Chlamydial Infections

Margaret R. Hammerschlag

Chlamydiae are obligate intracellular bacteria that are ubiquitous in nature. Members of the genus possess both DNA and RNA, divide by binary fission, contain their own ribosomes, and are susceptible to antimicrobial agents. Although chlamydiae have a gram-negative envelope without detectable peptidoglycan, recent genomic analysis has revealed that both Chlamydia trachomatis and C. pneumoniae encode for proteins forming a nearly complete pathway for synthesis of peptidogylcan, including penicillin-binding proteins. All members of the genus share a common (group) lipopolysaccharide antigen. They also share a unique developmental cycle involving an infectious, metabolically inactive extracellular form, the elementary body (EB), and a noninfectious metabolically active intracellular form, the reticulate body (RB). The EBs, which are 200 to 400 μm in diameter, attach to the host cell by a process of electrostatic binding and are taken into the cell by endocytosis independent of the microtubule system. Once within the host cell, the EB remains within a membrane-lined phagosome. Fusion of the phagosome with the host cell lysosome fails to occur. The EBs differentiate into RBs, which undergo binary fission. After some 36 hours, the RBs differentiate back into EBs. At perhaps 48 hours, release may occur by cytolysis or by a process of exocytosis or extrusion of the whole inclusion, leaving the host cell intact. Thus, a biologic basis exists for prolonged subclinical infection.

Chlamydiae cause a variety of diseases in animal species at virtually all phylogenic levels. Until recently, the order contained one genus, Chlamydia, with four recognized species: C. trachomatis, C. psittaci, C. pneumoniae, and C. pecorum. C. trachomatis and C. pneumoniae are the most significant human pathogens. C. psittaci is an important zoonosis. Recent taxonomic analysis using the 16S and 23S rRNA genes has suggested splitting the genus Chlamydia into two genera, Chlamydia and Chlamydophila. Two new species, Chlamydia muridarum (formerly the agent of mouse pneumonitis-MoPn) and Chlamydia suis (causes conjunctivitis, nasopharyngitis, and enteritis in pigs) would join C. trachomatis. Chlamydophila would contain C. pecorum (infections in sheep, cattle and koalas), C. pneumoniae, and C. psittaci, as well as three new species split off from C. psittaci: Chlamydia abortus, Chlamydia caviae (formerly C. psittaci Guinea pig conjunctivitis strain), and Chlamydia felis (causes feline keratoconjunctivitis). Controversy continues regarding this reclassification, but we will continue to refer to Chlamydia in this chapter. The routes of transmission, susceptible populations, and clinical presentations differ markedly for the three species that cause infection in humans (Table 143.1).

INFECTION CAUSED BY CHLAMYDIA PSITTACI

C. psittaci is widespread among many avian species, with psittacine birds, such as parrots and parakeets, and turkeys being the most common; it is a major cause of respiratory and gastrointestinal disease. Humans usually contract the disease from infected birds. The birds may be ill, but inapparent
infection also can occur. Psittacosis is likely to occur in poultry workers, veterinarians, and bird fanciers. Person-to-person spread is unusual. Psittacosis is a major problem for the poultry industry worldwide. Several serious outbreaks in turkey farms in the United States occurred during the late 1970s. In 1995, the Centers for Disease Control and Prevention (CDC) investigated an outbreak of avian chlamydiosis in a shipment of more than 700 pet birds sent from a Florida bird distributor to the Atlanta, Georgia area. Affected birds included parrots, parakeets, finches, lovebirds, cockatiels, conures, and canaries. Clinical psittacosis or serologic evidence of C. psittaci infection was found in 30.7% of households with birds from the infected flock. An average of 21 days (range, 1 to 47) elapsed between purchase of the bird and the onset of symptoms. Most infected individuals had mild or asymptomatic illnesses. Among persons in exposed households, illness occurred more frequently if the recently purchased bird had become ill or had died. Kissing or nuzzling, handling, and feeding the birds all were associated significantly with the development of clinical psittacosis, but in contrast to earlier studies, cleaning the birdcage was not. The risk of developing clinical psittacosis varied significantly by the type of bird to which the individual was exposed. The attack rate was highest for individuals exposed to parrots. Inhalation of infectious aerosols derived from feces, fecal dust, or secretions of C. psittaci-infected animals is thought to be the primary route of infection. The source birds can be infected asymptomatically or can show signs of infection such as anorexia, ruffled feathers, depression, and watery green droppings. Psittacosis frequently is a systemic infection in birds. The turkey strains can induce severe pericarditis. The gastrointestinal tract commonly is infected also.

