1887
  1. Home
  2. Eurosurveillance
  3. Volume 23, Issue 45, 08/Nov/2018
  4. Article
Research article Open Access
Like 0
Download

Abstract

Background

The gene is a transferable resistance determinant against colistin, a last-resort antimicrobial for infections caused by multi-resistant Gram-negatives.

Aim

To study carriage of antibiotic-resistant bacteria in healthy school children as part of a helminth control and antimicrobial resistance survey in the Bolivian Chaco region.

Methods

From September to October 2016 we collected faecal samples from healthy children in eight rural villages. Samples were screened for - and genes. Antimicrobial susceptibility testing was performed, and a subset of 18 isolates representative of individuals from different villages was analysed by whole genome sequencing (WGS).

Results

We included 337 children (mean age: 9.2 years, range: 7–11; 53% females). The proportion of carriers was high (38.3%) and present in all villages; only four children had previous antibiotic exposure. One or more -positive isolates were recovered from 129 positive samples, yielding a total of 173 isolates (171 , 1 , 1 ). No was detected. Co-resistance to other antimicrobials varied in -positive . All 171 isolates were susceptible to carbapenems and tigecycline; 41 (24.0%) were extended-spectrum β-lactamase producers and most of them (37/41) carried -type genes. WGS revealed heterogeneity of clonal lineages and -genetic supports.

Conclusion

This high prevalence of -like carriage, in absence of professional exposure, is unexpected. Its extent at the national level should be investigated with priority. Possible causes should be studied; they may include unrestricted use of colistin in veterinary medicine and animal breeding, and importation of -positive bacteria via food and animals.

© Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Loading

Article metrics loading...

/content/10.2807/1560-7917.ES.2018.23.45.1800115
2018-11-08
2024-11-05
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2018.23.45.1800115
Loading
Loading full text...

Full text loading...

/deliver/fulltext/eurosurveillance/23/45/eurosurv-23-45-4.html?itemId=/content/10.2807/1560-7917.ES.2018.23.45.1800115&mimeType=html&fmt=ahah

