Chlamydia and Gonorrhea: The Most Common Treatable STIs
Chlamydial trachomatis and Neisseria gonorrhea infections are the most and second most frequently reported sexually transmitted infections (STIs) in the United States.1-2 They can result in more serious consequences than the acute infection. In women they can lead to pelvic inflammatory disease (PID), tubal infertility, ectopic pregnancy, and chronic pelvic pain.1 Reactive arthritis can occur in men and women following symptomatic or asymptomatic chlamydial infection. The arthritis sometimes occurs as part of a triad of symptoms with urethritis and conjunctivitis which is sometimes referred to as Reiter’s Syndrome.3
Diagnosis and treatment of chlamydial and gonorrhea infections are important because if untreated they can spread from the cervix to the upper reproductive tract causing PID.4 Symptomatic PID occurs in about 10 to 15 percent of women with untreated chlamydia.5 Chlamydia can also cause subclinical inflammation of the upper genital tract or “subclinical PID”. Both symptomatic and subclinical PID can cause permanent damage to the fallopian tubes, uterus, and surrounding tissues. This damage can lead to chronic pelvic pain, tubal infertility, and ectopic pregnancy.6 Some patients with chlamydial PID develop liver perihepatitis (Fitz-Hugh-Curtis Syndrome).4 In pregnant women, untreated chlamydia has been associated with pre-term delivery, as well as ophthalmia neonatorum (conjunctivitis) and pneumonia in the newborn.7 If left untreated, gonorrhea can spread to the blood and cause disseminated gonococcal infection. This is most commonly characterized by arthritis, tenosynovitis, and/or dermatitis.8
The purpose of this article is to increase the awareness and adoption of current CDC STI diagnosis and treatment guidelines. It is also designed to help healthcare providers describe the burden of disease and epidemiology of STI's in the United States and to plan appropriate testing for optimal screening and diagnosis of STI's. As testing methods continue to improve and evolve, newer testing methods offer faster, more sensitive and more accurate options that offer more effective diagnosis, treatment and higher cure rates.1
Epidemiology and Burden of Disease
In 2016, 1,598,354 cases of chlamydia and 468,514 cases of gonorrhea were reported to CDC from the United States.2 A large additional number of cases are often not reported because most people with chlamydia and gonorrhea are asymptomatic and some do not seek screening or testing. Both infections are most common among young people. Almost two-thirds of new chlamydia infections occur among 15-24 year olds.9 It is estimated that 1 in 20 sexually active young women aged 14-24 years has chlamydia.10
Substantial racial/ethnic disparities in these infections exist. Prevalence among non-Hispanic blacks is 5.6 times the prevalence among non-Hispanic whites (1,125.9 and 199.8 cases per 100,000 population, respectively).2 The rate of reported cases of gonorrhea remained highest among Blacks (481.2 cases per 100,000 population) and among American Indians/Alaska Natives (242.9 cases per 100,000 population).2 Chlamydia and gonorrhea are also common among men who have sex with men (MSM). Among MSM screened for rectal chlamydial infection, positivity has ranged from 3.0% to 10.5%.11-12 The prevalence of pharyngeal gonorrhea and pharyngeal chlamydia among MSM has been found to be 7.3% and 2.3%, respectively. 1
Chlamydia can also be spread perinatally from an untreated mother to her baby during childbirth, resulting in ophthalmia neonatorum (conjunctivitis) or pneumonia in some exposed infants. Studies show that chlamydial conjunctivitis has been identified in 18-44% and chlamydial pneumonia in 3-16% of infants born to women with untreated chlamydial cervical infection at the time of delivery.13-16 The prevalence of gonorrhea infection in infants depends on the prevalence of infection among pregnant women, whether they are screened and treated, and whether newborns receive eye prophylaxis. Other manifestations of neonatal gonorrhea infections range from rhinitis, vaginitis, and urethritis to arthritis, meningitis, and sepsis. 1
Groups at Risk
Patient groups at increased risk for Chlamydia and gonorrhea infections are shown in Table 1. The highest reported rates of chlamydia and gonorrhea infections among females and males are during their adolescent and early adult years. 2 Fortunately, all 50 states and the District of Columbia explicitly allow minors to consent for their own health services for STDs. 1 Other factors associated with increased risk of C. trachomatis and N. gonorrhea infection include a new sex partner, a sex partner with concurrent partners, or a sex partner who has a sexually transmitted infection. Women ≤35 and men <30 years in correctional facilities are also at increased risk of infections. 1
MSM are also at risk for chlamydial and gonorrhea infections since they can be transmitted by oral or anal sex. 1 Among MSM screened for rectal chlamydial infection, positivity has ranged from 3.0% to 10.5%. 11, 12 Among MSM screened at STD clinics for pharyngeal chlamydial infection, positivity has ranged from 0.5% to 2.3%.12, 17
Table 1. Groups at risk for Chlamydia trachomatis and Neisseria gonorrhea Infections 1, 11, 12, 17
Adolescent females and males
A new sex partner
A sex partner with concurrent partners
A sex partner who has a STI.
