(Redirected from Pneumocystis pneumonia (PCP))'''Pneumocystis'' pneumonia' ('PCP') is a form of
pneumonia caused by the yeast-like
fungal ''Pneumocystis jirovecii'' (Jirovecii is pronounced "yee row vet zee eye"). The causal agent was originally described as a protozoan and spelled ''P. jiroveci'' and prior to then was classified as a form of ''Pneumocystis carinii'', a name still in common usage.
[ A new name (''Pneumocystis jiroveci'') for ''Pneumocystis'' from humans, Stringer JR, Beard CB, Miller RF, Wakefield AE, , , Emerg Infect Dis, 2002 ][ ''Pneumocystis'' and ''Trypanosoma cruzi'': nomenclature and typifications, Redhead SA, Cushion MT, Frenkel JK, Stringer JR, , , J Eukaryot Microbiol, 2006 ] These names are discussed below. As a result, 'Pneumocystis pneumonia (PCP)' has also been known as 'Pneumocystis jiroveci[i] pneumonia' and as 'Pneumocystis carinii pneumonia', as is also explained below.
[ Chapter 34. ''Pneumocystis carinii''. In: Collier, L., Balows, A. & Sussman, M. (ed.), Topley and Wilson's Microbiology and Microbial Infections 9th ed. Arnold and Oxford Press, New York., Cushion MT ., , , , 1998 ][ Taxonomy, genetic organization, and life cycle of ''Pneumocystis carinii'', Cushion MT, , , Semin. Respir. Infect, 1998 ][ ''Pneumocystis'': unraveling the cloak of obscurity, Cushion MT, , , Trends Microbiol, 2004 ]
It is relatively rare in people with normal immune systems but common among people with
weakened
immune systems, such as premature or severely malnourished children, the elderly, and especially
AIDS patients, in whom it is most commonly observed today.
[ Sherris Medical Microbiology, Ryan KJ; Ray CG (editors), , , McGraw Hill, 2004, ISBN 0838585299 ] PCP can also develop in patients who are taking
immunosuppressant medications (e.g. patients who have undergone
solid organ transplantation) and in patients who have undergone
bone marrow transplantation.
The organism is distributed worldwide
[ Current Epidemiology of Pneumocystis Pneumonia, Morris A et al, , , Emerg Infect Dis, 2004 ][1].
Epidemiology
Pneumocystis pneumonia has been described in all continents except Antarctica.
[ It was originally described as a rare cause of pneumonia in neonates. It is believed to be an environmental organism, and human-to-human transmission is thought not to occur (although in one outbreak of 12 cases among transplant patients in Leiden it was postulated, but not proven, that human-to-human spread may have occurred).[1] Greater than 75% of children are seropositive by the age of 4, which suggest a high background exposure to the organism.]
Since the start of the HIV pandemic, PCP has been closely associated with AIDS. Because it only occurs in an immunocompromised host, it may be the first clue to a new AIDS diagnosis if the patient has no other reason to be immunocompromised (e.g. taking immunosuppressive drugs for organ transplant). An unusual rise in the number of PCP cases in North America, noticed when physicians began requesting large quantities of the rarely used antibiotic pentamidine, was the first clue to the existence of AIDS in the early 1980s.[2][3]
Prior to the development of more effective treatments, PCP was a common and rapid cause of death in persons living with AIDS. Much of the incidence of PCP has been reduced by instituting a standard practice of using oral co-trimoxazole to prevent the disease in people with CD4 counts less than 200/mm³. In populations that do not have access to preventative treatment, PCP continues to be a major cause of death in AIDS.
In immunocompromised patients (e.g. cancer patients on chemotherapy, or persons living with AIDS with a CD4+ T-cell count below 200/μl), prophylaxis with regular pentamidine inhalations or sulfamethoxazole/trimethoprim (co-trimoxazole or TMP-SMX) may be necessary to prevent PCP.
Symptoms
Symptoms of PCP include fever, non-productive cough, shortness of breath (especially on exertion), weight loss and night sweats. There is usually not a large amount of sputum with PCP unless the patient has an additional bacterial infection. The fungus can invade other visceral organs, such as the liver, spleen and kidney, but only in a minority of cases.
