More research about fungal infections required

Globally, there has been a rise in the incidence and a change in the pattern of fungal diseases in the past few decades posing unique clinical and public health problems due to the diagnostic challenges and the high morbidity and mortality associated with fungal diseases. Serious fungal diseases often occur because of comorbid medical conditions including human immunodeficiency viruses (HIV), chronic respiratory diseases (e.g., asthma, pulmonary tuberculosis, and chronic obstructive pulmonary disease), primary immunodeficiency, and other non-HIV immunocompromising states, such as cancers, solid-organ, and hematopoietic stem cell transplantation and long-term corticosteroid administration. Fungal infections are more often than not neglected by social and political communities. Fungal diseases, antifungal drug resistance and the development of new antifungal drugs gets little media coverage.


However, fungal disease affects more than a billion people worldwide, resulting in approximately 12 million life-threatening infections and more than 1.5 million deaths annually. Mortality due to serious fungal diseases is comparable to that of tuberculosis (∼1.7 million deaths) and more than that due to malaria (∼0.5 million deaths annually). Low- and middle-income countries (LMICs) are disproportionately affected by serious fungal diseases due to factors such as high burden of HIV/AIDS, limited access to health services, limited availability of diagnostics, poor infection control practices, and access to antifungal medications. In addition, there is insufficient knowledge on the prevention, diagnosis, and treatment of serious fungal infections amongst health workers. However, epidemiological studies are important for fungal diseases surveillance and institution of tailored interventions. However, research and routine surveillance of fungal diseases to inform policy and public health actions are non-existent in most of the nations of the world.


While many fungal diseases are neglected and/or insufficiently addressed by public health authorities, some fit the World Health Organization (WHO) definition of Neglected Tropical Diseases (NTDs). Among fungal diseases, the WHO designated mycetoma as an NTD in 2013 and chromoblastomycosis, with “other deep mycoses”, in 2017. This is a great step forward from the perspective of improving the outcomes of patients with these serious diseases. The WHO Global Report on Antimicrobial Resistance Surveillance dedicates fewer than 10% of its pages to fungi, reflecting the limited resources allocated for monitoring and reducing antifungal drug resistance. Indeed, the WHO has no funded programmes specifically targeting fungal diseases. Fewer than 10 countries have national surveillance programs for fungal infections, and fewer than 20 have fungal reference diagnostic laboratories. Many of the diagnostic tests that do exist are not available in developing countries, and well-established antifungal drugs such as amphotericin B and flucytosine that would cure disease do not reach people who need them, a large proportion of which are in Africa.


Training to bridge the gap in knowledge on the prevention, diagnosis, and treatment of serious fungal infections amongst health workers is the first step to build capacity in African countries. After his postgraduate training in Mycology (MSc medical Mycology) at the University of Manchester in 2014, Mr Kwizera returned to Uganda where he is building capacity of mycology based at Makerere University. His initial goal was to estimate and raise awareness about the burden of fungal diseases in Uganda. Since data were limited, he has since then published on fungal disease burden in Uganda using systematic reviews, retrospective studies and a few prospective epidemiological studies. With his laboratory background, he has carried out and published a number of studies on improving fungal diagnostics, especially for cryptococcal meningitis, pulmonary Histoplasmosis and pulmonary Aspergillosis to improve on their advocacy in Uganda. With strong collaborations from the USA and UK, he is developing translational research and supporting research for fungal diseases at Makerere University College of health sciences and Mulago national referral hosptial. He is currently collaborating on a number of fungal studies at the infectious diseases institute and the lung institute at Makerere University. He is a member of the cryptococcus team investigating the outcomes of HIV patients with cryptococcal meningitis, and he is attached to the research team evaluating the incidence of chronic pulmonary aspergillosis in HIV patients with past TB. With funding from DELTAS Africa, Mr Kwizera is currently pursuing a PhD under the THRiVE consortium, with a main aim of investigating the burden of fungal asthma caused by Aspergillus species among Ugandan asthmatics, exploring the relationship between fungal allergy and severe asthma among Ugandans while detailing factors associated with fungal asthma in this population. In the same study, he is also evaluating the diagnostic performance of a point of care test for fungal asthma in the same population. He is a co-founder of the Ugandan Association for Medical Mycology.



With all the above efforts and working together with his local and international collaborators, Mr Kwizera has managed to a certain extent popularise fungal disease research in Uganda. He advises that in order to popularise and uplift research in this area, organisations/ institutions must actively advocate to include more antifungal drugs on the WHO Essential Medicines List. There is need to build laboratory capacity and improve the availability and affordability of diagnostics, train laboratory technologists and clinicians in fungal disease diagnosis and treatment, and ensure that antifungals are available globally. Funding is also urgently needed to advance our understanding of fungal pathogenesis and drug resistance, develop new diagnostics and antifungal strategies, and improve monitoring of infection and antifungal resistance, as this will ultimately inform new strategies to tackle fungal infections.


Challenges in the diagnosis of fungal infections

With the exception of cryptococcal disease which can be diagnosed reliably by antigen testing, diagnosis of other deep fungal infections is not straightforward. Conventional culture on Sabouraud dextrose agar is the gold standard diagnosis for each of the deep fungal infections and also allows antifungal susceptibility testing; however they display low sensitivities and take days to weeks to yield positive results. Molecular-based techniques are becoming increasingly important in the species-level identification of invasive fungal disease, however, they currently costly, lack methodological standardization and validation, and unclear interpretation of the results thus not widely used routinely in resource-limited settings. Serology and biomarkers also play an important role in the diagnosis of invasive fungal diseases owing to their speed and specificity.

Managing serious mycoses: challenges in resource-limited countries

Many challenges exist in the management of serious fungal infections in resource-limited countries, such as; high disease burden, lack of diagnostics, limited awareness, low resource allocation, rare public health response, lack of a recognised international authority on public health mycology, lack of epidemiological data and antifungal drugs. Management of fungal infections is also still a challenge since clinicians do not know which patient to be treated due to lack of diagnosis and epidemiological data. Prophylaxis is not being used since they do not know the magnitude of the problem in the at-risk populations. Data are lacking on when to stop empiric antifungal therapy. In addition, antifungal drugs are not available in most developing countries. Besides, patients cannot afford the antifungal drugs. Therapeutic drug monitoring is not available in most centers. The role of radiology and histology in diagnosis of invasive fungal disease is not well exploited.