Chapter 207

### Definition and Description

Pneumocystis is an opportunistic fungal pulmonary pathogen that is an important cause of pneumonia in the immunocompromised host. Although organisms within the Pneumocystis genus are morphologically very similar, they are genetically diverse and host-specific. P. jirovecii infects humans, whereas P. carinii—the original species described in 1909—infects rats. For clarity, only the genus designation Pneumocystis will be used in this chapter.

Developmental stages of the organism include the trophic form, the cyst, and the precyst (an intermediate stage). The life cycle of Pneumocystis probably involves sexual and asexual reproduction, although definitive proof awaits the development of a reliable culture system. Pneumocystis contains several different antigen groups, the most prominent of which are the 95- to 140-kDa major surface glycoprotein (MSG) and kexin (KEX1).

### Epidemiology

Serologic surveys have demonstrated that Pneumocystis has a worldwide distribution and that most healthy children have been exposed to the organism by 3–4 years of age. Airborne transmission of Pneumocystis has been documented in animal studies; person-to-person transmission has been suggested by hospital outbreaks of Pneumocystis pneumonia (PcP) and by molecular epidemiologic analysis of isolates. Data suggest that the cyst is the transmissible form.

### Pathogenesis and Pathology

Studies over the past several years have shown that Pneumocystis commonly colonizes patients who are immunosuppressed or who have chronic obstructive pulmonary disease. This colonization elicits an inflammatory response and is associated with a decline in lung function.

The host factors that predispose to the development of PcP include defects in cellular and humoral immunity. The risk of PcP among HIV-infected patients rises markedly when circulating CD4+ T cell counts fall below 200/μL. Other persons at risk for PcP are patients receiving immunosuppressive agents (particularly glucocorticoids) for cancer and organ transplantation; those receiving biologic agents such as infliximab and etanercept for rheumatoid arthritis and inflammatory bowel disease; children with primary immunodeficiency diseases; and premature malnourished infants.

The principal host effector cells against Pneumocystis are alveolar macrophages, which ingest and kill the organism, releasing a variety of inflammatory mediators. Proliferating organisms remain extracellular within the alveolus, attaching tightly to type I cells. Alveolar damage results in increased alveolar-capillary permeability and surfactant abnormalities, including a fall in phospholipids and an increase in surfactant proteins A and D. The host inflammatory response to lung injury leads to increases in levels of interleukin 8 and in neutrophil counts in bronchoalveolar lavage (BAL) fluid. These changes correlate with disease severity.

On lung sections stained with hematoxylin and eosin, the alveoli are filled with a typical foamy, vacuolated exudate. Severe disease may include interstitial edema, fibrosis, and hyaline membrane formation. The host inflammatory changes usually consist of hypertrophy of alveolar type II cells, a typical reparative response, and a mild mononuclear cell interstitial infiltrate. Malnourished infants display an intense plasma cell infiltrate that gave the disease its ...

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