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The Still Underestimated Problem of Fungal Diseases Worldwide

Fausto Almeida, Marcio L. Rodrigues, Carolina Coelho

Frontiers in Microbiology · 2019 · Review

doi:10.3389/fmicb.2019.00214

Abstract

In the past few years, fungal diseases caused estimated over 1.6 million deaths annually and over one billion people suffer from severe fungal diseases (Brown et al., 2012; Anonymous, 2017b). Public health surveillance of fungal diseases is generally not compulsory, suggesting that most estimates are conservative (Casadevall, 2017; Anonymous, 2017a). Fungal disease can also damage plants and crops, causing major losses in agricultural activities and food production (Savary et al., 2012). Animal pathogenic fungi are threatening bats, amphibians and reptiles with extinction (Casadevall, 2017). It is estimated that fungi are the highest threat for animal-host and plant-host species, representing the major cause (approximately 65%) of pathogen-driven host loss (Fisher et al., 2012). In this complex scenario, it is now clear that the global warming and accompanying climate changes have resulted in increased incidence of many fungal diseases (Garcia-Solache and Casadevall, 2010). On the basis of all these factors, concerns on the occurrence of a pandemic of fungal origin in a near future have been raised (Casadevall, 2017). In this context, to stop forgetting and underestimating fungal diseases is mandatory.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 18, 2026. Paragraph numbers are ours, so an answer can point at one.

The Burden of Human Fungal Infections

Currently, there are few antifungal drugs approved for use in humans. The last antifungals approved for human use were characterized in 2002. This scenario may be linked to an imbalance between funding and mortality rates in the field of fungal diseases. For instance, cryptococcal meningitis results in approximately 180 000 deaths annually globally, as compared to 429 000 deaths caused by malaria or 1.6 million tuberculosis-deaths (as estimated by WHO in 2015 and 2017, respectively). However, cryptococcosis received less than 0.5% of the global research and development funding, while malaria and tuberculosis received together 35.5% of the total investment in research and development in infectious diseases. Current therapeutic to treat fungal diseases remain unsatisfactory, and to develop novel therapeutic alternatives a significant investment in dedicated research is required. Novel antifungal are in different clinical development stages, and these new compounds such as AR-12, BHBM, CD101, E1210/11, F901318, Ilicicolin H, Nikkomycin Z, Sampangine, Scy-078, Sertraline, T-2307, Tamoxifen, and VT-1129. Some of these (VT-119 and Nikkomycin Z, for example) belong to new classes of drugs, i.e., they act through different mechanisms and molecular targets than the already approved drugs, and may provide a much-needed extension to the limited therapies currently available. Programs specifically offering funding to mycological research are necessary to potentiate further development of effective antifungal therapy and ultimately reduce mortality from fungal diseases.

The Impact of Fungal Infections on Food Crops and Disproportionate Impact in Developing Countries

Fungal diseases in developing countries demand special attention. Many of the fungal diseases in Latin America are often overlooked, although they clearly fulfill the criteria to be classified as neglected human diseases. The general impact of fungal pathogens on human health goes beyond the ability of fungi to infect humans, since they destroy a third of all food crops annually, causing economical loss and impacting global poverty. Statistics from the 2009–2010 world harvest (www.fao.org or FAOSTAT1) suggest fungi-induced losses in five of the most important crops globally (rice, wheat, maize, potatoes, and soybean). If those losses were mitigated, these crops would have been enough to feed 8.5% of the seven billion populations in 2011. Furthermore, in a hypothetical event where these five crops were affected simultaneously, approximately 61% of the world’s population would not have food. The most economically devastating fungi are Magnaporthe oryzae, affecting rice and wheat, followed by Botrytis cinerea, which has a broad host range and Puccinia spp., affecting wheat. Several high-value crops produced in the tropics, such as bananas, coffee, cacao, spices, mangos, and several nuts, are currently affected by fungal infections and these crops are not produced colder climates. Therefore dependence of crop produced in tropical regions aggravated with a lack of biodefense and preparedness might result in disastrous economical consequences worldwide.

