Publications by authors named "Dyson Z"

The Antimicrobial Resistance - Genomes, Big Data and Emerging Technologies Conference explored key topics including measuring the burden of AMR, global public health pathogen genomics infrastructure and surveillance, translation and implementation of genomics for AMR control, use of techniques such as wastewater surveillance, mathematical and statistical modelling, and Artificial Intelligence (AI) to aid understanding of AMR. This report describes research presented during plenary sessions and discussions, keynote presentations and posters.

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  • Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A, poses a significant public health issue due to rising antimicrobial resistance, complicating treatment options and worsening health outcomes.
  • *The study sequenced bacteria samples from blood cultures of febrile patients in urban sites of Dhaka (Bangladesh), Kathmandu (Nepal), and Blantyre (Malawi) to analyze their genetic characteristics and resistance mechanisms.
  • *Findings revealed that different genotypes of S. Typhi were present across the sites, with high rates of multidrug resistance in Blantyre and Dhaka but not in Kathmandu, highlighting diverse transmission dynamics and resistance patterns.
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Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58 lineage, a lineage that arose comparatively recently before becoming globally disseminated.

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Background: Ciprofloxacin is the first-line drug for treating typhoid fever in many countries in Africa with a high disease burden, but the emergence of non-susceptibility poses a challenge to public health programmes. Through enhanced surveillance as part of vaccine evaluation, we investigated the occurrence and potential determinants of ciprofloxacin non-susceptibility in Blantyre, Malawi.

Methods: We conducted systematic surveillance of typhoid fever cases and antibiotic prescription in two health centres in Blantyre, Malawi, between Oct 1, 2016, and Oct 31, 2019, as part of the STRATAA and TyVAC studies.

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Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000).

Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch.