References

  1. Poirel L, Jayol A, Nordmann P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin Microbiol Rev. 2017;30(2):557-96.  https://doi.org/10.1128/CMR.00064-16  PMID: 28275006 
  2. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161-8.  https://doi.org/10.1016/S1473-3099(15)00424-7  PMID: 26603172 
  3. Giamarellou H. Epidemiology of infections caused by polymyxin-resistant pathogens. Int J Antimicrob Agents. 2016;48(6):614-21.  https://doi.org/10.1016/j.ijantimicag.2016.09.025  PMID: 27865627 
  4. Schwarz S, Johnson AP. Transferable resistance to colistin: a new but old threat. J Antimicrob Chemother. 2016;71(8):2066-70.  https://doi.org/10.1093/jac/dkw274  PMID: 27342545 
  5. Shen Z, Wang Y, Shen Y, Shen J, Wu C. Early emergence of mcr-1 in Escherichia coli from food-producing animals. Lancet Infect Dis. 2016;16(3):293.  https://doi.org/10.1016/S1473-3099(16)00061-X  PMID: 26973308 
  6. Rebelo AR, Bortolaia V, Kjeldgaard JS, Pedersen SK, Leekitcharoenphon P, Hansen IM, et al. Multiplex PCR for detection of plasmid-mediated colistin resistance determinants, mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 for surveillance purposes. Euro Surveill. 2018;23(6):17-00672.  https://doi.org/10.2807/1560-7917.ES.2018.23.6.17-00672  PMID: 29439754 
  7. Xavier BB, Lammens C, Ruhal R, Kumar-Singh S, Butaye P, Goossens H, et al. Identification of a novel plasmid-mediated colistin-resistance gene, mcr-2, in Escherichia coli, Belgium, June 2016. Euro Surveill. 2016;21(27):30280.  https://doi.org/10.2807/1560-7917.ES.2016.21.27.30280  PMID: 27416987 
  8. Yin W, Li H, Shen Y, Liu Z, Wang S, Shen Z, et al. Novel plasmid-mediated colistin resistance gene mcr-3 in Escherichia coli. MBio. 2017;8(4):e01166-17.  https://doi.org/10.1128/mBio.01166-17  PMID: 28811346 
  9. Carattoli A, Villa L, Feudi C, Curcio L, Orsini S, Luppi A, et al. Novel plasmid-mediated colistin resistance mcr-4 gene in Salmonella and Escherichia coli, Italy 2013, Spain and Belgium, 2015 to 2016. Euro Surveill. 2017;22(31):30589.  https://doi.org/10.2807/1560-7917.ES.2017.22.31.30589  PMID: 28797329 
  10. Borowiak M, Fischer J, Hammerl JA, Hendriksen RS, Szabo I, Malorny B. Identification of a novel transposon-associated phosphoethanolamine transferase gene, mcr-5, conferring colistin resistance in d-tartrate fermenting Salmonella enterica subsp. enterica serovar Paratyphi B. J Antimicrob Chemother. 2017;72(12):3317-24.  https://doi.org/10.1093/jac/dkx327  PMID: 28962028 
  11. AbuOun M, Stubberfield EJ, Duggett NA, Kirchner M, Dormer L, Nunez-Garcia J, et al. mcr-1 and mcr-2 variant genes identified in Moraxella species isolated from pigs in Great Britain from 2014 to 2015. J Antimicrob Chemother. 2017;72(10):2745-9.  https://doi.org/10.1093/jac/dkx286  PMID: 29091227 
  12. Yang YQ, Li YX, Lei CW, Zhang AY, Wang HN. Novel plasmid-mediated colistin resistance gene mcr-7.1 in Klebsiella pneumoniae. J Antimicrob Chemother. 2018;73(7):1791-5.  https://doi.org/10.1093/jac/dky111  PMID: 29912417 
  13. Wang X, Wang Y, Zhou Y, Li J, Yin W, Wang S, et al. Emergence of a novel mobile colistin resistance gene, mcr-8, in NDM-producing Klebsiella pneumoniae. Emerg Microbes Infect. 2018;7(1):122.  https://doi.org/10.1038/s41426-018-0124-z  PMID: 29970891 
  14. Pan American Health Organization (PAHO)/World Health Organization (WHO). Epidemiological Alert: Enterobacteriaceae with plasmid-mediated transferable colistin resistance, public health implications in the Americas, 10 June 2016. Washington, D.C./Geneva: PAHO/WHO; 2016. Available from: http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=270&gid=35007&lang=en
