- Email: [email protected]
Chlamydia trachomatis: time for screening?
EDITORIAL
10.1111/j.1469-0691.2005.01187.x
Chlamydia trachomatis: time for screening? A. Spiliopoulou1,2, V. Lakiotis1,3, A. Vittoraki1,4, D. Zavou1,5 and D. Mauri1,6 1
Panhellenic Association for Continual Medical Research (PACMeR), Public Health Task-Force, PACMeR, Microbiology, Patra, 3PACMeR, Public Health, Patra, 4PACMeR, Microbiology, Athens, 5 PACMeR, Gynecology and Woman Health, Alexandroupoli and 6PACMeR, Oncology, Ioannina, Greece 2
ABSTRACT Genital Chlamydia trachomatis infection is the leading cause of bacterial sexually transmitted disease in industrialised countries, particularly among young people. The consequences of chlamydial infection may involve urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, epididymitis and prostatitis. In addition, chlamydial infection increases the risk of acquisition of human immunodeficiency virus and has been associated with cervical cancer. Although screening programmes exist in a number of countries, the continuously increasing prevalence of chlamydial infections demonstrates the necessity for health authorities to establish effective screening policies, and the importance of defining a comprehensive European screening policy is emerging. Keywords
Chlamydia trachomatis, genital infection, screening programme, sexually transmitted disease
Clin Microbiol Infect 2005; 11: 687–689
Genital chlamydial infection is the leading cause of bacterial sexually transmitted disease (STD) in industrialised countries. The prevalence of lower genital tract infection with Chlamydia trachomatis is 2–25%, and is highest in young people [1]. Since 50–70% of genital infections are asymptomatic [2], and it is estimated that < 10% of prevalent infections are diagnosed [3], the morbidity and sequelae of the disease impact dramatically on the health of women. In the USA, there are an estimated 4 million new cases annually, and 50 000 women annually become infertile as a result of infection [2]. The WHO has estimated that there were 89 million new cases of genital chlamydial infections worldwide in 1995 [2] and 92 million in 1999 [4]. In England, the national screening pilot found that 13.8% of those aged < 16 years, 10.5% of those aged 16–19 years and 7.2% of those aged 20–24 years were infected, with > 60 000 cases reported from genitourinary medicine clinics in 2000 [3]. In Denmark, almost 13 000 infections were diagnosed in 1998 (75% among females), corresponding to a prevalence of 4.5% [5]. In Greece, the prevalence of the disease Corresponding author and reprint requests: D. Mauri, Oncology, Ioannina University Hospital, Ioannina, Greece E-mail: [email protected]
among women aged 18–35 years has been estimated at 7–10.6% [6,7]. According to the WHO, chlamydial prevalence rates among pregnant women in the 1990s were 2.7% in Italy, 3.9% in France, 4.9% in The Netherlands, 5.4% in Hungary, 6.2% in the UK, 6.7% in Denmark and 8% in Iceland [4]. In women, chlamydial infection can cause urethritis, cervicitis, pelvic inflammatory disease and, at a later stage, chronic pelvic pain, ectopic pregnancy and tubal factor infertility. Anti-chlamydial antibodies have been documented in 81.5% of infertile women with damaged fallopian tubes, and in 43.5% of infertile women with normal tubes [8]. Furthermore, when giving birth, an infected woman can pass the infection on to her child, who can develop neonatal conjunctivitis or pneumonia as a result. In men, chlamydial infection can cause urethritis, epididymitis and, probably, prostatitis and infertility. In both sexes, it can cause mucosal inflammation of the throat and rectum. Individuals with bacterial STDs, including chlamydial infection, are also at increased risk of acquiring human immunodeficiency virus. Strengthening the control of STDs through education and access to diagnosis and treatment has been reported to result in a 42% reduction in the
2005 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
688 Clinical Microbiology and Infection, Volume 11 Number 9, September 2005
incidence of human immunodeficiency virus infection over a 2-year period [2]. Current data [9–11] also indicate that cervical cancer is associated with infection with STD agents other than oncogenic human papillomavirus. C. trachomatis infection may induce chronic inflammation, epithelial damage, cytologic cervical atypia and cervical metaplasia, which in turn may increase the risk of cervical neoplasia. Serum chlamydial antibodies have been associated with a 1.8-fold increased risk of invasive squamous cervical cancer [11]. Enzyme immunoassay is the diagnostic method used most commonly, but has a lower detection limit of 10 000 elementary bodies, and thus lacks the sensitivity required for screening applications. Nucleic acid-based amplification tests using PCR, ligase chain reaction or transcription-mediated amplification technology have a detection limit of 1–10 elementary bodies and a specificity comparable to that of culture. The improved sensitivity of these assays allows the use of non-invasive specimens, such as