Characterizing the transitioning epidemiology of herpes simplex virus type 1 in the USA: model-based predictions

Abstract

Background: Herpes simplex virus type 1 (HSV-1) is a prevalent lifelong infection that appears to be undergoing an epidemiologic transition in the United States (US). Using an analytical approach, this study aimed to characterize HSV-1 transitioning epidemiology and estimate its epidemiologic indicators, past, present, and future.

Methods: An age-structured mathematical model was developed to describe HSV-1 transmission through oral and sexual modes of transmission. The model was fitted to the National Health and Nutrition Examination Surveys, 1976-2016 data series.

Results: HSV-1 seroprevalence was projected to decline from 61.5% in 1970 to 54.8% in 2018, 48.5% in 2050, and 42.0% in 2100. In < 3 decades, seroprevalence declined by > 30% for those aged 0-19 years, but < 5% for those aged > 60. Meanwhile, the number of new infections per year (oral and genital) was persistent at 2,762,000 in 1970, 2,941,000 in 2018, 2,933,000 in 2050, and 2,960,000 in 2100. Of this total, genital acquisitions contributed 252,000 infections in 1970, 410,000 in 2018, 478,000 in 2050, and 440,000 in 2100-a quarter of which are symptomatic with clinical manifestations. For those aged 15-49 years, nearly 25% of incident infections are genital. Most genital acquisitions (> 85%) were due to oral-to-genital transmission through oral sex, as opposed to genital-to-genital transmission through sexual intercourse.

Conclusion: HSV-1 epidemiology is undergoing a remarkable transition in the US, with less exposure in childhood and more in adulthood, and less oral but more genital acquisition. HSV-1 will persist as a widely prevalent infection, with ever-increasing genital disease burden.

Keywords: Genital herpes; Herpes simplex virus type 1; Incidence; Mathematical model; Oral herpes; Prevalence; United States.

Fig. 1

Fitting of the age-specific distribution of HSV-1 seroprevalence in the US. The fitted HSV-1 seroprevalence in each 5-year age band, compared to the National Health and Nutrition Examination Surveys (NHANES) data from 1976 up to 2016

Fig. 2

Temporal evolution of HSV-1 seroprevalence in the US. a Estimated HSV-1 seroprevalence in people aged 10–49 years, compared to the National Health and Nutrition Examination Surveys (NHANES) data. b Estimated reduction in HSV-1 seroprevalence per age group between 1976–1980 and 2013–2014, compared to the measured reduction in NHANES data. c Estimated asymptomatic as well as ever-symptomatic and clinically diagnosed genital herpes prevalence in HSV-1-antibody-positive and HSV-2-antibody-negative 20–49 years old population—the latter compared to self-reported NHANES data. HSV-1 genital herpes is defined as any HSV-1 infection acquired genitally, regardless of presence or absence of disease or clinical manifestations

Fig. 3

Age-specific relative contribution of orally acquired versus genitally acquired HSV-1 among prevalent HSV-1 infections in the US. Estimated age-specific distribution of oral herpes prevalence versus genital herpes prevalence in the total HSV-1-antibody-positive population in 2018 (a), 2050 (b), and 2100 (c). HSV-1 oral herpes is defined as any HSV-1 infection acquired orally, regardless of the presence or absence of disease or clinical manifestations. HSV-1 genital herpes is defined as any HSV-1 infection acquired genitally, regardless of the presence or absence of disease or clinical manifestations

Fig. 4

Relative contribution of oral herpes versus genital herpes to HSV-1 incidence in the US. a, b Contribution of orally acquired versus genitally acquired HSV-1 among new (incident) infections in the total population of all ages. c, d Contribution of orally acquired versus genitally acquired HSV-1 among new infections in those aged 15–29, 30–49, and > 60 years. Of note is that the different panels have different y-axis scales

Fig. 5

Relative contribution of the different HSV-1 modes of transmission to HSV-1 incidence in the US. a Projected contribution to HSV-1 oral herpes incidence of oral-to-oral transmission versus genital-to-oral (through oral sex) transmission. b Projected contribution to HSV-1 genital herpes incidence of oral-to-genital (through oral sex) transmission versus genital-to-genital (through sexual intercourse) transmission. c New HSV-1 oral herpes acquisitions by mode of transmission versus age in 2050. d New HSV-1 genital herpes acquisitions by mode of transmission versus age in 2050. HSV-1 oral herpes is defined as any HSV-1 infection acquired orally, regardless of the presence or absence of disease or clinical manifestations. HSV-1 genital herpes is defined as any HSV-1 infection acquired genitally, regardless of the presence or absence of disease or clinical manifestations

Fig. 6

Temporal evolution of key epidemiologic indicators of HSV-1 infection in the total population of all ages of the US. a Estimated orally acquired HSV-1 seroprevalence versus genitally acquired HSV-1 seroprevalence. b Estimated orally acquired HSV-1 incidence rate versus genitally acquired HSV-1 incidence rate. c Estimated annual number of new (incident) orally acquired versus genitally acquired HSV-1 infections. Of note that the y-axis scales are different for the oral versus genital estimates