1887

Abstract

Ovine and caprine brucellosis, caused by , is one of the world’s most widespread zoonoses and is a major cause of economic losses in domestic ruminant production. In Italy, the disease remains endemic in several southern provinces, despite an ongoing brucellosis eradication programme. In this study, we used whole-genome sequencing to detail the genetic diversity of circulating strains, and to examine the origins of the predominant sub-lineages of in Italy. We reconstructed a global phylogeny of , strengthened by 339 new whole-genome sequences, from Italian isolates collected from 2011 to 2018 as part of a national livestock surveillance programme. All Italian strains belonged to the West Mediterranean lineage, which further divided into two major clades that diverged roughly between the 5th and 7th centuries. We observed that Sicily serves as a brucellosis burden hotspot, giving rise to several distinct sub-lineages. More than 20 putative outbreak clusters of ovine and caprine brucellosis were identified, several of which persisted over the 8 year survey period despite an aggressive brucellosis eradication campaign. While the outbreaks in Central and Northern Italy were generally associated with introductions of single clones of and their subsequent dissemination within neighbouring territories, we observed weak geographical segregation of genotypes in the southern regions. Biovar determination, recommended in routine analysis of all strains by the World Organisation for Animal Health (OIE), could not discriminate among the four main global clades. This demonstrates a need for updating the guidelines used for monitoring transmission and spread, both at the national and international level, and to include whole-genome-based typing as the principal method for identification and tracing of brucellosis outbreaks.

Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000446
2020-10-08
2020-10-20
Loading full text...

Full text loading...

/deliver/fulltext/mgen/10.1099/mgen.0.000446/mgen000446.html?itemId=/content/journal/mgen/10.1099/mgen.0.000446&mimeType=html&fmt=ahah

