EDITORIAL URRENT C OPINION
The molecular biology–clinical interface of sexually transmitted infections for evaluating pathophysiology, transmission, resistance and treatment Karen E. Rogstad
This edition concentrates on the interplay between new molecular technology and what we can learn about transmission, pathogenicity, emergence of resistance and treatment programmes from ‘old’ sexually transmitted infections (STIs) and potential new ones such as Ebola virus. The authors chosen have recently researched these areas themselves and consider their own work and that of others, which has emerged in their field. Two linked articles consider syphilis in which, since the advent of penicillin as a treatment, there has been little progress in alternative treatments and there is ongoing controversy about optimal management, particularly in the context of dual infection with HIV. Lawrence et al. [1] set the scene by considering the diversity in recommended treatment options and how practice remains different to guidelines, with many U.S. and UK physicians giving additional treatment to those dually infected with HIV [2,3]. They discuss that previous systematic reviews, on which guidelines are based, are at odds with the more recent evidence that rates of neurosyphilis may be higher in HIV patients. This is particularly relevant as new data shows poorer neurocognitive outcomes in patients who have had syphilis, as measured by a higher Global Deficit Score and impaired learning [4,5]. Neurosyphilis is more likely to be diagnosed if a lumbar puncture is undertaken, and in the presence of laboratory indicators, irrespective of the symptoms, the authors suggest there should be a low threshold for performing a lumbar puncture, particularly with a CD4 count of under 350 cells/mm or a venereal disease research laboratory (VDRL) titre of more than 1 : 32. The very high serological cure rates in the author’s unit, where a neuropenetrative regimen of procaine penicillin is always used, add further weight to the evidence for treating those who are coinfected differently [6]. Regarding alternative treatments, the UK guidelines of azithromycin as an alternative are at odds with the international ones,
and data just published from Australia needs to be considered which shows that the A2058G mutation, conferring macrolide resistance, is as high as 84.4% and more common in MSM [7]. An additional study of particular interest is the prevention of syphilis through the use of doxycycline prophylaxis, which requires larger studies to be performed to see whether this approach should be recommended [8]. Tipple and Taylor [9], in a complementary paper, consider new data, which may assist in answering these controversies in the future. Some of the problems identified by Lawrence et al. [1] regarding identifying disease stage, monitoring response to therapy and predicting who will develop complications may be solved through the use of PCR technology. PCR sensitivity for genital and anal chancres is high, and may also be useful in blood sampling with highest sensitivities for congenital and secondary disease. Quantitative PCR may also allow disease stage to be identified as there is a link between disease stage and viral load. Detection of syphilis bacteraemia can predict not only the disease stage, but also the risk of adverse neonatal outcomes, with 80% of mothers with early disease who delivered babies with congenital syphilis being PCR positive [10]. Syphilis bacteraemia may also be helpful in identifying early syphilis when serological response is delayed. Genotyping may have a role in addressing treatment issues, as an initial study by Marra [11] found
HIV and Sexual Health, Sheffield Teaching Hospitals NHS Foundation Trust and Undergraduate Dean, University of Sheffield School of Medicine, Royal Hallamshire Hospital, Sheffield, UK Correspondence to Karen E. Rogstad, HIV and Sexual Health, Sheffield Teaching Hospitals NHS Foundation Trust and Undergraduate Dean, University of Sheffield School of Medicine, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK. Tel: +44 114 271 1900; e-mail: [email protected] Curr Opin Infect Dis 2015, 28:41–43 DOI:10.1097/QCO.0000000000000134
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Sexually transmitted diseases
that the newly identified 14d/f subtype was associated with neurosyphilis. The issue of determining whether a cure rate has been achieved, which is currently based on the changes to serological titres, may in the future be assisted by PCR, with a preliminary study monitoring bacterial clearance after treatment, finding that the average time for clearance is 32 h, with cure being identified at 1 month [12]. Advances in molecular typing methods are revolutionizing our understanding of transmission networks and disease management for Chlamydia trachomatis serovars. In their study, Vries et al. [13] describe how multilocus sequence typing (MLST) methodologies are superior to older methods such as serological or ompA typing. As a result, cluster and network analysis can be improved. It has enabled the identification of two genetically distinct C. trachomatis populations in heterosexuals (men and women) and MSMs, with little overlap between the two. Interestingly, using MLST, there is no difference between strains in MSM in the USA, Sweden, and the Netherlands, but there is in heterosexuals [14]. New variants of C. trachomatis lymphogranuloma venereum (LGV) serovars have been recently described. These L2c (which is a recombinant of L2 and D) and L2/L2f types appear to have different pathophysiological and clinical properties [15,16]. On a more practical note, LGV typing methodology allows for the differentiation of LGV and non-LGV genovars. Currently, this is usually only performed on MSM with anal symptoms, but 27% of men in Amsterdam were asymptomatic [17], indicating that all rectal