Pub Date : 2024-11-01DOI: 10.1016/S2666-5247(24)00138-1
Christine Chevillon PhD , Benoît de Thoisy PhD , Alex W Rakestraw MSc , Kayla M Fast MSc , Jennifer L Pechal PhD , Sophie Picq PhD , Prof Loïc Epelboin MD PhD , Paul Le Turnier MD , Magdalene Dogbe MSc , Heather R Jordan PhD , Michael W Sandel PhD , Prof Mark Eric Benbow PhD , Prof Jean-François Guégan PhD
Predicting the outbreak of infectious diseases and designing appropriate preventive health actions require interdisciplinary research into the processes that drive exposure to and transmission of disease agents. In the case of mycobacterial diseases, the epidemiological understanding of the scientific community hitherto was based on the clinical studies of infections in vertebrates. To evaluate the information gained by comprehensively accounting for the ecological and evolutionary constraints, we conducted literature searches assessing the role of mycobacteria interactions with non-vertebrate species in the origin of their pathogenicity and variations in disease risk. The reviewed literature challenges the current theory of person-to-person transmission for several mycobacterial infections. Furthermore, the findings suggest that diverse non-vertebrate organisms influence virulence, mediate transmission, and contribute to pathogen abundance in relation to vertebrate exposure. We advocate that an ecological and evolutionary framework provides novel insights to support a more comprehensive understanding of the prevention and management of diseases in vertebrates.
{"title":"Ecological and evolutionary perspectives advance understanding of mycobacterial diseases","authors":"Christine Chevillon PhD , Benoît de Thoisy PhD , Alex W Rakestraw MSc , Kayla M Fast MSc , Jennifer L Pechal PhD , Sophie Picq PhD , Prof Loïc Epelboin MD PhD , Paul Le Turnier MD , Magdalene Dogbe MSc , Heather R Jordan PhD , Michael W Sandel PhD , Prof Mark Eric Benbow PhD , Prof Jean-François Guégan PhD","doi":"10.1016/S2666-5247(24)00138-1","DOIUrl":"10.1016/S2666-5247(24)00138-1","url":null,"abstract":"<div><div>Predicting the outbreak of infectious diseases and designing appropriate preventive health actions require interdisciplinary research into the processes that drive exposure to and transmission of disease agents. In the case of mycobacterial diseases, the epidemiological understanding of the scientific community hitherto was based on the clinical studies of infections in vertebrates. To evaluate the information gained by comprehensively accounting for the ecological and evolutionary constraints, we conducted literature searches assessing the role of mycobacteria interactions with non-vertebrate species in the origin of their pathogenicity and variations in disease risk. The reviewed literature challenges the current theory of person-to-person transmission for several mycobacterial infections. Furthermore, the findings suggest that diverse non-vertebrate organisms influence virulence, mediate transmission, and contribute to pathogen abundance in relation to vertebrate exposure. We advocate that an ecological and evolutionary framework provides novel insights to support a more comprehensive understanding of the prevention and management of diseases in vertebrates.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 11","pages":"Article 100906"},"PeriodicalIF":20.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S2666-5247(24)00163-0
Richard T Davey Jr. MD , Gary L Collins MS , Nadine Rouphael MD , Guillaume Poliquin MD , Rosemary McConnell RN , Gabrielle Grubbs BS , Susan L Moir PhD , Joanne M Langley MD , Marc Teitelbaum MD , Angela L Hewlett MD , Prof Susan L F McLellan MD , Nahid Bhadelia MD , Vanessa N Raabe MD , Prof Mark J Mulligan MD , Irina Maljkovic Berry PhD , Bonnie Dighero-Kemp BSc , Jonathan R Kurtz PhD , Lisa E Hensley PhD , Nelson C E Dozier MS , Lindsay C B Marron MS , Prof James D Neaton PhD
