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LIFE Newsletter - Leading International Fungal Education

June 2014

Welcome to LIFE's June Newsletter.

The Burden of disease of 6 more European Countries, and Vietnam the first SE Asian country, along with Iraq and Qatar- covering 340 million people have been presented at the ECCMID conference in Barcelona in May. Notably different from other countries include high rates of Candida bloodstream infections in Denmark (8/100,000), increasing Pneumocystis pneumonia rates in the UK and Germany (0.94 and 1.2/100,000) and high rates of both chronic pulmonary aspergillosis (61/100,000) and Tinea capitis (457/100,000) in Vietnam. Ukraine appears to have generally very high frequencies of several key infections. Read more

Therapeutic drug monitoring (TDM) is often done in patients on azole antifungals and flucytosine.  Please complete our short survey here on the availability and response times of TDM in your city.


IV posaconazole approved by the FDA

First approved in 2006, posaconazole is the most broad spectrum antifungal available. Approval by the US Food and Drug Administration of the intravenous formulation will allow many patients whose blood levels are low or predicted to be low with posaconazole solution, to be successfully treated. Also approved are tablets, which only need to be taken once daily, and promise more reliable bioavailability.Noxafil The new IV formulation [NOXAFIL® (18mg/ml)] is indicated in adults for prophylaxis against invasive Aspergillus and Candida infections in high-risk patients, such as hematopoietic stem cell transplant recipients with GVHD, HIV patients or those with leukaemia..

In clinical bridging studies, the most frequently reported adverse reactions were diarrhoea (32%), hypokalemia (22%), fever (21%) and nausea (19%). The IV formulation will be beneficial to those patients who can't tolerate the oral posaconazole or those who may need IV administration for other reasons. Posaconazole tablets are sustained release and because of better absorption, the dose is only 300mg daily compared with 600-800mg daily with solution. There is also not restriction on timing with food. More info

Mucormycosis outbreak associated with hospital linens

An outbreak of mucormycosis over an 11 month period led to the deaths of 5 children in the New Orleans Children’s Hospital. According to a report just published in Paediatric Infectious Disease Journal. Environmental sampling from all areas and surfaces in the hospital was examined subsequently, but an initial failure to link the cases led to significant delays. Three of the cases had conditions which can result in immunosuppression, and were therefore susceptible to fungal infections like mucormycosis, while 2 had cardiac conditions with persistent acidosis. Hospital linens were the only exposure identified as common to the patients. Rhizopus species were recovered from 26 (42%) of 62 environmental samples from clean linens and associated areas and from 1 (4%) of 25 samples from non linen-related items. All the patients here were infected with Rhizopus delemar, which was also isolated from cultures of clean linens and clean linen delivery bins from the off-site laundry facility. More info

Limited availability of generic antifungals across the world

In a global analysis, GAFFI has identified major gaps in antifungal drug provision for common fungal infections. From multiple sources—most directly from individual countries—it shows flucytosine availability in 24% (map), amphotericin B deoxycholate in 49% (map), itraconazole in 93% (map) and fluconazole in 98% (map) of countries (including PEPFAR provision). No vital antifungals are available in Afghanistan. Interactive versions of our availability and pricing maps are available here.
Fluconazole was only found in one formulation in 17 countries—usually only as a single 150mg capsule for vaginal candidiasis. In other countries multiple generic preparations and dosages are available (eg 38 in Greece and 98 in India). Itraconazole is not available in Eritrea, Senegal, Burundi, Algeria, Dominican Republic or Ukraine. Only one preparation was available in a total of 28 countries; this is in contrast to multiple preparations in several countries. An assessment of the variation in drug cost showed a dramatic variation. More info

News from the Brazilian Society of Infectious Diseases

The FIFA World Cup Brazil-2014 is ongoing in 12 host cities, including the state of São Paulo, which will receive 15 delegations, with the presence of visitors from several states and countries.
Mixing of different cultures can bring health concerns. Diseases eradicated in Brazil, which still exist in other countries may be reintroduced, as well as endemic diseases in our country such as paracoccidioidomycosis and coccidioidomycosis, can constitute a risk for tourists.
For visitors to the World Cup 2014, the Center for Epidemiological Surveillance (CVE) produced the "Guide to Health Cup - Epidemiological Surveillance". This document details some diseases for which reporting is mandatory, and other diseases of importance in the State of São Paulo, with emphasis on public health emergencies and health promotion.
To facilitate the dissemination of the material, the Brazilian Society of Infectious Diseases has provided the document on its website at: www.infectologia.org.br, together with information about major diseases that can be caused by food contamination, such as botulism and diarrhoea; by physical contact, such as conjunctivitis, tuberculosis, and sexually transmitted infections; and animals, insects and/or parasites, such as sporotrichosis from stray cats,dengue, histoplasmosis (from caves) and yellow fever.
All material is available in three languages: Portuguese, English and Spanish, increasing its accessibility to all travellers.

