Penicillium marneffei
Encyclopedia
Penicillium
species are usually regarded as unimportant in terms of causing human disease
. Penicillium marneffei, discovered in 1956, is different. This is the only known thermally dimorphic
species of Penicillium, and it can cause a lethal systemic infection (penicilliosis
) with fever
and anaemia similar to disseminated
cryptococcosis
.
patients in SE Asia; 10% of patients in Hong Kong
get penicillosis as an AIDS-related illness. Cases of P. marneffei human infections (penicillosis) have also been reported in HIV
-positive patients in Australia
, Europe
, Japan
, the UK
and the U.S.
. All the patients, except one, had visited Southeast Asia
previously.
Discovered in bamboo rat
s (Rhizomys
) in Vietnam
, it is associated with these rats and the tropical Southeast Asia
area. Penicillium marneffei is endemic in Burma (Myanmar), Cambodia
, Southern China
, Indonesia
, Laos
, Malaysia, Thailand
and Vietnam
.
Although both the immunocompetent and the immunocompromised can be infected, it is extremely rare to find systemic infections in HIV-negative patients.
The incidence of P. marneffei is increasing as HIV spreads throughout Asia. An increase in global travel and migration means it will be of increased importance as an infection in AIDS sufferers.
Penicillium marneffei has been found in bamboo rat faeces, liver
, lungs and spleen
. It has been suggested that these animals are a reservoir for the fungus. It is not clear whether the rats are affected by P. marneffei or are merely asymptomatic carriers of the disease.
One study of 550 AIDS patients showed that the incidence was higher during the rainy season
, which is when the rats breed but also when conditions are more favorable for production of fungal spores (conidia) that can become airborne and be inhaled by susceptible individuals.
Another study could not establish contact with bamboo rats as a risk factor
, but exposure to the soil
was the critical risk factor. However, soil samples failed to yield much of the fungus.
It is not known whether people get the disease by eating infected rats, or by inhaling fungi from their faeces.
There is an example of an HIV-positive physician who was infected while attending a course on tropical microbiology
. He did not handle the organism, though students in the same laboratory did. It is presumed he contracted the infection by inhaling aerosol containing P. marneffei conidia. This shows that airborne infections are possible.
are thermally dimorphic as well. Cultures should be done from bone marrow
, skin, blood and sputum samples.
Plating samples out onto two Sabouraud
agar plate
s, then incubating one at 30°C and the other at 37°C, should result in two different morphologies. A mold-form will grow at 30°C, and a yeast-form at 37°C.
Mycelial
colonies will be visible on the 30°C plate after two days. Growth is initially fluffy and white and eventually turns green and granular after sporulation has occurred. A soluble red pigment is produced, which diffuses into the agar, causing the reverse side of the plate to appear red or pink. The periphery of the mold may appear orange-coloured, and radial sulcate folds will develop.
Under the microscope, the mold phase will look like a typical Penicillium
, with hyaline, septate and branched hyphae; the conidiophores are located both laterally and terminally. Each conidiophore gives rise to three to five phialide
s, where chains of lemon-shaped conidia are formed.
On the 37°C plate, the colonies grow as yeasts. These colonies can be cerebriform, convoluted, or smooth. There is a decreased production in pigment, the colonies appearing cream/light-tan/light-pink in colour. Microscopically, sausage-shaped cells are mixed with hyphae-like structures. As the culture ages, segments begin to form. The cells divide by binary fission, rather than budding. The cells are not yeast cells, but rather arthroconidia.
Culturing isn't the only method of diagnosis. A skin scraping can be prepared, and stained with Wright's stain
. Many intracellular and extracellular yeast cells with crosswalls are suggestive of P. marneffei infection. Smears from bone marrow aspirates may also be taken; this is regarded as the most sensitive method. These samples can be stained with the Giemsa stain
. Histological examination can also be done on skin, bone marrow or lymph node
s.
The patient's history also is a diagnostic help. If they have traveled to Southeast Asia and are HIV-positive, then there is an increased risk of them having penicilliosis.
Antigen
testing of urine and serum, and PCR amplification of specific nucleotide
sequences have been tried, with high sensitivity and specificity.
Rapid identification of penicilliosis is sought, as prompt treatment is critical. Treatment should be provided as soon as penicilliosis is suspected.
