1. Blood and Tissue Flagellates – Chapter 5 Phylum Euglenozoa Class Kinetoplasta Order Trypanosomatida The Order Trypanosomatida contains members which are _________________________ - live in blood or fixed tissues of vertebrates at some time in their life cycle. Life cycles involve ___________________________ - represent the original hosts of these parasites. All forms utilize ___________________________ - absorb nutrients from their hosts through the cell membrane (no phagocytosis or cytostomal ingestion)

2. Morphological Characteristics All species possess a_____________________________, _______________________________, & _____________________________ __________________________ – structure that gives rise to the flagellum __________________________ - dense area of mitochondrial DNA that gives rise to a mitochondrion - located just posterior to kinetosome Kinetosome and kinetoplast are very close together – the kinetosome is too small to be resolved – only the kinetoplast is seen

3. Four Morphological Forms 1. _______________________________ (Leishman-Donovan [L-D] body) - intracellular form - ovoid; 3 - 4 µm in size - _____________________________ ______________________________ Flagellum Kinetosome Kinetoplast Nucleus

4. Four Morphological Forms 2. ______________________________ - elongate form - 15 - 30 µm long - ____________________________ - ____________________________ _____________________________ Flagellum Kinetosome Kinetoplast Nucleus anterior posterior

7. Leishmania and Trypanosoma Of the seven genera in the Family Trypanosomatidae, only 2 genera, Leishmania and Trypanosoma , are important parasites of humans. Not all parasites in the family possess all 4 morphological forms: Leishmania spp. - possesses only amastigote & promastigote forms Trypanosoma brucei - has only epimastigote & trypomastigote Trypanosoma cruzi - has all four forms

8. Leishmania Of the 12 species of Leishmania , 5 major recognized species infect humans: Leishmania tropica Leishmania major Leishmania braziliensis - 3 subspecies Leishmania mexicana - 3 subspecies Leishmania donovani - 2 subspecies

12. Leishmania tropica and Leishmania major These two species have similar life cycles and clinical symptoms. Both produce a cutaneous ulcer - disease is called _________________________ or CUTANEOUS LEISHMANIASIS (many other local names as well) DISTRIBUTION: L. tropica - densely populated areas of Middle East & India L. major - sparsely populated regions in Africa, Middle East & SW Asia

13. Leishmania tropica and Leishmania major Both are vectored by Phlebotomus sandflies. Reservoir hosts include ____________________________. Disease is enzootic in these hosts and is capable of being transmitted from these reservoir hosts via sandflies to humans; thus, these parasites are ZOONOSIS.

15. Leishmania tropica & Leishmania major pathology L. tropica lesion is dry and persists for months. In both species, the lesion eventually dries up to produce a depressed, depigmented scar. Immunity? L. major lesion bleeds quickly and is of short duration.

18. Leishmania tropica and Leishmania major Major concern now is that many US soldiers are being exposed to these parasites in Iraq and Afghanistan. Over ____________cases have been reported from 2003-present. A soldier with hundreds of sandfly bites received in one night . Officer holding Iraqi child with Leishmania tropica on face Soldier in Afghanistan with Leishmania tropica on hand

19. Leishmania mexicana Causative agent of ___________________________________ Originally thought to be a subspecies of L. braziliensis , it has recently been recognized as a separate species. DISTRIBUTION – VECTOR - Lutzomyia sandflies

20. Leishmania mexicana RESERVOIR HOSTS - ______________________________ - Is a _______________________________, as these rodents are common source of infection to persons clearing forests or harvesting - Chicle in forests is harvested for use in gum by chicleros who are bitten by sandfly vectors

21. Leishmania mexicana PATHOLOGY: 1. 2. If sandfly bites the ________________, amastigotes cause _________________________________________________________________________________. Ear lesions may last for many years.

