Background. Influenza A viruses cause occasional pandemics and frequent epidemics. Licensed influenza vaccines that induce high antibody titers to the highly polymorphic viral surface antigen hemagglutinin must be re-formulated and readministered annually. A vaccine providing protective immunity to the highly conserved internal antigens could provide longer-lasting protection against multiple influenza subtypes.Methods. We prepared a Modified Vaccinia virus Ankara (MVA) vector encoding nucleoprotein and matrix protein 1 (MVA−NP+M1) and conducted a phase I clinical trial in healthy adults.Results. The vaccine was generally safe and well tolerated, with significantly fewer local side effects after intramuscular rather than intradermal administration. Systemic side effects increased at the higher dose in both frequency and severity, with 5 out of 8 volunteers experiencing severe nausea/vomiting, malaise, or rigors. Ex vivo T-cell responses to NP and M1 measured by IFN-γ ELISPOT assay were significantly increased after vaccination (prevaccination median of 123 spot-forming units/million peripheral blood mononuclear cells, postvaccination peak response median 339, 443, and 1443 in low-dose intradermal, low-dose intramuscular, and high-dose intramuscular groups, respectively), and the majority of the antigen-specific T cells were CD8+.Conclusions. We conclude that the vaccine was both safe and remarkably immunogenic, leading to frequencies of responding T cells that appear to be much higher than those induced by any other influenza vaccination approach. Further studies will be required to find the optimum dose and to assess whether the increased T-cell response to conserved influenza proteins results in protection from influenza disease.

A single vaccination with MVA-NP+M1 boosts T-cell responses to conserved influenza antigens in humans. Protection against influenza disease and virus shedding was demonstrated in an influenza virus challenge study.

In 2019, an estimated 2.55 million new sexually transmitted infections (STIs) were reported in the US, 1 with a projected direct medical cost of approximately $1.1 billion for gonorrhea, chlamydia, and syphilis in 2018. 2 In 2018, there were approximately 67.6 million prevalent infections in the US, suggesting that an estimated 1 in 5 adults had an STI. 3 People with STIs are at greater risk of transmitting HIV to others. Among people without HIV, STIs increase rates of HIV acquistion. 4,5 STIs also increase rates of infertility, chronic pelvic pain, ectopic pregnancy, miscarriage, fetal death, and congenital and neonatal infections. [6][7][8][9] This review summarizes current evidence regarding the epidemiology, diagnosis, treatment, and prevention of gonorrhea, chlamydia, syphilis, Mycoplasma genitalium, trichomoniasis, and genital herpes. For the purposes of clarity, in this article, the terms male and female refer to those assigned male or female at birth, respectively (see eTable 1 in the Supplement for additional clinician resources). MethodsWe searched PubMed and Cochrane databases using Medical Subject Headings for English-language studies of the epidemiology, diagnosis, and treatment of gonorrhea, chlamydia (including lymphogranuloma venereum), syphilis, Mycoplasma genitalium, trichomoniasis, and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) between October 1, 2010, and October 31, 2021. We manually searched the references of selected articles for additional relevant studies (including older studies). Randomized clinical trials, meta-analyses, systematic reviews, and national and international clinical practice guidelines were prioritized for inclusion. Of 1896 reports identified, 81 were included, consisting of 8 randomized trials, 7 meta-analyses, 27 systematic reviews, 5 clinical practice guidelines, 28 observational studies, 3 modeling studies, and 3 retrospective case series. 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,...

Effective treatment of sexually transmitted infections (STIs) is limited by diagnostics that cannot deliver results rapidly while the patient is still in the clinic. The gold standard methods for identification of STIs are nucleic acid amplification tests (NAATs), which are too expensive for widespread use and have lengthy turnaround times. To address the need for fast and affordable diagnostics, we have developed a portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) polymerase chain reaction (PCR) test. We show that it can detect Neisseria gonorrhoeae, the pathogen causing gonorrhea, with simultaneous genotyping of the pathogen for resistance to the antimicrobial drug ciprofloxacin in <15 min. The duplex test was integrated into a low-cost thermoplastic cartridge with automated processing of penile swab samples from patients using magnetic beads. A compact instrument conducted DNA extraction, PCR, and analysis of results while relaying data to the user via a smartphone app. This platform was tested on penile swab samples from sexual health clinics in Baltimore, MD, USA (n = 66) and Kampala, Uganda (n = 151) with an overall sensitivity and specificity of 97.7% (95% CI, 94.7 to 100%) and 97.6% (95% CI, 94.1 to 100%), respectively, for N. gonorrhoeae detection and 100% concordance with culture results for ciprofloxacin resistance. This study paves the way for delivering accessible PCR diagnostics for rapidly detecting STIs at the point of care, helping to guide treatment decisions and combat the rise of antimicrobial resistant pathogens.

