When we are awakened at 2:00 in the morning by the sound of 'high C,' we'll from now on wonder whether this buzzing mosquito is loaded," muses Andrew Spielman, professor of tropical public health in the Department of Immunology and Infectious Diseases. "We'll from now on wonder, Is this one the end of my life?" This possible future that Spielman describes is one in which West Nile virus--a sometimes-lethal, mosquito-borne pathogen--has become a permanent fixture in Northern America. With researchers anticipating new viral outbreaks across this region, his vision may very well become reality--a reality that Spielman and his colleagues are hoping to prevent.

Never before diagnosed in the Western Hemisphere, West Nile encephalitis made its debut in New York City in the summer of 1999, killing seven residents, afflicting more than 60, and infecting at least 1,900. Although researchers hoped that the causal virus would not survive the winter, this past March they discovered that some of New York City's hibernating mosquitoes--Culex pipiens, which are most likely responsible for spreading the disease--still harbored the infection. Only days later Westchester County officials announced that a dead red- tailed hawk tested positive for West Nile virus. With more and more infected dead birds turning up in New Jersey, Connecticut, and Massachusetts this summer, there are now concerns that infected migratory birds will introduce the disease into outlying regions across the United States. "Why not Boston, Chicago, or Washington, D.C.?" asks Spielman. "If you've seen one city, you've seen them all in terms of West Nile virus requirements: the same mosquitoes, the same birds, the same humans."

West Nile virus was first isolated in the Province of Uganda in 1937 and is now commonly found across Africa, Asia, the Middle East, and increasingly in parts of Europe. Mosquitoes are the vectors, or carriers, of the virus and acquire it when they feed on infected birds, which act as the pathogen's reservoir, a hospitable place where it can safely mature and multiply. After an incubation period of ten days to two weeks, infected mosquitoes can transmit the virus to humans and animals. In humans, encephalitic symptoms include head and body aches, swollen lymph glands, high fever, and sometimes a rash. The disease can be fatal, particularly for the elderly, children, and those with compromised immune systems. Although it is not known exactly how or when the virus was introduced into Northern America, an infected traveler, a mosquito that endured an international flight, or imported birds may have played a role.

The concern at present, however, is not how it reached the U.S. but how the virus can be contained now that it has. Eradication of mosquitoes is not an effective option, being costly and environmentally intrusive, and eradication of the virus is a virtual impossibility; but one method of curtailing the spread of the virus may be to target its reservoir. Determining the reservoir of the virus is a future area of research for Spielman. In April his lab was awarded a $875,000 grant from the National Institutes of Health to support a five-year study of West Nile encephalitis and Eastern equine encephalitis. The latter is another arbovirus, which is indigenous to Massachusetts, thus constituting a major local public health concern. In addition to Spielman, the research team includes Co-Principal Investigator Richard Pollack; one post-doctoral student, Tony Kiszewski; and two predoctoral students, Chris Mores and Jennifer Wegbreit.

Although West Nile encephalitis and Eastern equine encephalitis differ epidemiologically, in terms of human infection they have similar modes of transmission--both involve birds and mosquitoes. Therefore defining the characteristics of their reservoir will be beneficial for understanding both encephalitides. One objective of the team's research is to determine whether the transmission cycle is more efficient in the birds' roost sites than elsewhere. Certain birds, such as robins, starlings, blackbirds, and crows, have roost fidelity, meaning they return to the same site night after night, which may impact how effectively the virus is passed on. Another area of interest is the reservoir's tolerance. Some birds appear to withstand viral infection quite well and congregate in large populations where mosquitoes can feed and the virus can multiply; other bird species, however, may not tolerate the virus at all and die as a result of infection. Determining the intensity of the infection in various avian species and the resultant effect on the birds, the mosquitoes, and the virus are very important in understanding the force of viral transmission and the efficacy of the reservoir. Ultimately, this information will enable researchers to better design ways to impede the pathogen's performance.

"Knowledge of this kind is power," declares Spielman. "We can focus our efforts, conserve the environment, and develop unique interventions"--interventions such as applying residual insecticides to the roost or disrupting certain roosts at specific times. For example, if a roost site consisting of only 20 trees were isolated, that discreet area could be sprayed with pesticide. Another creative means of prevention could be to use systemic insecticidal baits in bird feeders.

As evidenced by Spielman's recent NIH grant, the outbreak of West Nile virus has precipitated an outpouring of funds, which has justified an effort to rebuild arbovirus surveillance and research programs. "The outbreak of West Nile virus has really helped younger researchers," says Gregory Ebel, who graduated from the School in June to assume a research scientist position with the New York Department of Health. "There are jobs now." Although government funding expanded the testing of birds and mosquitoes over the summer, Ebel hopes that the additional resources and support will soon exist for exploring other arbovirus venues. "For years people have been talking about this kind of outbreak," remarks Ebel. "Given the way that commerce works, given that there are hundreds of transatlantic flights a day, it really wasn't a question of if it was going to happen, but when. This is the kind of problem that we can now confidently say is going to be recurring with some regularity." Therefore, it's still possible that West Nile virus might change the quality of life in Northern America. But if Spielman and his colleagues have their way, someday perhaps the mosquito's buzz will presage only a sleepless night rather than an ominous health threat.

by Chelsea Merz