Хламидийная инфекция (ХИ) продолжает оставаться одной из наиболее распространенных инфекций, передаваемых половым путем, в гинекологической практике. Аналитические данные свидетельствуют о росте заболеваемости ХИ, несмотря на доступность диагностических тестов и проводимый скрининг. Фундаментальные исследования последних лет позволили прояснить вопросы восприимчивости к ХИ, а также установить роль генных мутаций в возникновении долгосрочных осложнений у женщин.
Совершенствование методов амплификации нуклеиновых кислот (МАНК) привело к возможности забора материала самими пациентами, что в ближайшие годы может полностью поменять существующую систему скрининга. Российские МАНК, оставаясь недорогими, соответствуют коммерческим зарубежным тест-системам по чувствительности и специфичности. Мутации в локусах плазмидной ДНК хламидий способны приводить к ложноотрицательным результатам МАНК.
Азитромицин благодаря уникальным фармакодинамическим свойствам наиболее часто используется в лечении ХИ в Российской Федерации и за рубежом. Препарат доказал свою безопасность и эффективность при беременности. Данные посттерапевтического скрининга свидетельствуют о необходимости увеличения дозы препарата. Клинические исследования подтверждают его эффективность при воспалительных заболеваниях органов малого таза.
Chlamydia infection (CI) continues to be one of the most common sexually transmitted infections in the gynecological practice. The analytical data indicates an increase in the incidence of CI despite the availability of diagnostic tests and screenings. Fundamental studies in recent years have allowed to clarify the problems of susceptibility to CI, as well as to establish the role of gene mutations in long term complications emergence in women.
Nucleic acid amplification methods (SIA) improvement of has led to the possibility of collecting the material by patients themselves which, in the coming years can completely change the current system of screening. Russian IASC by remaining inexpensive are still able to match the commercial demands of the foreign test system in terms of sensitivity and specificity. Mutations in the loci of plasmid DNA of Chlamydia can lead to false-negative results of the IASC.
Azithromycin, due to its unique pharmacodynamic properties, is most commonly used in the treatment of CI in Russia and abroad. The drug proved to be safe and effective in pregnancy. The results of post-therapeutic screenings indicate the need of increasing the drug dose. Clinical studies have confirmed its efficacy in the PID.
1. Lanjouw E, Ossewaarde JM, Stary A et al. 2010 European guideline for the management of Chlamydia trachomatis infections. Int J STD AIDS 2010; 21 (11): 729–37.
2. Agrawal T, Vats V, Salhan S, Mittal A. Mucosal and peripheral immune responses to chlamydial heat shock proteins in women infected with Chlamydia trachomatis. Clin Exp Immunol 2007; 148: 461–8.
3. Batteiger BE, Tu W, Ofner S et al. Repeated Chlamydia trachomatis genital infections in adolescent women. J Infect Dis 2010; 201 (1): 42–51.
Doi: 10.1086/648734.
4. Bhengraj AR, Vardhan H, Srivastava P et al. Decreased susceptibility to azithromycin and doxycycline in clinical isolates of Chlamydia trachomatis obtained from recurrently infected female patients in India. Chemotherapy 2010; 56 (5): 371–7.
5. Bragina EY, Gomberg MA, Dmitriev GA. Electron microscopic evidence of persistent chlamydial infection following treatment. J Eur Acad Dermatol Venerеol 2001; 15 (5): 405–9.
6. European center for diseases prevention and control. Ann Epidemiol Report 2012. http://www.ecdc.europa.eu/en/publications/Publications/Annual-Epidemiological-Report-2012.pdf.
7. Freeman AH, Bernstein KT, Kohn RP et al. Evaluation of self-collected versus clinician-collected swabs for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae pharyngeal infection among men who have sex with men. Sex Transm Dis 2011; 38 (11): 1036–9.
8. Geisler WM, Lensing SY, Press CG. Spontaneous Resolution of Genital Chlamydia trachomatis Infection in Women and Protection from Reinfection. J Infect Dis 2013.
