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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 Using both published and unpublished datasets from field diagnostic trials of visceral leishmaniasis in the past ten years, we show the potential effects of unrecognised sources of bias including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.

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.

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 counts0.8 × 10

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 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 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.

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.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.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.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.

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.

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.

Accurate serologic tests to detect host antibodies to SARS-CoV-2 will be critical for the public health response to the COVID-19 pandemic. This article discusses key use cases for SARS-CoV-2 antibo...

To estimate the impact of implementing in-hospital enterovirus (EV) polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) with same-day turn-around-time (TAT) on length-of-stay (LOS), antibiotic use and on cost per patient with suspected EV meningitis, compared with testing at an outside reference laboratory. A model-based analysis using a retrospective cohort of all hospitalized children with CSF EV PCR testing done between November 2013 and 2017. The primary outcome measured was the potential date of discharge if the EV PCR result had been available on the same day. Patients with positive EV PCR were considered for potential earlier discharge once clinically stable with no reason for hospitalization other than intravenous antibiotics. Descriptive statistics and cost-sensitivity analyses were performed. CSF EV PCR testing was done on 153 patients, of which 44 (29%) had a positive result. Median test TAT was 5.3 days (IQR 3.9-7.6). Median hospital LOS was 5 days (IQR 3-12). Most (86%) patients received intravenous antibiotics with mean duration of 5.72 ± 6.51 days. No patients with positive EV PCR had a serious bacterial infection. We found that same-day test TAT would reduce LOS and duration of intravenous antibiotics by 0.50 days (95%CI 0.33-0.68) and 0.67 days (95%CI 0.42-0.91), respectively. Same-day test TAT was associated with a cost reduction of 342.83CAD (95%CI 178.14-517.00) per patient with suspected EV meningitis. Compared with sending specimens to a reference laboratory, performing CSF EV PCR in-hospital with same-day TAT was associated with decreased LOS, antibiotic therapy, and cost per patient.

ImportanceLongitudinal 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 implementation of accurate self-performed RADT testing where people live, work, or attend school.ObjectiveTo 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. We compared results using the instructions provided by the manufacturer to those with modified instructions that were informed by the most frequent or most critical errors we observed.DesignRepeated cross-sectional, diagnostic accuracy study performed prospectively in the field.SettingBusinesses in Montreal, Quebec, Canada, with at least 2 active cases of SARS-CoV-2 infection.ParticipantsUntrained, asymptomatic persons in their workplace, not meeting Public Health quarantine criteria.ExposuresA Modified Quick Reference Guide compared to the original manufacturer’s instructions.Main Outcome(s) and Measure(s)The difference in the proportions of correctly performed procedural steps, and the difference in proportions of correctly interpreted RADT proficiency panel results. The secondary outcome, among subjects with two self-testing visits, compared the second to the first self-test visit using the same measures.ResultsOverall, 1892 tests were performed among 647 subjects. For self-test visit 1, significantly better accuracy in test interpretation was observed using the Modified Quick Reference Guide for weak positive (55.6% vs. 12.3%; 43.3 percentage point improvement, 95% confidence interval [CI] 33.0%-53.8%), positive (89.6% vs. 51.5%; 38.1% difference, 95%CI 28.5%-47.5%), strong positive (95.6% vs. 84.0%; 11.6% improvement, 95%CI 6.8%-16.3%) and invalid (87.3% vs. 77.3%; 10.0% improvement, 95%CI 3.8%-16.3%) tests. Use of the modified guide was associated with smaller, statistically significant, improvements on self-test visit 2. For procedural steps identified as critical for the validity of test results, adherence to procedural testing steps did not differ meaningfully according to instructions provided or reader experience.Conclusions and RelevanceLongitudinal mass RADT testing for SARS-CoV-2 can be accurately self-performed in an intended-use setting; this work provides evidence for how to optimise performance.Key PointsQuestioDo untrained users correctly perform and interpret the results of SARS-CoV-2 rapid antigen detection tests (RADT) in the workplace, and how can their performance be optimised?FindingsIn this prospective field evaluation of self-performed SARS-CoV-2 RADT in an intended-use setting, we found that the accuracy of RADT interpretation was poor when the manufacturer’s instructions were used. A Modified Quick Reference Guide yielded significantly better user performance.MeaningLongitudinal mass RADT testing for SARS-CoV-2 can be accurately self-performed in an intended-use setting; this work provides evidence for how to optimise performance.

BackgroundWe aimed to assess the specificity of SARS-CoV-2 antibody detection assays among people with known tissue-borne parasitic infections.MethodsWe tested three SARS-CoV-2 antibody-detection assays (cPass SARS-CoV-2 Neutralization Antibody Detection Kit, Abbott SARS-CoV-2 IgG assay, and STANDARD Q COVID-19 IgM/IgG Combo Rapid Test) among 559 pre-COVID-19 sera.ResultsThe specificity of assays was 95-98% 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 75-95]), visceral leishmaniasis (SD RDT IgG; 80% [95%CI 30-99]), and from patients with recent malaria from a holoendemic area of Senegal (ranging from 91% for Abbott Architect and SD RDT IgM to 98-99% 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 98-100%. The majority (>85%) of false-positive results were positive by only one assay.ConclusionsThe 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.

