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<article xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" article-type="brief-report"><?properties open_access?><front><journal-meta><journal-id journal-id-type="nlm-ta">Emerg Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Emerging Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">EID</journal-id><journal-title-group><journal-title>Emerging Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">1080-6040</issn><issn pub-type="epub">1080-6059</issn><publisher><publisher-name>Centers for Disease Control and Prevention</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">29048296</article-id><article-id pub-id-type="pmc">5652452</article-id><article-id pub-id-type="publisher-id">17-0758</article-id><article-id pub-id-type="doi">10.3201/eid2311.170758</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Letter</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Letter</subject></subj-group><subj-group subj-group-type="TOC-title"><subject><italic>Chlamydia trachomatis</italic> Biovar L2 Infection in Women in South Africa</subject></subj-group></article-categories><title-group><article-title><italic>Chlamydia trachomatis</italic> Biovar L2 Infection in Women in South Africa</article-title><alt-title alt-title-type="running-head"><italic>Chlamydia trachomatis</italic> Biovar L2 Infection in Women in South Africa</alt-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Peters</surname><given-names>Remco P.H.</given-names></name><xref ref-type="fn" rid="FN1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Doyle</surname><given-names>Ronan</given-names></name><xref ref-type="fn" rid="FN1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Redelinghuys</surname><given-names>Mathys J.</given-names></name></contrib><contrib contrib-type="author"><name><surname>McIntyre</surname><given-names>James A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Verjans</surname><given-names>Georges M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Breuer</surname><given-names>Judith</given-names></name></contrib><contrib contrib-type="author"><name><surname>Kock</surname><given-names>Marleen M.</given-names></name></contrib><aff id="aff1">University of Pretoria, Pretoria, South Africa (R.P.H. Peters, M.J. Redelinghuys, M.M. Kock): </aff><aff id="aff2">Maastricht University Medical Centre, Maastricht, the Netherlands (R.P.H. Peters); </aff><aff id="aff3">Anova Health Institute, Johannesburg, South Africa (R.P.H. Peters, J.A. McIntyre); </aff><aff id="aff4">University College London, London, United Kingdom (R. Doyle, J. Breuer); </aff><aff id="aff5">University of Cape Town, Cape Town, South Africa (J.A. McIntyre); </aff><aff id="aff6">Erasmus Medical Centre, Rotterdam, the Netherlands (G.M. Verjans); </aff><aff id="aff7">National Health Laboratory Service, Pretoria (M.M. Kock)</aff></contrib-group><author-notes><corresp id="cor1">Address for correspondence: Remco P.H. Peters, University of Pretoria, Faculty of Health Sciences, Department of Medical Microbiology, Pathology Bldg, Rm 3-11, Private Bag X323, Pretoria, 0001, South Africa; email: <email xlink:href="rph.peters@gmail.com">rph.peters@gmail.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2017</year></pub-date><volume>23</volume><issue>11</issue><fpage>1913</fpage><lpage>1915</lpage><abstract><p>We detected <italic>Chlamydia trachomatis</italic> biovar L2 in vaginal swab specimens of 7 women with vaginal discharge in South Africa. Whole-genome sequencing directly from clinical specimens identified a closely related cluster of strains. The clinical role of this infection in the context of syndromic management should be clarified.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords: </title><kwd><italic>Chlamydia trachomatis</italic></kwd><kwd>bacteria</kwd><kwd>lymphogranuloma venereum</kwd><kwd>serovar L</kwd><kwd>biovar L2</kwd><kwd>genital infection</kwd><kwd>sexually transmitted infections</kwd><kwd>South Africa</kwd></kwd-group></article-meta></front><body><p>Infection with <italic>Chlamydia trachomatis</italic> biovar L is known as lymphogranuloma venereum (LGV). This infection usually presents as genital ulcers, followed by an invasion of the lymphatic system resulting in buboes, painful swelling of lymph nodes (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>). In the past 2 decades, another manifestation of LGV has emerged in North America and Europe: rectal LGV infection causing proctocolitis among men who have sex with men (MSM) (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>). In this population, urethral LGV also occurs (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>).