Filoviruses Notes

NOTES NOTES FILOVIRUSES MICROBE OVERVIEW Genetic material ▪ Single-stranded negative-sense RNA virus family; causes viral hemorrhagic fever Taxonomy ▪ Genera: Ebolavirus, Marburgvirus, Cuevavirus Morphology ▪ Enveloped virions; filamentous, nonsegmented morphology Replication ▪ Transcription, replication mediated by virus-encoded polymerase in infected cell cytoplasm ▫ Transcription: negative-sense RNA genome transcribed into monocistronic, polyadenylated RNA species using host cell ribosomes, tRNA etc. → translated into seven proteins ▫ Replication: positive-sense antigenome serves as template for negative-sense genomes Transmission ▪ Zoonotic infection ▫ Natural host: unknown (bats, especially fruit bats considered infection source) ▫ Intermediate host: Often nonhuman primates (gorillas, chimpanzees) Structural proteins ▪ Viral RNA encodes seven structural proteins ▫ Nucleoprotein ▫ Polymerase cofactor (VP35) ▫ Viral proteins VP40, VP24 ▫ Glycoprotein: projecting spikes from lipid bilayer (attachment to host cell receptors) ▫ Transcription activator ▫ RNA-dependent RNA polymerase EBOLA VIRUS osms.it/ebola-virus PATHOLOGY & CAUSES ▪ Ebola virus: causative agent of severe, often fatal hemorrhagic fever ▪ Species: Zaire, Sudan, Tai Forest, Bundibugyo, Reston ▪ Transmission ▫ Animal-human: direct infected-animal tissue, body-fluid contact; butchering, consuming undercooked meat 388 OSMOSIS.ORG ▫ Human-human: direct tissue, body fluid contact with ill/deceased ▫ Potential transmission: contaminated surface/object contact PATHOLOGY ▪ Inoculation → incubation: 6–12 days average (ranges 2–21 days) ▫ Host cell attachment, virus endocytosis → nucleocapsid release in cytoplasm →

Chapter 72 Filoviruses ▪ ▪ ▪ ▪ replication → nucleocapsid formation → viral shedding, cell necrosis Initially macrophages, dendritic cells infected → sentinel lymph node spread → bloodstream → many cell types infected (endothelial cells, fibroblasts, hepatocytes, epithelial cells, adrenal-gland cells) with lymphocyte/neuron exception ▫ Although uninfected, inflammatory mediators; support signal loss from dendritic cells → “bystander” apoptosis of lymphocytes Multifocal necrosis in various tissues (e.g. liver, spleen) Systemic inflammatory syndrome: proinflammatory mediator, cytokine release from infected macrophages, dendritic cells, necrotic cell breakdown products, etc. → vasodilation, ↑ vascular permeability → vascular leakage, shock, multiorgan failure Dendritic cell dysfunction, “bystander” lymphocyte apoptosis → impaired adaptive immunity ▪ Spontaneous abortion, vaginal bleeding in infected pregnant individuals (100% third trimester maternal, fetal mortality) ▪ Fatality ranges ▫ 40% to 80–90% (depending upon species) RISK FACTORS ▪ Healthcare workers without appropriate protective equipment, adequate training ▪ Inadequate infected waste product, corpse handling ▪ Sexual intercourse with person recovering from Ebola in previous three months ▪ Travel to endemic/Ebola epidemic areas ▪ Wild animal contact (mostly nonhuman primates) COMPLICATIONS ▪ Gastrointestinal dysfunction ▫ Fluid loss, hypotension, acute kidney injury, shock ▪ Neurologic ▫ Meningoencephalitis, meningitis ▪ Coagulopathy ▫ Infected macrophages produce tissue factor (TF), stimulate extrinsic coagulation pathway → disseminated intravascular coagulation (DIC) ▪ Respiratory failure ▪ Coinfection/superinfection ▪ Impaired adaptive immunity → bacterial sepsis Figure 72.1 A scanning electron micrograph of an ebola virus demonstrating the typical filamentous structure seen in its class, Filoviridae. SIGNS & SYMPTOMS Initial nonspecific symptoms ▪ Fever, chills, fatigue, headache, appetite loss, malaise, sore throat, myalgias, lumbosacral pain Dermatological ▪ Diffuse erythematous; nonpruritic maculopapular/morbilliform rash, especially on torso/face Gastrointestinal ▪ Watery diarrhea (up to 10L/2.2gal); nausea; vomiting; epigastric, abdominal pain; abdominal tenderness OSMOSIS.ORG 389

Hemorrhage ▪ Commonly hematochezia, followed by hematemesis, melena, metrorrhagia, purpura, petechiae, ecchymoses, mucosal bleeding, venipuncture site bleeding ▫ Often occur later in disease course; not all infected individuals develop significant bleeding; host susceptibilitydependent (genetically determined viral immune response difference), different species’ pathogenicity Neurologic ▪ Meningoencephalitis symptoms (altered level of consciousness, hyperreflexia, myopathy, stiff neck, gait instability, seizure) Ocular ▪ Conjunctival injection, uveitis symptoms (blurred vision, photophobia, blindness) Respiratory ▪ Tachypnea, dyspnea Convalescent period ▪ Can persist > two years often followed by symptoms such as arthralgia, blurred vision, retro-orbital pain, hearing loss, alopecia, difficulty swallowing, insomnia ▪ Infectious virus/viral RNA can persist in body fluid (semen, breast milk, urine, cerebrospinal fluid, aqueous humor) < nine months after not detectable in blood → variable transmission risk DIAGNOSIS ▪ Diagnostic criteria ▫ Clinical manifestation ▫ Travel to endemic/Ebola epidemic areas (within three weeks prior to disease onset) ▫ Infected individual contact during acute disease LAB RESULTS ▪ Reverse-transcription polymerase chain reaction (RT-PCR) ▫ Detectable Ebola virus in blood samples within three days after symptom onset ▪ Rapid chromatographic immunoassay (ReEBOV) 390 OSMOSIS.ORG ▪ Laboratory findings ▫ Leukopenia; thrombocytopenia; ↑ ↓ hematocrit; ↑ aspartate aminotransferase (AST), alanine aminotransferase (ALT) ▫ Prolonged prothrombin (PT), partial thromboplastin time (PTT) ▫ Proteinuria, ↑ blood urea nitrogen, ↑ creatinine ▫ Hyponatremia, hypocalcemia, hyperkalemia TREATMENT ▪ No cure ▪ Infected individual isolation; placement in negative airflow room advised MEDICATIONS ▪ Complications treatment ▫ Coinfection/superinfection: empiric antimicrobial therapy with broad spectrum antibiotics ▫ Shock: intravenous fluids, vasoconstrictors ▫ Fever reduction: antipyretic agents OTHER INTERVENTIONS ▪ Complications treatment ▫ Fluid, electrolyte loss correction ▫ Acute kidney injury: renal replacement therapy (dialysis) ▫ Respiratory failure: supplemental oxygen therapy, mechanical ventilation (if necessary, barotrauma risk)