<div><h3>Background</h3><div>rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation.</div></div><div><h3>Methods</h3><div>In this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36 in participants who had received a homologous booster dose at month 18 following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18 years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×10<sup>7</sup> plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18 months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18 months after randomisation) for all randomly assigned participants who completed the 36 months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18 but were masked to summary data by randomisation group after month 18. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT02788227</span><svg><path></path></svg></span>).</div></div><div><h3>Findings</h3><div>Of the 248 participants who enrolled and received their primary immunisation, 114 proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57 participants (24 [42%] of whom were female; median age was 42 years [IQR 35–50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42 years [IQR 36–51]) to the no-booster group. Of those randomly assigned, 92 participants (45 in the booster group and 47 in the no-booster group) completed 36 months of follow-up. At 18 months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10 ELISA units (EU)/mL (95% CI 7–14) to 1451 EU/mL (1118–1882)
{"title":"Safety and immunogenicity of a delayed booster dose of the rVSVΔG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial","authors":"Richard T Davey Jr. MD , Gary L Collins MS , Nadine Rouphael MD , Guillaume Poliquin MD , Rosemary McConnell RN , Gabrielle Grubbs BS , Susan L Moir PhD , Joanne M Langley MD , Marc Teitelbaum MD , Angela L Hewlett MD , Prof Susan L F McLellan MD , Nahid Bhadelia MD , Vanessa N Raabe MD , Prof Mark J Mulligan MD , Irina Maljkovic Berry PhD , Bonnie Dighero-Kemp BSc , Jonathan R Kurtz PhD , Lisa E Hensley PhD , Nelson C E Dozier MS , Lindsay C B Marron MS , Prof James D Neaton PhD","doi":"10.1016/S2666-5247(24)00163-0","DOIUrl":"10.1016/S2666-5247(24)00163-0","url":null,"abstract":"<div><h3>Background</h3><div>rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation.</div></div><div><h3>Methods</h3><div>In this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36 in participants who had received a homologous booster dose at month 18 following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18 years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×10<sup>7</sup> plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18 months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18 months after randomisation) for all randomly assigned participants who completed the 36 months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18 but were masked to summary data by randomisation group after month 18. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (<span><span>NCT02788227</span><svg><path></path></svg></span>).</div></div><div><h3>Findings</h3><div>Of the 248 participants who enrolled and received their primary immunisation, 114 proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57 participants (24 [42%] of whom were female; median age was 42 years [IQR 35–50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42 years [IQR 36–51]) to the no-booster group. Of those randomly assigned, 92 participants (45 in the booster group and 47 in the no-booster group) completed 36 months of follow-up. At 18 months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10 ELISA units (EU)/mL (95% CI 7–14) to 1451 EU/mL (1118–1882)","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 11","pages":"Article 100923"},"PeriodicalIF":20.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S2666-5247(24)00131-9
Shaojun Pei PhD , Zexuan Song MS , Wei Yang PhD , Wencong He PhD , Xichao Ou MS , Bing Zhao MS , Ping He MS , Yang Zhou MS , Hui Xia PhD , Shengfen Wang PhD , Prof Zhongwei Jia PhD , Timothy M Walker DPhil , Prof Yanlin Zhao PhD
<div><h3>Background</h3><div>WHO issued the first edition catalogue of <em>Mycobacterium tuberculosis</em> complex (MTBC) mutations associated with drug resistance in 2021. However, country-specific issues might lead to arising complex and additional drug-resistant mutations. We aimed to fully reflect the characteristics of drug resistance mutations in China.</div></div><div><h3>Methods</h3><div>We analysed MTBC isolates from the nationwide drug-resistant tuberculosis surveillance with 70 counties in 31 provinces, municipalities, and autonomous regions in China. Three types of MYCOTB plates were used to perform drug susceptibility testing for 12 antibiotics (rifampicin, isoniazid, ethambutol, levofloxacin, moxifloxacin, amikacin, kanamycin, ethionamide, clofazimine, linezolid, delamanid, and bedaquiline). Mutations were divided into five groups according to their odds ratios, positive predictive values, false discovery rate-corrected p values, and 95% CIs: (1) associated with resistance; (2) associated with resistance—interim; (3) uncertain significance; (4) not associated with resistance—interim; and (5) not associated with resistance. The Wilcoxon rank-sum and Kruskal–Wallis tests were used to quantify the association between mutations and minimum inhibitory concentrations (MICs). Our dataset was compared with the first edition of the WHO catalogue.