Genomics of the Argentinian cholera epidemic elucidate the contrasting dynamics of epidemic and endemic Vibrio cholerae.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
01 10 2020
Historique:
received: 02 04 2020
accepted: 03 09 2020
entrez: 2 10 2020
pubmed: 3 10 2020
medline: 21 10 2020
Statut: epublish

Résumé

In order to control and eradicate epidemic cholera, we need to understand how epidemics begin, how they spread, and how they decline and eventually end. This requires extensive sampling of epidemic disease over time, alongside the background of endemic disease that may exist concurrently with the epidemic. The unique circumstances surrounding the Argentinian cholera epidemic of 1992-1998 presented an opportunity to do this. Here, we use 490 Argentinian V. cholerae genome sequences to characterise the variation within, and between, epidemic and endemic V. cholerae. We show that, during the 1992-1998 cholera epidemic, the invariant epidemic clone co-existed alongside highly diverse members of the Vibrio cholerae species in Argentina, and we contrast the clonality of epidemic V. cholerae with the background diversity of local endemic bacteria. Our findings refine and add nuance to our genomic definitions of epidemic and endemic cholera, and are of direct relevance to controlling current and future cholera epidemics.

Identifiants

pubmed: 33004800
doi: 10.1038/s41467-020-18647-7
pii: 10.1038/s41467-020-18647-7
pmc: PMC7530988
doi:

Substances chimiques

DNA, Bacterial 0

Banques de données

figshare
['10.6084/m9.figshare.11310131']

Types de publication

Comparative Study Historical Article Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4918

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206194
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : KL2 TR001448
Pays : United States