IntroductionConventional care packages around screening for sexually transmitted infections (STIs) entail multiple clinic visits and precipitate losses to follow-up. To prevent these losses, multiplexed technologies for STIs (immunochromatographic tests/devices/assays and molecular assays that can screen multiple pathogens or multiple strains of one STI) can yield same-day results in a single visit. Research evidence of patient-centred (preference, satisfaction) and clinical health outcomes (feasibility, case positivity, uptake, impact) has not been synthesised. We conducted a systematic review to fill this gap.MethodsFor the period 2009–2020, two independent reviewers searched PubMed and Embase, retrieved 4440 citations and abstracted data from 42 relevant studies.ResultsOf 42 studies, 10 (23.8%) evaluated multiplexed immunochromatographic and 32 (76.2%) molecular assays. Outcomes were reported as follows: preference (n=3), satisfaction (n=2), uptake (n=1), feasibility (n=2), case positivity (n=42) and impact (n=11). Screened populations included various at-risk groups. A majority (86.1%–92.4%) of participants preferred (60.2%–97.2%) multiplexed technologies (over conventional testing). Compared with conventional lab-based testing, test uptake improved by 99.4% (hepatitis C), 99.6% (Trichomonas vaginalis), 78.6% (hepatitis B) and 42.0% (HIV). Varying case positivities were documented depending on populations screened: HIV (1.8%–29.3%), hepatitis B (1.1%–23.9%), hepatitis C (0.5%–42.2%), Chlamydia trachomatis (2.8%–30.2%), Neisseria gonorrhoeae (0.0%–30.3%) and T. vaginalis (0.0%–32.7%). Regarding impact, 70.0%–100.0% of screened participants were linked to care, with result turnaround times ranging from 14 min (immunochromatographic assays) to 300 min (molecular assays).ConclusionsCompared with conventional lab-based testing, rapid multiplexed technologies were preferred by testees and led to quicker turnaround times for many STIs yielding same-day results thereby allowing to initiate rapid linkages to care. They were further shown to be highly feasible and impactful for detection and treatment facilitation. Based on these promising results, multiplexed technologies offer potential to screen at-risk populations to reduce onward STI transmission worldwide.

In low-resource hospitals of central Africa, neurological disorders are frequent and etiologies very diverse. The difficulty to identify invasive bacterial infections in this setting results in major antibiotic overuse. Biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) may help discriminate these conditions. We retrospectively determined the concentrations of CRP and PCT in the sera of patients consecutively enrolled from 2012 to 2015 in an etiological study on neurological disorders at the rural hospital of Mosango, Democratic Republic of Congo. Invasive bacterial infection had been diagnosed by the demonstration of a bacterial pathogen in cerebrospinal fluid or blood cultures or the presence of radiological pneumonia. Sera of 313 (89.2%) and 317 (90.3%) of the 351 enrolled participants were available for determination of CRP and PCT concentrations respectively. Areas under the receiver operating characteristic curves for invasive bacterial infection, diagnosed in 19 tested cases, were 94.3% for CRP and 91.7% for PCT. No single case had a normal CRP concentration (

Travelers' diarrhea affects up to 60% of visitors to tropical and subtropical regions. Although symptoms are generally self-limited, some infections are associated with significant morbidity and occasional mortality. Newer molecular diagnostic techniques allow for highly sensitive, specific, and expeditious testing of a wide range of potential pathogens. Identification of the causative pathogen of travelers' diarrhea allows for targeted therapy and management and a reduction in empiric broad-spectrum coverage.

BACKGROUNDEssential workers are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We did a prospective study to estimate the yield, acceptability, and costs of workplace-based systematic SARS-CoV-2 testing of asymptomatic essential workers.METHODSWe recruited non-healthcare essential businesses, in Montréal, Canada. Mobile teams, composed of two non-healthcare professionals each, visited businesses. Consenting, asymptomatic employees provided saline gargle specimens under supervision. Mobile team members self-sampled weekly. Specimens were analyzed using reverse-transcription polymerase chain reaction (RT-PCR). If an outbreak was detected (≥2 positives), we retested all initially negative participants. We did logistic regression for factors associated with a positive test. We estimated costs ($CAD) of this strategy.RESULTSFrom 27 January to 12 March 2021, 69 essential businesses were visited. Of an estimated 2348 employees onsite, 2128 (90.6%) participated. Across 2626 tests, 53 (2.0%) were positive. Self-reported non-Caucasian ethnicity (aOR 3.7, 95% CI: 1.4-9.9) and a negative SARS-CoV-2 test before the study (0.4, 0.2-0.8) were positively and negatively associated with a positive test, respectively. Five businesses—3 manufacturing/supplier and 2 meat processing— were experiencing an outbreak. At these businesses, 40 (4.4%) of 917 participants were positive on the initial test. We repeated testing at three of these businesses over 2-3 weeks: 8/350 (2.3%) were positive on the second test, and zero were positive on the third and fourth test (148 tests); no employer reported new positives to 26 March 2021. In all other businesses, 1211 participants were tested once—5 (0.4%) were positive at three childcare enterprises, one grocery store, and one manufacturing/supplier. Per person, RT-PCR costs were $34.00 and all other costs $8.67. No mobile team member tested positive.INTERPRETATIONOnsite sampling of essential workers with saline gargle is safe, acceptable, and inexpensive. Repeat testing appeared to eliminate outbreaks. Systematic testing should be considered part of SARS-CoV-2 preventive efforts.