</div></div><div><h3>Findings</h3><div>We analysed 10 146 MTBC isolates, of which 9071 (89·4%) isolates were included in the final analysis. 744 (8·2%) isolates were resistant to rifampicin and 1339 (14·8%) to isoniazid. 208 (1·9%) of 11 065 mutations were classified as associated with resistance or associated with resistance—interim. 33 (97·1%) of 34 mutations in group 1 and 92 (52·9%) of 174 in group 2 also appeared in groups 1 or 2 of the WHO catalogue. Of 81 indel mutations in group 2, 15 (18·5%) were in the WHO catalogue. The newly discovered mutation <em>gyrA</em>_Ala288Asp was associated with levofloxacin resistance. MIC values for rifampicin, isoniazid, moxifloxacin, and levofloxacin corresponding to resistance mutations in group 1 were significantly different (p<0·0001), and 12 high-level resistance mutations were detected. 61 mutations in group 3 occurred as solo in at least five phenotypically susceptible isolates, but with MIC values moderately higher than other susceptible isolates. Among 945 phenotypically resistant but genotypically susceptible isolates, 433 (45·8%) were mutated for at least one efflux pump gene.</div></div><div><h3>Interpretation</h3><div>Our analysis reflects the complexity of drug resistance mutations in China and suggests that indel mutations, efflux pump genes, protein structure, and MICs should be fully considered in the WHO catalogue, especially in countries with a high tuberculosis burden.</div></div><div><h3>Funding</h3><div>National Key Research and Development Program of China and the Science and Technology Major Project of Tibetan Autonomous Region of Ch
{"title":"The catalogue of Mycobacterium tuberculosis mutations associated with drug resistance to 12 drugs in China from a nationwide survey: a genomic analysis","authors":"Shaojun Pei PhD , Zexuan Song MS , Wei Yang PhD , Wencong He PhD , Xichao Ou MS , Bing Zhao MS , Ping He MS , Yang Zhou MS , Hui Xia PhD , Shengfen Wang PhD , Prof Zhongwei Jia PhD , Timothy M Walker DPhil , Prof Yanlin Zhao PhD","doi":"10.1016/S2666-5247(24)00131-9","DOIUrl":"10.1016/S2666-5247(24)00131-9","url":null,"abstract":"<div><h3>Background</h3><div>WHO issued the first edition catalogue of <em>Mycobacterium tuberculosis</em> complex (MTBC) mutations associated with drug resistance in 2021. However, country-specific issues might lead to arising complex and additional drug-resistant mutations. We aimed to fully reflect the characteristics of drug resistance mutations in China.</div></div><div><h3>Methods</h3><div>We analysed MTBC isolates from the nationwide drug-resistant tuberculosis surveillance with 70 counties in 31 provinces, municipalities, and autonomous regions in China. Three types of MYCOTB plates were used to perform drug susceptibility testing for 12 antibiotics (rifampicin, isoniazid, ethambutol, levofloxacin, moxifloxacin, amikacin, kanamycin, ethionamide, clofazimine, linezolid, delamanid, and bedaquiline). Mutations were divided into five groups according to their odds ratios, positive predictive values, false discovery rate-corrected p values, and 95% CIs: (1) associated with resistance; (2) associated with resistance—interim; (3) uncertain significance; (4) not associated with resistance—interim; and (5) not associated with resistance. The Wilcoxon rank-sum and Kruskal–Wallis tests were used to quantify the association between mutations and minimum inhibitory concentrations (MICs). Our dataset was compared with the first edition of the WHO catalogue.</div></div><div><h3>Findings</h3><div>We analysed 10 146 MTBC isolates, of which 9071 (89·4%) isolates were included in the final analysis. 744 (8·2%) isolates were resistant to rifampicin and 1339 (14·8%) to isoniazid. 208 (1·9%) of 11 065 mutations were classified as associated with resistance or associated with resistance—interim. 33 (97·1%) of 34 mutations in group 1 and 92 (52·9%) of 174 in group 2 also appeared in groups 1 or 2 of the WHO catalogue. Of 81 indel mutations in group 2, 15 (18·5%) were in the WHO catalogue. The newly discovered mutation <em>gyrA</em>_Ala288Asp was associated with levofloxacin resistance. MIC values for rifampicin, isoniazid, moxifloxacin, and levofloxacin corresponding to resistance mutations in group 1 were significantly different (p<0·0001), and 12 high-level resistance mutations were detected. 