Chlamydia infection is a general term that may refer to a variety of diseases triggered by bacterial pathogens belonging to the family of Chlamydiaceae. Genital infections with Chlamydia trachomatis serovars D and respiratory disease induced by Chlamydophila pneumoniae are the most common types of Chlamydia infection in industrialized nations. Other conditions triggered by Chlamydiaceae include, but are not limited to, trachoma, lymphogranuloma venereum, and ornithosis.
Chlamydia infection may comprise distinct organ systems, and clinical symptoms largely depend on the causative agent.
C. trachomatis serovars D-K account for a major disease burden and most commonly affect the urogenital tract  . Patients may develop symptoms several weeks after contracting the respective sexually transmitted infection: Dysuria due to chlamydial urethritis may be described and may be accompanied by mucopurulent or purulent vaginal/penile discharge. Bleeding after sexual intercourse has also been reported. Upon anal exposure, patients may develop rectal inflammation manifesting in pain, tenesmus, discharge, and hemorrhages. Oral sex may predispose to pharyngeal infections .
Another very common pathogen is Cp. pneumoniae, biovar TWAR. It is spread through aerosolized respiratory secretions and induces acute respiratory infections manifesting in sinusitis, laryngitis, pharyngitis, bronchitis, and atypical pneumonia. Patients with preexisting respiratory disorders may experience an exacerbation of symptoms. In sum, the severity of symptoms developed after an incubation time of about three weeks varies largely and ranges from asymptomatic or mild disease to severe community-acquired pneumonia. Most infections follow a mild course. Symptoms like fever, chills, myalgia, hoarseness, and cough are non-specific and don't allow for the clinical confirmation of Cp. pneumoniae infection . Other triggers of respiratory infections have to be considered during the workup, including Cp. psittaci .
Both C. trachomatis and Cp. pneumoniae have been related to reactive arthritis, as have other intracellular pathogens and Gram-negative bacteria. Affected individuals usually have a history of genital or respiratory Chlamydia infections, and they may present with arthralgia, joint swelling, joint effusion, stiffness, and reduced motion range. Contrary to what had initially been assumed, Chlamydia-induced reactive arthritis is associated with persistent, intraarticular infections, and Chlamydia may be detected in synovial fluid samples  . Furthermore, Cp. pneumoniae has been related to atherosclerosis, but its role in the pathogenesis of this cardiovascular disease remains poorly defined .
Other Chlamydiaceae may provoke conjunctivitis (C. trachomatis serovars A-C and Cp. felis), inguinal lymphadenitis, proctitis, and proctocolitis (C. trachomatis serovars L1, L2, and L3), and abortion (Cp. abortus).
Chlamydia infection is ideally diagnosed by providing evidence for the presence of Chlamydiaceae in the affected organ system. Mucosal swabs are generally analyzed to this end, but other types of samples may be used depending on the clinical presentation. In the workup of genital infections, first-void urine samples may replace endocervical, urethral, and vaginal swabs, while placenta and fetal tissues should be examined in the case of an abortion possibly caused by Cp. abortus . Molecular biological techniques are commonly applied to detect nucleic acids of Chlamydiaceae . Such assays yield reliable results within a short period of time and have been shown to be more sensitive than bacteriological cultures . Nevertheless, Chlamydiaceae may be grown in host cells, which are ideally collected alongside the specimens for microbiological analysis . These samples may subsequently be subjected to microscopic and immunohistochemical analyses.
There is a variety of serological assays available to confirm prior exposure to Chlamydiaceae. These tests may be specific at the family, species, or serovar level. It should be noted, though, that previous exposure to ubiquitous pathogens like C. trachomatis serovars and Cp. pneumoniae is not sufficient to prove a causal relation.
Antibiotic therapy is the mainstay of treatment. Uncomplicated urogenital infections should be treated with azithromycin or doxycycline. The former is administered as a single dose of 1 g, while doxycycline is applied at a dose of 100 mg, twice daily for seven days. Both regimens are equally effective and should be followed in both sexual partners, if feasible, to prevent reinfections . Still, reinfections are likely and retesting for C. trachomatis is strongly recommended about 3 months after the completion of treatment .
Besides the aforementioned compounds, other macrolide and tetracycline antibiotics may be employed in the management of Chlamydia infection. For instance, erythromycin and tetracycline have been recommended to treat respiratory infections triggered by Cp. pneumoniae . If contraindicated or ineffective, fluoroquinolones may be used .
Prolonged treatment is required to combat Chlamydia-induced reactive arthritis. Affected individuals are typically treated for six months and may receive azithromycin, doxycycline, or rifampicin plus azithromycin or doxycycline  . Infectious elementary bodies are not affected by antibiotics, so an interruption of antibiotic therapy may be considered after three months of treatment - to induce persistent bacteria to return to active reproduction .
