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 [1] [2]. 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 [3].

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 [4]. Other triggers of respiratory infections have to be considered during the workup, including Cp. psittaci [5].

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 [6] [7]. Furthermore, Cp. pneumoniae has been related to atherosclerosis, but its role in the pathogenesis of this cardiovascular disease remains poorly defined [8].

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).

• Inguinal Lymphadenopathy

  lymphadenopathy (or bubo), but it may also present with proctitis, extragenital lymphadenopathy, and systemic symptoms, including fever. 1 Response to treatment of early infection is usually excellent. [bmj.com]

  Other subtypes of the same species induce lymphogranuloma venereum, which is characterized by inguinal lymphadenopathy as well as hemorrhagic inflammation of the rectum and/or colon. [symptoma.com]

• Infertility

  CONCLUSIONS: This systematic review demonstrates the absence of valid evidence on the attributable risk of post-infective tubal factor infertility after genital chlamydial infection. [ncbi.nlm.nih.gov]

  (Conclusion) There was a high prevalence (24.1%) of serum IgA and/or IgG-antibodies against C. trachomatis from infertility patients. [doi.org]

• Asymptomatic

  Abstract The present study aimed to determine whether pelvic examinations change clinical management of women with asymptomatic chlamydia infection. [ncbi.nlm.nih.gov]

  These calculations assume that an infected asymptomatic woman is equally likely to present for testing at any stage during her infection. [stdjournal.com]

  Many infected individuals are asymptomatic. In women, there may be cervical inflammation or yellow, cloudy discharge from the cervical os. In men, there may be a discharge from the penis. [bestpractice.bmj.com]

  While the majority of Chlamydia infections is readily treatable, asymptomatic disease is common and rarely diagnosed. [symptoma.com]

• Fever

  Though it’s possible to contract it without knowing it, symptoms of a chlamydia infection in your throat include cough, fever, and sore throat. [healthline.com]

  In men: Epididymitis - infection of the tubes that carry sperm to the testicles, which can result in fever, scrotal pain and swelling. [avert.org]

  Symptoms that may occur include: a painful or burning sensation when urinating, an unusual discharge from the penis, testicular pain or swelling, or fever. [en.wikipedia.org]

  Symptoms in women include Abnormal vaginal discharge, which may have a strong smell A burning sensation when urinating Pain during intercourse If the infection spreads, you might get lower abdominal pain, pain during sex, nausea, or fever. [nlm.nih.gov]

  Prostatitis may result in pain during or after sex, fever and chills, painful urination, and lower back pain. Infections in newborns. [mayoclinic.org]

• Inflammation

  Specimens from patients with nonspecific inflammation of the urogenital tract were studied and healthy volunteers served as controls. [ncbi.nlm.nih.gov]

  Other symptoms may include inflammation of the neck of the womb (cervicitis), inflammation of the fallopian tubes (salpingitis) and inflammation of the glands that produce sexual lubricant mucus (bartholinitis). [web.archive.org]

  Cervicitis - inflammation of the lower part of the womb (cervix). Salpingitis - inflammation of the fallopian tubes (tubes that carry fertilised eggs from the ovaries to the uterus), preventing an egg from travelling from the ovary to the womb. [avert.org]

  In men, those with a chlamydial infection show symptoms of infectious inflammation of the urethra in about 50% of cases. [en.wikipedia.org]

• Lymphadenopathy

  (or bubo), but it may also present with proctitis, extragenital lymphadenopathy, and systemic symptoms, including fever. 1 Response to treatment of early infection is usually excellent. [bmj.com]

  Other subtypes of the same species induce lymphogranuloma venereum, which is characterized by inguinal lymphadenopathy as well as hemorrhagic inflammation of the rectum and/or colon. [symptoma.com]

• Pneumonia

  Chlamydophila pneumoniae is an ubiquitious pathogen causing respiratory infections. Affected individuals may present with sinusitis, laryngitis, pharyngitis, bronchitis, or pneumonia. [symptoma.com]

  We tested for immunoglobulins M, G and A as retrospective evidence of C. pneumoniae infection using the micro-immunofluorescence method. Past C. pneumoniae infection was defined by IgG titer > 16 < or = 512. [ncbi.nlm.nih.gov]

