Public Enemy

June 4, 2003

As a graduate student, Baylor biology chair W. Keith Hartberg planned to study the reproductive ecology of salamanders. Then, he became fascinated with nature's most effective, if accidental, bioterrorist: the mosquito.
By semester's end, he faced the difficult task of telling his graduate adviser that his loyalties had changed. The salamander man was philosophical. "He said, 'Well, Hartberg, you're making a good choice. They'll pay you to work on mosquitoes and they won't pay you to work on salamanders.'"
Those words have proved prophetic. Governmental agencies spend millions of dollars each year on mosquito surveillance, identification and control, and with good reason. Mosquitoes are the world's No. 1 vector, or illness carrier, accounting for more than a million deaths worldwide each year, according to the American Mosquito Control Association.
Mosquitoes have changed the course of history. Yellow fever, a virus carried by the Aedes aegypti species, killed 90 percent of Napoleon's expedition and figured in the decision to sell the Louisiana Territory. Later, it kept the French from completing the Panama Canal. Although yellow fever still is a threat in Africa and South America, it has been eradicated in the United States -- largely due to lifestyle changes that include the use of window screens.

Crucial public health battle

Most people go to great lengths to avoid mosquitoes, but Dr. Hartberg and associate professor of biology and director of graduate studies Richard Duhrkopf, volunteered to spend their lives on the front line of one of the world's most crucial public health battles.
Dr. Duhrkopf says war is a good analogy for their work. "You have to know your enemy, just like in war. You have to have good intelligence, you have to know where your enemy is, you have to know how strong your enemy is, you have to know how much of a threat it is," he says. And as in war, one must anticipate the next battle, in this case the dengue fever poised to move north across the Texas-Mexico border.
For decades, the United States has faced sporadic outbreaks of several mosquito-borne viruses that cause brain inflammation such as St. Louis encephalitis, Eastern equine encephalitis and Western equine encephalitis. Yet, it took another encephalitic illness -- the U.S. West Nile virus (WNV) outbreak that began in New York in 1999 -- to call the attention of average citizens to the pests, Dr. Hartberg says. 
Most mosquitoes are picky eaters -- only a small percentage of the approximately 2,700 varieties in the world ever bite humans. The rest prefer specific birds, amphibians or other mammals. In fact, for most encephalitic diseases, humans are considered "dead-end hosts" because they are so poor at amplifying the disease-causing agents in their blood. Because of that, WNV needs an intermediate host -- in this case, birds. This virus is transmitted from infected mosquito to bird to mosquito to human by female Culex quinquefasciatius, Culex restuans and Culex salinarius mosquitoes, which must have a blood meal to nourish their eggs. Intermediate hosts are helpful for researchers because, along with a program to capture and test mosquitoes, they can be used as sentinels to determine whether local mosquito populations carry disease.

Misperceptions abound

Drs. Hartberg and Duhrkopf agree that while there are many misperceptions about mosquitoes, foremost among them is that all mosquitoes carry disease to humans. The majority of mosquitoes are just a nuisance, they say. Even within a disease-carrying species, only a small percentage of individual mosquitoes actually are carrying a disease at any given time. Spraying indiscriminately, as once was the norm, harms mosquito predators such as dragonflies and certain minnows that voraciously feast on tiny, spaghetti-like mosquito larvae known as "wigglers." It also builds the mosquitoes' immunity to the pesticide. "If you eradicate anything, you open up some niche that something worse may come in to take," Dr. Hartberg says. 
Another misperception is that last year's outbreaks of WNV will predict the location this year. "We don't know (what this year holds), but I can tell you that people are very, very concerned," Dr. Duhrkopf said upon returning from last spring's annual meeting of the American Mosquito Control Association, for which he serves as South Central regional director. "We had a really bad year last year with various forms of encephalitis, and generally it was a low year for mosquitoes, according to the numbers found in the surveillance traps."
So much depends upon the weather, he says. For instance, St. Tammany Parish around Baton Rouge, La., was one of the hardest-hit parts of the country last summer, despite having one of the nation's best mosquito-control programs, because it experienced a "perfect storm" mosquito-breeding weather pattern. "They had a couple of inches of rain a week and warm temperatures," Dr. Duhrkopf says.
No one knows why the most virulent West Nile outbreaks last year were in the Midwest. According to the Centers for Disease Control and Prevention Web site, the states reporting the most cases and deaths were Illinois (879 cases, 60 deaths), Michigan (614/51) and Ohio (441/31). Those states were followed by Louisiana (330/24), Indiana (291/11) and Texas (202/12). Although most people have mild flu-like symptoms, people age 50 and older and those with a compromised immune system are most at risk of encephalitis, which occurs in an estimated 1 percent of WNV cases and can be fatal.

Ongoing research

Work by entomologists such as Drs. Hartberg and Duhrkopf, both of whom have served as president of the Texas Mosquito Control Association, is solving many mosquito mysteries. Scientists at the U.S. Department of Agriculture's Research Service laboratory in Gainesville, Fla., recently isolated a virus that is lethal to mosquitoes that spread WNV. Although this is a promising development, commercial use of the virus as a potential mosquito-control pesticide is expected to be at least two years away, according to a Cox News Service story.
Nevertheless, today's basic research could contribute to tomorrow's best-defense insect control strategy. "Almost everything you do with mosquitoes has some value to it because, as a vector, any information that we get is important," Dr. Duhrkopf says.
Dr. Hartberg has traveled the world researching mosquitoes. Even before he completed his doctorate, the World Health Organization moved him, his wife, their 1-year-old daughter and his mother-in-law to Dar Es Salaam, Tanzania, to study mosquitoes. "We had cheetahs in the back yard, monkeys in the trees around the house," he recalls. "You could go out the front door, and 30 meters across the street there were mud huts. In a few yards, you could go from the Stone Age to the 20th century."
During his two years in Tanzania, he made an expedition to Mauritius, a tiny island in the Indian Ocean that is the only place on Earth where a mosquito known as Aedes mascarensis is found. At one time, it was thought to be a subspecies of the Aedes aegypti, the major vector of yellow fever and dengue fever. Dr. Hartberg, who also is a geneticist, disproved that hypothesis by showing that the two types are reproductively isolated. He now is researching mosquitoes' color preference.

