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Considered to have an intermediate and isolated position between Basidiomycota and Ascomycota, the genus Pneumocystis was recently classified in class Archiascomycetes, phylum Ascomycota together with Schizosaccharomyces .
Initially reported by Chagas in 1909 as a morphologic form of Trypanosoma cruzi, this microorganism later proved to be a separate genus and was named Pneumocystis carinii. Pneumocystis carinii was classified as a protozoan until late 1980s. The reasons that led to this classification were its morphologic features that were similar to those of protozoa, the lack of ergosterol in its cell membrane and the resulting resistance to ergosterol biosynthesis inhibitors, favorable activity of some anti-protozoal drugs against Pneumocystis, and the inability to grow this microorganism on routine laboratory media.
It was in 1988 when a complete revision of Pneumocystis taxonomy appeared to be mandatory following rRNA analysis. The molecular data demonstrated that despite the absence of ergosterol and the lack of growth in culture, rRNA and mitochondrial sequence of Pneumocystis were homologous to those of the fungi. There were additional features that suggested the validity of this new taxonomy; ultrastructural features similar to those of fungi, presence of ß-1,3 D-glucan in its cell wall, favorable activity of glucan synthesis inhibitors against Pneumocystis, existence of lamellar cristae in its mitochondria, presence of elongation factor-3 which is unique to fungi, presence of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) as distinct proteins in a fashion homologous to the situation for Saccharomyces cerevisiae and as opposed to TS and DHFR being a single protein in protozoa, cross-reactivity of its monoclonal antibodies with fungi, and the similarity between its sporogenous state and the ascospore formation in some yeasts . Although it took some time for the new taxonomy to be accepted, Pneumocystis is now classified as a fungus, not a protozoan.
Pneumocystis can infect humans and animals, including rat, ferret, mouse, horse, pig, and rabbit. Genetic variations and DNA sequence polymorphisms are often observed, suggesting the existence of numerous strains even in a single species of Pneumocystis [999, 2350]. The natural habitats of Pneumocystis and the modes of transmission of Pneumocystis infections in humans are areas of current interest. Pneumocystis DNA was detected in air and water [393, 2349]. However, the organism could not be visualized by microscopic examination of the environmental samples. These data may suggest that the free forms of Pneumocystis may survive in the environment long enough to infect a susceptible host. However, there is little information on this at present. There appears to be three sources for human Pneumocystis infections which may also serve as the reservoir of the organism; patients infected with Pneumocystis, immunosuppressive patients colonized with Pneumocystis, and immunocompetent individuals transiently parasitized with Pneumocystis. As stated in more detail below, human and non-human Pneumocystis species have been shown to be different and host-specific, now disproving the idea of transmission of the infection from animals to humans [550, 2181].
The name Pneumocystis carinii was assigned to the organism within a few years following the initial report by Chagas. This name by then referred wholely to a newly defined species. However, further work revealed that Pneumocystis from humans and other animals are quite different and there are multiple species in this genus. First, the analysis of protein sizes showed that the organism tends to be host-specific. This was followed by suggestion of the name Pneumocystis jiroveci (pronounced as ""yee row vet zee") in 1976 by Frenkel for the Pneumocystis species isolated from humans. However, this name did not gain acceptance when first proposed. Later and more recently obtained DNA analysis data confirmed that human-derived samples of Pneumocystis contained the DNA of only P. jiroveci and the name P. jiroveci was re-proposed by Frenkel in 1999 to indicate the Pneumocystis infecting humans .