Antibiotic resistances have rarely been reported, and if patients comply with treatment recommendations, they use to respond well to therapy. Thus, the prognosis of treated patients is very good. Long-term sequelae are feasible, though, if the infection persists. The majority of asymptomatic patients remains undiagnosed, and irreversible tissue damage may occur until complications arise. In this context, the generation of a protracted inflammatory response in the female reproductive organs may cause tubal scarring and occlusion, leading to infertility in women . Male infertility has similarly been related to Chlamydia infection .
Chlamydia infection may refer to distinct entities caused by different bacterial pathogens. In this context, the family of Chlamydiaceae comprises two relevant genera, namely Chlamydia (C.) and Chlamydophila (Cp.). The following representatives of these genera have been shown to be pathogenic in humans :
C. trachomatis is the causative agent of one of the most common sexually transmitted diseases. According to estimates published by the World Health Organization, about 4.2% of women worldwide are infected with this pathogen. Regional values range from 1.8% to 7.6%, with the highest prevalence rates reported in the Americas and Western Pacific Region. Similar regional trends have been observed in the male population, but the overall prevalence among men is significantly lower. It amounts to 2.7% on a global scale. The annual incidence of C. trachomatis infection ranges from 33-38 per 1,000 persons .
Similarly, Cp. pneumoniae is widely spread throughout industrialized and developing countries. Serological evidence of prior exposure to the pathogen is found in about 50% of young adults and >75% of the elderly . Due to the large share of asymptomatic and mildly symptomatic cases, the overall incidence of Cp. pneumoniae infections is difficult to establish.
Incidence and prevalence of zoonotic Chlamydia infections vary largely. In most countries with surveillance programs, <1 case of ornithosis per 1,000,000 inhabitants is reported annually . The occurrence of hot spots has been confirmed occasionally but may be more common than generally assumed . Mild cases may not be reported, thereby distorting the epidemiological picture. The same may apply to other forms of Chlamydia infection, which are supposed to be even rarer. Furthermore, the complete host range of Chlamydiaceae is not yet known and new species are likely to be described in the near future . It can only be speculated whether these species account for or contribute to known entities.
Chlamydiaceae are obligate intracellular bacteria characterized by a unique biphasic developmental cycle. This cycle comprises the conversion of infectious elementary bodies to replicative reticulate bodies and vice versa. Elementary bodies infect epithelial cells by binding to pathogen recognition receptors and inducing endocytosis. Once inside the host cell, elementary bodies differentiate into reticulate bodies. This is a prerequisite for the replication of Chlamydiaceae. Reticulate bodies are metabolically active, grow, divide by binary fission, form microcolonies, and eventually condense to form elementary bodies . The latter are released upon cell lysis and may subsequently infect other cells of the same host or be transmitted to another one.
The risk of contracting Chlamydia infection via the sexual route may significantly be diminished by the correct and consistent use of condoms, the reduction of the number of sexual partners, and abstinence . Of note, the infectivity of genital secretions is maintained during a short symptomatic and a much longer asymptomatic period, so the absence of symptoms does not protect from spreading the disease. The overall infectious period for C. trachomatis has been estimated to about one year .
Chlamydia infection is caused by Chlamydiaceae spp. All members of this family are obligate intracellular bacteria that share common biological features, e.g., a reproductive cycle comprising infectious, extracellular elementary bodies and replicative, intracellular reticulate bodies . The family of Chlamydiaceae comprises two genera, namely Chlamydia and Chlamydophila, and there are at least five human pathogen species  :
These species are implied in a variety of disorders that are most reliably diagnosed by the genetic confirmation of the causative agent. Distinct species may trigger similar diseases (e.g., atypical pneumonia may be caused by Cp. pneumoniae and Cp. psittaci), and different conditions may be attributed to the same species (e.g., C. trachomatis may cause genital infections and conjunctivitis).
This article aims at summarizing the diversity of Chlamydia infections but will focus on genital infections with C. trachomatis and respiratory infections induced by Cp. pneumoniae. With regards to other entities related to Chlamydiaceae, the interested reader is referred to the respective articles available on this platform.
Chlamydia infection is a general term referring to a variety of diseases caused by bacteria belonging to the family of Chlamydiaceae. In this context, Chlamydia trachomatis, Chlamydophila pneumoniae, and - in rare cases - Chlamydophila felis, Chlamydophila abortus, and Chlamydophila psittaci should be considered as potential triggers. Accordingly, Chlamydia infection may comprise distinct organ systems, and clinical symptoms largely depend on the causative agent:
While it is increasingly difficult to prevent infections with Chlamydophila pneumoniae, safer sex may considerably reduce the risk of contracting those types of Chlamydia trachomatis that are related to genital infections. While the majority of Chlamydia infections is readily treatable, asymptomatic disease is common and rarely diagnosed. Persistent infections, however, may have long-term consequences, such as irreversible scarring of the Fallopian tubes and infertility in women and men. Similarly, ocular infections should be treated as soon as possible to prevent permanent vision loss.