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Pneumocystis Carinii Pneumonia Thorax 1985;40:561-570 Thorax: first published as 10.1136/thx.40.8.561 on 1 August 1985. Downloaded from Editorial Pneumocystis carinii pneumonia The first description of pneumocysts is credited to biologists will need to become familiar with the Chagas' in 1909, who mistook them for trypano- diagnosis and treatment of pneumocystosis. somes in guineapig lungs. Carini reported similar structures in rat lungs infected with Trypanosoma The organism cruzi. Subsequently Dr and Madame Delanoe in Paris found pneumocysts in sewer rats without The taxonomy of P carinii continues to cause trypanosomiasis and proposed the name debate. At times it has been considered both as a Pneumocystis carinii in honour of the Brazilian trypanosome and as a fungus, largely owing to its Carini.' Although Chagas probably reported the ability to take up silver stains. It is now generally first human case of pneumocystosis, its importance held to be a sporozoan with a life cycle similar to was not recognised until the second world war, when that of Toxoplasma gondii. This conclusion is sup- outbreaks of pneumonia occurred throughout ported by its susceptibility to antiparasitic agents. Europe in malnourished children in overcrowded Although there are minor antigenic differences bet- orphanages.23 Histologically, the lungs of such ween strains isolated from various animal sources, patients showed considerable mononuclear cell they would all appear to belong to a single species interstitial infiltration and foamy vacuolated alveo- since the similarities are greater than the differ- lar exudates. The condition was named interstitial ences. copyright. plasma cell pneumonia. A definite association with The life cycle remains incompletely understood. P carinii infection was made in 1952.4 Subsequently, Nevertheless detailed morphological studies of pneumocystis pneumonia was diagnosed in infants infected human and animal lungs by light and elec- with congenital immunodeficiency states. Epidemic tron microscopy have increased our knowledge in pneumocystis pneumonia has virtually disappeared recent years.78 The parasite exists in both http://thorax.bmj.com/ from Europe, but is still recognised in parts of the trophozoite and cystic forms within the lung. The world where malnutrition and poverty prevail.' 2 5 trophozoites are pleomorphic and 1-4 ,um in diame- Until recently pneumocystis pneumonia largely ter, staining well with Giemsa. In contrast, the cysts affected patients receiving immunosuppressive are 5-7 gm in diameter, possess a thick wall, and treatment and corticosteroids for cancer, organ stain best with methenamine silver stain, which transplantation, and other conditions. Reports from makes them readily identifiable in tissues, although 1981 onwards, however, detailed the association they are often outnumbered by the trophozoite between pneumocystis pneumonia, other oppor- forms at certain stages of the infection. The thick tunistic infections, and Kaposi's sarcoma in previ- walled cysts contain up to eight smaller bodies or on September 30, 2021 by guest. Protected ously well homosexual men and drug abusers.6 The sporozoites. These are thought to emerge and acquired immune deficiency syndrome (AIDS) has develop into trophozoites, which may or may not caused intense interest in the medical and lay press. undergo binary fission before maturing and develop- Recently, 169 cases of AIDS have been recorded in ing into cysts to repeat the life cycle. Electron mic- the United Kingdom, 762 in Europe, and 8495 in roscopic studies have shown the cyst to undergo the United States (Communicable Disease Surveil- maturation with the liberation of trophozoites lance Center, 1985, unpublished), As pneumocystis before collapse.9 The trophozoite possesses a nuc- pneumonia is by far the commonest opportunistic leus but few cytoplasmic organelles, although tubu- infection (85%) in AIDS, clinicians and micro- lar extensions of the surface cytoplasm, or filopodia, can be visualised. Koch's postulates have yet to be fulfilled in rela- tion to pneumocystis pneumonia. Isolation of the Address for correspondence: Dr JT Macfarlane, City Hospital, parasite from the human lung, first reported by Pifer Nottingham NG5 1PB. and her colleagues,'" is not routinely possible. Vari- (Reprints will not be available.) ous cell lines permit isolation of the parasite in tissue 561 562 Thorax: first published as 10.1136/thx.40.8.561 on 1 August 1985. Downloaded from culture. These include Vero, CEL, WI-38, MRC 5, Models of infection and Chang liver cells.'0-'2 The most successful so far appears to be the use of the Vero cell line with min- The principle animal model has been the rat treated imal essential medium and 2% fetal bovine serum.'3 with corticosteroids. This