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Background: Quality surveillance data used to build tuberculosis (TB) transmission models are frequently unavailable and may overlook community intrinsic dynamics that impact TB transmission. Social network analysis (SNA) generates data on hyperlocal social-demographic structures that contribute to disease transmission. Methods: We collected social contact data in five villages and built SNA-informed village-specific stochastic TB transmission models in remote Madagascar. A name-generator approach was used to elicit individual contact networks. Recruitment included confirmed TB patients, followed by snowball sampling of named contacts. Egocentric network data were aggregated into village-level networks. Network- and individual-level characteristics determining contact formation and structure were identified by fitting an exponential random graph model (ERGM), which formed the basis of the contact structure and model dynamics. Models were calibrated and used to evaluate WHO-recommended interventions and community resiliency to foreign TB introduction. Results: Inter- and intra-village SNA showed variable degrees of interconnectivity, with transitivity (individual clustering) values of 0.16, 0.29, and 0.43. Active case finding and treatment yielded 67%–79% reduction in active TB disease prevalence and a 75% reduction in TB mortality in all village networks. Following hypothetical TB elimination and without specific interventions, networks A and B showed resilience to both active and latent TB reintroduction, while Network C, the village network with the highest transitivity, lacked resiliency to reintroduction and generated a TB prevalence of 2% and a TB mortality rate of 7.3% after introduction of one new contagious infection post hypothetical elimination. Conclusion: In remote Madagascar, SNA-informed models suggest that WHO-recommended interventions reduce TB disease (active TB) prevalence and mortality while TB infection (latent TB) burden remains high. Communities' resiliency to TB introduction decreases as their interconnectivity increases. "Top down" population level TB models would most likely miss this difference between small communities. SNA bridges large-scale population-based and hyper focused community-level TB modeling. [ABSTRACT FROM AUTHOR]

Objectives: Despite the large body of research on violence against women, violence that specifically targets women's reproductive autonomy and control over their reproductive health, called reproductive coercion (RC), is poorly documented in Canada. The purpose of this study is to determine the prevalence of RC behaviors in an adult Canadian community sample and to explore associated factors. Study design: A self-report online questionnaire was administered from September 2020 to April 2021 in Quebec and Ontario, Canada. Participants were recruited via social media, sexual and reproductive health clinics, community-based anti-violence organizations, and the project's partner organizations. The questionnaire contained validated RC questionnaire items and new items drawn from previous qualitative work. The sample comprised 427 participants, mostly self-identified as women (92%), aged 18 to 55 years (M = 29.01; SD = 6.64). Descriptive analyses and binary logistic regressions were conducted using SPSS 27. Results: The results of this study show that 63.9% of participants reported at least one lifetime experience of RC. According to our data, contraceptive sabotage was the most common form (62.8%). Of the participants who had been pregnant, 9.8% reported control of pregnancy outcomes. Each RC category shows a different pattern of correlates. The findings also reveal that intimate partner violence (IPV) increases the likelihood of contraceptive sabotage. Moreover, the study suggests that low education level and IPV increase the risk for control of pregnancy outcomes. Conclusion: These findings underscore the importance of RC in the lives of many Canadian individuals with the capacity to be pregnant, and they highlight certain factors that place individuals at greater risk for RC. This knowledge can inform the development of prevention efforts and clinical interventions. [ABSTRACT FROM AUTHOR]

We diagnosed Mycobacterium tuberculosis in captive lemurs and a fossa in Antananarivo, Madagascar. We noted clinical signs in the animals and found characteristic lesions during necropsy. The source of infection remains unknown. Our results illustrate the potential for reverse zoonotic infections and intraspecies transmission of tuberculosis in captive wildlife. [ABSTRACT FROM AUTHOR]

Targeted Next Generation Sequencing (tNGS) and Whole Genome Sequencing (WGS) are increasingly used for genotypic drug susceptibility testing (gDST) of Mycobacterium tuberculosis. Thirty-two multi-drugs resistant and 40 drug susceptible isolates from Madagascar were tested with Deeplex® Myc-TB and WGS using the Mykrobe analysis pipeline. Sixty-four of 72 (89 %) yielded concordant categorical gDST results for drugs tested by both assays. Mykrobe didn't detect pncA K96T, pncA Q141P, pncA H51P, pncA H82R, rrs C517T and rpsL K43R mutations, which were identified as minority variants in corresponding isolates by tNGS. One discrepancy (rrs C517T) was associated with insufficient sequencing depth on WGS. Deeplex® Myc-TB didn't detect inhA G-154A which isn't covered by the assay's amplification targets. Despite those targets being included in the Deeplex® Myc-TB assay, a pncA T47A and a deletion in gid were not identified in one isolate respectively. The evaluated WGS and tNGS gDST assays show high but imperfect concordance. [ABSTRACT FROM AUTHOR]

