Intravenous Liposomal Amphotericin B Efficacy and Safety for Cutaneous and Mucosal Leishmaniasis: A Systematic Review and Meta-analysis.

Background: Tegumentary leishmaniasis is often subject to limited funding, underpowered studies, and a paucity of high-quality interventional studies. Intravenous liposomal amphotericin B (L-AmB) has been increasingly used to treat cutaneous and mucosal leishmaniasis (CL and ML, respectively) despite the lack of well-conducted interventional studies. We conducted a systematic review to consolidate the descriptive evidence on the efficacy and safety of L-AmB in treating CL and ML. Methods: Several online databases and the reference lists of included studies were searched to extract data from 132 studies comprising both case reports and case series. The population, intervention, comparison, outcome, and study design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Results: Of 132 studies included, 92 were case reports and 40 were case series. Of the 92 cases, 65 (82.3%) were considered cured after receiving L-AmB as part of their treatment regimen. Twenty-one of the 92 (22.8%) cases reported adverse reactions to L-AmB. A pooled cure rate of 87.0% (95% CI, 79.0%-92.0%) was reported for the 38 case series that reported on treatment efficacy; 40.7% of the cases were associated with an adverse reaction. Conclusions: Observational data on cure rates using L-AmB suggest efficacy between 80% and 90%, similar to rates reported for other antileishmanial drugs. The highest efficacy rates were observed when a single cycle of L-AmB was administered to patients with mild-moderate CL and ML. The limitations of this study include the heterogeneity observed among the included studies and the increased likelihood of publication bias associated with the inclusion of case reports and case series. This systematic review further illustrates the need for high-quality comparative trials of intravenous L-AmB for the treatment of tegumentary leishmaniasis.

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.

Monkeypox in Montréal: Epidemiology, Phylogenomics, and Public Health Response to a Large North American Outbreak.

BACKGROUND: Monkeypox, a viral zoonotic disease, is causing a global outbreak outside of endemic areas. OBJECTIVE: To characterize the outbreak of monkeypox in Montréal, the first large outbreak in North America. DESIGN: Epidemiologic and laboratory surveillance data and a phylogenomic analysis were used to describe and place the outbreak in a global context. SETTING: Montréal, Canada. PATIENTS: Probable or confirmed cases of monkeypox. MEASUREMENTS: Epidemiologic, clinical, and demographic data were aggregated. Whole-genome sequencing and phylogenetic analysis were performed for a set of outbreak sequences. The public health response and its evolution are described. RESULTS: Up to 18 October 2022, a total of 402 cases of monkeypox were reported mostly among men who have sex with men (MSM), most of which were suspected to be acquired through sexual contact. All monkeypox genomes nested within the B.1 lineage. Montréal Public Health worked closely with the affected communities to control the outbreak, becoming the first jurisdiction to offer 1 dose of the Modified Vaccinia Ankara-Bavarian Nordic vaccine as preexposure prophylaxis (PrEP) to those at risk in early June 2022. Two peaks of cases were seen in early June and July (43 and 44 cases per week, respectively) followed by a decline toward near resolution of the outbreak in October. Reasons for the biphasic peak are not fully elucidated but may represent the tempo of vaccination and/or several factors related to transmission dynamics and case ascertainment. LIMITATIONS: Clinical data are self-reported. Limited divergence among sequences limited genomic epidemiologic conclusions. CONCLUSION: A large outbreak of monkeypox occurred in Montréal, primarily among MSM. Successful control of the outbreak rested on early and sustained engagement with the affected communities and rapid offer of PrEP vaccination to at-risk persons. PRIMARY FUNDING SOURCE: None.

Dengue outbreak amongst travellers returning from Cuba-GeoSentinel surveillance network, January-September 2022.

Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June to September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.

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.

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.

Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18-64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials.

