Chlamydiosis is a common sexually transmitted disease (STD) caused by infection with a Gram-negative bacteria Chlamydia trachomatis. The family Chlamydiaceae contains besides C.trachomatis two important pathogenic species, C. psittaci and C.pneumoniae.
The importance of C.trachomatis as a sexually transmitted agent became apparent in the mid-1970-s, with reports of pelvic inflammatory disease (PID), endometritis and salpingitis, resulting in ectopic pregnancy and infertility, as well as conjunctivitis (paratrachoma) and pneumonia of the newborns. In men, untreated chlamydial infections can lead to urethritis and epididymoorchitis, and primarily in men, chlamydiosis is known to cause autoimmune disease, reactive arthritis. Besides these conditions, in poor developing countries C. trachomatis could cause trachoma, a specific ocular disease, which is one of the leading causes of blindness, as well as systemic sexually transmitted disease called lymphogranuloma venereum (LGV).
C. trachomatis develops in biphasic cycle. The bacterium is normally found in two highly specialized morphologic forms — the extracellular, metabolically inactive, infectious elementary body (EB) and the metabolically active, dividing, non-infective intracellular form known as reticulate body (RB). The infectious EB enters the mucosal host cells via endocytosis. Inside endosome EBs reorganize into RBs. RBs divide by binary fission, filling the endosome with hundreds of RBs. Multiplication ceases after 48 – 72 h, and RBs transform into metabolically inactive infectious EBs. The EBs are released from the cell by cell rupture or exocytosis, and target new host cells.
In women, C. trachomatis infection may involve not only cervix, but also endometrium and fallopian tubes in around 10% of individuals. The disease sequelae caused by this process include PID and its complications. After PID has occurred, even with treatment, it could cause significant reproductive and gynaecological morbidity, including infertility, ectopic pregnancy, and chronic pelvic pain. In one study, 18% of women developed infertility after clinically diagnosed single episode of PID; the risk of infertility increases considerably after every new episode of PID [Ness et al., 2002].
Infertility or subfertility are the result of damage to the cilia lining the fallopian tubes, fallopian tube blockage or closure, or adhesion formation among pelvic organs. The issue of whether chlamydial PID is a consequence of persistent infection, immunopathology, or autoimmune reaction remains unresolved.
Chlamydia can also spread perinatally from an untreated mother to her baby during childbirth, resulting in paratrachoma, urethritis, proctitis, nasopharyngeal infection or pneumonia in many exposed infants. The risk of neonatal chlamydiosis in children born through an infected birth canal is around 15%. Conjunctival infections are detected within the first 22 days of life, eventually followed by nasopharyngeal infections and pneumonia, rectal and vaginal infections during the first several month of life.
Chlamydiosis is known as a ‘silent’ infection because most infected people, especially women, are asymptomatic and lack abnormal physical examination findings. Unfortunately, there might not be a relationship between the severity of symptoms and the severity of the disease. The symptoms of cervicitis may appear 1-3 weeks after infection, and may include mucopurulent endocervical discharge and easily induced endocervical bleeding; if cervicitis develops into PID, abdominal and/or pelvic pain could arise.
C. trachomatis is transmitted if infected secretions from urethra, cervix, rectum, conjunctivae and throat come into contact with mucous membranes of the above-mentioned organs. Chlamydiosis is usually transmitted by sex. Therefore, young people (up to 25 years) are at highest risk of acquiring chlamydiosis. In addition, an infected mother can infect her baby during vaginal delivery.
C.trachomatis is grouped into 18 separate serovars, which are distinguished by the antigenic and molecular polymorphism within major outer membrane protein, OmpA. Serovars A-C infect the conjunctive epithelium and lead to ocular infections that can progress to trachoma; serovars L1-L3 are able to infect not only the genital epithelium, but also monocytes and lead to LGV; classical sexually transmitted non-LGV infections are caused by serovars D-K. Protective immunity to chlamydiosis is not absolute, being much stronger to the same serovar; therefore, reinfections are usually by the heterologous serovar.
