Topic Editor: Becky Box, MBBS
Review Date: 11/11/2012
Definition 
Chlamydia is a common sexually transmitted disease (STD) caused by the atypical bacterium Chlamydia trachomatis. Patients are frequently asymptomatic or have non-specific symptoms. Chlamydia can be a low grade chronic infection or may present acutely, with a spectrum of complications or presentations, such as pelvic inflammatory disease (PID), ectopic pregnancy, infertility, cervicitis, urethritis or chronic pelvic pain in women and epidymo-orchitis, urethritis, or prostatitis in men. During pregnancy vertical transmission can result in ocular or pulmonary infection of the neonate. There is some evidence to suggest an association with chorioamnionitis and adverse pregnancy outcomes.
Description
- Genitourinary Chlamydial infection is the most common bacterial sexually transmitted disease in the United States
- The prevalence of infection is highest in adolescents and young adults
25 years of age - Chlamydia trachomatis species are divided into several serovariants based on the properties of their major outer membrane proteins
- Serovars D through K are responsible for causing Chlamydial infections in human. These serovars infect columnar epithelium of the eye, rectum and genitalia resulting in conjunctivitis, proctitis, cervicitis and urethritis
- Chlamydial infection is transmitted exclusively by sexual intercourse or through vertical transmission to neonates of infected mothers
- Vertical transmission to neonates presents as neonatal ophthalmia or pneumonia
- Chlamydial infection is asymptomatic in at least 50% of men and up to 70% of women.
- Symptomatic women may present with pelvic pain, vaginal discharge, dysuria, intermenstrual or post-coital bleeding. Symptomatic men may present with penile discharge, dysuria, tenesmus or rectal pain
- The serious complications associated with untreated Chlamydial infection place a large economic burden on society
Epidemiology
Incidence/Prevalence
- The incidence of Chlamydial infection appears to be rising over the past 10 years. This increase may be due to the implementation of improved screening programs and reporting, however the overall prevalence of infection is believed to be under-reported due to the asymptomatic nature of the disease
- In 2010, the incidence of chlamydia in the US was 426 cases per 100,000 population
- Approximately 100,000 neonates in the US are exposed to chlamydia infection annually
- The annual incidence of Chlamydia is estimated at 90 million new cases worldwide
- The World Health Organization (WHO) estimates the prevalence of chlamydia at >140 million individuals globally
- The prevalence in population studies varies between 1-40% depending on the population being tested
Age- The prevalence of chlamydia in the US (2010 data) was highest among females aged 15 to19 years, and males aged 20 to 24 years, with peak incidence among those in their late teens and early 20's
Gender
- Infection rates are 2.5-3.5 times higher in females than males. This may relate to increased testing and reporting in females as compared to males
- Females have an increased risk of long-term complications
Race
- The increased incidence of chlamydial infection in the US among African-Americans, Hispanics and Native Americans may be associated with individual sexual history, contraceptive use, and socioeconomic conditions
Risk factors
- African-American/Hispanic/Native American and Alaskan ethnicity
- Cervical ectopy
- Genetic predispositions such as cytokine polymorphisms and Toll-like receptor 1 and 4 genes
- Multiple sexual partners
- Not married or in a longer term exclusive relationship
- Poor socioeconomic status
- Previous or current co-infection with other STDs
- Sexual intercourse without barrier contraceptive
- Younger age (15 to 24 years)
Etiology
- The causative organism responsible for chlamydia is C. trachomatis
- C. trachomatis belongs to the phylum Chlamydiae, which are small gram-negative obligate intracellular bacteria which target squamocolumnar epithelial cells
- Among the 18 known serovars of C. trachomatis, servovars D through K are responsible genital tract infections, conjunctivitis, and pneumonia
- Serovars A through C result in Trachoma, a major cause of preventable blindness in developing countries
- Serovars L1-L3 results in lymphogranuloma venereum which causes genital ulcers and blocks lymphatic drainage
- Chlamydia requires a host cell to replicate. The life cycle consists of two main forms; Elementary and reticulate bodies. Elementary bodies are the infectious form, once in contact with the host cell, they induce endocytosis at the membrane. Once inside the cell membrane they germinate to form reticulate bodies. The reticulate bodies are responsible for replication, which then return to their elementary form and are shed from the cell via exocytosis
