Everything about Pneumocystis totally explained
Pneumocystis pneumonia (
PCP) is a form of
pneumonia caused by the yeast-like
fungus,
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. 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. |
ICD9 = |
ICDO = |
Image = Pneumocystis.jpg |
Caption =
Pneumocystis jirovecii cysts from bronchoalveolar lavage, stained with
Toluidin blue O stain |
OMIM = |
OMIM_mult = |
MedlinePlus = 000671 |
eMedicineSubj = med |
eMedicineTopic = 1850 |
DiseasesDB = 10160 |
MeshID = D011020 |
}}
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's most commonly observed today. PCP can also develop in patients who are taking
immunosuppressant medications (for example patients who have undergone
solid organ transplantation) and in patients who have undergone
bone marrow transplantation.
The organism is distributed worldwide
(External Link
).
Epidemiology
Pneumocystis pneumonia has been described in all continents except Antarctica. 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 (for example 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.
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 don't have access to preventive treatment, PCP continues to be a major cause of death in AIDS.
In
immunocompromised patients (for example 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. 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; therefore,
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 (CO
2) 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 (pO
2) 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
(External Link).
Pneumocystis infection can also be diagnosed by
immunofluorescent or
histochemical staining of the specimen, and more recently by molecular analysis of
polymerase chain reaction products comparing
DNA samples. Notably, simple molecular detection of
Pneumocystis jirovecii in lung fluids doesn't 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.
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 can't 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 isn't 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 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. The rediscovery of
Pneumocystis cysts was reported by
Antonio Carini in 1910 also in
Brazil. 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.
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. 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. The following year (1952) Jírovec reported "
P. carinii" as the cause of
interstitial pneumonia in
neonates. Following the realization that
Pneumocystis from humans couldn't infect experimental animals such as rats, and that the rat form of
Pneumocystis differed physiologically and had different
antigenic properties, Frenkel 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, 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. Every tested
primate, including humans, appears to have their own type of
Pneumocystis that's incapable of cross-infecting other host species and has
co-evolved with each
mammal species. Currently only 5 species have been formally named:
P. jirovecii from humans,
P. carinii as originally named from rats,
P. murina from mice,
P. wakefieldiae also from rats, and
P. oryctolagi from rabbits.
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 doesn't 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. [orf. sp.]
hominis, while the original rat infecting form was called
Pneumocystis carinii f. [orf. 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. As of yet, they're cryptic taxa.
Pneumocystis Genome Project
Pneumocystis species can't be grown in culture. Therefore, there's 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
Further Information
Get more info on 'Pneumocystis'.
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