Donald C. Anderson

The disease generally known as Pneumocystis carinii pneumonia (or PCP) is an opportunistic infection of increasing importance to pediatricians. A marked increase in the prevalence of this disorder in the United States since the 1970s has paralleled therapeutic advances in the management of immunologic and neoplastic diseases that have resulted in longer survival of children with these underlying disorders. Most important, this infection is occurring now in epidemic proportions in association with the acquired immunodeficiency syndrome (AIDS). PCP is especially common in human immunodeficiency virus (HIV)—infected infants in central, western, and southern Africa, where it is the cause of death in 30% to 50% of HIV-infected infants younger than 6 month old.


Pneumocystis organisms were described first by Chagas in 1909 as possible morphologic variants of Trypanosoma cruzi. From the time of its discovery until late in the 1980s, Pneumocystis was widely thought to be a protozoan to be classified with Toxoplasma, but some microbiologists argued that Pneumocystis organisms exhibit morphologic similarities to those of fungi. It behaves as a protozoan in response to antiprotozoal drugs and as a fungus with respect to its periodic acid–Schiff and silver staining characteristics. In 1988, definitive classification using DNA analysis confirmed that P. carinii is a fungus, albeit an unusual example, lacking in ergosterol and very difficult to propagate in culture. Subsequent genotypic studies of diverse Pneumocystis species in different mammals showed that the organism that causes human PCP is distinct. It is now termed P. jiroveci in recognition of the Czech parasitologist, Otto Jirovec, who is credited with the seminal descriptions of the microbe in humans. Changing the organism’s name (in 1999) does not preclude the use of the acronym PCP because it can be read “Pneumocystis pneumonia.”


Three developmental forms of P. jiroveci have been identified by light microscopy: cysts, sporozoites, and trophozoites. When they are identified in lung tissue or respiratory secretions, cysts are spheric or crescent-shaped structures approximately 5 μm in diameter, containing as many as eight oval bodies or sporozoites that are 1 to 2 μm in diameter. The natural habitat of P. jiroveci and its mode of transmission in humans remain largely unknown. The occurrence of this organism has been recognized in many wild and laboratory animal species over a wide geographic distribution, but an association between animal reservoirs and human infection has not been established. Before and during World War II, epidemics of interstitial plasma cell pneumonitis secondary to P. jiroveci were recognized in debilitated and premature infants throughout European institutions and nursing homes. The interruption of outbreaks by the introduction of strict isolation of affected patients suggested the
probable importance of person-to-person spread of the disease within that setting. In the United States, PCP was not reported until 1956. In contrast to the early European patterns, U.S. cases primarily have been sporadic and have occurred almost exclusively in children with impaired host defenses. Necropsy studies have demonstrated that apparent (asymptomatic) infection occurs frequently in patients with cancer or other conditions that cause immunocompromise, but the epidemiologic importance of these asymptomatic carriers in the transmission of pneumocystic disease is unknown. Pneumocystis organisms are detected frequently in the sputum, pharyngeal secretions, or tracheal aspirates of symptomatic patients, and cysts have been shown to survive for several months in dried lung specimens maintained at room temperature. These observations suggest that infection probably occurs as a result of inhalation of the organism, which justifies respiratory isolation of symptomatic patients who are exposed to other highly susceptible patients.

