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Asymptomatic Penicillium marneffei fungemia in an HIV-infected patient

2007; Elsevier BV; Volume: 11; Issue: 3 Linguagem: Inglês

10.1016/j.ijid.2006.04.004

1878-3511

Teresa K. F. Wang, Kwok‐Yung Yuen, Samson S. Y. Wong,

Plant-Microbe Interactions and Immunity

Penicillium marneffei is an AIDS-defining endemic mycosis in Southeast Asia. Patients usually present with fever, weight loss, mucocutaneous lesions, lymphadenopathy, hepatomegaly, or pulmonary infiltrates.1Supparatpinyo K. Khamwan C. Baosoung V. Nelson K.E. Sirisanthana T. Disseminated Penicillium marneffei infection in southeast Asia.Lancet. 1994; 344: 110-113Abstract PubMed Scopus (507) Google Scholar We hereby report the first case of asymptomatic P. marneffei fungemia in an HIV-infected patient. A 47-year-old male was admitted on July 6, 2002 for one week's history of dyspnea. He had been receiving isoniazid, rifampin, pyrazinamide, and ethambutol for three months for treatment of disseminated tuberculosis affecting the lung, terminal ileum, mesenteric lymph nodes, and peritoneum (key clinical and laboratory findings are summarized in Table 1). On admission, he was hypoxic with a temperature of 37.8 °C. There were fine crepitations over bilateral lung bases and a chest radiograph showed bilateral ground-glass infiltrates. Cultures of sputum, bronchoalveolar lavage, and blood were all negative for bacteria and acid-fast bacilli, but transbronchial biopsy confirmed Pneumocystis jiroveci pneumonitis. No fungal pathogens were seen in the sections or bronchoalveolar lavage. Serology for HIV-1 was positive by enzyme-linked immunosorbent and Western blot assays. His CD4+ T-lymphocyte count was 81 cells/μL with a viral load of 100 000 copies/mL. The pneumonitis responded well to two weeks of cotrimoxazole, and he was discharged completely asymptomatic. However, a blood culture taken on the first day of this admission (BACTEC Myco/F Lytic culture bottle, BACTEC 9000, Becton–Dickinson, Maryland, USA), intended for detection of mycobacteria in blood, was positive for a fungus five weeks later. Subcultures on Sabouraud agar showed thermal dimorphism with yeast-like colonies and mould form at 37 °C and 25 °C, respectively. A diffusible red pigment was noted in the mould culture, which was characteristic of P. marneffei (Figure 1). There were no mucocutaneous lesions, lymphadenopathy, or hepatosplenomegaly at any time. Repeated chest radiographs showed marked improvement without any hilar shadows. Repeated blood cultures were negative. Despite the negative physical findings, oral itraconazole 200 mg twice daily was given for two weeks followed by 200 mg daily for maintenance. The patient did not develop overt penicilliosis in the following 34 months.Table 1Summary of clinical events and laboratory findings of the patientDateClinical eventsLaboratory findingsApril 4, 2002Weight loss; right lower abdominal mass; computed tomography showed thickened bowel wall at terminal ileum with enlarged mesenteric lymph nodesStool showed acid-fast bacilli on Ziehl–Neelsen stain; stool and sputum grew Mycobacterium tuberculosisApril 5, 2002Started anti-tuberculous treatment with rifampin, isoniazid, ethambutol, and pyrazinamideApril 22, 2002Sudden onset of epigastric pain with peritonism; laparotomy found perforated terminal ileum with pelvic abscessPeritoneal swab grew M. tuberculosisJune 8, 2002Discharged home; continued anti-tuberculous treatmentJuly 6, 2002Dyspnea and hypoxemiaTransbronchial biopsy found Pneumocystis jiroveci. All other cultures were negative.July 7, 2002Blood culture takenGrew Penicillium marneffei after 5 weeks of incubationJuly 10, 2002HIV serology checkedPositive HIV-1 serologyJuly 13, 2002Discharged homeAugust 16, 2002Blood taken on July 7, 2002 reported positive for P. marneffeiAugust 22, 2002Readmitted for clinical evaluation of asymptomatic P. marneffei fungemiaTwo sets of blood culture repeated and remained negative after 8 weeks of incubationSeptember 7, 2002Started itraconazoleSeptember 20, 2002Discharged home and referred to AIDS clinicOctober 17, 2002Started antiretroviral treatment with indinavir, ritonavir, and combivir Open table in a new tab Penicilliosis is a potentially fatal opportunistic infection in AIDS patients and its classical manifestations have been described.1Supparatpinyo K. Khamwan C. Baosoung V. Nelson K.E. Sirisanthana T. Disseminated Penicillium marneffei infection in southeast Asia.Lancet. 1994; 344: 110-113Abstract PubMed Scopus (507) Google Scholar However, our patient has several notable features that are different from the previously reported cases. Firstly, he remained asymptomatic despite the episode of documented fungemia. The isolation of P. marneffei should be considered as genuine fungemia as the fungus has never been known to cause contamination of blood cultures. Secondly, the fungemia appeared to be transient as the fungus was not isolated from the patient again even before the antifungal agent was given. Asymptomatic fungal infections have been reported in patients with pulmonary cryptococcosis and paracoccidioidomycosis.2Zuger A. Abnormal cryptococcal serology in an asymptomatic patient.AIDS Clin Care. 1995; 7: 48-52PubMed Google Scholar, 3dos Santos J.W. Debiasi R.B. Miletho J.N. Bertolazi A.N. Fagundes A.L. Michel G.T. Asymptomatic presentation of chronic pulmonary paracoccidioidomycosis: case report and review.Mycopathologia. 2004; 157: 53-57Crossref PubMed Scopus (9) Google Scholar This case suggests that transient asymptomatic P. marneffei fungemia is also possible. From a previously reported serological study, there could be a significant number of clinically asymptomatic individuals infected with P. marneffei, particularly among those living in endemic areas.4Chongtrakool P. Chaiyaroj S.C. Vithayasai V. Trawatcharegon S. Teanpaisan R. Kalnawakul S. et al.Immunoreactivity of a 38-kilodalton Penicillium marneffei antigen with human immunodeficiency virus-positive sera.J Clin Microbiol. 1997; 35: 2220-2223PubMed Google Scholar Similarly, an immunocompromised patient with Waldenström's macroglobulinemia developed mixed Candida tropicalis and P. marneffei fungemia during hospitalization, pointing to the possibility of reactivation of a latent infection.5Wong S.S. Woo P.C. Yuen K.Y. Candida tropicalis and Penicillium marneffei mixed fungemia in a patient with Waldenstrom's macroglobulinaemia.Eur J Clin Microbiol Infect Dis. 2001; 20: 132-135PubMed Google Scholar We postulate that in HIV-infected patients, asymptomatic P. marneffei infection could have occurred earlier in life and the fungus may remain latent thereafter. As the course of HIV infection progresses and the patient becomes increasingly immunocompromised, or when immunosuppressing diseases occur in HIV-negative patients, the latent infection may develop into overt penicilliosis. HIV patients living in, or those with a history of traveling to areas where P. marneffei is endemic should ideally be tested for previous exposure to the fungus and primary antifungal prophylaxis be considered. Unfortunately, there are currently no good tests available for this purpose, and seropositivity alone cannot differentiate past infection from latency. A positive fungal culture, even in the absence of the typical manifestations of penicilliosis, should be considered as clinically significant and antifungal treatment and/or prophylaxis should be considered. Further studies would be required to prove that antifungal prophylaxis is beneficial in preventing the development of overt penicilliosis from latent infections. Conflict of interest: No conflict of interest to declare.