Clinical Review & Education
JAMA Dermatology Clinical Evidence Synopsis
Screening Recommendations for Chlamydia and Gonorrhea Victoria R. Sharon, MD, DTMH; April W. Armstrong, MD, MPH
CLINICAL QUESTION Dermatologists diagnose and treat sexually transmitted infections with varying frequency, and have an opportunity to monitor at-risk individuals for chlamydia and gonorrhea. What are the recommended screening guidelines for chlamydia and gonorrhea in men and women in the United States? BOTTOM LINE While the evidence for screening men for chlamydia and gonorrhea remains insufficient at this time, all sexually active females younger than 25 years and all older women at risk for infection should be screened for both chlamydia and gonorrhea.
Introduction Although there were more than 1.4 million cases of chlamydia and 330 000 cases of gonorrhea reported in 2012, the Centers for Disease Control and Prevention (CDC) estimates that more than double the reported new cases of infection exist.1 Chlamydial and gonorrheal infections are not infrequently asymptomatic, permitting transmission without awareness of infection. The burden of morbidity of untreated chlamydia and gonorrhea is high, and these sexually transmitted infections (STIs) can result in pelvic inflammatory disease (PID) in 10% to 20% of untreated infections, ectopic pregnancy, and chronic pelvic pain in women, and urethritis, epididymitis, and proctitis in men. Newborns of women infected with chlamydia during pregnancy can have neonatal chlamydial pneumoniae or chlamydial ophthalmia. In both sexes, chlamydia and gonorrhea can enhance transmissibility of human immunodeficiency virus infection. Apart from younger age, factors that place individuals at risk for chlamydia and gonorrhea include a prior or coexisting STI, new or multiple sex partners, a sex partner who has concurrent partners, a partner with an STI, inconsistent condom use in a non–mutually exclusive sexual relationship, and receiving money or drugs in exchange for sexual activity. Dermatologists throughout the country treat STIs with varying frequency, the most common of which are herpes simplex virus and human papilloma virus, as patients are more likely to seek care for visibly apparent and symptomatic infections. Thus, dermatologists have a unique opportunity to recommend screening for those at risk for chlamydia and gonorrhea to improve diagnosis of silent infections by reaching women who may not otherwise seek evaluation from a health care professional. Therefore, understanding the most recent screening guidelines is highly relevant for any practicing dermatologist.
Summary of Findings This summary of the screening recommendations for chlamydia and gonorrhea incorporates data from the US Preventive Services Task Force (USPSTF) based on its 2014 update2 but also encompasses data from 2 trials included in the USPSTF’s 2005 and 2007 screening guidelines for gonorrhea and chlamydia, respectively (Table). Since 2007, only 1 randomized clinical trial (RCT)3 met inclusion criteria for the 2014 USPSTF analysis. No studies met inclusion criteria for gonorrhea screening in both sexes or for chlamydia screening in men. Three trials reviewed by the USPSTF are summarized here. jamadermatology.com
Evidence Profile No. of trials: 3 No. of randomized clinical trials: 3 Study years: 1996 to 2010 No. of patients: 6836 Male: 0% Female: 100% (from 3 trials [5914 participants]) Race/ethnicity: Unavailable Age: 15 to 34 years (data available in 3 trials) Settings: High school and university students; health maintenance organization Countries: Denmark, United Kingdom, United States (1 each) Intervention: Immediate clinic or home screening vs deferred chlamydia screening Primary outcomes: Incidence of pelvic inflammatory disease in all females; incidence of new chlamydial infections in all females Secondary outcomes: None
