AIRBORNE
Researchers have found a way to save Hantavirus victims from death, the first time any such treatment was tried in treating this disease.
Written by Suzanna Cisneros Martinez
The Navajo Indians believed that mice were the bearers of illness. Folklore says the Navajo elders predicted healthy young men would become sick and die throughout generations with an illness that came with the rains. In 1993 there were many unexplained deaths among young Native Americans in the Four Corners area of the United States. Researchers would eventually give the illness a name, Hantavirus Cardiopulmonary Syndrome (HCPS).
The 1993 outbreak came to the normally semi-arid region of the Four Corners, the only point in the United States where four states -- Utah, New Mexico, Colorado, and Arizona -- share a common border. The preceding year, El Nino's weather pattern brought uncommon rains to the area, causing the rodent populations to explode because of an extra supply of pinon nuts, the primary food of Peromyscus maniculatus, the deer mouse.
Researchers say the virus that causes Hantavirus Cardiopulmonary Syndrome is carried by rodents such as the deer mouse. The increase of infected rodents exposed the victims, many of which were of the Navajo Nation, to the rodent droppings. During the 1993 outbreak, 13 deaths were confirmed as due to Hantavirus Cardiopulmonary Syndrome (HCPS).
Hantavirus Cardiopulmonary Syndrome is used to describe one of two diseases caused by the many strains of Hantavirus. Since the 1993 outbreak, HCPS had been found in more than half of the states in the United States. Although it recently has been recognized in North America, Hantavirus was given its name back during the Korean War. Researchers had named a virus that caused the Hemorragic Fever after the Hantaan River in Korea, which ran through the region where the virus was most prevalent.
Texas Tech University Health Sciences Center's David Waagner, M.D., associate professor of pediatrics, says the biology of the Hantavirus is interesting in the sense that the disease is different in various parts of the world. "'Old World' Hantaviruses in Europe and Asia predominantly cause kidney disease and bleeding. It's a very different illness from Hantavirus Cardiopulmonary Syndrome, which is caused by the 'New World' Hantavirus," he says.
The patient may present with mild flu-like symptoms, headaches, mild aches and pains, vomiting, fatigue, fever and some diarrhea. Researchers know that the virus seldom targets the old or young. "We don't know why, but Hantavirus predominantly targets healthy individuals, not the very young or the elderly," says Waagner. "This is unusual because one would expect infants to have a higher risk of exposure. Likewise, one would expect the elderly to have more severe disease with underlying baseline pulmonary disease. Yet, this has not been observed."
Waagner notes that a 45 percent fatality rate exists in the reported cases of Hantavirus. Through May of 2000, a total of 250 Hantavirus Cardiopulmonary Syndrome cases were reported in the United States. Although most of the cases affected Navajo Indians in the 1993 outbreak, Hantavirus Cardiopulmonary Syndrome can strike anyone.
American Indians account for 20 percent of the cases, African-Americans for 2 percent, Asians for 1 percent, Hispanics for 10 percent and Anglos account for 77 percent of all cases. The Centers for Disease Control and Prevention states that 60 percent of reported cases have been male and 40 percent female.
Waagner is quick to point out that the virus is acquired through exposure to aerosolization, or the dispersal of fine particles in the air, of infected rodent droppings and not by person-to-person contact. "In North America, there haven't been any confirmed cases of person-to-person transmission," says Waagner. "However in South America, there have been a few cases which are suspicious for person-to-person transmission."
After someone is exposed to the infected rodents, symptoms appear one to five weeks later. The illness begins with symptoms that resemble the common cold. Patients with Hantavirus Cardiopulmonary Syndrome rapidly develop pneumonia, shortness of breath and respiratory distress.
"We have a basic supportive care that we use for an illness that's called ARDS, acute respiratory distress syndrome, and that is a syndrome that can be due to a wide variety of different causes, hantavirus being one of them," says Michael Romano, M.D., associate professor of pediatrics at Texas Tech Health Sciences Center.
"The virus causes the lungs to fail, and we use a mechanical ventilator and oxygen to support those patients," says Romano.
Texas Tech researchers may have found one way to save Hantavirus victims from death. In 1996, 16-year-old Heath Henderson made a trip with his family from Merkel, a small town in West Texas, to Lubbock to attend a Texas Tech Red Raider football game. After struggling with a fever and other pains and aches for a week, Heath's condition became worse, and he was taken to the emergency room at University Medical Center. Two days later, his condition deteriorated.
Doctors from the Texas Tech Medical Center worked to find the solution to his condition. Doctors Robert Rosenberg, Waagner and Romano determined that Henderson potentially had been exposed to Hantavirus. What they did next would be the first in the treatment of Hantavirus Cardiopulmonary Syndrome.
"Although Heath was the first pediatric patient in our region to present with Hantavirus, his symptoms, X-ray findings and laboratory results were very similar to those described in the initial outbreak in New Mexico," said Waagner.
"Patients with Hantavirus usually have very leaky blood vessels with fluid leaking out of the blood vessels into the lungs. Therefore, their blood is rather concentrated," says Waagner. "Hantavirus patients typically have blood hematocrits of 45 percent or greater. Heath was brought in at 51 to 52 percent, and that was our red flag."