Women ≤35 years in correctional facilities
Men <30 years in correctional facilities
Men who have sex with men
Studies have shown that chlamydia screening programs reduce the rates of PID in women. 18 Women with chlamydia or gonorrhea are at risk of serious complications regardless of the presence or severity of symptoms. 19, 20 The USPSTF and the CDC recommends routine annual screening for C. trachomatis and N gonorrhea for all sexually active females aged <25 years. Screening is also recommended in older women at increased risk such as those with a new sex partner, a sex partner who has an STI, or concurrent multiple sex partners. 1, 21 Although routine screening of men is not recommended, the screening of sexually active young men should be considered in clinical settings with a high prevalence of chlamydia (e.g. adolescent clinics, correctional facilities, and STD clinics) or in populations with high burden of infection such as MSM.1, 21 Recommended screening for MSM include a test for N. gonorrhea and C. trachomatis of the urethral or rectum in men who have had insertive intercourse during the preceding year. Urine testing using a nucleic acid amplification test (NAAT) is the CDC recommended approach. 1 The CDC also recommends testing for N. gonorrhea in men who have had receptive oral intercourse during the preceding year using a NAAT of a pharyngeal sample. Testing for C. trachomatis pharyngeal infection is not recommended. Women ≤35 and men <30 years in correctional facilities should be screened for chlamydia and gonorrhea at intake. 1
Chlamydia and gonorrhea are commonly referred to as ‘silent’ infections because many infected people are asymptomatic.4, 8 Only about 10% of men and between 5-30% of women with laboratory-confirmed chlamydial infection develop recognizable symptoms.22 Symptoms in women, especially of gonorrhea, are often so mild and nonspecific that they are mistaken for other urogenital infections and may include dysuria, vaginal discharge, and/or intermenstrual vaginal bleeding. Signs may include a mucopurulent endocervical discharge and easily induced endocervical bleeding.4
Urethral infections in men caused by N. gonorrhea can produce symptoms that cause them to seek treatment. Men who are symptomatic typically have urethritis with a mucoid or watery urethral discharge and dysuria. 1 A minority of infected men develop epididymitis, presenting with unilateral testicular pain, tenderness, and swelling.23 Symptoms of rectal infection in both men and women may be absent or may include anal discharge, itching, soreness, bleeding, or painful bowel movements.24 Pharyngeal infections are typically asymptomatic but may present as a sore throat.25
NAATs have the advantage that they have high sensitivity for the widest variety of specimen types including endocervical swabs, vaginal swabs, urethral swabs in men, and urine from both men and women. 1 Different tests from different NAAT manufacturers have specific collection methods and different approved specimen types.1 NAATs are the most sensitive tests and are recommended by the CDC for detecting C. trachomatis infection. FDA approved specimens to diagnose urogenital C. trachomatis infection can be collected in women as first-catch urine or swabs from the cervical os or vagina. NAATs that are FDA-cleared for use with vaginal swab specimens can be collected by a provider or self-collected in a clinical setting. Self-collected vaginal swab specimens are equivalent in sensitivity and specificity to those collected by a clinician using NAATs.26 Patients find this screening strategy to be highly acceptable.27 Diagnosis of C. trachomatis urethral infection in men can be made by testing a urethral swab or first-catch urine specimen. 1
Rectal and oropharyngeal C. trachomatis infection can be diagnosed by collecting samples from these areas. Although NAATs are not FDA-cleared for use with rectal or oropharyngeal swab specimens, they have been demonstrated to have improved sensitivity and specificity compared with culture for the detection of C. trachomatis. 1 Data indicate that performance of NAATs on self-collected rectal swabs is comparable to clinician-collected rectal swabs, and this specimen collection strategy for rectal C. trachomatis screening is highly acceptable. 1 Some NAATs have been FDA-cleared for use on liquid-based cytology specimens.
Bacterial culture and gram stain are also available for the detection of genitourinary N. gonorrhea infection. 1 Culture requires endocervical swab specimens in women or urethral swab specimens in men. Culture may be used for detection of rectal, oropharyngeal, and conjunctival gonococcal infection. N. gonorrhea is a fastidious organism that has demanding nutritional and environmental growth requirements. The best results are achieved when specimens are inoculated directly to specific growth medium and then promptly placed and incubated in an increased CO2 environment.28
Gram stain of urethral secretions in symptomatic men that demonstrate polymorphonucleocytes with intracellular Gram-negative diplococci are considered diagnostic for N. gonorrhea infection because of its >99% specificity and >95% sensitivity. The sensitivity is lower in asymptomatic men, so this method cannot be used for screening or to rule out infection. 1
Recommended treatment regimens for urogenital chlamydia and gonorrhea infections are shown in the Table 2. These recommended chlamydia regimen produces microbial cure rates of 97% - 98%.29 This urogenital gonorrhea recommended regimen produces microbial cure rates of 99.2% for uncomplicated urogenital and anorectal infections and 98.9% of pharyngeal infections.30 When azithromycin allergy is present, doxycycline 100 mg orally twice a day for 7 days) may be substituted for azithromycin. 1 More detailed treatment information can be found at https://www.cdc.gov/std/tg2015/default.htm.