P. jiroveci has garnered some initial acceptance , but it does have its drawbacks. First, it is not clear that this name actual has priority over some other plausible alternatives . Second, the introduction of a new name for a well-established species can be associated with significant confusion rather producing clarity. Third, it appears that the name is formed incorrectly. International Code of Botanical Nomenclature (ICBN) Article 60C.1(b) states that "If the personal name ends with a consonant (except -er), substantive epithets are formed by adding -i- (stem augmentation) plus the genitive inflection appropriate to the sex and number of the person(s) honoured (e.g. lecard-ii for Lecard (m), wilson-iae for Wilson (f), verlot-iorum for the Verlot brothers, braun-iarum for the Braun sisters)." Thus, Dr. Otto Jirovec's name would become 'jirovecii'. Finally, there is nothing yet published by ICBN that suggests that this name change has been formally accepted. We'll all have to wait and see how this one turns out! Although we did for a time support this new nomenclature without caveat, it now appears more appropriate to use to use "P. carinii (P. jirovecii?)" as a reminder of the current state of confusion.
P. carinii is the most widely used name for Pneumocystis from humans. P. jiroveci or, perhaps more correctly P. jirovecii (see above), has been proposed as an alternative.
Pneumocystis carinii is still the correct name for this organism when found in hosts other than man.
Pneumocystis is one of the major causes of opportunistic mycoses in immunocompromised patients, including those with congenital immunodeficiencies, AIDS, and cases receiving prolonged corticosteroid therapy for any underlying pathology or intensive immunosuppressive therapy for treatment of cancer or prevention of transplant rejection [444, 497, 509, 523, 641, 1213, 1568, 1955, 2065, 2078].
P. carinii (P. jirovecii?) infections, referred to overall as pneumocystosis, are observed in four clinical forms; asymptomatic infections, infantile (interstitial plasma cell) pneumonia, pneumonia in immunocompromised host, and extrapulmonary infections. Pneumonia due to Pneumocystis is frequently labeled with the acronym PCP. This acronym can be retained despite the proposed change in the species name if it is taken to refer to Pneumocystis pneumonia .
Infantile pneumonia is epidemic in origin and mostly encountered in premature and malnourished infants. Pneumonia of immunocompromised host, on the other hand, is sporadic and may affect any host with a congenital or acquired immunodeficiency, including agammaglobulinemia, severe combined immunodeficiency syndrome (SCID), AIDS, and the use of intensive chemotherapy for various reasons. Although the incidence of Pneumocystis pneumonia in patients with AIDS has been in decline [1571, 2037] particularly after the introduction of HAART (highly active antiretroviral therapy) in 1996, it is still among the most significant AIDS-related diseases. Cellular immunodeficiency stands as the major predisposing factor for development of Pneumocystis infections . Extrapulmonary infections result from dissemination of the infection from lungs to other organs, including lymph nodes, spleen, bone marrow, liver, kidneys, heart, brain, pancreas, skin, and other organs. These infections are encountered in patients with AIDS. The mechanism of dissemination of the infection is yet unclear [550, 1244].
Beyond these clinical pictures, recent data suggest that Pneumocystis infection may be associated with sudden infant death syndrome (SIDS) .
A number of investigators have attempted to cultivate and grow the primary isolates of Pneumocystis extracted from mammalian hosts by using monolayer cell tissue cultures and artifical media. However only a limited replication could be provided following inoculation and the growth of the organism declined after few passages in these systems . This lack of maintanence on monolayer-based and cell-free systems is one of the significant limitations of Pneumocystis research.
The life cycle and morphology of Pneumocystis still remain poorly understood. This primarily originates from the lack of a reliable, long-term culture system for growing the organism. The related available information is mostly derived from histochemical and ultrastructural analysis of the lung tissue of rodents (experimental model) and infected human.
The presumed life cycle of Pneumocystis includes an asexual and a sexual growth phase. Current knowledge suggests that the trophic (trophozoite) forms are produced during asexual development. These forms are usually pleomorphic and found in clusters. They are probably capable of replicating asexually by binary fission. These haploid trophic forms also replicate sexually. By conjugation, they produce a diploid zygote which undergoes meiosis and subsequent mitosis, resulting in the formation of a precyst initially, and then an early cyst and a mature cyst eventually. During differentiation of the organism from precyst to mature cyst, 8 intracystic spores or "daughter cells" are produced. These intracystic spores are subsequently released as the mature cyst ruptures and develop into trophic forms. Several points, including whether this cycle is relevant in the environment and/or within the infected host, the factors that trigger the sexual and asexual reproduction and release of the intracystic spores remain unclarified  .
