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Njamkepo, E.

Publications and source records attributed to Njamkepo, E..

7 recordsLinked to original sources

Continued genomic surveillance of Vibrio cholerae O1 isolates from cholera cases in Europe, 2023-2024

Background: Following the global resurgence of cholera in 2022, 51 cholera cases were reported by European countries. We previously characterised 49 Vibrio cholerae O1 isolates from these cases using whole genome sequencing. In 2023 and 2024, 59 additional cholera cases were reported by 11 European countries. Aim: We aimed to confirm that V. cholerae O1 isolates associated with cholera cases reported in Europe in 2023-2024 belonged to the epidemic seventh pandemic El Tor (7PET) lineage rather than to non-epidemic V. cholerae O1 lineages, and to characterise their virulence, antimicrobial resistance (AMR) determinants and phylogenetic relationships. Methods: Fifty V. cholerae O1 isolates were available for whole genome sequencing, of which 49 yielded genomes of sufficient quality for analysis. Genomes were analysed together with more than 1,500 publicly available 7PET genomes to place the European isolates into a global phylogenetic context. Results: All 49 genomes belonged to the 7PET lineage and Wave 3. Four sub-lineages were identified: BD1.2 (2/49), AFR12 (6/49), AFR13 (8/49) and Pre-AFR15 (33/49). The predominance of Pre-AFR15 confirms its continued contribution to the ongoing global cholera resurgence. In contrast to our 2022 survey, eight highly drug-resistant AFR13 isolates were detected, documenting the international spread of this highly drug-resistant clone resistant to multiple first-line antimicrobial agents. Conclusion: Whole genome sequencing should be routinely used by reference laboratories to distinguish epidemic 7PET from non-epidemic V. cholerae O1 lineages and to monitor the emergence and international spread of AMR clones. Continued collaborative genomic surveillance of travel-associated cholera cases can provide early insights into the emergence, international spread and antimicrobial resistance of 7PET sub-lineages.

genomics↗

Evolution of multidrug-resistant IncC plasmids in the seventh pandemic Vibrio cholerae O1 El Tor lineage between 1979 and 2024

IncC plasmids played an important role in driving antimicrobial drug resistance development in the seventh pandemic Vibrio cholerae O1 El Tor (7PET) lineage during the 1970s and these have begun to re-emerge. In this study, we investigated a comprehensive dataset for 28 complete IncC plasmids -- including 17 newly sequenced plasmid genomes -- from 7PET isolates collected on various continents between 1979 and 2024 and distributed across the global phylogenetic tree for 7PET isolates. IncC type 2 predominated among the V. cholerae plasmids studied, and five new core genome sequence types (cgSTs) were identified. The antimicrobial resistance genes (ARGs) were arranged in islands inserted at specific hotspots within the common IncC backbone and were significantly associated with IncC types or islands. The IncC plasmid backbone has remained stable over the last 50 years, but the ARGs and their associated genomic islands displayed remarkable diversity, underscoring the complex evolution patterns of the 7PET lineage of V. cholerae and its considerable adaptability under selective pressure.

microbiology↗

Global diversity and evolution of Salmonella Panama, an understudied serovar causing gastrointestinal and invasive disease worldwide: a genomic epidemiology study

