DISSEMINATED PENICILLIOSIS MARNEFFEI Authors: TZ Kyaw1, LG Tan2, A Francis2 1 Pathology Department, Hospital Sibu, Sarawak, Malaysia. 2 Pathology Department, Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia. NMRR-16-372-29943 Introduction Disseminated penicilliosis marneffei is a fatal systemic mycosis caused by Penicillium marneffei, a facultative intracellular pathogen and the only thermally dimorphic fungus of the genus Penicillium [1]. Penicillium marneffei was discovered in 1956 from the hepatic lesions of bamboo rat (Rhizomys sinensis) in Vietnam [2]. The first naturally occurring human case of P. marneffei infection was described in 1973 by Di Salvo and collaborators [3] in a patient with Hodgkin’s disease. Before the first case was reported in human immunodeficiency virus (HIV) infected patient in 1988, human penicilliosis was uncommon with less than 40 cases reported in Southeast Asia [4, 5]. However, the incidence of penicilliosis increased rapidly thereafter with the development of HIV pandemic and the infection has emerged to become one of the most important opportunistic infections among HIV-infected patients who are living in or have traveled to endemic areas such as Southeast Asia, Northeastern India and Southern China [5, 6]. Case Report We reported a 52 year single Chinese man presented with prolonged fever and weight loss. He had no significant past medical history. No specific risk factors for HIV infection were elicited despite careful questioning. There was no history of travelling to malaria endemic areas. Physical examination revealed oral thrush, maculopapular skin lesions including umbilicated lesions (Figure A&B) and mild hepatomegaly. Blood for malaria parasites was negative on three occasions. His liver and renal functions were deranged. Full blood count showed hemoglobin of 89 g/L, white cell count of 5.3 x 109/L and platelet count of 54 x 109/L. Peripheral blood smear exhibited leucoerythroblastic picture with intracellular yeast cells in neutrophils (Figure C). Central septation is evident in some yeast cells. A presumptive diagnosis of disseminated penicilliosis marneffei was made and patient was promptly treated with with intravenous amphotericin B 0.6mg/kg/day for 2 weeks. Confirmatory blood culture on Sabouraud’s dextrose agar at 30ºC after 5 days revealed granular greenish-yellow colonies with diffusible red pigment diagnostic of Penicillium marneffei infection (Figure D). Microscopy of the fungus showed hyaline septated hyphae with fruiting structures composing of branching metulae and phialides which produce spherical conidia in chain (Figure E). Test for anti-HIV antibodies was positive. Absoloute CD4 count was markedly reduced at 4/µL. The patient was discharged on day 17th with itraconazole 400mg/day orally in two divided doses. Anti-retroviral therapy (HAART) was planned to be initiated in the next follow up. (A) (B) (C) (D) (E) Figure (A& B): Maculopapular skin lesions including umbilicated lesions (arrows) characteristics of Penicilliosis. Figure (C): Peripheral blood smear showing intracellular yeast cells including yeast cell with central septation (arrows). Figure (D): Penicillium marneffei colonies with a characteristic red diffusible pigment on Sabouraud’s dextrose agar. Figure (E): Microscopy of the mycelial form of Penicillium marneffei showing septated hyaline hyphae bearing conidiophores. Discussion This report describes a newly diagnosed HIV-infected patient diagnosed to have disseminated penicilliosis marneffei. Although P. marneffei infection may occur among non-HIV immunocompromised individuals, the great majority of the reported cases are linked to HIV/AIDS [7]. In HIV infected individuals, penicilliosis is mostly seen in their late stage of disease with CD4 count less than 100/µL as noted in this case [8, 9]. Disseminated P. marneffei infection includes molluscum contagiosum-like skin lesions with central umbilication, hepatosplenomegaly mimicking visceral leishmaniasis, and tuberculosis-like cavitating pulmonary infection [1]. Diagnosis requires isolation of the organism from specimens such as bone marrow, skin biopsy and blood culture. The differential diagnoses in patients presented with prolonged fever, umbilicated skin lesions and intracellular yeast cells include disseminated penicilliosis, histoplasmosis and cryptococcosis. The presence of yeast cells with central transverse septum in peripheral blood smear suggested the high possibility of Penicillium marneffei infection which was later confirmed by blood culture. The nature of thermal dimorphism is evidenced by the ability to grow as mycelium below 37°C and as a yeast at 37°C in peripheral blood sample (Figure C,D& E). In view of the long culture incubation time and very high mortality rate, high index of clinical suspicion, early establishment of diagnosis and prompt initiation of systemic antifungal therapy are critical in the management of patients with disseminated penicilliosis [8]. This report highlights the importance of careful examination of peripheral blood film which can give an important clue to the early diagnosis of disseminated penicilliosis marneffei. Keywords: Penicillium marneffei, HIV/AIDS, fungal, penicilliosis C7 T6 Reference Duong TA. Infection due to Penicillium marneffei, an emerging pathogen: review of 155 reported cases. Clinical Infectious Diseases 1996;23(1):125–130. Capponi M, Sureau P, and Segretain G. Pe´nicillose de Rhizomyssinensis. Bull Soc Pathol Exot 1956;49:418–421. Di Salvo AF, Fickling AM, and Ajello L. Infection caused by Penicillium marneffei: description of first natural infection in man. Am J Clin. Pathol 1973;59:259–263. M. R. Piehl, R. L. Kaplan, and M. 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