Pub Date : 2024-12-01DOI: 10.1016/S2666-5247(24)00171-X
Claire von Mollendorf PhD , Tuya Mungun MPH , Munkhchuluun Ulziibayar MPH , Cattram D Nguyen PhD , Purevsuren Batsaikhan MD , Bujinlkham Suuri MPH , Dashtseren Luvsantseren MPH , Dorj Narangerel MPH , Bilegtsaikhan Tsolmon PhD , Sodbayar Demberelsuren MD , Belinda D Ortika MMS , Casey L Pell BSc , Ashleigh Wee-Hee MSc , Monica L Nation MEpi , Jason Hinds PhD , Eileen M Dunne PhD , E K Mulholland MD , Catherine Satzke PhD
<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>lytA</em> 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.</div></div><div><h3>Findings</h3><div>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 <em>vs</em> 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 <em>vs</em> 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
{"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 PhD , Tuya Mungun MPH , Munkhchuluun Ulziibayar MPH , Cattram D Nguyen PhD , Purevsuren Batsaikhan MD , Bujinlkham Suuri MPH , Dashtseren Luvsantseren MPH , Dorj Narangerel MPH , Bilegtsaikhan Tsolmon PhD , Sodbayar Demberelsuren MD , Belinda D Ortika MMS , Casey L Pell BSc , Ashleigh Wee-Hee MSc , Monica L Nation MEpi , Jason Hinds PhD , Eileen M Dunne PhD , E K Mulholland MD , Catherine Satzke PhD","doi":"10.1016/S2666-5247(24)00171-X","DOIUrl":"10.1016/S2666-5247(24)00171-X","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>lytA</em> 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.</div></div><div><h3>Findings</h3><div>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 <em>vs</em> 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 <em>vs</em> 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 ","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100929"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.lanmic.2024.07.004
Olivo Miotto PhD , Prof Alfred Amambua-Ngwa PhD , Lucas N Amenga-Etego PhD , Prof Muzamil M Abdel Hamid PhD , Prof Ishag Adam PhD , Enoch Aninagyei PhD , Tobias Apinjoh PhD , Prof Gordon A Awandare PhD , Philip Bejon PhD , Gwladys I Bertin PhD , Prof Marielle Bouyou-Akotet MD , Antoine Claessens PhD , Prof David J Conway PhD , Prof Umberto D'Alessandro PhD , Prof Mahamadou Diakite DPhil , Prof Abdoulaye Djimdé PhD , Prof Arjen M Dondorp MD , Patrick Duffy MD , Rick M Fairhurst PhD , Caterina I Fanello PhD , Prof Dominic P Kwiatkowski FRS
Background
The population structure of the malaria parasite Plasmodium falciparum can reveal underlying adaptive evolutionary processes. Selective pressures to maintain complex genetic backgrounds can encourage inbreeding, producing distinct parasite clusters identifiable by population structure analyses.
Methods
We analysed population structure in 3783 P falciparum genomes from 21 countries across Africa, provided by the MalariaGEN Pf7 dataset. We used Principal Coordinate Analysis to cluster parasites, identity by descent (IBD) methods to identify genomic regions shared by cluster members, and linkage analyses to establish their co-inheritance patterns. Structural variants were reconstructed by de novo assembly and verified by long-read sequencing.
Findings
We identified a strongly differentiated cluster of parasites, named AF1, comprising 47 (1·2%) of 3783 samples analysed, distributed over 13 countries across Africa, at locations over 7000 km apart. Members of this cluster share a complex genetic background, consisting of up to 23 loci harbouring many highly differentiated variants, rarely observed outside the cluster. IBD analyses revealed common ancestry at these loci, irrespective of sampling location. Outside the shared loci, however, AF1 members appear to outbreed with sympatric parasites. The AF1 differentiated variants comprise structural variations, including a gene conversion involving the dblmsp and dblmsp2 genes, and numerous single nucleotide polymorphisms. Several of the genes harbouring these mutations are functionally related, often involved in interactions with red blood cells including invasion, egress, and erythrocyte antigen export.
