Penicillium marneffei exhibits thermal dimorphism by growing in living tissue or in culture at 37C as a yeast-like fungus or in culture at temperatures below 30C as a mould. It has a propensity to cause disease in the normal host, as well as in immunosuppressed patients, but significantly, it has now become a major opportunistic pathogen in HIV positive patients in Indochina. Over 300 cases have been reported with the majority of these coming from Chiang Mai in northern Thailand. Other predisposing factors include lymphoproliferative disorders, bronchiectasis and tuberculosis, autoimmune diseases and corticosteroid therapy. To date, all naturally occurring infections have been in residents of, or travellers to, southeast Asia; especially northern Thailand, Vietnam, Hong Kong, Taiwan and southern China. Imported cases of P. marneffei infections have been reported from Australia, France, Italy, Netherlands, UK and USA.
In patients with normal immunity, P. marneffei infection may either be disseminated or focal. In the latter, both clinical and histological appearances may strongly resemble tuberculosis (eg. suppurative lymphadenopathy). In HIV patients, P. marneffei infection is usually disseminated at diagnosis. Commonly the skin, reticuloendothelial system, lung and gut are infected. Fungaemia is present in the majority of cases and other organ systems including kidney, bones, joints and pericardium may also be involved. Patients usually present with non-specific symptoms of fever, anaemia and weight loss. Skin lesions are most commonly papules often with a central necrotic umbilication similar in appearance to those seen in molluscum contagiosum and are usually located on the face, trunk and extremities. In many cases numerous subcutaneous abscesses ulcerate over time. It is important to note that the clinical symptoms of disseminated infection by P. marneffei mimic those seen in AIDS patients with disseminated cryptococcal infection or disseminated histoplasmosis.
"Molluscum contagiosum" lesions caused by P. marneffei on the neck of an HIV+ patient.
Typical papules often with a central necrotic umbilication due to P. marneffei.
"Molluscum contagiosum" lesions caused by P. marneffei in the buccal cavity.
"Molluscum contagiosum" lesions caused by P. marneffei below the eye and on the cornea.
Finally, little is known about the ecology, epidemiology or pathogenesis of P. marneffei infection. Although bamboo rats are known to be asymptomatic carriers of the fungus, it is unclear whether they are an important reservoir for human infection or only a sentinel animal that is susceptible to infection from an environmental source. Human infections have been reported following traumatic implantation, enteric spread following the eating of bamboo rats as "game cuisine" and by inhalation of spores from soil or possibly a specific host plant. P. marneffei has been isolated from bamboo rat burrows and the current consensus would favour soil as the most likely reservoir with transmission to humans via the respiratory route, similar to that seen with other dimorphic fungi. However this remains to be proven and for now the natural habitat of the fungus and an explanation for its geographic restriction remain unknown.
1. Clinical material: Penicillium marneffei is the only dimorphic member of the genus Penicillium and is readily detected by direct microscopy and culture of infected tissues, especially skin lesions, bone marrow, blood and lymph nodes.
2. Direct Microscopy: A Giemsa stained touch smear of a skin biopsy or bone marrow aspirate is a rapid and sensitive diagnostic method that readily demonstrates the presence of typical yeast-like cells with a central septa, either within histiocytes or scattered through the tissue. The yeast-cells are spherical to ellipsoidal, 2 to 6 um in diameter, and divide by fission rather than budding, a characteristic visible on stained touch smears that distinguishes P. marneffei from Histoplasma capsulatum.
A Giemsa stained touch smear (left) and a GMS stained tissue section (right) showing typical septate yeast-like cells of P. marneffei. In the latter preparation the cells closely resemble those seen in histoplasmosis.
Tissue sections show small, oval to elliptical yeast-like cells, 3um in diameter, either packed within histiocytes or scattered through the tissue. Occasional, large, elongated sausage shaped cells, up to 8 um long, with distinctive septa may be present. Note: tissue sections need to be stained by Grocott's methenamine silver method to clearly see the yeast-like cells, which are often difficult to observe in H&E preparations.
3. Culture: Clinical specimens should be inoculated onto primary isolation media, like Sabouraud's dextrose agar.
Culture showing a common green saprophytic Penicillium sp. and the typical yellow-pink colony with distinctive red diffusable pigment of Penicillium marneffei.
4. Serology: There are currently no commercially available serological procedures for the diagnosis of Penicilliosis marneffei.
5. Identification: Clinical history, tissue morphology and culture identification.
Ajello L and R.J. Hay. 1997. Medical Mycology Vol 4 Topley & Wilson's Microbiology and Infectious Infections. 9th Edition, Arnold London.
Kwon-Chung KJ and JE Bennett 1992. Medical Mycology Lea & Febiger.
Vanittanakom N and T. Sirisanthana. 1997. Penicillium marmeffei infection in patients infected with Human Immunodeficiency Virus. Current Topics in Medical Mycology 8:35-42.