Pneumocystis jirovecii

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Chapter 236 Pneumocystis jirovecii

Pneumocystis jirovecii pneumonia (interstitial plasma cell pneumonitis) in an immunocompromised person is a life-threatening infection. Primary infection in the immunocompetent person is usually subclinical and goes unrecognized. The disease most likely results from new or repeat acquisition of the organism rather than reactivation of latent organisms. Even in the most severe cases, with rare exceptions, the organisms remain localized to the lungs.

Epidemiology

Serologic surveys show that most humans are infected with P. jirovecii before 4 yr of age. In the immunocompetent child, these infections are usually asymptomatic. P. jirovecii DNA can occasionally be detected in nasopharyngeal aspirates of normal infants. Pneumonia caused by P. jirovecii occurs almost exclusively in severely immunocompromised hosts, including those with congenital or acquired immunodeficiency disorders or malignancies and in organ transplant recipients. Small numbers of P. jirovecii can be found in the lungs of infants who have died with the diagnosis of sudden infant death syndrome. This observation could indicate a cause-and-effect relationship or simply indicate that there is overlap in the timing of the primary infection with P. carinii and sudden infant death syndrome.

Without chemoprophylaxis, approximately 40% of infants and children with AIDS, 70% of adults with AIDS, 12% of children with leukemia, and 10% of patients with organ transplants experience P. jirovecii pneumonia. Epidemics that occurred among debilitated infants in Europe during and after World War II are attributed to malnutrition. The use of new biological immunosuppressive agents has expanded at-risk populations. The addition of tumor necrosis factor-α inhibitors to the management of patients with inflammatory bowel disease has resulted in a demonstrable increase in P. jirovecii pneumonia among this patient population.

The natural habitat and mode of transmission to humans are unknown, but animal studies have clearly demonstrated airborne transmission. Animal-to-human transmission is unlikely because of the host specificity of P. jirovecii. Thus, person-to-person transmission is likely but has not been conclusively demonstrated.

Pathogenesis

Two forms of P. jirovecii are found in the alveolar spaces: cysts 5-8 µm in diameter that contain up to 8 pleomorphic intracystic sporozoites (or intracystic bodies) and extracystic trophozoites (or trophic forms), which are 2-5 µm cells derived from excysted sporozoites. The terminology of sporozoites and trophozoites is based on the morphologic similarities to protozoa, because there are no exact correlates for these forms of the organism among the fungi. P. jirovecii attaches to type I alveolar epithelial cells, possibly by adhesive proteins such as fibronectin and or mannose-dependent ligands.

Control of infection depends on intact cell-mediated immunity. Studies in patients with AIDS show an increased incidence of P. jirovecii pneumonia with markedly decreased CD4+ T-lymphocyte counts. The CD4+ cell count provides a useful indicator in both older children and adults of the need for prophylaxis for P. jirovecii pneumonia. Although normally functioning CD4+ T cells are central to controlling infection by P. jirovecii, the final effector pathway for destruction of P. jirovecii is poorly understood. A likely role for CD4+ T cells could be to provide help for the production of specific antibody that is then involved in the clearance of organisms through interaction with complement, phagocytes, or T cells or through direct activation of alveolar macrophages.

In the absence of an adaptive immune response, as can be modeled in severe combined immunodeficient (SCID) mice, infection with P. jirovecii produces little alteration in lung histology or function until late in the course of the disease. If functional lymphocytes are given to SCID mice infected with P. jirovecii, there is a rapid onset of an inflammatory response that results in an intense cellular infiltrate, markedly reduced lung compliance, and significant hypoxia, which are the characteristic changes of P. jirovecii pneumonia in humans. These inflammatory changes are also associated with marked disruption of surfactant function. T-cell subset analysis has shown that CD4+ T cells produce an inflammatory response that clears the organisms but also results in lung injury. CD8+ T cells are ineffective in the eradication of P. jirovecii. CD8+ T cells do help modulate the inflammation produced by CD4+ T cells, but in the absence of CD4+ T cells the ineffectual inflammatory response of CD8+ T cells contributes significantly to lung injury. These various T-cell effects are likely responsible for the variations in presentation and outcome of P. jirovecii