mononucleosis is caused by a pathogen abbreviated as

Antibiotics don't work against viral infections such as mono. Using major histocompatability complex (MHC) II tetramers, it was shown that several lytic antigens are recognized by CD4 T cells during acute infection and that these cells are maintained at low levels in the blood of EBV infected hosts (Long et al. EBV infection in particular has come to be highly associated with occurrence of MS. EBV as a causation factor in MS was first proposed over thirty years ago (Warner and Carp 1981). Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Takeuchi K, Tanaka-Taya K, Kazuyama Y, Ito YM, Hashimoto S, Fukayama M, Mori S. Prevalence of Epstein-Barr virus in Japan: trends and future prediction. Work from Williams et al. However, you can get it at any age. Sokal EM, Hoppenbrouwers K, Vandermeulen C, Moutschen M, Leonard P, Moreels A, Haumont M, Bollen A, Smets F, Denis M. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults. 2010; Pakpoor et al. Centers for Disease Control and Prevention. Mononucleosis - Symptoms & causes The symptoms of EBV and LCV are very similar, and LCV can be given orally to emulate natural infection routes in humans. Balfour HH, Jr, Forte FA, Simpson RB, Zolov DM. High viral loads in both the oral cavity and blood are detected around the time of symptom onset in infectious mononucleosis and accompanied by production of IgM antibodies to EBV VCA and an extraordinary expansion of CD8 T lymphocytes (Balfour et al. Strautins K, Tschochner M, James I, Choo L, Dunn DS, Pedrini M, Kermode A, Carroll W, Nolan D. Combining HLA-DR risk alleles and anti-Epstein-Barr virus antibody profiles to stratify multiple sclerosis risk. Table 3.1 shows the frequency of signs and their median duration in 72 undergraduate students studied prospectively. The Epstein-Barr virus ( EBV ), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. Alotaibi S, Kennedy J, Tellier R, Stephens D, Banwell B. Epstein-Barr virus in pediatric multiple sclerosis. A well-documented case was reported by Svedmyr et al. These NHANEs findings were confirmed (Condon et al., 2014) and extended to include younger children (18 months to 6 years of age) living in the Minneapolis-St. Paul metropolitan area. False positive heterophile tests have been reported in a myriad of conditions including other acute infections, autoimmune disease, and cancer (Sadoff and Goldsmith 1971; Phillips 1972; Horwitz et al. On average, the prodrome phase lasts three . Interestingly, the difference in antibody prevalence between whites and non-whites diminished during the teenage years. 2008). 2013). For example influenza specific CD8+ T cells might cross-react with EBV (Clute et al. 2013). Association of EB-virus infection with the post-perfusion syndrome. Epstein-Barr virus and its association with disease - a review of Levitskaya J, Sharipo A, Leonchiks A, Ciechanover A, Masucci MG. Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1. Mono is sometimes called the "kissing disease" because it is spread through saliva. Clute SC, Watkin LB, Cornberg M, Naumov YN, Sullivan JL, Luzuriaga K, Welsh RM, Selin LK. Unpublished observations). Table 3.2 shows reported complications divided into those estimated to occur in at least 1% of patients and those that are seen in fewer than 1% of cases (Hoagland and Henson 1957; White and Karofsky 1985; Robinson 1988; Connelly and DeWitt 1994; Jenson 2000). Interestingly, the strong genetic association of MS with particular human leukocyte antigen (HLA) alleles primarily reflects the association with anti-EBV responses (Rubicz et al. This theory is supported by the incidence of infectious mononucleosis in family groups. EBV belongs in this group because it only infects primates. 2008). In particular, the roles of certain subsets of cells have been interrogated through the depletion of these populations prior to infection with EBV. 1975; Crowcroft et al. 2011) and infected with the B95.8 strain of EBV and monitored for signs of infectious mononucleosis such as CD8 lymphocytosis and viremia. Chapter 7 HSC Flashcards Unpublished observations). The site is secure. Therefore it is possible that the HLA locus influences the response to infection rather than the infection rate per se. Sumaya CV, Henle W, Henle G, Smith MH, LeBlanc D. Seroepidemiologic study of Epstein-Barr virus infections in a rural community. Hjalgrim H, Askling J, Sorensen P, Madsen M, Rosdahl N, Storm HH, Hamilton-Dutoit S, Eriksen LS, Frisch M, Ekbom A, Melbye M. Risk of Hodgkins disease and other cancers after infectious mononucleosis. 2013). 2007). It was discovered that the main deficiency involved with XLP is in the signaling lymphocytic activation molecule associated protein (SAP), which is encoded by the human gene SH2D1A. Antibodies against EBNA-1 are slow to appear with a median first day of detection of 91 days (Figure 1). Everyone who experiences a primary EBV infection develops IgG antibodies to VCA (Balfour et al. Besides deep kissing, primary EBV infection can also be transmitted by blood transfusion (Gerber et al. 1998; Bauer 2001). Levin LI, Munger KL, OReilly EJ, Falk KI, Ascherio A. National Library of Medicine Non-human primates are the other major option for investigating EBV infection in vivo. Appointments Contact Us Massa J, Munger KL, OReilly EJ, Falk KI, Ascherio A. Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus. Bethesda, MD 20894. Balfour HH., Jr Progress, prospects, and problems in Epstein-Barr virus vaccine development. Robinson RG. On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis. EBV is a double-stranded DNA virus. Once infected, your body retains the virus for life. It is possible that adolescents receive a larger initial virus inoculum when transmission occurs through deep kissing. Long HM, Chagoury OL, Leese AM, Ryan GB, James E, Morton LT, Abbott RJ, Sabbah S, Kwok W, Rickinson AB. These include familial hemophagocytic lymphohistiocytosis 2 (FHL2), x-linked lymphoproliferative syndrome (XLP), XIAP deficiency, and x-linked immunodeficiency with Mg+2 defect (XMEN) disorders, and are discussed in detail in another chapter of this book. 1998), maternal education (Figueira-Silva and Pereira 2004), day care attendance (Hesse et al. EBV is considered the etiologic agent in 95% of cases of eBL, which occur in regions where malaria is common (Brady et al. 2001). Symptoms of Creutzfeldt-Jakob disease can be similar to those of Alzheimer's disease. Babies born with CMV can have brain, liver, spleen, lung, and growth problems. Infectious Mononucleosis: Rapid Evidence Review Heterophile tests are relatively inexpensive and easy to perform. Thus, family environment and/or social practices may differ among white and non-white families, which could account for this disparity in antibody prevalence in younger children. Hjalgrim H, Friborg J, Melbye M. The epidemiology of EBV and its association with malignant disease. 2011), a brief discussion of CD8 T cell and B cell responses follows. Prevalence of Epstein-Barr virus antibodies in healthy children and adolescents in Vitoria, State of Espirito Santo, Brazil. Splenic rupture is the most feared complication, which has kept many athletes out of competition for weeks. government site. That this is the case, however, is not clear and may have to do more with accumulation of protein released from cells for cross presentation. 1975; Venkitaraman et al. Systemic lupus erythematosus presenting as infectious mononucleosis with a false positive monospot test. (1984) in which the kissing event occurred 38 days prior to onset of symptoms (Svedmyr et al. Hoagland RJ. Azzi T, Lunemann A, Murer A, Ueda S, Beziat V, Malmberg KJ, Staubli G, Gysin C, Berger C, Munz C, Chijioke O, Nadal D. Role for early-differentiated natural killer cells in infectious mononucleosis. EBV is a -herpesvirus that infects at least 90% of the population worldwide. (1996) used polymorphisms in the EBV BAMHI-K fragment length and size polymorphisms in EBV nuclear antigen (EBNA) -1, -2 and -3 proteins to identify the specific blood donor responsible for transmitting EBV to a 16-year-old liver transplant recipient who subsequently developed infectious mononucleosis. Review of the clinical manifestations, laboratory findings, and complications of infectious mononucleosis. EBV has been shown to be the causative agent of about one percent of the worldwide human cancer burden. A reasonable supposition is that they are infected by their parents or siblings who are carriers of the virus and who intermittently shed it in their oral secretions (Sumaya and Ench 1986). 2012), which can promote the maturation and maintenance of type I interferon producing plasmacytoid DCs (Fancke et al. Centers for Disease Control and Prevention 2014, http://www.cdc.gov/epstein-barr/laboratory-testing.html, Airway obstruction due to oropharyngeal inflammation, Neurologic disorders (other than meningoencephalitis, Inexpensive, easy to perform, becomes negative 312 months postinfection, Nonspecific (false positives due to acute infections and autoimmune diseases); may be negative during first week of illness and persistently negative in young children, Specific, becomes negative 312 months postinfection, Not usually performed at point of care sites, Best test for diagnosis of past EBV infection, Best test to distinguish acute from convalescent EBV infection, Not usually performed at point of care sites; 510% of patients never become positive, Absent in 2040% of acute illnesses; persists for years in ~20% of cases, Can be used to stage infection (acute, convalescent, past), Correlates with severity of illness; best test to monitor infection in the immuncompromised host, Viremia is short-lived and may be missed in immunocompetent patients, Cannot be used to diagnose acute infection because virtually all antibody-positive adults shed oral virus intermittently, National Health and Nutrition Examination Survey, Signaling lymphocytic activation molecule associated protein. unpublished observations), where it is probably maintained latently in resting memory phenotype B cells (Hadinoto et al. You can get it through kissing, but you can also be exposed by sharing a glass or food utensils with someone who has mono. Most patients (75%) will have VCA IgM antibodies at the onset of clinical illness and 95% eventually make them (Table 5.1). Cells specific for some late antigens tend to emerge only after the patient has been infected for some time as discovered by generating T cell clones from infectious mononucleosis patients (Abbott et al. It can be caused by a number of pathogens, but this chapter considers it as disease resulting from primary Epstein-Barr virus (EBV) infection and is focused on the immunocompetent host. Allosteric competitive inactivation of hematopoietic CSF-1 signaling by the viral decoy receptor BARF1. 