BACKGROUND: Seasonal influenza remains a substantial public health threat despite the availability of egg-derived and other vaccines. Plant-based manufacturing might address some of the limitations of current vaccines. We describe two phase 3 efficacy studies of a recombinant quadrivalent virus-like particle (QVLP) influenza vaccine manufactured in plants, one in adults aged 18-64 years (the 18-64 study) and one in older people aged 65 years and older (the 65-plus study). METHODS: We did two randomised, observer-blind, multinational studies in the northern hemisphere in the 2017-18 (the 18-64 study) and 2018-19 (the 65-plus study) influenza seasons. The 18-64 study was done at 73 sites and the 65-plus study was done at 104 sites, both across Asia, Europe, and North America. In the 18-64 study, inclusion criteria were body-mass index less than 40 kg/m2; age 18-64 years at screening visit; and good health. In the 65-plus study, inclusion criteria were body-mass index of maximum 35 kg/m2; aged 65 years or older at screening visit; not living in a rehabilitation centre or care home; and no acute or evolving medical problems. Participants in the 18-64 study were randomly assigned (1:1) to receive either QVLP vaccine (30 µg haemagglutinin per strain) or placebo. Participants in the 65-plus study were randomly assigned (1:1) to receive QVLP vaccine (30 µg haemagglutinin per strain) or quadrivalent inactivated vaccine (QIV; 15 µg haemagglutinin per strain). The primary outcome in the 18-64 study was absolute vaccine efficacy to prevent laboratory-confirmed, respiratory illness caused by antigenically matched influenza strains. The primary outcome in the 65-plus study was relative vaccine efficacy to prevent laboratory-confirmed influenza-like illness caused by any influenza strain. The primary analyses were done in the per-protocol population and safety was assessed in all participants who received the assigned treatment. These studies are registered with ClinicalTrials.gov (18-64 study NCT03301051; 65-plus study NCT03739112). FINDINGS: In the 18-64 study, between Aug 30, 2017, and Jan 15, 2018, 10 160 participants were randomly assigned to receive either QVLP vaccine (5077 participants) or placebo (5083 participants). The per-protocol population consisted of 4814 participants in the QVLP group and 4812 in the placebo group. The study did not meet its primary endpoint of 70% absolute vaccine efficacy for the QVLP vaccine (35·1% [95% CI 17·9 to 48·7]) against respiratory illness caused by matched strains. 55 (1·1%) of 5064 participants in the QVLP group versus 51 (1·0%) of 5072 in the placebo group had a serious adverse event. Four (0·1%) and six [0·1%] participants had severe treatment-related treatment-emergent adverse events. In the 65-plus study, between Sept 18, 2018, and Feb 22, 2019, 12 794 participants were randomly assigned to receive either QVLP vaccine (6396 participants) or QIV (6398 participants). The per-protocol population consisted of 5996 participants in the QVLP group and 6026 in the QIV group. The study met its primary non-inferiority endpoint with a relative vaccine efficacy of the QVLP vaccine for the prevention of influenza-like illness caused by any strain of 8·8% (-16·7 to 28·7). 263 (4·1%) of 6352 participants in the QVLP group versus 266 (4·2%) of 6366 in the QIV group had serious adverse events (one [<0·1%] vs two [<0·1%] were considered treatment-related); one (<0·1%) versus three (<0·1%) participants had severe treatment-related treatment-emergent adverse events. INTERPRETATION: These efficacy studies are the first large-scale studies of any plant-derived human vaccine. Together, they show that the plant-derived QVLP vaccine can provide substantial protection against respiratory illness and influenza-like illness caused by influenza viruses in adults. QVLP vaccine was well tolerated and no major safety signal arose in participants who received QVLP vaccine across the two studies. FUNDING: Medicago.

Prolonged empirical antibiotic therapy is correlated with bloodstream infections and increased mortality in a tertiary care hospital in Ethiopia: bacteriology testing matters.

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 < 0.0001). After testing, DOT were comparable between the two groups (20 versus 18 days, respectively). 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.

Decision Tool for Herpes B Virus Antiviral Prophylaxis after Macaque-Related Injuries in Research Laboratory Workers.

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<0.001). Compared with using universal postexposure prophylaxis, using a decision tool can lead to a standardization of practice and a reduction in prescriptions for antiviral medication.

First Human Case of Metacestode Infection Caused by Versteria sp. in a Kidney Transplant Recipient.

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.

Travel-Related Infections Among Pregnant Travellers to the Tropics: An Overview.

Infectious diseases acquired during travel pose a significant health risk to pregnant travellers, who are more susceptible to both acquiring certain infections and developing severe complications. A review of the literature focusing on recent evidence-based guidelines was conducted with attention to tropical infections in the pregnant patient. A summary meant to serve as a succinct reference for health care professionals caring for pregnant women is presented. Magnitude of risk, clinical features, management, and preventive strategies of major travel-acquired infections of pertinence to the pregnant traveller are summarized, including malaria, arboviral infections, foodborne infections, helminthic infections, and influenza. Tables with details on specific infections within each group and guidance for reducing travel-related health risks in the pregnant patient are presented.

Randomized Trials Comparing Inactivated Vaccine After Medium- or High-titer Measles Vaccine With Standard Titer Measles Vaccine After Inactivated Vaccine: A Meta-analysis.