Published in 2010, the Prevention of Pelvic Infection trial recruited 2529 sexually active women in London to determine whether screening for chlamydia reduced the incidence of PID over 1 year; 2377 women completed the trial and were available for analysis.3 Incidence of PID was 1.3% in the screened group compared with 1.9% in the control group (relative risk [RR], 0.65; 95% CI, 0.34-1.22; P = .19). The estimated number needed to screen to prevent 1 case of PID in 1 year was 147. Although this trial was determined to be of good quality, it was limited by testing for chlamydia outside of the study in approximately 20% of the participants and difficulty in confirming subsequent PID diagnoses, which may have led to an underpowered study with dilution of the effect of screening. Moreover, the majority of cases of PID occurred in women who had a negative screening result at baseline, suggesting that additional screening in a high-risk population may be worthwhile. In an RCT of low quality owing to a high dropout rate (approximately 50%) published in 2000, a total of 1700 adolescent girls were recruited from 17 high schools in Aarhus, Denmark, to compare a single home-screening method with conventional care; 930 girls completed the trial and were available for analysis.4 Of the participants who were available for follow-up after 1 year, 13 of 443 (2.9%) (Reprinted) JAMA Dermatology Published online July 15, 2015
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Alabama-Birmingham User on 07/17/2015
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Clinical Review & Education JAMA Dermatology Clinical Evidence Synopsis
Table. Relative Risk of Deferred Chlamydia Screening in Females Aged 15 to 34 Years Total Participants Participants, No. Screened, No.
Screening Deferred, No.
Relative Risk (95% CI)
No. Needed to Screen to Prevent PID
Oakeshott et al, 20103 (POPI trial)
2377a
1191
1186
0.65 (0.34-1.22)
147
Østergaard et al, 20004
930a
443
487
0.50 (0.23-1.08)
48
a
Patients unavilable for follow-up not included.
1598
0.44 (0.20-0.90)
85
b
Individuals screened for chlamydia; intention-to-screen analysis.
Source
Scholes et al, 19965
2607
1009 (645b)
of those screened compared with 32 of 487 (6.6%) of those in the control group developed new chlamydial infections, while 9 of 443 (2.0%) of those screened compared with 20 of 487 (4.1%) of those in the control group developed PID. The authors concluded that screening sexually active adolescent girls reduced the rates of chlamydia infection (P = .03) and resultant PID at 1 year (RR, 0.50; 95% CI, 0.23-1.08; P = .045). In a high-quality RCT published in 1996, a total of 2607 women aged 18 to 34 years (mean age, 22 years) were recruited from a health maintenance organization in Washington State. Using an intentionto-screen analysis, 9 women in the group screened for chlamydia compared with 33 in the control group developed PID within 1 year. The authors concluded that there was a statistically significant reduction in the incidence of PID after 1 year of follow-up among women screened for chlamydia (RR, 0.44; 95% CI, 0.20-0.90).5 In summary, all 3 trials support a reduction in the incidence of PID with screening asymptomatic females for chlamydia.
Discussion Based on review of the aforementioned trials, as of 2014, the USPSTF recommends that all sexually active females younger than 25 years and older women at risk for infection undergo screening for chlamydia and gonorrhea. They conclude, however, that there is not yet sufficient evidence to recommend chlamydia and gonorrhea screening in men. Limitations
The studies were few in number and variable in quality and did not address many key questions owing to a lack of published prospective clinical trials. Among these questions are screening for chlamydia and gonorrhea in men, screening for gonorrhea in women, and screening for chlamydia and gonorrhea in pregnant women and women not at increased risk for infection. Furthermore, the trials were limited to 1 year of follow-up and primarily evaluated PID as the only outcome. Future studies should consider adding secondary outcomes including assessment of longterm sequelae, such as delayed PID complications, between groups. All studies were limited by difficulty in ascertaining PID diagnoses, as authors relied on patient self-reporting and medical records owing to the invasiveness of confirmatory laparoscopy. It is therefore possiblethatnotallcasesidentifiedasPIDweretrulyPID,whileothercases of mild or asymptomatic infection may have gone undiagnosed. The
ARTICLE INFORMATION Author Affiliations: Department of Dermatology, University of California, Davis, Sacramento (Sharon); Department of Dermatology, University of Colorado, Denver, Aurora (Armstrong).
