Review of Medical Microbiology and Immunology, 13th Edition

25. Chlamydiae

CHAPTER CONTENTS

Introduction

Chlamydia trachomatis

Chlamydia pneumoniae

Chlamydia psittaci

Self-Assessment Questions

Summaries of Organisms

Practice Questions: USMLE & Course Examinations

INTRODUCTION

Chlamydiae are obligate intracellular bacteria (i.e., they can grow only within cells). They are the agents of common sexually transmitted diseases, such as urethritis and cervicitis, as well as other infections, such as pneumonia, psittacosis, trachoma, and lymphogranuloma venereum.

Diseases

Chlamydia trachomatis causes eye (conjunctivitis, trachoma), respiratory (pneumonia), and genital tract (urethritis, lymphogranuloma venereum) infections. C. trachomatis is the most common cause of sexually transmitted disease in the United States. Infection with C. trachomatis is also associated with Reiter’s syndrome, an autoimmune disease.

Chlamydia pneumoniae (formerly called the TWAR strain) causes atypical pneumonia. Chlamydia psittaci causes psittacosis (Table 25–1).

TABLE 25–1 Chlamydiae of Medical Importance

image

C. pneumoniae and C. psittaci are sufficiently different molecularly from C. trachomatis that they have been reclassified into a new genus called Chlamydophila. Taxonomically, they are now Chlamydophila pneumoniae and Chlamydophila psittaci. However, from a medical perspective, they are still known as Chlamydia pneumoniae and Chlamydia psittaci, and those are the names that are used in this book.

Important Properties

Chlamydiae are obligate intracellular bacteria. They lack the ability to produce sufficient energy to grow independently and therefore can grow only inside host cells. They have a rigid cell wall but do not have a typical peptidoglycan layer. Their cell walls resemble those of gram-negative bacteria but lack muramic acid.

Chlamydiae have a replicative cycle different from that of all other bacteria. The cycle begins when the extracellular, metabolically inert, “sporelike” elementary body enters the cell and reorganizes into a larger, metabolically active reticulate body (Figure 25–1). The latter undergoes repeated cycles of binary fission to form daughter reticulate bodies, which then develop into elementary bodies, which are released from the cell. Within cells, the site of replication appears as an inclusion body, which can be stained and visualized microscopically (Figure 25–2). These inclusions are useful in the identification of these organisms in the clinical laboratory.

image

FIGURE 25–1 Life cycle of Chlamydia. The extracellular, inert elementary body enters an epithelial cell and changes into a reticulate body that divides many times by binary fission. The daughter reticulate bodies change into elementary bodies and are released from the epithelial cell. The cytoplasmic inclusion body, which is characteristic of chlamydial infections, consists of many daughter reticulate and elementary bodies. (Modified and reproduced with permission from Ryan K et al. Sherris Medical Microbiology. 3rd ed. Originally published by Appleton & Lange. Copyright 1994 by McGraw-Hill.)

image

FIGURE 25–2 Chlamydia trachomatis—light microscopy of cell culture. Long arrow points to cytoplasmic inclusion body of C. trachomatis; short arrow points to nucleus of cell. (Figure courtesy of Dr. E. Arum and Dr. N. Jacobs, Public Health Image Library, Centers for Disease Control and Prevention.)

All chlamydiae share a group-specific lipopolysaccharide antigen, which is detected by complement fixation tests. They also possess species-specific and immunotype-specific antigens (proteins), which are detected by immunofluorescence. C. psittaci and C. pneumoniae each have 1 immunotype, whereas C. trachomatis has at least 15 immunotypes.

Transmission & Epidemiology

C. trachomatis infects only humans and is usually transmitted by close personal contact (e.g., sexually or by passage through the birth canal). Individuals with asymptomatic genital tract infections are an important reservoir of infection for others. In trachoma, C. trachomatis is transmitted by finger-to-eye or fomite-to-eye contact. C. pneumoniae infects only humans and is transmitted from person to person by aerosol. C. psittaci infects birds (e.g., parrots, pigeons, and poultry, and many mammals). Humans are infected primarily by inhaling organisms in dry bird feces.

