Monday, January 17, 2022

Chlamydia trachomatis Case File

Posted By: Medical Group - 1/17/2022 Post Author : Medical Group Post Date : Monday, January 17, 2022 Post Time : 1/17/2022
Chlamydia trachomatis Case File
Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 5
A 19-year-old woman presents for the evaluation of pelvic pain. The pain has progressively worsened over the past week. She has also been having some burning with urination and a vaginal discharge. She is sexually active, has had four lifetime partners, takes oral contraceptive pills, and occasionally uses condoms. On examination, she appears in no acute distress and does not have a fever. Her abdomen is soft with moderate lower abdominal tenderness. On pelvic examination, she is noted to have a yellow cervical discharge and significant cervical motion tenderness. No uterine or adnexal masses are palpated, but mild tenderness is also noted. A Gram stain of the cervical discharge reveals only multiple polymorphonuclear leukocytes. A direct DNA probe test subsequently comes back positive for Chlamydia trachomatis.

How does C. trachomatis enter a target cell?
What are the two stages of the C. trachomatis life cycle?


ANSWERS TO CASE 5: Chlamydia trachomatis

Summary: A 19-year-old woman with probable pelvic inflammatory disease has a positive DNA probe assay for C. trachomatis.

How C. trachomatis enters a target cell: The elementary body of C. trachomatis binds to receptors on the host and induces endocytosis.
Two stages of the C. trachomatis life cycle: The elementary body and the reticulate body.


CLINICAL CORRELATION

Chlamydia trachomatis is the causative agent of the most common sexually transmitted disease in the United States, and it is also the greatest cause of preventable blindness around the world. Chlamydial disease affects women five times more often than men, and approximately two-thirds of those affected
lack symptoms and thus, do not know that they are infected. Many of those infected with gonorrheal disease are also infected with Chlamydia, as both organisms infect the columnar epithelial cells of the mucous membranes. Chlamydial disease usually affects those of lower socioeconomic standing and is prevalent in underdeveloped countries. Children are also a main reservoir, transmitting the disease by hand-to-hand transfer of infected eye fluids or by sharing contaminated towels or clothing.


APPROACH TO SUSPECTED CHLAMYDIAL INFECTION
Objectives
  1. Know the characteristics of the Chlamydia species.
  2. Know the virulence factors and diseases associated with Chlamydia bacteria.

Definitions

Elementary body: Nondividing 300-nm infectious particle. This particle has an outer membrane with disulfide linkages which allows it to survive extracellularly.
Chandelier sign: Cervical motion tenderness during the bimanual exam, characteristic of pelvic inflammatory disease (PID).
Exudate: Material, such as fluids, cells or debris, which has extravasated from vessels and has been deposited on tissue surfaces or in tissue.
Papule: Small palpable elevated lesion that is less than 1 cm.


DISCUSSION
Characteristics of Chlamydia trachomatis

Chlamydia trachomatis is a gram-negative obligate intracellular parasite with a unique life cycle. It is coccoid in morphology and is very small, usually about 350 nm in diameter. Although C. trachomatis is classified as gramnegative bacteria, it lacks a peptidoglycan layer and muramic acid, which are present in other gram-negative organisms. There are many disulfide linkages present in the outer membrane which stabilize the organism. Its extracellular form is called the elementary body, which has a small, spore-like structure. It attaches to columnar, cuboidal, or transitional epithelial cells in structures lined by mucous membranes. The elementary body binds to receptors on susceptible cells and induces endocytosis into the host. These membraneprotected structures are known as inclusions. The elementary body undergoes reorganization into a larger, more metabolically active form known as the reticulate body. Reticulate bodies grow and multiply by binary fission to create larger intracellular inclusions. Reticulate bodies transform back into elementary bodies, which are released from the epithelial cell by exocytosis and which can then infect other cells. The life cycle of C. trachomatis lasts approximately 48–72 hours. Table 5-1 lists in sequential order are the stages of the life cycle.

Chlamydia trachomatis appears to be an obligate human pathogen with approximately 15 serotypes. It is the most common bacterial cause of sexually transmitted diseases in humans and also causes conjunctivitis and ocular trachoma. Infection of the conjunctiva by C. trachomatis results in scarring and inflammation. This fibrosis pulls the eyelid inward causing the eyelashes to rub against the cornea. Because the eyelid is rolled inward, the individual is unable to completely close the eye resulting in the inability to maintain moisture on the surface of the eye. It is the combination of the lack of surface moisture and constant abrasion by the eyelashes that causes corneal scarring and blindness. Ocular trachoma is one of the leading causes of blindness worldwide.