22. Leishmania mexicana DIAGNOSIS AND TREATMENT: Identify ______________________ in smears from ____________________________. _____________________________are used to treat skin sores

23. Leishmania braziliensis Causative agent of espundia, uta, or ___________________________ _________________________________. DISTRIBUTION - central Mexico through Central and South America to northern Argentina VECTOR - sandflies in the genus Lutzomyia RESERVOIR HOSTS - ______________________________________

24. Leishmania braziliensis pathology 1. Promastigotes inoculated into ________________transform into amastigotes and enter ___________________________causing a small, ulcerating lesion , at sandfly bit site similar to oriental sore.

26. - mucous membranes and cartilaginous tissues of the lips, nose, palate, and pharynx are destroyed; larynx may also be involved, destroying voice - condition is chronic, lasting for many years - death often results from ______________________________ and ______________________________________

28. Leishmania donovani Causative agent of _____________________________________, or visceral leishmaniasis Identified by William Leishman in 1900 from a soldier who died of fever in Dum-Dum, India. Charles Donovan identified the parasites in the spleen of an infected person in 1903. Parasite is named in honor of these two men. William Boog LEISHMAN (1865-1926) Charles DONOVAN (1863-1915)

30. Leishmania donovani VECTOR - many species of Phlebotomus RESERVOIR HOSTS - ______________________are most common reservoir hosts; thus, it is a __________________ There are often campaigns to eliminate ____________________ in endemic areas.

34. Leishmania donovani 4. A secondary condition called _________________________________ _________________________________ commonly occurs in India. Involves formation of reddish skin nodules on the face. Cause?

35. Leishmania donovani DIAGNOSIS – identify _____________________________ in smear from ______________________ ________________________________ . Such a diagnosis is risky. TREATMENT - injection of________________________________ Drugs are highly toxic; thus, many quit taking the drug or reduce its dosage (develop dermal leishmanoid). Trials underway on new drugs: 1. Antifungal drug amphotericin B 2. Antibiotic paromomycin 3. Anticancer drug meltifosine

36. Prevention for all species of Leishmania 1. 2. 3. 4.

37. Trypanosoma spp. Members of the genus Trypanosoma are parasitic in all classes of vertebrates. Most species are transmitted to the vertebrate via a vector - usually a bloodsucking insect.

38. Trypanosoma spp. Trypanosomes are divided into 2 sections based on where they develop in their vectors: SECTION ______________________________ - parasites develop in the anterior part of the vector's digestive tract (= anterior station development) – parasites are transmitted to vertebrate through vector bite. SECTION _______________________________ - parasites develop in the hindgut of vector (= posterior station development) - parasites are transmitted to vertebrate via vector fecal contamination. Parasites of medical and veterinary importance occur in both sections.

39. SECTION SALIVARIA - Trypanosoma brucei Consists of 3 subspecies - Trypanosoma brucei brucei Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense These subspecies are morphologically identical and have similar life cycles. Differences? They were originally considered as 3 separate species: Trypanosoma brucei brucei represents the ancestral form. T. b. gambiense and T. b. rhodesiense have evolved from it.

40. SECTION SALIVARIA - Trypanosoma brucei Identified by ___________________________________. He also identified the _____________________________________

41. SECTION SALIVARIA - Trypanosoma brucei All utilize the _________________________________as the vector. ID by _________________________________ in wing.

42. Trypanosoma brucei life cycle Only 2 stages in life cycle -________________________ ________________________ 1. Uninfected tsetse fly (Glossina ) bites an infected vertebrate host and ingests ________________________ circulating in the bloodstream. 2. Trypomastigotes multiply by longitudinal binary fission in __________________________________________________

43. Trypanosoma brucei life cycle 3. Trypomastigotes migrate to the salivary glands and transform into ______________________________ and multiply for several generation. 4. Epimastigotes transform back into ______________________ (short stumpy forms) in the salivary glands. These form the ___________________________ . 5. Tsetse fly bites a human or ruminant host and inoculates _______________________________ into bloodstream. 6. Trypomastigotes live and multiply in the ______________________. In some cases, trypomastigotes migrate to the _________________________________ _________________________________