BackgroundSARS-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, detecting antibodies that block RBD/ACE-2 interaction. We aimed to evaluate cPass to inform its use and assess its added value compared to anti-RBD ELISA assays.MethodsSerum 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 IgG, IgM, and IgA antibodies at a single timepoint and across intervals from onset of symptoms of SARS-CoV-2 infection.ResultsCompared to PRNT-50, cPass sensitivity ranged from 77% - 100% and specificity was 95% - 100%. Sensitivity was also high compared to the pseudotyped lentiviral neutralization assay (93% [95%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.ConclusionsThe added value of cPass compared to an IgG anti-RBD ELISA was modest.

Summary 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.

BackgroundMany studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making.MethodsIn this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634.ResultsWe identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4–8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6% in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (pDiscussionMost of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.

The Canadian Arctic has a long history with diarrheal disease, including outbreaks of campylobacteriosis, giardiasis, and salmonellosis. Due to climate change, the Canadian Arctic is experiencing rapid environmental transformation, which not only threatens the livelihood of local Indigenous Peoples, but also supports the spread, frequency, and intensity of enteric pathogen outbreaks. Advances in diagnostic testing and detection have brought to attention the current burden of disease due to Cryptosporidium, Campylobacter, and Helicobacter pylori. As climate change is known to influence pathogen transmission (e.g., food and water), Arctic communities need support in developing prevention and surveillance strategies that are culturally appropriate. This review aims to provide an overview of how climate change is currently and is expected to impact enteric pathogens in the Canadian Arctic.

Background The epidemiology of human cysticercosis and neurocysticercosis, caused by the larval stage of the pork tapeworm Taenia solium, is not well known in the Democratic Republic of Congo (DRC). Within a multicenter etiological and diagnostic study conducted by the NIDIAG consortium (“Better Diagnosis for Neglected Infections”) and investigating several challenging syndromes, we consecutively evaluated from 2012 to 2015 all patients older than 5 years presenting with neurological disorders (neurology cohort) and with fever > 7 days (persistent fever cohort) at the rural hospital of Mosango, province of Kwilu, DRC. In both cohorts, etiological diagnosis relied on a systematic set of reference laboratory assays and on pre-established clinical case definitions. No neuroimaging was available in the study hospital. In this study, we determined the frequency of T. solium infection in both cohorts and explored in the neurology cohort its association with specific neurological presentations and final etiological diagnoses. Methods We conducted a post-hoc descriptive and analytic study on cysticercosis in the neurology and persistent fever cohorts, based on the presence in serum samples of circulating T. solium antigen using the B158/B60 enzyme-linked immunosorbent assay (ELISA) and of cysticercosis IgG using the LDBIO Cysticercosis Western Blot IgG assay. Results For the neurology cohort, 340 samples (of 351 enrolled patients) were available for analysis (males: 46.8%; mean age: 38.9 years). T. solium antigen positivity was found in 43 participants (12.6%; 95% confidence interval [CI] 9.3–16.7%), including 9 of 60 (15%) patients with epilepsy. Among the 148 samples available from the persistent fever cohort (males: 39.9%; mean age: 19.9 years), 7 were positive in the T. solium antigen ELISA (4.7%; 95% CI 1.9–9.5%; P = 0.009 when compared to the neurology cohort). No significant association was found within the neurology cohort between positivity and clinical presentation or final diagnoses. Of note, the IgG antibody-detecting assay was found positive in only four (1.3%) of the participants of the neurology cohort and in none of the persistent fever cohort. Conclusions T. solium antigen positivity was found in at least 10% of patients admitted with neurological disorders in the Kwilu province, DRC, with no specific pattern of presentation. Further neuroimaging studies should be used to confirm whether neurocysticercosis is prevalent in this region.

BackgroundMany studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making.MethodsIn this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634.ResultsWe identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4-8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6 % in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (pDiscussionMost of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.FundingPublic Health Agency of Canada through the COVID-19 Immunity Task Force.

Background Of all microbiological tests performed, blood cultures have the most impact on patient care. Timely results are essential, especially in the management of sepsis. While there are multiple available blood culture systems on the market, they have never been compared in a prospective study in a critically ill population. Methods We performed an analysis of the FABLED study cohort to compare culture results and time to positivity (TTP) of 2 widely used blood culture systems: BacT/Alert and BACTEC. In this multisite prospective study, patients with severe manifestations of sepsis had cultures drawn before antibiotics using systematic enrollment criteria and blood drawing methodology allowing for minimization of pre-analytical biases. Results We enrolled 315 patients; 144 had blood cultures (47 positive) with BacT/Alert and 171 with BACTEC (53 positive). Patients whose blood cultures were processed using the BacT/Alert system were younger (median, 64 vs 70 years; P = .003), had a higher proportion of HIV (9.03% vs 1.75%; P = .008) and a lower qSOFA (P = .003). There were no statistically significant differences in the most commonly identified bacterial species. TTP was shorter for BACTEC (median [interquartile range {IQR}], 12.5 [10–14] hours) compared with BacT/Alert (median [IQR], 17 [14–21] hours; P Conclusions In this large prospective multi-centre study comparing the two blood culture systems among patients with severe manifestations of sepsis, and using a rigorous pre-analytical methodology, the BACTEC system yielded positive culture results 4.5 hours earlier than BacT/Alert. These results apply to commonly isolated bacteria. However, our study design did not allow direct comparison of TTP for unusual pathogens nor of clinical sensitivity between systems. More research is needed to determine the clinical implications of this finding.

