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Comparison of Talaromyces marneffei infection in HIV positive and HIV negative patients in China

June 16 2016

Talaromyces marneffei (formerly called Penicillium marneffei) is a dimorphic fungus which causes systemic fungal infections formerly referred to as penicilliosis. T. marneffei was commonly diagnosed in HIV-infected individuals from endemic areas (Southeast Asia and Southern China and nearby countries including Thailand, Laos and Malaysia), prior to the era of highly-active antiretroviral therapy (HAART), and was an important cause of morbidity and mortality. The widespread use of HAART has led to a significant decline in T. marneffei infections among HIV-infected patients in these areas.

T. marneffei is believed to be acquired by inhalation of microconidia from the mycelial phase of the organism. T. marneffei infections typically develop in immunocompromised individuals, especially those with HIV infection at the advance stage of disease (CD4 cell count < 100 cells/L). However, it has also been described in patients from endemic areas in Asia who were HIV-negative and had CD4 cell counts within normal limits (1). Some of these patients had other underlying diseases (e.g. autoimmune disorders, cancer or diabetes) and those without underlying diseases were found to have auto-antibodies to interferon gamma as a reason for their increased susceptibility to disseminated infection (2).

 
Culture of Talaromyces marneffei showing the granular colony appearance with diffusible red pigment in the agar (Sabouraud medium).
 

Little is known about T. marneffei infection in HIV-negative patients. A descriptive retrospective study in 19 HIV-positive and 7 HIV-negative patients with T. marneffei infection has been carried out in a tertiary centre in Fujian, China, to compare clinical characteristics and outcomes after therapy in both groups. 

Patients with disseminated disease usually develop fever, anaemia, weight loss and skin lesions that typically occur on the face, extremities and genitalia. Such patients may also have thrombocytopenia, hepatosplenomegaly and various symptoms of the pulmonary and digestive systems. In the reported study, the HIV-negative and HIV-positive groups both had typical symptoms of systemic infection, including fever, weight loss, anaemia and hepatosplenomegaly. Lymph node enlargement, diarrhoea and necrotic skin rash were common in the HIV-negative group whereas dyspnoea was more common in the HIV-positive group (57% vs 5%, p=0.010). Most of the patients were males (HIV-positive group 86%; HIV-negative group 79%). Time from symptom onset to diagnosis of T. marneffei infection was significantly longer in the HIV-negative patient group (60 days vs 30 days, p=0,041) which may be because T. marneffei infection progresses more rapidly in HIV-positive patients.

In the HIV-negative group, two thirds of patients had an underlying disease related to immune dysfunction. It was also reported that more than 70% of the HIV-positive patients were co-infected with other opportunistic infections at the time of diagnosis, mostly fungi, herpes and syphilis, but none with tuberculosis or cytomegalovirus.

Rapid diagnosis and treatment of T. marneffei infection are critical because untreated patients have greatly increased risk of mortality from sepsis. Clinical guidelines recommend 2 weeks of intravenous liposomal amphotericin B (3-5mg/kg body weight per day) and then oral itraconazole (400mg qd) for 10 weeks as a standard treatment for an HIV-infected patient (3). However, in China itraconazole treatment is not possible in most patients due to its high cost. Therefore, in the study a combined therapy of amphotericin B and fluconazole was used in most patients with success

Bibliography and link:

Talaromyces marneffei

1.       Kawila R, Chaiwarith R, Supparatpinyo K. Clinical and laboratory characterics of peniciliosis marneffei among patients with and without HIV infection in Northern Thauland: a retrospective study. Infect Dis, 2013; 13:464.

2.       Browne SK, Burdelo PD, Chetchotisakd P, et al. Adult-onset immunodeficiency in Thailand and Taiwan. N Engl J Med, 2012;367(8):725-34.

3.       Masur H, Brooks JT, Benson CA, et al. National Institutes of health. Prevention and treatment of opportunistic infections in HIV-infected adults and adolescent: updated guidelines from the Centres for Disease Control and Prevention; HIV Medicine Association of the Infectious Diseases Society of America.