C. trachomatis-positive samples on MSM should have LGV typing performed. Molecular high-resolution typing has also enabled the identification of LGV in specific high-risk communities, which can be used to target interventions. It can also be an important surveillance tool in identifying new variant disease, such as that which occurred in Sweden. One of the most neglected STIs in terms of research and academic interest has been that of Trichomonas vaginalis. Hirt and Sherrard [18] use a molecular pathobiology approach to offer new insights into this organism and to correlate this with the potential for its use in the future in a clinical setting. Molecular phylogeny has revealed a close association between human T. vaginalis and that in birds, and that the two human Trichomonas types T. vaginalis (genital) and T. tenax (oral) have more in common with avian T. vaginalis species than they do to each other. The study of T. vaginalis proteomics is allowing us to gain an understanding of the changes that occur when T. vaginalis alters from a flagellated organism to one that is amoeboid and binds to, and migrates through, human tissues. Exosomal protein identification allows for the potential for vaccine 42
www.co-infectiousdiseases.com
development. They also postulate that T. vaginalis macrophage inhibitory factor may have a role in the development of prostatic cancer and explain the science behind this [19]. The ability of T. vaginalis to upgrade the macrophage proinflammatory response is associated with M. hominis [20] in vitro, and a new species of Mycoplasma has just been identified, which is strongly associated with T. vaginalis infection [21], suggesting there may be different T. vaginalis–Mycoplasma consortia that have clinical relevance. The potential that the proinflammatory response associated with treatment of T. vaginalis with metronidazole may be implicated in adverse pregnancy is raised. Advances in the clinical management of T. vaginalis, in contrast, are less impressive, including for resistant T. vaginalis, which is estimated currently at 5% in the USA. In contrast, molecular testing methods are described, which have improved detection. The problems created by new methodologies are discussed by Ross [22], who considers the potential for nucleic acid amplification test (NAAT) methodology to result in false-positive results in the clinical setting because of contamination of surfaces in healthcare facilities. A study in a sexual health facility found multiple areas of RNA of Neisseria gonorrhoeae and C. trachomatis contamination, particularly in the patient toilet area [23]. However, the actual occurrence of contamination appears to be low as shown by processing ‘dummy’ urine samples [24]. It is also reassuring that attempts to culture NAAT-positive samples for N. gonorrhoeae or C. trachomatis have been negative [23], indicating that transmission of infection is extremely unlikely. In the final paper [25], I review the potential for Ebola to be an STI, which is suggested by NAAT methodology. In fact, despite the theoretical risk, there has been no published case of sexual transmission of this so far. Molecular data theoretically implies that the risk early in the disease may be greater from oral contact as a result of an early rise in salivary samples, whereas semen samples rise later in the course of the illness, when victims are likely to be too sick for sexual intercourse. In survivors, however, there is a persistence of RNA in faecal and stool samples for 29 days, the vagina for 33 days, and semen for 3 months or longer (http://www.cdc.gov/ vhf/ebola/transmission/human-transmission.html; last accessed 2 November 2014). Therefore, despite no confirmed transmissions, the WHO and the U.S. Centers for Disease Control and Prevention recommend avoidance of sexual intercourse including oral, or if this cannot be avoided, condom use, for up to 3 months after recovery (http://www.cdc.gov/ vhf/ebola/transmission/index.html?s_cid=cs_3923; last accessed 2 November 2014). Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Clinical interface of sexually transmitted infections Rogstad
Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
REFERENCES 1. Lawrence D, Cresswell F, Whetham J, Fisher M. Syphilis treatment in the presence of HIV: the debate goes on. Curr Opin Infect Dis 2015; 28:44–52. 2. Dowell D, Polgreen PM, Beekmann SE, et al. Dilemmas in the management of syphilis: a survey of infectious diseases experts. Clin Infect Dis 2009; 49:1526–1529. 3. Fisher M. How to manage syphilis in HIV. In: Presented at the 14th European AIDS Conference; Brussels, Belgium; 2013. 4. Marra CM, Deutsch R, Collier AC, et al. Neurocognitive impairment in HIVinfected individuals with previous syphilis. Int J STD AIDS 2013; 24:351– 355. 5. Vera J, Garvey L, Tipple C, et al. A past history of syphilis is associated with poorer performance in the cognitive domains of memory and learning in HIVinfected subjects on stable cart. HIV Med 2012; 13:51. 6. Warwick Z, Dean G, Fisher M. Should syphilis be treated differently in HIVpositive and HIV-negative individuals? Treatment outcomes at a university hospital, Brighton, UK. Int J STD AIDS 2009; 20:229–230. 7. Read P, Jeoffreys N, Tagg K, et al. Azithromycin-resistant syphilis-causing strains in Sydney, Australia: prevalence and risk factors. J Clin Microbiol 2014; 52:2776–2781. 8. Bolan RK, Beymer M, Klausner JD, et al. Doxycycline prophylaxis for syphilis in a persistently high risk HIV infected population. Sex Transm Infect 2013; 89 (Suppl. 1):A283–A1283. 9. Tipple C, Taylor GP. Syphilis testing, typing, and treatment follow-up: a new era for an old disease. Curr Opin Infect Dis 2015; 28:53–60. 10. Casal C, Arau´jo Eda C, Corvelo TC. Risk factors and pregnancy outcomes in women with syphilis diagnosed using a molecular approach. Sex Transm Infect 2013; 89:257–261.