9. Geisler WM, Wang C, Morrison SG et al. The natural history of untreated Chlamydia trachomatis infection in the interval between screening and returning for treatment. Sex Transm Dis 2008; 35: 119–23.
10. Geisler WM. Duration of untreated, uncomplicated Chlamydia trachomatis genital infection and factors associated with chlamydia resolution: a review of human studies. J Infect Dis 2010; 201 (Suppl. 2): S104–13.
11. Gomberg MA. Combined treatment of persisting urogenital chlamydia infection with sumamed and interferon alfa. Antibiot Khimioter 2002; 47 (5): 12–5.
12. Gomes JP, Borrego MJ, Atik B et al. Correlating Chlamydia trachomatis infectious load with urogenital ecological success and disease pathogenesis. Microbes Infect 2006; 8: 16–26.
13. Öhman H, Tiitinen A, Halttunen M et al. Cytokine Polymorphisms and Severity of Tubal Damage in Women with Chlamydia-Associated Infertility. University of Helsinki, Finland. J Infect Dis 2009; 199: 1353–9.
14. Haddix AC, Hillis SD, Kassler WJ. The cost effectiveness of azithromycin for Chlamydia trachomatis infections in women. Sex Transm Dis 1995; 22 (5): 274–80.
15. Handsfield H. Questioning Azithromycin for Chlamydial Infection. Sex Transm Dis 2011; 38 (11): 1028–9.
16. Hartog JE, Ouburg S, Land JA. Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women? BMC Infect Dis 2006; 6: 122.
17. Heal C, Cheffins T, Larkins S et al. Genital Chlamydia trachomatis infection – a study of general practice management in northern Queensland. Aust Fam Physician 2012; 41 (7): 519–21.
18. Horner PJ, Crowley T, Leece J et al. Chlamydia trachomatis detection and the menstrual cycle. Lancet 1998; 351: 341–2.
19. Horner PJ. Azithromycin antimicrobial resistance and genital Chlamydia trachomatis infection: duration of therapy may be the key to improving efficacy. Sex Transm Infect 2012; 88 (3): 154–6.
20. Horner P. The case for further treatment studies of uncomplicated genital Chlamydia trachomatis infection. Sex Transm Infect 2006; 82 (4): 340–3.
21. http://clinicaltrials.gov/show/NCT00980148.
22. http://www.mednet.ru/ images/stories/files /statistika /dermatovenerologicheskaya_ sluzhba/2008 /zabolevaemost_ hlamidiinoi_ infekciei_v_subektah _rf_2007.pdf.
23. Jensen IP, Thorsen P, Moller BR. Sensitivity of ligase chain reaction assay of urine from pregnant women for Chlamydia trachomatis. Lancet 1997; 349: 329–30.
24. Joyner JL, Douglas JM, Foster M et al. Persistence of Chlamydia trachomatis infection detected by polymerase chain reaction in untreated patients. Sex Transm Dis 2002; 29: 196–200.
25. Land JA, Van Bergen JE, Morré SA. Epidemiology of Chlamydia trachomatis infection in women and the cost-effectiveness of screening. Hum Reprod Update 2010; 16 (2): 189–204.
26. Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Sex Transm Dis 2002; 29: 497–502.
27. Lea AP, Lamb HM. Azithromycin. A pharmacoeconomic review of its use as a single-dose regimen in the treatment of uncomplicated urogenital Chlamydia trachomatis infections in women. Pharmacoeconomics 1997; 12 (5): 596–611.
28. Magid D, Douglas JM, Schwartz JS. Doxycycline compared with azithromycin for treating women with genital Chlamydia trachomatis infections: an incremental cost-effectiveness analysis. Ann Intern Med 1996; 124 (4): 389–99.
29. Michel CE, Sonnex C, Carne CA et al. Chlamydia trachomatis load at matched anatomic sites: implications for screening strategies. J Clin Microbiol 2007; 45: 1395–402.