TABLE 143.1. CHARACTERISTICS OF THREE CHLAMYDIAL SPECIES THAT CAUSE DISEASE IN HUMANS

Characteristic	C. trachomatis	C. psittaci	C. pneumoniae
Number of serovars	15	At least 4	1
Percent DNA homology to C. pneumoniae	<5	<10	94–100
Plasmid	Yes	Yes	No
Contains glycogen	Yes	No	No
Sensitive to sulfonamides	Yes	No	No
Morphology of elementary body	Round	Round	Round or pear shaped
Natural host	Humans	Birds	Humans, koalas, other mammals, amphibians
Population	Sexually active adults, infants	Poultry workers, veterinarians, bird fanciers	All ages
Mode of transmission	Sexual, mother to infant	Aerosol: bird to person	Aerosol: person to person
Diseases	Nongonococcal urethritis, cervicitis, salpingitis, neonatal conjunctivitis, infantile pneumonia, lymphogranuloma venereum	Pneumonia: “psittacosis”	Pneumonia, bronchitis

TABLE 143.2. LABORATORIES THAT TEST HUMAN SPECIMENS FOR CHLAMYDIA PSITTACI

Laboratory	Tests Performed	Telephone Number
Respiratory Diseases Laboratory	MIF	(404) 639–3563
Section, Centers for Disease Control and Prevention, Atlanta, GA	CF PCR Culture
Focus Technologies, Cypress, CA	IFA PCR Culture	(800) 445–4032
Laboratory Corp. of America	Culture	(800) 334–5161
Burlington, NC	Polyclonal antibody
Specialty Labs, Santa Monica, CA	MIF	(800) 421–4449
CF, complement fixation; IFA, immunofluorescent antibody; MIF, microimmunofluorescence; PCR, polymerase chain reaction. Reprinted from Centers for Disease Control and Prevention. Compendium of measures to control Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis). Morb Mortal Wkly Rep MMWR 2000;49(RR-8):3.

The clinical course of psittacosis in humans varies, with incubation periods of 7 to 15 days or longer. Often, it starts suddenly with chills and high fever (38^° to 40.5^°C). Headache, often diffuse and severe, is a common chief complaint, as are malaise and nausea. The headache can be so severe that meningitis can be considered a possibility; 33% of the patients in one series underwent lumbar punctures. A persistent dry, hacking cough usually is present. The physical findings may belie the extent of the pulmonary involvement as seen on chest radiography. Rales may be heard, but changes indicative of consolidation usually are not seen. Chest radiography reveals soft, patchy infiltrates radiating from the hilum or, less frequently, a reticulonodular pattern. Most of the individuals in the Atlanta outbreak had very mild disease characterized by fever, headache, and cough.

The diagnosis of human infection caused by C. psittaci has not changed substantially for many years. The mainstay of diagnosis remains serology using the complement fixation (CF) test. According to the recommendations from the CDC for the year 2000, a confirmed case of psittacosis requires a compatible clinical illness, usually with a good history of avian exposure. Laboratory confirmation can be made by one of the three following methods: (a) culture of C. psittaci from respiratory secretions, (b) a fourfold or greater increase in CF or microimmunofluorescence (MIF) titer in sera collected at least 2 weeks apart, and (c) MIF immunoglobulin M titer of 16 or greater. A probable case should be epidemiologically linked to a confirmed case or have a single CF or MIF antibody titer of 32 or greater in a least one serum obtained after onset of symptoms. Early initiation of treatment may delay antibody response for several weeks. In its current recommendations for the control of C. psittaci infection among humans and pet birds, the CDC provides a list of laboratories that test human specimens (Table 143.2).

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