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Volume 9, Issue 3

Phylogenomic investigation of an outbreak of fluoroquinolone-resistant subsp. serovar Paratyphi A in Phnom Penh, Cambodia Open Access

Abstract

In early 2020, the Medical Biology Laboratory of the Pasteur Institute of Cambodia isolated an unusually high number of fluoroquinolone-resistant subspecies serovar Paratyphi A strains during its routine bacteriological surveillance activities in Phnom Penh, Cambodia. A public-health investigation was supported by genome sequencing of these Paratyphi A strains to gain insights into the genetic diversity and population structure of a potential outbreak of fluoroquinolone-resistant paratyphoid fever. Comparative genomic and phylodynamic analyses revealed the 2020 strains were descended from a previously described 2013–2015 outbreak of Paratyphi A infections. Our analysis showed sub-lineage 2.3.1 had remained largely susceptible to fluoroquinolone drugs until 2015, but acquired chromosomal resistance to these drugs during six separate events between late 2012 and 2015. The emergence of fluoroquinolone resistance was rapidly followed by the replacement of the original susceptible Paratyphi A population, which led to a dramatic increase of fluoroquinolone-resistant blood-culture-confirmed cases in subsequent years (2016–2020). The rapid acquisition of resistance-conferring mutations in the Paratyphi A population over a 3 year period is suggestive of a strong selective pressure on that population, likely linked with fluoroquinolone use. In turn, emergence of fluoroquinolone resistance has led to increased use of extended-spectrum cephalosporins like ceftriaxone that are becoming the drug of choice for empirical treatment of paratyphoid fever in Cambodia.

  • Received:
  • Accepted:
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Keyword(s): antimicrobial resistance , Cambodia , phylogenomics , Salmonella enterica Paratyphi A and whole-genome sequencing
© 2023 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2023-03-24
2024-04-26
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References

