This chapter should be cited as follows:
Welch K, Chi A, et al, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.419973
The Continuous Textbook of Women’s Medicine Series – Gynecology Module
Volume 12
Infections in gynecology
Volume Editors:
Professor Francesco De Seta, Department of Medical, Surgical and Health Sciences, Institute for Maternal and Child Health, University of Trieste, IRCCS Burlo Garofolo, Trieste, Italy
Dr Pedro Vieira Baptista, Lower Genital Tract Unit, Centro Hospitalar de São João and Department of Gynecology-Obstetrics and Pediatrics, Faculdade de Medicina da Universidade do Porto, Portugal
Chapter
Chlamydia and Gonorrhea
First published: September 2023
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INTRODUCTION
Sexually transmitted infections (STIs) are frequent worldwide. According to global estimates, the population acquires more than 1 million curable STIs every day. Chlamydia trachomatis (CT) and Neisseria gonorrhoea (NG) are two of the most common.
There is higher disease-burden of STIs in low- and middle-income countries (LMIC). This is likely due to a multitude of factors including long-standing poverty, poor access to healthcare, inadequate screening, social stigma, females lacking agency in healthcare, lower sexual health education, issues with antibiotic access and resistance. In high-income countries, access to molecular diagnostic testing is often readily available with rapid turnaround times that allow for accurate treatment.1
Untreated, these infections may lead to long-term irreversible outcomes such as chronic pelvic pain, infertility, adverse perinatal outcomes, and neonatal complications including ophthalmia neonatorum acquired at birth.2 Further, there is increased risk for ectopic pregnancy after chlamydial infection. Chlamydial infection during pregnancy increases the risk of premature rupture of membranes, preterm birth, and decreased birth weight.3,4
This chapter presents the specifics of CT and NG infection. These organisms share many common features and concomitant infections are common. Therefore, we encourage the reader to consider each infection both individually and as potentially paired conditions.
CHLAMYDIA TRACHOMATIS
Chlamydia is the most common bacterial source of sexually transmitted infection.1,2 This infection is often asymptomatic, leading to continued transmission. Specifically, most infected females are asymptomatic. Left untreated serious complications may ensue. These include pelvic inflammatory disease, chronic pelvic pain, infertility, ectopic pregnancy, and subsequent neonatal complications.1
Almost all CT is sexually transmitted. It is caused by a Gram-negative bacterium that is an obligate intracellular parasite. The incubation period ranges from 5 to 14 days following exposure. In 2020, the WHO estimated 129 million new cases of chlamydia.5 In the United States, the Center for Disease Control (CDC) reported an incidence of 552.8 cases per 100,000 people in 2019.5 Infection in females is higher than in males likely reflecting higher screening rates in females. Prevalence of chlamydial infection is highest in 14–24 year olds.1,2 Incidence and prevalence vary by race, ethnicity, and geography, as well as economic disadvantage.6
- Risks of infection:
Risk of repeat infection with CT is high. In a systemic review of 38 studies reinfection with chlamydia for females was 13.9%.7 Co-infections with other sexually transmitted infections are common, especially with gonorrhea.4 Trichomoniasis is also found to occur with CT infection.5 This emphasizes the importance of screening for other sexually transmitted infections in patients with positive CT infection.
