97 results on '"Baker, Stephen"'
Search Results
2. Incidence of invasive salmonella disease in sub-Saharan Africa: a multicentre population-based surveillance study.
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Marks F, von Kalckreuth V, Aaby P, Adu-Sarkodie Y, El Tayeb MA, Ali M, Aseffa A, Baker S, Biggs HM, Bjerregaard-Andersen M, Breiman RF, Campbell JI, Cosmas L, Crump JA, Espinoza LMC, Deerin JF, Dekker DM, Fields BS, Gasmelseed N, Hertz JT, Van Minh Hoang N, Im J, Jaeger A, Jeon HJ, Kabore LP, Keddy KH, Konings F, Krumkamp R, Ley B, Løfberg SV, May J, Meyer CG, Mintz ED, Montgomery JM, Niang AA, Nichols C, Olack B, Pak GD, Panzner U, Park JK, Park SE, Rabezanahary H, Rakotozandrindrainy R, Raminosoa TM, Razafindrabe TJL, Sampo E, Schütt-Gerowitt H, Sow AG, Sarpong N, Seo HJ, Sooka A, Soura AB, Tall A, Teferi M, Thriemer K, Warren MR, Yeshitela B, Clemens JD, and Wierzba TF
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- Adolescent, Africa South of the Sahara epidemiology, Child, Child, Preschool, Drug Resistance, Multiple, Family Characteristics, Female, Fever etiology, Fever microbiology, Humans, Incidence, Male, Salmonella Infections microbiology, Typhoid Fever microbiology, Salmonella isolation & purification, Salmonella Infections epidemiology, Typhoid Fever epidemiology
- Abstract
Background: Available incidence data for invasive salmonella disease in sub-Saharan Africa are scarce. Standardised, multicountry data are required to better understand the nature and burden of disease in Africa. We aimed to measure the adjusted incidence estimates of typhoid fever and invasive non-typhoidal salmonella (iNTS) disease in sub-Saharan Africa, and the antimicrobial susceptibility profiles of the causative agents., Methods: We established a systematic, standardised surveillance of blood culture-based febrile illness in 13 African sentinel sites with previous reports of typhoid fever: Burkina Faso (two sites), Ethiopia, Ghana, Guinea-Bissau, Kenya, Madagascar (two sites), Senegal, South Africa, Sudan, and Tanzania (two sites). We used census data and health-care records to define study catchment areas and populations. Eligible participants were either inpatients or outpatients who resided within the catchment area and presented with tympanic (≥38·0°C) or axillary temperature (≥37·5°C). Inpatients with a reported history of fever for 72 h or longer were excluded. We also implemented a health-care utilisation survey in a sample of households randomly selected from each study area to investigate health-seeking behaviour in cases of self-reported fever lasting less than 3 days. Typhoid fever and iNTS disease incidences were corrected for health-care-seeking behaviour and recruitment., Findings: Between March 1, 2010, and Jan 31, 2014, 135 Salmonella enterica serotype Typhi (S Typhi) and 94 iNTS isolates were cultured from the blood of 13 431 febrile patients. Salmonella spp accounted for 33% or more of all bacterial pathogens at nine sites. The adjusted incidence rate (AIR) of S Typhi per 100 000 person-years of observation ranged from 0 (95% CI 0-0) in Sudan to 383 (274-535) at one site in Burkina Faso; the AIR of iNTS ranged from 0 in Sudan, Ethiopia, Madagascar (Isotry site), and South Africa to 237 (178-316) at the second site in Burkina Faso. The AIR of iNTS and typhoid fever in individuals younger than 15 years old was typically higher than in those aged 15 years or older. Multidrug-resistant S Typhi was isolated in Ghana, Kenya, and Tanzania (both sites combined), and multidrug-resistant iNTS was isolated in Burkina Faso (both sites combined), Ghana, Kenya, and Guinea-Bissau., Interpretation: Typhoid fever and iNTS disease are major causes of invasive bacterial febrile illness in the sampled locations, most commonly affecting children in both low and high population density settings. The development of iNTS vaccines and the introduction of S Typhi conjugate vaccines should be considered for high-incidence settings, such as those identified in this study., Funding: Bill & Melinda Gates Foundation., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)
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- 2017
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3. Prevalence of Salmonella Excretion in Stool: A Community Survey in 2 Sites, Guinea-Bissau and Senegal.
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Im J, Nichols C, Bjerregaard-Andersen M, Sow AG, Løfberg S, Tall A, Pak GD, Aaby P, Baker S, Clemens JD, Espinoza LM, Konings F, May J, Monteiro M, Niang A, Panzner U, Park SE, Schütt-Gerowitt H, Wierzba TF, Marks F, and von Kalckreuth V
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- Adolescent, Adult, Anti-Bacterial Agents pharmacology, Child, Child, Preschool, Cross-Sectional Studies, Drug Resistance, Bacterial, Female, Guinea-Bissau epidemiology, Humans, Infant, Infant, Newborn, Male, Prevalence, Salmonella isolation & purification, Senegal epidemiology, Young Adult, Feces microbiology, Salmonella drug effects, Salmonella Infections epidemiology, Salmonella Infections microbiology
- Abstract
Background: Chronic and convalescent carriers play an important role in the transmission and endemicity of many communicable diseases. A high incidence of Salmonella enterica serovar Typhi and invasive nontyphoidal Salmonella (NTS) infection has been reported in parts of sub-Saharan Africa, yet the prevalence of Salmonella excretion in the general population is unknown., Methods: Stool specimens were collected from a random sample of households in 2 populations in West Africa: Bissau, Guinea-Bissau, and Dakar, Senegal. Stool was cultured to detect presence of Salmonella, and antimicrobial susceptibility testing was performed on the isolated organisms., Results: Stool was cultured from 1077 and 1359 individuals from Guinea-Bissau and Senegal, respectively. Salmonella Typhi was not isolated from stool samples at either site. Prevalence of NTS in stool samples was 24.1 (95% confidence interval [CI], 16.5-35.1; n = 26/1077) per 1000 population in Guinea-Bissau and 10.3 (95% CI, 6.1-17.2; n = 14/1359) per 1000 population in Senegal., Conclusions: Evidence of NTS excretion in stool in both study populations indicates a possible NTS transmission route in these settings., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)
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- 2016
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4. Genomic comparison of Salmonella enterica serovars and Salmonella bongori by use of an S. enterica serovar typhimurium DNA microarray.
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Chan K, Baker S, Kim CC, Detweiler CS, Dougan G, and Falkow S
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- Bacterial Proteins genetics, Humans, Nucleic Acid Hybridization, Salmonella genetics, Salmonella pathogenicity, Salmonella enterica genetics, Salmonella enterica pathogenicity, Salmonella typhimurium genetics, Sensitivity and Specificity, Serotyping, Genome, Bacterial, Oligonucleotide Array Sequence Analysis methods, Salmonella classification, Salmonella enterica classification
- Abstract
The genus Salmonella consists of over 2,200 serovars that differ in their host range and ability to cause disease despite their close genetic relatedness. The genetic factors that influence each serovar's level of host adaptation, how they evolved or were acquired, their influence on the evolution of each serovar, and the phylogenic relationships between the serovars are of great interest as they provide insight into the mechanisms behind these differences in host range and disease progression. We have used an Salmonella enterica serovar Typhimurium spotted DNA microarray to perform genomic hybridizations of various serovars and strains of both S. enterica (subspecies I and IIIa) and Salmonella bongori to gain insight into the genetic organization of the serovars. Our results are generally consistent with previously published DNA association and multilocus enzyme electrophoresis data. Our findings also reveal novel information. We observe a more distant relationship of serovar Arizona (subspecies IIIa) from the subspecies I serovars than previously measured. We also observe variability in the Arizona SPI-2 pathogenicity island, indicating that it has evolved in a manner distinct from the other serovars. In addition, we identify shared genetic features of S. enterica serovars Typhi, Paratyphi A, and Sendai that parallel their unique ability to cause enteric fever in humans. Therefore, whereas the taxonomic organization of Salmonella into serogroups provides a good first approximation of genetic relatedness, we show that it does not account for genomic changes that contribute to a serovar's degree of host adaptation.
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- 2003
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5. Environmental Surveillance as a Tool for Identifying High-risk Settings for Typhoid Transmission
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Andrews, Jason R, Yu, Alexander T, Saha, Senjuti, Shakya, Jivan, Aiemjoy, Kristen, Horng, Lily, Qamar, Farah, Garrett, Denise, Baker, Stephen, Saha, Samir, and Luby, Stephen P
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Vaccine Related ,Emerging Infectious Diseases ,Foodborne Illness ,Biodefense ,Infectious Diseases ,Rare Diseases ,Digestive Diseases ,2.2 Factors relating to the physical environment ,Aetiology ,Infection ,Good Health and Well Being ,Clean Water and Sanitation ,Environmental Monitoring ,Humans ,Salmonella paratyphi A ,Salmonella typhi ,Typhoid Fever ,Typhoid-Paratyphoid Vaccines ,typhoid ,enteric fever ,Salmonella ,water ,environment ,Salmonella ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
Enteric fever remains a major cause of morbidity in developing countries with poor sanitation conditions that enable fecal contamination of water distribution systems. Historical evidence has shown that contamination of water systems used for household consumption or agriculture are key transmission routes for Salmonella Typhi and Salmonella Paratyphi A. The World Health Organization now recommends that typhoid conjugate vaccines (TCV) be used in settings with high typhoid incidence; consequently, governments face a challenge regarding how to prioritize typhoid against other emerging diseases. A key issue is the lack of typhoid burden data in many low- and middle-income countries where TCV could be deployed. Here we present an argument for utilizing environmental sampling for the surveillance of enteric fever organisms to provide data on community-level typhoid risk. Such an approach could complement traditional blood culture-based surveillance or even replace it in settings where population-based clinical surveillance is not feasible. We review historical studies characterizing the transmission of enteric fever organisms through sewage and water, discuss recent advances in the molecular detection of typhoidal Salmonella in the environment, and outline challenges and knowledge gaps that need to be addressed to establish environmental sampling as a tool for generating actionable data that can inform public health responses to enteric fever.
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- 2020
6. Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia
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Panzner, Ursula, Mogeni, Ondari Daniel, Adu-Sarkodie, Yaw, Toy, Trevor, Jeon, Hyon Jin, Pak, Gi Deok, Park, Se Eun, Enuameh, Yeetey, Owusu-Dabo, Ellis, Van Tan, Trinh, Aseffa, Abraham, Teferi, Mekonnen, Yeshitela, Biruk, Baker, Stephen, Rakotozandrindrainy, Raphael, and Marks, Florian
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- 2022
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7. A retrospective investigation of the population structure and geospatial distribution of Salmonella Paratyphi A in Kathmandu, Nepal.
