BMS2052 Week 4

LO1 · Parasite (definition)

An OBLIGATE parasite: must live on (ectoparasite) or in (endoparasite) a host in order to sustain life and reproduce.

LO1 · Pathogen (definition)

Can reproduce without a host, in the external environment. Causes disease only after establishing an infection in a host. Most fungi are pathogens.

LO1 · What do parasites and pathogens have in common?

Both establish a PARASITIC relationship with the host: the microbe benefits at the host's expense.

LO1 · Ectoparasite + examples

Lives ON the host. Arthropods: mosquitoes, fleas, ticks, lice. Many act as VECTORS that transmit endoparasites (e.g. mosquito transmits the malaria parasite).

LO1 · Endoparasite + examples

Lives IN the host, extracellularly or intracellularly. Protozoa (e.g. malaria parasite) and helminths (e.g. tapeworms).

LO1 · Definitive host

The host in which SEXUAL reproduction occurs. Generates genetic diversity.

LO1 · Intermediate host

Any other host in the life cycle. Only ASEXUAL reproduction occurs, so no genetic diversity is generated.

LO1 · The 4 eukaryotic kingdoms (and which is polyphyletic)

3 monophyletic (share a common ancestor): Plantae, Fungi, Animalia. 1 polyphyletic (does not): Protista = everything else; taxonomy in constant flux.

LO1 · Kingdom Plantae — identifying features

Multicellular; chloroplasts; cellulose cell walls.

LO1 · Kingdom Fungi — identifying features

Uni- or multicellular; heterotrophic; CHITIN cell walls.

LO1 · Kingdom Animalia — identifying features

Multicellular; heterotrophic; NO cell wall.

LO1 · Which microbes in Protista cause disease?

Protozoa — unicellular, heterotrophic ('first animals'). Algae (photosynthetic) and slime moulds (unicellular amoebae that aggregate into colonial slugs) do not.

LO1 · Which microbes in Fungi cause disease?

Yeasts (unicellular) and moulds (filamentous).

LO1 · Which microbes in Animalia cause disease?

Nematodes (round worms) and platyhelminths (flat worms).

LO1 · Apicomplexans — supergroup, feature, example

SAR clade. Apicoplast — site of fatty acid biosynthesis; a target for antimalarial drugs. Example: Plasmodium spp.

LO1 · Ciliates — supergroup, feature, example

SAR clade. Ciliated, which allows movement. Example: Balantidium coli (the only known ciliate parasite of humans).

LO1 · Kinetoplastids — supergroup, feature, examples

Excavates. Kinetoplast — modified mitochondrion; mitochondrial DNA sits near the basal body of the flagellum to generate energy for movement. Examples: Trypanosoma spp., Leishmania spp.

LO1 · Diplomonads — supergroup, feature, example

Excavates. Mitosomes — reduced mitochondria that do NOT make ATP but do carry out Fe-S cluster synthesis. Example: Giardia duodenalis.

LO1 · Parabasalids — supergroup, feature, example

Excavates. NO mitochondria at all. Example: Trichomonas vaginalis.

LO1 · Entamoebae — supergroup, feature, example

Amoebozoa. Form cysts, allowing survival in the external environment during transmission. Example: Entamoeba histolytica.

LO1 · Nematodes — key features

Round worms. PSEUDOCOELOMATE (body cavity lined by mesoderm and endoderm); round bodies; NOT segmented.

LO1 · Trematodes — key features

Flukes; a platyhelminth. ACOELOMATE (no body cavity); flattened bodies; not segmented; SUCKERS for host tissue attachment.

LO1 · Cestodes — key features

Tapeworms; a platyhelminth. Acoelomate; flattened bodies; SEGMENTED into proglottids (hermaphroditic reproductive units); head region = SCOLEX with hooks and/or suckers.

LO1 · What separates nematodes from platyhelminths?

Body cavity and body shape: nematodes are pseudocoelomate and round; platyhelminths are acoelomate and flattened. Being non-segmented is shared by nematodes AND trematodes, so it does not separate the two phyla.

LO1 · Which fungi are pathogens and which are parasites?

PATHOGENIC: Mucormycetes, Ascomycetes, Basidiomycetes. PARASITIC: Microsporidia — obligate intracellular replication only.

LO1 · Why were Microsporidia reclassified?

Originally thought to be protozoa; reclassified as fungi after chitin was found in the cell wall.

LO1 · Dikaryotic (definition + which phyla)

A cell with 2 genetically distinct nuclei (n then n+n then 2n). Most disease-causing fungi are dikaryotic: Ascomycetes and Basidiomycetes.