Fungal infections of invertebrate hosts may also impact agricultural crises due to ecological imbalance. For instance, bee broods are susceptible to fungal infections caused by genera of Ascosphaera and Aspergillus, and the agricultural production worldwide is highly dependent on pollination mediated by bees. Fungal infection of bees may precipitate a disaster, with unpreceded impact on agriculture and various plant species.

The Impact of Fungal Infections on Animal Species

When fungi cause animal disease the outcomes are quite dramatic and scientists have been trying to raise attention to the effects of fungal infections in decreasing biodiversity, an effect aggravated (if not triggered) by global warming. Bat decimation caused by Geomyces destructans and several frog species by Batrachochytrium dendrobatidis are well known events. In invertebrates we already mentioned the case of bees, and further species may be affected but further research is needed. For example, there is a debate regarding if a marine Aspergillus spp. is associated with the decline of coral reefs. Overall, the examples of species decimation in mammals, plants, and bees by fungal pathogens should prompt investigation of similar phenomenon in a wider scale, for example, other insects and in aquatic life.

Critical Interactions of Fungi With the Environment

It is important to highlight that most of the plant-fungal interactions are beneficial to both plants and fungi, with this symbiotic interaction improving plant growth, development, foraging, acquisition of soil resources, and tolerance to stress. For instance, Trichoderma induces biofertilization of crops. The addition of Trichoderma hamatum or Trichoderma koningii to the production fields can increase crop productivity up to 300%. Trichoderma spp. also acts in the mycoparasitism, the direct attack of one fungal species on another, being described as potential biological control agent against important phytopathogenic fungi such as Fusarium spp., Rhizoctonia solani, Sclerotium rolfsii, Sclerotinia sclerotiorum, B. cinerea, and Pythium spp.. Thus, mycoparasitism-based strategies could decrease the use of agrochemicals and antifungals in crop cultivation. In this sense, a better understanding of the fungal diversity and its impact on plant-fungal interactions would be highly beneficial to improve phytopathogen control.

The Urgency of Combatting Fungal Infections

The reduced number of antifungals impact human health not only due to lack of therapy to cure human patients. Medically approved antifungal drugs have been used for agricultural purposes for decades. Most human pathogens have environmental niches, implying that the agricultural use of medically-approved drugs imposes the concrete risk of fostering drug resistance. Emergence of antifungal resistance can endanger the already limited treatments options, with calamitous effects for treatment outcomes. The development of new antifungal drugs is urgent to improve both human health and agricultural production.

The worsening of global warming opens a Pandora box for fungal diseases. Some thermally intolerant fungi with current pathogenic potential should acquire the ability to survive at mammalian temperatures. This threat is heightened since some fungi can take advantage of a natural selection-adaptation strategy, and consequently to adapt to higher temperature by thermal selection.

The collaboration between all these affected disciplines would be critical in facilitating at detecting epidemics early on and preventing further spread. The concept of One Health, with integration and communication between medical doctors, veterinarians, and food safety officials has been implemented with remarkable success and should become a standard for transmissible diseases. We have included a table summarizing basic information regarding distribution and etiological agent of important human mycoses (Table 1).

The negative impact of any infectious disease is usually higher in neglected populations. Lack of access to healthcare, underfunded healthcare, and delayed diagnosis lead to higher burden of fungal diseases. The economy of countries in developing countries strongly relies on agricultural production. Another fungal blight, if not managed properly, can still have disastrous economical and societal consequences.

The old adage “know your enemy” illustrates the major point of this essay: significant investment in fungal research, including fungal biology, human and plant pathogenicity, therapeutic agents, diagnostic tools, and vaccines, has the potential to avoid a global catastrophe. This call has been made by most, if not all, prominent fungal researchers. We urge more attention to fungal biology and pathogenesis globally with special attention to diseases affecting developing countries, as a safeguard for prevention of losses in agriculture, environmental losses, and damage to human health.

Author Contributions

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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