11. Marra CM, Sahi SK, Tantalo LC, et al. Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis 2010; 202:1380–1388. 12. Tipple C, Hodson L, Jones R, et al. O05.2 Measuring syphilis: quantitative PCR can be used to monitor treatment response. Vienna, Austria: International Society for STD Research; 2013. 13. de Vries HJC, Schim van der Loeff MF, Bruisten SM. High-resolution typing of Chlamydia trachomatis: epidemiological and clinical uses. Curr Opin Infect Dis 2015; 28:61–71. 14. Christerson L, Bom RJ, Bruisten SM, et al. Chlamydia trachomatis strains show specific clustering for men who have sex with men compared to heterosexual populations in Sweden, the Netherlands, and the United States. J Clin Microbiol 2012; 50:3548–3555. 15. Somboonna N, Wan R, Ojcius DM, et al. Hypervirulent Chlamydia trachomatis clinical strain is a recombinant between lymphogranuloma venereum (L(2)) and D lineages. MBio 2011; 2:e00045-11. 16. Rodriguez-Dominguez M, Puerta T, Menendez B, et al. Clinical and epidemiological characterization of a lymphogranuloma venereum outbreak in Madrid, Spain: co-circulation of two variants. Clin Microbiol Infect 2014; 20:219–225. 17. De Vrieze NH, van Rooijen M, Schim van der Loeff MF, de Vries HJ. Anorectal and inguinal lymphogranuloma venereum among men who have sex with men in Amsterdam, the Netherlands: trends over time, symptomatology and concurrent infections. Sex Transm Infect 2013; 89:548–552. 18. Hirt RP, Sherrard J. Trichomonas vaginalis origins, molecular pathobiology and clinical considerations. Curr Opin Infect Dis 2015; 28:72–79. 19. Twu O, Dessi D, Vu A, et al. Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses. Proc Natl Acad Sci USA 2014; 111:8179–8184. 20. Fiori PL, Diaz N, Cocco AR, et al. Association of Trichomonas vaginalis with its symbiont Mycoplasma hominis synergistically upregulates the in vitro proinflammatory response of human monocytes. Sex Transm Infect 2013; 89: 449–454. 21. Fettweis JM, Serrano MG, Huang B, et al. An emerging Mycoplasma associated with trichomoniasis, vaginal infection and disease. PLoS One 2014; 9:e110943. 22. Ross JDC. Nucleic acid contamination in sexual health clinics. Curr Opin Infect Dis 2015; 28:80–82. 23. Lewis N, Dube G, Carter C, et al. Chlamydia and gonorrhoea contamination of clinic surfaces. Sex Transm Infect 2012; 88:418–421. 24. Chan SY, Jose S, King R, et al. How likely is environmental or patient crosscontamination of Chlamydia trachomatis DNA to lead to false positive results in patients attending our clinic? Sex Transm Infect 2013; 89:105–107. 25. Rogstad KE, Tunbridge A. Ebola virus as a sexually transmitted infection. Curr Opin Infect Dis 2015; 28:83–85.