  Infant Pneumonia Caused by C. trachomatis Chlamydia pneumonia in infants typically occurs at 1–3 months and is a subacute pneumonia. [cdc.gov]

• Rectal Pain

  Infection of the anus (rectum) presents with rectal pain, discharge, or bleeding. Self-Care Guidelines Seek medical care if you suspect chlamydia. Avoid any sexual activity until a week after treatment is finished. [skinsight.com]

  If symptoms of a rectal infection do occur, however, they may include rectal pain, discharge, or bleeding. Additionally, women can develop a throat infection if they perform oral sex on someone with the infection. [healthline.com]

  […] men or women), it can cause rectal pain, discharge, and/or bleeding. [nlm.nih.gov]

  While these infections often cause no signs or symptoms, you may experience rectal pain, discharge or bleeding. It's also possible to acquire chlamydial eye infections (conjunctivitis) through contact with infected secretions. [mayoclinic.org]

  While these infections often cause no symptoms, they can cause Rectal pain; Discharge; Bleeding. You should be examined by your doctor if you notice any of these symptoms or if your partner has an STD or symptoms of an STD. [cdc.gov]

• Lower Abdominal Pain

  She has diffuse abdominal pain with significant tenderness in both the right lower and upper quadrants. [pedsinreview.aappublications.org]

  In women, symptoms include: Vaginal discharge Burning or pain while urinating Lower abdominal pain Nausea Fever Pain during intercourse Bleeding between periods In men, symptoms include: Penis discharge Burning or pain while urinating Burning or itching [livescience.com]

  Symptoms in women include Abnormal vaginal discharge, which may have a strong smell A burning sensation when urinating Pain during intercourse If the infection spreads, you might get lower abdominal pain, pain during sex, nausea, or fever. [nlm.nih.gov]

  Women may experience a change in vaginal discharge, cystitis (pain when passing water) and mild lower abdominal pain. If the disease is untreated, it can lead to severe pelvic pain, pain during intercourse or, more rarely, bleeding between periods. [web.archive.org]

  Signs and symptoms of chlamydia trachomatis infection may include: Painful urination Lower abdominal pain Vaginal discharge in women Discharge from the penis in men Painful sexual intercourse in women Bleeding between periods and after sex in women Testicular [mayoclinic.org]

• Nausea

  Other symptoms might include belly or low back pain, nausea, fever, or pain with sexual intercourse. Men with infection may have pus or fluid from the opening of their penis (urethra) or itching or burning with urination. [skinsight.com]

  In women, symptoms include: Vaginal discharge Burning or pain while urinating Lower abdominal pain Nausea Fever Pain during intercourse Bleeding between periods In men, symptoms include: Penis discharge Burning or pain while urinating Burning or itching [livescience.com]

  Symptoms in women include Abnormal vaginal discharge, which may have a strong smell A burning sensation when urinating Pain during intercourse If the infection spreads, you might get lower abdominal pain, pain during sex, nausea, or fever. [nlm.nih.gov]

  Symptoms of PID include pain in your lower abdomen or back, pain during sex, vaginal bleeding, fever, and nausea. [babycenter.com]

  The symptoms of this are: : Pain or bleeding during sex Bleeding (or 'spotting') between periods Nausea or fever Abdominal, lower back pain or a heavy feeling around the hips Order treatment or test kit No results found. [dred.com]

• Vomiting

  Hospitalization is required if a patient is pregnant; has severe illness, nausea and vomiting, or high fever; has tuboovarian abscess; is unable to follow or tolerate the outpatient oral regimen; or has disease that has been unresponsive to oral therapy [web.archive.org]

  Fitz-Hugh-Curtis syndrome (perihepatitis) may cause right upper quadrant pain, fever, and vomiting. [msdmanuals.com]

  If patients vomit the dose of azithromycin within one to two hours of taking the medication, an alternative treatment should be considered ( Table 1 ). 2 View/Print Table TABLE 1 CDC-Recommended Regimens for Uncomplicated Urogenital Chlamydial Infection [aafp.org]

