Arboviruses

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Initial stages of alphaviruses

- All alphavirus infections are similar in initial stages: 1. replicate in skeletal muscle fibroblasts or Langerhans cells in the skin 2. virus is transported to lymph nodes draining the site of inoculation that may also become infected 3. Induce substantial plasma viremia in their hosts 4. Secondary invasion of the nervous system (encephalitides)

Chikungunya Virus

- Chikungunya ("that which bends up") - Chikungunya fever: debilitating illness characterized by fever, HA, fatigue, NV, muscle pain, rash, and joint pain -incubation period of 2-12 days (usually 3-7) - symptoms usually last a week, but muscle and joint pain can persist for WEEKS TO MONTHS -diagnosis: serum or CSF testing for virus specific IgM and neutralizing antibodies -no vaccine or antiviral

Arboviruses

- a group of viruses transmitted by arthropod vectors through insect bites (saliva) -ARthropod-BOrne Viruses -typically the arbovirus does not exert deleterious effect on vector -however, the virus may be extremely pathogenic to vertebrate hosts, especially tangential (abnormal) hosts

Zika diagnosis and treatment

-Diangosis is based on a person's travel history, symptoms, and laboratory test results -RT PCR for virus present in serum or urine if within the first 14 days after the symptom onset -RT PCR testing is recommended for symptomatic pregnant women who have traveled to areas with active Zika transmission within 2 weeks of the date of last possible exposure -ELISA testing for Zika specific antibodies if RT PCR is negative or if >14 days after the onset of symptoms -no vaccine or specific treatment is available; supportive therapy -prevention

Dengue Type 1 (1st infection)

-Infects monocytes -mild febrile illness -recovery with Ab to type I

Pathogenesis of arboviral encephalitis

-Initial viremia from lymphoid system -- little or no recognized disease during viremic phase -CNS invasion --- CNS disease from neuronal infection and damage associated with edema and inflammation -SYMPTOMS: fever, HA, photophobia, weakness, seizures, neck stiffness and limbs, slowness in movement, clumsiness, convulsions, coma

Clinical feature of DHF/DSS

-Occurs following secondary infection with a different serotype -initial fever, HA, joint pain, malaise, vomiting -mild to moderate liver damage (liver enzymes) -capillary leakage accompanied by thrombocytopenia -fluid loss into tissue spaces results in shock-- highest risk of mortality -hemorrhagic manifestations: purpura, ecchymoses, gingival, nasal & GI bleeding

Clinical features of dengue fever

-abrupt onset of febrile illness that lasts for 1-2 weeks: fever, HA, muscle and back pain, maculopapular rash (2-7 days), sever bone and joint pain ("break-bone fever"), petechial hemorrhages

Alphaviruses

-alphavirus genus includes MOST arthropod-borne viruses -enveloped single stranded positive sense RNA viruses -measure 70nm in external diameter - Glycoprotein spikes (80) contain trimers of E1-E2 heterodimers---- interact with erythrocyte membranes --- HEMAGGLUTINATION -replicate rapidly in most vertebrate cell lines with progeny virus release within 4-6 hours after infection - infection causes extensive CPE: cell rounding, shrinkage, cytoplasmic blebbing, cell death

Viral Encephalitis

-classified as acute inflammation in the brain -can be caused by bacterial and parasitic agents, but most commonly associated with infection by a virus (enterovirus, herpesviruses, adenoviruses, and arboviruses) -brain damage can result as the inflamed brain pushes again the skull, and can lead to death or severe neurological impairment

Flavivirus Hemorrhagic Fevers: Yellow Fever Virus

-flavivirus; enveloped; ssRNA; positive sense - Africa and South America -Aedes mosquito transmission (urban) - Initial flulike symptoms, 15% develop severe disease: hemorrhagic fever -20-50% mortality with GI hemorrhage, black vomitus, jaundice, shock -prevention: single dose live vaccine for travelers to endemic regions (proof required; protective immunity in 1 week and good for 10 years) -No vaccine for infants, pregnant women, egg hypersensitivity

Eastern Equine Encephalitis Virus

-found along hte coast from New England to South America -Mosquito vector (Culiseta melanura) mostly feeds on horses and birds -outbreaks among humans -severe encephalitis in horses and birds; vaccine available for horses -most virulent of the encephalitic alphaviruses (50% mortality in humans)

