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Start Over Author "Baker, Stephen" Publication Year Range Last 10 years Journal plos neglected tropical diseases
26 results on '"Baker, Stephen"'

1. The frequency and associated factors of typhoid carriage in patients undergoing cholecystectomy for gallbladder disease in Pakistan: A cross-sectional study

Author

Qureshi, Sonia, primary, Maria, Noshi, additional, Chawla, Tabish, additional, Iqbal, Junaid, additional, Kazi, Abdul Momin, additional, Adnan, Mehreen, additional, Hotwani, Aneeta, additional, Rahman, Najeeb, additional, Sadiq, Muhammed Wahhaab, additional, Charles, Richelle, additional, Baker, Stephen, additional, and Qamar, Farah Naz, additional

Published
2024
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2. A retrospective investigation of the population structure and geospatial distribution of Salmonella Paratyphi A in Kathmandu, Nepal.

Author

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

Subjects
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]

Published
2024
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3. The seroincidence of childhood Shigella sonnei infection in Ho Chi Minh City, Vietnam

Author

Jones, Nick K., primary, Thu, Trang Nguyen Hoang, additional, de Alwis, Ruklanthi, additional, Thompson, Corinne, additional, Tuyen, Ha Thanh, additional, Nhu, Tran Do Hoang, additional, Phat, Voong Vinh, additional, Trung, Pham Duc, additional, Lam, Phung Khanh, additional, Tien, Bui Thi Thuy, additional, Tuyet, Hoang Thi Diem, additional, Vi, Lu Lan, additional, Van Vinh Chau, Nguyen, additional, Le Thi Quynh, Nhi, additional, and Baker, Stephen, additional

Published
2023
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4. Whole genome sequence analysis of Salmonella Typhi provides evidence of phylogenetic linkage between cases of typhoid fever in Santiago, Chile in the 1980s and 2010–2016

Author

Maes, Mailis, primary, Sikorski, Michael J., additional, Carey, Megan E., additional, Higginson, Ellen E., additional, Dyson, Zoe A., additional, Fernandez, Alda, additional, Araya, Pamela, additional, Tennant, Sharon M., additional, Baker, Stephen, additional, Lagos, Rosanna, additional, Hormazábal, Juan Carlos, additional, Levine, Myron M., additional, and Dougan, Gordon, additional

Published
2022
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5. An age-stratified serosurvey against purified Salmonella enterica serovar Typhi antigens in the Lao People´s Democratic Republic

Author

Hefele, Lisa, primary, Black, Antony P., additional, Van Tan, Trinh, additional, Tri Minh, Nguyen, additional, Duc Hoang, Nguyen, additional, Virachith, Siriphone, additional, Muller, Claude P., additional, Hübschen, Judith M., additional, Russell, Paula, additional, Bartholdson Scott, Josefin, additional, Ngoc Minh, Chau Nguyen, additional, Thieu Nga, Tran Vu, additional, and Baker, Stephen, additional

Published
2021
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7. A genomic snapshot of Salmonella enterica serovar Typhi in Colombia

Author

Guevara, Paula Diaz, primary, Maes, Mailis, additional, Thanh, Duy Pham, additional, Duarte, Carolina, additional, Rodriguez, Edna Catering, additional, Montaño, Lucy Angeline, additional, Dan, Thanh Ho Ngoc, additional, Nguyen, To Nguyen Thi, additional, Carey, Megan E., additional, Campos, Josefina, additional, Chinen, Isabel, additional, Perez, Enrique, additional, and Baker, Stephen, additional

Published
2021
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8. Surveillance of Salmonella enterica serovar Typhi in Colombia, 2012–2015

Author

Diaz-Guevara, Paula, primary, Montaño, Lucy Angeline, additional, Duarte, Carolina, additional, Zabaleta, Gabriela, additional, Maes, Mailis, additional, Martinez Angarita, Julio Cesar, additional, Thanh, Duy Pham, additional, León-Quevedo, William, additional, Castañeda-Orjuela, Carlos, additional, Alvarez Alvarez, Claudia Jimena, additional, Guerrero, Jaime, additional, Moroni, Miriam, additional, Campos, Josefina, additional, Pérez, Enrique, additional, and Baker, Stephen, additional

