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There is an urgent need for innovative methods to reduce transmission of bloodborne pathogens like HIV and HCV among people who inject drugs (PWID). We investigate if PWID who acquire non-pathogenic bloodborne viruses like anelloviruses and pegiviruses might be at greater risk of acquiring a bloodborne pathogen. PWID who later acquire HCV accumulate more non-pathogenic viruses in plasma than matched controls who do not acquire HCV infection. Additionally, phylogenetic analysis of those non-pathogenic virus sequences reveals drug use networks. Here we find first in Baltimore and confirm in San Francisco that the accumulation of non-pathogenic viruses in PWID is a harbinger for subsequent acquisition of pathogenic viruses, knowledge that may guide the prioritization of the public health resources to combat HIV and HCV.

ObjectivesCurrent guidelines recommend screening sexually active persons with HIV (PWH) for Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) at least annually. Yet, screening rates in many HIV clinics remain low. In this study, we estimated the number needed to screen (NNS) to detect a NG and/or CT infection at each anatomic site among different subpopulations of PWH. NNS provides a concrete, practical measure to aid in assessing the practical impact of screening. METHODS : We included adults in care at three HIV Research Network sites in 2011-2014. Restricting to first tests within each year, annual NNS was defined as number of persons tested divided by number positive. We computed urogenital and extragenital NNS by age and risk group (women, men who have sex with women (MSW) and men who have sex with men (MSM)). RESULTS : A total of 16 864 NG/CT tests were included. Among patients aged ≤25 years, urogenital NNS was similar among women (15 (95% CI 6 to 71)), MSW (21 (95% CI 6 to 167)) and MSM (20 (95% CI 12 to 36)). Over 25, urogenital NNS increased to a greater extent for women (363 (95% CI 167 to 1000)) and MSW (160 (95% CI 100 to 333)) than MSM (46 (95% CI 38 to 56)). The increase for women versus MSM >25 remained significant (p25 years and pharyngeal NNS values were 8 (95% CI 5 to 13) and 20 (95% CI 16 to 24).ConclusionsThese findings suggest the importance of regular, at least annual NG/CT screening, particularly extragenital, of HIV positive MSM of all ages. They provide some support for age-based cutoffs for women and MSW (eg, universal screening for those aged ≤25 and targeted screening for those aged >25 years).

BackgroundAn understanding of the biological reasons why 25% to 35% of women resist infection during vaginal intercourse with a man infected with Neisseria gonorrhoeae could lead to novel control measures. We sought modifiable biological bases for infection resistance by comparing women in the same core-mixing group who did or did not become infected after sexual exposure.MethodsWe enrolled 61 female contacts of index men with gonorrhea seen at Baltimore City Health Department clinics from January 2008 through May 2012. Exposure and sexual practices and histories, co-infections, physical signs on exam, patient symptom report, and menstrual history were collected.ResultsThirty-eight (62.3%) of the exposed women developed cervical infections. Multiple logistic regression found that a vaginal pH of 4.5 or higher at presentation to clinic was significantly associated with gonococcal infection (adjusted odds ratio, 5.5; P = 0.037) in women who presented within one menstrual cycle, 35 days. In this group of women, there was a significant association between acquiring an N. gonorrhoeae cervical infection and sexual exposure during menstruation (adjusted odds ratio 12.5; P = 0.05).ConclusionsModification of vaginal pH could be explored as novel strategy for reducing the risk of N. gonorrhoeae infections in women.