Penicillium
Penicillium is a genus of ascomycetous fungi of major importance in the natural environment as well as food and drug production. Members of the genus produce penicillin, a molecule that is used as an antibiotic, which kills or stops the growth of certain kinds of bacteria inside the body...
species are usually regarded as unimportant in terms of causing human disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
. Penicillium marneffei, discovered in 1956, is different. This is the only known thermally dimorphic
Thermally dimorphic fungus
Dimorphic fungi are fungi that can reproduce as either a mycelial or a yeast-like state. Generally the mycelial saprotrophic form grows at 25° C, and the yeast-like pathogenic form at 37° C...
species of Penicillium, and it can cause a lethal systemic infection (penicilliosis
Penicilliosis
Penicilliosis is an infection caused by Penicillium marneffei.It is a dimorphic fungus.-Epidemiology:Once considered rare, its occurrence has increased due to AIDS...
) with 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 anaemia similar to disseminated
Dissemination
To disseminate , in terms of the field of communication, means to broadcast a message to the public without direct feedback from the audience. Dissemination takes on the theory of the traditional view of communication, which involves a sender and receiver...
cryptococcosis
Cryptococcosis
Cryptococcosis, or cryptococcal disease, is a potentially fatal fungal disease. It is caused by one of two species; Cryptococcus neoformans and Cryptococcus gattii. These were all previously thought to be subspecies of C...
.
Epidemiology
There is a high incidence of penicilliosis in AIDSAIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
patients in SE Asia; 10% of patients in Hong Kong
Hong Kong
Hong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...
get penicillosis as an AIDS-related illness. Cases of P. marneffei human infections (penicillosis) have also been reported in 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...
-positive patients in Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
, Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
, the UK
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
and the U.S.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. All the patients, except one, had visited Southeast Asia
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...
previously.
Discovered in bamboo rat
Bamboo rat
The bamboo rats are four species of rodents of the subfamily Rhizomyinae. They are the sole living representatives of the tribe Rhizomyini. All are found in the eastern half of Asia.The species are:...
s (Rhizomys
Rhizomys
Rhizomys is a genus of rodent in the Spalacidae family.It contains the following species:* Hoary Bamboo Rat * Chinese Bamboo Rat * Large Bamboo Rat...
) in Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...
, it is associated with these rats and the tropical Southeast Asia
Southeast Asia
Southeast Asia, South-East Asia, South East Asia or Southeastern Asia is a subregion of Asia, consisting of the countries that are geographically south of China, east of India, west of New Guinea and north of Australia. The region lies on the intersection of geological plates, with heavy seismic...
area. Penicillium marneffei is endemic in Burma (Myanmar), Cambodia
Cambodia
Cambodia , officially known as the Kingdom of Cambodia, is a country located in the southern portion of the Indochina Peninsula in Southeast Asia...
, Southern China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
, Indonesia
Indonesia
Indonesia , officially the Republic of Indonesia , is a country in Southeast Asia and Oceania. Indonesia is an archipelago comprising approximately 13,000 islands. It has 33 provinces with over 238 million people, and is the world's fourth most populous country. Indonesia is a republic, with an...
, Laos
Laos
Laos Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ Sathalanalat Paxathipatai Paxaxon Lao, officially the Lao People's Democratic Republic, is a landlocked country in Southeast Asia, bordered by Burma and China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...
, Malaysia, Thailand
Thailand
Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...
and Vietnam
Vietnam
Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...
.
Although both the immunocompetent and the immunocompromised can be infected, it is extremely rare to find systemic infections in HIV-negative patients.
The incidence of P. marneffei is increasing as HIV spreads throughout Asia. An increase in global travel and migration means it will be of increased importance as an infection in AIDS sufferers.
Penicillium marneffei has been found in bamboo rat faeces, 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...
, lungs and 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...
. It has been suggested that these animals are a reservoir for the fungus. It is not clear whether the rats are affected by P. marneffei or are merely asymptomatic carriers of the disease.
One study of 550 AIDS patients showed that the incidence was higher during the rainy season
Wet season
The the wet season, or rainy season, is the time of year, covering one or more months, when most of the average annual rainfall in a region occurs. The term green season is also sometimes used as a euphemism by tourist authorities. Areas with wet seasons are dispersed across portions of the...
, which is when the rats breed but also when conditions are more favorable for production of fungal spores (conidia) that can become airborne and be inhaled by susceptible individuals.
Another study could not establish contact with bamboo rats as a risk factor
Risk factor
In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...
, but exposure to the soil
Soil
Soil is a natural body consisting of layers of mineral constituents of variable thicknesses, which differ from the parent materials in their morphological, physical, chemical, and mineralogical characteristics...
was the critical risk factor. However, soil samples failed to yield much of the fungus.