We diagnosed tuberculosis in an illegally wild-captured pet ring-tailed lemur manifesting lethargy, anorexia, and cervical lymphadenopathy. Whole-genome sequencing confirmed the Mycobacterium tuberculosis isolate belonged to lineage 3 and harbored streptomycin resistance. We recommend reverse zoonosis prevention and determination of whether lemurs are able to maintain M. tuberculosis infection. [ABSTRACT FROM AUTHOR]

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory disease of the breast. Various clinical management approaches have been described, but their efficacy and optimal sequential order remain uncertain. We describe the first Canadian cohort of patients with IGM, discuss treatment outcomes and outline a practical management approach. This retrospective study included patients diagnosed with biopsy-confirmed IGM between 2014 and 2023, aged over 18 years. Based on a scoping review of the literature, a diagnostic and management approach was developed, and we present here the disease course and outcomes using this approach. 22 females were included, with a mean age of 40 (24-65) years, mostly presenting with a breast lump (n =22, 100%) and breast pain (n = 15, 68%). Mean rheumatology follow-up was 28.7 months (range 3-79). Mean time from first symptom to diagnosis was 3.5 months (range 1-13). Corynebacterium kroppenstedtii was found in 8 patients. Treatment including lipophilic antibiotics, corticosteroids and disease modifying anti-rheumatic drugs (DMARDs), led to complete remission in 95% of patients, in a mean time of 11.6 months (range 1-36), and relapse in only 1 patient. 11 patients required DMARDs (50%), most commonly methotrexate (n=9). We highlight the variable severity of IGM and the benefits of a severity-based treatment approach. A diligent evaluation and work-up is essential to manage IGM. The proposed severity-based management approach with medical treatment and less aggressive surgical intervention led to complete remission in 95%., Competing Interests: Declarations. Ethical approval: Approval by our Ethics Committee was granted on May 31st, 2023 (project number 2024–11386, 23.022). Patient consent: Patient consent was obtained through our Ethics Committee (see above). Conflict of interest: All authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Mycobacterial culture is routinely performed to diagnose tuberculosis (TB) in Canada. Globally, meta-analyses suggest that up to 2% of positive cultures are falsely positive for Mycobacterium tuberculosis due to laboratory cross-contamination. Five patients from distinct clinical institutions in Montréal were diagnosed with culture-positive TB as their clinical samples were processed in a centralized mycobacteria laboratory. Cross-contamination was suspected due to culture positivity in an organ donor with low TB pre-test probability. We describe a TB pseudo-outbreak due to laboratory cross-contamination and assess the role of conventional typing (i.e., mycobacterial interspersed repetitive unit variable number of tandem repeats [MIRU-VNTR]) and whole-genome sequencing (WGS) in supporting the investigation., Methods: Patients' epidemiological risk factors and clinical presentations were reviewed. The trajectories of pre- and per-analytic samples were retraced to identify potential cross-contamination events. Tuberculosis isolates were characterized by MIRU-VNTR and WGS using Oxford Nanopore Technology (ONT). The bioinformatic pipeline tbpore (v0.7.1) cluster was used for phylogenetic analyses., Results: Two patients had previous exposure to endemic settings and clinical symptoms compatible with TB. Culture media inoculation overlapped in time for four patients, including one with suspected pulmonary cavitary disease and an organ donor whose organs had been transplanted in three different receivers. The MIRU-VNTR and WGS typing confirmed isolates from those four patients to be identical., Conclusion: Clinical, laboratory and molecular typing data, including results from ONT sequencing, were considered sufficiently robust to confirm laboratory cross-contamination and TB therapy was discontinued including in all organ transplant recipients., Competing Interests: Competing interests None.

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic., (© 2024. The Author(s).)

