Paeds · infectious-diseases
Epstein-Barr virus and cytomegalovirus infection
Also known as Infectious mononucleosis · Glandular fever · Epstein-Barr virus infection · Cytomegalovirus infection · Congenital cytomegalovirus · Heterophile-negative mononucleosis
Fellowship topic on Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection in children: EBV as a gamma-herpesvirus transmitted by saliva that infects B cells via the CD21 receptor, whose CD8 T-cell response produces the atypical lymphocytes and the symptoms of infectious mononucleosis; CMV as a beta-herpesvirus and the most common congenital infection, causing direct cytopathic injury and sensorineural hearing loss; the classic adolescent mononucleosis triad and the amoxicillin rash, and the symptomatic congenital CMV newborn with petechiae, jaundice and thrombocytopenia; the differential of heterophile-positive versus heterophile-negative mononucleosis and of the sick neonate; heterophile antibody, EBV-specific serology, CMV IgG/IgM and PCR, and the 21-day saliva/urine PCR window; stepwise management from supportive care and activity restriction for EBV through corticosteroids for airway obstruction, valganciclovir for symptomatic congenital CMV, and pre-emptive ganciclovir for CMV in the immunocompromised; the splenic-rupture and return-to-play rules, EBV-lymphoproliferation, the EBV-multiple-sclerosis association, and congenital CMV screening; and ANZ/UK/US/Canada guidance.
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Target exams
Red flags
- An adolescent with infectious mononucleosis who develops drooling, dysphagia, a muffled voice or stridor — impending airway obstruction from tonsillar hypertrophy is an ENT and anaesthetic emergency; give corticosteroids
- Abdominal or shoulder-tip pain with hypotension and falling haemoglobin in a child with mononucleosis — splenic rupture is a surgical emergency
- A newborn with petechiae, jaundice, hepatosplenomegaly, thrombocytopenia or microcephaly — think congenital CMV and obtain saliva or urine PCR within 21 days of life
- A transplant or immunocompromised child with a rising quantitative CMV PCR and fever, colitis, pneumonitis or retinitis — pre-emptive antiviral therapy prevents progression to end-organ disease
- Fulminant EBV infection with fever, hepatosplenomegaly, pancytopenia and hyperferritinaemia — EBV-haemophagocytic lymphohistiocytosis, and consider X-linked lymphoproliferative disease in a boy
Life stages
Care settings
Clinical exam formats
Board mappings
- General Paediatrics and Infectious Diseases: infectious mononucleosis — clinical features, diagnosis and supportive management
- Neonatology: congenital CMV — recognition, the 21-day PCR window and valganciclovir for symptomatic disease
- Infectious diseases: EBV and CMV in the immunocompromised host — pre-emptive therapy, lymphoproliferation and haemophagocytic lymphohistiocytosis
- Community and population child health: congenital CMV screening, hearing-loss surveillance and prevention through maternal counselling
- General Paediatrics: the adolescent with infectious mononucleosis — diagnosis, amoxicillin rash, splenic rupture and return to play
- Neonatology: the symptomatic newborn with suspected congenital CMV — diagnostic window, valganciclovir and audiology
- Long Case / Structured discussion: congenital CMV — diagnosis, antiviral treatment, hearing and developmental outcomes, family counselling
- Communication station: explaining infectious mononucleosis, activity restriction and the amoxicillin-rash interaction to an adolescent and family
- Level 2 / 3 — Infection: EBV and CMV as common herpesvirus infections; clinical syndromes, diagnosis and management
- Neonatology and public health: congenital CMV screening, hearing loss and the role of antiviral treatment
- Foundation of Practice (FOP): infectious mononucleosis triad, amoxicillin rash, splenomegaly and complications
- Applied Knowledge in Practice (AKP): congenital CMV diagnosis, the 21-day PCR window, valganciclovir and heterophile-negative mononucleosis
- History-taking and management: the adolescent with prolonged fever, sore throat and fatigue
- Communication: explaining congenital CMV, hearing surveillance and antiviral treatment to a family
- General Pediatrics Content Outline — EBV infectious mononucleosis and congenital CMV: diagnosis, management and complications
- Infectious Diseases: heterophile antibody and EBV-specific serology, CMV PCR, valganciclovir and pre-emptive therapy
- Neonatology: the symptomatic congenital CMV newborn and the diagnostic window
