Pneumocystis pneumonia (PCP) occurs almost exclusively in the severely immunocompromised host, especially patients with congenital immunodeficiency diseases, acquired immunodeficiency syndrome (AIDS), and cancer, and those who have had organ transplantation. The increasing use of biologics, such as anti–tumor necrosis factor (TNF), is now putting a new group of patients at risk for developing PCP. Once pneumonia is apparent, the fatality rate is near 100% if untreated. Effective therapeutic and prophylactic drugs are available. The causative agent is an atypical fungus known for the past decade as Pneumocystis jirovecii.
PATHOGENESIS AND EPIDEMIOLOGY
The portal of entry for Pneumocystis is believed to be the respiratory tract via the airborne route. In the infected lung, the organism is found in both cystic and extracystic forms. The description of Pneumocystis morphology is a carryover from when the organism was felt to be a protozoan. The cyst is a round, oval, or cup-shaped structure approximately 4 to 6 μm in diameter (Fig. 348-1). Within the mature cyst are as many as 8 daughter cells, referred to as sporozoites (or intracystic bodies) that are pleomorphic and often crescent shaped. These cells eventually excyst through breaks in the cyst wall. Outside the cyst, the daughter cell, now termed a trophozoite (or trophic form) varies from 2 to 5 μm in diameter. These thin-walled trophozoites tend to cluster in masses.
Cyst forms of Pneumocystis as seen in a bronchoalveolar lavage specimen stained with Gomori methenamine silver nitrate method.
In the normal, healthy individual, Pneumocystis may lie dormant in the alveoli, eliciting no tissue response and leaving the host asymptomatic. In the severely immunocompromised host, organisms replicate to large numbers, and an extensive diffuse alveolar disease and interstitial infiltration may progress to death.
Pneumocystis attaches to the alveolar epithelial cells, and alveolar macrophages ingest and degrade the organisms; this provokes neutrophil, lymphocyte, and monocyte infiltration and cytokine release. Alveolar disruption impedes gas exchange and leads to respiratory failure. The CD4+ T lymphocyte serves to recruit and activate other immune effector cells. There is an increase in CD8+ lymphocytes in the lungs. Surfactant phospholipids are reduced in PCP, further impairing pulmonary function. In untreated patients, this leads to respiratory failure and death.
Pneumocystis infection is recognized among humans and lower animals worldwide. The natural habitat and mode of transmission in man are unknown, but animal studies suggest animal-to-animal transmission occurs by the airborne route. Animal-to-human transmission has not been reported, and available evidence suggests that human-to-human transmission is possible. Symptomatic infection occurs sporadically in nonimmunocompromised individuals.
PCP was first recognized in humans by Van der Meer and Brug in 1942. During this time, epidemics of interstitial plasma cell pneumonitis were occurring in European infants. In the 1950s, several reports confirmed that Pneumocystis was ...