Chlamydia is one of the most common sexually transmitted infections (STIs) worldwide, with millions of new cases reported annually. It is caused by the bacterium Chlamydia trachomatis and primarily affects the urogenital tract. Many individuals infected with C. trachomatis are asymptomatic, which may result in delayed diagnosis and an increased risk of complications, including pelvic inflammatory disease, ectopic pregnancy, and infertility.
Transmission typically occurs through unprotected vaginal, anal, or oral sex with an infected partner. Symptoms, when present, may include abnormal genital discharge, dysuria, and, in some cases, lower abdominal pain or testicular discomfort. Due to the non-specific nature of these symptoms, Chlamydia can be misdiagnosed or overlooked. Routine screening is recommended, particularly among sexually active individuals under the age of 25 or those at higher risk.
Preventive measures include consistent condom use, mutual monogamy, and regular STI testing. Public health strategies focusing on education, early detection, and access to diagnostic and treatment services have been shown to reduce transmission rates. Chlamydia is typically treatable with antibiotics, and prompt treatment can prevent most complications.
Etiology and Pathogenesis
The etiology of chlamydia is attributed to Chlamydia trachomatis, a Gram-negative, obligate intracellular bacterium. It is the most common bacterial cause of sexually transmitted infections (STIs) worldwide, with an estimated 129 million new cases occurring annually according to the World Health Organization (WHO). The pathogen primarily targets columnar epithelial cells in the urogenital tract, rectum, conjunctiva, and, less commonly, the pharynx.
Once inside host epithelial cells, C. trachomatis undergoes a unique biphasic developmental cycle alternating between the infectious elementary body (EB) and the replicative reticulate body (RB). This intracellular replication can induce a host immune response characterized by the release of pro-inflammatory cytokines, including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α). Persistent or repeated infections can lead to chronic inflammation, tissue damage, and complications such as pelvic inflammatory disease (PID), ectopic pregnancy, and tubal factor infertility, particularly in women.
Transmission of C. trachomatis occurs predominantly through unprotected vaginal, anal, or oral sexual contact. It can also be vertically transmitted from mother to neonate during childbirth, potentially causing conjunctivitis or pneumonia in the newborn. Asymptomatic infections are common—up to 70–80% in women and 50% in men—contributing to delayed diagnosis and increased transmission within the population.
Epidemiology
Chlamydia, caused by Chlamydia trachomatis, is one of the most prevalent STIs worldwide. The World Health Organization (WHO) estimates approximately 129 million new cases annually, while global data from 2009–2016 indicate about 127 million new infections per year among people aged 15–49. In 2015, the global point prevalence was about 4.2% in women and 2.7% in men, with an overall infection rate of approximately 61 million active cases at a given time.
Rates are highest in the 15–24 age group, with young women particularly affected—epidemiological surveys show prevalence rates of 14.6% in women under 25, compared to 4.3% in older women. In the U.S., 55.8% of all cases reported in 2023 occurred in individuals aged 15–24, and there were 1.65 million reported cases (492 per 100,000 population). Earlier data from 1999–2002 suggested prevalence of 2.2% among people aged 14–39, declining slightly to 1.7% by 2007–2012.
Risk factors include being younger, having multiple sexual partners, inconsistent condom use, and a history of prior STIs . Socioeconomic and demographic factors—such as low educational attainment, urban residence, and Black ethnicity—are also independently correlated with higher infection rates .
Screening strategies are central to control efforts: the U.S. CDC and USPSTF recommend annual NAAT-based screening for all sexually active women under 25, and for older women with risk factors. Retesting approximately three months after treatment is advised; pregnant women under 25 should be screened again in the third trimester . Evidence shows that screening reduces complications such as pelvic inflammatory disease (PID). However, only about 56% of sexually active women aged 15–24 actually undergo testing—often due to stigma, lack of awareness, or provider oversight.
Emerging trends include a 72% increase in chlamydia cases among men who have sex with men (MSM) from 2018 to 2022 in Europe, with reporting rates varying widely from 0.1 to 709 cases per 100,000.
Clinical Manifestations
Chlamydia trachomatis infection presents a broad spectrum of clinical manifestations that often vary between men and women. Notably, up to 70–80% of infected women and 50% of infected men are asymptomatic, which facilitates silent transmission and increases the risk of long-term complications. Infections may also involve extra-genital sites such as the rectum, conjunctiva, and pharynx, especially in individuals engaging in oral or anal sex.