1987; Hille et al. Association between lymphoproliferative cancers, especially Hodgkin lymphoma and Burkitt lymphoma, and infectious mononucleosis are well-established. Mononucleosis is a contagious (but not highly contagious) disease, mostly caused by Epstein-Barr virus ( EBV) infection. EBV enters into your body commonly through saliva. The symptoms of mono are extreme fatigue, fever, sore throat, and swollen lymph nodes. Kimura H, Hoshino Y, Kanegane H, Tsuge I, Okamura T, Kawa K, Morishima T. Clinical and virologic characteristics of chronic active Epstein-Barr virus infection. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. This is likely because BZLF1 is expressed by cells undergoing viral reactivation and thus is more frequently presented to B cells in latently infected hosts in comparison to proteins that are coded for later in the viral replication process (Massa et al. If you're pregnant or if your immune system is weakened, CMV is cause for concern. leukocytosis Krabbe S, Hesse J, Uldall P. Primary Epstein-Barr virus infection in early childhood. The term "infectious mononucleosis" was first used in the 1920s to describe a group of students with a similar pharyngeal illness and blood laboratory findings of lymphocytosis and atypical mononuclear cells. We dont have an approved specific treatment for EBV infections. Treatment There's no specific therapy available to treat infectious mononucleosis. 2010). Lang DJ, Garruto RM, Gajdusek DC. Sadoff L, Goldsmith O. False-positive infectious mononucleosis spot test in pancreatic carcinoma. There is no currently accepted specific treatment for infectious mononucleosis. Emerging evidence suggests that previous presentation with infectious mononucleosis can increase the risk of HL (Hjalgrim et al. Many correlative observations for this trend exist, including a low incidence of infectious mononucleosis and MS in developing countries, and MS usually first manifests after the adolescent years during which EBV would be acquired, increasing at a rate of 11% per year following primary EBV (Ascherio and Munger 2010). Researchers recently treated an MS patient with autologous T cells expanded by exposure to EBV antigens. 2010). Rather NK cells expressing NKG2A and CD54 could be found in higher numbers in the tonsils of EBV carriers (Lunemann et al. Other factors implicated are socioeconomic status (Henle et al. Within each race/ethnicity group, older age, lack of health insurance, and lower household education and income were statistically significantly associated with higher antibody prevalence. 2007). EBV is a -herpesvirus that infects at least 90% of the population worldwide. However, we have not seen evidence of influenza-EBV dual specific CD8+ T cells in our cohort (Odumade et al. Because of this, the presence of EBNA-1 antibodies during an acute illness rules out primary EBV infection. Mononucleosis - Diagnosis & treatment 2001; DeLorenze et al. Epstein-Barr is the virus that causes mononucleosis. The infection is common among teenagers and young adults. Infection of T lymphocytes in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children of non-Asian origin. Infectious mononucleosis (IM) is characterized by a triad of fever, tonsillar pharyngitis, and lymphadenopathy [ 1 ]. Comparative evaluation of the use of immunoblots and of IgG avidity assays as confirmatory tests for the diagnosis of acute EBV infections. CD8+ T cell responses to lytic EBV infection: late antigen specificities as subdominant components of the total response. Depicted are viral loads in whole blood, saliva, and oral cell pellets (black lines) as well as IgM and IgG antibodies to VCA and IgG to EBNA1 (colored lines). Annually, 10% to 20% of EBV-naive persons become infected, and 30% to 50% develop IM . Humanized mice have only become a viable option for studying human diseases within the last ten years or so due to low engraftment of human cells even in animals with severe combined immunodeficiency (SCID) or knockout of one of the recombinase activating genes (RAG). Viral genomes can sometimes be detected in the peripheral blood as early as three weeks prior to symptom onset and consistently at least one week prior to illness (Dunmire et al. Finally, we dont know the mechanism by which EBV induces malignancies or autoimmune diseases. Henry H. Balfour, Jr., Department of Laboratory Medicine and Pathology, Department of Pediatrics, University of Minnesota, University of Minnesota Medical School, Minneapolis, MN 55455. Pender MP, Csurhes PA, Smith C, Beagley L, Hooper KD, Raj M, Coulthard A, Burrows SR, Khanna R. Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis. Mononucleosis (mono) is a contagious infection caused by a herpes virus called Epstein-Barr. Bethesda, MD 20894, Web Policies Probably the most interesting phenomenon that occurs during this phase of infection is related to the levels of antibody that are produced and maintained by latently infected hosts. 