Incidence of herpes simplex virus type 2 positivity among women living with human immunodeficiency virus in South Africa.

BACKGROUND: For women living with HIV (WLHIV), co-infection with herpes simplex virus type 2 (HSV-2) causes severe genital ulcers and presents additional challenges for their HIV care. To inform preventive strategies, we aimed to determine the incidence and risk factors of HSV-2 positivity in a prospective cohort of South African women. METHODS: The CAPRISA 002 study enrolled women at acute HIV infection between 2004 and 2020. HSV-2 testing was conducted by multiplex polymerase chain reaction (PCR) assay on collected vaginal swabs up to twice annually during follow-up. We calculated incidence as the number of new cases per 100 person-years (PYs) and used Cox-proportional-hazard regression to identify factors associated with time-to-HSV-2 PCR positivity. RESULTS: At enrolment, the median age of 171 women was 24 years, interquartile range (IQR 21-28), and the estimated median days since HIV infection was 42 (IQR 22-65). Of participants tested at enrolment, HSV-2 antibody prevalence was 81.4% (105/129), and 10.6% (12/113) were positive by PCR. Among 147 women with a prior negative HSV-2 PCR diagnosis, we observed 47 new HSV-2 PCR positive cases over 424.4 PYs of follow-up, yielding an incidence rate of 11.1 cases per-100-PYs. HSV-2 PCR positivity incidence was higher among younger women (<25 years: adjusted Hazard Ratio [aHR] = 5.91, 95%CI 3.02-11.6), those with bacterial vaginosis (BV) (Nugent score 7-10: aHR = 2.17, 95%CI 1.15-4.10) and lower CD4 counts (<500 cells/µl: aHR = 2.04, 95%CI 1.08-3.87). CONCLUSION: After acute HIV infection in women, the incidence of HSV-2 PCR positivity was associated with younger age, BV diagnosis and lower CD4 count.

Is the level of varicella-zoster virus IgG associated with symptomatic status of genital herpes simplex virus infection? A case-control study.

BACKGROUND: Herpes simplex virus (HSV) is a common infection, affecting the majority of the population by age of 50. Recurrent symptomatic outbreaks, experienced by a minority, have significant psychological and psychosexual effects. The varicella zoster virus (VZV), resembling HSV, shows potential for a functional cure via vaccination. This study seeks to investigate if there is an association between low VZV antibody levels and recurrent HSV outbreaks. METHODS: A total of 110 patients with symptomatic and asymptomatic HSV were recruited during their sexual health screen. Serum samples were collected between Aug 2019 - July 2022; breaks in the study occurred due to COVID. The primary outcome measure was the serological status of HSV and VZV IgG titre level. RESULTS: The average age was 37.3 years (range 21-65 years). For people with asymptomatic genital HSV2 the average VZV IgG titre was 2373.9 IU/mL (n = 17); and 1219.0 IU/mL for the symptomatic group (n = 67); p ≤ 0.00001), with similar results for HSV1. CONCLUSION: There is a strong association between average higher varicella-zoster virus (VZV) IgG level and being an asymptomatic carrier of herpes simplex sirus (HSV)1&2. A feasibility study to assess the use of the VZV vaccine as a treatment of HSV is planned.

Dramatic Shift in the Etiology of Genital Ulcer Disease Among Patients Visiting a Sexually Transmitted Infections Clinic in Lilongwe, Malawi.

BACKGROUND: Genital ulcer diseases (GUDs) are a common syndrome associated with sexually transmitted infections. Genital ulcer diseases increase the risk of HIV transmission, necessitating appropriate diagnosis and treatment. We provide an updated GUD etiology assessment in Malawi to guide diagnostic development and treatment algorithms. METHODS: We enrolled patients 18 years or older presenting with GUD at a sexually transmitted infection clinic in Lilongwe, Malawi, between May and October 2021. We purposively sampled by HIV status. Swabs of ulcers were tested for Treponema pallidum, herpes simplex virus (HSV)-1 and HSV-2, Haemophilus ducreyi, and Chlamydia trachomatis using polymerase chain reaction. Blood was collected for syphilis and HSV-2 serologies and acute HIV testing. Participants were treated per Malawi guidelines. Ulcer resolution (size reduced by >50%) was evaluated 14 days later. RESULTS: Fifty participants enrolled (30 without HIV, 2 with acute HIV infection, 18 with HIV seropositivity; 32 men, 18 women). Forty-six (92%) had an etiology identified. Syphilis was more common among those without HIV (22 of 30 [73%]) than participants with HIV (PWH; 8 of 20 [40%]; P = 0.04). Herpes simplex virus was more common among PWH (11 of 20 [55%]) than participants without (2 of 30 [7%]; P = 0.0002). One-fifth (9 of 50 [18%]) had H. ducreyi. Among those who returned for follow-up (n = 45), 9 (20%) had unresolved ulcers; persistent GUD was slightly more common in PWH (6 of 19 [32%]) than participants without (3 of 26 [12%]; P = 0.14). CONCLUSIONS: We observed a dramatic increase in syphilis ulcer proportion in a population whose GUDs were previously HSV predominant. Observed differences in etiology and resolution by HIV status could play an important role in the ongoing transmission and treatment evaluation of GUD.

