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Bacterial relatedness measured using select chromosomal loci forms the basis of public health genomic surveillance. While approximating vertical evolution through this approach has proven exceptionally valuable for understanding pathogen dynamics, it excludes a fundamental dimension of bacterial evolution-horizontal gene transfer. Incorporating the accessory genome is the logical remediation and has recently shown promise in expanding epidemiological resolution for enteric pathogens. Employing k-mer-based Jaccard index analysis, and a novel genome length distance metric, we computed pangenome (i.e., core and accessory) relatedness for the globally important pathogen Salmonella enterica serotype Typhi (Typhi), and graphically express both vertical (homology-by-descent) and horizontal (homology-by-admixture) evolutionary relationships in a reticulate network of over 2,200 U.S. Typhi genomes. This analysis revealed non-random structure in the Typhi pangenome that is driven predominantly by the gain and loss of mobile genetic elements, confirming and expanding upon known epidemiological patterns, revealing novel plasmid dynamics, and identifying avenues for further genomic epidemiological exploration. With an eye to public health application, this work adds important biological context to the rapidly improving ways of analyzing bacterial genetic data and demonstrates the value of the accessory genome to infer pathogen epidemiology and evolution.IMPORTANCEGiven bacterial evolution occurs in both vertical and horizontal dimensions, inclusion of both core and accessory genetic material (i.e., the pangenome) is a logical step toward a more thorough understanding of pathogen dynamics. With an eye to public, and indeed, global health relevance, we couple contemporary tools for genomic analysis with decades of research on mobile genetic elements to demonstrate the value of the pangenome, known and unknown, annotated, and hypothetical, for stratification of Salmonella enterica serovar Typhi (Typhi) populations. We confirm and expand upon what is known about Typhi epidemiology, plasmids, and antimicrobial resistance dynamics, and offer new avenues of exploration to further deduce Typhi ecology and evolution, and ultimately to reduce the incidence of human disease.
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Genoma Bacteriano , Sequências Repetitivas Dispersas , Salmonella typhi , Salmonella typhi/genética , Genoma Bacteriano/genética , Sequências Repetitivas Dispersas/genética , Plasmídeos/genética , Evolução Molecular , Humanos , Filogenia , Febre Tifoide/microbiologia , Febre Tifoide/epidemiologiaRESUMO
BACKGROUND: While vaccination is the most effective way to prevent influenza infection and adverse outcomes, and despite WHO recommendations to vaccinate pregnant persons, access to seasonal influenza vaccines remains low. We explored knowledge, attitudes, and practices of pregnant persons about seasonal influenza vaccines to inform actions to improve vaccine uptake among this priority population. METHODS: We pooled individual-level data from cross-sectional surveys assessing pregnant persons' attitudes toward seasonal influenza vaccines in eight low- and middle-income countries during 2018-2019. The eight countries used a standard protocol and questionnaire to measure attitudes and intents toward influenza vaccination. We stratified by country-level (presence/absence of a national influenza vaccination program, country income group, geographic region) and individual-level factors. FINDINGS: Our analysis included 8,556 pregnant persons from eight low- and middle-income countries with and without seasonal influenza vaccination programs. Most pregnant persons (6,323, 74%) were willing to receive influenza vaccine if it was offered for free. Willingness differed by presence of an existing influenza vaccination program; acceptance was higher in countries without influenza vaccination programs (2,383, 89%) than in those with such programs (3,940, 67%, p < 0.001). INTERPRETATION: Most pregnant persons in middle-income countries, regardless of influenza vaccination program status, were willing to be vaccinated against influenza if the vaccine was provided free of charge. National investments in influenza vaccination programs may be well-received by pregnant persons, leading to averted illness both in pregnant persons themselves and in their newborn babies. FUNDING: US Centers for Disease Control and Prevention.
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Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica 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. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).
Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium's analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps.
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Salmonella typhi , Febre Tifoide , Humanos , Salmonella typhi/genética , Febre Tifoide/epidemiologia , Antibacterianos/farmacologia , Viagem , Farmacorresistência Bacteriana/genética , CiprofloxacinaRESUMO
Objective: To assess the stability of improvements in global respiratory virus surveillance in countries supported by the United States Centers for Disease Control and Prevention (CDC) after reductions in CDC funding and with the stress of the coronavirus disease 2019 (COVID-19) pandemic. Methods: We assessed whether national influenza surveillance systems of CDC-funded countries: (i) continued to analyse as many specimens between 2013 and 2021; (ii) participated in activities of the World Health Organization's (WHO) Global Influenza Surveillance and Response System; (iii) tested enough specimens to detect rare events or signals of unusual activity; and (iv) demonstrated stability before and during the COVID-19 pandemic. We used CDC budget records and data from the WHO Global Influenza Surveillance and Response System. Findings: While CDC reduced per-country influenza funding by about 75% over 10 years, the number of specimens tested annually remained stable (mean 2261). Reporting varied substantially by country and transmission zone. Countries funded by CDC accounted for 71% (range 61-75%) of specimens included in WHO consultations on the composition of influenza virus vaccines. In 2019, only eight of the 17 transmission zones sent enough specimens to WHO collaborating centres before the vaccine composition meeting to reliably identify antigenic variants. Conclusion: Great progress has been made in the global understanding of influenza trends and seasonality. To optimize surveillance to identify atypical influenza viruses, and to integrate molecular testing, sequencing and reporting of severe acute respiratory syndrome coronavirus 2 into existing systems, funding must continue to support these efforts.
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COVID-19 , Vacinas contra Influenza , Influenza Humana , COVID-19/epidemiologia , COVID-19/prevenção & controle , Centers for Disease Control and Prevention, U.S. , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Pandemias/prevenção & controle , Vigilância da População , Estados Unidos/epidemiologiaRESUMO
Foodborne botulism is an intoxication caused by ingestion of food containing botulinum neurotoxin. Cases of foodborne botulism are usually sporadic (single, unrelated) but outbreaks of two or more cases occur. In this mini-review we will examine the following for the period 2001-2017, in the United States: botulism surveillance data, outbreaks of botulism affecting 10 or more people, and the public health preparedness and response approach.