Effect of Prophylactic Valacyclovir on the Presence of Human Herpesvirus DNA in Saliva of Healthy Individuals after Dental Treatment

Abstract

Human herpesviruses (HHVs) are ubiquitous pathogens that intermittently reactivate from latency. Transmission is believed to be facilitated by their frequent appearance in saliva. This study sought to understand the factors that influence the appearance of these viruses in saliva by examining the prevalence, pattern, and quantity of all eight HHVs in saliva of immunocompetent adults with a history of recurrent oral herpes simplex virus (HSV) infections following dental treatment and antiviral therapy. Valacyclovir or matched placebo was given (2 g twice on the day of treatment and 1 g twice the following day) to 125 patients in a randomized, double-blind controlled trial. Saliva, collected on the day of dental treatment and 3 and 7 days later, was analyzed using real-time quantitative PCR. At all visits, HHVs coinfected saliva. Over the course of the week, the DNAs of HHV-6 and HHV-7 were detected significantly more often (97% to 99% of patients) than Epstein-Barr virus (EBV; 64.8%), HSV-1 (13.0%), HHV-8 (3.2%), cytomegalovirus (2.4%), HSV-2 (0%), and varicella-zoster virus (0%), irrespective of drug treatment (P < 0.002). Mean genome copy numbers were highest for HSV-1 and HHV-6. Dental treatment did not influence asymptomatic viral shedding patterns. However, valacyclovir treatment resulted in significantly fewer patients shedding EBV at both postoperative visits compared with placebo (P < 0.008). These results suggest that HHVs are simultaneously present in the saliva of healthy adults at levels that could facilitate transmission, and valacyclovir therapy decreases the prevalence of EBV in saliva but has little effect on HHV-6 and HHV-7.Herpesviruses are ubiquitous pathogens that infect many animal species, including humans. Eight distinct members of the human Herpesviridae family have been identified. They include herpes simplex virus type 1 (HSV-1), HSV-2, varicellazoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV-7, and HHV-8 (Kaposi's sarcoma herpesvirus [KSHV]) (62, 81). These large DNA viruses each express more than 70 genes that specify a number of proteins and enzymes that can cause destruction of infected cells during the lytic infection (12,63). Following the initial lytic infection, HHVs establish a latent state in a diverse group of cells that ensures survival of the viral genome throughout the life of the host. Periodic reactivation and viral recrudescence (i.e., appearance with or without clinical symptoms) occur after stress and alterations in immune surveillance. Frank immunosuppression is associated with more severe disease and complications (e.g., encephalitis, pneumonia, hepatitis, and various forms of cancer) (2,7,13,14,40,53,57,60,67,68,78,83,84).Over 95% of the adult population are infected with HHVs (28,39,70,71,86). Infections occur following intimate contact with virus-laden secretions and in some case by fomites (e.g., nurseries, day care centers) (22,72). Saliva harbors most of the HHVs and appears to be an important mode for viru...

High Prevalence of Multiple Human Herpesviruses in Saliva from Human Immunodeficiency Virus-Infected Persons in the Era of Highly Active Antiretroviral Therapy

“…Of the bodily secretions and fluids documented to harbor HHVs, saliva appears important for transmission of several HHVs (11,16,17,33,52,53,55,56,69). The amount and frequency of HHVs appearing in saliva are likely determinants of risk for transmission (48).…”

“…They are shed in saliva asymptomatically and simultaneously at various rates and levels (48). The rates and viral loads detected are influenced by the biological properties of the virus, method of detection, frequency of sampling, oral health, and social behaviors and immunological status of the patient (46,49).…”

“…The rates and viral loads detected are influenced by the biological properties of the virus, method of detection, frequency of sampling, oral health, and social behaviors and immunological status of the patient (46,49). By sensitive PCR assay, the mean detection rates for EBV (30,31,48,63), CMV (15,44), HSV-1 (15,27,48,49,67), and HHV-8 (7,14,36,38,44,48) nucleic acids in the oral cavity of healthy adults at a single visit are approximately 31%, 9%, 6%, and Ͻ1%, respectively. The prevalence of HHVs in the saliva of human immunodeficiency virus (HIV)-seropositive patients has been less often reported, with reports generally focusing on individual prevalence, not the simultaneous presence of HHVs.…”

Cytomegalovirus Infection in Liver Transplantation

“…With age the increased prevalence of antibodies is common. This may not depend on the geographical area, but the socio-economic status may be important [10,[23][24][25][26][27][28]. The seroprevalence of CMV in populations at high socioeconomic level varies from 40% to 60%, increases after infection of early childhood and approximately 10% to 20% of children have their first infection episode before puberty [10].…”

Oral Ulcers Induced by Cytomegalovirus Infection: Report on Two Cases

“…Surprisingly, its only natural reservoir is the human body. [4][5] Viral transmission occurs by direct contact with secretions containing the virus, such as semen, cervical secretions, urine, saliva, breast milk, blood products, or transplantation of organs and tissues. 6 Primary CMV infection usually occurs in childhood.…”