Friday, 29 November 2013

FDA Approves NOXAFIL Delayed Release Tablets - Posaconazole Dosing is Now Once Per Day!

The US drug regulatory body FDA have just approved a new form of the antifungal drug posaconazole that is slowly released into the bloodstream after the patient takes the tablet. This provides two important advantages over the current formulation of posaconazole (which is a liquid that has to be taken by mouth three times a day).

  1. for the most part a single dose is taken per day. This improves convenience for the patient and potentially improves compliancy as it may be more reliable for some people to remember to take a dose once per day
  2. a single dose, slow release regimen encourages a more consistent blood level of the drug and possibly a higher overall blood level
Posaconazole (NOXAFIL) is an important antifungal for the treatment of several forms of aspergillosis and is used as a prophylactic for those patients undergoing treatment that makes them extremely immunocompromised. This improvement in dosing technology will hopefully contribute to improving outcomes in those cases.

The drug is predicted to be available in the second quarter of 2014.

Wednesday, 27 November 2013

Aspergillosis in animals

We routinely discuss fungal infections in humans, especially those due to Aspergillus, but fungal disease is anything but limited to humans. From the fungi which cause skin conditions (such as Tinea capitis) to those which can cause invasive infections (e.g. Candida albicans or Aspergillus fumigatus), they are all found to affect a wide range of animals including cats, dogs, horses and cattle. Not only that, but also more exotic animals like parakeets or whales.

As with humans, diagnosis of fungal infections in animals is a significant hindrance to successful treatment. Diagnostic tests for galactomannan, regularly used in humans, have been found useful in the diagnosis of feline aspergillosis. Most cases do require imaging tests to determine if signs of certain infections are present, such as aspergilloma.

In the UK there are only seven licensed antifungal drugs for veterinary use, a number much smaller than those available to humans for dermatological and systemic fungal infections. The only systemic antifungal available for veterinary use is griseofulvin, effective only against dermatophytes, and even that is only registered for use in cattle and horses. For regular pets such as cats and dogs, there are several drugs to treat skin infections but none licensed to treat systemic infection.

So how do veterinarians treat diseases such as nasal or invasive aspergillosis in common pets like cats and dogs? They have to use drugs licensed in humans but off-license in animals, including the triazole drugs such as itraconazole and drugs such as amphotericin B. Similar to human use, these drugs must be monitored even more carefully given their unregulated nature in animals. If the disease is limited to the nasal sinuses, often surgical procedures are used in addition to antifungal drug treatment.

Wednesday, 20 November 2013

Universal health care

A recent article in the BMJ discusses the trials and tribulations associated with implementation of universal healthcare globally. However, it also notes the great progress that is being made (even in countries engrained in medical insurance culture such as the United States) and notes that an increase of 10% in governmental, prepaid funds for healthcare could save around 500,000 children under 5 in India and Nigeria alone (Save The Children report, 2013).

Low and middle income citizens in less developed nations often have to pay what is termed 'catastrophic healthcare spending' to pay for treatment, with billions of people worldwide resorting to selling assets, acquiring large debts or keeping children out of school in order to fund often inadequate healthcare. (Health Affairs, 2009) The authors suggest moving away from medical insurance models such as those throughout Africa, and towards the UK/France/Canada model where taxes pay for healthcare, ultimately redistributing wealth from the rich to the poor and encouraging access to healthcare on the basis of who needs it, rather than who can afford it.

This is particularly beneficial for diseases of a chronic nature, which require long-term and often multiple sessions of treatments to cure. The data that GAFFI is acquiring will increase public awareness to the costs that people worldwide have to pay for often fatal fungal diseases.

Importantly, medicine costs can seem low to people in Western countries; for example, people in Bangladesh pay just under $1 USD for a daily treatment of fluconazole, an essential antifungal drug. However, the proportion of people living on less than $2 USD a day in Bangladesh is around 75%, meaning that 75% of people would have to spend half their daily earnings on just one day's worth of treatment.