Published
2020
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9. Ascertaining the burden of invasive Salmonella disease in hospitalised febrile children aged under four years in Blantyre, Malawi

Author

Msefula, Chisomo L., primary, Olgemoeller, Franziska, additional, Jambo, Ndaru, additional, Segula, Dalitso, additional, Van Tan, Trinh, additional, Nyirenda, Tonney S., additional, Nedi, Wilfred, additional, Kennedy, Neil, additional, Graham, Matthew, additional, Henrion, Marc Y. R., additional, Baker, Stephen, additional, Feasey, Nicholas, additional, Gordon, Melita, additional, and Heyderman, Robert S., additional

Published
2019
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10. One hypervirulent clone, sequence type 283, accounts for a large proportion of invasive Streptococcus agalactiae isolated from humans and diseased tilapia in Southeast Asia

Author

Barkham, Timothy, primary, Zadoks, Ruth N., additional, Azmai, Mohammad Noor Amal, additional, Baker, Stephen, additional, Bich, Vu Thi Ngoc, additional, Chalker, Victoria, additional, Chau, Man Ling, additional, Dance, David, additional, Deepak, Rama Narayana, additional, van Doorn, H. Rogier, additional, Gutierrez, Ramona A., additional, Holmes, Mark A., additional, Huong, Lan Nguyen Phu, additional, Koh, Tse Hsien, additional, Martins, Elisabete, additional, Mehershahi, Kurosh, additional, Newton, Paul, additional, Ng, Lee Ching, additional, Phuoc, Nguyen Ngoc, additional, Sangwichian, Ornuma, additional, Sawatwong, Pongpun, additional, Surin, Uraiwan, additional, Tan, Thean Yen, additional, Tang, Wen Ying, additional, Thuy, Nguyen Vu, additional, Turner, Paul, additional, Vongsouvath, Manivanh, additional, Zhang, Defeng, additional, Whistler, Toni, additional, and Chen, Swaine L., additional

Published
2019
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11. Diagnostic metabolite biomarkers of chronic typhoid carriage

Author

Näsström, Elin, primary, Jonsson, Pär, additional, Johansson, Anders, additional, Dongol, Sabina, additional, Karkey, Abhilasha, additional, Basnyat, Buddha, additional, Tran Vu Thieu, Nga, additional, Trinh Van, Tan, additional, Thwaites, Guy E., additional, Antti, Henrik, additional, and Baker, Stephen, additional

Published
2018
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12. A 23-year retrospective investigation of Salmonella Typhi and Salmonella Paratyphi isolated in a tertiary Kathmandu hospital

Author

Zellweger, Raphaël M., primary, Basnyat, Buddha, additional, Shrestha, Poojan, additional, Prajapati, Krishna G., additional, Dongol, Sabina, additional, Sharma, Paban K., additional, Koirala, Samir, additional, Darton, Thomas C., additional, Dolecek, Christiane, additional, Thompson, Corinne N., additional, Thwaites, Guy E., additional, Baker, Stephen G., additional, and Karkey, Abhilasha, additional

Published
2017
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13. A cross-sectional seroepidemiological survey of typhoid fever in Fiji

Author

Watson, Conall H., primary, Baker, Stephen, additional, Lau, Colleen L., additional, Rawalai, Kitione, additional, Taufa, Mere, additional, Coriakula, Jerimaia, additional, Thieu, Nga Tran Vu, additional, Van, Tan Trinh, additional, Ngoc, Dung Tran Thi, additional, Hens, Niel, additional, Lowry, John H., additional, de Alwis, Ruklanthi, additional, Cano, Jorge, additional, Jenkins, Kylie, additional, Mulholland, E. Kim, additional, Nilles, Eric J., additional, Kama, Mike, additional, and Edmunds, W. John, additional

Published
2017
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14. Comparative genomics of Cryptococcus neoformans var. grubii associated with meningitis in HIV infected and uninfected patients in Vietnam