Interpretation
We propose that AF1 parasites have adapted to some unidentified evolutionary niche, probably involving interactions with host erythrocytes. This adaptation involves a complex compendium of interacting variants that are rarely observed in Africa, which remains mostly intact despite recombination events. The term cryptotype was used to describe a common background interspersed with genomic regions of local origin.
{"title":"Identification of complex Plasmodium falciparum genetic backgrounds circulating in Africa: a multicountry genomic epidemiology analysis","authors":"Olivo Miotto PhD , Prof Alfred Amambua-Ngwa PhD , Lucas N Amenga-Etego PhD , Prof Muzamil M Abdel Hamid PhD , Prof Ishag Adam PhD , Enoch Aninagyei PhD , Tobias Apinjoh PhD , Prof Gordon A Awandare PhD , Philip Bejon PhD , Gwladys I Bertin PhD , Prof Marielle Bouyou-Akotet MD , Antoine Claessens PhD , Prof David J Conway PhD , Prof Umberto D'Alessandro PhD , Prof Mahamadou Diakite DPhil , Prof Abdoulaye Djimdé PhD , Prof Arjen M Dondorp MD , Patrick Duffy MD , Rick M Fairhurst PhD , Caterina I Fanello PhD , Prof Dominic P Kwiatkowski FRS","doi":"10.1016/j.lanmic.2024.07.004","DOIUrl":"10.1016/j.lanmic.2024.07.004","url":null,"abstract":"<div><h3>Background</h3><div>The population structure of the malaria parasite <em>Plasmodium falciparum</em> can reveal underlying adaptive evolutionary processes. Selective pressures to maintain complex genetic backgrounds can encourage inbreeding, producing distinct parasite clusters identifiable by population structure analyses.</div></div><div><h3>Methods</h3><div>We analysed population structure in 3783 <em>P falciparum</em> genomes from 21 countries across Africa, provided by the MalariaGEN Pf7 dataset. We used Principal Coordinate Analysis to cluster parasites, identity by descent (IBD) methods to identify genomic regions shared by cluster members, and linkage analyses to establish their co-inheritance patterns. Structural variants were reconstructed by de novo assembly and verified by long-read sequencing.</div></div><div><h3>Findings</h3><div>We identified a strongly differentiated cluster of parasites, named AF1, comprising 47 (1·2%) of 3783 samples analysed, distributed over 13 countries across Africa, at locations over 7000 km apart. Members of this cluster share a complex genetic background, consisting of up to 23 loci harbouring many highly differentiated variants, rarely observed outside the cluster. IBD analyses revealed common ancestry at these loci, irrespective of sampling location. Outside the shared loci, however, AF1 members appear to outbreed with sympatric parasites. The AF1 differentiated variants comprise structural variations, including a gene conversion involving the <em>dblmsp</em> and <em>dblmsp2</em> genes, and numerous single nucleotide polymorphisms. Several of the genes harbouring these mutations are functionally related, often involved in interactions with red blood cells including invasion, egress, and erythrocyte antigen export.</div></div><div><h3>Interpretation</h3><div>We propose that AF1 parasites have adapted to some unidentified evolutionary niche, probably involving interactions with host erythrocytes. This adaptation involves a complex compendium of interacting variants that are rarely observed in Africa, which remains mostly intact despite recombination events. The term cryptotype was used to describe a common background interspersed with genomic regions of local origin.</div></div><div><h3>Funding</h3><div>Bill & Melinda Gates Foundation.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100941"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630078","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 : 2024-12-01DOI: 10.1016/j.lanmic.2024.06.004
Jenny L Schnyder MD , Bache E Bache MSc , Matthijs R A Welkers PhD , René Spijker MSc , Prof Frieder Schaumburg MD , Abraham Goorhuis PhD , Martin P Grobusch FRCP , Hanna K de Jong PhD
Background
Yellow fever vaccination is considered to provide effective long-term immunity. However, yellow fever breakthrough infections in vaccinated patients have been reported. In this systematic review and meta-analysis we aimed to identify and summarise all documented symptomatic yellow fever breakthrough infections in the literature occurring less than 10 years and 10 years or more after primary yellow fever vaccination.