Table 2. CDC 2015 recommended treatments for Uncomplicated Chlamydia trachomatis and Neisseria gonorrhea Infections1
Expedited Partner Therapy (EPT) involves treating the sex partners of persons who are diagnosed with an STI and is recommended by the CDC unless it is prohibited by law. It usually consists of providing prescriptions or medications with enough medication for the patient’s partner. EPT is legal in most but not all states, and providers can check the legal status of EPT at http://www.cdc.gov/std/ept. As of the end of 2017, all states allow some form of EPT except Kentucky and South Carolina. Clinical trials indicate that more partners are treated when patients are offered EPT and there are statistically significant declines in the rate of reinfection. 1, 31 Reduction in chlamydia prevalence at follow-up is about 20% and gonorrhea about 50%.1 EPT should not be used in MSM with gonorrhea because of the high risk for coexisting infections (including HIV infection) and because no data exist on efficacy in this population.
Test of Cure
A patient diagnosed with and treated for chlamydia should have a test-of-cure to detect therapeutic failure. Men and women who have been treated for chlamydia should be retested approximately 3 months after treatment, regardless of whether they believe that their sex partners were treated. 1 If retesting at 3 months is not possible, clinicians should retest whenever persons next present for medical care in the year following initial treatment. Testing less than 3–4 weeks after completing therapy is contraindicated unless therapeutic adherence is in question, symptoms persist, or reinfection is suspected. Testing too early increases the risk of a false positive test since the very sensitive NAAT test may detect the DNA from dead organisms or bacterial residue that has not yet cleared. In cases of suspected treatment failure, perform culture with antimicrobial susceptibility testing to determine if antimicrobial resistance is present. 1
A patient diagnosed with and treated for uncomplicated urogenital or rectal gonorrhea with any of the recommended or alternative regimens does not require a test-of-cure. All person with pharyngeal gonorrhea should return 14 days after treatment for a test-of-cure. If a NAAT is positive, a confirmatory culture with antimicrobial susceptibility testing should be performed. If symptoms persist after treatment, the patient should receive a culture for N. gonorrhea with antimicrobial susceptibility testing. 1
A high prevalence of C. trachomatis and N. gonorrhea infection has been observed in women and men who were treated during the preceding several months.32 Most post-treatment infections do not result from treatment failure, but rather from reinfection caused by the failure of sex partners to receive treatment or the initiation of sexual activity with a new infected partner. Repeat infections confer an elevated risk for PID and other complications in women. This reinforces the importance of EPT. 1
In the United States best practices for the diagnosis and treatment of STIs are described in the 2015 Sexually Transmitted Diseases Treatment Guidelines. Diagnosis and treatment of patients with chlamydia or gonorrhea is important to reduce the risk of serious complications. NAATs have the advantage for testing for these diseases because they have high sensitivity for the widest variety of specimen types. They also give providers and patients the widest range of choices to test since self-collected NAATs vaginal swab specimens have a similar sensitivity and specificity compared to those collected by a clinician.
- Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015 Jun 5;64(RR-03):1-137.
- Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2016. Atlanta: U.S. Department of Health and Human Services; 2017. https://www.cdc.gov/std/stats.
- Carter JD, Inman RD. Chlamydia-induced reactive arthritis: hidden in plain sight? Best practice & research Clinical rheumatology 2011;25:359-74.
- CDC. Chlamydia - CDC Fact Sheet. https://www.cdc.gov/std/chlamydia/stdfact-chlamydia-detailed.htm#_ENREF_3. Accessed 11/23/17
- Oakeshott P, Kerry S, Aghaizu A, et al. Randomized controlled trial of screening for Chlamydia trachomatis to prevent pelvic inflammatory disease: the POPI (prevention of pelvic infection) trial. BMJ (Clinical research ed) 2010; 340:c1642.
- Westrom L, Joesoef R, Reynolds G, Hagdu A, Thompson SE. Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sexually transmitted diseases 1992; 19:185-92.
- Rours GI, Duijts L, Moll HA, et al. Chlamydia trachomatis infection during pregnancy associated with preterm delivery: a population-based prospective cohort study. European journal of epidemiology 2011; 26:493-502.
