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

Author

Carey, Megan, Dyson, Zoe, Ingle, Danielle, Amir, Afreenish, Aworh, Mabel, Chattaway, Marie, Chew, Ka, Crump, John, Feasey, Nicholas, Howden, Benjamin, Keddy, Karen, Maes, Mailis, Parry, Christopher, Van Puyvelde, Sandra, Webb, Hattie, Afolayan, Ayorinde, Alexander, Anna, Anandan, Shalini, Andrews, Jason, Ashton, Philip, Basnyat, Buddha, Bavdekar, Ashish, Bogoch, Isaac, Clemens, John, da Silva, Kesia, De, Anuradha, de Ligt, Joep, Diaz Guevara, Paula, Dolecek, Christiane, Dutta, Shanta, Ehlers, Marthie, Francois Watkins, Louise, Garrett, Denise, Godbole, Gauri, Gordon, Melita, Greenhill, Andrew, Griffin, Chelsey, Gupta, Madhu, Hendriksen, Rene, Heyderman, Robert, Hooda, Yogesh, Hormazabal, Juan, Ikhimiukor, Odion, Iqbal, Junaid, Jacob, Jobin, Jenkins, Claire, Jinka, Dasaratha, John, Jacob, Kang, Gagandeep, Kanteh, Abdoulie, Kapil, Arti, Karkey, Abhilasha, Kariuki, Samuel, Kingsley, Robert, Koshy, Roshine, Lauer, A, Levine, Myron, Lingegowda, Ravikumar, Luby, Stephen, Mackenzie, Grant, Mashe, Tapfumanei, Msefula, Chisomo, Mutreja, Ankur, Nagaraj, Geetha, Nagaraj, Savitha, Nair, Satheesh, Naseri, Take, Nimarota-Brown, Susana, Njamkepo, Elisabeth, Okeke, Iruka, Perumal, Sulochana, Pollard, Andrew, Pragasam, Agila, Qadri, Firdausi, Qamar, Farah, Rahman, Sadia, Rambocus, Savitra, Rasko, David, Ray, Pallab, Robins-Browne, Roy, Rongsen-Chandola, Temsunaro, Rutanga, Jean, Saha, Samir, Saha, Senjuti, Saigal, Karnika, Sajib, Mohammad, Seidman, Jessica, Shakya, Jivan, Shamanna, Varun, Shastri, Jayanthi, Shrestha, Rajeev, Sia, Sonia, Sikorski, Michael, Singh, Ashita, Smith, Anthony, Tagg, Kaitlin, Tamrakar, Dipesh, Tanmoy, Arif, Thomas, Maria, and Thomas, Mathew

Subjects
S. enterica serovar typhi, antimicrobial resistance, epidemiology, genomics, global health, infectious disease, microbiology, typhoid conjugate vaccine, typhoid fever, Humans, Salmonella typhi, Typhoid Fever, Anti-Bacterial Agents, Travel, Drug Resistance, Bacterial, Ciprofloxacin
Abstract

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal sentinel surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortiums aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]).

Published
2023

3. Pathogen diversity and antimicrobial resistance transmission of Salmonella enterica serovars Typhi and Paratyphi A in Bangladesh, Nepal, and Malawi: a genomic epidemiological study

Author

Banda, Happy C, Biswas, Prasanta K, Bhuiyan, Md A I, Blohmke, Christoph, Darton, Thomas C, Dolecek, Christiane, Dongol, Sabina, Mujadidi, Yama F, Hill, Jennifer, Hoang, Nhu T, Jere, Tikhala M, Mbewe, Maurice, Msuku, Harrison, Nga, Tran V T, Nkhata, Rose, Rahman, Sadia IA, Rahman, Nazia, Saad, Neil J, Tan, Trinh V, Thindwa, Deus, Voysey, Merryn, Wachepa, Richard, Dyson, Zoe A, Ashton, Philip M, Khanam, Farhana, Chunga Chirambo, Angeziwa, Shakya, Mila, Meiring, James E, Tonks, Susan, Karkey, Abhilasha, Msefula, Chisomo, Clemens, John D, Dunstan, Sarah J, Baker, Stephen, Dougan, Gordon, Pitzer, Virginia E, Basnyat, Buddha, Qadri, Firdausi, Heyderman, Robert S, Gordon, Melita A, Pollard, Andrew J, and Holt, Kathryn E

Published
2024
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4. Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study

Author

Biswas, Prasanta Kumar, Bhuiyan, Md Amiruli Islam, Blohmke, Christoph, Darton, Thomas C, Dolecek, Christiane, Dongol, Sabina, Farooq, Yama, Hill, Jennifer, Hoang, Nhu Tran, Makhaza Jere, Tikhala, Msuku, Harrison, Nga, Tran Vu Thieu, Nkhata, Rose, Rahman, Sadia Isfat Ara, Rahman, Nazia, Saad, Neil J, Van Tan, Trinh, Thindwa, Deus, Voysey, Merryn, Wachepa, Richard, Pollard, Andrew, Ashton, Philip M, Chunga Chirambo, Angeziwa, Meiring, James E, Patel, Priyanka D, Mbewe, Maurice, Silungwe, Niza, Chizani, Kenneth, Banda, Happy, Heyderman, Robert S, Dyson, Zoe A, MacPherson, Peter, Henrion, Marc Y R, Holt, Kathryn E, and Gordon, Melita A

