Case Study • 17-year-old high school student • No prior major illnesses • Low grade fever • Malaise- several days • Sore throat • Swollen cervical lymph nodes • Increasing fatigue • Discomfort in left upper quadrant of abdomen • Sore throat, lymphadenopathy and fever resolve over next two weeks • Full energy level does not return for another six weeks
Herpesviruses • Linear genome • dsDNA with nicks or gaps • Enveloped • Icosahedral capsid • Infect humans • Remain latent within host cell after primary infection and may become activated
EBV vs. Cytomegalovirus (CMV) CMV Infection • Human herpesvirus type 5 • Severe systemic disease can develop in infants • Negative heterophile antibody test and serology • EBV Infection • Human herpesvirus type 4 • Usually asymptomatic in infants • Severe pharyngitis
Tests Performed: • CBC count • Liver function test • Heterophile antibody test - differential absorption - heterophile antibody titers - monospot • EBV serology • Imaging Studies
CBC count • 40%-70% of patients have leukocytosis with a WBC count of 10,000-20,000 cells/mL. 10% of patients will have a WBC count greater than 25,000 cells/mL by the second week. • 80-90% of patients have lymphocytosis with more than 50% lymphocytes. 20-40% of the lymphocytes are atypical. The illness typically lasts for 2-6 weeks. • The atypical lymphocytes appear larger, have a lower nuclear-to-cytoplasmic ratio, and have a nucleus that is less dense than that of normal lymphocytes.
Liver function test • 80-100% patients have elevated liver function test results. • Alkaline phosphatase, aspartate aminotransferase (AST), and bilirubin levels peak 5-14 days after onset, and gama-glutamyltransferase (GGT) levels peak at 1-3 weeks after onset. • Lactic acid dehydrogenase (LDH) levels are increased in approximately 95% of patients. • Most liver function test results return to normal within 3 months.
Differential absorption test • Bovine RBCs absorb infectious mononucleosis heterophile antibodies, but Guinea pig kidney cells do not. • Serum from a patient with infectious mononucleosis agglutinates sheep RBCs after absorption with guinea pig cells, but no agglutination occurs after absorption with bovine RBCs.
Heterophile antibody titers • The titer of heterophile antibody is determined with tube dilution. A titer of 1:40 after absorption with guinea pig cells is considered positive for acute infectious mononucleosis. • 60-90% of patients have test results that are positive for heterophile antibodies in the second or third weeks. Then it begins to decline until less than 1:40 within 2-3 months. • As many as 20% of patients still have positive titer resutls within 1-2 years. 75% of patients have positive horse RBC agglutinin findings at 1 year. • 10-30% of children younger than 2 years and 50-75% of children aged 2-4 years develop heterophile antibodies with primary EBV infection.
EBV serology • Antibodies to EBV antigens include antibodies to viral capsid antigen (VCA), early antigens (EAs), and EBNA. • They are measured with enzyme immunoassays, indirect immunofluorescence assays, and immunoblot assays. • Antibody to the restricted component of early antigens (EA/R) is measurable in children younger than 4 years with primary EBV infection or in patients with nonsymptomatic infection. • 80% of the patients with infectious mononucleosis have antibodies to the diffuse-staining component of EA (EA/D). • Patients who are immunocompromised and have persistent or reactivated EBV infections often have high levels of antibodies to EA/D or EA/R.
EBV serology • In patients with a more prolonged symptomatic illness, EA/D may become umeasurable, and EA/R results may become positive. • The antibody pattern in 3-12 months includes positive findings for VCA-IgG and EBNA antibodies, negative VCA-IgM antibodies, and positive EA antibodies. • After 12 months, EA antibodies are not present.
EBV serology Kit Components Peptide-coated paddles, IgM Enzyme conjugate, IgG Enzyme conjugate, Substrate 1, Substrate 2, Substrate mixing vial, Wetting agent /wash solution, Stop solution, Paddle storage bag. Positive and negative controls available separatly. Indirect immunofluorescence assay designed for qualitative and/or semi-quantitative detection of IgM antibodies to Epstein-Barr Virus viral capsid antigen (EBV-VCA) in human serum.
Monospot • Slide tests use either horse RBCs or bovine RBCs. • Bovine RBCs are specific for acute infectious mononucleosis heterophile antibodies, while horse RBCs are more sensitive. • Low sensitivity (63%-84%), with a negative predictive value of more than 10%. • Rarely yield false-positive results in patients.