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
43
The molecular biology–clinical interface of sexually transmitted infections for evaluating pathophysiology, transmission, resistance and treatment Karen E. Rogstad
This edition concentrates on the interplay between new molecular technology and what we can learn about transmission, pathogenicity, emergence of resistance and treatment programmes from ‘old’ sexually transmitted infections (STIs) and potential new ones such as Ebola virus. The authors chosen have recently researched these areas themselves and consider their own work and that of others, which has emerged in their field. Two linked articles consider syphilis in which, since the advent of penicillin as a treatment, there has been little progress in alternative treatments and there is ongoing controversy about optimal management, particularly in the context of dual infection with HIV. Lawrence et al. [1] set the scene by considering the diversity in recommended treatment options and how practice remains different to guidelines, with many U.S. and UK physicians giving additional treatment to those dually infected with HIV [2,3]. They discuss that previous systematic reviews, on which guidelines are based, are at odds with the more recent evidence that rates of neurosyphilis may be higher in HIV patients. This is particularly relevant as new data shows poorer neurocognitive outcomes in patients who have had syphilis, as measured by a higher Global Deficit Score and impaired learning [4,5]. Neurosyphilis is more likely to be diagnosed if a lumbar puncture is undertaken, and in the presence of laboratory indicators, irrespective of the symptoms, the authors suggest there should be a low threshold for performing a lumbar puncture, particularly with a CD4 count of under 350 cells/mm or a venereal disease research laboratory (VDRL) titre of more than 1 : 32. The very high serological cure rates in the author’s unit, where a neuropenetrative regimen of procaine penicillin is always used, add further weight to the evidence for treating those who are coinfected differently [6]. Regarding alternative treatments, the UK guidelines of azithromycin as an alternative are at odds with the international ones,
and data just published from Australia needs to be considered which shows that the A2058G mutation, conferring macrolide resistance, is as high as 84.4% and more common in MSM [7]. An additional study of particular interest is the prevention of syphilis through the use of doxycycline prophylaxis, which requires larger studies to be performed to see whether this approach should be recommended [8]. Tipple and Taylor [9], in a complementary paper, consider new data, which may assist in answering these controversies in the future. Some of the problems identified by Lawrence et al. [1] regarding identifying disease stage, monitoring response to therapy and predicting who will develop complications may be solved through the use of PCR technology. PCR sensitivity for genital and anal chancres is high, and may also be useful in blood sampling with highest sensitivities for congenital and secondary disease. Quantitative PCR may also allow disease stage to be identified as there is a link between disease stage and viral load. Detection of syphilis bacteraemia can predict not only the disease stage, but also the risk of adverse neonatal outcomes, with 80% of mothers with early disease who delivered babies with congenital syphilis being PCR positive [10]. Syphilis bacteraemia may also be helpful in identifying early syphilis when serological response is delayed. Genotyping may have a role in addressing treatment issues, as an initial study by Marra [11] found
HIV and Sexual Health, Sheffield Teaching Hospitals NHS Foundation Trust and Undergraduate Dean, University of Sheffield School of Medicine, Royal Hallamshire Hospital, Sheffield, UK Correspondence to Karen E. Rogstad, HIV and Sexual Health, Sheffield Teaching Hospitals NHS Foundation Trust and Undergraduate Dean, University of Sheffield School of Medicine, Royal Hallamshire Hospital, Glossop Road, Sheffield, S10 2JF, UK. Tel: +44 114 271 1900; e-mail: [email protected] Curr Opin Infect Dis 2015, 28:41–43 DOI:10.1097/QCO.0000000000000134
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Sexually transmitted diseases
