Penicilliosis

# Overview
Penicilliosis is an infection caused by Penicillium marneffei. Once considered rare, its occurrence has increased due to AIDS. It is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia.

# Epidemiology
There is a high incidence of penicilliosis in AIDS patients in SE Asia; 10% of patients in Hong Kong get penicillosis as a 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 had visited Southeast Asia previously.
Discovered in bamboo rats (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.

# Symptoms
The most common symptoms are fever, skin lesions, anemia, generalized lymphadenopathy, and hepatomegaly.

# Diagnosis
Diagnosis is usually made by identification of the fungi from clinical specimens. Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology.

# Treatment
Penicillium marneffei demonstrates in vitro susceptibility to multiple antifungal agents including ketoconazole, itraconazole, miconazole, flucytosine, and amphotericin B. Without treatment patients have a poor prognosis.

## Antimicrobial Regimen
- 1. Mild disease
- Preferred regimen: Itraconazole 200 mg PO bid for 8 to 12 weeks without amphotericin B induction therapy
- Alternative regimen: Voriconazole 400 mg PO bid on day 1 THEN 200 mg PO bid for 12 weeks
- 2. Moderate-severe disease
- Preferred regimen: Liposomal Amphotericin B 3-5 mg/kg/day IV qd OR Amphotericin B lipid complex 5 mg/kg/day IV qd for 2 weeks THEN Itraconazole 200 mg PO bid for 10 weeks
- Alternative regimen:  Voriconazole 6 mg/kg IV q12h on day 1 THEN 4 mg/kg q12h for at least 3 days THEN Voriconazole 200 mg PO bid for a total of 12 weeks
- 3. Maintenance therapy
- Preferred regimen Itraconazole 200 mg PO qd
- Alternative regimen: Voriconazole 200 mg PO bid
- Note: Voriconazole and Itraconazole use require serum levels to be monitored to ensure adequate absorption.