Author

Day, Jeremy N., primary, Qihui, Seet, additional, Thanh, Lam Tuan, additional, Trieu, Phan Hai, additional, Van, Anh Duong, additional, Thu, Nha Hoang, additional, Chau, Tran Thi Hong, additional, Lan, Nguyen P. H., additional, Chau, Nguyen Van Vinh, additional, Ashton, Philip M., additional, Thwaites, Guy E., additional, Boni, Maciej F., additional, Wolbers, Marcel, additional, Nagarajan, Niranjan, additional, Tan, Patrick B. O., additional, and Baker, Stephen, additional

Published
2017
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16. Whole Genome Sequence Analysis of Salmonella Typhi Isolated in Thailand before and after the Introduction of a National Immunization Program

Author

Dyson, Zoe A., primary, Thanh, Duy Pham, additional, Bodhidatta, Ladaporn, additional, Mason, Carl Jeffries, additional, Srijan, Apichai, additional, Rabaa, Maia A., additional, Vinh, Phat Voong, additional, Thanh, Tuyen Ha, additional, Thwaites, Guy E., additional, Baker, Stephen, additional, and Holt, Kathryn E., additional

Published
2017
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17. Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam

Author

Phu Huong Lan, Nguyen, primary, Le Thi Phuong, Tu, additional, Nguyen Huu, Hien, additional, Thuy, Le, additional, Mather, Alison E., additional, Park, Se Eun, additional, Marks, Florian, additional, Thwaites, Guy E., additional, Van Vinh Chau, Nguyen, additional, Thompson, Corinne N., additional, and Baker, Stephen, additional

Published
2016
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18. The Molecular and Spatial Epidemiology of Typhoid Fever in Rural Cambodia

Author

Pham Thanh, Duy, primary, Thompson, Corinne N., additional, Rabaa, Maia A, additional, Sona, Soeng, additional, Sopheary, Sun, additional, Kumar, Varun, additional, Moore, Catrin, additional, Tran Vu Thieu, Nga, additional, Wijedoru, Lalith, additional, Holt, Kathryn E., additional, Wong, Vanessa, additional, Pickard, Derek, additional, Thwaites, Guy E., additional, Day, Nicholas, additional, Dougan, Gordon, additional, Turner, Paul, additional, Parry, Christopher M., additional, and Baker, Stephen, additional

Published
2016
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19. A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions

Author

Makendi, Carine, primary, Page, Andrew J., additional, Wren, Brendan W., additional, Le Thi Phuong, Tu, additional, Clare, Simon, additional, Hale, Christine, additional, Goulding, David, additional, Klemm, Elizabeth J., additional, Pickard, Derek, additional, Okoro, Chinyere, additional, Hunt, Martin, additional, Thompson, Corinne N., additional, Phu Huong Lan, Nguyen, additional, Tran Do Hoang, Nhu, additional, Thwaites, Guy E., additional, Le Hello, Simon, additional, Brisabois, Anne, additional, Weill, François-Xavier, additional, Baker, Stephen, additional, and Dougan, Gordon, additional

Published
2016
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20. The Ecological Dynamics of Fecal Contamination and Salmonella Typhi and Salmonella Paratyphi A in Municipal Kathmandu Drinking Water

Author

Karkey, Abhilasha, primary, Jombart, Thibaut, additional, Walker, Alan W., additional, Thompson, Corinne N., additional, Torres, Andres, additional, Dongol, Sabina, additional, Tran Vu Thieu, Nga, additional, Pham Thanh, Duy, additional, Tran Thi Ngoc, Dung, additional, Voong Vinh, Phat, additional, Singer, Andrew C., additional, Parkhill, Julian, additional, Thwaites, Guy, additional, Basnyat, Buddha, additional, Ferguson, Neil, additional, and Baker, Stephen, additional

Published
2016
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22. Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model

Author

De Jong, Hanna K., primary, Achouiti, Ahmed, additional, Koh, Gavin C. K. W., additional, Parry, Christopher M., additional, Baker, Stephen, additional, Faiz, Mohammed Abul, additional, van Dissel, Jaap T., additional, Vollaard, Albert M., additional, van Leeuwen, Ester M. M., additional, Roelofs, Joris J. T. H., additional, de Vos, Alex F., additional, Roth, Johannes, additional, van der Poll, Tom, additional, Vogl, Thomas, additional, and Wiersinga, Willem Joost, additional

Published
2015
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23. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa.

