Togaviruses Notes

NOTES NOTES TOGAVIRUSES MICROBE OVERVIEW ▪ Pathogenic viruses in Togaviridae family ▪ Capsid symmetry: icosahedral ▪ RNA structure: linear, positive polarity EASTERN EQUINE ENCEPHALITIS VIRUS (EEEV) osms.it/eastern-equine-encephalitis PATHOLOGY & CAUSES ▪ Highly pathogenic; causes central nervous system illness in humans, horses (equines) ▪ Genus: Alphavirus ▪ Spherical, approx. 69nm diameter (including glycoprotein spikes) ▪ Enveloped, single-stranded, positive-sense RNA genome ▪ Glycoproteins associated with neurovirulence, cellular apoptosis ▪ Potential bioterrorism agent use (aerosol route) ▪ Range ▫ Atlantic, Gulf-coast states in eastern USA ▪ Four lineages ▫ Group I: endemic in North America, Caribbean (causes most human disease) ▫ Groups IIA, IIB, III: primarily cause equine illness in Central, South America ▪ Viral life-cycle: wild birds, Culiseta melanura mosquito (enzootic vector) ▫ C. melanura rarely bites humans ▫ Human transmission requires other mosquito species (e.g. Aedes, Coquillettidia, Culex) to bridge between infected birds, humans ▫ Infected mosquito bite → 4–10 day incubation period → prodromal period → neurological symptom development occurs rarely RISK FACTORS ▪ Rural residence; living in/visiting woodland habitats, swampy areas ▪ Outdoor occupation/recreational activity COMPLICATIONS ▪ Encephalitis; cerebral edema; coma; residual brain damage (mild–severe, esp. young children); death (some) SIGNS & SYMPTOMS ▪ May be asymptomatic ▪ Prodromal period: high fever, headache, nausea, vomiting ▪ Neurologic presentation: cranial nerve palsy, seizure, stupor → coma ▪ Infants: fever, bulging fontanel, generalized flaccid/spastic paralysis OSMOSIS.ORG 565

DIAGNOSIS TREATMENT DIAGNOSTIC IMAGING ▪ No specific treatment MRI ▪ Focal lesions in basal ganglia, thalamus, brainstem MEDICATIONS LAB RESULTS ▪ Leukocytosis; left shift ▪ Hyponatremia ▪ Serology ▫ IgM antibody presence ▪ Cerebrospinal fluid (CSF) examination ▪ Lymphocytic pleocytosis, ↑ neutrophils; ↑ protein; IgM antibodies (assay); virus isolation ▪ Supportive: anticonvulsants, corticosteroids (↓ inflammation) OTHER INTERVENTIONS ▪ Supportive: IV fluid, respiratory support, monitor intracranial pressure ▪ Prevention ▫ Insect repellent (DEET, picaridin, IR3535, oil of lemon eucalyptus) ▫ Protective clothing ▫ Vector control OTHER DIAGNOSTICS Electroencephalography (EEG) ▪ Generalized slowing; disorganized pattern RUBELLA VIRUS osms.it/rubella-virus PATHOLOGY & CAUSES ▪ Highly communicable virus → German measles ▪ Enveloped, positive-sense, single-stranded RNA virus ▪ Family: Togaviridae ▪ Genus: Rubivirus ▪ Three structural proteins ▫ C: capsid protein surrounding virion RNA ▫ E1, E2: glycosylated proteins forming transmembrane antigenic sites ▪ Humans are the only natural hosts ▪ Transmission: droplet inhalation/direct contact with infectious nasopharyngeal secretion ▪ Viral contact → 12–23 day incubation → nasopharyngeal cell, regional lymph 566 OSMOSIS.ORG node viral replication → viremia → maculopapular rash eruption → rash resolution (approx. two days) ▫ Contagious via virus shedding before, after rash appears ▫ ↑ contagiousness during rash eruption ▪ Spreads transplacentally RISK FACTORS ▪ Unvaccinated ▪ Travel (especially abroad) ▪ Contact with febrile rash individuals COMPLICATIONS ▪ Thrombocytopenic purpura ▪ Encephalitis (rare) ▪ If infected during pregnancy: congenital rubella syndrome (CRS)