SummaryThis is the first report examining vitamin D status and bone mass in African women with HIV infection using dual-energy X-ray absorptiometry (DXA) with an appropriate HIV-negative control group. Unlike previous publications, it demonstrates no difference in bone mineral density (BMD) or vitamin D status in HIV-positive patients, at different disease stages, vs. HIV-negative subjects.IntroductionLow bone mass and poor vitamin D status have been reported among HIV-positive patients; suggesting HIV or its treatment may increase the risk of osteoporosis, a particular concern for women in countries with high HIV prevalence such as South Africa. We describe bone mass and vitamin D status in urban premenopausal South African women, who were HIV positive but not on antiretroviral therapy (ARV).MethodsThis study is a cross-sectional measurement of BMD and body composition by DXA and vitamin D status by serum 25-hydroxyvitamin D (25(OH)D) concentration. Subjects were recruited into three groups: HIV negative (n = 98) and HIV positive with preserved CD4 cell count (non-ARV; n = 74) or low CD4 cell counts prior to ARV initiation (pre-ARV; n = 75).ResultsThe mean (standard deviation (SD)) age of women was 32.1 (7.2) years. Mean CD4 (SD) counts (×106/l) were 412 (91) and 161 (69) in non-ARV and pre-ARV groups (p < 0.0001). Pre-ARV women were significantly lighter and had lower mean BMI than the other two groups (p < 0.002). The pre-ARV group also had significantly less fat and lean mass compared with non-ARV and HIV-negative subjects (p ≤ 0.05). After full adjustment, there were no significant differences in BMD at any site (p > 0.05) between the groups, nor was vitamin D status significantly different between groups (p > 0.05); the mean (SD) cohort 25(OH)D being 60 (18) nmol/l.ConclusionContrary to previous studies, these HIV-positive women did not have lower BMD or 25(OH)D concentrations than HIV-negative controls, despite the pre-ARV group being lighter with lower BMI.Electronic supplementary materialThe online version of this article (doi:10.1007/s00198-013-2373-y) contains supplementary material, which is available to authorized users.

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ObjectivesControl of the tuberculosis (TB) epidemic is a global health priority and one that is likely to be achieved only through vaccination. The critical overlap with the HIV epidemic requires any effective TB vaccine regimen to be safe in individuals who are infected with HIV. The objectives of this clinical trial were to evaluate the safety and immunogenicity of a leading candidate TB vaccine, MVA85A, in healthy, HIV-infected adults.DesignThis was an open-label Phase I trial, performed in 20 healthy HIV-infected, antiretroviral-naïve subjects. Two different doses of MVA85A were each evaluated as a single immunisation in 10 subjects, with 24 weeks of follow-up. The safety of MVA85A was assessed by clinical and laboratory markers, including regular CD4 counts and HIV RNA load measurements. Vaccine immunogenicity was assessed by ex vivo interferon γ (IFN-γ) ELISpot assays and flow-cytometric analysis.ResultsMVA85A was safe in subjects with HIV infection, with an adverse-event profile comparable with historical data from previous trials in HIV-uninfected subjects. There were no clinically significant vaccine-related changes in CD4 count or HIV RNA load in any subjects, and no evidence from qPCR analyses to indicate that MVA85A vaccination leads to widespread preferential infection of vaccine-induced CD4 T cell populations. Both doses of MVA85A induced an antigen-specific IFN-γ response that was durable for 24 weeks, although of a lesser magnitude compared with historical data from HIV-uninfected subjects. The functional quality of the vaccine-induced T cell response in HIV-infected subjects was remarkably comparable with that observed in healthy HIV-uninfected controls, but less durable.ConclusionMVA85A is safe and immunogenic in healthy adults infected with HIV. Further safety and efficacy evaluation of this candidate vaccine in TB- and HIV-endemic areas is merited.

HIV infection and antiretroviral therapy (ART) are associated with bone loss and poor vitamin D status in Caucasian populations, though their relative roles are not known. No previous studies have examined longitudinal changes in areal bone mineral density (aBMD), measured by DXA, or in vitamin D status in HIV-positive African women. Of 247 premenopausal, urban, black African women from Soweto, South Africa, initially recruited, 187 underwent anthropometry, DXA scanning and blood and urine collections at both baseline and 12 months. Of these, 67 were HIVnegative throughout (Nref), 60 were HIV-positive with preserved CD 4 counts at baseline (Ppres) and 60 were HIV-positive with low CD 4 counts at baseline, eligible for ART by South African standards of care at the time (Plow). No participant had been exposed to ART at baseline. By 12 months, 51 Plow women had initiated ART, >85% of whom took combined tenofovir disoproxil fumarate (TDF), lamivudine and efavirenz. By 12 months, Plow and Nref, but not Ppres, increased in body weight and fat mass (group-by-timepoint p ≤0.001, p=0.002 respectively). Plow had significant decreases in aBMD of 2-3%, before and after size adjustment, at the femoral neck (p ≤0.002) and lumbar spine (p ≤0.001), despite significant weight gain. These decreases were associated with increased bone turnover but there were no significant differences or changes over time in vitamin D status, serum phosphate concentrations or renal phosphate handling. Excluding data from 9 Plow women unexposed to ART and 11 Ppres women who had initiated ART accentuated these findings, suggesting the bone loss in Plow was related to ART exposure. This is the first study describing DXA-defined bone loss in HIV-positive Sub-Saharan African women in Authors responsibilities: MMH, AP and JMP designed the study; MMH conducted the study; JMP and SAN provided senior oversight of the study in South Africa; KW provided senior oversight and interpretation of the DXA data; AP provided senior oversight and interpretation of the biochemical data; MMH and AP jointly conducted the statistical analysis and drafted the paper; all authors had full access to the data and contributed to interpretation of the findings. MMH and AP have responsibility for data integrity. All authors approved the manuscript for publication.The authors state that they have no conflicts of interest. Europe PMC Funders Group