Methods
We searched MEDLINE (Ovid), Embase (Ovid), and Global Index Medicus for records published between Jan 1, 1936 (introduction of yellow fever vaccination) and June 16, 2023. We included prospective and retrospective cohort studies, case series and reports, and epidemiological reports from national and international health organisations reporting symptomatic yellow fever among individuals vaccinated 30 days or more before symptom onset. We excluded cases vaccinated less than 30 days before symptom onset. The primary outcome for the meta-analysis was the proportions of vaccinees among virologically confirmed and probable cases of yellow fever (IgM seroconversion without seroconversion to other flaviviruses). Risk of bias was assessed with an adapted version of the Newcastle-Ottawa Scale. Records of moderate or good quality (probable or confirmed yellow fever diagnosis with documented proof of previous vaccination) were included for random-effects meta-analysis. This systematic review and meta-analysis is registered with PROSPERO, number CRD42023450205.
Findings
After reviewing 1975 records, 37 records reported a total of 6951 yellow fever cases, of which 537 were vaccinated. 31 records were of low quality. Nine confirmed and 24 probable cases with proof of previous yellow fever vaccination were identified, all from Brazil. Confirmed cases were vaccinated 3 months to 3 years before symptom onset; of these patients two fell severely ill and died. The pooled proportion of verified yellow fever breakthrough infections among probable and confirmed cases was 3% (95% CI 1–19%). No confirmed yellow fever breakthrough infections were identified occurring 10 years or more after yellow fever vaccination.
Interpretation
Yellow fever breakthrough infections documented in literature are rare, and not necessarily more common 10 years or more after primary yellow fever vaccination. This finding suggests that a single dose of yellow fever vaccination is sufficient to provide lifelong protective immunity against symptomatic yellow fever.
{"title":"Yellow fever breakthrough infections after yellow fever vaccination: a systematic review and meta-analysis","authors":"Jenny L Schnyder MD , Bache E Bache MSc , Matthijs R A Welkers PhD , René Spijker MSc , Prof Frieder Schaumburg MD , Abraham Goorhuis PhD , Martin P Grobusch FRCP , Hanna K de Jong PhD","doi":"10.1016/j.lanmic.2024.06.004","DOIUrl":"10.1016/j.lanmic.2024.06.004","url":null,"abstract":"<div><h3>Background</h3><div>Yellow fever vaccination is considered to provide effective long-term immunity. However, yellow fever breakthrough infections in vaccinated patients have been reported. In this systematic review and meta-analysis we aimed to identify and summarise all documented symptomatic yellow fever breakthrough infections in the literature occurring less than 10 years and 10 years or more after primary yellow fever vaccination.</div></div><div><h3>Methods</h3><div>We searched MEDLINE (Ovid), Embase (Ovid), and Global Index Medicus for records published between Jan 1, 1936 (introduction of yellow fever vaccination) and June 16, 2023. We included prospective and retrospective cohort studies, case series and reports, and epidemiological reports from national and international health organisations reporting symptomatic yellow fever among individuals vaccinated 30 days or more before symptom onset. We excluded cases vaccinated less than 30 days before symptom onset. The primary outcome for the meta-analysis was the proportions of vaccinees among virologically confirmed and probable cases of yellow fever (IgM seroconversion without seroconversion to other flaviviruses). Risk of bias was assessed with an adapted version of the Newcastle-Ottawa Scale. Records of moderate or good quality (probable or confirmed yellow fever diagnosis with documented proof of previous vaccination) were included for random-effects meta-analysis. This systematic review and meta-analysis is registered with PROSPERO, number CRD42023450205.</div></div><div><h3>Findings</h3><div>After reviewing 1975 records, 37 records reported a total of 6951 yellow fever cases, of which 537 were vaccinated. 