Références

Evins, G. M. et al. The emerging diversity of the electrophoretic types of Vibrio cholerae in the Western hemisphere. J. Infect. Dis. 172, 173–179 (1995).
pubmed: 7797907 doi: 10.1093/infdis/172.1.173 pmcid: 7797907
Popovic, T., Bopp, C., Olsvik, O. & Wachsmuth, K. Epidemiologic application of a standardized ribotype scheme for Vibrio cholerae O1. J. Clin. Microbiol 31, 2474–2482 (1993).
pubmed: 7691876 pmcid: 265780 doi: 10.1128/JCM.31.9.2474-2482.1993
Wachsmuth, I. K. et al. The molecular epidemiology of cholera in Latin America. J. Infect. Dis. 167, 621–626 (1993).
pubmed: 7680060 doi: 10.1093/infdis/167.3.621 pmcid: 7680060
Pollitzer, R., Swaroop, S. & Burrows, W. Cholera (WHO, 1959).
Pan American Health Organization. Cholera in the Americas. Bull. PAHO 25, 267–273 (1991).
Pan American Health Organization. Cholera situation in the Americas. Epidemiol. Bull. 12, 1–24 (1991).
Domman, D. et al. Integrated view of Vibrio cholerae in the Americas. Science 358, 789–793 (2017).
pubmed: 29123068 doi: 10.1126/science.aao2136 pmcid: 29123068
Chin, C.-S. et al. The origin of the Haitian cholera outbreak strain. N. Engl. J. Med. 364, 33–42 (2011).
pubmed: 21142692 doi: 10.1056/NEJMoa1012928 pmcid: 21142692
Mutreja, A. et al. Evidence for several waves of global transmission in the seventh cholera pandemic. Nature 477, 462–465 (2011).
pubmed: 21866102 pmcid: 3736323 doi: 10.1038/nature10392
Mata, L. Cholera El Tor in Latin America, 1991–1993. Ann. NY Acad. Sci. 740, 55–68 (1994).
pubmed: 7840479 doi: 10.1111/j.1749-6632.1994.tb19853.x pmcid: 7840479
Wilson, M. M. & Chelala, C. Cholera is walking South. J. Am. Med Assoc. 272, 1226–1227 (1994).
doi: 10.1001/jama.1994.03520150100051
Hendriksen, R. S. et al. Population genetics of Vibrio cholerae from Nepal in 2010: evidence on the origin of the Haitian outbreak. mBio 2, e00157-11 (2011).
pubmed: 21862630 pmcid: 3163938 doi: 10.1128/mBio.00157-11
Kumate, J., Sepúlveda, J. & Gutiérrez, G. Cholera epidemiology in Latin America and perspectives for eradication. Bull. Inst. Pasteur. 96, 217–226 (1998).
doi: 10.1016/S0020-2452(99)80002-5
Castañeda, N. C. et al. Genetic characterization of Vibrio cholerae isolates from Argentina by V. cholerae repeated sequences–polymerase chain reaction. Diagn. Microbiol. Infec. Dis. 53, 175–183 (2005).
doi: 10.1016/j.diagmicrobio.2005.05.008
Wilson, M. M., Juliá, C. M. & Chelala, C. How Argentina benefited from a cholera epidemic. Lancet 349, 1375 (1997).
doi: 10.1016/S0140-6736(05)63219-9
Rivas, M. & Pichel, M. Red nacional de diarreas y patógenos bacterianos de transmisión alimentaria (ANLIS, 2014).
Pan American Health Organization. Cholera situation in the Americas, 1996. Epidemiol. Bull. 18, 5–7 (1997).
Pan American Health Organization. Cholera situation in the Americas — Update. Epidemiol. Bull. 13, 11–12 (1992).
Pan American Health Organization. Cholera in the Americas. Epidemiol. Bull. 14, 14 (1993).
Pan American Health Organization. Cholera situation in the Americas. Epidemiol. Bull. 15, 13–16 (1994).
Pan American Health Organization. Cholera in the Americas. Epidemiol. Bull. 16, 11–12 (1995).
Tauxe, R. V., Mintz, E. D. & Quick, R. E. Epidemic cholera in the new world: translating field epidemiology into new prevention strategies. Emerg. Infect. Dis. 1, 141–146 (1995).
pubmed: 8903186 pmcid: 2626892 doi: 10.3201/eid0104.950408
Petroni, A. et al. Plasmidic extended-spectrum β-lactamases in Vibrio cholerae O1 El Tor isolates in Argentina. Antimicrob. Agents Ch. 46, 1462–1468 (2002).
doi: 10.1128/AAC.46.5.1462-1468.2002
Binsztein, N. et al. Viable but nonculturable Vibrio cholerae O1 in the aquatic environment of Argentina. Appl Environ. Microbiol. 70, 7481–7486 (2004).
pubmed: 15574951 pmcid: 535145 doi: 10.1128/AEM.70.12.7481-7486.2004
Pichel, M. et al. Genetic diversity of Vibrio cholerae O1 in Argentina and emergence of a new variant. J. Clin. Microbiol. 41, 124–134 (2003).
pubmed: 12517837 pmcid: 149600 doi: 10.1128/JCM.41.1.124-134.2003
Rossi, A. et al. Unusual multiresistant Vibrio cholerae 01 El Tor in Argentina. Lancet 342, 1172–1173 (1993).
pubmed: 7901493 doi: 10.1016/0140-6736(93)92155-M pmcid: 7901493