Published
2024
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6. Evaluating the relationship between ciprofloxacin prescription and non-susceptibility in Salmonella Typhi in Blantyre, Malawi: an observational study

Author

Ashton, Philip M, primary, Chunga Chirambo, Angeziwa, additional, Meiring, James E, additional, Patel, Priyanka D, additional, Mbewe, Maurice, additional, Silungwe, Niza, additional, Chizani, Kenneth, additional, Banda, Happy, additional, Heyderman, Robert S, additional, Dyson, Zoe A, additional, MacPherson, Peter, additional, Henrion, Marc Y R, additional, Biswas, Prasanta Kumar, additional, Bhuiyan, Md Amiruli Islam, additional, Blohmke, Christoph, additional, Darton, Thomas C, additional, Dolecek, Christiane, additional, Dongol, Sabina, additional, Farooq, Yama, additional, Hill, Jennifer, additional, Hoang, Nhu Tran, additional, Makhaza Jere, Tikhala, additional, Msuku, Harrison, additional, Nga, Tran Vu Thieu, additional, Nkhata, Rose, additional, Rahman, Sadia Isfat Ara, additional, Rahman, Nazia, additional, Saad, Neil J, additional, Van Tan, Trinh, additional, Thindwa, Deus, additional, Voysey, Merryn, additional, Wachepa, Richard, additional, Pollard, Andrew, additional, Holt, Kathryn E, additional, and Gordon, Melita A, additional

Published
2024
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7. Multiple Introductions of Salmonella enterica Serovar Typhi H58 with Reduced Fluoroquinolone Susceptibility into Chile

Author

Maes, Mailis, Dyson, Zoe A., Higginson, Ellen E., Fernandez, Alda, Araya, Pamela, Tennant, Sharon M., Baker, Stephen, Lagos, Rosanna, Levine, Myron M., Hormazabal, Juan Carlos, and Dougan, Gordon

Subjects
Salmonella -- Distribution -- Genetic aspects, Microbial drug resistance -- Distribution -- Genetic aspects, Company distribution practices, Health
Abstract

Salmonella enterica serovars Typhi, Paratyphi A, and Paratyphi B are the etiologic agents of typhoid and paratyphoid fever. Each year, [approximately equal to] 11-21 million cases and 128,000-161,000 typhoid-related deaths [...]

Published
2020
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8. A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch

Author

Argimón, Silvia, Yeats, Corin A., Goater, Richard J., Abudahab, Khalil, Taylor, Benjamin, Underwood, Anthony, Sánchez-Busó, Leonor, Wong, Vanessa K., Dyson, Zoe A., Nair, Satheesh, Park, Se Eun, Marks, Florian, Page, Andrew J., Keane, Jacqueline A., Baker, Stephen, Holt, Kathryn E., Dougan, Gordon, and Aanensen, David M.

Published
2021
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14. Unlocking the Potential of Genomic Data to Inform Typhoid Fever Control Policy: Supportive Resources for Genomic Data Generation, Analysis, and Visualization

Author

Carey, Megan E, primary, Dyson, Zoe A, additional, Argimón, Silvia, additional, Cerdeira, Louise, additional, Yeats, Corin, additional, Aanensen, David, additional, Mboowa, Gerald, additional, Baker, Stephen, additional, Tessema, Sofonias K, additional, Smith, Anthony M, additional, Okeke, Iruka N, additional, and Holt, Kathryn E, additional

Published
2023
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15. Global diversity and antimicrobial resistance of typhoid fever pathogens:Insights from a meta-analysis of 13,000 Salmonella Typhi genomes

