Chlamydia trachomatis

Microbiology

C. trachomatis is a member of the Chlamydia genus and a significant human pathogenic microorganism. The other two members of the genus are Chlamydia psittaci and Chlamydia pneumoniae. While C. psittaci primarily causes infection in the animal world, the recently described C. pneumoniae is exclusively a human pathogen. Both species primarily cause respiratory infections.
The L type of C. trachomatis causes lymphogranuloma venereum (LGV). This illness occurs most frequently in the tropics, although it should also be considered in Hungary when presented with the rare case of genital ulcers.
Some of the clinical pictures caused by C. trachomatis – specifically, non-gonococcal urethritis (NGU) and conjunctivitis (inflammation of the outermost layer of the eye) – have been known since the end of the 19th and the beginning of the 20th century. Although the classical clinical descriptions of these disorders are still valid, only relatively primitive means were available for their diagnosis until just recently. The spread of the cell culture technique first described by Gordon and Quan at the end of the 1960’s and later refined made it possible to recognize the diseases caused by C. trachomatis and to understand their epidemiological and social effects. The use of cell cultures in the industrially developed countries since the 1960’s led to the recognition that the D-K serotypes of C. trachomatis are the most important agents of sexually transmitted diseases.
C. trachomatis is an obligate intracellular parasite, which goes through a distinctive developmental cycle. It exists in two forms: the intracellular, vegetative, non-infectious state (reticular body) and the extracellular, infectious form (elementary body, EB).
The EB is a round, 200-300 nm formation, which does not demonstrate signs of life and most closely resembles a bacterial spore. It can only be seen using special staining procedures (immunoflurorescent stains).
The infectious EB’s are absorbed through a phagocytosis-like process by the host cells (e.g., the columnar epithelial cells of the urethra and cervix). Chlamydia goes through several phases of development in the host cell via binary division, resulting in the larger formations called reticular bodies, which later disintegrate into EB’s; these leave the infected cell and continue the process of infection of new host cells. A single developmental cycle takes 48-72 hours. From the point of view of the clinical progression of the infection, it is significant that it is possible to block the intracellular phase of the cycle using various chemicals (gamma interferon, antibiotics). This is probably the explanation for the frequently occurring asymptomatic or only weakly symptomatic forms of Chlamydia infections.

Chlamydia utilizes the high-energy phosphate bonds of the host cell, therefore requiring living cells in order to grow. This is why Chlamydia is also called energy parasite.


Significant diseases caused by C. trachomatis

C. trachomatis consists of 3 biotypes: causative agents for trachoma (A, B, Ba, C), the agent for lymphogranuloma venereum (L1, L2, L3), and the serotypes causing oculogenital infections (D-K). Several new serotypes have been described in the latter group in recent years.


Epidemiology

The D-K serotypes of C. trachomatis cause urinary and genital diseases throughout the world. It has been proven that 1/3 of all sexually active young adults acquire the infection at least once.
The bacteria spread mainly through sexual contact, but other possible routes of direct and indirect infection by genital secretions should not be excluded (e.g., indirectly caused conjunctivitis).
The probability of transmission of C. trachomatis from males to females during a single, unprotected sexual act is 70-80%, while transmission from females to males shows a lower probability.
Screening of asymptomatic young adults – military, pregnancy, etc. – shows an infection rate of 10-20% in females and 10% in males.
There are significant age-related differences in chlamydiasis. The 17-23 year-old group shows a 5-10 times greater infection rate than the 32-35 year-old group with similar sexual habits.
Frequent changes in sexual partners and casual sexual contacts are risk factors. Nevertheless, it would be a mistake to believe that this is only a disease of promiscuous youths. The latent or persistent presence of the agent may manifest itself in the appearance of disease during a stable, monogamous relationship.
In both sexes, the asymptomatic or weakly symptomatic form – most frequently in women – makes the disease difficult to track epidemiologically. Mapping of contacts and their treatment with regard to chlamydiasis is an important task in terms of epidemic prevention and control.
Not only is the disease highly contagious, the incidence of serious complications (infertility, ectopic pregnancies, sterility) is also high. For this reason, chlamydiasis is also an important demographic issue.

