Chlamydia spp.

‍Chlamydia spp. are a group of obligate intracellular bacteria responsible for various human and animal diseases, including respiratory infections, eye infections like trachoma, and genital infections—the most common sexually transmitted diseases worldwide. 

These pathogens thrive within host cells by manipulating cellular processes to create a conducive environment for their replication while evading immune defenses. Despite the absence of an effective vaccine, antibiotic treatment remains essential, though concerns about resistance, particularly to tetracyclines, have emerged. 

Advances in proteomics and genetics have deepened our understanding of Chlamydia-host interactions, offering new avenues for research and potential treatments. 

This article will explore the characteristics, diagnosis, and management of infections caused by Chlamydia spp., with a focus on respiratory, ocular, and genital infections.

What is Chlamydia spp.?

Chlamydia spp. are obligate intracellular bacteria that cause various diseases in humans and animals, including atypical pneumonia, eye infections like trachoma (the leading cause of bacterial blindness globally), and genital infections, making it the most common cause of sexually transmitted diseases (STDs) [5.]. 

These pathogens replicate within a specialized membrane compartment in host cells, employing secreted effectors to survive in the hostile intracellular environment [11.].

Chlamydia spp. depend on the host for metabolic requirements while evading immune defenses [11.]. They manipulate host cytoskeletal and membrane trafficking pathways to create a replication-competent niche [26.].

With no effective vaccine available, antibiotic treatment is essential, but concerns about tetracycline resistance have emerged [7., 11.].

Host defense peptides (HDPs) show promise as alternative antimicrobial agents, with C. trachomatis being particularly sensitive to their effects [7.]. 

Recent advances in chlamydial proteomics and genetics have improved our understanding of Chlamydia-host interactions, paving the way for new research avenues [11.].

Diseases Associated with Chlamydia spp.

Respiratory Infections

Chlamydia pneumoniae is a widely prevalent intracellular bacterium that primarily causes respiratory infections, including pneumonia, bronchitis, sinusitis, and pharyngitis [12.].

It is transmitted through respiratory droplets and is known for its high reinfection rate throughout life [2., 12.].

It can also be transmitted to infants during birth, causing ocular or severe respiratory infections [4.].

While most infections are asymptomatic or mildly symptomatic, about 30% can progress to severe respiratory illnesses [12.].

The symptoms of C. pneumoniae infections are similar to those caused by other respiratory pathogens but often present a subacute onset with pharyngitis that may resolve before bronchitis or pneumonia develops. A prolonged cough and slow recovery, even with antibiotic therapy, are common [2., 3., 13., 14.].

Beyond its acute respiratory effects, C. pneumoniae has been implicated in chronic conditions such as asthma, chronic obstructive pulmonary disease (COPD), and cardiovascular diseases like atherosclerosis and coronary heart disease [2., 12.].

The bacterium's ability to persist in the body, even after antibiotic treatment, poses significant challenges, highlighting the need for further research into its pathogenesis and effective treatment strategies [2.].

Ocular Infections

Chlamydia trachomatis is a major cause of sexually transmitted infections worldwide, leading to millions of new cases annually [21., 28.,]. C. trachomatis has an affinity for the columnar epithelium of the cervix, urethra, and rectum, as well as sites such as the lungs and eyes.

This intracellular bacterium can infect various tissues; C. trachomatis eye infections cause a range of ocular conditions [17.].

Trachoma, a chronic conjunctivitis, is the leading preventable cause of blindness globally, affecting millions [18., 21.].

Chlamydial eye infections can also manifest as newborn conjunctivitis, when the bacterium is passed from mother to infant [28.].

The pathogen's unique life cycle and ability to establish persistent infections contribute to its success as a human pathogen [18.].

Ocular chlamydial infections present a spectrum of symptoms, ranging from mild conjunctivitis to potentially blinding conditions like trachoma [17.].

Common symptoms include follicular conjunctival reaction, mucoid discharge, and occasionally peripheral corneal vascularization or keratitis [6.].

Chlamydial conjunctivitis is most prevalent in young adults aged 16-20 years, with decreasing frequency in older age groups [25.]. Unilateral symptoms are typical, and pseudoptosis may occur in some cases [25.].

The condition can have a prolonged course if left untreated [25.]. 

Screening is recommended for women under 25, pregnant women, and those at increased risk, while it's not currently advised for men [21.].

Genital Infections

As mentioned above, C. trachomatis has an affinity for the columnar epithelium of the cervix, urethra, and rectum, as well as sites such as the lungs and eyes [21.].

Chlamydia trachomatis is a major cause of sexually transmitted infections (STIs) worldwide, with an estimated 4 million cases annually in the United States alone [29.].

This intracellular bacterium primarily affects the genital and urinary tracts, causing infections that can be transmitted through various forms of sexual contact [4., 24.]. 

C. trachomatis can also be vertically transmitted from mother to newborn during childbirth, potentially leading to conjunctivitis or severe respiratory infections in infants [4.]. 

The infection often remains asymptomatic in approximately 50% of infected men and 70% of infected women [31.].

When symptomatic, it can manifest as urethritis, cervicitis, or epididymitis [32.]. In women, untreated infections can lead to serious complications such as pelvic inflammatory disease, ectopic pregnancy, and tubal factor infertility [32.].

The asymptomatic nature of many infections contributes to sustained transmission within communities [33.]. 

When symptoms are present, chlamydial genital infections can present with a variety of symptoms in both females and males. 