Lab environment

Visitors who enter the Baylor researchers' lab are met by a continuous blast from an air pressure system that keeps errant mosquitoes from escaping. In addition, two outer chambers -- the first for computers, the second filled with lab benches -- further isolate the specimens. A third room, which looks like a meat freezer but feels tropically steamy, holds hundreds of thousands of mosquitoes in various life stages. Adults live in cardboard cylinders topped with ultra-fine netting, on which rest lumps of sugar. Blood meals from anesthetized laboratory mice are provided when the researchers need to breed the insects. Nearby shelves hold covered plastic tubs of water and larvae. Eggs and larvae, not adults, are used to establish lab colonies, because the immature insects do not feed on infected animals and so are disease-free.
Dr. Duhrkopf's newest research program is practically in Baylor's back yard. The U.S. Corps of Engineers will raise the level of Lake Waco seven feet, destroying some of its forestland. Federal law requires mitigation of the land loss to replace wildlife habitat, and the city opted for a wetlands area 10 miles west of Waco. Wetlands are mosquito habitat, and Dr. Duhrkopf will help determine what mosquitoes are present in the new wetlands and how the change in habitat affects their population. He goes out most afternoons to set traps and returns the next morning to collect the mosquitoes and bring them back to the lab. 
Of course, that requires placing himself in the line of fire. Although neither researcher can pinpoint ever having a mosquito-borne illness, Dr. Duhrkopf had an unusual experience as a postdoc in tropical medicine in Baltimore. "I just had this extraordinary headache, and I was paralyzed from the waist down," he recalls. "I had a very, very high fever, and I was unconscious for 24 hours." 
He recovered, and doctors never knew what afflicted him. Nothing in the lab in which he was working was considered virulent. Still, the medical community couldn't take any chances. 
"We are intentionally out where there are mosquitoes. When you put yourself in harm's way, sometimes you get harmed," he says with a shrug, adding that although he never considered his illness mosquito-related, the doctors were correct to be cautious.

Avoiding mosquitoes

There are many things people can do to avoid mosquito bites such as staying inside at dawn and dusk, when the Culex species is most likely to bite. Wear light-colored clothing, but know that mosquitoes can bite through thin cloth. Keep arms and legs covered and use insect repellents containing DEET (N,N-diethyl-meta-toluamide) or permithrins, which are absorbed and broken down by the skin, so they should be sprayed only on clothing, Dr. Duhrkopf says.
The most important thing is to eliminate the stagnant water where mosquitoes breed by emptying flower pot saucers, pet dishes and birdbaths at least every couple of days. Culex mosquitoes, the major vector for WNV, are known as a "dirty mosquito" with a goat-like appetite for domestic animals and even alligators. A little-known fact is that those mosquitoes lay their eggs in sewage treatment plants, backed-up septic systems and in storm sewers -- sources of potential infection that thread through every urban area, Dr. Hartberg says.
The reason public health officials stress keeping backyard containers dry is to deter other, more threatening mosquitoes that prefer clean water: the Aedes aegypti, the yellow fever mosquito, and the Aedes albopictus, nicknamed the Asian tiger mosquito, which is believed to have come to this country a few years ago in shipments of tires.
Those two species can carry dengue fever, which has been kept from moving north by several unusually hot, dry summers, the researchers say. "It's called break-bone fever because it is so painful. My mother-in-law had it when we were in Africa," Dr. Hartberg says. Only an estimated 1 percent of people exposed to WNV get even mild symptoms, compared to 80 percent to 90 percent of those infected with dengue fever who experience symptoms of the disease.
A first case of dengue is painful but mild. A second case can be fatal because there are four different strains of dengue fever, and they do not provide cross immunity. The World Health Organization reports evidence that a potentially fatal complication called dengue hemorrhagic fever seems more likely when people who have had one strain get a second one, Dr. Duhrkopf says.
According to the CDC Web site, "a global pandemic of dengue began in Southeast Asia after World War II and has intensified during the last 15 years. ... By 1975, it had become a leading cause of hospitalization and death among children in many countries in that region." 
The North American Free Trade Agreement has increased traffic across the border, making it easier for mosquitoes infected with dengue to cross over, too, Dr. Hartberg says, adding that international travel and shipping are efficient ways to spread disease. The WNV is believed to have come to the United States from Africa, most likely as a result of importation of birds by a zoo in the New York area. The strain found in the United States is one of the most virulent, but is genetically identical to a strain in Africa. Still, dengue is worse, he says.
"If you don't have birds, you don't have West Nile," Dr. Hartberg says. "Dengue is spread from mosquito to person to mosquito to person. You don't have an early warning system like you have with West Nile." 
Ranking mosquito-borne illnesses is sometimes like deciding whether to be more worried about getting hit by a car or by a bus, the two men say. "West Nile is of greater public and probably practical concern at the moment," Dr. Hartberg says. "But in terms of looking at the level of mortality, if you want to talk about something that scares us in the field, it's dengue fever."