References

  1. Spink WW, Hall JW, Finstad J, Mallet E. Immunization with viable Brucella organisms. Results of a safety test in humans. Bull World Health Organ 1962; 26:409–419[PubMed]
    [Google Scholar]
  2. Whatmore AM. Current understanding of the genetic diversity of Brucella, an expanding genus of zoonotic pathogens. Infect Genet Evol 2009; 9:1168–1184 [CrossRef][PubMed]
    [Google Scholar]
  3. Corbel MJ. Brucellosis: an overview. Emerg Infect Dis 1997; 3:213–221 [CrossRef][PubMed]
    [Google Scholar]
  4. World Organisation for Animal Health Brucellosis (Brucella abortus, B. melitensis and B. suis) (infection with B. abortus, B. melitensis and B. suis). Manual of Diagnostic Tests and Vaccines for Terrestrial Animals Paris: World Organisation for Animal Health; 2016
    [Google Scholar]
  5. Refai M. Incidence and control of brucellosis in the Near East region. Vet Microbiol 2002; 90:81–110 [CrossRef][PubMed]
    [Google Scholar]
  6. Di Giannatale E, De Massis F, Ancora M, Zilli K, Alessiani A. Typing of Brucella field strains isolated from livestock populations in Italy between 2001 and 2006. Vet Ital 2008; 44:383–388[PubMed]
    [Google Scholar]
  7. Godfroid J, Al Dahouk S, Pappas G, Roth F, Matope G et al. A "one health" surveillance and control of brucellosis in developing countries: moving away from improvisation. Comp Immunol Microbiol Infect Dis 2013; 36:241–248 [CrossRef][PubMed]
    [Google Scholar]
  8. McDermott J, Grace D, Zinsstag J. Economics of brucellosis impact and control in low-income countries. Rev Sci Tech 2013; 32:249–261 [CrossRef][PubMed]
    [Google Scholar]
  9. Zhang N, Huang D, Wu W, Liu J, Liang F et al. Animal brucellosis control or eradication programs worldwide: a systematic review of experiences and lessons learned. Prev Vet Med 2018; 160:105–115 [CrossRef][PubMed]
    [Google Scholar]
  10. Franco MP, Mulder M, Gilman RH, Smits HL. Human brucellosis. Lancet Infect Dis 2007; 7:775–786 [CrossRef][PubMed]
    [Google Scholar]
  11. Dean AS, Crump L, Greter H, Schelling E, Zinsstag J. Global burden of human brucellosis: a systematic review of disease frequency. PLoS Negl Trop Dis 2012; 6:e1865 [CrossRef][PubMed]
    [Google Scholar]
  12. Zheng R, Xie S, Lu X, Sun L, Zhou Y et al. A systematic review and meta-analysis of epidemiology and clinical manifestations of human brucellosis in China. Biomed Res Int 2018; 2018:5712920 [CrossRef][PubMed]
    [Google Scholar]
  13. Lv F-H, Peng W-F, Yang J, Zhao Y-X, Li W-R et al. Mitogenomic meta-analysis identifies two phases of migration in the history of eastern Eurasian sheep. Mol Biol Evol 2015; 32:2515–2533 [CrossRef][PubMed]
    [Google Scholar]
  14. Pereira F, Amorim A. Origin and spread of goat pastoralism. Encyclopedia of Life Sciences Chichester: Wiley; 2010
    [Google Scholar]
  15. Moreno E. Retrospective and prospective perspectives on zoonotic brucellosis. Front Microbiol 2014; 5:213 [CrossRef][PubMed]
    [Google Scholar]
  16. Pisarenko SV, Kovalev DA, Volynkina AS, Ponomarenko DG, Rusanova DV et al. Global evolution and phylogeography of Brucella melitensis strains. BMC Genomics 2018; 19:353 [CrossRef][PubMed]
    [Google Scholar]
  17. Al Dahouk S, Flèche PL, Nöckler K, Jacques I, Grayon M et al. Evaluation of Brucella MLVA typing for human brucellosis. J Microbiol Methods 2007; 69:137–145 [CrossRef][PubMed]
    [Google Scholar]
  18. Whatmore AM, Koylass MS, Muchowski J, Edwards-Smallbone J, Gopaul KK et al. Extended multilocus sequence analysis to describe the global population structure of the genus Brucella: phylogeography and relationship to biovars. Front Microbiol 2016; 7:2049 [CrossRef][PubMed]
    [Google Scholar]
  19. Garofolo G, Ancora M, Di Giannatale E. MLVA-16 loci panel on Brucella spp. using multiplex PCR and multicolor capillary electrophoresis. J Microbiol Methods 2013; 92:103–107 [CrossRef][PubMed]
    [Google Scholar]
  20. Lounes N, Cherfa MA, Le Carrou G, Bouyoucef A, Jay M et al. Human brucellosis in Maghreb: existence of a lineage related to socio-historical connections with Europe. PLoS One 2014; 9:e115319 [CrossRef][PubMed]
    [Google Scholar]