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Mylona, Elli, Pham Thanh, Duy, Keane, Jacqueline A., Dongol, Sabina, Basnyat, Buddha, Dolecek, Christiane, Voong Vinh, Phat, Tran Vu Thieu, Nga, Nguyen Thi Nguyen, To, Karkey, Abhilasha, and Baker, Stephen
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SALMONELLA enterica serovar Typhi ,TYPHOID fever ,LOCATION data ,SALMONELLA typhi ,WHOLE genome sequencing ,SALMONELLA - Abstract
Salmonella Paratyphi A, one of the major etiologic agents of enteric fever, has increased in prevalence in recent decades in certain endemic regions in comparison to S. Typhi, the most prevalent cause of enteric fever. Despite this increase, data on the prevalence and molecular epidemiology of S. Paratyphi A remain generally scarce. Here, we analysed the whole genome sequences of 216 S. Paratyphi A isolates originating from Kathmandu, Nepal between 2005 and 2014, of which 200 were from patients with acute enteric fever and 16 from the gallbladder of people with suspected chronic carriage. By exploiting the recently developed genotyping framework for S. Paratyphi A (Paratype), we identified several genotypes circulating in Kathmandu. Notably, we observed an unusual clonal expansion of genotype 2.4.3 over a four-year period that spread geographically and systematically replaced other genotypes. This rapid genotype replacement is hypothesised to have been driven by both reduced susceptibility to fluoroquinolones and genetic changes to virulence factors, such as functional and structural genes encoding the type 3 secretion systems. Finally, we show that person-to-person is likely the most common mode of transmission and chronic carriers seem to play a limited role in maintaining disease circulation. Author summary: Enteric (typhoid) fever is caused by bacteria of Salmonella enterica species, specifically Salmonella Typhi and Salmonella Paratyphi A. While the former is most commonly identified as the causative agent of enteric fever, S. Paratyphi A is increasing in prevalence in many endemic areas like Nepal. However, the understanding of the phylogenetic structure and population dynamics of this organism, as well as transmission patterns, remains incomplete. Here, we provide a detailed phylogenetic analysis of S. Paratyphi A isolated from enteric fever patients in Nepal through whole genome sequence analysis, combined with epidemiological observations, such as water source use, and chronological and location data. We observed an unusual expansion of a genotype (genetic ID) that replaced other genotypes in the area, indicative of changes in circulating population composition. This expansion is hypothesised to have been driven by reduction in antibiotic susceptibility and changes on bacterial structures that are important for pathogenicity. Our data also suggest person-to-person as the most likely mode of transmission for this pathogen. Understanding of S. Paratyphi A population structure, sources of infection, and transmission will help develop policies for enteric fever management, particularly prior to vaccine introduction, as changes in population composition may affect vaccine efficacy. [ABSTRACT FROM AUTHOR]
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- 2024
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8. The Genome of Salmonella enterica Serovar Typhi
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Baker, Stephen and Dougan, Gordon
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- 2007
9. Detection of Salmonella Typhi nucleic acid by RT-PCR and anti-HlyE, -CdtB, -PilL, and -Vi IgM by ELISA at sites in Ghana, Madagascar and Ethiopia
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Panzner, Ursula, Mogeni, Ondari Daniel, Adu-Sarkodie, Yaw, Toy, Trevor, Jeon, Hyon Jin, Pak, Gi Deok, Park, Se Eun, Enuameh, Yeetey, Owusu-Dabo, Ellis, Van Tan, Trinh, Aseffa, Abraham, Teferi, Mekonnen, Yeshitela, Biruk, Baker, Stephen, Rakotozandrindrainy, Raphael, Marks, Florian, and Apollo - University of Cambridge Repository
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Corneal Dystrophies, Hereditary ,Male ,HlyE-/CdtB-/PilL-/Vi-antigen ,Surveillance ,Adolescent ,Fever ,Reverse Transcriptase Polymerase Chain Reaction ,Enzyme-Linked Immunosorbent Assay ,Febrile illness ,Salmonella typhi ,Ghana ,Infectious Diseases ,Immunoglobulin M ,Salmonella ,Nucleic Acids ,Madagascar ,Humans ,ELISA ,Female ,Ethiopia ,Typhoid Fever - Abstract
Background We aimed to assess the prevalence of Salmonella Typhi through DNA and IgM-antibody detection methods as a prelude to extended surveillance activities at sites in Ghana, Madagascar, and Ethiopia. Methods We performed species-specific real-time polymerase reaction (RT-PCR) to identify bacterial nucleic acid, and enzyme-linked immunosorbent assay (ELISA) for detecting HlyE/STY1498-, CdtB/STY1886-, pilL/STY4539- and Vi-antigens in blood and biopsy specimens of febrile and non-febrile subjects. We generated antigen-specific ELISA proxy cut-offs by change-point analyses, and utilized cumulative sum as detection method coupled with 1000 repetitive bootstrap analyses. We computed prevalence rates in addition to odds ratios to assess correlations between ELISA outcomes and participant characteristics. Results Definitive positive RT-PCR results were obtained from samples of febrile subjects originating from Adama Zuria/Ethiopia (1.9%, 2/104), Wolayita Sodo/Ethiopia (1.0%, 1/100), Diego/Madagascar (1.0%, 1/100), and Kintampo/Ghana (1.0%, 1/100), and from samples of non-febrile subjects from Wolayita Sodo/Ethiopia (1%, 2/201). While IgM antibodies against all antigens were identified across all sites, prevalence rates were highest at all Ethiopian sites, albeit in non-febrile populations. Significant correlations in febrile subjects aged p = 0.034) in Adama Zuria/Ethiopia, STY1498 (OR: 3.21, p = 0.008), STY1886 (OR: 2.31, p = 0.054) and STY4539 (OR: 2.82, p = 0.022) in Diego/Madagascar, and STY1498 (OR: 2.45, p = 0.034) in Kintampo/Ghana. We found statistical significance in non-febrile male versus female subjects for STY1498 (OR: 1.96, p = 0.020) in Adama Zuria/Ethiopia, Vi (OR: 2.84, p = 0.048) in Diego/Madagascar, and STY4539 (OR: 0.46, p = 0.009) in Kintampo/Ghana. Conclusions Findings indicate non-discriminatory stages of acute infections, though with site-specific differences. Immune responses among non-febrile, presumably healthy participants may mask recall and/or reporting bias leading to misclassification, or asymptomatic, subclinical infection signs induced by suppression of inflammatory responses. As most Ethiopian participants were ≥ 15 years of age and not at high-risk, the true S. Typhi burden was likely missed. Change-point analyses for generating ELISA proxy cut-offs appeared robust, though misclassification is possible. Our findings provided important information that may be useful to assess sites prior to implementing surveillance for febrile illness including Salmonella disease.
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- 2021
10. Circulation of Third-Generation Cephalosporin Resistant Salmonella Typhi in Mumbai, India.
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Argimón, Silvia, Nagaraj, Geetha, Shamanna, Varun, Sravani, Dharmavaram, Vasanth, Ashwini Kodlipet, Prasanna, Akshatha, Poojary, Aruna, Bari, Anurag Kumar, Underwood, Anthony, Kekre, Mihir, Baker, Stephen, Aanensen, David M, and Lingegowda, Ravikumar Kadahalli
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GENETIC mutation ,FLUOROQUINOLONES ,TYPHOID fever ,THIRD generation cephalosporins ,SALMONELLA ,BETA lactamases ,DRUG resistance in microorganisms ,MICROBIAL sensitivity tests - Abstract
We report the persistent circulation of third-generation cephalosporin resistant Salmonella Typhi in Mumbai, linked to the acquisition and maintenance of a previously characterized IncX3 plasmid carrying the ESBL gene bla
SHV-12 and the fluoroquinolone resistance gene qnrB7 in the genetic context of a triple mutant also associated with fluoroquinolone resistance. [ABSTRACT FROM AUTHOR]- Published
- 2022
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11. Determining the Best Immunization Strategy for Protecting African Children Against Invasive Salmonella Disease
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Jeon, Hyon Jin, Pak, Gi Deok, Im, Justin, Owusu-Dabo, Ellis, Adu-Sarkodie, Yaw, Gassama Sow, Amy, Bassiahi Soura, Abdramane, Gasmelseed, Nagla, Keddy, Karen H, Bjerregaard-Andersen, Morten, Konings, Frank, Aseffa, Abraham, Crump, John A, Chon, Yun, Breiman, Robert F, Park, Se Eun, Cruz Espinoza, Ligia Maria, Seo, Hye Jin, May, Jürgen, Meyer, Christian G, Andrews, Jason R, Panzner, Ursula, Von Kalckreuth, Vera, Wierzba, Thomas F, Rakotozandrindrainy, Raphaël, Dougan, Gordon, Levine, Myron M, Hombach, Joachim, Kim, Jerome H, Clemens, John D, Baker, Stephen, Marks, Florian, Dougan, Gordon [0000-0003-0022-965X], Baker, Stephen [0000-0003-1308-5755], Marks, Florian [0000-0002-6043-7170], Apollo - University of Cambridge Repository, and Graduate School
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Adult ,Vaccines, Conjugate ,Adolescent ,Fever ,iNTS disease ,Incidence ,Typhoid-Paratyphoid Vaccines ,Infant, Newborn ,Infant ,Salmonella typhi ,immunization ,Young Adult ,Cost of Illness ,Salmonella ,Child, Preschool ,Epidemiological Monitoring ,Salmonella Infections ,Humans ,typhoid conjugate vaccine ,Child ,Articles and Commentaries ,Africa South of the Sahara - Abstract
Background The World Health Organization recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons ≥6 months to 45 years residing in typhoid fever (TF)–endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations. Methods The Typhoid Fever Surveillance in Africa Program (TSAP) was a blood culture-based surveillance of febrile patients from defined populations presenting at healthcare facilities in 10 African countries. TF and invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0–10 year-olds in one-year age increments. Results Salmonella Typhi and iNTS were the most frequently isolated pathogens; 135 and 94 cases were identified, respectively. Analysis from three countries was excluded (incomplete person-years of observation (PYO) data). Thirty-seven of 123 TF cases (30.1%) and 71/90 iNTS disease cases (78.9%) occurred in children aged, A significant burden of typhoid fever in children aged
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- 2018
12. Tebipenem as an oral alternative for the treatment of typhoid caused by XDR Salmonella Typhi.
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Mylona, Elli, Vinh, Phat Voong, Qureshi, Sonia, Karkey, Abhilasha, Dongol, Sabina, Thanh, Tuyen Ha, Walson, Judd, Ballell, Lluis, Álvaro, Elena Fernández, Qamar, Farah, Baker, Stephen, Voong Vinh, Phat, Ha Thanh, Tuyen, and Fernández Álvaro, Elena
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SALMONELLA typhi ,ORAL drug administration ,RESPIRATORY infections ,TYPHOID fever ,SALMONELLA diseases ,DRUG efficacy ,RESEARCH ,CLINICAL trials ,RESEARCH methodology ,EVALUATION research ,COMPARATIVE studies ,SALMONELLA ,RESEARCH funding ,CARBAPENEMS ,ANTIBIOTICS ,PHARMACODYNAMICS - Abstract
Background: Antimicrobial therapy is essential for the treatment of enteric fever, the infection caused by Salmonella serovars Typhi and Paratyphi A. However, an increase in resistance to key antimicrobials and the emergence of MDR and XDR in Salmonella Typhi poses a major threat for efficacious outpatient treatments.Objectives: We recently identified tebipenem, an oral carbapenem licensed for use for respiratory tract infections in Japan, as a potential alternative treatment for MDR/XDR Shigella spp. Here, we aimed to test the in vitro antibacterial efficacy of this drug against MDR and XDR typhoidal Salmonella.Methods: We determined the in vitro activity of tebipenem in time-kill assays against a collection of non-XDR and XDR Salmonella Typhi and Salmonella Paratyphi A (non-XDR) isolated in Nepal and Bangladesh. We also tested the efficacy of tebipenem in combination with other antimicrobials.Results: We found that both XDR and non-XDR Salmonella Typhi and Salmonella Paratyphi A are susceptible to tebipenem, exhibiting low MICs, and were killed within 8-24 h at 2-4×MIC. Additionally, tebipenem demonstrated synergy with two other antimicrobials and could efficiently induce bacterial killing.Conclusions: Salmonella Paratyphi A and XDR Salmonella Typhi display in vitro susceptibility to the oral carbapenem tebipenem, while synergistic activity with other antimicrobials may limit the emergence of resistance. The broad-spectrum activity of this drug against MDR/XDR organisms renders tebipenem a good candidate for clinical trials. [ABSTRACT FROM AUTHOR]- Published
- 2021
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13. Genetic diversity of Salmonella Paratyphi A isolated from enteric fever patients in Bangladesh from 2008 to 2018.
