Opinion article by Prof Carolina Pohl-Albertyn, NRF SARChI Research Chair in Pathogenic Yeasts, Department of Microbiology and Biochemistry, University of the Free State.

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On 25 October 2022, the World Health Organisation (WHO) released the first ever fungal priority pathogens list in order to guide research, development, and public health action. This document recognises that although the rising resistance of bacteria to antibiotics and other antimicrobials is a serious health threat, directly causing more than a million deaths annually and indirectly contributing to almost five million deaths per year, the rise of serious fungal infections can no longer be ignored. Fungal infections are estimated to affect more than one billion people each year, of which more than 150 million cases are severe and life-threatening, especially to immune-compromised people. These infections cause almost two million deaths every year. The WHO highlights the fact that, despite researchers and doctors raising alarm about this, fungal infections still receive very little attention and resources, including research funding. This means that there is a lack of quality data on the distribution of fungal diseases and their associated drug resistance, making it impossible to accurately estimate the exact burden of fungal disease – meaning that these numbers are probably an underestimation. 

Therefore, in an attempt to shine the spotlight on these serious but neglected infections, the WHO has published a list of fungal pathogens that are of concern, because they can cause deadly invasive infections. It also proposes actions that need to be taken to deal with this threat. These are:

• Strengthening laboratory capacity and surveillance (i.e., monitoring the environment for these fungi)

• Sustainable investments in research, development, and innovation

• Public health interventions

Sub-Saharan Africa is not exempt from these infections. As an example, a recent survey found that one third of women in sub-Saharan Africa suffer from vaginal infections due to the fungus, Candida albicans, with pregnant women having a 6% higher risk of this infection. This can have serious implications for the health of the baby, as these types of infections can cause premature birth as well as systemic infections and even death of the newborn. 

Closer to home, recently published estimates put the burden of disease due to fungal infection in South Africa at more than three million cases per year. The National Institute for Communicable Diseases (NICD) investigated the cases of fungal bloodstream infections in South Africa between 2019 and 2021 and found that 12 959 confirmed cases of Candida bloodstream infections were reported. Most of these reports (71%) came from the private sector. What is very worrying is that there has been a significant increase in the proportion of cases of Candida auris infections (17% in 2019 to 31% in 2021). Candida auris can be easily transmitted between patients in a hospital and cause outbreaks in these health-care facilities. It can survive on surfaces for long periods and is resistant to many routinely used disinfectants. In addition, 90% of Candida auris strains are resistant to at least one class of antifungal drugs, and about 30% are resistant to two or all three classes of antifungal drugs, effectively meaning that infections caused by these yeasts cannot be treated. 

In addition to the fungi causing infections in all areas of the world, South Africa also faces unique challenges, such as the fungus, Emergomyces africanus, which was first described in South Africa in 2013. This fungus infects immune-compromised patients, including HIV-positive persons, and has quickly become one of the most diagnosed causes of infection by this groups of fungi in South Africa. This unique challenge is also the reason why the WHO highlights the importance of considering the regional variations and national contexts when prioritising research on specific pathogenic fungi. 

The Department of Microbiology and Biochemistry has a long history of research on fungi. Since 2006, research has been performed on some of the pathogenic fungi (Candida albicans, Candida auris, and Cryptococcus neoformans) ranked as ‘critical’ on the WHO list, because of their ability to cause deadly disease as well as the fact that they are often very resistant to antifungal treatment. This led to the awarding of an NRF SARChI Research Chair in Pathogenic Yeasts to Prof Carlien Pohl-Albertyn in 2019. 

Together with Prof Koos Albertyn, Prof Olihile Sebolai, Dr Onele Gcilitshana, Prof Trudi O’Neill, and their postgraduate students, the group is working on a better comprehension of these pathogenic fungi, in order to understand how they are able to cause disease. Since we also urgently need to find new treatment options beyond the established antifungals, research conducted under the SARChI chair also includes the evaluation of compounds as potential novel antifungals; repurposing of existing drugs for other diseases as possible antifungal drugs; as well as finding new drug targets that may be exploited in the development of novel antifungals. 

We are also starting to focus more on environmental surveillance for pathogenic fungi, since many of these organisms also occur in places that we visit every day. We recently published the results of the first survey of Cryptococcus in bird droppings in Bloemfontein, showing that this yeast can be found in many of the samples collected in the city. Similarly, a recent study showed that many different pathogenic yeasts, including the Candida species listed as ‘critical’ or ‘serious’ on the WHO list, can be found on the plastic pollution that is common in the streams running through Bloemfontein. 

It is hoped that the publication of this priority list will spark greater interest in this crucial research among scientists, research funders, and the general public.