Detecting asymptomatic Trichomonas vaginalis in females using the BD ProbeTec™ Trichomonas vaginalis Qx nucleic acid amplification test.

Trichomonas vaginalis (TV) rates in women are increasing and many are asymptomatic. Nucleic acid amplification tests (NAATs) are becoming the 'gold standard' for diagnosis. We aimed to establish our asymptomatic TV rates by testing all women attending Oxfordshire's Sexual Health service, regardless of symptoms, using the BD ProbeTec™ TV Qx NAATs (BDQx). During BDQx's verification process, the sensitivity and specificity were calculated using results of 220 endocervical samples from symptomatic women, compared with culture. BDQx was subsequently implemented and prospectively evaluated over 6 months in female attendees. Wet mount microscopy was also performed in symptomatics. Demographic and clinical characteristics of those diagnosed were analysed. From 220 samples tested by BDQx and culture: 5 were positive on both and one solely using BDQx, giving a sensitivity and specificity of 100% and 99.53%, respectively. In the prospective cohort, of 5775 BDQx tests, 33 (0.57%) were positive. 11/33 (33%) patients were asymptomatic. All patients diagnosed had risk factors: age >25 years (85%), residence in a deprived area (79%) and black ethnicity (21%). Despite BDQx being highly sensitive and specific, with our low TV prevalence universal screening may not be justified. Targeted screening using local demographic data merits further investigation.

Increasing burden of community-acquired pneumonia leading to hospitalisation, 1998-2014.

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of mortality and morbidity in many countries but few recent large-scale studies have examined trends in its incidence. METHODS: Incidence of CAP leading to hospitalisation in one UK region (Oxfordshire) was calculated over calendar time using routinely collected diagnostic codes, and modelled using piecewise-linear Poisson regression. Further models considered other related diagnoses, typical administrative outcomes, and blood and microbiology test results at admission to determine whether CAP trends could be explained by changes in case-mix, coding practices or admission procedures. RESULTS: CAP increased by 4.2%/year (95% CI 3.6 to 4.8) from 1998 to 2008, and subsequently much faster at 8.8%/year (95% CI 7.8 to 9.7) from 2009 to 2014. Pneumonia-related conditions also increased significantly over this period. Length of stay and 30-day mortality decreased slightly in later years, but the proportions with abnormal neutrophils, urea and C reactive protein (CRP) did not change (p>0.2). The proportion with severely abnormal CRP (>100 mg/L) decreased slightly in later years. Trends were similar in all age groups. Streptococcus pneumoniae was the most common causative organism found; however other organisms, particularly Enterobacteriaceae, increased in incidence over the study period (p<0.001). CONCLUSIONS: Hospitalisations for CAP have been increasing rapidly in Oxfordshire, particularly since 2008. There is little evidence that this is due only to changes in pneumonia coding, an ageing population or patients with substantially less severe disease being admitted more frequently. Healthcare planning to address potential further increases in admissions and consequent antibiotic prescribing should be a priority.

Self-reactive IgE exacerbates interferon responses associated with autoimmunity.

Canonically, immunoglobulin E (IgE) mediates allergic immune responses by triggering mast cells and basophils to release histamine and type 2 helper cytokines. Here we found that in human systemic lupus erythematosus (SLE), IgE antibodies specific for double-stranded DNA (dsDNA) activated plasmacytoid dendritic cells (pDCs), a type of cell of the immune system linked to viral defense, which led to the secretion of substantial amounts of interferon-α (IFN-α). The concentration of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC function by triggering phagocytosis via the high-affinity FcɛRI receptor for IgE, followed by Toll-like receptor 9 (TLR9)-mediated sensing of DNA in phagosomes. Our findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses.

Urban legacies and soil management affect the concentration and speciation of trace metals in Los Angeles community garden soils.