Sexually transmitted disease caused by C. trachomatis occurs worldwide, but trachoma is most frequently found in developing countries in dry, hot regions such as northern Africa. Trachoma is a leading cause of blindness in those countries.

Patients with a sexually transmitted disease are coinfected with both C. trachomatis and Neisseria gonorrhoeae in approximately 10% to 30% of cases.

Pathogenesis & Clinical Findings

Chlamydiae infect primarily epithelial cells of the mucous membranes or the lungs. They rarely cause invasive, disseminated infections. C. psittaci infects the lungs primarily. The infection may be asymptomatic (detected only by a rising antibody titer) or may produce high fever and pneumonia. Human psittacosis is not generally communicable. C. pneumoniae causes upper and lower respiratory tract infections, especially bronchitis and pneumonia, in young adults.

C. trachomatis exists in more than 15 immunotypes (A–L). Types A, B, and C cause trachoma, a chronic conjunctivitis endemic in Africa and Asia. Trachoma may recur over many years and may lead to blindness but causes no systemic illness. Types D–K cause genital tract infections, which are occasionally transmitted to the eyes or the respiratory tract. In men, it is a common cause of nongonococcal urethritis (often abbreviated NGU), which is characterized by a urethral discharge (Figure 25–3). This infection may progress to epididymitis, prostatitis, or proctitis. In women, cervicitis develops and may progress to salpingitis and pelvic inflammatory disease (PID). Repeated episodes of salpingitis or PID can result in infertility or ectopic pregnancy.

image

FIGURE 25–3 Nongonococcal urethritis. Note watery, nonpurulent discharge caused by Chlamydia trachomatis. The urethral discharge caused by Neisseria gonorrhoeae is more mucoid and purulent. (Courtesy of Seattle STD/HIV Prevention Training Center.)

Infants born to infected mothers often develop mucopurulent conjunctivitis (neonatal inclusion conjunctivitis) 7 to 12 days after delivery, and some develop chlamydial pneumonitis 2 to 12 weeks after birth. Chlamydial conjunctivitis also occurs in adults as a result of the transfer of organisms from the genitals to the eye. Patients with genital tract infections caused by C. trachomatis have a high incidence of Reiters syndrome, which is characterized by urethritis, arthritis, and uveitis. Reiter’s syndrome is an autoimmune disease caused by antibodies formed against C. trachomatis cross-reacting with antigens on the cells of the urethra, joints, and uveal tract (see Chapter 66).

C. trachomatis L1–L3 immunotypes cause lymphogranuloma venereum, a sexually transmitted disease with lesions on genitalia and in lymph nodes.

Infection by C. trachomatis leads to formation of antibodies and cell-mediated reactions but not to resistance to reinfection or elimination of organisms.

Laboratory Diagnosis

Chlamydiae form cytoplasmic inclusions, which can be seen with special stains (e.g., Giemsa stain) or by immunofluorescence (Figure 25–2). The Gram stain is not useful. In exudates, the organism can be identified within epithelial cells by fluorescent-antibody staining or hybridization with a DNA probe. Chlamydial antigens can also be detected in exudates or urine by enzyme-linked immunosorbent assay (ELISA). Nucleic acid amplification tests (NAATs) using the patient’s urine are widely used to diagnose chlamydial sexually transmitted disease. Tests not involving culture, such as NAAT, are now more commonly used than culture-based tests (see below).

Chlamydiae can be grown in cell cultures treated with cycloheximide, which inhibits host cell but not chlamydial protein synthesis, thereby enhancing chlamydial replication. In culture, C. trachomatis forms inclusions containing glycogen, whereas C. psittaci and C. pneumoniae form inclusions that do not contain glycogen. The glycogen-filled inclusions are visualized by staining with iodine. Exudates from the eyes, respiratory tract, or genital tract give positive cultures in about half of cases.