- Patient Care: diagnosis and stepwise management of EBV and CMV disease across age groups and immune status
- Systems-Based Practice and Population Health: congenital CMV screening, hearing-loss surveillance and prevention
- Medical Knowledge: herpesvirus biology, latency, lymphoproliferation and the amoxicillin-rash interaction
- Medical Expert: EBV and CMV diagnosis, treatment and complications across the age spectrum
- Health Advocate and Collaborator: congenital CMV screening, audiology surveillance and transplant coordination
- Communicator: explaining activity restriction, antiviral treatment and long-term outcomes to families
Two viruses, two faces
EBV — the teenager
CMV — the newborn
VCA IgM says acute infection now. VCA IgG says infected at some point, past or present. EBNA (EBV nuclear antigen) means past infection — it appears late and persists for life. EA (early antigen) suggests recent primary infection or reactivation. The pair an examiner rewards: VCA IgM positive with EBNA negative = acute primary EBV. [1] [2]
Overview & Definition
Picture a sixteen-year-old brought to the emergency department with a week of fever, a sore throat so severe she cannot swallow her own saliva, and a exhaustion so complete she has stopped going to school. Her tonsils meet in the midline, her neck is draped in lymph nodes, and the registrar reaches for amoxicillin — only to see a confluent maculopapular rash erupt across her trunk two days later. This is Epstein-Barr virus infectious mononucleosis, and recognising the pattern — and withholding the antibiotic — is the clinical act that defines the encounter. [1] [2]
Now picture a different child: a ten-day-old baby on the postnatal ward who is jaundiced, covered in petechiae, and has a head circumference below the third centile. This is congenital cytomegalovirus, the most common congenital infection in the developed world, and the baby who will lose his hearing before his second birthday if the diagnosis is missed. The saliva or urine PCR must be sent now, inside the 21-day window, because once that window closes the chance to prove the infection is congenital is gone. [10] [9]
Epstein-Barr virus and cytomegalovirus are both human herpesviruses, and both establish lifelong latency after primary infection — but their clinical burden falls on entirely different patients. EBV is the adolescent's glandular fever: a self-limiting lymphoproliferative illness whose symptoms are largely the host immune response. CMV is the newborn's congenital infection and the immunocompromised host's opportunistic threat: a virus whose direct cytopathic injury damages brain, ear, blood and gut. The clinician's job is to recognise which child sits in front of them, to use the right test in the right window, and to match treatment to the host — supportive for the well adolescent, antiviral for the symptomatic newborn and the transplant recipient. [1] [8]
References13ShowHide
- [1]Cohen JI Epstein-Barr virus infection. N Engl J Med, 2000.PMID 10944566
- [2]Ebell MH Epstein-Barr virus infectious mononucleosis. Am Fam Physician, 2004.PMID 15508538
- [3]Peter J; Ray CG Infectious mononucleosis. Pediatr Rev, 1998.PMID 9707718
- [4]Taylor GS; Long HM; Brooks JM; Rickinson AB; Hislop AD The immunology of Epstein-Barr virus-induced disease. Annu Rev Immunol, 2015.PMID 25706097
- [5]Bjornevik K; Cortese M; Healy BC; Kuhle J; et al Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science, 2022.PMID 35025605
- [6]Abreu A; Nunes S; Botelho C Eosinophilia in Amoxicillin-Induced Rash in Infectious Mononucleosis. Cureus, 2023.PMID 36756024
- [7]Putukian M; McGrew CA; Benjamin HJ; et al American Medical Society for Sports Medicine Position Statement: Mononucleosis and Athletic Participation. Clin J Sport Med, 2023.PMID 37186809
- [8]Kimberlin DW; Jester PM; Sánchez PJ; Ahmed A; et al Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med, 2015.PMID 25738669
- [9]Rawlinson WD; Boppana SB; Fowler KB; Kimberlin DW; et al Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis, 2017.PMID 28291720
- [10]Fowler KB; Boppana SB Congenital cytomegalovirus infection. Semin Perinatol, 2018.PMID 29503048
- [11]Boppana SB; Ross SA; Shimamura M; Palmer AL; et al Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med, 2011.PMID 21631323
- [12]Kenneson A; Cannon MJ Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol, 2007.PMID 17579921
- [13]Jones CE; Bailey H; Bamford A; Galm F; et al Managing challenges in congenital CMV: current thinking. Arch Dis Child, 2023.PMID 36442957