Pneumocystis pneumonia
Encyclopedia
Pneumocystis pneumonia or pneumocystosis is a form of pneumonia
, caused by the yeast-like fungus
(which had previously been erroneously classified as a protozoa
n) Pneumocystis jirovecii
. This pathogen is specific to humans; it has not been shown to infect other animals, while other species of Pneumocystis that parasitize other animals have not been shown to infect humans.
Pneumocystis is commonly found in the lungs of healthy people, but being a source of opportunistic infection
it can cause a lung infection in people with a weak immune system
. Pneumocystis pneumonia is especially seen in people with cancer, HIV/AIDS and the use of medications that affect the immune system.
The older name Pneumocystis carinii, (which now only applies to the Pneumocystis species that is found in rats), is still in common usage. As a result, Pneumocystis pneumonia (PCP) is also known as Pneumocystis jiroveci[i] pneumonia and (incorrectly) as Pneumocystis carinii pneumonia.
Regarding nomenclature, when the name of Pneumocystis pneumonia changed from P. carinii pneumonia to P. jirovecii pneumonia, it was at first felt that it could no longer be referred to as "PCP". However, because the term PCP was already in common usage, it was rationalized that the term PCP could continue to be used, as it stood for PneumoCystis (jirovecii) Pneumonia.
s, such as premature or severely malnourished children, the elderly, and especially persons living with HIV/AIDS, in whom it is most commonly observed. PCP can also develop in patients who are taking immunosuppressive medications
. It can occur in patients who have undergone solid organ transplantation
or bone marrow transplantation and after surgery. Infections with Pneumocystis pneumonia are also common in infants with hyper IgM syndrome
, an X-linked or autosomal recessive trait.
The causative organism of PCP is distributed worldwide and 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. A post-mortem study conducted in Chile of 96 persons who died of unrelated causes (suicide, traffic accidents, and so forth) found that 65 (68%) of them had pneumocystis in their lungs, which suggests that asymptomatic pneumocystis infection is extremely common.
Pneumocystis jirovecii was originally described as a rare cause of pneumonia
in neonates. It is commonly believed to be a commensal organism (dependent upon its human host for survival). The possibility of person-to-person transmission has recently gained credence, with supporting evidence coming from many different genotyping studies of Pneumocystis jirovecii isolates from human lung tissue. For example, in one outbreak of 12 cases among transplant patients in Leiden, it was suggested as likely, but not proven, that human-to-human spread may have occurred.
epidemic, 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.
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 preventive treatment, PCP continues to be a major cause of death in AIDS.
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.
Pneumothorax is a well-known complication of PCP. An acute history of chest pain with breathlessness and diminished breath sounds is typical of pneumothorax.
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 histological identification of the causative organism in sputum
or bronchio-alveolar lavage
(lung rinse). Staining with toluidine blue, silver stain or periodic-acid schiff or immunofluorescence assay
, which will show characteristic cyst
s. The cysts resemble crushed ping-pong balls and are present in aggregates of 2 to 8 (not to be confused with Histoplasma or Cryptococcus which typically do not form aggregates of spores or cells). A lung biopsy would show thickened alveolar septa with fluffy eosinophilic exudate in the alveoli. Both the thickened septa and the fluffy exudate contribute to dysfunctional diffusion capacity which is characteristic of this pneumonia.
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 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.
positive cell 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
(CO2) levels, stimulates ventilation
, thereby causing dyspnea
.
, 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
, pafuramidine maleate (under investigation), 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 effect
s. These include acute pancreatitis
, renal failure
, hepatotoxicity
, leukopenia
, rash
, fever
, and hypoglycaemia.
or regular pentamidine
inhalations may help prevent PCP.
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
, caused by the yeast-like fungus
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
(which had previously been erroneously classified as a protozoa
Protozoa
Protozoa are a diverse group of single-cells eukaryotic organisms, many of which are motile. Throughout history, protozoa have been defined as single-cell protists with animal-like behavior, e.g., movement...
n) Pneumocystis jirovecii
Pneumocystis jirovecii
Pneumocystis jirovecii is a yeast-like fungus of the genus Pneumocystis. The causative organism of Pneumocystis pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. Prior to its discovery as a human-specific pathogen, P. jirovecii was known as P...
