Chlamydia psittaci (Psittacosis)

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MICROBIOLOGY

Like other chlamydiae, C. psittaci is an obligate intracellular parasite, has a cell wall resembling that of Gram-negative bacteria, and is susceptible to some antibiotics. Its developmental cycle is complex and includes two forms. An (infective) elementary body attaches to host cells and enters the cell by phagocytosis or receptor-mediated endocytosis. Phagolysosomal fusion is inhibited early, and the elementary body reorganizes into the reticulate body, which uses the host cell as an energy source. Contained in a phagosome, this dividing reticulate body enlarges and divides repeatedly by binary fusion, forming an enlarging cytoplasmic inclusion that can be stained with Giemsa or by immunofluoroscent antibodies. The enlarging and dividing reticulate body ultimately condenses back into elementary bodies, which are then released from the ruptured cell and begin the cycle anew (10, 16, 26).

EPIDEMIOLOGY

Psittacosis is a systemic infection caused by inhalation of Chlamydia psittaci. The source is usually an infected bird, which may be asymptomatic. Discharge from beaks, eyes, feces, and urine are all infectious and contaminate the bird’s feathers and the surrounding dust. Occasionally, psittacosis is spread to humans from mammals (birth fluids and placentas of sheep, goats and cattle, and cats with conjunctivitis); person-to-person spread is rare, and possible nosocomial transmission has been described (8). A recently-described epidemiologic risk is the growing practice of pet-assisted therapy in nursing homes (5).

CLINICAL MANIFESTATIONS

Patients may develop one of several syndromes: a mononucleosis-like illness, a typhoidal form, a nonspecific febrile illness, or atypical pneumonia. The most common signs and symptoms are fever, cough, headache, pharyngeal erythema, and rales. Particularly helpful clinical clues are hepatosplenomegaly, hemoptysis, epistaxis, rash, and relative bradycardia.

LABORATORY DIAGNOSIS

Diagnosis is usually made serologically, by complement fixation (CF) or microimmunofluorescence (MIF) The CF is more commonly used, although it is not species-specific and may reflect infection with C. pneumoniae or C. trachomatis. Diagnosis requires a 4-fold increase in titer to a reciprocal titer of 32, or an MIF IgM of 16. A single titer of 32 defines a probable case. PCR is species-specific but is not generally available and has been insensitive in human blood and throat swab samples (17).

PATHOGENESIS

Disease is spread by inhalation of infective materials, usually dust or aerosolized discharges from infected birds; rarely, direct contact or even a bite may result in disease.

SUSCEPTIBILITY IN VITRO AND IN VIVO

Single Drug

In vitro testing is not routinely performed; it has not been standardized, although it may be carried out in cell culture. The general process is cell culture with antibiotic-free monolayers. Endpoints are the dilution of antibiotic that prevents inclusion formation (MIC) and then identification of the highest dilution that prevents viable chlamydia from being detected in passage (MBC). Agents most active in vitro are tetracycline, doxycycline, macrolides, rifampin, quinolones, and clindamycin (2, 12, 20, 21). A comparison of moxifloxacin, minocycline and azithromycin showed good inhibitory activity for all three drugs; the MIC and MBCs of moxifloxacin were the same, whereas azithromycin and minocin had MICs 2-4 times lower that their MBCs (3).

Combination Drugs

There are no data on combination therapy.

ANTIMICROBIAL THERAPY

Drug of Choice

The therapy of psittacosis is primarily based on anecdotal experience in humans and animals. Controlled trials in humans are not available, and in vitro testing is not standardized to use as a basis for therapy selection. Thus, the treatment recommendations given below represent a consensus based on clinical practice, anecdotal reports, and limited in vitro data.

The tetracyclines are widely considered the drugs of choice for treatment of psittacosis, either tetracycline hydrochloride or doxycycline (7,10, 14, 27, 30). They suppress growth and replication but do not eradicate the agent from the host (10). Although the clinical response may be dramatic, with objective and subjective improvement in 24 to 48 h, some patients respond slowly or not at all (27). Sensitivity to tetracycline appears to be universal. Resistant mutants have been seen but are extremely rare (10).

Doses administered are tetracycline hydrochloride 500 mg orally four times daily or doxycycline 100 mg twice daily orally or intravenously. Duration of therapy is usually 10 to 14 days, although some observers suggest extending the therapy to 21 days to prevent relapse. The need for therapy beyond 2 weeks is controversial (14, 33).

Children under the age of 8 years should be treated with erythromycin unless they are severely ill or do not respond to erythromycin, in which case tetracycline or doxycycline should be used.