  1. Crump JA, Sjölund-Karlsson M, Gordon MA, Parry CM. Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella infections. Clin Microbiol Rev 2015; 28:901–937 [View Article]
     [Google Scholar]
  2. Stanaway JD, Reiner RC, Blacker BF, Goldberg EM, Khalil IA et al. The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis 2019; 19:369–381 [View Article] [PubMed]
     [Google Scholar]
  3. Public Health Laboratory Service Waterborne infectious disease in Britain. J Hyg 1978; 81:139–149 [View Article]
     [Google Scholar]
  4. Ochiai RL, Wang X, von Seidlein L, Yang J, Bhutta ZA et al. Salmonella Paratyphi A rates, Asia. Emerg Infect Dis 2005; 11:1764–1766 [View Article]
     [Google Scholar]
  5. Sood S, Kapil A, Dash N, Das BK, Goel V et al. Paratyphoid fever in India: an emerging problem. Emerg Infect Dis 1999; 5:483–484 [View Article]
     [Google Scholar]
  6. Kuijpers LMF, Phe T, Veng CH, Lim K, Ieng S et al. The clinical and microbiological characteristics of enteric fever in Cambodia, 2008–2015. PLoS Negl Trop Dis 2017; 11:e0005964 [View Article]
     [Google Scholar]
  7. Simanjuntak CH, Totosudirjo H, Haryanto P, Suprijanto E, Paleologo FP et al. Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet 1991; 338:1055–1059 [View Article]
     [Google Scholar]
  8. Holt KE, Thomson NR, Wain J, Phan MD, Nair S et al. Multidrug-resistant Salmonella enterica serovar Paratyphi A harbors IncHI1 plasmids similar to those found in serovar Typhi. J Bacteriol 2007; 189:4257–4264 [View Article]
     [Google Scholar]
  9. WHO Background Document: the Diagnosis, Treatment and Prevention of Typhoid Fever Geneva: World Health Organization; 2003
     [Google Scholar]
  10. Mirza SH, Beeching NJ, Hart CA. The prevalence and clinical features of multi-drug resistant Salmonella typhi infections in Baluchistan, Pakistan. Ann Trop Med Parasitol 1995; 89:515–519 [View Article]
     [Google Scholar]
  11. Mandal S, Mandal MD, Pal NK. Antibiotic resistance of Salmonella enterica serovar Paratyphi A in India: emerging and reemerging problem. J Postgrad Med 2006; 52:163–166
     [Google Scholar]
  12. Butt T, Ahmad RN, Salman M, Kazmi SY. Changing trends in drug resistance among typhoid salmonellae in Rawalpindi, Pakistan. East Mediterr Health J 2005; 11:1038–1044 [PubMed]
     [Google Scholar]
  13. Chandel DS, Chaudhry R, Dhawan B, Pandey A, Dey AB. Drug-resistant Salmonella enterica serotype Paratyphi A in India. Emerg Infect Dis 2000; 6:420–421 [View Article]
     [Google Scholar]
  14. Woods CW, Murdoch DR, Zimmerman MD, Glover WA, Basnyat B et al. Emergence of Salmonella enterica serotype Paratyphi A as a major cause of enteric fever in Kathmandu, Nepal. Trans R Soc Trop Med Hyg 2006; 100:1063–1067 [View Article]
     [Google Scholar]
  15. Maskey AP, Day JN, Phung QT, Thwaites GE, Campbell JI et al. Salmonella enterica serovar Paratyphi A and S. enterica serovar Typhi cause indistinguishable clinical syndromes in Kathmandu, Nepal. Clin Infect Dis 2006; 42:1247–1253 [View Article]
     [Google Scholar]
  16. Grimont P, Weill F-X. Antigenic Formulae of the Salmonella Serovars, 9th edn Paris: WHO Collaborating Centre for Reference and Research on Salmonella, Institute Pasteur; 2007
     [Google Scholar]
  17. Nair S, Patel V, Hickey T, Maguire C, Greig DR et al. Real-time PCR assay for differentiation of typhoidal and nontyphoidal Salmonella. J Clin Microbiol 2019; 57:e00167-19 [View Article]
     [Google Scholar]
  18. EUCAST Breakpoint Tables for Interpretation of MICs and Zone Diameters, version 11.0 Växjö: European Committee on Antimicrobial Susceptibility Testing; 2021
     [Google Scholar]
  19. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
     [Google Scholar]
  20. Menardo F, Loiseau C, Brites D, Coscolla M, Gygli SM et al. Treemmer: a tool to reduce large phylogenetic datasets with minimal loss of diversity. BMC Bioinformatics 2018; 19:164 [View Article] [PubMed]
     [Google Scholar]
  21. Tanmoy AM, Hooda Y, Sajib MSI, da Silva KE, Iqbal J et al. Paratype: a genotyping tool for Salmonella Paratyphi A reveals its global genomic diversity. Nat Commun 2022; 13:7912 [View Article]
     [Google Scholar]
  22. Seemann T. Shovill v1.1.0; 2022 https://github.com/tseemann/shovill
  23. Feldgarden M, Brover V, Gonzalez-Escalona N, Frye JG, Haendiges J et al. AMRFinderPlus and the reference gene catalog facilitate examination of the genomic links among antimicrobial resistance, stress response, and virulence. Sci Rep 2021; 11:12728 [View Article]
     [Google Scholar]
  24. Seemann T. Snippy v4.6.0; 2022 https://github.com/tseemann/snippy
  25. Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 2010; 26:589–595 [View Article]
     [Google Scholar]
  26. Danecek P, Bonfield JK, Liddle J, Marshall J, Ohan V et al. Twelve years of SAMtools and BCFtools. Gigascience 2021; 10:giab008 [View Article] [PubMed]
     [Google Scholar]
  27. Garrison E, Marth G. Haplotype-based variant detection from short-read sequencing. arXiv:12073907 [q-bio]. 2012 [cited 18 Feb 2022]; 2012 http://arxiv.org/abs/1207.3907
  28. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article] [PubMed]
     [Google Scholar]
  29. Arndt D, Grant JR, Marcu A, Sajed T, Pon A et al. PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res 2016; 44:W16–W21 [View Article]
     [Google Scholar]
  30. Leigh JW, Bryant D. Popart: full-feature software for haplotype network construction. Methods Ecol Evol 2015; 6:1110–1116 [View Article]
     [Google Scholar]
  31. Bandelt HJ, Forster P, Röhl A. Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol 1999; 16:37–48 [View Article] [PubMed]
     [Google Scholar]
  32. Nguyen L-T, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article]
     [Google Scholar]