Author

Carey, Megan E, Dyson, Zoe A, Ingle, Danielle J, Amir, Afreenish, Aworh, Mabel K, Chattaway, Marie Anne, Chew, Ka Lip, Crump, John A, Feasey, Nicholas A, Howden, Benjamin P, Keddy, Karen H, Maes, Mailis, Parry, Christopher M, Van Puyvelde, Sandra, Webb, Hattie E, Afolayan, Ayorinde Oluwatobiloba, Alexander, Anna P, Anandan, Shalini, Andrews, Jason R, Ashton, Philip M, Basnyat, Buddha, Bavdekar, Ashish, Bogoch, Isaac I, Clemens, John D, da Silva, Kesia Esther, De, Anuradha, de Ligt, Joep, Diaz Guevara, Paula Lucia, Dolecek, Christiane, Dutta, Shanta, Ehlers, Marthie M, Francois Watkins, Louise, Garrett, Denise O, Godbole, Gauri, Gordon, Melita A, Greenhill, Andrew R, Griffin, Chelsey, Gupta, Madhu, Hendriksen, Rene S, Heyderman, Robert S, Hooda, Yogesh, Hormazabal, Juan Carlos, Ikhimiukor, Odion O, Iqbal, Junaid, Jacob, Jobin John, Jenkins, Claire, Jinka, Dasaratha Ramaiah, John, Jacob, Kang, Gagandeep, Kanteh, Abdoulie, Kapil, Arti, Karkey, Abhilasha, Kariuki, Samuel, Kingsley, Robert A, Koshy, Roshine Mary, Lauer, AC, Levine, Myron M, Lingegowda, Ravikumar Kadahalli, Luby, Stephen P, Mackenzie, Grant Austin, Mashe, Tapfumanei, Msefula, Chisomo, Mutreja, Ankur, Nagaraj, Geetha, Nagaraj, Savitha, Nair, Satheesh, Naseri, Take K, Nimarota-Brown, Susana, Njamkepo, Elisabeth, Okeke, Iruka N, Perumal, Sulochana Putli Bai, Pollard, Andrew J, Pragasam, Agila Kumari, Qadri, Firdausi, Qamar, Farah N, Rahman, Sadia Isfat Ara, Rambocus, Savitra Devi, Rasko, David A, Ray, Pallab, Robins-Browne, Roy, Rongsen-Chandola, Temsunaro, Rutanga, Jean Pierre, Saha, Samir K, Saha, Senjuti, Saigal, Karnika, Sajib, Mohammad Saiful Islam, Seidman, Jessica C, Shakya, Jivan, Shamanna, Varun, Shastri, Jayanthi, Shrestha, Rajeev, Sia, Sonia, Sikorski, Michael J, Singh, Ashita, Smith, Anthony M, Tagg, Kaitlin A, Tamrakar, Dipesh, Tanmoy, Arif Mohammed, Thomas, Maria, Thomas, Mathew S, Thomsen, Robert, Thomson, Nicholas R, Tupua, Siaosi, Vaidya, Krista, Valcanis, Mary, Veeraraghavan, Balaji, Weill, François-Xavier, Wright, Jackie, Dougan, Gordon, Argimón, Silvia, Keane, Jacqueline A, Aanensen, David M, Baker, Stephen, Holt, Kathryn E, Carey, Megan E, Dyson, Zoe A, Ingle, Danielle J, Amir, Afreenish, Aworh, Mabel K, Chattaway, Marie Anne, Chew, Ka Lip, Crump, John A, Feasey, Nicholas A, Howden, Benjamin P, Keddy, Karen H, Maes, Mailis, Parry, Christopher M, Van Puyvelde, Sandra, Webb, Hattie E, Afolayan, Ayorinde Oluwatobiloba, Alexander, Anna P, Anandan, Shalini, Andrews, Jason R, Ashton, Philip M, Basnyat, Buddha, Bavdekar, Ashish, Bogoch, Isaac I, Clemens, John D, da Silva, Kesia Esther, De, Anuradha, de Ligt, Joep, Diaz Guevara, Paula Lucia, Dolecek, Christiane, Dutta, Shanta, Ehlers, Marthie M, Francois Watkins, Louise, Garrett, Denise O, Godbole, Gauri, Gordon, Melita A, Greenhill, Andrew R, Griffin, Chelsey, Gupta, Madhu, Hendriksen, Rene S, Heyderman, Robert S, Hooda, Yogesh, Hormazabal, Juan Carlos, Ikhimiukor, Odion O, Iqbal, Junaid, Jacob, Jobin John, Jenkins, Claire, Jinka, Dasaratha Ramaiah, John, Jacob, Kang, Gagandeep, Kanteh, Abdoulie, Kapil, Arti, Karkey, Abhilasha, Kariuki, Samuel, Kingsley, Robert A, Koshy, Roshine Mary, Lauer, AC, Levine, Myron M, Lingegowda, Ravikumar Kadahalli, Luby, Stephen P, Mackenzie, Grant Austin, Mashe, Tapfumanei, Msefula, Chisomo, Mutreja, Ankur, Nagaraj, Geetha, Nagaraj, Savitha, Nair, Satheesh, Naseri, Take K, Nimarota-Brown, Susana, Njamkepo, Elisabeth, Okeke, Iruka N, Perumal, Sulochana Putli Bai, Pollard, Andrew J, Pragasam, Agila Kumari, Qadri, Firdausi, Qamar, Farah N, Rahman, Sadia Isfat Ara, Rambocus, Savitra Devi, Rasko, David A, Ray, Pallab, Robins-Browne, Roy, Rongsen-Chandola, Temsunaro, Rutanga, Jean Pierre, Saha, Samir K, Saha, Senjuti, Saigal, Karnika, Sajib, Mohammad Saiful Islam, Seidman, Jessica C, Shakya, Jivan, Shamanna, Varun, Shastri, Jayanthi, Shrestha, Rajeev, Sia, Sonia, Sikorski, Michael J, Singh, Ashita, Smith, Anthony M, Tagg, Kaitlin A, Tamrakar, Dipesh, Tanmoy, Arif Mohammed, Thomas, Maria, Thomas, Mathew S, Thomsen, Robert, Thomson, Nicholas R, Tupua, Siaosi, Vaidya, Krista, Valcanis, Mary, Veeraraghavan, Balaji, Weill, François-Xavier, Wright, Jackie, Dougan, Gordon, Argimón, Silvia, Keane, Jacqueline A, Aanensen, David M, Baker, Stephen, and Holt, Kathryn E