CLINICAL MANIFESTATIONS OF CHLAMYDIA
Cervicitis | Most females with cervical infection are asymptomatic. In one screening study of high-risk females, only 6–14% were symptomatic. Symptoms include change in vaginal discharge, bleeding between periods, and bleeding after sexual intercourse.1,6 |
Conjunctivitis | Infection of the conjunctivae may occur. This typically results from direct contact with genital secretions. This generally presents as erythema of the conjunctivae without purulent discharge. In the infected newborn exposed to vaginal secretions at birth, this is known as ophthalmia neonatorum. |
Genitourinary tract infection | The cervix is the most commonly infected site in females.8 Some will also have urethral infection. Without treatment, cervical infection can cause pelvic inflammatory disease (PID). Complications of PID include chronic pain and infertility. Presence of cervical ectropion is associated with increased risk of chlamydia infection. There appears to be a link between chlamydial infection and a subsequent risk of cervical dysplasia.9,10 |
Urethritis | Many females with urethral infection are asymptomatic. Some will note symptoms typical of a urinary tract infection. This may confound the diagnosis unless testing is performed for CT. |
Pelvic inflammatory disease | Ascension into the upper reproductive tract (uterus, uterine tubes, and ovaries) can occur with CT infection leading to pelvic inflammatory diseases (PID).11 Some studies suggest a PID rate as high as 30% when CT is treated with antibiotics that were ineffective against the infection.12 Paradoxically, other studies show no cases of clinically detected PID after a year without treatment for CT infection.13 Unfortunately, PID often goes undiagnosed until sequalae of the disease present in conditions like infertility of tubal origin.14 |
Perihepatitis | This is defined as inflammation of the liver capsule and peritoneum often seen incidentally through laparoscopy as filmy adhesions between the liver and anterior abdominal wall. It may present as frequently as 5–15% of the time in conjunction with PID. |
Pharyngitis | Chlamydial infection seldom causes pharyngitis but should be considered a potential source of infection.15 |
Rectum | Infection in distal rectal mucosa occurs primarily in males who have sex with males (MSM). In females, it is often asymptomatic and can occur with or without receptive anal intercourse. Symptoms may occur in females but at a lower frequency than in MSM.16 |
Lymphogranuloma venereum | Lymphogranuloma venereum (LGV) is endemic in East and West Africa, India, Southeast Asia, and the Caribbean. It is a genital ulcer disease that chronically infects the lymphoid tissue and is caused by a more invasive strain of Chlamydia trachomatis. It is more common in males than females, particularly among MSM and HIV+ persons.17 |
Reactive arthritis | This can occur as sequelae from a STI. Chlamydia is the most common cause. It includes a triad of arthritis, conjunctivitis or uveitis, and urethritis or cervicitis.18,19 |
DIAGNOSIS
Nucleic acid amplification testing (NAAT) is the preferred method for detection of CT. The method consists of amplifying DNA or RNA sequences by polymerase chain reaction (PCR), strand displacement amplification, or transcription mediation amplification.1
- Specimens for testing in females:
- vaginal swab (can be self-collected)
- endocervical sample done at the time of speculum examination
- first catch urine.
- Specimens for testing in males:
- urethral swab (can be self-collected)
- first catch urine.
For diagnosis of rectal infection, a rectal swab can be collected and NAAT testing is recommended.20 NAAT can also be used to diagnose conjunctivitis.21
SCREENING
Screening aims to prevent complications associated with infection with CT. It is formally recommended by the US Preventative Task Force (USPSTF).22 Recommendations for screening for CT infection are listed below.1
- Females:
- sexually active females <25 years old
- sexually active females ≥25 years old if at increased risk
- retest 3 months after treatment.
- Pregnant female:
- all pregnant females <25 years
- sexually active females ≥25 years old if at increased risk
- retest third trimester <25 years at risk
- if positive for chlamydia retest 4 weeks after treatment and after 3 months.
There is currently insufficient evidence to recommend routine testing in males who have sex with females. More frequent testing should be considered in high-risk populations (HIV positive, immune suppressed, or multiple partners). Routine screening should be offered to transgender men who have a cervix based on the above guidelines.1
TREATMENT
Goals of treatment are multi-faceted. They include resolving symptoms, mitigating sequelae of chlamydial infection, decreasing risk of transmission, and preventing reinfection.
Chlamydia and gonorrhea are both reportable health conditions in the United States. Contact tracing, or partner notification, is a central component of controlling infections, by reducing transmission and repeat infections. Traditionally public health departments would notify sexual partners, however given limited resources and staffing this is generally not feasible.23 Thus, all patients with positive chlamydia and/or gonorrhea test results should notify their sex partner(s) so that they can receive appropriate treatment.