Epidemiology of herpes simplex virus type 1 in Canada: systematic review, meta-analyses, and meta-regressions.

Background: The objective of this study was to characterize herpes simplex virus type 1 (HSV-1) epidemiology in Canada. Methods: HSV-1 publications as recent as December 6, 2021 were systematically reviewed, synthesized, and reported following PRISMA guidelines. Meta-analyses and meta-regressions were conducted. Results: HSV-1 measures were extracted from 22 studies and included 32 overall seroprevalence measures (79 stratified), 2 overall proportions of HSV-1 detection in clinically diagnosed genital ulcer disease (2 stratified), and 8 overall proportions of HSV-1 detection in laboratory-confirmed genital herpes (27 stratified). Pooled mean seroprevalence was 19.1% [95% confidence interval (CI): 12.6-26.4%] among healthy children and 51.4% (95% CI: 47.3-55.5%) among healthy adults. Pooled mean seroprevalence among healthy general populations increased with age, with the lowest being 35.7% (95% CI: 29.1-42.6%) among individuals <20 years of age, and the highest being 70.0% (95% CI: 54.8-83.2) among individuals ≥40 years. Seroprevalence increased by 1.02-fold (95% CI: 1.01-1.04) per year. Pooled mean proportion of HSV-1 detection in genital ulcer disease was 30.8% (95% CI: 12.6-52.8%). Pooled mean proportion of HSV-1 detection in genital herpes was 37.4% (95% CI: 29.5-45.6%) and was highest in women and in young persons. Proportion of HSV-1 detection in genital herpes increased by 1.04-fold (95% CI: 1.00-1.08) per year. Conclusions: HSV-1 epidemiology in Canada appears to be shifting toward less oral acquisition in childhood and more genital acquisition in adulthood, particularly among youth. Both HSV-1 seroprevalence and proportion of HSV-1 detection in genital herpes are increasing with time.

Seroprevalence and Vaginal Shedding of Herpes Simplex Virus Type 2 in Pregnant Adolescents and Young Women from Morelos, Mexico.

Adolescents and young people are particularly vulnerable to contracting STIs, including HSV-2; furthermore, vaginal shedding of HSV-2 during pregnancy can cause vertical transmission and neonatal herpes. To evaluate the seroprevalence of HSV-2 and vaginal HSV-2 shedding in adolescent and young pregnant women, a cross-sectional study was carried out in 496 pregnant women-adolescents and young women. Venous blood and vaginal exudate samples were taken. The seroprevalence of HSV-2 was determined by ELISA and Western blot. Vaginal HSV-2 shedding was assessed by qPCR of the HSV-2 UL30 gene. The seroprevalence of HSV-2 in the study population was 8.5% (95% CI 6-11), of which 38.1% had vaginal HSV-2 shedding (95% CI 22-53). Young women presented a higher seroprevalence of HSV-2 (12.1%) than adolescents (4.3%), OR = 3.4, 95% CI 1.59-7.23. Frequent alcohol consumption was significantly associated with HSV-2 seroprevalence, OR = 2.9, 95% CI 1.27-6.99. Vaginal HSV-2 shedding is highest in the third trimester of pregnancy, but this difference is not significant. The seroprevalence of HSV-2 in adolescents and young women is similar to that previously reported in other studies. However, the proportion of women with vaginal shedding of HSV-2 is higher during the third trimester of pregnancy, increasing the risk of vertical transmission.

An Ulcer by Any Other Name: Non-herpes and Non-syphilis Ulcerative Sexually Transmitted Infections.

