Two-phase Bayesian latent class analysis to assess diagnostic test performance in the absence of a gold standard: COVID-19 serological assays as a proof of concept.

BACKGROUND AND OBJECTIVES: In this proof-of-concept study, which included blood donor samples, we aimed to demonstrate how Bayesian latent class models (BLCMs) could be used to estimate SARS-CoV-2 seroprevalence in the absence of a gold standard assay under a two-phase sampling design. MATERIALS AND METHODS: To this end, 6810 plasma samples from blood donors who resided in Québec (Canada) were collected from May to July 2020 and tested for anti-SARS-CoV-2 antibodies using seven serological assays (five commercial and two non-commercial). RESULTS: SARS-CoV-2 seroprevalence was estimated at 0.71% (95% credible interval [CrI] = 0.53%-0.92%). The cPass assay had the lowest sensitivity estimate (88.7%; 95% CrI = 80.6%-94.7%), while the Héma-Québec assay had the highest (98.7%; 95% CrI = 97.0%-99.6%). CONCLUSION: The estimated low seroprevalence (which indicates a relatively limited spread of SARS-CoV-2 in Quebec) might change rapidly-and this tool, developed using blood donors, could enable a rapid update of the prevalence estimate in the absence of a gold standard. Further, the present analysis illustrates how a two-stage BLCM sampling design, along with blood donor samples, can be used to estimate the performance of new diagnostic tests and inform public health decisions regarding a new or emerging disease for which a perfect reference standard does not exist.

Rapid diagnostic testing for syphilis in Arctic communities (the STAR study): a multisite prospective field diagnostic accuracy study in an intended-use setting.

OBJECTIVES: We evaluated the field diagnostic accuracy of a syphilis rapid test (RDT), using serum and whole blood by non-laboratorians in two Canadian Arctic communities. METHODS: We implemented a multisite prospective field evaluation wherein patients were screened by an RDT containing treponemal and non-treponemal components (Chembio DPP® Syphilis Screen & Confirm) between January 2020 and December 2021. Venous whole blood and serum were collected for rapid testing and compared with laboratory-based serology reference testing using a reverse sequence algorithm of treponemal and rapid plasma reagin (RPR) testing. RESULTS: Overall, 135 whole blood and 139 serum specimens were collected from 161 participants during clinical encounters. Treponemal-RDT sensitivity against a treponemal-reference standard (38/161 confirmed cases) was similar for serum (78% [95% CI: 61-90%]) and whole blood (81% [95% CI: 63-93%]). In those with RPR titres ≥1:8 (i.e. suggestive of recent/active infection), sensitivity increased to 93% (95% CI: 77-99%) for serum and 92% (95% CI: 73-99%) for whole blood. Treponemal-RDT specificity was excellent (99% [95% CI: 95-100%]) for both specimen types. Non-treponemal-RDT sensitivity against RPR was 94% (95% CI: 80-99%) for serum and 79% (95% CI: 60-92%) for whole blood. Sensitivity increased to 100% (95% CI: 88-100%) for serum and 92% (95% CI: 73-99%) for whole blood when RPR titres ≥1:8. RDT performance with whole blood was similar to that with serum. DISCUSSION: Non-laboratorians using the RDT accurately identified individuals with infectious syphilis under real-world conditions in an intended-use setting at the point of care. Implementing the RDT can eliminate treatment delays and may enhance disease control.

Hidden sources of bias in diagnostic studies: the example of visceral leishmaniasis in east Africa.

A clear understanding of the accuracy of diagnostic tests is essential for the management of infections such as visceral leishmaniasis in endemic areas. Using both published and unpublished datasets from field diagnostic trials of visceral leishmaniasis in the past ten years, we show the potential effects of unrecognised sources of bias including work-up bias, referral bias, and reference test bias on the results. We outline why these biases, which can occur in diagnostic studies of any disease, can go unrecognised despite adherence to current STARD and QUADAS-2 guidelines. Using these examples and referring to others seen in studies of bacterial and viral infections, we make specific recommendations on how these biases might be avoided through specific steps in study design, study reporting, and the locations where studies are conducted.

Laboratory Features of Trichinellosis and Eosinophilia Threshold for Testing, Nunavik, Quebec, Canada, 2009-2019.

Prolonged eosinophilia is characteristic of trichinellosis. To determine the optimal eosinophil threshold for reflex Trichinella testing, we examined all 43 cases in Nunavik, Quebec, Canada, during 2009-2019. Using receiver operating characteristic analysis, we determined that eosinophil counts >0.8 × 109 cells/L should prompt consideration of trichinellosis and testing to rapidly identify potential outbreaks.

