Chlamydia infection

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2], Aysha Anwar, M.B.B.S[3]

Chlamydia is a common sexually transmitted disease (STD) caused by the gram negative bacterium Chlamydia trachomatis. Chlamydia is the most frequently reported bacterial sexually transmitted infection in the United States and is a major infectious cause of human eye and genital disease.^[1] Chlamydia infection must be differentiated from other genital tract infections, such as gonorrhea infection, bacterial vaginosis, vaginal candidiasis, infection with Trichomonas vaginalis, and mycoplasma infection.^[2] Almost two-thirds of new chlamydia infections occur among youth aged 15-24 years. Females are more commonly affected with chlamydia infection than males. The female to male ratio is approximately 1.52 to 1.^[3] Common risk factors in the development of chlamydia infection include unprotected sexual activity, multiple sexual partners, age, men who have sex with men, and low socioeconomic status.^[3][4][5] According to the 2015 Sexually Transmitted Diseases Treatment Guidelines released by the CDC, screening for chlamydia is recommended for sexually active individuals under 25 years of age, women over 25 who are at increased risk, all pregnant women under 25 years, pregnant women over 25 who are at increased risk, men who have sex with men, and individuals with HIV.^[3] If left untreated, chlamydia can cause pelvic inflammatory disease in females and epididymitis and orchitis in males.^[3][5] Common complications of chlamydia among women include cervicitis, infertility, ectopic pregnancy, and chronic pelvic pain. Complications of chlamydia in men include proctitis, epididymitis, and sterility. Prognosis of chlamydia is generally good with adequate treatment. Common symptoms of chlamydia infection among women include abnormal vaginal bleeding or discharge, abdominal pain, painful sexual intercourse, painful urination, and urinary urgency. Symptoms of chlamydia infection among men include penile discharge and pruritus, testicular pain or swelling, and pain during urination.^[6] Physical examination of women with chlamydia infection is usually remarkable for a cloudy, yellow mucoid cervical discharge; a friable appearance of the cervix; and cervical motion tenderness.^[3][7] Common physical examination findings of chlamydia infection among men include a clear or white urethral discharge, testicular tenderness, and testicular swelling.^[3][7] Transvaginal ultrasound, pelvic MRI, and laboratory nucleic acid amplification tests (NAAT) may be used in the diagnosis of chlamydia infection. The mainstay of therapy for chlamydia is antimicrobial therapy with doxycycline. Effective measures for the primary prevention of chlamydia infection include practicing abstinence, avoiding high-risk sexual behaviors such as unprotected sex or multiple sexual partners, and using latex condoms.^[3][5] Secondary prevention of chlamydia infection includes early detection, treatment of sexual partners, and treatment of other sexually transmitted infections (such as gonorrhea).

Chlamydia trachomatis was first discovered in 1907 by Halberstaedter and von Prowazek.^[8] The inclusion bodies of Chlamydia trachomatis were first described in 1942.^[3]

C. trachomatis is naturally found living only inside human cells. Chlamydia can be transmitted during vaginal, anal, or oral sex, and can be passed from an infected mother to her baby during vaginal childbirth.

Chlamydia is a common sexually transmitted infection (STI) caused by the gram-negative bacterium Chlamydia trachomatis.

Chlamydia must be differentiated from other genital tract infections such as gonorrhea infection, bacterial vaginosis, vaginal candidiasis, infection with Trichomonas vaginalis, and mycoplasma infection.^[2]

In 2014, the incidence of chlamydia was estimated to be 439 cases per 100,000 individuals in the United States.^[3] The incidence of chlamydia in women has increased greatly between 1987 and 2003 from 79 to 467 cases per 100,000 individuals.^[7] Almost two-thirds of new chlamydia infections occur among young adults aged 15-24 years. It is estimated that 1 in 20 sexually active young women aged 14-24 years has chlamydia.^[3] Females are more commonly affected with chlamydia infection than males. The female to male ratio is approximately 1.52 to 1.^[3] The prevalence of chlamydia among non-Hispanic African Americans is 6.7 times the prevalence among non-Hispanic Whites.^[3]

Common risk factors in the development of chlamydia infection include unprotected sexual activity, multiple sexual partners, age, men who have sex with men, and low socio-economic status.^[3][4][5]

According to the 2015 Sexually Transmitted Diseases Treatment Guidelines by the CDC, screening for chlamydia is recommended for sexually active under 25 years, women over 25 who are at increased risk, all pregnant women under 25 years, pregnant women over 25 who are at increased risk, men who have sex with men, and individuals with HIV.^[3]

If left untreated, chlamydia can cause pelvic inflammatory disease in women and epididymitis and orchitis in males.^[3][5] Common complications of chlamydia among women include cervicitis, infertility, ectopic pregnancy, and chronic pelvic pain. Complications of chlamydia in men include proctitis, epididymitis, and sterility. Other complications of chlamydia include reactive arthritis.^[9] Prognosis of chlamydia is generally good with adequate treatment.