- Lysis of the infected host cell causes mucosal epithelial cells to become necrotic, which invokes the acute inflammatory response leading eventually to scarring and fibrosis. The acute inflammatory response is responsible for clinical presentations with conjunctivitis, pneumonitis, prostatitis, cervicitis and urethritis. Subsequent scarring leads to chronic PID and infertility due to tubular dysfunction
[Outline]
History
Patients should be evaluated for the following
- Contraceptive use
- History of STDs
- History of symptoms with onset date
- Number of sexual partners
- Sexual history
- Unsafe sexual practices
- Women
- Up to 70% of infected females are asymptomatic
- Infertility
- Dyspareunia
- Dysuria
- Fever in the case of PID
- Others may have symptoms such as:
- Progressive lower abdominal pain
- Rectal discharge in the case of anal sex with a proctitis
- Vaginal bleeding
- Vaginal discharge
- Men
- Fever
- Nearly 50% of infected males are asymptomatic
- Other may show symptoms such as
- Dysuria or perimeatal tingling being common
- Rectal discharge in the case of anal sex with a proctitis
- Unilateral scrotal pain/swelling (occasionally bilateral)
- Urethral discharge
- Neonates
- Symptoms of pneumonia, wheezing and coughing, usually in the absence of fever and/or conjunctivitis (eye swelling and discharge) occurring ~ 5-12 days of life
Physical findings on examination
- Men
- Dysuria
- Epididymal tenderness
- Frequency or urgency on urination
- Fullness in perineal region secondary to prostatitis
- Mucopurulent rectal discharge with proctitis
- Mucopurulent urethral discharge
- Neonates
- Conjunctivitis: Conjunctival erythema and discharge, or periorbital swelling
- Pneumonia: Cough, wheezing, crackles, and fever (fever often absent)
- Women
- Abnormal bleeding (non-menstrual)
- Cervical excitation or inflammation (cervicitis)
- Dysuria
- Fitz-Hugh-Curtis syndrome
- Friable and inflamed cervix
- Mucopurulent endocervical discharge
- Mucopurulent rectal discharge with proctitis
- Mucopurulent urethral discharge
- Pelvic adnexal tenderness
- Tenderness of the lower abdomen
[Outline]
Blood test findings
- Serology
- Serologic tests are not useful in the diagnosis of non-LGV C. trachomatis due to their low sensitivity, specificity, and predictive values
Other laboratory test findings
- Cell culture
- Culture is considered gold-standard with nearly 100% specificity. Sensitivity of cell cultures varies across laboratories (70% to 90%)
- C. trachomatis can be cultured on cell lines such as McCoy and HeLa cells. Giemsa stains or immunofluorescent staining may be used to identify intracytoplasmic inclusions
- Cell culture is usually preferred for confirming infections in legal cases, i.e. involving rape or sexual abuse. This is because it detects only viable infectious chlamydial elementary bodies
- Disadvantages of culture include a high cost, difficulty in test standardization and that they are technically difficult
- Nucleic acid amplification test (NAAT)
- Use of NAAT has revolutionized diagnostic testing for Chlamydia. Sensitivity is greater than cultures (>90%) with specificity paralleling cultures (99%)
- This test uses amplification and detection of nucleic acid sequences unique to Chlamydia. Subsequently, these tests can be conducted on urine specimens allowing for less invasive screening
- NAATs have been developed for analyzing self-collected vaginal swab specimens
- NAATs can also effectively detect C. trachomatis on rectal specimens
- Disadvantages relate to cost and reduced performance in urine samples in the presence of estrogens, nitrates or crystals, which can act as inhibitors
- Direct fluorescent antibody test (DFA)
- DFA has a sensitivity of 50% to 80% and a specificity of 99%, and can be used for confirmation of other assays
- The test requires specimens obtained from invasive sampling (endocervical or penile urethral swab), requires significant operator expertise, and can be labor intensive
- Enzyme immunoassay (EIA)
- EIA may be considered in cases where there is no availability of NAATs. EIA has a much lower sensitivity compared to NAAT (40% to 70%) and may provide false-negative results
- EIA also requires specimens obtained from invasive sampling (endocervical or penile urethral swab)
- Other tests
- Other effective detection techniques include polymerase chain reaction (PCR), ligase chain reaction (LCR), and nucleic acid hybridization
- These tests are highly sensitive, but are not considered to be cost-effective
[Outline]
Genitourinary Infection
- Bacterial vaginosis
- Cervicitis, gonococcal
- Epididymitis-viral
- Endometritis-post partum/retained products
- Fitz-Hugh-Curtis syndrome
- Herpes simplex
- Orchitis - mumps
- Pelvic inflammatory disease-due to another organism or associated with IUD
- Periurethral abscess
- Trichomoniasis
- Tubo-ovarian abscess
- Ureaplasma infections
- Urinary tract infections
- Vaginal candidiasis
Pulmonary Infection/Inflammation
- Meconium aspiration
- Mycoplasma/legionella, typical or viral pneumonia
- Viral pneumonitis
Conjunctivitis
- Viral
- Allergic
- Bacterial-staph/streptococcus or haemophilus
Other
- Ectopic pregnancy
- Endometriosis
- Proctitis - inflammatory