Stopping syphilis transmission in Arctic communities through rapid diagnostic testing: The STAR study protocol.

BACKGROUND: Intense transmission of syphilis has emerged in some Canadian Arctic communities despite screening and prevention efforts. The remoteness of most communities and limited diagnostic infrastructure yield long delays (≥14 days) between screening and treatment of cases. These hamper syphilis control efforts and may contribute to sustained transmission. Syphilis rapid diagnostic tests (RDTs) have been developed to make screening more accessible and to inform clinical decision-making within the same clinical encounter. These RDTs have been successfully deployed in several countries, but not yet in Canada. METHODS AND DESIGN: We describe the methodology of the "Stopping Syphilis Transmission in Arctic Communities Through Rapid Diagnostic Testing" (STAR) study, wherein the clinical and epidemiological impact of deploying a dual syphilis RDT in the context of ongoing transmission in Nunavut and Nunavik will be evaluated. In this prospective multisite field evaluation, sexually active individuals aged ≥14 years at risk for syphilis will be offered screening by an RDT at the point-of-care by non-laboratory trained registered nurses. Whole blood and serum specimens will be concurrently collected, when feasible, for rapid testing with an RDT containing both treponemal and non-treponemal components (Chembio DPP® Syphilis Screen & Confirm) and compared to laboratory-based reference testing according to a reverse sequence algorithm. The diagnostic accuracy of the RDT, using both whole blood and centrifuged serum specimens, will be validated under real-world conditions in remote Northern settings, outside of specialized laboratories. Additionally, screening-to-treatment time, case detection rates, and the number of infectious contacts averted by using the RDT relative to reference testing will be estimated. The impact of both diagnostic approaches on syphilis transmission dynamics will also be modeled. DISCUSSION: This study will provide much needed evidence for strengthening rapid responses to emerging syphilis outbreaks in remote Arctic regions, by supplementing traditional diagnostic strategies with an RDT to rapidly triage patients likely in need of treatment. These results will also inform the development and tailoring of future diagnostic strategies and public health responses to emerging outbreaks in the North.

Accuracy of C-reactive Protein and Procalcitonin for Diagnosing Bacterial Infections Among Subjects With Persistent Fever in the Tropics.

Background: In low-resource settings, inflammatory biomarkers can help identify patients with acute febrile illness who do not require antibiotics. Their use has not been studied in persistent fever (defined as fever lasting for ≥7 days at presentation). Methods: C-reactive protein (CRP) and procalcitonin (PCT) levels were measured in stored serum samples of patients with persistent fever prospectively enrolled in Cambodia, the Democratic Republic of Congo, Nepal, and Sudan. Diagnostic accuracy was assessed for identifying all bacterial infections and the subcategory of severe infections judged to require immediate antibiotics. Results: Among 1838 participants, CRP and PCT levels were determined in 1777 (96.7%) and 1711 (93.1%) samples, respectively, while white blood cell (WBC) count was available for 1762 (95.9%). Areas under the receiver operating characteristic curve for bacterial infections were higher for CRP (0.669) and WBC count (0.651) as compared with PCT (0.600; P <.001). Sensitivity for overall and severe bacterial infections was 76.3% (469/615) and 88.2% (194/220) for CRP >10 mg/L, 62.4% (380/609) and 76.8% (169/220) for PCT >0.1 µg/L, and 30.5% (184/604) and 43.7% (94/215) for WBC >11 000/µL, respectively. Initial CRP level was <10 mg/L in 45% of the participants who received antibiotics at first presentation. Conclusions: In patients with persistent fever, CRP and PCT showed higher sensitivity for bacterial infections than WBC count, applying commonly used cutoffs for normal values. A normal CRP value excluded the vast majority of severe infections and could therefore assist in deciding whether to withhold empiric antibiotics after cautious clinical assessment.

Evaluation of Strongyloides Awareness and Knowledge among Canadian Physicians Caring for Patients At Risk for Severe Strongyloidiasis: A National Cross-sectional Survey.

