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DRAKE

Saunders Pharmaceutical Word Book

neumocystis carinii pneumonia (PCP), an opportunistic infection, has been the major cause of illness and death in immunocompromised individuals. Pneumocystis has been known for nearly a century, but only recently have scientists been able to analyze its DNA sequence. Pneumocystis can be found in most mammals, and until recently, scientists thought the same “bug” (P. carinii) infected all. After analyzing the DNA of Pneumocystis collected from various animals, they discovered that Pneumocystis organisms differ, depending on which host animal is carrying the infection. In fact, the differences from host to host are so great that they warrant a separate species name. In other words, DNA analysis has revealed that the Pneumocystis bug that infects a rat is a different species than that which infects a monkey, which is different than that which infects a human.

The organism that causes PCP in humans is now named Pneumocystis jiroveci (pronounced: yee row VET zee), in honor of the Czech parasitologist Otto Jirovec, who first described the microbe in humans.

“PCP” acronym retained. The biggest objection to renaming the microbe in humans was the huge body of medical literature that uses the acronym “PCP” for the disease caused by P. jiroveci. A change in the acronym is not necessary, however, since the species identifier can simply be removed from the disease name. “PCP” now stands for “Pneumocystis pneumonia.” This simple modification also allows the acronym’s use for describing the disease in every host species (none of which, except for rats, will be infected by P. carinii).

History of the organism. Pneumocystis organisms were first reported in 1909 by Dr. Carlos Chagas. He thought it to be a variant of the protozoa Trypanosoma cruzi, which causes his eponymic disease. Within a few years it was discovered not to be a trypanosome, but rather a new species, and was named Pneumocystis carinii. From the time of its discovery until the late 1980s, P. carinii was thought to be a protozoan, for a number of complex reasons that only a taxonomist could love. In 1988, DNA analysis proved that it is actually a fungus, although a very unusual variant that does not respond to antifungal drugs.

History of the disease. The disease associated with the organism has been reported in immunocompromised patients for many decades, including outbreaks among malnourished children in orphanages in the 1950s. The disease can affect patients that are immunocompromised for any number of reasons, including chemotherapy and organ transplants, but the disease had only slight impact until the beginning of the AIDS epidemic in the 1980s. Since then, PCP has been the most serious AIDS- defining infection in the U.S.

A common childhood infection. P. jiroveci infection is common in young children. In fact, it has been found in most infants’ environments and in the nasopharyngeal aspirates of children with mild respiratory infections. While it has been weakly linked to some childhood illnesses, such infection is not life-threatening in normal, healthy children. Most children develop anti-Pneumocystis antibodies early in life, and those antibodies increase with age. Seroconversion develops by 20 months of age in 85% of children.

The source of AIDS infections. Due to the fact that almost everyone is infected with P. jiroveci in childhood, it was first hypothesized that a compromised immune system simply allows the latent organism from childhood to reactivate. The latency issue is important for several reasons. First, if the source of life-threatening PCP is internal, it would be of little use to institute measures to minimize person-to-person transmission of the disease in HIV- infected adults. And concern that the organism might develop drug resistance would be unfounded, since each new infection would come from an untreated, childhood strain. Researchers have now almost completely rejected this hypothesis.

Although infection in children is common, there is little evidence of lifelong latancy. First, no P. jiroveci organisms have been found in healthy adults that have no contact with children. Second, when a person has relocated after childhood, the strain of P. jiroveci found in the immunocompromised adult is consistent with the strain found in the adult’s current environment, not the environment of his childhood. And finally, an immunocompromised adult with recurrent episodes of PCP can have several different genotypes of P. jiroveci organisms, suggesting infection and reinfection with P. jiroveci from multiple sources.

Since it is likely that P. jiroveci infections in immunocompromised adults come from their current environment, the question then becomes, from what part of their environment? Because PCP infection is so common in young children, it is quite likely that an adult’s PCP infection came from a young child. Young children are “reservoirs” of infectious P. jiroveci. Normal, healthy adults have an immune system that prevents the organism’s transfer from the children they contact, but not so with immunocompromised adults. Therefore, the best advice to adults engaging in behavior known to compromise their immune system is to stay away from children under two years of age.