Performance evaluation of the LumiraDx quantitative microfluidic point-of-care CRP test.

C-reactive protein (CRP) is an established acute-phase marker for infection, inflammation and tissue injury, used to guide clinical decision-making in primary and secondary care. This study compared the analytical performance of the quantitative microfluidic point-of-care LumiraDx CRP Test to a laboratory-based reference method (Siemens RCRP Flex assay on the Dimension® Xpand®) and evaluated equivalence of sample matrices (blood versus plasma) in point-of-care settings using samples from patients presenting with symptoms of infection or inflammation. The LumiraDx CRP Test demonstrated close agreement with the lab reference test (range, 5.1 to 245.2 mg/L, r = 0.992, slope = 0.998, intercept = -0.476; n = 205) and notable agreement between fingerstick and venous blood and plasma (r = 0.974-0.983; n = 44). Paired replicate precision had mean coefficients of variation of 6.4 % (plasma), 6.6 % (capillary direct) and 8.1 % (venous blood); overall error rates were 2.9 %. The quantitative LumiraDx CRP Test showed robust analytical performance across sample matrices and close agreement compared to the laboratory reference method when used at the point of care.

Surveillance for Avian Bornavirus in Colorado and Wyoming, USA, Raptor Populations.

Avian bornavirus (ABV) is known to infect at least 80 avian species and is associated with avian bornaviral ganglioneuritis (ABG). Avian bornaviral ganglioneuritis is characterized by a lymphoplasmacytic infiltration of the nervous tissue, mainly affecting the nerves that supply the gastrointestinal tract of birds. This disease is diagnosed commonly in psittacines under human care and has been demonstrated in wild bird species; however, its occurrence in raptors is largely unknown. Because of the commonality of ABV in the pet bird population, there is concern about the spread of this virus to other companion avian species, such as falconry birds, as well as wildlife. This prospective study used reverse-transcription quantitative PCR (RT-qPCR) to survey free-ranging Colorado and Wyoming, US, raptor populations for ABV. Quantitative PCR was performed on mixed conjunctival-choanal-cloacal swabs collected from live birds (n=139). In dead birds, a combination of mixed swabs (n=265) and tissue samples of the brain (n=258), heart (n=162), adrenal glands (n=162), liver (n=162), kidney (n=139), spinal cord (n=139), and brachial plexus (n=139) were evaluated. All 1,565 swab and tissue samples RT-qPCR results from the 404 birds evaluated were negative. Based on these results and a lack of clinical signs suggestive of ABG, ABV is likely not a prevalent pathogen in Colorado and Wyoming raptor populations at this time.

Cryptococcal meningitis.

Cryptococcus neoformans and Cryptococcus gattii species complexes cause meningoencephalitis with high fatality rates and considerable morbidity, particularly in persons with deficient T cell-mediated immunity, most commonly affecting people living with HIV. Whereas the global incidence of HIV-associated cryptococcal meningitis (HIV-CM) has decreased over the past decade, cryptococcosis still accounts for one in five AIDS-related deaths globally due to the persistent burden of advanced HIV disease. Moreover, mortality remains high (~50%) in low-resource settings. The armamentarium to decrease cryptococcosis-associated mortality is expanding: cryptococcal antigen screening in the serum and pre-emptive azole therapy for cryptococcal antigenaemia are well established, whereas enhanced pre-emptive combination treatment regimens to improve survival of persons with cryptococcal antigenaemia are in clinical trials. Short courses (≤7 days) of amphotericin-based therapy combined with flucytosine are currently the preferred options for induction therapy of cryptococcal meningitis. Whether short-course induction regimens improve long-term morbidity such as depression, reduced neurocognitive performance and physical disability among survivors is the subject of further study. Here, we discuss underlying immunology, changing epidemiology, and updates on the management of cryptococcal meningitis with emphasis on HIV-associated disease.

Highly Pathogenic Avian Influenza A(H5N1) Virus Clade 2.3.4.4b Infections in Wild Terrestrial Mammals, United States, 2022.

