Chlamydia


Article Author:
Michael Mohseni
Sharon Sung


Article Editor:
Veronica Takov


Editors In Chief:
Casey Ciresi


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
8/5/2019 5:31:24 PM

Introduction

Chlamydia is a sexually transmitted infectious disease caused by the bacterium Chlamydia trachomatis. In the United States, it is the most commonly reported bacterial infection. Globally, it is the most common sexually transmitted diseases. It causes an ocular infection called "trachoma," which is the leading infectious cause of blindness worldwide. In females, infertility and ectopic risks increase with Chlamydia trachomatis infections, leading to high medical costs.[1] Lymphogranuloma venereum (LGV), caused by distinct serovars of Chlamydia trachomatis, is a less common disease characterized by enlarged lymph nodes or severe proctocolitis.[2]

Etiology

Chlamydia trachomatis is part of the chlamydophila genus. These bacteria are gram-negative, anaerobic, intracellular obligates that replicate within eukaryotic cells. C. trachomatis differentiates into 18 serovars (serologically variant strains) based on monoclonal antibody-based typing assays. These serovars correlate with multiple medical conditions as follows[3]:

  • Serovars A, B, Ba, and C: Trachoma is a serious eye disease endemic in Africa and Asia that is characterized by chronic conjunctivitis and can lead to blindness

  • Serovars D-K: Genital tract infections

  • Serovars L1-L3: Lymphogranuloma venereum (LGV), which correlates with genital ulcer disease in tropical countries

Epidemiology

Urogenital chlamydia infections are the most commonly reported bacterial infections in the U.S and the most common cause of sexually transmitted disease in the world. The overall rate of urogenital infection amongst U.S. women is twice that among U.S. men, with a higher prevalence in women 15-24 years of age and a higher incidence in men between 20-24 years of age. 

Pathophysiology

Chlamydia is unique among bacteria, having an infectious cycle and two developmental forms.  These include the infectious form called the elementary body (EB) and the reticulate body (RB). The EB is metabolically inactive and is taken up by host cells. Within the host cell, the EB will differentiate into the metabolically active RB. The RB will then use host energy sources and amino acids to replicate and form new EB which can then infect additional cells. The target cells of C. trachomatis are the squamocolumnar epithelial cells of the endocervix and upper genital tract in women, and the conjunctiva, urethra, and rectum in both men and women. 

The bacterium is transmitted through direct contact with infected tissue, including vaginal, anal or oral sex, and can even be passed from an infected mother to the newborn during childbirth.

Histopathology

Typical intracytoplasmic inclusions and free chlamydiae are identifiable in Giemsa-stained cell scrapings from the eye. Stained conjunctival scrapings are positive in 90% of infants with neonatal conjunctivitis, and 50% of adults with inclusion conjunctivitis. Cytology techniques can be used to evaluate endocervical scrapings, but the sensitivity and specificity are low.[4]

History and Physical

C. trachomatis can lead to many urogenital infections including cervicitis, pelvic inflammatory disease, urethritis, epididymitis, prostatitis and lymphogranuloma venereum. Extragenital infections caused by C. trachomatis include conjunctivitis, perihepatitis, pharyngitis, reactive arthritis, and proctitis. 

Most commonly, patients remain asymptomatic reservoirs of the disease. In the minority of patients that are symptomatic, clinical signs depend on the location of the infection. Below are the common signs and symptoms associated with C. trachomatis urogenital infections.

  • Cervicitis: Approximately 70% of women will be asymptomatic or have mild symptoms such as vaginal discharge, bleeding, abdominal pain and dysuria.[5] Only a minority of women have the classic presentation of mucopurulent cervicitis with discharge and easily-induced endocervical bleeding.  
  • Pelvic Inflammatory Disease: This occurs when C. trachomatis ascends to the upper reproductive tract. Most commonly these patients will have abdominal or pelvic pain with or without signs and symptoms of cervicitis.
  • Urethritis: It is most commonly seen in men. There are subtle clinical differences between gonococcal urethritis and chlamydial urethritis, but making a reliable distinction without testing is not possible. It presents with dysuria and urethral discharge which is typically white, gray or sometimes clear, and may only be evident after penile "stripping" or during morning hours. 
  • Epididymitis: Typically, men will present with unilateral testicular pain and tenderness, possible hydrocele, palpable swelling of the epididymis and fever. 
  • Proctitis: Patients complain of rectal pain, discharge and bleeding in the setting of receptive anal intercourse. 
  • Lymphogranuloma venereum: Patients will present with a non-painful, small genital ulcer followed by the development of inguinal lymphadenopathy.

