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Jennifer S. Smith, N. Information on age- and sex-specific prevalence of herpes simplex virus HSV types 2 and 1 infections is essential to optimize genital herpes control strategies, which increase in importance because accumulating data indicate that HSV-2 infection may increase acquisition and transmission of human immunodeficiency virus. This review summarizes data from peer-reviewed publications of type-specific HSV seroepidemiologic surveys. HSV-2 prevalence is, in general, highest in Africa and the Americas, lower in western and southern Europe than in northern Europe and North America, and lowest in Asia. HSV-2 and -1 prevalence, overall and by age, varies markedly by country, region within country, and population subgroup.


Herpes simplex virus type 2 HSV-2 infection causes ificant disease globally. Adolescent and adult infection may present as painful genital ulcers. Neonatal infection has high morbidity and mortality. The global burden of HSV-2 infection was last estimated for Here we present new global estimates for of the burden of prevalent existing and incident new HSV-2 infection among females and males aged 15—49 years, using updated methodology to adjust for test performance and estimate by World Health Organization WHO region.

We conducted a literature review of HSV-2 prevalence studies world-wide since Prevalence values were adjusted for test sensitivity and specificity.

Persistent genital herpes simplex virus-2 shedding years following the first clinical episode

The model estimated prevalence and incidence by sex for each WHO region to obtain global burden estimates. Uncertainty bounds were computed by refitting the model to reflect the variation in the underlying prevalence data. Inwe estimate that there were million people aged 15—49 years range: — million living with HSV-2 infection world-wide We also estimate that in The highest burden was in Africa.

However, despite lower prevalence, South-East Asia and Western Pacific regions also contributed large s to the global totals because of large population sizes. The global burden of HSV-2 infection is large, leaving over million people at increased risk of genital ulcer disease, HIV acquisition, and transmission of HSV-2 to partners or neonates.

These estimates highlight the critical need for development of vaccines, microbicides, and other new HSV prevention strategies. Editor: William P. This is an open-access article distributed under the terms of the Creative Commons Attributionwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. WHO commissioned the study, advised as required during the study, co-ordinated data requests, helped with redrafts, and approved the manuscript submission.

KJL had full access to all the data in the study and had final responsibility for the decision to submit for publication. Competing interests: The authors have declared that no competing interests exist. Herpes simplex virus type 2 HSV-2 infection is mainly sexually transmitted, causing genital herpes. Genital herpes is characterised by periodic symptomatic or asymptomatic viral shedding [1]and causes a ificant burden of disease, most notably, the periodic appearance of often painful genital ulcers and accompanying psychological morbidity in a proportion of those infected [1].

However, the clinical presentation of infection is variable, and the majority of individuals are unaware they are infected [2].

Herpes simplex virus type 2 igg antibodies in sera of umbilical cord as a proxy for placental infection in asymptomatic pregnant women

Although rare, infection in the neonate is associated with a high risk of severe morbidity and mortality [3][4]. HSV-2 infection has received renewed attention in recent years, due to improvements in the understanding of the epidemiological synergy between HSV-2 and HIV. HSV-2 infection increases the risk of HIV acquisition by approximately three-fold [5]and the increase in risk is even greater in those with newly-acquired incident HSV-2 infection [6][7]. The high burden of HSV-2 infection is thought to have contributed substantially to HIV prevalence in a of settings, most notably in sub-Saharan Africa [5][13]although it is difficult to control for shared sexual risk driving both epidemics [14].

Daily suppressive antiviral therapy against HSV-2 has been shown to reduce symptomatic recurrences and asymptomatic HSV shedding; however, in clinical trials, suppressive therapy did not reduce the excess risk of HIV acquisition or transmission due to HSV-2 nor fully suppress HSV-2 shedding [15] — [17].

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Efforts to develop a vaccine against HSV are advancing. In clinical trials, a prophylactic vaccine failed to prevent HSV-2 infection and disease [18]. However, preliminary from ongoing trials of post-exposure therapeutic vaccines against genital HSV-2 infection have been encouraging, demonstrating reductions in HSV-2 shedding in vaccine recipients compared to placebo [19][20].

Further are anticipated soon and there are other vaccines in the pipeline [21].

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The global burden of HSV-2 infection has not been evaluated since estimates were published inwhen we estimated for the first time that million people had existing prevalent and This followed an earlier review of HSV seroprevalence [24] that did not pool prevalence nor estimate the global or regional burden of infection. In this analysis we present new global estimates for of the burden of prevalent and incident HSV-2 infection for females and males aged 15—49 years by WHO region, including adjustment for test performance.

Such estimates are critical not only for understanding the epidemiology of HSV infection, but also for guiding development of vaccines, microbicides, diagnostics and therapeutics, and for advocating support for STI prevention and control efforts.

Genital herpes – cdc fact sheet (detailed)

The methods employed are similar to those used for the estimates [23]but with some notable refinements described in detail below. Most importantly, in these estimates adjustment was done for test sensitivity and specificity, while adjustment was not done for the estimates. In addition, for this set of estimates we applied a cut-off year of or later for inclusion of study data, while there was no cut-off for the estimates, which used data from all studies published up to the date of search in Finally, the regional groupings used differ in this set of revised estimates.