Abstract

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control s

Published
2023

18. Technical Report: GenoTyphi Implementation in Mykrobe

Author

Holt, Kathryn, Ingle, Danielle, Hawkey, Jane, Dyson, Zoe, and Hunt, Martin

Subjects
genotyping, typhi, typhoid
Abstract

The GenoTyphi genotyping scheme divides theSalmonella enterica serovarTyphi ("Typhi") population into 4 major lineages, and >75 different clades and subclades.The scheme was introduced in the paper"An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid", Wong et al, 2016, Nature Communications. Subsequent updates, including new genotypes and mutations conferring resistance to fluoroquinolones and azithromycin, are summarised in"Five years of GenoTyphi: updates to the global Salmonella Typhi genotyping framework", Dyson & Holt, 2021, Journal of Infectious Diseases. The original code that was made available for assigning GenoTyphi genotypes to Typhi genomes, implemented in Python, tookas input BAM or VCF files that the user has already generated by mapping Illumina reads to the reference genome for Typhi CT18. Here we describe a new kmer-based approach to assigning GenoTyphi genotypes to Typhi genomes, implemented in the Mykrobe open-source software platform and taking raw sequencing reads (FASTQ files) as input. This implementation also includes five newly defined genotypes, taking the total to n=87. We tested the new implementation on n=12,848 Typhi genomes, and found near-perfect concordance with the original mapping-based implementation. Code is available athttps://github.com/katholt/genotyphi(v2.0, doi: 10.5281/zenodo.7430538).

Published
2022
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21. Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes.

Author

Carey, Megan E., Dyson, Zoe A., Ingle, Danielle J., Amir, Afreenish, Aworh, Mabel K., Chattaway, Marie Anne, Ka Lip Chew, Crump, John A., Feasey, Nicholas A., Howden, Benjamin P., Keddy, Karen H., Maes, Mailis, Parry, Christopher M., Van Puyvelde, Sandra, Webb, Hattie E., Afolayan, Ayorinde Oluwatobiloba, Alexander, Anna P., Anandan, Shalini, Andrews, Jason R., and Ashton, Philip M.

Subjects
*SALMONELLA enterica serovar Typhi, *TYPHOID fever, *SALMONELLA typhi, *DRUG resistance in microorganisms, *GENOMES
Abstract

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (=3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). [ABSTRACT FROM AUTHOR]

Published
2023
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22. The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa

Author

Park, Se Eun, Pham, Duy Thanh, Boinett, Christine, Wong, Vanessa K., Pak, Gi Deok, Panzner, Ursula, Espinoza, Ligia Maria Cruz, von Kalckreuth, Vera, Im, Justin, Schütt-Gerowitt, Heidi, Crump, John A., Breiman, Robert F., Adu-Sarkodie, Yaw, Owusu-Dabo, Ellis, Rakotozandrindrainy, Raphaël, Soura, Abdramane Bassiahi, Aseffa, Abraham, Gasmelseed, Nagla, Keddy, Karen H., May, Jürgen, Sow, Amy Gassama, Aaby, Peter, Biggs, Holly M., Hertz, Julian T., Montgomery, Joel M., Cosmas, Leonard, Olack, Beatrice, Fields, Barry, Sarpong, Nimako, Razafindrabe, Tsiriniaina Jean Luco, Raminosoa, Tiana Mirana, Kabore, Leon Parfait, Sampo, Emmanuel, Teferi, Mekonnen, Yeshitela, Biruk, El Tayeb, Muna Ahmed, Sooka, Arvinda, Meyer, Christian G., Krumkamp, Ralf, Dekker, Denise Myriam, Jaeger, Anna, Poppert, Sven, Tall, Adama, Niang, Aissatou, Bjerregaard-Andersen, Morten, Løfberg, Sandra Valborg, Seo, Hye Jin, Jeon, Hyon Jin, Deerin, Jessica Fung, Park, Jinkyung, Konings, Frank, Ali, Mohammad, Clemens, John D., Hughes, Peter, Sendagala, Juliet Nsimire, Vudriko, Tobias, Downing, Robert, Ikumapayi, Usman N., Mackenzie, Grant A., Obaro, Stephen, Argimon, Silvia, Aanensen, David M., Page, Andrew, Keane, Jacqueline A., Duchene, Sebastian, Dyson, Zoe, Holt, Kathryn E., Dougan, Gordon, Marks, Florian, and Baker, Stephen