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Rahman, Sadia Isfat Ara, Nguyen, To Nguyen Thi, Khanam, Farhana, Thomson, Nicholas R., Dyson, Zoe A., Taylor-Brown, Alyce, Chowdhury, Emran Kabir, Dougan, Gordon, Baker, Stephen, and Qadri, Firdausi
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TYPHOID fever ,SALMONELLA enterica serovar Typhi ,GENETIC variation ,WHOLE genome sequencing ,SALMONELLA ,SALMONELLA typhi ,SALMONELLA enterica - Abstract
Background: The proportion of enteric fever cases caused by Salmonella Paratyphi A is increasing and may increase further as we begin to introduce typhoid conjugate vaccines (TCVs). While numerous epidemiological and genomic studies have been conducted for S. Typhi, there are limited data describing the genomic epidemiology of S. Paratyphi A in especially in endemic settings, such as Bangladesh. Principal findings: We conducted whole genome sequencing (WGS) of 67 S. Paratyphi A isolated between 2008 and 2018 from eight enteric disease surveillance sites across Bangladesh. We performed a detailed phylogenetic analysis of these sequence data incorporating sequences from 242 previously sequenced S. Paratyphi A isolates from a global collection and provided evidence of lineage migration from neighboring countries in South Asia. The data revealed that the majority of the Bangladeshi S. Paratyphi A isolates belonged to the dominant global lineage A (67.2%), while the remainder were either lineage C (19.4%) or F (13.4%). The population structure was relatively homogenous across the country as we did not find any significant lineage distributions between study sites inside or outside Dhaka. Our genomic data showed presence of single point mutations in gyrA gene either at codon 83 or 87 associated with decreased fluoroquinolone susceptibility in all Bangladeshi S. Paratyphi A isolates. Notably, we identified the pHCM2- like cryptic plasmid which was highly similar to S. Typhi plasmids circulating in Bangladesh and has not been previously identified in S. Paratyphi A organisms. Significance: This study demonstrates the utility of WGS to monitor the ongoing evolution of this emerging enteric pathogen. Novel insights into the genetic structure of S. Paratyphi A will aid the understanding of both regional and global circulation patterns of this emerging pathogen and provide a framework for future genomic surveillance studies. Author summary: Salmonella enterica serovar Paratyphi A is an understudied cause of enteric fever which has started replacing Salmonella Typhi in some endemic regions. Currently, there are limited genomic epidemiology data to understand the true disease burden of disease caused by S. Paratyphi A in poor resource settings like Bangladesh. Our genomic data revealed that the population structure of S. Paratyphi A in Bangladesh comprised of only previously defined lineages A, C and F and carried single point mutation in gyrA gene associated with decreased fluoroquinolone susceptibility with no evidence of multi-drug resistance. Additionally, the global context revealed the clustering of organisms associated with neighboring countries in South Asia. We identified the pHCM2-like cryptic plasmid among our collection, which was not found in any S. Paratyphi A isolates previously. A comparative plasmid analysis showed that S. Paratyphi A pHCM2-like plasmid was highly similar to the plasmid found in S. Typhi but significantly different to a similar plasmid from non-invasive Salmonella Paratyphi B variant Java isolate from Bangladesh. This present study highlights the importance of sustained genomic surveillance to monitor the ongoing evolution of antimicrobial resistant determinants and plasmids in Bangladesh and transmission between different countries. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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14. Bactericidal activities and post-antibiotic effects of ofloxacin and ceftriaxone against drug-resistant Salmonella enterica serovar Typhi.
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Wain, John, Simpson, Julie A, Nga, Luong Thi Diem, Diep, To Song, Duy, Pham Thanh, Baker, Stephen, Day, Nicholas P J, White, Nicholas J, Parry, Christopher M, Thi Diem Nga, Luong, Song Diep, To, Thanh Duy, Pham, Luong, Thi Diem Nga, To, Song Diep, and Pham, Thanh Duy
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SALMONELLA enterica serovar Typhi ,CEFTRIAXONE ,TYPHOID fever ,SALMONELLA diseases ,BACTERICIDAL action ,RESEARCH ,RESEARCH methodology ,MEDICAL cooperation ,EVALUATION research ,COMPARATIVE studies ,SALMONELLA ,DRUGS ,RESEARCH funding ,QUINOLONE antibacterial agents ,MICROBIAL sensitivity tests ,ANTIBIOTICS ,PHARMACODYNAMICS - Abstract
Background: The clinical response to ceftriaxone in patients with typhoid fever is significantly slower than with ofloxacin, despite infection with Salmonella enterica serovar Typhi (S. Typhi) isolates with similar susceptibilities (MIC 0.03-0.12 mg/L). The response to ofloxacin is slower if the isolate has intermediate susceptibility (MIC 0.25-1.0 mg/L).Objectives: To determine the bactericidal activity and post-antibiotic effect (PAE) of ceftriaxone and ofloxacin against S. Typhi.Methods: The mean time to reach a 99.9% reduction in log10 count (bactericidal activity) and PAE of ceftriaxone and ofloxacin were determined for 18 clinical isolates of S. Typhi in time-kill experiments (MIC range for ofloxacin 0.06-1.0 mg/L and for ceftriaxone 0.03-0.12 mg/L).Results: The mean (SD) bactericidal activity of ofloxacin was 33.1 (15.2) min and 384.4 (60) min for ceftriaxone. After a 30 min exposure to ofloxacin, the mean (SD) duration of PAE was 154.7 (52.6) min. There was no detectable PAE after 1 h of exposure to ceftriaxone. For ofloxacin, bactericidal activity and PAE did not significantly differ between isolates with full or intermediate susceptibility provided ofloxacin concentrations were maintained at 4×MIC.Conclusions: Infections with S. Typhi with intermediate ofloxacin susceptibility may respond to doses that maintain ofloxacin concentrations at 4×MIC at the site of infection. The slow bactericidal activity of ceftriaxone and absent PAE may explain the slow clinical response in typhoid. [ABSTRACT FROM AUTHOR]- Published
- 2021
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15. Very long O‐antigen chains of Salmonella Paratyphi A inhibit inflammasome activation and pyroptotic cell death.
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Mylona, Elli, Sanchez‐Garrido, Julia, Hoang Thu, Trang Nguyen, Dongol, Sabina, Karkey, Abhilasha, Baker, Stephen, Shenoy, Avinash R., and Frankel, Gad
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CELL death ,SALMONELLA ,SALMONELLA typhimurium ,EPITHELIAL cells ,TYPHOID fever - Abstract
Salmonella Paratyphi A (SPtA) remains one of the leading causes of enteric (typhoid) fever. Yet, despite the recent increased rate of isolation from patients in Asia, our understanding of its pathogenesis is incomplete. Here we investigated inflammasome activation in human macrophages infected with SPtA. We found that SPtA induces GSDMD‐mediated pyroptosis via activation of caspase‐1, caspase‐4 and caspase‐8. Although we observed no cell death in the absence of a functional Salmonella pathogenicity island‐1 (SPI‐1) injectisome, HilA‐mediated overexpression of the SPI‐1 regulon enhances pyroptosis. SPtA expresses FepE, an LPS O‐antigen length regulator, which induces the production of very long O‐antigen chains. Using a ΔfepE mutant we established that the very long O‐antigen chains interfere with bacterial interactions with epithelial cells and impair inflammasome‐mediated macrophage cell death. Salmonella Typhimurium (STm) serovar has a lower FepE expression than SPtA, and triggers higher pyroptosis, conversely, increasing FepE expression in STm reduced pyroptosis. These results suggest that differential expression of FepE results in serovar‐specific inflammasome modulation, which mirrors the pro‐ and anti‐inflammatory strategies employed by STm and SPtA, respectively. Our studies point towards distinct mechanisms of virulence of SPtA, whereby it attenuates inflammasome‐mediated detection through the elaboration of very long LPS O‐polysaccharides. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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16. The Current Status of Enteric Fever Diagnostics and Implications for Disease Control.
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Baker, Stephen, Blohmke, Christoph J, Maes, Mailis, Johnston, Peter I, and Darton, Thomas C
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SALMONELLA , *SANITATION , *SERODIAGNOSIS , *TYPHOID fever , *TYPHOID vaccines , *GENE expression profiling , *MIDDLE-income countries , *LOW-income countries , *DISEASE eradication , *METABOLOMICS ,TYPHOID fever diagnosis - Abstract
Enteric (typhoid) fever remains a problem in low- and middle-income countries that lack the infrastructure to maintain sanitation and where inadequate diagnostic methods have restricted our ability to identify and control the disease more effectively. As we move into a period of potential disease elimination through the introduction of typhoid conjugate vaccine (TCV), we again need to reconsider the role of typhoid diagnostics in how they can aid in facilitating disease control. Recent technological advances, including serology, transcriptomics, and metabolomics, have provided new insights into how we can detect signatures of invasive Salmonella organisms interacting with the host during infection. Many of these new techniques exhibit potential that could be further explored with the aim of creating a new enteric fever diagnostic to work in conjunction with TCV. We need a sustained effort within the enteric fever field to accelerate, validate, and ultimately introduce 1 (or more) of these methods to facilitate the disease control initiative. The window of opportunity is still open, but we need to recognize the need for communication with other research areas and commercial organizations to assist in the progression of these diagnostic approaches. The elimination of enteric fever is now becoming a real possibility, but new diagnostics need to be part of the equation and factored into future calculations for disease control. [ABSTRACT FROM AUTHOR]
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- 2020
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17. Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi.
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Msefula, Chisomo L., Olgemoeller, Franziska, Jambo, Ndaru, Segula, Dalitso, Van Tan, Trinh, Nyirenda, Tonney S., Nedi, Wilfred, Kennedy, Neil, Graham, Matthew, Henrion, Marc Y. R., Baker, Stephen, Feasey, Nicholas, Gordon, Melita, and Heyderman, Robert S.
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SALMONELLA diseases ,TYPHOID fever ,VACCINE effectiveness ,BLOOD volume ,CHILDREN - Abstract
Typhoid fever is endemic across sub-Saharan Africa. However, estimates of the burden of typhoid are undermined by insufficient blood volumes and lack of sensitivity of blood culture. Here, we aimed to address this limitation by exploiting pre-enrichment culture followed by PCR, alongside routine blood culture to improve typhoid case detection. We carried out a prospective diagnostic cohort study and enrolled children (aged 0–4 years) with non-specific febrile disease admitted to a tertiary hospital in Blantyre, Malawi from August 2014 to July 2016. Blood was collected for culture (BC) and real-time PCR after a pre-enrichment culture in tryptone soy broth and ox-bile. DNA was subjected to PCR for invA (Pan-Salmonella), staG (S. Typhi), and fliC (S. Typhimurium) genes. A positive PCR was defined as invA plus either staG or fliC (CT<29). IgM and IgG ELISA against four S. Typhi antigens was also performed. In total, 643 children (median age 1.3 years) with nonspecific febrile disease were enrolled; 31 (4.8%) were BC positive for Salmonella (n = 13 S. Typhi, n = 16 S. Typhimurium, and n = 2 S. Enteritidis). Pre-enrichment culture of blood followed by PCR identified a further 8 S. Typhi and 15 S. Typhimurium positive children. IgM and IgG titres to the S. Typhi antigen STY1498 (haemolysin) were significantly higher in children that were PCR positive but blood culture negative compared to febrile children with all other non-typhoid illnesses. The addition of pre-enrichment culture and PCR increased the case ascertainment of invasive Salmonella disease in children by 62–94%. These data support recent burden estimates that highlight the insensitivity of blood cultures and support the targeting of pre-school children for typhoid vaccine prevention in Africa. Blood culture with real-time PCR following pre-enrichment should be used to further refine estimates of vaccine effectiveness in typhoid vaccine trials. [ABSTRACT FROM AUTHOR]
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- 2019
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18. Typhoid conjugate vaccines: a new tool in the fight against antimicrobial resistance.
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Andrews, Jason R, Baker, Stephen, Marks, Florian, Alsan, Marcella, Garrett, Denise, Gellin, Bruce G, Saha, Samir K, Qamar, Farah Naz, Yousafzai, Mohammad Tahir, Bogoch, Isaac I, Antillon, Marina, Pitzer, Virginia E, Kim, Jong-Hoon, John, Jacob, Gauld, Jillian, Mogasale, Vittal, Ryan, Edward T, Luby, Stephen P, and Lo, Nathan C
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TYPHOID fever , *ACUTE diseases , *FEDERAL government , *DISEASES , *ANIMAL fighting , *PRESCRIPTION writing , *ANTIBIOTICS , *COST effectiveness , *DRUG resistance in microorganisms , *IMMUNIZATION , *SALMONELLA , *TYPHOID vaccines , *VACCINES , *DISEASE incidence - Abstract
Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines. [ABSTRACT FROM AUTHOR]
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- 2019
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19. Diagnostic metabolite biomarkers of chronic typhoid carriage.