We describe the pathology of natural infection with highly pathogenic avian influenza A(H5N1) virus of Eurasian lineage Goose/Guangdong clade 2.3.4.4b in 67 wild terrestrial mammals throughout the United States during April 1‒July 21, 2022. Affected mammals include 50 red foxes (Vulpes vulpes), 6 striped skunks (Mephitis mephitis), 4 raccoons (Procyon lotor), 2 bobcats (Lynx rufus), 2 Virginia opossums (Didelphis virginiana), 1 coyote (Canis latrans), 1 fisher (Pekania pennanti), and 1 gray fox (Urocyon cinereoargenteus). Infected mammals showed primarily neurologic signs. Necrotizing meningoencephalitis, interstitial pneumonia, and myocardial necrosis were the most common lesions; however, species variations in lesion distribution were observed. Genotype analysis of sequences from 48 animals indicates that these cases represent spillover infections from wild birds.

Baseline Cytomegalovirus Viremia at Cryptococcal Meningitis Diagnosis Is Associated With Long-term Increased Incident TB Disease and Mortality in a Prospective Cohort of Ugandan Adults With HIV.

Background: Adults with HIV-associated cryptococcal meningitis have overlapping burdens of cytomegalovirus (CMV) and tuberculosis (TB) coinfections. CMV infection/reactivation is strongly associated with CMV-specific memory T-cell activation and upregulation of type 1 interferons, which may lead to increased risk of TB disease and poor outcomes. Methods: We conducted a cohort study of 2-week survivors of cryptococcal meningitis during 2010-2021 to determine TB incidence and all-cause mortality over time stratified by baseline CMV status. Results: We followed 497 Ugandans with HIV-associated cryptococcal meningitis for a median (interquartile range) of 4.6 (2.6-53.9) months. Overall, 42% (210/497) developed incident TB disease or died. One-fifth (98/497, 19.7%) developed incident TB disease, and 29% (142/497) of participants died during follow-up. Of 259 participants with CMV viral load measured at baseline, 37% (96/259) had concurrent CMV viremia (defined as anyone with detectable CMV DNA in plasma/serum by qualitative polymerase chain reaction [PCR] detection). Of 59 with measured CMV immunoglobulin G (IgG), 100% had positive CMV IgG antibody serology (≥10 enzyme-linked immunosorbent assay units/mL). CMV viremia was positively associated with higher HIV viral load (196 667 vs 73 295 copies/mL; P = .002) and higher cerebrospinal fluid fungal burden (68 500 vs 14 000 cfu/mL; P = .002) compared with those without. Participants with high-level CMV viremia (defined as CMV viral load ≥1000 IU/mL) had twice the risk of incident TB (subdistribution adjusted hazard ratio [aHR], 2.18; 95% CI, 1.11-4.27) and death (aHR, 1.99; 95% CI, 1.14-3.49) compared with participants with no or low-level CMV viremia. There was no association between the CMV IgG index and the incidence of TB/death (P = .75). Conclusions: CMV viremia >1000 IU/mL at meningitis diagnosis was associated with increased incident TB disease and mortality during long-term follow-up. Future studies to determine the causal relationship and potential for therapeutic intervention are warranted.

Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial.

BACKGROUND: Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed. METHODS: In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus-associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g/d oral LNC amphotericin through 2 weeks with 100 mg/kg/d flucytosine, then 1.2 g/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA). RESULTS: We randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)/mL/d for all-oral LNC amphotericin, 0.42 log10  Cryptococcus CFU/mL/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU/mL/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin.Grade 3-4 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P = .05), particularly for anemia (21% vs 44%; P = .01) and potassium (5% vs 17%; P = .04). CONCLUSIONS: This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin. CLINICAL TRIALS REGISTRATION: NCT04031833.

Prevalence of Histoplasma Antigenuria among Outpatient Cohort with Advanced HIV in Kampala, Uganda.

In sub-Saharan Africa, an estimated 25% of people with HIV present with advanced HIV and are at high risk of opportunistic infections. Whereas histoplasmosis has occasionally been seen in Uganda, the understanding of the local risk of acute infection is limited. We sought to determine the prevalence of Histoplasma antigenuria using an enzyme immunoassay (EIA, clarus Histoplasma GM EIA, IMMY; Norman, OK, USA) in a cohort of outpatients with advanced HIV disease in Kampala, Uganda. Among the persons with positive urine Histoplasma antigen tests, we assessed their clinical presentation and outcomes. The EIA was run on stored urine samples as per the manufacturer's instructions. Specimens ≥1 EIA units were considered positive. Among the 388 tested urine samples, 4 (1.2%) were positive for Histoplasma antigen. The histoplasmosis prevalence among participants with a CD4 < 100 cells/mcL was 2.5% (4/158). Three of the four participants with a positive Histoplasma antigen test reported systemic symptoms consistent with histoplasmosis. All four participants had a positive urine lipoarabinomannan test and were treated for tuberculosis. By the four-week follow-up visit, all participants were clinically improved, alive, and in care without antifungal therapy. In advanced HIV, the clinical presentations of tuberculosis and histoplasmosis overlap. The value of histoplasmosis screening and pre-emptive treatment is an area of future research.