. This pathogen is specific to humans; it has not been shown to infect other animals, while other species of Pneumocystis that parasitize other animals have not been shown to infect humans.
Pneumocystis is commonly found in the lungs of healthy people, but being a source of opportunistic infection
Opportunistic infection
An opportunistic infection is an infection caused by pathogens, particularly opportunistic pathogens—those that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system...
it can cause a lung infection in people with a weak immune system
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
. Pneumocystis pneumonia is especially seen in people with cancer, HIV/AIDS and the use of medications that affect the immune system.
The older name Pneumocystis carinii, (which now only applies to the Pneumocystis species that is found in rats), is still in common usage. As a result, Pneumocystis pneumonia (PCP) is also known as Pneumocystis jiroveci[i] pneumonia and (incorrectly) as Pneumocystis carinii pneumonia.
Regarding nomenclature, when the name of Pneumocystis pneumonia changed from P. carinii pneumonia to P. jirovecii pneumonia, it was at first felt that it could no longer be referred to as "PCP". However, because the term PCP was already in common usage, it was rationalized that the term PCP could continue to be used, as it stood for PneumoCystis (jirovecii) Pneumonia.
Epidemiology
The disease PCP is relatively rare in people with normal immune systems, but common among people with weakened immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
s, such as premature or severely malnourished children, the elderly, and especially persons living with HIV/AIDS, in whom it is most commonly observed. PCP can also develop in patients who are taking immunosuppressive medications
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...
. It can occur in patients who have undergone solid organ transplantation
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
or bone marrow transplantation and after surgery. Infections with Pneumocystis pneumonia are also common in infants with hyper IgM syndrome
Hyper IgM syndrome
Hyper IgM syndrome is a family of genetic disorders in which the level of Immunoglobulin M antibodies is relatively high. The most common type is a result of a defect in a Th2 cell protein . The disorder causes immunodeficiencies, including a higher than normal susceptibility to various types of...
, an X-linked or autosomal recessive trait.
The causative organism of PCP is distributed worldwide and 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. A post-mortem study conducted in Chile of 96 persons who died of unrelated causes (suicide, traffic accidents, and so forth) found that 65 (68%) of them had pneumocystis in their lungs, which suggests that asymptomatic pneumocystis infection is extremely common.
Pneumocystis jirovecii was originally described as a rare cause of pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
in neonates. It is commonly believed to be a commensal organism (dependent upon its human host for survival). The possibility of person-to-person transmission has recently gained credence, with supporting evidence coming from many different genotyping studies of Pneumocystis jirovecii isolates from human lung tissue. For example, in one outbreak of 12 cases among transplant patients in Leiden, it was suggested as likely, but not proven, that human-to-human spread may have occurred.
PCP and AIDS
Since the start of the AIDSAIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
epidemic, 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
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
). 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
Pentamidine
Pentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection...
, 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
Co-trimoxazole
Trimethoprim/sulfamethoxazole or co-trimoxazole is a sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections.The name co-trimoxazole is the British Approved Name, and has been marketed worldwide...
to prevent the disease in people with CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
counts less than 200/mm³. In populations that do not have access to preventive treatment, PCP continues to be a major cause of death in AIDS.
Symptoms
Symptoms of PCP include fever, non-productive cough (because sputum is too viscous to become productive), shortness of breath (especially on exertion), weight loss and night sweats. There is usually not a large amount of sputumSputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
with PCP unless the patient has an additional bacterial infection. The fungus can invade other visceral organs, such as the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
and kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, but only in a minority of cases.
Pneumothorax is a well-known complication of PCP. An acute history of chest pain with breathlessness and diminished breath sounds is typical of pneumothorax.
Diagnosis
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
which shows widespread pulmonary infiltrates, and an arterial oxygen level
Arterial blood gas
An arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
(pO2) strikingly lower than would be expected from symptoms. The diagnosis can be definitively confirmed by histological identification of the causative organism in sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
or bronchio-alveolar lavage
Bronchoalveolar lavage
Bronchoalveolar lavage is a medical procedure in which a bronchoscope is passed through the mouth or nose into the lungs and fluid is squirted into a small part of the lung and then recollected for examination. BAL is typically performed to diagnose lung disease...
