Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes.

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.

Comparative Genomics of Clinical and Environmental Isolates of Vibrio spp. of Colombia: Implications of Traits Associated with Virulence and Resistance.

There is widespread concern about the increase in cases of human and animal infections caused by pathogenic Vibrio species due to the emergence of epidemic lineages. In Colombia, active surveillance by the National Institute of Health (INS) has confirmed the presence of Vibrio; however, in routine surveillance, these isolates are not genomically characterized. This study focused on the pangenome analysis of six Vibrio species: V. parahaemolyticus, V. vulnificus, V. alginolyticus, V. fluvialis, V. diabolicus and V. furnissii to determine the genetic architectures of potentially virulent and antimicrobial resistance traits. Isolates from environmental and clinical samples were genome sequenced, assembled and annotated. The most important species in public health were further characterized by multilocus sequence typing and phylogenomics. For V. parahaemolyticus, we found the virulent ST3 and ST120 genotypes. For V. vulnificus, we identified isolates belonging to lineages 1 and 2. Virulence gene homologues between species were found even in non-pathogenic species such as V. diabolicus. Annotations related to the mobilome, integrative mobile and conjugative elements and resistance genes were obtained from environmental and clinical isolates. This study contributes genomic information to the intensified surveillance program implemented by the INS to establish potential sources of vibriosis in Colombia.

Surveillance of Salmonella enterica serovar Typhi in Colombia, 2012-2015.

Salmonella Typhi (S. Typhi) is the causative agent of typhoid fever; a systemic disease affecting ~20 million people per year globally. There are little data regarding the contemporary epidemiology of typhoid in Latin America. Consequently, we aimed to describe some recent epidemiological aspects of typhoid in Colombia using cases reported to the National Public Health Surveillance System (Sivigila) between 2012 and 2015. Over the four-year reporting period there were 836 culture confirmed cases of typhoid in Colombia, with the majority (676/836; 80.1%) of reported cases originated from only seven departments. We further characterized 402 S. Typhi isolates with available corresponding data recovered from various departments of Colombia through antimicrobial susceptibility testing and molecular subtyping. The majority (235/402; 58.5%) of these typhoid cases occurred in males and were most commonly reported in those aged between 10 and 29 years (218/402; 54.2%); there were three (0.74%) reported fatalities. The overwhelming preponderance (339/402; 84.3%) of S. Typhi were susceptible to all tested antimicrobials. The most common antimicrobial to which the organisms exhibited non-susceptibility was ampicillin (30/402;7.5%), followed by nalidixic acid (23/402, 5.7%). Molecular subtyping identified substantial genetic diversity, which was well distributed across the country. Despite the diffuse pattern of S. Typhi genotypes, we identified various geographical hotspots of disease associated with local dominant genotypes. Notably, we found limited overlap of Colombian genotypes with organisms reported in other Latin American countries. Our work highlights a substantial burden of typhoid in Colombia, characterized by sustained transmission in some regions and limited epidemics in other departments. The disease is widely distributed across the country and associated with multiple antimicrobial susceptible genotypes that appear to be restricted to Colombia. This study provides a current perspective for typhoid in Latin America and highlights the importance of pathogen-specific surveillance to add insight into the limited epidemiology of typhoid in this region.

Vigilancia por laboratorio de Salmonella enterica en casos clínicos humanos en Colombia 2005 a 2011 / Laboratory surveillance of Salmonella enterica from human clinical cases in Colombia 2005-2011

Introducción: Salmonella spp. es un enteropatógeno que se transmite a los humanos a través de alimentos o agua contaminada. En 1997, el Grupo de Microbiología del Instituto Nacional de Salud de Colombia inició el programa de vigilancia de enfermedad diarreica aguda y fiebre tifoidea, que incluye Salmonella spp. Este informe presenta los resultados fenotípicos y genotípicos de los aislamientos recuperados de 2005 a 2011 como parte de la vigilancia. Métodos: Un total de 4.010 aislamientos de Salmonella spp. fueron analizados por serotipificación con el esquema Kauffmann-White-LeMinor, patrones de sensibilidad antimicrobiana y de electroforesis en gel de campos pulsados (PFGE). Resultados: Se identificaron un total de 93 serovares, con 9 predominantes, Typhimurium, Enteritidis, Typhi, Dublin, Panama, Derby, Braenderup, Saintpaul y Uganda. Salmonella spp. presentó altos porcentajes de resistencia a tetraciclina y ácido nalidíxico. El 52,4% (2.101/4.010) de los aislamientos fueron sensibles a todos los antibióticos. La multirresistencia se observó en el 54,9% de los aislamientos de Typhimurium, representada por 81 combinaciones. Por PFGE se analizaron 51,9% aislamientos (2.083/4.010) de 34 serovares, generando 828 patrones electroforéticos XbaI. De estos, 8 se reportaron en al menos 2 países en Latinoamérica. Conclusión: La vigilancia de Salmonella spp. permite conocer la distribución de los serovares, su resistencia y la identificación de clones endémicos en Colombia, aportando bases para un tratamiento óptimo en las infecciones generadas por este patógeno y en el diseño de programas para disminuir la dispersión de aislamientos multirresistentes (AU)

