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LIFE Newsletter - Leading International Fungal Education

May 2015

GAFFI calls for a change in the way the world views fungal disease

At the ISHAM conference in Melbourne on May 5th, GAFFI (Global Action Fund for Fungal Infections) Logo 95-95has launched the project ‘95-95 by 2025’, calling on all national governments and public health agencies to reduce the toll of death and blindness from fungal diseases. 95-95 means 95 percent of patients with life or sight-threatening fungal disease are diagnosed and 95 percent treated. Currently the figures are at best 50 percent and, at worst, as low as one in three.
GAFFI states that:

  • Simple antifungal remedies are unavailable to half the world's population
  • Public health agencies ignore fungal diseases, despite 1.5 million deaths per year
  • People are dying needlessly although medicines to save them have been around for over 50 years
Tania SorrellSignificant advances in diagnostics for fungal pneumonia and meningitis have been made over the last 15 years, but are only available in a few countries. One key example is the antifungal drug amphotericin B, which was first used in 1959, but it is still not available in 76 countries, despite it being critical for the treatment of fungal meningitis. 

GAFFI has launched a 10 year roadmap outlining the way forward and objectives that must be addressed in order to change course and save the unecessary loss of many lives.

Professor Tania Sorrell who chaired the launch commented: “95-95 by 2025 is a bold and necessary call to action for fungal disease experts, the diagnostic and pharmaceutical industry and the public health community to really make an impact, especially among the disadvantaged in the world.” 
GAFFI roadmap; News item; More information;


NEWS

ABPA found in 26% of paediatric patients with poorly controlled asthma in India

Many adults with asthma are sensitised to fungi, especially those with severe asthma. Total IgE level is regarded as a good marker for allergic bronchopulmonary aspergillosis (ABPA) - rising during exacerbations and falling during remissions. However there is little data on ABPA in paediatric patients with asthma.
In a study from India, (Singh et al 2015) ABPA was found in 26% of 100 paediatric patients with poorly controlled asthma. ABPA diagnosis was obtained using approved criteria. There was  a significant difference in the forced expiratory volume (FEV1) between ABPA positive and negative children, which is consistent with adult ABPA.

Many more boys were affected with ABPA than girls, with a ratio or 4 to 1, compared with those without ABPA in whom the ratio was 3:1. This study indicates a higher rate of ABPA in paediatric patients with problematic asthma than expected from other studies – but also that a higher cut off value of total IgE 1200 IU/mL is proposed as a predictive parameter for ABPA in children with asthma, rather than the 1000 IU/ml used in adults.
The results from this study provoke the question as to whether paediatric patients with poorly controlled asthma should be tested for fungal sensitivity and offered antifungal therapy at an early stage in their management. More information

Fungal disease burdens from 9 more countries presented at ECCMID, ISHAM & API

The burden of fungal disease from nine countries and covering a further 490.5 million head of population has been estimated by LIFE collaborators and presented at these conferences. Data from Nepal and Thailand, Canada, Ecuador and Chile, Jordan and Egypt and Indonesia and New Zealand were presented. Some of the notable findings were: a high rate of asthma and likely ABPA in New Zealand, Egypt, Jordan and Chile. High rates of cryptococcal disease in Thailand, higher than average rates of disseminated histoplasmosis and cryptococcosis in HIV patients in Ecuador.
Also fungal keratitis is common in Nepal, Thailand and Egypt
(19,938, 9,765 and 11,550 cases annually in each country) but rare in New Zealand (31 cases). More information

How to bolster the antifungal pipeline

The last new class of antifungal emerged in 2002 and no new antifungals have been licensed since 2006. An estimated 300 million people worldwide have serious fungal disease with 1.3- 2 million dying and new agents are desperately needed. Prof Denning and Dr Bromley highlight the problems for doctors in a recent article. Dr Bromley, a Lecturer at Manchester University is trying to identify new drugs, he commented ‘New antifungals are tough to find, partly because the human cell machinery is quite similar to fungi, so killing a fungal cell without damaging a human cell is tricky. We have several promising leads however, which we are working on as fast as resources allow.’

Very low numbers of funded positions in this area - in the UK and USA (few grants awarded), greatly impedes research in the area. Also high drug resistance rates for Candida and Aspergillus are of serious concern as there are limited types of antifungals available. 

More information

Improved 12-month survival when community support is given with cryptococcal antigen screeening in HIV

Around 10 million people in Africa receive antiretroviral therapy (ART)  for HIV infection, but mortality in the first few months and during the first year is higher than in Europeans. Tuberculosis and cryptococcal meningitis account for the majority of deaths in Africa in HIV patients. A paper published in the Lancet online this week has highlighted that the provision of a short period of community support from lay workers alongside screening for cryptococcal antigen, substantially reduces mortality in patients with advanced HIV disease, who are commencing antiretroviral therapy.
More information
See more News here


Featured LIFE website section: Fungal keratitis

Infections of the cornea can give rise to corneal opacity and potentially blindness if not identified rapidly and treated correctly. Characteristically a diagnosis may be suspected when an observation of white/yellow infiltrates in the corneal stroma are seen along with an epithelial tear or injury, and signs of inflammation. An eye trauma - particularly associated with plant & crop material as a source of injury is common before onset of fungal keratitis.