  21. Foster JT, Walker FM, Rannals BD, Hussain MH, Drees KP et al. African lineage Brucella melitensis isolates from Omani livestock.. Front Microbiol 2018; 8:2702 [CrossRef][PubMed]
    [Google Scholar]
  22. Pappas G, Papadimitriou P, Akritidis N, Christou L, Tsianos EV. The new global map of human brucellosis. Lancet Infect Dis 2006; 6:91–99 [CrossRef][PubMed]
    [Google Scholar]
  23. Rossetti CA, Arenas-Gamboa AM, Maurizio E. Caprine brucellosis: a historically neglected disease with significant impact on public health. PLoS Negl Trop Dis 2017; 11:e0005692 [CrossRef][PubMed]
    [Google Scholar]
  24. Musallam II, Abo-Shehada MN, Hegazy YM, Holt HR, Guitian FJ. Systematic review of brucellosis in the middle East: disease frequency in ruminants and humans and risk factors for human infection. Epidemiol Infect 2016; 144:671–685 [CrossRef][PubMed]
    [Google Scholar]
  25. European Food Safety Authority and European Centre for Disease Prevention and Control (EFSA and ECDC) The European Union summary report on trends and sources of zoonoses, zoonotic agents and food-borne outbreaks in 2017. EFSA J 2018; 16:e05500 [CrossRef][PubMed]
    [Google Scholar]
  26. Corbel MJ. Brucellosis in Humans and Animals Geneva: World Health Organization; 2006
    [Google Scholar]
  27. Dadar M, Shahali Y, Whatmore AM. Human brucellosis caused by raw dairy products: a review on the occurrence, major risk factors and prevention. Int J Food Microbiol 2019; 292:39–47 [CrossRef][PubMed]
    [Google Scholar]
  28. De Massis F, Di Girolamo A, Petrini A, Pizzigallo E, Giovannini A. Correlation between animal and human brucellosis in Italy during the period 1997-2002. Clin Microbiol Infect 2005; 11:632–636 [CrossRef][PubMed]
    [Google Scholar]
  29. Godfroid J. Brucellosis in livestock and wildlife: zoonotic diseases without pandemic potential in need of innovative one health approaches. Arch Public Health 2017; 75:34 [CrossRef][PubMed]
    [Google Scholar]
  30. European Comission 93/52/EEC: Commission decision of 21 December 1992 recording the compliance by certain member states or regions with the requirements relating to brucellosis (B. melitensis) and according them the status of a member state or region officially free of the disease. P. 14–15 ( https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A31993D0052) 1992
    [Google Scholar]
  31. De Massis F, Petrini A, Giovannini A. Reliability evaluation of sampling plan fixed by Council Directive 91/68/EEC for the maintenance of officially brucellosis-free flock status. J Vet Med B Infect Dis Vet Public Health 2005; 52:284–290 [CrossRef][PubMed]
    [Google Scholar]
  32. Graziani C, Mancini FR, Adone R, Maranelli C, Pasquali P et al. La brucellosi in Italia dal 1998 al 2011. Istituto Superiore di Sanit, Roma; 2013; Rapporti ISTISAN 13/45
  33. [Google Scholar]
  34. De Massis F, Zilli K, Di Donato G, Nuvoloni R, Pelini S et al. Distribution of Brucella field strains isolated from livestock, wildlife populations, and humans in Italy from 2007 to 2015. PLoS One 2019; 14:e0213689 [CrossRef][PubMed]
    [Google Scholar]
  35. [Google Scholar]
  36. Facciolà A, Palamara MAR, D'Andrea G, Marano F, Magliarditi D et al. Brucellosis is a public health problem in southern Italy: burden and epidemiological trend of human and animal disease. J Infect Public Health 2018; 11:861-866 [CrossRef][PubMed]
    [Google Scholar]
  37. Janowicz A, De Massis F, Ancora M, Cammà C, Patavino C et al. Core genome multilocus sequence typing and single nucleotide polymorphism analysis in the epidemiology of Brucella melitensis infections. J Clin Microbiol 2018; 56:e00517-18 [CrossRef][PubMed]
    [Google Scholar]
  38. Sacchini L, Wahab T, Di Giannatale E, Zilli K, Abass A et al. Whole genome sequencing for tracing geographical origin of imported cases of human brucellosis in Sweden. Microorganisms 2019; 7:398 [CrossRef][PubMed]
    [Google Scholar]
  39. Andrews S. FastQC Babraham Bioinformatics, UK; 2010 https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
  40. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [CrossRef][PubMed]
    [Google Scholar]
  41. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [CrossRef][PubMed]
    [Google Scholar]