61 mutations in group 3 occurred as solo in at least five phenotypically susceptible isolates, but with MIC values moderately higher than other susceptible isolates. Among 945 phenotypically resistant but genotypically susceptible isolates, 433 (45·8%) were mutated for at least one efflux pump gene.</div></div><div><h3>Interpretation</h3><div>Our analysis reflects the complexity of drug resistance mutations in China and suggests that indel mutations, efflux pump genes, protein structure, and MICs should be fully considered in the WHO catalogue, especially in countries with a high tuberculosis burden.</div></div><div><h3>Funding</h3><div>National Key Research and Development Program of China and the Science and Technology Major Project of Tibetan Autonomous Region of Ch","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 11","pages":"Article 100899"},"PeriodicalIF":20.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/S2666-5247(24)00152-6
Samuel Lipworth DPhil , Prof Derrick Crook FRCP , Prof A Sarah Walker PhD , Prof Tim Peto FRCP , Prof Nicole Stoesser DPhil
<div><h3>Background</h3><div>Antimicrobial resistance (AMR) in <em>Escherichia coli</em> is a global problem associated with substantial morbidity and mortality. AMR-associated genes are typically annotated based on similarity to variants in a curated reference database, with the implicit assumption that uncatalogued genetic variation within these is phenotypically unimportant. In this study, we evaluated the performance of the AMRFinder tool and, subsequently, the potential for discovering new AMR-associated gene families and characterising variation within existing ones to improve genotype-to-susceptibility phenotype predictions in <em>E coli</em>.</div></div><div><h3>Methods</h3><div>In this cross-sectional study of international genome sequence data, we assembled a global dataset of 9001 <em>E coli</em> sequences from five publicly available data collections predominantly deriving from human bloodstream infections from: Norway, Oxfordshire (UK), Thailand, the UK, and Sweden. 8555 of these sequences had linked antibiotic susceptibility data. Raw reads were assembled using Shovill and AMR genes (relevant to amoxicillin–clavulanic acid, ampicillin, ceftriaxone, ciprofloxacin, gentamicin, piperacillin–tazobactam, and trimethoprim) extracted using the National Center for Biotechnology Information AMRFinder tool (using both default and strict [100%] coverage and identity filters). We assessed the predictive value of the presence of these genes for predicting resistance or susceptibility against US Food and Drug Administration thresholds for major and very major errors. Mash was used to calculate the similarity between extracted genes using Jaccard distances. We empirically reclustered extracted gene sequences into AMR-associated gene families (≥70% match) and antibiotic-resistance genes (ARGs; 100% match) and categorised these according to their frequency in the dataset. Accumulation curves were simulated and correlations between gene frequency in the Oxfordshire and other datasets calculated using the Spearman coefficient. Firth regression was used to model the association between the presence of <em>bla</em><sub>TEM-1</sub> variants and amoxicillin–clavulanic acid or piperacillin–tazobactam resistance, adjusted for the presence of other relevant ARGs.</div></div><div><h3>Findings</h3><div>The performance of the AMRFinder database for genotype-to-phenotype predictions using strict 100% identity and coverage thresholds did not meet US Food and Drug Administration thresholds for any of the seven antibiotics evaluated. Relaxing filters to default settings improved sensitivity with a specificity cost. For all antibiotics, most explainable resistance was associated with the presence of a small number of genes. There was a proportion of resistance that could not be explained by known ARGs; this ranged from 75·1% for amoxicillin–clavulanic acid to 3·4% for ciprofloxacin. Only 18 199 (51·5%) of the 35 343 ARGs detected had a 100% identity and coverage mat