It is crucial to collect a detailed and thorough sexual history from the patient. Specific areas of focus when obtaining a history include number and type of sexual partners (new, casual, or regular), contraception use, and previous history of chlamydia infection or other sexually transmitted diseases.^[7][9][4] The majority of women with chlamydia infection are asymptomatic or present with minimal symptoms.^[7][9] Common symptoms of chlamydia infection among women include abnormal vaginal bleeding or discharge, abdominal pain, painful sexual intercourse, painful urination, and urinary urgency. Symptoms of chlamydia infection among men include penile discharge and pruritus, testicular pain or swelling, and pain during urination.^[6]

Patients with chlamydia infection usually appear to be in good health. A fever may be present. Physical examination of women with chlamydia infection is usually remarkable for a cloudy, yellow mucoid cervical discharge; a friable appearance of the cervix; and cervical motion tenderness.^[3][7] Common physical examination findings of chlamydia infection among men include a clear or white urethral discharge, testicular tenderness, and testicular swelling.^[3][7]

Laboratory tests used in the diagnosis of chlamydia infection include nucleic acid amplification tests (NAAT) such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement assay (SDA). NAAT for chlamydia infection may be performed on swab specimens sampled from the cervix (women) or urethra (men), on self-collected vaginal swabs, or on voided urine.^[6]

Transvaginal ultrasound may be helpful in the diagnosis of chlamydia infection when pelvic inflammatory disease has occurred. Findings on ultrasound suggestive of pelvic inflammatory disease include thickened/dilated fallopian tubes, incomplete septa in the fallopian tube, increased vascularity around the fallopian tubes, and positive cogwheel sign (thickened loops of fallopian tubes).^[3]

Other imaging studies for chlamydia infection include pelvic MRI, which demonstrates an ill-defined adnexal mass containing fluid with various signal intensities.^[3]

The mainstay of therapy for chlamydia is antimicrobial therapy with doxycycline. Recent sex partners (i.e., individuals having sexual contact with the patient within the 60 days preceding onset of symptoms or chlamydia diagnosis) should also be referred for evaluation, testing, and treatment.^[10][11]

Effective measures for the primary prevention of chlamydia infection include practicing abstinence, avoidance of high-risk sexual behaviors such as unprotected sex or multiple sexual partners, and use of latex condoms.^[3][5]

Secondary prevention of chlamydia infection includes early detection, treatment of sexual partners, and treatment of other sexually transmitted infections (such as gonorrhea).^[7]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

Chlamydia trachomatis was first discovered in 1907 by Halberstaedter and von Prowazek.^[1] The inclusion bodies of Chlamydia trachomatis were first described in 1942.^[2]

• Chlamydia trachomatis was first discovered in 1907 by Halberstaedter and von Prowazek.^[1]
• The inclusion bodies of Chlamydia trachomatis were first described in 1942.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2], Aysha Anwar, M.B.B.S[3]

Chlamydia infection may be transmitted during vaginal, anal, or oral sex, and can be passed from an infected mother to her baby during childbirth. Chlamydiae are obligate intracellular bacterial pathogens which have the ability to establish long-term associations with host cells. These pathogens have evolved a distinct biphasic life cycle wherein they alternate between two functionally and morphologically distinct forms: elementary body (EB) and reticulate body (RB).^{[1][2][3][4][5][6][7][8]}

Chlamydia infection can be transmitted during vaginal, anal, or oral sex, and can be passed from an infected mother to her baby during childbirth.

Chlamydiae are obligate intracellular bacterial pathogens, which means they are unable to replicate outside of a host cell. However, to disseminate effectively, these pathogens have evolved a distinct biphasic life cycle wherein they alternate between two functionally and morphologically distinct forms.^[9][10]