Published
2018
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24. 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, Sikorski, Michael J, Carey, Megan E, Higginson, Ellen E, Dyson, Zoe A, Fernandez, Alda, Araya, Pamela, Tennant, Sharon M, Baker, Stephen, Lagos, Rosanna, Hormazábal, Juan Carlos, Levine, Myron M, Dougan, Gordon, Maes, Mailis [0000-0002-0266-6557], Apollo - University of Cambridge Repository, Baker, Stephen [0000-0003-1308-5755], and Dougan, Gordon [0000-0003-0022-965X]

Subjects
Medicine and health sciences, FOS: Computer and information sciences, Computer and information sciences, Biology and life sciences, Whole Genome Sequencing, Public Health, Environmental and Occupational Health, Salmonella typhi, bacterial infections and mycoses, complex mixtures, Infectious Diseases, Humans, People and places, Chile, Typhoid Fever, Phylogeny, Research Article
Abstract

Typhoid fever epidemiology was investigated rigorously in Santiago, Chile during the 1980s, when Salmonella enterica serovar Typhi (S. Typhi) caused seasonal, hyperendemic disease. Targeted interventions reduced the annual typhoid incidence rates from 128-220 cases/105 population occurring between 1977-1984 to 5 from 1992 onwards. As such, Santiago represents a contemporary example of the epidemiologic transition of an industrialized city from amplified hyperendemic typhoid fever to a period when typhoid is no longer endemic. We used whole genome sequencing (WGS) and phylogenetic analysis to compare the genotypes of S. Typhi cultured from acute cases of typhoid fever occurring in Santiago during the hyperendemic period of the 1980s (n=74) versus the nonendemic 2010s (n=80) when typhoid fever was rare. The genotype distribution between “historical” (1980s) isolates and “modern” (2011-2016) isolates was similar, with genotypes 3.5 and 2 comprising the majority of isolations, and 73/80 (91.3%) of modern isolates matching a genotype detected in the 1980s. Additionally, phylogenomically ‘ancient’ genotypes 1.1 and 1.2.1, uncommon in the global collections, were also detected in both eras, with a notable rise amongst the modern isolates. Thus, genotypes of S. Typhi causing acute illness in the modern nonendemic era match the genotypes circulating during the hyperendemic 1980s. The persistence of historical genotypes may be explained by chronic typhoid carriers originally infected during or before the 1980s.Author summaryStudies of Salmonella Typhi (the cause of typhoid fever) rarely include isolates collected both before and after the interruption of hyperendemic transmission because this typically occurred decades before modern bacteria preservation methods. After interruption, it was assumed that sporadic cases and infrequent outbreaks were due to either chronic biliary carriers or importations, but this was difficult to characterize with low resolution bacterial typing methods. In Santiago, Chile, typhoid fever persisted at hyperendemic levels through the 1980s until organized control efforts in the 1980s and changes to wastewater policy in 1991 caused annual typhoid incidence to plummet.In this study, we used whole genome sequencing (WGS) to investigate whether recent sporadic cases occurring in Santiago in the 2010s were genomically similar to S. Typhi circulating in the 1980s, or dissimilar, possibly representing importations of S. Typhi from outside of Chile. We found concordance amongst S. Typhi genotypes between the 1980s and 2010s, and differences from genotypes circulating in Southeast Asia and Africa where typhoid remains hyperendemic. Our findings suggest that a proportion of modern, rare typhoid cases in Santiago are autochthonous, and that chronic carriers or another unknown reservoir likely contribute. Broadly, our findings corroborate the epidemiologic importance of long-term reservoirs of typhoid fever decades after typhoid elimination.

Published
2022
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25. The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study

Author

da Silva, Kesia Esther, primary, Tanmoy, Arif Mohammad, additional, Pragasam, Agila Kumari, additional, Iqbal, Junaid, additional, Sajib, Mohammad Saiful Islam, additional, Mutreja, Ankur, additional, Veeraraghavan, Balaji, additional, Tamrakar, Dipesh, additional, Qamar, Farah Naz, additional, Dougan, Gordon, additional, Bogoch, Isaac, additional, Seidman, Jessica C, additional, Shakya, Jivan, additional, Vaidya, Krista, additional, Carey, Megan E, additional, Shrestha, Rajeev, additional, Irfan, Seema, additional, Baker, Stephen, additional, Luby, Steve P, additional, Cao, Yanjia, additional, Dyson, Zoe Anne, additional, Garrett, Denise O, additional, John, Jacob, additional, Kang, Gagandeep, additional, Hooda, Yogesh, additional, Saha, Samir K, additional, Saha, Senjuti, additional, and Andrews, Jason R, additional

Published
2022
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26. Multiplex PCR assay to detect high risk lineages of Salmonella Typhi and Paratyphi A

Author

Khokhar, Fahad, primary, Pickard, Derek, additional, Dyson, Zoe, additional, Iqbal, Junaid, additional, Pragasam, Agila, additional, John, Jobin Jacob, additional, Veeraraghavan, Balaji, additional, Qamar, Farah, additional, Dougan, Gordon, additional, MacQueen, Hilary, additional, Rigas, Sushila, additional, Holmes, Mark, additional, and Mutreja, Ankur, additional