In Canada, a substantial proportion of migrants come from strongyloidiasis-endemic regions. Systematic screening for Strongyloides is not performed in immunocompromised patients in whom this infection could be potentially fatal. We aim to assess the level of Strongyloides awareness and knowledge among Canadian physicians caring for immunocompromised patients and identify factors currently associated with screening. Using an online survey distributed through Canadian medical associations, we collected information on physicians' demographics, practice setting, overall awareness and knowledge of Strongyloides, and current practices. Descriptive analysis and logistic regression models were performed to identify the factors associated with Strongyloides screening. Nineteen national and provincial medical associations agreed to participate. Between November 2020 and August 2021, 368 of 5,194 (7%) physicians that were contacted responded to our survey. Quebec (46%) and Ontario (24%) were the most responsive. Sixty-nine percent of respondents practiced medicine in academic settings. Infectious disease (ID) specialists/medical microbiologists (38%) followed by nephrologists (33%) were the most represented. Most respondents (95%) had heard about Strongyloides. However, 36% of non-ID specialists considered themselves unfamiliar. Forty percent of respondents did not or rarely performed screening for strongyloidiasis in high-risk populations. Screening was associated with younger-aged physicians (odds ratio [OR] 2.35; 95% confidence interval [CI] 1.07-5.18), physicians who frequently served migrants (OR 3.33; 95% CI 1.44-7.66), or those who had training in global health and ID/medical microbiology (OR 3.71; 95% CI 1.21-11.34 and OR 46.42; 95% CI 15.89-135.59, respectively). Our survey suggests a general lack of knowledge of Strongyloides among Canadian physicians that is associated with low rates of screening in high-risk populations.

Cutaneous leishmaniasis in travellers and migrants: a 10-year case series in a Canadian reference centre for tropical diseases.

BACKGROUND: Cutaneous leishmaniasis is increasingly encountered in returned travellers and migrants to nonendemic countries. We sought to describe the clinical characteristics and treatment outcomes of cases of cutaneous leishmaniasis diagnosed at our reference centre over a 10-year period. METHODS: This case series included all laboratory-confirmed cases of cutaneous leishmaniasis in travellers and migrants for whom complete clinical data were available, diagnosed between January 2008 and October 2018 at the J.D. MacLean Centre for Tropical Diseases in Montréal. We examined the number of cases each year. We used descriptive statistics to summarize variables (e.g., demographic characteristics, travel history, clinical presentation, diagnostic methods, treatments, adverse events) extracted from the patients' electronic medical records. The primary outcome for evaluating clinical response to treatment was defined as the complete re-epithelialization of the wound surface at 1 year. RESULTS: We identified 48 patients who received diagnoses of cutaneous leishmaniasis in the 10-year study period, including 33 exposed in the Americas and 15 exposed in other regions (median age 43.5 [range 1-75] yr); 28 [58%] males). The annual number of cases increased from 9 in 2008/09 to 16 in 2017/18. The median time from onset to diagnosis was 89 (IQR 58-134) days. Liposomal amphotericin B was the most commonly used initial treatment (20 [53%] patients). Thirty-five patients completed their follow-up, and 11 had successful response to 1 course of liposomal amphotericin B. Adverse events (including acute kidney injury, increased pancreatic enzymes and fatigue) were reported in 6 (30%) patients. Clinical cure was achieved within 1 year for 32 (91%) of the 35 patients who completed follow-up. INTERPRETATION: This study showed an increase in the number of cases of cutaneous leishmaniasis seen in our centre over the study period, likely because of increased travel and migration. This diagnosis should be considered in travellers and migrants with a chronic cutaneous lesion.

Multiplexed rapid technologies for sexually transmitted infections: a systematic review.

Multiplexed technologies for sexually transmitted infections offer a convenient diagnostics option to screen, confirm, and treat multiple pathogens simultaneously. Due to scarce published real-world diagnostic performance data, we did a systematic review. Two reviewers searched major databases for data published between Jan 1, 2009, and April 20, 2020, and abstracted and analysed sensitivity and specificity data from 24 studies, which assessed 17 multiplex rapid nucleic acid amplification test platforms and seven multiplex immunochromatographic devices. Overall, these studies evaluated 19 sexually transmitted infections in 26 126 individuals. High sensitivity and specificity were shown for rapid nucleic acid amplification platform tests and immunochromatographic devices, with performance varying by pathogen, device, seropositivity, and subpopulation screened. As most devices yielded more than 95% sensitivity and specificity, immunochromatographic tests and rapid nucleic acid amplification test platforms can be advised for screening and confirmatory use. These highly accurate devices are appropriate for integrated, rapid screening initiatives for sexually transmitted infections to screen and treat many of these infections simultaneously, for antimicrobial stewardship, and for disease elimination programmes.

Systematic on-site testing for SARS-CoV-2 infection among asymptomatic essential workers in Montréal, Canada: a prospective observational and cost-assessment study.

