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Pathogenic Leptospira are spirochete bacteria which cause leptospirosis, a re-emerging zoonotic disease of global importance. Here, we use a recently described lineage of environmental-adapted leptospires, which are evolutionarily the closest relatives of the highly virulent Leptospira species, to explore the key phenotypic traits and genetic determinants of Leptospira virulence. Through a comprehensive approach integrating phylogenomic comparisons with in vitro and in vivo phenotyping studies, we show that the evolution towards pathogenicity is associated with both a decrease of the ability to survive in the environment and the acquisition of strategies that enable successful host colonization. This includes the evasion of the mammalian complement system and the adaptations to avoid activation of the innate immune cells by the highly-virulent Leptospira species (also called P1+ species), unlike other species belonging to the phylogenetically related P1- and P2 groups, as well as saprophytes. Moreover, our analysis reveals specific genetic determinants that have undergone positive selection during the course of evolution in Leptospira , contributing directly to virulence and host adaptation as demonstrated by gain-of-function and knock-down studies. Taken together, our findings define a new vision on Leptospira pathogenicity, identifying virulence attributes associated with clinically relevant species, and provide insights into the evolution and emergence of these life-threatening pathogens.

Ensuring that protected areas (PAs) maintain the biodiversity within their boundaries is fundamental in achieving global conservation goals. Despite this objective, wildlife abundance changes in PAs are patchily documented and poorly understood. Here, we use linear mixed effect models to explore correlates of population change in 1,902 populations of birds and mammals from 447 PAs globally. On an average, we find PAs are maintaining populations of monitored birds and mammals within their boundaries. Wildlife population trends are more positive in PAs located in countries with higher development scores, and for larger-bodied species. These results suggest that active management can consistently overcome disadvantages of lower reproductive rates and more severe threats experienced by larger species of birds and mammals. The link between wildlife trends and national development shows that the social and economic conditions supporting PAs are critical for the successful maintenance of their wildlife populations. Protected areas are intended to safeguard wildlife, but their effectiveness has at times been questioned. Barnes, Craigie, and colleagues show that protected areas do offer refuge—maintaining their bird and mammal abundances—but with greater success for larger-bodied species and in more developed nations.

Site-specific endonucleases that exclusively cut single-stranded DNA have hitherto never been described and constitute a barrier to the development of ssDNA-based technologies. We identify and characterize one such family, from the GIY-YIG superfamily, of widely distributed s ite-specific s ingle-stranded n ucleases (Ssn) exhibiting unique ssDNA cleavage properties. By first comprehensively studying the Ssn homolog from Neisseria meningitidis , we demonstrate that it interacts specifically with a sequence (called NTS) present in hundreds of copies and surrounding important genes in pathogenic Neisseria . In this species, NTS/Ssn interactions modulate natural transformation and thus constitute an additional mechanism shaping genome dynamics. We further identify thousands of Ssn homologs and demonstrate, in vitro, a range of Ssn nuclease specificities for their corresponding sequence. We demonstrate proofs of concept for applications including ssDNA detection and digestion of ssDNA from RCA. This discovery and its applications set the stage for the development of innovative ssDNA-based molecular tools and technologies. Site-specific endonucleases that exclusively cut single-stranded DNA have hitherto never been described and constitute a barrier to the development of ssDNA-based technologies. Here the authors identify and characterize a family of such enzymes that could be the basis of innovative molecular tools.

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 × 10 cells/L should prompt consideration of trichinellosis and testing to rapidly identify potential outbreaks.