Fraga, S. G. Búsqueda de Reservorios Ambientales de Vibrio cholerae O1 en Diferentes Regiones del País y Caracterización de V. cholerae O1 Variante Tucumán. Thesis, Univ. Buenos Aires (2010).
Weill, F.-X. et al. Genomic history of the seventh pandemic of cholera in Africa. Science 358, 785–789 (2017).
pubmed: 29123067 doi: 10.1126/science.aad5901 pmcid: 29123067
Allué-Guardia, A., Echazarreta, M., Koenig, S. S. K., Klose, K. E. & Eppinger, M. Closed genome eequence of Vibrio cholerae O1 El Tor Inaba strain A1552. Genome Announc. 6, e00098–18 (2018).
pubmed: 29496831 pmcid: 5834340 doi: 10.1128/genomeA.00098-18
Yildiz, F. H. & Schoolnik, G. K. Role of rpoS in stress survival and virulence of Vibrio cholerae. J. Bacteriol. 180, 773–784 (1998).
pubmed: 9473029 pmcid: 106954 doi: 10.1128/JB.180.4.773-784.1998
Tonkin-Hill, G., Lees, J. A., Bentley, S. D., Frost, S. D. W. & Corander, J. Fast hierarchical Bayesian analysis of population structure. Nucleic Acids Res. 47, 5539–5549 (2019).
pubmed: 31076776 pmcid: 6582336 doi: 10.1093/nar/gkz361
Domman, D. et al. Defining endemic cholera at three levels of spatiotemporal resolution within Bangladesh. Nat. Genet. 50, 951–955 (2018).
pubmed: 29942084 pmcid: 6283067 doi: 10.1038/s41588-018-0150-8
Weill, F.-X. et al. Genomic insights into the 2016–2017 cholera epidemic in Yemen. Nature 565, 230–233 (2019).
pubmed: 30602788 pmcid: 6420076 doi: 10.1038/s41586-018-0818-3
Didelot, X. et al. The role of China in the global spread of the current cholera pandemic. PLoS Genet. 11, e1005072 (2015).
pubmed: 25768799 pmcid: 4358972 doi: 10.1371/journal.pgen.1005072
Hu, D. et al. Changing molecular epidemiology of Vibrio cholerae outbreaks in Shanghai, China. mSystems. 4, e00561-19 (2019).
pubmed: 31771974 pmcid: 6880041 doi: 10.1128/mSystems.00561-19
Paul, K., Ghosh, A., Sengupta, N. & Chowdhury, R. Competitive growth advantage of nontoxigenic mutants in the stationary phase in archival cultures of pathogenic Vibrio cholerae strains. Infect. Immun. 72, 5478–5482 (2004).
pubmed: 15322049 pmcid: 517435 doi: 10.1128/IAI.72.9.5478-5482.2004
Dupont, M. J., Jouvenot, M., Couetdic, G. & Michel-Briand, Y. Development of plasmid-mediated resistance in Vibrio cholerae during treatment with trimethoprim-sulfamethoxazole. Antimicrob. Agents Ch. 27, 280–281 (1985).
doi: 10.1128/AAC.27.2.280
Centers for Disease Control and Prevention. in Laboratory Methods for the Diagnosis of Vibrio cholerae Ch. 6 (CDC, 2018). 
Alam, M. T. et al. Major shift of toxigenic V. cholerae O1 from Ogawa to Inaba serotype isolated from clinical and environmental samples in Haiti. PLoS Negl. Trop. Dis. 10, e0005045 (2016).
pubmed: 27716803 pmcid: 5055329 doi: 10.1371/journal.pntd.0005045
European Medicines Agency. Dukoral. EMA  https://www.ema.europa.eu/en/medicines/human/EPAR/dukoral (2018).
Khan, A. I. et al. Comparison of clinical features and immunological parameters of patients with dehydrating diarrhoea infected with Inaba or Ogawa serotypes of Vibrio cholerae O1. Scand. J. Infect. Dis. 42, 48–56 (2010).
pubmed: 19883159 pmcid: 3786431 doi: 10.3109/00365540903289688
Chatterjee, S. N. & Chaudhuri, K. Lipopolysaccharides of Vibrio cholerae. I. Physical and chemical characterization. Biochim. Biophys. Acta. 1639, 65–79 (2003).
pubmed: 14559113 doi: 10.1016/j.bbadis.2003.08.004 pmcid: 14559113
Stroeher, U. H., Karageorgos, L. E., Morona, R. & Manning, P. A. Serotype conversion in Vibrio cholerae O1. Proc. Natl Acad. Sci. USA 89, 2566–2570 (1992).
pubmed: 1372980 doi: 10.1073/pnas.89.7.2566 pmcid: 1372980
Ito, T., Hiramatsu, K., Ohshita, Y. & Yokota, T. Mutations in the rfbT gene are responsible for the Ogawa to Inaba serotype conversion in Vibrio cholerae O1. Microbiol Immunol. 37, 281–288 (1993).
pubmed: 7688846 doi: 10.1111/j.1348-0421.1993.tb03211.x pmcid: 7688846
Sheehy, T. W., Sprinz, H., Augerson, W. S. & Formal, S. B. Laboratory Vibrio cholerae infection in the United States. J. Am. Med Assoc. 197, 321–326 (1966).
doi: 10.1001/jama.1966.03110050059016
Sack, R. B. & Miller, C. E. Progressive changes of Vibrio serotypes in germ-free mice infected with Vibrio cholerae. J. Bacteriol. 99, 688–695 (1969).
pubmed: 5370274 pmcid: 250082 doi: 10.1128/JB.99.3.688-695.1969
Vugia, D. J. et al. Epidemic cholera in Trujillo, Peru 1992: utility of a clinical case definition and shift in Vibrio cholerae O1 serotype. Am. J. Trop. Med. Hyg. 50, 566–569 (1994).