Symptoms in Men
In men, symptomatic infections usually manifest 1–3 weeks after exposure. Common clinical features include:
- Urethritis: The most common presentation, characterized by dysuria (painful urination), urethral discharge (mucoid or purulent), and urethral itching. Microscopic evidence of ≥5 polymorphonuclear leukocytes (PMNs) per high-power field on urethral smear is diagnostic.
- Epididymitis: Typically unilateral and presents with testicular pain, tenderness, and swelling. It may be accompanied by scrotal erythema and fever. Chlamydia is responsible for up to 40% of epididymitis cases in men under 35 years.
- Prostatitis: Although less common, chlamydia can lead to chronic pelvic pain syndrome or inflammatory prostatitis, with symptoms such as perineal discomfort, urinary hesitancy, and painful ejaculation.
- Proctitis: Particularly in men who have sex with men (MSM), rectal chlamydia may cause anorectal pain, discharge, and tenesmus.
- Reactive Arthritis (Reiter’s Syndrome): An autoimmune complication affecting up to 1–4% of infected men, involving arthritis, conjunctivitis, and urethritis.
Because asymptomatic infections are frequent, routine screening is recommended for sexually active men who have sex with men (annually or every 3–6 months if high-risk), and for males with new or multiple sexual partners.
Symptoms in Women
Chlamydia is a major cause of reproductive tract infections in women, with symptoms often subtle or absent. When present, they typically appear within 7–21 days post-exposure:
- Cervicitis: The most common finding, featuring mucopurulent cervical discharge, contact bleeding (e.g., postcoital bleeding), and friability on exam. Microscopy shows >10 PMNs per high-power field.
- Urethritis: Can present as dysuria, urinary frequency, and sterile pyuria (white cells in urine without bacterial growth).
- Pelvic Inflammatory Disease (PID): Ascending infection leading to endometritis, salpingitis, and oophoritis. Clinical features include lower abdominal pain, cervical motion tenderness, fever, and adnexal tenderness. Chlamydia is identified in 20–40% of PID cases. Untreated PID can result in ectopic pregnancy, chronic pelvic pain, and tubal infertility—affecting up to 10–15% of infected women.
- Perihepatitis (Fitz-Hugh–Curtis Syndrome): A rare complication marked by right upper quadrant pain due to inflammation of the liver capsule, often in conjunction with PID.
- Conjunctivitis and Neonatal Infection: In perinatal transmission, newborns may develop conjunctivitis (18–44% of exposed infants) or chlamydial pneumonia (3–16%).
Due to the high asymptomatic rate, CDC and WHO recommend annual screening for all sexually active women under age 25, and for older women with risk factors (e.g., new or multiple sex partners).
Conjunctivitis and Reactive Arthritis
Chlamydia can lead to specific conditions like conjunctivitis, characterized by redness, swelling, and discharge from the eye. This can occur through direct contact with infected genital secretions.
Reactive arthritis, an inflammatory response, may develop following chlamydia infection. It typically causes joint pain and swelling, affecting areas such as knees, ankles, and feet. Other symptoms may include inflammation of the eyes and urinary tract symptoms.
Complications and Risks
If left untreated, chlamydia poses several risks:
- Infertility: In women, chronic infection can cause scarring of the fallopian tubes, leading to tubal factor infertility. It is estimated that 10–15% of untreated chlamydial infections result in pelvic inflammatory disease (PID), and ~20% of PID cases result in infertility.
- In men, recurrent epididymitis and inflammation can impair sperm motility and function, although complete infertility is less common.
- Ectopic Pregnancy: Tubal damage from chronic inflammation increases the likelihood of implantation outside the uterus. Up to 9% of women with a history of PID develop ectopic pregnancies, a potentially life-threatening condition.
- Increased HIV Risk: Chlamydia-induced mucosal inflammation recruits HIV target cells (CD4+ T-cells and dendritic cells) to the genital tract, increasing the risk of HIV acquisition. Studies suggest that women with chlamydia are 2–3 times more likely to contract HIV if exposed.
Diagnosis
Diagnosing Chlamydia trachomatis infection involves a combination of laboratory testing, diagnostic imaging, and careful differentiation from other potential conditions. Early and accurate diagnosis is vital to prevent complications such as infertility, pelvic inflammatory disease (PID), and ongoing transmission.