has allowed the study of The ratio of organisms to cells appears to be critical, changes in the lung and growth characteristics of P as do the conditions of incubation. An atmosphere carinii.8 30 Rats treated with cortisone for eight of 5% oxygen and 10% carbon dioxide favours weeks show progressive increase in the intensity of growth, which is often maximal within a few days.'4 the P carinii infection. This is enhanced by a low There is a trend towards a greater predominance of protein diet. Control rats not treated with cortisone cystic forms over the trophozoites with more pro- show only a low level of infection throughout. The longed incubation. More recently P carinii has been pneumonia occurs by reactivation of latent infection cultivated in cell lines derived from lung.'5 and there is no experimental animal that can reliably The ready isolation of the parasite from the be infected with exogenous P carinii. Rats treated human lung would undoubtedly facilitate diagnosis with cortisone for only four weeks show a gradual and allow cultivation of large numbers of cysts and decrease in the intensity of infection after steroids trophozoites. This in turn would lead to a greater are withdrawn, although organisms were still evi- understanding of the parasite, its antigenic deter- dent up to 21 weeks later. minants, and factors governing its various stages of Light microscopy shows that in mild infection growth. organisms lie in small numbers along alveolar walls. As infection increases, more alveoli become filled Pathogenesis with clumps of organisms, alveolar lining cells hypertrophy, and there is a mild mononuclear cell P carinii has been found to exist saprophytically in interstitial infiltration. Foamy eosinophilic material the lungs of a wide range of animal species, includ- appears in the alveolar spaces, which eventually ing man.'6 There is evidence to suggest that it is become completely filled. When the steroids are frequently acquired in early childhood, where it stopped at four weeks, however, there is a dramatic usually causes inapparent infections, coinciding with increase in the interstitial cellular infiltration and copyright. loss of maternally acquired antibody.'7 18 Infection alveolar macrophages. Interstitial fibrosis may presumably occurs by inhalation, although in view of appear subsequently.8 the reports of congenital infection transplacental Electron microscopy shows that the P carinii infection cannot be excluded.'9 It probably remains trophozoites lie in tight apposition to type I reac- in a latent state for many years and undergoes pneumocytes and are covered by the liquid alveolar http://thorax.bmj.com/ tivation in response to immune suppression, lining layer.8 3" Increased permeability of the alveolar although case clustering has raised the possibility of capillary membrane (as shown by leakage of horse- hospital acquired infection.20 The main predisposing radish peroxide) is the first change seen in alveolar conditions include lymphatic leukaemia,2' malignant structure after infection.32 Later the type I pneumo- lymphoma, and organ transplantation.2224 More cytes degenerate, denuding the alveolar wall, and recently pneumocystis pneumonia has proved the the trophozoites come into direct contact with the major infectious complication among those with basement membrane. Some are found below the AIDS.25 Other, less frequent predisposing causes epithelium or in the interstitium. Extrapulmonary are collagen vascular disease,26 solid tumours, other spread has been seen rarely in man,33 most com- on September 30, 2021 by guest. Protected haematological conditions, and primary monly in lymph nodes and spleen. The foamy immunodeficiency states,27 and it occasionally eosinophilic material in the alveoli probably repres- occurs in immunocompetent neonates.28 In all these ents degenerative membranes of the organism and circumstances, except in starvation and AIDS, P alveolar cells, surfactant, and protein exudate. The carinii infection is uncommon unless corticosteroids evolution of these alveolar changes explains why or cytotoxic agents have been used.26 Of the two dyspnoea is the earliest manifestation of classes of agents, corticosteroids are the major pre- pneumocystis pneumonia. disposing factor and this is reflected in the various Healthy rats usually have no serum antibodies to animal models of pneumocystis pneumonia.8 P carinii when young, but these appear with age. Among the cytotoxic and immunosuppressive drugs Corticosteroid treatment and protein malnutrition azathioprine, methotrexate, and the vinca alkaloids stimulate heavy infection but depress antibody pro- are the most frequently identified.26 There is little duction. When corticosteroids are stopped high doubt that the frequency of pneumocystis
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