Early observations from the HIV self-testing program among key populations and sexual partners of pregnant mothers in Kampala, Uganda: A cross sectional study

Background HIV self-testing (HIVST) was adopted for key populations (KPs) and sexual partners of pregnant and lactating women (mothers) in Uganda in October 2018. We report early observations during HIVST implementation in Kampala, Uganda. Methods HIVST was rolled out to reach those with unknown HIV status at 38 public health facilities, using peer-to-peer community-based distribution for female sex workers (FSW) and men who have sex with men (MSM) and secondary distribution for mothers, who gave HIVST kits to their partners. Self-testers were asked to report results within 2 days; those who did not report received a follow-up phone call from a trained health worker. Those with HIV-positive results were offered confirmatory testing at the facility using the standard HIV-testing algorithm. Data on kits distributed, testing yield, and linkage to care were analysed. Results We distributed 9,378 HIVST kits. Mothers received 5,212 (56%) for their sexual partners while KPs received 4,166 (44%) (MSM, 2192 [53%]; FSW1, 974, [47%]). Of all kits distributed, 252 (3%) individuals had HIV-positive results; 126 (6.5%) FSW, 52 (2.3%) MSM and 74 (1.4%) partners of mothers. Out of 252 individuals who had HIV-positive results, 170 (67%) were confirmed HIV-positive; 36 (2%) were partners of mothers, 99 (58%) were FSW, and 35 (21%) were MSM. Linkage to treatment (126) was 74%. Conclusions HIVST efficiently reached, tested, identified and modestly linked to care HIV positive FSW, MSM, and partners of mothers. However, further barriers to confirmatory testing and linkage to care for HIV-positive self-testers remain unexplored.

P.045 Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody Testing in Calgary: A Quality Improvement Review

Background: Despite the availability of cell-based assays for aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies provincially, outside confirmatory testing is often performed (typically Mayo Clinic Laboratories, USA) when results deviate from expected. It is unknown how often this costly undertaking (upwards of $1,200 CAN) alters diagnosis and management. Methods: We undertook a quality improvement project evaluating the concordance/discordance rate with select chart review in all patients who had cell-based AQP4 or MOG IgG antibody testing at Mitogen Diagnostics (MitogenDx; Calgary, Alberta) and subsequent testing at Mayo Clinic Laboratories from as early as 2010 to July 2020. Results: Preliminary review of data from January 2016 to July 2020 retrieved 145 paired tests; 10 of which were discordant (concordance rate: 93.1%). Chart review confirmed 9 truly discordant cases, often associated with AQP4 or MOG weak-positive results (7/9 cases) or presumed false negative AQP4 results in prototypical neuromyelitis optica spectrum disorder (2/9 cases). Conclusions: Discordant results were rare when comparing MitogenDx local AQP4/MOG antibody test results to those referred out to Mayo Clinic Laboratories, impacting diagnosis and treatment in only 3 patients out of the total. Our results suggest costly outside confirmatory testing of AQP4/MOG antibodies could be reduced.

742. Evaluation of Chagas Disease Diagnostic Testing Practices in Four Hospital Systems in California and Texas

Background Chagas disease (CD) is a neglected parasitic disease that affects >6 million people in the Americas, including >200,000 people in the United States (US). Medical provider knowledge of CD is key to decreasing morbidity and transmission; however, few studies have assessed diagnostic practices in US health systems serving at-risk patients. Our study aimed to describe existing provider approaches to diagnosing CD in California and Texas. Methods Site-based research teams at four hospital systems (the University of California [UC] San Francisco [UCSF], San Diego [UCSD], Irvine [UCI], and the Harris Health System [HHS] in Houston, TX) retrospectively identified patients ≥18 years old tested for CD between 2016-2019 and systematically extracted electronic medical record data using complementary electronic data entry forms. Specifically, eligible patients were identified using laboratory orders at UCSF and UCI, while the remaining sites employed SlicerDicer (Epic Systems). This study was approved by institutional review boards at each site. Results We identified 333 patients tested for CD, including 109 from UCSF, 88 from UCSD, 25 from UCI, and 111 from HHS. These patients had 125, 99, 31, and 181 tests sent to commercial laboratories, respectively. Test reactivity varied by system with the greatest percent reactivity among tests ordered at UCI (23%) followed by UCSD (16%), HHS (15%), and UCSF (10%). Among patients who screened positive for CD by commercial assays, confirmatory testing through the Centers for Disease Control and Prevention was sought for 100% at UCI; 59% at HHS, 55% at UCSF, and 40% at UCSD. The medical specialty that most often ordered CD testing was Cardiology at all UC sites (UCSF, 50%; UCSF, 55%; UCI, 35%) and Internal Medicine at HHS (46%; Cardiology ordered 13%). Only one recorded CD test was ordered by an Obstetrics/Gynecology service at any site. Conclusion These early results report positivity rates between our healthcare systems and demonstrate inconsistency in attaining recommended confirmatory testing, as well as a paucity of CD testing ordered through Obstetrics/Gynecology despite risk of congenital transmission. These findings suggest areas of opportunity to improve provider awareness and lay a foundation for standardizing CD diagnostic practices in the US. Disclosures Caryn Bern, MD, MPH, UpToDate (Wolters Kluwer) (Other Financial or Material Support, Author Royalties)

Head-to-head evaluation of seven different seroassays including direct viral neutralisation in a representative cohort for SARS-CoV-2

