Epstein-Barr Virus EBV

Introduction

  • Widely disseminated herpesvirus

  • Spread by intimate contact and asymptomatic shedders

  • Causes Infectious Mononucleosis

  • Associated with lymphoma

  • Reactivation not common

Epidemiology

  • Most infection subclinical

  • 95% of adults have positive AB

Virology

  • Latency phase

  • Human host is B and T lymphocytes, NK cells, monocytes + myocytes

Primary Infection

Acute Infectious Mononucleosis

  • Malaise, headache, low-grade fever

  • Tonsillitis + pharyngitis

  • Enlarged Cx lymphadenopathy, bilateral

  • Atypical lymphocytosis

  • Severe fatigue

  • Palatal petechiae, periorbital oedema, rashes

  • Nausea, vomiting, anorexia

Other

  • Infants and kids - variety of symptoms

  • Can affect any organ - pneumonia, myocarditis, pancreatitis, myositis, glomerulonephritis, genital ulcers, neurological syndrome like GBS, meningitis, optic neuritis, anaemia, DIC.

Complications

  • Rash - morbiliform

  • Airway obstruction - lymphoid hyperplasia and mucosal oedema

  • Splenic rupture - often spontaneous, typically days 4 to 21 of illness

  • Lemierre’s disease - infection spreads up with thrombophlebitis IJV

  • Chronic active EBV infection - Rare, life-threatening lymphoproliferative disorder

  • Oral hairy leukoplakia

  • Haemophagocytic lymphohistiocytosis - Fever, hepatosplenomegaly, cytopenia

  • Lymphoid granulomatosis

Malignancy

  • Burkitt Lymphoma - Jaw

  • Malignancy + HIV

  • Non-Hodgkin, Hodgkin, Nasopharyngeal carcinoma, Gastric cancer

Infectious Mononucleosis

  • Childhood EBV is often subclinical, <10% have clinical symptoms

  • Uncommon in adults

Transmission

  • Person to person

  • Breastfeeding

  • Sexual transmission

Pathogenesis

  • EBV contacts oropharyngeal epithelial cells

  • Virus replication

  • Infection B cells in the lymphoid-rich areas of the oropharynx

  • Incubation period 4 to 8 weeks

  • Circulating AB directed against virus

  • EBV-specific T lymphocytes are essential for acute and reactivation infection

  • T-cell activation

  • T helper cell activation + IL2

  • Atypical lymphocytes appear CD8+ T-cells and CD16+ NK cells

Clinical manifestations

  • As above

Labs

  • Lymphocytosis

  • Atypical lymphocytes

  • WC 12 to 18

  • Sometimes mild neutropenia and thrombocytopaenia

  • Elevated ALT AST

  • EBV antibodies usually not necessary

  • IgM and IgG have high sensitivity 97% and specificity 94%

Diagnosis

  • Symptoms + if needed serology

DDx

  • Strep

  • CMV

  • HIV

  • Toxoplasmosis

EBV-negative mononucleosis

  • 10% of illness is not caused by EBV

  • HIV

  • Hep B

  • CMV

  • Toxo

  • HHV-6 and 7

Treatment

  • Symptomatic

  • Corticosteroids

  • Antivirals - Aciclovir

Prevention

  • Reduce exposure

Return to sport

  • No earlier than 21 days, for high contact at least 28 days

Prognosis

  • Most individuals recover uneventfully and develop durable immunity

  • Fatigue and poor functional status can persist for months

  • 10% have fatigue for 6 months or more

  • Female sex and premorbid conditions increase risk

  • Reason for prolonged fatigue not clear

  • Maybe abnormal mitochondrial function and message levels for a variety of regulatory molecules

References