BackgroundMany individuals with HIV in the USA are unaware of their diagnosis, and therefore cannot be engaged in treatment services, have worse clinical outcomes and are more likely to transmit HIV to others. Mobile van testing may increase HIV testing and diagnosis. Our objective was to characterise risk factors for HIV seroconversion among individuals using mobile van testing.MethodsA case cohort study (n=543) was conducted within an HIV surveillance dataset of mobile van testing users with at least two HIV tests between September 2004 and August 2009 in Baltimore, Maryland. A subcohort (n=423) was randomly selected; all additional cases were added from the parent cohort. Cases (n=122 total, two from random subcohort) had documented seroconversion at the follow-up visit. A unique aspect of the analysis was use of Department of Corrections data to document incarceration between the times of initial and subsequent testing. Multivariate Cox proportional hazards models were used to compare HIV transmission risk factors between individuals who seroconverted and those who did not.ResultsOne hundred and twenty-two HIV seroconversions occurred among 8756 individuals (1.4%), a rate higher than that in Baltimore City Health Department's STD Clinic clients (1%). Increased HIV seroconversion risk was associated with men who have sex with men (MSM) (HR 32.76, 95% CI 5.62 to 191.12), sex with an HIV positive partner (HR 70.2, 95% CI 9.58 to 514.89), and intravenous drug use (IDU) (HR 5.65, 95% CI 2.41 to 13.23).ConclusionsHIV testing is a crucial first step in the HIV care continuum and an important HIV prevention tool. This study confirmed the need to reach high-risk populations (MSM, sex with HIV-positive individuals, individuals with IDU) and to increase comprehensive prevention services so that high-risk individuals stay HIV uninfected. HIV testing in mobile vans may be an effective outreach strategy for identifying infection in certain populations at high risk for HIV.

ObjectivesAnnual screening for gonorrhea [Neisseria gonorrhoeae (NG)] and chlamydia [Chlamydia trachomatis (CT)] is recommended for all sexually active persons living with HIV but is poorly implemented. Studies demonstrating no increases in NG and/or CT (NG/CT) case detection in clinics that successfully expanded NG/CT screening raise questions about this broad screening approach. We evaluated NG/CT case detection in the HIV Research Network during 2004-2014, a period of expanding testing.MethodsWe analyzed linear time trends in annual testing (patients tested divided by all patients in care), test positivity (patients positive divided by all tested), and case detection (the number of patients with a positive result divided by all patients in care) using multivariate repeated measures logistic regression. We determined trends overall and stratified by men who have sex with men (MSM), men who have sex exclusively with women, and women.ResultsAmong 15,614 patients (50% MSM, 26% men who have sex exclusively with women, and 24% women), annual NG/CT testing increased from 22% in 2004 to 60% in 2014 [adjusted odds ratio (AOR) per year 1.22 (1.21-1.22)]. Despite the increase in testing, test positivity also increased [AOR per year 1.10 (1.07-1.12)], and overall case detection increased from 0.8% in 2004 to 3.9% in 2014 [AOR per year 1.20 (1.17-1.22)]. Case detection was highest among MSM but increased over time among all 3 groups.ConclusionsNG/CT case detection increased as testing expanded in the population. This supports a broad approach to NG/CT screening among persons living with HIV to decrease transmission and complications of NG/CT and of HIV.

We review key concepts in the diagnosis, treatment, and follow-up of individuals with neurosyphilis. We describe the epidemiology of syphilis in the United States, highlight populations that are markedly affected by this infection, and attempt to estimate the burden of neurosyphilis. We describe the cardinal clinical features of early and late (tertiary) neurosyphilis and characterize the clinical significance of asymptomatic neurosyphilis in the antibiotic era. We review the indications for cerebrospinal fluid (CSF) examination and the performance characteristics of different CSF assays including treponemal and lipoidal antibodies, white cell count, and protein concentration. Future biomarkers and the role of imaging are briefly considered. We review preferred and alternative treatments for neurosyphilis and evidence for their use, including evidence for the use of enhanced intramuscular benzathine penicillin G to supplement intravenous penicillin. [ABSTRACT FROM AUTHOR]

Screening persons living with HIV for gonorrhea and chlamydia has been recommended since 2003. We compared annual gonorrhea/chlamydia testing to syphilis and lipid testing among 19,368 adults (41% men who have sex with men, 30% heterosexual men, and 29% women) engaged in HIV care. In 2004, 22%, 62%, and 70% of all patients were tested for gonorrhea/chlamydia, syphilis, and lipid levels, respectively. Despite increasing steadily [odds ratio per year (95% confidence interval): 1.14 (1.13 to 1.15)], gonorrhea/chlamydia testing in 2010 remained lower than syphilis and lipid testing (39%, 77%, 76%, respectively). Interventions to improve gonorrhea/chlamydia screening are needed. A more targeted screening approach may be warranted.