30. Molano M, Meijer CJ, Weiderpass E et al. The natural course of Chlamydia trachomatis infection in asymptomatic Colombian women: a 5-year follow-up study. J Infect Dis 2005; 191: 907–16.
31. Moller JK, Andersen B, Olesen F et al. Impact of menstrual cycle on the diagnostic performance of LCR, TMA, and PCE for detection of Chlamydia trachomatis in home obtained and mailed vaginal flush and urine samples. Sex Transm Infect 1999; 75: 228–30.
32. Morré SA, van den Brule AJ, Rozendaal L et al. The natural course of asymptomatic Chlamydia trachomatis infections: 45% clearance and no development of clinical PID after one-year follow-up. Int J STD AIDS 2002; 13 (Suppl. 2): 12–8.
33. Paavonen J. Chlamydia trachomatis infections of the female genital tract: state of the art. Ann Med 2012; 44 (1): 18–28. Doi: 10.3109/07853890.2010.546365. Epub 2011.
34. Renault CA, Israelski DM, Levy V et al. Time to clearance of Chlamydia trachomatis ribosomal RNA in women treated for chlamydial infection. J Sex Health 2011; 8 (1): 69–73.
35. Ripa T, Nilsson PA. A Chlamydia trachomatis strain with a 377-bp deletion in the cryptic plasmid causing false-negative nucleic acid amplification tests. Sex Transm Dis 2007; 34 (5): 255–6.
36. Rogers SM, Miller WC, Turner CF et al. Concordance of Chlamydia trachomatis infections within sexual partnerships. Sex Transm Infect 2008; 84: 23–8.
37. Santos F, Sheehy O, Perreault S et al. Trends in anti-infective drugs use in pregnancy. J Popul Ther Clin Pharmacol 2012; 19 (3): e460-5.
38. Savaris RF, Teixeira LM, Torres TG et al. Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol 2007; 110 (1): 53–60.
39. Schachter J, Chernesky MA, Willis DE et al. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicenter evaluation of the APTIMA assays for both infections. Sex Transm Dis 2005; 32 (12): 725–8.
40. Schwebke JR, Rompalo A, Taylor S et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens – a randomized clinical trial. Clin Infect Dis 2011; 52 (2): 163–70. Doi: 10.1093/cid/ciq074.
41. Seña AC, Lensing S, Rompalo A et al. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonasvaginalis infections in men with nongonococcal urethritis: predictors and persistence after therapy. J Infect Dis 2012; 206 (3): 357-65. Doi: 10.1093/infdis/jis356. Epub 2012.
42. Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. Centers for Disease Control and Prevention (CDC). MMWR Recomm Rep 2010; 59 (RR-12): 1–110.
43. Sheffield JS, Andrews WW, Klebanoff MA et al. Spontaneous resolution of asymptomatic Chlamydia trachomatis in pregnancy. Obstet Gynecol 2005; 105: 557–62.
44. Shima K, Klinger M, Solbach W et al. Activity of first choice antimicrobials against IFN-γ treated Chlamydia trachomatis differs in hypoxia. Antimicrob Agents Chemother 2013.
45. Shipitsyna E, Zolotoverkhaya E, Agné-Stadling I et al. First evaluation of six nucleic acid amplification tests widely used in the diagnosis of Chlamydia trachomatis in Russia. J Eur Acad Dermatol Venereol 2009; 23 (3): 268–76. Doi: 10.1111/j.1468-3083.2008.03038.x. Epub 2008.
46. Stamm WE, Batteiger BE, McCormack WM et al. A randomized, double-blind study comparing single-dose rifalazil with single-dose azithromycin for the empirical treatment of nongonococcal urethritis in men. Sex Transm Dis 2007; 34 (8): 545–52.
