IMPORTANCE: Approximately 1 in 5 adults in the US had a sexually transmitted infection (STI) in 2018. This review provides an update on the epidemiology, diagnosis, and treatment of gonorrhea, ...chlamydia, syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes. OBSERVATIONS: From 2015 to 2019, the rates of gonorrhea, chlamydia, and syphilis increased in the US; from 1999 to 2016, while the rates of herpes simplex virus type 1 (HSV-1) and HSV-2 declined. Populations with higher rates of STIs include people younger than 25 years, sexual and gender minorities such as men and transgender women who have sex with men, and racial and ethnic minorities such as Black and Latinx people. Approximately 70% of infections with HSV and trichomoniasis and 53% to 100% of extragenital gonorrhea and chlamydia infections are asymptomatic or associated with few symptoms. STIs are associated with HIV acquisition and transmission and are the leading cause of tubal factor infertility in women. Nucleic acid amplification tests have high sensitivities (86.1%-100%) and specificities (97.1%-100%) for the diagnosis of gonorrhea, chlamydia, M genitalium, trichomoniasis, and symptomatic HSV-1 and HSV-2. Serology remains the recommended method to diagnose syphilis, typically using sequential testing to detect treponemal and nontreponemal (antiphospholipid) antibodies. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles, such as metronidazole, are effective treatments for gonorrhea, chlamydia, syphilis, M genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral treatment options for gonorrhea and M genitalium. No cure is available for genital herpes. Effective STI prevention interventions include screening, contact tracing of sexual partners, and promoting effective barrier contraception. CONCLUSIONS AND RELEVANCE: Approximately 1 in 5 adults in the US had an STI in 2018. Rates of gonorrhea, chlamydia, and syphilis in the US have increased, while rates of HSV-1 and HSV-2 have declined. Ceftriaxone, doxycycline, penicillin, moxifloxacin, and the nitroimidazoles are effective treatments for gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, and trichomoniasis, respectively, but antimicrobial resistance limits oral therapies for gonorrhea and Mycoplasma genitalium, and no cure is available for genital herpes.
To evaluate the risks of herpes zoster (HZ) and herpes simplex virus (HSV) infection associated with tofacitinib compared with biologic agents among patients with rheumatoid arthritis (RA).
Using ...health plan data from 2010 to 2014, patients with RA initiating tofacitinib or biologics with no history of HZ or HSV were identified, as were incident cases of HZ or HSV. Crude incidence rates were calculated by drug exposure. Cox proportional hazards models evaluated the adjusted association between tofacitinib and HZ, and a composite outcome of HZ or HSV.
A total of 2526 patients initiating tofacitinib were compared with initiations of other biologics: anti-tumour necrosis factor (TNF) (n=42 850), abatacept (n=12 305), rituximab (n=5078) and tocilizumab (n=6967). Patients receiving tofacitinib were somewhat younger (mean age 55 years) versus those on other biologics, and somewhat less likely to use concomitant methotrexate (MTX) (39% vs 43%-56%, depending on drug). Crude incidence of HZ associated with tofacitinib was 3.87/100 patient-years (py). After multivariable adjustment, HZ risk was significantly elevated, HR 2.01 (95% CI 1.40 to 2.88) compared with abatacept. Rates and adjusted HRs for all other RA biologics were comparable with each other and abatacept. Older age, female sex, prednisone >7.5 mg/day, prior outpatient infection and greater number of hospitalisations were also associated with increased HZ risk. Incidence rates for the combined outcome were greatest for tofacitinib (7.61/100 py) and also significantly elevated after adjustment (HR=1.40, 95% CI 1.09 to 1.81).
The rate of zoster associated with tofacitinib was approximately double that observed in patients using biologics.
In this randomized, controlled trial involving more than 15,000 participants 50 years of age or older, a varicella–zoster virus subunit vaccine with AS01B adjuvant was found to have an efficacy of ...more than 96% in preventing herpes zoster.
Herpes zoster, or shingles, results from the reactivation of latent varicella–zoster virus (VZV) in the dorsal-root or cranial-nerve ganglia, usually decades after primary infection.
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Herpes zoster is characterized by a vesicular rash with a unilateral and dermatomal distribution and is almost always accompanied by pain. More than 90% of adults have been infected with VZV and are at risk for herpes zoster.
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Although herpes zoster is most frequent in adults who are 50 years of age or older owing to immunosenescence, it can occur at any age, especially when cell-mediated immunity is decreased as a result of disease . . .
Background. The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine ...efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. Methods. Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups. Results. The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8. Conclusions. Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.
