Medical Microbiology & Immunology

Lecture 28 Arthropod-Borne and Other Zoonotic Viruses (Hemorrhagic Fever and Encephalitis Viruses)

1)  To know the family of viruses that cause encephalitis and hemorrhagic fever.

Arboviruses (transmitted by blood sucking insects such as mosquitoes, ticks, and sandflies (arthropod-borne): Togaviruses, Flaviviruses, Bunyaviruses, Reoviruses.

Other zoonotic RNA viruses are generally transmitted by infected animals (non-arthropod borne): Rhabdoviruses, Arenaviruses, Filoviruses

See question three.

2)  To describe the structure, replication and pathogenesis of zoonotic viruses.

Virus / Structure / Replication
Togaviruses Flaviviruses / ss(+)RNA, enveloped virions containing hemagglutinin and lipoproteins, 40-70 nm in external diameter / Can occur in the cells of infected arthropods invertebrate hosts
Bunyaviruses / Spherical, enveloped and ss(-)RNA seg. 90-100 nm in external diameter, Four genera; bunyavirus (-) RNA, phlebovirus (+/-) RNA, nairovirus and Hantavirus (-) RNA / Mature by budding with smooth surfaced vesicles or near Golgi region of infected cells.
Reoviruses / Spherical, uneveloped, ds RNA seg. About 80 nm in diameter.
Arenaviruses / Spherical, eveloped, and ssRNA two segments (ambisense +/-), 50-300 nm in diameter. / Maturation by budding from host cell, contain host ribosomes
Filioviruses / Envelope, ss(-)RNA, filamentous and highly pleomorphic, 80 nm in diameter and 300-1400 nm long / Similar to other (-) RNA viruses, rapid packaging of genome, maturation by budding from cell membrane.

Pathogenesis: three manifestations of arbovirus disease exist: 1) viral tropisms for human organs, if CNS, aseptic meningitis or encephalitis, 2) particular damage to major organ systems (e.g. liver and yellow fever), 3) hemorrhagic fever with damage to small blood vessels resulting in hemorrhage (e.g. intestines)

3)  To recognize the diseases caused by arboviruses.

Classification / Virus / 1° Vector / Disease
Togaviruses (Alphaviruses) / Western Equine Encephalitis / Mosquito / 1/1000 cause symptoms, mild, nonspecific febrile illness, aseptic meningitis, encephalitis (5% mortality).
1/25 cause severe illness in children <1-year, 60% of survivors have permanent neurologic impairment
Eastern Equine Encephalitis / Mosquito / Virus can cause severe encephalitis.
Highest attack rate in infants and children.
Flaviviruses / St. Louis Encephalitis / Mosquito / Major cause of arbovirus in the US, disease spectrum similar to Western equine, rate of infection, morbidity, and mortality among adults >40-years
Yellow Fever / Mosquito (urban) / Abrupt onset of fever, chills, headache, and hemorrhage. May progress to severe vomiting (sometimes with gastric hemorrhage), bradycardia, jaundice, and shock. Caribbean, Central and South America (maybe SE US)
Dengue / Mosquito (urban or sylvatic) / Fever, an erythematous rash, severe backing joint pain. Severe form in the Far East - shock, pleural effusion, and hemorrhage often followed by death. Worldwide distribution, all cases in the US imported.
Japanese B. Encephalitis / Mosquito / High proportion of human infections are subclinical: especially in children. Development of encephalitis is severe and often fatal. Transmission cycle is similar to St. Louis encephalitis and Western equine encephalitis viruses.
West Nile Fever Virus / Mosquito (tick)
2° birds / Incubation 1-6 days, typically mild, fever, headache, backache, generalized myalgia, generalized lymphadenopathy (common), pharyngitis in gastrointestinal symptoms (nausea, vomiting, abdominal pain).
May also result in aseptic meningitis or meningoencephalitis - death in a small number of patients (elderly).
Lab findings include leukopenia, CSF pleocytosis and elevated protein.
Linked to several deaths in the US (1999) and Arizona (2003)
Powassan Virus / Tick / Isolated in Ontario and fetal human case of encephalitis, not significantly related to humans.
Bunyaviruses / Bunyavirus (California) / Mosquito / Abrupt onset of encephalitis frequently with seizures (5-18 years of age), widely distributed in the Midwest CA, WI, MN, OH, IN.
Hantaviruses / Rodents / Hemorrhagic fever (Korean War), US outbreak related to deer mice (1993), fulminant respiratory disease with high mortality (67%), transmission by inhalation of infected rodent excreta (conjunctival route or direct contact with skin breaks). No human to human transmission in US. Ribavirin.
Reoviruses / Colorado Tick Fever / Tick / Incubation 3-6 days, sudden onset of headache, muscle pain, fever, and occasionally encephalitis, leukopenia (consistent feature). 1% symptomatic.

4)  To discuss the diagnosis, treatment and prevention of encephalitis and hemorrhagic fever.

Disease / Diagnosis / Treatment and prevention
Encephalitis
Hemorrhagic fever / Virus culture,
Viremia in blood,
Antibody test,
Nucleic Acid genome - PCR,
Detection of IgM - specific antibody within few days of infection / Treatment: supportive care
Prevention: primarily of avoidance of contact with potentially infected arthropods.
Vaccination: Western, Eastern equine encephalitis virus infection for horses, but can be used for laboratory personnel, yellow fever vaccine (live attenuated) single subcutaneous dose (lasts 16-19 years) 10-year boosters