Background Hospital-associated infection (HAI) and antimicrobial resistance (AMR) are major health threats in low- and middle-income countries (LMICs). Because diagnostic capacity is lacking throughout most of Africa, patients are commonly managed with prolonged empirical antibiotic therapy. Our goal was to assess mortality in relation to HAI and empirical therapy in Ethiopia’s largest referral hospital. Methods Cohort study of patients with suspected HAI at Tikur Anbessa Specialized Hospital from October 2016 to October 2018. Blood culture testing was performed on an automated platform. Primary outcomes were proportion of patients with bloodstream infection (BSI), antibiotic resistance patterns and 14 day mortality. We also assessed days of therapy (DOT) pre- and post-blood culture testing. Results Of 978 enrolled patients, 777 had blood culture testing; 237 (30%) had a BSI. Enterobacteriaceae were isolated in 49%; 81% of these were cephalosporin resistant and 23% were also carbapenem resistant. Mortality at 14 days was 31% and 21% in those with and without BSI, respectively. Ceftriaxone resistance was strongly correlated with mortality. Patients with BSI had longer DOT pre-blood culture testing compared with those without BSI (median DOT 12 versus 3 days, respectively, P Conclusions BSI are frequent and fatal among patients with suspected HAI in Ethiopia. Highly resistant blood isolates are alarmingly common. This study provides evidence that investing in systematic blood culture testing in LMICs identifies patients at highest risk of death and that empirical management is frequently inappropriate. Major investments in laboratory development are critical to achieve better outcomes.

Background: Access to clinical bacteriology in low resource settings (LRS) is a key bottleneck preventing individual patient management of treatable severe infections, detection of antimicrobial resistance (AMR), and implementation of effective stewardship interventions. We sought to demonstrate the feasibility of a practical bundle of interventions aimed at implementing sustainable clinical bacteriology services at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on cost and intensity of supervision. Methods: Starting in Dec 2015, an intervention based on the CLSI QMS01-A guideline was established, consisting of (i) an initial needs assessment, (ii) development of key standard operating procedures, (iii) adaptation of processes for LRS, (iv) training and supervision of laboratory staff via consultant visits and existing online resources, and (v) implementation of a practical quality systems approach. A guiding principle of the bundle was sustainability of all interventions post implementation. Outcomes and challenges: An initial investment of ~US$ 26,200 for laboratory reagents, and a total of 50 visit-days per year from three Canadian and Norwegian microbiologists were committed. Twelve SOPs, including antimicrobial susceptibility testing, were adapted, and an automated blood culture platform was donated (bioMerieux). In the first 18 months of implementation of the intervention, the average volume of specimens analyzed in the lab went from 15/day to 75/day. The number of blood cultures tested increased from an average of 2/day to over 45/day. Antimicrobial susceptibility testing was introduced and cumulative antibiograms were generated for the institution. Quality control was implemented for all procedures and quality assurance tools implemented included external quality assurance and proficiency testing of six technologists with longitudinal follow-up. The laboratory is on the path toward SLIPTA accreditation by the African Society for Laboratory Medicine. Reagent costs, staff training and retention, and engagement of clinical personnel with the lab proved to be manageable challenges. Key external challenges include in-country supply-chain management issues, lack of competition among distributors, and foreign-currency exchange distortions. Conclusions: Using a relatively low-intensity intervention based on existing training tools and accreditation schemes, we demonstrate that establishment of reasonable-quality clinical bacteriology is not only within reach but also a critical step toward assessing the burden of AMR in settings like this one and implementing effective stewardship strategies.

Diagnostic testing to identify persons infected with severe acute respiratory syndrome–related coronavirus-2 (SARS–CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction–based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS–CoV-2 infection. Here, the authors review the current array of tests for SARS–CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions., Diagnostic testing to identify infected persons is central to efforts to control the COVID-19 pandemic. This review synthesizes current knowledge of diagnostic options available to clinicians, highlights key gaps in current diagnostic capacity, and discusses potential solutions.

