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LIFE Newsletter - Leading International Fungal Education

September 2016

MILLIONS DEPRIVED OF LIFE-SAVING ANTIFUNGAL MEDICINES

A report published in August in the Journal of Antimicrobial Chemotherapy, documents how many countries do not have life-saving antifungal therapies resulting in 1.6 million per year dying from lack of treatment of serious fungal infections. That number is equivalent to the populations of Philadelphia, Kampala or Prague.

GAFFI (The Global Action Fund for Fungal Infections) has published the largest survey ever undertaken from 159 countries and found that a pair of critical antifungal medicines for AIDS patients are not available in over 95 countries. One of these antifungals has been available since the 1950’s and the other since the 1970’s.
Key findings:

  • One of the critical drugs for fungal meningitis (amphotericin B) is not available in 42 countries.
  • The other key drug for fungal meningitis, flucytosine is not licensed in and is unavailable in 89 of 125 (71.2%) and 95 of 125 (76.0%) countries, respectively, representing an unserved population of 2898 million. The daily price of flucytosine varied from $4.60 to $1409.
    Yet both amphotericin B and flucytosine have been available in Europe and the US for over 40 years. The World Health Organisation recommends they are used together to bring down mortality from 100% to 25%. (Fungal meningitis is the commonest form of meningitis in sub-sarahan Africa because of AIDS).
  • The 25 year old drug, fluconazole is available in all countries and itraconazole is unavailable in just five countries. However, being available is not enough – cost matters as patients pay for their care in many countries. The daily cost of fluconazole varied from <$1 to $31 and itraconazole from <$1 to $102.
    In South Africa, which has the largest AIDS burden in the world and a massive TB problem, itraconazole costs about £11.60 per day – unaffordable for most people there.

    flucytosine availabilty map
    Flucytosine world availability map

    More information. Full article

NEWS

Molecular methods for the diagnosis of chronic fungal rhinosinusitis

Chronic rhinitis, sometimes with nasal polyps, is a common disorder affecting an estimated 0–17% of all people and many cases are attributable to fungi called chronic fungal rhinosinusitis or CFRS The sensitivity of testing for the presence of fungi by fungal cultures from mucus is known to be low and the specificity from nasal wash or swab is also poor, as fungi are commonly cultured from the nose because it acts as an air filter. The epidemiology of CFRS is likely to be under estimated because of the lack of a sensitive detection method. this article sets out to establish the sensitivity of molecular diagnosis CFRS in 61 patients with CRS.

Molecular detection by ITS1/2 proved far superior to both culture (51% sensitivity) and histology (48% senstitivity). The molecular ITS1/2/method had the advantage over conventional diagnostic tests of identifying the fungal species in 46/47 samples. Aspergillus was the most commonly identified (37/47) of which 31 were A. fumigatus, whilst A. nidulansCladosporium cladosporoides, & Scedosporium spp. were found equally in 8.5 % of samples each. This study demonstrates that molecular tools such as PCR are important for establishing a diagnosis of FCRS and for it's aetiology.

More information; Article

 

Cryptococcal meningitis persists despite 90-90-90 Botswana experience

At the EMBO Mycoses in AIDS meeting in Cape Town, Dr Joe Jarvis working in Gabarone, Botswana questioned the value of 90-90-90 in reducing cryptococcal meningitis.
Botswana's record in rolling out 90-90-90 antiretroviral therapy was published in Lancet HIV in July.  Botswana achieved: 83·3% individuals knew their HIV status, among these 87·4%, were receiving ART and 96·5%, had a viral load of <400 copies per mL - 70·2% with virological suppression, close to the UNAIDS target of 73%. This performance is probably the best in Africa and exceeds performance for most countries across the world, with the exception of several European countries.

Cryptococcal meningitis in Botswana
Fig: Change in cryptococcal meningitis observed (red line)
Despite this the rate of cryptococcal meningitis has not changed The majority of patients with cryptococcal meningitis were patients in care, not newly presenting patients with a new diagnosis of AIDS.
Dr Jarvis commented; “Cryptococcal meningitis is not going away any time soon. If Botswana, with its strong HIV treatment program, still has a continuing problem with cryptococcal meningitis, the situation across sub-Saharan Africa must be worse. Cryptococcal meningitis requires a rethink – only 40% of these patients are still alive at 12 months.”

More information, Article

 

Global emergence of multidrug- resistant yeast Candida auris.

Many of the world's Public Health agencies including the CDC and the UK's PHE is alerting healthcare facilities to be on the lookout for Candida auris in their patients having received reports from international healthcare facilities, that this emerging multidrug resistant yeast is causing invasive infections with high mortality.
There is particular concern because as it is often multidrug resistant, it is difficult to identify with standard laboratory methods and it has already caused outbreaks in hospital settings.