BACKGROUND: Essential workers are at increased risk for SARS-CoV-2 infection. We aimed to estimate the yield, acceptability and cost of systematic workplace-based testing of asymptomatic essential workers for SARS-CoV-2 infection. METHODS: From Jan. 27 to Mar. 12, 2021, we prospectively recruited non-health care essential businesses in Montréal, Canada, through email or telephone contact. Two trained mobile teams, each composed of 2 non-health care professionals, visited businesses. Consenting asymptomatic employees provided saline gargle samples under supervision. Samples were analyzed by means of reverse transcription polymerase chain reaction (RT-PCR). At businesses with outbreaks (≥ 2 participants with a positive result), we retested all participants with a negative result on initial testing. Our primary outcomes were yield (proportion of test results that were positive), acceptability (proportion of participants estimated to be present at the business who agreed to participate) and costs (including training, sample collection and analysis, and communicating results). Our secondary outcome was identification of factors associated with a positive test result on multivariable logistic regression. RESULTS: Of the 366 businesses contacted, 69 (18.8%) agreed to participate. Nineteen businesses (28%) were manufacturers or suppliers, 12 (17%) were in auto sales or repair, and 11 (16%) were in childcare; the corresponding number of employees was 1225, 242 and 113. The median number of participants per business was 13 (interquartile range [IQR] 8-22). Of an estimated 2348 employees on site, 2128 (90.6%) participated (808 [38.0%] female, median age 48 [IQR 37-57] yr). Of the 2626 tests performed, 53 (2.0%) gave a positive result. Self-reported nonwhite ethnicity (adjusted odds ratio [OR] 3.7, 95% confidence interval [CI] 1.4-9.9) and a negative SARS-CoV-2 test result before the study (adjusted OR 0.4, 95% CI 0.2-0.8) were associated with a positive test result. Five businesses were experiencing an outbreak; at these businesses, 40/917 participants (4.4%) had a positive result on the initial test. We repeated testing for employees with initially negative results at 3 of these businesses over 2-3 weeks: 8/350 participants (2.3%) had a positive result on the second test, and none had a positive result on the third and fourth tests; no employer reported new positive results after our final visit (up to Mar. 26, 2021). At the remaining 64 businesses, 1211 participants were tested once, of whom 5 (0.4%) had a positive result. The per-person RT-PCR cost was $34, and all other costs, $8.67. INTERPRETATION: On-site saline gargle sampling of essential workers for SARS-CoV-2 testing was acceptable and of modest cost, and appears most useful in the context of outbreaks. This sampling strategy should be evaluated further as a component of efforts to prevent SARS-CoV-2 transmission. PREPRINT: medRxiv - doi:10.1101/2021.05.12.21256956.

Adequacy of Serial Self-performed SARS-CoV-2 Rapid Antigen Detection Testing for Longitudinal Mass Screening in the Workplace.

Importance: Longitudinal mass testing using rapid antigen detection tests (RADT) for serial screening of asymptomatic persons has been proposed for preventing SARS-CoV-2 community transmission. The feasibility of this strategy relies on accurate self-testing. Objective: To quantify the adequacy of serial self-performed SARS-CoV-2 RADT testing in the workplace, in terms of the frequency of correct execution of procedural steps and accurate interpretation of the range of possible RADT results. Design, Setting, and Participants: This prospective repeated cross-sectional study was performed from July to October 2021 at businesses with at least 2 active cases of SARS-CoV-2 infection in Montreal, Canada. Participants included untrained persons in their workplace, not meeting Public Health quarantine criteria (ie, required quarantine for 10 days after a moderate-risk contact with someone infected with SARS-CoV-2). Interpretation and performance were compared between participants who received instructions provided by the manufacturer vs those who received modified instructions that were informed by the most frequent or most critical errors we observed. Data were analyzed from October to November 2021. Exposures: RADT testing using a modified quick reference guide compared with the original manufacturer's instructions. Main Outcomes and Measures: The main outcome was the difference in correctly interpreted RADT results. Secondary outcomes included difference in proportions of correctly performed procedural steps. Additional analyses, assessed among participants with 2 self-testing visits, compared the second self-test visit with the first self-test visit using the same measures. Results: Overall, 1892 tests were performed among 647 participants, of whom 278 participants (median [IQR] age, 43 [31-55] years; 156 [56.1%] men) had at least 1 self-testing visit. For self-test visit 1, significantly better accuracy in test interpretation was observed among participants using the modified quick reference guide than those using the manufacturer's instructions for reading results that were weak positive (64 of 115 participants [55.6%] vs 20 of 163 participants [12.3%]; difference, 43.3 [95% CI, 33.0-53.8] percentage points), positive (103 of 115 participants [89.6%] vs 84 of 163 participants [51.5%]; difference, 38.1 [95% CI, 28.5-47.5] percentage points), strong positive (219 of 229 participants [95.6%] vs 274 of 326 participants [84.0%]; difference, 11.6 [95% CI, 6.8-16.3] percentage points), and invalid (200 of 229 participants [87.3%] vs 252 of 326 participants [77.3%]; difference, 10.0 [95% CI, 3.8-16.3] percentage points). Use of the modified guide was associated with improvements on self-test visit 2 for results that were weak positive (difference, 15.4 [95% CI, 0.7-30.1] percentage points), positive (difference, 19.0 [95% CI, 7.2-30.9] percentage points), and invalid (difference, 8.0 [95% CI, 0.8-15.4] percentage points). For procedural steps identified as critical for test validity, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience. Conclusions and Relevance: In this cross-sectional study of self-performed SARS-CoV-2 RADT in an intended-use setting, a modified quick reference guide was associated with significantly improved accuracy in RADT interpretations.

