Isavuconazole phase III trial demonstrates non inferiority versus voriconazole
October 03 2013
Astellas who developed the new antifungal drug isavuconazole, have published results from their phase III trials on the treatment of invasive aspergillosis, indicating favourable data for isavuconazole in comparison to voriconazole (Wall Street Journal report).
"The randomized, double-blind isavuconazole study achieved its primary objective in demonstrating non-inferiority versus voriconazole for the primary treatment of invasive fungal disease caused by Aspergillus species or certain other filamentous fungi. Isavuconazole was effective as determined by the primary endpoint of all-cause mortality through day 42 in the intent-to-treat population (N=516). The all-cause-mortality was 18.6% in the isavuconazole treatment group and 20.2% in the voriconazole group".
Access to Medicines Foundation
September 12 2013
About 2 billion people have no access to modern medicines, according to the Access to Medicines Foundation’s Founder and CEO Wim Leereveld. In a perspective piece in the New England Journal of Medicine, Hans Hogerzeil of Groningen, also in the Netherlands, reviews the 2012 index rankings of the major global pharmaceutical companies in terms of their efforts to make their products more available, affordable, and accessible in developing countries.
The Foundation sees the companies as being a key part of the solution to improving access, but the index extends further than simply provision to include commitment, transparency, performance and innovation in addition Hogerzeil writes: “The index focuses on what companies do to bring medicines, vaccines, diagnostic tests, and other health technologies to people in 93 low-income and lower middle-income countries, plus 10 upper-middle-income countries with large within-country disparities in development, such as Algeria, China, Jordan, South Africa, and Thailand. Companies’ rankings take into account drugs for a number of specific diseases, including the 10 communicable diseases and 10 noncommunicable diseases that account for the highest disease burden in developing countries, 14 neglected tropical diseases, and a range of maternal and neonatal conditions.”
Mycetoma is added to the WHO list of neglected tropical diseases
September 04 2013
Mycetoma is a chronic, progressively destructive morbid inflammatory disease usually of the foot but any part of the body can be affected. Infection is most probably acquired by traumatic inoculation of certain fungi and bacteria into the subcutaneous tissue. Mycetoma was described in the modern literature in 1694 but was first reported in the mid-19th century in the Indian town of Madura, and hence was initially called Madura foot and commonly affects young adults particularly males.
As mycetoma is a badly neglected disease, accurate data on its incidence and prevalence are not available, the organisms that cause it are found worldwide but it is particularly endemic in Chad, Ethiopia, India, Mauritania, Bolivarian rep. of Venezuela, Mexico, Senegal, Somalia, Sudan and Yemen. More than 20 species of fungi and actinomycetes are implicated in this disease. Mycetoma is currently not a notifiable disease.
Thanks to the hard work of members of the ISHAM working group Mycetoma, and the Mycetoma research Center in Khartoum, this fungal infection is now on the WHO List of Neglected Tropical Diseases. (Link)
Professor Rod Hay of the International Foundation for Dermatology said; "Mycetoma has long been a neglected infection, partly because of its rarity, partly because of its geographical isolation in poor communities and partly because of its diagnostic and treatment complexity. It is a real milestone forward that the WHO have agreed to accept it as a Neglected Disease, and hopefully this will drive substantial improvements in care for these disabled and stigmatised patients."
Assessment of fluconazole and itraconazole for birth defects
September 02 2013
In a study of nearly a million Danish pregnant women of whom 7352 were exposed to fluconazole and 687 to itraconazole in the first trimester, Ditte Molgaard-Nielsen and colleagues from the Serums Staten Institute in Copenhagen found a 3-fold increase in the heart defect tetralogy of Fallot and a 2-fold increase in hypoplastic left heart with fluconazole exposure. Numerous other birth defects were not associated with fluconazole exposure. No birth defect was associated with itraconazole exposure.
Most prescriptions for fluconazole in pregnancy are for Candida vaginitis. The standard dose is 150mg as a single dose, but larger doses are used for patients with recurrence or non-responsive disease. There did not appear to be a dose relationship with tetralogy of Fallot occurrence. However the exposures are quite modest by comparison (350-6000mg total dose) with women requiring long term fluconazole maintenance therapy. Fluconazole is extensively used in patients with AIDS to suppress cryptococcal meningitis and oesphageal candidiasis, and avoidance of fluconazole in early pregnancy is clearly required. Whether much higher doses would confer additional is not known, but the lack of a dose response in the large Danish cohort is suggestive that it does not.
How many fungal species are on our planet?
August 27 2013
Professor Xingzhong Liu of the Institute of Microbiology, Chinese Academy of Sciences in Beijing addressed this question at the 13th Asian Mycological Congress on 22nd August (meeting Aug 19th -23 rd Beijing). The current listing of fungi in the Dictionary of Fungi includes ~100,000 species, up from ~50,000 in 1970. But novel molecular methods are identifying large numbers of presumptive species, many of which are not yet cultured or are unculturable with current growth methods. In diversity studies, ratios if cultured to uncultured fungi detected are 1:9, suggesting at least 10-fold more than the current list. In addition, “Several environments and potential habitats have barely been sampled and analysed, such as plants, lichens, insects and tropical forests”, said Professor Lui. Another contributor to diversity are cryptic species which also are being discovered at a phenomenal rate currently.