first-catch urine specimens, which are more acceptable to patients. PCR tests using first-catch urine specimens have been shown to have sensitivities of 87–97% for men and 82–93% for women, with specificities of 98–100% for both genders [2]. They also offer all the advantages of non-culture tests in terms of specimen transport, batching, rapid processing time and automation. The high sensitivity and specificity of nucleic acidbased amplification tests, combined with the ease of collection and transport of urine specimens, makes screening feasible in an outpatient setting and cost-effective among populations with a Chlamydia prevalence as low as 3.2%. Pooling of urine specimens may reduce costs further without influencing sensitivity [2]. As most infected individuals are asymptomatic and act as a reservoir that maintains the prevalence of the infection, population screening is the only way to eliminate transmission of Chlamydia. Universal screening offers the potential to identify and treat as many infections as possible, thus decreasing the incidence of future illness and the economic consequences of sequelae, but is not as cost-effective as selective screening programmes. Such selective programmes target the portion of the population at highest risk and identify most chlamydial infections without testing all women. Selective screening programmes are therefore used more commonly, and most recommend
active screening of women aged < 25 years, as is recommended in the USA [12], Sweden [1] and England [13,14]. In 1996, the CDC provided $12.9 million for the Infertility Prevention Program. In order to prevent infertility as a consequence of chlamydial infection, the CDC recommended testing all women with evidence of mucopurulent cervitis and all women aged < 20 years of age. Testing was also suggested for: (1) women aged 20–23 years who had not consistently used barrier contraception, or who had a new sexual partner, or more than one sexual partner, during the previous 90 days; and (2) women aged > 24 years who had not consistently used barrier contraception, or had a new sexual partner, or more than one sexual partner, during the previous 90 days. In a study performed in Baltimore [15], universal screening was compared to selective screening (both by age and according to CDC criteria). Agebased screening provided the greatest cost-effectiveness, with a prevalence of chlamydial infection of 6.6%. The authors of the Baltimore study also suggested that universal screening should become the elective strategy if the prevalence of infection is 6.6–10.2%, and that no screening modality would be cost-effective with a prevalence of < 1.1%. Considering the high prevalence of C. trachomatis infection in European countries, and the farreaching consequences of the disease, medical societies and health authorities should define guidelines and a European-wide screening policy. Although there are clearly difficulties related to the structure and economics of individual national healthcare systems, the development of a comprehensive screening policy will, in time, prove cost-effective, as it will decrease the significant costs involved in treating the sequelae of the infection. Attention should be given to both primary and secondary prevention. Primary-care physicians should be involved and educated to contribute to this initiative [16]. REFERENCES 1. Honey E, Augood C, Templeton A et al. Cost effectiveness for screening for Chlamydia trachomatis: a review of published studies. Sex Transm Infect 2002; 78: 406–412. 2. Peeling RW, Toye B, Jessamine P, Gemmill I. Pooling of urine specimens for PCR testing: a cost saving strategy for Chlamydia trachomatis control programmes. Sex Transm Infect 1998; 74: 66–70.
2005 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 687–689
Spiliopoulou et al.
3. Moens V, Baruch G, Fearon P. Opportunistic screening for Chlamydia at a community based contraceptive service for young people. BMJ 2003; 326: 1252–1255. 4. Anonymous. Global prevalence and incidence of selected curable sexually transmitted infection, revised edition. Geneva: World Health Organization, 2001. http://www.who.int 5. Jensen P, Fogh H, Prag J. Diagnosis of Chlamydia trachomatis infections in a sexually transmitted disease clinic: evaluation of a urine sample tested by enzyme immunoassay and polymerase chain reaction in comparison with a cervical and ⁄ or a urethral swab tested by culture and polymerase chain reaction. Clin Microbiol Infect 2003; 9: 194–201. 6. Kostoula AG, Bobojianni CC, Dea AD et al. Detection of Chlamydia trachomatis antigen using the direct immunofluorescent technique: a four year survey in Northwestern Greece. G Batteriol Virol Immunol 1994; 86: 11–14. 7. Arkoulis T, Decavalas G, Papapetropoulou M et al. Prevalence of asymptomatic carriers of Chlamydia trachomatis among pregnant and non-pregnant women in southwestern Greece. Eur J Epidemiol 1989; 5: 526–528. 8. Kalogeropoulos A, Frantzidou F, Klearchou N et al. Chlamydia trachomatis in infertile Greek women. A serologic and laparoscopic study. Eur J Obstet Gynecol Reprod Biol 1993; 48: 107–110.
