Pneumocystis pneumonia

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For patient information click here Template:DiseaseDisorder infobox Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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.[1][2] 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.[3][4][5]

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.[6] 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[7][2].

Epidemiology

Pneumocystis pneumonia has been described in all continents except Antarctica.[7] 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).[8] 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.[9][10]

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.

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.[11] 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 [3].

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.[12]

X-ray of Pneumocystis jirovecii pneumonia There is increased white (opacity) in the lower lungs on both sides, characteristic of Pneumocystis pneumonia

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.

Guidelines

To read about guidelines for prevention and treatment of Pneumocystis pneumonia Infections in HIV-Infected Adults and Adolescents, click here.

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[1] and that name is typified by an isolate from rats.[2] The International Code of Botanical Nomenclature (ICBN) requires that the name to be spelled jirovecii rather than jiroveci. The latter spelling originated when Pneumocystis was believed to be a protozoan, rather than a fungus, and therefore was spelled using the International Code of Zoological Nomenclature; both spellings are commonly used. A change in the ICBN in 2005 now recognizes the validity of the 1976 publication, making the 1999 proposal redundant, and cites Pneumocystis and P. jirovecii as examples of the change in ICBN Article 45, Ex 8. The name P. jirovecii is typified (both lectotypified and epitypified) by samples from human autopsies dating from the 1960s.[2]

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 Pneumocystis pneumonia rather than Pneumocystis carinii pneumonia.

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. ↑ 1.0 1.1 Stringer JR, Beard CB, Miller RF, Wakefield AE (2002). "A new name (Pneumocystis jiroveci) for Pneumocystis from humans". Emerg Infect Dis. 8 (9): 891–6. PMID 12194762.
  2. ↑ 2.0 2.1 2.2 Redhead SA, Cushion MT, Frenkel JK, Stringer JR (2006). "Pneumocystis and Trypanosoma cruzi: nomenclature and typifications". J Eukaryot Microbiol. 53 (1): 2–11. PMID 16441572.
  3. ↑ Cushion MT . (1998). "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": 645–683.
  4. ↑ Cushion MT (1998). "Taxonomy, genetic organization, and life cycle of Pneumocystis carinii". Semin. Respir. Infect. 13 (4): 304–312.
  5. ↑ Cushion MT (2004). "Pneumocystis: unraveling the cloak of obscurity". Trends Microbiol. 12 (5): 243–249.
  6. ↑ Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology (4th ed. ed.). McGraw Hill. ISBN 0838585299.
  7. ↑ 7.0 7.1 Morris A; et al. (2004). "Current Epidemiology of Pneumocystis Pneumonia". Emerg Infect Dis. 10 (10): 1713–1720. PMID 15504255.
  8. ↑ de Boer M, Bruijnesteijn van Coppenraet L, Gaasbeek A; et al. (2007). "An outbreak of Pneumocystis jiroveci pneumonia with 1 predominant genotype among renal transplant recipients: interhuman transmission or a common environmental source?". Clin Infect Dis. 44 (9): 1143&ndash, 49. PMID 17407029. line feed character in |title= at position 79 (help)
  9. ↑ Fannin S, Gottlieb MS, Weisman JD; et al. (1982). "A Cluster of Kaposi's Sarcoma and Pneumocystis carinii pneumonia among homosexual male residents of Los Angeles and Range Counties, California". MMWR Weekly. 31 (32): 305&ndash, 7.
  10. ↑ Masur H, Michelis MA, Greene JB; et al. (1981). "An outbreak of community-acquired Pneumocystis carinii pneumonia". N Engl J Med. 305: 1431–8.
  11. ↑ Hughes WT (1996). Pneumocystis Carinii. In: Barron's Medical Microbiology (Barron S et al, eds.) (4th ed. ed.). Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1.
  12. ↑ Medrano FJ; et al. (2005). "Pneumocystis jirovecii in General Population". Emerg Infect Dis. 11 (2): 245–250. PMID 15752442.

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