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LIFE Newsletter - Leading International Fungal Education

March 2016

Global Action Fund calls for stakeholders to address histoplasmosis

A campaign to convince Latin American countries to do more to tackle a problem which is the leading cause of death in AIDS and yet is poorly understood, often misdiagnosed and frequently left untreated has been launched by GAFFI - The Global Action Fund for Fungal Infections. With more than 80,000 AIDS deaths worldwide attributed to histoplasmosis GAFFI have sent out an open letter to every pan American health organisation requesting that the deadly fungal disease is adopted as a priority by key public health agencies.
GAFFI’s President, David Denning who is Professor of Infectious Diseases in Global Health at The University of Manchester and 38 signatories from 13 countries want greater awareness of this deadly disease and more reliable and practical tests made available now, in those countries most affected.

A rough estimate of disseminated histoplasmosis in AIDS is HIV patient with histoplasmosis100,000 cases worldwide and 80,000 deaths mostly due to lack of diagnosis and partly unavailability of treatment. If the UNAIDS target of reducing AIDS deaths to under 500,000 is to be achieved, action needs to be taken now on disseminated histoplasmosis. A group of institutions from the Americas recently declared HIV associated histoplasmosis a neglected disease and described it as: "an invisible elephant out of the radar of International Health authorities, organizations and funders". They estimated that histoplasmosis was responsible for 1 in 5 AIDS-related deaths in the Americas, more than or at least equivalent to the burden of HIV-tuberculosis and 100 times more than malaria (view article).
Disseminated histoplasmosis in AIDS is well recognised in the USA where awareness, laboratory capacities and access to effective antifungal therapy are all fully developed. But in Central and South America, and in Africa and SE Asia, it is usually undiagnosed or misdiagnosed as tuberculosis. It is grossly under-diagnosed because of the low sensitivity (average 50%) of stained smears and the slow growth of organism in special medium culture (which is not available in many locations). In AIDS, the culture usually becomes positive after the patient has died (at 10-21 days). The unavailability of even culture and microscopy in many countries, contributes to difficulties in identification of cases and prompt treatment initiation. A briefing document is here.
Professor Denning signed the letter on behalf of 38 key Physicians, Consultants, Health Directors, Infectious Disease Specialists and Mycologists globally.
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Please support GAFFI's petition " Reducing fungal infection deaths in AIDS"


Pneumocystis pneumonia - colonisation versus infection in both HIV positive and negative patients

Pneumocystis pneumonia (PCP) caused by P. jirovecii is a serious opportunistic infection frequently seen in HIV positive patients. Despite highly active antiretroviral therapy (HAART), it is still a serious life threatening opportunistic infection. Quantitative PCR on respiratory samples is the most sensitive and specific laboratory test, but the actual cut-off to define a case has been a matter for debate.
In a recently published retrospective study to examine qPCR cut-offs (Louis et al 2015) PCP was identified in BAL fluids in 56 HIV-positive and in 49 HIV-negative patients indicating that PCP is a significant occurrence in immunocompromised groups other than HIV. The direct fluorescence assay regarded as the gold standard for PCP diagnosis, showed a 92.8% sensitivity in HIV positive patients but only a 55.1% sensitivity in HIV negative patients; a lower fungal burden is seen in HIV negative patients.
A single cut-off at 1.5x104 copies/ml allowed the differentiation between colonized and infected HIV-positive patients with 100% sensitivity and specificity. In HIV-negative patients, cut-off values of 2.9x104 and 3.4x103 copies/ml resulted in 100% specificity and sensitivity, respectively.
Asymptomatic colonisation represents a real drawback to PCP diagnosis, especially using PCR. 
Concordance between four real time PCR assays is discussed (Sasso et al. 2016). The genome of P. jiroveciii has recently been sequenced and its ability to survive in lungs better understood. Article.
More information