{"title":"Exploring uncatalogued genetic variation in antimicrobial resistance gene families in Escherichia coli: an observational analysis","authors":"Samuel Lipworth DPhil , Prof Derrick Crook FRCP , Prof A Sarah Walker PhD , Prof Tim Peto FRCP , Prof Nicole Stoesser DPhil","doi":"10.1016/S2666-5247(24)00152-6","DOIUrl":"10.1016/S2666-5247(24)00152-6","url":null,"abstract":"<div><h3>Background</h3><div>Antimicrobial resistance (AMR) in <em>Escherichia coli</em> is a global problem associated with substantial morbidity and mortality. AMR-associated genes are typically annotated based on similarity to variants in a curated reference database, with the implicit assumption that uncatalogued genetic variation within these is phenotypically unimportant. In this study, we evaluated the performance of the AMRFinder tool and, subsequently, the potential for discovering new AMR-associated gene families and characterising variation within existing ones to improve genotype-to-susceptibility phenotype predictions in <em>E coli</em>.</div></div><div><h3>Methods</h3><div>In this cross-sectional study of international genome sequence data, we assembled a global dataset of 9001 <em>E coli</em> sequences from five publicly available data collections predominantly deriving from human bloodstream infections from: Norway, Oxfordshire (UK), Thailand, the UK, and Sweden. 8555 of these sequences had linked antibiotic susceptibility data. Raw reads were assembled using Shovill and AMR genes (relevant to amoxicillin–clavulanic acid, ampicillin, ceftriaxone, ciprofloxacin, gentamicin, piperacillin–tazobactam, and trimethoprim) extracted using the National Center for Biotechnology Information AMRFinder tool (using both default and strict [100%] coverage and identity filters). We assessed the predictive value of the presence of these genes for predicting resistance or susceptibility against US Food and Drug Administration thresholds for major and very major errors. Mash was used to calculate the similarity between extracted genes using Jaccard distances. We empirically reclustered extracted gene sequences into AMR-associated gene families (≥70% match) and antibiotic-resistance genes (ARGs; 100% match) and categorised these according to their frequency in the dataset. Accumulation curves were simulated and correlations between gene frequency in the Oxfordshire and other datasets calculated using the Spearman coefficient. Firth regression was used to model the association between the presence of <em>bla</em><sub>TEM-1</sub> variants and amoxicillin–clavulanic acid or piperacillin–tazobactam resistance, adjusted for the presence of other relevant ARGs.</div></div><div><h3>Findings</h3><div>The performance of the AMRFinder database for genotype-to-phenotype predictions using strict 100% identity and coverage thresholds did not meet US Food and Drug Administration thresholds for any of the seven antibiotics evaluated. Relaxing filters to default settings improved sensitivity with a specificity cost. For all antibiotics, most explainable resistance was associated with the presence of a small number of genes. There was a proportion of resistance that could not be explained by known ARGs; this ranged from 75·1% for amoxicillin–clavulanic acid to 3·4% for ciprofloxacin. Only 18 199 (51·5%) of the 35 343 ARGs detected had a 100% identity and coverage mat","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 11","pages":"Article 100913"},"PeriodicalIF":20.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/S2666-5247(24)00171-X
Claire von Mollendorf, Tuya Mungun, Munkhchuluun Ulziibayar, Cattram D Nguyen, Purevsuren Batsaikhan, Bujinlkham Suuri, Dashtseren Luvsantseren, Dorj Narangerel, Bilegtsaikhan Tsolmon, Sodbayar Demberelsuren, Belinda D Ortika, Casey L Pell, Ashleigh Wee-Hee, Monica L Nation, Jason Hinds, Eileen M Dunne, E K Mulholland, Catherine Satzke
<p><strong>Background: </strong>Data on changes in pneumococcal serotypes in hospitalised children following the introduction of the pneumococcal conjugate vaccine (PCV) in low-income and middle-income countries are scarce. In 2016, Mongolia introduced the 13-valent PCV (PCV13) into the national immunisation programme. We aimed to describe the trend and impact of PCV13 introduction on pneumococcal carriage in hospitalised children aged 2-59 months with pneumonia in Mongolia over a 6-year period.</p><p><strong>Methods: </strong>In this active surveillance programme, children aged 2-59 months with pneumonia who met the study case definition (cough or difficulty breathing with either respiratory rate ≥50 beats per min, oxygen saturation <90%, or clinical diagnosis of severe pneumonia) were enrolled between April 1, 2015, and June 30, 2021, from four districts in Ulaanbaatar. We tested nasopharyngeal samples collected at enrolment for pneumococci using lytA real-time quantitative PCR and conducted molecular serotyping and detection of antimicrobial resistance (AMR) genes with DNA microarray. We used log-binomial regression to estimate prevalence ratios (PRs) of pneumococcal carriage, comparing prevalence in the periods before and after the introduction of PCV13 and between vaccinated and unvaccinated children for three outcomes: overall, PCV13 vaccine-type, and non-PCV13 vaccine-type carriage. PRs were adjusted with covariates that were identified by use of a directed acyclic graph, informed by relevant literature.