Herpes infections soar globally as new study reveals massive disease burden

Unveiling a global crisis: groundbreaking research highlights the immense impact of HSV infections on health, urging a shift towards vaccine innovation and prevention measures.

Study: Estimated global and regional incidence and prevalence of herpes simplex virus infections and genital ulcer disease in 2020: mathematical modelling analyses. Image Credit: sokolova_sv / Shutterstock

In a recent study published in the journal Sexually Transmitted Infections, a group of researchers estimated the global and regional incidence and prevalence of genital herpes simplex virus (HSV) infections and associated genital ulcer disease (GUD) in 2020, disaggregated by World Health Organization (WHO) region, sex, and HSV type.

Background

HSV type 1 and type 2 cause lifelong infections with significant global prevalence, resulting in substantial disease and economic burdens. Both types involve frequent subclinical shedding and symptomatic reactivations, adversely affecting quality of life, sexual health, and mental health, including depression and anxiety.

HSV-2 increases the risk of HIV acquisition and transmission threefold, demonstrating a synergistic relationship between the two infections. HSV-2 is primarily transmitted through sexual contact and is the leading cause of recurrent GUD. Neonatal herpes, which is transmitted during birth or through postnatal oral contact, has a high fatality rate and poses significant public health challenges.

HSV-1, typically acquired orally in childhood, can also cause serious complications, including neurological, corneal, and mucocutaneous conditions, and has emerged as a major cause of genital herpes in high-income countries. Further research is essential to develop effective prevention and treatment strategies, including vaccines.

About the Study

The study utilized data from systematic reviews and meta-analyses to provide the model input, updated as of March 30, 2022, to ensure completeness for all WHO regions. Only data collected up to 2020 were included, with country-level data reorganized into WHO region groupings.

The study also incorporated methodological enhancements, including refined calibration techniques and updated prevalence data, to improve the accuracy of its estimates. The validity of HSV diagnostic assays was assessed to address limitations such as sensitivity, specificity, and cross-reactivity between HSV-1 and HSV-2 antibodies.

Studies using unreliable laboratory methods were excluded. To ensure accuracy, assays had to detect type-specific antibodies, such as glycoprotein G-2 for HSV-2.

Meta-analyses were conducted using DerSimonian-Laird random-effects models, and pooled prevalence estimates were stratified by sex and age. These estimates were used to calibrate a mathematical model based on the WHO HSV estimation framework. Calibration incorporated prevalence data using a constant incidence rate model while adjusting for demographic shifts and sparse data in specific regions.

The study generated incidence and prevalence estimates for genital HSV-1 and HSV-2 infections among individuals aged 15-49 and oral HSV-1 infections for ages 0-49. GUD estimates were derived by applying natural history parameters to infection estimates. Uncertainty intervals were calculated using Monte Carlo simulations.

Study Results

HSV-2 remains the leading cause of genital infections and recurrent GUD. In 2020, the estimated number of new HSV-2 infections globally among individuals aged 15-49 years was 25.6 million (95% uncertainty interval [UI]: 23.1-29.4 million), with females accounting for 15.6 million cases and males 10.0 million.

The African region reported the highest incidence, contributing to 38.3% of all infections. Incidence rates were notably higher among younger adults, particularly in Africa and the Americas. This reflects both demographic trends and differing sexual behavior patterns across regions.

The estimated global prevalence of HSV-2 in the same age group was 519.5 million cases (95% UI: 464.3-611.3 million), with a higher prevalence in females (17.0%, 95% UI: 14.9-20.1%) compared to males (9.7%, 95% UI: 8.0-13.0%).

For genital HSV-1 infections, the number of new cases globally in 2020 among individuals aged 15-49 years was 16.8 million (95% UI: 10.6-22.4 million), evenly distributed between sexes. The Western Pacific region recorded the highest incidence.

The global prevalence of genital HSV-1 infections in the same demographic was estimated at 376.2 million cases (95% UI: 235.6-483.5 million), with slightly higher prevalence in females (10.5%, 95% UI: 6.4-13.8%) than males (9.9%, 95% UI: 5.9-13.4%).

Overall, the combined global incidence of genital HSV infections (HSV-1 and HSV-2) among individuals aged 15-49 years was 42.4 million (95% UI: 33.7-51.8 million), while the prevalence was 846.1 million (95% UI: 661.1-1034.2 million). GUD prevalence due to HSV-2 in this age group was 4.8% (95% UI: 3.0-7.5%), affecting an estimated 187.9 million people, with females experiencing a higher prevalence (6.2%, 95% UI: 3.8-9.6%) than males (3.5%, 95% UI: 2.2-5.8%).

For HSV-1, GUD prevalence was 0.5% (95% UI: 0.3-0.7%), affecting 16.7 million people globally. This results in a combined GUD burden of 204.6 million individuals, with significant psychosocial and economic consequences. The total number of person-days with HSV-related GUD was estimated at 8.8 billion (95% UI: 5.8-15.4 billion).

Regarding oral HSV-1 infections, the global prevalence in 2020 among individuals aged 0-49 years was 58.6% (95% UI: 53.5-62.1%), equating to approximately 3.4 billion people. The African region exhibited the highest oral HSV-1 prevalence, while the Western Pacific had the largest number of infected individuals.

Conclusions

To summarize, in 2020, 26 million individuals aged 15-49 acquired new HSV-2 infections, with 520 million living with HSV-2 and 188 million experiencing HSV-2-related GUD. Similarly, 17 million acquired new genital HSV-1 infections, with 376 million living with genital HSV-1 and 17 million experiencing HSV-1-related GUD.

Despite advances in treatment, prevention efforts remain inadequate, highlighting the critical need for HSV vaccines to curb transmission and reduce the disease burden. HSV-2 is primarily sexually transmitted, while HSV-1 is mostly acquired orally in childhood, though genital transmission is increasing. Genital HSV-1 infections are less recurrent than HSV-2.