The myriad presentations of ulcerative sexually transmitted infections, other than genital herpes and syphilis, challenge even the most astute clinician given the considerable overlap in clinical presentation and lack of widely available diagnostic resources, such as nucleic acid testing, to confirm the diagnosis. Even so, case prevalence is relatively low, and incidence of chancroid and granuloma inguinale are declining. These diseases still cause substantial morbidity and increased chance for HIV acquisition, and with the recent advent of mpox as a cause, it remains imperative to identify and treat accurately.

Seroprevalence of antibodies to herpes simplex virus 1 and 2 in patients with HIV positive from Ebonyi State, Nigeria: a cross-sectional study.

OBJECTIVES: To assess the seroprevalence of herpes simplex virus (HSV) types 1 and 2 in patients infected with HIV in Nigeria. DESIGN: Cross-sectional design from January to June 2019. SETTING: Federal Teaching Hospital, Ebonyi State, Nigeria. PARTICIPANTS: A total of 276 patients with HIV were analysed using ELISA method for the presence of HSV-1 and HSV-2 specific IgG antibodies. OUTCOMES: Fisher's exact test was used to determine the association between the seroprevalence of HSV and demographic variables (statistically significant=p value ≤0.05). RESULTS: Totally, 212 (76.8%) and 155 (56.2%) patients with HIV were seropositive for HSV-1 and HSV-2 IgG antibodies, respectively. The seroprevalence of HSV-1 was significantly higher than the HSV-2 in patients with HIV (p value <0.0001). HSV-1 and HSV-2 seroprevalence were higher in patients aged more than 30 years. The seroprevalence of HSV-1 was significantly higher (p=0.01) in females (82.4%, 131/159) than males (69.2%, 81/117), but there was no significant difference in seroprevalence of HSV-2 in females (57.9%, 92/159) compared with males (53.8%, 63/117) (p=0.51). Professional drivers had a higher seroprevalence of HSV-1 and HSV-2 and there was a significant association between the occupation and the HSV-1 and HSV-2 seropositivity (p>0.05). The seroprevalence of HSV-1 was significantly higher in the singles (87.4%, 90/103) than the married patients with HIV (p=0.001). However, HSV-2 seroprevalence was significantly higher in the married patients with HIV (63.6%, 110/173) (p=0.001). CONCLUSIONS: Prevalence of 76.8% for HSV-1 and 56.2% for HSV-2 among patients with HIV was seen. The HSV-1 was significantly higher in the singles while HSV-2 seroprevalence was significantly higher in the married patients with HIV with HSV-1 and HSV-2 coinfection rate of 7.6%. This study became very imperative to provide an important insight into the hidden dynamics of HSV infections.

Seroprevalence of Herpes Simplex Viruses Types 1 and 2 in a Population, Age 15-35 Years, of Mashhad City.

Background: Considering the high prevalence and clinical importance of herpes simplex virus (HSV) infection worldwide, we aimed to evaluate the seroprevalence of HSV-1 and HSV-2 in a population aged between 15 and 35 years in Mashhad, Iran. Methods: This cross-sectional study was conducted on 916 cases composed of 288 (31.4%) men and 628 (68.6%) women. Using ELISA method, the presence of IgM and IgG antibodies against HSV-1 and HSV-2 was assessed. Results: Among the population studied, 681 (74.3%) cases were positive for anti-HSV antibodies, while 235 (25.7%) cases were negative. Moreover, no IgMs were found and all positive subjects had IgG antibodies. Age (p < 0.001), occupation (p < 0.001), education (p = 0.006), smoking (p = 0.029), and BMI (p = 0.004) demonstrated a significant association with HSV-1 and HSV-2 infection. Conclusion: Our study indicates a high seroprevalence of HSV infection; however, there was no cases positive for IgM antibodies, suggesting the high prevalence of latent infection.

The population impact of herpes simplex virus type 2 (HSV-2) vaccination on the incidence of HSV-2, HIV and genital ulcer disease in South Africa: a mathematical modelling study.