31 records were of low quality. Nine confirmed and 24 probable cases with proof of previous yellow fever vaccination were identified, all from Brazil. Confirmed cases were vaccinated 3 months to 3 years before symptom onset; of these patients two fell severely ill and died. The pooled proportion of verified yellow fever breakthrough infections among probable and confirmed cases was 3% (95% CI 1–19%). No confirmed yellow fever breakthrough infections were identified occurring 10 years or more after yellow fever vaccination.</div></div><div><h3>Interpretation</h3><div>Yellow fever breakthrough infections documented in literature are rare, and not necessarily more common 10 years or more after primary yellow fever vaccination. This finding suggests that a single dose of yellow fever vaccination is sufficient to provide lifelong protective immunity against symptomatic yellow fever.</div></div><div><h3>Funding</h3><div>None.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100937"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142630084","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 : 2024-12-01DOI: 10.1016/j.lanmic.2024.100959
Qian-qian Du , Ya-hong Hu , Qing-hong Meng , Dan Yu , Kai-hu Yao
{"title":"Unique factors to consider when exploring the surge in reported pertussis cases in China","authors":"Qian-qian Du , Ya-hong Hu , Qing-hong Meng , Dan Yu , Kai-hu Yao","doi":"10.1016/j.lanmic.2024.100959","DOIUrl":"10.1016/j.lanmic.2024.100959","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100959"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009669","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 : 2024-12-01DOI: 10.1016/j.lanmic.2024.100970
Xi Li , Jiayao Yao , Longjie Zhou , Hua Zhou , Jintao He
{"title":"Endemicity and diversification of Morganella spp and carbapenemase-producing Morganella spp","authors":"Xi Li , Jiayao Yao , Longjie Zhou , Hua Zhou , Jintao He","doi":"10.1016/j.lanmic.2024.100970","DOIUrl":"10.1016/j.lanmic.2024.100970","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100970"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142113314","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 : 2024-12-01DOI: 10.1016/j.lanmic.2024.100994
Joziana Muniz de Paiva Barçante , José Cherem
{"title":"Surge in Oropouche fever: the tip of the iceberg in a new public health challenge in Brazil","authors":"Joziana Muniz de Paiva Barçante , José Cherem","doi":"10.1016/j.lanmic.2024.100994","DOIUrl":"10.1016/j.lanmic.2024.100994","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100994"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142356165","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 : 2024-12-01DOI: 10.1016/S2666-5247(24)00169-1
Yuan Li PhD , Joy Rivers BS , Saundra Mathis BS , Zhongya Li BS , Sopio Chochua MD PhD , Benjamin J Metcalf PhD , Bernard Beall PhD , Lesley McGee PhD
<div><h3>Background</h3><div>Clusters of invasive group A streptococcal (iGAS) infection, linked to genomically closely related group A streptococcal (GAS) isolates (referred to as genomic clusters), pose public health threats, and are increasingly identified through whole-genome sequencing (WGS) analysis. In this study, we aimed to assess the risk of genomic cluster formation among iGAS cases not already part of existing genomic clusters.</div></div><div><h3>Methods</h3><div>In this WGS and population-based surveillance study, we analysed iGAS case isolates from the Active Bacterial Core surveillance (ABCs), which is part of the US Centers for Disease Control and Prevention’s Emerging Infections Program, in ten US states from Jan 1, 2015, to Dec 31, 2019. We included all residents in ABCs sites with iGAS infections meeting the case definition and excluded non-conforming GAS infections and cases with whole-genome assemblies of the isolate containing fewer than 1·5 million total bases or more than 150 contigs. For iGAS cases we collected basic demographics, underlying conditions, and risk factors for infection from medical records, and for isolates we included <em>emm</em> types, antimicrobial resistance, and presence of virulence-related genes. Two iGAS cases were defined as genomically clustered if their isolates differed by three or less single-nucleotide