Nature's Assassins

Tracking Killers That Know No Borders

BY AMY ELLIS NUTT

BROWNSVILLE, Texas -- Her skin was blistering, her gums were bleeding, and her urine was the color of rust.

Delirious with fever, lying in isolation at the Brownsville hospital, Norma Santoy told her husband she felt possessed by a "mosquito spirit" that had stolen her brain.

A week earlier, a rash and intense back pain had brought the 33-year-old mother of two to her childhood doctor over the border in Matamoros, Mexico. He told her it probably was dengue fever, a mosquito-borne virus common to tropical and subtropical areas of the world. Matamoros, only a few hundred yards from Brownsville across the Rio Grande, had experienced annual dengue outbreaks for the past decade.

There is no cure, no treatment, he said; they would hope for a mild case.

Within days, however, Santoy's condition worsened and she was hospitalized back in Texas, where she told an American physician about the diagnosis in Mexico.

"There is no dengue in the U.S.," the doctor responded.

Santoy, who had not traveled outside Texas in the weeks before becoming ill, wanted to believe him. But each hour the sound of the mosquito spirit grew louder, and her body weaker.

Dengue -- called dengue hemorrhagic fever in its most severe form -- originated as a disease of the rain forests, of rural outposts and undeveloped countries. For years it was referenced by the location of its most recent outbreak: Singapore hemorrhagic fever, Thai hemorrhagic fever, Philippine hemorrhagic fever. There had never been a Texas hemorrhagic fever -- until now.

After weeks of pain and extreme fatigue, Santoy recovered. The warning, however, had been delivered: Dengue was in the United States.

The dengue virus is one of hundreds with the potential to steal into the country and create a crisis of public health. Called zoonoses, the viruses pass between animals and humans. For most, science has no answer -- no vaccine, no treatment, no cure. And the number of zoonotic outbreaks has risen steadily during the past two decades, even as researchers admit they cannot predict when or where the next will occur.

West Nile virus, transmitted from birds to humans by mosquitoes, is the zoonosis that has won the most attention in this country. But of the 20,000 cases reported since the disease emerged in 1999, fewer than 4 percent have ended in death.

Without treatment, dengue hemorrhagic fever -- called "hemorrhagic" for the bleeding from body openings and internal organs -- will kill 40 percent to 50 percent of those infected.

The virus that attacked Santoy may have been borne by a mosquito that flew less than half a mile from Matamoros to Brownsville. In Mexico, 40,000 residents have been infected since 2001. But it also could have come from a native-born mosquito that acquired the virus by biting someone already infected.

Never has the divide between animal and man been so porous -- or the threat to public health more urgent. Global travel, overpopulation, urbanization and climate change are speeding the spread of zoonotic diseases with names so exotic and unfamiliar they seem to belong to the pages of National Geographic.

"In the history of medicine, this has never happened before. We're in the midst of a resurgence of old diseases and new diseases on a global scale," said Paul Epstein, associate director of the Center for Health and the Global Environment at Harvard Medical School.

It does not take much today for a disease to emerge from the jungle. The invisible disease-causing agent -- the pathogen -- can be carried out by a human, a live animal or animal product, or by an intermediary -- a tick, a mosquito. When that happens, all borders are vulnerable.

More than half a billion people travel internationally each year, and the 36 hours it takes to circle the world is far less than the incubation period for most infectious diseases. Suspicion that a traveler might be infected often is of little consequence -- of the 317 ports of entry into the United States, only 18 have quarantine stations.

And while live animals frequently harbor diseases benign to them but highly dangerous to humans, inspections of cargo are declining even as animal imports, legal and illegal, increase, according to a 2005 study by Congress' Government Accountability Office. It is estimated that tens of thousands of exotic animals are smuggled into the United States each year, part of a $4.2 billion global black market.

No single government agency is responsible for monitoring both human and animal diseases. None conducts general surveillance of zoonoses, although several track individual diseases, such as West Nile or avian influenza. And while hundreds of state and local public health boards are the first lines of defense in any disease crisis, there is no standard plan for action.

Tuberculosis, measles and smallpox -- now passed from person to person -- are all zoonotic diseases that emerged thousands of years ago following the domestication of wild cattle. A recent zoonosis to emerge -- in nonhuman primates such as great apes -- and then jump the species barrier altogether is the human immunodeficiency virus, or HIV.

Like HIV, nearly half the world's 1,415 infectious diseases are emerging for the first time or re-emerging in a new place, or with greater frequency or more extreme symptoms. Three out of every four of these diseases (including 11 of the last 12 discovered) come from animals.

"Twenty years ago, no one had any idea that West Nile could be a global pathogen," said Florida entomologist and mosquito expert Phil Lounibos. "Well, there are a lot more out there, and hardly anyone is studying them."

Other zoonoses have made their way to the United States:

 -- Monkey pox. Two years ago the disease caused 80 people in seven states to become ill, many of them hospitalized with fever, skin lesions, headache, back pain and swollen lymph nodes. The first U.S. outbreak occurred when contaminated African rodents, imported into the United States, were housed next to prairie dogs. The virus passed from the prairie dogs to humans after the animals were sold as pets.