Chlamydia trachomatis is universally sensitive to tetracyclines and macrolides as well as some fluoroquinolones.24
- Choice of antibiotic:1
- Preferred
- Doxycycline 100 mg twice daily for 7 days
- Alternatives
- Azithromycin 1000 mg once
- Preferred in pregnant females
- If concern for compliance with doxycycline regimen
- Levofloxacin 500 mg for 7 days
- Not superior to doxycycline
- Azithromycin 1000 mg once
- Preferred
Doxycycline is preferred to azithromycin as there are superior microbiologic outcomes. Clinical resolution of symptoms is similar.25 Adverse effects are similar with doxycycline and azithromycin.26 The advantage to azithromycin is single-dose administration, thus improving adherence to the treatment regimen. Penicillins and erythromycin are inferior and should be reserved for pregnant patients that cannot take other agents.1
Due to high likelihood for co-infection, all patients with chlamydia should be offered testing for gonorrhea. If testing for gonorrhea is not available, treatment is recommended in high-risk patients or dependent upon high local prevalence rates of greater than 5%. It is not recommended to presumptively treat gonorrhea in all patients that are positive for chlamydia. Testing for other sexually transmitted infections is recommend. Further, screening is recommended for gonorrhea, HIV, and syphilis. All patients should return at 3 months after treatment (or, if that is not possible, within 12 months of treatment) for retesting. This is recommended regardless of partner treatment status.1
Certain patients should undergo a test of cure at 4 weeks after treatment. These include pregnant patients, those with continued symptoms, concern for incomplete treatment, and those treated with inferior regimens.1
PATIENT COUNSELING AND PARTNER THERAPY
Patients should be counseled regarding the importance of completing the entire course of medication. To prevent reinfection, patients should be advised to avoid sexual activity until the entire course of treatment is completed. This includes abstinence for 7 days following single-dose treatment.
All patients with positive chlamydia test results should notify their sex partner(s) so that they can receive appropriate treatment. Contact tracing, or partner notification, is a central component of controlling infections, by reducing transmission and repeat infections. Historically, a healthcare provider informs, evaluates, and treats the sex partners of persons infected with STIs. However, there are barriers for sex partners to access this care leading to delays in treatment.
An effective alternative approach to ensure treatment of partners is expedited partner therapy (EPT). This approach is explained in an upcoming paragraph.
GONORRHEA
Gonorrhea is the second most reported bacterial communicable disease. Like chlamydia, infected females are often asymptomatic. As of 2020, the WHO estimates that there are 82.4 million new cases of gonorrhea among adults and adolescents (15–49 years old) each year.
The precise global burden of gonococcal infections is difficult to establish because of the discrepancies in diagnostics and/or reporting systems in many parts of the world. Geographic distribution varies by region.1,2,27 Importantly, major racial disparities exist and rates are particularly high in specific subpopulations. For more on this discussion, refer to the paragraph on special populations.
Not only are gonorrhea and chlamydial co-infections common, NG has an important epidemiologic association with HIV. The acquisition of gonococcal infection itself is a risk factor for HIV infection. Gonococcal infection appears to facilitate both the transmission and acquisition of HIV, and conversely, the presence of HIV infection is associated with increased acquisition of NG.28
NG antibiotic resistance is a global concern. Surveillance efforts demonstrate increased resistance worldwide to multiple classes of antibiotics. Specifically, drug resistance to cephalosporins suggests the potential for untreatable NG in the near future.29,30,31
Similar to CT, NG is an intracellular organism. Gonococcal infection is initiated when the bacterium attaches to the mucosal cell surface, then invades, grows and causes either a local inflammatory response or systemic dissemination.32
CLINICAL PRESENTATION
Cervicitis | The cervix is the most common mucosal site of infection. At least 70% of infections are asymptomatic, however if symptoms are present, they are vaginal pruritus, mucopurulent discharge, intermenstrual bleeding or heavy vaginal bleeding. Upon examination, the cervix may or may not have discharge present and can appear friable or normal.33 |
Urethritis | At least 90% of patients with concurrent gonococcal cervicitis have urethritis. In females with a history of hysterectomy the urethra is the main site of a genital gonococcal infection.34 |
Pelvic inflammatory disease | Current literature suggests that up to 50% of PID cases are attributed to either chlamydia or gonorrhea1 |
Inflammation of the greater vestibular gland (Bartholinitis) | Uncommon cause of gonococcal infections |
SCREENING/RISK ASSESSMENT
Since a large portion of infections are asymptomatic, proper diagnosis relies on robust screening programs and a high index of suspicion. In the United States, the Center for Disease Control (CDC) recommends annual screening in all sexually active females under 25 years and those at increased risk of infection (new sex partner, more than one sex partner, a sex partner with concurrent sex partners, or a sex partner who has an STI). Additional risk factors for gonorrhea include inconsistent condom use among persons who are not in mutually monogamous relationships, previous or coexisting STIs, and exchanging sex for money or drugs. Culture and NAAT are suitable testing modalities. NAAT is the test of choice. Notably, patient collected swabs are acceptable. However, culture is needed for antibiotic resistance testing and should be obtained from the endocervix. Clinicians are advised to review NAAT product inserts for specific recommendation for screening.1
In resource-limited settings, it is recommended to treat based on risks and symptoms using tools that are available.