Etiological spectrum of persistent fever in the tropics and predictors of ubiquitous infections: a prospective four-country study with pooled analysis.

BACKGROUND: Persistent fever, defined as fever lasting for 7 days or more at first medical evaluation, has been hardly investigated as a separate clinical entity in the tropics. This study aimed at exploring the frequencies and diagnostic predictors of the ubiquitous priority (i.e., severe and treatable) infections causing persistent fever in the tropics. METHODS: In six different health settings across four countries in Africa and Asia (Sudan, Democratic Republic of Congo [DRC], Nepal, and Cambodia), consecutive patients aged 5 years or older with persistent fever were prospectively recruited from January 2013 to October 2014. Participants underwent a reference diagnostic workup targeting a pre-established list of 12 epidemiologically relevant priority infections (i.e., malaria, tuberculosis, HIV, enteric fever, leptospirosis, rickettsiosis, brucellosis, melioidosis, relapsing fever, visceral leishmaniasis, human African trypanosomiasis, amebic liver abscess). The likelihood ratios (LRs) of clinical and basic laboratory features were determined by pooling all cases of each identified ubiquitous infection (i.e., found in all countries). In addition, we assessed the diagnostic accuracy of five antibody-based rapid diagnostic tests (RDTs): Typhidot Rapid IgM, Test-itTM Typhoid IgM Lateral Flow Assay, and SD Bioline Salmonella typhi IgG/IgM for Salmonella Typhi infection, and Test-itTM Leptospira IgM Lateral Flow Assay and SD Bioline Leptospira IgG/IgM for leptospirosis. RESULTS: A total of 1922 patients (median age: 35 years; female: 51%) were enrolled (Sudan, n = 667; DRC, n = 300; Nepal, n = 577; Cambodia, n = 378). Ubiquitous priority infections were diagnosed in 452 (23.5%) participants and included malaria 8.0% (n = 154), tuberculosis 6.7% (n = 129), leptospirosis 4.0% (n = 77), rickettsiosis 2.3% (n = 44), enteric fever 1.8% (n = 34), and new HIV diagnosis 0.7% (n = 14). The other priority infections were limited to one or two countries. The only features with a positive LR ≥ 3 were diarrhea for enteric fever and elevated alanine aminotransferase level for enteric fever and rickettsiosis. Sensitivities ranged from 29 to 67% for the three RDTs targeting S. Typhi and were 9% and 16% for the two RDTs targeting leptospirosis. Specificities ranged from 86 to 99% for S. Typhi detecting RDTs and were 96% and 97% for leptospirosis RDTs. CONCLUSIONS: Leptospirosis, rickettsiosis, and enteric fever accounted each for a substantial proportion of the persistent fever caseload across all tropical areas, in addition to malaria, tuberculosis, and HIV. Very few discriminative features were however identified, and RDTs for leptospirosis and Salmonella Typhi infection performed poorly. Improved field diagnostics are urgently needed for these challenging infections. TRIAL REGISTRATION: NCT01766830 at ClinicalTrials.gov.

qSOFA does not predict bacteremia in patients with severe manifestations of sepsis.

