Talaromyces (previously Penicllium) marneffei is the third most common AIDS-associated opportunistic infection in many parts of SE Asia. As a dimorphic fungus, it grows as a fission year in those with AIDS, usually causing skin lesions (80%) and positive blood cultures (70%). It is highly susceptible to both amphotericin B and itraconazole, and prior work showed itraconazole prophylaxis was effective at reducing infections. For this reason, and being oral. it was usually used as first line therapy to avoid the toxicities of amphotericin B
In a 440 patients study in Vietnam, Dr Thuy Le and colleagues show that conventional amphotericin B is superior to itraconazole for the treatment of talaromycosis in AIDS.
Their paper published this month in the New England Journal of Medicine, finds no difference in 2 week mortality (6,2%), but a substantially higher mortality at 24 weeks in the itraconazole arm (21% vs, 10%). They also found a faster time to clinical resolution, more rapid clearance of blood cultures, and fewer relapses and episodes of immune reconstitution inflammatory syndrome (IRIS) in the amphotericin B arm.
In this study, the primary endpoint was 2 week mortality which did not differ, and had the authors done a short term study, the important clinical findings of a 10% improved 6 month survival would have been missed. The antifungal-attributable adverse events were higher in the amphotericin B group (infusion related reactions, anaemia, hypokalaemia, hypomagnesaemia and renal failure). However all serious adverse events (including poor control of infection, death and drug side effects) were more common overall in the itraconazole group (46% vs 27%).
Patients were enrolled from 5 hospitals in Vietnam over 3 years and 3 months, 135 per year. This suggests that the published estimate of an annual total of 206 cases in the country (Beardsley et al, 2015) is a substantial under-estimate.
Poor farmers fungal skin condition gets approval from WHO as a neglected disease
The World Health Organisation (WHO) has classed the disease known as chromoblastomycosis (see here for more information) - a disfiguring fungal disease of poor farmers in South America, Africa, and Asia - as a neglected tropical disease (NTD) after lobbying by GAFFI.
Chromoblastomycosis also known as chromomycosis, is one of the most prevalent implantation fungal infections in tropical and subtropical regions around the globe. It is a chronic fungal disease of the skin and subcutaneous tissues, first described in the beginning of the 20th century from Brazil, Cuba and Madagascar. It occurs on a worldwide scale, particularly in rural areas and among poor men aged between 30 and 50.
This chronic, mutilating disease is rarely fatal, but gross disfigurement and amputation of limbs is too commonly necessary. Inoculation of the fungus through the skin of plants or soil contamination leads to infection. Thus farmers, animal breeders and foresters are most at risk.
Prof Denning of GAFFI said " This is an occupational disease and could be prevented with the right clothing and protection and good hygiene advice”.
Chronic pulmonary mucormycosis: an emerging fungal infection in diabetes mellitus
Three cases of chronic pulmonary mucormycosis have been reported from Pakistan in patients (all females in their 60s) with poorly controlled diabetes mellitus and with no other underlying conditions.
Mucormycosis occurs in patients with poorly controlled diabetes, leukemic disorders, and patients undergoing solid organ or hematopoietic stem cell transplantation or neutropenia. The most common presentation being gastrointestinal tract, skin, lungs, central nervous system, eye orbit and the paranasal sinuses disease. Pulmonary mucormycosis is rare, often acute, and is associated with very high morbidity and mortality.
The clinical and radiological manifestations of chronic pulmonary mucormycosis mimics pulmonary tuberculosis imposing a major diagnostic challenge especially in areas were TB is endemic.
In this report by Igbal et al 2017, productive cough, fever, haemoptysis and shortness of breath were the main clinical presentations of chronic pulmonary mucormycosis; all the patients had poorly controlled diabetes with HbA1c ranging from 9.4 to 13.1%. Diagnostic bronchoscopy was performed on all the patients with subsequent histopathology demonstrating numerous aseptate hyphae.
Two patients with unilateral disease improved on intravenous amphotericin B deoxycholate and surgery (lobectomy/pneumonectomy). A patient with bilateral disease in whom surgery was not advisable responded on amphotericin B deoxycholate treatment only.
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Fungal meningitis still kills over 180,000 people per year despite the drugs being available
International HIV experts on fungal meningitis in AIDS report finding nearly 250,000 cases annually, 73% in sub-Saharan Africa. The prior estimate published in 2009 was a million cases with a wide range of uncertainty, now reduced by many more epidemiological studies and partly with more anti-retroviral therapy coverage.
Fungal meningitis due to the Cryptococcus fungus typically affects those in the prime of life, 35 years old. Of those affected an estimated 181,000 people die, despite the existence of a simple blood test and long developed life saving medicines.
Deaths from Cryptococcal Meningitis in AIDS are 15% of all 1,100,000 AIDS-related deaths. Yet, the vast majority of those who survive do so without complications and with treatment of their HIV infection, go on to make a full recovery.
Published in the prestigious journal Lancet Infectious Diseases, Radha Rajasingham and colleagues from the University of Minnesota, which also runs a major research program on fungal meningitis in Kampala in Uganda, used 46 studies from around world to estimate current case numbers. The resurgence of interest in fungal meningitis arises from excellent diagnostic tests that take 10 minutes to perform and cost only about £5/$8.
Dr David Boulware, Associate Professor of Infectious Diseases at the University of Minnesota, and senior author of the study, said: “Still too many HIV-infected people enter care late and Cryptococcal Meningitis is an unfortunate excellent metric of HIV treatment programme failure. In 2017, no person with HIV should develop fungal meningitis, yet in a failed cascade of HIV care, too often Cryptococcus is a final death sentence.”
Molloy and 22 colleagues from around the world have made the case for cryptococcal meningitis to be regarded as a neglected tropical disease (view).
View Video: Fungal meningitis in Africa – what would make a difference
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