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No access to life-saving drugs for cryptococcal meningitis in sub-Saharan Africa

June 10 2013

Cryptococcal meningitis kills everyone affected unless treated and this is not possible in several of the most needy African countries because the drugs are not available. In 2010 the Infectious Disease Society of America recommended combination amphotericin B and flucytosine. Despite this and the extraordinary 25 year international response to HIV, numerous sub-Saharan countries remain without either drug, and all without flucytosine. The alternative fluconazole is only 50% effective at best. Yet both amphotericin B and flucytosine have been available across the world-for over 50 years. Dr Angela Loyse and colleagues most from St George’s Hospital, London have reviewed this access to treatment problem in a paper published this week in Lancet Infectious Diseases. They make a number of recommendations including: • Improve estimates of cryptococcal meningitis disease burden • Ensure wider dissemination of best clinical practice • Include all cryptococcal meningitis drugs on WHO core Essential Medicines List • Register antifungals in low-income and middle-income countries • Pooled procurement of antifungals • Increase competition through generation of generics • Ensure preferential pricing for low-income and middle-income countries by pharmaceutical companies • Ensure socially responsible licensing of intellectual property for new antifungals or formulations developed by research organisations • Optimise existing antifungal strategies in clinical trials in low-income and middle-income countries • Stimulate research and development of novel antifungals by designation of cryptococcal meningitis as a neglected disease Other institutions involved included the HIV Department, World Health Organisation; Medicines Sans Frontieres, Cape Town; Mycotic Disease Branch, Centres for Disease Control, Atlanta; and the National Institute for Communicable Diseases, Johannesburg.
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Bioconference -Opportunities for better outcomes for systemic fungal disease: not relying on culture

May 28 2013

Online Bioconference LIVE on May 29 -31st, 2013. Featured Speaker Professor David Denning. Topic: "Opportunities for better outcomes for systemic fungal disease by not relying on culture". This Bioconference is free. Synopsis: Early diagnosis of life-threatening fungal infection is critical to good outcomes. Numerous studies attest to the poor yield from fungal culture and the much better yield of antigen, real-time PCR and antibody tests. The new cryptococcal antigen lateral flow device is a simple point of care test, that is highly sensitive on serum, plasma, urine and CSF to detect occult antigenemia prior to meningitis or for diagnosing cryptococcal meningitis. Only about 50% of Candida bloodstream infections are detected by blood culture, which is further compromised by fluconazole use. Blood cultures take 24-72 hours to be positive in most instances and an additional 24 hours for identification. Real-time PCR is much faster and more sensitive, but no test is yet FDA approved or CE-marked. Beta-D-glucan testing on blood is useful for Candida infections although does not distinguish genera or species, and so is best used as a rule out test. Blood cultures for Aspergillus are uniformly negative, whereas antigen and real-time PCR on both blood and respiratory fluids has a 80-95% sensitivity.
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Nearly 5 million asthmatics have ABPA and could benefit from antifungal therapy

May 08 2013

Researchers in Toronto and Manchester estimate that 4,837,000 adults with asthma have allergic bronchoplulmonary aspergillosis or ABPA, which usually improves substantially with antifungal treatment. Their work, published today in the journal Medical Mycology, has re-estimated the total number of asthmatics worldwide – a remarkable 193 million, of whom 24 million live in the USA, 20 million each in India and China, 13 million in Brazil and 7 million in Japan and the UK. Of these an estimated 1 in 40 (2.5%) suffer from ABPA. This estimate is based on referral to a chest specialist in hospital in 5 countries. This is the first time that a global estimate of ABPA numbers has been made.
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Multi-country burden of fungal disease presented at ECCMID conference

April 29 2013

The number of people suffering and dying from fungal infections has been estimated in 12 countries in which 3.1 billion people live, 45% of the world’s population. Posters presented at the ECCMID meeting in Berlin revealed especially high incidence rates of Candida bloodstream infection in Brazil (15/100,000) and Spain (10.7/100,000), an extremely high rate of mucormycosis in India (170,000 cases annually, 13/100,000) related to the burgeoning epidemic of diabetes there, over 160,000 cases of invasive aspergillosis in China (11.9/100,000), over 2,783 cases of cryptococcal meningitis in AIDS in Uganda (8/100,000, 75% mortality) and 75,000 and 18,000 cases of Pneumocystis pneumonia in Nigeria (48/100,000) and Brazil (39.6/100,000) respectively. Even more prevalent were allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) complicating asthma. For example, an estimated 390,000 ABPA cases were estimated for Brazil (201/100,000), 491,000 cases for China (36.1/100,000) and at least 592,000 ABPA cases in India (47/100,000). The prevalence of SAFS was estimated to be higher, but has yet to be studied epidemiologically. Estimates of tinea capitis were very high in Africa, notably 15,580,000 cases in Nigeria (~50% of 155 million population are children) (1000/100,000) and 1,700,000 children affected in Kenya (4,300/110,000). More prevalent still, was recurrent Candida vaginitis (vulvovaginal candidiasis) in which the estimated prevalence rate in 15 to 50 year old women varied from 874 (Spain) to 3,800 (Nigeria) per 100,000 females.
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Better treatment for cryptococcal meningitis with flucytosine in combination with amphotericin B

April 22 2013

A three-way randomised study of cryptococcal meningitis in Vietnam has convincingly shown the benefit of flucytosine with amphotericin B. Jeremy Day and 22 colleagues in Ho Chi Minh City at the Oxford University Clinical Research Unit studied 299 patients, all with AIDS and cryptococcal meningitis and found that the 100 patients who received amphotericin B (1 mg/Kg/d) and flucytosine (100mg/Kg/d) had a 40% lower chance of dying than amphotericin B alone or combined with fluconazole (800mg/d). In addition to the 14 day survival benefit, the 70 day and 182 day survival was better with flucytosine as was the speed of yeast clearance from the cerebrospinal fluid. Commenting on the results, Professor John Perfect of Duke University said; “Robust studies like this trial provide important insights for how to manage cryptococcal meningitis better, and it is our job to implement its initial therapeutic principles, such as the use of rapid fungicidal regimens, worldwide.”
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