Monospot test Qualitative or semi-quantitative differential slide agglutination test for detection of infectious mononucleosis heterophile antibodies in human serum or plasma. The test is based on fresh horse RBC. Kit Components Guinea Pig Antigen (Reagent I), Beef RBC Antigen (Reagent II), Horse RBC (Indicator cells), Positive control, Negative control, Glass Slide, Microcapillary Pipettes, Rubber Bulbs, Plastic Pipettes, Wooden Applicators
Imaging Studies • Not for diagnosing acute infectious mononucleosis. • Chest radiography can detect lymph node enlargement, but should prompt consideration of other diagnoses. • Abdominal CT scanning can reveal splenic rupture. • Ultrasonography, radionuclide scanning or the spleen may assist diagnosis.
Diagnosis • Symptoms and age of patient • Increased percentage of atypical mononuclear cells • Positive reaction to “mono spot” test - Positive for heterophile antibodies • Serology results: -Positive EA, VCA-IgM, VCA-IgG, EBNA
Epstein-Barr Virus • Also known as Human Herpesvirus 4 • Infectious mononucleosis; hepatitis; retinitis; pneumonia; colitis; Burkitt’s lymphoma, certain B-cell tumors; nasopharyngeal carcinoma • EBV remains dormant or latent throughout lifetime • Affects 95% of the population • Only 5% of patients acquire EBV from someone who has an acute infection • More transmission in areas of lower socioeconomic groups and crowded conditions • Patients that are immunocompromised (organ allograft recipients or HIV-infected) are at greater risk. • Infections do not occur in epidemics
Infectious Mononucleosis • Transmission: -Intimate contact of oral saliva; usually between an uninfected person and EBV-seropositive person who is shedding the virus asymptomatically -Transfusion of blood products • Widespread; infection apparent chiefly in young adults
Symptoms: • Fatigue- usually lasts 2-3 weeks. • Splenomegaly- occurs in about 50% of cases in 2nd-3rd week and lasts 6-8 weeks. This can cause anemia = fatigue. • Fever- peaks in afternoon • Pharyngitis- may be severe and painful • Lymphadenopathy- usually symmetric, involves group of nodes; may be the only manisfestation • Cardiac, jaundice, periorbital edema, palatal enanthema, maculopapular eruptions, CNS problems (rare) • Complications: neurological, hematologic, splenic rupture, respiratory, and hepatic • Incubation period is about 30-50 days • Asymptomatic in young children • Not fatal Palatal petechiae, erosions and a greyish exudate in a patient with infectious mononucleosis.
Treatment: • No specific treatment • Rest • No specific antiviral drug • Corticosteroids can be used for swelling of pharyngitis, airway obstruction, severe thrombocytopenia, and hemolytic anemia.
References: 1. Bennett, N. (2007, July 9). eMedicine from WebMD. Retrieved October 31, 2007, from http://www.emedicine.com/ped/topic705.htm 2. Canada.com. Retrieved November 14, 2007, from http://bodyandhealth.canada.com/condition _info_popup.asp?channel_id=1020&disease_id=75§ion_name=channel_ condition_info 4. Common Viral Infections. Retrieved November 15, 2007, from http://www.link.med.ed.ac.uk/RIDU/Viral.htm 5. eMedicineHealth. Retrieved November 14, 2007, from http://www.emedicinehealth.com/swollen_lymph_glands/page2_em.htm 6. Lab Tests Online. Retrieved October 30, 2007, from http://www.labtestsonline.org/understanding/analytes/mono/multiprint/html 7. Mayo Clinic Staff. (2006, November 10). Mayo Clinic.com. Retrieved November 14, 2007, from http://www.mayoclinic.com/health/enlarged-spleen/DS00871 8. MedlinePlus. Retrieved October 30, 2007 from http://www.nlm.nih.gov/medlineplus/print/ecy/article/003513.htm 9. MedlinePlus. Retrieved November 13, 2007 from http://www.nlm.nih.gov/medlineplus/ency/article/000591.htm 10. MedlinePlus. Retrieved November 15, 2007 from http://www.nlm.nih.gov/medlineplus/ency/article/003276.htm 11. National Center for Infectious Diseases. Retrieved October 30, 2007, from http://www.cdc.gov/ncidoc/diseases/ebv/htm 12. The Merck Manuals Online Medical Library. Retrieved October 31, 2007, from http://www.merck.com/mmhe/print/sec17/ch198/ch198g.htm 13. Smith, C.H. (1956, June). Infectious Mononucleosis. The American Journal of Nursing, 56 (6). Retrieved November 14, 2007, from http://www.jstor.org