Prolonged exposure to fine particulate matter (PM2.5) is a known risk to respiratory health, causing chronic lung impairment. Yet, the immediate, acute effects of PM2.5 exposure on respiratory symptoms, such as cough, are less understood. This pilot study aims to investigate this relationship using objective PM2.5 and cough monitors. Fifteen participants from rural Madagascar were followed for three days, equipped with an RTI Enhanced Children's MicroPEM PM2.5 sensor and a smartphone with the ResApp Cough Counting Software application. Univariable Generalized Estimating Equation (GEE) models were applied to measure the association between hourly PM2.5 exposure and cough counts. Peaks in both PM2.5 concentration and cough frequency were observed during the day. A 10-fold increase in hourly PM2.5 concentration corresponded to a 39% increase in same-hour cough frequency (incidence rate ratio (IRR) = 1.40; 95% CI: 1.12, 1.74). The strength of this association decreased with a one-hour lag between PM2.5 exposure and cough frequency (IRR = 1.21; 95% CI: 1.01, 1.44) and was not significant with a two-hour lag (IRR = 0.93; 95% CI: 0.71, 1.23). This study demonstrates the feasibility of objective PM2.5 and cough monitoring in remote settings. An association between hourly PM2.5 exposure and cough frequency was detected, suggesting that PM2.5 exposure may have immediate effects on respiratory health. Further investigation is necessary in larger studies to substantiate these findings and understand the broader implications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zimmer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Computer-aided detection (CAD) algorithms for automated chest X-ray (CXR) reading have been endorsed by the World Health Organization for tuberculosis (TB) triage, but independent, multi-country assessment and comparison of current products are needed to guide implementation., Methods: We conducted a head-to-head evaluation of five CAD algorithms for TB triage across seven countries. We included CXRs from adults who presented to outpatient facilities with at least two weeks of cough in India, Madagascar, the Philippines, South Africa, Tanzania, Uganda, and Vietnam. The participants completed a standard evaluation for pulmonary TB, including sputum collection for Xpert MTB/RIF Ultra and culture. Against a microbiological reference standard, we calculated and compared the accuracy overall, by country and key groups for five CAD algorithms: CAD4TB (Delft Imaging), INSIGHT CXR (Lunit), DrAid (Vinbrain), Genki (Deeptek), and qXR (qure.AI). We determined the area under the ROC curve (AUC) and if any CAD product could achieve the minimum target accuracy for a TB triage test (≥90% sensitivity and ≥70% specificity). We then applied country- and population-specific thresholds and recalculated accuracy to assess any improvement in performance., Results: Of 3,927 individuals included, the median age was 41 years (IQR 29-54), 12.9% were people living with HIV (PLWH), 8.2% living with diabetes, and 21.2% had a prior history of TB. The overall AUC ranged from 0.774-0.819, and specificity ranged from 64.8-73.8% at 90% sensitivity. CAD4TB had the highest overall accuracy (73.8% specific, 95% CI 72.2-75.4, at 90% sensitivity), although qXR and INSIGHT CXR also achieved the target 70% specificity. There was heterogeneity in accuracy by country, and females and PLWH had lower sensitivity while males and people with a history of TB had lower specificity. The performance remained stable regardless of diabetes status. When country- and population-specific thresholds were applied, at least one CAD product could achieve or approach the target accuracy for each country and sub-group, except for PLWH and those with a history of TB., Conclusions: Multiple CAD algorithms can achieve or exceed the minimum target accuracy for a TB triage test, with improvement when using setting- or population-specific thresholds. Further efforts are needed to integrate CAD into routine TB case detection programs in high-burden communities., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest. The installation and use of the different CAD software evaluated in this manuscript was provided free of charge by all CAD vendors to FIND. CAD vendors did not have any role in the study design, data collection, analysis, the decision to publish or the preparation of the manuscript.

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic., Competing Interests: COMPETING INTERESTS The authors declare no competing interest.

