1. Schedule of activities

2. RECAP Flagellated protists Trypanosomes Leishmania complex
T. brucei complex
Salivaria, Glossina, Africa
T. cruzi
Stercoraria, Reduviidae, Americas
Leishmania complex
tropical sore-visceral leishmaniasis
Antigenic variation (T. brucei spp),
hiding from host immunity (T. cruzi, Leishmania spp.)
Tissue destruction neurological problems, immune response problems, death
Socio-economical and control issues

3. ANIMAL PHYLOGENY PROTOSTOMIA BILATRERIA ANIMALIA
CHORDATA
HEMICHORDATA
DEUTEROSTOMIA
ECHINODERMATA
ARTHROPODA
TARDIGRADA
ONYCHOPHORA
NEMATODA
ECDYSOZOA
NEMATOMORPHA
PRIAPULIDA
KINORHYNCHA
PROTOSTOMIA
BILATRERIA
ANIMALIA
BRYOZOA
BRACHIOPODA
PHORONIDA
ANNELIDA
LOPHOTROCHOZOA
MOLLUSCA
SIPUNCULIDA
PLATYHELMITHES
PLACOZOA
CNIDARIA
PRE-BILATERIANS
PORIFERA
PROTISTA
MODIFIED FROM Valentine et al., 1999

4. PROTISTA Unicellular, basal eukaryotes Pseudopods Flagella (Cilia)
Apical complex Apicomplexa

6. Contact and boring into host cell
Contact and boring into host cell
rhoptries, micronemes, (dense granules), conoid, polar rings, subpellicular microtubules

10. subpellicular microtubules: singlet microtubules that extend from regularly spaced attachment points on the outer polar ring  Morisette et al. (1997).
polar rings: ring-shaped microtubular structures that presumably act in host cell invasion. 
conoid:  a truncated cone composed of tubulin fibers, located in the center of the polar rings.  The conoid intermittently protrudes beyond the apical end of the microtubules.  Protrusion of the conoid is sensitive to parasite cytoplasmic calcium concentration Hu et al. (2002).

11. microneme: convoluted tubular organelles
microneme: convoluted tubular organelles. Secrete micronemal proteins involved in the recognition of host cell receptors. Redistribution of these receptor-ligand complexes toward the posterior pole of the parasites is presumed to drive parasite gliding motility and host cell penetration.  Carruthers & Sibley (1999); Lovett et al. (2002).  
dense granules: contents are discharged during the invasion of the host cell.  
rhoptry: secretory organelles, emptied out during host cell invasion, and rhoptry proteins are found within the lumen and the membrane of very early stages of the forming of the parasitophorous vacuole Sam-Yellowe et al. (1988).  

13. http://www. impact-malaria

14. CONTINUED DISCOVERY Purification of the conoid/apical complex
Sequence proteins
Inner membrane complex, calcium binding proteins, dynein, MORN (membrane occupation and recognition nexus) protein, centrins

15. thrombospondin-related anonymous protein (TRAP)

17. From Soldati et al (2004) Current Opinion in Cell Biology 16,32-40.

18. How many apicomplexa?

19. Eimeria tenella: parasite of chickens

20. Eimeria tenella: parasite of chickens
Mortality up to 50%.
Signs
Depression.
Ruffled feathers.
Closed eyes.
Inappetance.
Diarrhoea, blood in faeces.
Post-mortem lesions
Petechiae.
Thickening, ecchymoses of caecal mucosa.
Accumulation of varying quantities of blood and caseous necrotic material in the caecum.

21. Cryptosporidium parvum
“projectile diarrhea”

22. Toxoplasma gondii :TOXOPLASMOSIS
Human infection:
A) undercooked infected meat containing Toxoplasma cysts
B) ingested oocyst (fecally contaminated hands or food)
C) organ transplantation or blood transfusion
D) transplacental transmission
The parasites form tissue cysts, most commonly in skeletal muscle, myocardium, and brain; these cysts may remain throughout the life of the host.
Geographic Distribution: Cosmopolitan.
High prevalence of infection in France has been related to a preference for eating raw or undercooked meat, while high prevalence in Central America has been related to the frequency of stray cats in a climate favoring survival of oocysts. The Netherlands 80-90% prevalence
The overall seroprevalence in the United States 22.5%,
seroprevalence among women of childbearing age (15 to 44 years) of 15%.