Intense antibiotic consumption in Low- and Middle-Income Countries (LMICs) is fueled by critical gaps in laboratory infrastructure and entrenched syndromic management of infectious syndromes. Few data inform the achievability and impact of antimicrobial stewardship interventions, particularly in Sub-Saharan Africa. Our goal was to demonstrate the feasibility of a pharmacist-led laboratory-supported intervention at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on antimicrobial use and clinical outcomes associated with the intervention. Methods: This was a single-center prospective quasi-experimental study conducted in two phases: (i) an intervention phase (November 2017 to August 2018), during which we implemented weekly audit and immediate (verbal and written) feedback sessions on antibiotic prescriptions of patients admitted in 2 pediatric and 2 adult medicine wards, and (ii) a post-intervention phase (September 2018 to January 2019) during which we audited antibiotic prescriptions but provided no feedback to the treating teams. The intervention was conducted by an AMS team consisting of 4 clinical pharmacists (one trained in AMS) and one ID specialist. Our primary outcome was antimicrobial utilization (measured as days of therapy (DOT) per 1,000 patient-days and duration of antibiotic treatment courses); secondary outcomes were length of hospital stay and in-hospital all-cause mortality. A multivariable logistic regression model was used to explore factors associated with all-cause in-hospital mortality. Results: We collected data on 1,109 individual patients (707 during the intervention and 402 in the post-intervention periods). Ceftriaxone, vancomycin, cefepime, meropenem, and metronidazole were the most commonly prescribed antibiotics; 96% of the recommendations made by the AMS team were accepted. The AMS team recommended to discontinue antibiotic therapy in 54% of cases during the intervention period. Once the intervention ceased, total antimicrobial use increased by 51.6% and mean duration of treatment by 4.1 days/patient. Mean LOS stay as well as crude mortality also increased significantly in the post-intervention phase (LOS: 24.1 days vs. 19.8 days; in hospital death 14.7 vs. 6.9%). The difference in mortality remained significant after adjusting for potential confounders. Conclusions: A pharmacist-led AMS intervention focused on duration of antibiotic treatment was feasible and had good acceptability in our setting. Cessation of audit-feedback activities was associated with immediate and sustained increases in antibiotic consumption reflecting a rapid return to baseline (pre-intervention) prescribing practices, and worse clinical outcomes (increased length of stay and in-hospital mortality). Pharmacist-led audit-feedback activities can effectively reduce antimicrobial consumption and result in better-quality care, but require organizational leadership's commitment for sustainable benefits.

Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.

Background There is an urgent need for integrated diagnosis of febrile syndromes able to account for multiple pathogens and to inform decisions for clinical care and public health. Aims To reflect on the evolving roles of laboratory-based testing for non-malarial febrile illnesses (NMFIs) in low-resource settings, and to consider how advances in diagnostics, in connectivity and transport, and in implementation of quality systems may substantially enhance the capacity of reference laboratories to bridge the current gap between remote passive surveillance and clinically meaningful integrated fever diagnosis. Sources Iterative search of PubMed databases, organizational reports, and expert consultation. Content Implementation of new technologies—such as very broad molecular panels for surveillance and mass spectrometry—may considerably diminish capability gaps in reference laboratories in low-resource settings. Although the need for clinical bacteriology diagnostics is now recognized, the lack of new simple and rapid phenotypic tests for antimicrobial resistance remains a key deficiency. Several initiatives to strengthen diagnostic preparedness for infectious disease outbreaks have highlighted the need for functional tiered laboratory networks. Recently, dramatic headway in connectivity—such as combining automated readers with the image processing and data transmission capabilities of smartphones—now allows for more complex testing and interfacing with distant laboratory information systems while reducing workload and errors. Together with connectivity to transmit and receive results, new approaches to specimen collection and transport—such as the validation of rectal swabs and the use of aerial drones to transport specimens to distant laboratories—now make remote testing feasible. The above innovations also open up the possibility of implementing quality systems through community-level diagnostic stewardship. Finally, strengthened laboratory networks actively support the feasibility of implementing quality-assured point-of-care testing where it is needed. Implications Recent advances offer the present-day possibility of innovations to re-invent the relationship between distant reference laboratories and end-users for integrated diagnosis of NMFIs.

Objectives To estimate the diagnostic accuracy of HAT Sero K-SeT for the field diagnosis of second-stage human African trypanosomiasis (HAT). Design A phase III diagnostic accuracy design. Consecutive patients with symptoms clinically suggestive of HAT were prospectively enrolled. We compared results of the index test HAT Sero K-SeT with those of a composite reference standard: demonstration of trypanosomes in cerebrospinal fluid (CSF), or trypanosomes detected in any other body fluid AND white blood cell count in CSF > 5/μl. Setting Rural hospital in the Democratic Republic of the Congo. Participants All patients above five years old presenting at Mosango hospital with a neurological problem of recent onset at the exclusion of trauma. Interventions n.a. Main Outcome Measures Sensitivity and specificity of HAT Sero K-SeT test. Results The sensitivity of the HAT Sero K-SeT was 8/8 or 100.0% (95% confidence interval: 67.6 to 100.0%) and the specificity was 258/266 or 97.0% (94.2% to 98.5%). Conclusion The high sensitivity of the HAT Sero K-SeT is in line with previously published estimates, though the sample of HAT cases in this study was small. The specificity estimate was very high and precise. This test, when negative, allows the clinician to rule out HAT in a clinical suspect in a hospital setting in this endemic region., Highlights • The HAT Sero K-SeT was evaluated in a rural hospital on patients with a neurological syndrome. • This new rapid diagnostic test for sleeping sickness was highly sensitive and specific. • A negative HAT Sero K-SeT test allows to rule out sleeping sickness in this setting. Rapid Diagnostic Tests (RDT) are promising tools for clinical management of sleeping sickness or Human African Trypanosomiasis (HAT), as most patients live in remote rural areas in Central or West Africa. We evaluated the HAT Sero-K-SeT, a novel RDT in a series of consecutively enrolled patients with clinical symptoms suggestive of second-stage sleeping sickness. This design is known as phase III in diagnostic accuracy studies, as the patient set is representative of future use of the RDT. The test showed high sensitivity and specificity. We conclude that in such patients, an RDT for HAT should be done. If negative, HAT can be ruled out. If positive, the likelihood of HAT is very high.