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Abbreviations: PID, pelvic inflammatory disease; POPI, Prevention of Pelvic Infection.
scope of evaluation was limited to screening tests cleared by the US Food and Drug Administration, restricting the studies to genitourinaryonly testing and excluding rectal and pharyngeal swab evaluation. Comparison of Findings With Current Guidelines
These recommendations are in accordance with those of the American Academy of Family Physicians and the American College of Physicians.2 Like the USPSTF, the CDC similarly recommends screening for chlamydia and gonorrhea in sexually active females younger than 26 and 25 years, respectively, and in older women at risk for infection.2 In contrast to the USPSTF, the CDC recommends routine annual genital and extragenital screening for chlamydia and gonorrhea in sexually active men who have sex with men. The CDC also recommends consideration of screening sexually active young men for chlamydia in settings of high prevalence. According to the CDC, all pregnant women and high-risk pregnant women should be screened for chlamydia and gonorrhea, respectively, at the initial prenatal visit. Last, the CDC states that all individuals who continue to be at high risk for these infections should receive consideration for additional screening more frequently than annually. The American Academy of Pediatrics and the American Medical Association follow the recommendations of the CDC. The American Congress of Obstetricians and Gynecologists similarly recommends that all sexually active females younger than 26 and 25 years receive chlamydia and gonorrhea screening, respectively, but also recommends consideration of screening for chlamydia in adolescent and young men in communities with a high prevalence of infection.2 Areas in Need of Future Study
Future studies are needed to evaluate screening for gonorrhea in all populations as well as screening for chlamydia in men and pregnant women. It would also be valuable to address methods to improve the identification of those at increased risk for infection along with studying the efficacy of different screening intervals in a highrisk population of women and men. More than half of chlamydial and gonorrheal infections in men are carried in the rectum or oropharynx and are mostly asymptomatic. This allows for transmission and facilitation of the spread of human immunodeficiency virus. Therefore, it would be judicious to expand the scope of screening in future research to include testing at extragenital sites of carriage, including the rectum and oropharynx in men.
Corresponding Author: Victoria R. Sharon, MD, DTMH, Department of Dermatology, University of California, Davis, 3301 C St, Ste 1400, Sacramento, CA 95816 ([email protected]). Published Online: July 15, 2015. doi:10.1001/jamadermatol.2015.1987.
Conflict of Interest Disclosures: None reported. REFERENCES 1. Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria
JAMA Dermatology Published online July 15, 2015 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Alabama-Birmingham User on 07/17/2015
jamadermatology.com
JAMA Dermatology Clinical Evidence Synopsis Clinical Review & Education
gonorrhoeae—2014. MMWR Recomm Rep. 2014;63 (RR-02):1-19. 2. Nelson HD, Zakher B, Cantor A, Deagas M, Pappas M. Screening for Gonorrhea and Chlamydia: Systematic Review to Update the US Preventive Services Task Force Recommendations. Rockville, MD: Agency for Healthcare Research and Quality; 2014. Report No. 13-05184-EF-1.
jamadermatology.com
3. Oakeshott P, Kerry S, Aghaizu A, et al. Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (Prevention of Pelvic Infection) trial. BMJ. 2010;340:c1642. 4. Østergaard L, Andersen B, Møller JK, Olesen F. Home sampling versus conventional swab sampling for screening of Chlamydia trachomatis in women:
a cluster-randomized 1-year follow-up study. Clin Infect Dis. 2000;31(4):951-957. 5. Scholes D, Stergachis A, Heidrich FE, Andrilla H, Holmes KK, Stamm WE. Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med. 1996;334(21): 1362-1366.
