HHV-6 associated with ‘fever of unknown origin’ and cough in pediatric patients

HHV-6 associated with ‘fever of unknown origin’ and cough in pediatric patients

A Chinese study found HHV-6 DNA in whole blood samples from children with unexplained fever at significantly higher levels than in patients without fever. In addition, HHV-6 DNAemia was clinically associated with a cough, when compared to controls. The percentage with EBV DNAemia was also elevated in children with FUO, and both EBV and HHV-7 were found to be clinically associated with hepatitis.

Cases of fever without identified etiology are classified as “fever of unknown origin,” or FUO, and are then further divided into four subclasses: classic, nosocomial, immune-deficient and human immunodeficiency virus (HIV)-associated FUO. Infection is by far the most commonly identified etiology of FUO in all pediatric studies, and typical infections include brucellosis, tuberculosis, typhoid fever and common bacterial infections.

Blood samples were collected from 186 patients (151 children, 35 adults) with classic FUO and 143 normal individuals, and analyzed via multiplex PCR for the presence of HHV DNA, Herpes simplex virus (HSV)-1/2, Varicella zoster virus (VZV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Human herpes virus (HHV)-6 and -7. Herpesvirus DNA was detected in 63 (33.9%) of the FUO patients, and HHV-6 was detected in 14% of the FUO population vs. 4.9% of controls (P=0.007), while EBV was found in 9.7% of FUO patients vs. 2.8% of controls (P=0.013).  HHV-7 was found in 4.8% of patients with fever, compared to 0% of controls (p=0.02)

Fever is a very common presentation in children, and accounts for nearly one-third of all pediatric outpatient visits worldwide. Herpesvirus testing is currently not recommended in the diagnostic workup for FUO in children. The standard practice is to test only for bacteria by culture, HIV by serology and tuberculosis by skin testing. Occasionally testing is done for brucellosis, tularemia, EBV, CMV, toxoplasmosis, bartonellosis and fungal infections. The study was sponsored by the National Institute for Viral Disease Control and Prevention in Beijing.

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