Diagnosis and treatment of Penicillium (Talaromyces) marneffei infection
- Khuanchai Supparatpinyo, MD
Khuanchai Supparatpinyo, MD
- Professor of Medicine
- Chiang Mai University
- Thira Sirisanthana, MD
Thira Sirisanthana, MD
- Professor of Medicine
- Chiang Mai University
Talaromyces marneffei (formerly Penicillium marneffei) is an important cause of morbidity and mortality in HIV-infected and other immunosuppressed patients who live in or are from Southeast Asia, and can occasionally cause disease in such patients who have had travel-related exposure to this organism . Penicillium marneffei was renamed Talaromyces marneffei in 2015; however, the disease is still referred to as penicilliosis.
For HIV-infected individuals, this systemic fungal infection was commonly diagnosed prior to the era of potent antiretroviral therapy (ART). The widespread use of ART has led to a significant decline of opportunistic infections (OIs), including T. marneffei infection in highly endemic areas. However, despite the widespread availability of ART, T. marneffei infection continues to cause considerable morbidity and mortality in AIDS patients who are unaware of their HIV infection, who do not have access to ART, or who have a suboptimal response to HIV therapy.
The diagnosis and treatment of P. marneffei will be reviewed here. The mycology, epidemiology, and clinical manifestations of P. marneffei are discussed elsewhere. (See "Epidemiology and clinical manifestations of Penicillium (Talaromyces) marneffei infection".)
The diagnosis of penicilliosis should be considered in patients who live in or are from Southeast Asia, northern Australia, South Asia (including India), and China and present with fever, weight loss, non-productive cough, skin lesions, hepatosplenomegaly, and/or generalized lymphadenopathy. Penicilliosis typically occurs in patients who are severely immunocompromised (eg, those with AIDS); however, cases have also been reported in those with other underlying conditions (eg, autoimmune disorders, cancer, diabetes) [2,3]. (See "Epidemiology and clinical manifestations of Penicillium (Talaromyces) marneffei infection", section on 'Epidemiology'.)
A definitive diagnosis is usually made by culture of the fungus from blood, skin biopsy, bone marrow, or lymph nodes. However, given the need for early treatment, a presumptive diagnosis can be made by demonstrating the characteristic morphologic findings of this fungus in biopsy material or in blood smears of patients with fungemia (picture 1) [1,4,5]. T. marneffei (formerly P. marneffei) appear as oval or elongated yeast-like organisms with a clearly defined central septum. The presence of a centrally located transverse septum (eg, "cross wall") differentiates T. marneffei from Histoplasma capsulatum (picture 2) .
- Supparatpinyo K, Khamwan C, Baosoung V, et al. Disseminated Penicillium marneffei infection in southeast Asia. Lancet 1994; 344:110.
- Kawila R, Chaiwarith R, Supparatpinyo K. Clinical and laboratory characteristics of penicilliosis marneffei among patients with and without HIV infection in Northern Thailand: a retrospective study. BMC Infect Dis 2013; 13:464.
- Browne SK, Burbelo PD, Chetchotisakd P, et al. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med 2012; 367:725.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on September 21, 2016).
- Supparatpinyo K, Sirisanthana T. Disseminated Penicillium marneffei infection diagnosed on examination of a peripheral blood smear of a patient with human immunodeficiency virus infection. Clin Infect Dis 1994; 18:246.
- Hung YT, Yang SP. Pancytopenia in a Southeast Asian Woman with HIV Infection. Clin Infect Dis 2009; 49:122.
- Jayanetra P, Nitiyanant P, Ajello L, et al. Penicilliosis marneffei in Thailand: report of five human cases. Am J Trop Med Hyg 1984; 33:637.
- So SY, Chau PY, Jones BM, et al. A case of invasive penicilliosis in Hong Kong with immunologic evaluation. Am Rev Respir Dis 1985; 131:662.
- Louthrenoo W, Thamprasert K, Sirisanthana T. Osteoarticular penicilliosis marneffei. A report of eight cases and review of the literature. Br J Rheumatol 1994; 33:1145.
