Pneumocystis jiroveci Pneumonia

Introduction

• Opportunistic fungi
• Human isolate -P. jiroveci
•  P. carinii is found in rats.
• Cannot be cultured 

Taxonomic classification of Pneumocystis as a fungus is based on factors: 

1. Analysis of gene sequence for ribosomal RNA, mitochondria, proteins and major enzymes
2. Presence of b-1, 3 glucan in the cell wall
3. The efficacy of antifungal drugs that inhibit b-glucan synthesis. 

In contrast to most fungi.

• Pneumocystis lacks ergosterol
• Not susceptible to antifungal drugs that inhibit ergosterol synthesis.

Two distinct forms:(seen in tissue)

1. Thin walled trophozoites.
2. Thick walled spherical or elliptical cysts

• Contain four to eight nuclei. 
• Cyst can be stained with silver stain. toulidine blue, calcoflour white.

Antigens

Most prominent antigen:

• Major surface glycoprotein 
• Shows antigenic variation
• Facilitates its adherence.

Antigen is 35-55kDa:

• Acts as a marker of infection

Pathogenesis

• inhaled
• kills type I pneumocytes
• type II pneumocytes over replicate and damage alveolar epithelium
• fluid leaks into alveoli producing an exudate
• seen as honeycomb appearance on H&E

Persons at risk for Pneumocystic disease (Pneumocystosis)

• AIDS
• Patients receiving Immunosuppressive therapy (especially Glucocorticoids) for cancer, organ transplantation etc.
• Children with primary immunodeficiency diseases
• Premature malnourished infants (immunodeficient)

Clinical Manifestations

• Diffuse interstitial pneumonia
• Fever
• Non-productive cough
• Dyspnea on exertion
• Tachypnea
• Profound weight loss
• Fatigue
• Impaired oxygenation

Lab Diagnosis

• Pneumocystis infection is usually diagnosed by sputum examination
• Histopathological Findings:
• Methenamine silver, toludine blue stain cell wall 
• Wright-Gietnsa stain the nuclei.
• Immunofluorescence with monoclonal antibodies; more sensitive
• The most characteristic is predominantly alveolar, foamy vacuolated, eosinophilic exudates.
• Fiberoptic bronchoscopy with BAL:
•  forms the mainstay of diagnosis for Pneumocystic Pneumonia
• demonstrates small, “hat- shaped” structures in alveoli /Cup shaped cyst
• Transbronchial biopsy and open lung biopsy 
• Chest X-Ray
• B/L diffuse infiltrate in perihilar region.
• Nodular densities, cavitary lesion
•  Pneumothorax can also occur.
• Inc. frequency of upper lobe infiltrate in patient who take aerosolized pentamidine. 

Treatment

• DOC cotrimoxazole
• Alternative for mild to moderate case –
• Trimethoprim + dapsone and clindamycin +primaquine.
• Alternative for moderate to severe – 
• Pentamidine slow IV
• Adjunctive therapy-
• Glucocorticoid in HIV patient with moderate to severe pneumocystosis 
• Whose pulmonary function deteriorates on taking anti-pneumocystis drugs.

Prophylaxis is indicated for

• Patients with CD4- cell counts of< 200
• History of oropharyngeal candidiasis

Secondary prophylaxis is indicated for

• Both HIV infected and non HIV infected patients.
• Who have recovered from pneumocystosis.
• Primary and secondary prophylaxis may be discontinued in HIV infected persons once.
• CD4+ counts have risen to > 200 and remained at that level for 3 months.

First choice agent for the prophylaxis

• Trimethoprim, sulphamethoxazole.

Other agents used in prophylaxis.

• Dapsone, pentamidine.