Antibiotic prescribing and risk of herpes zoster: a case-control study

Study type
Protocol
Date of Approval
Study reference ID
20_134
Lay Summary

Both bacteria and viruses are extremely common throughout the human body. These colonies are collectively known as the microbiome. The microbiome is particularly large in the human gut but is also present elsewhere, in the nose/back of the mouth, the lungs, the skin, etc. A ‘healthy microbiome’ is believed to be important for human health. In previous research we have tried to assess whether antibiotics, given against a bacterial infection, damage the microbiome so resulting in higher risk of other diseases. We have shown increased risk for meningitis, rheumatoid arthritis and colorectal cancer following antibiotic consumption, often years earlier.

Antibiotics are effective against bacteria but not viruses. Yet one of our earlier findings was that prior antibiotics increased the risk for both bacterial and viral meningitis. The mechanism is unclear but possibly linked to the ecological relationships between bacteria and viruses in the human microbiome. We would like to examine this effect further by investigating whether taking antibiotics triggers shingles, a viral infection caused by reactivation of chickenpox virus that has lain dormant in the body usually from childhood. If there is a relationship, we would later like to investigate whether a ‘damaged microbiome’ caused by previous antibiotic consumption increases vulnerability to other viruses, in particular covid-19.

Technical Summary

Antibiotics, given to combat a specific infection, may produce collateral damage to the microbiome. This effect may be important as a ‘healthy microbiome’ seems to be implicated in its host’s health. Our group has been investigating this phenomenon in a series of case control studies using primary care data. In these studies we have shown that prior antibiotics increased the risk of bacterial meningitis, we hypothesise by damaging the nasopharyngeal microbiome in which meningitis organisms are often commensals; we have also shown increased risk of rheumatoid arthritis, we hypothesise by interfering with the immune response that is known to be an important function of the gut microbiome; and we have shown an increased risk of colorectal cancer, we hypothesise through damage to the protective effect of gut bacteria. One of the surprising findings in these studies was that prior antibiotics increased the risk of viral meningitis just as much as bacterial meningitis. Antibiotics have no direct effect on viruses so we surmise that change in the bacterial microbiome results in changes in the viral microbiome whether through affecting some immune response or by other ecological mechanisms. We would now like to investigate further this (indirect) relationship of antibiotics to the viral microbiome by seeing whether prior antibiotics increase the risk of reactivating herpes zoster. We therefore propose carrying out a case control study, comparing the antibiotic history of patients with herpes zoster with a control group without the disease. If there is an effect, it may have an important bearing on vulnerability to other viral infections such as covid-19.

Health Outcomes to be Measured

The main outcome measure of the study is shingles/herpes zoster. Diagnoses of shingles will be identified using Read medical codes.

Collaborators

David Armstrong - Chief Investigator - King's College London (KCL)
Alex Dregan - Corresponding Applicant - King's College London (KCL)
Mark Ashworth - Collaborator - King's College London (KCL)
Patrick White - Collaborator - King's College London (KCL)