BACKGROUND: Evidence suggests HSV-2 infection increases HIV acquisition risk and HIV/HSV-2 coinfection increases transmission risk of both infections. We analysed the potential impact of HSV-2 vaccination in South Africa, a high HIV/HSV-2 prevalence setting. METHODS: We adapted a dynamic HIV transmission model for South Africa to incorporate HSV-2, including synergistic effects with HIV, to evaluate the impact of: (i) cohort vaccination of 9-year-olds with a prophylactic vaccine that reduces HSV-2 susceptibility; (ii) vaccination of symptomatically HSV-2-infected individuals with a therapeutic vaccine that reduces HSV shedding. FINDINGS: An 80% efficacious prophylactic vaccine offering lifetime protection with 80% uptake could reduce HSV-2 and HIV incidence by 84.1% (95% Credibility Interval: 81.2-86.0) and 65.4% (56.5-71.6) after 40 years, respectively. This reduces to 57.4% (53.6-60.7) and 42.1% (34.1-48.1) if efficacy is 50%, 56.1% (53.4-58.3) and 41.5% (34.2-46.9) if uptake is 40%, and 29.4% (26.0-31.9) and 24.4% (19.0-28.7) if protection lasts 10 years. An 80% efficacious therapeutic vaccine offering lifetime protection with 40% coverage among symptomatic individuals could reduce HSV-2 and HIV incidence by 29.6% (21.8-40.9) and 26.4% (18.5-23.2) after 40 years, respectively. This reduces to 18.8% (13.7-26.4) and 16.9% (11.7-25.3) if efficacy is 50%, 9.7% (7.0-14.0) and 8.6% (5.8-13.4) if coverage is 20%, and 5.4% (3.8-8.0) and 5.5% (3.7-8.6) if protection lasts 2 years. INTERPRETATION: Prophylactic and therapeutic vaccines offer promising approaches for reducing HSV-2 burden and could have important impact on HIV in South Africa and other high prevalence settings. FUNDING: WHO, NIAID.

Epidemiology of herpes simplex virus type 1 and genital herpes in Australia and New Zealand: systematic review, meta-analyses and meta-regressions.

Herpes simplex virus type 1 (HSV-1) infection is a lifelong infection that is acquired primarily orally and during childhood. We aimed to characterise HSV-1 epidemiology in Australia and New Zealand. HSV-1-related data as recent as 6 December 2021 were systematically reviewed, synthesised and reported, following PRISMA guidelines. Pooled mean seroprevalence and proportions of HSV-1 detection in genital ulcer disease (GUD) and in genital herpes were calculated using random-effects meta-analyses. Meta-regressions were also conducted. HSV-1 measures were retrieved from 21 eligible publications. Extracted HSV-1 measures included 13 overall seroprevalence measures (27 stratified) in Australia, four overall proportions of HSV-1 detection in clinically diagnosed GUD (four stratified) in Australia, and ten overall proportions of HSV-1 detection in laboratory-confirmed genital herpes (26 stratified) in Australia and New Zealand. Pooled mean seroprevalence among healthy adults in Australia was 84.8% (95% confidence interval (CI) 74.3-93.1%). Pooled mean seroprevalence was 70.2% (95% CI 47.4-88.7%) among individuals <35 years of age and 86.9% (95% CI 79.3-93.0%) among individuals ≥35 years. Seroprevalence increased by 1.05-fold (95% CI 1.01-1.10) per year. Pooled mean proportion of HSV-1 detection in GUD was 8.2% (95% CI 0.4-22.9%). Pooled mean proportion of HSV-1 detection in genital herpes was 30.5% (95% CI 23.3-38.3%), and was highest in young individuals. Proportion of HSV-1 detection in genital herpes increased by 1.04-fold (95% CI 1.00-1.08) per year. Included studies showed heterogeneity, but 30% of the heterogeneity in seroprevalence and 42% of the heterogeneity in proportion of HSV-1 detection in genital herpes were explained in terms of epidemiological factors. HSV-1 seroprevalence is higher in Australia than in other Western countries. HSV-1 epidemiology in Australia and New Zealand appears to be transitioning towards less oral acquisition in childhood, but more genital acquisition among youth.

Epidemiology of herpes simplex virus type 2 in the Middle East and North Africa: Systematic review, meta-analyses, and meta-regressions.

Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with poorly characterized prevalence in the Middle East and North Africa (MENA) region. This study characterized HSV-2 epidemiology in MENA. HSV-2 reports were systematically reviewed as guided by the Cochrane Collaboration Handbook and findings were reported following PRISMA guidelines. Random-effects meta-analyses and meta-regressions were performed to estimate pooled mean outcome measures and to assess predictors of HSV-2 antibody prevalence (seroprevalence), trends in seroprevalence, and between-study heterogeneity. In total, sixty-one overall (133 stratified) HSV-2 seroprevalence measures and two overall (four stratified) proportion measures of HSV-2 detection in laboratory-confirmed genital herpes were extracted from 37 relevant publications. Pooled mean seroprevalence was 5.1% (95% confidence interval [CI]: 3.6%-6.8%) among general populations, 13.3% (95% CI: 8.6%-18.7%) among intermediate-risk populations, 20.6% (95% CI: 5.3%-42.3%) among female sex workers, and 18.3% (95% CI: 3.9%-39.4%) among male sex workers. Compared to Fertile Crescent countries, seroprevalence was 3.39-fold (95% CI: 1.86-6.20) and 3.90-fold (95% CI: 1.78-8.57) higher in Maghreb and Horn of Africa countries, respectively. Compared to studies published before 2010, seroprevalence was 1.73-fold (95% CI: 1.00-2.99) higher in studies published after 2015. Pooled mean proportion of HSV-2 detection in genital herpes was 73.8% (95% CI: 42.2%-95.9%). In conclusion, MENA has a lower HSV-2 seroprevalence than other world regions. Yet, 1 in 20 adults is chronically infected, despite conservative prevailing sexual norms. Seroprevalence may also be increasing, unlike other world regions. Findings support the need for expansion of surveillance and monitoring of HSV-2 infection in MENA.

Herpes Simplex Virus Type 2 Prevalence and Association with Inflammatory Cytokines Among Sexual and Gender Minorities Living With and Without HIV-1 from Lagos, Nigeria.

Herpes simplex virus type 2 (HSV-2) is common globally and contributes significantly to the risk of acquiring HIV-1, yet these two sexually transmitted infections have not been sufficiently characterized for sexual and gender minorities (SGM) across Sub-Saharan Africa. To help fill this gap, we performed a retrospective study using plasma and serum samples from 183 SGM enrolled at the Lagos site of the TRUST/RV368 cohort in Nigeria, assayed them for HSV-2 antibodies with the Kalon ELISA and plasma cytokines and chemokines with Luminex, and correlated the findings with HIV-1 viral loads (VLs) and CD4 counts. We found an overall HSV-2 prevalence of 36.6% (49.5% and 23.9% among SGM with and without HIV-1, respectively, p < .001). Moreover, HSV-2-positive status was associated with high circulating concentrations of CCL11 among antiretroviral therapy-treated (p = .031) and untreated (p = .015) participants, and with high concentrations of CCL2 in the untreated group (p = .004), independent of VL. Principal component analysis revealed a strong association of cytokines with HIV-1 VL independent of HSV-2 status. In conclusion, our study finds that HSV-2 prevalence among SGM with HIV-1 is twice as high than HSV-2 prevalence among SGM without HIV-1 in Lagos and suggests that this is associated with higher levels of certain systemic cytokines. Additional work is needed to further characterize the relationship between HSV-2 and HIV-1 in SGM and help develop targeted therapies for coinfected individuals.

Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion.

OBJECTIVES: To examine innate immunity predictors of HIV-1 acquisition as biomarkers of HSV-2 risk and biological basis for epidemiologically established HIV-1 predisposition in HSV-2 infected women. METHODS: We analysed longitudinal samples from HIV-1 negative visits of 1019 women before and after HSV-2 acquisition. We measured cervical and serum biomarkers of inflammation and immune activation previously linked to HIV-1 risk. Protein levels were Box-Cox transformed and ORs for HSV-2 acquisition were calculated based on top quartile or below/above median levels for all HSV-2 negative visits. Bivariate analysis determined the likelihood of HSV-2 acquisition by biomarker levels preceding infection. Linear mixed-effects models evaluated if biomarkers differed by HSV-2 status defined as negative, incident or established infections with an established infection cut-off starting at 6 months. RESULTS: In the cervical compartment, two biomarkers of HIV-1 risk (low SLPI and high BD-2) also predicted HSV-2 acquisition. In addition, HSV-2 acquisition was associated with IL-1ß, IL-6, IL-8, MIP-3α, ICAM-1 and VEGF when below median levels. Systemic immunity predictors of HSV-2 acquisition were high sCD14 and IL-6, with highest odds when concomitantly increased (OR=2.23, 1.49-3.35). Concomitant systemic and mucosal predictors of HSV-2 acquisition risk included (1) serum top quartile sCD14 with cervical low SLPI, VEGF and ICAM-1, or high BD-2; (2) serum high IL-6 with cervical low VEGF and ICAM-1, SLPI, IL-1ß and IL-6; and (3) serum low C reactive protein with cervical high BD-2 (the only combination also predictive of HIV-1 acquisition). Most cervical biomarkers were decreased after HSV-2 acquisition compared with the HSV-2 negative visits, with incident infections associated with a larger number of suppressed cervical biomarkers and lower serum IL-6 levels compared with established infections. CONCLUSIONS: A combination of systemic immunoinflammatory and cervical immunosuppressed states predicts HSV-2 acquisition. A persistently suppressed innate immunity during incident HSV-2 infection may add to the increased HIV-1 susceptibility.