(lung rinse). Staining with toluidine blue, silver stain or periodic-acid schiff or immunofluorescence assay
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
, which will show characteristic cyst
Cyst
A cyst is a closed sac, having a distinct membrane and division on the nearby tissue. It may contain air, fluids, or semi-solid material. A collection of pus is called an abscess, not a cyst. Once formed, a cyst could go away on its own or may have to be removed through surgery.- Locations :* Acne...
s. The cysts resemble crushed ping-pong balls and are present in aggregates of 2 to 8 (not to be confused with Histoplasma or Cryptococcus which typically do not form aggregates of spores or cells). A lung biopsy would show thickened alveolar septa with fluffy eosinophilic exudate in the alveoli. Both the thickened septa and the fluffy exudate contribute to dysfunctional diffusion capacity which is characteristic of this pneumonia.
Pneumocystis infection can also be diagnosed by immunofluorescent
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
or histochemical staining of the specimen, and more recently by molecular analysis of polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
products comparing DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
samples. Notably, simple molecular detection of Pneumocystis jirovecii in lung fluids does not mean that a person has Pneumocystis pneumonia or infection by HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
. The fungus appears to be present in healthy individuals also in the general population.
Disease course
The risk of pneumonia due to Pneumocystis jirovecii increases when CD4CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
positive cell levels are less than 200 cells/μl. In these immunosuppressed
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
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
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
which can be fatal if not treated aggressively; therefore, LDH
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
levels increase and gas exchange is compromised. Oxygen is less able to diffuse into the blood, leading to hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
. Hypoxia, along with high arterial carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
(CO2) levels, stimulates ventilation
Ventilation (physiology)
In respiratory physiology, ventilation is the rate at which gas enters or leaves the lung. It is categorized under the following definitions:-Sample values:...
, thereby causing dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
.
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 co-trimoxazoleCo-trimoxazole
Trimethoprim/sulfamethoxazole or co-trimoxazole is a sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections.The name co-trimoxazole is the British Approved Name, and has been marketed worldwide...
, but some patients are unable to tolerate this treatment due to allergies. Other medications that are used, alone or in combination, include pentamidine
Pentamidine
Pentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection...
, trimetrexate
Trimetrexate
Trimetrexate is a quinazoline derivative. It is a dihydrofolate reductase inhibitor.-Uses:It has been used with leucovorin in treating pneumocystis pneumonia.It has been investigated for use in treating leiomyosarcoma....
, dapsone
Dapsone
Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...
, atovaquone
Atovaquone
Atovaquone is a chemical compound that belongs to the class of naphthalenes. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of ubiquinone, with antipneumocystic activity. Its average wholesale price is about US$2.13 per standard 250 mg. tablet...
, primaquine
Primaquine
Primaquine is a medication used in the treatment of malaria and Pneumocystis pneumonia. It is a member of the 8-aminoquinoline group of drugs that includes tafenoquine and pamaquine.-Radical cure:...
, pafuramidine maleate (under investigation), and clindamycin
Clindamycin
Clindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...
. Treatment is usually for a period of about 21 days.
Pentamidine
Pentamidine
Pentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection...
is less often used as its major limitation is the high frequency of side effect
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s. These include acute pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
, renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, hepatotoxicity
Hepatotoxicity
Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...
, leukopenia
Leukopenia
Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....
, rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, and hypoglycaemia.
Prevention
In immunocompromised patients, prophylaxis with co-trimoxazoleCo-trimoxazole
Trimethoprim/sulfamethoxazole or co-trimoxazole is a sulfonamide antibiotic combination of trimethoprim and sulfamethoxazole, in the ratio of 1 to 5, used in the treatment of a variety of bacterial infections.The name co-trimoxazole is the British Approved Name, and has been marketed worldwide...
or regular pentamidine
Pentamidine
Pentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection...
inhalations may help prevent PCP.