Introduction: Despite its high prevalence and significance, there is still no widely available method to quantify cough. In order to demonstrate agreement with the current gold standard of human annotation, emerging automated techniques require a robust, reproducible approach to annotation. We describe the extent to which a human annotator of cough sounds (a) agrees with herself (intralabeller or intrarater agreement) and (b) agrees with other independent labellers (interlabeller or inter-rater agreement); we go on to describe significant sex differences in cough sound length and epochs size., Materials and Methods: 24 participants wore an audiorecording smartwatch to capture 6-24 hours of continuous audio. A randomly selected sample of the whole audio was labelled twice by an expert annotator and a third time by six trained annotators. We collected 400 hours of audio and analysed 40 hours. The cough counts as well as cough seconds (any 1 s of time containing at least one cough) from different annotators were compared and summary statistics from linear and Bland-Altman analyses were used to quantify intraobserver and interobserver agreement., Results: There was excellent intralabeller (less than two disagreements per hour monitored, Pearson's correlation 0.98) and interlabeller agreement (Pearson's correlation 0.96), using cough seconds as the unit of analysis decreased annotator discrepancies by 50% in comparison to coughs. Within this data set, it was observed that the length of cough sounds and epoch size (number of coughs per bout or attach) differed between women and men., Conclusion: Given the decreased interobserver variability in annotation when using cough seconds (vs just coughs) we propose their use for manually annotating cough when assessing of the performance of automatic cough monitoring systems. The differences in cough sound length and epochs size may have important implications for equality in the development of cough monitoring tools., Trial Registration Number: NCT05042063., Competing Interests: Competing interests: MR, JCG, RM, LJ, MG and PS were or are employees of Hyfe and own equity in Hyfe. CCh has received consultancy fees and owns equity in Hyfe. All other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background : Emerging technologies to remotely monitor patients' cough show promise for various clinical applications. Currently available cough detection systems all represent a trade-off between convenience and performance. The accuracy of such technologies is highly contingent on the clinical settings in which they are intended to be used. Moreover, establishing gold standards to measure this accuracy is challenging. Objectives : We present the first performance evaluation study of the Hyfe Cough Tracker app, a passive cough monitoring smartphone application. We evaluate performance for cough detection using continuous audio recordings and cough counting by trained individuals as the gold standard. We propose standard procedures to use multi-observer cough sound annotation from continuous audio recordings as the gold standard for evaluating automated cough detection devices. Methods : This study was embedded in a larger digital acoustic surveillance study (clinicaltrial.gov NCT04762693). Forty-nine participants were included and instructed to produce a diverse series of solicited sounds in 10-minute sessions. Simultaneously, continuous audio recording was performed using a MP3 recorder and two smartphones running Hyfe Cough Tracker app monitored and identified cough events. All continuous audio recordings were independently labeled by three medically-trained researchers. Results : Hyfe Cough Tracker app showed sensitivity of 91% and specificity of 98% with a very high correlation between the cough rate measured by Hyfe and that of human annotators (Pearson correlation of 0.968). A standardized approach to establish an acoustic gold standard for identifying cough sounds with multiple observers is presented. Conclusion:  This is the first performance evaluation of a new smartphone-based cough monitoring system. Hyfe Cough Tracker can detect, record and count coughs from solicited cough-like explosive sounds in controlled acoustic environments with very high accuracy. Additional steps are required to validate the system in clinical and community settings., Competing Interests: Competing interests: MG, EK, GG, PM and MR are employees of Hyfe Inc. Hyfe had no role in the decision to submit this protocol for publication. CCH has received consultancy fees and owns equity from Hyfe Inc. No competing interests were disclosed for all other authors., (Copyright: © 2023 Galvosas M et al.)