Advanced HIV disease: A review of diagnostic and prophylactic strategies.

BACKGROUND: Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization's (WHO) 'test-and-treat' strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first-line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point-of-care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD. METHODS: We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions. RESULTS: While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non-sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource-poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care. CONCLUSIONS: Despite progress with HIV treatment and prevention, a persistent 20%-30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV-related morbidity and mortality. Investment in the development of additional POC or near-bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same-day results. However, in real-world scenarios, people with AHD have multiple comorbidities and imperfect follow-up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

Diagnostic performance of the IMMY cryptococcal antigen lateral flow assay on serum and cerebrospinal fluid for diagnosis of cryptococcosis in HIV-negative patients: a systematic review.

BACKGROUND: The incidence of cryptococcosis amongst HIV-negative persons is increasing. Whilst the excellent performance of the CrAg testing in people living with HIV is well described, the diagnostic performance of the CrAg LFA has not been systematically evaluated in HIV-negative cohorts on serum or cerebrospinal fluid. METHODS: We performed a systematic review to characterise the diagnostic performance of IMMY CrAg® LFA in HIV-negative populations on serum and cerebrospinal fluid. A systematic electronic search was performed using Medline, Embase, Global Health, CENTRAL, WoS Science Citation Index, SCOPUS, Africa-Wide Information, LILACS and WHO Global Health Library. Studies were screened and data extracted from eligible studies by two independent reviewers. A fixed effect meta-analysis was used to estimate the diagnostic sensitivity and specificity. RESULTS: Of 447 records assessed for eligibility, nine studies met our inclusion criteria, including 528 participants overall. Amongst eight studies that evaluated the diagnostic performance of the IMMY CrAg® LFA on serum, the pooled median sensitivity was 96% (95% Credible Interval (CrI) 68-100%) with a pooled specificity estimate of 96% (95%CrI 84-100%). Amongst six studies which evaluated the diagnostic performance of IMMY CrAg® LFA on CSF, the pooled median sensitivity was 99% (95%CrI 95-100%) with a pooled specificity median of 99% (95%CrI 95-100%). CONCLUSIONS: This review demonstrates a high pooled sensitivity and specificity for the IMMY CrAg® LFA in HIV-negative populations, in keeping with findings in HIV-positive individuals. The review was limited by the small number of studies. Further studies using IMMY CrAg® LFA in HIV-negative populations would help to better determine the diagnostic value of this test.

Effect of Coronavirus Disease 2019 Lockdowns on Identification of Advanced Human Immunodeficiency Virus Disease in Outpatient Clinics in Uganda.

Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019-January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre-coronavirus disease 2019 period).

Performance Evaluation of the Microfluidic Antigen LumiraDx SARS-CoV-2 and Flu A/B Test in Diagnosing COVID-19 and Influenza in Patients with Respiratory Symptoms.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) and influenza share similar symptoms, which hampers diagnosis. Given that they require different containment and treatment strategies, fast and accurate distinction between the two infections is needed. This study evaluates the sensitivity and specificity of the microfluidic antigen LumiraDx SARS-CoV-2 and Flu A/B Test for simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B from a single nasal swab. METHODS: Nasal samples were collected from patients as part of the ASPIRE (NCT04557046) and INSPIRE (NCT04288921) studies at point-of-care testing sites in the USA. ASPIRE study participants were included after developing COVID-19 symptoms in the last 14 days or following a positive SARS-CoV-2 test in the last 48 h. INSPIRE study participants were included after developing influenza symptoms in the last 4 days. Samples were extracted into proprietary buffer and analysed using the LumiraDx SARS-CoV-2 and Flu A/B Test. A reference sample was taken from each subject, placed into universal transport medium and tested using reference SARS-CoV-2 and influenza reverse transcription polymerase chain reaction (RT-PCR) tests. The test and reference samples were compared using the positive percent agreement (PPA) and negative percent agreement (NPA), together with their 95% confidence intervals (CIs). RESULTS: Analysis of the data from the ASPIRE (N = 124) and INSPIRE (N = 159) studies revealed high levels of agreement between the LumiraDx SARS-CoV-2 and Flu A/B Test and the reference tests in detecting SARS-CoV-2 (PPA = 95.5% [95% CI 84.9%, 98.7%]; NPA = 96.0% [95% CI 90.9%, 98.3%]), influenza A (PPA = 83.3% [95% CI 66.4%, 92.7%]; NPA = 97.7% [95% CI 93.4%, 99.2%]) and influenza B (PPA = 80.0% [95% CI 62.7%, 90.5%]; NPA = 95.3% [95% CI 90.2%, 97.9%]). CONCLUSIONS: The LumiraDx SARS-CoV-2 and Flu A/B Test shows a high agreement with the reference RT-PCR tests while simultaneously detecting and differentiating between SARS-CoV-2 and influenza A/B. TRIAL REGISTRATION: ClinicalTrials.gov identifiers NCT04557046 and NCT04288921.