Screening persons living with HIV for gonorrhea and chlamydia has been recommended since 2003. We compared annual gonorrhea/chlamydia testing to syphilis and lipid testing among 19,368 adults (41% men who have sex with men, 30% heterosexual men, and 29% women) engaged in HIV care. In 2004, 22%, 62%, and 70% of all patients were tested for gonorrhea/chlamydia, syphilis, and lipid levels, respectively. Despite increasing steadily [odds ratio per year (95% confidence interval): 1.14 (1.13 to 1.15)], gonorrhea/chlamydia testing in 2010 remained lower than syphilis and lipid testing (39%, 77%, 76%, respectively). Interventions to improve gonorrhea/chlamydia screening are needed. A more targeted screening approach may be warranted.

Neisseria gonorrhoeae lipooligosaccharides (LOSs) induce immunoglobulin G that protects men from experimental infection. This raises the possibility that an LOS vaccine might prevent gonorrhea. Gonococci make different LOS molecules, depending on whether 3 genes, lgtA, lgtC, and lgtD, are in frame (IF) or out of frame (OOF). Mispairing of polymeric guanine (polyG) tracts within each gene determines its frame during replication. We amplified lgtA, lgtC, and lgtD from diagnostic slides of urethral exudates and sequenced their polyG tracts. We found that lgtA in exudative bacteria is IF and that lgtC is OOF. The frame of lgtD varied widely: it was OOF in most but not all cases. This genotype would result in synthesis of polylactosamine α chains that could be sialylated. Polylactosamine α chains would enhance virulence, and their sialylation would enable gonococci to survive within polymorphonuclear cells; however, an active LgtD in a few bacteria could provide a survival advantage in other sites of infection.

Background Up to 26% of urogenital Chlamydia trachomatis infections spontaneously resolve between detection and treatment. Mechanisms governing natural resolution are unknown. We examined whether bacterial vaginosis (BV) was associated with greater chlamydia persistence versus spontaneous clearance in a large, longitudinal study. Methods Between 1999 and 2003, the Longitudinal Study of Vaginal Flora followed reproductive-age women quarterly for 1 year. Baseline chlamydia screening and treatment were initiated after ligase chain reaction testing became available midstudy, and unscreened endocervical samples were tested after study completion. Chlamydia clearance and persistence were defined between consecutive visits without chlamydia-active antibiotics (n = 320 persistence/n = 310 clearance). Associations between Nugent score (0–3, no BV; 4–10, intermediate/BV), Amsel-BV, and chlamydia persistence versus clearance were modeled with alternating and conditional logistic regression. Results Of chlamydia cases, 48% spontaneously cleared by the next visit (310/630). Nugent-intermediate/BV was associated with higher odds of chlamydia persistence (adjusted odds ratio [aOR] = 1.89; 95% confidence interval [CI], 1.30–2.74), and the findings were similar for Amsel-BV (aOR 1.39; 95% CI,.99–1.96). The association between Nugent-intermediate/BV and chlamydia persistence was stronger in a within-participant analysis of 67 participants with both clearance/persistence intervals (aOR = 4.77; 95% CI, 1.39–16.35). BV symptoms did not affect any results. Conclusions BV is associated with greater chlamydia persistence. Optimizing the vaginal microbiome may promote chlamydia clearance. [ABSTRACT FROM AUTHOR]