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Näsström, Elin, Jonsson, Pär, Johansson, Anders, Dongol, Sabina, Karkey, Abhilasha, Basnyat, Buddha, Tran Vu Thieu, Nga, Trinh Van, Tan, Thwaites, Guy E., Antti, Henrik, and Baker, Stephen
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TYPHOID fever diagnosis ,SALMONELLA typhi ,GALLBLADDER ,BIOLOGICAL tags ,METABOLITES - Abstract
Background: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic Salmonella carriers are typically asymptomatic, intermittently shedding bacteria in the feces, and contributing to disease transmission. Detecting chronic carriers is of public health relevance in areas where enteric fever is endemic, but there are no routinely used methods for prospectively identifying those carrying Salmonella in their gallbladder. Methodology/Principal findings: Here we aimed to identify biomarkers of Salmonella carriage using metabolite profiling. We performed metabolite profiling on plasma from Nepali patients undergoing cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage (and non-carriage controls) using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition modeling. We were able to significantly discriminate Salmonella carriage samples from non-carriage control samples. We were also able to detect differential signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared carriage metabolite profiles with profiles generated during acute infection; these data revealed substantial heterogeneity between metabolites associated with acute enteric fever and chronic carriage. Lastly, we found that Salmonella carriers could be significantly distinguished from non-carriage controls using only five metabolites, indicating the potential of these metabolites as diagnostic markers for detecting chronic Salmonella carriers. Conclusions/Significance: Our novel approach has highlighted the potential of using metabolomics to search for diagnostic markers of chronic Salmonella carriage. We suggest further epidemiological investigations of these potential biomarkers in alternative endemic enteric fever settings. [ABSTRACT FROM AUTHOR]
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- 2018
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20. A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital.
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Zellweger, Raphaël M., Basnyat, Buddha, Shrestha, Poojan, Prajapati, Krishna G., Dongol, Sabina, Sharma, Paban K., Koirala, Samir, Darton, Thomas C., Dolecek, Christiane, Thompson, Corinne N., Thwaites, Guy E., Baker, Stephen G., and Karkey, Abhilasha
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SALMONELLA typhi ,DISEASE susceptibility ,ANTI-infective agents ,TYPHOID fever treatment ,RETROSPECTIVE studies - Abstract
Background: Salmonella serovars Typhi (S. Typhi) and Paratyphi A (S. Paratyphi A), the causative agents of enteric fever, have been routinely isolated organisms from the blood of febrile patients in the Kathmandu Valley since the early 1990s. Susceptibility against commonly used antimicrobials for treating enteric fever has gradually changed throughout South Asia since this time, posing serious treatment challenges. Here, we aimed to longitudinally describe trends in the isolation of Salmonella enterica and assess changes in their antimicrobial susceptibility in Kathmandu over a 23-year period. Methods: We conducted a retrospective analysis of standardised microbiological data from April 1992 to December 2014 at a single healthcare facility in Kathmandu, examining time trends of Salmonella-associated bacteraemia and the corresponding antimicrobial susceptibility profiles of the isolated organisms. Results: Over 23 years there were 30,353 positive blood cultures. Salmonella enterica accounted for 65.4% (19,857/30,353) of all the bacteria positive blood cultures. S. Typhi and S. Paratyphi A were the dominant serovars, constituting 68.5% (13,592/19,857) and 30.5% (6,057/19,857) of all isolated Salmonellae. We observed (i) a peak in the number of Salmonella-positive cultures in 2002, a year of heavy rainfall and flooding in the Kathmandu Valley, followed by a decline toward pre-flood baseline by 2014, (ii) an increase in the proportion of S. Paratyphi in all Salmonella-positive cultures between 1992 and 2014, (iii) a decrease in the prevalence of MDR for both S. Typhi and S. Paratyphi, and (iv) a recent increase in fluoroquinolone non-susceptibility in both S. Typhi and S. Paratyphi isolates. Conclusions: Our work describes significant changes in the epidemiology of Salmonella enterica in the Kathmandu Valley during the last quarter of a century. We highlight the need to examine current treatment protocols for enteric fever and suggest a change from fluoroquinolone monotherapy to combination therapies of macrolides or cephalosporins along with older first-line antimicrobials that have regained their efficacy. [ABSTRACT FROM AUTHOR]
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- 2017
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21. Non-typhoidal Salmonella serovars associated with invasive and non-invasive disease in the Lao People's Democratic Republic.
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Phuong, Tu Le Thi, Rattanavong, Sayaphet, Vongsouvath, Manivanh, Davong, Viengmon, Lan, Nguyen Phu Huong, Campbell, James I, Thwaites, Guy E, Darton, Thomas C, Newton, Paul N, Dance, David A B, and Baker, Stephen
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SALMONELLA enterica serovar Typhi ,SALMONELLA food poisoning ,SALMONELLA enterica serovar enteritidis ,SALMONELLA ,CHILD mortality - Abstract
Background Invasive non-typhoidal Salmonella (iNTS) disease is a well-described cause of mortality in children and human immunodeficiency virus (HIV)-infected adults in sub-Saharan Africa. Additionally, there is an ill-defined burden of iNTS disease in Southeast Asia. Methods Aiming to investigate the causative serovars of non-invasive and iNTS disease and their associated antimicrobial susceptibility profiles in the Lao People's Democratic Republic, we performed multilocus sequence typing and antimicrobial susceptibility profiling on 168 NTS (63 blood and 105 faecal) organisms isolated in Lao between 2000 and 2012. Results Six different serovars were isolated from blood; Salmonella enterica serovar Enteritidis (n=28), S. enterica serovar Typhimurium (n=19) and S. enterica serovar Choleraesuis (n=11) accounted for >90% (58/63) of the iNTS disease cases. In contrast, the isolates from diarrhoeal faeces were comprised of 18 different serovars, the mostly commonly identified being S. enterica Typhimurium (n=28), S. enterica Weltevreden (n=14) and S. enterica Stanley (n=15). S. enterica Enteritidis and S. enterica Choleraesuis were significantly more associated with systemic disease than diarrhoeal disease in this patient group (p<0.001). Conclusions We find a differing distribution of Salmonella sequence types/serovars between those causing iNTS disease and non-invasive disease in Lao. We conclude that there is a small but not insignificant burden of iNTS disease in Lao. Further clinical and epidemiological investigations are required to assess mortality and the role of comorbidities such as HIV. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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22. A cross-sectional seroepidemiological survey of typhoid fever in Fiji.
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Watson, Conall H., Baker, Stephen, Lau, Colleen L., Rawalai, Kitione, Taufa, Mere, Coriakula, Jerimaia, Thieu, Nga Tran Vu, Van, Tan Trinh, Ngoc, Dung Tran Thi, Hens, Niel, Lowry, John, de Alwis, Ruklanthi, Cano, Jorge, Jenkins, Kylie, Mulholland, E. Kim, Nilles, Eric J., Kama, Mike, and Edmunds, W. John
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TYPHOID fever , *SALMONELLA enterica serovar Typhi , *IMMUNOGLOBULIN G , *IMMUNE system , *MULTIVARIABLE calculus - Abstract
Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks. [ABSTRACT FROM AUTHOR]
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- 2017
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23. The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study.
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Saad, Neil J., Bowles, Cayley C., Grenfell, Bryan T., Basnyat, Buddha, Arjyal, Amit, Dongol, Sabina, Karkey, Abhilasha, Baker, Stephen, and Pitzer, Virginia E.
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TYPHOID fever ,ANTI-infective agents ,DRUG resistance in microorganisms ,INFECTIOUS disease transmission - Abstract
Background: A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu. Methods: We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors. Results: Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections. Conclusions: Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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24. Blood culture-PCR to optimise typhoid fever diagnosis after controlled human infection identifies frequent asymptomatic cases and evidence of primary bacteraemia.
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Darton, Thomas C., Zhou, Liqing, Blohmke, Christoph J., Jones, Claire, Waddington, Claire S., Baker, Stephen, and Pollard, Andrew J.
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BACTEREMIA diagnosis ,TYPHOID fever diagnosis ,BACTEREMIA ,CULTURE media (Biology) ,DNA ,FEVER ,POLYMERASE chain reaction ,SALMONELLA ,TYPHOID fever ,HUMAN research subjects - Abstract
Background: Improved diagnostics for typhoid are needed; a typhoid controlled human infection model may accelerate their development and translation. Here, we evaluated a blood culture-PCR assay for detecting infection after controlled human infection with S. Typhi and compared test performance with optimally performed blood cultures.Methodology/principal Findings: Culture-PCR amplification of blood samples was performed alongside daily blood culture in 41 participants undergoing typhoid challenge. Study endpoints for typhoid diagnosis (TD) were fever and/or bacteraemia. Overall, 24/41 (59%) participants reached TD, of whom 21/24 (86%) had ≥1 positive blood culture (53/674, 7.9% of all cultures) or 18/24 (75%) had ≥1 positive culture-PCR assay result (57/684, 8.3%). A further five non-bacteraemic participants produced culture-PCR amplicons indicating infection; overall sensitivity/specificity of the assay compared to the study endpoints were 70%/65%. We found no significant difference between blood culture and culture-PCR methods in ability to identify cases (12 mismatching pairs, p = 0.77, binomial test). Clinical and stool culture metadata demonstrated that additional culture-PCR amplification positive individuals likely represented true cases missed by blood culture, suggesting the overall attack rate may be 30/41 (73%) rather than 24/41 (59%). Several participants had positive culture-PCR results soon after ingesting challenge providing new evidence for occurrence of an early primary bacteraemia.Conclusions/significance: Overall the culture-PCR assay performed well, identifying extra typhoid cases compared with routine blood culture alone. Despite limitations to widespread field-use, the benefits of increased diagnostic yield, reduced blood volume and faster turn-around-time, suggest that this assay could enhance laboratory typhoid diagnostics in research applications and high-incidence settings. [ABSTRACT FROM AUTHOR]- Published
- 2017
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25. Whole Genome Sequence Analysis of Salmonella Typhi Isolated in Thailand before and after the Introduction of a National Immunization Program.
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Dyson, Zoe A., Holt, Kathryn E., Thanh, Duy Pham, Vinh, Phat Voong, Thanh, Tuyen Ha, Rabaa, Maia A., Thwaites, Guy E., Baker, Stephen, Bodhidatta, Ladaporn, Mason, Carl Jeffries, and Srijan, Apichai
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SALMONELLA genetics ,NUCLEOTIDE sequencing ,SALMONELLA typhi ,TYPHOID fever ,TYPHOID vaccines ,IMMUNIZATION ,MEDICAL care ,GOVERNMENT policy ,DISEASE risk factors - Abstract
Vaccines against Salmonella Typhi, the causative agent of typhoid fever, are commonly used by travellers, however, there are few examples of national immunization programs in endemic areas. There is therefore a paucity of data on the impact of typhoid immunization programs on localised populations of S. Typhi. Here we have used whole genome sequencing (WGS) to characterise 44 historical bacterial isolates collected before and after a national typhoid immunization program that was implemented in Thailand in 1977 in response to a large outbreak; the program was highly effective in reducing typhoid case numbers. Thai isolates were highly diverse, including 10 distinct phylogenetic lineages or genotypes. Novel prophage and plasmids were also detected, including examples that were previously only reported in Shigella sonnei and Escherichia coli. The majority of S. Typhi genotypes observed prior to the immunization program were not observed following it. Post-vaccine era isolates were more closely related to S. Typhi isolated from neighbouring countries than to earlier Thai isolates, providing no evidence for the local persistence of endemic S. Typhi following the national immunization program. Rather, later cases of typhoid appeared to be caused by the occasional importation of common genotypes from neighbouring Vietnam, Laos, and Cambodia. These data show the value of WGS in understanding the impacts of vaccination on pathogen populations and provide support for the proposal that large-scale typhoid immunization programs in endemic areas could result in lasting local disease elimination, although larger prospective studies are needed to test this directly. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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26. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa.
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null, null, Wong, Vanessa K., Holt, Kathryn E., Okoro, Chinyere, Baker, Stephen, Pickard, Derek J., Marks, Florian, Page, Andrew J., Olanipekun, Grace, Munir, Huda, Alter, Roxanne, Fey, Paul D., Feasey, Nicholas A., Weill, Francois-Xavier, Le Hello, Simon, Hart, Peter J., Kariuki, Samuel, Breiman, Robert F., Gordon, Melita A., and Heyderman, Robert S.
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TYPHOID fever diagnosis ,TYPHOID fever ,PUBLIC health ,CHILDREN'S health ,PATIENTS ,MANAGEMENT - Abstract
Background: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. Methods: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. Results: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. Conclusions: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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27. Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam.