BackgroundNontyphoidal Salmonella (NTS) is a globally important bacterial pathogen, typically associated with foodborne gastrointestinal infection. Some NTS serovars can also colonise normally sterile sites in humans to cause invasive NTS (iNTS) disease. One understudied Salmonella enterica serovar which is responsible for a significant number of cases of iNTS disease is Panama. Despite global dissemination, numerous outbreaks, and a reported association with iNTS disease, S. enterica serovar Panama (S. Panama) has not been investigated in detail. MethodsUsing combined epidemiological and whole genome sequencing data we analysed 836 S. Panama genomes derived from historical collections, national surveillance datasets, and publicly available data. The collection represents all inhabited continents and includes isolates collected between 1931 and 2019. Maximum likelihood and Bayesian phylodynamic approaches were used to determine population structure & evolutionary history, and to infer geo-temporal dissemination. A combination of different bioinformatic approaches utilising short-read and long-read data were used to characterise geographic and clade-specific trends in antimicrobial resistance (AMR), and genetic markers for invasiveness. FindingsWe identified the presence of multiple geographically linked S. Panama clades, and regional trends in antimicrobial resistance profiles. Most isolates were pan-susceptible to antibiotics and belonged to clades circulating in the United States of America, Latin America, and the Caribbean. Multidrug resistant (MDR) isolates in our collection belonged to two phylogenetic clades circulating in Europe and Asia/Oceania, which exhibited the highest invasiveness indices based on the conservation of 196 extra-intestinal predictor genes. InterpretationThis first large-scale phylogenetic analysis of S. Panama revealed important information about population structure, AMR, global ecology, and genetic markers of invasiveness of the identified genomic subtypes. Our findings provide an important baseline for understanding S. Panama infection in the future. The presence of MDR clades with an elevated invasiveness index should be monitored by ongoing surveillance as such clades may pose an increased public health risk. FundingThe project was supported by both a Global Challenges Research Fund (GCRF) data & resources grant BBS/OS/GC/000009D and the BBSRC Core Capability Grant to the Earlham Institute BB/CCG1720/1. JCDH received a Wellcome Trust Investigator award (grant number 222528/Z/21/Z). CVP was supported by the John Lennon Memorial Scholarship from the University of Liverpool and a Fee Bursary Award from the Institute of Integrative Biology at the University of Liverpool. FXW was awarded the Institut Pasteur; Sante publique France; the Fondation Le Roch-Les Mousquetaires; and the French governments Investissement dAvenir programme, Laboratoire dExcellence "Integrative Biology of Emerging Infectious Diseases" (grant number ANR-10-LABX-62-IBEID). MDS was supported by a BBSRC grant (KSB: BB/V009184/1). RJBengtsson was supported by an MRC grant (KSB: MR/R020787/1). RJBennett was supported by a BBSRC DTP (BB/M011186/1). DJI was supported by a National Health and Medical Research Council (NHMRC) Emerging Leadership Fellowship (GNT1195210). BPH was supported by NHMRC Leadership Fellowship (GNT1196103). KSB and EVR are affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Gastrointestinal Infections at University of Liverpool in partnership with the United Kingdom Health Security Agency, in collaboration with University of Warwick. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health and Social Care or UKHSA. MAC is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) (NIHR200892) in Genomics and Enabling Data at University of Warwick in partnership with the UK Health Security Agency (UKHSA), in collaboration with Universities of Cambridge and Oxford. MAC is based at UKHSA. The views expressed are those of the author(s) and not necessarily those of the NIHR, the Department of Health and Social Care or the UK Health Security Agency. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. No payment was received by any pharmaceutical company or other agency to write this article. The authors were not precluded from accessing data in the study, and accept responsibility to submit for publication. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSalmonella Panama has consistently been reported as a frequently isolated Salmonella serovar in national surveillance datasets, causing both sporadic cases and larger outbreaks. However, this picture has been masked due to most of the focus being placed on the top two serovars associated with nontyphoidal Salmonella (NTS) and invasive NTS disease: Typhimurium and Enteritidis. Previous works on S. Panama have determined transmission to include human faeces and breast milk, as well as non-human sources such as environmental reservoirs and animals (reptiles and pigs used for food). In contrast to most of the Salmonella serovars causing gastroenteritis, S. Panama has also been associated with a range of systemic infections including septicaemia, meningitis, and osteomyelitis, mostly affecting infants. The patterns of antimicrobial resistance of this pathogen were not well known, with studies reporting a mixture of different antimicrobial resistance profiles. Added value of this studyHere we conducted a large-scale study of 836 globally relevant S. Panama isolates to understand global population structure and disease ecology. The S. Panama genomes used in this study were sourced from a combination of historical collections (including the first ever isolated strain of this serovar dating from 1931), national surveillance datasets, and publicly available data. Some of these isolates had been linked to travel, allowing an inferred location for understanding population structure. Overall, this assembled S. Panama collection spanned a range of 88 years and covered 45 countries and regions of all inhabited continents. We applied bacterial phylodynamic approaches to determine population structure, evolutionary history, and clade-specific trends of invasiveness and antimicrobial resistance correlated with geo-temporal parameters. Implications of all the available evidenceThis study revealed the population structure and global ecology of S. Panama, indicating that multidrug resistant S. Panama circulates in European and Asian regions, and presents an increased number of genetic markers for extra-intestinal invasiveness. The transmission and expansion of antimicrobial-resistant S. Panama strains presented in this study highlight the significance of supporting control and monitoring efforts from an international perspective.