pubmed: 8203704 doi: 10.4269/ajtmh.1994.50.566 pmcid: 8203704
Wang, H. et al. Genomic epidemiology of Vibrio cholerae reveals the regional and global spread of two epidemic non-toxigenic lineages. PLoS Negl. Trop. Dis. 14, e0008046 (2020).
pubmed: 32069325 pmcid: 7048298 doi: 10.1371/journal.pntd.0008046
Jain, C., Rodriguez-R, L. M., Phillippy, A. M., Konstantinidis, K. T. & Aluru, S. High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries. Nat. Commun. 9, 5114 (2018).
pubmed: 30504855 pmcid: 6269478 doi: 10.1038/s41467-018-07641-9
Dziejman, M. et al. Genomic characterization of non-O1, non-O139 Vibrio cholerae reveals genes for a type III secretion system. Proc. Natl Acad. Sci. USA 102, 3465–3470 (2005).
pubmed: 15728357 doi: 10.1073/pnas.0409918102 pmcid: 15728357
Carpenter, M. R. et al. CRISPR-Cas and contact-dependent secretion systems present on excisable pathogenicity islands with conserved recombination modules. J. Bacteriol. 199, e00842–16 (2017).
pubmed: 28264992 pmcid: 5405205 doi: 10.1128/JB.00842-16
Castillo, D. et al. Comparative genome analyses of Vibrio anguillarum strains reveal a link with pathogenicity traits. mSystems. 2, e00001-17 (2017).
pubmed: 28293680 pmcid: 5347184 doi: 10.1128/mSystems.00001-17
Wong, V. K. et al. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nat. Genet. 47, 632–639 (2015).
pubmed: 25961941 pmcid: 4921243 doi: 10.1038/ng.3281
Guglielmetti, P. et al. Population movements and cholera spread in Cordillera Province, Santa Cruz Department, Bolivia. Lancet 340, 113 (1992).
pubmed: 1351977 doi: 10.1016/0140-6736(92)90432-3 pmcid: 1351977
Shin, O. S. et al. Type III secretion is essential for the rapidly fatal diarrheal disease caused by non-O1, non-O139 Vibrio cholerae. mBio 2, e00106–e00111 (2011).
pubmed: 21673189 pmcid: 3111608 doi: 10.1128/mBio.00106-11
Cameron, D. N., Khambaty, F. M., Wachsmuth, I. K., Tauxe, R. V. & Barrett, T. J. Molecular characterization of Vibrio cholerae O1 strains by pulsed-field gel electrophoresis. J. Clin. Microbiol. 32, 1685–1690 (1994).
pubmed: 7929758 pmcid: 263762 doi: 10.1128/JCM.32.7.1685-1690.1994
Dalsgaard, A. et al. Molecular evolution of Vibrio cholerae O1 strains isolated in Lima, Peru, from 1991 to 1995. J. Clin. Microbiol. 35, 1151–1156 (1997).
pubmed: 9114398 pmcid: 232720 doi: 10.1128/JCM.35.5.1151-1156.1997
Pan American Health Organisation (PAHO). Cholera situation in the Americas. An update. Epidemiol. Bull. 12, 1–4 (1991).
World Health Organization. Ending cholera: a global roadmap to 2030 (WHO, 2017).
Dorman, M. J. et al. The history, genome and biology of NCTC 30: a non-pandemic Vibrio cholerae isolate from World War One. Proc. R. Soc. B 286, 20182025 (2019).
pubmed: 30966987 doi: 10.1098/rspb.2018.2025 pmcid: 30966987
Varela, P. et al. Direct detection of Vibrio cholerae in stool samples. J. Clin. Microbiol. 32, 1246–1248 (1994).
pubmed: 8051251 pmcid: 263658 doi: 10.1128/JCM.32.5.1246-1248.1994
Varela, P. et al. Identification of toxigenic Vibrio cholerae from the Argentine outbreak by PCR for ctxA1 and ctxA2-B. FEBS Lett. 315, 74–76 (1993).
pubmed: 8416815 doi: 10.1016/0014-5793(93)81136-N pmcid: 8416815
Administración Nacional de Laboratorios e Institutos de Salud  “Dr. Carlos G. Malbran”. Manual de procedimientos: Aislamiento, identificación y caracterización de Vibrio cholerae: WHO global Salmonella surveillance América del Sur (ANLIS, 2007).
Wood, D. E. & Salzberg, S. L. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol. 15, R46 (2014).
pubmed: 24580807 pmcid: 4053813 doi: 10.1186/gb-2014-15-3-r46
Bankevich, A. et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J. Comput. Biol. 19, 455–477 (2012).
pubmed: 22506599 pmcid: 3342519 doi: 10.1089/cmb.2012.0021
Page, A. J. et al. Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data. Microb. Genom. 2, e000083 (2016).
pubmed: 28348874 pmcid: 5320598
Seemann, T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069 (2014).
doi: 10.1093/bioinformatics/btu153
Page, A. J. et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 31, 3691–3693 (2015).
pubmed: 26198102 pmcid: 4817141 doi: 10.1093/bioinformatics/btv421
