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Ahead of Print -Evidence for Elizabethkingia anophelis Transmission from Mother to Infant, Hong Kong - Volume 21, Number 2—February 2015 - Emerging Infectious Disease journal - CDC

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Ahead of Print -Evidence for Elizabethkingia anophelis Transmission from Mother to Infant, Hong Kong - Volume 21, Number 2—February 2015 - Emerging Infectious Disease journal - CDC

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Volume 21, Number 2—February 2015


Evidence for Elizabethkingia anophelis Transmission from Mother to Infant, Hong Kong

Susanna K.P. Lau1, Alan K.L. Wu1, Jade L.L. Teng1, Herman Tse1, Shirly O.T. Curreem, Stephen K.W. Tsui, Yi Huang, Jonathan H.K. Chen, Rodney A. Lee, Kwok-Yung Yuen, and Patrick C.Y. WooComments to Author 
Author affiliations: The University of Hong Kong, Hong Kong (S.K.P. Lau, J.L.L. Teng, H. Tse, S.O.T. Curreem, Y. Huang, J.H.K. Chen, K.-Y. Yuen, P.C.Y. Woo)State Key Laboratory of Emerging Infectious Diseases, Research Centre of Infection and Immunology, Carol Yu Centre for Infection, Hong Kong (S.K.P. Lau, H. Tse, K.Y. Yuen, P.C.Y. Woo)Pamela Youde Nethersole Eastern Hospital, Hong Kong (A.K.L. Wu, R.A. Lee)School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (S.K.W. Tsui)


Elizabethkingia anophelis, recently discovered from mosquito gut, is an emerging bacterium associated with neonatal meningitis and nosocomial outbreaks. However, its transmission route remains unknown. We use rapid genome sequencing to investigate 3 cases of E. anophelis sepsis involving 2 neonates who had meningitis and 1 neonate’s mother who had chorioamnionitis. Comparative genomics revealed evidence for perinatal vertical transmission from a mother to her neonate; the 2 isolates from these patients, HKU37 and HKU38, shared essentially identical genome sequences. In contrast, the strain from another neonate (HKU36) was genetically divergent, showing only 78.6% genome sequence identity to HKU37 and HKU38, thus excluding a clonal outbreak. Comparison to genomes from mosquito strains revealed potential metabolic adaptations in E. anophelis under different environments. Maternal infection, not mosquitoes, is most likely the source of neonatal E. anophelis infections. Our findings highlight the power of genome sequencing in gaining rapid insights on transmission and pathogenesis of emerging pathogens.
Microbial genome sequencing can enhance diagnosis and control of infectious diseases (1,2). Its ultimate molecular resolution is superior to other phenotypic and genotypic tests and enables not only rapid microbial identification but also characterization of transmission events. The technique has been applied in large-scale infectious disease outbreaks such as those caused by Escherichia coli O104:H4, Staphylococcus aureus,Streptococcus pyogenesEnterococcus faeciumPseudomonas aeruginosaVibrio cholerae, and mycobacteria (314). However, the routine application of this method in diagnostic microbiology and infection control, especially for less well-defined, emerging pathogens, is yet to be explored.
Elizabethkingia anophelis is a recently discovered bacterium isolated from the midgut of the Anopheles gambiaemosquito in 2011 (15). The genus Elizabethkingia also includes E. meningoseptica (previously namedChryseobacterium/Flavobacterium meningosepticum) and E. miricola (16). E. meningoseptica causes neonatal sepsis and infections in immunocompromised persons. E. anophelis has also recently been reported to cause neonatal meningitis in the Central African Republic, and a nosocomial outbreak was reported in an intensive care unit in Singapore (1719). However, the role of mosquitoes or other sources in the transmission of E. anophelisremains unclear.
In 2012, we encountered 3 cases of Elizabethkingia sepsis associated with meningitis in 2 neonates and chorioamnionitis in a neonate’s mother in a hospital in Hong Kong. Three strains of Elizabethkingia-like, gram-negative bacilli sharing similar phenotypic characteristics were isolated from the 3 patients, but confident identification results were not obtained by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometry and 16S rRNA gene sequencing. Moreover, clinical and microbiological data did not provide adequate clues about the possible transmission route. We therefore attempted to use draft genome sequencing to rapidly dissect transmission pathways and confirm the identity of the species.
Thumbnail of Clinical course of illness in 3 patients infected with Elizabethkingia anophelis in whom sepsis developed and the mother of patient 1, who had culture-negative postpartum fever, Hong Kong, 2012. Locations where patients were treated at the hospital and times when they were home are noted.CSF, cerebrospinal fluid; leaking, leaking of amniotic fluid (membrane rupture).
Figure 1. Clinical course of illness in 3 patients infected with Elizabethkingia anophelisin whom sepsis developed and the mother of patient 1, who had culture-negative postpartum fever, Hong Kong, 2012. Locations where...
Dr. Lau is a clinical professor in the Department of Microbiology at The University of Hong Kong. Her research focuses on microbial genomics for studying emerging infectious diseases.


