Pneumocystis jirovecii

• Opportunistic fungal infection of the lower respiratory infection

Microbiology

• Yeast-like fungus in the Ascomycota phylum
• Has not been able to be grown in culture, and species within the genus have tropism for their specific host
• It's cell wall lacks ergosterol, so has inherent resistance to many antifungals
• β-1,3 glucan, however, is an important cell wall component
• The major immunogenic protein is major surface glycoprotein (Msg), or gpA

History

• P. jirovecii was previously thought to be P. carinii, but it was later realized that they were two species within the same genus
  • P. carinii and P. wakefieldiae infect rats, P. murina infects mice and P. jiroveci infects humans
• Also previously thought to be a protozoan, but reclassified as fungus based on phylogenetic analysis, most closely related to Schizosaccharomyces pombe

Epidemiology

• Worldwide distribution
• Only circulates within humans
• Most children have been exposed by age 2 or 3
• Children and immunocompromised patients being the reservoir
  • Includes asymptomatic carriage by patients with HIV, malignancy, and long-term steroid use, and in pregnant women
• Risk factors for infection:
  • HIV
  • Immune-suppression, e.g. from steroids

Pathophysiology

• After inhalation of cyst, trophic forms are released and adhere to type I pneumocytes in the alveolar epithelium
• The immune response involves a combination of humoral and cell-mediated immunity
  • Alveolar macrophages are the first response, but require CD4 cells to respond fully
  • IgM antibodies recognize common fungal carbohydrate antigens
  • CD4 cells are important for the memory response
• The alveolus fills with Pneumocystis
• The inflammatory response may damage the lung

Presentation

• Shortness of breath on exertion

Investigations

• CXR
• Typical: bilateral diffuse patchy disease
• Atypical:
  • Normal (15%)
  • Localized
  • Pneumothorax
  • Upper lobe, if on pentamidine
• LDH increased
• CBC often normal

Diagnosis

• Induced sputum or brochoalveolar lavage (normal sputum not sensitive enough)
• 6min walk test: will desaturate, even if well-oxygenated at rest

Treatment

• Septra 5-6mg/kg po BID for 3 weeks
• If pO2 <70mmHg or A-a gradient ≥35: prednisone
• Alternative: clindamycin-primaquine or IV pentamidine
• Duration is 21 days (3 weeks)

Prophylaxis

• Usually instituted if the risk of PJP is greater than 3.5% per year