Objectives: To clarify perceived benefits, barriers and facilitators of Mycobacterium tuberculosis next-generation sequencing implementation in Madagascar and Canada, towards informing implementation of this diagnostic technology in public health agencies and clinical settings in and beyond these settings., Design: This qualitative study involved conducting semistructured interviews with key stakeholders engaged with next-generation sequencing implementation in Madagascar and Canada. Team-based descriptive analysis supported by Nvivo V.12.0 was used to identify key themes., Setting: The study was conducted with participants involved at the clinical, diagnostic and surveillance levels of tuberculosis (TB) management from Madagascar and Canada., Participants: Eighteen participants were interviewed (nine Madagascar and nine Canada) and included individuals purposively sampled based on involvement with TB surveillance, laboratory diagnosis and clinical management., Results: The following five themes emerged in the analysis of Malagasy and Canadian interviews: (1) heterogeneity in experience with established TB diagnostics, (2) variable understanding of new sequencing-based diagnostics potential; (3) further evidence as being key to expand adoption; (4) ethical arguments and concerns; (5) operational and system-level considerations., Conclusion: There persists important lack of familiarity with TB next-generation sequencing (TB NGS) applications among stakeholders in Canada and Madagascar. This translates into skepticism on the evidence underlying its use and its true potential value added within global public health systems. If deployed, TB NGS testing should be integrated with clinical and surveillance programmes. Although this is perceived as a priority, leadership and funding responsibilities for this integration to happen remains unclear to clinical, laboratory and public health stakeholders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Universal access to drug susceptibility testing for newly diagnosed tuberculosis patients is recommended. Access to culture-based diagnostics remains limited, and targeted molecular assays are vulnerable to emerging resistance mutations. Improved protocols for direct-from-sputum Mycobacterium tuberculosis sequencing would accelerate access to comprehensive drug susceptibility testing and molecular typing. We assessed a thermo-protection buffer-based direct-from-sample M. tuberculosis whole-genome sequencing protocol. We prospectively analyzed 60 acid-fast bacilli smear-positive clinical sputum samples in India and Madagascar. A diversity of semiquantitative smear positivity-level samples were included. Sequencing was performed using Illumina and MinION (monoplex and multiplex) technologies. We measured the impact of bacterial inoculum and sequencing platforms on genomic read depth, drug susceptibility prediction performance, and typing accuracy. M. tuberculosis was identified by direct sputum sequencing in 45/51 samples using Illumina, 34/38 were identified using MinION-monoplex sequencing, and 20/24 were identified using MinION-multiplex sequencing. The fraction of M. tuberculosis reads from MinION sequencing was lower than from Illumina, but monoplexing grade 3+ samples on MinION produced higher read depth than Illumina ( P <  0.05) and MinION multiplexing ( P <  0.01). No significant differences in sensitivity and specificity of drug susceptibility predictions were seen across sequencing modalities or within each technology when stratified by smear grade. Illumina sequencing from sputum accurately identified 1/8 (rifampin) and 6/12 (isoniazid) resistant samples, compared to 2/3 (rifampin) and 3/6 (isoniazid) accurately identified with Nanopore monoplex. Lineage agreement levels between direct and culture-based sequencing were 85% (MinION-monoplex), 88% (Illumina), and 100% (MinION-multiplex). M. tuberculosis direct-from-sample whole-genome sequencing remains challenging. Improved and affordable sample treatment protocols are needed prior to clinical deployment.

Objectives: We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings., Design and Setting: This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures., Results: Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases., Conclusion: SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available., Trial Registration: clinicaltrials.gov identifier: NCT05411562., Competing Interests: The authors declare no conflicts of interest related to this article., (© The Author(s) 2023.)