A foamy eosinophilic material is observed in the lungs during Pneumocystis infection. This material is composed of masses of the organism, alveolar macrophages, desquamated epithelial alveolar cells, polymorphonuclear leukocytes, adhesive matrix glycoproteins, surfactant components, immunoglobulins, and other host proteins [462, 769]. Gomoris methenamine silver (GMS) and Giemsa stain may be used for microscopic visualization of Pneumocystis. Flourescence antibody staining technique is now frequently used for this purpose with high efficacy . Polymerase chain reaction (PCR)  also appears to be useful in diagnosis of PCP.
Based on the lack of growth in artificial media, standard vitro antifungal susceptibility testing methods are not applicable. However, novel methods; such as a quantitative broth microdilution technique comparing the total number of microorganisms in treated and drug-free cultures by using Giemsa staining has been employed. Using this method, sordarins have been found to be significantly more potent than pentamidine, atovaquone, and TMP-SMX against Pneumocystis . In vitro activity of sordarins has been determined by measuring the inhibition of the uptake and incorporation of radiolabelled methionine into newly synthesized proteins as well . By this method, sordarins again proved very efficacious in vitro against Pneumocystis . Importantly, mutations observed in Pneumocystis dihydropteorate synthase (DHPS) gene suggest the emergence of resistance to sulfa drugs in a number of Pneumocystis strains .
Trimethroprim-sulfamethoxazole is the drug of choice for treatment and prophylaxis of Pneumocystis infections. Pentamidine and atovaquone are the alternative therapeutic agents. Importantly and promisingly, echinocandins [1102, 1839], sordarins [144, 1451] and azasordarins  appear efficacious in treatment of pneumocystosis in animal models. One of the novel echinocandins, micafungin has been found to be effective in prevention of PCP in mice by inhibiting the cyst wall formation (with no activity against trophozoite proliferation) .
Of note, terbinafine has been found to be efficacious in treatment of pneumocystosis in animal models . Also, IFN-gamma and trimethoprim/sulfamethoxazole have proven to be synergistic in treatment of PCP in rats  and mice .
PubMed search for P. carinii
PubMed search for P. jiroveci
PubMed search for P. jirovecii
GenBank search for P. carinii
GenBank search for P. jiroveci
GenBank search for P. jirovecii
144. Aviles, P., E. M. Aliouat, A. Martinez, E. Dei-Cas, E. Herreros, L. Dujardin, and D. Gargallo-Viola. 2000. In vitro pharmacodynamic parameters of sordarin derivatives in comparison with those of marketed compounds against Pneumocystis carinii isolated from rats. Antimicrob. Agents Chemother. 44:1284-1290.
393. Casanova-Cardiel, L., and M. J. Leibowitz. 1997. Presence of Pneumocystis carinii DNA in pond water. J Eukaryot Microbiol. 44 (Suppl.):28.
444. Cisneros, J. M., P. Munoz, J. Torre-Cisneros, M. Gurgui, M. J. Rodriguez-Hernandez, J. M. Aguado, and A. Echaniz. 1998. Pneumonia after heart transplantation: A multiinstitutional study. Clin Infect Dis. 27:324-331.
462. Collier, L., A. Balows, and M. Sussman. 1998. Topley & Wilson's Microbiology and Microbial Infections, 9th ed, vol. 4. Arnold, London, Sydney, Auckland, New York.
469. Contini, C., E. Angelici, and R. Canipari. 1999. Structural changes in rat Pneumocystis carinii surface antigens after terbinafine administration in experimental P. carinii pneumonia. J Antimicrob Chemother. 43:301-304.
