SOMAscan is an aptamer-based proteomics assay capable of measuring 1,305 human protein analytes in serum, plasma, and other biological matrices with high sensitivity and specificity. In this work, we ...present a comprehensive meta-analysis of performance based on multiple serum and plasma runs using the current 1.3 k assay, as well as the previous 1.1 k version. We discuss normalization procedures and examine different strategies to minimize intra- and interplate nuisance effects. We implement a meta-analysis based on calibrator samples to characterize the coefficient of variation and signal-over-background intensity of each protein analyte. By incorporating coefficient of variation estimates into a theoretical model of statistical variability, we also provide a framework to enable rigorous statistical tests of significance in intervention studies and clinical trials, as well as quality control within and across laboratories. Furthermore, we investigate the stability of healthy subject baselines and determine the set of analytes that exhibit biologically stable baselines after technical variability is factored in. This work is accompanied by an interactive web-based tool, an initiative with the potential to become the cornerstone of a regularly updated, high quality repository with data sharing, reproducibility, and reusability as ultimate goals.
Abstract
Background
In 2018, Philadelphia County ranked 7th, 8th and 16th for chlamydia (CT), gonorrhea (GC), and syphilis cases, respectively, in the Centers for Disease Control (CDC) STI ...Surveillance Report. Asymptomatic presentations and lack of routine screening, especially at extragenital (i.e., pharyngeal and rectal) sites, increase the challenge of timely diagnosis and treatment. We determined extent of screening, reported symptoms, and asymptomatic infections.
Methods
We analyzed records of 372 patients receiving care at an urban, university-based Ryan White HIV clinic from 2016-2018. Outcomes included: positive GC/CT nucleic acid amplification tests from genital, pharyngeal, and rectal sites as well as new diagnoses of syphilis. We collected demographic data, risk factors for HIV transmission, time from HIV diagnosis, number of clinic visits, multiple sex partners, partner with STI, and injection drug use. We used logistic regression to model factors associated with STIs and determined prevalence of asymptomatic STIs.
Results
Of 372 participants, 234 (63%) were men, 262 (70%) were Black, 245 (66%) were over 40 years old, 148 (40%) identified as MSM, 140 (38%) reported inconsistent condom use, 89 (24%) reported multiple sex partners, 35 (9%) reported injection drug use, 141 (38%) had past STI, and 26 (7%) had partner with past STI. Mean time from HIV diagnosis was 12.3 years (SD, 8.8) and mean number of clinic visits was 2/year. Testing included 720 GC/CT urine, 176 GC/CT pharyngeal, 143 GC/CT rectal swabs and 887 syphilis blood tests. Asymptomatic GC/CT infections were seen in urine 6/22 (27%), pharyngeal 12/14 (86%) and rectal 28/31 (90%) swabs. And, of 39 new diagnoses of syphilis, 23 (59%) were asymptomatic. In multivariate analysis, men (aOR, 12.2, 95%CI, 2.7-55.3), < 40 years (3.2, 1.7-6.1), with clinic visit in 2018 (1.4, 1.2-1.8), and partner with STI (1.7, 0.9-2.8) were more likely to have a positive GC/CT test. Patients with positive syphilis test were more likely men (4.6, 1.1-20.2), with multiple sex partners (3.7, 1.7-8.0), and more recent HIV diagnosis (1.1, 1.0-1.1).
Prevalence of Asymptomatic STIs
Conclusion
Results indicate the importance of routine, site-specific STI screening among patients living with HIV. Our findings can inform screening strategies among urban HIV populations.
Disclosures
All Authors: No reported disclosures
BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 ...encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov NCT01443936 and NCT01806909.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C).
BACKGROUND. To understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 ...encoding influenza virus H5 HA (Ad4-H5Vtn) administered as an oral capsule or via tonsillar swab or nasal spray. METHODS. Viral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays. RESULTS. Ad4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4· and CD8· T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine. CONCLUSION. Replicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets. TRIAL REGISTRATION. ClinicalTrials.gov NCT01443936 and NCT01806909. FUNDING. Intramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C).
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