  15. Fernandes MR, Moura Q, Sartori L, Silva KC, Cunha MP, Esposito F, et al. Silent dissemination of colistin-resistant Escherichia coli in South America could contribute to the global spread of the mcr-1 gene. Euro Surveill. 2016;21(17):30214.  https://doi.org/10.2807/1560-7917.ES.2016.21.17.30214  PMID: 27168587 
  16. Rapoport M, Faccone D, Pasteran F, Ceriana P, Albornoz E, Petroni A, et al. MCR Group. First description of mcr-1-mediated colistin resistance in human infections caused by Escherichia coli in Latin America. Antimicrob Agents Chemother. 2016;60(7):4412-3.  https://doi.org/10.1128/AAC.00573-16  PMID: 27090181 
  17. Delgado-Blas JF, Ovejero CM, Abadia-Patiño L, Gonzalez-Zorn B. Coexistence of mcr-1 and blaNDM-1 in Escherichia coli from Venezuela. Antimicrob Agents Chemother. 2016;60(10):6356-8.  https://doi.org/10.1128/AAC.01319-16  PMID: 27431212 
  18. Dalmolin TV, Martins AF, Zavascki AP, de Lima-Morales D, Barth AL. Acquisition of the mcr-1 gene by a high-risk clone of KPC-2-producing Klebsiella pneumoniae ST437/CC258, Brazil. Diagn Microbiol Infect Dis. 2018;90(2):132-3.  https://doi.org/10.1016/j.diagmicrobio.2017.09.016  PMID: 29169659 
  19. Saavedra SY, Diaz L, Wiesner M, Correa A, Arévalo SA, Reyes J, et al. Genomic and Molecular characterization of clinical isolates of Enterobacteriaceae harboring mcr-1 in Colombia, 2002 to 2016. Antimicrob Agents Chemother. 2017;61(12):e008441-17.  https://doi.org/10.1128/AAC.00841-17  PMID: 28893788 
  20. Ortega-Paredes D, Barba P, Zurita J. Colistin-resistant Escherichia coli clinical isolate harbouring the mcr-1 gene in Ecuador. Epidemiol Infect. 2016;144(14):2967-70.  https://doi.org/10.1017/S0950268816001369  PMID: 27586373 
  21. Sennati S, Di Pilato V, Riccobono E, Di Maggio T, Villagran AL, Pallecchi L, et al. Citrobacter braakii carrying plasmid-borne mcr-1 colistin resistance gene from ready-to-eat food from a market in the Chaco region of Bolivia. J Antimicrob Chemother. 2017;72(7):2127-9.  https://doi.org/10.1093/jac/dkx078  PMID: 28333311 
  22. Monte DF, Mem A, Fernandes MR, Cerdeira L, Esposito F, Galvão JA, et al. Chicken meat as a reservoir of colistin-resistant Escherichia coli strains carrying mcr-1 genes in South America. Antimicrob Agents Chemother. 2017;61(5):e02718-16.  https://doi.org/10.1128/AAC.02718-16  PMID: 28193665 
  23. Tijet N, Faccone D, Rapoport M, Seah C, Pasterán F, Ceriana P, et al. Molecular characteristics of mcr-1-carrying plasmids and new mcr-1 variant recovered from polyclonal clinical Escherichia coli from Argentina and Canada. PLoS One. 2017;12(7):e0180347.  https://doi.org/10.1371/journal.pone.0180347  PMID: 28678874 
  24. Fernandes MR, Sellera FP, Esposito F, Sabino CP, Cerdeira L, Lincopan N. Colistin-resistant mcr-1-positive Escherichia coli on public beaches, an infectious threat emerging in recreational waters. Antimicrob Agents Chemother. 2017;61(7):e00234-17.  https://doi.org/10.1128/AAC.00234-17  PMID: 28416556 
  25. Aires CAM, da Conceição-Neto OC, Tavares E Oliveira TR, Dias CF, Montezzi LF, Picão RC, et al. Emergence of the plasmid-mediated mcr-1 gene in clinical KPC-2-producing Klebsiella pneumoniae Sequence Type 392 in Brazil. Antimicrob Agents Chemother. 2017;61(7):e00317-17.  https://doi.org/10.1128/AAC.00317-17  PMID: 28438940 
  26. Sellera FP, Fernandes MR, Sartori L, Carvalho MPN, Esposito F, Nascimento CL, et al. Escherichia coli carrying IncX4 plasmid-mediated mcr-1 and blaCTX-M genes in infected migratory Magellanic penguins (Spheniscus magellanicus). J Antimicrob Chemother. 2017;72(4):1255-6. PMID: 28031274 