C. auris can enter the bloodstream and spread throughout the body, causing serious invasive infections  & often does not respond to commonly used antifungal drugs, making infections difficult to treat. Some strains of C. auris have elevated minimum inhibitory concentrations (MICs) to the three major classes of antifungals, severely limiting treatment options. No MIC breakpoints exist for C. auris, but testing of an international collection of isolates demonstrated that they were nearly all highly resistant to fluconazole, more than half were voriconazole resistant. In addition one third of isoaltes were amphotericin B resistant and a few resistant to echinocandins. Alarmingly some isolates showed elevated MICs to all three major classes of antifungals. Read more

Now the first outbreak of C. auris in South America has been reported. Bloodstream isolates of C. auris were obtained from 18 critically ill patients admitted to a medical centre in Maracaibo, Venezuela over a 16 month period. Read More

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Please assist LIFE to identify voriconazole availability in your country by clicking on this 3 question survey click here LIFE would also appreciate your help to tell us if you have antifungal eyedrops in your country, click here.

 

Featured LIFE website section: Intra abdominal candidiasis

Candida peritonitis (intra-abdominal candidiasis) is an uncommon but very serious complication of a perforated segment of bowel, pancreatitis, liver or intestinal transplantation, and other forms of sepsis in the abdomen, notably cholecystitis. It may arise spontaneously – primary Candida peritonitis. Another form of disease is related to chronic ambulatory peritoneal dialysis (CAPD), which is highly problematic as the dialysis catheter needs to be removed, usually permanently.
LIFE section


World's first e-learning fungal microscopy course is launched

Experts in Manchester have now developed the world’s first Fungal Microscopy online course. It is aimed at doctors, clinical scientists and laboratory technologists across the world, and because it is online, students in poorer countries where the need for information is greatest will now be able to learn how to recognize most pathogenic fungi.
The number of people with expertise in fungal microscopy is at an historic low globally. Despite major technical developments in diagnostics and treatment the availability of rapid diagnostic methods is very poor in many parts of the world. This deficit contributes to the annual death toll of over 1,600,000 people from fungal disease each year.
blastomycosisPulmonary blastomycosis
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 now at www.microfungi.net Watch video


Top Diagnostic Tip : Combat related injuries - finding fungal hyphae in tissue

A direct comparison of the GMS and PAS stains with other histopathological methods for identifying fungal elements was carried out in a population of 66 combat injured military personnel. Both GMS and PAS were similar for identifying fungal elements, but GMS had a false negative rate of 15% as opposed to 44% for PAS.

Where frozen sections were compared with fixed sections there was no attributable advantage of using frozen sections but the sensitivity of frozen sections was only 60 % of permanent sections, therefore although frozen sections may give a rapid indication, they should not be used as the only method because of lower sensitivity. Article: Heaton et al. BMC Clinical Pathology (2016) 16:11 DOI 10.1186/s12907-016-0033-9
GMS : Gomori methenamine silver stain, PAS: Periodic acid-Schiffs stain

 

Really Important Review: Point of care (POC) tests for fungal infections

Point of care tests have great potential for rapid diagnosis in clinic or at the bedside. They are at their strongest when a positive test means a disease that needs therapy, and is not one of several pieces of information that together arrive at a diagnosis. So a positive antigen test for Histoplasma in an HIV patient is essentially diagnostic for disseminated histoplasmosis, whereas Aspergillus antigen is respiratory fluids may represent invasive, chronic or allergic aspergillosis, or possibly colonisation, although still valuable information.   The latest data on all these assays is summarised in the attached review (and there is a separate recent excellent review on cryptococcal antigen testing). One potential drawback  with point of care testing is not capturing this key data in patients records and especially within their ‘laboratory’ results, as the data is often generated away from normal laboratory IT systems
Prattes et al. Curr Fungal Infect Rep (2016) 10:43–50 DOI 10.1007/s12281-016-0254-5 Article; and Cryptococcal LFA POC diagnostic (Tang et al): Article

Books

 

Koneman's Color Atlas & Textbook of Diagnostic Microbiology: by G Procop and E Koneman

This 7th Edition of Koneman's gold standard text presents all the principles and practices readers need for a solid grounding in all aspects of clinical microbiology bacteriology, mycology, parasitology, and virology. Comprehensive, easy-to-understand, and filled with high quality images.

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Courses

 

Venezuela - 2year Postagraduate course in Medical Mycology at the Instituto Nacional de Higiene “Rafael Rangel”. contact emailmore informationwebsite.

 Web-based course 'Invasive Mycoses in Hematologic Malignancies: Disarming the Fungal Saboteur' is running between the 4th November 2016 and 4th October 2017. More information

A scientific workshop of the ISHAM Working Group Dermatophytes to discuss latest achievements will take place at CBS, Utrecht, The Netherlands on 29-30th October 2016. More information,
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