Introduction: Salmonella is an enteropathogen acquired through contaminated food or water. In Colombia, Salmonella spp. is included in the national surveillance of Acute Diarrhoeal Diseases and typhoid fever initiated in 1997. This report shows the phenotype and genotype results obtained from 2005 to 2011. Methods: A total of 4010 isolates of Salmonella enterica were analysed by serotyping with Kauffmann-White-LeMinor, antimicrobial resistance patterns, and pulse-field gel electrophoresis (PFGE). Results: A total of 93 serovars were identified, of which, Typhimurium, Enteritidis, Typhi, Dublin, Panama, Derby, Braenderup, Saintpaul, and Uganda were prominent. The highest levels of resistance were found for tetracycline and nalidixic acid. Susceptibility was observed in 52.4% (2101/4010) of the isolates. Multi-resistance was recorded in 54.9% of Typhimurium isolates, with 81 different combinations. Using PFGE, 51.9% (2083/4010) isolates were analysed in 34 serovars, and 828 electrophoretic patterns were obtained. From these, 8 patterns were found in at least two Latin-American countries. Conclusion: The surveillance of Salmonella spp. provides information on the serovar distribution, antimicrobial resistance, and clonal distribution in Colombia, as well as information to treat this disease and control the spread of antimicrobial bacterial resistance (AU)

Laboratory surveillance of Salmonella enterica from human clinical cases in Colombia 2005-2011. / Vigilancia por laboratorio de Salmonella enterica en casos clínicos humanos en Colombia 2005 a 2011.

INTRODUCTION: Salmonella is an enteropathogen acquired through contaminated food or water. In Colombia, Salmonella spp. is included in the national surveillance of Acute Diarrhoeal Diseases and typhoid fever initiated in 1997. This report shows the phenotype and genotype results obtained from 2005 to 2011. METHODS: A total of 4010 isolates of Salmonella enterica were analysed by serotyping with Kauffmann-White-LeMinor, antimicrobial resistance patterns, and pulse-field gel electrophoresis (PFGE). RESULTS: A total of 93 serovars were identified, of which, Typhimurium, Enteritidis, Typhi, Dublin, Panama, Derby, Braenderup, Saintpaul, and Uganda were prominent. The highest levels of resistance were found for tetracycline and nalidixic acid. Susceptibility was observed in 52.4% (2101/4010) of the isolates. Multi-resistance was recorded in 54.9% of Typhimurium isolates, with 81 different combinations. Using PFGE, 51.9% (2083/4010) isolates were analysed in 34 serovars, and 828 electrophoretic patterns were obtained. From these, 8 patterns were found in at least two Latin-American countries. CONCLUSION: The surveillance of Salmonella spp. provides information on the serovar distribution, antimicrobial resistance, and clonal distribution in Colombia, as well as information to treat this disease and control the spread of antimicrobial bacterial resistance.

Epidemiología de Salmonella spp, Listeria monocytogenes y Campylobacter spp, en la cadena productiva avícola / Epidemiology of Salmonella spp., Listeria monocytogenes and Campylobacter spp., in the poultry chain production system / Epidemiologia de Salmonella spp., Listeria mono-cytogenes y Campylobacter spp., na cadeia produtiva avícola

Salmonella spp., Campylobacter spp. y Listeria monocytogenes son patógenos zoonóticos causantes de enfermedades transmitidas por alimentos asociadas al consumo de productos de origen animal contaminados. En este estudio se determinaron la prevalencia y los factores de riesgo asociados a la presencia de estos microorganismos en todos los eslabones de producción de pollos de engorde en dos empresas integradoras avícolas colombianas (EI-I y EI-II). En la EI-I, se aislaron Campylobacter spp., y Salmonella spp., del 10 % y el 4,4 % de las muestras, y el serotipo predominante de esta última fue S. Heildelberg. Se encontró Salmonella spp., en 6 % de las muestras de manos y materia fecal de los trabajadores, y S. Saphra fue el serotipo más común. En la EI-II, la prevalencia de Campylobacter spp., y Salmonella spp., en muestras de animales fue del 7 % y el 17 %, respectivamente. No se detectó L. monocytogenes. Este trabajo estableció la prevalencia de los patógenos zoonóticos a lo largo de la cadena productiva, evidenció la presencia de trabajadores/manipuladores portadores de los patógenos y determinó, que “la falta de reconocimiento médico de los empleados en el último año” constituye un posible factor de riesgo para la portación de Salmonella spp.

Salmonella spp., Campylobacter spp., and L. monocytogenes are zoonotic foodborne pathogens, associated with the consumption of contaminated foods of animal origin. In this study we determined the prevalence and risk factors associated with the presence of these microorganisms at all stages of the production system, in two Colombian poultry companies (EI-EI-I and II). In EI-I, Campylobacter spp., and Salmonella spp., were isolated from 10 % and 4.4 % of the specimens, and S. Heidelberg was the predominant serotype. Salmonella spp., was found in 6 % of hands and stool samples of workers. S. Saphra was the most prevalent serotype. In EI-II, the prevalence of Campylobacter spp., and Salmonella spp., from animal specimens was 7 % and 17 %, respectively. L. monocytogenes was not detected. This study established the prevalence of these zoonotic pathogens through the production chain and showed the presence of pathogen carriers among workers/food handlers. “Lack of medical examination of employees in the previous year” was found to be a possible risk factor for carriage of Salmonella spp.