• The elementary body (EB) is infectious, but metabolically inert (much like a spore), and can survive for limited amounts of time in the extracellular milieu. Once the EB attaches to a susceptible host cell, it mediates its own internalization through pathogen-specified mechanisms (via type III secretion system) that allow for the recruitment of actin with subsequent engulfment of the bacterium.
• The internalized EB, within a membrane-bound compartment, immediately begins differentiation into the reticulate body (RB). RBs are metabolically active but non-infectious; in many regards, they resemble normal replicating bacteria. The intracellular bacteria rapidly modifies its membrane-bound compartment into the so-called chlamydial inclusion so as to prevent phagosome-lysosome fusion. The inclusion is thought to have no interactions with the endocytic pathway and apparently inserts itself into the exocytic pathway as it retains the ability to intercept sphingomyelin-containing vesicles.
• The mechanism by which the host cell protein is trafficked to the inclusion through the exocytic pathway is not fully understood. As the RBs replicate, the inclusion grows as well to accommodate the increasing numbers of organisms. Through unknown mechanisms, RBs begin a differentiation program back to the infectious EBs, which are released from the host cell to initiate a new round of infection. Because of their obligate intracellular nature, Chlamydiae have no tractable genetic system, unlike E. coli, which makes Chlamydiae and related organisms difficult to investigate.

Chlamydiae have the ability to establish long-term associations with host cells. When an infected host cell is starved for various nutrients such as amino acids (e.g. tryptophan),^[3] iron, or vitamins, this has a negative consequence for Chlamydiae since the organism depends upon the host cell for these nutrients. The starved chlamydiae enter a persistent growth state wherein they stop cell division and become morphologically aberrant by increasing in size.^[4] Persistent organisms remain viable as they are capable of returning to a normal growth state once conditions in the host cell improve. There is much debate as to whether persistence has in-vivo relevance. Many believe that persistent chlamydiae are the cause of chronic chlamydial diseases. Some antibiotics, such as β-lactams, can also induce a persistent-like growth state, which can contribute to the chronicity of chlamydial diseases.

Chlamydia trachomatis can cause the following conditions:^[5][6][7][8]

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To learn about other chlamydial infections caused by species other than C. trachomatis, click here.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]

• Chlamydia trachomatis, an obligate intracellular human pathogen, is one of four bacterial species in the genus Chlamydia.^[1]
• C. trachomatis is a Gram-negative bacterium, therefore its cell wall components retain the counter-stain safranin and appear pink under a light microscope.^[2] It is ovoid in shape.^[3]

• C. trachomatis includes three human biovars, based on variations in the major outer membrane protein (MOMP):

• serovars Ab, B, Ba, or C — cause trachoma: infection of the eyes, which can lead to blindness
• serovars D-K — cause urethritis, pelvic inflammatory disease, ectopic pregnancy, neonatal pneumonia, and neonatal conjunctivitis
• serovars L1, L2 and L3 — lymphogranuloma venereum (LGV)^[4]

• The L2 serovar can be further differentiated into L2, L2′, L2a, and L2b based on significant amino acid differences^[5]

• Many, but not all, C. trachomatis strains have an extrachromosomal plasmid.^[6]

• Chlamydia can exchange DNA between its different strains, thus the evolution of new strains is common.^[7]

Chlamydia species are readily identified and distinguished from other Chlamydia species using DNA-based tests.

Most strains of C. trachomatis are recognized by monoclonal antibodies (mAbs) to epitopes in the VS4 region of MOMP.^[8] However, these mAbs may also cross-react with two other Chlamydia species, C. suis and C. muridarum.

Chlamydiae are obligate intracellular bacterial pathogens, which means they are unable to replicate outside of a host cell. However, to facilitate effective dissemination, these pathogens have evolved a distinct biphasic life cycle wherein they alternate between two functionally and morphologically distinct forms.

• The elementary body (EB) is infectious, but metabolically inert (much like a spore), and can survive for limited amounts of time in the extracellular milieu. Once the EB attaches to a susceptible host cell, it mediates its own internalization through pathogen-specified mechanisms (via type III secretion system) that allows for the recruitment of actin with subsequent engulfment of the bacterium.
• The internalized EB, within a membrane-bound compartment, immediately begins differentiation into the reticulate body (RB). RBs are metabolically active but non-infectious, and in many regards, resemble normal replicating bacteria. The intracellular bacteria rapidly modifies its membrane-bound compartment into the so-called chlamydial inclusion so as to prevent phagosome-lysosome fusion. The inclusion is thought to have no interactions with the endocytic pathway and apparently inserts itself into the exocytic pathway as it retains the ability to intercept sphingomyelin-containing vesicles.
• The mechanism by which the host cell protein is trafficked to the inclusion through the exocytic pathway is not fully understood. As the RBs replicate, the inclusion grows as well to accommodate the increasing numbers of organisms. Through unknown mechanisms, RBs begin a differentiation program back to the infectious EBs, which are released from the host cell to initiate a new round of infection. Because of their obligate intracellular nature, Chlamydiae have no tractable genetic system, unlike E. coli, which makes Chlamydiae and related organisms difficult to investigate.