  27. Rossi F, Girardello R, Morais C, Cury AP, Martins LF, da Silva AM, et al. Plasmid-mediated mcr-1 in carbapenem-susceptible Escherichia coli ST156 causing a blood infection: an unnoticeable spread of colistin resistance in Brazil? Clinics (Sao Paulo). 2017;72(10):642-4.  https://doi.org/10.6061/clinics/2017(10)09  PMID: 29160428 
  28. Bartoloni A, Cutts F, Leoni S, Austin CC, Mantella A, Guglielmetti P, et al. Patterns of antimicrobial use and antimicrobial resistance among healthy children in Bolivia. Trop Med Int Health. 1998;3(2):116-23.  https://doi.org/10.1046/j.1365-3156.1998.00201.x  PMID: 9537273 
  29. Bartoloni A, Pallecchi L, Riccobono E, Mantella A, Magnelli D, Di Maggio T, et al. Relentless increase of resistance to fluoroquinolones and expanded-spectrum cephalosporins in Escherichia coli: 20 years of surveillance in resource-limited settings from Latin America. Clin Microbiol Infect. 2013;19(4):356-61.  https://doi.org/10.1111/j.1469-0691.2012.03807.x  PMID: 22414066 
  30. Bartoloni A, Sennati S, Di Maggio T, Mantella A, Riccobono E, Strohmeyer M, et al. Antimicrobial susceptibility and emerging resistance determinants (blaCTX-M, rmtB, fosA3) in clinical isolates from urinary tract infections in the Bolivian Chaco. Int J Infect Dis. 2016;43:1-6.  https://doi.org/10.1016/j.ijid.2015.12.008  PMID: 26686940 
  31. Bartoloni A, Riccobono E, Magnelli D, Villagran AL, Di Maggio T, Mantella A, et al. Methicillin-resistant Staphylococcus aureus in hospitalized patients from the Bolivian Chaco. Int J Infect Dis. 2015;30:156-60.  https://doi.org/10.1016/j.ijid.2014.12.006  PMID: 25486009 
  32. Pallecchi L, Malossi M, Mantella A, Gotuzzo E, Trigoso C, Bartoloni A, et al. Detection of CTX-M-type beta-lactamase genes in fecal Escherichia coli isolates from healthy children in Bolivia and Peru. Antimicrob Agents Chemother. 2004;48(12):4556-61.  https://doi.org/10.1128/AAC.48.12.4556-4561.2004  PMID: 15561825 
  33. World Health Organization (WHO)/Department of control of neglected tropical diseases. Helminth control in school-aged children, a guide for managers of control programs. Geneva: WHO; 2012. Available from:http://www.who.int/neglected_diseases/resources/9789241548267/en/
  34. Coppi M, Cannatelli A, Antonelli A, Baccani I, Di Pilato V, Sennati S, et al. A simple phenotypic method for screening of MCR-1-mediated colistin resistance. Clin Microbiol Infect. 2018;24(2):S1198-743X(17)30457-3.
  35. Pacheco AB, Guth BE, Soares KC, Nishimura L, de Almeida DF, Ferreira LC. Random amplification of polymorphic DNA reveals serotype-specific clonal clusters among enterotoxigenic Escherichia coli strains isolated from humans. J Clin Microbiol. 1997;35(6):1521-5. PMID: 9163473 
  36. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICs and zone diameters. Version 8.0. Växjö: EUCAST; 1 Jan 2018. Available from:http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_8.0_Breakpoint_Tables.pdf
  37. European Committee on Antimicrobial Susceptibility Testing (EUCAST). EUCAST guideline for the detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance. Version 2.0. Växjö: EUCAST; July 2016. Available from:http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Resistance_mechanisms/EUCAST_detection_of_resistance_mechanisms_170711.pdf
  38. Giani T, Antonelli A, Caltagirone M, Mauri C, Nicchi J, Arena F, et al. Evolving beta-lactamase epidemiology in Enterobacteriaceae from Italian nationwide surveillance, October 2013: KPC-carbapenemase spreading among outpatients. Euro Surveill. 2017;22(31):30583.  https://doi.org/10.2807/1560-7917.ES.2017.22.31.30583  PMID: 28797330 