 -- Sin Nombre virus. In the first six months of this year, this strain of the Asian hantavirus sickened 22 people in eight states. Ten have died. Sin Nombre causes severe pulmonary illness, the result of inhaling the dust from the dried feces of deer mice, which are found virtually everywhere in North America. It is thought the strain of hantavirus that gave rise to Sin Nombre was carried by infected mice aboard a ship.

It is just a matter of time, scientists say, until other, even more virulent, zoonoses arrive. They include:

 -- Nipah virus. Discovered in Malaysia in 1999, it killed 105 people, nearly half those infected. Farm workers became ill after exposure to sick pigs, which had picked up the virus from fruit scraps dropped by infected bats.

While the initial outbreak caused encephalitis, subsequent outbreaks in Malaysia have given rise to respiratory infections, causing scientists to consider the possibility not only of mutation, but of human-to-human transmission -- a worst-case scenario for any infectious disease.

 -- Lassa fever. Endemic in several areas of Africa, Lassa was discovered in 1969 when it killed two American missionaries in Nigeria. In some outbreaks, the mortality rate reached 50 percent. In 2004 a 38-year-old New Jersey resident, Joseph Ghoson, died of Lassa fever after returning from Sierra Leone. It was the fifth time the virus had been imported into the United States since 1969.

 -- Rift Valley fever. Another mosquito-borne virus that originated in Kenya, Rift made its first appearance outside Africa in 2000 when it killed 600 people in Saudi Arabia. Rift infects not only humans but domestic animals, including cattle, sheep, buffalo and goats, which act as reservoirs of the disease. Mosquitoes can pick up the virus from an animal, then infect a human. It is the zoonosis that many U.S. scientists fear the most.

"I don't think it's unreasonable that Rift will appear here," said Sonja Gerrard, an expert in hemorrhagic fevers at the University of Michigan's School of Public Health. "Hundreds of thousands can be infected at the same time. We're good hosts. The virus replicates fast and our immune system doesn't have time to get on top of it."

The result of such an "explosive outbreak," Gerrard said, would be grim: "We can't treat it. If you get the hemorrhagic or encephalitis forms, the chances are pretty good you'll die."

Prior to 1970 only nine countries had experienced dengue hemorrhagic fever epidemics. Twenty-five years later, some 40 countries had reported epidemics of the virus. By 2003, the severe strain was present in 24 countries in the Americas.

Major outbreaks of classic dengue used to occur decades apart. Today epidemics occur on average every two to three years. The disease is endemic in more than 100 tropical countries, where it kills some 30,000 people each year, according to the World Health Organization.

Increasingly, dengue infections are being reported in cities and towns -- urban environments previously thought not to be in jeopardy from mosquito-borne diseases. The insects breed best in small pools of standing water and can be in such disparate locations as piles of used tires and vases in cemeteries -- even in the finger holes of a discarded bowling ball.

This year the Brownsville area, including Matamoros across the Mexican border, has seen more than 1,000 cases of dengue fever. And the federal Centers for Disease Control and Prevention estimates another 1,500 people along Texas' Rio Grande Valley have been exposed.

"In other words, they have antibodies to the virus and you don't have dengue antibodies unless you've had the virus," said Richard Duhrkopf, a biologist at Baylor University. "We've never seen numbers like this before. If it does spread from the valley it can spread over the state. ... And that is not unlikely. It's only a matter of time before we see it in San Antonio and Corpus Christi."

According to U.S. Transportation Department statistics, nearly 3 million pedestrians and 22 million cars and trucks crossed between Brownsville and Matamoros in 2004. With more than 30,000 Mexicans infected by dengue since 2005, the opportunities for transmission across the border are considerable.

Still, U.S. doctors -- emergency room and primary care physicians, as well as infectious disease specialists -- are not familiar with the disease.

Zoonotic infections are tropical in origin and usually are not included in U.S. medical school textbooks. They have remained the purview of academicians because the threat of those diseases reaching the United States has been considered remote.

Which may explain why Norma Santoy nearly died last November.

After seeing the doctor in Mexico and before being hospitalized, Santoy visited a clinic in Brownsville, less than a mile from her home. She shivered inside her red jacket, its fur-trimmed hood pulled up over her head despite the day's 70-degree weather.

"I think you have a sinus infection," the doctor said after examining her.

Santoy told him about the Mexican physician's dengue diagnosis.

"To them everything is dengue," the doctor said.

Santoy received two injections -- an antibiotic and a steroid. "You'll be fine by dinner," the doctor told her.

Forty-eight hours later she was in the hospital.

Not until Norma Santoy's blood platelet count dropped from a norm of 400,000 to 22,000 did her doctors consider that she might have dengue. And only after massive transfusions of platelets and weeks of rest at her mother's home did Santoy feel strong enough to return to her husband and children. It took another eight months before she felt fully recovered.