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:
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 1
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
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
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 period3
For renal transplantation, AST guidelines recommend 6-12 months after transplantation and European guidelines recommend 4 months after transplantation4
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
References
^Julien Senécal, Elizabeth Smyth, Olivier Del Corpo, Jimmy M. Hsu, Alexandre Amar-Zifkin, Amy Bergeron, Matthew P. Cheng, Guillaume Butler-Laporte, Emily G. McDonald, Todd C. Lee. Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clinical Microbiology and Infection. 2022;28(1):23-30. doi:10.1016/j.cmi.2021.08.017.
^Po-Yi Chen, Chong-Jen Yu, Jung-Yien Chien, Po-Ren Hsueh. Anidulafungin as an alternative treatment for Pneumocystis jirovecii pneumonia in patients who could not tolerate Trimethoprim/sulfamethoxazole. International Journal of Antimicrobial Agents. 2019. doi:10.1016/j.ijantimicag.2019.10.001.
^L. Cooley, C. Dendle, J. Wolf, B. W. Teh, S. C. Chen, C. Boutlis, K. A. Thursky. Consensus guidelines for diagnosis, prophylaxis and management ofPneumocystis jiroveciipneumonia in patients with haematological and solid malignancies, 2014. Internal Medicine Journal. 2014;44(12b):1350-1363. doi:10.1111/imj.12599.
^N. Goto, S. Oka. Pneumocystis jirovecii pneumonia in kidney transplantation. Transplant Infectious Disease. 2011;13(6):551-558. doi:10.1111/j.1399-3062.2011.00691.x.