BACKGROUND: Bloodstream infections in septic patients may be missed due to preceding antibiotic therapy prior to obtaining blood cultures. We leveraged the FABLED cohort study to determine if the quick Sequential Organ Failure Assessment (qSOFA) score could reliably identify patients at higher risk of bacteremia in patients who may have false negative blood cultures due to previously administered antibiotic therapy. METHODS: We conducted a multi-centre diagnostic study among adult patients with severe manifestations of sepsis. Patients were enrolled in one of seven participating centres between November 2013 and September 2018. All patients from the FABLED cohort had two sets of blood cultures drawn prior to the administration of antimicrobial therapy, as well as additional blood cultures within 4 hours of treatment initiation. Participants were categorized according to qSOFA score, with a score ≥2 being considered positive. RESULTS: Among 325 patients with severe manifestations of sepsis, a positive qSOFA score (defined as a score ≥2) on admission was 58% sensitive (95% CI 48% to 67%) and 41% specific (95% CI 34% to 48%) for predicting bacteremia. Among patients with negative post-antimicrobial blood cultures, a positive qSOFA score was 57% sensitive (95% CI 42% to 70%) and 42% specific (95% CI 35% to 49%) to detect patients who were originally bacteremic prior to the initiation of therapy. CONCLUSIONS: Our results suggest that the qSOFA score cannot be used to identify patients at risk for occult bacteremia due to the administration of antibiotics pre-blood culture.

HISTORIQUE: Les infections sanguines peuvent rester non diagnostiquées chez les patients septiques avant l'obtention des cultures sanguines, en raison d'une antibiothérapie antérieure. Les chercheurs ont puisé dans l'étude de cohorte FABLED pour déterminer si le score rapide de l'évaluation séquentielle d'insuffisance des organes (Sequential Organ Failure Assessment, qSOFA) pourrait dépister les patients à plus haut risque de bactériémie avec fiabilité, malgré la possibilité de cultures sanguines faussement négatives en raison d'une antibiothérapie antérieure. MÉTHODOLOGIE: Les chercheurs ont réalisé une étude diagnostique multicentrique chez des patients adultes ayant de graves manifestations de sepsis. Les patients ont été inscrits dans l'un des sept centres participants entre novembre 2013 et septembre 2018. Tous les patients de l'étude de cohorte FABLED avaient subi deux séries de cultures sanguines avant de recevoir une thérapie antimicrobienne, de même qu'une autre série de cultures sanguines dans les quatre heures suivant le début du traitement. Les participants ont été classés en fonction de leur score de qSOFA, un score d'au moins 2 étant considéré comme positif. RÉSULTATS: Chez les 325 patients ayant de graves manifestations de sepsis, un score de qSOFA positif (défini comme un score d'au moins 2) à l'admission était sensible à 58 % (IC à 95 %, 48 % à 67 %) et spécifique à 41 % (IC à 95 %, 34 % à 48 %) pour prédire la bactériémie. Chez les patients dont les cultures sanguines étaient négatives après la prise d'antimicrobiens, un score de qSOFA positif était sensible à 57 % (IC à 95 %, 42 % à 70 %) et spécifique à 42 % (IC à 95 %, 35 % à 49 %) pour dépister les patients atteints d'une bactériémie avant le début du traitement. CONCLUSIONS: Selon les résultats, le score de qSOFA ne peut pas être utilisé pour dépister les patients à risque de bactériémie occulte à cause de l'administration d'antibiotiques avant la culture sanguine.

Specificity of SARS-CoV-2 Antibody Detection Assays against S and N Proteins among Pre-COVID-19 Sera from Patients with Protozoan and Helminth Parasitic Infections.

We aimed to assess the specificity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody detection assays among people with tissue-borne parasitic infections. We tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 neutralization antibody detection kit [cPass], Abbott SARS-CoV-2 IgG assay [Abbott Architect], and Standard Q COVID-19 IgM/IgG combo rapid diagnostic test [SD RDT IgM/SD RDT IgG]) among 559 pre-COVID-19 seropositive sera for several parasitic infections. The specificity of assays was 95 to 98% overall. However, lower specificity was observed among sera from patients with protozoan infections of the reticuloendothelial system, such as human African trypanosomiasis (Abbott Architect; 88% [95% CI, 75 to 95]) and visceral leishmaniasis (SD RDT IgG; 80% [95% CI, 30 to 99]), and from patients with recent malaria in areas of Senegal where malaria is holoendemic (ranging from 91% for Abbott Architect and SD RDT IgM to 98 to 99% for cPass and SD RDT IgG). For specimens from patients with evidence of past or present helminth infection overall, test specificity estimates were all ≥96%. Sera collected from patients clinically suspected of parasitic infections that tested negative for these infections yielded a specificity of 98 to 100%. The majority (>85%) of false-positive results were positive by only one assay. The specificity of SARS-CoV-2 serological assays among sera from patients with tissue-borne parasitic infections was below the threshold required for decisions about individual patient care. Specificity is markedly increased by the use of confirmatory testing with a second assay. Finally, the SD RDT IgG proved similarly specific to laboratory-based assays and provides an option in low-resource settings when detection of anti-SARS-CoV-2 IgG is indicated.