Overlooked monkeypox cases among men having sex with men during the 2022 outbreak - a retrospective study.

OBJECTIVES: The aim of this study was to characterize overlooked cases of patients with monkeypox infection in the 2022 outbreak. METHODS: Clinical characteristics of 26 patients who were misdiagnosed with other diseases were described. RESULTS: Of the 26 patients who were misdiagnosed, six (23%) were given a diagnosis of bacterial tonsillitis, six (23%) were diagnosed with primary syphilis, five (19.2%) with oral or genital herpes, and four (15.3%) with bacterial proctitis or anal abscess. The average time interval between missed and right diagnosis was 4.4 days. There was no difference in the missed cases between the early and the later month of the outbreak. CONCLUSION: Monkeypox might still be commonly overlooked, especially in patients presenting with fever and sore throat or solitary ulcer as sole manifestations.

Investigating the survival of herpes simplex virus on toothbrushes and surrogate phallic devices.

BACKGROUND: Herpes simplex virus-1 (HSV-1) is a member of the alphaherpesvirus (alphaherpesvirinae) subfamily, allowing it to affect a wide range of hosts. Herpes simplex virus-1 affects 3.7 billion people, or 67% of the population, under the age of 50. With a vast number of people infected by the virus, everyday objects are often contaminated with this agent. In this study we determined how long HSV-1 can remain viable on contaminated fomites. METHODS: Fomites were selected for their use near potentially contaminated orifices and variable frequency of sanitization. Toothbrushes and surrogate phallic devices (SPDs) were cut, sterilized, and contaminated. After contaminating the fomites, we collected samples over a 24 h period, then used plaque assays to determine viral titers at prescribed time points. RESULTS: The quantity of replication-competent virus present appears to decrease significantly 2 h post-contamination, then steadily declines over time, nearing zero at 24 h. CONCLUSIONS: Our findings suggest that different surfaces influence HSV-1 survival. Proper cleaning must be performed for these types of fomites, especially if shared in an environment where someone with active genital or oral herpes lesions uses one of these fomites shortly after someone else.

Estimated economic burden of genital herpes and HIV attributable to herpes simplex virus type 2 infections in 90 low- and middle-income countries: A modeling study.