A number of seroassays are available for SARS-CoV-2 testing; yet, head-to-head evaluations of different testing principles are limited, especially using raw values rather than categorical data. In addition, identifying correlates of protection is of utmost importance, and comparisons of available testing systems with functional assays, such as direct viral neutralisation, are needed.We analysed 6658 samples consisting of true-positives (n=193), true-negatives (n=1091), and specimens of unknown status (n=5374). For primary testing, we used Euroimmun-Anti-SARS-CoV-2-ELISA-IgA/IgG and Roche-Elecsys-Anti-SARS-CoV-2. Subsequently virus-neutralisation, GeneScriptcPass, VIRAMED-SARS-CoV-2-ViraChip, and Mikrogen-recomLine-SARS-CoV-2-IgG were applied for confirmatory testing. Statistical modelling generated optimised assay cut-off thresholds. Sensitivity of Euroimmun-anti-S1-IgA was 64.8%, specificity 93.3% (manufacturer’s cut-off); for Euroimmun-anti-S1-IgG, sensitivity was 77.2/79.8% (manufacturer’s/optimised cut-offs), specificity 98.0/97.8%; Roche-anti-N sensitivity was 85.5/88.6%, specificity 99.8/99.7%. In true-positives, mean and median Euroimmun-anti-S1-IgA and -IgG titres decreased 30/90 days after RT-PCR-positivity, Roche-anti-N titres decreased significantly later. Virus-neutralisation was 80.6% sensitive, 100.0% specific (≥1:5 dilution). Neutralisation surrogate tests (GeneScriptcPass, Mikrogen-recomLine-RBD) were >94.9% sensitive and >98.1% specific. Optimised cut-offs improved test performances of several tests. Confirmatory testing with virus-neutralisation might be complemented with GeneScriptcPassTM or recomLine-RBD for certain applications. Head-to-head comparisons given here aim to contribute to the refinement of testing strategies for individual and public health use.

Urine Drug Screening in the Era of Designer Benzodiazepines: Comparison of Three Immunoassay Platforms, LC-QTOF-MS, and LC-MS/MS

ABSTRACT This study investigated the presence of designer benzodiazepines in 35 urine specimens obtained from emergency department patients undergoing urine drug screening. All specimens showed apparent false-positive benzodiazepine screening results (i.e., confirmatory testing using a 19-component LC-MS/MS panel showed no prescribed benzodiazepines at detectable levels). The primary aims were to identify the possible presence of designer benzodiazepines, characterize the reactivity of commercially available screening immunoassays with designer benzodiazepines, and evaluate the risk of inappropriately ruling out designer benzodiazepine use when utilizing common urine drug screening and confirmatory tests. Specimens were obtained from emergency departments of a single US Health system. Following clinically ordered drug screening using Abbott ARCHITECT c assays and lab-developed LC-MS/MS confirmatory testing, additional characterization was performed for investigative purposes. Specifically, urine specimens were screened using two additional assays (Roche cobas c502, Siemens Dimension Vista) and LC-QTOF-MS to identify presumptively positive species, including benzodiazepines and non-benzodiazepines. Finally, targeted, qualitative LC-MS/MS was performed to confirm the presence of 12 designer benzodiazepines. Following benzodiazepine detection using the Abbott ARCHITECT, benzodiazepines were subsequently detected in 28/35 and 35/35 urine specimens, respectively, using Siemens and Roche assays. LC-QTOF-MS showed the presumptive presence of at least one non-FDA approved benzodiazepine in 30/35 specimens: flubromazolam (12/35), flualprazolam (11/35), flubromazepam (2/35), clonazolam (4/35), etizolam (9/35), metizolam (5/35), nitrazepam (1/35), and pyrazolam (1/35). Two or three designer benzodiazepines were detected concurrently in 13/35 specimens. Qualitative LC-MS/MS confirmed the presence of at least one designer benzodiazepine or metabolite in 23/35 specimens, with 3 specimens unavailable for confirmatory testing. Urine benzodiazepine screening assays from three manufacturers were cross-reactive with multiple non-US FDA-approved benzodiazepines. Clinical and forensic toxicology laboratories using traditionally designed LC-MS/MS panels may fail to confirm the presence of non-US FDA-approved benzodiazepines detected by screening assays, risking inappropriate interpretation of screening results as false-positives.

Epidemiological, clinical and laboratory features of acute Q fever in a cohort of hospitalized patients in a regional hospital, Israel, 2012-2018

Introduction Acute Q fever is endemic in Israel, yet the clinical and laboratory picture is poorly defined. Methods A retrospective study reviewing the medical records of acute Q fever patients, conducted in a single hospital in the Sharon district, Israel. Serum samples from suspected cases were preliminary tested by a qualitative enzyme immunoassay (EIA). Confirmatory testing at the reference laboratory used an indirect immunofluorescence assay (IFA). Positive cases were defined as fever with at least one other symptom and accepted laboratory criteria such as a single-phase II immunoglobulin G (IgG) antibody titer ≥1:200. Cases not fulfilling these criteria and in which acute Q fever was excluded, served as a control group. Results Between January 2012 and May 2018, 484 patients tested positive. After confirmatory testing, 65 (13.4%) were positive for acute Q fever (with requisite clinical picture), 171 (35.3%) were definitely not infected, the remaining 248 were excluded because of past/chronic/undetermined infection. The average age was 58 years and 66% were males. Most resided in urban areas with rare animal exposure. Pneumonia was seen in 57% of cases and a combination with headache/hepatitis was highly suggestive of acute Q fever diagnosis. Syncope/presyncope, fall and arthritis were more common in acute Q fever cases. Laboratory indexes were similar to the control group, except for erythrocyte sedimentation rate (ESR) which was more common and higher in the study group. Conclusion Acute Q fever in the Sharon district could be better diagnosed by using a syndromic approach in combination with improved rapid diagnostic testing.