No other restrictions were made, including with regard to language. Reference lists were also searched.

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Note that although the last set of estimates were forthe review of prevalence values informing these estimates was done in and applied to population s. Inclusion and exclusion criteria followed the reviews [23][24] with some refinement.

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HSV-2 incidence studies were eligible for inclusion if they reported the rate or risk of incident detection of type-specific IgG to HSV-2 or if we could calculate this from the of cases and reported s or time at risk. Prevalence values based on IgM were excluded since we were measuring established infection which is shown by the presence of IgG [25]. Studies were required to give some detail of the study location minimum: country and some detail of participants' age. Prevalence and incidence were extracted by sex and by age as well as overall, but not for any other characteristic.

Estimated values were read from figures if exact s were not available.

Genital herpes in pregnancy

Prevalence that was weighted or adjusted to for selection bias was used where reported. Unresolved equivocal samples were excluded from both numerator and denominator. Where comparison from more than one test were presented, we retained from the assay or method judged to be the most robust e.

If more than one publication presented findings from the same study, then all relevant data were extracted. However, if findings from the same subset of participants were repeated e. Studies were also excluded for the following reasons: 1 if study participants were selected on the basis of having a medical condition, since this may be associated with HSV infection, and the findings may not be generalisable examples of excluded studies were studies of transplant recipients, eye infections, atherosclerosis and atopy ; 2 if study individuals were selected on the basis of having a specific genital or urinary tract infection e.

Studies which selected individuals on the basis of being infected with HIV were not excluded, as these individuals are a specific interest group; however these were summarised separately. Where possible, seroincidence was extracted only for individuals in the control arm of any interventions which might affect HSV incidence, and on an intention-to-treat basis.

To estimate the s of people with prevalent and incident HSV-2 infection globally, only HSV-2 prevalence values from general populations and stratified by sex were used. Age-stratified prevalence values were used in preference over unstratified values.

Only publications with study year mid-point or publication year if not known of or later were used. Studies used in the estimates paper which were still sufficiently recent were also included. A minimum sample size of 20 was required; small sample sizes by age were combined as necessary. The mean or median age was used where reported.


If prevalence was reported by age in ranges then the mid-point of the age range was taken. Sample sizes for age strata where not given were estimated from the total sample size and widths of the age strata. Age strata without finite age limits e. Zero prevalence values were recoded as 0. We adjusted each prevalence value for the sensitivity and specificity of the assay used [26]according to the package insert of the assay or published test performance [27] and using the following equation: with prevalence, sensitivity and specificity expressed as proportions.

For those studies used in the estimates, we were able to re-obtain the original publications and extract the required information on type of assay used since the of publications was small. A comparison of the regions used in the and estimates is shown in S1 Table.

Genital and oral herpes testing

Six regions were used for the estimates to enable direct comparison with other disease burden estimates produced by WHO. The s of individuals with prevalent and incident HSV-2 infection in was calculated using a similar method to the estimates [23]. For each WHO region, pooled prevalence values by sex and 5-year age group 15—49 years were generated in Stata Stata 13; StataCorp, College Station, Texas, USA using the metan command to pool the raw log odds of infection weighted by the standard error of the log odds for those prevalence values with sample ages within the boundaries of each 5-year age category.

A random-effect model was used for pooling, which s for between- as well as within-study variation. HSV-2 incidence by sex was calibrated from these pooled prevalence values using a constant-incidence model [28]. This modelling step additionally incorporated a calibrated term for the maximum proportion able to be infected to allow prevalence to saturate at low or moderate prevalence where the pooled prevalence values indicated this e.

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Thus, these estimates apply to the year for population size but use prevalence data from onwards, with prevalence assumed not to vary over the period. The s of people with incident HSV-2 infection by region in were obtained by applying the model incidence to the population sizes able to be infected.

Specifically, the s of new cases of HSV-2 infection at each single year of age, I awere calculated as: where N a is the total of individuals i. Estimates were then summed across these ages in each 5-year age category. Model incidence was used rather than reported incidence due to a lack of reported incidence values across all ages and regions. Global estimates were obtained by summing values over all 6 regions. An uncertainty analysis was performed for the s of people with prevalent and incident HSV-2 infection in as follows.

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Confidence intervals for the pooled age- and region-specific prevalence values from the meta-analysis describe the variation based on sample size and study-to-study population differences. The lower and upper bounds were summed across all regions to compute lower and upper bounds for the global estimates. The reason for doing the latter was that there is evidence of differing test performance by study population [30]with the performance of the Focus assay being the best studied due to it being the most frequently used.

The studies used in the estimates were re-analysed with the same 6 WHO groupings, for comparison, and using population sizes from the United Nations Population Division [29]. Test adjustment was not done for the re-analysis due to the large of studies which precluded re-obtaining the relevant publications to extract full information on type of assay used. A total of publications were identified: and from PubMed and Embase, respectively Fig.

Removal of duplicates left publications. The abstract of each or title if not available was examined for potential relevance, resulting in exclusion of publications on the basis of the inclusion and exclusion criteria see Methods.

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Genital herpes simplex virus HSV infections are among the most commonly seen sexually transmitted infections in the world.


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This was fact checked by our expert Medical Review Board for accuracy and objectivity.