The timely identification and treatment of the disease – thereby preventing the development of complications – can result in significant financial savings. In this regard, the screening of risk groups – teenagers, abortion patients, users of oral contraceptives, young men and the sexual partners of patients – is very significant.

Risk groups

  • Sexually active young people, until the age of 25
  • Users of oral contraceptives
  • Frequent change of sexual partners
  • New partner within 2 months


Clinical picture

The D-K serotypes of C. trachomatis cause infectious diseases, most of which are urogenital infections, a smaller percentage being extragenital.
The clinical picture can be acute, but asymptomatic, latent infections, subacute and chronic forms occur more frequently. 50-70% of infections occurring in women are asymptomatic or just weakly symptomatic, while this percentage is lower in men. Since the infection is often not associated with a conscious awareness of disease which would lead to medical care, most occurrences of the disease are not identified and treated. The risk of these subclinical infections is the frequent appearance of medical complications.


Urogenital infections

Inflammation of the urethra (urethritis)

Distribution by disease
Disease Mode of transmission Serotype
Trachoma Flies, infected secretions of the eye A, B, Ba, C
Oculogenital infections Sexual contact D-K
Lymphogranuloma venereum Sexual contact L1, L2, L3
Distribution by sex
Sex Disease
Men Non-gonococcal urethritis (NGU), post-gonococcal urethritis (PGU), epydidymitis
Women Cervicitis, Acute urethral syndrome, Pelvic inflammation, Fitz-Hugh-Curtis syndrome
Both sexes Sexually acquired reactive arthritis (SARA), Conjuctivitis
Newborns Conjuctivitis, Pneumonia

C. trachomatis is the agent which causes non-gonococcal urethritis (NGU) in 30-50% of cases and postgonococcal urethritis (PGU) in 50-60% of cases.
Clinical Picture
Following an incubation period of 7-21 days, the major symptom is painful urination and a small or medium amount of whitish or clear, mucous discharge, which tends to be more pronounced in the morning. Sometimes a purulent discharge can be observed, which looks deceptively like gonococcal urethritis.
Untreated cases may become asymptomatic within a few weeks, but a recurrence of varying duration is frequently observed.
In the case of chronic infections, symptoms tend to be less intensive with each recurrence, but the subjective complaints become more pronounced. The relapse may be due to treatment with an inappropriate antibiotic, the effect of an antibiotic prescribed for a different reason, the reactivation of the bacteria’s previously blocked developmental cycle, or a re-infection by the sexual partner.

Differential diagnosis

The discharge is more pronounced and purulent in acute gonorrhea. It is not unusual for the patient to be infected with both bacteria, in which case the course of the illness occurs in two phases due to the distinctly different incubation period of acute gonorrhea (2-6 days).


Epididymitis (inflammation of the epididymis)

C. trachomatis is the causative agent in 50% of cases for patients under the age of 35, while intestinal bacteria are usually responsible for the condition in older patients.
Clinical picture
Symptoms usually appear in the 4-6th week following sexual contact; alternatively, a longer incubation period may be followed by sudden proliferation and symptoms: sharp scrotal “pulling” pain radiating into one testicle, swelling, sensitivity, fever, complaints of dysuria, frequent urination. Discharge can be observed in only 50% of cases. Serious complications are abscesses and testicular torsion, as well as infertility.

Differential diagnosis

Testicular torsion, neoplasms, epididymal neuralgia and scrotal pain not due to inflammation.


Prostatitis

  • The pathogenic role of C. trachomatis in prostatitis is debated.
  • Clinical picture
  • Scrotal pain, dysuria, perineal discomfort.


