17.3 — Fungi and Parasites

Fungi are eukaryotes, more closely related to animals than to plants (Chapter 3.7). Which is precisely why antifungal drugs are harder to design than antibacterials — there is far less that is uniquely fungal to attack.

Parasites infect over a billion people, cause enormous morbidity, and are among the cheapest and most treatable conditions in global health — which is what makes them a story about resources rather than about medicine.

Fungal infection

Two categories, and they are almost different subjects.

Superficial — common, mild, treatable.

Tinea — athlete's foot, ringworm, jock itch, scalp and nail infection (Chapter 14.5). Named by site rather than by organism.

Candida — thrush of the mouth, vagina or skin folds. Commoner after antibiotics, in diabetes, and in immunosuppression, because the bacteria that normally compete with it have been removed (Chapter 13.1).

Treated with topical or, for nails and scalp, oral antifungals — and nail treatment takes months because the nail must grow out (Chapter 14.3).

Invasive — uncommon, serious, and almost entirely a disease of impaired immunity.

Aspergillus — inhaled mould spores, which everyone breathes daily and healthy people clear. In neutropenia it invades lung tissue and blood vessels, with high mortality.

Cryptococcus — meningitis, and a leading cause of death in advanced HIV worldwide.

Pneumocystis jirovecii — pneumonia in immunosuppression, and historically the presenting illness of AIDS.

Candida in the bloodstream — in intensive care, with lines and broad-spectrum antibiotics.

Candida auris — emerged in the 2010s, resistant to multiple antifungal classes, and a growing hospital problem.

Endemic fungi — histoplasmosis, coccidioidomycosis, blastomycosis — geographically restricted, and worth knowing because travel history makes the diagnosis.

Mucormycosis — rare, aggressive, invading blood vessels. Strongly associated with uncontrolled diabetes, particularly ketoacidosis, and there was a substantial outbreak among COVID-19 patients in India who had received steroids.

Why antifungals are limited

Only a handful of exploitable differences.

Ergosterol — fungal membranes use it where ours use cholesterol. Amphotericin B binds it and punches holes; the azoles block its synthesis. This is the main target.

The cell wall — fungi have one and we do not. Echinocandins block its synthesis, and they are the most selective antifungals available for that reason.

And the consequences of having so few targets: more toxicity — amphotericin B is nicknamed "amphoterrible" for its kidney effects and infusion reactions; more interactions — the azoles are potent inhibitors of the liver enzymes handling other drugs (Chapter 1.5); longer courses; and rising resistance with fewer alternatives.

Which is why azole-resistant Aspergillus, driven partly by agricultural azole fungicide use, is a genuine concern.

Parasites

Three groups.

Protozoa

Single-celled (Chapter 3.7).

Malaria — Chapter 17.7, and by far the most important.

Giardia — from contaminated water. Prolonged watery diarrhoea, bloating and foul-smelling flatulence, often after travel or camping. Treated with metronidazole.

Entamoeba histolytica — amoebic dysentery, and liver abscess. A liver abscess in someone who has travelled to an endemic area is amoebic until proven otherwise, and it responds to drugs rather than requiring drainage.

Toxoplasma — from cat faeces and undercooked meat. Harmless in health, serious in pregnancy (Chapter 4.6) and in immunosuppression, where it reactivates in the brain.

Trypanosoma — sleeping sickness in Africa, Chagas disease in South America. Chagas causes heart failure and gut dilation decades after infection, and it is now found worldwide through migration.

Leishmania — from sandflies. Disfiguring skin ulcers, or a fatal visceral form.

Helminths (worms)

And these infect over a billion people, overwhelmingly in low-income settings.

Soil-transmitted helminths — roundworm, whipworm, hookworm.

Hookworm deserves specific mention. The larvae penetrate skin — typically bare feet — migrate to the lungs, are coughed up and swallowed, and attach to the small intestine, where they feed on blood.

The result is chronic iron deficiency anaemia, and in children it causes impaired growth and cognitive development. It is a leading cause of anaemia worldwide and it is cured by a tablet costing a few pence.

Schistosomiasis — from freshwater snails, affecting around 200 million people. The worms live in blood vessels and their eggs cause chronic inflammation — bladder cancer in one form, liver fibrosis in another.

Filariasis — mosquito-borne worms lodging in lymphatics, causing elephantiasis (Chapter 7.8).

Onchocerciasis (river blindness) — from blackflies.

Tapeworms — from undercooked beef, pork or fish. Usually mild in the gut form.

And one serious form: neurocysticercosis. Eating pork tapeworm eggs — from contaminated food or poor hygiene, not from eating pork — leads to larval cysts in the brain. It is the leading cause of adult-onset epilepsy in many low-income countries.

Threadworm (pinworm) — extremely common in children everywhere. Itching around the anus at night. Treated with a single dose for the whole household, repeated after two weeks.

Ectoparasites

Scabies and head lice (Chapter 14.5). Bedbugs, fleas, ticks.

The good news, which is substantial

Mass drug administration is one of the most cost-effective interventions in all of health.

A single annual dose of albendazole or mectizan-class drugs treats several helminths at once, costs a few pence, and is delivered through schools.

And the effects go beyond the infection. Deworming programmes have been associated with improved school attendance, growth and later earnings, though the size of those effects has been genuinely debated in the economics literature.

Elimination is happening. Guinea worm has gone from 3.5 million cases in 1986 to a handful a year — on course to be the second human disease eradicated after smallpox, and achieved almost entirely by water filtration and behaviour change rather than by any drug.

River blindness and lymphatic filariasis have been eliminated from multiple countries.

Trachoma, the leading infectious cause of blindness, is being eliminated country by country through a combination of surgery, antibiotics, face washing and environmental improvement.

Ivermectin's discovery earned William Campbell and Satoshi Ōmura a share of the 2015 Nobel Prize, alongside Tu Youyou for artemisinin (Chapter 3.7). The donation programmes that followed have treated billions of doses free of charge.

These are diseases of poverty rather than of medical difficulty, and the tools to eliminate them largely exist.

What the next page fixes

Chapter 17.4 covers how infection spreads — the chain from source to susceptible host, and where each link can be broken. It is the logic behind every infection control measure you have ever been asked to follow.