Cost-utility analysis of antimicrobial stewardship programme at a tertiary teaching hospital in Ethiopia.

OBJECTIVE: Antimicrobial stewardship (AMS) significantly reduces inappropriate antibiotic use and improves patient outcomes. In low-resource settings, AMS implementation may require concurrent strengthening of clinical microbiology capacity therefore additional investments. We assessed the cost-effectiveness of implementing AMS at Tikur Anbessa Specialised Hospital (TASH), a tertiary care hospital in Ethiopia. DESIGN: We developed a Markov cohort model to assess the cost-utility of pharmacist-led AMS with concurrent strengthening of laboratory capacity compared with usual care from a 'restricted societal' perspective. We used a lifetime time horizon and discounted health outcomes and cost at 3% annually. Data were extracted from a prospective study of bloodstream infections among patients hospitalised at TASH, supplemented by published literature. We assessed parameter uncertainty using deterministic and probabilistic sensitivity analyses. SETTING: Tertiary care hospital in Ethiopia, with 800 beds and serves over half a million patients per year. POPULATION: Cohort of adults and children inpatient population aged 19.8 years at baseline. INTERVENTION: Laboratory-supported pharmacist-led AMS compared with usual care. Usual care is defined as empirical initiation of antibiotic therapy in the absence of strong laboratory and AMS. OUTCOME MEASURES: Expected life-years, quality-adjusted life-years (QALYs), costs (US$2018) and incremental cost-effectiveness ratio. RESULTS: Laboratory-supported AMS strategy dominated usual care, that is, AMS was associated with an expected incremental gain of 38.8 QALYs at lower expected cost (incremental cost savings:US$82 370) per 1000 patients compared with usual care. Findings were sensitive to medication cost, infection-associated mortality and AMS-associated mortality reduction. Probabilistic sensitivity analysis demonstrated that AMS programme was likely to be cost-effective at 100% of the simulation compared with usual care at 1%-51% of gross domestic product/capita. CONCLUSION: Our study indicates that laboratory-supported pharmacist-led AMS can result in improved health outcomes and substantial healthcare cost savings, demonstrating its economic advantage in a tertiary care hospital despite greater upfront investments in a low-resource setting.

Dried blood spot specimens for SARS-CoV-2 antibody testing: A multi-site, multi-assay comparison.

The true severity of infection due to COVID-19 is under-represented because it is based on only those who are tested. Although nucleic acid amplifications tests (NAAT) are the gold standard for COVID-19 diagnostic testing, serological assays provide better population-level SARS-CoV-2 prevalence estimates. Implementing large sero-surveys present several logistical challenges within Canada due its unique geography including rural and remote communities. Dried blood spot (DBS) sampling is a practical solution but comparative performance data on SARS-CoV-2 serological tests using DBS is currently lacking. Here we present test performance data from a well-characterized SARS-CoV-2 DBS panel sent to laboratories across Canada representing 10 commercial and 2 in-house developed tests for SARS-CoV-2 antibodies. Three commercial assays identified all positive and negative DBS correctly corresponding to a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (95% CI = 72.2, 100). Two in-house assays also performed equally well. In contrast, several commercial assays could not achieve a sensitivity greater than 40% or a negative predictive value greater than 60%. Our findings represent the foundation for future validation studies on DBS specimens that will play a central role in strengthening Canada's public health policy in response to COVID-19.

Epidemiology associated with the exposure to Toxoplasma gondii in Nunavik's Inuit population using the 2017 Qanuilirpitaa cross-sectional health survey.