Cervicitis (inflammation of the cervix of the uterus)

Similarly to N. gonorrhoea, C. trachomatis attacks the columnar epithelial cells of the endocervix. The causative agent can be demonstrated in the cervix of the sexual partners of 50-70% of C. trachomatis-positive men, who are frequently asymptomatic. The incubation period of the infection is 1-5 weeks.
Clinical picture
In the cases where symptoms are observed, most frequently muco-puruluent cervical inflammation is present. Muco-purulent discharge can be observed from the cervix, edema of the mucous membrane, swelling, cervical sores. The urethra and more rarely, the Bartholin cysts may also be involved.
In the case of Bartholinitis, purulent discharge can be squeezed out of the cyst. The symptoms of chlamydiasis often influence or mask the symptoms of other vaginal infections (candidiasis, bacterial vaginosis, trichomoniasis). It is important to realize, that asymptomatic patients may be infectious.
Differential diagnosis
Routine bacterial culture required to demonstrate possible joint infection with N. gonorrhea or other agents.


Acute urethral syndrome

The urethra of sexually active young women may frequently be infected with C. trachomatis, without the involvement of the cervix.
Clinical picture
Painful, frequent urination, pus in urine.
Differential diagnosis
Exclusion of bacterial pyuria via culture.


Inflammation of the internal female organs

Inflammation of the fallopian tubes and the uterus – jointly known as Pelvic Inflammatory Disease (PID) – develops as a complication in 10-20% of cervical infections. A one-time inflammation may result in infertility in 15-20%of cases, but repetitive inflammation may cause this risk to increase to up to 75%, and the future risk of ectopic pregnancies may increase 6-10-fold.
C. trachomatis is the precedent in 25-40% of pelvic inflammation, in addition to being a co-infection with N. gonorrhoeae and numerous other anaerobic and aerobic agents.
Clinical Picture
Spontaneous or lower abdominal pain upon palpation, sensitivity, bleeding disorder, pain experienced during sexual intercourse, fever. Often just one of these symptoms is present. The joint presence of all of the above symptoms occurs in only about 20% of cases.
Pelvic inflammation due to C. trachomatis usually presents with milder symptoms than that due to No. gonorrhoeae, but the development of complications is more frequent.
Differential diagnosis
Appendicitis, tumor.


Proctitis (inflammation of the lower part of the rectum and anus)

The disorder can occur in both sexes. The development of the infection is tied primarily to sexual habits, it is therefore mainly a homosexual disorder. Nevertheless, it occurs increasingly in heterosexual relationships. Vaginal infection can spread to rectal infection in women.
Clinical picture
Proctitis due to Chlamydia results in milder symptoms, than that caused by other agents. Rectal drip, pain, cramping associated with bowel movements are the most frequent symptoms.
Differential diagnosis
The demonstration of other pathogens via bacterial culture. Hemorrhoids, fissures, neoplasms, foreign body.


Extragenital disorders

Perihepatitis (Fitz-Hugh-Curtis syndrome)

Infection of the fallopian tubes can spread along the abdominal membranes to cause infection of the hepatic peritoneum. This should be considered in the case of Chlamydia and N.gonorrhoeae infections.
Clinical picture
Severe, acute pain and sensitivity to pressure on the right-sided hypochondrium, which may mask symptoms of a possible pelvic inflammation.
Diffrential diagnosis
Rule out cholecystitis, pleuritis, appendicitis.


Sexually acquired reactive arthritis (SARA)

Reactive arthritis develops as a complication of chlamydia and gonorrhea infections. Ten times as frequent in men as in women. Develops primarily in HLA-B27 positive individuals. Occurs in about 1 % of patients with non-gonococcal urethritis, at least 1 month following appearance of genital symptoms.
Clinical picture
Asymmetrically developing arthritis of the large joints, which may be jointly present with genital and skin symptoms.
Differential diagnosis
Rule out Reiter’s syndrome caused by other pathogens (N. gonorrhoeae, Shigella, Campylobacter, Mycoplamsa). Rheumatic arthritis, SLE.


Neonatal conjunctivitis (inflammation of the conjunctiva of newborns)

May occur in the 3-7th day following birth and may persist up to the third week of life.
Clinical picture
Marked discharge, swelling of the eyes, keratitis rarely.
Differential diagnosis
Differentiate from conjunctivitis caused by N. gonorrhoeae with bacterial culture.