It is not known whether people get the disease by eating infected rats, or by inhaling fungi from their faeces.
There is an example of an HIV-positive physician who was infected while attending a course on tropical microbiology
Microbiology
Microbiology is the study of microorganisms, which are defined as any microscopic organism that comprises either a single cell , cell clusters or no cell at all . This includes eukaryotes, such as fungi and protists, and prokaryotes...
. He did not handle the organism, though students in the same laboratory did. It is presumed he contracted the infection by inhaling aerosol containing P. marneffei conidia. This shows that airborne infections are possible.
Laboratory diagnosis
The fact that Penicillium marneffei is thermally dimorphic is a relevant clue when trying to identify it. However, it should be kept in mind that other human-pathogenic fungiPathogenic fungi
Pathogenic fungi are fungi that cause disease in humans or other organisms. The study of pathogenic fungi is referred to as medical mycology. Although fungi are eukaryotic organisms many pathogenic fungi are also microorganisms.-Candida:...
are thermally dimorphic as well. Cultures should be done from bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, skin, blood and sputum samples.
Plating samples out onto two Sabouraud
Raymond Sabouraud
Raymond Sabouraud was a French physician born in Nantes. He specialized in dermatology and mycology, and was also an accomplished painter and sculptor....
agar plate
Agar plate
An agar plate is a Petri dish that contains a growth medium used to culture microorganisms or small plants like the moss Physcomitrella patens.Selective growth compounds may also be added to the media, such as antibiotics....
s, then incubating one at 30°C and the other at 37°C, should result in two different morphologies. A mold-form will grow at 30°C, and a yeast-form at 37°C.
Mycelial
Mycelium
thumb|right|Fungal myceliaMycelium is the vegetative part of a fungus, consisting of a mass of branching, thread-like hyphae. The mass of hyphae is sometimes called shiro, especially within the fairy ring fungi. Fungal colonies composed of mycelia are found in soil and on or within many other...
colonies will be visible on the 30°C plate after two days. Growth is initially fluffy and white and eventually turns green and granular after sporulation has occurred. A soluble red pigment is produced, which diffuses into the agar, causing the reverse side of the plate to appear red or pink. The periphery of the mold may appear orange-coloured, and radial sulcate folds will develop.
Under the microscope, the mold phase will look like a typical Penicillium
Penicillium
Penicillium is a genus of ascomycetous fungi of major importance in the natural environment as well as food and drug production. Members of the genus produce penicillin, a molecule that is used as an antibiotic, which kills or stops the growth of certain kinds of bacteria inside the body...
, with hyaline, septate and branched hyphae; the conidiophores are located both laterally and terminally. Each conidiophore gives rise to three to five phialide
Phialide
Phialide .*A flask-shaped projection from the vesicle of certain fungi.*Projects from the mycelium without increasing in length unless there is a subsequent increase in the formation of conidia....
s, where chains of lemon-shaped conidia are formed.
On the 37°C plate, the colonies grow as yeasts. These colonies can be cerebriform, convoluted, or smooth. There is a decreased production in pigment, the colonies appearing cream/light-tan/light-pink in colour. Microscopically, sausage-shaped cells are mixed with hyphae-like structures. As the culture ages, segments begin to form. The cells divide by binary fission, rather than budding. The cells are not yeast cells, but rather arthroconidia.
Culturing isn't the only method of diagnosis. A skin scraping can be prepared, and stained with Wright's stain
Wright's stain
Wright's stain is a histologic stain that facilitates the differentiation of blood cell types. It is used primarily to stain peripheral blood smears and bone marrow aspirates which are examined under a light microscope...
. Many intracellular and extracellular yeast cells with crosswalls are suggestive of P. marneffei infection. Smears from bone marrow aspirates may also be taken; this is regarded as the most sensitive method. These samples can be stained with the Giemsa stain
Giemsa stain
Giemsa stain, named after Gustav Giemsa, an early German microbiologist, is used in cytogenetics and for the histopathological diagnosis of malaria and other parasites.-Uses:...
. Histological examination can also be done on skin, bone marrow or lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
s.
The patient's history also is a diagnostic help. If they have traveled to Southeast Asia and are HIV-positive, then there is an increased risk of them having penicilliosis.
Antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
testing of urine and serum, and PCR amplification of specific nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...
sequences have been tried, with high sensitivity and specificity.
Rapid identification of penicilliosis is sought, as prompt treatment is critical. Treatment should be provided as soon as penicilliosis is suspected.