Evaluation

Among C. trachomatis infections, only trachoma is diagnosable on clinical grounds. Other chlamydial infections are associated with specific clinical syndromes but require laboratory confirmation. The gold standard for diagnosis of urogenital chlamydia infections is nucleic acid amplification testing (NAAT). This test is run on either the vaginal swabs for women or first-catch urine for men. Testing can also be performed on endocervical or urethral swabs. Alternative methods of testing include culture, rapid testing, serology, antigen detection and genetic probes. If there is no testing available, treatment is recommended based on clinical presentation.

Treatment / Management

The goal of treatment is the prevention of complications associated with infection (e.g., PID, perihepatitis), to decrease the risk of transmission, and the resolution of symptoms.  Treatment for uncomplicated urogenital chlamydia infection is with azithromycin. Doxycycline is an alternative, but azithromycin is preferred as it is a single-dose therapy.

Chlamydial infection and gonococcal infections often coexist. In men, the driver behind co-treatment for urogenital gonococcal infection should be by detection of the organism on NAAT or gram stain. In women, the gram stain is less helpful due to the possibility of normal Neisseria species colonization within the vaginal flora. Therefore, co-treatment should be dependent on an assessment of individual patient risk and local prevalence rates.

Patients should have partners identified and tested. They should also be counseled on high-risk behaviors, avoid sexual activity for one week after initiating therapy, and should consider testing for HIV.

Verification of cure should occur either three weeks after treatment completion, and retesting should be performed at three months after treatment.

If symptoms persist after treatment, consider coinfection with a secondary bacterium or reinfection. 

Differential Diagnosis

In the differential diagnoses, one should consider other infections that infiltrate the genital and urinary systems of men and women. Such diseases include: 

  • Bacterial vaginosis
  • Fitz-Hugh-Curtis syndrome
  • Mycoplasma genitalium infection
  • Periurethral abscess
  • Prostatitis
  • Salpingitis
  • Tubo-ovarian abscess
  • Ureaplasma infection

Treatment Planning

Uncomplicated Genital Chlamydia:

The World Health Organization (WHO) recommendations for treatment of uncomplicated genital chlamydia infections are the following:

  • Azithromycin 1 g by mouth as a single dose or
  • Doxycycline 100 mg by mouth twice daily for 7 days, or one of these alternatives: tetracycline 500 mg orally 4 times daily for 7 days, erythromycin 500 mg orally twice daily for 7 days, or ofloxacin 200-400 mg orally twice daily for 7 days

Anorectal Chlamydial infection:

In anorectal chlamydial infections, the WHO recommendation is oral doxycycline 100 mg twice daily for 7 days over oral azithromycin 1 g as a single dose.

Chlamydial infection in pregnancy:

WHO recommends the following for the treatment of chlamydial infection in pregnancy:

  • Azithromycin recommended over erythromycin, amoxicillin, and erythromycin
  • Azithromycin 1 g by mouth as a single dose or
  • Amoxicillin 500 mg orally 3 times daily for 7 days or
  • Erythromycin 500 mg orally twice daily for 7 days

Lymphogranuloma Venereum:

The WHO recommends the following for the treatment of lymphogranuloma venereum (LGV):

  • In adults and adolescents with LGV, the guidelines suggest doxycycline 100 mg orally twice a day for 21 days over azithromycin 1 g orally weekly for 3 weeks.
  • Good practice dictates the treatment of LGV, particularly for men who have sex with men and for people with HIV infection.
  • When contraindications to doxycycline are present, azithromycin should be the therapeutic choice.
  • When neither treatment is available, erythromycin 500 mg orally 4 times a day for 21 days is an alternative.
  • Doxycycline should not be used in pregnancy.

Prognosis

Antibiotic treatment has a 95% effectiveness rate for first-time therapy. The prognosis is excellent with prompt initiation of treatment early and with the completion of the entire course of antibiotics. Although treatment failures with primary therapies are quite rare, relapse may occur. Reinfection is common, and is usually related to nontreatment of infected sexual partners or acquisition from a new partner. Death is rare but can be caused by progression to salpingitis and tubo-ovarian abscess with rupture and peritonitis. The most significant morbidity occurs with repetitive infection with chlamydiae, which leads to scarring of the fallopian tubes and subsequent sterility.

