Aspergillus galactomannan antigenemia in penicilliosis marneffei

Abstract

Penicillium marneffei usually causes pneumonia and other systemic diseases in HIV-infected patients, especially those who live in or travel to endemic areas [1]. In recent years, this organism has emerged in Taiwan among immunocompromised patients, particularly in HIV-infected patients in whom aspergillosis was rarely encountered [2]. The detection of galactomannan by the Platelia enzyme-linked immunosorbent assay (ELISA; Bio-Rad, Hercules, California, USA) has been widely used in diagnosing invasive aspergillosis [3]. False positives have been identified in patients receiving certain batches of piperacillin–tazobactam, amoxicillin–clavulanic acid [4,5]. In-vitro cross-reactivity of the Platelia ELISA with Penicillium galactomannan and Cryptococcus galactoxylomannan have been reported, and this cross-reactivity has also been reported in a human case with penicilliosis marneffei [6–8]. Patient A, a 47-year-old male heroin abuser with HIV infection, was referred with cough and fever lasting for one month. The blood culture at admission revealed Mycobacterium avium-intracellulare complex. A chest computed tomography scan revealed a cavitation over the left lower lung field. The serum galactomannan sent for suspicious Aspergillosis was positive [optical density (OD) index 4.419] and bronchial washing culture on the next day revealed P. marneffei. His blood culture (Bactec 9240 Myco/F Lytic bottle; Becton Dickinson, Sparks, Maryland, USA) was negative for P. marneffei and the serum galactomannan OD index remained positive 33 days after treatment (OD index 6.527; Fig. 1).Fig. 1: Serial optical density index of serum galactomannan for three patients with penicilliosis marneffei. ♦ Patient A; ▪ patient B; ▴ patient C.Patient B was a 34-year-old man with HIV infection suffering from fever and dry cough for half a month. A chest radiograph revealed a patchy lesion over the right upper lung region. Blood culture at admission revealed P. marneffei. The serum galactomannan test before initiating amphotericin B treatment was positive (OD index 7.752) and remained positive 27 days after treatment when the blood culture was sterile (OD index 1.586). Patient C was a 39-year-old man with HIV infection known for 2 years with poor drug compliance. He was admitted for fever and diarrhea lasting for one month. The chest radiograph showed a ground glass lesion over the left perihilar area. Blood culture at admission revealed P. marneffei. The serum galactomannan test before starting amphotericin B treatment was positive (OD index 10.48) and remained positive 15 days after treatment when the blood culture was sterile (OD index 7.356). The initial CD4 cell counts of these three AIDS patients were 9, 30 and 4 cells/μl for patients A, B, and C, respectively. None of the three patients received piperacillin–tazobactam or amoxicillin–clavunalic acid during their hospital stay. All three patients were not neutropenic and survived the episodes of penicilliosis marneffei. No Aspergillus species was ever isolated from their sputum or any clinical specimens. The results confirm the cross-reactivity of the Platelia ELISA kit with P. marneffei and with serum from patients with penicilliosis marneffei, which remained positive even after effective treatment. The length of galactomannan antigenemia might have been caused by the possibly lower clearance rate of Penicillium galactomannan compared with Aspergillus galactomannan or the presence of Penicillium in the lesion, with a continuous secretion of galactomannan, which enters the bloodstream. The cross-reactivity could be used as a rapid diagnosis for penicilliosis marneffei, although the test was not performed before positive cultures for P. marneffei were obtained. Effective treatment does not, however, decrease the titer but instead remains positive, indicating that this test may not be useful for monitoring treatment outcomes.