Lymphatic Viruses PDF

Lymphatic Viruses ANDREA GAIL M. VILLAVICENCIO, DVM, MPVM Outline Ebola virus Cytomegalovirus Epstein-Barr virus Ebola virus  Ebola virus Species Animals Susceptible % Mortality Sudan ebolavirus (SUDV) Humans...

Lymphatic Viruses ANDREA GAIL M. VILLAVICENCIO, DVM, MPVM Outline Ebola virus Cytomegalovirus Epstein-Barr virus Ebola virus  Ebola virus Species Animals Susceptible % Mortality Sudan ebolavirus (SUDV) Humans 50-60% Zaire ebolavirus (EBOV) Humans 63-88% Tai Forest ebolavirus (TAFV) Primates (inc. humans) 0% Bundibugyp ebolavirus (BDBV) Humans 30-40% Resron ebolavirus (RESTV) Nonhuman primates, swine 0%  Ebola virus Morphology Diameter: 80nm Length: 1000-140000nm Envelope: (+) with glycoprotein spikes Symmetry: helical Shape: filamentous, pleomorphic (U-shaped, 6-shaped), flexible with extensive branching Prominent structures: 3 layers with 7 proteins a. envelope - GP b. matrix space - VP40, VP24 c. nucleocapsid - NP, VP35, L, VP30  Ebola virus Transmission direct contact raw meat sexual contact breast milk consumption Ebola virus Pathogenesis  Ebola virus Transmission release of pro-inflammatory cytokines -> endothelial leakage hepatocellular necrosis -> reduced synthesis of clotting factors Ebola virus Transmission  Ebola virus Transmission sweat sputum vomit blood shedding urine semen feces  Ebola virus Clinical Signs fever myalgia headache malaise diarrhea abdominal pain epistaxis vomiting loss of rash red eyes appetite (subconjunctival hemorrhage)  Ebola virus Diagnosis ELISA Antigen detection: high sensitivity in acute phase Antibody detection: IgM (1-2 wks after onset of symptoms) RT-PCR gold standard should be repeated in subsequent samples to avoid false negative results portable PCR techniques currently in development Next Generation Sequencing (NGS) genomic analysis identification of viral vairants Ebola virus Treatment, Control & Prevention 2 vaccines approved for Zaire ebolavirus NO SPECIFIC VACCINE OR TREATMENT (supportive therapy only) rehydration nutrition analgesics blood transfusion prophylactic antimicrobials (3rd gen cephalosporins) in development: favipiravir, BCX4430, brincidofovir immunotherapy (convalescent whole blood & plasma, hyperimmune serum,  Ebola virus Treatment, Control & Prevention proper hygiene cleaning & disinfection 3% acetic acid avoid contact with body 1% gluteraldehyde PPE fluids and raw meat alcohol-based products 0.5% bleach isolation  CDC Teams: epidemiology infection control laboratory analysis medical care emergency management information technology health communication behavioral science anthropology logistics planning other disciplines  Cytomegalovirus Order: Herpesvirales Family: Herpesviridae Subfamily: Betaherpesvirinae Morphology 240kbp Length: 150-200nm Envelope: (+), icosahedral nucleocapsid Symmetry: linear dsDNA Prominent structures: outer lipid envelope tegument nucleocapsid internal nucleoprotein core  Cytomegalovirus Normal Hosts 4-8wk IP systemic - infectious monucleosis-like syndrome mostly subclinical, lifelong latent infections fever, sore throat, swollen glands hepatitis (occasionally) typical mononucleosis syndrome: acute febrile illness with an increase of 50% or more in lymphocytes/monocytes at least 10% of lymphocytes are atypical Cytomegalovirus  Cytomegalovirus Immunosuppressed Hosts organ transplant recipients, patients undergoing chemotherapy, AIDS+ pneumonia: most common complication reactivation more common  Cytomegalovirus Newborn and Infants intrauterine fetal infection and congenital CMV infants born to mothers who developed primary CMV infection during pregnancy transmission in approximately 40% of cases clinical manifestations: mild, nonspecific findings to severe, multiple-organ system involvement petechial rash, jaundice with hepatosplenomegaly, neurologic abnormalities such as microcephaly and lethargy, chorioretinitis and optic nerve atrophy, and prematurity and low birth weight  Cytomegalovirus Patients with HIV CMV-induced end-organ damage commonly in the form of retinitis painless blurred vision unilateral floaters light flashes extraocular dermatologic lungs -> pneumonitis (Pneumocystis jirovecii, Aspergillus fumigatus) GIT -> esophagitis, gastritis, colitis, hepatitis, pancreatitis  Congenital and Perinatal Infections 1 in 200 babies born with CMV infection ~1 in 5 babies will have birth defects or long-term health problems  direct contact breast Transmission saliva or milk urine organ preg- sexual transplant nancy contact and blood transfusion  Epidemiological factors geographic age socioeconomic location status developing older pop’n crowded and poorer countries communities serology viral culture Ab detection tube culture, (IgG, IgM) shell-vial assay Diagnosis antigenemia molecular pp65 Ag PCR, non-PCR amplification  Treatment anti-CMV agents halt CMV replication but do not eliminate the virus ganciclovir (IV) poor bioavailability orally valganciclovir (oral) second-line agents: foscarnet and cidofovir undergoing trials: brincidofovir letermovir maribavir Prevention Epstein-Barr Virus human gammaherpesvirus 4 infectious agent for Kissing Disease/Mono/Infectious Mononucleosis at least 1 out of 4 infected teenagers and young adults develop infectious mononucleosis  Epstein-Barr Virus Order: Herpesvirales Family: Orthoherpesviridae Subfamily: Gammaherpesvirinae Morphology Length: 122-180nm Envelope: (+), icosahedral nucleocapsid Symmetry: helical Tropism: B cells and epithelial cells  Pathogenesis overactive immune response -> infectious mononucleosis saliva lack of effective immune response -> lymphoma oropharynx transmitted via salivary exchange or blood transfusion pharyngeal epithelial cells usually self-limited IP: 30-50 days  Infectious Mononucleosis Glandular fever acute self-limited illness usually in nonimmune young adults IP: 4-8wks in most patients, spleen is palpable and liver dysfunction present self-limited disease lasts at about 2-4wks  Lymphoma-Associated Disorders B-cell tumors in immunocompromised px Hodgkin lymphoma Nasopharyngeal carcinoma Burkitt’s lymphoma common in Chinese males aggressive B-cell lymphoma aged 20-50 y/o endemic in central Africa inaccessible to surgery or malaria is a recognized co-factor chemotherapy 30% of childhood lymphomas in the US  Clinical Manifestations fever peaks in afternoon or early evening, 39.5-40.5C sore throat lymphadenopathy (esp neck and armpits) maculopapular rashes pharyngitis  Diagnosis Serology heterophile antibody test specific Ab testing detection of up to 30% morphologically atypical lymphocytes differential: HIV, CMV, Hepatitis B, Influenza B, Rubella, other viral ds, toxoplasmosis  Prevention and Treatment NO VACCINE AVAILABLE recovery usually around 2-4 weeks treatment is usually supportive care  References Johannsen EC, Kaye KM: Epstein-Barr Virus (Infectious Mononucleosis, Epstein-Barr Virus–Associated Malignant Diseases, and Other Diseases). 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