The major burden of serious invasive fungal infection is borne by low- and middle-income countries. The creation of dedicated research units in the worst impacted regions is a critical tool in the effort to tackle devastating fungal diseases worldwide.
Specialised units can, through research, develop a deeper understanding of the diseases affecting people in a particular geographical area, in turn developing targeted diagnostic approaches and treatments. And, crucially, units can train new scientists and clinicians in local regions.
At the MRC Centre for Medical Mycology we are addressing overseas need by establishing specialist Medical Mycology units in key locations across the globe. The specialist units will work ‘hand in glove’ with the UK based Centre – the MRC Centre for Medical Mycology (CMM) – and are to be located in countries where they can have an impact across large regions.
To address the need for a dedicated unit to tackle fungal disease in Africa, the Universities of Exeter and Cape Town (UCT) joined forces to create the world’s first international research centre for tackling fungal infections; the AFRICA CMM Medical Mycology Unit, which opened in Cape Town in August 2017.
The AFRICA Unit provides a centre of operations in Africa and has established research programmes to target the priority areas in fungal diseases that are relevant to the African continent.
Directed by Professor Gordon Brown, the AFRICA Unit is based at UCT’s Institute of Infectious Disease and Molecular Medicine (IDM) headed by Professor Valerie Mizrahi. With the primary focus being HIV and Tuberculosis, the IDM combines basic, clinical and public health research relevant to the needs of African people and is a powerhouse of research that makes a real-world difference through the creation of new therapies, medical procedures and diagnostics.
The AFRICA Unit is led locally by Dr J. Claire Hoving, whose research aims to understand host immune responses in people with HIV-related fungal infections. Her current major focus is understanding the immune response to Pneumocystis jirovecii, that is a common cause of pneumonia and death in patients with HIV/AIDS in Africa and is estimated to kill over 250 000 worldwide every year.
Undertaking research at the AFRICA Unit is Dr Rachael Dangarembizi, a neuroscientist in the Department of Human Biology and the Neuroscience Institute at the University of Cape Town whose main research interest is immune responses to fungal infections affecting the brain.
Her current research focusses on the inflammatory response to Cryptococcus neoformans infection in the brain. Dr Dangarembizi is one of very few neurobiologists in the world who is researching the impact of fungal diseases on the brain.
There are plans to recruit a further two researchers to lead on new research projects at the AFRICA Unit.
Stakeholders including the MRC CMM and AFRICA Unit members1, and Centres for Disease Control and prevention in the USA, have come together to launch urgent efforts to end HIV-associated cryptococcal deaths by 2030.
HIV-related cryptococcal meningitis is responsible for over 180,000 deaths per year, accounting for approximately 20% of the annual worldwide burden of HIV related deaths.
HIV-related deaths are no longer decreasing, despite improved antiretroviral treatment for HIV infection. This is due in part to late diagnosis of HIV, and also to people dropping out from care, stopping taking their HIV medicines, and then becoming sick again. Late diagnosis of HIV is often accompanied by invasive fungal disease caused by HIV-related immune deficiency. The World Health Organisation has now recognized that to further reduce HIV deaths there is an urgent need to improve the treatment of complications such as cryptococcal meningitis.
The AFRICA Unit and MRC CMM are contributing to this effort by working to advance scientific understanding of the fungal pathogen Cryptococcus neoformans. Developing a better understanding of Cryptococcus, and the way it interacts with the human immune system, will enable improved diagnosis, prevention and treatment of cryptococcal meningitis.
And clinical trials in African hospitals, such as the AMBITION trial and the ACTA trial – both led by Prof. Tom Harrison, aim to address diagnostic and therapeutic gaps, so as to develop the best treatments to reduce the fatality rate from this fungal disease.
Recent progress has been made, notably by the ACTA trial that showed that combination treatments that include a drug called flucytosine could halve deaths rates from 70% to 30-35%.
1 Prof. Tom Harrison, Dr Tihana Bicanic, Dr Carolina Coelho , Dr Liliane Mukaremera, Dr Rhys Farrer, Dr Rachel Dangarembizi
Members of the AFRICA Unit and MRC Centre for Medical Mycology are collaborating on a Pneumocystis project involving Dr J. Claire Hoving, Dr Olga Nev and Professor Al Brown. Together with collaborators in Exeter (Prof Ivana Gudelj), France (Drs Adama Ouattara and Wassim Abou-Jaoudé) and the USA (Professor Jay Kolls), the team is investigating how the fungal pathogen Pneumocystis jirovecii has evolved to become dependent on the human lung environment for its survival. As mentioned earlier, Pneumocystis jirovecii is a common cause of pneumonia and death in patients with HIV/AIDS in Africa and is estimated to kill over 250 000 worldwide every year. The hope is that, in the longer term, this will facilitate therapeutic discovery programmes to help tackle lung diseases caused by this fungus.
For example, week-long workshops bring together African scientists and clinicians at all career stages to receive lectures and practical courses that focus on the key fungal pathogens and their diseases in Africa, covering the microbiological, immunological and clinical aspects of fungal diseases.
Another example is the triennial international AIDS-related mycoses meetings host by the AFRICA Unit in Cape Town, South Africa. The most recent (2019) meeting was focussed on highlighting the continuing problem of advanced HIV and the contribution of mycoses to AIDS deaths. The programme addressed public health, novel prevention and treatment strategies, basic science of host-pathogen interactions, immunology, antifungal resistance and genomics. The meeting led to six key action points that were published here: Hoving et al. AIDS-Related Mycoses: Updated Progress and Future Priorities (2019). Trends in Microbiology 28 (6): 425-428.
MRC CMM are also building local capacity by working with national funding agencies (such as the National Research Foundation and the South African Medical Research Council) to recruit and train Masters and PhD-students, and postdoctoral scientists in medical mycology. Alongside this, the Centre hosts students from other laboratories across Africa, so that they can learn new techniques and approaches specific to medical mycology. For example, the AFRICA Unit is currently hosting a PhD student from a laboratory in Botswana that is involved in the AMBITION trial.
A group of MRC Centre for Medical Mycology researchers, led by Dr. Ivy Dambuza, have established the Imhotep Mentorship programme and Café All Things Fungi with the aim of supporting young researchers in Africa to develop careers in medical mycology through networks and mentorship.
You can follow their news and updates via Twitter @ImhotepMentors1 and @CafeFungi
Following the success of the AFRICA Unit in Cape Town, the MRC Centre for Medical Mycology plans to establish a further two international units between 2022-2027.
One new Unit will be based in Brazil, and the other Unit will be located in South East Asia.
The new Units will enable research that tackles fungal diseases endemic to those geographic regions and will facilitate training and capacity building in medical mycology. As with the AFRICA Unit, research and training will be developed collaboratively between the MRC Centre for Medical Mycology at the University of Exeter, and each of the international Units. The global network of Medical Mycology Units will, for the first time, establish an integrated global research programme and network focused on medical mycology.
The MRC Centre for Medical Mycology vision for a global solution to deadly fungal infections represents the an ambitious and strategic effort to change the story for millions, worldwide.
