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Journal of Clinical Microbiology, March 2007, p. 1029-1031, Vol. 45, No. 3
0095-1137/07/$08.00+0     doi:10.1128/JCM.02389-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Lymphogranuloma Venereum in Australia: Anorectal Chlamydia trachomatis Serovar L2b in Men Who Have Sex with Men{triangledown}

D. Stark,1* S. van Hal,1 R. Hillman,2 J. Harkness,1 and D. Marriott1

Department of Microbiology, St. Vincent's Hospital, Sydney, Australia,1 STI Research Centre, University of Sydney, Sydney, Australia2

Received 27 November 2006/ Accepted 11 January 2007


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ABSTRACT
 
Lymphogranuloma venereum (LGV) is a sexually transmitted infection that is causing an ongoing epidemic in men who have sex with men (MSM) in Europe, the United Kingdom, and North America. Twenty-nine rectal swabs positive for Chlamydia trachomatis were analyzed by real-time PCR for the presence of LGV serovars. Genotyping revealed an identical L2b serovar from four specimens. All patients were MSM and human immunodeficiency virus infected. Three of the four presented with severe ulcerative proctitis. We report a cluster of rectal LGV serovar L2b infections in Sydney, Australia.


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TEXT
 
Chlamydia trachomatis is an important human pathogen and a common cause of sexually transmitted disease worldwide (12). The C. trachomatis species is divided into 15 prototypic serovars labeled A to K, L1, L2, and L3 on the basis of analysis of the major outer membrane protein (2). On the basis of disease manifestation, serovars A, B, Ba, and C cause trachoma, serovars D to K are associated with urogenital infection, and serovars L1, L2, and L3 are responsible for lymphogranuloma venereum (LGV) (6). The L2 serovar can be further separated into L2, L2', L2a, or L2b according to amino acid differences (16).

Unlike other chlamydial urogenital infections that are generally restricted to epithelial surfaces, L serovars are invasive and cause severe inflammation, often with systemic symptoms, and have a preference for lymphatic tissue (3). The manifestations of LGV infection may vary depending on the site of infection. It can present as an inguinal syndrome with painful inguinal lymphadenopathy or an anorectal syndrome with acute proctitis, inflammation of the colon and rectum, and excessive proliferation of intestinal and perirectal lymphatic tissue which may mimic Crohn's disease (5, 12). Untreated, the infection may cause chronic complications including fistulae, strictures, and genital elephantiasis (12). The correct diagnosis is essential as treatment for LGV infection requires a prolonged course of antimicrobial therapy. Incorrect treatment may result in progressive invasive disease with tissue destruction.

Until recently, LGV has been largely restricted to developing regions and was only rarely seen in industrialized countries. Early sporadic reports of LGV in men who have sex with men (MSM) are present in the literature (16). However, since 2003 there have been outbreaks of LGV in MSM from The Netherlands, Belgium, France, Germany, Sweden, the United Kingdom, and North America (1, 7, 10, 15, 17, 19, 20). To date, most LGV strains have been identified as serovar L2b (18). Only two cases of LGV in MSM have been reported in Australia. One patient was a bisexual male who developed an inguinal lymphadenopathy, while the other presented with anorectal LGV (4, 14). The infections were locally acquired in Melbourne and responded to appropriate therapy. There have been no reports of confirmed anorectal LVG serovar L2b in Australia.

We undertook a prospective review of all patients with a rectal swab positive for C. trachomatis during a 10-month period to determine the incidence of LGV in a high-risk population of MSM.

All rectal swabs submitted to St. Vincent's Hospital, Darlinghurst, Australia, for C. trachomatis nucleic acid testing over a 10-month period (October 2005 to July 2006) were included in this study. Swabs were extracted with the QIAGEN QIAamp DNA mini kit in accordance with the manufacturer's instructions and underwent strand displacement amplification with the ProbTec system (Becton Dickinson).

Samples in which C. trachomatis DNA was detected underwent real-time PCR (RT-PCR) to confirm the presence of LGV serovars. RT-PCR was performed by targeting the pmp gene and using a Minor Groove Binding TaqMan probe as previously described (13).

Furthermore, all positive samples underwent PCR and sequencing targeting the omp1 gene as described by Jurstrand et al. (9). Sequencing was performed in both directions to ensure sufficient sequence overlap and fidelity on an ABI Prism 3730 automated sequencer at the SUPAMAC facility (Royal Prince Alfred Hospital, Sydney, Australia). The entire omp1 gene sequences obtained from the four samples were aligned, along with existing sequence data from LGV strains already deposited in GenBank, with the PILEUP program (version 8; Genetics Computer Group, Madison, WI). The individual sequences were then compared to those available in the GenBank databases with the BLASTN program run on the National Center for Biotechnology Information Server (htpp://www.ncbi.nlm.nih.gov?BLAST/).