</p><p><strong>Findings: </strong>A total of 17 688 children were enrolled, of whom 17 607 (99·5%) met the study case criteria. 6545 (42·5%) of 15 411 collected nasopharyngeal swabs were tested for pneumococci. In all age groups, a similar prevalence of pneumococcal carriage was shown between the pre-PCV13 period and post-PCV13 period (882 [48·0%] of 1837 vs 2174 [46·2%] of 4708; adjusted PR 0·98 [95% CI 0·92-1·04]; p=0·60). Overall, vaccine-type carriage reduced by 43·6% after the introduction of PCV13 (adjusted PR 0·56 [95% CI 0·51-0·62]; p<0·0001). Younger children (aged 2-23 months) showed a 47·7% reduction in vaccine-type carriage (95% CI 41·2-53·5; adjusted PR 0·52 [95% CI 0·46-0·59]; p<0·0001), whereas children aged 24-59 months had a 29·3% reduction (12·6-42·8; 0·71 [0·57-0·87]; p=0·0014). Prevalence of 6A, 6B, 14, 19F, and 23F decreased following the introduction of PCV13; however, 19F and 6A remained common (5·8% and 2·9%). Non-vaccine-type carriage increased (adjusted PR 1·49 [95% CI 1·32-1·67]), with 15A, NT2, and 15B/C being the most prevalent serotypes. Overall, 1761 (89·3%) of 1978 analysed samples contained at least one AMR gene. The percentage of samples with any AMR gene decreased with vaccine introduction (92·3% in the pre-PCV13 period vs 85·3% in the post-PCV13 period; adjusted odds ratio 0·49 [95% CI 0·34-0·70]), with similar decreases for samples with at least three AMR genes (46·8% vs 27·6%; 0·44 [0·36-0·55]).</p><p><
{"title":"Effect of pneumococcal conjugate vaccination on pneumococcal carriage in hospitalised children aged 2-59 months in Mongolia: an active pneumonia surveillance programme.","authors":"Claire von Mollendorf, Tuya Mungun, Munkhchuluun Ulziibayar, Cattram D Nguyen, Purevsuren Batsaikhan, Bujinlkham Suuri, Dashtseren Luvsantseren, Dorj Narangerel, Bilegtsaikhan Tsolmon, Sodbayar Demberelsuren, Belinda D Ortika, Casey L Pell, Ashleigh Wee-Hee, Monica L Nation, Jason Hinds, Eileen M Dunne, E K Mulholland, Catherine Satzke","doi":"10.1016/S2666-5247(24)00171-X","DOIUrl":"https://doi.org/10.1016/S2666-5247(24)00171-X","url":null,"abstract":"<p><strong>Background: </strong>Data on changes in pneumococcal serotypes in hospitalised children following the introduction of the pneumococcal conjugate vaccine (PCV) in low-income and middle-income countries are scarce. In 2016, Mongolia introduced the 13-valent PCV (PCV13) into the national immunisation programme. We aimed to describe the trend and impact of PCV13 introduction on pneumococcal carriage in hospitalised children aged 2-59 months with pneumonia in Mongolia over a 6-year period.</p><p><strong>Methods: </strong>In this active surveillance programme, children aged 2-59 months with pneumonia who met the study case definition (cough or difficulty breathing with either respiratory rate ≥50 beats per min, oxygen saturation <90%, or clinical diagnosis of severe pneumonia) were enrolled between April 1, 2015, and June 30, 2021, from four districts in Ulaanbaatar. We tested nasopharyngeal samples collected at enrolment for pneumococci using lytA real-time quantitative PCR and conducted molecular serotyping and detection of antimicrobial resistance (AMR) genes with DNA microarray. We used log-binomial regression to estimate prevalence ratios (PRs) of pneumococcal carriage, comparing prevalence in the periods before and after the introduction of PCV13 and between vaccinated and unvaccinated children for three outcomes: overall, PCV13 vaccine-type, and non-PCV13 vaccine-type carriage. PRs were adjusted with covariates that were identified by use of a directed acyclic graph, informed by relevant literature.</p><p><strong>Findings: </strong>A total of 17 688 children were enrolled, of whom 17 607 (99·5%) met the study case criteria. 