In females, when symptoms are present, they may include vaginal discharge, bleeding after sexual intercourse or between menstrual periods, lower abdominal pain, pelvic pain, painful intercourse, and dysuria (painful urination) [8.].

In males, symptoms, if present, can include dysuria, urethral discharge, and scrotal pain or swelling [8.].

C. trachomatis mainly causes genital and may also cause eye infections, while other species in the Chlamydiae group such as C. psittaci and C. pneumoniae (now classified under the genus Chlamydophila), primarily cause respiratory infections [24.].

Naming and Classification of Chlamydia spp. [14., 19.] 

Chlamydia pneumoniae is part of the Chlamydiae order, which contains obligate intracellular pathogens. 

The order initially comprised one genus, Chlamydia, with four recognized species: C. trachomatis, C. psittaci, C. pneumoniae, and C. pecorum. 

C. trachomatis and C. pneumoniae are primary human pathogens, while C. psittaci causes zoonosis.

Recent taxonomic analysis has led to a proposed reclassification, suggesting the division of the genus Chlamydia into two genera: Chlamydia and Chlamydophila. 

Under this new classification, C. trachomatis would be joined by two new species, Chlamydia muridarum and Chlamydia suis. 

The genus Chlamydophila would include C. pecorum, C. pneumoniae, and C. psittaci, along with three new species derived from C. psittaci: Chlamydophila abortus, Chlamydophila caviae, and Chlamydophila felis. Despite ongoing controversy regarding this reclassification, the term Chlamydia is still commonly used.

Chlamydia pneumoniae, also known as TWAR, is distinguished from C. trachomatis and C. psittaci by its unique elementary body morphology and less than 10% DNA homology. 

Laboratory Testing for Chlamydia spp.

Testing Recommendations for Chlamydia spp. Infections

The CDC's guidelines for testing Chlamydia trachomatis emphasize nucleic acid amplification tests (NAATs) as the preferred diagnostic tool due to their superior sensitivity, specificity, and versatility across various specimen types [20., 23.]. 

The polymerase chain reaction (PCR) test is one example of this type of testing [27.].

NAATs are recommended for detecting genital, ocular, and respiratory chlamydial infections, as well as anorectal and oropharyngeal infections, except in specific cases such as child sexual assault or potential treatment failures, where culture and susceptibility testing may be required [23.].

Testing for Respiratory Chlamydial Infections

For chlamydial respiratory infections, serology, particularly microimmunofluorescence (MIF), is the preferred method for diagnosing acute infections, typically requiring both acute and convalescent samples [9.].

Molecular methods are also widely used due to their high sensitivity and specificity, while imaging can suggest pneumonia but cannot reliably identify the causative agent.

Testing for Ocular Chlamydial Infections

In diagnosing ocular chlamydial infections, while tissue culture is a traditional method, newer point-of-care dipstick assays have proven more accurate than clinical signs for identifying ocular trachoma [10.]. 

Rapid diagnostic tests based on PCR also show promise for effective point-of-care testing, enhancing the ability to detect and manage chlamydial infections.

Testing for Genital Chlamydia Infections

For genital infections, which are often asymptomatic, NAATs are considered the gold standard, capable of detecting the infection in urine, vaginal swabs, and other mucosal swabs. 

Although culture was once the gold standard for diagnosing chlamydia, it is no longer recommended for routine use due to its lower sensitivity, longer turnaround time, and technical complexity, but it remains essential in certain cases like pediatric or medico-legal situations [8., 20., 23.].

Sample Collection

Nucleic acid amplification tests (NAATs) are often performed on urine and swab samples. 

These tests can be performed on non-invasive samples such as first-catch urine (FCU) and self-obtained vaginal swabs (SVS), making them more acceptable to patients than traditional invasive methods [16.].

To diagnose an ocular infection, an ocular swab sample is typically taken from the conjunctiva (or other relevant site if testing for non-ocular infections) using a sterile swab [15.].

Serology testing for IgM and IgG antibodies against Chlamydia spp. requires a blood sample, obtained through venipuncture. Acute and convalescent samples are typically required. In contrast, molecular methods or culture may be performed on a variety of specimen types [9.].

Treatments for Chlamydia spp. Infections

C. trachomatis Genital Infection Treatments [8.].

The CDC's 2021 guidelines recommend doxycycline 100 mg orally twice daily for 7 days as the first-line treatment for Chlamydia trachomatis genital infections. 

For pregnant patients, the preferred treatment is a single dose of azithromycin 1 g orally. 

Patients should abstain from sexual intercourse until completing the 7-day treatment or for 7 days after the single-dose regimen, and until their sexual partners have been treated. 

Routine test of cure is not necessary except in cases of pregnancy, suspected nonadherence, persistent symptoms, or suspected reinfection. 

Screening for reinfection is advised for all patients 3 months after treatment.

Trachoma Treatments [10.]

Oral azithromycin is the treatment of choice. 

Antibiotics may reduce active trachoma, but evidence is not consistent. 

C. pneumoniae Respiratory Infection Treatments [9.]

Most patients with Chlamydia pneumoniae infection recover without treatment. 

However, for those with acute respiratory infections, first-line treatment options include macrolides (azithromycin, erythromycin, or clarithromycin), tetracyclines (tetracycline or doxycycline, though tetracyclines should be avoided in children under 8 years old), and fluoroquinolones (levofloxacin or moxifloxacin) for patients intolerant to other options.