Herpes simplex virus 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Over the last 15 years, human genetic and immunological studies have provided ...proof-of-principle that childhood HSE can result from inborn errors of central nervous system (CNS)-specific, cell-intrinsic immunity to HSV-1. HSE-causing mutations of eight genes disrupt known (TLR3-dependent IFN-α/β immunity) and novel (dependent on DBR1 or snoRNA31) antiviral mechanisms. Monogenic inborn errors confer susceptibility to forebrain (TLR3-IFN or snoRNA31) or brainstem (DBR1) HSE. Most of these disorders display incomplete clinical penetrance, with the possible exception of DBR1 deficiency. They account for a small, but non-negligible proportion of cases (about 7%). These findings pave the way for the gradual definition of the genetic and immunological architecture of childhood HSE, with both biological and clinical implications.
Two of the most prevalent human viruses worldwide, herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2, respectively), cause a variety of diseases, including cold sores, genital herpes, herpes ...stromal keratitis, meningitis and encephalitis. The intrinsic, innate and adaptive immune responses are key to control HSV, and the virus has developed mechanisms to evade them. The immune response can also contribute to pathogenesis, as observed in stromal keratitis and encephalitis. The fact that certain individuals are more prone than others to suffer severe disease upon HSV infection can be partially explained by the existence of genetic polymorphisms in humans. Like all herpesviruses, HSV has two replication cycles: lytic and latent. During lytic replication HSV produces infectious viral particles to infect other cells and organisms, while during latency there is limited gene expression and lack of infectious virus particles. HSV establishes latency in neurons and can cause disease both during primary infection and upon reactivation. The mechanisms leading to latency and reactivation and which are the viral and host factors controlling these processes are not completely understood. Here we review the HSV life cycle, the interaction of HSV with the immune system and three of the best-studied pathologies: Herpes stromal keratitis, herpes simplex encephalitis and genital herpes. We also discuss the potential association between HSV-1 infection and Alzheimer's disease.
Herpes simplex encephalitis can trigger autoimmune encephalitis that leads to neurological worsening. We aimed to assess the frequency, symptoms, risk factors, and outcomes of this complication.
We ...did a prospective observational study and retrospective analysis. In the prospective observational part of this study, we included patients with herpes simplex encephalitis diagnosed by neurologists, paediatricians, or infectious disease specialists in 19 secondary and tertiary Spanish centres (Cohort A). Outpatient follow-up was at 2, 6, and 12 months from onset of herpes simplex encephalitis. We studied another group of patients retrospectively, when they developed autoimmune encephalitis after herpes simplex encephalitis (Cohort B). We compared demographics and clinical features of patients who developed autoimmune encephalitis with those who did not, and in patients who developed autoimmune encephalitis we compared these features by age group (patients ≤4 years compared with patients >4 years). We also used multivariable binary logistic regression models to assess risk factors for autoimmune encephalitis after herpes simplex encephalitis.
Between Jan 1, 2014, and Oct 31, 2017, 54 patients with herpes simplex encephalitis were recruited to Cohort A, and 51 were included in the analysis (median age 50 years IQR 5–68). At onset of herpes simplex encephalitis, none of the 51 patients had antibodies to neuronal antigens; during follow-up, 14 (27%) patients developed autoimmune encephalitis and all 14 (100%) had neuronal antibodies (nine 64% had NMDA receptor NMDAR antibodies and five 36% had other antibodies) at or before onset of symptoms. The other 37 patients did not develop autoimmune encephalitis, although 11 (30%) developed antibodies (n=3 to NMDAR, n=8 to unknown antigens; p<0·001). Antibody detection within 3 weeks of herpes simplex encephalitis was a risk factor for autoimmune encephalitis (odds ratio OR 11·5, 95% CI 2·7–48·8; p<0·001). Between Oct 7, 2011, and Oct 31, 2017, there were 48 patients in Cohort B with new-onset or worsening neurological symptoms not caused by herpes simplex virus reactivation (median age 8·8 years IQR 1·1–44·2; n=27 male); 44 (92%) patients had antibody-confirmed autoimmune encephalitis (34 had NMDAR antibodies and ten had other antibodies). In both cohorts (n=58 patients with antibody-confirmed autoimmune encephalitis), patients older than 4 years frequently presented with psychosis (18 58% of 31; younger children not assessable). Compared with patients older than 4 years, patients aged 4 years or younger (n=27) were more likely to have shorter intervals between onset of herpes simplex encephalitis and onset of autoimmune encephalitis (median 26 days IQR 24–32 vs 43 days 25–54; p=0·0073), choreoathetosis (27 100% of 27 vs 0 of 31; p<0·001), decreased level of consciousness (26 96% of 27 vs seven 23% of 31; p<0·001), NMDAR antibodies (24 89% of 27 vs 19 61% of 31; p=0·033), and worse outcome at 1 year (median modified Rankin Scale 4 IQR 4–4 vs 2 2–3; p<0·0010; seizures 12 63% of 19 vs three 13% of 23; p=0·001).