  39. Ribeiro TG, Novais Â, Branquinho R, Machado E, Peixe L. Phylogeny and comparative genomics unveil independent diversification trajectories of qnrB and genetic platforms within particular Citrobacter species. Antimicrob Agents Chemother. 2015;59(10):5951-8.  https://doi.org/10.1128/AAC.00027-15  PMID: 26169406 
  40. Chavda KD, Chen L, Fouts DE, Sutton G, Brinkac L, Jenkins SG, et al. Comprehensive genome analysis of carbapenemase-producing Enterobacter spp.: new insights into phylogeny, population structure, and resistance mechanisms. MBio. 2016;7(6):e02093-16.  https://doi.org/10.1128/mBio.02093-16  PMID: 27965456 
  41. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. Cold Spring Harbor, NY: Cold Spring Harbor Press; 1989.
  42. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M, Kulikov AS, et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol. 2012;19(5):455-77.  https://doi.org/10.1089/cmb.2012.0021  PMID: 22506599 
  43. Bi Z, Berglund B, Sun Q, Nilsson M, Chen B, Tärnberg M, et al. Prevalence of the mcr-1 colistin resistance gene in extended-spectrum β-lactamase-producing Escherichia coli from human faecal samples collected in 2012 in rural villages in Shandong Province, China. Int J Antimicrob Agents. 2017;49(4):493-7.  https://doi.org/10.1016/j.ijantimicag.2016.12.018  PMID: 28263896 
  44. Purohit MR, Chandran S, Shah H, Diwan V, Tamhankar AJ, Stålsby Lundborg C. Antibiotic resistance in an Indian rural community: a ‘One-Health’ observational study on commensal coliform from humans, animals, and water. Int J Environ Res Public Health. 2017;14(4):386-13.  https://doi.org/10.3390/ijerph14040386  PMID: 28383517 
  45. Trung NV, Matamoros S, Carrique-Mas JJ, Nghia NH, Nhung NT, Chieu TTB, et al. Zoonotic transmission of mcr-1 colistin resistance gene from small-scale poultry farms, Vietnam. Emerg Infect Dis. 2017;23(3):529-32.  https://doi.org/10.3201/eid2303.161553  PMID: 28221105 
  46. Zhong LL, Zhang YF, Doi Y, Huang X, Zhang XF, Zeng KJ, et al. Co-production of MCR-1 and NDM-1 by colistin-resistant Escherichia coli isolated from a healthy individual. Antimicrob Agents Chemother. 2016;61(1):6. PMID: 27821458 
  47. Zurfluh K, Stephan R, Widmer A, Poirel L, Nordmann P, Nüesch HJ, et al. Screening for fecal carriage of MCR-producing Enterobacteriaceae in healthy humans and primary care patients. Antimicrob Resist Infect Control. 2017;6(28):28.  https://doi.org/10.1186/s13756-017-0186-z  PMID: 28316780 
  48. Lu X, Hu Y, Luo M, Zhou H, Wang X, Du Y, et al. MCR-1.6, a New MCR variant carried by an IncP plasmid in a colistin-resistant Salmonella enterica Serovar Typhimurium isolate from a healthy individual. Antimicrob Agents Chemother. 2017;61(5):e02632-16-13.
  49. Wang Y, Tian GB, Zhang R, Shen Y, Tyrrell JM, Huang X, et al. Prevalence, risk factors, outcomes, and molecular epidemiology of mcr-1-positive Enterobacteriaceae in patients and healthy adults from China: an epidemiological and clinical study. Lancet Infect Dis. 2017;17(4):390-9.  https://doi.org/10.1016/S1473-3099(16)30527-8  PMID: 28139431 
  50. Zhang X-F, Doi Y, Huang X, Li H-Y, Zhong L-L, Zeng K-J, et al. Possible transmission of mcr-1-harboring Escherichia coli between companion animals and human. Emerg Infect Dis. 2016;22(9):1679-81.  https://doi.org/10.3201/eid2209.160464  PMID: 27191649 
  51. Zhang R, Huang Y, Chan EW, Zhou H, Chen S, Zhang R, et al. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis. 2016;16(3):291-2.  https://doi.org/10.1016/S1473-3099(16)00062-1  PMID: 26973306 
  52. Chen K, Chan EW, Xie M, Ye L, Dong N, Chen S. Widespread distribution of mcr-1-bearing bacteria in the ecosystem, 2015 to 2016. Euro Surveill. 2017;22(39):17-00206.