Resistance detection straight from the blood culture bottle

Bloodstream Candida infections have a high mortality, and swift and appropriate treatment is vital as delays of just hours may significantly increase mortality.
In many countries, including Pakistan, C. tropicalis is the most predominant species, with a notable rise of frequency more recently. Also, growing resistance to fluconazole has become a serious concern and rapid antifungal susceptibility testing is necessary.
Jabeen and colleagues (2015) compared the gold standard conventional disk diffusion susceptibility test, with direct disk diffusion testing from positive blood bottles for fluconazole, voriconazole and amphotericin B. Excellent agreement was found between the conventional method and the direct disk diffusion method for all the azole drugs, but disk diffusion (both direct and conventional) was not an acceptable method for amphotericin B susceptibility testing (E-test MICs did not correlate with zone diameter).
The present study confirms that the disk method on direct blood culture bottles as a rapid and cost effective method of resistance detection.

Randomised study of adjunctive dexamethasone in cryptococcal meningitis shows worse outcomes:

A study of 451 patients form Vietnam, Laos, Indonesia, Uganda and Malawi who received adjunctive dexamethasome with either amphotericin B or fluconazole led to more disability, more adverse events and a slower clearance of C. neoformans from the CSF, writes Justin Beardsley in the New England Journal of Medicine. DexamethasoneIt was hypothesised that dexamethasone would improve outcomes which was NOT the case and the study was halted early because of the worse outcomes and adverse effects in the dexamethasone arm of the trial.

The authors concluded "With no effective adjunctive therapy yet identified, improving access to the most effective antifungal treatments, including flucytosine, must remain a global priority.”
More information; Link to article

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Featured LIFE website section: Corticosteroids and fungal infection

Corticosteroids are a key risk factor for developing many fungal infections including candidaemia, invasive candidiasis, invasive aspergillosis, pneumocystis pneumonia, cryptococcal meningitis and histoplasmosis. So for cancer patients, HIV patients and anyone who is immunosuppressed who is also on corticosteroids, the benefit of using corticosteroids must outweigh the elevated risk of developing a serious fungal infection.

The implications of corticosteroid use and the impacts, both negative and positive on potential fungal infections is reviewed in this section. LIFE website.

Top Diagnostic Tip : Acute pulmonary histoplasmosis

Combining antigen and enzyme immunoassay (EIA) antibody testing provides an optimal method for diagnosis of acute pulmonary histoplasmosis. In 80 patients, involved in small outbreaks and thought to have acute pulmonary histoplasmosis, 87.5% showed IgG antibodies and antigen testing in 42.7% in urine and 63.3% in serum. Combining both antigen and antibody detection, increased the sensitivity to 96.3%. (Richer et al, Clin Inf Dis, Feb, 2016).

We need your support to sign our petition to reduce death from AIDS by focusing on lethal fungal diseases.

GAFFI has put a petition to the Department for International Development (UK-Gov). Please support our campaign for DFID, WHO and USAID to prioritise saving lives from AIDS. There are too many young people dying from AIDS, about 1,500,000 each year, about 50% due to fungal diseases, and 20% due to TB.The average age at death is 35 years. You can sign the petition here. 



Medical Mycology Current Trends and Future Prospects: by Mehdi Razzaghi-Abyaneh, Masoomeh Shams-Ghahfarokhi and Mahendra Rai (Eds.)

The identification of medically important fungi has been an important area of study that warrants further research. The use of traditional and molecular methods of identification, provides new insights into differentiation of species and ultimately into the line of treatment to be taken. This book reviews a diverse group of medically important fungi and diseases, and determines the identity of medically important fungi by using modern techniques such as PCH and MALDI-TOF: a rapid and new approach in fungal diagnosis and differentiation.

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Myology Masters course in Manchester - watch a Youtube video about the course here.
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

The 7th Singapore Allergy & Rhinology course and 3rd SARC FESS Workshop is being held on the 5-7th May and 7-8th May 2016 respectively in SingaporeMore information

The 15th ESCMID Summer School is being held on the 2-9th of July 2016 in Seville, Spain. More information

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