Previous spaceflight studies indicate that reactivation of varicella zoster virus (VZV), particularly during longer duration spaceflights, can potentially lead to clinical disease including zoster, chronic neuropathic pain, vision loss, stroke, and cognitive impairment. Continued viral shedding after spaceflight may cause clinical disease in crew contacts including uninfected or immunocompromised individuals, as well as newborn infants. It is essential to develop countermeasures to prevent VZV reactivation during spaceflight to ensure the health of the crew, as well as the health of their contacts upon return.
In this investigation, VZV shedding in Antarctic expeditioners having patterns of VZV DNA shedding in saliva similar to patterns in astronauts will be studied. Investigators hypothesize that prophylactic administration of 1 gram daily of the antiviral drug valacyclovir to the Antarctic expeditioners will significantly reduce salivary shedding of VZV compared to placebo controls. Measures of stress and immune dysregulation should remain unaltered.
Countermeasure efficacy of valacyclovir will be determined by measuring VZV reactivation and shedding in saliva as well as measuring the physiological stress biomarkers (cortisol, DHEA, and salivary amylase) and immune markers (inflammatory cytokines) before, during, and after the winter-over period.
Specific aims are to:
- Study the effect of antiviral drugs on the reactivation and shedding of VZV in the saliva of Antarctic expeditioners before, during, and after winter-over.
- Study the effect of antiviral drugs on stress hormones and immune biomarkers (inflammatory cytokines,
etc.) in the saliva of Antarctic expeditioners before, during, and after winter-over
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Forty subjects will be selected to participate in the study. Potential subjects with a history of renal dysfunction, chronic headaches, or allergies to valacyclovir or similar drugs will be excluded from the study as will those over 65 years of age with declining renal function, those with known renal dysfunction, and those on other potentially nephrotoxic medications.
Twenty subjects will be randomly placed in the treatment group and twenty subjects in the control group.
The treatment group will receive valacyclovir treatment, (1 gram daily), during the Antarctic winter-over period. The control group will receive a daily placebo. VZV DNA, as well as other herpesviruses including herpes simplex virus type 1 (HSV1) and Epstein-Barr virus (EBV), will be measured before, during, and after the expedition.
Samples, consisting of 2.0 ml of passive drool saliva, will be collected once in the two months preceding winter-over (baseline), monthly (twelve times) during winter-over (deployment), and once in the two months after winter-over (return). Sampling will be done on five consecutive days at each time point. Then, samples will be frozen until processed.
Assays will be performed to monitor viral DNA, salivary stress hormones and salivary cytokines.
This investigation is in progress and results are not yet available. However, this experiment is expected to determine if prophylactic administration of valacyclovir is an effective countermeasure for reactivation and shedding of VZV during long-duration spaceflight missions.
Dehydroepiandrosterone (DHEA), salivary
Epstein - Barr virus (EBV) DNA, salivary
Herpes simplex virus type 1 (HSV1) DNA, salivary
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Interferon gamma (IFNg), salivary
Interleukin-1 (IL-1), salivary
Interleukin-10 (IL-10), salivary
Interleukin-12 (IL-12), salivary
Interleukin-13 (IL-13), salivary
Interleukin-2 (IL-2), salivary
Interleukin-4 (IL-4), salivary
Interleukin-5 (IL-5), salivary
Interleukin-6 (IL-6), salivary
Interleukin-7 (IL-7), salivary
Interleukin-8 (IL-8), salivary)
Varicella zoster virus (VZV) DNA, salivary
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
and performance, providing essential countermeasures and technologies for human space exploration.
Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify
the approach and research activities planned to address these risks, which are assigned to specific
Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.
The Human Research Roadmap is located at: https://humanresearchroadmap.nasa.gov/
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for information of how this experiment is contributing to the HRP's path for risk reduction.