Laboratory Testing
Laboratory testing remains the gold standard for diagnosing chlamydia. The most reliable method is the use of nucleic acid amplification tests (NAATs), which detect the genetic material of the bacterium with high sensitivity and specificity—often exceeding 95%. NAATs can be performed on a variety of specimen types, including first-catch urine or swabs collected from the cervix (in women), urethra (in men), and rectum or oropharynx in individuals engaging in receptive anal or oral sex. Self-collected vaginal swabs are also considered clinically acceptable and have comparable accuracy to clinician-collected specimens.
Specimen collection is straightforward and minimally invasive. For men, first-void urine samples are usually sufficient, while women may undergo a cervical or vaginal swab. Testing for chlamydia is frequently conducted in tandem with gonorrhea testing, given the high rate of co-infection—reported in 10–40% of individuals diagnosed with either infection. Comprehensive STI panels may also screen for Trichomonas vaginalis, Mycoplasma genitalium, HIV, and syphilis depending on the clinical setting and risk profile.
Rapid antigen tests and point-of-care tests are available in some settings, especially where laboratory infrastructure is limited. However, these tests typically have lower sensitivity compared to NAATs and may miss up to 30–40% of infections, especially in asymptomatic individuals. Thus, follow-up and confirmation through NAAT-based testing are recommended when possible. Routine screening is advised for all sexually active women under age 25 and for older individuals with risk factors such as multiple sex partners, new partners, or inconsistent condom use.
Diagnostic Imaging
Although not routinely used for diagnosing uncomplicated chlamydia, can be invaluable in identifying complications like PID. Pelvic ultrasound is often the first-line imaging modality used to assess for tubo-ovarian abscesses, hydrosalpinx (fluid-filled fallopian tubes), or endometrial thickening. These findings are indicative of more advanced or chronic infection. In severe or equivocal cases, computed tomography (CT) scans may be employed to assess the extent of pelvic or abdominal involvement. CT provides higher-resolution images and may be especially helpful in differentiating chlamydia-related sequelae from other abdominal or pelvic pathologies, such as appendicitis or ovarian torsion.
Differential Diagnosis
The process of differential diagnosis is critical in distinguishing chlamydia from other conditions with overlapping symptoms. For example, urethral discharge, dysuria, and pelvic pain may also be seen in gonorrhea, trichomoniasis, bacterial vaginosis, and urinary tract infections (UTIs). In such cases, clinicians rely on a combination of patient history, physical examination, and targeted laboratory testing to arrive at the correct diagnosis. Co-infections are common and must be considered—especially in populations at high risk, such as men who have sex with men (MSM), sex workers, and individuals with a prior STI history.
In complex or recurrent cases, additional tests such as HIV screening, syphilis serology, and cultures for antibiotic susceptibility (especially in treatment failures) may be necessary. For individuals presenting with atypical symptoms or persistent infection despite treatment, evaluating for Mycoplasma genitalium or antibiotic resistance patterns may also be warranted.
Timely and accurate identification of chlamydia is essential not only for effective treatment but also to interrupt transmission chains and prevent long-term complications. Integrating sensitive diagnostic methods with comprehensive STI screening protocols enhances public health outcomes and reduces disease burden globally.
Treatment
Effective treatment of Chlamydia trachomatis infection relies on the timely use of antibiotics, adherence to evidence-based treatment regimens, and comprehensive management of sexual partners to prevent reinfection. Addressing treatment failures and ensuring appropriate follow-up are also critical components of successful case resolution and long-term prevention.
Antibiotic therapy remains the cornerstone of chlamydia treatment. The Centers for Disease Control and Prevention (CDC) currently recommends two first-line regimens:
- Doxycycline: 100 mg orally twice daily for seven days
- Azithromycin: 1 gram orally in a single dose
Recent studies have shown doxycycline to have superior efficacy, particularly in rectal chlamydial infections, with cure rates exceeding 95%, compared to slightly lower rates for azithromycin in such cases. However, azithromycin remains widely used due to its simplicity and single-dose administration, which improves adherence—especially in populations where follow-up may be difficult.