Special Infection

Endocarditis presents a special difficulty because of the desirability of bactericidal therapy to eradicate valvular infection. Although there are reports of medical cures, these are infrequent and difficult to evaluate. Thus, Walker and Adgey reported a cure with doxycycline, but the patient described had also received penicillin for 3 weeks with a definite clinical response (31). Regan et al. treated a patient with erythromycin for 4 months and then Doxycycline for 1 year. When the patient subsequently underwent valve replacement, there was no evidence of valvular infection. However, the patient had received penicillin and ampicillin therapy prior to the erythromycin, making it difficult to evaluate the effect of erythromycin and doxycycline therapy (24). Jariwalla et al. reported a patient treated with 16 weeks of rifampin 600 mg daily (9), but there is general concern about emergence of resistance when this drug is used alone (26). Most authors stress the need for valve replacement or permanent antibiotic therapy for ultimate disease-free survival (11,13,23,29).

Special Situation

Pregnant patients present a problem. Although tetracyclines are generally avoided in pregnancy, Chermon found erythromycin ineffective in a pregnant patient who improved only after delivery of the placenta. Also, the erythromycin did not appear to protect the fetus. It may be advisable to use tetracycline in these patients, although the optimal approach is unknown (4).

Alternative Therapy

Erythromycin is the alternative therapy of choice. Controversy surrounds comparison of erythromycin with the tetracyclines. Some feel it is at least as good as tetracycline (6), while others feel it is less effective, especially for severe disease (10, 14, 30). The newer macrolides (e.g., azithromycin) may eventually prove useful, especially in view of the accumulation of azithromycin in host cells and the intracellular location of C. psittaci (21). One study reported good results with azithromycin in a small number of patients with presumed psittacosis; regimens used were either a single dose of 1.5 grams or 500 mg daily for 3 days. However, serologic documentation was incomplete (28).

Additional potential alternatives include chloramphenicol, which has a reputation ranging from "ineffective" to a "viable alternative to tetracycline" (1, 14, 27). it probably would be acceptable with mild disease, since it is less active by weight than tetracycline, and patients have tended to respond slowly and to relapse (10).

Penicillin represents another theoretical alternative. Since chlamydia have a cell wall, a penicillin effect is not surprising. Morphologically defective forms are produced when chlamydia are exposed to penicillin, but its in vivo effectiveness does not compare with that of tetracycline. However, occasional patients treated with penicillin appear to have improved, and penicillin might be helpful in large doses, in a manner reminiscent of its effect on certain Gram-negative bacteria (10, 15).

Rifampin is the most active antibiotic on a weight basis, but there are theoretical concerns about development of resistance, as noted above. Clinical data are sparse and anecdotal (9, 25).

Sulfonamides have not helped most patients in whom they have been used, unlike the situation with C. trachomatis, which synthesizes folate and thus is susceptible to sulfonamides. Aminoglycosides and vancomycin should not be used as therapy, since they permit chlamydial growth in vitro (10).

The quinolones, particularly some of the newer compounds, show promise in vitro and in animal models of psittacosis (19, 22). Their role in therapy of human infection awaits further laboratory and clinical evaluation.

Combination Therapy

There are no clinical data on combination therapy on which to base recommendations.

ADJUNCTIVE THERAPY

Ventilatory support is often required in severe cases, and extracorporeal assist has been described in fulminant psittacosis with ARDS (32).

ENDPOINTS FOR MONITORING THERAPY

The most important parameter is clinical; usually, patients report subjective improvement in the first 24 hours of therapy. Objective signs of improvement are defervescence and improvement in respiratory function. Radiologic improvement is slow and characteristically lags the signs of clinical resolution.

VACCINES

There are no human vaccines commercially available.

PREVENTION OR INFECTION CONTROL MEASURES

C. psittaci resists drying and may remain infectious for months, so that cages of infected birds must be disinfected thoroughly. Sick birds should be treated, and their handlers should wear protective clothing and a high-efficiency respirator (N95 rating or higher). Imported birds should be treated routinely during their 30-day quarantine period, and the USDA even recommends extending this prophylaxis to 45 days, although this practice is not always observed (18).

CONTROVERSIES, CAVEATS OR COMMENTS

There are several uncertainties regarding the treatment of psittacosis. It is still not clear what the best approach to endocarditis is and, if the decision to replace the valve has been made, when in the course of therapy this action should be undertaken. Another area of uncertainty is the best alternative if neither tetracycline nor erythromycin can be used. Finally, as described above, the best approach for the pregnant patient and for the severely ill young patient is uncertain, regarding the advisability of assuming the risks of tetracycline therapy for efficacy that may be superior to that of erythromycin.

The most important caveat regarding the treatment of psittacosis is to be sure of the diagnosis. The differential diagnosis for psittacosis is extensive, and early diagnosis is difficult. Also, if treatment is failing, the diagnosis should be secured, since patients with bird exposures may acquire other illnesses; on the other hand, not all patients with psittacosis report contact with birds.

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