that the newly identified 14d/f subtype was associated with neurosyphilis. The issue of determining whether a cure rate has been achieved, which is currently based on the changes to serological titres, may in the future be assisted by PCR, with a preliminary study monitoring bacterial clearance after treatment, finding that the average time for clearance is 32 h, with cure being identified at 1 month [12]. Advances in molecular typing methods are revolutionizing our understanding of transmission networks and disease management for Chlamydia trachomatis serovars. In their study, Vries et al. [13] describe how multilocus sequence typing (MLST) methodologies are superior to older methods such as serological or ompA typing. As a result, cluster and network analysis can be improved. It has enabled the identification of two genetically distinct C. trachomatis populations in heterosexuals (men and women) and MSMs, with little overlap between the two. Interestingly, using MLST, there is no difference between strains in MSM in the USA, Sweden, and the Netherlands, but there is in heterosexuals [14]. New variants of C. trachomatis lymphogranuloma venereum (LGV) serovars have been recently described. These L2c (which is a recombinant of L2 and D) and L2/L2f types appear to have different pathophysiological and clinical properties [15,16]. On a more practical note, LGV typing methodology allows for the differentiation of LGV and non-LGV genovars. Currently, this is usually only performed on MSM with anal symptoms, but 27% of men in Amsterdam were asymptomatic [17], indicating that all rectal C. trachomatis-positive samples on MSM should have LGV typing performed. Molecular high-resolution typing has also enabled the identification of LGV in specific high-risk communities, which can be used to target interventions. It can also be an important surveillance tool in identifying new variant disease, such as that which occurred in Sweden. One of the most neglected STIs in terms of research and academic interest has been that of Trichomonas vaginalis. Hirt and Sherrard [18] use a molecular pathobiology approach to offer new insights into this organism and to correlate this with the potential for its use in the future in a clinical setting. Molecular phylogeny has revealed a close association between human T. vaginalis and that in birds, and that the two human Trichomonas types T. vaginalis (genital) and T. tenax (oral) have more in common with avian T. vaginalis species than they do to each other. The study of T. vaginalis proteomics is allowing us to gain an understanding of the changes that occur when T. vaginalis alters from a flagellated organism to one that is amoeboid and binds to, and migrates through, human tissues. Exosomal protein identification allows for the potential for vaccine 42
www.co-infectiousdiseases.com
development. They also postulate that T. vaginalis macrophage inhibitory factor may have a role in the development of prostatic cancer and explain the science behind this [19]. The ability of T. vaginalis to upgrade the macrophage proinflammatory response is associated with M. hominis [20] in vitro, and a new species of Mycoplasma has just been identified, which is strongly associated with T. vaginalis infection [21], suggesting there may be different T. vaginalis–Mycoplasma consortia that have clinical relevance. The potential that the proinflammatory response associated with treatment of T. vaginalis with metronidazole may be implicated in adverse pregnancy is raised. Advances in the clinical management of T. vaginalis, in contrast, are less impressive, including for resistant T. vaginalis, which is estimated currently at 5% in the USA. In contrast, molecular testing methods are described, which have improved detection. The problems created by new methodologies are discussed by Ross [22], who considers the potential for nucleic acid amplification test (NAAT) methodology to result in false-positive results in the clinical setting because of contamination of surfaces in healthcare facilities. A study in a sexual health facility found multiple areas of RNA of Neisseria gonorrhoeae and C. trachomatis contamination, particularly in the patient toilet area [23]. However, the actual occurrence of contamination appears to be low as shown by processing ‘dummy’ urine samples [24]. It is also reassuring that attempts to culture NAAT-positive samples for N. gonorrhoeae or C. trachomatis have been negative [23], indicating that transmission of infection is extremely unlikely. In the final paper [25], I review the potential for Ebola to be an STI, which is suggested by NAAT methodology. In fact, despite the theoretical risk, there has been no published case of sexual transmission of this so far. Molecular data theoretically implies that the risk early in the disease may be greater from oral contact as a result of an early rise in salivary samples, whereas semen samples rise later in the course of the illness, when victims are likely to be too sick for sexual intercourse. In survivors, however, there is a persistence of RNA in faecal and stool samples for 29 days, the vagina for 33 days, and semen for 3 months or longer (http://www.cdc.gov/ vhf/ebola/transmission/human-transmission.html; last accessed 2 November 2014). Therefore, despite no confirmed transmissions, the WHO and the U.S. Centers for Disease Control and Prevention recommend avoidance of sexual intercourse including oral, or if this cannot be avoided, condom use, for up to 3 months after recovery (http://www.cdc.gov/ vhf/ebola/transmission/index.html?s_cid=cs_3923; last accessed 2 November 2014). Volume 28 Number 1 February 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Clinical interface of sexually transmitted infections Rogstad
Acknowledgements None. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.