Published
2022
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27. Paratype:a genotyping tool for Salmonella Paratyphi A reveals its global genomic diversity

Author

Tanmoy, Arif M., Hooda, Yogesh, Sajib, Mohammad S.I., da Silva, Kesia E., Iqbal, Junaid, Qamar, Farah N., Luby, Stephen P., Dougan, Gordon, Dyson, Zoe A., Baker, Stephen, Garrett, Denise O., Andrews, Jason R., Saha, Samir K., Saha, Senjuti, Tanmoy, Arif M., Hooda, Yogesh, Sajib, Mohammad S.I., da Silva, Kesia E., Iqbal, Junaid, Qamar, Farah N., Luby, Stephen P., Dougan, Gordon, Dyson, Zoe A., Baker, Stephen, Garrett, Denise O., Andrews, Jason R., Saha, Samir K., and Saha, Senjuti

Abstract

Salmonella Paratyphi A, the primary etiology of paratyphoid, is estimated to cause 3.4 million infections annually, worldwide. With rising antimicrobial resistance and no licensed vaccines, genomic surveillance is key to track and monitor transmission, but there is currently no reliable genotyping framework for this pathogen. Here, we sequence 817 isolates from South Asia and add 562 publicly available genomes to build a global database representing 37 countries, covering 1917–2019. We develop a single nucleotide polymorphism-based genotyping scheme, Paratype, that segregates Salmonella Paratyphi A population into three primary and nine secondary clades, and 18 genotypes. Each genotype is assigned a unique allele definition located on an essential gene. Using Paratype, we identify spatiotemporal genomic variation and antimicrobial resistance markers. We release Paratype as an open-access tool that can use raw read files from both Illumina and Nanopore platforms, and thus can assist surveillance studies tracking Salmonella Paratyphi A across the globe.

Published
2022

28. The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi:a genomic epidemiology study

Author

da Silva, Kesia Esther, Tanmoy, Arif Mohammad, Pragasam, Agila Kumari, Iqbal, Junaid, Sajib, Mohammad Saiful Islam, Mutreja, Ankur, Veeraraghavan, Balaji, Tamrakar, Dipesh, Qamar, Farah Naz, Dougan, Gordon, Bogoch, Isaac, Seidman, Jessica C., Shakya, Jivan, Vaidya, Krista, Carey, Megan E., Shrestha, Rajeev, Irfan, Seema, Baker, Stephen, Luby, Steve P., Cao, Yanjia, Dyson, Zoe Anne, Garrett, Denise O., John, Jacob, Kang, Gagandeep, Hooda, Yogesh, Saha, Samir K., Saha, Senjuti, Andrews, Jason R., da Silva, Kesia Esther, Tanmoy, Arif Mohammad, Pragasam, Agila Kumari, Iqbal, Junaid, Sajib, Mohammad Saiful Islam, Mutreja, Ankur, Veeraraghavan, Balaji, Tamrakar, Dipesh, Qamar, Farah Naz, Dougan, Gordon, Bogoch, Isaac, Seidman, Jessica C., Shakya, Jivan, Vaidya, Krista, Carey, Megan E., Shrestha, Rajeev, Irfan, Seema, Baker, Stephen, Luby, Steve P., Cao, Yanjia, Dyson, Zoe Anne, Garrett, Denise O., John, Jacob, Kang, Gagandeep, Hooda, Yogesh, Saha, Samir K., Saha, Senjuti, and Andrews, Jason R.

Abstract

Background: The emergence of increasingly antimicrobial-resistant Salmonella enterica serovar Typhi (S Typhi) threatens to undermine effective treatment and control. Understanding where antimicrobial resistance in S Typhi is emerging and spreading is crucial towards formulating effective control strategies. Methods: In this genomic epidemiology study, we sequenced the genomes of 3489 S Typhi strains isolated from prospective enteric fever surveillance studies in Nepal, Bangladesh, Pakistan, and India (between 2014 and 2019), and combined these with a global collection of 4169 S Typhi genome sequences isolated between 1905 and 2018 to investigate the temporal and geographical patterns of emergence and spread of antimicrobial-resistant S Typhi. We performed non-parametric phylodynamic analyses to characterise changes in the effective population size of fluoroquinolone-resistant, extensively drug-resistant (XDR), and azithromycin-resistant S Typhi over time. We inferred timed phylogenies for the major S Typhi sublineages and used ancestral state reconstruction methods to estimate the frequency and timing of international and intercontinental transfers. Findings: Our analysis revealed a declining trend of multidrug resistant typhoid in south Asia, except for Pakistan, where XDR S Typhi emerged in 2016 and rapidly replaced less-resistant strains. Mutations in the quinolone-resistance determining region (QRDR) of S Typhi have independently arisen and propagated on at least 94 occasions, nearly all occurring in south Asia. Strains with multiple QRDR mutations, including triple mutants with high-level fluoroquinolone resistance, have been increasing in frequency and displacing strains with fewer mutations. Strains containing acrB mutations, conferring azithromycin resistance, emerged in Bangladesh around 2013 and effective population size of these strains has been steadily increasing. We found evidence of frequent international (n=138) and intercontinental transfers (n=5