  53. Gröndahl-Yli-Hannuksela K, Lönnqvist E, Kallonen T, Lindholm L, Jalava J, Rantakokko-Jalava K, et al. The first human report of mobile colistin resistance gene, mcr-1, in Finland. APMIS. 2018;126(5):413-7.  https://doi.org/10.1111/apm.12834  PMID: 29696722 
  54. Servicio Nacional de Sanidad Agropecuaria e Inocuidad Alimentaria (SENASAG). [National Service of Agricultural Health and Food Safety]. Registro de Productos de Uso Veterinario e Insumos Pecuarios. [Registration of Products for Veterinary Use and Livestock Supplies]. Bolivia: SENASAG; 2018. Spanish. Available from: http://190.129.48.189/egp/productosVeterinarios.html
High prevalence of carriage of mcr-1-positive enteric bacteria among healthy children from rural communities in the Chaco region, Bolivia, September to October 2016
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Tommaso+Giani&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Giani Tommaso</a>, <a href="/search?value1=Samanta+Sennati&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Sennati Samanta</a>, <a href="/search?value1=Alberto+Antonelli&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Antonelli Alberto</a>, <a href="/search?value1=Vincenzo+Di+Pilato&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Di Pilato Vincenzo</a>, <a href="/search?value1=Tiziana+di+Maggio&option1=author&noRedirect=true" class="nonDisambigAuthorLink">di Maggio Tiziana</a>, <a href="/search?value1=Antonia+Mantella&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Mantella Antonia</a>, <a href="/search?value1=Claudia+Niccolai&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Niccolai Claudia</a>, <a href="/search?value1=Michele+Spinicci&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Spinicci Michele</a>, <a href="/search?value1=Joaqu%C3%ADn+Monasterio&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Monasterio Joaquín</a>, <a href="/search?value1=Paul+Castellanos&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Castellanos Paul</a>, <a href="/search?value1=Mirtha+Martinez&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Martinez Mirtha</a>, <a href="/search?value1=Fausto+Contreras&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Contreras Fausto</a>, <a href="/search?value1=Dorian++Balderrama+Villaroel&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Balderrama Villaroel Dorian </a>, <a href="/search?value1=Esther+Damiani&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Damiani Esther</a>, <a href="/search?value1=Sdenka+Maury&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Maury Sdenka</a>, <a href="/search?value1=Rodolfo+Rocabado&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Rocabado Rodolfo</a>, <a href="/search?value1=Lucia+Pallecchi&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Pallecchi Lucia</a>, <a href="/search?value1=Alessandro+Bartoloni&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Bartoloni Alessandro</a>, <a href="/search?value1=Gian+Maria+Rossolini&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Rossolini Gian Maria</a></span>. High prevalence of carriage of mcr-1-positive enteric bacteria among healthy children from rural communities in the Chaco region, Bolivia, September to October 2016. <a href="/content/ecdc">Euro Surveill.</a> 2018;23(45):pii=1800115. <a href="https://doi.org/10.2807/1560-7917.ES.2018.23.45.1800115" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2018.23.45.1800115</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 12 Mar 2018;&nbsp;&nbsp; <span class="generated">Accepted</span>: 10 Jul 2018 </span> </p>
/content/10.2807/1560-7917.ES.2018.23.45.1800115
/content/10.2807/1560-7917.ES.2018.23.45.1800115
Loading

Data & Media loading...

Submit comment
Close
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error