'X-ray of Pneumocystis jirovecii pneumonia' There is increased white (opacity) in the lower lungs on both sides, characteristic of ''Pneumocystis'' pneumonia
Pathophysiology
The risk of pneumonia due to Pneumocystis jirovecii increases when CD4 levels are less than 200 cells/μl. In these immunosuppressed individuals the manifestations of the infection are highly variable.[4] The disease attacks the interstitial, fibrous tissue of the lungs, with marked thickening of the alveolar septa and alveoli and leading to significant hypoxia which can be fatal if not treated aggressively; ergo, LDH levels increase and gas exchange is compromised. Oxygen is less able to diffuse into the blood, leading to hypoxia. Hypoxia, along with high arterial carbon dioxide (CO2) levels, stimulates ventilation, thereby causing dyspnea.
Diagnosis
The diagnosis can be confirmed by the characteristic appearance of the chest x-ray which shows widespread pulmonary infiltrates, and an arterial oxygen level (pO2) strikingly lower than would be expected from symptoms. The diagnosis can be definitively confirmed by pathologic identification of the causative organism in induced sputum or bronchial washings obtained by bronchoscopy with coloration by toluidine blue or immunofluorescence assay, which will show characteristic cysts [2].
''Pneumocystis'' infection can also be diagnosed by immunofluorescent or histochemical staining of the specimen, and more recently by molecular analysis of PCR products comparing DNA samples. Notably, simple molecular detection of ''Pneumocystis jirovecii'' in lung fluids does not mean that a person has Pneumocystis pneumonia or infection by HIV. The fungus appears to be present in healthy individuals also in the general population.[ ''Pneumocystis jiroveci''i in General Population, Medrano FJ et al, , , Emerg Infect Dis, 2005 ]
Life-cycle
The complete life-cycles of any of the species of ''Pneumocystis'' are not known, but presumably all resemble the others in the genus. The terminology follows zoological terms, rather than mycological terms, reflecting the initial misdetermination as a protozoan parasite. All stages are found in lungs and because they cannot be cultured, direct observation of living ''Pneumocystis'' is difficult. The trophozoite stage is the vegetative state. It is single-celled and appears amoeboid (multilobed) and closely associated with host cells. Globular cysts eventually form that have a thicker wall. Within these ascus-like cysts, eight spores form which are released through rupture of the cyst wall. The cysts often collapse forming crescent-shaped bodies visible in stained tissue. It is not known for certain if meiosis takes place within the cysts, or what the genetic status is of the various cell types - see DPDx life-cycle diagram.
Treatment
Antipneumocystic medication is used with concomitant steroids in order to avoid inflammation, which causes an exacerbation of symptoms about four days after treatment begins if steroids are not used. By far the most commonly used medication is a combination of trimethoprim and sulfamethoxazole (co-trimoxazole, with the tradenames Bactrim, Septrin, or Septra), but some patients are unable to tolerate this treatment due to allergies. Other medications that are used, alone or in combination, include pentamidine, trimetrexate, dapsone, atovaquone, primaquine, and clindamycin. Treatment is usually for a period of about 21 days.
Pentamidine is less often used as its major limitation is the high frequency of side effects. These include acute pancreatitis, renal failure, hepatotoxicity, leukopenia, rash, fever and hypoglycaemia.
Nomenclature
The name ''P. jirovecii'', to distinguish the organism found in humans from physiological variants of ''Pneumocystis'' found in other animals, was first proposed in 1976, in honor of Otto Jirovec, who described ''Pneumocystis'' pneumonia in humans in 1952. After DNA analysis showed significant differences in the human variant, the proposal was made again in 1999 and has come into common use; ''P. carinii'' still describes the species found in rats
The term PCP, which was widely used by practitioners and patients, has been retained for convenience, with the rationale that it now stands for the more general 'P'neumo'c'ystis 'p'neumonia rather than 'P'neumocystis 'c'arinii 'p'neumonia.
