodents. Personally, I think this is an indication of co-evolution of rodents and their passenger viruses,” Ksiazek said.
By summer's end Ksiazek suspected that more strains of hantaviruses remained to be uncovered in North America, and many hundreds of cases of ARDS, kidney disease, and hypertension in the United States every year would turn out to have been caused by these rodent viruses. While only forty-two cases of hanta-ARDS were confirmed by the CDC as of October 29, Ksiazek was convinced that they represented the tiny tip of a vast disease iceberg. Retrospective analysis showed that the earliest identifiable
case occurred in July 1991. Since then, patients had ranged in age from twelve to sixty-nine years, and 62 percent had died. Half the victims were American Indians: presumably due to lifestyle, not genetic, factors.
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case occurred in July 1991. Since then, patients had ranged in age from twelve to sixty-nine years, and 62 percent had died. Half the victims were American Indians: presumably due to lifestyle, not genetic, factors.
18
Â
Throughout history, rats and mice have taken advantage of human movements to gain access to new ecologies around the world. The arrival of
R. rattus
and its cousins in the Americas is undoubtedly recent, probably having occurred less than 500 years ago when rodent stowaways made their way to American soil from the boats of European explorers and slave traders. And they may have been on the European continent for only some 1,200 to 1,500 years prior to that, having stowed away on traders' ships and caravans from the Middle East and the Far East.
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R. rattus
and its cousins in the Americas is undoubtedly recent, probably having occurred less than 500 years ago when rodent stowaways made their way to American soil from the boats of European explorers and slave traders. And they may have been on the European continent for only some 1,200 to 1,500 years prior to that, having stowed away on traders' ships and caravans from the Middle East and the Far East.
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