23. Toxoplasma gondii in Cats: Fecal Stages Identified as Coccidian Oocysts
J. K. FRENKEL, J. P. Dubey, and N. L. Miller, Department of Pathology and Oncology, University of Kansas School of Medicine, Kansas City 66103
Isospora-type oocysts were excreted by cats following the ingestion of TOXOPLASMA from infected mice. Oocysts appeared 3 to 5 days after cysts were ingested and 8 to 10 days after trophozoites were ingested, and also 21 to 24 days after the administration of infective fecal suspensions from cats. A close quantitative and biologic correlation between oocysts and TOXOPLASMA infectivity of the feces was observed which could not be separated by density gradient centrifugation and filtration methods. TOXOPLASMA is an intestinal coccidian of cats which is fecally spread. It has evolved to multiply in brain and muscle and in other species, making it possible for carnivorism to become another means of transmission.
Science 6 February 1970: Vol no. 3919, pp DOI: /science

26. bradyzoites from tissue cyst OR
sporozoites from mature oocyst
OR tachyzoites from prey
merogeny
tachyzoites
merozoites
tachyzoites
tachyzoites
gametogony
bradyzoites in cyst
Sporogeny
takes several days!

27.
Stages of Toxoplasma gondii. Scale bar in A-D= 20 µm, in E-G = 10 µm. A. Tachyzoites in impression smear of lung. Note crescent-shaped individual tachyzoites (arrows), dividing tachyzoites (arrowheads) compared with size of host red blood cells and leukocytes. Giema stain. B. Tissue cysts in section of muscle. The tissue cyst wall is very thin (arrow) and encloses many tiny bradyzoites (arrowheads). Hematoxylin and eosin stain.
C. Tissue cyst separated from host tissue by homogenization of infected brain. Note tissue cyst wall (arrow) and hundreds of bradyzoites (arrowheads). Unstained. D. Schizont (arrow) with several merozoites (arrowheads) separating from the main mass. Impression smear of infected cat intestine. Giemsa stain. E. A male gamete with two flagella (arrows). Impression smear of infected cat intestine. Giemsa stain. F. Unsporulated oocyst in fecal float of cat feces. Unstained. Note double layered oocyst wall (arrow) enclosing a central undivided mass. G. Sporulated oocyst with a thin oocyst wall (large arrow), 2 sporocysts (arrowheads). Each sporocyst has 4 sporozoites (small arrow) which are not in complete focus. Unstained.

28. Toxoplasmosis Generally an asymptomatic infection in normal adults.
Some (10% to 20%) patients with acute infection may develop cervical lymphadenopathy and/or a flu-like illness.
The clinical course is benign and self-limited; symptoms usually resolve within a few months to a year.
Tissue cysts (containing "bradyzoites" or "hypnozoites") maintain immunity
Cysts can re-activate, if immune status should be compromised (AIDS). The infection is then severe and fulminant, unless treated.
Fulminant is any event or process that occurs suddenly and quickly, and is intense and severe to the point of lethality, i.e., it has an explosive character. Fulminare (Latin): to strike with lightning.

29. Martina Navratilova
Lost US-open 1982
suffered from toxoplasmosis

30. congenital toxoplasmosis
Congenital infection, acquired by transplacental spread of the organism. Profound effects with extensive inflammatory necrotic foci in the brain, which may later calcify.
Death of fetus, hydrocephalus, vision and learning problems later in life.
                                             
Hydrocephalus
Intracranial calcification in cerebral cortex

31. Prevention Immune status (acute, chronic, old infection)
Avoid contact with developed oocysts
Sandboxes, cat litterboxes, dog noses
Avoid raw/undercooked meat that has not been frozen previously
Rinse vegetables

32. Diagnosis
Observation of parasites in patient specimens, such as bronchoalveolar lavage material from immunocompromised patients, or lymph node biopsy.
Isolation of parasites from blood or other body fluids, by intraperitoneal inoculation into mice or tissue culture. 
Detection of parasite genetic material by PCR, especially in detecting congenital infections in utero.
Serologic testing is the routine method of diagnosis, because the techniques described above are technically complex and generally not rewarding.
Treatment: Treatment is not needed for a healthy person who is not pregnant. Symptoms will usually go away within a few weeks.  Treatment (various antibiotics) may be recommended for pregnant women or persons who have weakened immune systems. 

33. JUST AN INFECTION?