</p><p>There have been only sporadic reports of rectal and genital LGV infection in women living in the industrialized world (<xref rid="R3" ref-type="bibr"><italic>3</italic></xref>,<xref rid="R4" ref-type="bibr"><italic>4</italic></xref>). Cross-sectional studies from France, Switzerland, and the Netherlands did not detect biovar L in specimens from women with genital or rectal <italic>C. trachomatis</italic> infection (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>,<xref rid="R5" ref-type="bibr"><italic>5</italic></xref><italic>&#x02013;</italic><xref rid="R7" ref-type="bibr"><italic>7</italic></xref>). Because lymphatic manifestation has become relatively rare, LGV infection is considered an outbreak mainly among MSM in Europe and North America (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>). Lymphatic LGV is endemic to Africa, but before our study, it was unknown whether <italic>C. trachomatis</italic> biovar L infections occurred in women in Africa. Thus, we determined the prevalence of this infection in South Africa. </p><p>To determine whether genital <italic>C. trachomatis</italic> biovar L infections occur in women living in South Africa, we analyzed 82 DNA samples extracted from vaginal swab specimens that were positive by a molecular detection assay for <italic>C. trachomatis</italic> infection at the Department of Medical Microbiology at the University of Pretoria. The Faculty of Health Sciences Research Ethics Committee at the University of Pretoria approved the studies in which these specimens were collected. These swab specimens had been collected during 2012&#x02013;2016 from women attending different healthcare settings: a mobile health clinic in rural Mopani District (n = 52) and 3 departments at the academic hospital in Pretoria: obstetrics and gynecology clinic (n = 14), antiretroviral treatment clinic (n = 10), and sexually transmitted infection (STI) clinic (n = 6). We assessed the presence of LGV in these genital specimens by using specific PCRs for <italic>C. trachomatis</italic> serovar L and serovar L2b (<xref rid="R8" ref-type="bibr"><italic>8</italic></xref>). For positive PCR results, we confirmed the diagnosis by conducting whole-genome sequencing (WGS) of <italic>C. trachomatis</italic> directly from the clinical specimen as described elsewhere (<xref rid="R9" ref-type="bibr"><italic>9</italic></xref>).</p><p>Whereas <italic>C. trachomatis</italic> biovar L&#x02013;specific PCR showed positive results for 7 specimens obtained from women at the antiretroviral treatment (n = 5) and STI (n = 2) clinics in Pretoria, we did not detect LGV in any of the 52 specimens from women in Mopani District. All PCR test results for serovar L2b were negative. The 7 women with genital LGV all had vaginal discharge and were co-infected with another STI (<xref ref-type="table" rid="T1">Table</xref>).</p><table-wrap id="T1" position="float"><label>Table</label><caption><title>Characteristics of 7 women with vaginal discharge and a positive PCR result for <italic>Chlamydia trachomatis</italic> biovar L, Pretoria, South Africa, 2012&#x02013;2016*</title></caption><table frame="hsides" rules="groups"><col width="39" span="1"/><col width="59" span="1"/><col width="58" span="1"/><col width="94" span="1"/><col width="121" span="1"/><col width="49" span="1"/><col width="59" span="1"/><thead><tr><th valign="bottom" align="left" scope="col" rowspan="1" colspan="1">Patient&#x02028;ID</th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">Healthcare setting</th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">HIV status</th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">Co-infection</th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1"><italic>C. trachomatis </italic>WGS result</th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">Mean read depth</th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">Genome coverage, %</th></tr></thead><tbody><tr><td valign="top" align="left" scope="row" rowspan="1" colspan="1">1</td><td valign="top" align="center" rowspan="1" colspan="1">ART clinic</td><td valign="top" align="center" rowspan="1" colspan="1">Positive</td><td valign="top" align="center" rowspan="1" colspan="1"><italic>Trichomonas vaginalis</italic></td><td valign="top" align="center" rowspan="1" colspan="1">L2 confirmed</td><td valign="top" align="center" rowspan="1" colspan="1">41</td><td valign="top" align="center" rowspan="1" colspan="1">99.5</td></tr><tr><td valign="top" align="left" scope="row" rowspan="1" colspan="1">2</td><td valign="top" align="center" rowspan="1" colspan="1">ART clinic</td><td valign="top" align="center" rowspan="1" colspan="1">Positive</td><td valign="top" align="center" rowspan="1" colspan="1"><italic>T. vaginalis</italic></td><td valign="top" align="center" rowspan="1" colspan="1">L2 confirmed</td><td valign="top" align="center" rowspan="1" colspan="1">12</td><td valign="top" align="center" rowspan="1" colspan="1">98.3</td></tr><tr><td valign="top" align="left" scope="row" rowspan="1" colspan="1">3</td><td valign="top" align="center" rowspan="1" colspan="1">ART clinic</td><td valign="top" align="center" rowspan="1" colspan="1">Positive</td><td valign="top" align="center" rowspan="1" colspan="1"><italic>Mycoplasma genitalium</italic></td><td valign="top" align="center" rowspan="1" colspan="1">L2 confirmed</td><td valign="top" align="center" rowspan="1" colspan="1">21</td><td valign="top" align="center" rowspan="1" colspan="1">98.6</td></tr><tr><td valign="top" align="left" scope="row" rowspan="1" colspan="1">4</td><td valign="top" align="center" rowspan="1" colspan="1">ART clinic</td><td valign="top" align="center" rowspan="1" colspan="1">Positive</td><td valign="top" align="center" rowspan="1" colspan="1"><italic>M.a genitalium</italic></td><td valign="top" align="center" rowspan="1" colspan="1">L2 confirmed</td><td valign="top" align="center" rowspan="1" colspan="1">72</td><td valign="top" align="center" rowspan="1" colspan="1">99</td></tr><tr><td valign="top" align="left" scope="row" rowspan="1" colspan="1">5</td><td valign="top" align="center" rowspan="1" colspan="1">ART clinic</td><td valign="top" align="center" rowspan="1" colspan="1">Positive</td><td