Pneumocystis jiroveci - Pneumocystosis

Pneumocystosis

Pneumocystis jiroveci, previously known as Pneumocystis cari-nii, is the causative agent of P. carinii pneumonia (PCP). PCPis the most common opportunistic infection in HIV-infected patients.

Pneumocystis jiroveci

Pneumocystis is a unicellular fungus found in the respiratorytracts of many mammals and humans. The genus Pneumocystis was initially mistaken for trypanosome, then later as a proto-zoan. Biochemical analysis of the nucleic acid composition of Pneumocystis rRNA and mitochondrial DNA in 1980s estab-lished it as a fungus. The cyst wall closely resembles that of fungi. However, it does not have ergosterol in its membrane as do the fungi, but instead has cholesterol.

Properties

The organism has three distinct morphologic stages:

·           The trophozoite or tropic form, where it often exists in clusters,

·           The sporozoite, which is a precystic form, and

·           The cyst, which contains several intracystic bodies known as spores.

Pathogenesis and Immunity

Transmission of infection occurs by inhalation. Once inhaled, the tropic form of the organism attaches to the alveoli. Defects in both cellular immunity and humoral immunity allow for uncontrolled replication of the organism and development of the disease. Activated alveolar macrophages without CD4 cells fail to eradicate the organism.

Clinical Syndromes

P. jiroveci causes PCP in HIV patients with their CD4 cellscount below 200/ L. It also causes PCP in other patients with primary immune deficiencies including hypogammaglobu-linemia and severe combined immunodeficiency, in organ (e.g., heart, lung, liver kidney)-transplant recipients’ long-term immunosuppressive regimens, and in patients with hemato-logic and nonhematologic malignancies. Most cases of PCP are asymptomatic.

In symptomatic cases, sudden onset of fever, nonproduc-tive cough, dyspnea, and tachypnea are typical manifesta-tions. Bilateral rales and ronchi are present. Extrapulmonary manifestations are rare. It occurs in AIDS patients during their advanced stage.

Epidemiology

Pneumocystis first came to attention when it was found to causeinterstitial pneumonia in Central and Eastern Europe during World War II in severely malnourished and premature infants. Prior to 1981, there were only few reports (less than 100) from the United States. However, in 1981, CDC in the United States reported the occurrence of PCP in five healthy homosexual males residing in the Los Angeles. Now P. jiroveci is recognized as one of the common causes of life-threatening opportunistic infections in patients with HIV infection worldwide.

Lungs of healthy individuals are the habitat of the fungus. Most children are believed to have been exposed to the organ-ism by age 3 or 4 years.

PCP causes a mortality of 10–20% in patients with HIV depending on the stage of the disease. It also causes a consid-erable degree of mortality and morbidity in non-HIV patients.

In developing countries many of the cases are not being reported due to nonavailability of modern healthcare. Pneumocystis is found to be responsible for up to 80% ofHIV-infected infants with pneumonia in Africa.

Laboratory Diagnosis

Chest radiographs in most patients show diffuse bilateral infil-trates extending from the perihilar region. Patchy asymmetric infiltrates and pneumatoceles are less common finding.

Treatment

P. jiroveci, although considered a fungus, does not respondto treatment with antifungal agents. A combination of trimethoprim and sulfamethoxazole is the drug of choice for treatment of PCP. Pentamidine and atovaquone are alternative drugs.

Prevention and Control

Chemoprophylaxis with trimethoprim and sulfamethoxazole or aerosolized pentamidine is useful for prevention of infection in patients with CD4 counts below 200/ L.