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      Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012

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          Abstract

          Background

          Herpes simplex virus type 1 (HSV-1) commonly causes orolabial ulcers, while HSV-2 commonly causes genital ulcers. However, HSV-1 is an increasing cause of genital infection. Previously, the World Health Organization estimated the global burden of HSV-2 for 2003 and for 2012. The global burden of HSV-1 has not been estimated.

          Methods

          We fitted a constant-incidence model to pooled HSV-1 prevalence data from literature searches for 6 World Health Organization regions and used 2012 population data to derive global numbers of 0-49-year-olds with prevalent and incident HSV-1 infection. To estimate genital HSV-1, we applied values for the proportion of incident infections that are genital.

          Findings

          We estimated that 3709 million people (range: 3440–3878 million) aged 0–49 years had prevalent HSV-1 infection in 2012 (67%), with highest prevalence in Africa, South-East Asia and Western Pacific. Assuming 50% of incident infections among 15-49-year-olds are genital, an estimated 140 million (range: 67–212 million) people had prevalent genital HSV-1 infection, most of which occurred in the Americas, Europe and Western Pacific.

          Conclusions

          The global burden of HSV-1 infection is huge. Genital HSV-1 burden can be substantial but varies widely by region. Future control efforts, including development of HSV vaccines, should consider the epidemiology of HSV-1 in addition to HSV-2, and especially the relative contribution of HSV-1 to genital infection.

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          Most cited references38

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          Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

          To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. Systematic review and meta-analysis of longitudinal studies. PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.
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            Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda.

            The probability of HIV-1 transmission per coital act in representative African populations is unknown. We aimed to calculate this probability overall, and to estimate how it is affected by various factors thought to influence infectivity. 174 monogamous couples, in which one partner was HIV-1 positive, were retrospectively identified from a population cohort in Rakai, Uganda. Frequency of intercourse and reliability of reporting within couples was assessed prospectively. HIV-1 seroconversion was determined in the uninfected partners, and HIV-1 viral load was measured in the infected partners. Adjusted rate ratios of transmission per coital act were estimated by Poisson regression. Probabilities of transmission per act were estimated by log-log binomial regression for quartiles of age and HIV-1 viral load, and for symptoms or diagnoses of sexually transmitted diseases (STDs) in the HIV-1-infected partners. The mean frequency of intercourse was 8.9 per month, which declined with age and HIV-1 viral load. Members of couples reported similar frequencies of intercourse. The overall unadjusted probability of HIV-1 transmission per coital act was 0.0011 (95% CI 0.0008-0.0015). Transmission probabilities increased from 0.0001 per act at viral loads of less than 1700 copies/mL to 0.0023 per act at 38 500 copies/mL or more (p=0.002), and were 0.0041 with genital ulceration versus 0.0011 without (p=0.02). Transmission probabilities per act did not differ significantly by HIV-1 subtypes A and D, sex, STDs, or symptoms of discharge or dysuria in the HIV-1-positive partner. Higher viral load and genital ulceration are the main determinants of HIV-1 transmission per coital act in this Ugandan population.
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              Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review.

              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. Age-specific HSV-2 prevalence is usually higher in women than men and in populations with higher risk sexual behavior. HSV-2 prevalence has increased in the United States but national data from other countries are unavailable. HSV-1 infection is acquired during childhood and adolescence and is markedly more widespread than HSV-2 infection. Further studies are needed in many geographic areas.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 October 2015
                2015
                : 10
                : 10
                Affiliations
                [1 ]School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
                [2 ]Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America
                [3 ]Department of Reproductive Health and Research, World Health Organization, Geneva, Switzerland
                University of Pittsburgh School of Medicine, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KJL LMN. Performed the experiments: KJL. Analyzed the data: KJL ASM MTM KMET PV SLG LMN. Contributed reagents/materials/analysis tools: KJL ASM MTM KMET PV. Wrote the paper: KJL ASM MTM KMET PV SLG LMN. Contributed to the ongoing progress and direction of the research: KJL ASM MTM KMET PV SLG LMN. Provided technical expertise and input: KJL ASM MTM KMET PV SLG LMN.

                Article
                PONE-D-15-35461
                10.1371/journal.pone.0140765
                4624804
                26510007
                54f8d5f8-0a0a-42f6-8fe1-a13615674b06

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

                Page count
                Figures: 2, Tables: 5, Pages: 17
                Product
                Funding
                This work was funded by the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction ( http://www.who.int/reproductivehealth/hrp/en/). 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. KJL received funding from the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Evaluation of Interventions, Health Protection Scotland and Sexual Health 24 during the course of this study. ASM received funding from the National Institutes of Health (NIH P01-A1-030731-23) during the study. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.
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