#22: Clinical Significance of Human Herpes Virus 6 Positivity in Children

Background Human Herpes Virus 6 (HHV6) is a common childhood disease that is typically mild, however, cases where it is the causative agent of meningitis/encephalitis (ME) have been reported. The treatment for HHV6 ME consists of ganciclovir, which is associated with bone marrow suppression and renal insufficiency. While the clinical significance of the presence of HHV6 in cerebrospinal fluid (CSF) in adults has been studied, there is a paucity of research on the clinical significance of HHV6 in the CSF of children with ME. We want to determine if there is clinical significance to HHV6 positivity in the CSF of children. Methods 20 patients were included whose CSF tested positive for HHV6 on the CSF ME panel from Jan 1, 2017 to May 20, 2020. We obtained a sample of 80 patients whose CSF tested negative for every pathogen on the same CSF ME panel from the same period. Logistic regression was used based on age, sex, race/ethnicity, admission to neonatal intensive care unit (NICU)/pediatric intensive care unit (PICU), clinical presentation, and presence of abnormalities on neuroimaging to determine the propensity score matching (PSM) for each patient. (Table I) The HHV6 positive patients were matched with patients who tested negative for every pathogen on the panel at a 1:1 ratio and within a caliper size of 0.25. The odds ratio (OR) of neurological sequelae at discharge was determined by performing a logistic regression based on HHV6 status in both the group with PSM and without PSM. The length of stay between the HHV6 positive group and the control group were compared with and without PSM using Mann-Whitney U test with p<0.05 considered significant Results The OR for HHV6 positivity and experiencing neurological sequelae is 1.35 with a 95% confidence interval (CI) 0.133,13.721 (p=0.799) when compared to the control group without PSM. The OR for HHV6 positivity and experiencing neurological sequelae is 1 with a 95% CI 0.063, 15.988 (p=0.549) when compared to the control group with PSM. Table I shows the neurological sequelae between the HHV6 positive group, control group without PSM and the control group with PSM. It shows the Mann-Whitney U test comparing HHV6 status to the median length of hospital stay in both unmatched- and matched cohorts. We failed to reject the null hypothesis that there was a difference in the median length of hospital stay between HHV6 positive patients and all negative patients with and without PSM. Conclusion There is no clinical significance of HHV6 detection on the CSF ME panel in children as well as no statistical significance between the median length of hospital stay among HHV6 positive patients and all negative patients. Further, 10% of the HHV6 positive patients were inappropriately started on ganciclovir. Development of a consensus statement is in place regarding releasing the result of a positive HHV6 from the ME panel only among immunocompromised children to prevent inappropriate antiviral therapy.

Temporal lobe epilepsy associated with human herpes virus 6

Human herpes virus 6 (HHV-6) is a ubiquitous and most common pathogen that affects humans. Human herpes virus 6B (HHV-6B) is a wide spread human herpesvirus that infects most people when they are children, establishes latent infections in the central nervous system (CNS), especially in the hippocampus and amygdala, and induces neurologic diseases. HHV-6 can establish a latent infection and be reactivated by various stimuli. Recently, viral genomic DNA of HHV-6B has been detected in surgically removed brain tissues of intractable epilepsy patients, suggesting the involvement of HHV-6B in the pathogenesis of epilepsy. Temporal lobe epilepsy (TLE) has been shown to be closely related with HHV-6B. TLE patients with HHV-6B in their brains suffer from reiterative attacks of febrile seizures and hippocampal sclerosis. However, the mechanisms underlying the contribution of this virus to the development of TLE remains unknown. The direct damage and immune activation caused by the virus are involved in the process of neuron damage, abnormal neural circuit formation and glial cell proliferation. In addition, some cytokines like interleukin-17A (IL-17A), nuclear factor-kappa B (NF-κb), transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK) and phospholipase A2 are up-regulated and involved in the pathological process of TLE. More studies are needed to clarify the mechanisms underlying the link between HHV-6B and epilepsy, and identify biomarkers to recognize different patient groups for anti-inflammatory or immunomodulatory therapies.

Targeted treatment in viral associated inflammatory cardiomyopathy

Though generally self-limited, viral myocarditis can lead to acute cardiac failure or chronic dilated cardiomyopathy. We describe three cases of human herpes virus 6 (HHV6) associated -myocarditis unresponsive to conventional therapies, with detection of HHV-6 evidences and initiation of antiviral treatment, we observed significant improvement in clinical status of patients.

Human herpes virus-6 (HHV-6) pneumonitis and meningitis with viraemia in an immunocompetent adult patient

Human herpes virus-6 (HHV-6) infection is a common infection in the paediatric population and is increasingly reported in immunosuppressed adult patients. It has been reported as the causative agent of disease in few case reports in immunocompetent adults. We report herein an unusual case of HHV-6-associated viraemia, pneumonitis and meningitis in a patient who presented with dyspnoea, hypoxia, dry cough and headache. She was treated for atypical pneumonia with no improvement. Meningitis was suspected as headache kept worsening. HHV-6B was detected by PCR in the cerebrospinal fluid, and subsequently, in the bronchoalveolar lavage and serum samples. Studies were negative for the most common primary and secondary immunodeficiency syndromes, and serology could not be performed to differentiate virus reactivation from a primary infection. The patient was successfully treated with ganciclovir and had no residual sequelae.