Low-resource settings are disproportionately burdened by infectious diseases and antimicrobial resistance. Good quality clinical bacteriology through a well functioning reference laboratory network is necessary for effective resistance control, but low-resource settings face infrastructural, technical, and behavioural challenges in the implementation of clinical bacteriology. In this Personal View, we explore what constitutes successful implementation of clinical bacteriology in low-resource settings and describe a framework for implementation that is suitable for general referral hospitals in low-income and middle-income countries with a moderate infrastructure. Most microbiological techniques and equipment are not developed for the specific needs of such settings. Pending the arrival of a new generation diagnostics for these settings, we suggest focus on improving, adapting, and implementing conventional, culture-based techniques. Priorities in low-resource settings include harmonised, quality assured, and tropicalised equipment, consumables, and techniques, and rationalised bacterial identification and testing for antimicrobial resistance. Diagnostics should be integrated into clinical care and patient management; clinically relevant specimens must be appropriately selected and prioritised. Open-access training materials and information management tools should be developed. Also important is the need for onsite validation and field adoption of diagnostics in low-resource settings, with considerable shortening of the time between development and implementation of diagnostics. We argue that the implementation of clinical bacteriology in low-resource settings improves patient management, provides valuable surveillance for local antibiotic treatment guidelines and national policies, and supports containment of antimicrobial resistance and the prevention and control of hospital-acquired infections.

This case presents a hydatid cyst of the thigh in a 57-year-old patient born and raised in rural Montenegro. He presented with a painful erythematous mass on the lateral aspect of the right thigh at the site of a previous cystic mass resection 13 years earlier. Complete surgical resection was conducted, histopathology revealed laminated membranes and polymerase chain reaction was positive for Echinococcus granulosus. Primary musculoskeletal hydatidosis is a rare entity and diagnosis is challenging. Any cystic lesion in a patient from an endemic area should raise the possibility of echinococcosis, regardless of anatomic location. The key aspects of diagnosis, albendazole treatment and surgical management are discussed.

We report the case of a 64-year-old woman found to have urban-acquired Trypanosoma brucei (T.b.) gambiense human African trypanosomiasis (HAT) as the cause of sustained fever starting 9 months after returning to Canada from Democratic Republic of the Congo, in the context of concomitant multiple myeloma and HIV-1 coinfection. Approaches for the management of both clinical stages of T.b. gambiense HAT are well defined for endemic settings using current diagnostics and treatments. However, few data inform the diagnosis and management of patients with bone marrow suppression from active malignancy, recent anticancer therapy, or HIV coinfection. We discuss the implications of immunosuppression for diagnosis and management of T.b. gambiense HAT.

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.

ObjectiveAntimicrobial 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.DesignWe 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.SettingTertiary care hospital in Ethiopia, with 800 beds and serves over half a million patients per year.PopulationCohort of adults and children inpatient population aged 19.8 years at baseline.InterventionLaboratory-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 measuresExpected life-years, quality-adjusted life-years (QALYs), costs (US$2018) and incremental cost-effectiveness ratio.ResultsLaboratory-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.ConclusionOur 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.

There is little published information on the epidemiology of neurological disorders in rural Central Africa, although the burden is considered to be substantial. This study aimed to investigate the pattern, etiology, and outcome of neurological disorders in children > 5 years and adults admitted to the rural hospital of Mosango, province of Kwilu, Democratic Republic of Congo, with a focus on severe and treatable infections of the central nervous system (CNS). From September 2012 to January 2015, 351 consecutive patients hospitalized for recent and/or ongoing neurological disorder were prospectively evaluated by a neurologist, subjected to a set of reference diagnostic tests in blood or cerebrospinal fluid, and followed-up for 3–6 months after discharge. No neuroimaging was available. Severe headache (199, 56.7%), gait/walking disorders (97, 27.6%), epileptic seizure (87, 24.8%), and focal neurological deficit (86, 24.5%) were the predominant presentations, often in combination. Infections of the CNS were documented in 63 (17.9%) patients and mainly included bacterial meningitis and unspecified meningoencephalitis (33, 9.4%), second-stage human African trypanosomiasis (10, 2.8%), and human immunodeficiency virus (HIV)-related neurological disorders (10, 2.8%). Other focal/systemic infections with neurological manifestations were diagnosed in an additional 60 (17.1%) cases. The leading noncommunicable conditions were epilepsy (61, 17.3%), psychiatric disorders (56, 16.0%), and cerebrovascular accident (23, 6.6%). Overall fatality rate was 8.2% (29/351), but up to 23.8% for CNS infections. Sequelae were observed in 76 (21.6%) patients. Clinical presentations and etiologies of neurological disorders were very diverse in this rural Central African setting and caused considerable mortality and morbidity.