Treatment regimens may vary in special populations, such as pregnant individuals. In pregnancy, doxycycline is contraindicated due to risks of fetal tooth discoloration and bone growth inhibition. Instead, the CDC recommends:
- Azithromycin: 1 gram orally in a single dose (preferred)
- Amoxicillin: 500 mg orally three times daily for seven days (alternative)
Erythromycin may also be used in certain cases, though it is often associated with gastrointestinal side effects. Pregnant individuals treated for chlamydia should undergo a test of cure three to four weeks after treatment, followed by repeat testing at three months, given the high risk of reinfection and potential for vertical transmission during delivery.
All individuals diagnosed with chlamydia—regardless of symptoms—should be retested three months after treatment. Studies have found that up to 20% of treated individuals may be reinfected within this time frame, often due to untreated sexual partners.
Management of sexual partners is essential to prevent reinfection and further transmission. The CDC recommends that all sexual partners from the preceding 60 days before diagnosis be notified, tested, and treated. If the most recent sexual contact occurred more than 60 days ago, the most recent partner should still be evaluated and treated.
One of the most effective public health strategies in partner management is Expedited Partner Therapy (EPT). EPT allows healthcare providers to offer medication or prescriptions to patients for their sexual partners without requiring a prior medical evaluation of the partner. This approach has been shown to significantly reduce reinfection rates and is legally permitted in many U.S. states and other countries, though its availability varies by jurisdiction.
Treatment failure, though uncommon, can occur and requires careful evaluation. The most common reasons for failure include:
- Nonadherence to the prescribed regimen
- Reinfection from an untreated partner
- Coinfection with another STI (e.g., Mycoplasma genitalium)
- Antibiotic resistance, although rare in Chlamydia trachomatis
In cases where symptoms persist after appropriate antibiotic therapy, re-testing using nucleic acid amplification tests (NAATs) should be performed at least three weeks after treatment completion to avoid detecting residual nonviable bacterial DNA. If infection is confirmed, alternative antibiotics such as levofloxacin (500 mg once daily for 7 days) or ofloxacin (300 mg twice daily for 7 days) may be considered.
Additionally, providers should consider evaluating for coexisting infections, especially if the clinical presentation is atypical or if symptoms recur shortly after treatment. In such scenarios, a full STI screen—including gonorrhea, HIV, syphilis, and Mycoplasma genitalium—may be warranted.
Preventive education is a key element of treatment. Patients should receive counseling on consistent condom use, risk reduction strategies, the importance of partner treatment, and the need for follow-up testing. Strengthening patient awareness helps reduce the overall burden of chlamydia and limits the spread of infection within communities.
Prevention
Preventing Chlamydia trachomatis infection requires a multi-pronged approach involving widespread screening programs, behavioral interventions targeting at-risk populations, and continued research into effective vaccination strategies. These public health efforts are critical in reducing transmission rates and minimizing the long-term health consequences associated with untreated infections.
Screening Programs
Screening programs are among the most effective tools for early detection and prevention. According to the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), sexually active women aged under 25 years, as well as older women with new or multiple sex partners, should undergo annual chlamydia screening. In men, routine screening is recommended for those in high-prevalence settings—such as correctional facilities, STI clinics, and among men who have sex with men (MSM)—though universal male screening is still debated due to cost-effectiveness concerns.
Studies have shown that organized screening programs can reduce the prevalence of chlamydia by up to 60% in targeted populations over a 3–5 year period. Screening methods typically involve non-invasive urine samples or genital swabs, both of which are suitable for nucleic acid amplification tests (NAATs). Community outreach initiatives, mobile STI clinics, and at-home testing kits have also expanded access, particularly for populations facing healthcare barriers. These efforts are crucial in identifying asymptomatic cases, which comprise approximately 70–80% of infections in women and 50% in men.
Behavioral Interventions
Behavioral interventions are central to reducing risky sexual behaviors associated with chlamydia transmission. These interventions include:
- Comprehensive sex education that emphasizes consistent condom use
- Condom distribution programs in schools, universities, and community centers
- Public health campaigns that destigmatize STI testing and encourage routine checkups
- Partner communication training, helping individuals discuss STI history and testing openly
Programs targeting adolescents, young adults, sex workers, and LGBTQ+ communities have been particularly effective. According to a meta-analysis published in The Lancet Infectious Diseases, school-based behavioral interventions reduced chlamydia incidence by 20–30% over 12 months, especially when paired with easy access to screening and treatment.
