Dengue, a major public health problem throughout subtropical and tropical regions, is an acute infectious disease characterized by biphasic fever, headache, pain in various parts of the body, prostration, rash, lymphadenopathy, and leukopenia. In more severe or complicated dengue, patients present with a severe febrile illness characterized by abnormalities of hemostasis and increased vascular permeability, which in some instances results in a hypovolemic shock. Four distinct serotypes of the dengue virus (dengue-1, dengue-2, dengue-3, and dengue-4) exist, with numerous virus strains found worldwide. Molecular cloning methods have led to a greater understanding of the structure of the RNA genome and definition of virus-specific structural and nonstructural proteins. Progress towards producing safe, effective dengue virus vaccines, a goal for over 45 years, has been made. Images

The dengue viruses.

Over the last four decades, a number of arthropod-borne infections have been recognized for the first time. Some have become of considerable public health importance, such as dengue hemorrhagic fever (DHF), and others are spreading geographically and their incidence is increasing. There has been an important recrudescence of several long-known vector-borne diseases. Malaria, leishmaniasis, dengue, and plague have resurged in numerous foci, in some cases where they were thought to be under effective control. In most instances, the appearance of new diseases and syndromes and the resurgence of old can be associated with ecological changes that have favored increased vector densities. Dam construction, irrigation and other development projects, urbanization, and deforestation have all resulted in changes in vector population densities that appear to have enabled the emergence of new diseases and the resurgence of old diseases. Greatly increased human travel has spread infectious agents, introducing them into areas in which they had been hitherto absent. It is essential to understand the factors that caused increased vector densities and hence the transmission of disease to prevent the emergence and resurgence of more diseases, as well as to serve as a basis for effective control.

Emerging and resurging vector-borne diseases

Of more than 500 arboviruses recognized worldwide, 5 were first isolated in Canada and 58 were first isolated in the United States. Six of these viruses are human pathogens: western equine encephalitis (WEE) and eastern equine encephalitis (EEE) viruses (family Togaviridae, genus Alphavirus), St. Louis encephalitis (SLE) and Powassan (POW) viruses (Flaviviridae, Flavivirus), LaCrosse (LAC) virus (Bunyaviridae, Bunyavirus), and Colorado tick fever (CTF) virus (Reoviridae, Coltivirus). Their scientific histories, geographic distributions, virology, epidemiology, vectors, vertebrate hosts, transmission, pathogenesis, clinical and differential diagnoses, control, treatment, and laboratory diagnosis are reviewed. In addition, mention is made of the Venezuelan equine encephalitis (VEE) complex viruses (family Togaviridae, genus Alphavirus), which periodically cause human and equine disease in North America. WEE, EEE, and SLE viruses are transmitted by mosquitoes between birds; POW and CTF viruses, between wild mammals by ticks; LAC virus, between small mammals by mosquitoes; and VEE viruses, between small or large mammals by mosquitoes. Human infections are tangential to the natural cycle. Such infections range from rare to focal but are relatively frequent where they occur. Epidemics of WEE, EEE, VEE, and SLE viruses have been recorded at periodic intervals, but prevalence of infections with LAC and CTF viruses typically are constant, related to the degree of exposure to infected vectors. Infections with POW virus appear to be rare. Adequate diagnostic tools are available, but treatment is mainly supportive, and greater efforts at educating the public and the medical community are suggested if infections are to be prevented.

https://cmr.asm.org/content/cmr/7/1/89.full.pdf

Medically important arboviruses of the United States and Canada.

Scrapie in mice. Agent-strain differences in the distribution and intensity of grey matter vacuolation.

The encephalitides caused by Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are important natural diseases of horses and humans and potential agents of biowarfare or bioterrorism. No licensed vaccines or specific therapies exist to prevent or treat human infections with VEEV, EEEV, or WEEV. Well-characterized animal models are needed to support the development of such medical countermeasures under the United States Food and Drug Administration's "Animal Rule." This review focuses on the pathological features and pathogenetic mechanisms of these alphaviral encephalitides in animal models, with an emphasis on aerosol infections. Infection of mice, nonhuman primates, and other species with VEEV, EEEV, and WEEV causes encephalitis and often death. There is great variability in the specific manifestations of disease in the different models, however. Many aspects of the disease in animal models and in humans remain to be characterized using modern methods. Especially needed is a better understanding of the fundamental mechanisms involved in 3 key phases of the pathogenesis of alphavirus encephalitis. These are the early extraneural phase, the process of neuroinvasion itself, and virus and host factors related to neurovirulence. A greater understanding of these aspects could provide avenues for the development of medical countermeasures and better establish suitable animal models of alphavirus encephalitis for testing them under the Animal Rule.

https://journals.sagepub.com/doi/pdf/10.1177/0300985810372508

N. Nathanson

Papers

Eastern equine encephalitis. Distribution of central nervous system lesions in man and Rhesus monkey.

Pathogenesis of type 1 dengue virus infection in suckling, weaning and adult mice. II. Immunofluorescent and histological studies.