CHAPTER 16 Arthropod-Borne and Other Zoonotic Viruses The zoonotic viruses comprise more than 400 agents, one or more of which occur in most parts of the world. Members of the group have their ultimate reservoirs in insects or lower vertebrates. They are from diverse taxonomic families of RNA viruses that primarily include the togaviruses, flaviviruses, bunyaviruses, reoviruses, arenaviruses, and filoviruses. The zoonotic viruses discussed here are divided into two groups. The arboviruses are transmitted to humans by infected bloodsucking insects such as mosquitoes, ticks, and Phlebotomus flies (sandflies). The other zoonotic RNA viruses are generally believed to be transmitted by inhalation of infected animal excretions, by the conjunctival route, or occasionally by direct contact with infected animals (non-arthropod zoonotic viruses). Arboviruses I. VIROLOGY 1. Generally named after place of first isolation A. TOGAVIRUSES 1. Enveloped RNA viruses contain glycoproteins that are hemagglutinin and lipoproteins 2. RNA genome is encapsidated in an icosahedral capsid that measures approximately 40 nm in size. 3. Lipid bilayer envelope contains viral encoded glycoproteins, E1 and E2 4. Replication occurs both in cells of infected arthropods and vertebrate hosts 5. Replicates by synthesizing RNA-dependent RNA polymerase and other nonstructural and structural proteins 6. Virions mature by budding from cellular membranes 7. Alphavirus genus includes most arthropod-borne viruses B. FLAVIVIRUSES 1. 2. 3. 4. 5. Positive sense single-stranded RNA, icosahedral capsid, enveloped viruses Capsid (C) protein and the matrix (M) proteins cover the core Lipid bilayer envelope membrane contains envelope (E) protein Flavivirus genus comprises of most arboviruses Whole positive sense RNA genome is translated into a polyprotein which is cleaved into individual mature proteins 6. Virus assembly takes place in the cytoplasm and the envelope is acquired by budding into intracellular vesicles and released upon cell lysis 7. Cause a lytic response in vertebrate hosts and a persistent infection in invertebrate hosts C. BUNYAVIRUSES 1. Spherical, enveloped RNA viruses with L, M and S nucleocapsids and mature by budding of cytoplasmic membranes 2. M segment encodes structural proteins and L and S segments encode polymerase and nonstructural proteins D. REOVIRUSES 1. The most important North American arbovirus of this family, which is a member of the genus Coltivirus, causes Colorado tick fever. 2. Unenveloped RNA viruses are prominent in North America E. ARENAVIRUSES 1. Pleomorphic, bi-segmented, enveloped RNA viruses 2. The virion contains host cell ribosomes in their interior which confer a granular appearance 3. Most significant infections in humans are the hemorrhagic fevers, including Lassa fever 4. Replicate in the cytoplasm of infected host’s cell using the strategy of negative sense RNA genomes 5. Like Bunyaviruses, arenaviruses also lack a matrix (M) protein, a characteristic of enveloped viruses 6. Mature by budding from the host cell plasma membrane 7. Arenaviruses cause persistent infection in rodents and are also transmitted to humans from the excreta of infected rodents. F. FILOVIRUSES 1. Filoviruses, Marburg and Ebola viruses, are the cause of Marburg and Ebola fevers, two highly fatal hemorrhagic fevers 2. Enveloped filamentous RNA viruses with filamentous and highly pleomorphic virions 3. The nucleocapsid binds to the RNA genome to form the nucleocapsid, which is enclosed in a matrix protein and buds from plasma membrane containing viral glycoproteins G. HENIPAVIRUSES 1. Two zoonotic paramyxoviruses involving humans and animals appeared in Australia and Southeast Asia 2. Hendra and Nipah viruses, now classified in the Henipavirus genus of Paramyxoviridae II. ARBOVIRUS DISEASE A. EPIDEMIOLOGY 1. 2. 3. 4. 5. Reservoirs are in nonhuman vertebrates Sometimes maintained by vertical transmission in vector Multiplication in vector is required Sustained viremia required for vertebrate host to be significant reservoir Season-to-season survival has multiple mechanisms a. Cycles of arbovirus transmission i. Urban 1. Urban cycle is favored by the presence of relatively large numbers of humans living in close proximity to arthropod (usually mosquito) species capable of virus transmission 2. Examples include urban dengue, urban yellow fever, and occasional urban outbreaks of St. Louis encephalitis. ii. Sylvatic 1. In the sylvatic cycle a single nonhuman vertebrate reservoir may be involved 2. Examples include western equine encephalitis, eastern equine encephalitis, and California viruses 3. Sylvatic cycle occurs with many viruses 4. Humans are tangential hosts through accidental intrusion iii. Arthropod-Sustained 1. Arthropod sustained by tick transovarial transmission 2. Weather, swamps, and ponds alter conditions 3. Mosquito increases create risk for blind-end human infection B. PATHOGENESIS 1. 2. 3. 4. 5. CNS, visceral, and hemorrhagic fever are major syndromes After bite, viremia and viral tissue tropism define disease In CNS, aseptic meningitis and encephalitis follow cell injury Liver often the target, with necrosis of hepatocytes Dengue hemorrhagic fevers involve perivascular and endothelial injury 6. 