Pneumocystis jirovecii

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Pneumocystis jirovecii / (Redirected from Pneumocystis)
  • Opportunistic fungal infection of the lower respiratory infection

Background

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
    • May be environmental, associated with outdoor activities and spaces (but not clear)
    • Human-to-human transmission is possible
  • Only circulates within humans, with reservoirs including children and immunocompromised patients
    • Primary infection occurs in infants, who are likely the natural host; most have been exposed by 2-3 years of age
    • Includes asymptomatic carriage by patients with HIV, malignancy, and long-term steroid use, and in pregnant women
  • Colonization is common, associated with the following:
    • Immunosuppressive conditions (HIV, low CD4 cell count, cancer, autoimmune diseases, organ transplantation)
    • Immunosuppressive drugs (corticosteroids, TNF-α inhibitors)
    • COPD and other chronic lung disorders
    • Other conditions (pregnancy, cigarette smoking)
    • Lack of surfactant
    • But also 20% of healthy people
  • Infection is mostly associated with HIV
    • Much higher risk with HIV/AIDS with low CD4 count <200
    • More common in Asian and South/Central America
  • Infection is still possible in immunocompetent hosts
    • TNF-alpha inhibitors, B-cell inhibitors, and corticosteroid use

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

Clinical Manifestations

Infants

  • Interstitial plasma cell pneumonia between 6 weeks and 4 months
  • Typically in orphanages under crowded conditions
  • Insidious onset with poor feeding, progressing to cyanosis

Adults

  • Worsening exertional dyspnea, fever, and non-productive cough
    • Symptoms usually more insidious in severe HIV
    • Symptoms may develop after tapering immunosupressive drugs like steroids
  • Tachypnea and tachycardia with exertional hypoxemia
  • CXR may initially be normal, then progresses to whiteout
    • Can also show unilateral consolidation, nodules, cysts, pneumatoceles, mediastinal lymphadenopathy, and pleural effusions
  • High LDH from lung damage
  • In advanced HIV, can disseminate to lymph nodes, spleen, liver, bone marrow, GI tract, eyes, thyroid, adrenal glands, and kidneys

Investigations

  • CXR
    • Typical: bilateral diffuse patchy disease
    • Atypical:
      • Normal (15%)
      • Localized
      • Pneumothorax
      • Upper lobe, if on pentamidine
  • 6min walk test: will desaturate, even if well-oxygenated at rest
  • LDH increased, though it has an LR+ of 1.5 and LR– of 0.61, so neither sensitive nor specific
  • CBC often normal

Diagnosis

  • Cannot be cultured
  • Specimens include sputum (best), BAL, or biopsy
    • Test characteristics of non-invasive (i.e. non-BAL) samples are summarized in senécal2022no
  • Microscopy
    • The gold standard
    • Direct fluorescent antibody (DFA) staining from induced sputum or BAL (about 75% sensitive from sputum)
    • Can also use Gomori Methenamine-Silver or Diff-Quik staining
  • Molecular
    • PCR from induced sputum or BAL (about 99% sensitive)
    • Nasopharyngeal aspirate is about 90% sensitive
    • Whole serum is about 80% sensitivty and specific
    • Can detect lower burden of PJP, especially in immunocompetent hosts where it is likely not causing disease but is instead helping to circulate it among the population
  • Serology
    • Not sensitive or specific
    • 1,3-β-D glucan levels may be elevated (Sn 95%, Sp 86%)
      • diagnostic accuracy was not different between HIV positive and HIV negative patients
      • Can be used as a screening tool
      • False positives with other IFIs, Candida, IV amoxicillin-clavulanic acid, treatment of patients with immunological preparations (albumins or globulins), use of cellulose membranes and filters made from cellulose in hemodialysis, and use of cotton gauze swabs/packs/pads and sponges during surgery

Management

  • First-line: TMP-SMX 15-20 mg/kg IV or PO divided q6-8h
    • If mild-moderate, can give TMP-SMX DS 2 tabs PO tid
  • Alternatives:
  • Adjunctive: Prednisone 40 mg PO bid for 5 days, followed by 40 mg PO daily for 5 days, followed by 20 mg po daily for 11 days
    • Can use methylprednisolone at 75% of predisone dose
    • Typically indicated if PaO2 ≤70 mmHg or A-a O2 gradient >35 mmHg
  • Duration is 21 days (3 weeks)

Prevention

Prophylaxis

  • Indicated in population with risk of PJP >3.5% per year
  • First-line: TMP-SMX DS or SS 1 tab PO daily
  • Alternatives:
  • No consensus on when to stop prophylaxis
    • Although there are no clear data guiding when to stop prophylaxis, it is probably reasonable to stop once the dose prednisone drops below 15-20 mg daily or equivalent
    • In patients with HIV, stopping once CD4 count is above 200 for 3 months
    • In patients receiving chemotherapy, at least one guideline recommends continuing for 6 weeks after the steroid-tapering periodcooley2014co
    • For renal transplantation, AST guidelines recommend 6-12 months after transplantation and European guidelines recommend 4 months after transplantationgoto2011pn

Further Reading

  • Pneumocystis Colonization Is Highly Prevalent in the Autopsied Lungs of the General Population. Clin Infect Dis. 2010;50:347. doi: 10.1086/649868
  • Near-Universal Prevalence of Pneumocystis and Associated Increase in Mucus in the Lungs of Infants With Sudden Unexpected Death. Clin Infect Dis. 2013;56:171. doi: 10.1093/cid/cis870