497. Cunha, B. A. 2001. Pneumonias in the compromised host. Infect Dis Clin N Amer. 15:591-612,X.
509. Danes, C., J. Gonzalez-Martin, T. Pumarola, A. Rano, N. Benito, A. Torres, A. Moreno, M. Rovira, and J. P. de la Bellacasa. 2002. Pulmonary infiltrates in immunosuppressed patients: Analysis of a diagnostic protocol. J Clin Microbiol. 40:2134-2140.
523. De Bock, R., and A. Z. Middelheim. 2000. Febrile neutropenia in allogeneic transplantation. Int J Antimicrobial Agents. 16:177-180.
531. de Hoog, G. S., J. Guarro, J. Gene, and M. J. Figueras. 2000. Atlas of Clinical Fungi, 2nd ed, vol. 1. Centraalbureau voor Schimmelcultures, Utrecht, The Netherlands.
550. Dei-Cas, E. 2000. Pneumocystis infections: the iceberg? Med. Mycol. 38 (Suppl. I):23-32.
641. Dykewicz, C. A., H. W. Jaffe, and J. E. Kaplan. 2000. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients - Recommendations of CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplation. Biol Blood Marrow Transplant. 6:659-713,715,717-727.
769. Frenkel, J. K. 1999. Pneumocystis pneumonia, an immunodeficiency-dependent disease: a critical historical overview. J Eukaryot Microbiol. 46 (Suppl.):89-92.
999. Hauser, P. M., D. S. Blanc, J. Bille, and P. Francioli. 1998. Typing methods to approach Pneumocystis carinii genetic heterogeneity. FEMS Immunol Med Microbiol. 22:27-35.
1020. Helweg-Larsen, J., T. L. Benfield, J. Eugen-Olsen, J. D. Lundgren, and B. Lundgren. 1999. Effects of mutations in Pneumocystis carinii dihydropteorate synthase gene on outcome of AIDS-associated P. carinii pneumonia. Lancet. 354:1347-1351.
1040. Herreros, E., C. M. Martinez, M. J. Almela, M. S. Marriott, F. G. De Las Heras, and D. Gargallo-Viola. 1998. Sordarins: in vitro activities of new antifungal derivatives against pathogenic yeasts, Pneumocystis carinii, and filamentous fungi. Antimicrob. Agents Chemother. 42:2863-9.
1081. Hughes, W. T. 2003. Pneumocystis carinii vs. Pneumocystis jiroveci: another misnomer (response to Stringer et al.). Emerg Infect Dis. 9:276-7; author reply 277-9.
1102. Ito, M., R. Nozu, T. Kuramochi, N. Eguchi, S. Suzuki, K. Hioki, T. Itoh, and F. Ikeda. 2000. Prophylactic effect of FK463, a novel antifungal lipopeptide, against Pneumocystis carinii infection in mice. Antimicrob. Agents Chemother. 44:2259-2262.
1123. Jimenez, E., A. Martinez, E. M. Aliouat, J. Caballero, E. Dei-Cas, and D. Gargallo-Viola. 2002. Therapeutic efficacies of GW471552 and GW471558, two new azasordarin derivatives, against pneumocystosis in two immunosuppressed-rat models. Antimicrob. Agents Chemother. 46:2648-2650.
1213. Klein, N. C., C. H. U. Go, and B. A. Cunha. 2001. Infections associated with steroid use. Infect Dis Clin N Amer. 15:423-432,VIII.
1244. Koziel, H. 2002. Pneumocystis carinii, p. 227-260. In R. A. Calderone and R. L. Cihlar (ed.), Fungal Pathogenesis-Principles and Clinical Applications. Marcel Dekker, Inc., New York.
1451. Martinez, A., P. Aviles, E. Jimenez, J. Caballero, and D. Gargallo-Viola. 2000. Activities of sordarins in experimental models of candidiasis, aspergillosis, and pneumocystosis. Antimicrob. Agents Chemother. 44:3389-3394.
1452. Martinez, A., and J. A. Kovacs. 1993. Development and characterization of a rapid screening assay for identifying antipneumocystis agents. Antimicrob. Agents Chemother. 37:1674-8.