Background: Mycobacterium tuberculosis whole-genome sequencing (WGS) has been widely used for genotypic drug susceptibility testing (DST) and outbreak investigation. For both applications, Illumina technology is used by most public health laboratories; however, Nanopore technology developed by Oxford Nanopore Technologies has not been thoroughly evaluated. The aim of this study was to determine whether Nanopore sequencing data can provide equivalent information to Illumina for transmission clustering and genotypic DST for M tuberculosis., Methods: In this genomic analysis, we analysed 151 M tuberculosis isolates from Madagascar, South Africa, and England, which were collected between 2011 and 2018, using phenotypic DST and matched Illumina and Nanopore data. Illumina sequencing was done with the MiSeq, HiSeq 2500, or NextSeq500 platforms and Nanopore sequencing was done on the MinION or GridION platforms. Using highly reliable PacBio sequencing assemblies and pairwise distance correlation between Nanopore and Illumina data, we optimise Nanopore variant filters for detecting single-nucleotide polymorphisms (SNPs; using BCFtools software). We then used those SNPs to compare transmission clusters identified by Nanopore with the currently used UK Health Security Agency Illumina pipeline (COMPASS). We compared Illumina and Nanopore WGS-based DST predictions using the Mykrobe software and mutation catalogue., Findings: The Nanopore BCFtools pipeline identified SNPs with a median precision of 99·3% (IQR 99·1-99·6) and recall of 90·2% (88·1-94·2) compared with a precision of 99·6% (99·4-99·7) and recall of 91·9% (87·6-98·6) using the Illumina COMPASS pipeline. Using a threshold of 12 SNPs for putative transmission clusters, Illumina identified 98 isolates as unrelated and 53 as belonging to 19 distinct clusters (size range 2-7). Nanopore reproduced 15 out of 19 clusters perfectly; two clusters were merged into one cluster, one cluster had a single sample missing, and one cluster had an additional sample adjoined. Illumina-based clusters were also closely replicated using a five SNP threshold and clustering accuracy was maintained using mixed Illumina and Nanopore datasets. Genotyping resistance variants with Nanopore was highly concordant with Illumina, having zero discordant SNPs across more than 3000 SNPs and four insertions or deletions (indels), across 60 000 indels., Interpretation: Illumina and Nanopore technologies can be used independently or together by public health laboratories performing M tuberculosis genotypic DST and outbreak investigations. As a result, clinical and public health institutions making decisions on which sequencing technology to adopt for tuberculosis can base the choice on cost (which varies by country), batching, and turnaround time., Funding: Academy for Medical Sciences, Oxford Wellcome Institutional Strategic Support Fund, and the Swiss South Africa Joint Research Award (Swiss National Science Foundation and South African National Research Foundation)., Competing Interests: Declaration of interests ZI, SGL, and NR had travel and accommodation costs reimbursed when speaking at an Oxford Nanopore Technology (ONT) conference in 2017. SGL and NR previously received consumables from ONT when establishing Nanopore sequencing capacity in Madagascar. ONT matched the contributions from the Longitude Prize Discovery Award to ZI and TMW in 2017 to provide consumables for sequencing in Viet Nam and India. All other authors declare no competing interests. ONT did not provide funding (direct or in kind) for this project, and had no input or knowledge of the design, data analysis, or paper writing. Funders had no input into the design, data analysis, or paper writing of this project., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Tecovirimat (TCV, TPOXX ® ) is an orthopox-specific antiviral drug indicated for the treatment of smallpox. There is also a mechanistic basis for its use in mpox infection. However, its approval was based on animal studies, and its efficacy and side-effect profile in human patients with disease is unknown., Methods: During the 2022 international mpox epidemic, clinicians in Canada accessed TCV from the Public Health Agency of Canada's National Emergency Strategic Stockpile for severe cases of mpox disease. We describe the use of TCV in nine adults with severe mpox virus infection in Montréal, Canada., Results: Five patients were treated for severe and potentially life-threatening head and neck symptoms, while four were treated for genitourinary or anorectal disease. Two-thirds of patients were also treated for suspected bacterial superinfection. All patients recovered (median time to resolution of severe symptoms: nine days) without relapse or hospital readmission. No patients reported adverse events attributable to TCV and no patients stopped their treatment early., Conclusion: Our experience suggests that TCV is well tolerated and may accelerate recovery in severe cases. These preliminary, observational data may also be explained by concomitant treatment for superinfection and are limited by the absence of a control group. Controlled, clinical trials should be conducted to clarify the attributable benefit of TCV in severe mpox infection., Competing Interests: Competing interests CT is the Pfizer/Université de Montréal Chair on HIV Translational Research.

Cough assessment is central to the clinical management of respiratory diseases, including tuberculosis (TB), but strategies to objectively and unobtrusively measure cough are lacking. Acoustic epidemiology is an emerging field that uses technology to detect cough sounds and analyze cough patterns to improve health outcomes among people with respiratory conditions linked to cough. This field is increasingly exploring the potential of artificial intelligence (AI) for more advanced applications, such as analyzing cough sounds as a biomarker for disease screening. While much of the data are preliminary, objective cough assessment could potentially transform disease control programs, including TB, and support individual patient management. Here, we present an overview of recent advances in this field and describe how cough assessment, if validated, could support public health programs at various stages of the TB care cascade., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

Objective: This study aimed to examine the link between friendship instability during emerging adulthood and depressive symptoms. The moderating role of gender and the pursuit (or not) of postsecondary education was also tested. Participants: A total of 268 participants (60.7% women) was interviewed annually between the ages of 22 and 26. Methods: Friendship instability was measured by asking the participants to name their three best friends each year and depressive symptoms were assessed at ages 22 and 26. Results: A multiple hierarchical regression analysis predicting depressive symptoms at age 26 (while controlling for symptoms at age 22) revealed a triple interaction between friendship instability, gender and the pursuit of postsecondary education. Specifically, friendship instability predicted depressive symptoms at age 26, but only among women pursuing postsecondary education. Conclusions: These results highlight the importance of maintaining friendships for these individuals.

