Pneumocystis carinii - MegaMicro

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Pneumocystis carinii

Microbiology > Mycology > Misc fungi
Pneumocystis jirovecii (previously known as P. carinii)

Structure:
• Originally considered to be a protozoan parasite, more recent evidence, including molecular and genetic data, the composition of their cell walls (beta-D-glucan) and structure of key enzymes support the classification of pneumocystis as a unicellular fungus.
• P. carinii was formerly the name of the species infecting humans; however, P. jirovecii is now the designated name for the species that infects humans and P. carinii the name for the species which infects rats.  The abbreviation “PCP” is still used to refer to the clinical entity of pneumocystis pneumonia for clarity and historical reasons.
• There are 3 distinct morphological stages:  trophozoite (1.5-5 um), sporozoite (precystic, 4-5 um) and cyst (5 um, containing up to 8 spores).

Epidemiology:
• Prior to the HIV/AIDs epidemic, PCP was uncommon (<100 cases/yr).  It soon became the most common opportunistic infection in HIV (+) patients.
• Other at-risk individuals include: premature or severely malnourished infants, persons with primary immunodeficiencies,  malignancies and patients on immunosuppressive medications.
• Numerous animal and human studies suggest PCP is transmitted from person to person by the airborne route.   Individuals with normal immune systems may have asymptomatic lung colonization and serve as a reservoir of infection for at risk persons.
• PCP has significantly decreased due to the use of anti-retroviral therapy in HIV (+) patients and prophylactic treatment of high risk patients with trimethoprim/sulfamethoxazole (TMP/SMX).

Pathobiology:
• The respiratory tract is the main portal of entry for human infection.  Once inhaled, the trophic form attaches to the alveoli.  The organism matures and develops into a uninucleated sporocyst and ultimately into a mature cyst containing spherical or oval intracystic spores. The mature cyst then ruptures to release the spores.
• A suppressed immune system allows for uncontrolled replication and development of pneumonia.

Disease Manifestations:
• Symptoms include fever, dry cough, difficulty breathing, chest pain, chills and fatigue.
• HIV (+) individuals tend to have a more subacute course with symptoms developing over several weeks.  The disease progresses more rapidly in non-HIV immunocompromised patients.
• On lung exam 50% of patients present with mild crackles and rhonchi, but the remaining patients may yield normal findings.
• Extrapulmonary infections are uncommon, but pneumocystis may present in almost any organ.

Laboratory Diagnosis:
• The most common diagnostic method is the microscopic exam of stained respiratory specimens as pneumocystis is not culturable.  Respiratory samples, usually obtained via bronchoalveolar lavage (BAL), are stained with methenamine silver, Calcofluor white, Giemsa, or fluorescein-labeled monoclonal antibodies. Rounded, cup-shaped cysts (like ping-pong balls with one side collapsed) are present within the intra-alveolar exudate.
• Direct fluorescent antibody (DFA) staining with monoclonal reagents of BAL specimens is approximately 90-95% sensitive.
• The microscopic exam of induced sputum specimens may be useful in AIDs patients where the organism burden is very high, however, the false negative rate ranges from 25-50%.
• PCR is now available for DFA negative specimens and may be performed on respiratory specimens (pleural fluid, BAL, lung tissue).
• The hallmark of PCP infection is an interstitial pneumonitis with plasma cell infiltrates. Chest X-rays classically demonstrate diffuse, bilateral infiltrates, but other patterns may be seen.
• Elevated serum beta-D-glucan levels in a patient with risk factors for PCP infection: pursue specific pneumocystis testing.

Differential diagnoses:
• Lymphocytic interstitial pneumonia, ARDS, pneumonia due to CMV, mycoplasma, viral mycobacterial (TB or MAI), legionella and pulmonary embolism.

Treatment:
• Although classified as a fungus, pneumocystis does not respond to antifungal therapy.
• The treatment of choice is TMP/SMX, with second line therapy including clindamycin + primaquine, pentamidine, dapsone or atovaquone.
• Steroids may be used as adjuvant therapy in HIV (+) patients with severe disease.

Prevention and control:
• TMP/SMX prophylaxis is given to at-risk individuals.
• Education regarding transmission of the organism and avoidance of close contact with pneumocystis infected patients.

Related concepts:
HIV/AIDS, Opportunistic Illness

Web links: cdc.gov/
pneumocystis

PCP cysts stained with methenamine silver   
PCP trophozoites in a BAL stained with Giemsa
DFA of PCP cysts in a BAL
PCP cysts in lung tissue stained with H&E
and methenamine silver stain

Images: from CDC image library
 
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