genomics↗

An unusual two-strain cholera outbreak in Lebanon, 2022-2023: a genomic epidemiology study

BackgroundCholera is a bacterial infection caused by the ingestion of contaminated water or food. It principally affects the gastrointestinal system and spreads easily, causing outbreaks. The first case of cholera in this outbreak was detected in Lebanon in October 2022. The outbreak lasted three months, with 8,007 suspected cases (671 laboratory-confirmed) and 23 deaths. We characterised the Vibrio cholerae strain responsible for this cholera outbreak. MethodsIn total, 34 Vibrio cholerae isolates collected by random sampling of stools, water and plant samples throughout the outbreak and over the affected regions were studied by phenotypic methods and microbial genomics. FindingsAll isolates were V. cholerae O1, serotype Ogawa strains from wave 3 of the seventh pandemic El Tor (7PET) lineage. Phylogenomic analysis unexpectedly revealed the presence of two different 7PET strains, a highly unusual finding outside the Bay of Bengal, where several sublineages circulate together. The dominant strain had a narrow antibiotic resistance profile and was phylogenetically related to South Asian V. cholerae isolates. The second strain, which was found exclusively in South Lebanon and Beqaa, was resistant to multiple antibiotics, including macrolides, third-generation cephalosporins and cotrimoxazole. It belonged to the AFR13 sublineage and clustered with V. cholerae isolates collected in Yemen from 2016 to 2019. This second Lebanese strain also harboured the same multidrug-resistance (MDR) IncC-type plasmid found in Yemeni isolates from 2018. InterpretationThe 2022-2023 Lebanese cholera outbreak was caused by the simultaneous introduction of two different 7PET strains. The MDR strain was geographically limited, but the spread of this clone or the horizontal transfer of the MDR plasmid to more susceptible clones could affect epidemic cholera case management. Genomic surveillance is crucial to prevent further spread, and to ensure a prompt and effective response to outbreaks. FundingThe study was funded by the Centers for Disease Control (CDC) award number BAA 75D301-21-C-12132, a grant awarded to the American University of Beirut, WHO country office Lebanon, the Lebanese University, and Institut Pasteur. RESEARCH IN CONTEXT PANELO_ST_ABSEvidence before this studyC_ST_ABSWhole-genome sequencing (WGS) has greatly advanced our understanding and the characterisation of Vibrio cholerae outbreaks. However, few studies in the Middle East and North Africa (MENA) region have used this powerful technology. We searched PubMed for studies investigating the molecular epidemiology of V. cholerae by WGS in the MENA region, including Lebanon, with the terms "cholera*" AND "a country name of MENA countries" with no restrictions on language or date. The very small number of studies identified concerned Yemen and Algeria. All the outbreaks in the MENA region investigated to date and many others worldwide were caused by a single strain introduced once, contrasting with the endemic setting (the Bay of Bengal) in which several lineages circulate together. One manuscript addressing the history of cholera in Africa from a genomic perspective assigned three Lebanese strains from past outbreaks in 1970 and 1993 as O1 Ogawa isolates from waves 1 and 2 of the seventh pandemic lineage (7PET). Added value of the studyWe provide the first comprehensive overview of the molecular epidemiology of the V. cholerae strains responsible for the 2022-2023 Lebanese cholera outbreak. The use of WGS made it possible to distinguish clearly between two phylogenetically distant strains from genomic wave 3 of the 7PET lineage responsible for the Lebanese outbreak and to assign their putative origins to South Asia and Yemen. Based on their different susceptibility patterns (a predominant strain with a narrow resistance profile and a minor strain with an extended resistance profile), WGS excluded the hypothesis of the multidrug-resistant (MDR) minor strain emerging from the susceptible dominant strain through the acquisition of the MDR plasmid, instead clearly demonstrating the seeding of the outbreak by two different introductions. Implications of all available evidenceThis study demonstrates the importance of WGS associated with national surveillance for obtaining new insights and perspectives, modifying our perception of V. cholerae outbreak. This unexpected occurrence of a two-strain outbreak in a setting considered non-endemic for V. cholerae requires tight control by the local health authorities to prevent the sporadic introduction and spread of additional strains. Our findings raise the question of the extent to which the strains identified, particularly those from South Asia, spread in Iraq and Syria, neighbouring countries that declared cholera outbreaks before Lebanon. It is difficult to answer this question due to the lack of strains collected from these countries. Regional surveillance of the causal agent of cholera is therefore essential, to unravel transmission events and monitor the emergence of antimicrobial drug-resistant strains observed in many countries around the world.