Harris, S. R. et al. Evolution of MRSA during hospital transmission and intercontinental spread. Science 327, 469–474 (2010).
pubmed: 20093474 pmcid: 2821690 doi: 10.1126/science.1182395
Li, H. et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 25, 2078–2079 (2009).
pubmed: 2723002 pmcid: 2723002 doi: 10.1093/bioinformatics/btp352
Croucher, N. J. et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res. 43, e15–e15 (2015).
pubmed: 25414349 doi: 10.1093/nar/gku1196 pmcid: 25414349
Page, A. J. et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microbial. Genom. 2, e000056 (2016).
Capella-Gutiérrez, S., Silla-Martínez, J. M. & Gabaldón, T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 25, 1972–1973 (2009).
pubmed: 19505945 pmcid: 2712344 doi: 10.1093/bioinformatics/btp348
Nguyen, L.-T., Schmidt, H. A., von Haeseler, A. & Minh, B. Q. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol. Biol. Evol. 32, 268–274 (2015).
pubmed: 25371430 pmcid: 25371430 doi: 10.1093/molbev/msu300
Lewis, P. O. A likelihood approach to estimating phylogeny from discrete morphological character data. Syst. Biol. 50, 913–925 (2001).
pubmed: 12116640 doi: 10.1080/106351501753462876 pmcid: 12116640
Guindon, S. et al. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst. Biol. 59, 307–321 (2010).
pubmed: 20525638 pmcid: 20525638 doi: 10.1093/sysbio/syq010
Hoang, D. T., Chernomor, O., von Haeseler, A., Minh, B. Q. & Vinh, L. S. UFBoot2: improving the ultrafast bootstrap approximation. Mol. Biol. Evol. 35, 518–522 (2018).
pubmed: 29077904 doi: 10.1093/molbev/msx281 pmcid: 29077904
Heller, K. A. & Ghahramani, Z. Bayesian hierarchical clustering. Proc. 22nd Int. Conf. Mach. Learning.  https://doi.org/10.1145/1102351.1102389  (2005).
Hunt, M. et al. ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads. Microbial. Genom. 3, e000131 (2017).
Hu, D. et al. Origins of the current seventh cholera pandemic. Proc. Natl Acad. Sci. USA 113, E7730–E7739 (2016).
pubmed: 27849586 doi: 10.1073/pnas.1608732113 pmcid: 27849586
Lebens, M. et al. Construction of novel vaccine strains of Vibrio cholerae co-expressing the Inaba and Ogawa serotype antigens. Vaccine 29, 7505–7513 (2011).
pubmed: 21807059 doi: 10.1016/j.vaccine.2011.06.121 pmcid: 21807059
Karlsson, S. L. et al. Retrospective analysis of serotype switching of Vibrio cholerae O1 in a cholera endemic region shows it is a non-random process. PLoS Negl. Trop. Dis. 10, e0005044 (2016).
pubmed: 27706170 pmcid: 5051702 doi: 10.1371/journal.pntd.0005044
Zankari, E. et al. Identification of acquired antimicrobial resistance genes. J. Antimicrob. Chemother. 67, 2640–2644 (2012).
pubmed: 22782487 pmcid: 22782487 doi: 10.1093/jac/dks261
Carattoli, A. et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob. Agents Ch 58, 3895–3903 (2014).
doi: 10.1128/AAC.02412-14
Letunic, I. & Bork, P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 44, W242–W245 (2016).
pubmed: 27095192 pmcid: 4987883 doi: 10.1093/nar/gkw290
Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer, 2016).
Wickham, H. Reshaping data with the reshape package. J. Stat. Softw. 21, 1–20 (2007).
doi: 10.18637/jss.v021.i12
Rutherford, K. et al. Artemis: sequence visualization and annotation. Bioinformatics 16, 944–945 (2000).
pubmed: 11120685 doi: 10.1093/bioinformatics/16.10.944 pmcid: 11120685
Carver, T. J. et al. ACT: the Artemis comparison tool. Bioinformatics 21, 3422–3423 (2005).
pubmed: 15976072 doi: 10.1093/bioinformatics/bti553 pmcid: 15976072
Carver, T., Thomson, N., Bleasby, A., Berriman, M. & Parkhill, J. DNAPlotter: circular and linear interactive genome visualization. Bioinformatics 25, 119–120 (2009).
pubmed: 18990721 doi: 10.1093/bioinformatics/btn578 pmcid: 18990721
Hadfield, J. et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics 34, 292–293 (2018).
pubmed: 29028899 doi: 10.1093/bioinformatics/btx610 pmcid: 29028899
Sullivan, M. J., Petty, N. K. & Beatson, S. A. Easyfig: a genome comparison visualizer. Bioinformatics 27, 1009–1010 (2011).
pubmed: 21278367 pmcid: 21278367 doi: 10.1093/bioinformatics/btr039
Argimón, S. et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microbial. Genom. 2, e000093 (2016).
Pan American Health Organization. Impact of hurricane Mitch on Central America. Epidemiol. Bull. 19, 1–13 (1998).