See more News here

Featured LIFE website section: Corticosteroids and fungal infection

Corticosteroids (glucocorticoids) have been used since the end of the 1950’s. There are several related corticosteroids including prednisolone, prednisone, methylprednisolone, dexamethasone and hydrocortisone being the most frequently used oral agents.
Whilst essential in the treatment of many conditions from cancer to transplantation the use of corticosteroids carries risks for the subsequent development of serious fungal infections. In studies of renal transplant and BMT patients the corticosteroid dose impacted very significantly on the risk of getting a fungal infection. For example in BMT patients a daily dose of 1.9mg/kg gave a risk of invasive aspergillosis of 5% but a 3mg/kg dose increased the risk to 14%.
Candidemia in premature neonates was 7.5 fold increased when treated with corticosteroids for hypotension, when compared to those not receiving it.
Corticosteroids are known risk factors in cancer and AIDS patients who develop PCP, cryptococcal meningitis, histoplasmosis and mucormycosis, although co-trimoxazole prophylaxis is important to avoid PCP.
Detailed information on the role of corticosteroids in many fungal infections can be viewed on the LIFE website.

Top Diagnostic Tip

Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology.

Deep cutaneous fungal infections (DCFI) cause significant morbidity and mortality. Discrepancies between identification of fungal infection by histopathology and culture techniques are often seen and present diagnostic challenges as described by Gonzalez Santiago in a 10 year retrospective review of DCFI patients.
There were a number of points to note from the study: Histology identified fungi in most of the samples - but were sometimes misclassified (20 %). In immunocompromised patients and those with deep lesions that potentially could be fungal - then it was better to send biopsies for both culture and histology.
Histology positive, culture negative samples were significant in number and should be treated, failure to do so led to a poor outcome. In patients whose skin biopsy cultures are negative- a non-skin tissue sample (eg skin discharge, sputum, urine) contributed to species identification and hence treatment.

Skin culture was deemed essential for accurate diagnosis of DCFI but sometimes cultures were negative despite the presence of histological evidence. Tissue homogenisation may be one possible explanation - where some fungi eg. Mucorales and Aspergillus spp. are prone to destruction by mechanical shear. Notably Histoplasma capsulatum and Paracoccidioides brasiliensis grow slowly in culture and may require extended incubation times ( ie. 30 + days).
Organisms identified in tissue cultures included Blastomyces dermatitidis, Alternaria, Rhizopus, Fusarium, Acremonium, Scedosporium, Trichophyton mentagrophytes, Coccidioides immitis, and Aspergillus..
It is not clear what the impact of therapy on culture yield is, but it's likely to reduce the number of positive cultures. More information


Really Important Reviews

Molecular diagnosis of endemic and invasive mycoses: advances and challenges
This review provides an overview of the current methods of molecular diagnosis of endemic and invasive fungal diseases, emphasising the need to standardize the different methods. The European Aspergillus PCR Initiative (EAPCRI) has made significant progress in developing a standard for Aspergillus polymerase chain reaction (PCR) but extensive clinical trials will be needed before it is completed.
Efforts should be implemented for the diagnosis of other mycoses in order to fully validate the existing methods or reinforce the need to design new ones. Gomez B L



Human Pathogenic Fungi: Molecular Biology and pathogenic mechanisms. Eds Derek J. Sullivan & Gary P. Moran.

The first six chapters review the transformative effect of applying state-of-the-art tools and innovative approaches to research. The second section of eight chapters, each dedicated to the molecular and cellular biology of a major fungal pathogen of humans: Candida, Aspergillus, Cryptococcus,dermatophytes, Histoplasma, Blastomyces, Pneumocystis and Paracoccidoides. These chapters provide a timely snapshot of the current state of research.

s.ISBN:978-81-312-3556-0 & ebook ISBN: 978-1-908230-66-9

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Free online learning opportunity (CME module)Fungal pulmonary infections: pulmonary aspergillosis in non-hematological patients.

Msc/Diploma in Medical Mycology (distance learning), University College London (2013-14)

Molecular Mycology: Current Approaches to Fungal Pathogenesis, Massachusetts, USA (July 2013). More information

Turkish Society for Medical Mycology organizes its first national congress of Medical Mycology in Ankara, Turkey, 24-26 September, 2014. A pre-congress on hyaline molds, aspergillosis and hyalohyphomycosis will be organized. For information, Emel Tumbay

Masters in Medical Mycology at Manchester University, UK. An MSc programme specially designed for graduates who wish to develop skills as Mycologists. This is a new MSc which is unique, combining much time in the  laboratory, with work experience in the NHS Mycology Reference Laboratory and clinics and ward rounds. The course can be full or part time taught programme.More information.

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Help us evaluate the global burden.

Global burden@LIFE copyright

We are looking for volunteers to assist with estimating the burden of fungal infection in the following countries:
Angola, Bulgaria, Cambodia, Central African Rep., Congo and DRC, Costa Rica, Ghana, Honduras, Madagascar, Nicaragua, Pakistan, Panama, Poland, Tunisia and Venezuela.
View here.
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