A new name for Pneumocystis from humans - Pneumocystis jiroveci - Perspective

Emerging Infectious Diseases, Sept, 2002 by James R. Stringer, Charles B. Beard, Robert F. Miller, Ann E. Wakefield

The disease known as Pneumocystis carinii pneumonia (PCP) is a major cause of illness and death in persons with impaired immune systems. While the genus Pneumocystis has been known to science for nearly a century, understanding of its members remained rudimentary until DNA analysis showed its extensive diversity. Pneumocystis organisms from different host species have very different DNA sequences, indicating multiple species. In recognition of its genetic and functional distinctness, the organism that causes human PCP is now named Pneumocystis jiroveci Frenkel 1999. Changing the organism's name does not preclude the use of the acronym PCP because it can be read "Pneumocystis pneumonia." DNA sequence variation exists among samples of P. jiroveci, a feature that allows reexamination of the relationships between host and pathogen. Instead of lifelong latency, transient colonization may be the rule.

**********

Clinical Importance of Pneumocystis

The disease known as Pneumocystis carinii pneumonia (PCP) is one of the leading causes of illness and death in persons with impaired immunity. The disease has been described in immunocompromised patients for many years, including outbreaks in malnourished young children in orphanages in Iran in the 1950s (1-6). The AIDS epidemic, however, marked the beginning of the disease's impact on a substantial number of patients. PCP has long been the most common serious AIDS-defining opportunistic infection in the United States. The introduction of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has been accompanied by substantial reductions in mortality and the incidence of opportunistic infections, including PCP (7). Despite these advances, Pneumocystis remains a major pathogen in HIV-infected persons who either are not receiving or are not responding to HAART and among those who are unaware of their HIV status. PCP is also of clinical importance in people immunocompromised for reasons other than HIV, such as organ transplantation or chemotherapy for malignant diseases (8). In addition, Pneumocystis infection has been documented recently in persons who are mildly immunocompromised, including those with chronic lung disease (9).

Need for a Change in Nomenclature

Pneumocystis organisms were first reported by Chagas in 1909 (10), but he mistook them for a morphologic form of Trypanosoma cruzi. Within a few years of this first report, further studies established that the microbe in question was not a trypanosome but a new species altogether, named Pneumocystis carinii (11).

From the time of its discovery, until late in the 1980s, Pneumocystis was widely thought to be a protozoan. These views were based on several criteria: 1) strong similarities in microbe morphology and host pathology, 2) absence of some phenotypic features typical of fungi, 3) presence of morphologic features typical of protozoa, 4) ineffectiveness of antifungal drugs, and 5) effectiveness of drugs generally used to treat protozoan infections. Some investigators pointed out that Pneumocystis organisms exhibit morphologic similarities to fungi (2). Nevertheless, the protozoan hypothesis remained predominant until 1988, when DNA analysis demonstrated that Pneurnocystis is a fungus, albeit an odd one, lacking in ergosterol and very difficult to grow in culture (12,13).

Soon after the proper classification of Pneumocystis had been determined at the kingdom level, additional DNA data showed that Pneurnocystis organisms in different mammals are quite different. These data led to interim name changes (14), but it was not until 1999 that the first valid new binomial appeared. The organism that causes human PCP is now named Pneumocystis jiroveci Frenkel 1999 (pronounced "yee row vet zee"), in honor of the Czech parasitologist Otto Jirovec, who is credited with describing the microbe in humans (15). The primary purpose of this article is to explain what led to the name change and why the new name is necessary, useful, and workable for all concerned. For a more extensive review of the systematics and nomenclature of Pneumocystis, see Stringer's review of workshops on the subject (16). The DNA sequence information that led to the renaming of Pneumocytsis organisms also provided the tools needed to better understand the relationships between these microbes and the hosts they inhabit. Thus, the secondary purpose of this article is to summarize data on these relationships, focusing on current views on the relationship between P. jiroveci and humans.

Complexity of the Genus

One reason that a definitive nomenclature has been slow to develop is that Pneumocystis organisms have been difficult to study. Attempts to develop an in vitro culture system have had limited success. Cultivation of Pneumocystis organisms in vitro requires a large seed population and supports rather modest increases in organism number for a very limited period of time (17). An exception to the rule was recently reported (18); however, this method has not been established in other laboratories. The fastidiousness of Pneumocystis organisms greatly hampered early efforts to understand them. Fortunately, advances in DNA analysis technology allowed progress in the absence of a robust culture system.