Publications by authors named "Louis Grandjean"

Background: The impact of antimicrobial resistance (AMR) on death at the patient level is challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK teaching hospital.

Methods: This retrospective study investigated all deceased patients in 2022.

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Unlabelled: Tuberculosis (TB) remains a significant global health challenge, exacerbated by the emergence of drug-resistant strains, such as those resistant to pyrazinamide (PZA). The current scarcity of affordable and precise quantitative diagnostic tests for PZA resistance underscores the urgent need for more accessible diagnostic tools. We evaluated PZA susceptibility in 264 TB-positive samples by quantifying pyrazinoic acid (POA) production, using both the MODS-Wayne qualitative assay and our newly developed quantitative approach (MODS-WQ).

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Carbapenems are broad-spectrum beta-lactam antibiotics that are increasingly being used worldwide to treat multidrug-resistant infections, but since their introduction, carbapenem resistance has emerged. This phenomenon has been well documented in the adult population, but there is a paucity of evidence from the neonatal and pediatric populations. A literature search of carbapenem-resistant infections in Latin American neonates and children was conducted via PubMed/Medline and SCOPUS: 551 titles were screened, and 17 articles were included in the review.

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Article Synopsis
  • The study aimed to examine the prevalence of non-communicable diseases, particularly diabetes, among household contacts of individuals with tuberculosis (TB).
  • A systematic review identified 39 studies, with 14 providing individual participant data and 25 offering aggregated data; the results showed a pooled diabetes prevalence of 8.8% among those tested properly.
  • Findings indicate that diabetes prevalence among household contacts is likely underestimated, highlighting the importance of targeted interventions during TB contact investigations to identify and address these health issues.
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Going back in time through a phylogenetic tree makes it possible to evaluate ancestral genomes and assess their potential to acquire key polymorphisms of interest over evolutionary time. Knowledge of this kind may allow for the emergence of key traits to be predicted and pre-empted from currently circulating strains in the future. Here, we present a novel genome-wide survival analysis and use the emergence of drug resistance in Mycobacterium tuberculosis as an example to demonstrate the potential and utility of the technique.

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Background: Drug resistance in tuberculosis (TB) poses a major ongoing challenge to public health. The recent inclusion of bedaquiline into TB drug regimens has improved treatment outcomes, but this advance is threatened by the emergence of strains of Mycobacterium tuberculosis (Mtb) resistant to bedaquiline. Clinical bedaquiline resistance is most frequently conferred by off-target resistance-associated variants (RAVs) in the mmpR5 gene (Rv0678), the regulator of an efflux pump, which can also confer cross-resistance to clofazimine, another TB drug.

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Six lineages of Mycobacterium tuberculosis sensu stricto (which excludes M. africanum) are described. Single-country or small observational data suggest differences in clinical phenotype between lineages.

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SARS-CoV-2 initially infects cells in the nasopharynx and oral cavity. The immune system at these mucosal sites plays a crucial role in minimizing viral transmission and infection. To develop new strategies for preventing SARS-CoV-2 infection, this study aimed to identify proteins that protect against viral infection in saliva.

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In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings.

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Article Synopsis
  • Accurate determination of infection transmission routes is vital for effective disease control and prevention in outbreaks.
  • Whole-genome sequencing has enhanced our ability to trace these transmission events, but many cases still face challenges due to minimal genetic variation between infected patients and their sources.
  • By incorporating within-sample genetic diversity into phylogenetic models, researchers can better identify transmission patterns in cases where previous methods fell short, as demonstrated using data from SARS-CoV-2 outbreaks.
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Article Synopsis
  • Healthcare workers (HCWs) faced increased risks of SARS-CoV-2 infection due to various socioeconomic factors, emphasizing the need to consider these variables in understanding exposure risks.
  • The Co-STARs study enrolled 3,679 HCWs and utilized multivariate logistic regression to assess the impact of demographic and socioeconomic factors on seropositivity to SARS-CoV-2.
  • Key findings indicated that household overcrowding, certain ethnicities, age, and lack of access to sick pay significantly increased infection risks, suggesting that improving access to sick pay could help reduce virus transmission in healthcare settings.
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Antimicrobial resistance (AMR) to all antibiotic classes has been found in the pathogen . The reported prevalence of these resistances varies, driven by within-host AMR evolution at the patient level, and between-host transmission at the hospital level. Without dense longitudinal sampling, pragmatic analysis of AMR dynamics at multiple levels using routine surveillance data is essential to inform control measures.

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Eight lineages of are described. Single-country or small observational data suggest differences in clinical phenotype between lineages. We present strain lineage and clinical phenotype data from 12,246 patients from 3 low-incidence and 5 high-incidence countries.

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Background: Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms.

Methods: In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve).

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Antimicrobial resistance (AMR) to all antibiotic classes has been found in the pathogen . The reported prevalence of these resistances vary, driven by within-host AMR evolution at the patient level, and between-host transmission at the hospital level. Without dense longitudinal sampling, pragmatic analysis of AMR dynamics at multiple levels using routine surveillance data is essential to inform control measures.

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People deprived of liberty have among the highest rates of tuberculosis globally. The incidence of tuberculosis is ten times greater than the incidence of tuberculosis in the general population. In 2021, WHO updated its guidance to strongly recommend systematic screening for tuberculosis in prisons and penitentiary systems.

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Tuberculosis phenotypic detection assays are commonly used in low-resource countries. Therefore, reliable detection methods are crucial for early diagnosis and treatment. The microscopic observation drug susceptibility (MODS) assay is a culture-based test to detect Mycobacterium tuberculosis and characterize drug resistance in 7-10 days directly from sputum.

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Genome-wide association studies (GWASs) are often confounded by population stratification and structure. Linear mixed models (LMMs) are a powerful class of methods for uncovering genetic effects, while controlling for such confounding. LMMs include random effects for a genetic similarity matrix, and they assume that a true genetic similarity matrix is known.

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While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with MIS-C (n = 12) and mild (n = 8) COVID-19.

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Background: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality.

Methods: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018.

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Sensitive serological testing is essential to estimate the proportion of the population exposed or infected with SARS-CoV-2, to guide booster vaccination and to select patients for treatment with anti-SARS-CoV-2 antibodies. The performance of serological tests is usually evaluated at 14-21 days post infection. This approach fails to take account of the important effect of time on test performance after infection or exposure has occurred.

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Most culture-based methods for tuberculosis diagnosis remain low-cost options for low- and mid-income countries. The MODS culture is a rapid and low-cost assay to diagnose tuberculosis and determine drug susceptibility. However, its implementation is limited due to the low accessibility to supplies required for the enriched medium.

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Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts.

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