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Phu Huong Lan, Nguyen, Le Thi Phuong, Tu, Nguyen Huu, Hien, Thuy, Le, Mather, Alison E., Park, Se Eun, Marks, Florian, Thwaites, Guy E., Van Vinh Chau, Nguyen, Thompson, Corinne N., and Baker, Stephen
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SALMONELLA diseases ,HIV infections ,TROPICAL medicine ,BACTEREMIA ,INSTITUTIONAL review boards - Abstract
Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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28. The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia.
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Pham Thanh, Duy, Thompson, Corinne N., Rabaa, Maia A, Sona, Soeng, Sopheary, Sun, Kumar, Varun, Moore, Catrin, Tran Vu Thieu, Nga, Wijedoru, Lalith, Holt, Kathryn E., Wong, Vanessa, Pickard, Derek, Thwaites, Guy E., Day, Nicholas, Dougan, Gordon, Turner, Paul, Parry, Christopher M., and Baker, Stephen
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MOLECULAR epidemiology ,TYPHOID fever ,SALMONELLA typhi ,NUCLEOTIDE sequencing ,EPIDEMIOLOGY - Abstract
Typhoid fever, caused by the bacterium Salmonella Typhi, is an endemic cause of febrile disease in Cambodia. The aim of this study was to better understand the epidemiology of pediatric typhoid fever in Cambodia. We accessed routine blood culture data from Angkor Hospital for Children (AHC) in Siem Reap province between 2007 and 2014, and performed whole genome sequencing (WGS) on the isolated bacteria to characterize the S. Typhi population. The resulting phylogenetic information was combined with conventional epidemiological approaches to investigate the spatiotemporal distribution of S. Typhi and population-level risk factors for reported disease. During the study period, there were 262 cases of typhoid within a 100 km radius of AHC, with a median patient age of 8.2 years (IQR: 5.1–11.5 years). The majority of infections occurred during the rainy season, and commune incidences as high as 11.36/1,000 in children aged <15 years were observed over the study period. A population-based risk factor analysis found that access to water within households and increasing distance from Tonle Sap Lake were protective. Spatial mapping and WGS provided additional resolution for these findings, and confirmed that proximity to the lake was associated with discrete spatiotemporal disease clusters. We confirmed the dominance of MDR H58 S. Typhi in this population, and found substantial evidence of diversification (at least seven sublineages) within this single lineage. We conclude that there is a substantial burden of pediatric typhoid fever in rural communes in Cambodia. Our data provide a platform for additional population-based typhoid fever studies in this location, and suggest that this would be a suitable setting in which to introduce a school-based vaccination programme with Vi conjugate vaccines. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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29. Variations of Invasive Salmonella Infections by Population Size in Asante Akim North Municipal, Ghana.
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Cruz Espinoza, Ligia M., Nichols, Chelsea, Adu-Sarkodie, Yaw, Al-Emran, Hassan M., Baker, Stephen, Clemens, John D., Dekker, Denise Myriam, Eibach, Daniel, Krumkamp, Ralf, Boahen, Kennedy, Im, Justin, Jaeger, Anna Jaeger, von Kalckreuth, Vera, Gi Deok Pak, Panzner, Ursula, Se Eun Park, Jin Kyung Park, Sarpong, Nimako, Schütt-Gerowitt, Heidi, and Toy, Trevor
- Abstract
Background. The Typhoid Fever Surveillance in Africa Program (TSAP) estimated adjusted incidence rates (IRs) for Salmonella enterica serovar Typhi and invasive nontyphoidal S. enterica serovars (iNTS) of >100 cases per 100 000 person-years of observation (PYO) for children aged <15 years in Asante Akim North Municipal (AAN), Ghana, between March 2010 and May 2012. We analyzed how much these rates differed between rural and urban settings. Methods. Children recruited at the Agogo Presbyterian Hospital and meeting TSAP inclusion criteria were included in the analysis. Towns with >32 000 inhabitants were considered urban; towns with populations <5200 were considered rural. Adjusted IRs for Salmonella bloodstream infections were estimated for both settings. Setting-specific age-standardized incidence rates for children aged <15 years were derived and used to calculate age-standardized rate ratios (SRRs) to evaluate differences between settings. Results. Eighty-eight percent (2651/3000) of recruited patients met inclusion criteria and were analyzed. IRs of Salmonella bloodstream infections in children <15 years old were >100 per 100 000 PYO in both settings. Among rural children, the Salmonella Typhi and iNTS rates were 2 times (SRR, 2.2; 95% confidence interval [CI], 1.3–3.5) and almost 3 times (SRR, 2.8; 95% CI, 1.9–4.3) higher, respectively, than rates in urban children. Conclusions. IRs of Salmonella bloodstream infections in children <15 years old in AAN, Ghana, differed by setting, with 2 to nearly 3 times higher rates in the less populated setting. Variations in the distribution of the disease should be considered to implement future studies and intervention strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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30. A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions.
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Makendi, Carine, Page, Andrew J., Wren, Brendan W., Le Thi Phuong, Tu, Clare, Simon, Hale, Christine, Goulding, David, Klemm, Elizabeth J., Pickard, Derek, Okoro, Chinyere, Hunt, Martin, Thompson, Corinne N., Phu Huong Lan, Nguyen, Tran Do Hoang, Nhu, Thwaites, Guy E., Le Hello, Simon, Brisabois, Anne, Weill, François-Xavier, Baker, Stephen, and Dougan, Gordon
- Subjects
SALMONELLA enterica ,BACTERIA phylogeny ,VIRULENCE of bacteria ,BACTERIAL genomes ,LABORATORY mice - Abstract
Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
31. Induction of Antimicrobial Resistance in Escherichia coli and Non-Typhoidal Salmonella Strains after Adaptation to Disinfectant Commonly Used on Farms in Vietnam.
- Author
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Nhung, Nguyen T., Thuy, Cao T., Trung, Nguyen V., Campbell, James, Baker, Stephen, Thwaites, Guy, Hoa, Ngo T., and Carrique-Mas, Juan
- Subjects
ANTI-infective agents ,DRUG resistance in bacteria ,DISINFECTION & disinfectants ,ESCHERICHIA coli ,SALMONELLA - Abstract
In Vietnam, commercial disinfectants containing quaternary ammonium compounds (QACs) are commonly used in pig and poultry farms to maintain hygiene during production. We hypothesized that sustained exposure to sub-bactericidal concentrations of QAC-based disinfectants may result in increased levels of antimicrobial resistance (AMR) among Enterobacteriacea due to the increase of efflux pump expression. To test this hypothesis we exposed six antimicrobial-susceptible Escherichia coli (E. coli) and six antimicrobial-susceptible non-typhoidal Salmonella (NTS) isolates to increasing concentrations of a commonly used commercial disinfectant containing a mix of benzalkonium chloride and glutaraldehyde. Over the 12-day experiment, strains exhibited a significant change in their minimum inhibitory concentration (MIC) of the disinfectant product (mean increase of 31% (SD ± 40)) (p = 0.02, paired Wilcoxon test). Increases in MIC for the disinfectant product were strongly correlated with increases in MIC (or decreases in inhibition zone) for all antimicrobials (Pearson's correlation coefficient 0.71-0.83, all p < 0.01). The greatest increases in MIC (or decreases in inhibition zone) were observed for ampicillin, tetracycline, ciprofloxacin, and chloramphenicol, and the smallest for gentamicin, trimethoprim/sulphamethoxazole. The treatment of 155 representative E. coli isolates from farmed and wild animals in the Mekong Delta (Vietnam) with phenyl-arginine beta-naphthylamide (PAßN), a generic efflux pump inhibitor, resulted in reductions in the prevalence of AMR ranging from 0.7% to 3.3% in these organisms, indicating a small contribution of efflux pumps on the observed prevalence of AMR on farms. These results suggest that the mass usage of commercial disinfectants, many of which contain QACs, is potentially a contributing factor on the generation and maintenance of AMR in animal production in Vietnam. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
32. Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model.
- Author
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De Jong, Hanna K., Achouiti, Ahmed, Koh, Gavin C. K. W., Parry, Christopher M., Baker, Stephen, Faiz, Mohammed Abul, van Dissel, Jaap T., Vollaard, Albert M., van Leeuwen, Ester M. M., Roelofs, Joris J. T. H., de Vos, Alex F., Roth, Johannes, van der Poll, Tom, Vogl, Thomas, and Wiersinga, Willem Joost
- Subjects
TYPHOID fever ,SALMONELLA enterica serovar Typhi ,SALMONELLA diseases ,CALPROTECTIN ,SALMONELLA ,SALMONELLA typhi ,CELL receptors - Abstract
Background: Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. Methods and principal findings: S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9
-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. Conclusion: S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice. Author Summary: Bacterial pathogens are recognized by the host upon infection through interactions between their virulence factors and host cell receptors leading to the activation and recruitment of innate immune cells. Salmonella Typhi, the etiologic agent for typhoid fever, however harbors a number of factors, such as a polysaccharide capsule, which prevent the detection of these virulence factors, and thereby dampens the innate host response. Besides bacterial virulence factors, the host can detect endogenous danger molecules which are released upon tissue damage. S100A8/A9, an extracellular protein complex, is such a danger signal that is able to further amplify the systemic inflammatory response upon infection. In the present study we investigated the role of S100A8/A9 during invasive Salmonella infection and observed a marked increase of this protein in patients with typhoid fever, which correlates with disease stage and severity. Furthermore we found that S100A8/A9 directly inhibited the growth of Salmonella species in vitro thereby functioning as an antimicrobial. When mice were infected with Salmonella, the levels of S100A8/A9 were also elevated but mice lacking this protein did not have an altered host response to infection. The role and importance of the elevated levels of S100A8/A9 in human typhoid fever requires further study. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
33. Differential Epidemiology of Salmonella Typhi and Paratyphi A in Kathmandu, Nepal: A Matched Case Control Investigation in a Highly Endemic Enteric Fever Setting.
- Author
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Karkey, Abhilasha, Thompson, Corinne N., Tran Vu Thieu, Nga, Dongol, Sabina, Le Thi Phuong, Tu, Voong Vinh, Phat, Arjyal, Amit, Martin, Laura B., Rondini, Simona, Farrar, Jeremy J., Dolecek, Christiane, Basnyat, Buddha, and Baker, Stephen
- Subjects
SALMONELLA typhi ,CASE-control method ,TYPHOID vaccines ,LOGISTIC regression analysis ,HEALTH behavior - Abstract
Background: Enteric fever, a systemic infection caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A, is endemic in Kathmandu, Nepal. Previous work identified proximity to poor quality water sources as a community-level risk for infection. Here, we sought to examine individual-level risk factors related to hygiene and sanitation to improve our understanding of the epidemiology of enteric fever in this setting. Methodology and principal findings: A matched case-control analysis was performed through enrollment of 103 blood culture positive enteric fever patients and 294 afebrile community-based age and gender-matched controls. A detailed questionnaire was administered to both cases and controls and the association between enteric fever infection and potential exposures were examined through conditional logistic regression. Several behavioral practices were identified as protective against infection with enteric fever, including water storage and hygienic habits. Additionally, we found that exposures related to poor water and socioeconomic status are more influential in the risk of infection with S. Typhi, whereas food consumption habits and migration play more of a role in risk of S. Paratyphi A infection. Conclusions and significance: Our work suggests that S. Typhi and S. Paratyphi A follow different routes of infection in this highly endemic setting and that sustained exposure to both serovars probably leads to the development of passive immunity. In the absence of a polyvalent vaccine against S. Typhi and S. Paratyphi A, we advocate better systems for water treatment and storage, improvements in the quality of street food, and vaccination with currently available S. Typhi vaccines. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
34. Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting.
