Epidemiology: few reported cases of Pneumocystis Jirovecii with CLL alone, however, risk appears to be the greatest in CLL patients that have received steroids and/or fludarabine
Physiology: little is known about the role of TNFα in the host defense against Pneumocystis Jirovecii, but infliximab decreases peripheral and gut mucosal CD4 counts in patients with Crohn’s Disease (Dig Dis Sci, 2004) [MEDLINE] (Gastroenterology, 1999) [MEDLINE]
Pneumocystis Jirovecii was First Identified by Carlos Chagas in Early 1900’s: using a guinea pig model
Although Formerly Thought to be a Protozoan, rRNA Subunit Analysis Links it Phylogenetically to the Ascomycetous Fungi: Pneumocystis Jirovecii was reclassified as a fungus in 1988
Pneumocystis Species Have Been Identified in Almost All Mammals
Humans Demonstrate Near Universal Seropositivity to Pneumocystis Jirovecii by Age 2
Pneumocystis Jirovecii is the Only Pneumocystis Species Which Infects Humans
Transmission: airborne person-to-person transmission is most likely the source on infection (although acquisition from environmental sources may also occur)
Despite the Probable Role of Airborne Transmission, Respiratory Isolation is Not Currently Recommended
Asymptomatic Carriage of Pneumocystis Jirovecii May Occur
Immune Defense Against Pneumocystis Jirovecii: although defense against Pneumocystis Jirovecii has classically been attributed to CD4 cells, animal data also indicates roles for B-cells and antibodies
This Likely Explains the Occurrence of Pneumocystis Jirovecii Following the Anti-B-Cell Agent Rituximab Therapy
Culture: Pneumocystis Jirovecii cannot be propagated in culture
Pneumocystis Jirovecii Colonization
Pneumocystis Jirovecii Colonization (PCR-Detected in the Absence of Infection) Has Been Associated with Upper Respiratory Tract Illness in Children
Pneumocystis Jirovecii Colonization (PCR-Detected in the Absence of Infection) Has Been Associated with Smoking and COPD in Adults (AIDS 2004) [MEDLINE] (Am J Respir Crit Care Med, 2004) [MEDLINE]
Animal Models Suggest an Association of Pneumocystis Jirovecii Colonization with the Development of COPD
Sensitivity (with Staining) in HIV-Related Cases: approximately 50-90%
Sensitivity is Lower in Non-HIV-Related Cases (Due to Decreased Organism Burden)
Staining for Pneumocystis Jirovecii
Gomori Methenamine Stain: useful to stain cyst forms
Wright–Giemsa Stain: can be used for identification of trophic forms within foamy exudates (sputum, bronchoalveolar lavage)
However, Requires a High Organism Burden and Expertise in Interpretation
Calcofluor White Stain: fungal cyst-wall stain that can be used for identification of cyst forms
Immunofluorescence Staining: can sensitively and specifically identify both pneumocystis trophic forms and cysts
Polymerase Chain Reaction (PCR) for Pneumocystis Jirovecii
Improves the Sensitivity for the Detection of Pneumocystis Jirovecii, Particularly in Non-HIV-Related Cases: however, due to high sensitivity, it may be difficult to differentiate organism carriage from infection
Sensitivity/Specificity (J Med Microbiol, 2002) [MEDLINE]
Epidemiology: respiratory failure (with ARDS) may occur (Chest, 2005) [MEDLINE]
Alveolar Pneumonia
Diagnosis
Serum Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase): elevation is highly sensitive, but not very specific (as can also be elevated in other pulmonary processes, such as bacterial pneumonia or tuberculosis)
Serum Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase): elevation is highly sensitive, but not very specific (as can also be elevated in other pulmonary processes, such as bacterial pneumonia or tuberculosis)
Chest X-Ray (CXR) (see Chest X-Ray): interstitial infiltrates
Example: 40 y/o white female on prednisone 40 mg PO qday, tapered to 30 mg qday 1 wk prior to admission (not on Pneumocystis Jirovecii prophylaxis), who presented with faint interstitial infiltrates on CXR 5 days prior to admission, then, worsening interstitial infiltrates on day of admission -> Pneumocystis Jirovecii was diagnosed by bronchoalveolar lavage
Epidemiology: may be seen in patients who have been receiving inhaled pentamidine prophylaxis
Diagnosis
Bronchoscopy with Bronchoalveolar Lavage (BAL) (see Bronchoscopy): typically higher BAL neutrophil counts and lower organism counts are seen in non-AIDS cases
Indications for Primary Prophylaxis: primary prophylaxis is indicated even in pregnant patients or patients on antiretroviral therapy
CD4 <200 Cells/μL or with History of Oropharyngeal Candidiasis
Indications for Secondary Prophylaxis
History of Pneumocystis Jirovecii: lifelong secondary prophylaxis is recommended (unless antiretroviral therapy results in immune reconstitution, as defined below))
Following Initiation of Antiretroviral Therapy, Once CD4 Increases to >200 Cells/μL x 3 mo, Prophylaxis Can Be Discontinued
If CD4 Decreases to <200 Cells/μL x 3 mo, Prophylaxis Should Be Restarted
Prophylaxis is Typically Administered for 6 mo After Engraftment (As Long as Immunosuppressives are Aministered)
Prophylaxis May Be Required for Longer in Patients Receiving Immunosuppression for Graft vs Host Disease
Autologous Stem Cell Transplant
Prophylaxis is Typically Administered for 3-6 mo