The dramatic nature of PCP tends to obscure the fact that its severity is the result of the susceptibility of the host rather than the virulence of the parasite. That P. jiroveci is an organism of low pathogenicity is emphasized clearly by the rare occurrence of infections in intact hosts. Since the middle to late 1960s, PCP has occurred almost exclusively in patients with primary or acquired immunologic disorders or in those receiving immunosuppressive treatment of oncologic disease or organ transplantation. Of 194 cases reported to the Centers for Disease Control and Prevention (CDC) from 1967 through 1970, 29 occurred in infants younger than 1 year, 83% of whom had primary immunodeficiency disorders. In contrast, acute lymphocytic leukemia was the most common underlying disease in children older than 1 year. Of 1,251 children with malignant diseases at the Saint Jude Children’s Research Hospital in Memphis, Tennessee, from 1962 to 1971, PCP occurred in 51 (4.1%). Within populations of patients with cancer, PCP occurs more commonly in individuals with generalized lymphoproliferative malignancy than in those with solid tumors. The risk of the development of Pneumocystis infections increases with the extent of malignant disease and the intensity of chemotherapy or radiotherapy provided. The precise mechanisms accounting for enhanced susceptibility in individual patients are not understood completely. PCP has been reported in association with congenital and acquired hypogammaglobulinemia, severe combined immunodeficiency disease, selective T-cell deficiency (DiGeorge syndrome), AIDS, and other secondary immunodeficiency states. The development of specific antibodies to Pneumocystis organisms in infected patients has been inconsistent. During the course of “epidemic” disease in malnourished infants, immunoglobulin M (IgM) values frequently increase markedly, with variable changes in IgG and IgA values. IgG antibody concentrations increase in the serum 4 to 6 weeks after infection and are thought to provide permanent immunity in those infants. Experimental evidence suggests that specific antibody fixes complement C3 fragments on the surface of Pneumocystis organisms and thereby enables their subsequent phagocytosis by alveolar macrophages. The importance of impaired cellular immunity in the pathogenesis of PCP is demonstrated by the ability of corticosteroids or cyclosporine to induce Pneumocystis infection in laboratory animals, the remarkable susceptibility of patients with AIDS to development of PCP (it occurs in at least 50% of these individuals), and the occurrence of PCP in malnourished hosts with significantly impaired cellular immune responses. In infants and children with AIDS, the quantity of peripheral blood CD4 T-helper lymphocytes serves as a useful predictor of PCP; as the level of CD4 lymphocytes decreases, the risk of developing this infectious complication increases.

P. jirovecii infections are unique in that the pathologic findings, with rare exceptions, are limited to the lungs, even in fatal cases. In the infantile epidemic form of the disease, essentially all alveoli contain large numbers of organisms. Extensive interstitial plasma cell infiltrates distend alveolar walls to five to 20 times their normal thickness, and almost no intraalveolar fibrinous exudate is noted.


In the childhood and adult forms of PCP, the histogenesis has been described in three stages. An initial stage is characterized by the presence of cysts and trophozoites attached to alveolar walls. No septal inflammatory or cellular responses are evident, and no clinical disease is associated with this stage. A second stage, which may or may not be associated with clinical signs and symptoms, is characterized by the desquamation of alveolar cells and an increase in the number of cysts within alveolar macrophages. A final stage that definitely is associated with clinical manifestations is typified by extensive reactive and desquamative alveolitis, manifested by marked cytoplasmic vacuolation of macrophages, mononuclear, and plasma cell infiltrates within alveolar septa, and clusters of organisms located predominantly within macrophages in the lumina of alveoli.

The natural course of Pneumocystis infections in children is highly variable and depends primarily on the status of host defenses in individual patients. Infantile epidemic pneumocystosis is typified in premature, debilitated, or marasmic infants between the ages of 2 and 6 months. These patients often have chronic diarrhea and weight loss before respiratory symptoms develop. Characteristically, the onset is insidious, with progression of cough, tachypnea, and respiratory distress occurring over a 1- to 4-week interval. Fever is either absent or low-grade in most cases. Symptoms in immunosuppressed children or adults may be more abrupt in onset and more rapidly progressive than in infantile epidemic cases; in these older patients, the severity and duration of disease before diagnosis is established are highly variable, but the mortality rate is approximately 100% if treatment is not provided. Unlike in infantile cases, fever generally is present and is high-grade, and it often precedes the onset of a nonproductive cough, tachypnea, and severe dyspnea or the appearance of pulmonary infiltrates on radiography.

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Jul 24, 2016 | Posted by in ORTHOPEDIC | Comments Off on PNEUMOCYSTIS JIROVECI Pneumonia
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