- Author
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Andrews, Jason R., Prajapati, Krishna G., Eypper, Elizabeth, Shrestha, Poojan, Shakya, Mila, Pathak, Kamal R., Joshi, Niva, Tiwari, Priyanka, Risal, Manisha, Koirala, Samir, Karkey, Abhilasha, Dongol, Sabina, Wen, Shawn, Smith, Amy B., Maru, Duncan, Basnyat, Buddha, Baker, Stephen, Farrar, Jeremy, Ryan, Edward T., and Hohmann, Elizabeth
- Subjects
SALMONELLA enterica ,TYPHOID fever ,BACTEREMIA ,GRAM-negative bacteria ,DRUG resistance in bacteria ,MEDICAL microbiology - Abstract
Background: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Methodology/Principal Findings: Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%–97.0%) and 96.0% (92.7%–98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. Conclusions/Significance: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
35. Enteric fever in Cambodian children is dominated by multidrug-resistant H58 Salmonella enterica serovar Typhi with intermediate susceptibility to ciprofloxacin
- Author
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Emary, Kate, Moore, Catrin E., Chanpheaktra, Ngoun, An, Khun Peng, Chheng, Kheng, Sona, Soeng, Duy, Pham Thanh, Nga, Tran Vu Thieu, Wuthiekanun, Vanaporn, Amornchai, Premjit, Kumar, Varun, Wijedoru, Lalith, Stoesser, Nicole E., Carter, Michael J., Baker, Stephen, Day, Nicholas P.J., and Parry, Christopher M.
- Subjects
TYPHOID fever ,FEVER in children ,MULTIDRUG resistance ,SALMONELLA enterica serovar Typhi ,MICROBIAL sensitivity tests ,CIPROFLOXACIN - Abstract
Abstract: Infections with Salmonella enterica serovar Typhi isolates that are multidrug resistant (MDR: resistant to chloramphenicol, ampicillin, trimethoprim–sulphamethoxazole) with intermediate ciprofloxacin susceptibility are widespread in Asia but there is little information from Cambodia. We studied invasive salmonellosis in children at a paediatric hospital in Siem Reap, Cambodia. Between 2007 and 2011 Salmonella was isolated from a blood culture in 162 children. There were 151 children with enteric fever, including 148 serovar Typhi and three serovar Paratyphi A infections, and 11 children with a non-typhoidal Salmonella infection. Of the 148 serovar Typhi isolates 126 (85%) were MDR and 133 (90%) had intermediate ciprofloxacin susceptibility. Inpatient antimicrobial treatment was ceftriaxone alone or initial ceftriaxone followed by a step-down to oral ciprofloxacin or azithromycin. Complications developed in 37/128 (29%) children admitted with enteric fever and two (1.6%) died. There was one confirmed relapse. In a sample of 102 serovar Typhi strains genotyped by investigation of a subset of single nucleotide polymorphisms, 98 (96%) were the H58 haplotype, the majority of which had the common serine to phenylalanine substitution at codon 83 in the DNA gyrase. We conclude that antimicrobial-resistant enteric fever is common in Cambodian children and therapeutic options are limited. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
36. The Microbiological and Clinical Characteristics of Invasive Salmonella in Gallbladders from Cholecystectomy Patients in Kathmandu, Nepal.
- Author
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Dongol, Sabina, Thompson, Corinne N., Clare, Simon, Thieu Nga, Tran Vu, Duy, Pham Thanh, Karkey, Abhilasha, Arjyal, Amit, Koirala, Samir, Khatri, Nely Shrestha, Maskey, Pukar, Poudel, Sanjay, Jaiswal, Vijay Kumar, Vaidya, Sujan, Dougan, Gordon, Farrar, Jeremy J., Dolecek, Christiane, Basnyat, Buddha, and Baker, Stephen
- Subjects
GALLBLADDER ,SALMONELLA ,CHOLECYSTECTOMY ,TYPHOID fever ,NEUTROPHILS - Abstract
Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining typhoid fever transmission. Bile and tissue was obtained from 1,377 individuals undergoing cholecystectomy in Kathmandu to investigate the prevalence, characteristics and relevance of invasive Salmonella in the gallbladder in an endemic area. Twenty percent of bile samples contained a Gram-negative organism, with Salmonella Typhi and Salmonella Paratyphi A isolated from 24 and 22 individuals, respectively. Gallbladders that contained Salmonella were more likely to show evidence of acute inflammation with extensive neutrophil infiltrate than those without Salmonella, corresponding with higher neutrophil and lower lymphocyte counts in the blood of Salmonella positive individuals. Antimicrobial resistance in the invasive Salmonella isolates was limited, indicating that gallbladder colonization is unlikely to be driven by antimicrobial resistance. The overall role of invasive Salmonella carriage in the gallbladder is not understood; here we show that 3.5% of individuals undergoing cholecystectomy in this setting have a high concentration of antimicrobial sensitive, invasive Salmonella in their bile. We predict that such individuals will become increasingly important if current transmission mechanisms are disturbed; prospectively identifying these individuals is, therefore, paramount for rapid local and regional elimination. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
37. The decline of typhoid and the rise of non-typhoid salmonellae and fungal infections in a changing HIV landscape: bloodstream infection trends over 15 years in southern Vietnam
- Author
-
Nga, Tran Vu Thieu, Parry, Christopher M., Le, Thuy, Lan, Nguyen Phu Huong, Diep, To Song, Campbell, James I., Hoang, Nguyen Van Minh, Dung, Le Thi, Wain, John, Dolecek, Christiane, Farrar, Jeremy J., Chau, Nguyen Van Vinh, Hien, Tran Tinh, Day, Jeremy N., and Baker, Stephen
- Subjects
HIV ,SALMONELLA ,MYCOSES ,SALMONELLA typhi ,CRYPTOCOCCUS neoformans ,ETIOLOGY of diseases - Abstract
Summary: The etiological spectrum of bloodstream infections is variable between industrialized and developing countries and even within a defined location over time. We investigated trends in bloodstream infections at an infectious disease hospital in Ho Chi Minh City, Vietnam, from 1994–2008. Amongst 66111 blood cultures performed, a clinically relevant pathogen was isolated in 7645 episodes (positivity rate; 116/1000 cultures). Salmonella Typhi was the predominant pathogen until 2002; however, a considerable annual decline in the proportion of S. Typhi was observed (OR 0.6993, 95% CI [0.6885, 0.7103], p<0.0001). Conversely, there was a significant increase in the proportions of non-typhoidal Salmonella (NTS), Cryptococcus neoformans and Penicillium marneffei, concurrent with increasing HIV prevalence. These data document a substantial longitudinal shift in bloodstream infection etiology in southern Vietnam. We propose such changes are related to increasing economic prosperity and HIV prevalence, and this pattern marks a substantial change in the epidemiology of invasive salmonellosis in Southeast Asia. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
38. The Burden and Characteristics of Enteric Fever at a Healthcare Facility in a Densely Populated Area of Kathmandu.
- Author
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Karkey, Abhilasha, Arjyal, Amit, Anders, Katherine L., Boni, Maciej F., Dongol, Sabina, Koirala, Samir, Phan Vu Tra My, Tran Vu Thieu Nga, Clements, Archie C. A., Holt, Kathryn E., Pham Thanh Duy, Day, Jeremy N., Campbell, James I., Dougan, Gordon, Dolecek, Christiane, Farrar, Jeremy, Basnyat, Buddha, and Baker, Stephen
- Subjects
SALMONELLA ,TYPHOID fever ,SALMONELLA diseases ,MEDICAL care ,POPULATION density ,INFECTIOUS disease transmission - Abstract
Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A) remains a major public health problem in many settings. The disease is limited to locations with poor sanitation which facilitates the transmission of the infecting organisms. Efficacious and inexpensive vaccines are available for S. Typhi, yet are not commonly deployed to control the disease. Lack of vaccination is due partly to uncertainty of the disease burden arising from a paucity of epidemiological information in key locations. We have collected and analyzed data from 3,898 cases of blood culture-confirmed enteric fever from Patan Hospital in Lalitpur Sub-Metropolitan City (LSMC), between June 2005 and May 2009. Demographic data was available for a subset of these patients (n = 527) that were resident in LSMC and who were enrolled in trials. We show a considerable burden of enteric fever caused by S. Typhi (2,672; 68.5%) and S. Paratyphi A (1,226; 31.5%) at this Hospital over a four year period, which correlate with seasonal fluctuations in rainfall. We found that local population density was not related to incidence and we identified a focus of infections in the east of LSMC. With data from patients resident in LSMC we found that the median age of those with S. Typhi (16 years) was significantly less than S. Paratyphi A (20 years) and that males aged 15 to 25 were disproportionately infected. Our findings provide a snapshot into the epidemiological patterns of enteric fever in Kathmandu. The uneven distribution of enteric fever patients within the population suggests local variation in risk factors, such as contaminated drinking water. These findings are important for initiating a vaccination scheme and improvements in sanitation. We suggest any such intervention should be implemented throughout the LSMC area. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
39. Mobilization of the incQ Plasmid R300B with a Chromosomal Conjugation System in Salmonella enterica Serovar Typhi.
- Author
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Baker, Stephen, Pickard, Derek, Whitehead, Sally, Farrar, Jeremy, and Dougan, Gordon
- Subjects
- *
SALMONELLA , *MICROORGANISMS , *PATHOGENIC microorganisms , *MOBILE genetic elements , *MOLECULAR genetics , *CHROMOSOMAL translocation , *GENOMICS , *GENOMES , *GENETICS - Abstract
Salmonella pathogenicity island 7 (SPI-7) in Salmonella enterica serovar Typhi appears to be related to other genomic islands. Evidence suggests that SPI-7 is susceptible to spontaneous circularization, loss, and transposition. Here, we demonstrate that a region within SPI-7 has the ability to mobilize the small incQ plasmid R300B. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
40. Analysis of the Hypervariable Region of the Salmonella enterica Genome Associated with tRNAleuX.
- Author
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Bishop, Anne L., Baker, Stephen, Jenks, Sara, Fookes, Maria, Gaora, Peadar Ó., Pickard, Derek, Anjum, Muna, Farrar, Jeremy, Hien, Tran T., Ivens, Al, and Dougan, Gordon
- Subjects
- *
SALMONELLA , *ESCHERICHIA coli , *ENTEROBACTERIACEAE , *BACTERIAL genetics , *BACTERIOLOGY , *BACTERIAL genomes - Abstract
The divergence of Salmonella enterica and Escherichia coli is estimated to have occurred approximately 140 million years ago. Despite this evolutionary distance, the genomes of these two species still share extensive synteny and homology. However, there are significant differences between the two species in terms of genes putatively acquired via various horizontal transfer events. Here we report on the composition and distribution across the Salmonella genus of a chromosomal region designated SPI-10 in Salmonella enterica serovar Typhi and located adjacent to tRNAleux. We find that across the Salmonella genus the tRNAleux region is a hypervariable hot spot for horizontal gene transfer; different isolates from the same S. enterica serovar can exhibit significant variation in this region. Many P4 phage, plasmid, and transposable element-associated genes are found adjacent to tRNAleux in both Salmonella and E. coli, suggesting that these mobile genetic elements have played a major role in driving the variability of this region. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
41. The Role of Prophage-like Elements in the Diversity of Salmonella enterica Serovars
- Author
-
Thomson, Nicholas, Baker, Stephen, Pickard, Derek, Fookes, Maria, Anjum, Muna, Hamlin, Nancy, Wain, John, House, Deborah, Bhutta, Zulfiqar, Chan, Kaman, Falkow, Stanley, Parkhill, Julian, Woodward, Martin, Ivens, Al, and Dougan, Gordon
- Subjects
- *
SALMONELLA , *AMINO acids , *GENOMICS , *MOLECULAR genetics - Abstract
The Salmonella enterica serovar Typhi CT18 (S. Typhi) chromosome harbours seven distinct prophage-like elements, some of which may encode functional bacteriophages. In silico analyses were used to investigate these regions in S. Typhi CT18, and ultimately compare these integrated bacteriophages against 40 other Salmonella isolates using DNA microarray technology. S. Typhi CT18 contains prophages that show similarity to the lambda, Mu, P2 and P4 bacteriophage families. When compared to other S. Typhi isolates, these elements were generally conserved, supporting a clonal origin of this serovar. However, distinct variation was detected within a broad range of Salmonella serovars; many of the prophage regions are predicted to be specific to S. Typhi. Some of the P2 family prophage analysed have the potential to carry non-essential “cargo” genes within the hyper-variable tail region, an observation that suggests that these bacteriophage may confer a level of specialisation on their host. Lysogenic bacteriophages therefore play a crucial role in the generation of genetic diversity within S. enterica. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
42. Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting
- Author
-
Andrews, Jason R., Prajapati, Krishna G., Eypper, Elizabeth, Shrestha, Poojan, Shakya, Mila, Pathak, Kamal R., Joshi, Niva, Tiwari, Priyanka, Risal, Manisha, Koirala, Samir, Karkey, Abhilasha, Dongol, Sabina, Wen, Shawn, Smith, Amy B., Maru, Duncan, Basnyat, Buddha, Baker, Stephen, Farrar, Jeremy, Ryan, Edward T., Hohmann, Elizabeth, and Arjyal, Amit
- Subjects
Medicine ,Diagnostic Medicine ,Clinical Laboratory Sciences ,Global Health ,Infectious Diseases ,Bacterial Diseases ,Salmonella - Abstract
Background: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. Methodology/Principal Findings Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%–97.0%) and 96.0% (92.7%–98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. Conclusions/Significance: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.
