Mgmt of PCP, Toxoplasmosis, HSV - P carinii Infection

Pneumocystis carinii Infection

In first decade of the AIDS epidemic, Pneumocystis carinii pneumonia (PCP) was the most common serious opportunistic infection associated with HIV disease; the infection occurred in approximately 80% of all HIV infected patients at some point during their illness.^[1] Currently, PCP can be controlled more successfully, but nevertheless caused approximately 50,000 cases per year in the United States before the widespread use of highly active antiretroviral therapy (HAART), with a mortality rate of 10% to 20%.^[2] Since the introduction of HAART, the incidence of PCP and other opportunistic infections has declined markedly.^[3]

Some animal studies have suggested that the pathogen, Pneumocystis carinii, is transmitted by aerosols^[4]; however, the environmental source for infectious aerosols remains uncertain. Most authorities believe that animals are not a reservoir for human P carinii, and hence, it is thought that the infection is transmitted from human to human, or from environmental reservoir to humans. Antibody studies suggest that most humans are infected with P carinii early in life, and the frequency of severe, primary PCP in infants with perinatally acquired HIV further illustrates early acquisition. There is some evidence of seasonality to the infection, lending support to the idea of environmental reservoirs of PCP.^[5]

An additional controversy regarding the epidemiology of P carinii is whether infection is transient or long-lived with periods of latency. The observation that certain cancer patients are at high risk of P carinii supports the latency hypothesis.^[6,7] On the other hand, evidence of transient infection has been reported from studies which demonstrate outbreaks of P carinii infection among immunosuppressed patients who have had long mutual exposures.^[8] In clinical practice, most experts recommend restricted contact between patients with active P carinii infection and other immunosuppressed individuals, but full-fledged respiratory isolation, such as that utilized for tuberculosis, is not considered necessary.

Pathogenesis of Pneumocystis carinii Infection

Pneumocystis carinii is a 1.5-5.0 ТЕm organism which was originally classified as a protozoan based on its morphologic features and susceptibility to anti-protozoal agents. Recently analyses of genes from P carinii have indicated that the organism is more closely related to fungi.^[9,10] P carinii has three morphological forms:

the trophozoite, is the most numerous stage, in which small clusters of Giemsa-staining organisms may be found;
the cyst is a large inclusion, containing as many as eight daughter bodies within; and,
the pre-cyst is an intermediate stage.

Figure 1. Wright-Giemsa stain of a pulmonary specimen from a patient with dyspnea, hypoxia, and HIV infection. The large darkly blue staining organisms are Pneumocystis carinii trophozoites. This smear is diagnostic of PCP. (Photo courtesy of J. Zenilman)

The pathogen establishes infection within the alveoli. Attachment between the trophozoite and the type I alveolar pneumocyte is believed to be the initiating event in infection.^[4] The organism does not invade human tissues or cells, but proliferates as an extracellular parasite within the alveolar space provided there is an absence of adequate host cell-mediated immunity. Over time the organism completely fills alveoli, leading to hypoxemia. Patients develop respiratory alkalosis, diminished lung compliance and total lung capacity, and reductions in oxygen diffusing capacity.

The most common presenting manifestations of P carinii pneumonia are dyspnea, non-productive cough, and fever.^[11] Physical findings include fever, tachypnea, occasional cyanosis, tachycardia, and occasional rales. Chest X-rays usually demonstrate diffuse bilateral interstitial infiltrates. However, there are numerous examples of atypical radiographic presentations of P carinii pneumonia including unilateral infiltrates, cavities, effusions, and nodules.^[12] Laboratory examination commonly reveals hypoxemia and elevations in the serum LDH, which probably results from lung damage. P carinii may also be found in extrapulmonary locations including lymph nodes, spleen, liver, and the bone marrow, according to a recent study.^[13] Extrapulmonary pneumocystosis is associated with aerosolized pentamidine therapy for prophylaxis.

Figure 2. Chest radiograph of patient with dyspnea, hypoxia, and HIV infection. The pattern of diffuse interstitial infiltrates as seen suggests a diagnosis of PCP.

In patients with HIV infection, Pneumocystis carinii is uncommon until the CD4+ lymphocyte count drops below 200 cells/mm³. This was well illustrated by the Multicenter AIDS Cohort Study which reported that the majority of patients who developed PCP within 12 months had initial CD4+ cell counts of less than 100 cells/mm³.^[14] In addition to the CD4+ count, fever and thrush are predictive of subsequent PCP. Unusual instances have been reported in which the patientт