TREATMENT/MANAGEMENT
Due to rising rates of gonococcal resistance to other agents (sulfonamides, penicillins, tetracyclines, and fluoroquinolones), third-generation cephalosporins are considered first-line monotherapy.1
Preferred regimen for uncomplicated gonococcal infections (CDC guidelines)
"High" dose intramuscular ceftriaxone – single-agent therapy with ceftriaxone is the preferred regimen for treatment of gonococcal infections.
- For individuals who weigh <150 kg – ceftriaxone 500 mg intramuscular (IM) in a single dose.
- For individuals who weigh ≥150 kg – ceftriaxone 1 g IM in a single dose.
- Alternative regimens:
- If cephalosporin allergy:
- Gentamicin 240 mg IM in single dose plus azithromycin 2 g orally in a single dose.
- If ceftriaxone administration is not available or not feasible:
- Cefixime 800 mg orally in a single dose.
- If cephalosporin allergy:
For any of the above regimens, if chlamydia infection has not been excluded, doxycycline 100 mg orally 2 times/day for 7 days should be offered, unless the patient is pregnant or has an allergy to doxycycline. Further, patients who present within 1–2 weeks of a potential or known exposure to gonorrhea, diagnostic testing should not be used to inform the decision to treat. Such patients should be treated empirically.1
In patients who have positive gonococcal testing, further evaluation for co-infection with CT, HIV, and syphilis is recommended. Decreased susceptibility of NG to cephalosporins and other antimicrobials is expected to continue. Regulated surveillance for antimicrobial resistance is crucial for guiding local therapy recommendations.1
Clinicians who diagnose NG infection in a person with suspected cephalosporin treatment failure should perform culture of relevant clinical specimens, consult an infectious disease specialist or an STD clinical expert (https://www.stdccn.org/render/Public) for guidance in clinical management. They should report the case to CDC through state and local public health authorities within 24 hours. Isolates should be saved and sent to CDC through local and state public health laboratory mechanisms. Cephalosporin treatment failure is the persistence of NG infection despite recommended cephalosporin treatment. Such failure is indicative of infection with cephalosporin-resistant gonorrhea among persons whose partners were treated and whose risk for reinfection is low. Suspected treatment failure has been reported among persons receiving oral and injectable cephalosporins. The majority of suspected treatment failures in the United States are likely to be reinfections rather than actual treatment failures.
To maximize adherence with recommended therapies and reduce complications and transmission, medication for GC infection should be provided on-site and directly observed.
Retesting – Patients diagnosed with gonorrhea are at risk for repeat infection as well as infections with other sexually transmitted infections. All patients should return at 3 months after treatment (or, if that is not possible, within 12 months of treatment) for retesting for NG infection.1
PATIENT COUNSELING
Similar to treatment of chlamydia, patients are generally counseled to avoid sexual activity until 7 days following treatment initiation.1 Patients should only resume having sex after symptoms have resolved and sex partners have been treated.
Patients diagnosed with NC infection should be tested for other STIs, including HIV, chlamydia, and syphilis.1 Additional screening can be offered.
Females should be offered pregnancy testing when appropriate.
Unlike chlamydia, patients who have completed treatment for uncomplicated urogenital or anorectal gonococcal infections do not need to return for a test of cure.1 However, the United States Centers for Disease Control and Prevention (CDC) recommends that a test of cure be performed in all individuals with oropharyngeal gonococcal infection.
Patients should be instructed to return to care for evaluation for treatment failure and antimicrobial resistance if they experience persistent or recurrent symptoms soon (e.g., 3–5 days) after completing therapy for gonorrhea. Treatment failure is also suspected in individuals who have a positive test of cure.1 Many of these cases are due to reinfection or other sexually transmitted infections.
In cases where reinfection is unlikely (e.g., if there were no additional sexual exposures following treatment), treatment failure and resistance are a greater concern. Specimens should be submitted for culture and NAAT for NG detection and culture isolates should be sent for susceptibility testing.1
Gonorrhea is a reportable health condition in the United States. Traditionally public health departments would notify sexual partners, however given limited resources and staffing this is generally not feasible.23 All patients with positive GC test results should notify their sex partner(s) so that they can receive appropriate treatment. Contact tracing, or partner notification are a central component of controlling infections by reducing transmission and repeat infections.
