Research Article: Risk factors for herpes simplex virus type-1 infection and reactivation: Cross-sectional studies among EPIC-Norfolk participants

Date Published: May 9, 2019

Publisher: Public Library of Science

Author(s): Harriet Forbes, Ben Warne, Lars Doelken, Nicole Brenner, Tim Waterboer, Robert Luben, Nicholas J. Wareham, Charlotte Warren-Gash, Effrossyni Gkrania-Klotsas, Michael Nevels.


The prevalence of, and risk factors for, herpes simplex virus type-1 (HSV-1) infection and reactivation in older individuals are poorly understood.

This is a prospective population-based study among community-dwelling individuals aged 40–79 years, followed from 1993, formed as a random subsample of the UK-based EPIC-Norfolk cohort. HSV-1 seropositivity was derived from immunoglobulin G measurements and frequent oro-labial HSV reactivation was self-reported. We carried out two cross-sectional studies using logistic regression to investigate childhood social and environmental conditions as risk factors for HSV-1 seropositivity and comorbidities as risk factors for apparent HSV oro-labial reactivation.

Of 9,929 participants, 6310 (63.6%) were HSV-1 IgG positive, and 870 (of 4,934 seropositive participants with reactivation data) experienced frequent oro-labial reactivation. Being born outside the UK/Ireland, contemporaneous urban living and having ≥4 siblings were risk factors for HSV-1 seropositivity. Ever diagnosed with kidney disease, but no other comorbidities, was associated with an increased risk of frequent HSV reactivation (adjOR 1.87, 95%CI: 1.02–3.40).

Apparent HSV-1 seropositivity and clinical reactivation are common within an ageing UK population. HSV-1 seropositivity is socially patterned while risk factors for oro-labial HSV reactivation are less clear. Further large studies of risk factors are needed to inform HSV-1 control strategies.

Partial Text

HSV-1 is one of eight herpesviruses that routinely infect humans.[1] It is thought to be transmitted via close contact in childhood and it establishes latency in sensory ganglia. HSV-1 reactivation causes outbreaks of oro-labial, oropharyngeal, or increasingly, genital ulcers,[2] but can also be asymptomatic. Oro-labial ulcers can also be caused by HSV-2 reactivation[3] and the two viruses are clinically indistinguishable. However, oro-labial HSV-2 reactivation is very infrequent.[3] The prevalence of HSV-1 infection varies by age, time and geographic setting, with European seroprevalence estimates ranging from around 50–80%.[4] Following infection only around 30% of individuals with serologic evidence of HSV-1 experience clinical reactivation[5] but the factors involved in infection susceptibility and control of latent infection are poorly understood.

In total 9,929 participants had HSV-1 serology data (first cohort) and 6,310 (64%) were seropositive for HSV-1 (Table 1). Of these seropositives, 4,934 participants (78%) had HSV reactivation data (second cohort—see Fig 1). The cohort was born between 1914 and 1957 and the median age of both cohorts was 62 years (IQR: 54–69) when serology specimens were collected. Compared to the main EPIC Norfolk cohort who attended the first health check, both the first and second cohort were more likely to be female and less likely to be >75 years, overweight and obese, current and former smokers and have high blood pressure (see S1 Table).

In this cohort of older community-dwelling individuals from England, we found a high prevalence of HSV-1 seropositivity (63.6%) and frequent apparent reactivation (17.6%). We found that childhood environmental and social conditions were associated with greater risk of HSV-1 seropositivity, specifically poorer socioeconomic status, having more siblings and living in an urban area. Common comorbidities were not associated with HSV reactivation with the exception of kidney disease, which was associated with a 2-fold increased risk, an association which was restricted to older females (≥65 years). Fatigue and stress increased the risk of HSV reactivation, as did having an outdoor job (an association restricted to males).

In this large population-based study, HSV-1 seropositivity and frequent reactivation in a community dwelling ageing population is common. Lower socioeconomic status, urban living and a greater number of siblings appear to be associated with a greater risk of HSV-1 infection. This study showed very little evidence that common clinical comorbidities increase the risk of orolabial HSV reactivation apart from possibly kidney disease, though the study was underpowered for some exposures. These data will help inform studies of HSV-1.




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