  33. Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods 2017; 14:587–589 [View Article] [PubMed]
     [Google Scholar]
  34. Bouckaert R, Vaughan TG, Barido-Sottani J, Duchêne S, Fourment M et al. BEAST 2.5: an advanced software platform for Bayesian evolutionary analysis. PLoS Comput Biol 2019; 15:e1006650 [View Article]
     [Google Scholar]
  35. Drummond AJ, Ho SYW, Phillips MJ, Rambaut A. Relaxed phylogenetics and dating with confidence. PLoS Biol 2006; 4:e88 [View Article]
     [Google Scholar]
  36. Drummond AJ, Rambaut A, Shapiro B, Pybus OG. Bayesian coalescent inference of past population dynamics from molecular sequences. Mol Biol Evol 2005; 22:1185–1192 [View Article] [PubMed]
     [Google Scholar]
  37. Zhou Z, McCann A, Weill F-X, Blin C, Nair S et al. Transient Darwinian selection in Salmonella enterica serovar Paratyphi A during 450 years of global spread of enteric fever. Proc Natl Acad Sci USA 2014; 111:12199–12204 [View Article]
     [Google Scholar]
  38. Kuijpers LMF, Le Hello S, Fawal N, Fabre L, Tourdjman M et al. Genomic analysis of Salmonella enterica serotype Paratyphi A during an outbreak in Cambodia, 2013-2015. Microb Genom 2016; 2:e000092 [View Article]
     [Google Scholar]
  39. Rambaut A, Drummond AJ, Xie D, Baele G, Suchard MA. Posterior summarization in Bayesian phylogenetics using tracer 1.7. Syst Biol 2018; 67:901–904 [View Article]
     [Google Scholar]
  40. Duchene S, Duchene DA, Geoghegan JL, Dyson ZA, Hawkey J et al. Inferring demographic parameters in bacterial genomic data using Bayesian and hybrid phylogenetic methods. BMC Evol Biol 2018; 18:95 [View Article] [PubMed]
     [Google Scholar]
  41. Rieux A, Khatchikian CE. TIPDATINGBEAST: an R package to assist the implementation of phylogenetic tip-dating tests using BEAST. Mol Ecol Resour 2017; 17:608–613 [View Article]
     [Google Scholar]
  42. Jacoby GA. Mechanisms of resistance to quinolones. Clin Infect Dis 2005; 41 Suppl 2:S120–6 [View Article]
     [Google Scholar]
  43. Nair S, Day M, Godbole G, Saluja T, Langridge GC et al. Genomic surveillance detects Salmonella enterica serovar Paratyphi A harbouring blaCTX-M-15 from a traveller returning from Bangladesh. PLoS One 2020; 15:e0228250 [View Article]
     [Google Scholar]
  44. Duchêne S, Holt KE, Weill F-X, Le Hello S, Hawkey J et al. Genome-scale rates of evolutionary change in bacteria. Microb Genom 2016; 2:e000094 [View Article]
     [Google Scholar]
  45. Kuijpers LMF, Veng CH, Sar D, Chung P, Phe T et al. Ongoing outbreak of Salmonella enterica serovar Paratyphi A infections, Phnom Penh, Cambodia. J Infect Dev Ctries 2015; 9:438–440 [View Article]
     [Google Scholar]
  46. Vlieghe E, Phe T, De Smet B, Veng CH, Kham C et al. Increase in Salmonella enterica serovar Paratyphi A infections in Phnom Penh, Cambodia, January 2011 to August 2013. Euro Surveill 2013; 18:20592 [View Article]
     [Google Scholar]
  47. Cantón R, Morosini M-I. Emergence and spread of antibiotic resistance following exposure to antibiotics. FEMS Microbiol Rev 2011; 35:977–991 [View Article] [PubMed]
     [Google Scholar]
  48. Hassing R-J, Goessens WHF, van Pelt W, Mevius DJ, Stricker BH et al. Salmonella subtypes with increased MICs for azithromycin in travelers returned to The Netherlands. Emerg Infect Dis 2014; 20:705–708 [View Article]
     [Google Scholar]
  49. Pokharel BM, Koirala J, Dahal RK, Mishra SK, Khadga PK et al. Multidrug-resistant and extended-spectrum beta-lactamase (ESBL)-producing Salmonella enterica (serotypes Typhi and Paratyphi A) from blood isolates in Nepal: surveillance of resistance and a search for newer alternatives. Int J Infect Dis 2006; 10:434–438 [View Article]
     [Google Scholar]
  50. Misra R, Prasad KN, Amrin N, Kapoor P, Singh S et al. Absence of multidrug resistance in Salmonella enterica serotypes Typhi and Paratyphi A isolates with intermediate susceptibility to ciprofloxacin. Trans R Soc Trop Med Hyg 2015; 109:538–540 [View Article]
     [Google Scholar]
  51. Om C, Daily F, Vlieghe E, McLaughlin JC, McLaws M-L. Pervasive antibiotic misuse in the Cambodian community: antibiotic-seeking behaviour with unrestricted access. Antimicrob Resist Infect Control 2017; 6:30 [View Article]
     [Google Scholar]
  52. Schanberg SH. The Death and Life of Dith Pran New York: Penguin; 1985
     [Google Scholar]
  53. Punda-Polić V, Kraljević KS, Bradarić N. War-associated cases of typhoid fever imported to Split-Dalmatia County (Croatia). Mil Med 2007; 172:1096–1098 [View Article]
     [Google Scholar]
  54. Octavia S, Wang Q, Tanaka MM, Kaur S, Sintchenko V et al. Delineating community outbreaks of Salmonella enterica serovar Typhimurium by use of whole-genome sequencing: insights into genomic variability within an outbreak. J Clin Microbiol 2015; 53:1063–1071 [View Article]
     [Google Scholar]
  55. Thompson L, Vipham J, Hok L, Ebner P. Towards improving food safety in Cambodia: current status and emerging opportunities. Glob Food Sec 2021; 31:100572 [View Article]
     [Google Scholar]
  56. WHO GLASS Whole-Genome Sequencing for Surveillance of Antimicrobial Resistance Geneva: World Health Organization; 2020
     [Google Scholar]
  57. Letunic I, Bork P. Interactive tree of life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 2021; 49:W293–W296 [View Article]
     [Google Scholar]
  58. QGIS Development Team QGIS Geographic Information System; 2021 https://www.qgis.org
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Phylogenomic investigation of an outbreak of fluoroquinolone-resistant Salmonella enterica subsp. enterica serovar Paratyphi A in Phnom Penh, Cambodia
M Gen 9, 000972 (2023); https://doi.org/10.1099/mgen.0.000972
/content/journal/mgen/10.1099/mgen.0.000972
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