Chlamydia trachomatis screening 689
9. Koskela P, Antila T, Bjorge T et al. Chlamydia trachomatis infection as risk factor for invasive cervical cancer. Int J Cancer 2000; 85: 35–39. 10. Wallin K-L, Wiklund F, Luostarinen T et al. A populationbased prospective study of Chlamydia trachomatis infection and cervical carcinoma. Int J Cancer 2002; 101: 371–374. 11. Smith JS, Bosetti C, Munoz N et al. Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer 2004; 111: 431–439. 12. Stamm WE. Chlamydia screening: expanding the scope. Ann Intern Med 2004; 141: 570–572. 13. Fenton KA, LaMontagne DS, Randall S. National screening programme for Chlamydia exists in England. BMJ 2004; 329: 172. 14. LaMontagne DS, Fenton KA, Randall S et al. Establishing the National Chlamydia Screening Programme in England: results from the first full year of screening. Sex Transm Infect 2004; 80: 335–341. 15. Howell MR, Quinn TC, Gaydos CA. Screening for Chlamydia trachomatis in asymptomatic women attending family planning clinics. Ann Intern Med 1998; 123: 277–284. 16. Verhoeven V, Avonts D, Van Royen P, Denekens J. Implementation of a pilot programme for screening for chlamydial infection in general practice. Eur J Gen Pract 2004; 10: 157.
2005 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 687–689
10.1111/j.1469-0691.2005.01187.x
Chlamydia trachomatis: time for screening? A. Spiliopoulou1,2, V. Lakiotis1,3, A. Vittoraki1,4, D. Zavou1,5 and D. Mauri1,6 1
Panhellenic Association for Continual Medical Research (PACMeR), Public Health Task-Force, PACMeR, Microbiology, Patra, 3PACMeR, Public Health, Patra, 4PACMeR, Microbiology, Athens, 5 PACMeR, Gynecology and Woman Health, Alexandroupoli and 6PACMeR, Oncology, Ioannina, Greece 2
ABSTRACT Genital Chlamydia trachomatis infection is the leading cause of bacterial sexually transmitted disease in industrialised countries, particularly among young people. The consequences of chlamydial infection may involve urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, epididymitis and prostatitis. In addition, chlamydial infection increases the risk of acquisition of human immunodeficiency virus and has been associated with cervical cancer. Although screening programmes exist in a number of countries, the continuously increasing prevalence of chlamydial infections demonstrates the necessity for health authorities to establish effective screening policies, and the importance of defining a comprehensive European screening policy is emerging. Keywords
Chlamydia trachomatis, genital infection, screening programme, sexually transmitted disease
Clin Microbiol Infect 2005; 11: 687–689
Genital chlamydial infection is the leading cause of bacterial sexually transmitted disease (STD) in industrialised countries. The prevalence of lower genital tract infection with Chlamydia trachomatis is 2–25%, and is highest in young people [1]. Since 50–70% of genital infections are asymptomatic [2], and it is estimated that < 10% of prevalent infections are diagnosed [3], the morbidity and sequelae of the disease impact dramatically on the health of women. In the USA, there are an estimated 4 million new cases annually, and 50 000 women annually become infertile as a result of infection [2]. The WHO has estimated that there were 89 million new cases of genital chlamydial infections worldwide in 1995 [2] and 92 million in 1999 [4]. In England, the national screening pilot found that 13.8% of those aged < 16 years, 10.5% of those aged 16–19 years and 7.2% of those aged 20–24 years were infected, with > 60 000 cases reported from genitourinary medicine clinics in 2000 [3]. In Denmark, almost 13 000 infections were diagnosed in 1998 (75% among females), corresponding to a prevalence of 4.5% [5]. In Greece, the prevalence of the disease Corresponding author and reprint requests: D. Mauri, Oncology, Ioannina University Hospital, Ioannina, Greece E-mail: [email protected]
among women aged 18–35 years has been estimated at 7–10.6% [6,7]. According to the WHO, chlamydial prevalence rates among pregnant women in the 1990s were 2.7% in Italy, 3.9% in France, 4.9% in The Netherlands, 5.4% in Hungary, 6.2% in the UK, 6.7% in Denmark and 8% in Iceland [4]. In women, chlamydial infection can cause urethritis, cervicitis, pelvic inflammatory disease and, at a later stage, chronic pelvic pain, ectopic pregnancy and tubal factor infertility. Anti-chlamydial antibodies have been documented in 81.5% of infertile women with damaged fallopian tubes, and in 43.5% of infertile women with normal tubes [8]. Furthermore, when giving birth, an infected woman can pass the infection on to her child, who can develop neonatal conjunctivitis or pneumonia as a result. In men, chlamydial infection can cause urethritis, epididymitis and, probably, prostatitis and infertility. In both sexes, it can cause mucosal inflammation of the throat and rectum. Individuals with bacterial STDs, including chlamydial infection, are also at increased risk of acquiring human immunodeficiency virus. Strengthening the control of STDs through education and access to diagnosis and treatment has been reported to result in a 42% reduction in the
