Date Published: March 10, 2016
Publisher: Public Library of Science
Author(s): Marcio L. Rodrigues, Joseph M. Vinetz. http://doi.org/10.1371/journal.pntd.0004429
Partial Text: It is estimated that fungal infections cause 1 million deaths annually, accounting for 50% of all AIDS-related deaths . In this specific patient group, data from 2009 revealed that fungal meningitis is responsible for approximately 500,000 deaths each year .
In the last 30 years, only one new class of antifungal drugs has been developed (echinocandins), with no efficacy against C. neoformans . Lack of innovation in the field may result from different reasons, including an international trend of exaggerated focus on basic sciences  and, possibly, reduced funding. Common antifungals used for human cryptococcosis are toxic (amphotericin B), not active (echinocandins), or quickly develop resistance (azoles) . Hence, the need for new, improved, and affordable antifungal treatments with greater safety and efficacy is clear . The gold standard antifungal regimen for the treatment of cryptococcal meningoencephalitis is the combination of amphotericin B (a six-decade-old polyene) with 5-fluorocytosine (an antimetabolite antifungal agent) . Amphotericin B has significant nephrotoxicity and requires costly intravenous administration , limiting its use in regions without strong medical infrastructure [9,10]. In fact, amphotericin B is not available in most of the African continent, according to the Global Action Fund for Fungal Infections . 5-Flucytosine is not widely available outside of resource-rich areas, and it has potential hematologic toxicities that must be monitored closely during medication administration . Fluconazole is often used as an alternative antifungal agent because of its lower cost and potential for oral administration. However, it is a decidedly inferior treatment option for this condition, associated with poorer outcomes and more frequent relapses . In South Africa, more than 60% of people with culture-positive relapsed disease had fluconazole resistance. It is estimated that more than 30% of patients with cryptococcal meningitis will have microbiological and/or clinical failure (and presumably die), despite receiving standard therapy . In summary, there are significant complexities in the management of cryptococcosis.
The Global Funding of Innovation for Neglected Diseases (G-FINDER) has recently reported on the 2014 global investment in research and development (R&D) of new products for neglected diseases, based on information provided by almost 200 organisations worldwide . This report, which covered R&D funding for 35 neglected diseases, revealed a total investment of US$3,377,000,000. As in previous reports, malaria and tuberculosis were among the “top tier” diseases, combining 35.5% of the total investment in neglected diseases. Despite the alarming mortality rates, cryptococcosis received less than 0.5% of the global R&D funding .
Meningitis caused by C. neoformans kills more than 500,000 individuals per year worldwide. Estimates for R&D funding for human cryptococcosis in 2014 revealed indices of support that were greatly disproportionate to its importance for global health, in comparison to other neglected diseases. This scenario reveals an urgent need for innovation and increased support for R&D in the field of cryptococcal meningitis.