These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field ...of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.
Vitamin D plays a critical role in bone development and maintenance, and in other physiological functions. The quantitation of endogenous levels of individual vitamin D and its metabolites is crucial ...for assessing several disease state conditions. With cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to the coronavirus disease 2019 (COVID-19) pandemic, there are several studies that have associated lower levels of serum vitamin D with severity of infection in COVID-19 patients. In this context, we have developed and validated a robust LC-MS/MS method for simultaneous quantitation of vitamin D and its metabolites in human dried blood spot (DBS) obtained from participants tested for COVID-19. The chromatographic separation for vitamin D and metabolites was performed using an ACE Excel C18 PFP column protected with a C18 guard column (Phenomenex, Torrance, CA, USA). The mobile phase consisted of formic acid in water (0.1%
/
) as mobile phase A and formic acid in methanol (0.1%
/
) as mobile phase B, operated at a flow rate of 0.5 mL/min. Analysis was performed utilizing the LC-MS/MS technique. The method was sensitive with a limit of quantification of 0.78 ng/mL for all analytes, and had a large dynamic range (200 ng/mL) with a total run time of 11 min. The inter- and intraday accuracy and precision values met the acceptance criteria per the US Food and Drug Administration guidelines. Blood concentrations of 25(OH)D3, vitamin D3, 25(OH)D2, and vitamin D2 over a range of 2-195.6, 0.5-121.5, 0.6-54.9, and 0.5-23.9 ng/mL, respectively, were quantified in 909 DBS samples. In summary, our developed LC-MS/MS method may be used for quantification of vitamin D and its metabolites in DBS, and may be applied to investigations of the emerging role of these compounds in various physiological processes.
Abstract
Genital herpes, caused by herpes simplex virus (HSV) type 1 or type 2, is a prevalent sexually transmitted infection (STI). Given that HSV is an incurable infection, there are important ...concerns about appropriate use of diagnostic tools, management of infection, prevention of transmission to sexual partners, and appropriate counseling. In preparation for updating the Centers for Disease Control and Prevention (CDC) STI treatment guidelines, key questions for management of genital herpes infection were developed with a panel of experts. To answer these questions, a systematic literature review was performed, with tables of evidence including articles that would change guidance assembled. These data were used to inform recommendations in the 2021 CDC STI treatment guidelines.
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.
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.
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.
The ethics of studying or collecting unprovenanced material is intrinsically tied to the issue of looting. In recent years looting has become increasingly facilitated by the current political ...instability in various parts of the world, with looted objects often serving as a highly lucrative source of income for insurgent or even terrorist groups. As international statutes and industry protocols aim to alleviate further threats to cultural heritage, consideration is also due to the future of the vast collections of unprovenanced and subsidiary material acquired through decades of cultural tourism and incipient archaeological exploration. A survey of Canadian and American academic institutions was conducted to determine the extent of department-held material collections, as well as the current pedagogical and research purposes to which they are directed.
To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 ...lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and myeloid dendritic cells (DCs), including cells expressing the C-type lectin receptor DC-SIGN, persisted at sites of HSV-2 reactivation for months after healing, even with daily antiviral therapy. The CD4(+) T cells that persisted reacted to HSV-2 antigen, were enriched for expression of the chemokine receptor CCR5, and were contiguous to DCs expressing the interleukin-3 receptor CD123 or DC-SIGN. Ex vivo infection with a CCR5-tropic strain of HIV-1 revealed greater concentrations of integrated HIV-1 DNA in cells derived from healed genital lesion biopsies than in cells from control skin biopsies. The persistence and enrichment of HIV receptor-positive inflammatory cells in the genitalia help explain the inability of anti-HSV-2 therapy to reduce HIV acquisition.
BACKGROUNDHerpes simplex virus type 1 (HSV-1) is prevalent worldwide and causes mucocutaneous infections of the oral area. We aimed to define the frequency and anatomic distribution of HSV-1 ...reactivation in the facial area in persons with a history of oral herpes.
METHODSEight immunocompetent HSV-1 seropositive adults were evaluated for shedding of HSV-1 from 12 separate orofacial sites (8 from oral mucosa, 2 from nose, and 2 from conjunctiva) 5 days a week and from the oral cavity 7 days a week for approximately 5 consecutive weeks by a HSV DNA PCR assay. Symptoms and lesions were recorded by participants.
RESULTSHerpes simplex virus type 1 was detected at least from 1 site on 77 (26.5%) of 291 days. The most frequent site of shedding was the oral mucosa, with widespread shedding throughout the oral cavity. Lesional shedding rate was 36.4% (4 of 11 days with lesions), and the asymptomatic rate was 27.1% (65 of 240 nonlesional days). In individual participants, the median rate of HSV shedding by HSV PCR was 19.7% of days (range, 11%–63%).
CONCLUSIONSReactivation of HSV-1 on the oral mucosa is common and usually asymptomatic. However, HSV-1 is rarely found in tears and nasal mucosa. Frequent oral shedding of HSV-1 may increase the risk for transmitting the virus to both oral and genital mucosa of sexual partners.
Helicase-primase inhibitor pritelivir for HSV-2 infection Wald, Anna; Corey, Lawrence; Timmler, Burkhard ...
New England journal of medicine/The New England journal of medicine,
01/2014, Letnik:
370, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of ...pritelivir in otherwise healthy persons with genital HSV-2 infection.
We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding.
HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval CI, 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups.
Pritelivir reduced the rates of genital HSV shedding and days with lesions in a dose-dependent manner in otherwise healthy men and women with genital herpes. (Funded by AiCuris; ClinicalTrials.gov number, NCT01047540.).
Herpes simplex virus 2 (HSV-2) is a DNA virus that is efficiently transmitted through intimate genital tract contact and causes persistent infection that cannot be eliminated. HSV-2 may cause ...frequent, symptomatic self-limited genital ulcers, but in most persons infection is subclinical. However, recent studies have demonstrated that the virus is frequently shed from genital surfaces even in the absence of signs or symptoms of clinical disease and that the virus can be transmitted during these periods of shedding. Furthermore, HSV-2 shedding is detected throughout the genital tract and may be associated with genital tract inflammation, which likely contributes to increased risk of HIV acquisition. This review focuses on HSV diagnostics, as well as what we have learned about the importance of frequent genital HSV shedding for (i) HSV transmission and (ii) genital tract inflammation, as well as (iii) the impact of HSV-2 infection on HIV acquisition and transmission. We conclude with discussion of future areas of research to push the field forward.
This study uses the Interactive Learning Model theory to explore the nature of self-awareness within each of three L2 learners. Using the Learning Connections Inventory (LCI), a validated and ...reliable learning instrument, each participant identified their combination of learning patterns. The subjects then recalled specific L2 learning experiences, relating them in first person narratives. Next, each subject composed anecdotes and reflections based on their narratives. They also participated in one-on-one interviews in which they described their learning experiences during basic L2 learning activities: vocabulary, grammar, writing, conversation, and passive listening during movies, live theatre, spectator sports, and television. Our analysis of the LCI outcomes and selfreported learning experiences demonstrated that the self-awareness gained from understanding their combination of learning patterns and expanded by the self-reflection activities, increased the participants’ ability to articulate the nature of their self-awareness and to identify evidence of their growth in self-awareness during L2 learning.