Heavy metals in urban soils can compromise human health, especially in urban gardens, where gardeners may ingest contaminated dust or crops. To identify patterns of urban garden metal contamination, we measured concentrations and bioavailability of Pb, As, and Cd in soils associated with twelve community gardens in Los Angeles County, CA. This included sequential extractions to partition metals among exchangeable, reducible, organic, or residual fractions. Proximity to road increased all metal concentrations, suggesting vehicle emissions sources. Reducible Pb increased with neighborhood age, suggesting leaded paint as a likely pollutant source. Exchangeable Cd and As both increased with road proximity. Only cultivated soils showed an increase in exchangeable As with road proximity, potentially due to reducing humic acid interactions while Cd bioavailability was mitigated by organic matter. Understanding the geochemical phases and metal bioavailability allows incorporation of contamination patterns into urban planning.

Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes.

Toll-like receptor-9 (TLR9) is largely responsible for discriminating self from pathogenic DNA. However, association of host DNA with autoantibodies activates TLR9, inducing the pathogenic secretion of type I interferons (IFNs) from plasmacytoid dendritic cells (pDCs). Here, we found that in response to DNA-containing immune complexes (DNA-IC), but not to soluble ligands, IFN-α production depended upon the convergence of the phagocytic and autophagic pathways, a process called microtubule-associated protein 1A/1B-light chain 3 (LC3)-associated phagocytosis (LAP). LAP was required for TLR9 trafficking into a specialized interferon signaling compartment by a mechanism that involved autophagy-related proteins, but not the conventional autophagic preinitiation complex, or adaptor protein-3 (AP-3). Our findings unveil a new role for nonconventional autophagy in inflammation and provide one mechanism by which anti-DNA autoantibodies, such as those found in several autoimmune disorders, bypass the controls that normally restrict the apportionment of pathogenic DNA and TLR9 to the interferon signaling compartment.

Practice patterns of testing waived under the clinical laboratory improvement amendments.

OBJECTIVES: To determine operational practices in laboratories operating under a Certificate of Wavier (waived laboratories), or equivalent, under the Clinical Laboratory Improvements Amendments (CLIA) of 1988 when performing tests designated as having an insignificant risk of an erroneous result (ie, waived tests). METHODS: Waived laboratories that were part of the Centers for Disease Control and Prevention Laboratory Sentinel Monitoring Network project in the states of Arkansas, New York, and Washington were surveyed about their quality control (QC) and quality assurances (QA) practices when performing waived testing. Arkansas and Washington sent out similar questionnaires, whereas on-site surveys were conducted in New York. The survey in Arkansas and Washington also included nonwaived laboratories. The New York visits were designed to pilot test a regulatory inspection program for limited testing sites, which, in New York, are roughly equivalent to laboratories operating under a CLIA Certificate of Wavier and/or Provider-Performed Microscopy but are generally not located in physicians' offices. Laboratories visited in New York were selected from a list of limited testing sites and were representative of that population. RESULTS: Arkansas received responses from 211 facilities (37% response rate), of which 38% had Certificates of Waiver. Washington received responses from 190 waived laboratories (71% response rate) and from 116 nonwaived laboratories (32% response rate). In New York, 607 of the 2751 limited testing laboratories were visited. Reporting laboratories in all 3 states most frequently performed testing for glucose, urinalysis, urine human chorionic gonadotropin, occult blood, and group A Streptococcus antigen, although other waived tests were performed less frequently. Washington found that 57% of waived laboratories followed manufacturers' QC requirements. Arkansas found that 58% of laboratories doing waived tests that required liquid controls performed these controls, and 59% performing waived testing requiring electronic controls used these controls. In New York, 68% of the laboratories complied with the manufacturer's QC requirements for a variety of tests. Being accredited by an external organization or affiliated with a more complex laboratory improved compliance. Nonwaived laboratories in Washington and Arkansas complied with manufacturer's instructions at a higher rate than did waived laboratories. Similar deficiencies in following CLIA requirements were found in other areas of laboratory operation. CONCLUSIONS: Just more than half of waived laboratories in 3 diverse states follow manufacturer's instructions for recommended QC and QA. These instructions help ensure that the test will produce results that have an insignificant chance of an error. Although we did not study the impact of this and other findings on patient care, the results show that imposing good laboratory practices by regulation alone was insufficient to ensure quality laboratory results in any location evaluated. A system that can continually provide accessible education on laboratory practices, coupled with new thoughts on the regulatory environment, is in order.