CHAPTER 61

• Pneumocystis jirovecii


  Opportunistic, atypical fungus that infects immunocompromised hosts and mostly manifests as PCP
• Pneumocystis jirovecii


  • Phylum Ascomycota
  • Originally was believed to be a trypanosome
  • Morphology is similar to that of protozoa
  • Clinically responds to antiprotozoal drugs but not to antifungal drugs in patients with pneumocystis
• Three forms of Pneumocystis jirovecii

  • Trophic form: trophozoite
  • Sporozoite: precyst
  • Ascus: cyst, diagnostic form
• Trophic form of Pneumocystis jirovecii


  Flexible-walled and susceptible to osmotic disturbance
• Pneumocystis jirovecii contains only one or two copies of the small ribosomal subunit gene, whereas most other fungi contain numerous copies of this gene
• DNA sequence analysis of the small ribosomal subunit gene in Pneumocystis jirovecii has disclosed a greater sequence homology with the fungi than with the protozoa
• Pneumocystis jirovecii


  • Worldwide distribution
  • Most commonly presents as pneumonia in an immunocompromised host
• Mode of transmission of Pneumocystis jirovecii

  Person-to-person via airborne particles
• Immunocompetent individuals


  Reservoir for Pneumocystis jirovecii, which is transmitted to immunodeficient individuals as a pathogen
• Children ages 2 to 4 years have antibodies to Pneumocystis, suggesting acquisition early in life
• Pneumocystis DNA was present in 24 of 72 infants, as determined from nasopharyngeal specimens, and seroconversion occurred in 85% of infants by 20 months of age
• Pneumocystis jirovecii is defined as the most common opportunistic infection among those with HIV or AIDS in the United States
• Introduction of highly active antiretroviral therapy (HAART) for patients with HIV has reduced the incidence of Pneumocystis jirovecii disease
• DNA testing demonstrate the detection of Pneumocystis jirovecii in immunocompetent populations
• Type I pneumocytes


  Thin squamous epithelial cells of the lungs where the trophic form of Pneumocystis jirovecii is adhered after inhalation
• The organisms replicate extracellularly while bathed in alveolar lining fluid
• Alveolar spaces fill with an eosinophilic foamy material, which can be detected with hematoxylin and eosin staining but does not provide direct staining of the organisms
• Methenamine silver or other fungal stain


  Used to identify the cyst form of Pneumocystis jirovecii in the lung tissue
• Infection and pathophysiologic changes caused by Pneumocystis jirovecii

  • Impaired oxygen-diffusing capacity
  • Hypoxemia
• Interstitial plasma cell pneumonia


  Formerly described due to predominantly interstitial mononuclear inflammatory response associated with Pneumocystis jirovecii pneumonia
• Symptoms of Pneumocystis jirovecii pneumonia (PCP)

  • Nonproductive cough
  • Low-grade fever
  • Dyspnea
  • Chest tightness
  • Night sweats
• Risk factors for Pneumocystis jirovecii pneumonia

  • HIV infection
  • Asthma
  • Chronic obstructive pulmonary disease (COPD)
  • Cystic fibrosis
  • Systemic lupus erythematosus (SLE)
  • Pregnancy
  • Rheumatoid arthritis
  • Infection with Epstein-Barr virus
  • Ulcerative colitis
  • High-dose corticosteroid therapy
• During treatment with an antiretroviral medication, patients show an improvement and an increase in CD4+ cells
• Immune reconstitution inflammatory syndrome


  Exaggerated immune response that occurs following a brief period of improvement, after which the patients begin to deteriorate
• Extrapulmonary sites where Pneumocystis jirovecii cysts have been predominantly identified

  • Lymph nodes
  • Spleen
  • Bone marrow
  • Liver
  • Adrenal glands
  • Gastrointestinal tract
  • Genitourinary tract
  • Thyroid
  • Ear
  • Pancreas
  • Eyes
  • Skin
• Multiple sites of Pneumocystis jirovecii infection typically indicate a more rapid disease progression and fatal outcome
• Respiratory specimens (bronchoalveolar lavage)


  Best for detection of Pneumocystis jirovecii
• Sputum specimen


  Should be induced sputum obtained by a trained respiratory therapist; otherwise, the rate of false-negative results may be unacceptably high
• Additional acceptable respiratory specimens for Pneumocystis jirovecii detection

  • Tracheal aspirates
  • Pleural fluid
  • Transbronchial biopsy
  • Cellular material from bronchial brushings
• Nasopharyngeal and oropharyngeal samples have demonstrated high sensitivity and specificity for the diagnosis of Pneumocystis jirovecii pneumonia when used in nucleic acid-based testing methods
• Collection for the diagnosis of extrapulmonary Pneumocystis


  Requires biopsy of the infected organ and histologic staining
• Diagnosis of Pneumocystis jirovecii pneumonia


  • Based on clinical presentation, radiographic studies, and direct or pathologic examination of respiratory samples or biopsy material
• Flexible-walled trophic forms of Pneumocystis jirovecii


  Predominant morphology of the organism, but these are difficult to visualize
• Giemsa-stained material of Pneumocystis jirovecii

  Stains somewhat discernible, with nuclei of various life stages appearing reddish purple and cytoplasm appearing light blue
• Firm-walled cyst form of Pneumocystis jirovecii


  • Exists although outnumbered by the trophozoites (10:1 ratio)
  • More easily recognized than the trophic form and may be definitively identified using a variety of stains such as calcofluor white, methenamine silver, and immunofluorescent staining
  • Spherical to concave, uniform in size (4-7 mm in diameter), do not bud, and contain distinctive intracystic bodies
• Four most common staining methods used for Pneumocystis jirovecii

  • Giemsa
  • Immunofluorescent
  • Calcofluor white
  • Methenamine silver
• Immunofluorescent method for Pneumocystis jirovecii

  Greater sensitivity but smaller predictive value, so a confirmatory method should be used due to high number of false-positive results
• (1-3)-beta-D-glucan


  Ascus (cyst) cell wall component used to successfully diagnose infections with Pneumocystis jirovecii
• Fungitell assay


  Uses patient serum for the detection of (1-3)-beta-D-glucan
• Important to use additional diagnostic information and confirmatory testing in conjunction with the (1-3)-beta-D-glucan test, because other yeast or fungi also secrete (1-3)-beta-D-glucan during infection