Chlamydia trachomatis can cause the following conditions:^{[9][10][11][12]}

• Cervicitis
• Conjunctivitis
• Fitz-Hugh-Curtis syndrome
• Lymphogranuloma venereum
• Pelvic inflammatory disease
• Pneumonia in infants
• Reactive arthritis
• Urethritis
• Rectal infection (proctitis)
• Prostatitis
• Ectopic pregnancy

• 
  Photomicrograph of Chlamydia trachomatis taken from a urethral scrape. From Public Health Image Library (PHIL). ^[13]
• 
  McCoy cell monolayers with Chlamydia trachomatis inclusion bodies (200X mag). From Public Health Image Library (PHIL). ^[13]
• 
  McCoy cell monolayers with Chlamydia trachomatis inclusion bodies (50X mag). From Public Health Image Library (PHIL). ^[13]
• 
  Photomicrograph depicts HeLa cells infected with Type-A Chlamydia trachomatis (400X mag). From Public Health Image Library (PHIL). ^[13]
• 
  Patient’s left eye with the upper lid retracted in order to reveal the inflamed conjunctival membrane lining the inside of both the upper and lower lids, due to what was determined to be a case of inclusion conjunctivitis caused by the bacterium, Chlamydia trachomatis. From Public Health Image Library (PHIL). ^[13]
• 
  From Public Health Image Library (PHIL). ^[13]

Bellaminutti, Serena; Seracini, Silva; De Seta, Francesco; Gheit, Tarik; Tommasino, Massimo; Comar, Manola (November 2014). “HPV and Chlamydia trachomatis Co-Detection in Young Asymptomatic Women from High Incidence Area for Cervical Cancer”. Journal of Medical Virology. 86 (11): 1920–1925. doi:10.1002/jmv.24041. Retrieved 13 November 2014.

• Chlamydiae.com
• Template:GPnotebook
• “Chlamydia trachomatis“. NCBI Taxonomy Browser. 813.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

Chlamydia infection must be differentiated from other genital tract infections such as gonorrhea infection, bacterial vaginosis, vaginal candidiasis, infection with Trichomonas vaginalis, mycoplasma infection, and syphilis.^[1]

Chlamydia infection must be differentiated from other genital tract infections such as:^[1]

• Gonorrhea infection
• Bacterial vaginosis
• Vaginal candidiasis
• Infection with Trichomonas vaginalis
• Mycoplasma infection
• Syphilis

Chlamydia pneumopnia must be differentiated from other diseases that cause atypical pneumonia such as Q fever and legionella pneumonia:

Disease	Prominent clinical features	Lab findings	Chest X-ray
Q fever	Q fever is characterized by abrupt onset of fever, myalgia, headache, and other constitutional symptoms. Cough is the most prominent respiratory symptom and it is usually dry.[2] Cough is associated with dyspnea and pleuritic chest pain.	Antibody detection using indirect immunofluorescence (IIF) is the preferred method for diagnosis. PCR can be used if IIF is negative, or very early once disease is suspected. C. burnetii does not grow on ordinary blood cultures, but can be cultivated on special media such as embryonated eggs or cell culture. A two-to-three fold increase in AST and ALT is seen in most patients.
Mycoplasma pneumonia	Mycoplasma pneumonia can be asymptomatic. Headache, nausea, and malaise usually precede the onset of symptoms.[2] Cough is intractable and nonproductive.	Postitve Coombs test Leukocytosis Thrombocytosis
Legionellosis	Legionellosis is characterized by cough that is slightly productive.[2] Constitutional symptoms such as chills, myalgia, and arthralgia. Gastrointestinal symptoms such as diarrhea, nausea, and vomiting.	Labs are nonspecific for diagnosing legionellosis Renal and hepatic dysfunction Thrombocytopenia and leukocytosis Hyponatremia
Chlamydia pneumonia	There are no specific clinical features of chlamydia pneumonia. Symptoms appear gradually. Chlamydia infection is usually associated with upper respiratory tract symptoms (pharyngitis, sinusitis, etc). It might be associated with extrapulmonary maifestations such as meningitis and Guillain-Barre syndrome.[2]	Chlamydia pneumonia is usually associated with normal WBC count. Diagnosed with the presence of antichlamydial antibody (through complement fixation or direct immunofluoroscence) or direct antigen detection.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2], Aysha Anwar, M.B.B.S[3]