(Reprinted) JAMA Dermatology Published online July 15, 2015
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Alabama-Birmingham User on 07/17/2015
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JAMA Dermatology Clinical Evidence Synopsis
Screening Recommendations for Chlamydia and Gonorrhea Victoria R. Sharon, MD, DTMH; April W. Armstrong, MD, MPH
CLINICAL QUESTION Dermatologists diagnose and treat sexually transmitted infections with varying frequency, and have an opportunity to monitor at-risk individuals for chlamydia and gonorrhea. What are the recommended screening guidelines for chlamydia and gonorrhea in men and women in the United States? BOTTOM LINE While the evidence for screening men for chlamydia and gonorrhea remains insufficient at this time, all sexually active females younger than 25 years and all older women at risk for infection should be screened for both chlamydia and gonorrhea.
Introduction Although there were more than 1.4 million cases of chlamydia and 330 000 cases of gonorrhea reported in 2012, the Centers for Disease Control and Prevention (CDC) estimates that more than double the reported new cases of infection exist.1 Chlamydial and gonorrheal infections are not infrequently asymptomatic, permitting transmission without awareness of infection. The burden of morbidity of untreated chlamydia and gonorrhea is high, and these sexually transmitted infections (STIs) can result in pelvic inflammatory disease (PID) in 10% to 20% of untreated infections, ectopic pregnancy, and chronic pelvic pain in women, and urethritis, epididymitis, and proctitis in men. Newborns of women infected with chlamydia during pregnancy can have neonatal chlamydial pneumoniae or chlamydial ophthalmia. In both sexes, chlamydia and gonorrhea can enhance transmissibility of human immunodeficiency virus infection. Apart from younger age, factors that place individuals at risk for chlamydia and gonorrhea include a prior or coexisting STI, new or multiple sex partners, a sex partner who has concurrent partners, a partner with an STI, inconsistent condom use in a non–mutually exclusive sexual relationship, and receiving money or drugs in exchange for sexual activity. Dermatologists throughout the country treat STIs with varying frequency, the most common of which are herpes simplex virus and human papilloma virus, as patients are more likely to seek care for visibly apparent and symptomatic infections. Thus, dermatologists have a unique opportunity to recommend screening for those at risk for chlamydia and gonorrhea to improve diagnosis of silent infections by reaching women who may not otherwise seek evaluation from a health care professional. Therefore, understanding the most recent screening guidelines is highly relevant for any practicing dermatologist.
Summary of Findings This summary of the screening recommendations for chlamydia and gonorrhea incorporates data from the US Preventive Services Task Force (USPSTF) based on its 2014 update2 but also encompasses data from 2 trials included in the USPSTF’s 2005 and 2007 screening guidelines for gonorrhea and chlamydia, respectively (Table). Since 2007, only 1 randomized clinical trial (RCT)3 met inclusion criteria for the 2014 USPSTF analysis. No studies met inclusion criteria for gonorrhea screening in both sexes or for chlamydia screening in men. Three trials reviewed by the USPSTF are summarized here. jamadermatology.com
Evidence Profile No. of trials: 3 No. of randomized clinical trials: 3 Study years: 1996 to 2010 No. of patients: 6836 Male: 0% Female: 100% (from 3 trials [5914 participants]) Race/ethnicity: Unavailable Age: 15 to 34 years (data available in 3 trials) Settings: High school and university students; health maintenance organization Countries: Denmark, United Kingdom, United States (1 each) Intervention: Immediate clinic or home screening vs deferred chlamydia screening Primary outcomes: Incidence of pelvic inflammatory disease in all females; incidence of new chlamydial infections in all females Secondary outcomes: None
Published in 2010, the Prevention of Pelvic Infection trial recruited 2529 sexually active women in London to determine whether screening for chlamydia reduced the incidence of PID over 1 year; 2377 women completed the trial and were available for analysis.3 Incidence of PID was 1.3% in the screened group compared with 1.9% in the control group (relative risk [RR], 0.65; 95% CI, 0.34-1.22; P = .19). The estimated number needed to screen to prevent 1 case of PID in 1 year was 147. Although this trial was determined to be of good quality, it was limited by testing for chlamydia outside of the study in approximately 20% of the participants and difficulty in confirming subsequent PID diagnoses, which may have led to an underpowered study with dilution of the effect of screening. Moreover, the majority of cases of PID occurred in women who had a negative screening result at baseline, suggesting that additional screening in a high-risk population may be worthwhile. In an RCT of low quality owing to a high dropout rate (approximately 50%) published in 2000, a total of 1700 adolescent girls were recruited from 17 high schools in Aarhus, Denmark, to compare a single home-screening method with conventional care; 930 girls completed the trial and were available for analysis.4 Of the participants who were available for follow-up after 1 year, 13 of 443 (2.9%) (Reprinted) JAMA Dermatology Published online July 15, 2015
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Alabama-Birmingham User on 07/17/2015
E1
Clinical Review & Education JAMA Dermatology Clinical Evidence Synopsis
Table. Relative Risk of Deferred Chlamydia Screening in Females Aged 15 to 34 Years Total Participants Participants, No. Screened, No.