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  • The global response to the SARS-CoV-2 pandemic underscored the importance of sharing genomic data with standardized information for tracking new variants.
  • The text advocates for the importance of sharing genomic data specifically for Typhi (the bacteria that causes typhoid fever) and highlights available platforms that aid in this effort.
  • Key initiatives mentioned include the Africa CDC's Pathogen Genomics Initiative, SEQAFRICA, Typhi Pathogenwatch, TyphiNET, and the Global Typhoid Genomics Consortium, which support the analysis and visualization of Typhi genomic data in Africa and beyond.
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  • Enteroinvasive E. coli (EIEC) and its related agents cause bacillary dysentery and evolved from a common ancestor through the acquisition of a virulence plasmid (pINV) that enables a type 3 secretion system (T3SS).
  • The recent emergence of Sequence Type (ST)99 O96:H19 EIEC clone, which is responsible for outbreaks in Europe and South America, showcases distinct groups of isolates based on their pINV status.
  • Research using zebrafish infection models revealed that ST99 EIEC's virulence is influenced by temperature, suggesting that virulence existed before pINV acquisition and that the acquisition of this plasmid allowed for enhanced pathogenicity and wider spread among human populations.
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  • Typhi and Paratyphi A are bacteria causing enteric fever, with Typhi being more common and resulting in limited data on Paratyphi A, particularly regarding genomic surveillance and antibiotic resistance.
  • A study conducted in Vadodara, India, identified different genotypes of Paratyphi A from December 2018 to December 2019 using whole-genome sequencing, finding that the majority belonged to the globally dominant genotype 2.4.2.
  • A specific mutation linked to reduced fluoroquinolone susceptibility was found in all outbreak isolates, indicating that Paratyphi A is becoming more significant in South Asia, especially with the potential use of Vi conjugate vaccines.
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  • Salmonella Paratyphi A causes approximately 3.4 million infections each year globally, with increasing antimicrobial resistance and no available vaccines.
  • The study sequenced 817 isolates from South Asia and combined them with 562 publicly available genomes to create a comprehensive global database of Salmonella Paratyphi A from 1917 to 2019.
  • Researchers developed Paratype, a genotyping tool that classifies the pathogen into three main and nine secondary clades, facilitating tracking of genomic variations and antimicrobial resistance, and is available as an open-access resource for global surveillance.
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  • * The dominant strain in South Asia, genotype 4.3.1 (H58), shows high antibiotic resistance, highlighting the need for quick detection methods to monitor and manage outbreaks.
  • * A new multiplex PCR assay was developed, achieving 100% specificity for identifying lineage-specific S. Typhi and S. Paratyphi A, offering a faster, cost-effective alternative to traditional sequencing methods for tracking these infections.
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  • Typhoid fever in Santiago, Chile saw a drastic reduction in cases from 128-220 per 100,000 people in the 1980s to less than 8 per 100,000 from the 1990s onwards due to targeted public health interventions.
  • Whole genome sequencing was used to compare the S. Typhi bacteria from the hyperendemic period of the 1980s to that of the nonendemic 2010s, revealing that the genotypes causing illness remained largely unchanged.
  • The persistence of certain historical genotypes suggests that chronic carriers from the 1980s may be responsible for the reoccurrence of the same strains, demonstrating a link between past and present typhoid cases
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  • The study focuses on the emergence and spread of antimicrobial-resistant Salmonella enterica serovar Typhi (S Typhi), highlighting its impact on treatment and control, especially in south Asia.
  • Researchers sequenced and analyzed over 7,600 S Typhi strains from various countries to understand the genetic patterns and resistance trends over time.
  • Findings indicate a decline in multidrug-resistant typhoid in most of south Asia except Pakistan, where extensively drug-resistant strains have rapidly increased, alongside the emergence of mutations leading to increased fluoroquinolone and azithromycin resistance.
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  • Typhoid fever, caused by Salmonella enterica serovar Typhi, remains a major health issue in low-income regions, particularly in the Asia-Pacific, and this study analyzes the S. Typhi populations in Papua New Guinea (PNG) over 30 years using whole genome sequencing.
  • The research found that PNG's S. Typhi is primarily made up of a single genotype (2.1.7) that originated in Indonesia, showing low evidence of cross-border transmission, and remains largely susceptible to traditional treatment drugs.
  • To effectively combat typhoid fever, PNG needs to maintain effective antimicrobial treatments while improving sanitation infrastructure and monitoring for any signs of antimicrobial resistance (AMR) emergence.
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  • - The study focuses on increasing cases of enteric fever caused by Salmonella Paratyphi A in Bangladesh, especially as typhoid conjugate vaccines are introduced, highlighting a lack of genomic data for this pathogen in endemic areas.
  • - Researchers conducted whole genome sequencing on 67 S. Paratyphi A isolates from various locations in Bangladesh and discovered that most belong to a dominant global lineage, with evidence of migration from neighboring countries and genetic similarities to S. Typhi.
  • - Findings include mutations linked to antibiotic resistance and the identification of a plasmid similar to those in S. Typhi, suggesting a need for continuous genomic surveillance to understand the evolving nature of this pathogen.
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  • The Paratyphi B complex includes different biotypes that can cause various diseases, including gastroenteritis and paratyphoid fever, but their prevalence in Bangladesh is poorly understood due to challenges in serotyping.
  • This study is the first to use whole-genome sequencing to analyze 79 Paratyphi B isolates from Bangladesh, revealing that they belong to the Java biotype and adding valuable data to existing global genetic classifications.
  • Surprisingly, these Bangladeshi isolates showed low levels of antimicrobial resistance genes, which is unexpected given the common availability of antibiotics without prescriptions, highlighting important public health implications.
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  • Understanding the dynamics of typhoid infection and carriage is essential for developing effective prevention strategies in endemic areas like Nairobi, Kenya.
  • A study involving 4,670 cases and 8,549 controls identified a carriage frequency of 1% among children under 16, with most cases linked to multidrug-resistant strains of Salmonella Typhi.
  • The results suggest that asymptomatic carriers significantly contribute to the spread of typhoid in the community, highlighting the need for targeted interventions.
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  • In 2016, a new genotyping tool called GenoTyphi was created to classify different strains of Salmonella Typhi, the bacteria causing typhoid fever, based on whole-genome sequencing.
  • Recent studies have discovered new subpopulations of S. Typhi that need updated classifications and improved software to identify antimicrobial resistance mutations.
  • Analysis of over 4,600 whole-genome sequences has shown that haplotype 58 (H58) is widespread globally, along with various strains that exhibit antimicrobial resistance.
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  • The increasing decentralization of whole-genome sequencing presents opportunities for international collaboration and data sharing to improve typhoid control measures.* -
  • Pathogenwatch is a web application designed to quickly identify antimicrobial resistance (AMR) markers in Salmonella enterica serovar Typhi, integrating genomic data for public health use.* -
  • The tool's clustering and AMR predictions align well with established methods and susceptibility data, highlighting its effectiveness in tracking high-risk S. Typhi strains using data from over 4,300 public genomes.*
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  • Antimicrobial resistance (AMR) is a significant threat to treating typhoid fever, with an outbreak of extensively drug-resistant Salmonella Typhi in Pakistan making azithromycin the last effective oral option in South Asia, though azithromycin-resistant strains have appeared in neighboring countries.
  • A study in Northern India analyzed 66 S. Typhi isolates using whole-genome sequencing and found 7 strains with a specific mutation linked to azithromycin resistance, along with mutations conferring ciprofloxacin resistance in 6 of those strains.
  • The emergence of these resistant strains emphasizes a growing AMR problem in South Asia and highlights the urgent need for introducing typhoid conjugate vaccines in the region.
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  • - Salmonella enterica serovar Typhi H58, which is resistant to antibiotics, is found worldwide but hasn't been seen in Latin America until now.
  • - Genetic analysis showed that there were 3 separate instances of Salmonella Typhi H58 being introduced into Chile, where it has lower susceptibility to fluoroquinolones.
  • - The study emphasizes the importance of increasing genomic monitoring for typhoid fever in Latin America to keep track of this emerging threat.
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The increase of antimicrobial resistance (AMR), and lack of new classes of licensed antimicrobials, have made alternative treatment options for AMR pathogens increasingly attractive. Recent studies have demonstrated anti-bacterial efficacy of a humanised monoclonal antibody (mAb) targeting the O25b O-antigen of Escherichia coli ST131. To evaluate the phenotypic effects of antibody binding to diverse clinical E.

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  • Antimicrobial resistance is becoming a critical problem in treating typhoid fever, especially with the emergence of extensively drug-resistant (XDR) Typhi strains in Pakistan.
  • Currently, azithromycin is the only effective oral treatment left, but researchers have identified a mutation in the Typhi gene that is linked to resistance against this drug.
  • This situation underscores the urgent need for the implementation of the typhoid conjugate vaccine in South Asia to help combat the spread of resistant strains and maintain effective treatment options.
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  • India has a high prevalence of enteric fever, and a study at St. John's Medical College Hospital analyzed differences in clinical presentations between adult and pediatric patients over one year.
  • Out of 113 cases, young adults (16-30 years) and children (<15 years) made up the majority, with common issues like anemia and unusual symptoms including arthritis and repeat infections.
  • The findings suggest that enteric fever presents with variable clinical features due to host and environmental factors, emphasizing the need for better surveillance and monitoring of the disease to improve treatment and prevention strategies.
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Background: Multi-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. Typhi in many regions.

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