"We were seeing a young, healthy adult who 16 hours after admission, complained of severe shortness of breath, with respiratory rates ranging from 40 to 50 breaths a minute," says Romano. "And if our suspicion of Hantavirus was correct, we knew Heath's conditions could easily become fatal."
After the traditional procedures had been tried, the doctors offered a new experimental study to treat Heath, which would save his life. "He qualified for using nitric oxide on the basis of an investigational protocol, that I had in place," said Rosenberg. "He therefore qualified because of the severity of the illness."
Rosenberg says that nitric oxide is not normally a treatment for Hantavirus. "Nitric oxide is a therapy for pulmonary hypertension, which can be a complication of Hantavirus Cardiopulmonary Syndrome, as well as many other disorders," explains Rosenberg. "Nitric oxide is used for example on newborns who experience pulmonary hypertension, and in patients with certain heart conditions."
Nitric oxide is a chemical that our bodies use to regulate blood pressure and is produced in a variety of cells. The relevant cells in this case are those that line blood vessels and produce nitric oxide. "When it's locally available, it causes the blood vessel muscles to relax, and the blood vessel gets larger making it easier for blood to get through the vessel, by lowering the resistance," says Rosenberg. "We delivered extra nitric oxide if you will, through the gas that the ventilator gives to the patients. We mix it with oxygen, give it through the lungs and it diffuses into the blood stream," adds Rosenberg. "And as it affects those blood vessels, it causes them to relax."
Rosenberg says the illness produces a situation where the blood vessels are not normal in the way they are regulating blood pressure in the lungs. The blood pressure tends to be too high. The nitric oxide interacts with the muscle cells and the blood vessels causing them to relax so that the blood pressure goes down.
"That's the theory as to why it should work. It makes it easier to get blood through the lungs and allows the heart to do less work to get the blood through the lungs," says Rosenberg. "We have other medications that cause blood vessels to relax, given intravenously. The problem is that those chemicals will indiscriminately cause blood vessels to relax all through the body, causing the patient's blood pressure to fall."
The small capillaries in the lungs adjust blood flow to various parts of the lung based on oxygen levels in the lung. As oxygen levels fall, blood flow is decreased. In this way, the lung does not "waste" blood going to areas where it can't pick up oxygen. The unique aspect of nitric oxide is that it is given by inhalation. In this way, only blood vessels to areas of the lung that are receiving oxygen open up. Nitric oxide has a very short half-life, so it breaks down before causing low blood pressure in the rest of the body.
The majority of patients who die with Hantavirus Cardiopulmonary Syndrome usually die within 48 hours of the onset of the severe respiratory illness. Waagner says most survivors of Hantavirus Cardiopulmonary Syndrome have little long-term aftereffects. If the patient survives, they usually return to normal activity with nor residual problems," says Waagner. Aggressive supportive care during this time is critical for a good outcome. In Heath's case, he went back to playing high school football."
Doctors Romano, Rosenberg and Waagner agree that Hantavirus is difficult to study. "Overall, it is a relatively rare disease, and most cases are clustered in a few geographic regions," says Romano.
"All of them are younger. That's why Dr. Rosenberg has done a recent collaboration with investigators in New Mexico, comparing our two cases with some of their cases and other cases from other parts of the country to combine data," says Romano.
Doctors warn individuals not to be frightened if they are exposed to mice. The chances of contracting Hantavirus are slim. "Almost all cases occur indoors in an area with rodents' droppings which are aerosolized typically by sweeping," says Waagner.
However, he says people can protect themselves from contracting Hantavirus. If a person is in an enclosed area, like a closet or an attic or storage shed, and sees evidence of mice droppings, then there are a couple of things one should do in order to clean up.
-- Wear a good filter mask, such as a painter's mask;
-- Use a bleach solution in a spray bottle to spray the area down, letting it set for a few hours before cleaning it out;
-- Avoid putting the particles in the air, for example by sweeping the area with a broom;
-- If you find live mice, dead mice or signs of mice, like droppings in the area, spray the area with a bleach solution, then using gloves, pick up the carcass with a plastic bag turning it inside out. Seal the bag and even double the bag before disposing of the carcass.
In Heath Henderson's case, doctors suspect that he was exposed by infected animals found in a closet used to store the family's hunting equipment. "A dead mouse and rodent droppings had been seen in the store room. Heath had a hunting vest that was somewhat dusty, and he shook it vigorously to air it out," says Waagner. "We postulate that might be the exposure, but we don't know for certain. The Texas Department of Health confirmed that rodents trapped in the immediate area tested positive for the virus."
The Texas Tech Health Sciences Center doctors add that research is being done to see if anything else can be done for patients with Hantavirus. "There is a protocol testing a potential drug for the Hantavirus Cardiopulmonary Syndrome," says Rosenberg. "But we are still looking at three or four years of testing to see if it works."
But for now patients like Henderson are happy to have a medical center like that at Texas Tech in the West Texas community. "At the time Heath received nitric oxide therapy, this was the only center within 250 to 350 miles that had this technology available," says Romano. "If he were not at Texas Tech, he would not have been able to access this therapy and perhaps may not have survived. This is a perfect example of an academic medical center like Texas Tech offers to the community."
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