Penicillium marneffei is emerging as an important opportunistic pathogen among human immunodeficiency virus (HIV)–infected and immunocompromised residents of (and travelers to) Southeast Asia, Northeastern India, and Southern China. No definitive mode of acquisition has been found, but inhalation has been implicated. The infection has been described in both immunocompromised (>80%) and immunocompetent individuals. Immunocompromised individuals develop disseminated disease involving the reticuloendothelial, skin, respiratory, and gastrointestinal systems. P. marneffei is commonly isolated from skin lesions (90%), blood (76%), bone marrow (100%), and lymph nodes (34%). There are 2 reports of isolation of P. marneffei from cerebrospinal fluid (CSF) of patients with penicilliosis. However, clinical details were lacking in these cases, and despite the fact that other members of the Penicillium genus are known to cause central nervous system (CNS) disease, penicilliosis presenting as a predominantly CNS infection has not been described. We report the clinical characteristics and outcomes of 21 HIV‐infected adult patients who presented with symptoms consistent with a CNS infection and who had P. marneffei isolated from CSF.
Patients. The Hospital for Tropical Diseases in Ho Chi Minh City is the largest referral center for infectious diseases in Vietnam, with >5000 HIV‐infected patients seen yearly. From January 2004 through December 2009, 677 incident cases of penicilliosis were retrospectively identified from our hospital records. Diagnosis was confirmed by culture of P. marneffei from skin scrapings, blood, lymph nodes, bone marrow, or other body tissue. Fifty‐eight (8.6%) of these patients had lumbar puncture performed for suspected CNS infection. A definitive diagnosis of CNS infection was established by CSF culture and/or microscopy (Gram, India, and Zielh‐Neelsen stains) for 29 patients (50%); 20 were due to P. marneffei, 7 to Cryptococcus neoformans, 1 to Mycobacterium tuberculosis, and 1 to both P. marneffei and C. neoformans. The study was approved by the Ethical Committee of the Hospital for Tropical Diseases.
The 21 patients were admitted to Hospital for Tropical Diseases from April 2004 through July 2009. All were HIV infected; the median CD4 count was 11 cells/μL (interquartile range [IQR], 10–12 cells/μL). The median age was 28 years (IQR, 25–31 years); 76% were men. The median duration of illness was 9 days (IQR, 3–30 days). Patients experienced fever (90%), anorexia (57%), fatigue (52%), cough (33%), and diarrhea (29%) prior to the onset of altered mentation that prompted the hospital visits (48%). The median duration of altered mentation was 2 days (IQR, 1.25–2 days). The median temperature was 38.3°C (IQR, 37°C–39°C). On examination, characteristic umbilicated skin lesions were present in 10 patients (photograph of skin lesions in Figure 1), oral thrush in 9, hepatosplenomegaly in 12, and lymphadenopathy in 3 patients. Blood tests showed anemia in 20 patients (median hemoglobin level, 7.2 g/dL; IQR, 5.6–9 g/dL), thrombocytopenia in all patients (median platelet count, 85,000 cells/μL; IQR, 31,000–125,500 cells/μL), and elevated transaminase levels in 18 patients (median alanine transaminase level, 220 units/L; IQR, 109–306 units/L; median aspartate transaminase level, 130 units/L; IQR, 86–181 units/L). Symptoms of altered mentation, including confusion, agitation, or drowsiness, were the presenting features in 10 patients and developed in all remaining patients during hospitalization. Headache was the presenting symptom in 2 patients. Signs of meningeal irritation were absent. Generalized convulsions and facial nerve palsy were observed in 2 and 1 patients, respectively. The CSF analysis is shown in Table 1. The CSF opening pressure was not routinely measured; in 1 patient it measured 180 mm CSF. CSF was clear in all patients and acellular in 14 patients. Among the 7 patients with CSF pleocytosis, the median nucleated cell count was 80 cells/mL (IQR, 19–170 cells/mL), with neutrophil predominance in 3 patients. CSF protein level was elevated (>0.45 g/dL) in 71% of patients, with a median protein level of 0.7 g/dL (IQR, 0.5–0.88 g/dL). The median CSF/serum glucose ratio was 0.65 (IQR, 0.5–0.78); 5 patients had CSF/serum glucose ratios <0.5. Gram stain of CSF was negative in all patients. India ink stain of CSF was positive in 1 of 19 patients tested, and C. neoformans was cultured from blood and CSF samples of this patient (patient 11). Zielh‐Neelsen stain of CSF was negative in all 17 patients examined. A diagnosis of tuberculosis was made in 2 patients by positive Zielh‐Neelsen stain of sputum and lymph node biopsy. The mean time to identify P. marneffei from CSF culture was 4.4 days (range, 2–8 days) and from blood culture was 4.3 days (range, 3–9 days). Blood culture was performed in 18 patients; 13 grew P. marneffei, 1 grew Escherichia coli, 1 grew Enterococcus species, 1 grew unidentified gram‐negative rods, and 1 grew both P. marneffei and C. neoformans.