Published
2022

30. 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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32. Whole genome sequence analysis of Salmonella Typhi in Papua New Guinea reveals an established population of genotype 2.1.7 sensitive to antimicrobials

Author

Dyson, Zoe Anne, primary, Malau, Elisheba, additional, Horwood, Paul F., additional, Ford, Rebecca, additional, Siba, Valentine, additional, Yoannes, Mition, additional, Pomat, William, additional, Passey, Megan, additional, Judd, Louise M., additional, Ingle, Danielle J., additional, Williamson, Deborah A., additional, Dougan, Gordon, additional, Greenhill, Andrew R., additional, and Holt, Kathryn E., additional

Published
2022
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33. Paratype: A genotyping framework and an open-source tool for Salmonella Paratyphi A

Author

Tanmoy, Arif M., primary, Hooda, Yogesh, additional, Sajib, Mohammad S. I., additional, Silva, Kesia E. da, additional, Iqbal, Junaid, additional, Qamar, Farah N., additional, Luby, Stephen P., additional, Dougan, Gordon, additional, Dyson, Zoe A., additional, Baker, Stephen, additional, Garrett, Denise O., additional, Andrews, Jason R., additional, Saha, Samir K., additional, and Saha, Senjuti, additional

Published
2021
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35. Whole genome sequence analysis of Salmonella Typhi in Papua New Guinea reveals an established population of genotype 2.1.7 sensitive to antimicrobials

Author

Dyson, Zoe A., primary, Malau, Elisheba, additional, Horwood, Paul F., additional, Ford, Rebecca, additional, Siba, Valentine, additional, Yoannes, Mition, additional, Pomat, William, additional, Passey, Megan, additional, Judd, Louise M., additional, Ingle, Danielle J., additional, Williamson, Deborah A., additional, Dougan, Gordon, additional, Greenhill, Andrew R., additional, and Holt, Kathryn E., additional

Published
2021
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36. Genome-wide analysis provides a deeper understanding of the population structure of the Salmonella enterica serotype Paratyphi B complex in Bangladesh

Author

Rahman, Sadia Isfat Ara, primary, Taylor-Brown, Alyce, additional, Khanam, Farhana, additional, Khan, Ashraful Islam, additional, Horesh, Gal, additional, Dyson, Zoe A., additional, Begum, Yasmin Ara, additional, Chowdhury, Emran Kabir, additional, Qadri, Firdausi, additional, Dougan, Gordon, additional, and Thomson, Nicholas R., additional

Published
2021
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37. Multiplex PCR Assay to Detect High Risk Lineages of Salmonella Typhi and Paratyphi A

Author

Khokhar, Fahad A, primary, Pickard, Derek JJ, additional, Dyson, Zoe A, additional, Iqbal, Junaid, additional, Pragasam, Agila K, additional, Jacob, Jobin John, additional, Veeraraghavan, Balaji, additional, Qamar, Farah N, additional, Dougan, Gordon, additional, MacQueen, Hilary, additional, Rigas, Sushila H, additional, Holmes, Mark A, additional, and Mutreja, Ankur, additional

Published
2021
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38. Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

Author

Kariuki, Samuel, primary, Dyson, Zoe A, primary, Mbae, Cecilia, additional, Ngetich, Ronald, additional, Kavai, Susan M, additional, Wairimu, Celestine, additional, Anyona, Stephen, additional, Gitau, Naomi, additional, Onsare, Robert Sanaya, additional, Ongandi, Beatrice, additional, Duchene, Sebastian, additional, Ali, Mohamed, additional, Clemens, John David, additional, Holt, Kathryn E, additional, and Dougan, Gordon, additional

Published
2021
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39. The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi

Author

da Silva, Kesia Esther, primary, Tanmoy, Arif Mohammad, additional, Pragasam, Agila Kumari, additional, Iqbal, Junaid, additional, Islam Sajib, Mohammad Saiful, additional, Mutreja, Ankur, additional, Veeraraghavan, Balaji, additional, Tamrakar, Dipesh, additional, Qamar, Farah Naz, additional, Dougan, Gordon, additional, Bogoch, Isaac, additional, Seidman, Jessica C, additional, Shakya, Jivan, additional, Vaidya, Krista, additional, Carey, Megan E., additional, Shrestha, Rajeev, additional, Irfan, Seema, additional, Baker, Stephen, additional, Luby, Steve P., additional, Cao, Yanjia, additional, Dyson, Zoe Anne, additional, Garrett, Denise O., additional, John, Jacob, additional, Kang, Gagandeep, additional, Hooda, Yogesh, additional, Saha, Samir K., additional, Saha, Senjuti, additional, and Andrews, Jason R., additional

