Valtrex Therapy for Epstein-Barr Virus Reactivation and Upper Respiratory Symptoms in Elite Runners

Amanda J.Cox; Maree Gleeson; David B. Pyne; Philo U. Saunders; Robert L. Clancy; Peter A. Fricker


Med Sci Sports Exerc. 2004;36(7) 

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This study demonstrated a significant reduction in EBV excretion into saliva in response to the prophylactic administration of Valtrex™ to elite distance runners during routine high volume training. Only one subject had detectable EBV excretion during Valtrex™ treatment. The mean viral load in this subject, as well as in the overall study cohort, was significantly lower during the Valtrex™ treatment month compared with the levels in the nontreatment months. The EBV viral load in the washout month between treatments was lower compared with the baseline and placebo months, suggesting a possible carry-over effect of Valtrex™ treatment beyond 1 month in those who had received Valtrex™ as the first arm of the study. The results confirm Valtrex™ as an effective antiviral agent for control of EBV. However, the study failed to demonstrate prophylactic Valtrex™ administration as an effective intervention for reducing URS in this cohort of elite runners.

The reactivation of EBV, and the detection of EBV in saliva, has been reported in a variety of groups exposed to physical and environmental stressors including 79-100% of Antarctic winter expeditioners,[17] 91% of astronauts during preparation for spaceflight,[21] and 64% of EBV seropositive elite swimmers during intense training.[10] Cytotoxic T (TC) cells have been identified as responsible for the control of EBV infected B lymphocytes.[21] TC cell function has been reported to be disrupted in response to physiological stress,[16] allowing reactivation and excretion of EBV in the oropharynx and offering one possible mechanism for the high level of EBV detection among these groups. Athletes may be at particular risk of EBV reactivation as studies have demonstrated that intense exercise reduces the number of circulating TC lymphocytes.[2,20] However, the consistent SIgA concentrations observed in this cohort of elite distance runners during the study indicates that the training programs did not adversely affect their mucosal immune function over the study period. The absence of any substantial mucosal immune suppression may have reduced the likelihood of EBV reactivation in this cohort, and could explain the lower frequency of EBV detected than had been anticipated from the earlier investigation of elite swimmers.[10]

The previous study of elite swimmers had indicated a temporal relationship between the excretion of EBV in saliva at times of mucosal immune suppression and the subsequent appearance of URS.[10] It was anticipated that reducing EBV excretion through the prophylactic administration of Valtrex™ would result in a reduction in URS in the EBV seropositive subjects during the Valtrex™ treatment month. However, the converse was observed and the proportion of the EBV seropositive subgroup reporting URS was highest during the Valtrex™ treatment month. In this cohort of distance runners, there was no significant temporal relationship between EBV excretion and the appearance of URS, suggesting that etiological agents other than EBV were the likely cause of the URS. If infections other than EBV were responsible for the URS in the current study, Valtrex™, an antiviral agent with specific actions against the herpes group of viruses only, would not be effective in reducing the incidence of URS. However, the absence of a mucosal immune response during episodes of URS also indicates that the URS were unlikely to be related to an infectious cause.

Similar to the report by Heath et al.,[11] findings from this study infer that elite distance runners may experience a higher incidence of URS than elite athletes participating in other sports. Calculation of an annual incidence of URS from this study conducted during the winter months must be viewed with caution but the average incidence of 1.9 episodes of URS per person over 4 months equates to an annual incidence of 5.7 episodes. This incidence is higher than the 2.4 episodes of URTI per year reported for the age-related Australian general population[4] and the 2.7 episodes per year reported for elite swimmers training at the same sporting institute.[5] The increased incidence of URS in the elite distance runners may be related to the nature of the athletic sport. Distance runners undertaking prolonged and intensive exercise ventilate large volumes of air through the respiratory tract which may lead to mucosal drying, increased exposure to airborne particles, and localized inflammation.[15] Several groups have suggested that drying of the mucosal surfaces of the upper airways contributes to the transient mucosal immunosuppression observed after intense exercise, through a reduced secretion of SIgA onto mucosal surfaces.[14,15] Although mucosal SIgA suppression was not observed in this cohort, it is possible that mucosal drying, causing physical damage to the mucosal surface and a subsequent inflammatory response, was perceived by the athletes as symptomatic of URTI.

The possibility of inflammation contributing to the incidence of URS in the elite distance runners is supported by evidence of increased plasma concentrations of the pro-inflammatory cytokines interleukin-1 (IL-1) and interleukin-6 (IL-6) after intense exercise.[18] Further support for URS in runners resulting from of an inflammatory process can be found from the findings of a double-blind, placebo-controlled trial conducted by Schwellnus et al.[24] in a group of competitive male distance runners. Schwellnus et al. found that the use of the topical antiinflammatory Fusafungine™ during a 9-d period after a 58-km ultra-marathon event was able to reduce the incidence of URS.

This study highlights that investigations of URS and therapeutic interventions are sport specific and conclusions drawn for one sport cannot be universally applied to all sports or groups of athletes. However, in EBV sero-positive athletes suffering recurrent URS and with evidence of immunosuppression, therapeutic intervention with Valtrex™ may be worthy of consideration. Further investigations are needed of the inflammatory processes after intense exercise and any association with the appearance of URS.

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