Essentials of Diagnosis
- Penicillium marneffei infection found in both immunocompetent and immunosuppressed patients.
- P marneffei found in Southeast Asia and southern China.
- Mold, septate hyphae 1.5-5 um in diameter.
- May be cultured from a variety of specimens including blood.
- Penicillium spp. other than P marneffei occur worldwide.
- Infection with Penicillium spp. is rare; occurs in immunosuppressed patients.
General Considerations
Epidemiology
Penicillium spp. are ubiquitous in nature and may be recovered with ease from a variety of sources within the hospital environment. These molds commonly contaminate clinical specimens and cause contamination in the laboratory. Colonization of nonsterile anatomical sites in humans is common. In most cases where Penicillium spp. are recovered from clinical specimens, they represent colonization. Nevertheless, colonization must be distinguished from the possibility of invasive disease.
Unique among the Penicillium spp., P marneffei is an endemic mycosis that is found in Southeast Asia and southern China. Most of the cases in the world literature have been reported from these areas; however, an increasing number of cases have been reported among individuals, particularly those with AIDS, who have traveled to or resided in the endemic parts of Southeast Asia and southern China. In Thailand, penicilliosis is the third most common opportunistic infection in patients with AIDS. Little is known about the environmental reservoir of P marneffei. Infection is acquired via inhalation, inoculation of the skin, and possibly ingestion. Person-to-person transmission does not occur. There is a marked predominance of male cases (~ 90%).
Microbiology
Penicillium spp. are among the most common filamentous fungi found in nature. These blue-green molds grow rapidly in the mycology laboratory and produce fine septate hyphae with 1.5-5 um wide elements. In tissue specimens, the mycelial elements are somewhat larger at 15-20 um in width and exhibit branching at ~ 45° angles. One of the Penicillium spp., P marneffei, is unique because of its dimorphic characteristic. In tissue specimens, it grows as a small yeast cell that resembles Histoplasma capsulatum. In the laboratory, P marneffei will grow as a mold with hyphal characteristics similar to the other Penicillium spp. The species may be distinguished by their characteristic conidia forms. Except for P marneffei, the Penicillium spp. are rarely speciated by mycology laboratories.
Pathogenesis
Infection caused by Penicillium spp. other than P marneffei occurs almost exclusively among profoundly immunosuppressed patients and is exceedingly rare. Penicillium spp. lack the necessary virulence factors to commonly cause human infection, and only in the setting of extreme immunodeficient states can invasive infection occur.
In contrast, P marneffei is capable of causing infection in both immunocompetent and immunocompromised patients. In immunocompetent patients, P marneffei infection may resemble histoplasmosis with a granulomatous reaction involving the reticuloendothelial system. The organism is capable of surviving within macrophages. On occasion, a more suppurative reaction can occur in immunocompetent patients, resulting in abscess formation in various organs, especially the lung, skin, liver, and subcutaneous tissues. P marneffei infection in immunosuppressed patients can be granulomatous or necrotizing and is likely to disseminate.
Clinical Findings
Signs and Symptoms
Infections caused by Penicillium spp. other than P marneffei are very rare, and recovery of Penicillium spp. from clinical specimens will almost always represent colonization; however, in the severely immunocompromised host, repeated recovery may represent opportunistic infection. Isolated case reports of invasive penicilliosis, including prosthetic valve endocarditis, peritonitis, endophthalmitis, and infections at other sites, have been reported in the literature.
The most common presentation of P marneffei infection is chronic illness with fever and weight loss (Box 4). A nonproductive cough is frequently present. Other specific symptoms may be present depending on the extent of infection. Because skin involvement occurs in nearly two-thirds of patients, skin lesions are usually present and are most commonly found on the face, upper trunk, and arms. They are papular in appearance and resemble molluscum contagiosum. Generalized lymphadenopathy is also often present. Hepatosplenomegaly may be detected on abdominal examination and is more common in children.
Laboratory Findings
Anemia is the most common laboratory abnormality present and is found in approximately three-quarters of patients. Blood cultures are positive in over half of patients. There are currently no serological tests to diagnose P marneffei infection.
Imaging
In patients with pulmonary involvement, the chest x-ray may show multiple infiltrates, abscesses, and cavitation. Hilar involvement may be present, but there is usually no hilar calcification.
Differential Diagnosis
P marneffei may closely resemble tuberculosis, particularly in patients with HIV infection. The disease also closely resembles histoplasmosis and cryptococcosis as it occurs in HIV-infected patients.
Diagnosis
The diagnosis of invasive disease by Penicillium spp. other than P marneffei must be based on histologic evidence of tissue invasion and recovery of the organism from tissue culture. In addition, recovery from a sterile body fluid such as blood or synovial fluid is suggestive of infection but must be interpreted with caution in view of the frequency with which Penicillium spp. contaminate laboratory specimens.
Infection with P marneffei occurs only in people who have lived or traveled in the endemic areas of Southeast Asia and southern China. An exposure history is critical in considering the diagnosis. Blood cultures will establish the diagnosis, but other specimens including bone marrow, skin, abscess fluid, lymph nodes, sputum, and others may yield the organism. P marneffei must be distinguished from Histoplasma capsulatum, which it closely resembles in the laboratory.
Treatment
The drug of choice for treatment of P marneffei infection is amphotericin B, although in vitro resistance has been described (Box 5). The addition of 5-flucytocine appears to enhance the efficacy of amphotericin B therapy especially in more severe cases. Itraconazole also appears to be highly active against the organism; however, it should be reserved for indolent cases or for use following an initial response to amphotericin B. A standard course of therapy is 2 weeks of amphotericin followed by 6 weeks of itraconazole. Relapse rarely occurs in immunocompetent patients but is common among AIDS patients. Chronic maintenance therapy with itraconazole is indicated in patients with AIDS.
Prognosis
With early diagnosis and initiation of appropriate fungal therapy, the prognosis is very good; however, among patients in whom the diagnosis is delayed, the mortality rate is high.
Prevention & Control
Because very little is known about the environmental niche of P marneffei, there are no recommendations or guidelines for prevention and control of this infection.
Read more
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360277/