History
The earliest report of this genus appears to have been that of Carlos Chagas in 1909[ Neue Trypanosomen, Chagas C, , , Vorläufige Mitteilung. Arch. Schiff. Tropenhyg., 1909 ] who discovered it in experimental animals but confused it with part of the life-cycle of ''Trypanosoma cruzi'' (causal agent of Chagas Disease) and later called both organisms '' 'Schizotrypanum cruzi' '' a form of trypanosome infecting humans[ Nova tripanozomiase humana: Estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem, Chagas C, , , Mem Inst Oswaldo Cruz, 1909 ] The rediscovery of ''Pneumocystis'' cysts was reported by Antonio Carini in 1910 also in Brazil.[ Formas des eschizogonia do ''Trypanosoma lewisi''., Carini A., , , Soc Med Cir São Paulo, 1910 ] The genus was again discovered in 1912 by Delanoë and Delanoë this time at the Pasteur Institute in Paris, France who found it in rats and who proposed the genus and species name ''Pneumocystis carinii'' after Carini.[ Sur les rapports des kystes de Carini du poumon des rats avec le ''Trypanosoma lewisi''., Delanoë P, Delanoë M., , , Comptes rendus de l’Academie des sciences., 1912 ]
''Pneumocystis'' was redescribed as a human pathogen in 1942 by two Dutch investigators, van der Meer and Brug who found it in three new cases: a 3-month-old infant with congenital heart disease and in 2 of 104 autopsy cases - a 4-month-old infant and a 21-year-old adult.[ Infection à ''Pneumocystis'' chez l’homme et chez les animaux., van der Meer MG, Brug SL., , , Amer Soc Belge Méd Trop, 1942 ] There being only one described species in the genus, they considered the human parasite to be ''P. carinii''. Nine years later (1951) Dr. Josef Vanek at Karls-Universität in Prague, Czechoslovakia showed in a study of lung sections from sixteen children that the organism labelled "''P. carinii''" was the causative agent of pneumonia in these children.[ Atypicka (interstitiálni) pneumonie detí vyvolaná ''Pneumocystis carinii'' (Atypical interstitial pneumonia of infants produced by ''Pneumocystis carinii'')., Vanek J., , , Casop lék cesk, 1951 ] The following year (1952) Jírovec reported "''P. carinii''" as the cause of interstitial pneumonia in neonates.[ ''Pneumocystis carinii'' puvodce t. zv intertitialnich plasmocelularnich pneumonii kojencw (''Pneumocystis carinii'', the cause of interstitial plasmacellular pneumonia in neonates), Jírovec O., , , P Csl. Hyg epid mikrob, 1952 ][ Interstitial plasma cell pneumonia in infants., Vanek J, Jírovec O, Lukes J., , , Ann Paediatrici, 1953 ][ ''Pneumocystis carinii''; etiologic agent of interstitial plasma cell pneumonia of premature and young infants., Gajdusek DC, , , Pediatrics, 1957 ] Following the realization that ''Pneumocystis'' from humans could not infect experimental animals such as rats, and that the rat form of ''Pneumocystis'' differed physiologically and had different antigenic properties, Frenkel[ ''Pneumocystis jiroveci'' n. sp. from man: morphology, physiology, and immunology in relation to pathology, Frenkel JK, , , Natl Cancer Inst Monogr, 1976 ] was the first to recognize the human pathogen as a distinct species. He named it ''Pneumocystis jirovecii'' (see nomenclature above). There has been controversy over the relabeling of ''P. carinii'' in humans as ''P. jirovecii'',[ ''Pneumocystis carinii'': has the name really been changed?, Gigliotti F, , , Clin Infect Dis, 2005 ][ which is why both names still appear in publications. However, only the name ''P. jirovecii'' is used exclusively for the human pathogen, whereas the name ''P. carinii'' has had a broader application to many species.][ Responsibility in naming pathogens: the case of Pneumocystis jirovecii, the causal agent of pneumocystis pneumonia, Hawksworth DL, , , Lancet Infect. Dis., 2007 ] Frenkel and those before him, believed that all ''Pneumocystis'' were protozoans, but soon afterwards evidence began accumulating that ''Pneumocystis'' was a fungal genus. Recent studies show it to be an unusual, in some ways a primitive genus of Ascomycota, related to a group of yeasts.