variants. An iGAS case not clustered with any previous cases at the time of detection, with a minimum trace-back time of 1 year, was defined as being at risk of cluster formation. We monitored each iGAS case at risk for a minimum of 1 year to identify any cluster formation event, defined as the detection of a subsequent iGAS case clustered with the case at risk. We used the Kaplan–Meier method to estimate the cumulative incidence of cluster formation events over time. We used Cox regression to assess associations between features of cases at risk upon detection and subsequent cluster formation. We developed a random survival forest machine-learning model based on a derivation cohort (random selection of 50% of cases at risk) to predict cluster formation risk. This model was validated using a validation cohort consisting of the remaining 50% of cases at risk.</div></div><div><h3>Findings</h3><div>We identified 2764 iGAS cases at risk from 2016 to 2018, of which 656 (24%) formed genomic clusters by the end of 2019. Overall, the cumulative incidence of cluster formation was 0·057 (95% CI 0·048–0·066) at 30 days after detection, 0·12 (0·11–0·13) at 90 days after detection, and 0·16 (0·15–0·18) at 180 days after detection. A higher risk of cluster formation was associated with <em>emm</em> type (adjusted hazard ratio as compared with <em>emm</em>89 was 2·37 [95% CI 1·71–3·30] for <em>emm</em>1, 2·72 [1·82–4·06] for <em>emm</em>3, 2·28 [1·49–3·51] for <em>emm</em>6, 1·47 [1·05–2·06] for <em>emm</em>12, and 2·21 [1·38–3·56] for <em>emm</em>92), homelessness (1·42 [1·01–1·99]), injection drug use (2·0
背景：侵袭性 A 组链球菌（iGAS）感染集群与基因组学上密切相关的 A 组链球菌（GAS）分离株相关联（称为基因组集群），对公共卫生构成威胁，并且越来越多地通过全基因组测序（WGS）分析进行鉴定。在本研究中，我们旨在评估尚未加入现有基因组集群的 iGAS 病例形成基因组集群的风险：在这项基于 WGS 和人群监测的研究中，我们分析了 2015 年 1 月 1 日至 2019 年 12 月 31 日期间美国十个州主动细菌核心监测（ABCs）中的 iGAS 病例分离物，该监测是美国疾病控制与预防中心新发感染项目的一部分。我们纳入了ABCs站点中所有符合病例定义的iGAS感染居民，并排除了不符合GAS感染和分离物全基因组组装总碱基少于100-500万或等位基因超过150个的病例。对于 iGAS 病例，我们从医疗记录中收集了基本的人口统计学特征、基础病症和感染风险因素；对于分离物，我们收集了 emm 类型、抗菌药耐药性和毒力相关基因的存在情况。如果两个 iGAS 病例的分离物存在三个或更少的单核苷酸变异，则将其定义为基因组集群病例。如果一个 iGAS 病例在检测时未与之前的任何病例发生聚类，且追溯时间至少为 1 年，则被定义为有形成聚类的风险。我们对每个有风险的 iGAS 病例进行了至少 1 年的监测，以确定是否有集群形成事件，集群形成事件的定义是随后检测到的 iGAS 病例与有风险的病例聚集在一起。我们使用 Kaplan-Meier 法估算了随着时间推移集群形成事件的累积发生率。我们使用 Cox 回归法来评估高危病例检测特征与后续集群形成之间的关联。我们在衍生队列（随机选择 50%的高危病例）的基础上开发了一个随机生存森林机器学习模型，用于预测集群形成风险。该模型通过由剩余 50% 高危病例组成的验证队列进行了验证：从2016年到2018年，我们共发现了2764例iGAS高危病例，其中656例（24%）在2019年底前形成了基因组集群。总体而言，集群形成的累积发生率在检测后30天为0-057（95% CI 0-048-066），检测后90天为0-12（0-11-0-13），检测后180天为0-16（0-15-0-18）。集群形成的较高风险与 emm 类型有关（与 emm89 相比，emm1 的调整危险比为 2-37 [95% CI 1-71-3-30]，emm3 为 2-72 [1-82-4-06]，emm6 为 2-28 [1-49-3-51]，emm12 为 1-47 [1-05-2-06]，emm3 为 2-21 [1-38-3-06]）、在多变量 Cox 回归分析中，还包括无家可归者（1-42 [1-01-1-99]）、注射吸毒（2-08 [1-59-2-72]）、居住在长期护理机构（1-78 [1-29-2-45]）和秋冬季节（1-34 [1-14-1-57]）。机器学习模型将验证队列（n=1382）分为低风险组（n=370）、中度风险组（n=738）和高风险组（n=274）。低风险组的 90 天集群形成风险为 0-03（95% CI 0-01-0-05），中度风险组为 0-10（0-08-0-13），高度风险组为 0-21（0-17-0-25）。这些结果与衍生队列的交叉验证结果一致：利用基于人群的监测数据，我们发现 iGAS 病例的病原体、宿主和环境因素与后续基因组集群形成的可能性增加有关。预测模型可以持续识别高风险群体，为预防策略提供依据，但未来还需要改进模型，纳入宿主接触模式和对 GAS 的免疫力等其他潜在风险因素，以提高其预测性能：美国疾病控制和预防中心。
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Pub Date : 2024-12-01DOI: 10.1016/S2666-5247(24)00175-7
Andrew J Lee PhD , Stephen Carson PhD , Marina I Reyne PhD , Andrew Marshall PhD , Daniel Moody PhD , Danielle M Allen PhD , Pearce Allingham MSc , Ashley Levickas BSc , Arthur Fitzgerald MSc , Stephen H Bell PhD , Jonathan Lock MSc , Jonathon D Coey PhD , Cormac McSparron PhD , Behnam F Nejad PhD , Evan P Troendle PhD , Prof David A Simpson PhD , David G Courtney PhD , Gisli G Einarsson PhD , James P McKenna PhD , Derek J Fairley PhD , Connor G G Bamford PhD
Background
Influenza A viruses (IAVs) are significant pathogens of humans and other animals. Although endemic in humans and birds, novel IAV strains can emerge, jump species, and cause epidemics, like the latest variant of H5N1. Wastewater-based epidemiology (WBE) has been shown capable of detecting human IAVs. We aimed to assess whether whole-genome sequencing (WGS) of IAVs from wastewater is possible and can be used to discriminate between circulating strains of human and any non-human IAVs, such as those of avian origin.
