Lecture 15: Parasitic Diseases

Unicellular Organism

Eukaryotic- unicellular, usually motile, lack a cell wall- distinct from bacteria (prokaryotes), viruses and prions (acellular)
- drug development for pathogenic protozoa difficult
Complex Life Cycles
- insect and mammalian stages

Reproduction
1. Asexual: mitosis followed by cytokinesis2. Sexual: exchange of of genetic information between protozoa of opposite mating types

- Parasitic Protozoa (ex. Giardia)

1) Cyst: "resting" form of the parasite- parasite enveloped in a cyst wall- Cyst functions: 1. provides protection from changes in environment 2. low metabolic activity 3. allows for transfer from one host to another- Encystation - formation of a cyst- Excystation - escape from the cyst; triggered by return to a favorable environment of by entry into a new host
2) Trophozoite: active, vegetative (capable of growth) form of the parasite

1) Food and water-borne protozoan infections:
- Toxoplasma (tissue cysts in meat)- Entamoeba (cysts in water) -Giardia (cysts in water)
2) Vector-borne protozoan infections:- Plasmodium (mosquito)- T.brucei (tsetse fly)- T.cruzi (triatomine "kissing" bug)- Leishmania (sand fly)
3) Sexually transmitted protozoan infections:- Trichomonas

1) Kinetoplastids: a group of single-cell flagellate protozoa- Leishmania spp.- Trypanosoma brucei- Trypanosoma cruzi
2) Apicomplexans: an apical complex structure- cryptosporidium- toxoplasma- plasmodium

3) Others:- Trichomonas- Entamoeba- GIARDIA

- intestinal disease caused by G. intestinalis- found worldwide- most common cause of waterborne diarrheal illness in the US (30,000 cases annually)- Transmission: 1. Cyst-contaminated water 2. Numerous animal reservoirs 3. Aysmptomatic human carriers (and shedders) are common: ~7% population

- "traveler's diarrhea"- causes intestinal disease in humans and animals. - cysts cause infection then differentiate into trophozoites- trophozoites attach to intestinal epithelium of the small intestine and interfere with nutrient absorption
Pathology: villus atrophy and crypt hyperplasia Protective host immunity?- Giardia undergoes antigenic variation - the mechanism which infectious organism alters its surface proteins in order to evade a host immune response - Immunity is genetic

Clinical manifestations:1. acute giardiasis - severe diarrhea, epigastric pain, cramps2. chronic gastritis - intermittent diarrhea with periodic appearance and remission of symptoms
Prevention, treatment, and control:- Avoid contaminated water- use filters, boiling, or iodine to treat drinking water- antiprotozoal agents can be used to treat infection

- blood infections caused by flagellated protozoa (also called kinetoplastids): - Leishmania spp. - Trypanosoma spp.- Complex life cycle involves vertebrate (often mammalian) and invertebrate (insect) hosts- Transmitted by bites of infected arthropods (arachnids, crustaceans, insects etc- infect blood and tissues of humans

Kinetoplast - specialized DNA-containing organelle located in the mitochondrion of a kinetoplastids. It contains catenated kDNA circles(looks like chain-linked DNA within that site) the encode proteins involved in mitochondrial energy production.
- catenated kDNA circle: this is one aspect of these parasites that is distinct from us, can be used as a potential target for drugs

Promastigote: often refers to insect stage
Amastigote: often refers to intracellular life cycle in the mammalian host

- Leishmania: flagellated protozoa- Cause different forms of human leismaniasis: cutaneous (skin) and visceral (internal organs)- Transmitted by sand flies when they take a blood meal; primary reservoirs are canines and rodents;sand flies transmit disease from animals to humans and from humans to humans
- sand flies are ~1/3 the size of mosquitoes- during feeding, sand flies introduce parasites into the skin- parasites are taken up by macrophages, where they replicate and spread

- Cutaneous/ Skin form (most common): 1. Mucocutaneous: lesion of mouth, nose, throat, and skin that cause extensive scarring and disfigurement. Destruction of nasal septum and causes deformity in nose and lip 2. Diffuse Cutaneous: papules at each inoculation site develop into crustated ulcers; healing occurs with scarring
- Visceral form: - infected marcrophages lodge in body tissues, lyse, and amastigote release continues the infection - results in organ and tissue damage -cause fever and enlarged spleen or liver