Auteurs

Matthew J Dorman (MJ)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.

Daryl Domman (D)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
Department of Internal Medicine, Center for Global Health, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Tomás Poklepovich (T)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.

Charlotte Tolley (C)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.

Gisella Zolezzi (G)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.

Leanne Kane (L)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK.

María Rosa Viñas (MR)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.

Marcela Panagópulo (M)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.

Miriam Moroni (M)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.

Norma Binsztein (N)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.

María Inés Caffer (MI)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina.

Simon Clare (S)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.

Gordon Dougan (G)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QW, UK.

George P C Salmond (GPC)

Department of Biochemistry, University of Cambridge, Cambridge, CB2 1QW, UK.

Julian Parkhill (J)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK.
Department of Veterinary Medicine, University of Cambridge, Cambridge, CB3 0ES, UK.

Josefina Campos (J)

Instituto Nacional de Enfermedades Infecciosas, INEI-ANLIS "Dr. Carlos G. Malbrán", Buenos Aires, Argentina. jcampos@anlis.gov.ar.

Nicholas R Thomson (NR)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, CB10 1SA, UK. nrt@sanger.ac.uk.
London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. nrt@sanger.ac.uk.

Articles similaires

Genome, Chloroplast Phylogeny Genetic Markers Base Composition High-Throughput Nucleotide Sequencing

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C

Classifications MeSH