Chlamydiosis is distributed across the world, with the highest rates in South-East Asia and Sub-Saharan Africa, where trachoma and LGV are endemic. In developed countries, 5-10% of women <25 years of age are infected with C.trachomatis, and the rate is much higher in some local populations. Neonatal chlamydiosis is a very common perinatal infection.
Humoral immunity under chlamydiosis is reliant on both systemic and local antibodies. In contrast to other mucosal secretions, the dominant immunoglobulin isotype in the cervico-vaginal fluid of the female genital tract is secretory IgG rather than secretory IgA. Localized chlamydial infections (e.g. paratrachoma) do not usually produce an antigenic stimulus strong enough to elicit a readily discernible systemic antibody response. Instead, there is increase in titers of local antibodies, usually two weeks after onset. A strong systemic antibody response could be detected in LGV and reactive arthritis. In the infections of female genital tract, the severity of disease correlates with antibody levels.
IgM antibodies are associated with acute disease, since they are known to persist for only 8 to 10 weeks after genital infections. Serum IgA antibodies are a marker for active ongoing infection. In contrast to IgM and IgA, serum IgG could persist for years after recovery. In infants with chlamydial infections, IgM is indicative of infection since it cannot cross the placenta and must be produced by the baby.
Purified elementary bodies, purified outer membrane complexes of C.trachomatis, and recombinant proteins are used as antigens for diagnostics. C.trachomatis OmpA protein has 3 immunogenic domains, which are variable and contain serovar-specific determinants. Another surface protein, OmpB, is a highly genus-conserved structural protein of all Chlamydia species, including human pathogens C.pneumoniae and C.psittaci. Surface lipopolysaccharide (LPS) is also genus-reactive. There is a number of chlamydial proteins with much broader cross-reactivity, i.e. proteins that mimic host self-proteins, such as chlamydial heat-shock proteins 60 and 10 (CHSP60 and CHSP10). CHSP60 is a highly conserved protein sharing antigenic epitopes not only between Chlamydia species but also between other bacteria and eucaryotic cells. Many complications of chlamydiosis are a consequence of an immune response to an epitope of chlamydial CHSP60 crossreactive with the human HSP60. High titres of antibodies to CHSP60 under chlamydiosis of female genital tract are more informative of tubal occlusion than general IgG antibodies or antibodies to MOMP.
Because of the potential for C. trachomatis infection to cause serious sequelae and its asymptomaticity, chlamydia screening and treatment programs have been implemented in many countries to prevent tubal damage among those infected and reduce C. trachomatis transmission. According to CDC recommendations, all pregnant women should be screened for chlamydia at their first prenatal visit. Pregnant women under 25 and those at increased risk for chlamydiosis should be screened again in their third trimester. Pregnant women with chlamydial infection should be retested 3 weeks and 3 months after completion of recommended therapy [Centers for Disease Control and Prevention, 2015; https://www.cdc.gov/std/chlamydia/stdfact-chlamydia-detailed.htm].
There is a variety of methods to diagnose C.trachomatis infections. Cell culture has long been considered the gold standard for diagnosis. However, its labor intensive methodology makes it less attractive for routine diagnostic testing. Performance of cell culture could be simplified by methods of direct immunofluorescence. PCR could be performed on vaginal swabs, endocervical or urethral swabs, and urine. PCR has reduced performance in the presence of inhibitors in urine samples (oestrogens, nitrates, crystals) resulting in false-negatives.
Immunoassays detecting both antibodies and C.trachomatis antigen has long been used in clinical practice (fixation of complement (CF), indirect immunofluorescence, ELISA, and RIA). Women seropositive for IgM at screening are at highest risk for preterm labor. The presence of IgG at high levels or of IgM/IgA at any level in the blood, and the presence of either IgG or IgA at any level in local discharges are useful indicators for the provisional diagnosis of chlamydiosis. Seropositivity for only IgG at low titres is usually interpreted as an evidence of past chlamydial infection, indicating probable tubal damage, and necessitating further management.
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