Prophylaxis Should Be Administered in Patients with an Underlying Hematologic Mlignancy (Lymphoma, Multiple Myeloma, Leukemia), Especially when Intensive Treatment Regimens have Included a Purine Analog (Cladribine, Fludarabine) or High-Dose Corticosteroids
Solid Organ Transplant
Prophylaxis is Indicated for 6 mo-1 yr After Transplant and For At Least 6 wks During Periods of High-Dose Immunosuppression (Such as During the Treatment of Acute Rejection)
Immunosuppressive Administration
Alemtuzumab (Campath, MabCampath, Campath-1H, Lemtrada) Administration (see Alemtuzumab)
Prophylaxis is Indicated for a Minimum of 2 mo After Completing Therapy or Until the CD4 Count is >200 Cells/μl
Prophylaxis Should Be Considered, Although This Has Not Been Adopted as a Standard of Care: especially if patient is also receiving corticosteroids (see Corticosteroids)
Concomitant Purine Analog (Cladribine, Fludarabine) + Cyclophosphamide Administration (see Fludarabine and Cyclophosphamide)
Prophylaxis is Indicated Until Recovery of Lymphopenia to CD4 >200 Cells/μL
Concomitant Temozolomide (Temodar, Temodal) + Radiation Therapy (see Temozolomide)
Prophylaxis is Indicated Until Recovery of Lymphopenia to CD4 >200 Cells/μL
Concomitant Temsirolimus + Corticosteroids or Other Immunosuppressives (see Temsirolimus)
Prophylaxis Should Be Considered in these Patients
HIV-Associated Pneumocystis Jirovecii: prednisone 40 mg PO BID x 5 days, then 40 mg PO qday on days 6-11, then 20 mg PO qday on days 12-21
Non-HIV-Associated Pneumocystis Jirovecii: prednisone 60 mg PO qday (better outcome has been demonstrated with higher prednisone dose in this population) (Chest, 1998) [MEDLINE]
Specific Treatment of Pneumocystis Jirovecii in the Setting of Human Immunodeficiency Virus (HIV) Infection
IRIS is a Common Complication of Anti-Retroviral Therapy for HIV in the Setting of Various AIDS-Defining Illnesses: it represents a paradoxical worsening of treated opportunistic infections or unmasking of previously subclinical, untreated infections
Clinical Data
Systematic Review and Meta-Analysis of IRIS (Lancet Infect Dis, 2010) [MEDLINE]
Incidence of IRIS is Variable Across Different AIDS-Defining Illnesses
Illnesses Associated with the Highest Incidence of IRIS: CMV retinitis, cryptococcal meningitis, tuberculosis
Illnesses Associated with the Lowest Incidence of IRIS: Kaposi sarcoma, herpes zoster
Incidence of IRIS is Inversely Correlated with the CD4 Count at Baseline
Higher Incidence of IRIS is Observed in Patients with CD4 <50 cells/μL: particularly in patients with tuberculosis, CMV-associated immune recovery uveitis, and cryptococcal meningitis
Higher Incidence of IRIS at Lower CD4 Counts is Not Surprising, Since CMV Retinitis is Typically an Infection Which Occurs at CD4 <50 cells/μL, Cryptococcal Meningitis Typically Occurs at Low CD4 Counts (While Tuberculosis and Kaposi Sarcoma Tend to Occur at Higher CD4 Counts)
Mortality Rate Associated with IRIS: 4%
Mortality Rate from IRIS is Much Higher with Cryptococcal Meningitis
Prognosis
Clinical Data
Comparative Small Taiwanese Study of Pneumocystis Jirovecii in Patients with/without HIV Infection (J Microbiol Immunol Infect, 2008) [MEDLINE]: n = 49
Most Common Immunocompromising Conditions in Study: HIV, malignancies
Mean CD4 Count: 110 cells/μL (higher in malignancy than in HIV, but difference was not statistically significant)
Mortality Rate of *Pneumocystis Jiroveciii HIV-Positive Patients: 6.7%*
Mortality Rate of *Pneumocystis Jirovecii in HIV-Negative Patients: 50%*
Retrospective Study of Pneumocystis Jirovecii Pneumonia in Lung Transplant Patients (Respir Med, 2020) [MEDLINE]: n = 47
Annual Incidence Rate: 2.7 Cases/1000 Lung Transplant Patients Per Year
Median time from LT was 2.4 ± 3.0 years
Sixty-five percent of patients were not on prophylaxis at the time of PCP while all patients were receiving steroids at the time of PCP
PCP was Associated with a High Mortality in Lung Transplant Patients
28-Day Mortality Rate: 15%
90-Day Mortality: 23%
Factors Associated with Increased Mortality in PJP in Lung Translant Patients
Decreased FEV1
Everolimus treatment
Pseudomonas aeruginosa coinfection
Fungal coinfection (especially Aspergillus sp.)
Mechanical Ventilation
Vasopressors
Factors Not Associated with Increased Mortality in PJP in Lung Translant Patients
PCP Primary Prophylaxis
Steroid Modification During PJP
Number of Immunosuppressive Molecules
Data Suggest the Need for Lifetime PJP Prophylaxis in Lung Transplant Patients
Benefit of Adjuvant Steroids Remains Unclear
References
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Pneumocystis carinii pneumonia in patients with connective tissue disease. Chest 1992; 101:375-378
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Use of adjunctive corticosteroids in severe adult non-HIV Pneumocystis carinii pneumonia. Chest 1998;113:1215-24 [MEDLINE]
Tumor necrosis factor alpha antibody (infliximab) therapy profoundly downregulates the inflammation in Crohn’s ileocolitis. Gastroenterology 1999; 116:22-28 [MEDLINE]
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Prognosis
Pneumocystis pneumonia after lung transplantation: a retrospective multicenter study. Respir Med. 2020 Aug;169:106019. doi: 10.1016/j.rmed.2020.106019 [MEDLINE]