Health counseling and educational workshops also play an important role in empowering individuals with knowledge. When people understand the risks of unprotected sex, reinfection, and untreated infections, they are more likely to adopt protective behaviors. These sessions often include tailored risk assessments, motivational interviewing, and peer-led discussions, all of which are proven to increase testing uptake and treatment compliance.
Vaccination Research
Vaccine development represents the next frontier in chlamydia prevention. Although no vaccine is currently approved for use, preclinical studies and early-phase clinical trials are showing promise. The most advanced candidate, CTH522, is a recombinant protein-based subunit vaccine that has completed Phase 1 human trials. It was shown to be safe and capable of inducing both systemic and mucosal immune responses, including specific IgG antibodies and IFN-γ-producing T cells.
The goal of a chlamydia vaccine would be two-fold: to prevent initial infection and to reduce the severity of complications, such as pelvic inflammatory disease (PID) and infertility. Modeling studies suggest that a vaccine with 70% efficacy and moderate population coverage could reduce chlamydia prevalence by up to 55% within 10 years. While further trials are ongoing, the potential impact of a licensed chlamydia vaccine is significant, especially in resource-limited settings where regular screening and treatment access may be constrained.
Public Health Considerations
Chlamydia remains a significant global public health concern due to its high prevalence, potential for severe reproductive health complications, and considerable economic burden. Effective control requires coordinated strategies in surveillance, healthcare delivery, education, and resource allocation.
Reporting and Data Collection
Accurate and timely data collection is essential for tracking trends in chlamydia incidence, evaluating public health interventions, and allocating resources. Chlamydia trachomatis is classified as a notifiable disease in many countries, meaning healthcare providers and laboratories are legally required to report confirmed cases to public health authorities.
In the United States, the Centers for Disease Control and Prevention (CDC) maintains national surveillance data through systems like:
- National Notifiable Diseases Surveillance System (NNDSS)
- National Health and Nutrition Examination Survey (NHANES)
According to the CDC, over 1.6 million cases of chlamydia were reported in the U.S. in 2022, making it the most commonly reported notifiable disease. However, it is estimated that actual infections may exceed 4 million annually, due to underreporting and asymptomatic cases—particularly in women.
Enhanced community outreach and access to confidential testing services have been shown to improve reporting rates. Public education initiatives targeting schools, youth centers, and high-risk communities also contribute to more robust surveillance and early detection efforts.
Impact on Reproductive Health
Chlamydia has profound implications for reproductive health, particularly among sexually active adolescents and young adults. If untreated, it can cause severe and irreversible damage to reproductive organs in both women and men.
Key complications include:
- Pelvic Inflammatory Disease (PID): Occurs in up to 10–15% of untreated women with chlamydia. PID can lead to chronic pelvic pain, ectopic pregnancy, and tubal infertility. It is one of the leading causes of infertility in women globally.
- Ectopic Pregnancy: Chlamydia-induced tubal scarring increases the risk of ectopic pregnancy by 6–10 times. These pregnancies can be life-threatening and often require surgical intervention.
- Male Infertility: Though less common, chlamydia can cause epididymitis and lead to impaired sperm function, resulting in subfertility or infertility.
- HIV Co-infection Risk: Chlamydia increases susceptibility to HIV infection by compromising the genital mucosa and increasing inflammatory cell recruitment, which serves as targets for HIV. Studies suggest a three- to five-fold increase in HIV acquisition among chlamydia-infected individuals.
Economic Burden
Chlamydia exerts a substantial economic toll on both individuals and healthcare systems due to direct medical costs and indirect societal impacts. These costs are compounded by the fact that many infections are asymptomatic and go untreated until complications arise.
Key economic aspects include:
- Healthcare Expenditures: In the U.S. alone, the annual direct medical cost of chlamydia and its complications is estimated to exceed $500 million, based on CDC analyses. This includes costs of screening, treatment, partner notification, and managing complications like PID and ectopic pregnancy.
- Productivity Losses: Missed work due to illness, doctor visits, or long-term fertility issues contributes to indirect costs, affecting personal income and workforce efficiency. Young adults, who represent the highest burden of infection, are also the most economically active demographic.
- Public Health Investments: Funding large-scale STI prevention programs, public education campaigns, and screening efforts involves substantial financial commitments. However, cost-effectiveness studies have shown that screening programs targeting women under 25 result in net savings by preventing expensive complications.