LO1 · Steps of the dikaryotic life cycle

1 Start haploid (n), reproducing asexually. 2 Plasmogamy — two haploid cells of different mating types fuse their cytoplasm. 3 Dikaryon formed (n+n). 4 Karyogamy — the two nuclei fuse, giving diploid (2n). 5 Meiosis gives spores, which germinate back to step 1.

LO1 · Ascomycete spores

Sexual: ascospores. Asexual: conidiospores and arthrospores.

LO1 · Basidiomycete spores

Sexual: basidiospores.

LO1 · Dimorphism (definition)

The ability to switch between unicellular YEAST and multicellular MOULD growth morphologies. Usually triggered by temperature change = thermal dimorphism.

LO1 · Thermal dimorphism — the core example

Talaromyces marneffei: mould at 25 degrees C, yeast at 37 degrees C.

LO1 · Which fungi ARE dimorphic?

Malassezia spp. (yeast on skin, hyphal form in infection), Sporothrix schenckii (mould in soil, yeast in body), Cryptococcus neoformans (mould in environment, yeast at body temperature), Talaromyces marneffei.

LO1 · Which fungi are NOT dimorphic?

Trichophyton spp. (septate hyphae then arthrospores), Candida albicans and Candida auris (yeast then PSEUDOhyphal, not true hyphae), Aspergillus spp. (mould/hyphal only).

LO1 · Which infectious stage is most common for fungi?

Spores — asexual (arthrospores, conidiospores) and sexual (ascospores, basidiospores). Yeast cells too, for some.

LO2 · Malaria — immune evasion strategy

Intracellular lifestyle plus sequestration. P. falciparum expresses PfEMP-1 on the surface of infected RBCs, which makes them adhere to vascular endothelium so they avoid being filtered out by the spleen.

LO2 · Consequences of PfEMP-1 expression

Infected RBCs stick to vascular endothelium, blocking capillaries, causing tissue damage and a strong inflammatory response, and never reaching the spleen. Also causes malaria even in people heterozygous for sickle cell.

LO2 · P. falciparum vs P. vivax — what differs

Pf (most virulent): PfEMP-1 adheres to vascular endothelium and blocks capillaries. Pv: does NOT adhere to endothelium; causes SPLENOMEGALY from RBC accumulation in the spleen.

LO2 · African trypanosomiasis — immune evasion strategy

ANTIGENIC VARIATION. By the time the adaptive immune response is mounted, the protozoan's surface antigen has already changed, so the antibodies fail to recognise it.

LO2 · Leishmaniasis — immune evasion strategy

Resists the complement-mediated lysis pathway, and resists macrophage phagocytosis by LIVING INSIDE macrophages (interferes with host immune signalling).

LO2 · Amoebiasis — immune evasion strategy

Phagocytoses immune cells and induces apoptosis.

LO2 · Cryptococcus neoformans — immune evasion strategy

Encapsulated yeast cells survive inside macrophages, and large 'titan cells' are resistant to phagocytosis.

LO2 · Mechanism of fever and chills in malaria

Merozoites replicate in RBCs, producing haemozoin pigment and GPI which build up in the schizont. The schizont ruptures and haemozoin is released into the blood; it is toxic and pro-inflammatory, giving fever and chills in waves roughly every 6-8 hours (the time it takes a merozoite to penetrate a new RBC).

LO2 · Mechanism of anaemia in malaria

Lysis of RBCs, when schizonts mature and release so many merozoites that they can no longer be contained in the RBC.

LO2 · Hypnozoite

The P. vivax dormant liver (hibernation) form. Can reactivate months to years later, which is a problem for travellers returning from P. vivax endemic regions because symptoms are delayed and diagnosis is difficult. P. falciparum does NOT remain dormant.

LO2 · Schistosomiasis — what actually causes the symptoms?

The HOST immune response. Eggs become encapsulated in tissue, provoking a granulomatous immune response, which gives chronic inflammation and organ damage.

LO2 · Where can the malaria liver stage be detected?

Nowhere — the liver stage is NOT detectable. Malaria can only be diagnosed at the blood stage, by blood smear and staining to visualise erythrocytic schizonts.

LO2 · Why is subclinical malaria infection protective in endemic areas?

Repeated infections build a level of immunity. Subclinically infected individuals with a normal immune system have increased immunity which protects them against superinfection.

LO3 · Malaria — transmission, definitive host

Vector-borne by the Anopheles mosquito. The MOSQUITO is the definitive host (site of sexual reproduction), not the human.

LO3 · African trypanosomiasis — transmission, definitive host

Vector-borne by the bite of the Tsetse fly. The Tsetse fly is the definitive host.

LO3 · Leishmaniasis — transmission, definitive host

Vector-borne by the sand fly. The sand fly is the definitive host.

