title: Molecular typing of Treponema pallidum: a systematic review and meta-analysis.
abstract: BACKGROUND
  Syphilis is resurgent in many regions of the world. Molecular typing is a robust tool for investigating strain diversity and epidemiology. This study aimed to review original research on molecular typing of Treponema pallidum (T. pallidum) with three objectives: (1) to determine specimen types most suitable for molecular typing; (2) to determine T. pallidum subtype distribution across geographic areas; and (3) to summarize available information on subtypes associated with neurosyphilis and macrolide resistance.
  
  
  RESULTS
  Two researchers independently searched five databases from 1998 through 2010, assessed for eligibility and study quality, and extracted data. Search terms included "Treponema pallidum," or "syphilis," combined with the subject headings "molecular," "subtyping," "typing," "genotype," and "epidemiology." Sixteen eligible studies were included. Publication bias was not statistically significant by the Begg rank correlation test. Medians, inter-quartile ranges, and 95% confidence intervals were determined for DNA extraction and full typing efficiency. A random-effects model was used to perform subgroup analyses to reduce obvious between-study heterogeneity. Primary and secondary lesions and ear lobe blood specimens had an average higher yield of T. pallidum DNA (83.0% vs. 28.2%, χ(2) = 247.6, p<0.001) and an average higher efficiency of full molecular typing (80.9% vs. 43.1%, χ(2) = 102.3, p<0.001) compared to plasma, whole blood, and cerebrospinal fluid. A pooled analysis of subtype distribution based on country location showed that 14d was the most common subtype, and subtype distribution varied across geographic areas. Subtype data associated with macrolide resistance and neurosyphilis were limited.
  
  
  CONCLUSIONS
  Primary lesion was a better specimen for obtaining T. pallidum DNA than blood. There was wide geographic variation in T. pallidum subtypes. More research is needed on the relationship between clinical presentation and subtype, and further validation of ear lobe blood for obtaining T. pallidum DNA would be useful for future molecular studies of syphilis.
authors.affiliation: National Center for STD Control, Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Dermatology, Nanjing, China.
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Peng
authors.forename: Alberta L
authors.initials: AL
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Tucker
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Yin
authors.forename: Xiang-Sheng
authors.initials: XS
authors.lastname: Chen
mesh_terms: D005838:Genotype; D006801:Humans; D017720:Molecular Epidemiology / Q000379:methods; D058889:Molecular Typing / Q000379:methods*; D058974:Phylogeography; D013587:Syphilis / Q000453:epidemiology* / Q000382:microbiology*; D014210:Treponema pallidum / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification
references.citation: Antimicrob Agents Chemother. 2010 Feb;54(2):583-9
references.pmid: 19805553
references.citation: Clin Infect Dis. 2006 Feb 1;42(3):337-45
references.pmid: 16392078
references.citation: Clin Infect Dis. 2007 May 1;44(9):1222-8
references.pmid: 17407043
references.citation: Sex Transm Infect. 2007 Jun;83(3):189-92
references.pmid: 17244664
references.citation: FEMS Immunol Med Microbiol. 2007 Mar;49(2):184-91
references.pmid: 17328752
references.citation: Clin Microbiol Rev. 2006 Jan;19(1):29-49
references.pmid: 16418521
references.citation: Int J STD AIDS. 2007 Dec;18(12):842-5
references.pmid: 18073019
references.citation: J Clin Microbiol. 2009 Jun;47(6):1668-73
references.pmid: 19339468
references.citation: Sex Transm Dis. 2005 Jan;32(1):1-6
references.pmid: 15614114
references.citation: CMAJ. 2006 Jan 31;174(3):349
references.pmid: 16446481
references.citation: PLoS Med. 2009 Jul 21;6(7):e1000097
references.pmid: 19621072
references.citation: PLoS Med. 2009 Jul 21;6(7):e1000100
references.pmid: 19621070
references.citation: J Clin Microbiol. 2009 Aug;47(8):2510-2
references.pmid: 19494073
references.citation: Sex Transm Infect. 2009 Oct;85(6):447-51
references.pmid: 19497918
references.citation: Sex Transm Dis. 1998 Sep;25(8):408-14
references.pmid: 9773432
references.citation: Sex Transm Dis. 2009 Dec;36(12):775-6
references.pmid: 19901863
references.citation: J Clin Microbiol. 2005 Aug;43(8):3743-6
references.pmid: 16081904
references.citation: J Infect Dis. 2006 Dec 15;194(12):1771-3
references.pmid: 17109351
references.citation: N Engl J Med. 2004 Jul 8;351(2):154-8
references.pmid: 15247355
references.citation: Lancet. 2007 Jan 13;369(9556):132-8
references.pmid: 17223476
references.citation: N Engl J Med. 2010 May 6;362(18):1658-61
references.pmid: 20445179
references.citation: Lancet Infect Dis. 2008 Apr;8(4):244-53
references.pmid: 18353265
references.citation: AIDS. 2004 Oct 21;18(15):2075-9
references.pmid: 15577629
references.citation: Sex Transm Dis. 2010 Nov;37(11):726-9
references.pmid: 20644500
references.citation: Sex Transm Dis. 2010 Oct;37(10):660-3
references.pmid: 20601928
references.citation: Infect Immun. 2007 Jun;75(6):2954-8
references.pmid: 17438037
references.citation: Clin Infect Dis. 2009 Aug 15;49(4):515-21
references.pmid: 19583516
references.citation: PLoS Negl Trop Dis. 2010 May 18;4(5):e690
references.pmid: 20502522
references.citation: Int J STD AIDS. 2006 Apr;17(4):221-7; quiz 228
references.pmid: 16595042
references.citation: Bull World Health Organ. 2004 Jun;82(6):402-9
references.pmid: 15356931
references.citation: J Clin Microbiol. 2002 Jan;40(1):256-8
references.pmid: 11773125
references.citation: J Infect Dis. 2010 Nov 1;202(9):1380-8
references.pmid: 20868271
references.citation: Acta Derm Venereol. 2010 Mar;90(2):206-7
references.pmid: 20169316
references.citation: N Engl J Med. 2005 Sep 22;353(12):1236-44
references.pmid: 16177249
references.citation: Sex Transm Dis. 2009 Oct;36(10):629-36
references.pmid: 19955874
references.citation: J Infect Dis. 2001 Jun 1;183(11):1601-6
references.pmid: 11343208
references.citation: Sex Transm Dis. 2010 Sep;37(9):544-8
references.pmid: 20539263
references.citation: J Clin Microbiol. 2001 Feb;39(2):485-93
references.pmid: 11158094
references.citation: J Clin Microbiol. 2008 Nov;46(11):3802-3
references.pmid: 18753355
references.citation: J Med Microbiol. 2009 Jun;58(Pt 6):832-836
references.pmid: 19429763
references.citation: J Med Microbiol. 2007 Jun;56(Pt 6):715-721
references.pmid: 17510254
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120