Foci of high seroprevalence against Toxoplasma gondii are observed in Nunavik, the Inuit land of Northern Quebec (Canada). Considering the rare occurrence of felids in the region, exposure is suspected to be driven by water- and food-borne transmission routes. Hypotheses were that drinking untreated water from natural sources and eating country food mostly raw increased the risk of exposure to the parasite. Data from 1,300 Inuit participants of the 2017 Nunavik Health Survey were included in three weighted robust Poisson regression models. The effect of three types of exposure variables: (1) water treatment (yes/no) and if country food was mostly eaten raw (yes/no); (2) main source of drinking water (bottled/municipal/natural) and frequency of country food consumption (continuous) and (3) drinking water risk (low/intermediate/high) and frequency of a raw country food consumption (continuous), on the presence of Toxoplasma antibodies were estimated. Models were adjusted for age, sex and ecological region, with multiple sensitivity analyses being performed. Toxoplasma gondii seroprevalences were consistently correlated with age quadratically, sex (prevalence ratio = PRwoman/man ranged from 1.18 to 1.22), ecological region (PRHudsonBay/HudsonStrait ranged from 2.18 to 2.41; PRHudsonBay/UngavaBay ranged from 1.52 to 1.59) and consuming bivalve mollusc/urchin (PR varied from 1.02 to 1.21) across all three models. Each increase of two consumptions per month of beluga (PR ranged from 1.01 to 1.03), seal liver (PR ranged from 1.01 to 1.02) and goose (PR ranged from 1.01 to 1.02) were also associated with seropositivity, albeit more clearly in models 2 and 3, while drinking water mainly from natural (PR of 1.47) or municipal (PR = 1.42) sources compared to bottled water, was correlated with seroprevalence, although results were compatible with the null. Our results suggest that both the oocyst- (mollusc/urchin, drinking water) and cyst-borne (walrus, seal liver and goose) transmission pathways could be present in Nunavik.

Neither Blood Culture Positivity nor Time to Positivity Is Associated With Mortality Among Patients Presenting With Severe Manifestations of Sepsis: The FABLED Cohort Study.

BACKGROUND: Sepsis is a leading cause of morbidity, mortality, and health care costs worldwide. METHODS: We conducted a multicenter, prospective cohort study evaluating the yield of blood cultures drawn before and after empiric antimicrobial administration among adults presenting to the emergency department with severe manifestations of sepsis. Enrolled patients who had the requisite blood cultures drawn were followed for 90 days. We explored the independent association between blood culture positivity and its time to positivity in relation to 90-day mortality. RESULTS: Three hundred twenty-five participants were enrolled; 90-day mortality among the 315 subjects followed up was 25.4% (80/315). Mortality was associated with age (mean age [standard deviation] in those who died was 72.5 [15.8] compared with 62.9 [17.7] years among survivors; P < .0001), greater Charlson Comorbidity Index (2 [interquartile range {IQR}, 1-3] vs 1 [IQR, 0-3]; P = .008), dementia (13/80 [16.2%] vs 18/235 [7.7%]; P = .03), cancer (27/80 [33.8%] vs 47/235 [20.0%]; P = .015), positive quick Sequential Organ Failure Assessment score (57/80 [71.2%] vs 129/235 [54.9%]; P = .009), and normal white blood cell count (25/80 [31.2%] vs 42/235 [17.9%]; P = .02). The presence of bacteremia, persistent bacteremia after antimicrobial infusion, and shorter time to blood culture positivity were not associated with mortality. Neither the source of infection nor pathogen affected mortality. CONCLUSIONS: Although severe sepsis is an inflammatory condition triggered by infection, its 90-day survival is not influenced by blood culture positivity nor its time to positivity. CLINICAL TRIALS REGISTRATION: NCT01867905.

Evaluation of a Commercial Culture-Free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syndrome-Related Coronavirus-2 and Comparison With an Antireceptor-Binding Domain Enzyme-Linked Immunosorbent Assay.

BACKGROUND: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) surrogate neutralization assays that obviate the need for viral culture offer substantial advantages regarding throughput and cost. The cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript) is the first such commercially available assay that detects antibodies that block receptor-binding domain (RBD)/angiotensin-converting enzyme (ACE)-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared with anti-RBD enzyme-linked immunosorbent assays (ELISAs). METHODS: Serum reference panels comprising 205 specimens were used to compare cPass to plaque-reduction neutralization test (PRNT) and a pseudotyped lentiviral neutralization (PLV) assay for detection of neutralizing antibodies. We assessed the correlation of cPass with an ELISA detecting anti-RBD immunoglobulin (Ig)G, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection. RESULTS: Compared with PRNT-50, cPass sensitivity ranged from 77% to 100% and specificity was 95% to 100%. Sensitivity was also high compared with the pseudotyped lentiviral neutralization assay (93%; 95% confidence interval [CI], 85-97), but specificity was lower (58%; 95% CI, 48-67). Highest agreement between cPass and ELISA was for anti-RBD IgG (r = 0.823). Against the pseudotyped lentiviral neutralization assay, anti-RBD IgG sensitivity (99%; 95% CI, 94-100) was very similar to that of cPass, but overall specificity was lower (37%; 95% CI, 28-47). Against PRNT-50, results of cPass and anti-RBD IgG were nearly identical. CONCLUSIONS: The added value of cPass compared with an IgG anti-RBD ELISA was modest.