2005 Copyright by the European Society of Clinical Microbiology and Infectious Diseases
688 Clinical Microbiology and Infection, Volume 11 Number 9, September 2005
incidence of human immunodeficiency virus infection over a 2-year period [2]. Current data [9–11] also indicate that cervical cancer is associated with infection with STD agents other than oncogenic human papillomavirus. C. trachomatis infection may induce chronic inflammation, epithelial damage, cytologic cervical atypia and cervical metaplasia, which in turn may increase the risk of cervical neoplasia. Serum chlamydial antibodies have been associated with a 1.8-fold increased risk of invasive squamous cervical cancer [11]. Enzyme immunoassay is the diagnostic method used most commonly, but has a lower detection limit of 10 000 elementary bodies, and thus lacks the sensitivity required for screening applications. Nucleic acid-based amplification tests using PCR, ligase chain reaction or transcription-mediated amplification technology have a detection limit of 1–10 elementary bodies and a specificity comparable to that of culture. The improved sensitivity of these assays allows the use of non-invasive specimens, such as first-catch urine specimens, which are more acceptable to patients. PCR tests using first-catch urine specimens have been shown to have sensitivities of 87–97% for men and 82–93% for women, with specificities of 98–100% for both genders [2]. They also offer all the advantages of non-culture tests in terms of specimen transport, batching, rapid processing time and automation. The high sensitivity and specificity of nucleic acidbased amplification tests, combined with the ease of collection and transport of urine specimens, makes screening feasible in an outpatient setting and cost-effective among populations with a Chlamydia prevalence as low as 3.2%. Pooling of urine specimens may reduce costs further without influencing sensitivity [2]. As most infected individuals are asymptomatic and act as a reservoir that maintains the prevalence of the infection, population screening is the only way to eliminate transmission of Chlamydia. Universal screening offers the potential to identify and treat as many infections as possible, thus decreasing the incidence of future illness and the economic consequences of sequelae, but is not as cost-effective as selective screening programmes. Such selective programmes target the portion of the population at highest risk and identify most chlamydial infections without testing all women. Selective screening programmes are therefore used more commonly, and most recommend
active screening of women aged < 25 years, as is recommended in the USA [12], Sweden [1] and England [13,14]. In 1996, the CDC provided $12.9 million for the Infertility Prevention Program. In order to prevent infertility as a consequence of chlamydial infection, the CDC recommended testing all women with evidence of mucopurulent cervitis and all women aged < 20 years of age. Testing was also suggested for: (1) women aged 20–23 years who had not consistently used barrier contraception, or who had a new sexual partner, or more than one sexual partner, during the previous 90 days; and (2) women aged > 24 years who had not consistently used barrier contraception, or had a new sexual partner, or more than one sexual partner, during the previous 90 days. In a study performed in Baltimore [15], universal screening was compared to selective screening (both by age and according to CDC criteria). Agebased screening provided the greatest cost-effectiveness, with a prevalence of chlamydial infection of 6.6%. The authors of the Baltimore study also suggested that universal screening should become the elective strategy if the prevalence of infection is 6.6–10.2%, and that no screening modality would be cost-effective with a prevalence of < 1.1%. Considering the high prevalence of C. trachomatis infection in European countries, and the farreaching consequences of the disease, medical societies and health authorities should define guidelines and a European-wide screening policy. Although there are clearly difficulties related to the structure and economics of individual national healthcare systems, the development of a comprehensive screening policy will, in time, prove cost-effective, as it will decrease the significant costs involved in treating the sequelae of the infection. Attention should be given to both primary and secondary prevention. Primary-care physicians should be involved and educated to contribute to this initiative [16]. REFERENCES 1. Honey E, Augood C, Templeton A et al. Cost effectiveness for screening for Chlamydia trachomatis: a review of published studies. Sex Transm Infect 2002; 78: 406–412. 2. Peeling RW, Toye B, Jessamine P, Gemmill I. Pooling of urine specimens for PCR testing: a cost saving strategy for Chlamydia trachomatis control programmes. Sex Transm Infect 1998; 74: 66–70.
