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LIFE Newsletter - Leading International Fungal Education

July 2017

Randomised trial establishes Amphotericin B as best therapy for Talaromyces marneffei in HIV
Talaromyces (previously Peniclliummarneffei 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.
ampho B
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.

Thuy Le et al, 2017  article    Beardsley et al, 2015 article

More information


NEWS

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.
chromoblastomycosis
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”.

More information. Chromoblastomycosis review article

 

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.
More information. Article

 

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
Read more; Article

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Featured LIFE website section: Coccidioidomycosis

 Coccidioidomycosis is restricted to the Americas. Coccidioides immitis and Coccidioides posadasii are the fungi responsible. An estimated 150,000 infections occur annually in the USA, and an unknown number in central and South America. Approximately 25,000 new, clinical cases of coccidioidomycosis are reported annually in the USA leading to ~75 deaths per year. Occasional epidemics occur. Case numbers have been rising in Arizona, possibly related to immigration to the state and building on previously wild desert areas, with 7 cases per 100,000 persons in 1990, increasing~75 cases per 100,000 persons in 2007. The most affected countries outside the USA are Mexico, Guatemala, Brazil, Paraguay and Argentina.

Initial infection results in symptoms in 40% of individuals which are self-limited in 80% of these people. Typical features are a ‘short-lived ‘flu-like’ syndrome (fever, cough and pleurisy), sometimes associated with erythema nodosum or erythema multiforme (especially in women). Most progressive disease involves the lungs, following a primary infection pulmonary nodules or cavitation may occur, which may or may not progress. Dissemination, which is usually clinically silent, may occur to any body site, the more common locations being the skin, meninges, bones or joints, lymph nodes and other soft tissues. The clinical presentation may be delayed weeks or months after the primary infection.
View full description: LIFE section.


Top Diagnostic Tips: Galactomannan in sputum and chromogenic agars.

Galactomannan (GM) detection is now a cornerstone test for detection of Aspergillus and is often the only microbiological test positive in invasive aspergillosis. It is a long carbohydrate found in blood in neutropenic patients with invasive aspergillosis (sensitivity ~80%) and bronchoscopy fluid from all forms of aspergillosis. It is also produced by Histoplasma and Fusarium and by a few bacteria, notably Bifidobacteria. It is also abundant in certain foods, cardboard and some antibiotics.
Just published is a paper investigating GM in sputum of those with allergic and chronic aspergillosis: Much higher levels are routinely detectable in sputum, the test (and Aspergillus PCR) is only of value in mucopurulent, purulent and/or bloody sputum specimens and it is not possible to establish a reliable cutoff. Half the samples had GM values over 6.5!

Chromogenic agars differ in their performance for yeasts:
A comparison of 6 chromogenic agars showed all able to distinguish Candida albicans, C. tropicals and C. krusei, but substantial differences in performance with C. glabrata, C. parapsilosis and C. lusitaniae. On this test, Brilliance candida agar (Oxoid) appears best. (link)

Article

 

Really Important Review: Oral fungal infections
A well illustrated broad review by David Telles and colleagues in Los Angeles of the many forms of oral candidiasis and rarer infections including mucormycosis and histoplasmosis are described here. A detailed discussion of the prevention and management of these infections is provided. Review

Book

Case Book of Invasive Fungal Infections: 1st Edition, 2017

Author: Rajeev Soman , Camilla Rodrigues 

Aavailable here

ISBN: 9789383989249

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Courses

 

A short course on Diagnosis and therapy of fungal diseases will be held between 9th and 10th October, 2017 in Belgrade, Serbia, following TIMM-8. More information and registration

Mycology MasterClass VIII will be held between the 26 and 28th October, 2017 at Mantra on Salt Beach, Kingscliff, Tweed Coast, NSW. More information  

A 5-day course on Fungi of the indoor and outdoor environment, organised by the Scientific Institute of Public Health is being held in BrusselsBelgium on the 23-27th October 2017. For registration, click here

E-learning course in direct microscopy for identifying fungal infections
Experts in Manchester have recently launched the first e-learning course in direct microscopy for identifying fungal infection, also teaching histological staining methods and interpretation of fungal elements. The course is accredited by the University of Manchester & will teach not only how to rapidly and accurately diagnose life-threatening fungal infections, but also how to set up direct microscopy in a diagnostic laboratory. It is available at www.microfungi.net and is now available in Spanish. The first 50 students to complete this course will be offered free ESCMID membership for one year.

Global burden@LIFE copyright

Now that itraconazole is an essential medicine (press release) we are seeking information about its availability and cost in countries: Morocco, Western Sahara, Mauritania, Mali, Niger, Chad, Sierra Leone, Liberia, Togo, Guinea, Gabon, Congo, Central African Republic, South Sudan, Eritrea, Angola, Lesotho, Swaziland, Paraguay, Moldova, Azerbaijan, Turkmenistan, Kryrgyzstan, Tajikstan, Bhutan, Cambodia  and Papua New Guinea.
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