Such data collection is essential to put pressure of pharmaceutical companies and governments to reduce point-of-care costs of medication to the poor. More must be done to reduce access costs to medication but this can only be tackled through global collaboration between national governments, pharmaceutical companies and global health organisations.

Wednesday, 13 November 2013

Poetry at the GAFFI Launch

Rupert Everett talking to patient Gail Iddon at the launch of GAFFI
During the launch of GAFFI last week (6th November) Rupert Everett read a series of poems each of which related to fungal disease in a different way. There were several new original works - perhaps most poignantly one written by a group of patients who have aspergillosis in its various forms and who meet once a month for a support meeting run by the National Aspergillosis Centre.

The Centre has a Poet in Residence (Caroline Hawkridge) who organises group writing events to take place at the meeting. The poetry is inspired by a number of influences, one by the hospital car park(!) but this one was inspired by the name of the daughter of a doctor who presented a talk at one of the meetings. Her name was Hope and from that we all contributed to the poem 'Hope is...' giving our individual impression of what hope means to each of us. There was a wide range of contribution, some from patients, some from carers and some from staff.

Rupert performed our poem outside the Houses of Parliament as video recording is not normally allowed within its walls. Watch & listen here (once on the website click on Rupert's picture).

Tuesday, 12 November 2013

Congratulations Tom Walsh

The European Journal of Clinical Investigation has published a study that attempts to list the 400 most influential biomedical researchers living between 1996 and 2011.

The authors make the point that it is ever more important to know who has the best experience of carrying out high-impact research, what it is that brings about work that has high impact:

The world of modern science has become increasingly competitive in recent years. Literature-based metrics are playing a greater role in decision-making than in the past [1]. Many researchers are highly aware of their so-called status, and check diverse metrics related to the impact of their work on a regular basis. The differing dimensions of impact and reasons for citing are receiving renewed discussion and analysis [2-6]. Although citation counts and related metrics (e.g. journal impact factor, h-index for individual researchers) are typically considered as proxy for impact [7], the nature of that impact is rarely, if ever, specified.
It is within this context of creating a better understanding of impact(s) that we have created a list of highly influential biomedical researchers. Ranking of scientists is explicitly not the main purpose of this list. Rather, we wanted to identify a pool of researchers who have had sustained success in highly influential work and who would thus presumably have substantial insight into differing features that could be associated with high impact. This list is being used in an ongoing survey where highly cited researchers are asked about the features of their most-cited articles. However, the list may be of use for many other purposes, as we discuss below.
Thomas Walsh is a leader in antimicrobial drug research including antifungal drugs and it is of great credit to him and his team that he is named on this list of the research & influence elite of the medical profession. His work has been cited nearly 29 000 times in the period covered by this study, which is a measure of the interest there is in his work amongst his peers. He published over 500 papers in the 15 years mentioned - a rate equivalent to one every 10 days! Phenomenal and inspirational!

Friday, 8 November 2013

Fungal infections in cystic fibrosis

Cystic fibrosis (CF) is the most common acquired genetic disease in the Caucasian population, with approximately 1 in 25 people in the UK being 'carriers' for the disease. When two carriers have children, there is a 1 in 4 chance that the child will have CF.

CF is characterised by abnormal ion transport in several cell types, but most notably in cells which line the airways. This leads to a build-up of thick mucus which sticks to the airways, resulting in a 'remodelling' of the lungs. This increases the prevalence of bacterial and fungal infections in the airways, though the underlying reason for this is still disputed. One theory is that the make-up of the secretions—which are different in CF sufferers compared to the general population—allow bacteria and fungi to evade the immune system with more success.

It's widely accepted that both Candida and Aspergillus species colonise the airways in CF patients, and this is most likely due to long-term exposure to antibiotics. Candida spp. are usually considered relatively benign in most patients, and there is insufficient scientific evidence to treat the presence of Aspergillus species unless it is present and causing allergic bronchopulmonary aspergillosis (ABPA).