Western Equine Encephalitis Virus

-prevalent in eastern Washington, Colorado, Texas, and parts of California (outbreaks in midwestern states) -horses and humans are dead-end hosts -only 1/1,000 infections cause clinical symptoms: commonly manifests as encephalitis (5% mortality) -Severe illness is more common in young infants (high mortality, permanent neurologic impairment)

Japanese B Encephalitis Virus

-primarily found in Asia (35-50,000 cases anually, 10-15,000 deaths) -less than 1% infected develop clinical symptoms -initial symptoms often include fever, HA, vomiting -can cause severe encephalitis (20-30% mortality) -Vaccine is approved for patients >17 years old. Recommended for long term travel to endemic areas Travel outside of urban areas If JE outbreaks are present

Diagnosis of arbovirus infection

-serologic assays include ELISA and indirect immunofluorescence assay IFA -hemaglutination (HA) and HA inhibition for alphavirus types (togaviridae) -RT-PCR (Reverse Transcriptase PCR) -Viruses an be isolated and cultured (less common) --- viremia is usually over when patient presents symptoms for treatment ---- viruses that produce fevers and rashes can usually be isolated from the blood during initial phases of illness

Treatment of arboviruses

-supportive care -fever control; fluids for dehydration

Dengue Type 2 (2nd infection)

-type 2 virus infects monocytes directly -Binding of cross reacting antibodies enhances uptake of virus by macrophages by 200 fold Virus-ab complex enters monocyte via Fc receptor ---> Ab enhances infection --> increased production of cytokines --> dengue hemorrhagic fever, dengue shock syndrome

Transmission of arboviruses

-virus enters the bloodstream or lymph of its victim, following a blood feeding by arthropods -successful infection depends on the amount of virus and absence of neutralizing antibodies

Flaviviruses

1. Dengue Virus 2. St Louis Encephalitis Virus (SLEV) 3. Yellow Fever Virus 4. West Nile Virus (WNV) Icosohedral enveloped

Togaviruses

1. Eastern Equine Encephalitis (EEE) 2. Western Equine Encephalitis (WEE) 3. Chikyngunya Icosohedral Enveloped

Zika Virus

A flavivirus spread by Ae. Aegypti and Ae. Albopictus mosquitos -sexual transmission and transmission through blood transfusions have also been reported -local transmission in the US (Miami) -Many people infected will not experience symptoms or only have mild symptoms lasting for several days to a week: fever, rash, joint pain, conjunctivitis, muscle pain, HA -Has been linked to Guillain-Barre Syndrome; symptoms can last for a few weeks to several months and include weakness of the arms and legs in severe cases; can affect the muscles that control breathing - can be passed from a pregnant women to her fetus and cause birth defects: microcephaly, eye defects, hearing loss, impaired growth

Bunyavirus

California encephalitis types, including La Crosse encephalitis virus Helical, enveloped

Togaviruses (alphaviruses)

Clinical symptoms follow one of two patterns: 1. Systemic phase following viremia that includes fever, chills, aches... then a secondary encephalitic phase (EEE, WEE). - EEE is most severe of arboviral encephalitis; particular in infants and elderly 2. Disease having only a systemic phase with fever, arthritis, and a rash (Chikungunya)

Reovirus

Colorado Tick Fever virus Icosohedral, no envelope

Largest US flavivirus concern

Encephalitis (west nile virus)

Dengue Virus

Flavivirus; positive sense; ssRNA -primarily transmitted by mosquito (Aedes species) -4 serotypes (DENV-1, -2, -3, and -4) -Immunity is type specific: 1. Cross reacting antibodies BIND to the virus 2. Cross reacting antibodies DO NOT NEUTRALIZE infectivity of the different serotype -man is not the dead end host

Arbovirus transmission characteristics

Insect-vertebrate cycle is continuous in the tropics, but the virus must find a spot to "WINTER OVER" in temperate areas: -Latent state in cold blooded animals (snakes or frogs) -may be reintroduced by migrating birds -may remain viable in some insects that hibernate -may remain in secondary hosts, such as rodents -transovarial transmission ---- infected female tramits virus to progeny

Japanese Encephalitis Virus (JEV)

Mosquito borne virus; not currently in the US

Yellow Fever Virus

Mosquito borne virus; not currently in the US

Chikungunya Virus (CHIKV)