Salmonella spp., Campylobacter spp. y L. monocytogenes são patógenos zoonóticos causantes de doenças transmitidas por alimentos associadas ao consumo de produtos de origem animal contaminados. Neste estudo se determinou a prevalência e os fatores de risco associados à presença destes microrganismos em todos os elos de produção do frango de engorda em duas empresas integradoras avícolas colombianas (EI-I y EI-II). Na EI-I, Campylobacter spp. e Salmonella spp. foram isolados de 10% e 4,4% das amostras, sendo S. Heildelberg ou serótipo predominante. Se encontrou Salmonella spp. em 6% das amostras de mãos e matéria fecal dos trabalhadores, sendo S. Saphra o serótipo mais comum. Na EI-II, a prevalência de Campylobacterspp. e Salmonella spp. em amostras animais foi de 7% e 17% respectivamente. L.monocytogenes não foi detectada. Este estudo estabeleceu a prevalência dos patógenos zoonóticos através da cadeia produtiva, evidenciou a presença de portadores dos patógenos entre os trabalhadores/manipuladores e determinou, “a falta de reconhecimento médico dos empregados no último ano” constitui um possível fator de risco para a porte de Salmonella spp.

Caracterización fenotípica y genotípica de Salmonella Typhimurium variante 5- asociada a un brote de enfermedad transmitida por alimentos en el municipio de Paz de Río, Boyacá, 2010 / Phenotypic and genotypic characterization of Salmonella Typhimurium variant 5- isolates associated with an outbreak of food-borne disease in Paz de Rio, Boyacá, Colombia, in 2010

Introducción: Salmonella enterica serotipo Typhimurium variante 5- es un patógeno muy relacionado con animales, especialmente con palomas, y asociado en pocos casos con infecciones esporádicas en humanos. Sin embargo, los sistemas de vigilancia epidemiológica han permitido detectarla en brotes en humanos. Objetivo: caracterizar por técnicas fenotípicas y genotípicas los aislamientos de Salmonella Typhimurium variante 5- asociados a un brote de enfermedad transmitida por alimentos (ETA) en el municipio de Paz de Río, Boyacá, en el 2010. Materiales y métodos: doce aislamientos de Salmonella spp., fueron remitidos para confirmación bioquímica, identificación del serotipo y perfil de susceptibilidad antimicrobiana. Se analizaron genotípicamente por electroforesis en gel de campo pulsado (PFGE) con las enzimas Xbal y Blnl. Resultados: todos los aislamientos se confirmaron como Salmonella spp., y presentaron resistencia a tetraciclina y estreptomicina y sensibilidad a los demás antibióticos ensayados; 11/12 se identificaron como Salmonella Typhimurium variante 5- y mostraron en la PFGE el patrón COIN10.JPX.X01.0168 con la enzima XbaI y dos aislamientos de este mismo grupo se confirmaron con la enzima BlnI obteniendo el patrón de PFGE COIN10.JPX.A26.0002. El aislamiento restante se identificó como Salmonella Typhimurium con patrón de PFGE con la enzima Xbal COIN10.JPX.X01.0221. Conclusión: se reporta por primera vez en Colombia un brote de ETA asociado epidemiológicamente con aislamientos de Salmonella Typhimurium variante 5- que estuvieron relacionados fenotípica y genéticamente.

Introduction: Salmonella enterica serotype Typhimurium variant 5- is a pathogen closely related to animals, especially pigeons, which has been also associated in rare cases with sporadic infections in humans. However, epidemiological surveillance systems have enabled the detection of this variant in human outbreaks. Objective: To characterize by means of phenotypic and genotypic techniques the isolates of Salmonella Typhimurium variant 5- associated with an outbreak of food-borne disease in Paz de Rio, Boyacá, Colombia (2010), in order to establish their molecular relationships. Materials and methods: Twelve isolates of Salmonella spp., were analyzed by biochemical, serotyping and antimicrobial susceptibility tests. Pulsed-field gel electrophoresis (PFGE) with XbaI and Blnl enzymes was used to establish their molecular relationships. Results: All isolates were confirmed as Salmonella spp. They were resistant to tetracycline and streptomycin and sensitive to the rest of antibiotics tested. Eleven isolates were identified as Salmonella Typhimurium variant 5- and grouped in COIN10.JPX.X01.0168 pattern using the enzyme XbaI; two isolates in this group were confirmed using the enzyme BlnI with the COIN10. JPX.A26.0002 pattern. One isolate was identified as Salmonella Typhimurium with COIN10.JPX.X01.0221 pattern with the enzyme XbaI. Conclusion: This is the first outbreak in Colombia of foodborne illness epidemiologically associated with isolates of Salmonella Typhimurium variant 5 -, which were phenotypically and genetically related.