- CDC. Gonorrhea - CDC Fact Sheet (Detailed Version) https://www.cdc.gov/std/gonorrhea/stdfact-gonorrhea-detailed.htm#ref1 Accessed 11/24/17
- Satterwhite CL et al, Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008. STD 2013;40(30):187-93
- Torrone E, Papp J, Weinstock H. Prevalence of Chlamydia trachomatis Genital Infection Among Persons Aged 14–39 Years — United States, 2007–2012. MMWR 2014; 63:834-8.
- Marcus JL, Bernstein KT, Stephens SC, et al. Sentinel surveillance of rectal chlamydia and gonorrhea among males–San Francisco, 2005-2008. Sexually transmitted diseases 2010; 37:59-61.
- Pinsky L, Chiarilli DB, Klausner JD, et al. Rates of asymptomatic nonurethral gonorrhea and chlamydia in a population of university men who have sex with men. Journal of American College Health: J of ACH 2012; 60:481-4.
- Frommell GT, Rothenberg R, Wang S, McIntosh K. Chlamydial infection of mothers and their infants. The Journal of pediatrics 1979; 95:28-32.
- Hammerschlag MR, Chandler JW, Alexander ER, English M, Koutsky L. Longitudinal studies on chlamydial infections in the first year of life. Pediatric infectious disease 1982; 1:395-401.
- Heggie AD, Lumicao GG, Stuart LA, Gyves MT. Chlamydia trachomatis infection in mothers and infants. A prospective study. American journal of diseases of children (1960) 1981; 135:507-11.
- Schachter J, Grossman M, Sweet RL, Holt J, Jordan C, Bishop E. Prospective study of perinatal transmission of Chlamydia trachomatis. JAMA : the journal of the American Medical Association 1986; 255:3374-7.
- Park J, Marcus JL, Pandori M, Snell A, Philip SS, Bernstein KT. Sentinel surveillance for pharyngeal chlamydia and gonorrhea among men who have sex with men–San Francisco, 2010. Sexually transmitted diseases 2012; 39:482-4.
- Low N, Redmond S, Uusküla A, van Bergen J, Ward H, Andersen B, Götz H. Screening for genital chlamydia infection. Cochrane Database Syst Rev. 2016; 13;9:CD010866.
- McCormack WM, Johnson K, Stumacher RJ, Donner A, Rychwalski R. Clinical spectrum of gonococcal infection in women. Lancet. 1977; 1(8023), 1182–1185.
- Curran J, Rendtorff R, Chandler R, Wiser W, Robinson H. Female gonorrhea: its relation to abnormal uterine bleeding, urinary tract symptoms, and cervicitis. Obstet Gynecol. 1975; 45(2), 195–198.
- Final Recommendation Statement: Chlamydia and Gonorrhea: Screening. U.S. Preventive Services Task Force. December 2016. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/chlamydia-and-gonorrhea-screening. Accessed 11/23/17
- Korenromp EL, Sudaryo MK, de Vlas SJ, et al. What proportion of episodes of gonorrhoea and chlamydia becomes symptomatic? International journal of STD & AIDS 2002; 13:91-101.
- Berger RE, Alexander ER, Monda GD, Ansell J, McCormick G, Holmes KK. Chlamydia trachomatis as a cause of acute “idiopathic” epididymitis. The New England journal of medicine 1978; 298:301-4.
- Klein EJ, Fisher LS, Chow AW, Guze LB. Anorectal gonococcal infection. Ann Intern Med 1997; 86:340–346.
- Bro-Jorgensen A, Jensen T. Gonococcal pharyngeal infections: report of 110 cases. Brit J Vener Dis. 1973; 49: 491–499.
- Masek BJ, Arora N, Quinn N, et al. Performance of three nucleic acid amplification tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae by use of self-collected vaginal swabs obtained via an Internet-based screening program. J Clin Microbiol 2009; 47:1663–7.
- Doshi JS, Power J, Allen E. Acceptability of chlamydia screening using self-taken vaginal swabs. Int J STD AIDS 2008; 19:507–9.
- Papp JR, Schachter J, Gaydos C, et al. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae-2014. MMWR Recomm Rep 2014; 63 (No. RR-02).
- 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.
- Moran JS, Levine WC. Drugs of choice for the treatment of uncomplicated gonococcal infections. Clin Infect Dis 1995; 20(Suppl 1):S47–65.
- Schillinger JA, Kissinger P, Calvet H, et al. Patient-delivered partner treatment with azithromycin to prevent repeated Chlamydia trachomatis infection among women - a randomized, controlled trial. Sex Transm Dis 2003; 30:49–56.
- Hosenfeld CB, Workowski KA, Berman S, et al. Repeat infection with chlamydia and gonorrhea among females: a systematic review of the literature. Sex Transm Dis 2009; 36:478–89.