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.

Strongyloides stercoralis prevalence in solid-organ and haematopoietic stem cell transplant candidates and recipients: a systematic review and meta-analysis protocol.

INTRODUCTION: Strongyloides stercoralis is an intestinal helminth ubiquitous in tropical and subtropical regions worldwide. It persists in the human host for a lifetime as a result of autoinfection and if undetected and untreated, can lead to increased morbidity and high mortality in immunocompromised individuals such as the transplant population. Transplant patients, including solid-organ and haematopoietic stem cell transplants (SOT and HSCT, respectively), are at a high risk of hyperinfection and disseminated strongyloidiasis. Unfortunately screening is often not systematically performed. Prevalence estimates of Strongyloides in this high-risk population is not well studied. Through this systematic review, we aim to summarise the descriptive evidence on Strongyloides prevalence in SOT and HSCT patients, including diagnostic and screening practices alongside the cases of hyperinfection, disseminated strongyloidiasis and the mortality rate in this population. METHODS AND ANALYSES: Through the use of various online library databases, we will conduct a systematic review including relevant literature on the prevalence of Strongyloides in SOT and HSCT patients as well as studies assessing hyperinfection and disseminated strongyloidiasis in this patient population. The Population, Intervention, Comparison, Outcome and Study Design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be used to determine a final subset of studies for analysis. Quality assessment for case series and case reports will be determined by a modified quality assessment tool developed by the National Heart, Lung, and Blood Institute (NIH), and the CARE guidelines, respectively. We will provide a narrative synthesis of the findings pertaining to the primary and secondary outcomes of interest (prevalence of Strongyloides and mortality rate in transplant population, respectively) alongside the associated 95% CI. Estimates from individual studies will be pooled using a random effects model. ETHICS AND DISSEMINATION: This systematic review does not require formal ethical approval since no primary data will be collected. Findings will be disseminated through a peer-reviewed publication and relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42021269305.

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.

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

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

Multiplexed technologies for sexually transmitted infections: global evidence on patient-centered and clinical health outcomes.

INTRODUCTION: Conventional 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. METHODS: For the period 2009-2020, two independent reviewers searched PubMed and Embase, retrieved 4440 citations and abstracted data from 42 relevant studies. RESULTS: Of 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). CONCLUSIONS: Compared 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.

Intravenous liposomal amphotericin B efficacy and safety for cutaneous and mucosal leishmaniasis: a systematic review and meta-analysis protocol.

INTRODUCTION: Treatment of cutaneous and mucosal leishmaniasis (CL and ML, respectively) must be individualised as there is no universal therapeutic approach. Intravenous liposomal amphotericin B (L-AmB) is an accessible and relatively safe treatment that has been increasingly used for the treatment of CL and ML. While several descriptive studies have been published on the efficacy and safety of L-AmB, there are no interventional studies. Moreover, the findings from published studies have not yet been integrated and synthesised. Therefore, we aim to evaluate and consolidate the descriptive evidence on the efficacy and the safety of Intravenous L-AmB treatment for CL and ML in both the New and Old World. METHODS AND ANALYSES: A systematic review of all relevant study types with no restriction on date or language of publication will be conducted. Online databases including MEDLINE, The Cochrane Library, EMBASE, EBSCO, Scopus, Ovid and WHO databases were searched on 3 April 2020. The search included all study types that assess Intravenous L-AmB treatment for CL and ML in humans. The Population, Intervention, Comparison, Outcome and Study Design strategy and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be used to determine which studies will be selected for final inclusion. The quality of included case series and case reports will be assessed using modified quality assessment tools. A narrative synthesis of the findings will be provided and the primary outcome and secondary outcome of interest, response rate and adverse events rate, respectively, and the 95% CI will be ascertained. Estimates from individual studies will be pooled using random-effects model. ETHICS AND DISSEMINATION: This systematic review does not require formal ethical approval since no primary data will be collected. Findings will be disseminated through a peer-reviewed publication and relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020173440.