PenicilliumPenicillium is a genus of ascomycetous fungi of major importance in the environment, food and drug production...
species are usually regarded as unimportant in terms of causing
human diseaseA disease or medical condition isan abnormal condition of an organism that impairs bodily functions, associated with specific symptoms and signs...
.
Penicillium marneffei, discovered in 1956, is different. This is the only known
thermally dimorphicDimorphic 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 infectionSystemic infection is a generic term for infection caused by microorganisms in animals or plants, where the causal agent has spread actively or passively in the host's anatomy and is disseminated throughout several organs in different systems of the host...
(
penicilliosisPenicilliosis is an infection caused by Penicillium marneffei.It is a dimorphic fungus.-Epidemiology:Once considered rare, its occurrence has increased due to AIDS...
) with
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
and anaemia similar to
disseminated cryptococcosisCryptococcosis, or cryptococcal disease, is a serious and potentially fatal fungal disease. It is caused by members of the Cryptococcus neoformans species complex, comprising the three variants C. neoformans v. gattii , C. neoformans v. neoformans, and C. neoformans v...
.
There is a high incidence of penicilliosis in
AIDSAcquired 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 KongHong Kong , officially the Hong Kong Special Administrative Region, is a highly autonomous territory of the People's Republic of China, facing Guangdong to the north and the South China Sea to the east, west and south...
get penicillosis as an AIDS-related illness.
PenicilliumPenicillium is a genus of ascomycetous fungi of major importance in the environment, food and drug production...
species are usually regarded as unimportant in terms of causing
human diseaseA disease or medical condition isan abnormal condition of an organism that impairs bodily functions, associated with specific symptoms and signs...
.
Penicillium marneffei, discovered in 1956, is different. This is the only known
thermally dimorphicDimorphic 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 infectionSystemic infection is a generic term for infection caused by microorganisms in animals or plants, where the causal agent has spread actively or passively in the host's anatomy and is disseminated throughout several organs in different systems of the host...
(
penicilliosisPenicilliosis is an infection caused by Penicillium marneffei.It is a dimorphic fungus.-Epidemiology:Once considered rare, its occurrence has increased due to AIDS...
) with
feverFever is a frequent medical sign that describes an increase in internal body temperature to levels above normal...
and anaemia similar to
disseminated cryptococcosisCryptococcosis, or cryptococcal disease, is a serious and potentially fatal fungal disease. It is caused by members of the Cryptococcus neoformans species complex, comprising the three variants C. neoformans v. gattii , C. neoformans v. neoformans, and C. neoformans v...
.
Epidemiology
There is a high incidence of penicilliosis in
AIDSAcquired 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 KongHong Kong , officially the Hong Kong Special Administrative Region, is a highly autonomous territory of the People's Republic of China, facing Guangdong to the north and the South China Sea to the east, west and south...
get penicillosis as an AIDS-related illness. Cases of
P. marneffei human infections (penicillosis) have also been reported in
HIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid,...
-positive patients in
AustraliaAustralia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the continental mainland , the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans...
,
EuropeEurope 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 water divide of the Ural Mountains, the Ural River, the Caspian Sea, the Caucasus Mountains , and the Black Sea to the southeast...
,
Japanis an island country in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, People's Republic of 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
UKThe United Kingdom of Great Britain and Northern Ireland is a sovereign state located off the northwestern coast of continental Europe. It is an island country, spanning an archipelago including Great Britain, the northeastern part of Ireland, and many small islands...
and the
U.S.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 AsiaManila
Bangkok
Ho Chi Minh City
Kuala Lumpur
Singapore
Yangon
Bandung
Hanoi
Surabaya
Taichung
Kaohsiung
Medan|-|}...
previously.
Discovered in
bamboo ratThe 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 (
RhizomysRhizomys is a genus of rodent in the Spalacidae family.It contains the following species:* Hoary Bamboo Rat * Chinese Bamboo Rat * Large Bamboo Rat...
) in
VietnamVietnam , 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 to the east...
, it is associated with these rats and the tropical
Southeast AsiaManila
Bangkok
Ho Chi Minh City
Kuala Lumpur
Singapore
Yangon
Bandung
Hanoi
Surabaya
Taichung
Kaohsiung
Medan|-|}...
area.
