DEFINING PRIMARY HHV-6 AND HHV7 INFECTIONS IN CHILDREN

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Human Herpesvirus-6 (HHV-6) and Human Herpesvirus-7 (HHV-7) are newly identified Herpesviruses. They are ubiquitous, infecting most individuals in the first two years of life. Like other Herpesviruses, infection appears to be chronic and is thought to reactivate periodically throughout life. Despite the fact that these are common infections, their natural history is not well defined. This application proposes three studies to answer basic questions regarding the epidemiology of primary infection with HHV-6 and HHV-7. To date, what is known about primary infection comes from studies of children seen in emergency departments. The first study we propose is a large, prospective, population-based study of 200 newborns to better define the full range of illness and to explore potential risk factors for more severe illness. Data from symptom diaries will be correlated with primary infection as defined by onset of the viruses in saliva. Documentation of seroconversion is the current gold standard for diagnosis of HHV-6 infection, but by definition, it is not helpful in the clinical management of children in the acute setting. Diagnosis can be made more quickly with PCR. However, the sensitivity and specificity of PCR testing of blood and saliva for rapid diagnosis has not yet been determined. The second study will investigate febrile children who present to the emergency department to evaluate a PCR test for the rapid diagnosis of primary HHV-6 infection. For this study, infants under the age of two years presenting to the emergency department with fever will have whole blood, plasma, and saliva tested by PCR for HHV-6. These PCR results will be compared to acute and convalescent serology for HHV-6 to define the value of PCR of various bodily fluids for rapid diagnosis of HHV-6. The utility of PCR testing in the management of febrile infants will also be modeled using these data. The frequency and clinical significance of congenital infection with HHV-6 and HHV-7 is unknown. The third study will evaluate healthy newborns and newborns with abnormalities including prematurity, congenital defects, and acute illness to evaluate fetal and infant morbidity due to these viral infections. Congenital infection will be defined by specific IgM antibodies detected in the cord blood or by the presence of viral DNA in the saliva or the infants' blood within the first week of life. Healthy newborns and newborns with abnormalities will be compared with regards to the frequency of HHV-6 and HHV-7 congenital infection. If a higher frequency of congenital infection is found in the infants with abnormalities, a sub-group analysis of the different abnormalities will be performed for the purpose of hypothesis generation. Infants and young children commonly become infected with HHV-6 and HHV-7. The proposed studies will further define the spectrum of disease in children, evaluate the utility of PCR in the rapid diagnosis of primary infection, and explore the clinical significance of congenital infection. These studies will also give me the opportunity to develop the required skills to perform clinical research and to reach my long term goal; to become an independent investigator in an academic institution.