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Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996.

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Medical Microbiology. 4th edition.

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Chapter 85Pneumocystis Carinii

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General Concepts

Clinical Manifestations

Respiratory manifestations—tachypnea, dyspnea and cough, and fever—are the usual symptoms of Pneumocystis pneumonia.

Structure

The spherical, oval, cup-shaped, thick-walled cyst, 6 to 8 μm in diameter, contains up to eight intracystic pleomorphic sporozoites. The extra-cystic trophozoite is thin-walled and varies in size from 2 to 6 μm.

Classification and Antigenic Types

It is not yet established whether P carinii is a fungus or a protozoan. Antigenic differences have been found in strains derived from the various mammalian hosts.

Multiplication

Multiplication is by a cyst—trophozoite—cyst cycle within the definitive host.

Pathogenesis

In normal individuals, asymptomatic infection of the lungs occurs in early life. The organism persists in an inactive or latent state unless the host becomes immunocompromised. Organisms attached to the alveolar septal wall replicate resulting in diffuse alveolitis and impaired oxygenation.

Host Defenses

A cell-mediated immune response is the major defense mechanism.

Epidemiology

Pneumocystis carinii infection is nonseasonal and worldwide. The organism is probably acquired by the respiratory route.

Diagnosis

Pneumonitis is diagnosed by radiography plus demonstration of P carinii in lung tissue for respiratory tract secretions.

Control

Trimethoprim-sulfamethoxazole is the preferred drug for treatment and prophylaxis.

Introduction

Pneumocystis carinii is a cause of diffuse pneumonia in immunocompromised hosts. Even in fatal cases, the organism and the disease remain localized to the lung. The pneumonia rarely, if ever, occurs in healthy individuals.

Pneumocystis carinii, an extracellular protozoan, has been observed in three forms. Diagnosis requires identification of P carinii in lung tissue, obtained by invasive techniques, or in lower airway fluids. Experimental studies have shown that the organism can be transmitted by inhalation.

Clinical Manifestations

Pneumocystis carinii causes bilateral diffuse pneumonitis in immunocompromised patients and no discernible disease in otherwise healthy individuals. Clinical features are to some extent age-dependent. In premature and debilitated infants, onset is subtle, starting with mild tachypnea. Within a week or so, respiratory distress is apparent, with marked tachypnea, flaring of the nasal alae, retractions, and cyanosis. The illness may last 4 to 6 weeks and has a mortality rate of 25 to 50 percent. In the immunodeficient child or adult onset is abrupt, with fever, tachypnea, and respiratory distress. Deterioration progresses to death in almost all cases if no treatment is given. In both types of patient, arterial oxygen tension is low, arterial pH usually increased, and carbon dioxide retention usually does not occur.

Structure

The structural forms of P carinii that have been recognized are the cyst, which is thick-walled; the sporozoite, an intracystic structure; and the thin-walled trophozoite (Fig. 85-1). The cyst is a spherical to ovoid structure 4 to 6 μm in diameter (Fig. 85-2). It contains up to eight pleomorphic sporozoites (Fig. 85-3). The trophozoite is a thin-walled extracystic cell representing an excysted sporozoite. Although the mode of replication has not been described, the organism can be briefly propagated in embryonic thick epithelial lung cells, Vero cells, and WI-38 cells. The organism does not enter the host cell, but instead attaches to its surface during a phase in the replicative cycle. There is no evidence of toxin production.

Figure 85-1. Stages in the life cycle of P carinii.

Figure 85-1

Stages in the life cycle of P carinii. The mode of replication is not known.

Figure 85-2. Pneumocystis carinii stained with Gomori's methenamine silver nitrate method.

Figure 85-2

Pneumocystis carinii stained with Gomori's methenamine silver nitrate method. Cysts stain brownish black and measure 4 to 6 μm in diameter. (From Hughes WT: Pneumocystis carinii pneumonia. In Kelley VC (ed): Practice of Pediatrics. Vol. 2. JB (more...)

Figure 85-3. Pneumocystis carinii stained with polychrome methylene blue.

Figure 85-3

Pneumocystis carinii stained with polychrome methylene blue. Intracystic sporozoites are visualized, but the cyst wall is not stained. Sporozoites measure 1 to 2 μm in diameter. (From Hughes WT; Pneumocystis carinii pneumonia. In Kelley VC (ed): (more...)

Classification and Antigenic Types

Antigenic differences have been demonstrated between organisms obtained from humans and from lower mammals such as the rat, rabbit, and ferret. The taxonomy of P carinii has not been established. It is either a protozoan or a fungus, although membership in a heretofore undescribed category cannot be excluded. Recent studies show rRNA sequences, thymidylate synthase, dihydrofolate reductase, beta tubulin, mitochondrial DNA and chitin in the cell wall of P carinii more closely resemble fungi than protozoa. Eriksson's treatise places P carinii in a new family, Pneumocystidaceae, and in a new order, Pneumocystidales (Ascomycota).