- Published
- 2013
- Full Text
- View/download PDF
43. Typhoid carriage in the gallbladder.
- Author
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Basnyat, Buddha and Baker, Stephen
- Subjects
- *
SALMONELLA enterica serovar Typhi , *SYMPTOMS , *DIAGNOSIS , *GALLBLADDER , *IMMUNOFLUORESCENCE , *CARRIER state (Communicable diseases) , *CHOLECYSTECTOMY , *CHOLECYSTITIS , *SALMONELLA ,TYPHOID fever diagnosis - Abstract
The article describes the case of a male patient with Salmonella enterica serovar S Typhi. It discusses the symptoms shown by the patient upon admission to Patan Hospital in Kathmandu, Nepal, the patient's diagnosis, and examination of the patient's gallbladder with the use of immunofluorescent labelling.
- Published
- 2015
- Full Text
- View/download PDF
44. Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder persistence.
- Author
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Gunn, John S., Marshall, Joanna M., Baker, Stephen, Dongol, Sabina, Charles, Richelle C., and Ryan, Edward T.
- Subjects
- *
SALMONELLA diseases , *CARRIER state (Communicable diseases) , *EPIDEMIOLOGY , *PUBLIC health , *CHILD death ,TYPHOID fever diagnosis - Abstract
Typhoid (enteric fever) remains a major cause of morbidity and mortality worldwide, causing over 21 million new infections annually, with the majority of deaths occurring in young children. Because typhoid fever-causing Salmonella have no known environmental reservoir, the chronic, asymptomatic carrier state is thought to be a key feature of continued maintenance of the bacterium within human populations. Despite the importance of this disease to public health, our understanding of the molecular mechanisms that catalyze carriage, as well as our ability to reliably identify and treat the Salmonella carrier state, have only recently begun to advance. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
45. Composition, Acquisition, and Distribution of the Vi Exopolysaccharide-Encoding Salmonella enterica Pathogenicity Island SPI-7.
- Author
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Pickard, Derek, Wain, John, Baker, Stephen, Line, Alexandra, Chohan, Sonia, Fookes, Maria, Barron, Andrew, Gaora, Peadar Ó., Chabalgoity, José A., Thanky, Niren, Scholes, Christoph, Thomson, Nicholas, Quail, Michael, Parkhill, Julian, and Dougan, Gordon
- Subjects
- *
SALMONELLA , *MICROBIAL exopolysaccharides , *BACTERIOLOGY - Abstract
Vi capsular polysaccharide production is encoded by the viaB locus, which has a limited distribution in Salmonella enterica serovars. In S. enterica serovar Typhi, viaB is encoded on a 134-kb pathogenicity island known as SPI-7 that is located between partially duplicated tRNA[sup pheU] sites. Functional and bioinformatic analysis suggests that SPI-7 has a mosaic structure and may have evolved as a consequence of several independent insertion events. Analysis of viaB-associated DNA in Vi-positive S. enterica serovar Paratyphi C and S. enterica serovar Dublin isolates revealed the presence of similar SPI-7 islands. In S. enterica serovars Paratyphi C and Dublin, the SopE bacteriophage and a 15-kb fragment adjacent to the intact tRNA[sup pheU] site were absent. In S. enterica serovar Paratyphi C only, a region encoding a type IV pilus involved in the adherence or S. enterica serovar Typhi to host cells was missing. The remainder of the SPI-7 islands investigated exhibited over 99% DNA sequence identity in the three serovars. Of 30 other Salmonella serovars examined, 24 contained no insertions at the equivalent tRNA[sup pheU] site, 2 had a 3.7-kb insertion, and 4 showed sequence variation at the tRNA[sup pheU]-phoN junction, which was not analyzed further. Sequence analysis of the SPI-7 region from S. enterica serovar Typhi strain CT18 revealed significant synteny with clusters of genes from a variety of saprophytic bacteria and phytobacteria, including Pseudomonas aeruginosa and Xanthomonas axonopodis pv. citri. This analysis suggested that SPI-7 may be a mobile element, such as a conjugative transposon or an integrated plasmid remnant. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
46. Mobility of antimicrobial resistance across serovars and disease presentations in non-typhoidal Salmonella from animals and humans in Vietnam
- Author
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Samuel Bloomfield, Vu Thuy Duong, Ha Thanh Tuyen, James I. Campbell, Nicholas R. Thomson, Julian Parkhill, Hoang Le Phuc, Tran Thi Hong Chau, Duncan J. Maskell, Gabriel G. Perron, Nguyen Minh Ngoc, Lu Lan Vi, Evelien M. Adriaenssens, Stephen Baker, Alison E. Mather, Parkhill, Julian [0000-0002-7069-5958], Baker, Stephen [0000-0003-1308-5755], and Apollo - University of Cambridge Repository
- Subjects
plasmids ,Vietnam ,Salmonella ,chromosome arrangements ,Drug Resistance, Bacterial ,Animals ,Humans ,General Medicine ,Typhoid Fever ,Antimicrobial resistance ,Serogroup ,insertion sequences ,Anti-Bacterial Agents - Abstract
Non-typhoidal Salmonella (NTS) is a major cause of bacterial enterocolitis globally but also causes invasive bloodstream infections. Antimicrobial resistance (AMR) hampers the treatment of these infections and understanding how AMR spreads between NTS may help in developing effective strategies. We investigated NTS isolates associated with invasive disease, diarrhoeal disease and asymptomatic carriage in animals and humans from Vietnam. Isolates included multiple serovars and both common and rare phenotypic AMR profiles; long- and short-read sequencing was used to investigate the genetic mechanisms and genomic backgrounds associated with phenotypic AMR profiles. We demonstrate concordance between most AMR genotypes and phenotypes but identified large genotypic diversity in clinically relevant phenotypes and the high mobility potential of AMR genes (ARGs) in this setting. We found that 84 % of ARGs identified were located on plasmids, most commonly those containing IncHI1A_1 and IncHI1B(R27)_1_R27 replicons (33%), and those containing IncHI2_1 and IncHI2A_1 replicons (31%). The vast majority (95%) of ARGS were found within 10 kbp of IS6/IS26 elements, which provide plasmids with a mechanism to exchange ARGs between plasmids and other parts of the genome. Whole genome sequencing with targeted long-read sequencing applied in a One Health context identified a comparatively limited number of insertion sequences and plasmid replicons associated with AMR. Therefore, in the context of NTS from Vietnam and likely for other settings as well, the mechanisms by which ARGs move contribute to a more successful AMR profile than the specific ARGs, facilitating the adaptation of bacteria to different environments or selection pressures.
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- 2022
47. An age-stratified serosurvey against purified Salmonella enterica serovar Typhi antigens in the Lao People´s Democratic Republic
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Lisa Hefele, Antony P. Black, Trinh Van Tan, Nguyen Tri Minh, Nguyen Duc Hoang, Siriphone Virachith, Claude P. Muller, Judith M. Hübschen, Paula Russell, Josefin Bartholdson Scott, Chau Nguyen Ngoc Minh, Tran Vu Thieu Nga, Stephen Baker, Tri Minh, Nguyen [0000-0002-1819-2296], Duc Hoang, Nguyen [0000-0003-2437-3568], Virachith, Siriphone [0000-0001-5049-0544], Hübschen, Judith M [0000-0002-5001-2128], Russell, Paula [0000-0003-2389-6631], Bartholdson Scott, Josefin [0000-0003-3380-4446], Thieu Nga, Tran Vu [0000-0003-3672-9867], Baker, Stephen [0000-0003-1308-5755], and Apollo - University of Cambridge Repository
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Bacterial Diseases ,Male ,Physiology ,Epidemiology ,RC955-962 ,Fevers ,Pathology and Laboratory Medicine ,Biochemistry ,Cohort Studies ,Medical Conditions ,Salmonella ,Immune Physiology ,Arctic medicine. Tropical medicine ,Typhoid ,Ethnicities ,Enzyme-Linked Immunoassays ,Child ,Immune System Proteins ,Age Factors ,Antibodies, Bacterial ,Bacterial Pathogens ,Infectious Diseases ,Serology ,Medical Microbiology ,Laos ,Child, Preschool ,Lao People ,Female ,Pathogens ,Public aspects of medicine ,RA1-1270 ,Research Article ,Adult ,Adolescent ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Microbiology ,Antibodies ,Young Adult ,Signs and Symptoms ,Asian People ,Enterobacteriaceae ,Humans ,Typhoid Fever ,Immunoassays ,Microbial Pathogens ,Medicine and health sciences ,Antigens, Bacterial ,Bacteria ,Biology and life sciences ,Public Health, Environmental and Occupational Health ,Organisms ,Proteins ,Infant ,Salmonella typhi ,Research and analysis methods ,Immunoglobulin G ,Immunologic Techniques ,Population Groupings ,Clinical Medicine ,People and places - Abstract
The epidemiology of typhoid fever in Lao People`s Democratic Republic is poorly defined. Estimating the burden of typhoid fever in endemic countries is complex due to the cost and limitations of population-based surveillance; serological approaches may be a more cost-effective alternative. ELISAs were performed on 937 serum samples (317 children and 620 adults) from across Lao PDR to measure IgG antibody titers against Vi polysaccharide and the experimental protein antigens, CdtB and HlyE. We measured the significance of the differences between antibody titers in adults and children and fitted models to assess the relationship between age and antibody titers. The median IgG titres of both anti-HylE and CdtB were significantly higher in children compared to adults (anti-HylE; 351.7 ELISA Units (EU) vs 198.1 EU, respectively; p, Author summary Typhoid fever is a serious bloodstream infection caused by the bacterium Salmonella Typhi. Estimating the burden of typhoid fever is complex due to the limitations, cost, and scalability of current diagnostic surveillance methods. The detection of specific antibody responses against the organism may be a more sustainable manner of measuring exposure and disease burden in endemic location. We measured antibody (IgG) in 937 serum samples (317 children and 620 adults) from across the Lao People`s Democratic Republic against a polysaccharide (Vi) and two experimental protein antigens, CdtB and HlyE, that may more appropriate markers of disease exposure. We measured the significance of the differences between antibody titers in adults and children and fitted models to assess the relationship between age and antibody titers. The median IgG titres against HylE and CdtB were significantly higher in children than adults. Conversely, the median IgG titres against Vi was significantly higher in adults than children. We identified a significant association between a peak in IgG titres against CdtB and HlyE in children aged under 5 years. These data are indicative of high level of typhoid fever exposure in children under 5 years of age in Lao PDR and we surmise that IgG titres against HylE and CdtB may be a superior measure of typhoid disease burden than IgG titres against Vi. Our approach is scalable and can be further validated to assess the burden of typhoid fever in countries where the disease may be endemic, and evidence is required for the introduction of typhoid vaccines.