Of the 29 samples C. trachomatis DNA positive by strand displacement amplification, 4 (14%) were positive for LGV by RT-PCR. All four samples gave identical sequences and showed 100% homology with that of the C. trachomatis L2b strain deposited under GenBank accession number DQ217607 and the prototype L2b strain from Amsterdam, AMSTLGVL2b (GenBank accession number AY586530).

The clinical presentation of the four patients is summarized in Table 1. All patients were human immunodeficiency virus (HIV)-positive MSM and were not immunosuppressed (CD4 cell counts ranged from 298 to 571/mm3). Two of the patients were initially misdiagnosed. In addition, all patients had concurrent or previous sexually transmitted infections (STIs) and participated in high-risk sexual behavior, with two of the four patients regularly attending MSM sex-on-premises venues. One patient had a risk factor for acquisition abroad, having lived in the United States prior to presentation. However, this occurred several years prior to the first documented cases. Therefore, all patients acquired the disease in Australia as there was no recent history of international travel. It is of interest that our four patients had CD4 cell counts of >250/mm3 so none were receiving azithromycin prophylaxis for Mycobacterium avium complex infection, which might have prevented LGV infection.


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  		TABLE 1. Summary of the clinical characteristics of patients with LGV reported in this study

LGV has become endemic in MSM in western developed countries. The first clusters of MSM with anorectal LGV were reported in Rotterdam in February 2003 (15). Since the initial reports of LGV in MSM, there have been numerous cases in other European countries, including The Netherlands, Belgium, France, Germany, Sweden, and Britain (7, 18, 19, 20). More recently, LGV has emerged in Canada and several of the United States (1, 10, 17). Most cases were caused by serovar L2b, with the majority of patients having concurrent HIV infection.

This is the first reported cluster of anorectal LGV serovar L2b infections among MSM in Australia. There have been two previous unrelated cases in Melbourne, Australia.

One case of locally acquired inguinal lymphadenopathy occurred in a bisexual male, and the second case of anorectal LGV acquired overseas occurred in an MSM (4, 14). Both cases were caused by an L2 serovar and not an L2b serovar as found in this study. This raises the possibility of two LGV variants currently circulating in Australia and is in keeping with the majority of previously documented LGV strains being serovar L2b.

Lister at al. (11) found no LGV strains in 47 anal swabs collected from MSM in Melbourne in 2004. Therefore, it appears that LGV has recently arrived in Australia. In addition, it seems that the infections were locally acquired. This has public health implications which, if not addressed, may lead to LGV becoming endemic in the MSM community in Australia.

The clinical characteristics of our patients correspond to those in previous reports (15, 18). LGV can result in significant disability and may facilitate the spread of HIV and other STIs and blood-borne infections, given the ulcerative nature of the disease. Correct diagnosis is also essential, as prolonged treatment (3 weeks) with doxycycline or a macrolide antibiotic is required for patients with LGV infections, in contrast to infection with other serovars, where only 1 week of treatment is required (18).

Current commercially available diagnostic test kits for C. trachomatis cannot distinguish the LGV serovars from the other serovars. Recently, RT-PCR targeting various membrane protein genes has been used. Morre et al. (16) used the polymorphic membrane protein H gene (pmp gene) as a PCR target because it has a unique gap in LGV strains of C. trachomatis, compared to other serovars, which makes it highly specific. While this RT-PCR can detect the LGV serovars, it cannot distinguish between them. Halse et al. (8) have recently described a multiplex RT-PCR that is specific for C. trachomatis serovar L2. RT-PCR provides a rapid screening method to determine if LGV serovars are present; however, it only detects serovar L2. We found direct sequencing to be a rapid and simple method to determine the serovar present.

In conclusion, we report a cluster of anorectal LGV serovar L2b infections among MSM in Sydney, Australia, which correspond to recent trends in MSM patients in other industrialized nations. Diagnosis and appropriate therapy, as well as public health initiatives and education of health care professionals, are crucial in preventing the dissemination and establishment of LGV as a common STI in Australia.


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ACKNOWLEDGMENTS
 
We thank S. Milliken for providing detailed clinical information about one of the patients.


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FOOTNOTES
 
* Corresponding author. Mailing address: Department of Microbiology, St. Vincent's Hospital, Darlinghurst 2010, NSW Australia. Phone: 61 2 8382 9196. Fax: 61 2 8382 2989. E-mail: dstark{at}stvincents.com.au. Back

{triangledown} Published ahead of print on 24 January 2007. Back


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Journal of Clinical Microbiology, March 2007, p. 1029-1031, Vol. 45, No. 3
0095-1137/07/$08.00+0     doi:10.1128/JCM.02389-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cunningham, K. A., Beagley, K. W. (2008). Male Genital Tract Chlamydial Infection: Implications for Pathology and Infertility. Biol. Reprod. 79: 180-189 [Abstract] [Full Text]  

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