title: Chlamydia trachomatis variant not detected by plasmid based nucleic acid amplification tests: molecular characterisation and failure of single dose azithromycin.
abstract: OBJECTIVE
  To characterise a Chlamydia trachomatis variant strain from a patient with non-gonococcal urethritis (NGU) whose first void urine (FVU) displayed discrepant Ctrachomatis test results and describe the clinical response to treatment.
  
  
  METHODS
  The FVU specimen was assayed with an immune based Chlamydia Rapid Test (CRT) and various nucleic acid amplification tests (NAATs) to establish C trachomatis infection. Sequencing of the major outer membrane protein gene (omp1 also known as ompA) was undertaken to identify the serovar of the variant strain. Polymerase chain reaction (PCR) analysis was also conducted to determine whether the strain harboured deletions in the cryptic plasmid or was plasmid free.
  
  
  RESULTS
  The FVU specimen was strongly reactive in CRT but negative with the plasmid based Amplicor PCR (Roche) and ProbeTec ET (Becton-Dickinson) assays. However, NAATs for 16S RNA (Aptima Combo 2, GenProbe), omp1 (RealArt CT PCR, Artus and in-house NAATs) or the outer membrane complex B protein gene (omcB) established C trachomatis infection. Sequencing of omp1 showed that the variant belonged to serovar I. PCR analysis indicated that the variant was plasmid free. The patient did not respond to single dose azithromycin treatment but subsequently responded to a course of doxycycline.
  
  
  CONCLUSIONS
  A pathogenic plasmid free C trachomatis variant was identified. Clinicians should be alerted to the possibility of undetected C trachomatis infection caused by such variants and the potential of azithromycin failure in patients with recurrent chlamydial NGU. The occurrence of this variant is rare and should not form the basis for judgment of the performance or usefulness of plasmid based NAATs for C trachomatis detection.
authors.affiliation: Department of Haematology, University of Cambridge, EABC Site, Long Road, Cambridge CB2 2PT, UK.
authors.forename: Jose Paolo V
authors.initials: JP
authors.lastname: Magbanua
authors.forename: Beng Tin
authors.initials: BT
authors.lastname: Goh
authors.forename: Claude-Edouard
authors.initials: CE
authors.lastname: Michel
authors.forename: Aura
authors.initials: A
authors.lastname: Aguirre-Andreasen
authors.forename: Sarah
authors.initials: S
authors.lastname: Alexander
authors.forename: Ines
authors.initials: I
authors.lastname: Ushiro-Lumb
authors.forename: Catherine
authors.initials: C
authors.lastname: Ison
authors.forename: Helen
authors.initials: H
authors.lastname: Lee
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D017963:Azithromycin / Q000008:administration & dosage*; D002690:Chlamydia Infections / Q000175:diagnosis* / Q000188:drug therapy; D002692:Chlamydia trachomatis / Q000235:genetics*; D004269:DNA, Bacterial / Q000032:analysis*; D006801:Humans; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D016133:Polymerase Chain Reaction; D017211:Treatment Failure; D014526:Urethritis / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D017963:Azithromycin