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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.

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Epidemiology and Demographics

Pneumocystis jirovecii pneumonia exists worldwide, in humans and animals. Serologic evidence indicates that most healthy children have been exposed by age 3 to 4. Pneumocystis pneumonia (PCP) occurs in immunosuppressed individuals and in premature, malnourished infants.

Pathophysiology & Etiology

Life cycle of Pneumocystis spp.

Pneumocystis jirovecii (previously classified as Pneumocystis carinii) was previously classified as a protozoa. Currently, it is considered a fungus based on nucleic acid and biochemical analysis.

This is a generalized life cycle proposed by John J. Ruffolo, Ph.D. (Cushion, MT, 1988) for the various species of Pneumocystis. These fungi are found in the lungs of mammals where they reside without causing overt infection until the host's immune system becomes debilitated. Then, an oftentimes lethal pneumonia can result. 1 Asexual phase: trophic forms replicate by mitosis 2 to 3. Sexual phase: haploid trophic forms conjugate 1 and produce a zygote or sporocyte (early cyst) 2. The zygote undergoes meiosis and subsequent mitosis to produce eight haploid nuclei (late phase cyst) 3. Spores exhibit different shapes (such as, spherical and elongated forms). It is postulated that elongation of the spores precedes release from the spore case. It is believed that the release occurs through a rent in the cell wall. After release, the empty spore case usually collapses, but retains some residual cytoplasm 4. A trophic stage, where the organisms probably multiply by binary fission is also recognized to exist. The organism causes disease in immunosuppressed individuals.

History and Symptoms

The symptoms of Pneumocystis pneumonia (PCP) include dyspnea, nonproductive cough, and fever. Chest radiography demonstrates bilateral infiltrates. Extrapulmonary lesions occur in a minority (<3%) of patients, involving most frequently the lymph nodes, spleen, liver, and bone marrow. Typically, in untreated PCP increasing pulmonary involvement leads to death.

Laboratory Findings

Microscopic

Pneumocystis jirovecii trophozoites
Pneumocystis jirovecii trophozoites

A: Pneumocystis jirovecii trophozoites in bronchoalveolar lavage (BAL) material. Giemsa stain. The trophozoites are small (size: 1 to 5 µm), and only their nuclei, stained purple, are visible (arrows). AIDS patient seen in Atlanta, Georgia.

Pneumocystis jirovecii cysts
Pneumocystis jirovecii cysts

Pneumocystis jirovecii cysts

B: 3 cysts in bronchoalveolar material, Giemsa stain; the rounded cysts (size 4 to 7 µm) contain 6 to 8 intracystic bodies, whose nuclei are stained by Giemsa; the walls of the cysts are not stained; note the presence of several smaller, isolated trophozoites.
C: Cysts in lung tissue, silver stain; the walls of the cysts are stained black; the intracystic bodies are not visible with this stain; baby who died with pneumonia in California.

Pneumocystis jirovecii cysts
Pneumocystis jirovecii cysts


D: Pneumocystis jirovecii cysts in bronchoalveolar lavage material; silver stain; this greater magnification shows the irregular, saucer shape of the cysts.

Pneumocystis jirovecii
Pneumocystis jirovecii

E: Indirect immunofluorescence using monoclonal antibodies against Pneumocystis jirovecii. Specimen from a patient with AIDS, seen in Georgia.

Molecular

Agarose gel - PCR for Pneumocystis
Agarose gel - PCR for Pneumocystis

Molecular methods for detection of P. jirovecii have shown very high sensitivity and specificity and constitute the gold standard for detection of this pathogen.

A: Agarose gel (2%) analysis of PCR-amplified products from DNA extracted from a bronchoalveolar lavage (BAL) diagnostic specimen of a patient with pulmonary symptoms.

  • Lane S: Molecular base pair standard (100-bp ladder). Black arrows show the size of standard bands.
  • Lane 1: Single step PCR amplification with the pAZ102-E/pAZ102-H primer pair1 - diagnostic band size: 346 bp.
  • Lane 2: Nested PCR amplification with the ITS nested PCR primers, 1724F/ITS2R (first round) and ITS1F/ITS2R1 (second round)2 - diagnostic band size: 550 bp.


Treatment

Pharmacotherapy

Trimethoprim-sulfamethoxazole is the drug of choice. Recommended alternatives include pentamidine; trimethoprim plus dapsone; atovaquone; and primaquine plus clindamycin.

References

  1. http://www.dpd.cdc.gov/dpdx/HTML/Pneumocystis.htm

Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.

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