NOVEL AVIBACTERIUM SPECIES ASSOCIATED WITH SINUSITIS AND CONJUNCTIVITIS IN A MERRIAM'S WILD TURKEY (MELEAGRIS GALLOPAVO MERRIAMI) FLOCK IN COLORADO, USA.

A Merriam's Wild Turkey (Meleagris gallopavo merriami) with periocular swelling and periocular skin crusting in Pueblo County, Colorado, USA, was diagnosed with severe catarrhal and fibrinous sinusitis and conjunctivitis. A novel clade of Avibacterium was detected in the exudate from this bird. Although eight additional turkeys culled from the affected flock did not have clinical signs or gross lesions, histologically all had mild-to-moderate chronic sinusitis, and infraorbital cultures yielded the same novel clade of Avibacterium that was found in the symptomatic turkey. The presence of this Avibacterium species in the absence of significant disease in some birds suggested that other factors might have been involved in the development of severe sinusitis and conjunctivitis in the symptomatic Wild Turkey. Negative culture results from a distant flock of Wild Turkeys, acquired with similar methods to the affected flock, suggested that this novel species of Avibacterium was not widespread throughout Wild Turkeys in Colorado.

Cytomegalovirus viremia as a risk factor for mortality in HIV-associated cryptococcal and tuberculous meningitis.

OBJECTIVES: CMV viremia is associated with increased mortality in persons with HIV. We previously demonstrated that CMV viremia was a risk factor for 10-week mortality in antiretroviral therapy (ART)-naïve persons with cryptococcal meningitis. We investigated whether similar observations existed over a broader cohort of patients with HIV-associated meningitis at 18 weeks. METHODS: We prospectively enrolled Ugandans with cryptococcal or TB meningitis into clinical trials in 2015-2019. We quantified CMV DNA concentrations from stored baseline plasma or serum samples from 340 participants. We compared 18-week survival between those with and without CMV viremia. RESULTS: We included 308 persons with cryptococcal meningitis and 32 with TB meningitis, of whom 121 (36%) had detectable CMV DNA. Baseline CD4+ T-cell counts (14 vs. 24 cells/µl; P = 0.07) and antiretroviral exposure (47% vs. 45%; P = 0.68) did not differ between persons with and without CMV viremia. The 18-week mortality was 50% (61/121) in those with CMV viremia versus 34% (74/219) in those without (P = 0.003). Detectable CMV viremia (adjusted hazard ratio [aHR] 1.60; 95% confidence interval [CI] 1.13-2.25; P = 0.008) and greater viral load (aHR 1.22 per log10 IU/ml increase; 95% CI 1.09-1.35; P <0.001) were positively associated with all-cause mortality through 18 weeks. CONCLUSION: CMV viremia at baseline was associated with a higher risk of death at 18 weeks among persons with HIV-associated cryptococcal or TB meningitis, and the risk increased as the CMV viral load increased. Further investigation is warranted to determine whether CMV is a modifiable risk contributing to deaths in HIV-associated meningitis or is a biomarker of immune dysfunction.

Clinical management of community-acquired meningitis in adults in the UK and Ireland in 2017: a retrospective cohort study on behalf of the National Infection Trainees Collaborative for Audit and Research (NITCAR).