Screening Deferred, No.
Relative Risk (95% CI)
No. Needed to Screen to Prevent PID
Oakeshott et al, 20103 (POPI trial)
2377a
1191
1186
0.65 (0.34-1.22)
147
Østergaard et al, 20004
930a
443
487
0.50 (0.23-1.08)
48
a
Patients unavilable for follow-up not included.
1598
0.44 (0.20-0.90)
85
b
Individuals screened for chlamydia; intention-to-screen analysis.
Source
Scholes et al, 19965
2607
1009 (645b)
of those screened compared with 32 of 487 (6.6%) of those in the control group developed new chlamydial infections, while 9 of 443 (2.0%) of those screened compared with 20 of 487 (4.1%) of those in the control group developed PID. The authors concluded that screening sexually active adolescent girls reduced the rates of chlamydia infection (P = .03) and resultant PID at 1 year (RR, 0.50; 95% CI, 0.23-1.08; P = .045). In a high-quality RCT published in 1996, a total of 2607 women aged 18 to 34 years (mean age, 22 years) were recruited from a health maintenance organization in Washington State. Using an intentionto-screen analysis, 9 women in the group screened for chlamydia compared with 33 in the control group developed PID within 1 year. The authors concluded that there was a statistically significant reduction in the incidence of PID after 1 year of follow-up among women screened for chlamydia (RR, 0.44; 95% CI, 0.20-0.90).5 In summary, all 3 trials support a reduction in the incidence of PID with screening asymptomatic females for chlamydia.
Discussion Based on review of the aforementioned trials, as of 2014, the USPSTF recommends that all sexually active females younger than 25 years and older women at risk for infection undergo screening for chlamydia and gonorrhea. They conclude, however, that there is not yet sufficient evidence to recommend chlamydia and gonorrhea screening in men. Limitations
The studies were few in number and variable in quality and did not address many key questions owing to a lack of published prospective clinical trials. Among these questions are screening for chlamydia and gonorrhea in men, screening for gonorrhea in women, and screening for chlamydia and gonorrhea in pregnant women and women not at increased risk for infection. Furthermore, the trials were limited to 1 year of follow-up and primarily evaluated PID as the only outcome. Future studies should consider adding secondary outcomes including assessment of longterm sequelae, such as delayed PID complications, between groups. All studies were limited by difficulty in ascertaining PID diagnoses, as authors relied on patient self-reporting and medical records owing to the invasiveness of confirmatory laparoscopy. It is therefore possiblethatnotallcasesidentifiedasPIDweretrulyPID,whileothercases of mild or asymptomatic infection may have gone undiagnosed. The
ARTICLE INFORMATION Author Affiliations: Department of Dermatology, University of California, Davis, Sacramento (Sharon); Department of Dermatology, University of Colorado, Denver, Aurora (Armstrong).