Multiplication

The mode of replication of P carinii has not been established. However, the stages in its life cycle have been characterized (Fig. 85-1). Sporozoites excyst through breaks in the cyst wall and then are termed trophozoites. The means by which the trophozoite form progresses to the cyst phase is not known.

Pathogenesis

The portal of entry for P carinii has not been firmly established; however, because with rare exceptions the organism has been found in only the lung, inhalation is a likely mode of transmission. Airborne transmission has been demonstrated in animals. In most individuals, the organism is dormant and sparsely dispersed in the lung, with no apparent host response (latent infection). In susceptible (immunocompromised) hosts, the organism occurs in massive numbers, filling the alveolar spaces and eliciting an active response of the alveolar macrophages and phagocytosis. In debilitated infants with Pneumocystis pneumonia, the alveolar septum is thickened and there is an interstitial plasma cell and lymphocyte infiltration. The infection results in impaired ventilation and severe hypoxia.

Host Defenses

With rare exceptions, P carinii causes disease only when natural mechanisms of host defense are compromised. Pneumonitis tends to occur in patients with impaired cell-mediated immunity, and it is a major infection in patients with the acquired immune deficiency syndrome (AIDS). Severe protein-calorie malnutrition alone may provoke the disease. Immunosuppressive drugs used for cancer or organ transplantation render the individual susceptible to P carinii pneumonitis. Both IgG and IgM antibody may appear in response to infection or experimental immunization, but humoral antibody does not protect against the disease. Alveolar macrophages actively engulf and digest the parasite in the presence of specific antibody. Infected infants show extensive plasma cell infiltration of the alveolar septae, but immunosuppressed children and adults do not.

Epidemiology

Pneumocystis carinii has been found in the lungs of rats, rabbits, mice, dogs, sheep, goats, ferrets, chimpanzees, guinea pigs, horses, and monkeys. The organism has been reported in lower animals and humans from all continents. Animal-to-animal transmission by the airborne route has been demonstrated. Because about 70 percent of healthy individuals may have humoral antibody to P carinii, subclinical infection must be highly prevalent.

Diagnosis

Tachypnea and fever are consistent features of the pneumonitis, and diffuse bilateral alveolar disease can be observed by radiography. Diagnosis requires the identification of P carinii in pulmonary tissue or lower airway fluids. Such specimens may be obtained by lung biopsy, inducement of sputum, bronchoalveolar lavage, or needle aspiration of the lung. The Gomori, Giemsa, fluorescence-labelled antibody, or toluidine blue O stains may be used to identify the organism. Serologic studies for antibodies and antigen are not helpful in establishing a specific diagnosis.

Control

Experimental studies show that immunization with P carinii does not protect the animal from pneumonia; however, the disease can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole, aerosolized pentamidine or dapsone.

Four drugs currently available for therapy of P carinii pneumonitis are pentamidine isethionate, trimethoprim-sulfamethoxazole, atovaquone and trimetrevate. Trimethoprim-sulfamethoxazole is preferred because of its low toxicity and greater efficacy.

References

  1. Edman JC, Kovacs JA, Masur H. et al. Ribosomal RNA sequence shows Pneumocystis carinii to be a member of the fungi. Nature. 1988;334:519. [PubMed: 2970013]
  2. Eriksson OE. Pneumocystis carinii, a parasite in lungs of mammals, referred to a new family and order (Pneumocystidaceae, Pneumocystidales, Ascomycota) System Ascomycetum. 1994;13:165.
  3. Gigliotti F, Hughes WT. Passive immunoprophylaxis with specific monoclonal antibody confers partial protection against Pneumocystis carinii pneumonitis in animal models. J Clin Invest. 1988;81:1666. [PMC free article: PMC442608] [PubMed: 2454947]
  4. Hughes WT: Pneumocystis carinii pneumonia. In Pizzo PA, Wilfert CM. Pediatric AIDS: The Challenge of HIV Infection in Infants, Children and Adolescents. 2nd ed. Williams and Wilkins, Baltimore, 1994 .
  5. Hughes WT: Recent advances in the prevention of Pneumocystis carinii pneumonia. Advances in Pediatric Infectious Diseases, in press . [PubMed: 8718463]
  6. Smulin AG, Walzer PD. The Biology of Pneumocystis carinii. Crit Rev Microbiol. 1992;18:191. [PubMed: 1554424]
  7. Wakefield AE, Peters SE, Banerji S. et al. Pneumocystis carinii shows DNA homology with ustomycetous red yeast fungi. Molec Microbiol. 1992;6:1903. [PubMed: 1508039]
Copyright © 1996, The University of Texas Medical Branch at Galveston.
Bookshelf ID: NBK8137PMID: 21413303
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