P. jiroveci causes pneumonia in immunocompromised patients; dissemination is rare. For years, P. jiroveci was thought to be a protozoan, but molecular biologic studies have proved that it is a fungus with a close relationship to ascomycetes. Pneumocystis species are present in the lungs of many animals (rats, mice, dogs, cats, ferrets, rabbits) but rarely cause disease unless the host is immunosuppressed. P. jiroveci is the human species, and the more familiar Pneumocystis carinii is found only in rats. Until the AIDS epidemic, human disease was confined to interstitial plasma cell pneumonitis in malnourished infants and immunosuppressed patients (corticosteroid therapy, antineoplastic therapy, and transplant recipients). Prior to the introduction of effective chemoprophylactic regimens, it was a major cause of death among AIDS patients. Chemoprophylaxis has resulted in a dramatic decrease in the incidence of pneumonia, but infections are increasing in other organs, primarily the spleen, lymph nodes, and bone marrow.
P. jiroveci has morphologically distinct forms: thin walled trophozoites and cysts, which are thick-walled, spherical to elliptical (4–6 µm), and contain four to eight nuclei. Cysts can be stained with silver stain, toluidine blue, and calcofluor white. In most clinical specimens, the trophozoites and cysts are present in a tight mass that probably reflects their mode of growth in the host. P. jiroveci contains a surface glycoprotein that can be detected in sera from acutely ill or normal individuals.
P. jiroveci is an extracellular pathogen. Growth in the lung is limited to the surfactant layer above the alveolar epithelium. In non-AIDS patients, infiltration of the alveolar spaces with plasma cells leads to interstitial plasma cell pneumonitis. Plasma cells are absent in AIDS-related Pneumocystis pneumonia. Blockage of the oxygen exchange interface results in cyanosis.
To establish the diagnosis of Pneumocystis pneumonia, specimens of bronchoalveolar lavage, lung biopsy tissue, or induced sputum are stained and examined for the presence of cysts or trophozoites. Appropriate stains include Giemsa, toluidine blue, methenamine silver, and calcofluor white. A specific monoclonal antibody is available for direct fluorescent examination of specimens. Pneumocystis cannot be cultured. While not clinically useful, serologic testing has been used to establish the prevalence of infection.
In the absence of immunosuppression, P. jiroveci does not cause disease. Serologic evidence suggests that most individuals are infected in early childhood, and the organ ism has worldwide distribution. Cell-mediated immunity presumably plays a dominant role in resistance to disease, as AIDS patients often have significant antibody titers, and Pneumocystis pneumonia is not usually seen until the CD4 lymphocyte count drops below 400/µL. Most patients have a positive test for 1,3-β-d-glucan (see Table 1).
Table1. Laboratory Tests for Fungal Antigens in Clinical Specimens
Acute cases of Pneumocystis pneumonia are treated with trimethoprim–sulfamethoxazole or pentamidine isethionate. Prophylaxis can be achieved with daily trimethoprim sulfamethoxazole or aerosolized pentamidine. Other drugs are also available.
No natural reservoir has been demonstrated, and the agent may be an obligate member of the normal flora. Per sons at risk are provided with chemoprophylaxis. The mode of infection is unclear, and transmission by aerosols may be possible.
