Vector-Borne Disease Ecology and Epidemiology

Paul R. Grimstad     Associate Professor Ph.D. University of Wisconsin-Madison Postdoctoral, University of Wisconsin-Madison, University of Notre Dame

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Some of the world's most severe infectious diseases, such as yellow fever, dengue hemorrhagic fever and a number of encephalitides, result from arthropod-borne virus (arbovirus) infection. Most arboviruses are mosquito-transmitted in nature, often involving complex vector- virus-host relationships. The focus of work in my laboratory has been the epidemiology and ecology of mosquito-borne encephalitis diseases, especially those found in the midwesternUnited States. Among these viruses are Eastern equine encephalitis (EEE), St. Louis encephalitis (SLE) and several members of the family Bunyaviridae, especially La Crosse (LAC), Jamestown Canyon (JC) and Cache Valley (CV) viruses. Work on LAC virus encephalitis epidemiology and ecology and the biology of its primary vector, Ochlerotatus triseriatus, has been conducted by my students, and those of the late Dr. George B. Craig, Jr., at Notre Dame since 1974. One of the first reports of geographic variation in susceptibility to an arbovirus in mosquitoes came from this early work. Following a major equine epizootic of EEE in southwestern Michigan in 1980, attention was focused also on this often fatal disease of equines and humans. Basic studies have included evaluation of vector status of suspect mosquito species, local field biology of the primary enzootic vector, Culiseta melanura, and surveillance for disease among Indiana and Michigan equine populations. One of the largest serologic surveys of a United States' human population for arboviral disease was conducted by my group. In that survey, more than 10,200 residents, representing every county in the State of Indiana, were serologically screened for evidence of past infection with LAC, SLE, EEE and Western equine encephalitis viruses.

Our group was the first to report severe human central nervous system disease caused by JC, a bunyavirus distributed over most of temperate North America. This virus is now recognized as the cause of numerous clinical infections that can result in severe disease and even death. The natural cycle is quite complex involving white-tailed deer as the primary vertebrate host and a variety of aedine mosquito species, some of which harbor the virus over winter in their eggs and thus serve as the reservoir tissue for JC virus from which it "emerges" in the spring with the hatch of the mosquito eggs. The same is true of LAC virus. Work continues on the natural JC virus cycle and the role of anopheline mosquito species in an alternate late summer transmission cycle. Evidence of transplacental virus transmission in deer has important implications for human maternal infection that is being explored by our group.

A second bunyavirus, CV, has been identified recently as the agent of an "emerging" human disease. Human infection with CV virus can result in a fatal encephalitis to more mild forms of central nervous system disease. This virus has also been linked to neural tube defects in infants born to mothers infected in the first trimester of pregnancy. Our group has been investigating the epidemiology and ecology of CV virus since the early 1990's and have found evidence of widespread infection in the upper Midwestern human population as well infection as of domestic animals and wildlife. Laboratory studies have implicated several mosquito species, and especially Anopheles quadrimaculatus, as potential vectors. Laboratory studies using pregnant mice have shown that early trimester infection results in the loss of many mouse embryos. Of concern is the possibility that CV virus infection may be a cause of first trimester miscarriage in women. Indeed, recent serologic analysis by one of my students of human cord bloods taken at birth has suggested a possible link between infection and spontaneous miscarriage or abortion in local residents.

Graduate students in my laboratory work from the level of the viral and/or vector mosquito genome to the natural disease cycle in the field. Critical to our understanding of viral pathogenesis for vertebrate hosts is the vector biology of the invertebrate mosquito host. Thus, field studies supported by state-of-the-art molecular laboratory studies are essential for the complete characterization of these disease cycles. The overall goal of these multiple studies is to better understand the dynamics of arbovirus transmission in natural foci, aid public health workers in case detection and surveillance and to use this information to minimize human infection and potentially improve means of vector control.

	Biomodal period of onset for human clinical Jamestown Canyon virus diease vs. unimodal LaCross virus infections.
	Immune profile of a deer population from birth of fawns (and acquisition of maternal antibody) through a primary infection of the second spring of life.