6 MO PROLONGED FEB FIT NORMAL CSF HHV 6 ON BIOFIRE C1117036

HHV-6 infects most children within the first two years of life [2,3], but rarely may be acquired in adulthood [4]. In developed countries, the rate of seroprevalence among adults is generally >70 percent.

Congenital infection — Congenital HHV-6 infection occurs in approximately 1 percent of newborn infants [15-17]. Prenatal transmission may occur transplacentally in the setting of maternal reactivation or primary infection (ie, initial infection or infection with a new strain) or through germ-line transmission of chromosomally integrated HHV-6 from either parent [15,18]. The majority of what was previously considered to be congenital infection has been found to be due to chromosomally integrated HHV-6. In utero transmission of reactivated virus to the fetus/infant occurs rarely.

Most congenital infections with HHV-6 are asymptomatic. However, subtle neurodevelopmental effects may occur [19]. Although congenital HHV-6 has been associated with more severe manifestations (eg, respiratory failure, cardiac and gastrointestinal anomalies), the causal role of HHV-6 could not be determined

Immune-competent children — The classic manifestations of primary HHV-6 infection in immunocompetent children are roseola infantum (also known as exanthem subitum and sixth disease) and acute febrile illnesses with or without a rash. Other nonspecific symptoms, such as fussiness and rhinorrhea, can occur with primary infection in the absence of fever [2]. Other clinical syndromes (eg, hepatitis, myocarditis, encephalitis) may occur, sometimes in the setting of coinfection with another viral illness

Acute febrile illness — Primary HHV-6 infection often presents as a febrile illness without a rash [2,3,23-26]. In a prospective study of 81 children with well-defined onset of primary HHV-6 infection, fever (57 percent), fussiness (69 percent), and rhinorrhea (65 percent) were the most frequent manifestations [2]. Cough, diarrhea, and rash occurred in a minority of children. In another prospective study of 160 children who presented to the emergency department for acute febrile illness and were found to have primary HHV-6 infection, the mean temperature at the time of presentation was 39.6°C (103.3°F), compared with 38.9°C (102.0°F) in children without HHV-6 [3]. Fever was most commonly accompanied by irritability, otitis media, upper and lower respiratory symptoms, or diarrhea. Seizures occurred in 13 percent.

●Febrile seizures – HHV-6 infection has been associated with febrile seizures

Meningoencephalitis – Encephalitis of variable severity can rarely occur as a complication of roseola or as the primary manifestation of HHV-6 infection in otherwise immunocompetent hosts [32-39]. Panencephalitis is most common, but a focal necrotic encephalitis mimicking herpes simplex virus encephalitis has been reported [34,38,40]. The detection of viral antigens in neural cells suggests that the encephalitis is caused by a direct viral effect, but immune-mediators also may play a role

Mesial temporal lobe epilepsy – HHV-6 has been associated with mesial temporal lobe epilepsy (MTLE). In pathology studies, HHV-6 DNA was recovered more frequently from brain biopsies from patients with MTLE than from patients without MTLE, suggesting that HHV-6 has pathologic effects

Mononucleosis-like syndrome – HHV-6 has also been reported in association with a mononucleosis-like syndrome in infants and adults

Hepatitis – HHV-6 has also been reported in association with hepatitis in infants and young children [48-50].

Unproven associations — HHV-6 may be activated by a number of acute illnesses. In many of these clinical syndromes, it is difficult to establish HHV-6 as the causative agent. Associations between HHV-6 and the following conditions have been proposed but remain unproven:

●Pneumonitis [51]

●Myocarditis, dilated cardiomyopathy, and congenital heart disease [52-55]

●Immune thrombocytopenia [56,57]

●Viral associated hemophagocytic syndrome [58-60]

●Langerhans cell histiocytosis [61]

●Papular-purpuric "gloves and socks" syndrome [62]

●Gianotti-Crosti syndrome [63]

●Purpura fulminans [64]

●Guillain-Barré syndrome [65]

●Facial nerve palsy [66]

●Drug reaction with eosinophilia and systemic symptoms, also known as drug-induced hypersensitivity syndrome (see "Drug reaction with eosinophilia and systemic symptoms (DRESS)", section on 'Virus reactivation')

Children with cancer — In children with lymphoma, HHV-6 has been associated with decreased white blood cell count and hemoglobin

Transplant recipients — HHV-6 reactivation syndromes occur in approximately 50 percent of hematopoietic cell transplant (HCT) recipients and 20 to 62 percent of solid organ transplant recipients [70,71]. Clinical manifestations of HHV-6 in HCT recipients are discussed in detail separately. HHV-6 encephalitis is the most clearly established clinical manifestation of HHV-6 reactivation in allogenic HCT recipients and is the most common cause of encephalitis in this population. Early recognition and empiric therapy are crucial.

Evidence of HHV-6 infection — A variety of tests can be used to provide evidence of HHV-6 infection. These include isolation of HHV-6 from, or detection of HHV-6 DNA in, clinical specimens (eg, whole blood, plasma, serum, cerebrospinal fluid [CSF], brain, respiratory secretions or specimens obtained with bronchoalveolar lavage, lung tissue) or demonstration of a rise in HHV-6 immunoglobulin G (IgG) antibodies.


Choice of therapy – When treatment of HHV-6 infection is necessary, ganciclovir or foscarnet generally is preferred to cidofovir [1], because cidofovir is nephrotoxic