- Prostatitis - idiopathic
- Reactive arthritis-gonococcal
- Urethral/vaginal foreign body
General treatment items
- Antibiotics are the standard treatment for uncomplicated Chlamydia. These should be initiated upon diagnosis or suspicion of genitourinary chlamydial infection depending on diagnostic resources available
- Treatment must include the sexual partner and abstinence for 7 days is recommended to prevent spread of infection
- Primary treatment options include azithromycin or doxycycline. A single dose of azithromycin has comparable microbiological and clinical cure rates to a 7 day course of doxycycline
- Single dose azithromycin therapy is the treatment of choice for patients who may experience compliance issues with multidose regimens
- Levofloxacin and ofloxacin are effective alternatives, but are not considered to be cost-effective
- Erythromycin is an alternative to azithromycin or doxycycline, though comparatively less effective and associated with gastrointestinal adverse effects
- Doxycycline, ofloxacin, and levofloxacin are contraindicated during pregnancy. Amoxicillin or erythromycin are preferred for pregnant women, azithromycin can be used but women should be informed it is category B in pregnancy
- HIV-positive patients with chlamydial infection should receive a treatment regimen similar to that in HIV-negative patients. Treatment of Chlamydia can reduce the transmission rate of HIV in affected patients
- Treatment of PID requires a longer 2 week course of antibiotics and should involve treatment for other organisms responsible. The recommended schedule is a single IM dose of ceftriaxone (treat gonococcal infection) and a 2 week course of doxycycline plus metronidazole. Treatment can be given in outpatient setting, but patients may require IV antibiotics in setting of severe pain or early signs of bacteremia/sepsis may require a more aggressive therapeutic approach and regimen of antimicrobials
- Treatment of Epidymo-orchitis also requires a 2 week treatment course and should include gonococcal cover, i.e. IM ceftriaxone. Standard treatment involves single dose azithromycin plus either a 2 week course of doxycycline OR further single dose azithromycin in one week
- Neonates with ophthalmia neonatorum or pneumonia based by C. trachomatis should receive treatment with erythromycin for a period of 14 and 21 days, respectively. Topical antibiotic therapy is usually insufficient and offers limited advantage when systemic therapy is administered
- Serological testing for venereal disease including syphilis, HIV, Hep B/C is also recommended
Medications indicated with specific doses
Antibiotics
- Amoxicillin [Oral]
- Azithromycin
- Doxycycline
- Erythromycin
- Levofloxacin
- Ofloxacin
Disposition
- The majority of uncomplicated cases may be treated in an outpatient setting
- In cases of substantial PID, or other complications, an inpatient setting may be required
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Prevention
- Sexually active individuals should avoid sexual intercourse with high-risk individuals
- Safe-sex practices such as use of condoms, and avoidance of multiple sex partners can significantly reduce the risk of transmission
- Patients with active infection should abstain from sexual intercourse until complete resolution of symptoms and an appropriate treatment with antibiotics has occurred
- Sexual partners should be tested and treated
Prognosis
- Chlamydia infections generally have an excellent prognosis with prompt antibiotic treatment
- The majority of patients are completely cured with appropriate antibiotic therapy
- Untreated or insufficiently treated infections can lead to complications. Mortality and morbidity associated with chlamydia is exclusively due to complications
- Untreated Chlamydia infections can result in chronic PID in up to 20 to 40% of affected patients. Additionally, 20% of patients with PID will experience infertility, 18% will have severe pelvic pain and 9% will have an ectopic pregnancy, which can be a life threat
- Re-infection can occur, especially in the setting of sexual partners not being treated for Chlamydia
Pregnancy/Pediatric effects on condition
- Chlamydia infection during pregnancy has been associated with adverse outcomes such as preterm delivery and premature rupture of membranes, but not with low birth weight and fetal death
- Without prophylaxis, approximately 50-70% of neonates born to infected mothers will acquire chlamydial infection. This can results in opthalmia neonatorum or pneumonia in neonates
- Retesting of women during the third trimester of pregnancy may help reduce postnatal complications and fetal transmission
- Chlamydial infection in preadolescent children should be investigated for possible sexual abuse
ICD-9-CM
- 099.4 Other nongonococcal urethritis
- 099.5 Other venereal diseases due to chlamydia trachomatis
ICD-10-CM
- A56.8 Sexually transmitted chlamydial infection of other sites
- A74.9 Chlamydial infection, unspecified
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