Published
2021
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41. Author response: Multiple introductions of multidrug-resistant typhoid associated with acute infection and asymptomatic carriage, Kenya

Author

Kariuki, Samuel, primary, Dyson, Zoe A, additional, Mbae, Cecilia, additional, Ngetich, Ronald, additional, Kavai, Susan M, additional, Wairimu, Celestine, additional, Anyona, Stephen, additional, Gitau, Naomi, additional, Onsare, Robert Sanaya, additional, Ongandi, Beatrice, additional, Duchene, Sebastian, additional, Ali, Mohamed, additional, Clemens, John David, additional, Holt, Kathryn E, additional, and Dougan, Gordon, additional

Published
2021
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43. Additional file 1 of Pathogen genomic surveillance of typhoidal Salmonella infection in adults and children reveals no association between clinical outcomes and infecting genotypes

Author

Britto, Carl D., Sitarah Mathias, Bosco, Ashish, Dyson, Zoe A., Dougan, Gordon, Savitha Raveendran, V. L. Abin, Sanju Jose, Savitha Nagaraj, Holt, Kathryn E., and Pollard, Andrew J.

Abstract

Additional file 1: Figure S1. Temporal distribution of typhoidal Salmonella serovars. Representation of typhoidal serovars, treatment status and genotype distribution as per the inset legends between adults and children over the study period. Figure S2. Phylogenetic tree of 4.3.1 (H58) S. Typhi isolates from Bengaluru and a global collection. This tree is made up of all 100 4.3.1 isolates from this study plus 1133 globally representative 4.3.1 isolates, and the rings are coloured according to the inset legend. The intermingling of isolates of children and adults is evident from the coloured branches and ring1. Branch lengths are indicative of the estimated number of substitutions rate per variable site; the tree was outgroup rooted using S. Paratyphi A strain AKU_12601. Figure S3. Radiological imaging of the right hip joint of a patient with septic arthritis due to S. Typhi (red arrows point to regions of interest as mentioned in the description of each panel). Panel A: CT image, transverse section, showing irregularity and erosions due to the infective process with no obvious breach in cortex. Panel B: MRI image, transverse section, showing involvement of the right iliac crest ,acetabular roof, head of the femur (cystic change), greater and lesser trochanter. Panel C: MRI image, T2W coronal view, shows the extent of bony involvement with effusion in the joint space. Panel D: MRI image, T2W, shows inflammation of the surrounding soft tissue including right iliacus muscle. Left hip joint appears normal.

Published
2020
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44. Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India

Author

Carey, Megan E, primary, Jain, Ruby, additional, Yousuf, Mohammad, additional, Maes, Mailis, additional, Dyson, Zoe A, additional, Thu, Trang Nguyen Hoang, additional, Nguyen Thi Nguyen, To, additional, Ho Ngoc Dan, Thanh, additional, Nhu Pham Nguyen, Quynh, additional, Mahindroo, Jaspreet, additional, Thanh Pham, Duy, additional, Sandha, Kawaljeet Singh, additional, Baker, Stephen, additional, and Taneja, Neelam, additional

Published
2021
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46. Spontaneous emergence of azithromycin resistance in independent lineages of Salmonella Typhi in Northern India

Author

Carey, Megan E., primary, Jain, Ruby, additional, Yousuf, Mohammad, additional, Maes, Mailis, additional, Dyson, Zoe A., additional, Thu, Trang Nguyen Hoang, additional, Nguyen, To Nguyen Thi, additional, Dan, Thanh Ho Ngoc, additional, Nguyen, Quynh Nhu Pham, additional, Mahindroo, Jaspreet, additional, Pham, Duy Thanh, additional, Sandha, Kawaljeet Singh, additional, Baker, Stephen, additional, and Taneja, Neelam, additional

Published
2020
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48. A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at Pathogenwatch

Author

Argimón, Silvia, primary, Yeats, Corin A., additional, Goater, Richard J., additional, Abudahab, Khalil, additional, Taylor, Benjamin, additional, Underwood, Anthony, additional, Sánchez-Busó, Leonor, additional, Wong, Vanessa K., additional, Dyson, Zoe A., additional, Nair, Satheesh, additional, Park, Se Eun, additional, Marks, Florian, additional, Page, Andrew J., additional, Keane, Jacqueline A., additional, Baker, Stephen, additional, Holt, Kathryn E., additional, Dougan, Gordon, additional, and Aanensen, David M., additional

Published
2020
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49. A novel therapeutic antibody screening method using bacterial high-content imaging reveals functional antibody binding phenotypes of Escherichia coli ST131

Author

Maes, Mailis, primary, Dyson, Zoe A., additional, Smith, Sarah E., additional, Goulding, David A., additional, Ludden, Catherine, additional, Baker, Stephen, additional, Kellam, Paul, additional, Reece, Stephen T., additional, Dougan, Gordon, additional, and Scott, Josefin Bartholdson, additional

Published
2020
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