Pneumocystosis

Background

Pneumocystosis is also known as PCP (Pneumocystis carinii pneumonia). The parasite Pneumocystis carinii, was once considered a protozoan, but has recently been reclassified as a fungus, although debate still exists over the correct taxonomic classification. Pneumocystis organisms are commonly found in the lungs of healthy humans and other mammals. Recent DNA analysis has shown Pneumocystis organisms from different host species have very different DNA sequences, indicating the existence of multiple species of Pneumocystis. This has led to the renaming of the organism that causes human disease to Pneumocystis jirovecii.

P. jirovecii is a ubiquitous parasite that is present worldwide. Most children have antibodies to Pneumocystis by age 3 or 4, suggesting prior exposure to the organism. In healthy individuals, P. jirovecii rarely causes disease. Pneumocystosis is an opportunistic infection, primarily seen in individuals with impaired immunity, such as patients with:

• HIV - pneumocystosis is the most common opportunistic infection in patients with HIV
• Lupus erythematosus
• Chronic mucocutaneous candidiasis
• Wegener granulomatosis
• Cancer
• Long-term treatment with immune suppressant medications e.g. in organ transplant recipients
• Other congenital and acquired immune deficiencies
• Severe malnutrition
• Premature malnourished infants

Clinical features

P. jirovecii infection is usually limited to the lungs, but can occasionally spread to other organs, including the skin. It has been estimated that 66% to 85% of all HIV infected individuals will have one or more episodes of pneumocystosis in their lifetime. Approximately 1% to 2.5% of all P. jirovecii infections spread outside the lungs (extra pulmonary). Involvement of the skin by P. jirovecii is even more rare.

• Symptoms of pneumocystosis are relatively non-specific and include breathlessness, fever, and nonproductive (dry) cough. These symptoms tend to develop more slowly (over several weeks) in patients with HIV infection, compared with pneumocystosis in patients with other immune conditions. The physical signs of pneumocystosis are also non-specific. Increased respiratory rate and heart rate are present in most patients, and lung examination may reveal mild crackles and rhonchi in around 50% of patients.
• Extra pulmonary disease – sites most frequently involved are the lymph nodes, spleen, liver, and bone marrow. Extra pulmonary disease is usually more severe in HIV-infected individuals compared with non-HIV infected individuals.
• Skin disease – patients usually present with red or skin-coloured non-tender papules (small bumps, less than 0.5cm diameter) or nodules (larger than 0.5cm). Secondary erosion (loss of the surface of the lesion) or ulceration may be seen. The lesions can be solitary or widespread. The ear, external auditory canal, and axilla (armpit) are the most common sites of involvement.

Diagnosis

The diagnosis of pneumocystosis is usually based on microscopic identification of P. jirovecii from bronchopulmonary (lung) secretions. Bronchopulmonary secretions can be obtained by: induced sputum (patient inhales a salt water mist to encourage a deep cough) bronchoalveolar lavage (a small tube is passed through the mouth or nose into the lungs, fluid is squirted into a small area of lung and is then recollected for examination) or lung biopsy

Different techniques can aid microscopic identification of P. jirovecii:

• Special stains (such as Giemsa or silver stains) can highlight the organism
• Direct immunofluorescence using monoclonal antibodies – antibodies to P. jirovecii are produced in the laboratory and dyed with fluoresceine. These antibodies bind to antigen in infected cells and the cells display fluorescence under the microscope.

Biopsy of any skin lesions, with subsequent staining and microscopy can also reveal the organism.

Treatment

The drug of choice for treating P. jirovecii infection is trimethoprim-sulphamethoxazole (TMP-SMZ). Patients infected with HIV tend to respond to treatment more slowly than patients without HIV and require longer duration of therapy (3 weeks of treatment as opposed to 2).

Alternative treatments include pentamidine and atovaquone.

(TMP-SMZ) can also be used as a prophylactic (preventive) agent in patients with HIV and in other patients with impaired immunity. In patients who cannot tolerate TMP-SMX, other options include dapsone, dapsone plus pyrimethamine, atovaquone, and aerosolised pentamidine.

Prognosis

Early diagnosis and treatment of pneumocystosis increases the likelihood of successful treatment. In patients with HIV infection, around 10-20% of cases will be fatal In patients without HIV infection, around 30-50% of cases will be fatal; the higher mortality rate is likely to be due to delayed diagnosis in this group

Draft 12 September 2009