Serologic tests are used to diagnose infections by C. psittaci and C. pneumoniae but are rarely helpful in diagnosing disease caused by C. trachomatis because the frequency of infection is so high that many people already have antibodies.

Treatment

All chlamydiae are susceptible to tetracyclines, such as doxycycline, and macrolides, such as erythromycin and azithromycin. The drug of choice for C. trachomatis sexually transmitted diseases is azithromycin. Because the rate of coinfection with gonococci and C. trachomatis is high, any patient with a diagnosis of gonorrhea should also be treated for C. trachomatis with azithromycin.

The drug of choice for neonatal inclusion conjunctivitis and pneumonia is oral erythromycin. The drug of choice for C. psittaci and C. pneumoniae infections and for lymphogranuloma venereum is a tetracycline, such as doxycycline.

Prevention

There is no vaccine against any chlamydial disease. The best preventive measure against C. trachomatis sexually transmitted diseases is to limit transmission by prompt treatment of both the patient and the sexual partners, including persons who are asymptomatic. Sexual contacts should be traced, and those who had contact within 60 days should be treated. Several types of sexually transmitted diseases are often present simultaneously. Thus diagnosis of one requires a search for other causative agents.

Oral erythromycin given to newborn infants of infected mothers can prevent inclusion conjunctivitis and pneumonitis caused by C. trachomatis. Note that erythromycin ointment used to prevent neonatal gonococcal conjunctivitis is much less effective against neonatal chlamydial conjunctivitis. Oral erythromycin should be used.

Psittacosis in humans is controlled by restricting the importation of psittacine birds, destroying sick birds, and adding tetracycline to bird feed. Domestic flocks of turkeys and ducks are tested for the presence of C. psittaci.

SELF-ASSESSMENT QUESTIONS

1. Your patient is a 20-year-old man with a urethral discharge. Gram stain of the pus reveals many neutrophils but no bacteria. You suspect this infection may be caused by Chlamydia trachomatis. Which one of the following is the laboratory result that best supports your clinical diagnosis?

(A) Gram stain of the pus reveals small gram-positive rods.

(B) The organism produces beta-hemolytic colonies on blood agar plates when incubated aerobically.

(C) The organism produces alpha-hemolytic colonies on blood agar plates when incubated anaerobically.

(D) Fluorescent-antibody staining of cytoplasmic inclusions in epithelial cells in the exudate

(E) Fourfold or greater rise in antibody titer against C. trachomatis

2. Regarding chlamydiae, which one of the following is the most accurate?

(A) Lifelong immunity usually follows an episode of disease caused by these organisms.

(B) The reservoir host for the three species of chlamydiae that cause human infection is humans.

(C) Their life cycle consists of elementary bodies outside of cells and reticulate bodies within cells.

(D) They can only replicate within cells because they lack the ribosomes to synthesize their proteins.

(E) The vaccine against C. pneumoniae contains the capsular polysaccharide as the immunogen conjugated to a carrier protein.

3. Which one of the following is the drug of choice for sexually transmitted disease (urethritis, cervicitis) caused by Chlamydia trachomatis?

(A) Ampicillin

(B) Azithromycin

(C) Ciprofloxacin

(D) Metronidazole

(E) Rifampin

ANSWERS

1. (D)

2. (C)

3. (B)

SUMMARIES OF ORGANISMS

Brief summaries of the organisms described in this chapter begin on page 663. Please consult these summaries for a rapid review of the essential material.

PRACTICE QUESTIONS: USMLE & COURSE EXAMINATIONS

Questions on the topics discussed in this chapter can be found in the Clinical Bacteriology section of PART XIII: USMLE (National Board) Practice Questions starting on page 693. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.