A Large Community Outbreak of Blastomycosis
August 15 2013
The largest ever reported outbreak of blastomycosis occurred in 2010 in Marathon County, Wisconsin. Blastomycosis is an infection caused by B dermatitidis a soil based dimorphic fungus. Health officials noticed an increase in the number of cases of blastomycosis in October 2009. Initial investigation showed clustering within neighbourhoods and households with a disproportionate number of cases amongst those of Hmong ethnicity. Originally from SE Asia many Hmong people settled in the US after the Vietnam war, particularly in Wisconsin. An epidemiological investigation to examine the high rates of blastomycosis in Marathon County, Wisconsin in June - July 2010 has now been published.
WHO reinstates Amphotericin B and flucytosine on the Essential medicines List
August 08 2013
Following representation from the Cryptococcal Meningitis Action Group (CryptoMAG), the 19th Expert Committee on Selection and Use of Essential Medicines has placed intravenous amphotericin B and flucytosine and oral flucytosine on WHO Model List of Essential Medicines (EML) for both adults and children. In addition to improved survival of patients with cryptococcal meningitis, both drugs have other uses, such as disseminated histoplasmosis, invasive candidiasis and aspergillosis.
The decision-making meeting was held in the WHO Headquarters in Geneva from 8 – 12 April 2013 and reviewed and updated the 17th WHO Model List of Essential Medicines and the 3rd list of WHO Essential Medicines for Children.
The CryptoMag group, (see news) partly funded by GAFFI, met prior to this to finalize the reviewer responses to a prior EML submission. The arguments were evidenced based, primarily on the definitive trial from Vietnam lead by Dr Jeremy Day (who trained in Manchester, showing that this combination yielded a 40% lower chance of death).
Commenting on this, GAFFI's President, Professor David Denning said; “The WHO’s enlightened decision opens the door to saving many thousands of lives weekly from this devastating fungal meningitis in AIDS. The challenge now is to translate this recommendation into local availability and actual treatment on the ground in every country.”
Ketoconazole withdrawn by FDA, for almost all indications
July 30 2013
Ketoconazole withdrawn by FDA, for almost all indications
Ketoconazole, the world’s first oral azole antifungal, is being retired by the FDA. First launched by Janssen Pharmaceutica (Belgium) in 1985, it transformed the treatment of oral and oesophageal candidiasis and some endemic mycoses such as coccidioidomycosis. This week, the FDA restricted its use to the occasional patient with endemic mycoses, as a last resort.
The FDA cites “severe liver injuries and adrenal gland problems, and advising that it can lead to harmful drug interactions with other medications”, as the reason for it shift in position. Early after launch, ketoconazole was extensively used for skin fungal infections, and was very effective for many and convenient. Unfortunately about 1 in 10,000-15,000 developed severe hepatic reactions, which were either fatal, or more recently required transplantation. Adrenal dysfunction is also a significant issue.
The European Medicines Agency’s (EMA's) Committee on Medicinal Products for Human Use has also recommended that the marketing authorisations of oral ketoconazole-containing medicines should be suspended throughout the European Union (EU). The CHMP concluded that the risk of liver injury is greater than the benefits in treating fungal infections. (EMA report). The EMA recommends that patients currently taking oral ketoconazole for fungal infections should make a non-urgent appointment with their doctor to discuss suitable alternative treatments.
Ketoconazole tablets are used throughout the world, as it is less expensive than other antifungals, but its use should be curtailed for all but the shortest courses. Fluconazole is a much safer alternative. Ketoconazole (Nizoral) shampoo carries no risk.
What are the point of care tests for fungal infections
July 22 2013
Over recent decades the application of modern technologies has transformed the diagnosis of infectious diseases. A recent article in the New England Journal of Medicine (link) re-emphasises the difficulties and challenges of performing complex analytical procedures in resource limited and urban areas. Microscopic examination of sputum for tuberculosis is a good example. To overcome this and many other problems there has been an unrelenting drive to develop point of care tests (POCs) that do not require a sophisticated laboratory. Very few of these approaches have been applied to fungal infections.
The first generation of POC tests were designed to detect biomarkers such as antigens, antibodies and simple biochemical reactions. Such biomarkers are increasingly used in POCs for a wide range of infectious diseases, for example, syphilis, hepatitis, measles, schistosomiasis and trichomoniasis. Although not exactly POCs, latex agglutination tests for cryptococcal antigen and numerous ELISA platforms for Aspergillus circulating antigens have been in use since the 1970s. More recently, lateral flow devices of various hues have been developed and validated for cryptococcal antigen and an exoantigen of Aspergillus fumigatus.
The NEJM article tantalises us with second and third generation POCs appearing on the horizon, made possible with recent industry and donor investment. Second generation tests detect more complex and less accessible biomarkers such as nucleic acids and cell surface markers, and take advantage of advances in microfluidics, microelectronics, optical systems, and laboratory-on-a-chip nucleic acid test (NAT)-based amplification and detection techniques. NAT-based technologies have been applied to tuberculosis and drug-resistance screening, and testing of HIV viral load. We are told that additional applications are in the pipeline for other blood-borne and respiratory infections. Will pulmonary fungal infections be included?
African conference on fungal infections in AIDS
July 08 2013
Cape Town, South Africa. An EMBO sponsored workshop integrating clinical, public health and fundamental science aspects of fungal infections in AIDS was held July 3rd to 5th, 2013. Attendees from all over Africa, Asia, and the Americas discussed the changing status of fungal infections in AIDS, with a particular focus on cryptococcal meningitis. The HIV burden in South Africa was a dominant theme, with over 2 million patients on antiretroviral therapy, but an estimated additional 4 million HIV infected people still needing treatment. A remarkable 30% of pregnant women test positive for HIV, placing enormous numbers of people at risk of deadly fungal complications.
Other fungal infections were also highlighted, notably oral thrush, penicilliosis in SE Asia, paracoccidioidomycosis in Brazil, histoplasmosis in central America and aspergillosis complicating TB and HIV in Uganda.
The meeting was chaired by Professor Gordon Brown from Aberdeen and Cape Town universities. He said of the meeting: “The challenge of fungal infections in AIDS remains a ‘Clear and present danger’ to so many HIV-infected people. This high level workshop was designed to share international experiences and push forward the research agenda across many fronts.”