We thank Cheung-Hing Foo for technical support in bacterial identification and members of the Centre for Genomic Sciences, The University of Hong Kong, for their technical support in genome sequencing.
This work was supported by Health and Medical Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region; Strategic Research Theme Fund, Committee for Research and Conference Grant, and University Development Fund, The University of Hong Kong; the Shaw Foundation; donation from Ms. Eunice Lam; and Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease for the HKSAR Department of Health.


  1. Loman NJConstantinidou CChan JZHalachev MSergeant MPenn CWHigh-throughput bacterial genome sequencing: an embarrassment of choice, a world of opportunity. Nat Rev Microbiol2012;10:599606 . DOIPubMed
  2. Fournier PEDrancourt MRaoult DBacterial genome sequencing and its use in infectious diseases. Lancet Infect Dis2007;7:71123 .DOIPubMed
  3. Shah MAMutreja AThomson NBaker SParkhill JDougan GGenomic epidemiology of Vibrio cholerae O1 associated with floods, Pakistan, 2010.Emerg Infect Dis2014;20:1320 . DOIPubMed
  4. Snyder LALoman NJFaraj LALevi KWeinstock GBoswell TCEpidemiological investigation of Pseudomonas aeruginosa isolates from a six-year-long hospital outbreak using high-throughput whole genome sequencing. Euro Surveill2013;18:20611 .PubMed
  5. Harris SRCartwright EJTörök MEHolden MTBrown NMOgilvy-Stuart ALWhole-genome sequencing for analysis of an outbreak of methicillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infect Dis2013;13:1306 . DOIPubMed
  6. Walker TMIp CLHarrell RHEvans JTKapatai GDedicoat MJWhole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis2013;13:13746DOIPubMed
  7. Bryant JMGrogono DMGreaves DFoweraker JRoddick IInns TWhole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study. Lancet2013;381:155160DOIPubMed
  8. Tse HBao JYDavies MRMaamary PTsoi HWTong AHMolecular characterization of the 2011 Hong Kong scarlet fever outbreak. J Infect Dis.2012;206:34151DOIPubMed
  9. Brown CCOlsen RJFittipaldi NMorman MLFort PLNeuwirth RSpread of virulent group A Streptococcus type emm59 from Montana to Wyoming, USA. Emerg Infect Dis2014;20:67981 . DOIPubMed
  10. Köser CUHolden MTEllington MJCartwright EJBrown NMOgilvy-Stuart ALRapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N Engl J Med2012;366:226775 . DOIPubMed
  11. Loman NJConstantinidou CChristner MRohde HChan JZQuick JA culture-independent sequence-based metagenomics approach to the investigation of an outbreak of Shiga-toxigenic Escherichia coli O104:H4. JAMA2013;309:150210DOIPubMed
  12. Price JRGolubchik TCole KWilson DJCrook DWThwaites GEWhole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit. Clin Infect Dis2014;58:60918DOIPubMed
  13. Pérez-Lago LComas INavarro YGonzález-Candelas FHerranz MBouza EWhole genome sequencing analysis of intrapatient microevolution inMycobacterium tuberculosis: potential impact on the inference of tuberculosis transmission. J Infect Dis2014;209:98108 . DOIPubMed
  14. Johnson PDBallard SAGrabsch EAStinear TPSeemann TYoung HLA sustained hospital outbreak of vancomycin-resistant Enterococcus faecium bacteremia due to emergence of vanB E. faecium sequence type 203. J Infect Dis2010;202:127886 . DOIPubMed
  15. Kämpfer PMatthews HGlaeser SPMartin KLodders NFaye IElizabethkingia anophelis sp. nov., isolated from the midgut of the mosquitoAnopheles gambiae. Int J Syst Evol Microbiol2011;61:26705DOIPubMed
  16. Kim KKKim MKLim JHPark HYLee STTransfer of Chryseobacterium meningosepticum and Chryseobacterium miricola to Elizabethkingia gen. nov. as Elizabethkingia meningoseptica comb. nov. and Elizabethkingia miricola comb. nov. Int J Syst Evol Microbiol2005;55:128793.DOIPubMed
  17. Frank TGody JCNguyen LBBerthet NLe Fleche-Mateos ABata PFirst case of Elizabethkingia anophelis meningitis in the Central African Republic. Lancet2013;381:1876DOIPubMed
  18. Bobossi-Serengbe GGody JCBeyam NEBercion RFirst documented case of Chryseobacterium meningosepticum meningitis in Central African Republic. Med Trop (Mars)2006;66:1824 .PubMed
  19. Teo JTan SYTay MDing YKjelleberg SGivskov MFirst case of E anophelis outbreak in an intensive-care unit. Lancet2013;382:8556.DOIPubMed
  20. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disk susceptibility tests. Approved standard, 11th ed. M02–A11. Wayne (PA): The Institute; 2012.