7. 8. 9. May progress to shock Lymphoid hyperplasia seen Virus–antibody complexes may trigger complement activation Cross reacting antibodies may enhance infection C. IMMUNITY 1. Neutralizing antibodies protective and last for years 2. Immunity is serotype specific III. ARBOVIRUS DISEASE: SPECIFIC ARBOVIRUSES A. Western Equine Encephalitis 1. The agent that causes western equine encephalitis is prevalent in the central valley of California, eastern Washington 2. Human and equine illness commonly manifested as encephalitis 3. Encephalitis is more likely in young infants B. Eastern Equine Encephalitis 1. New England to South America 2. Vector feeds on horses and birds C. St. Louis Encephalitis 1. Distribution and disease is similar to western equine encephalitis 2. More disease seen in adults D. West Nile Virus 1. 2. 3. 4. First appeared in United States in 1999 Most important arbovirus in North America Dead crows often herald spread of virus in nature Muscle weakness and flaccid paralysis can occur E. California Virus 1. Virus and vector common in suburban and rural areas 2. Chipmunk is reservoir host 3. Highest attack rate in those aged 5 to 18 years F. Yellow Fever 1. 2. 3. 4. Characterized by abrupt onset of fever, chills, headache, and hemorrhage It may progress to severe vomiting, jaundice, and shock Widespread in tropical areas Mosquito vector (Aedes aegypti) persists in United States G. Dengue 1. Vector same as yellow fever 2. Severe pain in back, muscles, and joints H. Japanese B Encephalitis 1. Flavivirus prevalent on the eastern coast of Asia, on its offshore islands (Japan, Taiwan, and Indonesia), and in India 2. Transmission is similar to St. Louis and western equine encephalitis I. Chikungunya Fever 1. Alphavirus transmitted by mosquitoes, particularly in urban areas of Asia, Africa and limited areas of Southern Europe 2. Illness is characterized by an abrupt onset of fever, accompanied by excruciating myalgia and polyarthritis J. Powassan Virus 1. Only known tick-borne Flavivirus species of North America 2. Tick-borne but uncertain human importance K. Colorado Tick Fever 1. Found in ticks (Dermacentor andersoni) which are also vectors for Rickettsia rickettsii. 2. Headache, muscle pains, fever, and occasionally encephalitis 3. Tick-borne throughout western United States 4. Most infections asymptomatic IV. ARBOVIRUS DISEASE: CLINICAL ASPECTS A. DIAGNOSIS 1. Blood is best culture source but must be early in disease 2. Multiple serologic methods used B. TREATMENT AND PREVENTION 1. Treatment is only supportive 2. Protection from bites and vector control are primary prevention 3. Yellow fever, tick-borne and Japanese B encephalitis vaccines are available OTHER RNA VIRUSES OF ZOONOTIC ORIGIN I. ARENAVIRUSES 1. Sustained in small rodent reservoirs 2. Vertical transmission in rodents 3. Spread to humans by aerosols and close contact A. Arenaviruses Associated with Hemorrhagic Fevers 1. Viruses in this group include the South American hemorrhagic fever agents, Machupo, and Lassa virus, the cause of Lassa fever in West Africa. 2. Person-to-person spread occurs by contact with body fluids 3. All cause fever, shock, and hemorrhage 4. Hepatitis and myocarditis also occur with Lassa fever 5. High mortality and risk of further transmission 6. Suggested by clinical findings and travel history 7. Diagnosis only in reference centers 8. Viremia may be prolonged B. Lymphocytic Choriomeningitis Virus 1. Most human illnesses traced to contact with rodent breeding colonies in research or pet supply centers and to pet hamsters in the home 2. Fever, headache, and myalgia although meningitis or meningoencephalitis also occurs 3. Transplacental infection in humans 4. Virus may be isolated in the early stages of disease by cell 5. Meningitis may persist for months II. FILOVIRUSES: MARBURG AND EBOLA VIRUSES 1. 2. 3. 4. 5. Initial cases transmitted from monkeys Viruses differ antigenically Reservoir may be small mammals Mortality high in symptomatic infection Diagnosis and precautions similar to arenavirus hemorrhagic fevers III. HANTAVIRUSES A. Hantavirus Hemorrhagic Fever 1. Causes of hemorrhagic fever during Korean War 2. Detected in lungs of wild rodents 3. Other viruses similar to KHF throughout northern Eurasia B. Other Hantavirus Infections 1. 2. 3. 4. Hantavirus among rodents in United States Southwestern US outbreak related to deer mice Humans infected by inhalation of aerosolized excreta No human-to-human transmission IV. ORTHOMYXOVIRUSES 1. Avian and animal influenza viruses may infect humans 2. Avian influenza viruses including H5N1, H7N2, H7N3, H7N7 and H9N2 have been documented to cause infections in humans V. HENIPAVIRUSES 1. Hendra virus human cases were characterized by pneumonia and encephalitis 2. Reservoir of henipaviruses is fruit bats which spread to humans and animals via aerosols VI. VESICULAR STOMATITIS VIRUS 1. Causes outbreaks of disease in cattle, pigs, and horses can be transmitted between animals by arthropods 2. Human infection is acquired by contact with infected animals consists of a self-limited febrile illness and occasional herpes-like eruptions over the lips and mucosa