Enhancing Healthcare Team Outcomes

In the United States and other developed countries, prevention of sexually transmitted genital infections and complications mainly focuses on screening and treating nonpregnant sexually active women aged 25 years or younger on an annual basis. Screening for pregnant women is recommended and screening and treatment of women over 25 years of age are recommendations if there are identifiable risk factors, such as new or multiple sexual partners. Screening of young men in high-risk settings (sexually transmitted disease and adolescent clinics, correctional facilities) should be a consideration if resources allow. Urine or endocervical NAAT are the recommended screening tests. The prognosis is excellent with prompt initiation of treatment early and with the completion of the entire course of antibiotics; antibiotic treatment is 95% effective for first-time therapy.

No vaccine is currently available for either trachoma or chlamydial genital infections. 

The healthcare team including clinicians, nurses, and pharmacists must work together to educate the patient on methods to avoid exposure and the importance of completing treatment.


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Chlamydia - Questions

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A 6-week-old female is brought to the emergency department with a cough, conjunctivitis, nasal congestion, and an infiltrate on chest x-ray. Her mother had no prenatal care but did receive empiric antibiotics during labor for prolonged rupture of membranes. On examination, the infant has a cobbled appearance to her conjunctiva, and she has a paroxysmal staccato cough. What is the most likely etiologic agent?



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A 17-year-old female presents with symptoms of urinary frequency, dysuria, and post-coital bleeding. She also claims to have lower back pain. She had a single sexual encounter with a stranger a few weeks ago and did not use a condom. Urine examination reveals 30 white blood cells and 4 red blood cells per high power field. There is no evidence of any bacteremia, fungus, or acid-fast bacilli. What is the most likely diagnosis?



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A 21-year-old female recently had her first Pap smear. Because she reported being sexually active, her physician also recommended sexually transmitted infection (STI) screening. She declined because she had no symptoms or problems. She now presents two weeks later with abnormal vaginal discharge, pelvic pain, and pain with intercourse. She is now receiving treatment for her current condition. Additionally, how should this patient be counseled regarding other potential consequences for her future health?



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A 23-year-old female presents to the emergency department reporting being the victim of a sexual assault. She reports that the alleged assailant was male, and he did penetrate her vaginally with his penis. The sexual assault team is called. Blood is drawn for the evaluation of hepatitis B, HIV, syphilis. A vaginal specimen is obtained for point-of-care testing for trichomonas, bacterial vaginosis, and candidiasis. What additional sexually transmitted infection (STI) testing should be obtained in this patient?



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A 17-year-old male presents to the school health clinic with complaints of dysuria. The physical exam was otherwise unremarkable apart from white urethral discharge. Further evaluation with urinalysis showed pyuria but was negative for nitrates or bacteria. The patient was given ceftriaxone, and his urine was sent for culture. Urine culture returned negative for bacterial growth, and he complains that his symptoms persist. What is the most appropriate treatment for this patient?



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A 34-year-old male presents to the public health clinic with complaints of groin swelling. He reports initially noticing some "sores" on his genitalia when he was trimming his pubic hair before the "swelling" occurred. On exam, the patient has significant inguinal lymphadenopathy. He also has several small, painless genital ulcers. What treatment is appropriate for this patient?



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A 27-year-old male was seen in his clinician's office for the complaint of dysuria. He recently had sexual intercourse with a prostitute, and they did not use a condom. The patient received a dose of ceftriaxone in the office, and he was given a prescription for oral antibiotics. He did not fill the prescription. Now he returns with continued dysuria and additional complaints of joint pain and eye redness. How should the clinician proceed?



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A newborn is evaluated by the pediatrician because of conjunctivitis. There is no purulence, and the conjunctiva has a cobbled appearance. The pediatrician begins treatment with erythromycin, and the newborn's condition improves. Which of the following may have prevented infection from occurring?



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A preterm infant in the neonatal intensive care unit has been having apneic spells. He was born vaginally to a woman with no prenatal care. Rales are heard on physical examination, and the infant has tachypnea, but he is afebrile. The healthcare provider has had to suction thick nasal secretions several times. A chest x-ray is performed and cultures are obtained, and the diagnosis is made. In addition to monitoring for clinical improvement, what additional precautions should be taken?



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A 17-year-old male is seen in his healthcare practitioner's office for a follow-up appointment. He initially presented with dysuria. His testing was positive for chlamydia, and he is feeling better after the empiric antibiotics he was given. He has had several sexual partners in the last month. How should this patient be counseled regarding partner notification?