LO3 · Amoebiasis — transmission, definitive host

Oral/faecal route. HUMANS are the definitive host.

LO3 · Ascariasis — transmission

Soil-transmitted helminth (STH): ingestion of embryonated eggs from contaminated soil or food. No intermediate host.

LO3 · Schistosomiasis — transmission and hosts

Found in fresh water; cercariae penetrate the skin barrier directly, NO vector required. Snails are the intermediate host; humans are the definitive host.

LO3 · Taeniasis — transmission and intermediate host

Eating undercooked or raw pork (T. solium) or beef (T. saginata) — faecal-oral route. Intermediate host: pig and cow muscle.

LO3 · Dracunculiasis — transmission and intermediate host

Ingestion of Cyclops water fleas carrying the worm larvae, from unfiltered water. Intermediate host: Cyclops copepods; domestic dogs are also a reservoir.

LO3 · The two different diseases caused by Taenia solium

Eating CYSTS in undercooked pork gives an adult tapeworm in the intestine = taeniasis. Eating T. solium EGGS gives cysts in human tissue = cysticercosis, and neurocysticercosis if in the brain.

LO3 · T. solium vs T. saginata scolex

T. solium (pork tapeworm): 4 suckers PLUS hooks. T. saginata (beef tapeworm): 4 suckers, NO hooks.

LO3 · Malaria — prevention

Bed nets (DEET impregnated), insecticides, insect repellents, long loose fitting clothing, removing stagnant water.

LO3 · African trypanosomiasis — prevention

Bed nets (DEET impregnated), insecticides, insect repellents, long loose fitting clothing.

LO3 · Leishmaniasis — prevention

Avoid dawn and dusk, insecticides, insect repellent, long loose fitting clothing.

LO3 · Amoebiasis — prevention

Sanitation, hand hygiene, water filtration. Note: chemical water treatment is not very effective because the cysts are resistant to many chemicals.

LO3 · Ascariasis — prevention

Sanitation, hand hygiene, avoiding faeces-contaminated soils.

LO3 · Schistosomiasis — prevention

Sanitation, avoid swimming in fresh water, boil water before bathing.

LO3 · Taeniasis — prevention

Sanitation, hand hygiene, fully cooking pork and beef products.

LO3 · Dracunculiasis — prevention

Isolating the patient from water during worm extraction, filtering or chemically treating water before domestic use, portable filter straws for drinking on the go.

LO3 · Malaria — diagnosis

Blood smear plus staining to visualise erythrocytic schizonts. Only diagnosable at the blood stage; the liver stage is not detectable.

LO3 · African trypanosomiasis — diagnosis

Blood smear (differs from malaria in that the parasite does not live inside host cells) and lymph node aspirate.

LO3 · Leishmaniasis — diagnosis

Light microscopy of stained macrophages — from skin in cutaneous disease, from bone marrow in visceral disease.

LO3 · Amoebiasis — diagnosis

Observe cysts in stool samples (4 nuclei); ELISA kits.

LO3 · Ascariasis — diagnosis

Observe eggs in stool samples; X-ray (a bolus of worms in the bowel will not fluoresce).

LO3 · Schistosomiasis — diagnosis

Observe eggs in stool or urine samples (wet mount).

LO3 · Taeniasis — diagnosis

Observe eggs or proglottids in stool samples (wet mount microscopy).

LO3 · Dracunculiasis — diagnosis

Only once the female worm penetrates through the lower extremities.

LO3 · Malaria — treatment

5 classes of antimalarials. Some malaria is highly resistant, some resistance is emerging. Intermittent treatment is given to at-risk groups without screening.

LO3 · African trypanosomiasis — treatment

Must be treated EARLY, before the parasite crosses the blood-brain barrier. Drugs are very toxic because off-target effects are hard to avoid, and different drugs are used for different variants.

LO3 · Leishmaniasis — treatment

Azoles and amphotericin B, depending on species and the local resistance profile. Local injection for cutaneous, IV for visceral.

LO3 · Amoebiasis — treatment

Rehydration for the diarrhoea, plus metronidazole (kills the trophozoite).

LO3 · Helminth treatment in general

Antihelminthics. Ascariasis may also need surgery for bowel obstruction. Schistosomiasis: preventative treatment of school children in endemic areas.

LO3 · Dracunculiasis — treatment

None. The only option is manual extraction of the worm over weeks, which is excruciatingly painful and risks secondary bacterial infection.

LO3 · Which eukaryotic diseases have a vaccine?

Essentially none for humans. Malaria: low efficacy. Taeniasis: a vaccine exists for PIGS only. Trypanosomiasis, leishmaniasis, amoebiasis, ascariasis, schistosomiasis and dracunculiasis: none.