47. Van Valkengoed IG, Morré SA, van den Brule AJ et al. Follow-up, treatment, and reinfection rates among asymptomatic Chlamydia trachomatis cases in general practice. Br J Gen Pract 2002; 52: 623–7.
48. Wiggins R, Graf S, Low N et al. Chlamydia Screening Studies (ClaSS) Study Group. Real-time quantitative PCR to determine chlamydial load in men and women in a community setting. J Clin Microbiol 2009; 47: 1824–9.
49. Чеботарев В.В., Чеботарева Н.В., Касымов Б.М., Гомберг М.А. Отдаленные результаты лечения больных осложненными формами урогенитального хламидиоза азитромицином по схеме 1-7-14. ИППП 3, 2003.
50. Pitsouni E, Iavazzo C, Athanasiou S et al. Single-dose azithromycin versus erythromycin or amoxicillin for Chlamydia trachomatis infection during pregnancy: a meta-analysis of randomised controlled trials. Int J Antimicrob Agents 2007; 30 (3): 213–21. Epub 2007.
________________________________________________
1. Lanjouw E, Ossewaarde JM, Stary A et al. 2010 European guideline for the management of Chlamydia trachomatis infections. Int J STD AIDS 2010; 21 (11): 729–37.
2. Agrawal T, Vats V, Salhan S, Mittal A. Mucosal and peripheral immune responses to chlamydial heat shock proteins in women infected with Chlamydia trachomatis. Clin Exp Immunol 2007; 148: 461–8.
3. Batteiger BE, Tu W, Ofner S et al. Repeated Chlamydia trachomatis genital infections in adolescent women. J Infect Dis 2010; 201 (1): 42–51.
Doi: 10.1086/648734.
4. Bhengraj AR, Vardhan H, Srivastava P et al. Decreased susceptibility to azithromycin and doxycycline in clinical isolates of Chlamydia trachomatis obtained from recurrently infected female patients in India. Chemotherapy 2010; 56 (5): 371–7.
5. Bragina EY, Gomberg MA, Dmitriev GA. Electron microscopic evidence of persistent chlamydial infection following treatment. J Eur Acad Dermatol Venerеol 2001; 15 (5): 405–9.
6. European center for diseases prevention and control. Ann Epidemiol Report 2012. http://www.ecdc.europa.eu/en/publications/Publications/Annual-Epidemiological-Report-2012.pdf.
7. Freeman AH, Bernstein KT, Kohn RP et al. Evaluation of self-collected versus clinician-collected swabs for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae pharyngeal infection among men who have sex with men. Sex Transm Dis 2011; 38 (11): 1036–9.
8. Geisler WM, Lensing SY, Press CG. Spontaneous Resolution of Genital Chlamydia trachomatis Infection in Women and Protection from Reinfection. J Infect Dis 2013.
9. Geisler WM, Wang C, Morrison SG et al. The natural history of untreated Chlamydia trachomatis infection in the interval between screening and returning for treatment. Sex Transm Dis 2008; 35: 119–23.
10. Geisler WM. Duration of untreated, uncomplicated Chlamydia trachomatis genital infection and factors associated with chlamydia resolution: a review of human studies. J Infect Dis 2010; 201 (Suppl. 2): S104–13.
11. Gomberg MA. Combined treatment of persisting urogenital chlamydia infection with sumamed and interferon alfa. Antibiot Khimioter 2002; 47 (5): 12–5.
12. Gomes JP, Borrego MJ, Atik B et al. Correlating Chlamydia trachomatis infectious load with urogenital ecological success and disease pathogenesis. Microbes Infect 2006; 8: 16–26.
13. Öhman H, Tiitinen A, Halttunen M et al. Cytokine Polymorphisms and Severity of Tubal Damage in Women with Chlamydia-Associated Infertility. University of Helsinki, Finland. J Infect Dis 2009; 199: 1353–9.
14. Haddix AC, Hillis SD, Kassler WJ. The cost effectiveness of azithromycin for Chlamydia trachomatis infections in women. Sex Transm Dis 1995; 22 (5): 274–80.