2005 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 687–689
Spiliopoulou et al.
3. Moens V, Baruch G, Fearon P. Opportunistic screening for Chlamydia at a community based contraceptive service for young people. BMJ 2003; 326: 1252–1255. 4. Anonymous. Global prevalence and incidence of selected curable sexually transmitted infection, revised edition. Geneva: World Health Organization, 2001. http://www.who.int 5. Jensen P, Fogh H, Prag J. Diagnosis of Chlamydia trachomatis infections in a sexually transmitted disease clinic: evaluation of a urine sample tested by enzyme immunoassay and polymerase chain reaction in comparison with a cervical and ⁄ or a urethral swab tested by culture and polymerase chain reaction. Clin Microbiol Infect 2003; 9: 194–201. 6. Kostoula AG, Bobojianni CC, Dea AD et al. Detection of Chlamydia trachomatis antigen using the direct immunofluorescent technique: a four year survey in Northwestern Greece. G Batteriol Virol Immunol 1994; 86: 11–14. 7. Arkoulis T, Decavalas G, Papapetropoulou M et al. Prevalence of asymptomatic carriers of Chlamydia trachomatis among pregnant and non-pregnant women in southwestern Greece. Eur J Epidemiol 1989; 5: 526–528. 8. Kalogeropoulos A, Frantzidou F, Klearchou N et al. Chlamydia trachomatis in infertile Greek women. A serologic and laparoscopic study. Eur J Obstet Gynecol Reprod Biol 1993; 48: 107–110.
Chlamydia trachomatis screening 689
9. Koskela P, Antila T, Bjorge T et al. Chlamydia trachomatis infection as risk factor for invasive cervical cancer. Int J Cancer 2000; 85: 35–39. 10. Wallin K-L, Wiklund F, Luostarinen T et al. A populationbased prospective study of Chlamydia trachomatis infection and cervical carcinoma. Int J Cancer 2002; 101: 371–374. 11. Smith JS, Bosetti C, Munoz N et al. Chlamydia trachomatis and invasive cervical cancer: a pooled analysis of the IARC multicentric case-control study. Int J Cancer 2004; 111: 431–439. 12. Stamm WE. Chlamydia screening: expanding the scope. Ann Intern Med 2004; 141: 570–572. 13. Fenton KA, LaMontagne DS, Randall S. National screening programme for Chlamydia exists in England. BMJ 2004; 329: 172. 14. LaMontagne DS, Fenton KA, Randall S et al. Establishing the National Chlamydia Screening Programme in England: results from the first full year of screening. Sex Transm Infect 2004; 80: 335–341. 15. Howell MR, Quinn TC, Gaydos CA. Screening for Chlamydia trachomatis in asymptomatic women attending family planning clinics. Ann Intern Med 1998; 123: 277–284. 16. Verhoeven V, Avonts D, Van Royen P, Denekens J. Implementation of a pilot programme for screening for chlamydial infection in general practice. Eur J Gen Pract 2004; 10: 157.
2005 Copyright by the European Society of Clinical Microbiology and Infectious Diseases, CMI, 11, 687–689