6545 (42·5%) of 15 411 collected nasopharyngeal swabs were tested for pneumococci. In all age groups, a similar prevalence of pneumococcal carriage was shown between the pre-PCV13 period and post-PCV13 period (882 [48·0%] of 1837 vs 2174 [46·2%] of 4708; adjusted PR 0·98 [95% CI 0·92-1·04]; p=0·60). Overall, vaccine-type carriage reduced by 43·6% after the introduction of PCV13 (adjusted PR 0·56 [95% CI 0·51-0·62]; p<0·0001). Younger children (aged 2-23 months) showed a 47·7% reduction in vaccine-type carriage (95% CI 41·2-53·5; adjusted PR 0·52 [95% CI 0·46-0·59]; p<0·0001), whereas children aged 24-59 months had a 29·3% reduction (12·6-42·8; 0·71 [0·57-0·87]; p=0·0014). Prevalence of 6A, 6B, 14, 19F, and 23F decreased following the introduction of PCV13; however, 19F and 6A remained common (5·8% and 2·9%). Non-vaccine-type carriage increased (adjusted PR 1·49 [95% CI 1·32-1·67]), with 15A, NT2, and 15B/C being the most prevalent serotypes. Overall, 1761 (89·3%) of 1978 analysed samples contained at least one AMR gene. The percentage of samples with any AMR gene decreased with vaccine introduction (92·3% in the pre-PCV13 period vs 85·3% in the post-PCV13 period; adjusted odds ratio 0·49 [95% CI 0·34-0·70]), with similar decreases for samples with at least three AMR genes (46·8% vs 27·6%; 0·44 [0·36-0·55]).</p><p><","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"100929"},"PeriodicalIF":20.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1016/j.lanmic.2024.101012
Amirhossein Rahmati, Shima Shahbaz, Mohammed Osman, Jan Willen Cohen Tervaert, Shokrollah Elahi
{"title":"Blood transcriptomic analyses do not support SARS-CoV-2 persistence in patients with post-COVID-19 condition with chronic fatigue syndrome.","authors":"Amirhossein Rahmati, Shima Shahbaz, Mohammed Osman, Jan Willen Cohen Tervaert, Shokrollah Elahi","doi":"10.1016/j.lanmic.2024.101012","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101012","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101012"},"PeriodicalIF":20.9,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.lanmic.2024.06.001
Judith Kikhney, Inna Friesen, Solveigh Wiesener, Laura Kursawe, Christoph Loddenkemper, Josef Zündorf, Beate Häuser, Esther P Cónsul Tejero, Dinah V Schöning, Kurosh Sarbandi, Doris Hillemann, Martin Kuhns, Miriam S Stegemann, Frieder Pfäfflin, Frank-Rainer Klefisch, Volker Düsterhöft, Sebastian Haller, Anja V Laer, Tim Eckmanns, Emmanuelle Cambau, Sarah Tschudin-Sutter, Barbara Hasse, Anette Friedrichs, Bernd Panholzer, Walter Eichinger, Petra Gastmeier, Volkmar Falk, Annette Moter
Background: Mycobacterium chelonae is a rare cause of infective endocarditis that is difficult to diagnose and treat. After we found M chelonae in a series of patients, we aimed to investigate its role in cardiovascular prosthesis dysfunction and contamination of bioprostheses as a possible cause of infection.
Methods: In this collaborative microbiological study, we report on nine patients treated in three cardiovascular surgical departments in Germany, who were found to have M chelonae infection after receiving BioIntegral bioprostheses. We performed fluorescence in-situ hybridisation (FISH) combined with broad-range 16S rRNA gene amplification and sequencing (FISHseq) on samples of native cardiovascular tissue and explanted bioprosthetic material, as well as on 12 unused BioIntegral prostheses. We confirmed FISHseq findings with histological examination by staining for acid-fast bacilli, and M chelonae was differentiated from M abscessus by molecular techniques.
Findings: Between Dec 1, 2020, and Feb 28, 2022, we identified M chelonae in BioIntegral bioprostheses from three initial patients treated in Berlin that were explanted following dysfunction or suspected endocarditis, visualising morphologically intact FISH-positive mycobacteria. Despite negative mycobacterial culture, we also detected M chelonae in all 12 unused BioIntegral prostheses. The competent authorities in the EU prompted an alert, leading to the identification of six additional patients between March 1, 2022, and July 31, 2023. To find other cases of M chelonae endocarditis, we reviewed the FISHseq results of 1237 cardiovascular samples that were analysed between Jan 1, 2015, and Aug 31, 2022, including 295 samples from 228 bioprostheses supplied by other manufacturers. M chelonae was only detected in six of 41 patients who had received BioIntegral products.
Interpretation: Bioprostheses manufactured by BioIntegral Surgical might be colonised by M chelonae, which can lead to implant dysfunction. These infections are likely to be missed by conventional routine diagnostics and should be considered in patients with BioIntegral implants and suspected infection or dysfunction. Cases should be reported to public health and regulatory authorities. Routine safety testing of bioprostheses during manufacture should be reconsidered.
Funding: German Federal Ministry of Education and Research.
