Human herpesvirus 6 (HHV-6) is a member of the herpesvirus family, which also includes the viruses responsible for chickenpox and cold sores. This virus is exceptionally common, with most people becoming infected during early childhood. Scientists have identified two types, HHV-6A and HHV-6B, now classified as separate viruses. HHV-6B is the far more prevalent variant and is responsible for a common childhood illness. The role of HHV-6A is less defined, though it is more frequently studied in the context of adult health conditions.
The Primary HHV-6 Infection
The initial encounter with HHV-6B for most individuals occurs in infancy or toddlerhood, usually between six and 24 months of age. This primary infection causes a childhood sickness called roseola infantum, also known as sixth disease. Roseola accounts for a significant percentage of febrile illnesses in infants, and the illness classically begins with a sudden, high-grade fever that can reach 104°F (40°C) and lasts for three to five days.
Despite the high fever, many children remain relatively active and playful. Other symptoms can accompany the fever, including:
- General irritability
- A runny nose
- Mild diarrhea
- Swollen lymph nodes
A diagnostic feature of roseola appears after the fever abruptly subsides. Within a day of the temperature returning to normal, a distinctive, non-itchy rash of small pink or red spots emerges. The rash usually starts on the trunk before spreading to the arms, neck, and sometimes the face, fading within a couple of days. While rare in adults, a primary HHV-6 infection may present as a mononucleosis-like syndrome. In a small percentage of children, the high fever can trigger febrile seizures, which are brief and do not cause lasting harm.
How HHV-6 Spreads
The transmission of HHV-6B is highly efficient, primarily occurring through contact with the saliva of an infected individual. These respiratory secretions allow the virus to spread easily, especially in environments where young children are in close contact, such as daycare centers. Studies estimate that up to 90% of children contract HHV-6B by the time they are two years old.
This high rate of infection leads to a seroprevalence of approximately 95% in the adult population, meaning nearly all adults carry antibodies from a past infection. The prevalence and transmission routes of HHV-6A are not as clearly understood, as it is acquired less frequently and later in life. Because HHV-6B is so common, preventing initial infection is difficult.
Viral Latency and Reactivation
Following the resolution of the primary infection, HHV-6 does not leave the body. Like all members of the herpesvirus family, it enters a dormant phase known as latency, residing within host cells like salivary glands, certain white blood cells, and brain tissue. In this inactive state, the virus does not cause symptoms in healthy individuals.
The virus can reawaken from this dormant state in a process called reactivation. This occurs during periods when the immune system is significantly weakened. Reactivation is a particular concern for individuals who are immunocompromised, such as organ transplant recipients or patients with advanced HIV, as it can cause serious illness.
Reactivated HHV-6 can lead to a range of severe complications, including encephalitis (inflammation of the brain), pneumonitis (inflammation of the lungs), and bone marrow suppression. For transplant recipients, HHV-6 reactivation can also be associated with graft rejection. The risk is highest in those with profoundly suppressed immune systems, such as recipients of hematopoietic stem cell transplants.
Connection to Other Medical Conditions
Research has explored the relationship between HHV-6 and several chronic conditions involving the nervous and immune systems. A notable area of investigation is the link between HHV-6 and Multiple Sclerosis (MS). Studies have detected HHV-6 DNA and proteins in the brain lesions of MS patients more frequently than in healthy tissue. Antibodies against an HHV-6A protein have also been positively associated with MS risk.
Another condition with a studied link is Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Patients with ME/CFS can have higher levels of antibodies to HHV-6, suggesting viral reactivation may be more frequent in this group. The virus is thought to potentially contribute to the complex immune dysfunction seen in the syndrome.
It is important to interpret these findings with caution. The scientific community has established a strong association or correlation between HHV-6 and these diseases, but a direct causal link remains unproven. The reactivated virus could be a contributing factor, a trigger for symptoms, or an opportunistic event in an already weakened immune system. For example, one theory for MS is “molecular mimicry,” where an immune response against an HHV-6 protein mistakenly attacks a similar protein in the nervous system.
Diagnosis and Treatment Options
For most healthy infants, roseola is diagnosed based on its clinical symptoms, mainly the pattern of high fever followed by a rash, and laboratory tests are not needed. In complicated situations, such as in immunocompromised patients or cases with severe symptoms, specific diagnostic tests are used. These include polymerase chain reaction (PCR) tests to detect viral DNA and serology tests to measure antibodies.
Treatment for roseola is supportive, focusing on fever control and hydration, as the illness resolves on its own. Antiviral medication is not required for healthy children.
Antiviral drugs like ganciclovir and foscarnet are reserved for severe cases of HHV-6 disease resulting from reactivation in immunocompromised individuals. These medications are used for serious complications like HHV-6 encephalitis and are administered intravenously. They are not used for routine infections due to potential side effects.