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LIFE Newsletter - Leading International Fungal Education

December 2015

Isavuconazole is available in Europe

This week isavuconazole (Cresemba) will be available in Europe for the first time. Following the FDA approval of this new antifungal in the US in March 2015, the European Commission approved isavuconazole in October, for the treatment of adult patients with invasive aspergillosis (first line) or mucormycosis, for whom amphotericin B is inappropriate. The European marketing authorization for isavuconazole is valid in all 28 EU member states, as well as in Iceland, Liechtenstein and Norway.
Isavuconazole is provided as a highly soluble pro-drug available intravenously or orally with excellent bioavailability which may be switched without dose adjustment. After the inital drug loading it is a once daily dose due largely to its slow elimination, good tissue distribution and high protein binding.

isavuconazole tabletIsavuconazole is active against a number of clinically important yeasts and molds, including Candida spp, Aspergillus spp, Cryptococcus neoformans, and Trichosporon spp and has variable activity against Mucorales spp.
The most commonly reported adverse events, which are mild, include nausea, diarrhoea and raised liver function tests. It exhibits less toxicity than voriconazole but for aspergillosis it is just as effective, suggesting isavuconazole may become the preferred drug of choice. Its drug interaction potential appears to be less than other azole antifungals - also a beneficial feature.
It remains to be ascertained whether plasma drug levels will require continuous monitoring; whether it has efficacy in sanctuary sites such as eye, brain and prostate; whether it can be used in paediatric patients; whether it has a role in chronic and allergic aspergillosis treatment and lastly its full spectrum of toxicity will only become clearer as its prescribing increases.

As an addition to the azole antifungal repertoire it promises to be useful. Review

Isavuconazole further information


Allergic fungal rhinosinusitis (AFRS) very common in Israel compared to India

Fungal diseases are a significant cause of morbidity and mortality in Israel, with invasive candidiasis and invasive aspergillosis accounting for the largest number of fungal related deaths. Estimations on disease burdens were recently published. Fungal rhinosinusitis takes many forms and is often associated with asthma, but not always. Around 800,000 (10%) Israelis are thought to suffer from rhinitis, and some 40,000 individuals were thought to have AFRS (5% of the total 800,000 chronic rhinosinusitis population).

A descriptive epidemiological study of fungal rhinosinusitis (FRS) was conducted in rural northern India in the form of house-to-house survey of villages of two districts each of Punjab and Haryana. Suspected cases were evaluated in the lab. Seasonal air counts of aspergillus spores showed raised counts (up 20%) of A.flavus in the winter months in the wheat threshing areas of Punjab. The study revealed a population prevalence of 0.11% of CFS with a possible association with the wheat harvesting season- which could be 1.3 million people if generalised to the whole population. They sub-classified most of these cases and found allergic FRS in 41 (56.1%), chronic granulomatous FRS in 13 (17.8%), eosinophilic FRS in 11 (15.0%), fungal ball in 7 (9.5%) and chronic invasive FRS in one (1.3%) (Chakrabarti et al, 2015).

The worldwide burden of allergic fungal rhinosinusitis is clearly highly variable and many more population studies are required to address this relatively common problem.

More information

Burden of diseases in 636 million people and across 15 new countries

Fungal diseases have been regarded as low priority problems in many countries and expertise is sadly lacking. Just published in "Mycoses" is a series of 15 articles covering population rates of serious fungal disease, varying from 1.7% to 12.5%, in the following countries Belgium, Czech Republic, Denmark, Hungary, Nepal, Qatar, Tanzania, Trinidad and Tobago, Uganda, Germany, Mexico, Senegal, Tanzania, Ukraine, Vietnam. These estimates have never been attempted before. 

The largest burdens are always recurrent vulvovaginal candidiasis and ‘fungal asthma’ (ABPA and SAFS). AIDS and TB related disease reflect the burdens of these problems in each country and how well HIV is treated. 
The burden of serious fungal diseases has now been estimated in around 5 billion - or 71% of the global population, as presented recently at the Trends in Medical Mycology meeting in Lisbon (info)
More information and view the papers

World's first guidelines for chronic pulmonary aspergillosis presented at ERS

The world’s first guidelines for chronic fungal lung infections for doctors and laboratories were presented at the European Respiratory Society (ERS meeting) and will shortly be published in the European Respiratory Journal (January issue). The guidelines have been drawn up in conjunction with the ERS and ESCMID.