BACKGROUND: Economic losses due to herpes simplex infections in low- and middle-income countries (LMICs) are unknown. We estimated economic and quality-of-life losses due to genital herpes in 2019, in 90 LMICs, and from 2020 to 2030 in 45 countries in the World Health Organization (WHO) Africa. We additionally estimated economic losses due to human immunodeficiency virus (HIV) attributable to herpes simplex virus type 2 (HSV-2) infections. METHODS AND FINDINGS: We estimated genital herpes-related spending on treatment, wage losses due to absenteeism, and reductions in quality of life, for individuals aged 15 to 49 years, living with genital herpes. Had HSV-2 had contributed to the transmission of HIV, we estimated the share of antiretroviral treatment costs and HIV-related wage losses in 2019 that can be attributed to incident and prevalent HSV-2 infections in 2018. For the former, we used estimates of HSV-2 incidence and prevalence from the global burden of disease (GBD) study. For the latter, we calculated population attributable fractions (PAFs), using the classic (Levin's) epidemiological formula for polytomous exposures, with relative risks (RRs) reported in literature. To extend estimates from 2020 to 2030, we modeled the transmission of HSV-2 in 45 African countries using a deterministic compartmental mathematical model, structured by age, sex, and sexual activity, which was fitted to seroprevalence gathered from a systematic review and meta-regression analysis. In the 90 LMICs, genital herpes contributed to US$813.5 million in treatment and productivity losses in 2019 (range: US$674.4 to US$952.2 million). Given observed care-seeking and absenteeism, losses are in the range of US$29.0 billion (US$25.6 billion to US$34.5 billion). Quality-of-life losses in the amount of 61.7 million quality-adjusted life years (QALYs) are also possible (50.4 million to 74.2 million). The mean annual cost of treatment and wage losses per infection is US$183.00 (95% CI: US$153.60 to US$212.55); the mean annual cost of quality-of-life losses is US$343.27 (95% CI: 272.41 to 414.14). If HSV-2 has fueled the transmission of HIV, then seroprevalent HSV-2 cases in 2018 can account for 33.2% of the incident HIV infections in 2019, with an associated antiretroviral therapy (ART) cost of US$186.3 million (range: US$163.6 to US$209.5 million) and 28.6% of HIV-related wage losses (US$21.9 million; range: US$19.2 to US$27.4 million). In the WHO Africa region, the 3.9 million seroprevalent genital herpes cases from 2020 to 2030 contributed to US$700.2 million in treatment and productivity losses. Additionally, quality-of-life losses in the range of 88 million to 871 million QALYs are also possible. If HSV-2 has contributed to the transmission of HIV, then in 2020, the PAF of HIV due to prevalent HSV-2 will be 32.8% (95% CI: 26.7% to 29.9%) and due to incident infections will be 4.2% (95% CI: 2.6% to 3.4%). The PAF due to prevalent infections will decline to 31.0% by 2030 and incident infections to 3.6%. Though we have accounted for the uncertainty in the epidemiological and economic parameter values via the sensitivity analysis, our estimates still undervalue losses due to limiting to the 15- to 49-year-old population. CONCLUSIONS: Economic losses due to genital herpes in LMICs can be large, especially when considering the lifelong nature of the disease. Quality-of-life losses outweigh spending on treatment and reductions in productivity. If HSV-2 has contributed to the spread of HIV in LMICs, then nearly one third of antiretroviral costs and HIV-related wage losses can be attributed to HSV-2. Given the magnitude of the combined losses, a vaccine against HSV-2 must be a global priority.

Herpes simplex virus type 2 seroprevalence and associated factors in fertility-treatment-seeking population: A cross-sectional survey in the United Arab Emirates.

Background: Herpes simplex virus type 2 (HSV-2) is a common genitally-transmitted viral infection affecting more than 400 million individuals globally. In the United Arab Emirates (UAE), in specific at-risk population groups, the burden of HSV-2 has not been reported. This study investigated the prevalence of HSV-2 IgG antibodies in patients seeking fertility treatment and characterized patients with seropositivity to HSV-2 IgG antibodies. Methodology: A cross-sectional sample of patients seeking fertility treatment in a major fertility clinic in Abu Dhabi, UAE was surveyed from April to May 2021. Patients were consecutively invited to complete self-administered questionnaires and provide blood for HSV-2 testing. Information on sociodemographics, medical history, and infertility was collected. Serum specimens were screened using an enzyme-linked immunosorbent assay for HSV-2 IgG antibodies detection. Results: Two hundred and ninety-nine patients were surveyed and provided blood samples. The mean age of the patients was 35.9 ± 6.8 [mean ± standard deviation (SD)] years with 89.3% being women. Sixty-six percent were overweight or obese, 25.0% had at least one chronic comorbidity, and 19.6% reported ever-had genital infection. More than two-thirds (68.3%) of the patients were infertile for ≥ 6 months. Of the 42 infertile males, 69.0% had an abnormal semen analysis. HSV-2 IgG antibodies was detected in 12.4% of patients. The HSV-2 IgG seropositive patients had a higher mean age (39.5 vs. 35.4 years; p < 0.001) compared to seronegative patients. HSV-2 IgG antibodies seropositivity was more common in males (15.6%) than females (12.0%), in patients with secondary (14.1%) vs. primary (9.2%) infertility, or in males with abnormal (10.3%) vs. normal (7.7%) semen. Conclusion: Exposure to HSV-2 at any time in patients seeking fertility treatment in the UAE was found to be slightly common in more than one out of 10 patients. Tailored health campaigns on HSV-2 prevention are warranted.

Update: Sexually transmitted infections, active component, U.S. Armed Forces, 2013-2021.