• Right Upper Quadrant Pain

  Fitz-Hugh-Curtis syndrome (perihepatitis) may cause right upper quadrant pain, fever, and vomiting. [msdmanuals.com]

  […] peritoneum, which is associated with right upper quadrant pain. [cdc.gov]

• Ulcer

  […] trachomatis urethritis Urethritis due to Chlamydia trachomatis ICD-9-CM Volume 2 Index entries containing back-references to 099.41 : Urethritis (abacterial) (acute) (allergic) (anterior) (chronic) (nonvenereal) (posterior) (recurrent) (simple) (subacute) (ulcerative [icd9data.com]

  LGV can cause ulcerating sores or lumps inside or outside of the genitals. For pregnant women, chlamydia can also cause miscarriage, preterm birth and low birth weight. [sexandu.ca]

  Common symptoms of STIs include vaginal discharge, urethral discharge or burning in men, genital ulcers, and abdominal pain. Scope of the problem STIs have a profound impact on sexual and reproductive health worldwide. [who.int]

• Pelvic Pain

  Symptoms may include intermenstrual or postcoital bleeding; an odourless, mucoid vaginal discharge; pelvic pain; or dysuria. In men, chlamydia infection can occur in the urethra, causing a penile discharge. [bestpractice.bmj.com]

  Untreated infections in women can result in pelvic inflammatory disease, infertility, ectopic pregnancy, and chronic pelvic pain. In men, the infection can be associated with urethritis, epididymitis, and, in men who have sex with men, proctitis. [nejm.org]

  To avoid severe sequelae such as female infertility, ectopic pregnancy, neonatal infection, such as ophthalmitis, and chronic pelvic pain prompt and appropriate antibiotic treatment seems the best policy in treating this group of patients. [ncbi.nlm.nih.gov]

  In women, the infection can result in pelvic inflammatory disease (PID), which can damage the ovaries, uterus and fallopian tubes and lead to infertility. The infection can also result in chronic pelvic pain. [livescience.com]

  However, in women, asymptomatic cervical infection may persist, resulting in chronic endometritis, salpingitis, or pelvic peritonitis and their sequelae—pelvic pain, infertility, and increased risk of ectopic pregnancy. [msdmanuals.com]

• Vaginal Discharge

  Signs of friability and purulent endocervical discharge were documented at gynaecological examination. Specimens for microscopy were taken from the endocervix and urethra as well as the vaginal discharge, and bacterial vaginosis was examined for. [ncbi.nlm.nih.gov]

  […] and having a thick, yellow liquid come from your vagina (vaginal discharge) Women who don't get treatment may have permanent damage making it difficult or impossible to have a baby If you're sexually active, talk to your doctor about a screening test [merckmanuals.com]

  Symptoms may include intermenstrual or postcoital bleeding; an odourless, mucoid vaginal discharge; pelvic pain; or dysuria. In men, chlamydia infection can occur in the urethra, causing a penile discharge. [bestpractice.bmj.com]

  Symptoms in women may include vaginal discharge or burning with urination. [play.google.com]

• Salpingitis

  Chlamydiae may also cause salpingitis, epididymitis, perihepatitis, neonatal conjunctivitis, and infant pneumonia. Untreated chlamydial salpingitis can become chronic, causing minimal symptoms but having serious consequences. [msdmanuals.com]

  People interested in this subject often clicked these ... [ Chlamydia ] Chlamydia (For series of 14 pictures, click Next>>> at bottom right) Freedom network, Rochester, Minnesota Chlamydial cervicitis | Chlamydial epididymitis | Chlamydial salpingitis [hardinmd.lib.uiowa.edu]

• Testicular Pain

  […] in opening of penis Testicular pain Swelling of the testicles (although this is uncommon) Complications of untreated chlamydia can be serious for both genders. [livescience.com]

  (for chlamydia in the eyes) Sore throat, cough, swollen lymph nodes, and/or fever (for chlamydia in the throat) Male: Itchy urethra Clear, watery or milky discharge from the penis Testicular pain or swelling Using condoms can help prevent the spread [sexandu.ca]