Diagnosis and clinical management of pulmonary infections in lung transplant patients are challenging. The increased diversity of bacterial species identified from clinical samples with novel proteomics-based systems can further complicate clinical decision making in this highly vulnerable population. Whether newly recognized organisms are colonizers or true pathogens often remains controversial since symptoms causality and impact on lung function is often unknown. We present the case of a 48-year-old female lung transplant patient with Pandoraea sp infection. We review and discuss the role of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for accurate bacterial identification. We report on therapeutic management and clinical outcome., Competing Interests: The authors have nothing to disclose., (Copyright © 2020, Association of Medical Microbiology and Infectious Disease Canada (AMMI Canada).)

Background: In Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar's MDR-TB cascade of care., Methods: For 2012-2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar's TB and MDR-TB cascade of care., Results: The geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients' sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival., Conclusions: An expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

This study compared the Altona RealStar™ VZV Kit 1.0 real time quantitative VZV PCR with in-house qualitative conventional VZV PCR on cerebrospinal fluid, mucocutaneous, and other uncommon clinical specimens. Overall, positive and negative agreement percentages were respectively 97.9% (95%CI: 93.8-99.6), 100.0% (95%CI: 93.1-100.0), and 96.3% (95%CI: 89.4-99.2) while Cohen's kappa statistic value was 0.96 (95%CI: 0.91-1.00). RealStar™ VZV quantitative PCR assay reported average quantitative viral loads of 4.4 × 10 5 and 1.1 × 10 7  copies/mL in cerebrospinal fluid and cutaneous specimens, respectively (P < 0.01). RealStar™ VZV PCR assay showed excellent agreement with in house conventional assay for various clinical specimens., (© 2017 Wiley Periodicals, Inc.)

Background: The detection of antibodies against Epstein-Barr viral capsid (VCA) and nuclear (EBNA) antigens is routinely performed with different commercially available immunoassays., Objectives: In this study, we evaluated the concordance and performance of the Architect(™) chemiluminescent microparticle immunoassays (CMIAs) using Captia(™) enzyme linked immunosorbent assays (ELISA) for VCA IgM, and standard immunofluorescence (IF) assays for VCA IgG and EBNA IgG as comparative techniques., Study Design: Sera were selected from a heterogeneous population including pediatric and adult patients., Results: Concordance between CMIAs and comparative assays was high with total agreement percentages of 84,1% (95% CI: 77.8-88.9) for VCA IgM, 90,6% (95% CI: 84.2-94.7) for EBNA IgG and 98,0% (95% CI: 93.9-99.6) for VCA IgG. Moreover, kappa statistic values showed good to excellent correlation with values of 0.68 (95% CI: 0.57-0.79) for VCA IgM, 0.73 (95% CI: 0.58-0.87) for EBNA IgG and 0.95 (95% CI: 0.89-1.00) for VCA IgG. A correlation was observed between positivity levels on CMIAs and semi-quantitative fluorescence intensity on IF for VCA IgG and EBNA IgG assays. With regard to an accepted gold standard IF assays, CMIA was 98,1% (95% CI: 93.3-99.8) sensitive and 97,4% (95% CI: 86.5-99.9) specific for the detection of VCA IgG. For the detection of EBNA IgG, it was 92,2% (95% CI: 85.1-96.6) sensitive and 84,6% (95% CI: 65.1-95.6) specific., Conclusion: In summary, we demonstrated that the CMIA EBV antibody detection panel has high performance and high concordance with other commercially available immunoassays., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: This integrative literature review aims to present a comprehensive portrayal of social violence experienced by first-generation immigrant children and adolescents, and its effects on their health and well-being., Method: A French and English languages literature search was conducted in eight databases, without restrictions on dates of publication. Thirty studies were selected. Results were summarized according to three aspects: 1) types of violence experienced by young immigrants; 2) conditions under which this violence occurs; 3) effects of such violence on the health and well-being of young immigrants., Synthesis: Immigrant children and adolescents can experience various forms of physical, verbal, and relational violence. This violence seems to be mostly instigated by their peers and it has mainly been studied in terms of discrimination. Victimization may vary depending on factors such as ethnic composition of schools or time of residence in the host society. Violence may have many effects on mental health of immigrant youth: it is associated with both increased psychopathological symptoms and poorer mental health. Finally, the experience of violence is related to a more negative attitude of young immigrants toward their host society and a more positive attitude toward their own cultural community., Conclusion: In addition to its having numerous adverse effects on their mental and social health and well-being, violence may prove to be a key factor in the experience of marginalization of immigrant youth. We propose certain research avenues to explore.