[ Reconstructing the early evolution of Fungi using a six-gene phylogeny, James TY et al, , , Nature, 2006 ] Every tested primate, including humans, appears to have their own type of ''Pneumocystis'' that is incapable of cross-infecting other host species and has co-evolved with each mammal species.[ Phylogenetic systematics and evolution of primate-derived ''Pneumocystis'' based on mitochondrial or nuclear DNA sequence comparison, Hugot J, Demanche C, Barriel V, Dei-Cas E, Guillot J, , , Syst Biol, 2003 ] Currently only 5 species have been formally named: ''P. jirovecii'' from humans, ''P. carinii'' as originally named from rats, ''P. murina'' from mice,[ Phylogenetic identification of ''Pneumocystis murina'' sp. nov., a new species in laboratory mice, Keely S, Fischer J, Cushion M, Stringer J, , , Microbiology, 2004 ] ''P. wakefieldiae''[ Molecular and phenotypic description of Pneumocystis wakefieldiae sp. nov., a new species in rats, Cushion MT, Keely SP, Stringer JR, , , Mycologia, 2004 ][ Validation of the name Pneumocystis wakefieldiae, Cushion MT, Keely SP, Stringer JR, , , Mycologia, 2005 ] also from rats, and ''P. oryctolagi'' from rabbits.[ Pneumocystis oryctolagi sp. nov., an uncultured fungus causing pneumonia in rabbits at weaning: review of current knowledge, and description of a new taxon on genotypic, phylogenetic and phenotypic bases, Dei-Cas E et al, , , FEMS Micriobiol. Rev., 2006 ]
Historical and even recent reports of ''P. carinii'' from humans are based upon older classifications (still used by many, or those still debating the recognition of distinct species in the genus ''Pneumocystis'') which does not mean that the true ''P. carinii'' from rats actually infects humans. In an intermediate classification system, the various taxa in different mammals have been called formae speciales or forms. For example the human "form" was called ''Pneumocystis carinii'' f. [or f. sp.] ''hominis'', while the original rat infecting form was called ''Pneumocystis carinii'' f. [or f. sp.] ''carinii''. This terminology is still used by some researchers. The species of ''Pneumocystis'' species originally seen by Chagas have not yet been named as distinct species.[ Many other undescribed species presumably exist and those that have been detected in many mammals are only known from molecular sample detection from lung tissue or fluids, rather than by direct physical observation.][ Phylogeny of ‘’Pneumocystis carinii’’ from 18 primate species confirms host specificity and suggests coevolution, Demanche C et al, , , J. Clinical Microbiol., 2001 ] As of yet, they are cryptic taxa.
Pneumocystis Genome Project
''Pneumocystis'' species cannot be grown in culture. Therefore, there is a limitation to the availability of the human disease causing agent, ''P. jirovecii''. Hence, investigation of the whole genome of a ''Pneumocystis'' is largely based upon true ''P. carinii'' available from experimental rats which can be maintained with infections. The project is described in the site linked here. Genetic material of other species, such as ''P. jirovecii'' can be compared to the genome of ''P. carinii''.
Pneumocystis Genome Project
References
1. An outbreak of Pneumocystis jiroveci pneumonia with 1 predominant genotype
among renal transplant recipients: interhuman transmission or a common environmental source?, de Boer M, Bruijnesteijn van Coppenraet L, Gaasbeek A, ''et al.'', , , Clin Infect Dis, 2007
2. A Cluster of Kaposi's Sarcoma and ''Pneumocystis carinii'' pneumonia among homosexual male residents of Los Angeles and Range Counties, California, Fannin S, Gottlieb MS, Weisman JD, ''et al.'', , , MMWR Weekly, 1982
3. An outbreak of community-acquired Pneumocystis carinii pneumonia, Masur H, Michelis MA, Greene JB, ''et al.'', , , N Engl J Med, 1981
4. Pneumocystis Carinii. ''In:'' Barron's Medical Microbiology ''(Barron S ''et al'', eds.), Hughes WT, , , Univ of Texas Medical Branch, 1996, (via NCBI Bookshelf) ISBN 0-9631172-1-1
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