Chronic pulmonary aspergillosis (CPA) is a subtle and insidious problem in patients with already damaged lungs. It kills about 80% of sufferers over five years, unless diagnosed and treated with long-term antifungals. Across Europe, an estimated 240,000 people have CPA, and worldwide around 3 million. CPA in lung with TB
The guidelines describe the 5 clinical phenotypes of CPA and how to diagnose and manage these patients.
The three minimum requirements for diagnosis and initial therapy include a. Imaging (radiological & CT scan) (grade A II) alongside b. Testing for Aspergillus IgG serology (grade A II); and c. Itraconazole treatment (grade A II) or other azole therapy depending on the patient.

The publication of these guidelines will assist and guide the training of medical professionals working with CPA patients. Image shows CPA with TB, chest X ray. More information

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Featured LIFE website section: Skin testing for endemic fungi

Skin testing is useful to know whether a person has been previously infected with an endemic fungus such as Histoplasma capsulatumCoccidioides immitis or C.posadasiiParacoccidioides brasiliensis, P. lutziior & Sporothrix schenckii. Unfortunately, these tests are of limited use for the diagnosis of acute disease caused by one of these pathogens, unless the patient has had a recent negative test. Once the test is positive, it remains positive for the rest of the patient's life unless the patient becomes immunosuppressed.coccy As many of the infections are asymptomatic, skin testing is a tool mainly used for epidemiologic purposes. In particular, skin test surveys in localised populations show how many patients have been infected with one of the endemic fungi. Notably patients with chronic or disseminated disease often have negative skin tests.
The FDA has now approved a skin test for Coccidioidomycosis (Spherusol) which is a granulomatous disease that stimulates a delayed-type hypersensitivity response when an antigen is intradermally inoculated. This is the basic principle of the skin test used since the 1940s that has been used to know the epidemiology of the disease as well as to assist in its clinical management.

LIFE website.


Top Diagnostic Tip : ITS sequence data & searchable database

An informed choice for proper anti-fungal treatment needs an definitive identification at the species level. DNA sequencing is an alternative to classical fungal identification. The Internal Transcribed Spacer (ITS) regions of the ribosomal DNA gene cluster is now widely used in clinical laboratories for fungal species identification. ISHAM have generated quality controlled ITS sequence data representing the actual sequence variation found in a species.

ITSThanks to eleven contributing research groups from all around the world the database currently contains more than 3200 sequences representing 524 human/animal pathogenic fungal species. Users are encouraged to submit their full dataset to the curators to enable a comprehensive global ITS database of clinically important fungal pathogens. View the database


Really Important Reviews

Return of delayed- type hypersensitivity reaction for Coccidioidomycosis (Wack et al 2015). Coccidioidomycosis accounts for 150,000 infections per year in the US. Coccidioidomycosis is a granulomatous disease that stimulates a cellular immune response and generates a delayed-type hypersensitivity (DTH) reaction to the intradermal inoculation of antigens prepared from the organism. This DTH response is commonly called a skin test (ST) conversion. Since the 1940s, DTH to coccidioidal extracts have been used both to study the epidemiology of coccidioidomycosis and to assist in the clinical management of patients. However, since the late 1990s, there has not been a commercial source of these reagents in the United States, so clinicians trained in the previous 20 years have little experience with skin testing for coccy.
The FDA has just approved a newly formulated antigen preparation for skin testing and this review discusses the clinical and epidemiological issues with previous skin tests and how the current preparation can be used.

Coccidioidomycosis cases have recently been reported from China in patients who have never travelled outside the country (Wang et al 2015). How they aquired this infection remains a mystery. Is soil being imported with plants from endemic areas? or is Coccidioides established in the soil in China? The new antigen for skin testing for coccidioidomycosis will help to monitor the potential spread of this fungus.


Do you have any images to share?

Do you have any images you would like to share with LIFE-worldwide.org if you have, do please send them to info@life-worldwide.org with details of the image and to whom copyright is attributed.

We are particularly looking for images of skin testing for Histoplasmosa antigen.

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The State-of-the-art infection models course studying molecular mechanisms of human fungal infections will be held in Jena, Germany on the14-27th February 2016More information.

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

ECMM Educational Symposium dedicated to 'Ecology and Mycology: from the Environment to the Patient's Bed' will be held in Tel Aviv, Israel, 14-16 February 2016. The program can be seen here

The 2nd EMBO Workshop on AIDS-related Mycoses is being held on the 13th to 15th July 2016 in Cape Town, South Africa. More information
More courses

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, Papua New Guinea, Poland.
 Can you help? Contact us