Chapter 101 Togaviruses ▫ ↑ risk of miscarriage, fetal death, stillbirth ▫ CRS: A ToRCHeS (see mnemonic) infection; ↑ first trimester risk; extramedullary hematopoiesis (“blueberry muffin” rash), cataract, heart defect, hearing impairment, intellectual disability MNEMONIC: ToRCHeS Perinatal infections passed from mother to child Toxoplasmosis, toxoplasma gondii Other infections Rubella Cytomegalovirus Herpes Simplex virus-2/ neonatal herpes simplex SIGNS & SYMPTOMS ▫ Reverse transcription-PCR (rubella virus RNA performed on amniotic fluid) OTHER DIAGNOSTICS ▪ Clinical diagnosis ▪ High suspicion index ▫ Febrile rash, unvaccinated status TREATMENT ▪ No specific antiviral therapy OTHER INTERVENTIONS ▪ Infection control measures ▫ Prompt isolation for seven days after rash development ▪ Vaccine: live-attenuated measles-mumpsrubella (MMR)/measles-mumps-rubellavaricella (MMRV) ▫ First dose: 12–15 months old ▫ Second dose: 4–6 years old ▪ Maculopapular rash ▫ Pink/light red macules: coalesce to form evenly-colored desquamating rash ▫ Initially: face → generalized rash within 24 hours ▫ Duration: three days ▪ Lymphadenopathy; primarily posterior auricular/suboccipital lymph ▪ Low-grade fever ▪ Mild nonexudative conjunctivitis ▪ Forchheimer spots on soft palate ▪ Arthralgias ▪ Orchitis ▪ Asymptomatic (half of cases) DIAGNOSIS LAB RESULTS ▪ Polymerase chain reaction (PCR) testing/ molecular typing ▫ Throat, nasal, urine specimens ▪ Serologic testing ▫ Enzyme immunoassay (EIA) detects rubella-specific IgM antibodies ▪ Pregnancy Figure 101.1 A child with rubella showing a characteristic maculopapular, erythematous rash. OSMOSIS.ORG 567

WESTERN EQUINE ENCEPHALITIS VIRUS (WEE) osms.it/western-equine-encephalitis PATHOLOGY & CAUSES ▪ Causes central nervous system illness in humans, horses (equines) ▪ Genus Alphavirus ▪ Spherical, approx. 69nm diameter (including glycoprotein spikes) ▪ Enveloped, single-stranded, positive-sense RNA genome ▪ Contain glycoproteins associated with neurovirulence, cellular apoptosis ▪ Range: most commonly US states, Canadian provinces west of Mississippi River ▪ Virus life-cycle: wild birds, other vertebrates, Culex tarsalis mosquito (enzootic vector) ▫ Culex tarsalis (another human vector) ▪ Potential bioterrorism agent use (aerosol route) ▪ Infected mosquito bite → 2–10 day incubation period → sudden onset of severe headache, fever/chills, dizziness, chills, myalgias, malaise, tremor, irritability, photophobia, neck stiffness → rapid neurological manifestation development → recovery ▫ Most adults: no residual neurological effects ▫ Infants, children: ↑ long-term neurologic sequelae risk RISK FACTORS ▪ Most cases June–September ▪ Bimodal age pattern: < one year; ↑ risk in elderly ▪ Biologically-female ▪ Rural residence ▪ Outdoor occupation/recreational activity 568 OSMOSIS.ORG COMPLICATIONS ▪ Encephalitis, coma, respiratory failure, death ▪ Infants: intellectual disability, cerebellar damage, spastic paralysis, developmental delay SIGNS & SYMPTOMS ▪ Neurological manifestations ▫ Generalized weakness; somnolence; hand, tongue, lip tremor; cranial nerve palsy; motor weakness; ↓ deep tendon reflexes ▪ Infants: poor feeding, fussiness, fever, vomiting, tense/bulging fontanelle DIAGNOSIS LAB RESULTS ▪ Serology ▫ Enzyme-linked immunosorbent assay (ELISA): IgM antibodies ▫ Hemagglutination-inhibition, neutralizing antibody presence ▪ CSF ▫ ELISA: IgM antibodies ▫ Lymphocytic pleocytosis ▫ ↑ protein TREATMENT ▪ No specific treatment MEDICATIONS ▪ Supportive: anticonvulsants, corticosteroids

Chapter 101 Togaviruses OTHER INTERVENTIONS Prevention ▪ Insect repellent (DEET, picaridin, IR3535, oil of lemon eucalyptus) ▪ Protective clothing ▪ Vector control OSMOSIS.ORG 569