LO3 · Ascariasis — key clinical features

Abdominal swelling, pain, diarrhoea leading to malabsorption and malnourishment (especially in children). Larvae migrate through lungs causing inflammation, cough, breathlessness, fever. Adult worm bolus can obstruct or perforate the bowel, usually the cause of death. Inflammation of spleen and liver.

LO3 · Schistosomiasis — key clinical features

Many subclinical and some asymptomatic. Fever, cough, fatigue, abdominal pain, diarrhoea. Portal hypertension leading to hepatomegaly. Lesions in liver and bladder, depending on where the eggs end up.

LO3 · Taeniasis — key clinical features

Abdominal pain, nausea, diarrhoea (more likely with T. saginata). If T. solium eggs are consumed: cysts in human tissue (cysticercosis) and cysts in brain (neurocysticercosis) — a major cause of epilepsy in impoverished regions, and of blindness.

LO3 · Amoebiasis — key clinical features

Invades the intestinal wall causing bloody diarrhoea and dysentery. Can migrate to cause extra-intestinal abscesses (rare) — liver, then lungs, then brain in order of frequency.

LO3 · African trypanosomiasis — key clinical features

Haemolymphatic stage (parasite confined to blood and lymph): headaches, fever, general malaise, possible hepato-splenomegaly. Then crosses the BBB causing meningoencephalitis: sleep disruption, hallucinations, manic behaviour, anxiety, organ failure, eventual death.

LO3 · Leishmaniasis — cutaneous vs visceral

Cutaneous: a cutaneous lesion at the bite site. Visceral (more severe): fever, malaise, weight loss, swollen lymph nodes, hepato-splenomegaly, anaemia, leukopenia, thrombocytopenia; may be life threatening.

LO3 · Dracunculiasis — status and timeline

Nematode (roundworm), close to eradication. No signs or symptoms until the female worm penetrates the lower extremities roughly a YEAR after ingestion.

LO4 · Superficial vs invasive fungal infection — how common?

Superficial infections are incredibly common. Invasive infections are almost always OPPORTUNISTIC — HIV/AIDS, immunosuppression therapy.

LO4 · Candida albicans — what and why

Causes candidiasis (oral and vaginal thrush). NOT dimorphic: yeast then PSEUDOhyphal growth form associated with disease. Part of normal microbiota of GI tract, urogenital tract and skin. Opportunistic: overgrowth after antibiotics kill the competing microbiota, or in the immunocompromised (infants, HIV/AIDS).

LO4 · Candida auris — why is it the fungal pathogen of most concern?

Not dimorphic (yeast then pseudohyphal); colonises skin without causing disease. Forms biofilms on ventilators, feeding tubes and catheters. Candidaemia in the bloodstream carries a high mortality rate. High resistance to azoles.

LO4 · Aspergillus — what and why

Almost always A. fumigatus, a soil microbe. Inhalation of spores gives an initial respiratory infection then an aspergilloma (masses of hyphae) in the lungs, which is invasive and can disseminate to other organs. Hyphal form associated with disease. Rare, usually only the immunocompromised.

LO4 · Aspergillus — secondary infection context

Occurs as a secondary infection in patients who have had severe viral respiratory illness, including influenza and COVID-19.

LO4 · Aspergillus — where does azole resistance develop?

In the SOIL, from the use of azoles in agriculture; and in the PATIENT, from long-term antifungal therapy.

LO4 · Cryptococcus neoformans — what and why

Dimorphic, found in soil associated with bird droppings: mould in the environment, yeast at body temperature. Inhalation of spores or desiccated yeast cells gives an initial respiratory infection, then disseminates through the blood, crosses the BBB (inside a macrophage) and forms brain abscesses plus cryptococcal meningitis, with roughly 30% mortality.

LO4 · Which invasive fungus also affects immunoCOMPETENT people?

Cryptococcus neoformans — the immunocompromised are most at risk, but it also infects immunocompetent individuals.

LO4 · Visceral leishmaniasis and HIV

Visceral leishmaniasis is an opportunistic manifestation in HIV/AIDS patients.

LO4 · Sporotrichosis in the immunocompromised

More invasive in immunocompromised individuals.

LO4 · Why does cracked skin from a superficial mycosis matter?

It creates a risk of secondary BACTERIAL infection, particularly in individuals who are already immunocompromised (e.g. AIDS). Superficial infections also become more invasive in AIDS.

LO4 · Malassezia — what and why

Part of the normal skin microbiota. Dimorphic: yeast on skin, HYPHAL form associated with infection, with upregulated lipase expression. Lipase breaks sebum fats down into fatty acids which it absorbs and uses.