View source for Pneumocystis jirovecii

*Opportunistic fungal infection of the lower respiratory infection

==Background==
===Microbiology===

*Yeast-like fungus in the [[Phylum::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 &lt;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 [[CiteRef::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: [[Is treated by::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:
**[[Is treated by::Clindamycin]] 600-900 mg IV q6-8h with [[Is treated by::primaquine]] 15 to 30 mg PO daily
**[[Is treated by::Pentamidine]] 4 mg/kg IV daily
**[[Is treated by::Trimethoprim]] 15 mg/kg PO divided q8h with [[Is treated by::dapsone]] 100 mg PO daily
**[[Is treated by::Atovaquone]] 750 mg PO bid (for mild-moderate only)
**Possibly [[anidulafungin]][[CiteRef::chen2019an]]
*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 PaO<sub>2</sub> ≤70 mmHg or A-a O<sub>2</sub> gradient &gt;35 mmHg
*Duration is 21 days (3 weeks)

==Prevention==

===Prophylaxis===

*Indicated in population with risk of PJP >3.5% per year
**'''HIV:''' prior ''Pneumocystis'' pneumonia; CD4 <200; oropharyngeal ''Candida'' regardless of CD4
**'''Medications:''' [[prednisolone]] ≥20 mg daily for >4 weeks; TNF-α inhibitors; [[steroids]] plus a steroid-sparing agent
**'''Cancer treatment:''' [[steroids]] and [[cyclophosphamide]]; [[alemtuzumab]] for at least 2 months after treatment and until CD4 >200; temozolomide and radiation therapy, until CD4 >200; [[fludarabine]] and T-cell depletion, until CD4 >200; any antileukemic therapy
**'''Rheumatology treatment:''' GPA receiving [[cyclophosphamide]], especially with [[steroids]]
**'''Transplantation:''' [[allogeneic stem cell transplantation]] for at least 180 days; [[autologous stem cell transplantation]] for at least 3 to 6 months
**'''Primary immunodeficiency:''' [[SCID]]; idiopathic CD4 lymphocytopenia; [[hyper-IgM syndrome]]
*First-line: [[TMP-SMX]] DS or SS 1 tab PO daily
*Alternatives:
**[[TMP-SMX]] DS 1 tab po tiw
**[[Dapsone]] 100 mg po daily, or 50 mg po bid
**[[Dapsone]] 50 mg po daily with [[pyrimethamine]] 50 mg po weekly and [[leucovorin]] 25 mg po weekly
**[[Pentamidine]] 300 mg inhaled monthly
**[[Atovaquone]] 1500 mg po daily (or 750 mg po bid)
**[[Atovaquone]] as above with [[pyrimethamine]] 25 mg po daily and [[leucovorin]] 10 mg po daily
*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 period[[CiteRef::cooley2014co]]
**For renal transplantation, AST guidelines recommend 6-12 months after transplantation and European guidelines recommend 4 months after transplantation[[CiteRef::goto2011pn]]

==Further Reading==

*''Pneumocystis'' Colonization Is Highly Prevalent in the Autopsied Lungs of the General Population. ''Clin Infect Dis''. 2010;50:347. doi: [https://doi.org/10.1086/649868 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: [https://doi.org/10.1093/cid/cis870 10.1093/cid/cis870]

{{DISPLAYTITLE:''Pneumocystis jirovecii''}}
[[Category:Fungi]]