15. Handsfield H. Questioning Azithromycin for Chlamydial Infection. Sex Transm Dis 2011; 38 (11): 1028–9.
16. Hartog JE, Ouburg S, Land JA. Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women? BMC Infect Dis 2006; 6: 122.
17. Heal C, Cheffins T, Larkins S et al. Genital Chlamydia trachomatis infection – a study of general practice management in northern Queensland. Aust Fam Physician 2012; 41 (7): 519–21.
18. Horner PJ, Crowley T, Leece J et al. Chlamydia trachomatis detection and the menstrual cycle. Lancet 1998; 351: 341–2.
19. Horner PJ. Azithromycin antimicrobial resistance and genital Chlamydia trachomatis infection: duration of therapy may be the key to improving efficacy. Sex Transm Infect 2012; 88 (3): 154–6.
20. Horner P. The case for further treatment studies of uncomplicated genital Chlamydia trachomatis infection. Sex Transm Infect 2006; 82 (4): 340–3.
21. http://clinicaltrials.gov/show/NCT00980148.
22. http://www.mednet.ru/ images/stories/files /statistika /dermatovenerologicheskaya_ sluzhba/2008 /zabolevaemost_ hlamidiinoi_ infekciei_v_subektah _rf_2007.pdf.
23. Jensen IP, Thorsen P, Moller BR. Sensitivity of ligase chain reaction assay of urine from pregnant women for Chlamydia trachomatis. Lancet 1997; 349: 329–30.
24. Joyner JL, Douglas JM, Foster M et al. Persistence of Chlamydia trachomatis infection detected by polymerase chain reaction in untreated patients. Sex Transm Dis 2002; 29: 196–200.
25. Land JA, Van Bergen JE, Morré SA. Epidemiology of Chlamydia trachomatis infection in women and the cost-effectiveness of screening. Hum Reprod Update 2010; 16 (2): 189–204.
26. Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Sex Transm Dis 2002; 29: 497–502.
27. Lea AP, Lamb HM. Azithromycin. A pharmacoeconomic review of its use as a single-dose regimen in the treatment of uncomplicated urogenital Chlamydia trachomatis infections in women. Pharmacoeconomics 1997; 12 (5): 596–611.
28. Magid D, Douglas JM, Schwartz JS. Doxycycline compared with azithromycin for treating women with genital Chlamydia trachomatis infections: an incremental cost-effectiveness analysis. Ann Intern Med 1996; 124 (4): 389–99.
29. Michel CE, Sonnex C, Carne CA et al. Chlamydia trachomatis load at matched anatomic sites: implications for screening strategies. J Clin Microbiol 2007; 45: 1395–402.
30. Molano M, Meijer CJ, Weiderpass E et al. The natural course of Chlamydia trachomatis infection in asymptomatic Colombian women: a 5-year follow-up study. J Infect Dis 2005; 191: 907–16.
31. Moller JK, Andersen B, Olesen F et al. Impact of menstrual cycle on the diagnostic performance of LCR, TMA, and PCE for detection of Chlamydia trachomatis in home obtained and mailed vaginal flush and urine samples. Sex Transm Infect 1999; 75: 228–30.
32. Morré SA, van den Brule AJ, Rozendaal L et al. The natural course of asymptomatic Chlamydia trachomatis infections: 45% clearance and no development of clinical PID after one-year follow-up. Int J STD AIDS 2002; 13 (Suppl. 2): 12–8.
33. Paavonen J. Chlamydia trachomatis infections of the female genital tract: state of the art. Ann Med 2012; 44 (1): 18–28. Doi: 10.3109/07853890.2010.546365. Epub 2011.
34. Renault CA, Israelski DM, Levy V et al. Time to clearance of Chlamydia trachomatis ribosomal RNA in women treated for chlamydial infection. J Sex Health 2011; 8 (1): 69–73.
