Parasitic Protozoa

Foodborne transmission:

undercooked meat, contaminated food by knives, cutting boards, …, drinking unpasteurized goat milk

Animal-to-Human (Zoonotic) transmission:

cats shed millions of cysts —> ingestion after cleaning cat’s litter box, gardening, unwashed fruits, contaminated water

Mother-to-Child (Congenital) transmission:

newly infected mother during / just before pregnancy

Rare transmisions —> organ transplant, blood transfusion

—> Apicomplexa

cyst-forming coccidia

high-prevalence in industrialzed countries

infecting worm-blooded animals

definite/final host: cat-like animals (house cat, wild cat, lynx, lions, …)

• infection in later pregnancy

• pre-existing immunity

sporozoites / bradyzoites infect human

1. parasites invade subepithelial cells + asexual multiplication

2. tachyzoites disseminated via blood

3. mulitplication of tachyzoites slows down (immune pressure)

4. bradyzoites develop

5. parasitophorus wall remodels into cyst wall

people get immunosuppression (AIDS) —> tachyzoites reactivate —> cause severe loacal inflammation (1 of 5 AIDS patients)

1 of 3 main groups of Parasitic Protozoa (Flagellates, Amoebae)

unicellular and spore-forming

unique form of organelle

1. Sporozoite

2. Schizogeny (asexual cycle): Trophozoite -> Schizont -> Merozoite -> Trophozoite …

3. Gamogeny (sexual): male / female Gametocyte

4. Sporogony (asexual): diploid Zygote -> Sporont -> Sporoblast

5. —-> 1.

Plasmodium falciparum (most common)

majority of fatal cases, in (sub)tropical regions

Plasmodium vivax (most common)

most widespread outside Africa, less severe than P. falciparum

—> known for ability to form dormant liver stages

Plasmodium malariae —> chronic, low-level infection

Plasmodium ovale —> less common

Plasmodium knowlesi —> primarly infects monkeys

• Liver parenchymal cells (Hepatocytes)

• Red Blood Cells (Erythrocytes)

• (other blood cells)

Cytoadherence (CA)

infected red blood cells (iRBCs) can adhere to entothelial cells lining blood vessels —> infected cells dont circulate in bloodstream —> dont reach spleen —> no destruction of infected erythrocytes in spleen

in animals: CA stronger in immunoreactive animals

why? TNF-a activates enothelial cells —> upregulates number of receptors —> increasing adherence

Ring - Trophozoites - Schozont - Gametocyte (f/m)

ring stage is very common feature for diagnostics

requiring two hosts

definite host —> mosquitoes (sex occurs)

intermediate host —> vertebrates (asexual amplification)

Parasitic Protozoa - Flagellates

smiling parasite :)

found in humans, and animals (cows, dogs, cats, …)

in environments like kennels(Zwinger), pet shops, animal shelters

—> 3rd most common cause of diarrhea

infectious cysts —> dormant stage, resistant

persist in environment

contains 4 nuclei, no flagella

swimming trophozoites with flagellates —> active, motile stage

contains 2 nuclei, 4 paris of flagella

replicate via binary fission

attaches to intestinal environment (cannot survive outside host)

Excystation = cyst —> trophozoite

Encystation = trophozoite —> cyst form

1. breach mucus layer (biochemical barrier)

2. attach to microvilli through

   • suction-based mechanism (with flagella movement + adhesive disk)

   • variety of chemical bonds (variant surface proteins VSPs)

Surface Antigen Variation —> alter expression of surface antigens

Immunomodulation —> can interfere with normal functioning of immune cells

Protease Activity —> produce preoteases that can degrade host antibodies

Secretion of immunomodulatory molecules —> may interfere with production + function of antibodies

4 pairs —> only in Trophozoites

Anterior Flagella —> long, on front end —> motililty and swimming

Posterior/Lateral F. —> shorter, on side —> stability, orientation

Caudal Flagella —> in tail region —> mainting position, movement

Ventral Flagella —> belly side —> undulating (wellenartig) movement —> propels

1. Trophotzoite in vaginal / prostratic secretions and urine

2. multiplies by binary fission

3. Trophozoite in vagina or orifice (Öffnung) of urethra

—> starts from beginning

human is only known host!!!

• freshley voided urine

• postratic secretions

• vaginal wet preparations

unlikely: shared towels, toilet seats, swimming pools

often carries Mycoplasma and Trichomonasvirus spp

Promastigote form in arthropode host (sandfly)

Amastigote form in vertebrate host (human)

1. Promastigote stage invades human cells (macrophages)

2. Promastigoes develop into amastigote form

3. multiplication of amastigotes

4. release

5. in insect gut: amastigote —> promastigote

6. P. attach to forgut cells

7. Metacyclic (infectious) promastigotes develops

8. female bites human

entry mechanism: Phagocytosis:

—> surface protein GP63 binds + activates complimental component of host’s immune system

Macrophages have receptors —> recognize these fragments —> leads to phagocytosis —> weak activation of host immunity

• delay fusion of parasitophorus vaculole with lysosomes

• inhibit phagolysosomal proteases by proton pump

• delay of host cell apoptosis

• suppress toxic oxygten and nitrogen products (o2- to H2O2)

• modulate macrophage cytokine production (IL-IO induction)

• inhibit antigen presentation and T-cell stimulation

Cutaneous Leishmania (skin)

red skin —> inflammatory papules (1-2 weeks) —> lesions enlarge and ulcerate (12 months)

—> healing spontaneous —> PERMANENT IMMUNITY

other:

Visceral Leishmania (Eingeweide)

infection of monocytes/macrophages in entire organism

—> enlargement of liver + spleen

Mucocutaneous Leishmania

ulceration of oral and nasal mucous membranes

untreated —> death, bc of superinfections

Humoral / Th2 response = involves antibodies and is associated with Th2 cells

—> less efficient in clearing parasite

Cellular / Th1 response = driven by interferon gemma (IFng) and mediated by Th1 cells

—> more protective (important in L. infrection)

bite around mouth area or eyes of sleeping humans —> kissing

—> swelling of bite site (2-3 weeks) —> fever, swollen lymph nodes —> brain inflammation

60% acute infection (cure 50-80%)

40% chronic infection (over years)

Chagas disease:

in chronic phase —> cardiac issus —> die of broken heart (biventricular heart failure)

Triatomine bugs (kissing bugs)

1. Triatomine bug takes blood meal —> passes metacyclic trypomastigoes in feces around wound

2. in cells: trypomastigotes —> amastigotes

3. amastigotes multiply (binary fission)

4. amastigotes —> trypomastigotes; burst out cell, enter blood stream

5. Triatomine bug takes trypmastigotes via blood meal

6. Epimastigotes in midgut, multiply

7. metacyclic Trypomastigotes in hindgut

Trypomastigote stage in vertebrates/humans

Epimastigote stage in Arthropod hosts

Promastigote stage in Arthropod hosts

Amastigote stage in vertebrates/humans

flagellum produces waveform —> generates force —> propels tryposome forward in a corkscrew-like manner

molecular mimicry in chagas disease

—> cross-reactive peptides (similar to endogenous peptide)

—> APCs (antigen-presenting cells) recognize them as human peptide —> activation of autoreactive Tcells

—> attacks b-adrenergic receptors in heart muscle —> heart-damage