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

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

doi:10.7554/eLife.85867

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

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

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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]).

Original language	English
Article number	e85867
Journal	eLife
Volume	12
Number of pages	46
ISSN	2050-084X
DOIs	https://doi.org/10.7554/eLife.85867
Publication status	Published - 2023

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Carey, M. E., Dyson, Z. A., Ingle, D. J., Amir, A., Aworh, M. K., Chattaway, M. A., Chew, K. L., Crump, J. A., Feasey, N. A., Howden, B. P., Keddy, K. H., Maes, M., Parry, C. M., Van Puyvelde, S., Webb, H. E., Afolayan, A. O., Alexander, A. P., Anandan, S., Andrews, J. R., ... Global Typhoid Genomics Consortium Group Authorship (2023). Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes. eLife, 12, Article e85867. https://doi.org/10.7554/eLife.85867

@article{50bb734781a04fdeb0d09284b929df6b,

title = "Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi 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]).",

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

year = "2023",

doi = "10.7554/eLife.85867",

language = "English",

volume = "12",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd.",

}

Carey, ME, Dyson, ZA, Ingle, DJ, Amir, A, Aworh, MK, Chattaway, MA, Chew, KL, Crump, JA, Feasey, NA, Howden, BP, Keddy, KH, Maes, M, Parry, CM, Van Puyvelde, S, Webb, HE, Afolayan, AO, Alexander, AP, Anandan, S, Andrews, JR, Ashton, PM, Basnyat, B, Bavdekar, A, Bogoch, II, Clemens, JD, da Silva, KE, De, A, de Ligt, J, Diaz Guevara, PL, Dolecek, C, Dutta, S, Ehlers, MM, Francois Watkins, L, Garrett, DO, Godbole, G, Gordon, MA, Greenhill, AR, Griffin, C, Gupta, M, Hendriksen, RS, Heyderman, RS, Hooda, Y, Hormazabal, JC, Ikhimiukor, OO, Iqbal, J, Jacob, JJ, Jenkins, C, Jinka, DR, John, J, Kang, G, Kanteh, A, Kapil, A, Karkey, A, Kariuki, S, Kingsley, RA, Koshy, RM, Lauer, AC, Levine, MM, Lingegowda, RK, Luby, SP, Mackenzie, GA, Mashe, T, Msefula, C, Mutreja, A, Nagaraj, G, Nagaraj, S, Nair, S, Naseri, TK, Nimarota-Brown, S, Njamkepo, E, Okeke, IN, Perumal, SPB, Pollard, AJ, Pragasam, AK, Qadri, F, Qamar, FN, Rahman, SIA, Rambocus, SD, Rasko, DA, Ray, P, Robins-Browne, R, Rongsen-Chandola, T, Rutanga, JP, Saha, SK, Saha, S, Saigal, K, Sajib, MSI, Seidman, JC, Shakya, J, Shamanna, V, Shastri, J, Shrestha, R, Sia, S, Sikorski, MJ, Singh, A, Smith, AM, Tagg, KA, Tamrakar, D, Tanmoy, AM, Thomas, M, Thomas, MS, Thomsen, R, Thomson, NR, Tupua, S, Vaidya, K, Valcanis, M, Veeraraghavan, B, Weill, F-X, Wright, J, Dougan, G, Argimón, S, Keane, JA, Aanensen, DM, Baker, S, Holt, KE & Global Typhoid Genomics Consortium Group Authorship 2023, 'Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes', eLife, vol. 12, e85867. https://doi.org/10.7554/eLife.85867