48. Trypanosoma brucei brucei Diagnosis – ID _________________________ in cow blood smear Treatment – drugs are available but these are expensive Most common one used is Berenil

49. Trypanosoma brucei gambiense Infects humans only causing ____________________________________ ____________________________________________________________ VECTOR - Glossina palpalis RESERVOIR HOSTS? DISTRIBUTION -

51. Trypanosoma brucei gambiense PATHOLOGY - produces a chronic disease with four progressive stages 1. ______________________ - skin sore develops at bite site where trypomastigotes are inoculated into bloodstream

55. Trypanosoma brucei gambiense TREATMENT - a number of drugs are useful – most common used are ____________________________________________________________ but they have severe side effects

58. Prevention of Trypanosoma brucei 1. _________________________________________________________ - use of DDT and other insecticides - use of male sterile techniques (discussed in movie) - clearing of bushes in grasslands - adult flies release their larvae from these bushes & larvae develop in shady soil beneath the bushes 2. ________________________________________________________ - not too popular among conservationists - not effective in T. b. gambiense infections 3. ____________________________________________________ (important in T. b. gambiense infections)

59. SECTION STERCORARIA – Trypanosoma cruzi Causative agent of _____________________________________ ____________________________________________________ Disease is named after ____________________________, a Brazilian who discovered T. cruzi in cone-nosed bugs in 1910. It was not until the early 1930's that the parasite was shown to cause a human disease.

60. Trypanosoma cruzi distribution Distribution – - infects over 15 million people (35 million are exposed) - disease is highly prevalent in Brazil; 30% of deaths are attributable to Chagas' disease - in U.S.?

61. Trypanosoma cruzi VECTOR - ____________________________ order Hemiptera – family Reduviidae (Text, chapter 37) - genera Triatoma, Panstrongylus, and Rhodnius - common names: cone-nosed bug, assassin bug, kissing bug, vinchuca - adobe huts – - control

62. Trypanosoma cruzi RESERVOIR HOSTS - __________________________ are important reservoir hosts in Central and South America - disease is a _______________________ - In the U.S. _____________________________ _________________________________________are infected in the southern states - recent identifications in mammals as far north as Indiana and Maryland are of concern that disease is moving northward

63. Trypanosoma cruzi life cycle . All 4 morphological forms exist: 1. Reduviid bug feeds on infected human (or reservoir host) and ingests _______________________ in blood meal. 2. In the midgut of the bug, trypomastigotes transform into _____________________________ that multiply by longitudinal binary fission. Epimastigotes are the predominant stage in bugs.

64. Trypanosoma cruzi life cycle 3. Epimastigotes migrate into the bug's hindgut and transform into ______________________________ 4. Trypomastigotes are passed in the _____________________________ (posterior station) and are infective to humans. How do they enter?

65. Trypanosoma cruzi life cycle 5. Trypomastigotes in human leave the bloodstream and transform into ______________________________ 6. Amastigotes multiply and eventually attack other cells - preference for what cells? _______________________________ _______________________________

66. Trypanosoma cruzi life cycle 7. Some amastigotes ruptured from cells transform into ___________________________ and ___________________________ in the tissue fluid 8. These then become ___________________________ as they enter the peripheral bloodstream where they are available to the biting bug

68. Morphology of Trypanosoma cruzi in humans ____________________ – occurs in pockets in cardiac ganglion cells or autonomic ganglion cells

69. Morphology of Trypanosoma cruzi in bugs __________________________ are the predominant stage in the reduviid bug. Characteristics of epimastigote? ____________________________ ____________________________

70. Pathology of Trypanosoma cruzi 1. Inoculation of trypomastigotes into human: (1) ______________________________ - inflammation of lymph nodes in region of bite (2) ______________________________ - swelling (edema) of eye if bug feces are rubbed into eye 2. Acute phase - occurs in children (age 5 or less) - amastigotes quickly invade many body cells including the ____________________________ where they cause destruction of _____________________________ (abnormal EKG's are common) - death?