{"title":"Endocarditis associated with contamination of cardiovascular bioprostheses with Mycobacterium chelonae: a collaborative microbiological study.","authors":"Judith Kikhney, Inna Friesen, Solveigh Wiesener, Laura Kursawe, Christoph Loddenkemper, Josef Zündorf, Beate Häuser, Esther P Cónsul Tejero, Dinah V Schöning, Kurosh Sarbandi, Doris Hillemann, Martin Kuhns, Miriam S Stegemann, Frieder Pfäfflin, Frank-Rainer Klefisch, Volker Düsterhöft, Sebastian Haller, Anja V Laer, Tim Eckmanns, Emmanuelle Cambau, Sarah Tschudin-Sutter, Barbara Hasse, Anette Friedrichs, Bernd Panholzer, Walter Eichinger, Petra Gastmeier, Volkmar Falk, Annette Moter","doi":"10.1016/j.lanmic.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.06.001","url":null,"abstract":"<p><strong>Background: </strong>Mycobacterium chelonae is a rare cause of infective endocarditis that is difficult to diagnose and treat. After we found M chelonae in a series of patients, we aimed to investigate its role in cardiovascular prosthesis dysfunction and contamination of bioprostheses as a possible cause of infection.</p><p><strong>Methods: </strong>In this collaborative microbiological study, we report on nine patients treated in three cardiovascular surgical departments in Germany, who were found to have M chelonae infection after receiving BioIntegral bioprostheses. We performed fluorescence in-situ hybridisation (FISH) combined with broad-range 16S rRNA gene amplification and sequencing (FISHseq) on samples of native cardiovascular tissue and explanted bioprosthetic material, as well as on 12 unused BioIntegral prostheses. We confirmed FISHseq findings with histological examination by staining for acid-fast bacilli, and M chelonae was differentiated from M abscessus by molecular techniques.</p><p><strong>Findings: </strong>Between Dec 1, 2020, and Feb 28, 2022, we identified M chelonae in BioIntegral bioprostheses from three initial patients treated in Berlin that were explanted following dysfunction or suspected endocarditis, visualising morphologically intact FISH-positive mycobacteria. Despite negative mycobacterial culture, we also detected M chelonae in all 12 unused BioIntegral prostheses. The competent authorities in the EU prompted an alert, leading to the identification of six additional patients between March 1, 2022, and July 31, 2023. To find other cases of M chelonae endocarditis, we reviewed the FISHseq results of 1237 cardiovascular samples that were analysed between Jan 1, 2015, and Aug 31, 2022, including 295 samples from 228 bioprostheses supplied by other manufacturers. M chelonae was only detected in six of 41 patients who had received BioIntegral products.</p><p><strong>Interpretation: </strong>Bioprostheses manufactured by BioIntegral Surgical might be colonised by M chelonae, which can lead to implant dysfunction. These infections are likely to be missed by conventional routine diagnostics and should be considered in patients with BioIntegral implants and suspected infection or dysfunction. Cases should be reported to public health and regulatory authorities. Routine safety testing of bioprostheses during manufacture should be reconsidered.</p><p><strong>Funding: </strong>German Federal Ministry of Education and Research.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"100934"},"PeriodicalIF":20.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1016/j.lanmic.2024.100992
Daniela Melchiorri, Tamarie Rocke, Richard A Alm, Alexandra M Cameron, Valeria Gigante
Antimicrobial resistance continues to evolve and remains a leading cause of death worldwide, with children younger than 5 years being among those at the highest risk. Addressing antimicrobial resistance requires a comprehensive response, including infection prevention efforts, surveillance, stewardship, therapy appropriateness and access, and research and development. However, antimicrobial research and development is limited and lags behind the output of other fields, such as that of cancer or HIV research. The 2023 WHO analysis of the global antibacterial clinical pipeline serves as a tool to monitor and guide research and development efforts. The analysis emphasises the remaining gaps in developing a robust and effective antibacterial drug pipeline, drawing insights from trend analyses and assessment of the innovation potential of candidate antimicrobials. In the present analysis, we evaluated the activity of antibiotics against the new WHO bacterial priority pathogens list 2024, which reflects changing trends in resistance patterns, distribution of bacterial infections, and the emergence of new resistance mechanisms.
{"title":"Addressing urgent priorities in antibiotic development: insights from WHO 2023 antibacterial clinical pipeline analyses.","authors":"Daniela Melchiorri, Tamarie Rocke, Richard A Alm, Alexandra M Cameron, Valeria Gigante","doi":"10.1016/j.lanmic.2024.100992","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.100992","url":null,"abstract":"<p><p>Antimicrobial resistance continues to evolve and remains a leading cause of death worldwide, with children younger than 5 years being among those at the highest risk. Addressing antimicrobial resistance requires a comprehensive response, including infection prevention efforts, surveillance, stewardship, therapy appropriateness and access, and research and development. However, antimicrobial research and development is limited and lags behind the output of other fields, such as that of cancer or HIV research. The 2023 WHO analysis of the global antibacterial clinical pipeline serves as a tool to monitor and guide research and development efforts. The analysis emphasises the remaining gaps in developing a robust and effective antibacterial drug pipeline, drawing insights from trend analyses and assessment of the innovation potential of candidate antimicrobials. In the present analysis, we evaluated the activity of antibiotics against the new WHO bacterial priority pathogens list 2024, which reflects changing trends in resistance patterns, distribution of bacterial infections, and the emergence of new resistance mechanisms.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"100992"},"PeriodicalIF":20.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1016/j.lanmic.2024.101011
Lianwei Zhou, Minye Wang, Wenbo Li
{"title":"Genomic epidemiology of Salmonella: the need to consider vaccination history and nutritional status in resistance transmission studies.","authors":"Lianwei Zhou, Minye Wang, Wenbo Li","doi":"10.1016/j.lanmic.2024.101011","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101011","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101011"},"PeriodicalIF":20.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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