2013). The role of NK cells in vivo was investigated using a humanized mouse model, where NOD-scid c-/- (NSG) mice were reconstituted with CD34+ lin- hematopoietic stem cells (Strowig et al. 2012). Figueira-Silva CM, Pereira FE. 1998). Neurologic complications of infectious mononucleosis. Our future challenge is to focus research on the following five gaps. Odumade OA, Hogquist KA, Balfour HH., Jr Progress and problems in understanding and managing primary Epstein-Barr virus infections. White LR, Karofsky PS. 2011). A heterophile test using one of number of commercially available antibody kits is most often done to support the clinical diagnosis (Table 5.1). Herpesvirus latency confers symbiotic protection from bacterial infection. Epstein-Barr virus, cytomegalovirus, and infectious mononucleosis. SLAM family receptors and SAP adaptors in immunity. Several instances of B cell tropic CAEBV have also been reported, but these fall into the minority of documented incidences (Schooley et al. Other findings, seen in fewer than 20% of cases in our experience, include abdominal pain, hepatomegaly, splenomegaly, nausea, vomiting, palatal petechiae, periorbital and eyelid edema, and rash. Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. The greatest disparity in antibody prevalence was among the younger children, especially the 6- to 8-year-olds. X-linked lymphoproliferative syndrome (XLP) is a disease characterized by anemia, hypergammaglobulinemia and lymphohistiocytosis. 2004; Strowig et al. Burrows SR, Sculley TB, Misko IS, Schmidt C, Moss DJ. Natural killer (NK) cells are also emerging as important players during infectious mononucleosis. Infectious Mononucleosis 2008). In a study of pediatric infectious mononucleosis patients, it was recently shown that CD56dim NKG2A+ KIR- NK cells preferentially proliferate in response to EBV infected cells during acute infection (Azzi et al. Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study. During primary infection, viral replication is first detected in the oral cavity (Balfour et al. Immunodominant epitopes for the most prevalent HLA types generally include those derived from latently expressed proteins, especially EBNA-2 and EBNA-3, although some patients develop a strong population of CD8 T cells specific for less readily expressed antigens such as EBNA-1 (Blake et al. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Of course, the specific type or subset of NK cells may be more important than total numbers. Class II MHC is also required for viral entry into the cell, although whether or not there are alterations in viral entry efficiency between HLAs prevalent in different racial groups has not been explored. People with mono experience extreme fatigue, fever and body aches. de-The G, Day NE, Geser A, Lavoue MF, Ho JH, Simons MJ, Sohier R, Tukei P, Vonka V, Zavadova H. Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study - a review. It is important to note, however, that study of EBV within this context may neglect important aspects of interplay between EBV and epithelial cells, which have been shown to be important during the replication of EBV, chiefly within the oropharynx (Borza and Hutt-Fletcher 2002). Patients may also notice a swollen neck that results from cervical lymph node enlargement. Mononucleosis (Mono) Tests: MedlinePlus Medical Test The second common presentation is the gradual onset of malaise, myalgia (body aches) and fatigue. These symptoms can last for two to four weeks. It is important to note that while early antigen IgG titers were maintained, VCA IgG antibodies were transient even when very high quantities of virus were used (Okuno et al. However, heterophile antibodies by definition are not specific. Leung C, Chijioke O, Gujer C, Chatterjee B, Antsiferova O, Landtwing V, McHugh D, Raykova A, Munz C. Infectious diseases in humanized mice. Adhikary D, Behrends U, Boerschmann H, Pfunder A, Burdach S, Moosmann A, Witter K, Bornkamm GW, Mautner J. Immunodominance of lytic cycle antigens in Epstein-Barr virus-specific CD4+ T cell preparations for therapy. Takashima K, Ohashi M, Kitamura Y, Ando K, Nagashima K, Sugihara H, Okuno K, Sairenji T, Hayashi K. A new animal model for primary and persistent Epstein-Barr virus infection: human EBV-infected rabbit characteristics determined using sequential imaging and pathological analysis. The virus is associated with another lymphoproliferative disease, African Burkitt's lymphoma, and with a malignancy of the nasopharynx, na and transmitted securely. Horwitz CA, Henle W, Henle G, Goldfarb M, Kubic P, Gehrz RC, Balfour HH, Jr, Fleisher GR, Krivit W. Clinical and laboratory evaluation of infants and children with Epstein-Barr virus-induced infectious mononucleosis: report of 32 patients (aged 1048 months). Subclinical hepatitis documented by elevated levels of alanine aminotransferase occurs in approximately 75% of prospectively followed patients and, in some cases (510%), overt hepatitis develops with tender hepatomegaly and jaundice (Balfour et al.
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