eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Herpesvirus 6 Infection
Updated: Apr 13, 2009
Introduction
Background
After the discovery of human immunodeficiency virus (HIV) 1, HIV 2, and human T-cell lymphotrophic viruses (HTLV) I and II, an enhanced interest arose in the scientific community to isolate novel viruses from cultured lymphocytes of patients with HIV and other patients who are immunocompromised. The discovery of human herpesvirus 6 (HHV-6) is a result of this pursuit.
Human herpesvirus 6 was isolated from interleukin-2–stimulated peripheral leukocytes of HIV and lymphoproliferative disorders. Initially named human B-cell lymphotropic virus (HBLV), the virus later was designated human herpesvirus 6. Later, several strains of human herpesvirus 6 were isolated from the lymphocytes of children with exanthem subitum and patients with chronic fatigue syndrome and from the saliva of patients with HIV and healthy individuals. Human herpesvirus 6 is now recognized to have an extremely widespread distribution.
Like other herpesviruses, human herpesvirus 6 causes an initial infection, a life-long latency, and a clinical reactivation, especially in hosts who are immunocompromised.1 Human herpesvirus 6 may be involved in the pathogenesis of multiple sclerosis; however, further studies are required to establish this association.
Pathophysiology
The infectious agent in roseola infantum/exanthem subitum was demonstrated to be present in blood by inoculating healthy infants with serum from ill infants, a procedure considered very dangerous by today's standards. Later, Yamashi et al isolated the virus from blood and demonstrated seroconversion to human herpesvirus 6 in infected infants.2
Human herpesvirus 6 belongs to the Betaherpesvirinae subfamily and to the Roseolovirus genus. Human herpesvirus 6 is divided further into variants A and B. The virion particle has a typical structure of a herpesvirus with a central core containing the viral DNA, a capsid, and a tegument layer that, in turn, is surrounded by a membrane. At the molecular level, human herpesvirus 6 encodes proteins similar to immune mediators in the chemokine family. The functional chemokine is encoded by an open reading frame U83; U12 and U51 encode the 7 transmembrane proteins analogous to the chemokine receptors. This molecular mimicry seems to help human herpesvirus 6 in immune invasion and long latency in the host cells.
Frequency
United States
Seroprevalence is almost 100%. The virus is shed in and probably spread through saliva of asymptomatic seropositive children. Human herpesvirus 6B is the cause of most symptomatic infections of human herpesvirus 6.
International
Almost 100% in Europe, seroprevalence in the rest of the world also is close to 100% with certain exceptions, such as Morocco, which has 20% seroprevalence.
Mortality/Morbidity
Human herpesvirus 6 infections are mainly uncomplicated infections and have a self-limited course. Rarely, human herpesvirus 6 can be associated with fatal dissemination and death; 8 fatal cases have been reported. The causes of death were encephalitis, hepatitis,3 sudden death in infancy, hemophagocytic lymphocytosis, and disseminated infections. In studies by Prezioso et al and Hoang et al, atypical monocyte infiltrate was found in multiple organs, including the brain, spleen, lungs, liver, heart, renal cortex, lymph nodes, and intestine.4,5
Age
Possibly due to maternal antibody protection before this age, seropositivity is at its peak in infants aged 6-12 months. The virus is shed in and probably spread through saliva of asymptomatic seropositive children. Most children contract human herpesvirus 6 before they are aged 5 years.
Clinical
History
- Human herpesvirus 6 (HHV-6) is the single most common cause of hospital visits in infants with fever.
- Roseola is characterized by an initial febrile phase of 3-5 days, with temperatures reaching 40°C.
- With the fever, some children exhibit bilateral periorbital edema in the prodrome.
- At or near the period of defervescence, a maculopapular rash is observed on the infant's trunk and neck; however, this rash is found in the minority of patients (10%).
- Children can contract primary human herpesvirus 6 without manifesting a rash.
- Human herpesvirus 6 can be isolated from the blood for the first 5 days and later is found intermittently or persistently in saliva, stool, and, rarely, urine.
- Complications of febrile seizures (10%) and, rarely, encephalitis may occur.6
Physical
- High-grade fever higher than 39.5°C (103°F) persists for 3-5 days and then resolves abruptly.
- Rash appears after 12-24 hours of resolution of fever. In many incidents of human herpesvirus 6, rash appears during defervescence or within a few hours.
- Rash of roseola is erythematous, nonpruritic, mildly elevated, and consists of rose-pink papules (roseola meaning pink-colored rash). The rash blanches on pressure and mainly is distributed on the trunk, arms, and neck.
- The rash fades in 1-2 days.
- Most children are playful despite high-grade fever; however, anorexia, irritability, and listlessness may be the presenting signs.
- Undifferentiated febrile illness without rash or localizing signs is possible.
- Acute febrile illnesses with cervical and postoccipital lymphadenopathy, GI or respiratory tract signs, and inflamed tympanic membranes may occur.
- Febrile seizures occur in 10-15% of primary infections.
A 9-month-old infant boy presented with a 1-day history of high-grade fever and irritability. In the emergency department, the patient had a septic workup including lumbar puncture (adhesive bandage) with normal cerebrospinal fluid analysis results. He was admitted to the hospital.
A 9-month-old infant boy presented with a 1-day history of high-grade fever and irritability. In the emergency department, the patient had a septic workup including lumbar puncture with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on the third day of hospitalization. Within a few hours, an erythematous, pink papular (roseola), nonpruritic rash appeared, mainly on the trunk.
A 9-month-old infant boy presented with a 1-day history of high-grade fever and irritability. In the emergency department, the patient had septic workup including lumbar puncture with normal cerebrospinal fluid analysis results. He was admitted to the hospital. High-grade fever abruptly resolved on the third day of hospitalization. Within a few hours, an erythematous, pink papular (roseola), nonpruritic rash appeared mainly on the trunk. Patient was playful after supportive therapy. Antibiotics discontinued after 2 days of negative culture. Rash is distributed mainly over the trunk.
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| References |
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References
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Further Reading
Keywords
herpesvirus 6 infection, HHV-6, diagnosis, treatment, exanthem subitum, roseola infantum, sixth disease, HIV, human immunodeficiency virus, lymphoproliferative disorders, multiple sclerosis, encephalitis, rash, hepatitis, sudden death, high-grade fever, rash, febrile seizures, skin rash, lymphadenopathy, anorexia