The results of our prospective study show that autoimmune encephalitis occurred in 27% of patients with herpes simplex encephalitis. It was associated with development of neuronal antibodies and usually presented within 2 months after treatment of herpes simplex encephalitis; the symptoms were age-dependent, and the neurological outcome was worse in young children. Prompt diagnosis is important because patients, primarily those older than 4 years, can respond to immunotherapy.
Mutua Madrileña Foundation, Fondation de l'Université de Lausanne et Centre Hospitalier Universitaire Vaudois, Instituto Carlos III, CIBERER, National Institutes of Health, Generalitat de Catalunya, Fundació CELLEX.
A 2017 systematic review and meta-analysis of 55 prospective studies found the adjusted risk of HIV acquisition to be at least tripled in individuals with herpes simplex virus type 2 (HSV-2) ...infection. We aimed to assess the potential contribution of HSV-2 infection to HIV incidence, given an effect of HSV-2 on HIV acquisition.
We used a classic epidemiological formula to estimate the global and regional (WHO regional) population attributable fraction (PAF) and number of incident HIV infections attributable to HSV-2 infection by age (15–24 years, 25–49 years, and 15–49 years), sex, and timing of HSV-2 infection (established vs recently acquired). Estimates were calculated by incorporating HSV-2 and HIV infection data with pooled relative risk (RR) estimates for the effect of HSV-2 infection on HIV acquisition from a systematic review and meta-analysis. Because HSV-2 and HIV have shared sexual and other risk factors, in addition to HSV-related biological factors that increase HIV risk, we only used RR estimates that were adjusted for potential confounders.
An estimated 420 000 (95% uncertainty interval 317 000–546 000; PAF 29·6% 22·9–37·1) of 1·4 million sexually acquired incident HIV infections in individuals aged 15–49 years in 2016 were attributable to HSV-2 infection. The contribution of HSV-2 to HIV was largest for the WHO African region (PAF 37·1% 28·7–46·3), women (34·8% 23·5–45·0), individuals aged 25–49 years (32·4% 25·4–40·2), and established HSV-2 infection (26·8% 19·7–34·5).
A large burden of HIV is likely to be attributable to HSV-2 infection, even if the effect of HSV-2 infection on HIV had been imperfectly measured in studies providing adjusted RR estimates, potentially because of residual confounding. The contribution is likely to be greatest in areas where HSV-2 is highly prevalent, particularly Africa. New preventive interventions against HSV-2 infection could not only improve the quality of life of millions of people by reducing the prevalence of herpetic genital ulcer disease, but could also have an additional, indirect effect on HIV transmission.
WHO.
To compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.
...Systematic review with bayesian meta-analysis and network meta-analysis.
Medline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.
Experimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.
27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).
Using the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.
Prospero CRD42017056389.
Our objective was to develop comprehensive national estimates of the total burden of herpes zoster (HZ) among U.S. adults, including direct (ie, medical costs) and indirect (ie, productivity losses) ...costs, as well as its psychosocial impact (ie, quality of life losses). Using a patient-level microsimulation model, we projected health and economic outcomes among U.S. adults aged 18 years and older using a 10-year time horizon. We conducted a comprehensive systematic literature review to generate parameter values and conducted simulation modeling to generate our outcomes, including numbers of cases of uncomplicated HZ, postherpetic neuralgia (PHN), and ocular complications, productivity losses, and losses in quality-adjusted life years (QALYs). We used a societal perspective for outcomes; the costing year was 2015. Projected outcomes for an unvaccinated population included 1.1 million HZ cases, 114,000 PHN cases, and 43,000 ocular complications annually, resulting in approximately 67,000 QALYs lost. HZ and its complications would incur costs of $2.4 billion in direct medical costs and productivity losses annually. Projected QALY losses were most sensitive to HZ and PHN health utility values in the model. Cost estimates were most sensitive to the probability of HZ and to the costs per episode of PHN. The national burden of direct, indirect, and psychosocial HZ costs is substantial. Our results can inform economic analyses for HZ vaccines. Comprehensive, national assessments of the total burden of other painful conditions would be very informative.
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