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Herpesviruses are enveloped, double-stranded DNA viruses (120-
240 kb) encoding for more than 35 proteins. After an acute
infection, lifelong latency follows with the potential for relapse
to occur later in life, especially if the individual becomes
Herpesviruses are divided into three groups:
Epidemiology and Pathogenesis
- α-herpesviruses are fast-growing cytolytic viruses that establish
latent infections in neurones (e.g. herpes simplex and varicella
- β-herpesviruses are slow-growing viruses that become latent in
secretory glands and kidneys (e.g. cytomegalovirus [CMV], HHV6
- λ-herpesviruses are latent in lymphoid tissues (e.g. Epstein-Barr
virus [EBV], HHV-8).
- Transmitted vertically or by close contact.
- Infection occurs later in life with increasing wealth.
- Approximately 50% of adults in the UK have been infected.
- Infection may be transmitted to the fetus before or after birth.
- Infection may also be acquired from blood transfusion or organ
- Neonatal infection can be severe (see Congenital and perinatal infections
), or may be
initially be asymptomatic, later leading to the development of
deafness and/or to developmental milestone delay.
- Postnatal infection is usually mild.
- Immunocompromised patients, especially those with HIV infection
or who have undergone organ transplantation, may develop
severe pneumonitis, retinitis or gut infection through reactivation
of latent infection or infection from the donor organ.
Treatment and Prevention
Epidemiology and Pathogenesis
- Severe infections that threaten life or sight should be treated
with ganciclovir, together with immunoglobulin in the case of
- Valganciclovir, the ester of ganciclovir, is an oral preparation
used for initial treatment and maintenance.
- Alternatives, all of which are more toxic, include foscarnet and
cidofovir, a DNA polymerase chain inhibitor.
- Appropriate screening of donor organs and blood products can
reduce the risk of transmission.
As with CMV, infection is generally found in the very young in
developing countries and in adults in industrialized countries.
Gaining entry via the pharynx, the virus infects B cells and disseminates
widely. EBV is capable of immortalization of B cells
causing neoplasia: Burkitt's lymphoma (found in sub-Saharan
Africa in association with malaria); nasopharyngeal carcinoma (in
China); and lymphoma (in immunocompromised patients including
- Infection is characterized by fever, malaise, fatigue, sore throat,
lymphadenopathy and, occasionally, by hepatitis.
- Symptoms usually last about 2 weeks.
- Persistent symptoms may develop in a few patients.
- EBV infection is associated with tumours (see above).
- Rapid slide agglutination technique.
- Definitive diagnosis is by detection of specific IgM to EBV viral
- NAAT-based diagnosis can now also be used.
The pattern of immune response to Epstein-Barr nuclear antigen
complex (EBNA), latent membrane protein, terminal protein, the
membrane antigen complex and the early antigen (EA) complex
allow the stage of infection to be determined.
Human herpesviruses 6 and 7
Human Kaposi sarcomavirus or human herpesvirus 8
- The sole member of the Roseolovirus genus, herpesvirus 6
(HHV-6) has two subtypes, A and B, which infect human T cells.
- Transmission is probably through infected saliva; almost all
individuals are infected by the end of their second year.
- The infection, known as 'exanthem subitum', is characterized by
a 3 to 5-day febrile illness that settles as the rash appears.
- Asymptomatic infection is common.
- It may be associated with febrile convulsions and encephalitis,
although the latter is rare.
- Hepatitis is another rare complication.
- An IgG enzyme immunoassay (EIA) is available and a quantitative
NAAT may be helpful in the diagnosis.
- Infection with HHV-7 is almost universal by the age of 5, but
there is no clear association with disease.
- Diagnosis is with paired sera to detect antibody levels.
The human Kaposi sarcomavirus (HHV-8) is a λ-herpesvirus.
Transmission can be vertical from mother to child, and in the
young is by mucosal (non-sexual) contact. Initial infection is characterized
by infectious mononucleosis-like syndrome. Later,
immunocompromised patients, especially those with AIDS, may
develop Kaposi sarcoma. Diagnosis is principally by NAAT in
suspect tissues. Serological tests using EIA and indirect fluorescence