REFERENCES 1. Lawrence D, Cresswell F, Whetham J, Fisher M. Syphilis treatment in the presence of HIV: the debate goes on. Curr Opin Infect Dis 2015; 28:44–52. 2. Dowell D, Polgreen PM, Beekmann SE, et al. Dilemmas in the management of syphilis: a survey of infectious diseases experts. Clin Infect Dis 2009; 49:1526–1529. 3. Fisher M. How to manage syphilis in HIV. In: Presented at the 14th European AIDS Conference; Brussels, Belgium; 2013. 4. Marra CM, Deutsch R, Collier AC, et al. Neurocognitive impairment in HIVinfected individuals with previous syphilis. Int J STD AIDS 2013; 24:351– 355. 5. Vera J, Garvey L, Tipple C, et al. A past history of syphilis is associated with poorer performance in the cognitive domains of memory and learning in HIVinfected subjects on stable cart. HIV Med 2012; 13:51. 6. Warwick Z, Dean G, Fisher M. Should syphilis be treated differently in HIVpositive and HIV-negative individuals? Treatment outcomes at a university hospital, Brighton, UK. Int J STD AIDS 2009; 20:229–230. 7. Read P, Jeoffreys N, Tagg K, et al. Azithromycin-resistant syphilis-causing strains in Sydney, Australia: prevalence and risk factors. J Clin Microbiol 2014; 52:2776–2781. 8. Bolan RK, Beymer M, Klausner JD, et al. Doxycycline prophylaxis for syphilis in a persistently high risk HIV infected population. Sex Transm Infect 2013; 89 (Suppl. 1):A283–A1283. 9. Tipple C, Taylor GP. Syphilis testing, typing, and treatment follow-up: a new era for an old disease. Curr Opin Infect Dis 2015; 28:53–60. 10. Casal C, Arau´jo Eda C, Corvelo TC. Risk factors and pregnancy outcomes in women with syphilis diagnosed using a molecular approach. Sex Transm Infect 2013; 89:257–261.
11. Marra CM, Sahi SK, Tantalo LC, et al. Enhanced molecular typing of Treponema pallidum: geographical distribution of strain types and association with neurosyphilis. J Infect Dis 2010; 202:1380–1388. 12. Tipple C, Hodson L, Jones R, et al. O05.2 Measuring syphilis: quantitative PCR can be used to monitor treatment response. Vienna, Austria: International Society for STD Research; 2013. 13. de Vries HJC, Schim van der Loeff MF, Bruisten SM. High-resolution typing of Chlamydia trachomatis: epidemiological and clinical uses. Curr Opin Infect Dis 2015; 28:61–71. 14. Christerson L, Bom RJ, Bruisten SM, et al. Chlamydia trachomatis strains show specific clustering for men who have sex with men compared to heterosexual populations in Sweden, the Netherlands, and the United States. J Clin Microbiol 2012; 50:3548–3555. 15. Somboonna N, Wan R, Ojcius DM, et al. Hypervirulent Chlamydia trachomatis clinical strain is a recombinant between lymphogranuloma venereum (L(2)) and D lineages. MBio 2011; 2:e00045-11. 16. Rodriguez-Dominguez M, Puerta T, Menendez B, et al. Clinical and epidemiological characterization of a lymphogranuloma venereum outbreak in Madrid, Spain: co-circulation of two variants. Clin Microbiol Infect 2014; 20:219–225. 17. De Vrieze NH, van Rooijen M, Schim van der Loeff MF, de Vries HJ. Anorectal and inguinal lymphogranuloma venereum among men who have sex with men in Amsterdam, the Netherlands: trends over time, symptomatology and concurrent infections. Sex Transm Infect 2013; 89:548–552. 18. Hirt RP, Sherrard J. Trichomonas vaginalis origins, molecular pathobiology and clinical considerations. Curr Opin Infect Dis 2015; 28:72–79. 19. Twu O, Dessi D, Vu A, et al. Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses. Proc Natl Acad Sci USA 2014; 111:8179–8184. 20. Fiori PL, Diaz N, Cocco AR, et al. Association of Trichomonas vaginalis with its symbiont Mycoplasma hominis synergistically upregulates the in vitro proinflammatory response of human monocytes. Sex Transm Infect 2013; 89: 449–454. 21. Fettweis JM, Serrano MG, Huang B, et al. An emerging Mycoplasma associated with trichomoniasis, vaginal infection and disease. PLoS One 2014; 9:e110943. 22. Ross JDC. Nucleic acid contamination in sexual health clinics. Curr Opin Infect Dis 2015; 28:80–82. 23. Lewis N, Dube G, Carter C, et al. Chlamydia and gonorrhoea contamination of clinic surfaces. Sex Transm Infect 2012; 88:418–421. 24. Chan SY, Jose S, King R, et al. How likely is environmental or patient crosscontamination of Chlamydia trachomatis DNA to lead to false positive results in patients attending our clinic? Sex Transm Infect 2013; 89:105–107. 25. Rogstad KE, Tunbridge A. Ebola virus as a sexually transmitted infection. Curr Opin Infect Dis 2015; 28:83–85.
0951-7375 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.co-infectiousdiseases.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
43