BACKGROUND: Observational studies have suggested that girls have higher mortality if their most recent immunization is an inactivated vaccine rather than a live vaccine. We therefore reanalyzed 5 randomized trials of early measles vaccine (MV) in which it was possible to compare an inactivated vaccines [after medium-titer MV (MTMV) or high-titer MV (HTMV)] and a live standard titer MV (after an initial inactivated vaccine). METHODS: The trials were conducted in Sudan, Senegal, The Gambia and Guinea-Bissau. The intervention group received live MTMV or HTMV from 4 to 5 months and then an inactivated vaccine from 9 to 10 months of age; the control children received inactivated vaccine/placebo from 4 to 5 months and standard titer MV from 9 to 10 months of age. We compared mortality from 9 months until end of study at 3 to 5 years of age for children who received inactivated vaccine (after MTMV or HTMV) and standard titer MV (after inactivated vaccine), respectively. The original datasets were analyzed using a Cox proportional hazards model stratified by trial. RESULTS: The mortality rate ratio (MRR) was 1.38 (95% confidence interval: 1.05-1.83) after an inactivated vaccine (after MTMV or HTMV) compared with a standard titer MV (after inactivated vaccine). Girls had a MRR of 1.89 (1.27-2.80), whereas there was no effect for boys, the sex-differential effect being significant (P = 0.02). Excluding measles cases did not alter these conclusions, the MRR after inactivated vaccines (after MTMV or HTMV) being 1.40 (1.06-1.86) higher overall and 1.92 (1.29-2.86) for girls. Control for variations in national immunization schedules for other vaccines did not modify these results. CONCLUSIONS: After 9 months of age, all children had been immunized against measles, and mortality in girls was higher when they had received inactivated vaccines (after MTMV or HTMV) rather than live standard titer MV (after an inactivated vaccine).

Recent advances in clinical parasitology diagnostics.

Microscopy has several limitations in the diagnosis of parasitic infection. New technologies have emerged to address some of these limitations. We review recent advances in three key areas. The detection of enteric protozoa is a commonly requested test, particularly with increasing travel to and migration from endemic countries. Microscopy is slow and labor intensive and requires a high level of technical expertise. It also lacks both sensitivity and specificity. Recently developed nucleic acid amplification tests are automated and rapid and show superior accuracy. Proteomics shows promise for both the diagnosis of infections where parasite detection is difficult and the potential for accurate assessment of cure in these cases. Finally, rapid and simple diagnostic tests suitable for use in low-resource settings are now allowing for improved study and control of infection in endemic regions.

Development of a rapid serological assay for the diagnosis of strongyloidiasis using a novel diffraction-based biosensor technology.

BACKGROUND: Strongyloidiasis is a persistent human parasitic infection caused by the intestinal nematode, Strongyloides stercoralis. The parasite has a world-wide distribution, particularly in tropical and subtropical regions with poor sanitary conditions. Since individuals with strongyloidiasis are typically asymptomatic, the infection can persist for decades without detection. Problems arise when individuals with unrecognized S. stercoralis infection are immunosuppressed, which can lead to hyper-infection syndrome and disseminated disease with an associated high mortality if untreated. Therefore a rapid, sensitive and easy to use method of diagnosing Strongyloides infection may improve the clinical management of this disease. METHODOLOGY/PRINCIPAL FINDINGS: An immunological assay for diagnosing strongyloidiasis was developed on a novel diffraction-based optical bionsensor technology. The test employs a 31-kDa recombinant antigen called NIE derived from Strongyloides stercoralis L3-stage larvae. Assay performance was tested using retrospectively collected sera from patients with parasitologically confirmed strongyloidiasis and control sera from healthy individuals or those with other parasitoses including schistosomiasis, trichinosis, echinococcosis or amebiasis who were seronegative using the NIE ELISA assay. If we consider the control group as the true negative group, the assay readily differentiated S. stercoralis-infected patients from controls detecting 96.3% of the positive cases, and with no cross reactivity observed in the control group These results were in excellent agreement (κ = 0.98) with results obtained by an NIE-based enzyme-linked immunosorbent assay (ELISA). A further 44 sera from patients with suspected S. stercoralis infection were analyzed and showed 91% agreement with the NIE ELISA. CONCLUSIONS/SIGNIFICANCE: In summary, this test provides high sensitivity detection of serum IgG against the NIE Strongyloides antigen. The assay is easy to perform and provides results in less than 30 minutes, making this platform amenable to rapid near-patient screening with minimal technical expertise.