  Signs and symptoms of chlamydia trachomatis infection may include: Painful urination Lower abdominal pain Vaginal discharge in women Discharge from the penis in men Painful sexual intercourse in women Bleeding between periods and after sex in women Testicular [mayoclinic.org]

  Symptoms that may occur include: a painful or burning sensation when urinating, an unusual discharge from the penis, testicular pain or swelling, or fever. [en.wikipedia.org]

• Dysuria

  Women are usually asymptomatic, although vaginal discharge, dysuria, increased urinary frequency and urgency, pelvic pain, dyspareunia, and symptoms of urethritis may occur. [msdmanuals.com]

  Symptoms may include intermenstrual or postcoital bleeding; an odourless, mucoid vaginal discharge; pelvic pain; or dysuria. In men, chlamydia infection can occur in the urethra, causing a penile discharge. [bestpractice.bmj.com]

  In men, the infection usually is symptomatic, with dysuria and a discharge from the penis. Untreated chlamydial infection in men can spread to the epididymis. [web.archive.org]

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 [9]. Molecular biological techniques are commonly applied to detect nucleic acids of Chlamydiaceae [3]. Such assays yield reliable results within a short period of time and have been shown to be more sensitive than bacteriological cultures [10]. Nevertheless, Chlamydiaceae may be grown in host cells, which are ideally collected alongside the specimens for microbiological analysis [4]. 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 [3]. Still, reinfections are likely and retesting for C. trachomatis is strongly recommended about 3 months after the completion of treatment [7].

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 [4]. If contraindicated or ineffective, fluoroquinolones may be used [3].

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 [3] [7]. 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 [6].

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 [11]. Male infertility has similarly been related to Chlamydia infection [12].

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 [13]:

• C. trachomatis, serovars A-C, which constitute biovar trachoma, etiologic agent of ocular infections referred to as trachoma
• C. trachomatis, serovars D-K, provoke chlamydial urethritis, one of the most frequent bacterial sexually transmitted diseases
• C. trachomatis, serovars L1, L2, and L3, which correspond to biovar LGV, causative agent of lymphogranuloma venereum
• Cp. pneumoniae, biovar TWAR, accounts for respiratory infections
• Cp. abortus, a zoonotic agent that may cause abortion in humans, primarily known as a trigger of endemic abortion in ruminants [9]
• Cp. felis, a zoonotic pathogen that may cause conjunctivitis in humans and cats [14]
• Cp. psittaci, causative agent of ornithosis in mammals including humans, as well as psittacosis in birds, mainly in parrots [5]

By far the most common species causing chlamydia infection are C. trachomatis and Cp. pneumoniae. Other Chlamydiaceae are mainly of veterinary importance but may trigger zoonoses like ornithosis.

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 [15].

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 [4]. 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 [16]. The occurrence of hot spots has been confirmed occasionally but may be more common than generally assumed [17]. 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 [18]. 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 [4]. 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 [3]. 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 [19].

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 [20]. The family of Chlamydiaceae comprises two genera, namely Chlamydia and Chlamydophila, and there are at least five human pathogen species [13] [21]:

• Chlamydia trachomatis
• Chlamydophila pneumoniae
• Chlamydophila felis
• Chlamydophila abortus
• Chlamydophila psittaci

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:

• There are two sexually transmitted diseases caused by Chlamydiaceae. On the one hand, certain subtypes of Chlamydia trachomatis may provoke an inflammation of the urethra, causing purulent vaginal or penile discharge and pain upon urination. When contracted anally, the disease may manifest in rectal pain, tenesmus, discharge, and hemorrhages. Other subtypes of the same species induce lymphogranuloma venereum, which is characterized by inguinal lymphadenopathy as well as hemorrhagic inflammation of the rectum and/or colon.
• Finally, Chlamydia trachomatis may cause ocular infections referred to as trachoma. Trachoma may result in severe corneal damage and blindness if not adequately treated.
• Chlamydophila pneumoniae is an ubiquitious pathogen causing respiratory infections. Affected individuals may present with sinusitis, laryngitis, pharyngitis, bronchitis, or pneumonia.

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.

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