valign="top" align="center" rowspan="1" colspan="1"><italic>T. vaginalis</italic></td><td valign="top" align="center" rowspan="1" colspan="1">Insufficient WGS read coverage</td><td valign="top" align="center" rowspan="1" colspan="1">0.5</td><td valign="top" align="center" rowspan="1" colspan="1">29</td></tr><tr><td valign="top" align="left" scope="row" rowspan="1" colspan="1">6</td><td valign="top" align="center" rowspan="1" colspan="1">STI clinic</td><td valign="top" align="center" rowspan="1" colspan="1">Unknown</td><td valign="top" align="center" rowspan="1" colspan="1"><italic>Neisseria gonorrhoeae</italic></td><td valign="top" align="center" rowspan="1" colspan="1">Insufficient clinical material</td><td valign="top" align="center" rowspan="1" colspan="1">ND</td><td valign="top" align="center" rowspan="1" colspan="1">ND</td></tr><tr><td valign="top" align="left" scope="row" rowspan="1" colspan="1">7<hr/></td><td valign="top" align="center" rowspan="1" colspan="1">STI clinic<hr/></td><td valign="top" align="center" rowspan="1" colspan="1">Unknown<hr/></td><td valign="top" align="center" rowspan="1" colspan="1"><italic>N. gonorrhoeae</italic><hr/></td><td valign="top" align="center" rowspan="1" colspan="1">Insufficient clinical material<hr/></td><td valign="top" align="center" rowspan="1" colspan="1">ND<hr/></td><td valign="top" align="center" rowspan="1" colspan="1">ND<hr/></td></tr><tr><td colspan="7" valign="top" align="left" scope="col" rowspan="1">*ART, antiretroviral therapy; ID, identification; ND, not determined; STI, sexually transmitted infection; WGS, whole-genome sequencing.</td></tr></tbody></table></table-wrap><p>WGS confirmed LGV (<italic>ompA</italic> sequence identical to those of the <italic>C. trachomatis</italic> L2 434/BU reference strain) in 4 cases with good mean read depth (<underline>&#x0003e;</underline>12) and high genome coverage (&#x0003e;98%). The 4 sequences clustered well with the L2 sequences previously published and away from L1 and L2b sequences. For 1 specimen, the mean read depth was insufficient to allocate a biovar; insufficient DNA was available from 2 other samples for WGS.</p><p>This report shows emergence of <italic>C. trachomatis</italic> biovar L2 genital infection in women living in South Africa, a region to which lymphatic LGV is endemic (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>). Instead of serologic analysis, we used molecular testing and WGS of clinical specimens to confirm the diagnosis, determine genetic relatedness, and identify the specific variant of genotype L. We observed LGV in specimens from women at the academic hospital in Pretoria, but not from women living in the Mopani District, &#x02248;400 km away. Although the distribution of risk factors may be different, the close relatedness of LGV strains suggests that this might be a localized outbreak of genital <italic>C. trachomatis</italic> L2 infection among women living in Pretoria.</p><p>The clinical role of genital <italic>C. trachomatis</italic> biovar L infection in women remains to be determined. Analogous to non-LGV <italic>C. trachomatis</italic> infection in women and rectal LGV in MSM, the clinical spectrum of genital LGV in women may vary from a mucosal ulcer with intrapelvic lymphadenopathy to cervicitis with vaginal discharge, or it may manifest without any symptoms at all as persistent asymptomatic infection. Although rectal <italic>C. trachomatis</italic> infections have been reported in African women, the occurrence of rectal LGV is unknown (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>).</p><p>The emergence of genital LGV in women poses a concern in our setting, which uses syndromic management for STIs, because it is unclear whether the infection would be treated adequately with the empirical regimen of azithromycin and ceftriaxone. The main limitation of this report is the lack of follow-up data to confirm whether syndromic management was effective for these biovar L <italic>C. trachomatis</italic> genital infections.</p><p>In conclusion, this report shows the emergence of genital <italic>C. trachomatis</italic> L2 infection in South African women. Further research about its distribution in the general population, clinical role, and the occurrence of rectal infections is warranted because it is unclear whether this STI is managed adequately under the current syndromic management guidelines.</p></body><back><fn-group><fn fn-type="citation"><p><italic>Suggested citation for this article</italic>: Peters RPH, Doyle R, Redelinghuys MJ, McIntyre JA, Verjans GM, Breuer J, et al. <italic>Chlamydia trachomatis</italic> biovar L2 infection in women in South Africa. Emerg Infect Dis. 2017 Nov [<italic>date cited</italic>]. <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3201/eid2311.170758">https://doi.org/10.3201/eid2311.170758</ext-link></p></fn><fn id="FN1"><label>1</label><p>These authors contributed equally to this article.</p></fn></fn-group><ack><title>Acknowledgments</title><p>We thank the students at the University of Pretoria and staff at the Anova Health Institute for their contributions to this project.</p><p>R.D. and the chlamydia genome sequencing were funded by the European Union FP7 PATHSEEK grant. We acknowledge the National Institute for Health Research University College London Hospitals/University College London Biomedical Research Centre and Medical Research Council&#x02013;funded Pathogen Genomics Unit. 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