Author

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.

Subjects
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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24. A genomic snapshot of Salmonella enterica serovar Typhi in Colombia

Author

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]

Subjects
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.

Published
2021

25. Diagnostic metabolite biomarkers of chronic typhoid carriage

Author

Sabina Dongol, Henrik Antti, Tan Trinh Van, Buddha Basnyat, Guy E. Thwaites, Pär Jonsson, Anders Johansson, Elin Näsström, Abhilasha Karkey, Nga Tran Vu Thieu, Stephen Baker, Näsström, Elin [0000-0001-6499-3281], Baker, Stephen [0000-0003-1308-5755], and Apollo - University of Cambridge Repository

Subjects
Male, Bacterial Diseases, 0301 basic medicine, Salmonella, Metabolite, medicine.medical_treatment, Fevers, Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy), Pathology and Laboratory Medicine, Salmonella typhi, medicine.disease_cause, Biochemistry, Salmonella Typhi, Plasma, chemistry.chemical_compound, Mathematical and Statistical Techniques, fluids and secretions, Metabolites, Medicine and Health Sciences, Prospective Studies, Principal Component Analysis, lcsh:Public aspects of medicine, Salmonella paratyphi A, Gallbladder, food and beverages, Middle Aged, Bacterial Pathogens, 3. Good health, Infectious Diseases, medicine.anatomical_structure, Liver, Medical Microbiology, Carrier State, Physical Sciences, Female, Pathogens, Anatomy, Statistics (Mathematics), Research Article, Adult, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030106 microbiology, Surgical and Invasive Medical Procedures, Research and Analysis Methods, Microbiology, complex mixtures, Gas Chromatography-Mass Spectrometry, Typhoid fever, Young Adult, Digestive System Procedures, 03 medical and health sciences, Signs and Symptoms, Nepal, Enterobacteriaceae, Diagnostic Medicine, medicine, Humans, Metabolomics, Cholecystectomy, Typhoid Fever, Statistical Methods, Microbial Pathogens, Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci), Aged, Bacteria, business.industry, Organisms, Public Health, Environmental and Occupational Health, Biology and Life Sciences, lcsh:RA1-1270, bacterial infections and mycoses, medicine.disease, Metabolism, 030104 developmental biology, Carriage, chemistry, Biliary System, Multivariate Analysis, Immunology, bacteria, business, Biomarkers, Mathematics
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., Author summary Enteric fever, caused by typhoidal Salmonella serovars, remains a substantial public health problem in many low- and middle-income countries. The human-restricted nature of these organisms combined with the development of new vaccines suggests that regional elimination of enteric fever should be possible. However, individuals that chronically carry Salmonella in their gallbladder, such as the notorious Typhoid Mary, complicates enteric fever transmission and maintain circulation of the organisms. The prospective detection of chronic Salmonella carriers is therefore a critical step for regional enteric fever elimination. However, there are currently no diagnostic methods routinely in use for this purpose. Here, we used a novel method for identifying chronic Salmonella carriers by comparing metabolite patterns in plasma samples from patients with chronic Salmonella carriage against non-carriage controls. We could significantly distinguish Salmonella carriers from non-carriers based on a large set of metabolites. Five metabolites were then highlighted, after comparing metabolite patterns obtained during chronic Salmonella carriage and acute enteric fever respectively, which could significantly distinguish Salmonella carriers from non-carriers. These potential biomarkers require further evaluation in epidemiological investigations of enteric fever in alternative endemic settings but this study provides a first step towards improved detection of Salmonella carriers.

Published
2018

26. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa.

Author

Wong VK, Holt KE, Okoro C, Baker S, Pickard DJ, Marks F, Page AJ, Olanipekun G, Munir H, Alter R, Fey PD, Feasey NA, Weill FX, Le Hello S, Hart PJ, Kariuki S, Breiman RF, Gordon MA, Heyderman RS, Jacobs J, Lunguya O, Msefula C, MacLennan CA, Keddy KH, Smith AM, Onsare RS, De Pinna E, Nair S, Amos B, Dougan G, and Obaro S

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., Competing Interests: The authors have declared that no competing interests exist.

Published
2016
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