Diagnosis is made from a corneal scrape of the infected area or biopsy when the infection is within the stroma. Material should be collected from the base and edges of the ulceration. Calcium alginate swabs premoistened with tryptone soy broth used for debridement may facilitate recovery of fungi in culture. Microscopy (lactophenol cotton blue, gram stain and Calcofluor white) and culture (and possibly PCR) are necessary, because of the wide variety of fungi involved. Prolonged culture (3 weeks) at 25ºC or 30ºC may be necessary. 
The invasive fungus is most often Fusarium spp, Aspergillus flavus, Aspergillus fumigatus or occasionally Candida albicans. Less common species include Curvularia lunataScedosporium apiospermum, Bipolaris spp., Lasiodiplodia theobromae amongst others.Aspergillus keratitis

Topical treatment with antifungal therapy is essential. In severe cases this may be given hourly in the first days of treatment. For superficial lesions caused by filamentous fungi, topical natamycin 5% (optimal treatment), or amphotericin B 0.15% or voriconazole 2-3% (50µg/ml) are used; oral therapy is usually used additionally, for severe cases visit the site here.

Topical treatment with natamycin has a 65-75% response rate with retention of vision; but fungal keratitis is associated with a high risk of perforation. Recovery of sight is much higher if the diagnosis is made early.

Fungal keratitis section; LIFE website.


Top Diagnostic Tip

Id or Dermatophytid reactions

 

Id or dermatophytid reactions are relatively common in tinea capitis, but little discussed in the literature. Id reactions are a type of secondary immunologic reaction provoked by many different stimuli, usually manifest as a ‘ rash' physically separate from the location of the stimulus. A dermatophytid reaction is an id reaction caused by dermatophyte infection. The treatment of a dermatophytid reaction is to treat the underlying fungal infection or dermatitis, and to avoid mis-diagnosis of a second dermatological disorder.  Dermatophytid reactions include eczematous eruptions or plaques, pruritic papules and angioedema-like reactions. Dermatophytid reactions tend to occur when the dermatophyte infection is at its zenith or may develop or worsen when systemic antifungal therapy is given. The frequency is unknown, but may be more common that appreciated, and can occur with any type of dermatophytosis. It may be more common with inflammatory tinea capitis, such as kerion celsi. A recent paper from Istanbul shows many vivid examples and overviews the topic.


Really Important Reviews

Chronic Aspergillosis of the Lungs: Unravelling the Terminology and Radiology: by S. R. Desai & V. Hedayati & K. Patel & D. M. Hansell.
A review covering the following areas: • The classification of Aspergillus-related lung disease is mired in confusion. • The chronic form of Aspergillus infection is associated with significant morbidity and mortality. • Progressive consolidation and cavitation with intracavitary material is the radiological hallmark.

Article


Books

 

Human Fungal Pathogens: Edited by Casadevall & Mitchell et al

This collection from Cold Spring Harbor Perspectives in Medicine provides a comprehensive review of the biology and diseases of fungal pathogens. Contributors examine their life cycles, nutritional and metabolic requirements, and morphological characteristics, as well as their interactions with humans—their modes of dissemination and penetration, the mechanisms they use to evade the immune system, and their effects on target organs. Specific chapters are devoted to the major disease-causing fungi, such as Candida, Aspergillus, and Cryptococcus species.


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Courses

 

HFP2015, the 6th FEBS Advanced Lecture Course on Human Fungal Pathogens, May 16-22, 2015 La Colle-sur-Loup, France: More info

New Antifungal Toolkit: The Pharmacopeia and Beyond is an Internet CME curriculum that will provide current information about new FDA-approved agents/formulations for the management of invasive fungal infections (IFIs) and evaluate the role of these newer options in strategies to optimize antifungal therapy.  More information

Mechanisms in Fungal Infections -From the science to the Clinical Setting (E-learning course)   Course with CME content developed by expert multidisciplinary specialists. Designed for oncologists, hematologists, and infectious disease specialists who treat patient groups at  risk from developing fungal infectionsMore 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, Bolivia, Bulgaria, Bosnia, Burkina Faso, Cambodia, Central African Rep., Chad, DRC, Costa Rica, Gabon, Honduras, Laos Mali, Myanmar, Nicaragua, Panama, Papua New Guinea, Poland, Slovak Republic, Tunisia.
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