Fungal diseases of humans

There are around a quarter of a million species of fungi on our planet, but only 300 or so can make humans sick. Common fungal infections include athlete’s foot, jock itch, vaginal thrush and ringworm. These can all be treated successfully. But there’s a growing threat of other infections that are much more difficult to overcome.

The rise in the rate of resistance to anti-fungal drugs is “unprecedented” and the impact on human health is “spiraling.” The threat of antimicrobial resistance is well established in bacteria, but has largely been neglected in fungi. The scale of the problem has been, until now, under-recognized and under-appreciated, but the threat to human health and the food chain are serious and immediate. Because fungi are more genetically similar to humans than bacteria, it’s difficult to produce a drug aimed at a fungus that won’t potentially cause great harm to us as well, so only four classes of anti-fungals are available for human use. The very limited number of anti-fungal drugs means that the emergence of resistance is leading to many common fungal infections becoming incurable.

The types of disease caused by fungi in humans can be divided into three categories: (1) respiratory allergies following sensitization due to inhalation of fungal antigens; (2) fungal intoxication due to ingestion of toxic substances such as amatatoxin and phallotoxin produced by certain poisonous mushrooms aflotoxins produced Aspergillus species which have been implicated in liver damage; (3) disease relating to specific infecting fungi.

More than 50 species of fungi cause disease in animals and man, forming two subsections: dermatophytoses, superficial infections of the skin, hair and nails; and mycoses, infections of the deeper tissues and organs. Dermatophytoses include ringworm and actinomycosis. Dermatophytoses are caused by fungi present on the surface of the skin; mycoses on the other hand live and grow independently of the host and infection is caused by inhaling or ingesting spores, or by the implantation of fungus under the skin through small punctures, cuts or bruises. Mycosis infections include Coccidioidomycosis, Histoplasmosis, Cryptococcosis, and Adiaspiromycosis. Most of the fungi causing these diseases have been found in soil.

Mycoses are caused by a variety of fungi which attack diverse structures of the body, and are divided accordingly into three groups:

(1) Cutaneous, or superficial, mycoses attack the epidermis only, involving skin, hair or nails without invasion of the tissues. These are known clinically as Tinea infections; Tinea capitis is the well known scalp infection that occurs in childhood and heals spontaneously in puberty. Superficial mycoses are most commonly caused by the so-called dermatophytes - Microsporum or Tricophyton spp. e.g. Microsporum canis, Microsporum gypsum and Trycophyton rubrum. Their natural habitat is either man, animal or soil. Infection is due to direct contact of the skin with the infected surroundings.

(2) Subcutaneous, or intermediate, mycoses attack the epidermis, but they may also attack deeper structures. One of the most common offending species is Candida albicans producing a form of moniliasis; the yeast is part of the normal endogenous respiratory tract flora and may be present in the digestive tract as a saprophyte. Infection takes place by direct contact or by inhalation and spreads via the bloodstream.

(3) Deep mycoses attack deep structures in the body, but may metastatically also invade the epidermis. Blastomyces, Coccidioides and Histoplasma are common fungal agents responsible for primary systemic disease; and each tend to occur in distinctive geographic locations, Blastomyces dermatitidis occurs mostly in North America (USA, Canada, and Mexico), Coccidioidies immitis mostly in the south-west USA and Latin America and Histoplasma capsulatum mostly in central USA.

Opportunistic fungi are mainly considered non-pathogenic but more and more often being found to cause disseminated infections in immuno-compromised and immunosuppressed individuals, or those weakened by a metabolic defect or who have undergone surgery. The infections caused may be subacute or chronic , some more like intermediate mycoses and some systemic. The diseases include aspergillosis, systemic candidosis and cryptococcosis. Exceptionally, other fungi that are normally not pathogenic, such as Trichosporon, Fusarium or Penicillium, may cause opportunistic systemic infections.

Human deaths from fungal diseases worldwide now exceed those of malaria and breast cancer.

Aspergillus is a fungus found in the soil, air, food, decaying organic material and damp walls. It can be a problem for those with serious lung conditions or suppressed immune systems; patients who have received a transplant, and those with cancer and HIV/AIDS, are especially vulnerable. However, even otherwise healthy young adults — as many as one in five — can be infected while being hospitalized with a severe flu infection. In 2018, the US Centers for Disease Control and Prevention reported that more than one-third of flu patients with invasive aspergillus infections — called aspergillosis — were otherwise healthy, with no documented immunosuppressive condition. These were people with healthy immune systems who first caught the flu, then got aspergillosis.

Surprisingly, almost no drug-resistant species of aspergillus were found by researchers in farmers’ crop fields in the UK. Instead, they were discovered in woods, public gardens and parks across southern England. They were also found in flower beds containing tulips, daffodils and crocuses. That’s because these bulbs are sprayed with anti-fungal chemicals. Drug resistance creates hotspots in the plants for incubating and releasing aspergillus spores into the atmosphere.