TY - JOUR

T1 - Global diversity and antimicrobial resistance of typhoid fever pathogens

T2 - Insights from a meta-analysis of 13,000 Salmonella Typhi genomes

AU - Carey, Megan E

AU - Dyson, Zoe A

AU - Ingle, Danielle J

AU - Amir, Afreenish

AU - Aworh, Mabel K

AU - Chattaway, Marie Anne

AU - Chew, Ka Lip

AU - Crump, John A

AU - Feasey, Nicholas A

AU - Howden, Benjamin P

AU - Keddy, Karen H

AU - Maes, Mailis

AU - Parry, Christopher M

AU - Van Puyvelde, Sandra

AU - Webb, Hattie E

AU - Afolayan, Ayorinde Oluwatobiloba

AU - Alexander, Anna P

AU - Anandan, Shalini

AU - Andrews, Jason R

AU - Ashton, Philip M

AU - Basnyat, Buddha

AU - Bavdekar, Ashish

AU - Bogoch, Isaac I

AU - Clemens, John D

AU - da Silva, Kesia Esther

AU - De, Anuradha

AU - de Ligt, Joep

AU - Diaz Guevara, Paula Lucia

AU - Dolecek, Christiane

AU - Dutta, Shanta

AU - Ehlers, Marthie M

AU - Francois Watkins, Louise

AU - Garrett, Denise O

AU - Godbole, Gauri

AU - Gordon, Melita A

AU - Greenhill, Andrew R

AU - Griffin, Chelsey

AU - Gupta, Madhu

AU - Hendriksen, Rene S

AU - Heyderman, Robert S

AU - Hooda, Yogesh

AU - Hormazabal, Juan Carlos

AU - Ikhimiukor, Odion O

AU - Iqbal, Junaid

AU - Jacob, Jobin John

AU - Jenkins, Claire

AU - Jinka, Dasaratha Ramaiah

AU - John, Jacob

AU - Kang, Gagandeep

AU - Kanteh, Abdoulie

AU - Kapil, Arti

AU - Karkey, Abhilasha

AU - Kariuki, Samuel

AU - Kingsley, Robert A

AU - Koshy, Roshine Mary

AU - Lauer, AC

AU - Levine, Myron M

AU - Lingegowda, Ravikumar Kadahalli

AU - Luby, Stephen P

AU - Mackenzie, Grant Austin

AU - Mashe, Tapfumanei

AU - Msefula, Chisomo

AU - Mutreja, Ankur

AU - Nagaraj, Geetha

AU - Nagaraj, Savitha

AU - Nair, Satheesh

AU - Naseri, Take K

AU - Nimarota-Brown, Susana

AU - Njamkepo, Elisabeth

AU - Okeke, Iruka N

AU - Perumal, Sulochana Putli Bai

AU - Pollard, Andrew J

AU - Pragasam, Agila Kumari

AU - Qadri, Firdausi

AU - Qamar, Farah N

AU - Rahman, Sadia Isfat Ara

AU - Rambocus, Savitra Devi

AU - Rasko, David A

AU - Ray, Pallab

AU - Robins-Browne, Roy

AU - Rongsen-Chandola, Temsunaro

AU - Rutanga, Jean Pierre

AU - Saha, Samir K

AU - Saha, Senjuti

AU - Saigal, Karnika

AU - Sajib, Mohammad Saiful Islam

AU - Seidman, Jessica C

AU - Shakya, Jivan

AU - Shamanna, Varun

AU - Shastri, Jayanthi

AU - Shrestha, Rajeev

AU - Sia, Sonia

AU - Sikorski, Michael J

AU - Singh, Ashita

AU - Smith, Anthony M

AU - Tagg, Kaitlin A

AU - Tamrakar, Dipesh

AU - Tanmoy, Arif Mohammed

AU - Thomas, Maria

AU - Thomas, Mathew S

AU - Thomsen, Robert

AU - Thomson, Nicholas R

AU - Tupua, Siaosi

AU - Vaidya, Krista

AU - Valcanis, Mary

AU - Veeraraghavan, Balaji

AU - Weill, François-Xavier

AU - Wright, Jackie

AU - Dougan, Gordon

AU - Argimón, Silvia

AU - Keane, Jacqueline A

AU - Aanensen, David M

AU - Baker, Stephen

AU - Holt, Kathryn E

AU - Global Typhoid Genomics Consortium Group Authorship

PY - 2023

Y1 - 2023

N2 - 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]).

AB - 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]).

U2 - 10.7554/eLife.85867

DO - 10.7554/eLife.85867

M3 - Journal article

C2 - 37697804

SN - 2050-084X

VL - 12

JO - eLife

JF - eLife

M1 - e85867

ER -

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

Abstract

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