Seroconversion and Infectious Mononucleosis - Essay Example

Seroconversion and Infectious Mononucleosis Introduction Mononucleosis encompasses infection with the Epstein-Barr virus (EBV) and cytomegalovirus (CMV). The virus is associated with the augmentation of mononuclear leucocytes or monocytes (WBC with single nucleus) in blood stream. Epstein-Barr virus (EBV) is a part of the human herpes-virus family, Herpesviridae, originally segregated from cultured Burkitt lymphoma cell line by Epstein et al. in 1964. Studies established EBV as the causal organism of infectious mononucleosis. Species infecting humans is referred as human CMV or human herpervirus-5 (HHV-5). Prolonged latency within the body is the characteristic feature of the virus. The infection is related to the salivary gland. In healthy individuals infection may not be noticed but in immuno-compromised individuals such as AIDS patients, organ transplantation cases and new born babies and infants, infection with HCMV could be deleterious. CMV is prevalent in all geographical locations and causes infection in 50-80% of the cases (Ryan, 2004; Higgins et al., 2007; Hoffbrand, Paul and Pettit, 2006). Mononucleosis caused by EBV Initial stages of infection are asymptomatic especially in childhood stages, while in adults it is self-restrictive communicable mononucleosis syndrome. EBV is associated with numerous human neoplasms together with hematopoietic, epithelial, and mesenchymal tumors. EBV eludes immune system and institutes dormant infection in memory B cells, where virus inhabits for lifetime without displaying any severe effects in most of the cases. Nevertheless, any discrepancy in the stability associated with an intrinsic virus alteration or changes in host immune system, it results in the formation of diverse tumors, for instance lymph proliferative disorders, Hodgkin’s lymphoma, Burkitt’s lymphoma, and nasopharyngeal carcinoma (Merlo et al., 2010; Ulff-møller et al., 2010). IM is normally self-limiting encompassing fleeting fever, lymphadenopathy and hepatosplenomegaly (Okano, 2011). Mononucleosis is an acute state with fever and swollen lymph nodes. Incubation period is 5-8 weeks (Dorothy et al., 2006). Symptoms Headache, generalized malaise, sore throat, fatigue, fever and enlarged cervical lymph nodes. Initial stages display granulocytopenia with normal white cell count, followed by enhanced WBC count, with a maximum of 50,000 approximately. Heterophil antibodies and Monospot tests are positive. Transmission is through kissing and hence called kissing disease or glandular fever or mono or mononucleosis. Cervical lymphadenopathy, severe pharyngitis encompassing diffuse pharyngeal swelling and tonsillar inflammation is reported. Bilateral edema of the upper eyelids, petechiae on hard/soft palates, inflammation of the anterior or posterior cervical lymph nodes. In later stages, splenomegaly occurs with acute mononucleosis. In 10% cases, hepatomegaly, augmented levels of ALT (alanine transaminase), AST (aspartate transaminase) and lactic acid dehydrogenase in blood may be reported. In 5% cases jaundice may occur. Key complications occur in 1-5% of the IM cases, encompassing lymphocytic meningitis, encephalitis, encephalomyelitis, polyneuritis, mononeuritis and Guillian-Barre syndrome, a trepidation resulting in respiratory paralysis, could be fatal. In rare cases splenic rupture occurs, tracheotomy becomes essential in severe tonsillitis else it blocks the airway (Chamberlain, 2010; Karen et al., 2010; Dorothy et al., 2006). Epidemiology EBV infection remains unnoticed in childhood but could be noticed between the ages of 15-25 years, virus is not contagious and requires continuous expose with the infected individual. Moreover, even after convalesce the individual harbours virus in the saliva for a few months (Chamberlain, 2010; Higgins et al., 2007). Pathogenesis Epithelial lining of the oropharynx are the portals of EBV. Oropharyngeal secretions have viral particles. EBV attacks B lymphocytes through CD21 receptor molecules, therefore EBV antigens are noticeable inside the lymphocyte nucleus, infected B cell spreads through the reticuloendothelial system encompassing liver, spleen and peripheral lymph nodes. EBV onsets the proliferation of B lymphocytes, the plasma cells and immortalization or memory B lymphocyte without any T-helper cells intervention. Thus, EBV acts as a B-cell mitogen inciting B lymphocyte transformation into antibody generating plasma cells, antibodies are found to be non-reactive with EBV antigens. Certain plasma cells generate antibodies that react with RBCs of other mammals (humoral response), the foundation of Monospot test. T lymphocyte reaction is important for controlling infection caused by EBV. The natural killer cells (NK) and CD8 cytotoxic T cells control proliferation of B