  42. Whatmore AM, Perrett LL, MacMillan AP. Characterisation of the genetic diversity of Brucella by multilocus sequencing. BMC Microbiol 2007; 7:34 [CrossRef][PubMed]
    [Google Scholar]
  43. Sahl JW, Beckstrom-Sternberg SM, Babic-Sternberg JS, Gillece JD, Hepp CM et al. The In Silico Genotyper (ISG): an open-source pipeline to rapidly identify and annotate nucleotide variants for comparative genomics applications. bioRxiv 2015015578
    [Google Scholar]
  44. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [CrossRef][PubMed]
    [Google Scholar]
  45. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K et al. The genome analysis toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010; 20:1297–1303 [CrossRef][PubMed]
    [Google Scholar]
  46. Kozlov AM, Darriba D, Flouri T, Morel B, Stamatakis A et al. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 2019; 35:4453–4455 [CrossRef][PubMed]
    [Google Scholar]
  47. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v4: recent updates and new developments. Nucleic Acids Res 2019; 47:W256–W259 [CrossRef][PubMed]
    [Google Scholar]
  48. Cheng L, Connor TR, Sirén J, Aanensen DM, Corander J. Hierarchical and spatially explicit clustering of DNA sequences with BAPS software. Mol Biol Evol 2013; 30:1224–1228 [CrossRef][PubMed]
    [Google Scholar]
  49. 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 [CrossRef][PubMed]
    [Google Scholar]
  50. 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 [CrossRef][PubMed]
    [Google Scholar]
  51. Bouckaert RR, Drummond AJ. bModelTest: Bayesian phylogenetic site model averaging and model comparison. BMC Evol Biol 2017; 17:42 [CrossRef][PubMed]
    [Google Scholar]
  52. Al Dahouk S, Neubauer H, Hensel A, Schöneberg I, Nöckler K et al. Changing epidemiology of human brucellosis, Germany, 1962-2005. Emerg Infect Dis 2007; 13:1895–1900 [CrossRef][PubMed]
    [Google Scholar]
  53. Georgi E, Walter MC, Pfalzgraf M-T, Northoff BH, Holdt LM et al. Whole genome sequencing of Brucella melitensis isolated from 57 patients in Germany reveals high diversity in strains from Middle East. PLoS One 2017; 12:e0175425 [CrossRef][PubMed]
    [Google Scholar]
  54. European Centre for Disease Prevention and Control Surveillance atlas of infectious diseases ( https://atlas.ecdc.europa.eu/public/index.aspx) [accessed 7 September 2019] 2019
    [Google Scholar]
  55. Tan K-K, Tan Y-C, Chang L-Y, Lee KW, Nore SS et al. Full genome SNP-based phylogenetic analysis reveals the origin and global spread of Brucella melitensis. BMC Genomics 2015; 16:93 [CrossRef][PubMed]
    [Google Scholar]
  56. Cañón J, García D, García-Atance MA, Obexer-Ruff G, Lenstra JA et al. Geographical partitioning of goat diversity in Europe and the Middle East. Anim Genet 2006; 37:327–334 [CrossRef][PubMed]
    [Google Scholar]
  57. Groeneveld LF, Lenstra JA, Eding H, Toro MA, Scherf B et al. Genetic diversity in farm animals - a review. Anim Genet 2010; 41 (Suppl. 1):6–31 [CrossRef][PubMed]
    [Google Scholar]
  58. Alberto FJ, Boyer F, Orozco-terWengel P, Streeter I, Servin B et al. Convergent genomic signatures of domestication in sheep and goats. Nat Commun 2018; 9:813 [CrossRef][PubMed]
    [Google Scholar]
  59. Lenstra JA. Econogene Consortium Evolutionary and demographic history of sheep and goats suggested by nuclear, mtDNA and Y-chromosome markers. Proceedings of the International Workshop – The Role of Biotechnology for the Characterization of Crop, Forestry, Animal and Fishery Genetic Resources,Turin, Italy, 57 March 2005
    [Google Scholar]
  60. Capasso L. Bacteria in two-millennia-old cheese, and related epizoonoses in Roman populations. J Infect 2002; 45:122–127 [CrossRef][PubMed]
    [Google Scholar]
  61. Kay GL, Sergeant MJ, Giuffra V, Bandiera P, Milanese M et al. Recovery of a medieval Brucella melitensis genome using shotgun metagenomics. mBio 2014; 5:e01337-14 [CrossRef][PubMed]
    [Google Scholar]
  62. Matteo S, Bellucci S. Africa Italia: Due Continenti si Avvicinano Santarcangelo di Romagna: Fara Editore; 1999
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000446
Loading
/content/journal/mgen/10.1099/mgen.0.000446
Loading

Data & Media loading...

Supplements

Supplementary material 1

EXCEL
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