Health care workers (HCW), particularly immigrants and ethnic minorities are at increased risk for SARS-CoV-2 infection. Outcomes during a COVID-19 associated hospitalization are not well described among HCW. We aimed to describe the characteristics of HCW admitted with COVID-19 including immigrant status and ethnicity and the associated risk factors for Intensive Care unit (ICU) admission and death. Adults with laboratory-confirmed community-acquired COVID-19 hospitalized from March 1 to June 30, 2020, at four tertiary-care hospitals in Montréal, Canada were included. Demographics, comorbidities, occupation, immigration status, country of birth, ethnicity, workplace exposures, and hospital outcomes (ICU admission and death) were obtained through a chart review and phone survey. A Fine and Gray competing risk proportional hazards model was used to estimate the risk of ICU admission among HCW stratified by immigrant status and region of birth. Among 1104 included persons, 150 (14%) were HCW, with a phone survey participation rate of 68%. HCWs were younger (50 vs 64 years; p<0.001), more likely to be female (61% vs 41%; p<0.001), migrants (68% vs 55%; p<0.01), non-White (65% vs 41%; p<0.001) and healthier (mean Charlson Comorbidity Index of 0.3 vs 1.2; p<0.001) compared to non-HCW. They were as likely to be admitted to the ICU (28% vs 31%; p = 0.40) but were less likely to die (4% vs. 17%; p<0.001). Immigrant HCW accounted for 68% of all HCW cases and, compared to Canadian HCW, were more likely to be personal support workers (PSW) (54% vs. 33%, p<0.01), to be Black (58% vs 4%) and to work in a Residential Care Facility (RCF) (59% vs 33%; p = 0.05). Most HCW believed that they were exposed at work, 55% did not always have access to personal protective equipment (PPE) and 40% did not receive COVID-19-specific Infection Control (IPAC) training. Immigrant HCW were particularly exposed to COVID-19 infection in the first wave of the pandemic in Quebec. Despite being young and healthy, one third of all HCW required ICU admission, highlighting the importance of preventing workplace transmission through strong infection prevention and control measures, including high COVID-19 vaccination coverage.

Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

Developmental biology often yields data in a temporal context. Temporal data in phylogenetic systematics has important uses in the field of evolutionary developmental biology and, in general, comparative biology. The evolution of temporal sequences, specifically developmental sequences, has proven difficult to examine due to the highly variable temporal progression of development. Issues concerning the analysis of temporal sequences and problems with current methods of analysis are discussed. We present here an algorithm to infer ancestral temporal sequences, quantify sequence heterochronies, and estimate pseudoreplicate consensus support for sequence changes using Parsimov-based genetic inference [PGi]. Real temporal developmental sequence data sets are used to compare PGi with currently used approaches, and PGi is shown to be the most efficient, accurate, and practical method to examine biological data and infer ancestral states on a phylogeny. The method is also expandable to address further issues in developmental evolution, namely modularity.

The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Likelihood-based methods are commonplace in phylogenetic systematics. Although much effort has been directed toward likelihood-based models for molecular data, comparatively less work has addressed models for discrete morphological character (DMC) data. Among-character rate variation (ACRV) may confound phylogenetic analysis, but there have been few analyses of the magnitude and distribution of rate heterogeneity among DMCs. Using 76 data sets covering a range of plants, invertebrate, and vertebrate animals, we used a modified version of MrBayes to test equal, gamma-distributed and lognormally distributed models of ACRV, integrating across phylogenetic uncertainty using Bayesian model selection. We found that in approximately 80% of data sets, unequal-rates models outperformed equal-rates models, especially among larger data sets. Moreover, although most data sets were equivocal, more data sets favored the lognormal rate distribution relative to the gamma rate distribution, lending some support for more complex character correlations than in molecular data. Parsimony estimation of the underlying rate distributions in several data sets suggests that the lognormal distribution is preferred when there are many slowly evolving characters and fewer quickly evolving characters. The commonly adopted four rate category discrete approximation used for molecular data was found to be sufficient to approximate a gamma rate distribution with discrete characters. However, among the two data sets tested that favored a lognormal rate distribution, the continuous distribution was better approximated with at least eight discrete rate categories. Although the effect of rate model on the estimation of topology was difficult to assess across all data sets, it appeared relatively minor between the unequal-rates models for the one data set examined carefully. As in molecular analyses, we argue that researchers should test and adopt the most appropriate model of rate variation for the data set in question. As discrete characters are increasingly used in more sophisticated likelihood-based phylogenetic analyses, it is important that these studies be built on the most appropriate and carefully selected underlying models of evolution.

Purpose of ReviewThe 2022 global mpox outbreak is a significant public health challenge. This review provides a summary of recent advancements in mpox phylogenetics, epidemiology, transmission, clinical presentation, treatment, and vaccination.Recent FindingsThe 2022 outbreak saw a shift in epidemiology, with human-to-human transmission, particularly among men who have sex with men (MSM), becoming the primary mode of spread. Among IIb.B.1 sequences, there is evidence for an emerging human-adapted monkeypox virus (MPXV). Antiviral treatments like tecovirimat have shown promise in severe cases. Two doses of the non-replicative 3rd generation vaccine MVA-BN provide better protection than a single dose.SummaryThis outbreak underscores the importance of global surveillance, prompt response, and effective vaccination strategies in managing emerging infectious diseases. Efforts to destigmatize the disease and increase awareness among high-risk populations are vital in curbing transmission. Continued research and international collaboration are essential for understanding the MPXV and improving preparedness for future outbreaks.