OBJECTIVES: To assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland. DESIGN: Retrospective cohort study. SETTING: 64 UK and Irish hospitals. PARTICIPANTS: 1471 adults with community-acquired meningitis of any aetiology in 2017. RESULTS: None of the audit standards, from the 2016 UK Joint Specialists Societies guideline on diagnosis and management of meningitis, were met in all cases. With respect to 20 of 30 assessed standards, clinical management provided for patients was in line with recommendations in less than 50% of cases. 45% of patients had blood cultures taken within an hour of admission, 0.5% had a lumbar puncture within 1 hour, 26% within 8 hours. 28% had bacterial molecular diagnostic tests on cerebrospinal fluid. Median time to first dose of antibiotics was 3.2 hours (IQR 1.3-9.2). 80% received empirical parenteral cephalosporins. 55% ≥60 years and 31% of immunocompromised patients received anti-Listeria antibiotics. 21% received steroids. Of the 1471 patients, 20% had confirmed bacterial meningitis. Among those with bacterial meningitis, pneumococcal aetiology, admission to intensive care and initial Glasgow Coma Scale Score less than 14 were associated with in-hospital mortality (adjusted OR (aOR) 2.08, 95% CI 0.96 to 4.48; aOR 4.28, 95% CI 1.81 to 10.1; aOR 2.90, 95% CI 1.26 to 6.71, respectively). Dexamethasone therapy was weakly associated with a reduction in mortality in both those with proven bacterial meningitis (aOR 0.57, 95% CI 0.28 to 1.17) and with pneumococcal meningitis (aOR 0.47, 95% CI 0.20 to 1.10). CONCLUSION: This study demonstrates that clinical care for patients with meningitis in the UK is not in line with current evidence-based national guidelines. Diagnostics and therapeutics should be targeted for quality improvement strategies. Work should be done to improve the impact of guidelines, understand why they are not followed and, once published, ensure they translate into changed practice.

Improving Technology to Diagnose Tuberculous Meningitis: Are We There Yet?

Diagnosis of tuberculous meningitis (TBM) remains challenging due to a paucity of high-performance diagnostics. Even those that have reasonable sensitivity are not adequate to 'rule out' TBM. Therefore, a combination of clinical factors alongside microbiological, molecular, and radiological investigations are utilized, depending on availability. A low threshold for starting empiric therapy in the appropriate clinical scenario remains crucial for good outcomes in many cases. Herein, we review the current TBM diagnostics landscape with a focus on limitations frequently encountered, such as diagnostic test performance, cost, laboratory infrastructure, and clinical expertise. Though molecular technologies, particularly GeneXpert MTB/Rif Ultra, have been a step forward, diagnosis of TBM remains difficult. We also provide an overview of promising technologies, such as cerebrospinal fluid (CSF) lactate, a new lipoarabinomannan test (FujiLAM), metagenomic next-generation sequencing, and transcriptomics that may further improve our TBM diagnostic capacity and lead to better outcomes.

UK guideline for the use of HIV post-exposure prophylaxis 2021.

We present the updated British Association for Sexual Health and HIV (BASHH) guidelines for post-exposure prophylaxis (PEP) to HIV following sexual exposures, occupational exposures and other nonoccupational exposures in the community. This serves as an update to the 2015 BASHH guideline on PEP following sexual exposures and the 2008 Expert Advisory Group on AIDS guidelines on HIV PEP. We aim to provide evidence-based guidance on best clinical practice in the provision, monitoring and support of PEP for the prevention of HIV acquisition following sexual, occupational and other nonoccupational exposures in the community. The guideline covers when to prescribe PEP, what antiretroviral agents to use and how to manage PEP. This includes (i) evidence of PEP efficacy; (ii) evidence relating to individual-level efficacy of antiretroviral therapy to prevent the sexual transmission of HIV; (iii) data on the detectable (transmissible) prevalence of HIV in specific populations; (iv) risk of HIV transmission following different types of sexual and occupational exposure; (v) baseline risk assessment; (vi) drug regimens and dosing schedules; (vii) monitoring PEP; (viii) baseline and follow-up blood-borne virus testing; (ix) the role of PEP within broader HIV prevention strategies, for example, HIV pre-exposure prophylaxis (PrEP). The guideline also covers special scenarios such as PEP in pregnancy, breastfeeding and chronic hepatitis B virus infection, and when PEP should be considered in people using HIV PrEP. The guidelines are aimed at clinical professionals directly involved in PEP provision and other stakeholders in the field. A proforma to assist PEP consultations is included. A public consultation process was undertaken prior to finalizing the recommendations.

Performance of the LumiraDx Microfluidic Immunofluorescence Point-of-Care SARS-CoV-2 Antigen Test in Asymptomatic Adults and Children.