Table 5-1
LIFE CYCLE OF Chlamydia trachomatis

1. Elementary body attaches to host cell.

2. Host cell phagocytizes the elementary body residing in a vacuole, inhibiting phagosome-lysome fusion.

3. The elementary body reorganizes to form a reticulate body.

4. The reticulate body divides by binary fusion.

5. Some reticulate bodies convert back into elementary bodies; elementary bodies are released into host cell.


Chlamydia trachomatis also causes other diseases including pneumonia, urethritis, epididymitis, lymphogranuloma venereum, cervicitis, and pelvic inflammatory disease. Lymphogranuloma venereum presents with a painless papule on the genitalia that heals spontaneously. The infection is then localized to regional lymph nodes where it resides for approximately 2 months. As time progresses, the lymph nodes begin to swell, causing pain, and may rupture and expel an exudate. Men with epididymitis present with fever, unilateral scrotal swelling, and pain. Women with cervicitis present with a swollen, inflamed cervix. There may also be a yellow purulent discharge present. PID occurs when the infection spreads to the uterus, fallopian tubes, and ovaries. PID presents with lower abdominal pain, dyspareunia, vaginal discharge, uterine bleeding, nausea, vomiting, and fever. Cervical motion tenderness during the bimanual exam is known as the “chandelier sign.” Recurrent PID may scar the fallopian tubes, resulting in infertility or ectopic pregnancy. Children may acquire chlamydial disease during birth via passage through an infected birth canal. Inflammation of the infant’s conjunctiva may occur with a yellow discharge and swelling of the eyelids within 2 weeks after birth. The presence of basophilic intracytoplasmic inclusion bodies from the conjunctiva is a helpful diagnostic clue. Neonatal pneumonia may also occur from passage through an infected birth canal. An infected child may present 4–11 weeks after birth with respiratory distress, cough, and tachypnea. The direct destruction of host cells due to chlamydial infection and then host’s inflammatory response produces the clinical symptoms associated with the various forms of chlamydial disease.

Other Chlamydial species are known to cause disease in humans. Atypical pneumonia is caused by Chlamydophila pneumonia, and presents with fever, headache, and a dry hacking cough. Additionally, psittacosis is another atypical pneumonia caused by Chlamydophila psittaci. This organism is acquired by inhalation of feces from infected birds, which serve as the reservoir.


Diagnosis

Infection with C. trachomatis can be rapidly diagnosed by detection of the bacterial nucleic acid in patient samples from the oropharynx, conjunctiva, urethra, or cervix. Other specimens such as the conjunctiva can be cultured using McCoy cells in a tissue culture assay. Diagnostic tests for nucleic acid detection include PCR amplification or direct DNA hybridization assays, measuring for specific 16S ribosomal RNA sequences can be performed on all of above specimens including urine.


Treatment and Prevention

Currently, the best method of preventing chlamydial infection is education and proper sanitation. Ocular infection of C. trachomatis can sometimes but not always be prevented by administration of topical tetracycline drops. It is the lack of this antibiotic in underdeveloped countries that makes C. trachomatis prevalent in these areas. Chlamydia trachomatis, C. psittaci, and C. pneumonia are all treated with tetracycline or erythromycin. Azithromycin is effective for cervicitis and urethritis. Pelvic inflammatory disease is treated with ceftriaxone and 2 weeks of doxycycline.


COMPREHENSION QUESTIONS

[5.1] A 32-year-old immigrant woman from Tanzania delivers a healthy baby boy. Because this woman had no regular doctor, no preliminary tests were performed prior to delivery. Thirteen days after delivery, the child develops swelling of both eyes with the presence of a yellow discharge. The presence of intracytoplasmic inclusion bodies is detected. Which antibiotic would be most appropriate in this situation?
A. Tetracycline
B. Ceftriaxone
C. Penicillin G
D. Doxycycline
E. Erythromycin

[5.2] Which diagnostic test is best to identify an infection with C. trachomatis?
A. Aerobic and anaerobic blood cultures
B. Stool culture
C. DNA probe
D. Urine culture
E. Culture and darkfield microscopy

[5.3] A 29-year-old bird collector presents to the local clinic with what he describes as flu-like symptoms. He doesn’t look ill, and has a slight fever, headache, and a dry hacking cough. He denies the production of sputum or hemoptysis. There are no crackles heard on auscultation, and a radiograph shows small streaks of infiltrate. It is determined that he has pneumonia. What is the most likely organism causing his disease?
A. Streptococcus pneumoniae
B. Chlamydophila psittaci
C. Haemophilus influenzae
D. Staphylococcus aureus
E. Chlamydophila pneumoniae


Answers

[5.1] E. The symptoms described are classic for inclusion conjunctivitis caused by C. trachomatis. The infection was most likely passed from the mother to child during vaginal delivery. The infection usually presents 2 weeks after delivery and is characterized by swollen eyes and a yellow discharge. The drug of choice for this infection is erythromycin eyedrops. Most children are given erythromycin eye drops prophylactically postbirth. Tetracyclines are not given to young children due to staining of teeth.

[5.2] C. The most specific test used to detect a chlamydial infection is a DNA probe. C. trachomatis is a gram-negative obligate intracellular parasite, and any blood or urine culture would not be helpful for diagnosis. Chlamydia trachomatis is not present in stool. Darkfield microscopy is used to view spirochetes, which C. trachomatis is not.

[5.3] B. Although all of the organisms listed above cause pneumonia, only two of them are atypical. Atypical pneumonia is characterized by a dry hacking cough, fever, and headache. These include C. psittaci and C. pneumoniae. The mention of birds should point you in the direction of C. psittaci, because they are the reservoir for the organism that is inhaled through dry feces. Typical pneumonias are characterized by hemoptysis of pus-laden sputum, and patients appear very sick.


MICROBIOLOGY PEARLS

Chlamydial disease is the most common STD in the United States.
Cervical motion tenderness and adnexal tenderness are common findings of pelvic inflammatory disease.
The elementary body is the infectious stage in C. trachomatis.
Chlamydia trachomatis is the most common preventable cause of worldwide blindness (Proper sanitation is important for prevention and the use of tetracycline or erythromycin is important for early treatment.).


REFERENCES

Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:412–420. 

Schneider AS, Szanto PA. Pathology Board Review Series, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2001:272, 280. 

Boman J, Gaydos C, Quinn T. Minireview: molecular diagnosis of Chlamydia pneumoniae infection. J Clin Microbiol 1999;37:3791–9.

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