Epstein-Barr virus: Difference between revisions
From IDWiki
No edit summary |
No edit summary |
||
Line 90: | Line 90: | ||
===Serology=== |
===Serology=== |
||
*Reviewed in [[CiteRef::de paschale2012se]] |
|||
*'''Anti-VCA''' (viral capsid antigens): most useful |
*'''Anti-VCA''' (viral capsid antigens): most useful |
||
**Anti-VCA IgM: appears by presentation and disappears within 4 to 6 weeks; most useful with acute and convalescent |
**Anti-VCA IgM: appears by presentation and disappears within 4 to 6 weeks; most useful with acute and convalescent |
Revision as of 01:35, 16 October 2020
Background
Microbiology
- A member of the Gammaherpesvirinae subfamily within the Herpesviridae family
- Double-stranded DNA inside an icosahedral protein nucleocapsid surrounded by a lipid envelope with glycoproteins
- Two strains (type 1 and 2) are serologically identical, but have unique epitopes
- Infection can remain quiescent in B cells for life
Epidemiology
- Acquired via oral secretions, e.g. by kissing or sharing of food
- Seroprevalence about 90-95% in adults, with about half of 5 year-olds already being seropositive
- Acquired earlier in low-income countries
- Highest morbidity is with young adults who develop infectious mononucleosis during primary disease
- Includes barracks and universities
Pathophysiology
- Acquired through mucous membrane contact of oral secretions
- Immune response primarily with cytotoxic T cells and NK cells
- Atypical lymphocytosis develops from CD8 cells
- Early response is against lytic antigens (including VCA and EA), and later response against latent proteins (EBNA1, EBNA2, EBNA3, and EBNALP)
- Response also creates IgM antibodies to sheep, horse, and cow RBCs, called heterophile antibodies
Clinical Manifestations
Childhood
- In childhood, mostly asymptomatic or mild febrile illness
- May develop rashes, neutropenia, or pneumonia
- Can cause lymphadenopathy
- Heterophile antibody may be negative if young; about 80% are positive by 4 years, though
Infectious Mononucleosis
- Caused by primary infection, typically in an adolescent or young adult
- EBV causes about 80% of mononucleosis, with the rest being CMV
- Incubation period 30 to 50 days, and can have asymptomatic viral shedding for up to a month before symptoms
- Symptoms include a triad of sore throat, fever, and lymphadenopathy (classically posterior cervical chain)
- Often preceded by prodromal symptoms of chils, sweats, anorexia, and malaise
- Can also have retro-orbital headaches, myalgias, and abdominal discomfort
- May have a rash which can take any form, and may have palatal petechiae
- Tonsils are sometimes exudative
- Often has splenomegaly, may have hepatomegaly, and rarely has jaundice
- With exposure to amoxicillin, almost all patients develop a diffuse maculopapular rash
- May have transient heterophile antibodies (see Diagnosis, below), as well as atypical lymphocytosis
- Resolves over 2 to 3 weeks, with fevers lasting up to 14 days, and fatigue lasting months
Complications
- Linked to a number of malignancies, including Burkitt lymphoma, nasopharyngeal carcinoma, and lymphoproliferative disorders
- Neurologic complications include meningitis, encephalitis, Guillain-Barré syndromes, optic neuritis, retrobulber neuritis, cranial nerve palsies, mononeuritis multiplex, brachial plexus neuropathy, seizures, subacute sclerosing panencephalitis, transverse, myelitis, psychosis, demyelination, and hemiplegia
Chronic Active EBV Disease
- See also Chronic active Epstein-Barr virus disease
- Classically in Japan and east Asia, possibly South America
- Progressive disease related to infection of NK or T cells rather than B cells
- Poor prognosis, with patients dying of progressive pancytopenia, hypogammaglobulinemia, or NK/T cell nasal lymphoma within a few years
Oral Hairy Leukoplakia
EBV-Associated Malignancies
Disease | EBV | Risk factors |
---|---|---|
Lymphoproliferative disease | 90% | Transplantation patients and immunosuppression |
Primary CNS lymphoma | 100% | HIV with low CD4 and immunosuppression |
Hodgkin lymphoma | 50% | Children and young adults |
Nasopharyngeal carcinoma | 100% | Southern Chinese, Inuit |
Gastric cancer | 4 to 100% | Unknown |
Endemic Burkitt lymphoma | 95% | African children |
Sporadic Burkitt lymphoma | 20% | HIV independent of CD4 |
Diagnosis
Point-of-Care Testing
- Monospot latex agglutination looking for heterophile antibodies
- 50% sensitive in the first week of illness, but up to 80-95% sensitive by the third week, and 98-100% specific, overall
- Less sensitive (10-50%) in young children (<4 years; lowest in those less than 2 years), with much lower negative predictive power
- Peak 2 to 5 weeks after symptom onset then usually decline quickly, but can persist for up to 6 to 12 months
- False positives are rare but can happen with rheumatoid disease, SLE, leukemia, lymphoma, and other infections including malaria, HIV, CMV, rubella, viral hepatitis and tularemia, and after administration of anti-thymocyte globulin
Serology
- Reviewed in 1
- Anti-VCA (viral capsid antigens): most useful
- Anti-VCA IgM: appears by presentation and disappears within 4 to 6 weeks; most useful with acute and convalescent
- Anti-VCA IgG: appears in acute phase, peaks at 2 to 4 weeks, then declines but remains positive for life
- Anti-EA (early antigen) IgG: appears in acute phase and falls to undetectable within 3 to 6 months (but may persist for years)
- Least useful test
- Anti-EBNA (EBV nuclear antigen): negative during acute phase converts after 2 to 4 months and stays positive for life
Immunocompetent Hosts
VCA-IgM | VCA-IgG | EBNA-IgG | Interpretation |
---|---|---|---|
– | – | – | Susceptible |
+ | Past infection or non-specific | ||
+ | – | Acute or past infection | |
+ | Past infection | ||
+ | – | – | Acute infection or non-specific |
+ | Uninterpretable | ||
+ | – | Acute infection | |
+ | Late primary infection or reactivation |
EBV-Associated Diseases
Disease | VCA-IgM | VCA-IgG | VCA-IgA | EA(D)-IgG | EA(R)-IgG | EA-IgA | EBNA-IgG |
---|---|---|---|---|---|---|---|
Chronic active infection | ± | ++ | ± | + | ++ | – | ± |
Burkitt lymphoma | – | ++ | – | ± | ++ | – | + |
ENT carcinoma | – | ++ | + | ++ | ± | + | + |
Hodgkin lymphoma | – | ++ | – | + | – | – | + |
Reactivation | ± | ++ | ± | + | ± | ± | ± |
PCR
- Useful for diagnosis of:
- Rare, chronic infection
- Early post-transplant lymphoproliferative disease
- Nasopharyngeal cancer
- As well as monitoring response to treatment
References
- ^ Massimo De Paschale. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions. World Journal of Virology. 2012;1(1):31. doi:10.5501/wjv.v1.i1.31.