OBJECTIVES: The LumiraDx SARS-CoV-2 Ag Test has previously been shown to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals symptomatic for coronavirus disease 2019 (COVID-19). This evaluation investigated the LumiraDx SARS-CoV-2 Ag Test as an aid in the diagnosis of SARS-CoV-2 infection in asymptomatic adults and children. METHODS: Asymptomatic individuals at high risk of COVID-19 infection were recruited in 5 point-of-care (POC) settings. Two paired anterior nasal swabs were collected from each participant, tested by using the LumiraDx SARS-CoV-2 Ag Test at the POC, and compared with results from reverse transcription-polymerase chain reaction (RT-PCR) assays (cobas 6800 [Roche Diagnostics] or TaqPath [Thermo Fisher Scientific]). We calculated positive percent agreement (PPA) and negative percent agreement (NPA), then stratified results on the basis of RT-PCR reference platform and cycle threshold. RESULTS: Of the 222 included study participants confirmed to be symptom-free for at least 2 weeks before testing, the PPA was 82.1% (95% confidence interval [CI], 64.4%-92.1%). The LumiraDx SARS-CoV-2 Ag Test correctly identified 95.8% (95% CI, 79.8%-99.3%) of the samples confirmed positive in fewer than 33 RT-PCR cycles and 100% (95% CI, 85.1%-100%) in fewer than 30 RT-PCR cycles while maintaining 100% NPA. CONCLUSIONS: This rapid, high-sensitivity test can be used to screen asymptomatic patients for acute SARS-CoV-2 infection in clinic- and community-based settings.

Oxygen levels are key to understanding "Anaerobic" protozoan pathogens with micro-aerophilic lifestyles.

Publications abound on the physiology, biochemistry and molecular biology of "anaerobic" protozoal parasites as usually grown under "anaerobic" culture conditions. The media routinely used are poised at low redox potentials using techniques that remove O2 to "undetectable" levels in sealed containers. However there is growing understanding that these culture conditions do not faithfully resemble the O2 environments these organisms inhabit. Here we review for protists lacking oxidative energy metabolism, the oxygen cascade from atmospheric to intracellular concentrations and relevant methods of measurements of O2, some well-studied parasitic or symbiotic protozoan lifestyles, their homeodynamic metabolic and redox balances, organism-drug-oxygen interactions, and the present and future prospects for improved drugs and treatment regimes.

Performance Evaluation of the Quantitative Point-of-Care LumiraDx D-Dimer Test.

INTRODUCTION: Fibrin degradation product D-dimer can be a valuable indicator for venous thromboembolism (VTE). The use of D-dimer testing in primary care settings can be limited by restricted access to laboratory services. This performance evaluation compares a quantitative, point-of-care (POC) D-dimer assay (LumiraDx D-Dimer Test) with a reference laboratory-based D-dimer assay. METHODS: Plasma samples from patients presenting to secondary care in the UK, USA, and Germany were analyzed centrally using the LumiraDx D-Dimer Test and the reference test (bioMérieux VIDAS D-Dimer Exclusion II immunoassay). Method comparison used Passing-Bablok regression analysis with pre-specified equivalence criteria of r ≥ 0.9 and slope of 0.9-1.1. The NOVEL-3 study (NCT04375982) compared equivalency of fingerstick, venous blood (VB), and plasma samples from the same patient, tested at US primary care clinics next to the patient using the POC LumiraDx D-Dimer device. Measurements obtained from fingerstick and VB samples were compared with results from plasma samples, using Deming regression. The healthy reference range was determined using plasma samples of healthy volunteers, collected by commercial suppliers in Germany and the USA, which were analyzed centrally using the LumiraDx D-Dimer Test and the reference test. RESULTS: The LumiraDx D-Dimer Test demonstrated agreement with the bioMérieux VIDAS D-Dimer Exclusion II immunoassay for plasma samples (r = 0.923, slope of 1.016, n = 1767). There was good agreement between fingerstick/VB samples and plasma samples (r = 0.980-0.986, n = 93) measured using the LumiraDx D-Dimer Test. Overall error rates were 1.8%. The healthy reference range 90% percentile for D-dimer was calculated as 533 µg/l fibrinogen equivalent units (FEU). CONCLUSIONS: The quantitative LumiraDx D-Dimer Test is easy to use and can accurately measure D-dimer levels in a range of blood sample types, including fingerstick samples, which could improve assessment of VTE cases in community and hospital near-patient settings.