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Fungal Infections

 

Disease name and synonyms

Talaromyces marneffei infection (formerly Penicillium marneffei infection or penicilliosis)

Fungi responsible (links to these)

Talaromyces marneffei .

Disease description

Most patients have fever, weight loss and malaise. Subcutaneous abscesses and papule-like ulcers are common. Sometimes the skin lesions are very small, like molluscum contagiosum. Anaemia, hepatosplenomegaly, lymphadenopathy and diarrhoea are also relatively common. As patients usually have very low CD+ counts, other concurrent opportunistic infections are common. Cough is common, but pneumonia is rare, despite this being the portal of entry of the organism. Occasionally a confusional state occurs, with abnormal cerebrospinal fluid findings.

Frequency and global burden

All cases originate from southeast Asia, notably Thailand, Vietnam, Hong Kong, southern China, Taiwan, India, Indonesia, Cambodia and Laos, unless laboratory acquired. 10% of AIDS patients in Hong Kong and ~30% of patients in N. Thailand present with a Talaromyces marneffei  infections. Patient with AIDS and penicilliosis present all over the world, following travel.

Underlying problems and at risk patients

Late HIV infection with CD4+ counts less than 100 x106/L.

Rarely other immunocompromised patients.

Diagnostic testing

For culture, bone marrow gives the highest yield (~100%), followed by skin biopsy (90%) and blood culture (76%). On gram stain of a positive blood culture, septated hyphae-like structures are seen, despite T. marneffei existing in yeast form at 37°C. These hyphae break down into arthroconidia-like yeast cells over time. Over 80% of patients with disseminated penicilliosis are galactomannan antigen (‘Aspergillus’) positive in sera.

In high grade fungaemia, intracellular yeast cells may be seen within monocytes on a peripheral blood smear. Fine-needle aspiration of lymph nodes, sputum cytology and touch smear of skin may show small yeasts within histiocytes or extracellularly. Tissue reaction is often muted. Talaromyces marneffei  may be confused with H. capsulatum but has a central transverse septum unlike any other common pathogenic yeast.

Treatments

The mortality of untreated T. marneffei infection is 100%. Treatment of choice is amphotericin B (0.6mg/kg) for 2 weeks followed by oral itraconazole 400mg per day for 10 weeks. Itraconazole treatment alone is effective but a higher relapse rate. Simultaneous initiation of anti-retroviral treatment with amphotericin B or at the start of itraconazole therapy is appropriate. Immune restoration inflammatory syndrome (IRIS) is rarely reported in patients with penicilliosis.  Anti-retroviral treatment should not be withheld because of concern for possible development of IRIS. Secondary prophylaxis with itraconazole 200mg/day is highly effective in reducing relapse.

Outlook and prognosis

If the diagnosis is made promptly, and initiation of antifungal therapy given, the outlook is good. Central nervous system involvement is more difficult to treat, with a poor outlook.

Images


Small skin lesions with septic appearance, a manifestation of dessiminated T. marneffei infection in AIDS acquired in Thailand presenting in the UK 


Molluscum contagiosum - like lesions on forehead of a lab acquired case of T. Marneffei infection in the context of unsuspected HIV infection.

Talaromyces marneffei  endophthalmitis as a part of disseminated infection in AIDS.


Geographical location of Talaromyces marneffei  in SE Asia.


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