This report summarizes incidence rates of the 5 most common sexually transmitted infections (STIs) among active component service members of the U.S. Armed Forces during 2013-2021. Infections with chlamydia were the most common, followed in decreasing order of frequency by infections with genital human papillomavirus (HPV), gonorrhea, genital herpes simplex virus (HSV), and syphilis. Compared to men, women had higher rates of all STIs except for syphilis. In general, compared to their respective counterparts, younger service members, non-Hispanic Black service members, those who were single and other/unknown marital status, and enlisted service members had higher incidence rates of STIs. Although rates of chlamydia and gonorrhea increased among both male and female service members during the latter half of the surveillance period, there was a notable decrease in the rates of chlamydia in both sexes from 2019 through 2021, and the rates of gonorrhea decreased slightly for both men and women during 2018-2021. Rates of syphilis generally increased during the first half of the surveillance period, decreased in 2020, then increased in 2021. Rates of genital HSV declined during the period from 2016 through 2021 for both male and female service members. The rates of genital HPV decreased steadily between 2012 and 2021 in men and declined between 2015 and 2021 among women. Similarities to and differences from the findings of the last MSMR update on STIs are discussed.

Genital Herpes Simplex Virus-An Updated Review.

The herpes virus was named by the Greek physician Hippocrates who called it herpes because the lesions appeared near each other and were vesicular. Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae are subfamilies of the human herpes virus family. The Alphaherpesvirinae subfamily includes the simplex viruses-HSV-1 and HSV-2-and varicellovirus-varicella zoster virus. There are more than 200 members of the Herpesviridae family capable of infecting different species, 8 of which are known to cause disease in humans. The simplex viruses can cause lifelong genital infections, and despite the prevalence of HSV-1 and HSV-2 infections in the United States decreasing in the past 20 years, infections with these viruses continue to contribute to significant clinical and psychological morbidities.

Increasing incidence rates of sexually transmitted infections from 2010 to 2019: an analysis of temporal trends by geographical regions and age groups from the 2019 Global Burden of Disease Study.

BACKGROUND: World Health Organization announced its goal of ending sexually transmitted infection (STI) epidemics by 2030. To provide a reference for tailored prevention strategies, we analyzed trends and differences in STIs by geographical regions and age groups from 1990 to 2019. METHODS: Annual number of new infections and age-standardized incidence rates (ASRs) of syphilis, chlamydia, gonorrhea, trichomoniasis, and genital herpes were recorded from the 2019 Global Burden of Disease study. We quantified the temporal trends of STIs by calculating changes in new infections and estimated annual percentage changes (EAPCs) of ASR. RESULTS: The ASRs of syphilis, chlamydia, trichomoniasis, and genital herpes increased by 1.70% (95% confidence interval [CI], 1.62-1.78%), 0.29% (95% CI 0.04-0.54%), 0.27% (95% CI 0.03-0.52%), and 0.40% (95% CI 0.36-0.44%) per year from 2010 to 2019 worldwide, respectively, while that of gonorrhea did not. The American regions had the greatest increase in ASR for syphilis (tropical Latin America: EAPC, 5.72; 95% CI 5.11-6.33), chlamydia (high-income North America: EAPC, 1.23; 95% CI 0.73-1.73), and gonorrhea (high-income North America: EAPC, 0.77; 95% CI 0.12-1.41). Additionally, southern sub-Saharan Africa and East Asia had the greatest increase in ASR for trichomoniasis (EAPC, 0.88; 95% CI 0.57-1.20) and genital herpes (EAPC, 1.44; 95% CI 0.83-2.06), respectively. In the most recent years, the population with the greatest incidence of syphilis tended to be younger globally (25-29 years in 2010 vs. 20-24 years in 2019) but older in North Africa and Middle East (20-24 year vs. 25-29 years); with chlamydia tended to be older in southern sub-Saharan Africa (25-29 years vs. 30-34 years) but younger in Australasia (40-44 years vs. 25-29 years); with genital herpes tended to be older in high-income North America (20-24 years vs. 25-29 years) and South Asia (25-29 years vs. 30-34 years). CONCLUSIONS: Syphilis, chlamydia, trichomoniasis, and genital herpes showed a trend of increasing ASR from 2010 to 2019. The differences in trends by geographical regions and age groups point to the need for more targeted prevention strategies in key regions and populations.