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A 42-year-old woman presents to her healthcare provider with complaints of postcoital bleeding and vaginal discharge. She is sexually active with a new boyfriend, and they do not use condoms. Her Pap test last year was negative. She has a history of heavy periods, but a transvaginal ultrasound performed two months ago was normal. On exam, she has a friable cervix with a mucopurulent discharge. A wet mount slide showed numerous white blood cells, but no clue cells, and an amine whiff test was negative. What additional testing should be obtained for this patient?



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A 16-year-old female presents to the office with complaints of abnormal vaginal discharge, dysuria, and postcoital bleeding. Her vital signs are normal. She has no medical history, and she takes no medications other than birth control. She does not use condoms, and she believes her partner was recently diagnosed "with something." She refuses an internal pelvic exam, but an external exam is normal. She does provide a urine sample for testing. Initial urinalysis is negative, and the remainder of the tests are pending. Based on the most likely cause of her symptoms, what is the most appropriate empiric treatment to administer at this time?



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A 34-year-old woman presents for her routine first prenatal visit. She is currently 10 weeks pregnant. She is up to date on her Pap smear, but her physician collects a swab to test for gonorrhea and chlamydia. The test returns positive for chlamydia. She is allergic to penicillin. What is the most appropriate antibiotic for this patient?



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A divorced 37-year-old female comes to the clinic for a routine visit. Her surgical history is significant for two prior cesarean sections, an appendectomy, and a complete hysterectomy. She reports being sexually active without condom use because she "can't get pregnant anyway." She now has a new sex partner, and she is concerned because he is not monogamous with her. How should this patient be counseled regarding the recommendations for chlamydia screening?



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A previously healthy 25-year-old female patient presents to the emergency department with nausea, vomiting, fevers, and right upper quadrant pain. She was seen by her primary care provider recently who prescribed a one-time dose of azithromycin, but she did not fill this antibiotic. She reports sexual activity with multiple partners. She has a normal appearing gallbladder on ultrasonography. What complication has the patient likely developed from her antibiotic nonadherence?



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Chlamydia - References

References

Owusu-Edusei K Jr,Chesson HW,Gift TL,Tao G,Mahajan R,Ocfemia MC,Kent CK, The estimated direct medical cost of selected sexually transmitted infections in the United States, 2008. Sexually transmitted diseases. 2013 Mar     [PubMed]
Mabey D,Peeling RW, Lymphogranuloma venereum. Sexually transmitted infections. 2002 Apr     [PubMed]
Morré SA,Rozendaal L,van Valkengoed IG,Boeke AJ,van Voorst Vader PC,Schirm J,de Blok S,van Den Hoek JA,van Doornum GJ,Meijer CJ,van Den Brule AJ, Urogenital Chlamydia trachomatis serovars in men and women with a symptomatic or asymptomatic infection: an association with clinical manifestations? Journal of clinical microbiology. 2000 Jun     [PubMed]
Mordhorst CH,Dawson C, Sequelae of neonatal inclusion conjunctivitis and associated disease in parents. American journal of ophthalmology. 1971 Apr     [PubMed]
Detels R,Green AM,Klausner JD,Katzenstein D,Gaydos C,Handsfield H,Pequegnat W,Mayer K,Hartwell TD,Quinn TC, The incidence and correlates of symptomatic and asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae infections in selected populations in five countries. Sexually transmitted diseases. 2011 Jun     [PubMed]
Pelvic inflammatory disease. American family physician. 2012 Apr 15;     [PubMed]
Kobayashi S,Kida I, Reactive arthritis: recent advances and clinical manifestations. Internal medicine (Tokyo, Japan). 2005 May;     [PubMed]
Schachter J,Grossman M,Sweet RL,Holt J,Jordan C,Bishop E, Prospective study of perinatal transmission of Chlamydia trachomatis. JAMA. 1986 Jun 27;     [PubMed]
Tipple MA,Beem MO,Saxon EM, Clinical characteristics of the afebrile pneumonia associated with Chlamydia trachomatis infection in infants less than 6 months of age. Pediatrics. 1979 Feb;     [PubMed]
Rours GI,Duijts L,Moll HA,Arends LR,de Groot R,Jaddoe VW,Hofman A,Steegers EA,Mackenbach JP,Ott A,Willemse HF,van der Zwaan EA,Verkooijen RP,Verbrugh HA, Chlamydia trachomatis infection during pregnancy associated with preterm delivery: a population-based prospective cohort study. European journal of epidemiology. 2011 Jun;     [PubMed]

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