35. Ripa T, Nilsson PA. A Chlamydia trachomatis strain with a 377-bp deletion in the cryptic plasmid causing false-negative nucleic acid amplification tests. Sex Transm Dis 2007; 34 (5): 255–6.
36. Rogers SM, Miller WC, Turner CF et al. Concordance of Chlamydia trachomatis infections within sexual partnerships. Sex Transm Infect 2008; 84: 23–8.
37. Santos F, Sheehy O, Perreault S et al. Trends in anti-infective drugs use in pregnancy. J Popul Ther Clin Pharmacol 2012; 19 (3): e460-5.
38. Savaris RF, Teixeira LM, Torres TG et al. Comparing ceftriaxone plus azithromycin or doxycycline for pelvic inflammatory disease: a randomized controlled trial. Obstet Gynecol 2007; 110 (1): 53–60.
39. Schachter J, Chernesky MA, Willis DE et al. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicenter evaluation of the APTIMA assays for both infections. Sex Transm Dis 2005; 32 (12): 725–8.
40. Schwebke JR, Rompalo A, Taylor S et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens – a randomized clinical trial. Clin Infect Dis 2011; 52 (2): 163–70. Doi: 10.1093/cid/ciq074.
41. Seña AC, Lensing S, Rompalo A et al. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonasvaginalis infections in men with nongonococcal urethritis: predictors and persistence after therapy. J Infect Dis 2012; 206 (3): 357-65. Doi: 10.1093/infdis/jis356. Epub 2012.
42. Workowski KA, Berman S. Sexually transmitted diseases treatment guidelines, 2010. Centers for Disease Control and Prevention (CDC). MMWR Recomm Rep 2010; 59 (RR-12): 1–110.
43. Sheffield JS, Andrews WW, Klebanoff MA et al. Spontaneous resolution of asymptomatic Chlamydia trachomatis in pregnancy. Obstet Gynecol 2005; 105: 557–62.
44. Shima K, Klinger M, Solbach W et al. Activity of first choice antimicrobials against IFN-γ treated Chlamydia trachomatis differs in hypoxia. Antimicrob Agents Chemother 2013.
45. Shipitsyna E, Zolotoverkhaya E, Agné-Stadling I et al. First evaluation of six nucleic acid amplification tests widely used in the diagnosis of Chlamydia trachomatis in Russia. J Eur Acad Dermatol Venereol 2009; 23 (3): 268–76. Doi: 10.1111/j.1468-3083.2008.03038.x. Epub 2008.
46. Stamm WE, Batteiger BE, McCormack WM et al. A randomized, double-blind study comparing single-dose rifalazil with single-dose azithromycin for the empirical treatment of nongonococcal urethritis in men. Sex Transm Dis 2007; 34 (8): 545–52.
47. Van Valkengoed IG, Morré SA, van den Brule AJ et al. Follow-up, treatment, and reinfection rates among asymptomatic Chlamydia trachomatis cases in general practice. Br J Gen Pract 2002; 52: 623–7.
48. Wiggins R, Graf S, Low N et al. Chlamydia Screening Studies (ClaSS) Study Group. Real-time quantitative PCR to determine chlamydial load in men and women in a community setting. J Clin Microbiol 2009; 47: 1824–9.
49. Чеботарев В.В., Чеботарева Н.В., Касымов Б.М., Гомберг М.А. Отдаленные результаты лечения больных осложненными формами урогенитального хламидиоза азитромицином по схеме 1-7-14. ИППП 3, 2003.
50. Pitsouni E, Iavazzo C, Athanasiou S et al. Single-dose azithromycin versus erythromycin or amoxicillin for Chlamydia trachomatis infection during pregnancy: a meta-analysis of randomised controlled trials. Int J Antimicrob Agents 2007; 30 (3): 213–21. Epub 2007.
Авторы
В.П.Ковалык
Федеральное медико-биологическое агентство РФ, Москва