lymphocytes infected with EBV. Thus, IM is known as glandular fever or Pfeiffer's disease (Chamberlain, 2010). During the log phase of the infection almost 20% of the B lymphocyte in circulation generate EBV antigens, 1% generate EBV antigens during the process of convalescence. EBV has the tendency to form immune complexes in the blood, cause of urtricarial or arthralgia rashes. (Web. Infectious mononucleosis). In severe condition it results in deadly states, hemophagocytic lymphohistiocytosis with fulminant hepatitis, fatal IM; chronic EBV-associated diseases, undifferentiated nasopharyngeal carcinoma, T-cell lymphoproliferative disorder (LPD)/lymphoma, natural killer-cell LPD including leukemia or lymphoma, gastric carcinoma, pyothorax-associated lymphoma and senile B-cell LPD. IM is also causes chronic active EBV infection and LPD/lymphoma in immunodeficiency/ immuno-compromised cases. Chronic life-threatening conditions are associated with the EBV infection with poor prognosis (Okano, 2011). Pathophysiology The clinical expression of EBV infection is determined by the T-lymphocyte cellular response. Unproductive T-cell retort cause uninhibited B-cell propagation, ensuing B-lymphocyte malignancies or B-cell lymphomas. Fever is due to immune response where cytokine liberation is followed by B-lymphocyte attack by EBV. Lymphocytosis and pharyngitis occur due proliferation of EBV-infected B lymphocytes (Higgins et al., 2007; Dorothy et al., 2006). Conclusion The virus possesses prolonged latency period, and displays symptoms like fever and sore throat which could be confusing with the common cold symptoms and also infection by other organisms such as Toxoplasma gondii. It is therefore essential to have a undergo differential diagnosis to confirm the acute infectious mononucleosis especially in immuno-compromised individuals. The present article is an effort to highlight the symptoms and confirmatory diagnostic tests to assess the IM cases. Although the disease condition is self-limiting but treatment with the antibiotic is recommended. Differential Diagnoses of Infectious Mononucleosis Clinical Parameters Epstein-Barr Virus Cyto-megalovirus Toxo-plasmosis Viral Hepatitis Symptoms Fatigue +++ + +/- + Malaise ++ + - + Mild sore throat + + +/- +/- Early maculopapular rash ± - - +/- Signs Early bilateral upper eyelid edema ± - - - Unilateral localized adenopathy - - + - Bilateral posterior cervical adenopathy + + - +/- Tender hepatomegaly +/- +/- - + Splenomegaly + +/- +/- - Laboratory abnormalities WBC count N*/- N/- N ¯ Elevated SGOT†/SGPT‡ ++ + +/- +++ Atypical lymphocytes (≥ 10%) + + - - Thrombocytopenia +/- +/- - +/- Elevated IgM§ CMV titer - + - - Elevated IgM EBV VCAII titer + - - - Elevated IgM toxoplasmosis titer - - + - Elevated hepatitis (eg, A, B, D) IgM titer - - - + *Normal † Serum glutamic-oxaloacetic transaminase ‡ Serum glutamic-pyruvic transaminase § Immunoglobulin M II Viral capsid antigen (Web. Infectious Mononucleosis Clinical Presentation). Reference List Chamberlain, N. R., ed. 21 January 2010. Infectious mononucleosis. [online] Available at: [Accessed 10 October 2012]. Dorothy H.C., Macsween, K.F., Higgins, C.D., Thomas, R., McAulay, K., Williams, H., Harrison, N., Reid, S. et al., 2006. A Cohort Study among University Students: Identification of Risk Factors for Epstein-Barr Virus Seroconversion and Infectious Mononucleosis. Clin Infect Dis, 43(3), pp. 276-282 Higgins, C.D. et al., 2007. A Study of Risk Factors for Acquisition of Epstein Barr Virus and Its Subtypes. The Journal of Infectious Diseases, 195, pp. 474-82. Hoffbrand, V., Paul, M. and Pettit, J. 2006. Essential Haematology, 5th ed. New Jersey, NYSE: John Wiley & Sons. Karen, F.M., Higgins, C.D., McAulay, K.A., Wlliams, H., Harrison, N., Swerdlow, A.J. and Crawford, D.H., 2010. Infectious Mononucleosis in University Students in the United Kingdom: Evaluation of the Clinical Features and Consequences of the Disease. Clinical Infectious Diseases, 50(5), pp. 699-706 Merlo, A., et al., 2010. The interplay between Epstein-Barr virus and the immune system: a rationale for adoptive cell therapy of EBV- related disorders. Hematologica, 95(10), pp. 1769-1777. Meaning of Infectious Mononucleosis, n.d. Hyperdictionary, [online]. Available at: [Accessed 10 October 2012]. Okano, M.M., and Gross, T.G., 2012. Acute or Chronic Life- Threatening Diseases Associated With Epstein-Barr Virus Infection. Am J. Med Sci, 343(6), pp. 483-89. Ryan, K.J. and Ray, C.G., 2004. Sherris Medical Microbiology: An Introduction to Infectious Diseases, 4th ed. New York, NY: McGraw Hill. pp. 566-69. Ulff-møller, C.J., Nielsen, N.M., Rostgaard, K., Hjalgrim, H. and Frisch, M., 2010. Epstein-Barr virus-associated infectious mononucleosis and risk of systemic lupus erythematosus. Rheumatology (Oxford, England), 49(9), pp.1706-12. Read More