- Vanittanakom N, Vanittanakom P, Hay RJ. Rapid identification of Penicillium marneffei by PCR-based detection of specific sequences on the rRNA gene. J Clin Microbiol 2002; 40:1739.
- Sekhon AS, Li JS, Garg AK. Penicillosis marneffei: serological and exoantigen studies. Mycopathologia 1982; 77:51.
- Chariyalertsak S, Sirisanthana T, Supparatpinyo K, et al. Case-control study of risk factors for Penicillium marneffei infection in human immunodeficiency virus-infected patients in northern Thailand. Clin Infect Dis 1997; 24:1080.
- Heath TC, Patel A, Fisher D, et al. Disseminated Penicillium marneffei: presenting illness of advanced HIV infection; a clinicopathological review, illustrated by a case report. Pathology 1995; 27:101.
- Yousukh A, Jutavijittum P, Pisetpongsa P, et al. Clinicopathologic study of hepatic Penicillium marneffei in Northern Thailand. Arch Pathol Lab Med 2004; 128:191.
- Chaiwun B, Khunamornpong S, Sirivanichai C, et al. Lymphadenopathy due to Penicillium marneffei infection: diagnosis by fine needle aspiration cytology. Mod Pathol 2002; 15:939.
- Vanittanakom N, Sirisanthana T. Penicillium marneffei infection in patients infected with human immunodeficiency virus. Curr Top Med Mycol 1997; 8:35.
- Cao L, Chan KM, Chen D, et al. Detection of cell wall mannoprotein Mp1p in culture supernatants of Penicillium marneffei and in sera of penicilliosis patients. J Clin Microbiol 1999; 37:981.
- Vanittanakom N, Mekaprateep M, Sittisombut N, et al. Western immunoblot analysis of protein antigens of Penicillium marneffei. J Med Vet Mycol 1997; 35:123.
- Wheat LJ. Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host. Transpl Infect Dis 2006; 8:128.
- Chaiyaroj SC, Chawengkirttikul R, Sirisinha S, et al. Antigen detection assay for identification of Penicillium marneffei infection. J Clin Microbiol 2003; 41:432.
- Vanittanakom N, Merz WG, Sittisombut N, et al. Specific identification of Penicillium marneffei by a polymerase chain reaction/hybridization technique. Med Mycol 1998; 36:169.
- Kaufman L, Standard PG, Jalbert M, et al. Diagnostic antigenemia tests for penicilliosis marneffei. J Clin Microbiol 1996; 34:2503.
- LoBuglio KF, Taylor JW. Phylogeny and PCR identification of the human pathogenic fungus Penicillium marneffei. J Clin Microbiol 1995; 33:85.
- Prariyachatigul C, Chaiprasert A, Geenkajorn K, et al. Development and evaluation of a one-tube seminested PCR assay for the detection and identification of Penicillium marneffei. Mycoses 2003; 46:447.
- Desakorn V, Simpson AJ, Wuthiekanun V, et al. Development and evaluation of rapid urinary antigen detection tests for diagnosis of penicilliosis marneffei. J Clin Microbiol 2002; 40:3179.
- Tsunemi Y, Takahashi T, Tamaki T. Penicillium marneffei infection diagnosed by polymerase chain reaction from the skin specimen. J Am Acad Dermatol 2003; 49:344.
- Huang YT, Hung CC, Liao CH, et al. Detection of circulating galactomannan in serum samples for diagnosis of Penicillium marneffei infection and cryptococcosis among patients infected with human immunodeficiency virus. J Clin Microbiol 2007; 45:2858.
- Huang YT, Hung CC, Hsueh PR. Aspergillus galactomannan antigenemia in penicilliosis marneffei. AIDS 2007; 21:1990.
- Vanittanakom N, Cooper CR Jr, Fisher MC, Sirisanthana T. Penicillium marneffei infection and recent advances in the epidemiology and molecular biology aspects. Clin Microbiol Rev 2006; 19:95.
- Mootsikapun P, Srikulbutr S. Histoplasmosis and penicilliosis: comparison of clinical features, laboratory findings and outcome. Int J Infect Dis 2006; 10:66.
- Wheat J, Wheat H, Connolly P, et al. Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses. Clin Infect Dis 1997; 24:1169.