Methods
Using a pan-IAV RT-quantitative PCR assay, six wastewater treatment works (WWTWs) across Northern Ireland were screened from Aug 1 to Dec 5, 2022. A nanopore WGS approach was used to sequence RT-qPCR-positive samples. Phylogenetic analysis of sequences relative to currently circulating human and non-human IAVs was performed. For comparative purposes, clinical data (PCR test results) were supplied by The Regional Virus Laboratory, Belfast Health and Social Care Trust (Belfast, Northern Ireland, UK).
Findings
We detected a dynamic IAV signal in wastewater from Sept 5, 2022, onwards across Northern Ireland, which did not show a clear positive relationship with the clinical data obtained for the region. Meta (mixed strain) whole-genome sequences were generated from wastewater samples displaying homology to only human and avian IAV strains. The relative proportion of IAV reads of human versus avian origin differed across time and sample site. A diversity in subtypes and lineages was detected (eg, H1N1, H3N2, and several avian). Avian segment 8 related to those found in recent H5N1 clade 2.3.4.4b was identified.
Interpretation
WBE affords a means to monitor circulating human and avian IAV strains and provide crucial genetic information. As such, WBE can provide rapid, cost-effective, year-round One Health surveillance to help control IAV epidemic and pandemic-related threats. However, optimisation of WBE protocols are necessary to ensure observed wastewater signals not only correlate with clinical case data, but yield information on the wider environmental pan-influenz-ome.
{"title":"Wastewater monitoring of human and avian influenza A viruses in Northern Ireland: a genomic surveillance study","authors":"Andrew J Lee PhD , Stephen Carson PhD , Marina I Reyne PhD , Andrew Marshall PhD , Daniel Moody PhD , Danielle M Allen PhD , Pearce Allingham MSc , Ashley Levickas BSc , Arthur Fitzgerald MSc , Stephen H Bell PhD , Jonathan Lock MSc , Jonathon D Coey PhD , Cormac McSparron PhD , Behnam F Nejad PhD , Evan P Troendle PhD , Prof David A Simpson PhD , David G Courtney PhD , Gisli G Einarsson PhD , James P McKenna PhD , Derek J Fairley PhD , Connor G G Bamford PhD","doi":"10.1016/S2666-5247(24)00175-7","DOIUrl":"10.1016/S2666-5247(24)00175-7","url":null,"abstract":"<div><h3>Background</h3><div>Influenza A viruses (IAVs) are significant pathogens of humans and other animals. Although endemic in humans and birds, novel IAV strains can emerge, jump species, and cause epidemics, like the latest variant of H5N1. Wastewater-based epidemiology (WBE) has been shown capable of detecting human IAVs. We aimed to assess whether whole-genome sequencing (WGS) of IAVs from wastewater is possible and can be used to discriminate between circulating strains of human and any non-human IAVs, such as those of avian origin.</div></div><div><h3>Methods</h3><div>Using a pan-IAV RT-quantitative PCR assay, six wastewater treatment works (WWTWs) across Northern Ireland were screened from Aug 1 to Dec 5, 2022. A nanopore WGS approach was used to sequence RT-qPCR-positive samples. Phylogenetic analysis of sequences relative to currently circulating human and non-human IAVs was performed. For comparative purposes, clinical data (PCR test results) were supplied by The Regional Virus Laboratory, Belfast Health and Social Care Trust (Belfast, Northern Ireland, UK).