Neonatal pneumonia (pulmonary inflammation of newborns)

C. trachomatis spreads from the nose and throat to the lower respiratory tract. Can develop in the 3rd week to the 3rd month of life.
Clinical picture
Gradually developing insidious illness, increasing severity, bursts of staccato-like coughing, good general condition, generally fever-free. Conjunctivitis may also be present. Weak aural diagnosis, generally only crepitations. Radiological findings: extensive, bilateral interstitial pneumonia. Moderate leukocytosis, possibly eosinophilia. Clinical symptoms may persist for several weeks. Decreasing symptoms precede radiological restitution.
Differential diagnosis
Approximately 10% of tested fluids are positive for chlamydia. Diagnosis of chlamydiasis is significant in choice of antibiotic.


Diagnostic procedures

The completion of diagnostic tests serves three purposes:

  • Identification of the causative pathogen
  • Selection of the appropriate therapy
  • Assessment of the epidemiological situation, for the purposes of disease control.

Diagnostic methods for C. trachomatis:

  • Direct demonstration of the pathogen from test material
  • Serological methods


Polimerase Chain Reaction (PCR)

Pathogens are identified by demonstrating their DNA in the tested material. The sample is transported to a special lab, where the result is expected within 7 days of processing.
Specimen collection
Collection of a proper specimen is perhaps the most important part of a diagnostic test. An inadequate specimen canot be compensated for by the the most modern of diagnostic procedures. In every case, the specimen must be taken using a special swab or other tool, developed for this particular purpose, so that an adequate amount of test material can be collected by rotating the swab.


Serological methods

The most commonly known and used serological diagnostic test is the complement fixation reaction . In the case of venereal diseases caused by C. trachomatis, this has practical significance only for the diagnosis of LGV. In assessing the result, it is extremely important that the history, the manifestation of the illness and the possibility of multiple exposures be taken into consideration.
Among the infections caused by the D-K serological groups of C. trachomatis, the test only has significance for neonatal pneumonia, since the value of serological tests for genital infections is doubtful. On the one hand, the IgG base titer may be high due to the cross-infection of the population; on the other hand, the time and extent of increased titer is uncertain in the case of infections without complications.
At least a four-fold increase in the IgM and IgG titers (e.g., IgM >1:128) is proof of an existing, acute infection. Increased titer is expected for pelvic inflammation and extragenital complications, but the titer does not change for a long period of time and IgM is no longer demonstrable by the time patients turn to their physicians.


Treatment

Infections by Chlamydia trachomatosis are treated by antibiotics. The selection of the antibiotic depends on the clinical picture, the progression of the illness (acute or chronic infection), the success of previous treatment(s), the patient’s tolerance of antibiotics (sensitivity to the medication, tolerance of side-effects, pregnancy, breastfeeding, other medications taken, etc.)
In the interest of effective treatment, a basic requirement is sexual abstinence on the part of the patient, i.e., the patient must abstain from sexual relations during the treatment and until a negative test result is received. The patient’s sexual partners must also be treated – even if they are free of symptoms and complaints and have a negative microbiological test – especially if there is epidemiological proof of the possibility of infections (during incubation and/or symptom-free period), since this is the only effective means of reducing the risk of reinfection. A test of cure examination of the patients is recommended 3 weeks following the conclusion of treatment.h4
Gradually developing insidious illness, increasing severity, bursts of staccato-like coughing, good general condition, generally fever-free. Conjunctivitis may also be present. Weak aural diagnosis, generally only crepitations. Radiological findings: extensive, bilateral interstitial pneumonia. Moderate leukocytosis, possibly eosinophilia. Clinical symptoms may persist for several weeks. Decreasing symptoms precede radiological restitution.

Collection of a proper specimen is perhaps the most important part of a diagnostic test. An inadequate specimen canot be compensated for by the the most modern of diagnostic procedures. In every case, the specimen must be taken using a special swab or other tool, developed for this particular purpose, so that an adequate amount of test material can be collected by rotating the swab.

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Béla Tóth MD
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