VZV in the Enteric Nervous System: Pathogenesis and Consequences

Varicella zoster virus (VZV) is the cause of chickenpox and shingles, but it also infects, becomes latent, and reactivates in nerve cells of the bowel to cause a gastrointestinal disorder ("enteric shingles"). The Investigators recently found that a chronic active VZV infection, a form of enteric shingles, is associated with achalasia, a severe disease in which the passage of food from esophagus to stomach is impaired. We now propose to eradicate VZV to determine whether its association with achalasia is causal, to identify the genetic basis behind VZV reactivation in the esophagus, and the relationship of mast cells to enteric shingles and abdominal pain.

Inclusion Criteria: * Male and female subjects aged 18-75 years old inclusive (females of childbearing potential should be on highly effective contraceptive methods) * Fluent in English and mentally capable to provide informed consent who present to Vanderbilt University Medical Center Digestive Diseases Center for treatment of achalasia. * Based on standard clinical practice, we anticipate that patients who undergo these treatments will have been formally diagnosed with achalasia and will be fit to undergo the selected treatment intervention. * All subjects must be able to undergo timed barium swallow testing, trans-nasal intubation for high-resolution manometry probe, and therapeutic intervention of a 2-month course of valacyclovir 1g TID and two injections of Shingrix over a two-month period. Exclusion Criteria: * Unstable medical illness with ongoing diagnostic work-up and treatment. Patients with well-controlled hypertension, diabetes and a remote history of ischemic heart disease that is deemed stable, as judged by the physician-investigator can be included. * Current neurologic or cognitive impairment which would make the patient an unsuitable candidate for a research trial.