Chlamydia trachomatis Biovar L2 Infection in Women in South Africa

Table

Remco P.H. Peters1

, Ronan Doyle1, Mathys J. Redelinghuys, James A. McIntyre, Georges M. Verjans, Judith Breuer, and Marleen M. Kock

Author affiliations: University of Pretoria, Pretoria, South Africa (R.P.H. Peters, M.J. Redelinghuys, M.M. Kock):; Maastricht University Medical Centre, Maastricht, the Netherlands (R.P.H. Peters); Anova Health Institute, Johannesburg, South Africa (R.P.H. Peters, J.A. McIntyre); University College London, London, United Kingdom (R. Doyle, J. Breuer); University of Cape Town, Cape Town, South Africa (J.A. McIntyre); Erasmus Medical Centre, Rotterdam, the Netherlands (G.M. Verjans); National Health Laboratory Service, Pretoria (M.M. Kock)

Cite This Article

Abstract

We detected Chlamydia trachomatis 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.

Infection with Chlamydia trachomatis 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 (1). 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) (1). In this population, urethral LGV also occurs (2).

There have been only sporadic reports of rectal and genital LGV infection in women living in the industrialized world (3,4). Cross-sectional studies from France, Switzerland, and the Netherlands did not detect biovar L in specimens from women with genital or rectal C. trachomatis infection (1,5–7). Because lymphatic manifestation has become relatively rare, LGV infection is considered an outbreak mainly among MSM in Europe and North America (1). Lymphatic LGV is endemic to Africa, but before our study, it was unknown whether C. trachomatis biovar L infections occurred in women in Africa. Thus, we determined the prevalence of this infection in South Africa.

To determine whether genital C. trachomatis 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 C. trachomatis 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 2012–2016 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 C. trachomatis serovar L and serovar L2b (8). For positive PCR results, we confirmed the diagnosis by conducting whole-genome sequencing (WGS) of C. trachomatis directly from the clinical specimen as described elsewhere (9).

Whereas C. trachomatis biovar L–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 (Table).

WGS confirmed LGV (ompA sequence identical to those of the C. trachomatis L2 434/BU reference strain) in 4 cases with good mean read depth (>12) and high genome coverage (>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.

This report shows emergence of C. trachomatis biovar L2 genital infection in women living in South Africa, a region to which lymphatic LGV is endemic (1). 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, ≈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 C. trachomatis L2 infection among women living in Pretoria.

The clinical role of genital C. trachomatis biovar L infection in women remains to be determined. Analogous to non-LGV C. trachomatis 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 C. trachomatis infections have been reported in African women, the occurrence of rectal LGV is unknown (10).

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 C. trachomatis genital infections.

In conclusion, this report shows the emergence of genital C. trachomatis 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.

Dr. Peters is a clinical program specialist at the Anova Health Institute in South Africa. He is a professor of medical microbiology at the University of Pretoria and at Maastricht University. His research interest is the molecular epidemiology of infectious diseases, with specific focus on sexually transmitted infections.

Acknowledgments

We thank the students at the University of Pretoria and staff at the Anova Health Institute for their contributions to this project.

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–funded Pathogen Genomics Unit. J.B. receives additional funding from the National Institute for Health Research University College London Hospitals/University College London Biomedical Research Centre.

References

Stoner BP, Cohen SE. Lymphogranuloma venereum 2015: clinical presentation, diagnosis, and treatment. Clin Infect Dis. 2015;61(Suppl 8):S865–73. DOI PubMed
de Vrieze NH, van Rooijen M, Speksnijder AG, de Vries HJ. Urethral lymphogranuloma venereum infections in men with anorectal lymphogranuloma venereum and their partners: the missing link in the current epidemic? Sex Transm Dis. 2013;40:607–8. DOI PubMed
Heiligenberg M, Verweij SP, Speksnijder AG, Morré SA, de Vries HJ, Schim van der Loeff MF. No evidence for LGV transmission among heterosexuals in Amsterdam, the Netherlands. BMC Res Notes. 2014;7:355. DOI PubMed
Gomes JP, Nunes A, Florindo C, Ferreira MA, Santo I, Azevedo J, et al. Lymphogranuloma venereum in Portugal: unusual events and new variants during 2007. Sex Transm Dis. 2009;36:88–91. DOI PubMed
de Jesús De Haro-Cruz M, Deleón-Rodriguez I, Escobedo-Guerra MR, López-Hurtado M, Arteaga-Troncoso G, Ortiz-Ibarra FJ, et al. Genotyping of Chlamydia trachomatis from endocervical specimens of infertile Mexican women. Enferm Infecc Microbiol Clin. 2011;29:102–8. DOI PubMed
Herida M, Kreplack G, Cardon B, Desenclos J-C, de Barbeyrac B. First case of urethritis due to Chlamydia trachomatis genovar L2b. Clin Infect Dis. 2006;43:268–9. DOI PubMed
Goldenberger D, Dutly F, Gebhardt M. Analysis of 721 Chlamydia trachomatis-positive urogenital specimens from men and women using lymphogranuloma venereum L2-specific real-time PCR assay. Euro Surveill. 2006;11:E061018.4.PubMed
Verweij SP, Catsburg A, Ouburg S, Lombardi A, Heijmans R, Dutly F, et al. Lymphogranuloma venereum variant L2b-specific polymerase chain reaction: insertion used to close an epidemiological gap. Clin Microbiol Infect. 2011;17:1727–30. DOI PubMed
Christiansen MT, Brown AC, Kundu S, Tutill HJ, Williams R, Brown JR, et al. Whole-genome enrichment and sequencing of Chlamydia trachomatisdirectly from clinical samples. BMC Infect Dis. 2014;14:591. DOI PubMed
Peters RP, Dubbink JH, van der Eem L, Verweij SP, Bos ML, Ouburg S, et al. Cross-sectional study of genital, rectal, and pharyngeal Chlamydia and gonorrhea in women in rural South Africa. Sex Transm Dis. 2014;41:564–9. DOI PubMed