Infectious Mononucleosis - EBV and CMV (PDF)

Infectious Mononucleosis EBV and CMV Beatrice Saviola Conflict of Interest Disclosure In relation to this presentation, Dr. Saviola has no financial interests or other conflicts that need to be discloses. 2  Objectives The stud...

Infectious Mononucleosis EBV and CMV Beatrice Saviola Conflict of Interest Disclosure In relation to this presentation, Dr. Saviola has no financial interests or other conflicts that need to be discloses. 2  Objectives The student should be able to describe the microbiological features of Epstein-Barr and CMV viruses, and to be able to describe their life cycle in vivo. The student should be able to identify clinical features of Epstein-Barr virus and CMV infection. The student should be able to describe various laboratory methods to identify an Epstein- Barr and CMV viral infection.  Reference Medical Microbiology and Immunology, Warren Levinson, Epstein-Barr Virus and CMV section of Chapter 37. https://accessmedicine-mhmedical- com.proxy.westernu.edu/book.aspx?bookid=3 123#261979831 Families of DNA Viruses  Herpesviridae Enveloped icosahedral nucleocapsids DNA genome Most can maintain a latent or chronic infection and can be reactivated after long periods of time.  Herpes viruses are sensitive to acid solvents, detergents, and drying. Herpesviruses have the capacity to establish latent and recurrent infections. Cell mediated immunity is important for controlling infection with theses viruses and causing symptoms. Herpesvirus infections are common.  Epstein-Barr Virus At least 70% of the population of the U.S. is infected by EBV by age 30. EBV is transmitted through saliva (kissing disease). Productive infection of B cells and epithelial cells of the oropharynx, such as the tonsils, promotes shedding of the virus into the saliva. Children generally have subclinical disease, however older individuals may have varying degrees of severity.  Epstein-Barr is a gammaherpesvirus, there are two strains EBV-1 and EBV-2. Epstein-Barr virus attaches to the type 2 Complement Receptor, CR2 (also known as CD21), on susceptible cells. Susceptible cells are oropharyngeal epithelial cells, B-lymphocytes, T lymphocytes, and monocytes. Virus also uses MHC class II molecules as a coreceptor. Latent infection is more common in B- cells.  In vivo, B-cell proliferation occurs and is indicated by production of nonspecific IgM antibodies. One of the antibodies produced is heterophile antibody which has affinity for sheep and horse red blood cells and can cause agglutination. Other antibodies can be directed against self antigens present on neutrophils, erythrocytes, and platelets. Antibodies can develop against non self antigens as well, such as ampicillin. Antibodies specific for the virus also appear. These should not be confused with the heterophile antibody. Ampicillin Rash  B-cell proliferation is usually controlled by CD 8 + T-cells. lymphocytosis results from activation and proliferation of T cells (to control B cell growth). T cells appear as atypical lymphocytes, Downey cells. T cell response causes swelling of lymph glands, spleen, and liver. The diseases of EBV result either from an overactive immune response (infectious mononucleosis) or a lack of an effective immune response (lymphoma). Splenic rupture  Heterophile Antibody Positive Infectious Mononucleosis Characterized by high fever, pharyngitis, malaise, swollen glands. The major complaint of people with infectious mononucleosis is fatigue.  Diagnosis Blood smear- atypical lymphocytes Heterophile Antibody (Elisa or Monospot) disappear after infection resolves EBV specific antibodies IgM- acute infection, wane after 3 months IgG persists for life- marker for prior EBV infection, but not chronic infection Antibody response to infection  Reactivation is increased in SARS-CoV-2 infection. Transplant recipients, patients with AIDS, and genetically immunodeficient people are at a higher risk for EBV associated lymphomas. Many Hodgkin’s lymphomas can be attributed to EBV. Continued B- cell proliferation may result in the development of lymphoma. Geographical distribution of EBV associated neoplasm indicates a possible association with cofactors. The immunosuppressive effects of malaria could contribute to African Burkitts lymphoma. People living in certain regions of China have an increased incidence of nasopharyngeal carcinoma linked to EBV.  Therapy No vaccine No need for treatment of uncomplicated disease Acyclovir has little activity against EBV It can be given in high doses for life- threatening EBV  CMV- a betaherpesvirus Human cytomegalovirus (CMV)- Causes heterophile antibody negative mononucleosis. Asymptomatic in most people with normal immune systems Some have a heterophile negative mononucleosis with jaundice, hepatosplenomegaly, There may be severe neurological damage to a human fetus infected in utero with first maternal infection (primary). CMV is considered a TORCH pathogen. Pneumonia, and chorioretinitis can occur in the immunocompromised.  Latency in monocytes. Reactivation may result in virus shedding in urine. It is also transmitted by intimate contact including sexual contact. It has been shown to be transmitted among toddlers in a day care setting (saliva and urine). Therefore, women previously uninfected who are pregnant should exercise caution especially if they work in a day care setting. TRANSMISSION OF CMV In utero Urine Early childhood (saliva, etc) Venereal in young adults Blood transplantation Organ transplantation 30 Primary infection of a pregnant woman with CMV PATHOGENESIS AND IMMUNITY TO CMV INFECTION CMV causes birth defects 31  CLINICAL FINDINGS Birth defects caused by CMV: Microcephaly Purpura 32 33 34 Immunocompetent- infected with CMV for first time (de novo, primary infection) Fever, lethargy Abnormal lymphocytes in peripheral blood Heterophile antibody negative 35 Immunosuppressed individuals CLINICAL FINDINGS 36  Diagnosis Fluorescent antibody staining Histological evidence of inclusion bodies in giant cells- owl’s eye appearance Antibody response PCR confirmation of CMV Detection of CMV antigen pp65 Heterophile antibody negative 37 Inclusion Bodies-Owl’s Eye appearance CMV Giant cells with inclusion bodies=cytomegalovirus 38 LABORATORY DIAGNOSIS: 39  Treatment No vaccine, but a number of candidates in development. Ganciclovir can be used in immunocompromised Immunoglobulin preparation (CytoGam) can be used to prevent disseminated infections 40 EBV: a)Infectious mononucleosis in immunocompetent subjects: fever, malaise, pharyngitis, fatigue b)Atypical lymphocytes and heterophile antibodies (disappear after infection resolves) c) Antibodies specific for EBV persist (IgG) d)EBV associated with various cancers CMV: a)Infectious mononucleosis in immunocompetent subjects b)Congenital birth defects in newborns c)Atypical lymphocytes are seen in infectious mononucleosis caused by CMV but there is no production of heterophile antibodies, owl’s eye d)Immunocompromised have more extensive infection 41