microbiology↗

Rapid emergence of extensively drug-resistant Shigella sonnei in France

Shigella sonnei, the main cause of bacillary dysentery in high-income countries, has become increasingly resistant to antibiotics. We monitored the antimicrobial susceptibility of 7,121 S. sonnei isolates collected in France between 2005 and 2021. We identified a dramatic increase in the proportion of extensively drug-resistant (XDR) isolates (i.e., simultaneously resistant to ciprofloxacin, third-generation cephalosporins and azithromycin), to 22.3% of all S. sonnei isolates in 2021. Our genomic analysis identified 13 different clusters of XDR isolates descended from a ciprofloxacin-resistant sublineage originating from South Asia. The 164 XDR isolates detected were resistant to azithromycin, principally through a pKSR100-like plasmid, and to third-generation cephalosporins through various genes and plasmids. This rapid emergence of XDR S. sonnei in different transmission networks, particularly among men who have sex with men, is a matter of concern, and good laboratory-based surveillance of Shigella infections will be crucial for informed decision-making and appropriate public health action.

microbiology↗

Genomic epidemiology of the cholera outbreak in Yemen reveals the spread of a multi-drug resistance plasmid between diverse lineages of Vibrio cholerae

The humanitarian crisis in Yemen led in 2016 to the biggest cholera outbreak documented in modern history, with more than 2.5 million suspected cases to date. In late 2018, epidemiological surveillance showed that V. cholerae isolated from cholera patients had turned multi-drug resistant (MDR). We generated genomes from 260 isolates sampled in Yemen between 2018 and 2019 to identify a possible shift in circulating genotypes. 84% of V. cholerae isolates were serogroup O1 belonging to the seventh pandemic El Tor (7PET) lineage, sublineage T13 - same as in 2016 and 2017 - while the remaining 16% of strains were non-toxigenic and belonged to divergent V. cholerae lineages, likely reflecting sporadic gut colonisation by endemic strains. Phylogenomic analysis reveals a succession of T13 clones, with 2019 dominated by a clone that carried an IncC-type plasmid harbouring an MDR pseudo-compound transposon (PCT). Identical copies of these mobile elements were found independently in several unrelated lineages, suggesting exchange and recombination between endemic and epidemic strains. Treatment of severe cholera patients with macrolides in Yemen from 2016 to early 2019 coincides with the emergence of the plasmid-carrying T13 clone. The unprecedented success of this genotype where an SXT-family integrative and conjugative element (SXT/ICE) and an IncC plasmid coinhabit show the stability of this MDR plasmid in the 7PET background, which may durably reduce options for epidemic cholera case management. We advocate a heightened genomic epidemiology surveillance of cholera to help control the spread of this highly-transmissible, MDR clone.

microbiology↗

The phylogenomic landscape of the genus Serratia

The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We show that Serratia is a diverse genus which displays striking plasticity and ability to adapt to its environment, including a highly-varied portfolio of plasmids, and provide evidence of different patterns of gene flow across the genus. This work provides an essential platform for understanding the emergence of clinical and other lineages of Serratia.

microbiology↗