1568. Montoya, J. G., L. F. Giraldo, B. Efron, E. B. Stinson, P. Gamberg, S. Hung, N. Giannetti, J. Miller, and J. S. Remington. 2001. Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center. Clin Infect Dis. 33:629-640.
1571. Moore, R. D., and R. E. Chaisson. 1996. Natural history of opportunistic disease in an HIV-infected urban clinical cohort. Ann. Intern. Med. 124:633-42.
1765. Pesanti, E. L. 1991. Interaction of cytokines and alveolar cells with Pneumocystis carinii in vitro. J. Infect. Dis. 163:611-6.
1839. Powles, M. A., P. Liberator, J. Anderson, Y. Karkhanis, J. F. Dropinski, F. A. Bouffard, J. M. Balkovec, H. Fujioka, M. Aikawa, D. McFadden, and D. Schmatz. 1998. Efficacy of MK-991 (L,743,872), a semisynthetic pneumocandin, in murine models of Pneumocystis carinii. Antimicrob. Agents Chemother. 42:1985-1989.
1891. Reiss, E., K. Tanaka, G. Bruker, V. Chazalet, D. Coleman, J. P. Debeaupuis, R. Hanazawa, J. P. Latge, J. Lortholary, K. Makimura, C. J. Morrison, S. Y. Murayama, S. Naoe, S. Paris, J. Sarfati, K. Shibuya, D. Sullivan, K. Uchida, and H. Yamaguchi. 1998. Molecular diagnosis and epidemiology of fungal infections. Med Mycol. 36:249-257.
1955. Rolston, K. V. I. 2001. The spectrum of pulmonary infections in cancer patients. Curr Opin Oncol. 13:218-223.
2037. Sax, P. E. 2001. Opportunistic infections in HIV disease: Down but not out. Infect Dis Clin N Amer. 15:433-455,VIII,IX.
2065. Scroggs, M. W., J. A. Wolfe, R. R. Bollinger, and F. Sanfilippo. 1987. Causes of death in renal transplant recipients. A review of autopsy findings from 1966 through 1985. Arch Pathol Lab Med. 111:983-7.
2078. Sepkowitz, K. A. 2002. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin Infect Dis. 34:1098-1107.
2090. Shear, H. L., G. Valladares, and M. A. Narachi. 1990. Enhanced treatment of Pneumocystis carinii pneumonia in rats with interferon-gamma and reduced doses of trimethoprim/sulfamethoxazole. Journal of Acquired Immune Deficiency Syndromes. 3:943-8.
2094. Shin, D. W., D. Y. Kang, Y. H. Lee, Y. E. Na, and K. J. Yun. 1992. [Study on the therapeutic effects of interferon and gamma-globulin in experimental Pneumocystis carinii pneumonia]. Kisaengchunghak Chapchi - Korean Journal of Parasitology. 30:219-26.
2181. Stringer, J. R., C. B. Beard, R. F. Miller, and A. E. Wakefield. 2002. A new name (Pneumocystis jiroveci) for Pneumocystis from humans. Emerging Infectious Diseases. 8:891-896.
2295. Vargas, S. L., C. A. Ponce, W. T. Hughes, A. E. Wakefield, J. C. Weitz, S. Donoso, A. V. Ulloa, P. Madrid, S. Gould, J. J. Latorre, R. Avila, S. Benveniste, M. Gallo, J. Belletti, and R. Lopez. 1999. Association of primary Pneumocystis carinii infection and sudden infant death syndrome. Clin Infect Dis. 29:1489-1493.
2349. Wakefield, A. E. 1996. DNA sequences identical to Pneumocystis carinii f. sp. carinii and Pneumocystis carinii f. sp. hominis in samples of air spora. J Clin Microbiol. 1996:1754-1759.
2350. Wakefield, A. E., J. R. Stringer, E. Tamburrini, and E. Dei-Cas. 1998. Genetics, metabolism and host specificity of Pneumocystis carinii. Med Mycol. 36:183-193.