E2
Abbreviations: PID, pelvic inflammatory disease; POPI, Prevention of Pelvic Infection.
scope of evaluation was limited to screening tests cleared by the US Food and Drug Administration, restricting the studies to genitourinaryonly testing and excluding rectal and pharyngeal swab evaluation. Comparison of Findings With Current Guidelines
These recommendations are in accordance with those of the American Academy of Family Physicians and the American College of Physicians.2 Like the USPSTF, the CDC similarly recommends screening for chlamydia and gonorrhea in sexually active females younger than 26 and 25 years, respectively, and in older women at risk for infection.2 In contrast to the USPSTF, the CDC recommends routine annual genital and extragenital screening for chlamydia and gonorrhea in sexually active men who have sex with men. The CDC also recommends consideration of screening sexually active young men for chlamydia in settings of high prevalence. According to the CDC, all pregnant women and high-risk pregnant women should be screened for chlamydia and gonorrhea, respectively, at the initial prenatal visit. Last, the CDC states that all individuals who continue to be at high risk for these infections should receive consideration for additional screening more frequently than annually. The American Academy of Pediatrics and the American Medical Association follow the recommendations of the CDC. The American Congress of Obstetricians and Gynecologists similarly recommends that all sexually active females younger than 26 and 25 years receive chlamydia and gonorrhea screening, respectively, but also recommends consideration of screening for chlamydia in adolescent and young men in communities with a high prevalence of infection.2 Areas in Need of Future Study
Future studies are needed to evaluate screening for gonorrhea in all populations as well as screening for chlamydia in men and pregnant women. It would also be valuable to address methods to improve the identification of those at increased risk for infection along with studying the efficacy of different screening intervals in a highrisk population of women and men. More than half of chlamydial and gonorrheal infections in men are carried in the rectum or oropharynx and are mostly asymptomatic. This allows for transmission and facilitation of the spread of human immunodeficiency virus. Therefore, it would be judicious to expand the scope of screening in future research to include testing at extragenital sites of carriage, including the rectum and oropharynx in men.
Corresponding Author: Victoria R. Sharon, MD, DTMH, Department of Dermatology, University of California, Davis, 3301 C St, Ste 1400, Sacramento, CA 95816 ([email protected]). Published Online: July 15, 2015. doi:10.1001/jamadermatol.2015.1987.
Conflict of Interest Disclosures: None reported. REFERENCES 1. Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria
JAMA Dermatology Published online July 15, 2015 (Reprinted)
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Alabama-Birmingham User on 07/17/2015
jamadermatology.com
JAMA Dermatology Clinical Evidence Synopsis Clinical Review & Education
gonorrhoeae—2014. MMWR Recomm Rep. 2014;63 (RR-02):1-19. 2. Nelson HD, Zakher B, Cantor A, Deagas M, Pappas M. Screening for Gonorrhea and Chlamydia: Systematic Review to Update the US Preventive Services Task Force Recommendations. Rockville, MD: Agency for Healthcare Research and Quality; 2014. Report No. 13-05184-EF-1.
jamadermatology.com
3. Oakeshott P, Kerry S, Aghaizu A, et al. Randomised controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (Prevention of Pelvic Infection) trial. BMJ. 2010;340:c1642. 4. Østergaard L, Andersen B, Møller JK, Olesen F. Home sampling versus conventional swab sampling for screening of Chlamydia trachomatis in women:
a cluster-randomized 1-year follow-up study. Clin Infect Dis. 2000;31(4):951-957. 5. Scholes D, Stergachis A, Heidrich FE, Andrilla H, Holmes KK, Stamm WE. Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection. N Engl J Med. 1996;334(21): 1362-1366.
(Reprinted) JAMA Dermatology Published online July 15, 2015
Copyright 2015 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a University of Alabama-Birmingham User on 07/17/2015
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