Whilst not itself an invasive disease, ABPA exacerbates existing CF disease through wheezing and, potentially, damaging the lung structure through scarring (fibrosis). Unfortunately the diagnosis of ABPA in CF patients is challenging, since many symptoms overlap. Strong laboratory evidence is essential to confirm diagnosis of ABPA. Once diagnosed, the gold standard treatment consists of steroid drugs to help suppress the excessive immune response, alongside itraconazole (an azole antifungal drug) to help prevent fungi taking advantage of any reduced immune response. This halts progression of disease and successfully manages most patient's symptoms.

Whilst Candida and Aspergillus make up the large majority of cultured fungi from CF patients, there are still  significant numbers of other pathogenic fungi which infect in CF. Scedosporium and Penicillium species are found in around 15% and 8% of cultures respectively. Similar treatment options exist to those of Aspergillus infections, with laboratory testing again essential to determine which drugs are most effective to the particular organism.

Thursday, 7 November 2013

Global Action Fund for Fungal Infections (GAFFI) Launched in London, New York

GAFFI was formally launched at the Houses of Parliament yesterday on the 6th of November during a glamorous event that featured world-renowned actor Rupert Everett performing several poetic works in support of the aims of GAFFI and the support and music of Singer/Songwriter Katie Melua.

Katie's music has sold 4 million albums so far, won several awards and memorably sang "Too Much Love Will Kill You" with Brian May at the 46664 concert in George, South Africa for Nelson Mandela 's HIV charity.

One of the poems performed by Rupert Everett was written with the Patients Support Group at the National Aspergillosis Centre as part of their creative writing project run by Poet-in-Residence Caroline Hawkridge. It is based on the theme of 'Hope' and was inspired by the name of the daughter of one of our doctors.

The launch in London began with a welcome from Paul Goggins MP, in who's constituency resides the National Aspergillosis Centre, University Hospital of South Manchester. GAFFI is about raising the awareness and funding for the need to be able to diagnose and treat all fungal infections throughout the world but aspergillosis is prominent in ongoing illness as a result of TB and in severe asthma (contributing to 1 350 000 deaths every year) and in the loss of sight caused by infection after damage to the eyes of tens of millions of people every year.

AIDS is an illness with very high public awareness and high levels of funding to attempt to treat infection with the HIV virus, but did you know many of the 1 350 000 deaths every year caused by fungi are AIDS sufferers?

We were then treated to a stunning presentation using the lyrics of Katie Melua's song 'I'd love to kill you (with a kiss)" to evoke a series of images of the suffering caused by fungal infection.

Most memorably two accounts of what it is like to live with a fungal disease were related by patients themselves. Gail Iddon and Woodrow Maitland-Brown shared their compelling stories of how beneficial access to good diagnosis and treatment can be when suffering from a fungal infection. Gail and Woodrow were great examples of how effective treatment can improve quality of life.

Professor of Global Health at Manchester University David Denning outlined the aims of GAFFI and made the striking (and very shocking) point that 150 people die from a fungal infection somewhere in the world every hour of every day, many more than that are severely disabled with life changing symptoms. In many poorer parts of the world this is highly preventable for a large proportion of cases (up to 75%).

The launch in London was brought to a close by Lord Turnberg (former president of the Royal College of Physicians).

David Perlin launches GAFFI in New York

In New York the launch was led and performed by Professor David Perlin, David Warnock (ex-CDC) and Liise-Anne Pirofski (Albert Einstein) to a packed audience.

We wish GAFFI well on its journey to make life better for many millions of people throughout the world.

Further information on GAFFI and this event can be found on their website

Katie Melua "I'd Love to Kill You"

Katie Melua singing "Too Much Love Will Kill You" at Nelson Mandela's Charity concert, 2005


GAFFI Leaflet - feel free to print out and distribute

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