BACKGROUND: Established in the Americas since late 2013, chikungunya is an emerging infection among travellers. OBJECTIVE: To examine demographic and travel correlates of chikungunya among Canadian travellers to establish a detailed epidemiological framework of this infection for Canadian practitioners encountering prospective and returned travellers. METHODS: Data regarding ill returned Canadian travellers presenting to a CanTravNet site between 2006 and 2015 were analyzed. RESULTS: During the study period, 22,387 ill travellers and immigrants presented to a CanTravNet site and, of these, 118 (0.5%) received a diagnosis of chikungunya. Those travelling for tourism were the most well-represented (n=49, 41.5%), followed by those travelling to visit friends and relatives (n=36, 30.5%). The Caribbean was the most likely source region, accounting for 64 (54.2%) diagnoses, followed by South Central Asia (n=18, 15.3%). Haiti was the most well-represented source country, accounting for 22 (18.6%) cases. India, a high-volume destination for Canadians and the next most well-represented source country, accounted for 15 cases (12.7%), as did Jamaica. Median trip duration of those with chikungunya was 14 days, with 51.7% (n=61) having a trip duration of ≤2 weeks and 21.2% (n=25) ≤1 week. Musculoskeletal complaints at presentation were noted in 89% (n=105), followed by fever in 54.2% (n=64). CONCLUSIONS: The present analysis provides an epidemiological framework of chikungunya for Canadian practitioners encountering prospective and returned travellers. It reflects the emergence of chikungunya in the Americas, the risk associated with short-duration travel and substantiates efforts to educate travellers about the need for mosquito avoidance.

Background The declining trend of malaria and the recent prioritization of containment of antimicrobial resistance have created a momentum to implement clinical bacteriology in low-resource settings. Successful implementation relies on guidance by a quality management system (QMS). Over the past decade international initiatives were launched towards implementation of QMS in HIV/AIDS, tuberculosis and malaria. Aims To describe the progress towards accreditation of medical laboratories and to identify the challenges and best practices for implementation of QMS in clinical bacteriology in low-resource settings. Sources Published literature, online reports and websites related to the implementation of laboratory QMS, accreditation of medical laboratories and initiatives for containment of antimicrobial resistance. Content Apart from the limitations of infrastructure, equipment, consumables and staff, QMS are challenged with the complexity of clinical bacteriology and the healthcare context in low-resource settings (small-scale laboratories, attitudes and perception of staff, absence of laboratory information systems). Likewise, most international initiatives addressing laboratory health strengthening have focused on public health and outbreak management rather than on hospital based patient care. Best practices to implement quality-assured clinical bacteriology in low-resource settings include alignment with national regulations and public health reference laboratories, participating in external quality assurance programmes, support from the hospital's management, starting with attainable projects, conducting error review and daily bench-side supervision, looking for locally adapted solutions, stimulating ownership and extending existing training programmes to clinical bacteriology. Implications The implementation of QMS in clinical bacteriology in hospital settings will ultimately boost a culture of quality to all sectors of healthcare in low-resource settings.

BACKGROUND: Widespread transmission of Zika virus in the Americas has occurred since late 2015. We examined demographic and travel-related characteristics of returned Canadian travellers with Zika infection acquired in the Americas to illuminate risk factors for acquisition and the clinical spectrum. METHODS: We analyzed demographic and travel-related data for returned Canadian travellers who presented to a CanTravNet site between October 2015 and September 2016 for care of Zika virus acquired in the Americas. Data were collected with use of the GeoSentinel Surveillance Network data platform. RESULTS: During the study period, 1118 travellers presented to a CanTravNet site after returning from the Americas, 41 (3.7%) of whom had Zika infection. Zika infection from the Americas was diagnosed at CanTravNet sites as often as dengue ( n = 41) over the study period. In the first half of the study period, Zika virus burden was borne by people visiting friends and relatives in South America. In the latter half, coincident with the increased spread of Zika throughout the Caribbean and Central America, Zika virus occurred more often in tourists in the Caribbean. Forty (98%) of the travellers with Zika infection acquired it through probable mosquito exposure, and 1 had confirmed sexual acquisition. Congenital transmission occurred in 2 of 3 pregnancies. Two (5%) of those with Zika had symptoms resembling those of Guillain–Barre syndrome, 1 of whom also had Zika viral meningitis. INTERPRETATION: Even in this small cohort, we observed the full clinical spectrum of acute Zika virus, including adverse fetal and neurologic outcomes. Our observations suggest that complications from Zika infection are underestimated by data arising exclusively from populations where Zika is endemic. Travellers should adhere to mosquito-avoidance measures and barrier protection during sexual activity.

Blastomyces dermatitidis is a thermally dimorphic fungus endemic to North America. Human infections predominantly occur in states bordering the Ohio and Mississippi River valleys of the United States and Canadian provinces bordering the Great Lakes and the Saint Lawrence River.1 Usually, primary infection is through inhalation of conidia into the lungs, but the clinical spectrum of illness ranges from asymptomatic or chronic indolent disease to fulminant multisystem failure and is usually more severe in immunocompromised hosts. Here we describe a fatal case of disseminated blastomycosis in a young man with rapid progression to multiorgan failure after exposure to corticosteroids.