Much like with chlamydia, expedited partner therapy (EPT) can be an effective alternative way of treating sexual partners without requiring them to present to a healthcare provider.
SPECIAL CONSIDERATIONS
Expedited or accelerated partner therapy
Ideally, the sex partner of the patient with an STI undergoes evaluation and treatment by their own clinician. Because this is not aways possible, healthcare providers should consider expedited partner therapy (EPT). This is the clinical practice of treating the sex partner(s) of those infected with an STI. The clinician provides medications or prescriptions to the infected person for distribution to their sex partner(s) without clinical assessment of the partner(s). While it is controversial to prescribe for a patient who has not been seen or evaluated by the clinician, it has been a common practice in the United States since 2006. However, it may be limited in some jurisdictions. The clinician is advised to be familiar with local regulations prior to practicing EPT.
The current CDC recommendation for chlamydia EPT therapy is the same as the index patient. The only-CDC recommendation for uncomplicated urogenital, anorectal, and pharyngeal GC EPT is monotherapy with a single intramuscular dose of ceftriaxone 500 mg. If EPT via injection is not feasible, the CDC recommend 800 mg cefixime orally in a single dose.1
There are some potential concerns about EPT. Some individuals receive unnecessary treatment since testing is not required beforehand. This potentially, increases antibiotic resistance and changes to their gut microbiome. Thus, in some countries, there are limitations to EPT. For example, in Australia, patient-delivered EPT is not recommended for those with multiple STIs, patients whose partners are pregnant; patients who have experienced recent sexual assault or might be at risk of partner violence, patients or partners who might be at increased risk of HIV or other sexually transmitted infections (such as men who have sex with men), and patients who have partners with any genital symptoms.1,35
Low- and middle-income countries
While the gold standard for treating chlamydia and gonorrhea is based in molecular diagnostic testing, these tests are largely unavailable in low- and middle-income countries (LMIC). Even when testing is available, it is often expensive and not widely accessible. Delays in receiving test results may lead to untimely or incomplete treatment.
LMICs often rely on syndromic management flow charts as the standard of care. These flow charts use consistent, easily recognizable signs and symptoms to guide treatment, without the use of laboratory tests. Examples include persistent urethral discharge syndrome, vaginal discharge syndrome, anorectal infection; genital ulcer disease syndrome, and lower abdominal pain syndrome. These algorithms can be obtained through the WHO: Guidelines for the management of symptomatic sexually transmitted infections (https://www.who.int/publications/i/item/9789240024168).
Sexual assault and abuse
CT and GC should be a part of the evaluation in cases of sexual assault and/or abuse. NAAT is preferred testing and its recommended to evaluate any exposed orifice. Empiric antimicrobial therapy should be performed. Please refer to the CDC or similar body for complete guidelines.1,36
Syndromic management allows for rapid, same-day treatment and avoids expensive and unavailable diagnostic tests; however, it can result in both over treatment and missed treatment, especially since the majority of STIs are asymptomatic. Thus, WHO recommends countries to augment syndromic management by gradually incorporating laboratory testing to support diagnoses, and to treat based on molecular diagnostic test results. If testing is limited, screening should be prioritized for those at higher risk of STIs, such as sex workers, men who have sex with men, adolescents, and pregnant females.1
PRACTICE RECOMMENDATIONS
- Due to the high likelihood for co-infection, all patients with positive chlamydia testing should be tested for gonorrhea. If testing for gonorrhea is not available, treatment is recommended in high-risk patients or dependent upon high local prevalence rates of greater than 5%. It is not recommended to presumptively treat gonorrhea in all patients that are positive for chlamydia. Testing for other sexually transmitted infections is recommend. Additional STI screening is recommended including HIV and syphilis.
- Expedited partner therapy (EPT) is the clinical practice of treating the sex partner(s) of patients infected with an STI without prior clinical assessment. This is generally implemented in those with limited means or unlikely to follow-up with their own clinician.
- Recommendations for chlamydia and gonorrhea are ever-changing. Follow CDC and WHO guidelines for management and treatment. The CDC has an STI Treatment (TX) Guideline app that serves as a quick reference on the identification and treatment of sexually transmitted diseases (STDs). It is free and downloadable to clinician smart phones to provide ready access to updated information (https://www.cdc.gov/std/treatment-guidelines/default-htm).
CONFLICTS OF INTEREST
The author(s) of this chapter declare that they have no interests that conflict with the contents of the chapter.
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