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- 2022
48. A genomic snapshot of Salmonella enterica serovar Typhi in Colombia
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To Nguyen Thi Nguyen, Duy Pham Thanh, Paula Diaz Guevara, Megan E Carey, Enrique Perez, Thanh Ho Ngoc Dan, Edna Catering Rodríguez, Mailis Maes, Stephen Baker, Carolina Duarte, Isabel Chinen, Lucy Angeline Montaño, Josefina Campos, Maes, Mailis [0000-0002-0266-6557], Thanh, Duy Pham [0000-0001-7029-9210], Duarte, Carolina [0000-0001-7596-8292], Rodriguez, Edna Catering [0000-0001-5537-1923], Montaño, Lucy Angeline [0000-0002-0083-211X], Carey, Megan E. [0000-0002-7797-9080], Campos, Josefina [0000-0003-1409-0441], Perez, Enrique [0000-0002-7730-899X], Apollo - University of Cambridge Repository, Baker, Stephen [0000-0003-1308-5755], and Carey, Megan E [0000-0002-7797-9080]
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Bacterial Diseases ,Epidemiology ,Single Nucleotide Polymorphisms ,RC955-962 ,Salmonella typhi ,Pathology and Laboratory Medicine ,Salmonella Typhi ,Geographical locations ,0302 clinical medicine ,Medical Conditions ,Salmonella ,Arctic medicine. Tropical medicine ,Typhoid ,030212 general & internal medicine ,Clade ,Data Management ,Genetics ,0303 health sciences ,Computer and information sciences ,Genomics ,3. Good health ,Bacterial Pathogens ,Anti-Bacterial Agents ,Phylogenetics ,Infectious Diseases ,Medical Microbiology ,Population Surveillance ,Pathogens ,Public aspects of medicine ,RA1-1270 ,Research Article ,Biology ,Colombia ,Disease Surveillance ,Microbiology ,complex mixtures ,Typhoid fever ,03 medical and health sciences ,Antibiotic resistance ,Enterobacteriaceae ,Microbial Control ,Drug Resistance, Bacterial ,Pulsed-field gel electrophoresis ,medicine ,Evolutionary Systematics ,Typhoid Fever ,Genotyping ,Microbial Pathogens ,030304 developmental biology ,Taxonomy ,Whole genome sequencing ,Pharmacology ,Medicine and health sciences ,Genetic diversity ,Evolutionary Biology ,Bacteria ,Biology and life sciences ,Public Health, Environmental and Occupational Health ,Organisms ,South America ,medicine.disease ,bacterial infections and mycoses ,Antimicrobial Resistance ,People and places - Abstract
Little is known about the genetic diversity of Salmonella enterica serovar Typhi (S. Typhi) circulating in Latin America. It has been observed that typhoid fever is still endemic in this part of the world; however, a lack of standardized blood culture surveillance across Latin American makes estimating the true disease burden problematic. The Colombian National Health Service established a surveillance system for tracking bacterial pathogens, including S. Typhi, in 2006. Here, we characterized 77 representative Colombian S. Typhi isolates collected between 1997 and 2018 using pulse field gel electrophoresis (PFGE; the accepted genotyping method in Latin America) and whole genome sequencing (WGS). We found that the main S. Typhi clades circulating in Colombia were clades 2.5 and 3.5. Notably, the sequenced S. Typhi isolates from Colombia were closely related in a global phylogeny. Consequently, these data suggest that these are endemic clades circulating in Colombia. We found that AMR in S. Typhi in Colombia was uncommon, with a small subset of organisms exhibiting mutations associated with reduced susceptibility to fluoroquinolones. This is the first time that S. Typhi isolated from Colombia have been characterized by WGS, and after comparing these data with those generated using PFGE, we conclude that PFGE is unsuitable for tracking S. Typhi clones and mapping transmission. The genetic diversity of pathogens such as S. Typhi is limited in Latin America and should be targeted for future surveillance studies incorporating WGS., Author summary Salmonella Typhi is the causative agent of typhoid fever, with between 9–13 million cases and 116,800 associated deaths annually. Typhoid fever is still a public health problem mainly in low and middle-income countries (LMICs), including in Latin America, which has a modelled incidence of up to 169 (32–642) cases per 100,000 person-years. Several international studies have aimed to fill data gaps regarding the global distribution and genetic landscape of typhoid; however, in spite of these efforts Latin America is still underrepresented. The globally dominant lineages of S. Typhi (e.g., H58), which often carry multi-drug resistance (MDR) plasmids, decreased fluoroquinolone susceptibility, and now azithromycin resistance, are not detectable by the accepted method (PFGE) used to track outbreaks of typhoid in Latin America. We compared PFGE with whole genome sequence (WGS) and found it correlated poorly, resulting in the over clustering of cases. We additionally found that unlike in most endemic countries, S. Typhi in Colombia are highly antimicrobial susceptible and restricted to a limited number of genotypes that are not as commonly identified in other S. Typhi endemic countries. Our study provides the first enhanced insights into the molecular epidemiology of S. Typhi in Colombia, using WGS data for the first time to investigate the population structure in Colombia and identifying predominant circulating genotypes. Our work demonstrates that routine surveillance with the integration of WGS is necessary not only to improve disease burden estimates, but also to track the national and regional transmission dynamics of S. Typhi.
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- 2021
49. Gallbladder carriage generates genetic variation and genome degradation in Salmonella Typhi
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To Nguyen Thi Nguyen, Maia A. Rabaa, Ho Ngoc Dan Thanh, Buddha Basnyat, Gordon Dougan, Sabina Dongol, Megan E Carey, Pham Thanh Duy, Abhilasha Karkey, Stephen Baker, Nga Tran Vu Thieu, Thanh Duy, Pham [0000-0001-7029-9210], Karkey, Abhilasha [0000-0002-5179-650X], Carey, Megan [0000-0002-7797-9080], Basnyat, Buddha [0000-0002-1125-2743], Rabaa, Maia A [0000-0003-0529-2228], Baker, Stephen [0000-0003-1308-5755], Apollo - University of Cambridge Repository, and Rabaa, Maia A. [0000-0003-0529-2228]
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Bacterial Diseases ,Male ,Single Nucleotide Polymorphisms ,Adaptation, Biological ,Pathology and Laboratory Medicine ,Salmonella typhi ,Biochemistry ,Medical Conditions ,Salmonella ,Genotype ,Typhoid ,Biology (General) ,Phylogeny ,Data Management ,0303 health sciences ,education.field_of_study ,Vi capsular polysaccharide vaccine ,Computer and information sciences ,030302 biochemistry & molecular biology ,Gallbladder ,Nonsense Mutation ,Phylogenetic Analysis ,Middle Aged ,Bacterial Pathogens ,3. Good health ,Anti-Bacterial Agents ,Phylogenetics ,Infectious Diseases ,medicine.anatomical_structure ,Liver ,Medical Microbiology ,Female ,Anatomy ,Pathogens ,medicine.drug ,Research Article ,Adult ,QH301-705.5 ,Immunology ,Population ,Biology ,Microbiology ,Typhoid fever ,03 medical and health sciences ,Enterobacteriaceae ,Virology ,DNA-binding proteins ,Genetic variation ,Genetics ,medicine ,Humans ,Evolutionary Systematics ,Genetic variability ,Typhoid Fever ,education ,Microbial Pathogens ,Molecular Biology ,Taxonomy ,030304 developmental biology ,Aged ,Medicine and health sciences ,Evolutionary Biology ,Bacteria ,Biology and life sciences ,Whole Genome Sequencing ,Organisms ,Proteins ,Genetic Variation ,RC581-607 ,medicine.disease ,Biliary System ,Mutation ,Parasitology ,Immunologic diseases. Allergy - Abstract
Despite recent advances in typhoid fever control, asymptomatic carriage of Salmonella Typhi in the gallbladder remains poorly understood. Aiming to understand if S. Typhi becomes genetically adapted for long-term colonisation in the gallbladder, we performed whole genome sequencing on a collection of S. Typhi isolated from the gallbladders of typhoid carriers. These sequences were compared to contemporaneously sampled sequences from organisms isolated from the blood of acute patients within the same population. We found that S. Typhi carriage was not restricted to any particular genotype or conformation of antimicrobial resistance genes, but was largely reflective of S. Typhi circulating in the general population. However, gallbladder isolates showed a higher genetic variability than acute isolates, with median pairwise SNP distances of 21 and 13 SNPs (p = 2.8x10-9), respectively. Within gallbladder isolates of the predominant H58 genotype, variation was associated with a higher prevalence of nonsense mutations. Notably, gallbladder isolates displayed a higher frequency of non-synonymous mutations in genes encoding hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. Specifically, we identified several gallbladder-specific non-synonymous mutations involved in LPS synthesis and modification, with some isolates lacking the Vi capsular polysaccharide vaccine target due to the 134Kb deletion of SPI-7. S. Typhi is under strong selective pressure in the human gallbladder, which may be reflected phylogenetically by long terminal branches that may distinguish organisms from chronic and acute infections. Our work shows that selective pressures asserted by the hostile environment of the human gallbladder generate new antigenic variants and raises questions regarding the role of carriage in the epidemiology of typhoid fever., Author summary Salmonella Typhi is the bacterium that causes typhoid. Salmonella Typhi is infamous for being able to be carried in the gallbladder, with Typhoid Mary being the best-known example of a typhoid carrier. Despite having new tools for typhoid control, we have made little progress in understanding this disease process. Aiming to understand if Salmonella Typhi is adapted for long-term survival in the gallbladder, we sequenced the genomes of 24 Salmonella Typhi isolated from the gallbladders of typhoid carriers. We compared these genomes to Salmonella Typhi from acute typhoid patients within the same population. The carriage of Salmonella Typhi was not restricted to any specific genotype or resistance to antibiotics, but reflective of the organisms causing acute disease. However, gallbladder isolates had higher genetic variability than acute isolates, with a higher frequency of mutations changing the amino acid sequences of hypothetical proteins, membrane lipoproteins, transport/binding proteins, surface antigens, and carbohydrate degradation. We identified several gallbladder-specific mutations involved in polysaccharide synthesis on the bacterial surface. Our work shows that selective pressures asserted by the hostile environment of the human gallbladder generates genetic variation, which is not observed in acute isolates, raising questions regarding the role of carriage in the epidemiology of typhoid.
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- 2020
50. Multicountry distribution and characterization of extended-spectrum β-lactamase-associated gram-negative bacteria from bloodstream infections in sub-Saharan Africa
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Morten Bjerregaard-Andersen, Trung Pham Duc, Nagla Gasmelseed, John D. Clemens, Kamala Thriemer, John A. Crump, Frank Konings, Heidi Schütt-Gerowitt, Mekonnen Teferi, Jürgen May, Leonard Cosmas, Denise Dekker, Hyon Jin Jeon, Benedikt Ley, Daniel Eibach, Biruk Yeshitela, Raphaël Rakotozandrindrainy, Ursula Panzner, Gi Deok Pak, Jin Kyung Park, Abroaham Aseffa, Jerome H. Kim, Tiana Mirana Raminosoa, Trevor Toy, Anna Jaeger, Yun Chon, Leon Parfait Kabore, Florian Marks, Amy Gassama Sow, Justin Im, Muna Ahmed El Tayeb, Thomas F. Wierzba, Robert F. Breiman, Ondari D. Mogeni, James Campbell, Julian T. Hertz, Sven Poppert, Ligia Maria Cruz Espinoza, Ralf Krumkamp, Peter Aaby, Christian Meyer, Emmanuel Sampo, Vera von Kalckreuth, Abdramane Bassiahi Soura, Se Eun Park, Aissatou Niang, Ellis Owusu-Dabo, Yaw Adu-Sarkodie, Nimako Sarpong, Stephen Baker, Baker, Stephen [0000-0003-1308-5755], Marks, Florian [0000-0002-6043-7170], and Apollo - University of Cambridge Repository
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Microbiology (medical) ,Adult ,Klebsiella ,Salmonella ,antibiotic resistance ,Adolescent ,Supplement Articles ,Microbial Sensitivity Tests ,medicine.disease_cause ,Typhoid fever ,beta-Lactamases ,Microbiology ,Young Adult ,Antibiotic resistance ,Drug Resistance, Multiple, Bacterial ,Multiplex polymerase chain reaction ,Gram-Negative Bacteria ,medicine ,Prevalence ,Humans ,Blood culture ,antimicrobial resistance ,Child ,Africa South of the Sahara ,medicine.diagnostic_test ,biology ,business.industry ,Infant, Newborn ,Infant ,Acinetobacter ,Middle Aged ,biology.organism_classification ,medicine.disease ,extended-spectrum β-lactamase ,Enterobacteriaceae ,Anti-Bacterial Agents ,Infectious Diseases ,ESBL ,Child, Preschool ,Africa ,surveillance ,business ,Gram-Negative Bacterial Infections ,Sentinel Surveillance - Abstract
Background Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum β-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa. Methods Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for β-lactamase were performed on all pathogens. Results Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity. Conclusions Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.
- Published
- 2020
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