Background Administering antimicrobial agents before obtaining blood cultures could potentially decrease time to treatment and improve outcomes, but it is unclear how this strategy affects diagnostic sensitivity. Objective To determine the sensitivity of blood cultures obtained shortly after initiation of antimicrobial therapy in patients with severe manifestations of sepsis. Design Patient-level, single-group, diagnostic study. (ClinicalTrials.gov: NCT01867905). Setting 7 emergency departments in North America. Participants Adults with severe manifestations of sepsis, including systolic blood pressure less than 90 mm Hg or a serum lactate level of 4 mmol/L or more. Intervention Blood cultures were obtained before and within 120 minutes after initiation of antimicrobial treatment. Measurements Sensitivity of blood cultures obtained after initiation of antimicrobial therapy. Results Of 3164 participants screened, 325 were included in the study (mean age, 65.6 years; 62.8% men) and had repeated blood cultures drawn after initiation of antimicrobial therapy (median time, 70 minutes [interquartile range, 50 to 110 minutes]). Preantimicrobial blood cultures were positive for 1 or more microbial pathogens in 102 of 325 (31.4%) patients. Postantimicrobial blood cultures were positive for 1 or more microbial pathogens in 63 of 325 (19.4%) patients. The absolute difference in the proportion of positive blood cultures between pre- and postantimicrobial testing was 12.0% (95% CI, 5.4% to 18.6%; P < 0.001). Sensitivity of postantimicrobial culture was 52.9% (CI, 42.8% to 62.9%). When the results of other microbiological cultures were included, microbial pathogens were found in 69 of 102 (67.6% [CI, 57.7% to 76.6%]) patients. Limitation Only a proportion of screened patients were recruited. Conclusion Among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment initiation. Primary Funding Source Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Sante-Quebec, and the Maricopa Medical Foundation.

Macaque-related injuries among primate workers can lead to a potentially fatal B virus encephalomyelitis. We describe a decision tool for evaluating the need for antiviral postexposure prophylaxis and provide a retrospective review of the injuries assessed in our center after its implementation in 2010. Among the injuries studied (n = 251), 40.6% were categorized as high-risk (prophylaxis recommended), 44.2% moderate-risk (consider prophylaxis), and 15.1% low-risk (prophylaxis not recommended). Ten percent of low-risk and 98% of high-risk injuries received prophylaxis (p

The optimal treatment for potential AmpC-producing Enterobacteriaceae, including Serratia, Providencia, Citrobacter, Enterobacter, and Morganella species, remains unknown. An updated systematic review and meta-analysis of studies comparing beta-lactam/beta-lactamase inhibitors with carbapenems in the treatment of bloodstream infections with these pathogens found no significant difference in 30-day mortality (OR, 1.13; 95% CI, 0.58 – 2.20)., The optimal treatment of bloodstream infections caused by potential AmpC-producing organisms is unsettled. A systematic review with meta-analysis found no significant difference in 30-day mortality in patients who were treated with beta-lactam/beta-lactamase inhibitors compared with carbapenems.

Background Global action plans to tackle antimicrobial resistance (AMR) include implementation of antimicrobial stewardship (AMS), but few studies have directly addressed the challenges faced by low and middle-income countries (LMICs). Our aim was to explore healthcare providers’ knowledge and perceptions on AMR, and barriers/facilitators to successful implementation of a pharmacist-led AMS intervention in a referral hospital in Ethiopia. Methods Tikur Anbessa Specialized Hospital (TASH) is an 800-bed tertiary center in Addis Ababa, and the site of an ongoing 4-year study on AMR. Between May and July 2017, using a mixed approach of quantitative and qualitative methods, we performed a cross-sectional survey of pharmacists and physicians using a pre-tested questionnaire and semi-structured interviews of purposively selected respondents until thematic saturation. We analyzed differences in proportions of agreement between physicians and pharmacists using χ2 and fisher exact tests. Qualitative data was analyzed thematically. Findings A total of 406 survey respondents (358 physicians, 48 pharmacists), and 35 key informants (21 physicians and 14 pharmacists) were enrolled. The majority of survey respondents (>90%) strongly agreed with statements regarding the global scope of AMR, the need for stewardship, surveillance and education, but their perceptions on factors contributing to AMR and their knowledge of institutional resistance profiles for common bacteria were less uniform. Close to 60% stated that a significant proportion of S. aureus infections were caused by methicillin-resistant strains (an incorrect statement), while only 48% thought a large proportion of gram-negative infections were caused by cephalosporin-resistant strains (a true statement). Differences were noted between physicians and pharmacists: more pharmacists agreed with statements on links between use of broad-spectrum antibiotics and AMR (p

Human enteric parasitoses, particularly from Cryptosporidium, were recently recognized as being highly prevalent in parts of the Arctic. This is important because cryptosporidiosis has been repeatedly associated with impaired growth and development and may synergize with other challenges faced by children in remote Arctic communities, such as overcrowding and food insecurity.

Ten Belgian travelers returned from Mali with a Schistosoma haematobium-Schistosoma bovis hybrid infection, confirmed by DNA sequencing from eggs. Clinical symptoms and laboratory findings resembled those of classic acute schistosomiasis, but the detected eggs were morphologically unusual.

In late summer, a previously healthy 52-year-old woman was swimming in a lake in southern Quebec when she was bitten by a marine animal. As she swam toward shore, she and a nearby friend recognized it as a river otter ( Lontra canadensis; see [Figure 1][1]), which began to aggressively pursue her