Penicillium marneffei is endemic in Burma (Myanmar),
CambodiaThe Kingdom of Cambodia , formerly known as Kampuchea , is a country in South East Asia with a population of over 14 million people. The kingdom's capital and largest city is Phnom Penh...
, Southern
ChinaChina is a cultural region, an ancient civilization, and, depending on perspective, a national or multinational entity extending over a large area in East Asia....
,
IndonesiaThe Republic of Indonesia is a country in Southeast Asia and Oceania. Indonesia comprises 17,508 islands. With an estimated population of around 237 million people, it is the world's fourth most populous country, with the world's largest population of Muslims.Indonesia is a republic, with an...
,
LaosLaos , officially the Lao People's Democratic Republic, is the only landlocked country in Southeast Asia, bordered by Burma and People's Republic of China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...
,
MalaysiaMalaysia is a country in Southeast Asia that consists of thirteen states and three Federal Territories, with a total landmass of . The capital city is Kuala Lumpur, while Putrajaya is the seat of the federal government. The population stands at over 28 million inhabitants...
,
ThailandThe Kingdom of Thailand is an independent country that lies in the heart of Southeast Asia.It is bordered to the north by Laos and Burma, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the west by the Andaman Sea and Burma...
and
VietnamVietnam , 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 to the east...
.
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,
liverThe 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
spleenThe 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, holds a reserve in case of hemorrhagic shock, especially in...
. 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 seasonThe 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 falls. The term green season is also sometimes used as a euphemism by tourist authorities. Areas with wet seasons are dispersed across portions of the tropics...
, 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 factorA risk factor is a variable associated with an increased risk of disease or infection. Risk factors are correlational and not necessarily causal, because correlation does not imply causation...
, but exposure to the
soilSoil 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. It is composed of particles of broken rock that have been altered by chemical and...
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
microbiologyMicrobiology is the study of microorganisms, which are unicellular or cell-cluster microscopic organisms. This includes eukaryotes such as fungi and protists, and prokaryotes. Viruses, though not strictly classed as living organisms, are also studied...
. 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 fungi are thermally dimorphic as well. Cultures should be done from
bone marrowBone marrow is the flexible tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells. It constitutes 4% of total body weight, i.e...
, skin, blood and sputum samples.
Plating samples out onto two
SabouraudRaymond Sabouraud was a French physician born in Nantes. He specialized in dermatology and mycology, and was also an accomplished painter and sculptor....
agar plateAn agar plate is a sterile Petri dish that contains a growth medium used to culture microorganisms or small plants like the moss Physcomitrella patens....
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.
Mycelialthumb|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 in many other substrates...
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
PenicilliumPenicillium is a genus of ascomycetous fungi of major importance in the environment, food and drug production...
, with hyaline, septate and branched hyphae; the conidiophores are located both laterally and terminally. Each conidiophore gives rise to three to five
phialidePhialide [Gr. phialis, diminutive of phiale, a broad, flat vessel]*A flask-shaped projection from the conidiophore of certain fungi.*Projects from the mycelium without increasing in length without 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 fissionBinary fission, or prokaryotic fission, is the form of asexual reproduction and cell division used by all prokaryotic and some eukaryotic organisms...
, 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 stainWright'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 stainGiemsa stain, named after Gustav Giemsa, an early malariologist, is used for the histopathological diagnosis of malaria and other parasites.-Uses:...
. Histological examination can also be done on skin, bone marrow or
lymph nodeA lymph node is an organ consisting of many types of cells, and is a part of the lymphatic system. Lymph nodes are found all through the body, and act as filters or traps for foreign particles. They contain white blood cells that use oxygen to process. Thus they are important in the proper...
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.
AntigenAn antigen is a substance that prompts the generation of antibodies and can cause an immune response. "Self" antigens are usually tolerated by the immune system; whereas "Non-self" antigens are identified as intruders and attacked by the immune system...
testing of urine and serum, and PCR amplification of specific
nucleotideNucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides play central roles in metabolism...
sequences have been tried, with high sensitivity and specificity.
Rapid identification of penicilliosis is sought, as rapid treatment is critical. Treatment should be provided as soon as penicilliosis is suspected.