Worldwide, the incidence of chlamydia is estimated to be 131 million cases per year.^[1] In 2014, the incidence of chlamydia was estimated to be 439 cases per 100,000 individuals in the United States.^[2] The incidence of chlamydia in women has increased greatly between 1987 and 2003, from 79 to 467 cases per 100,000 individuals.^[3] Almost two-thirds of new chlamydia infections occur among youth aged 15-24 years. It is estimated that 1 in 20 sexually active young women aged 14-24 years has chlamydia.^[2] Females are more commonly affected with chlamydia infection than males. The female to male ratio is approximately 1.52 to 1.^[4] The prevalence of chlamydia among non-Hispanic African Americans is 6.7 times the prevalence among non-Hispanic Whites.^[2]

• Worldwide, the incidence of chlamydia is estimated to be 131 million cases per year.^[1]
• In 2014, the incidence of chlamydia was estimated to be 439 cases per 100,000 individuals in the United States.^[2]
• The incidence of chlamydia in women has increased greatly between 1987 and 2003, from 79 to 467 cases per 100,000 individuals.^[3]

• In 2008, the prevalence of chlamydia in the adult population worldwide was estimated to be 9.1 million cases per year.
• It is estimated that 1 in 20 sexually active young women aged 14-19 years has chlamydia.^[2]

• Almost two-thirds of new chlamydia infections occur among youth aged 15-24 years.
• It is estimated that 1 in 20 sexually active young women aged 14-24 years has chlamydia.^[2]

• Females are more commonly affected with chlamydia infection than males.
• The female to male ratio is approximately 1.52 to 1.^[4]

• The prevalence of chlamydia among non-Hispanic African Americans is 6.7 times the prevalence among non-Hispanic Whites.^[2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

Common risk factors in the development of chlamydia infection include unprotected sexual activity, multiple sexual partners, age, men who have sex with men, and low socio-economic status.^[1][2][3]

Common risk factors in the development of chlamydia include:^[1][2][3]

• Unprotected sexual activity
• Multiple sexual partners
• Age (adolescents and young adults are more likely to be infected)
• Men who have sex with men
• Low socio-economic status

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2], Aysha Anwar, M.B.B.S[3]

According to the CDC’s 2015 Sexually Transmitted Diseases Treatment Guidelines, screening for chlamydia is recommended for sexually active women under 25 years, women over 25 who are at increased risk, all pregnant women under 25 years, pregnant women over 25 who are at increased risk, men who have sex with men, and individuals with HIV.^[1][2]

According to the CDC’s 2015 Sexually Transmitted Diseases Treatment Guidelines, screening for chlamydia is recommended. The guidelines are as follows:^[1][2]

• Sexually active women under 25 years of age
• Sexually active women aged 25 years and older if at increased risk
• Retest approximately 3 months after treatment if necessary

• All pregnant women under 25 years of age
• Pregnant women aged 25 and older if at increased risk
• Retest during the 3rd trimester for women under 25 years of age or at risk

• Consider screening young men in high-prevalence clinical settings or in populations with high burden of infection (e.g., MSM)
• At least annually for sexually active men who have sex with men (MSM) and then every 3 to 6 months if at increased risk

• For sexually active individuals, screen at first HIV evaluation and at least annually thereafter
• More frequent screening might be appropriate depending on individual risk behaviors and local epidemiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2]

If left untreated, chlamydia can cause pelvic inflammatory disease in women and epididymitis and orchitis in males.^[1][2] Common complications of chlamydia among women include cervicitis, infertility, ectopic pregnancy, and chronic pelvic pain. Complications of chlamydia in men include proctitis, epididymitis, and sterility. Other complications of chlamydia include an increased risk of acquiring HIV and reactive arthritis.^[3] The prognosis of chlamydia is generally good with adequate treatment.

If left untreated, chlamydia can cause pelvic inflammatory disease and infertility in women and epididymitis and orchitis in males, which may, in rare cases, lead to sterility.^[1][2]

The complications of chlamydia infection may be divided into genitourinary infections, pulmonary infections, ocular infections, and complications associated with pregnancy.^[2]

Complications of chlamydia infection in women include:^[1][3][4]

• Pelvic inflammatory disease
• Ectopic pregnancy
• Infertility
• Chronic pelvic pain
• Reactive arthritis
• Increased risk for acquiring HIV

Complications of chlamydia in pregnant patients include:^[2][5]

• Pre-term labor
• Premature rupture of membranes
• Intrauterine growth retardation
• Transmission of infection to newborn, neonatal conjunctivitis, and pneumonia in the newborn
• Postpartum endometritis

Complications of chlamydia infection in men may include:^[2][3]

• Epididymitis
• Orchitis
• Sterility
• Proctitis
• Reactive arthritis
• Increased risk for acquiring or transmitting HIV

The prognosis of chlamydia is generally good with adequate treatment.

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