- Supparatpinyo K, Nelson KE, Merz WG, et al. Response to antifungal therapy by human immunodeficiency virus-infected patients with disseminated Penicillium marneffei infections and in vitro susceptibilities of isolates from clinical specimens. Antimicrob Agents Chemother 1993; 37:2407.
- Ranjana KH, Priyokumar K, Singh TJ, et al. Disseminated Penicillium marneffei infection among HIV-infected patients in Manipur state, India. J Infect 2002; 45:268.
- Sirisanthana T, Supparatpinyo K, Perriens J, Nelson KE. Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients. Clin Infect Dis 1998; 26:1107.
- Cuenca-Estrella M, Gomez-Lopez A, Mellado E, et al. Activity profile in vitro of micafungin against Spanish clinical isolates of common and emerging species of yeasts and molds. Antimicrob Agents Chemother 2009; 53:2192.
- Cao C, Liu W, Li R, et al. In vitro interactions of micafungin with amphotericin B, itraconazole or fluconazole against the pathogenic phase of Penicillium marneffei. J Antimicrob Chemother 2009; 63:340.
- Al-Abdely HM. Management of rare fungal infections. Curr Opin Infect Dis 2004; 17:527.
- Le T, Huu Chi N, Kim Cuc NT, et al. AIDS-associated Penicillium marneffei infection of the central nervous system. Clin Infect Dis 2010; 51:1458.
- Supparatpinyo K, Chiewchanvit S, Hirunsri P, et al. An efficacy study of itraconazole in the treatment of Penicillium marneffei infection. J Med Assoc Thai 1992; 75:688.
- Spanakis EK, Aperis G, Mylonakis E. New agents for the treatment of fungal infections: clinical efficacy and gaps in coverage. Clin Infect Dis 2006; 43:1060.
- Perfect JR, Marr KA, Walsh TJ, et al. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis 2003; 36:1122.
- Supparatpinyo K, Schlamm HT. Voriconazole as therapy for systemic Penicillium marneffei infections in AIDS patients. Am J Trop Med Hyg 2007; 77:350.
- Supparatpinyo K, Perriens J, Nelson KE, Sirisanthana T. A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus. N Engl J Med 1998; 339:1739.
- Manosuthi W, Chaovavanich A, Tansuphaswadikul S, et al. Incidence and risk factors of major opportunistic infections after initiation of antiretroviral therapy among advanced HIV-infected patients in a resource-limited setting. J Infect 2007; 55:464.
- Gupta S, Mathur P, Maskey D, et al. Immune restoration syndrome with disseminated Penicillium marneffei and cytomegalovirus co-infections in an AIDS patient. AIDS Res Ther 2007; 4:21.
- Chaiwarith R, Charoenyos N, Sirisanthana T, Supparatpinyo K. Discontinuation of secondary prophylaxis against penicilliosis marneffei in AIDS patients after HAART. AIDS 2007; 21:365.
- Sun HY, Chen MY, Hsiao CF, et al. Endemic fungal infections caused by Cryptococcus neoformans and Penicillium marneffei in patients infected with human immunodeficiency virus and treated with highly active anti-retroviral therapy. Clin Microbiol Infect 2006; 12:381.
- Thai national guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2010. http://abm.digitaljournals.org/index.php/abm/article/viewFile/543/398 (Accessed on May 21, 2015).
- Chariyalertsak S, Supparatpinyo K, Sirisanthana T, Nelson KE. A controlled trial of itraconazole as primary prophylaxis for systemic fungal infections in patients with advanced human immunodeficiency virus infection in Thailand. Clin Infect Dis 2002; 34:277.
- Molecular diagnostics
- Galactomannan antigen detection
- DIFFERENTIAL DIAGNOSIS
- Treatment approach
- Available agents
- Induction therapy
- - Moderate to severe disease
- - Mild disease
- Maintenance therapy (secondary prophylaxis)
- Patient monitoring
- When to initiate antiretroviral therapy
- Discontinuing maintenance therapy
- Recurrent infection
- Initiating primary prophylaxis
- Discontinuation of primary prophylaxis
- SUMMARY AND RECOMMENDATIONS