</div></div><div><h3>Findings</h3><div>We detected a dynamic IAV signal in wastewater from Sept 5, 2022, onwards across Northern Ireland, which did not show a clear positive relationship with the clinical data obtained for the region. Meta (mixed strain) whole-genome sequences were generated from wastewater samples displaying homology to only human and avian IAV strains. The relative proportion of IAV reads of human versus avian origin differed across time and sample site. A diversity in subtypes and lineages was detected (eg, H1N1, H3N2, and several avian). Avian segment 8 related to those found in recent H5N1 clade 2.3.4.4b was identified.</div></div><div><h3>Interpretation</h3><div>WBE affords a means to monitor circulating human and avian IAV strains and provide crucial genetic information. As such, WBE can provide rapid, cost-effective, year-round One Health surveillance to help control IAV epidemic and pandemic-related threats. However, optimisation of WBE protocols are necessary to ensure observed wastewater signals not only correlate with clinical case data, but yield information on the wider environmental pan-influenz-ome.</div></div><div><h3>Funding</h3><div>Department of Health for Northern Ireland.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100933"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142477433","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 : 2024-12-01DOI: 10.1016/j.lanmic.2024.06.001
Judith Kikhney PhD , Inna Friesen MD , Solveigh Wiesener MD , Laura Kursawe MSc , Prof Christoph Loddenkemper MD , Josef Zündorf MD , Beate Häuser , Esther P Cónsul Tejero , Dinah v Schöning MD , Kurosh Sarbandi , Doris Hillemann PhD , Martin Kuhns MD , Miriam S Stegemann MD , Frieder Pfäfflin MD , Frank-Rainer Klefisch MD , Volker Düsterhöft MD , Sebastian Haller MD , Anja v Laer MD , Prof Tim Eckmanns MD , Prof Emmanuelle Cambau MD , Annette Moter MD
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 PhD , Inna Friesen MD , Solveigh Wiesener MD , Laura Kursawe MSc , Prof Christoph Loddenkemper MD , Josef Zündorf MD , Beate Häuser , Esther P Cónsul Tejero , Dinah v Schöning MD , Kurosh Sarbandi , Doris Hillemann PhD , Martin Kuhns MD , Miriam S Stegemann MD , Frieder Pfäfflin MD , Frank-Rainer Klefisch MD , Volker Düsterhöft MD , Sebastian Haller MD , Anja v Laer MD , Prof Tim Eckmanns MD , Prof Emmanuelle Cambau MD , Annette Moter MD","doi":"10.1016/j.lanmic.2024.06.001","DOIUrl":"10.1016/j.lanmic.2024.06.001","url":null,"abstract":"<div><h3>Background</h3><div><em>Mycobacterium chelonae</em> is a rare cause of infective endocarditis that is difficult to diagnose and treat. After we found <em>M chelonae</em> 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.</div></div><div><h3>Methods</h3><div>In this collaborative microbiological study, we report on nine patients treated in three cardiovascular surgical departments in Germany, who were found to have <em>M chelonae</em> 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 <em>M chelonae</em> was differentiated from <em>M abscessus</em> by molecular techniques.</div></div><div><h3>Findings</h3><div>Between Dec 1, 2020, and Feb 28, 2022, we identified <em>M chelonae</em> 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 <em>M chelonae</em> 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 <em>M chelonae</em> 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. <em>M chelonae</em> was only detected in six of 41 patients who had received BioIntegral products.</div></div><div><h3>Interpretation</h3><div>Bioprostheses manufactured by BioIntegral Surgical might be colonised by <em>M chelonae</em>, 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.</div></div><div><h3>Funding</h3><div>German Federal Ministry of Education and Research.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 12","pages":"Article 100934"},"PeriodicalIF":20.9,"publicationDate":"2024-12-01","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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