  21. Lau SKTang BSCurreem SOChan TMMartelli PTse CWMatrix-assisted laser desorption ionization–time of flight mass spectrometry for rapid identification of Burkholderia pseudomallei: importance of expanding databases with pathogens endemic to different localities. J Clin Microbiol.2012;50:31423DOIPubMed
  22. Woo PCLau SKTeng JLQue TLYung RWLuk WKL Hongkongensis study group. Association of Laribacter hongkongensis in community-acquired gastroenteritis with travel and eating fish: a multicentre case-control study. Lancet2004;363:19417DOIPubMed
  23. Lau SKCurreem SOLin CCFung AMYuen KYWoo PCStreptococcus hongkongensis sp. nov., isolated from a patient with an infected puncture wound and from a marine flatfish. Int J Syst Evol Microbiol2013;63:25706DOIPubMed
  24. Tse HTsoi HWLeung SPLau SKWoo PCYuen KYComplete genome sequence of Staphylococcus lugdunensis strain HKU09–01. J Bacteriol.2010;192:14712DOIPubMed
  25. Woo PCLau SKTse HTeng JLCurreem SOTsang AKThe complete genome and proteome of Laribacter hongkongensis reveal potential mechanisms for adaptations to different temperatures and habitats. PLoS Genet2009;5:e1000416DOIPubMed
  26. Delcher ALBratke KAPowers ECSalzberg SLIdentifying bacterial genes and endosymbiont DNA with Glimmer. Bioinformatics2007;23:6739.DOIPubMed
  27. Aziz RKBartels DBest AADeJongh MDisz TEdwards RAThe RAST server: rapid annotations using subsystems technology. BMC Genomics.2008;9:75DOIPubMed
  28. Liu BPop MARDB—antibiotic resistance genes database. Nucleic Acids Res2009;37:D4437 . DOIPubMed
  29. Auch AFKlenk HPGöker MStandard operating procedure for calculating genome-to-genome distances based on high-scoring segment pairs.Stand Genomic Sci2010;2:1428DOIPubMed
  30. Dussurget O. New insights into determinants of Listeria monocytogenes virulence. Int Rev Cell Mol Biol. 2008;270:1–38.
  31. Kreft JVázquez-Boland JAAltrock SDominguez-Bernal GGoebel WPathogenicity islands and other virulence elements in Listeria. Curr Top Microbiol Immunol2002;264:10925 .PubMed
  32. Hoffman JABadger JLZhang YHuang SHKim KSEscherichia coli K1 aslA contributes to invasion of brain microvascular endothelial cells in vitro and in vivo. Infect Immun2000;68:50627DOIPubMed
  33. Cheng CChen JFang CXia YShan YLiu YListeria monocytogenes aguA1, but not aguA2, encodes a functional agmatine deiminase: biochemical characterization of its catalytic properties and roles in acid tolerance. J Biol Chem2013;288:2660615DOIPubMed
  34. Matyi SAHoyt PRHosoyama AYamazoe AFujita NGustafson JE. Draft genome sequences of Elizabethkingia meningoseptica. Genome Announc.2013;1:e00444–13.
  35. Kukutla PLindberg BGPei DRayl MYu WSteritz MDraft genome sequences of Elizabethkingia anophelis strains R26T and Ag1 from the midgut of the malaria mosquito Anopheles gambiae. Genome Announc. 2013;1:e01030–13.
  36. Balm MNSalmon SJureen RTeo CMahdi RSeetoh TBad design, bad practices, bad bugs: frustrations in controlling an outbreak ofElizabethkingia meningoseptica in intensive care units. J Hosp Infect2013;85:13440DOIPubMed
  37. Quick JConstantinidou CPallen MJOppenheim BLoman NJ. Draft genome sequence of Elizabethkingia meningoseptica isolated from a traumatic wound. Genome Announc. 2014;2:e00355–14.
  38. Sarma SKumar NJha ABaveja USharma SElizabethkingia meningosepticum: an emerging cause of septicemia in critically ill patients. J Lab Physicians. 2011;3:623DOIPubMed
  39. Teo JTan SYLiu YTay MDing YLi YComparative genomic analysis of malaria mosquito vector-associated novel pathogen Elizabethkingia anophelis. Genome Biol Evol2014;6:115865DOIPubMed
  40. Holden MTFeil EJLindsay JAPeacock SJDay NPEnright MCComplete genomes of two clinical Staphylococcus aureus strains: evidence for the rapid evolution of virulence and drug resistance. Proc Natl Acad Sci U S A2004;101:978691DOIPubMed



Technical Appendix

Suggested citation for this article: Lau SKP, Wu AKL, Teng JLL, Tse H, Curreem SOT, Tsui SKW, et al. Evidence for Elizabethkingia anophelis transmission from mother to infant, Hong Kong. Emerg Infect Dis [Internet]. 2015 Feb [date cited]. http://dx.doi.org/10.3201/eid2102.140623
DOI: 10.3201/eid2102.140623
1These authors contributed equally to this article.

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