Chapter 25: Chlamydiae

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.

Additional information regarding the clinical aspects of infections caused by the organisms in this chapter is provided in Part IX entitled Infectious Diseases beginning on page 607.

Diseases

Chlamydia trachomatis causes eye (conjunctivitis, trachoma), respiratory (pneumonia), and genital tract (urethritis, lymphogranuloma venereum) infections. C. trachomatis is the most common bacterial cause of sexually transmitted disease in the United States. (Human papilloma virus infection is the most common sexually transmitted infection overall in the United States.) Infection with C. trachomatis is also associated with Reiter’s syndrome, an autoimmune disease. Approximately 40% of nongonococcal urethritis is caused by C. trachomatis.

Chlamydia pneumoniae causes atypical pneumonia. Chlamydia psittaci causes psittacosis, also a disease characterized mainly by pneumonia (Table 25–1).

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 C. pneumoniae and C. 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 in the cytoplasm, which can be stained and visualized microscopically (Figure 25–2). These inclusions are useful in the identification of these organisms in the clinical laboratory.

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 one 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 including humans). Humans are infected primarily by inhaling organisms in airborne 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 gonorrheae 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. trachomatis has 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. In men, it is a common cause of nongonococcal urethritis (often abbreviated NGU), which is characterized by dysuria and a watery, nonpurulent urethral discharge (Figure 25–3). The discharge may be slight, detectable only by staining of underwear overnight. This infection may progress to epididymitis, prostatitis, or proctitis. In women, cervicitis accompanied by a vaginal discharge develops and may progress to salpingitis and pelvic inflammatory disease (PID). Repeated episodes of salpingitis or PID can result in infertility or ectopic pregnancy. Urethritis accompanied by dysuria also occurs.

Asymptomatic infections are very common in both men and women.

Infants born to infected mothers often develop mucopurulent conjunctivitis (neonatal inclusion conjunctivitis) 7 to 12 days after delivery, and some develop chlamydial pneumonia 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 reactive arthritis and Reiter’s syndrome, which is characterized by urethritis, arthritis, and uveitis. These are autoimmune diseases 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.

C. pneumoniae causes upper and lower respiratory tract infections, especially bronchitis and pneumonia, in young adults. Most infections are mild or asymptomatic. The clinical picture resembles other atypical pneumonias, especially that caused by Mycoplasma pneumoniae. It is unclear whether C. pneumoniae causes upper respiratory infections such as sinusitis and otitis media.

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 from human to human.

Although most infections are mild, some are quite severe and involve organs other than the lung. The respiratory infection typically manifests with fever, cough, dyspnea, myalgias, and headache. The most common extrapulmonary organs involved are the liver (hepatomegaly, jaundice), heart (myocarditis, pericarditis), and nervous system (hearing loss, transverse myelitis, and encephalitis).

Laboratory Diagnosis

Chlamydiae form cytoplasmic inclusions, which can be seen with special stains (e.g., Giemsa stain) or by immunofluorescence (see Figure 25–2). In general, the Gram stain is not useful as the organisms are too small to visualize within the cytoplasm. However, a Gram stain of a urethral discharge that shows neutrophils but no gram-negative diplococci resembling N. gonorrheae is presumptive evidence for infection by C. trachomatis.

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 later).

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).

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 yield 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. Sex partners should be offered treatment.

The drug of choice for neonatal inclusion conjunctivitis and pneumonia caused by C. trachomatis 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 safe sex practices and 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. Screening of sexually active, asymptomatic young women and treatment of those who are positive is cost-effective because it may prevent PID and ectopic pregnancy.

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, treating or destroying sick birds, and adding tetracycline to bird feed. Domestic flocks of turkeys and ducks are tested for the presence of C. psittaci.