Chapter 5 — Trypanosomes Flashcards
1
Q
Who are people that have great history with trypanosome-related diseases & which disease (3)?
A
- Carlos Chagas — chagas’ disease
- David Bruce — Africa sleeping sickness
- David Livingston — arsenic (it killed the trypanosome organism, but the side affects would eventually kill them after a couple weeks —> year) and African sleeping sickness
2
Q
What kingdom and phyla is trypanosomes in?
A
- Kingdom Excavata
- Phylum Kinetoplastida
3
Q
What is a kinetoplast?
A
disc shaped, large mass of circular, mitochondrial DNA, visible with the light microscope
- contains many copies of the mitochondrial genome
4
Q
What are the 4 morphological stages in different life cycles?
A
- Trypomastigote
- Epimastigote (insect stage)
- Promastigote (insect stage — has simple flagella)
- amastigote stage
5
Q
What is the agent of chagas’ disease?
A
Trypanosoma cruzi — can get anywhere, common in texas and is expanding range each year (has been found in roanoke)
6
Q
Which 2 genera have insect intermediate hosts?
A
- trypanosoma (the trypanosomes)
- Leishmania
7
Q
What are some characteristics of the family trypanosomatidae?
A
- about 95-98% parasitic
- heterogenous life cycle (requiring at least 2 kinds of host
- Morphological changes during life cycle
8
Q
What are characteristics of the promastigote stage?
A
- vertebrate blood form
- free flagellum
- undulating membrane
9
Q
What are characteristics of the epimastigote form?
A
- insect form
- trypanosoma brucei (african form)
- trypanosoma cruzi
10
Q
What’s are some characteristics about the trypomastigote stage?
A
- vertebrate blood form
- trypanasoma cruzi
- trypanasoma brucei
- free flowing flagellum
- undulating membrane
11
Q
What is the amastigote stage?
A
- vertebrae tissue form
- typanosoma cruzi
-no flagellum
12
Q
What is the reason for the trypomastigote - epimastigoate change in trypanosoma brucei?
A
- adaptation to low (O2), glucose in blood
- in vertebrate blood —> high O2, glucose
- Insect gut —> low O2, glucose
(LOOK AT SLIDE 5)
13
Q
What is the anterior station development?
A
- transmitted by bite
- Trypanosoma brucei
- develops in insect
(look at diagram on slide 6)
14
Q
What is the posterior station development?
A
- transmitted by feces
- trypanosoma cruzi
(look at diagram on slide 6)
15
Q
How does the feces of posterior station get in the blood?
A
they lay their feces on your skin, which is itchy. you then itch your skin allowing the feces to get into the blood stream
16
Q
What are the 3 species of trypanosoma brucei? How can we distinguish between these?
A
- trypanosoma brucei brucei (nagana-only in animals)
- Trypanosoma brucei gambiense (west africa)
- Trypanosoma brucei rhodesiense
- can only distinguish using PCR, looks same under microscope
17
Q
What transmits trypanosoma?
A
- tsetse fly
- the bite hurts —> you will know if you get bight
- only occurs in africa
- highly pathogenic
- in both sexes
- flies are aggressive
18
Q
Can trypanosoma brucei brucei affect grazing animals?
A
yes!
- the native ruminants (bushbuck — no effect)
- domestic cattle — fatal
19
Q
Look at slide 11 for life cycle in the cattle to fly
A
draw out on paper!!!!
20
Q
Do all subspecies of trypanosoma brucei have multiple hosts?
A
no!
21
Q
Know infected and diagnostic stages
A
22
Q
What are the disease mechanisms of Trypanosoma brucei?
A
- invasion of CNS by trypomastigotes
- antibody mediated damage to blood vessels
- body responds but has proliferation of antibodies
23
Q
??
A
- antibody + complement —> parasite lysis
- Fragments stick to endothelium —> lysis of endothelial cells
24
Q
What is perivascular cuffing?
A
inflammation around the brian —- causes seepage of fluid into brain (cerebral edema)
25
What does cerebral edema lead to?
a coma —> death (results in disruption of brain function)
26
What does the severity of the disease depend on? What are some examples of these?
the host species
- antelope —> no disease
- domestic cattle —> death in several days
- dogs & horses —> death in 15 days
27
What is nagana? What species does it affect?
- causes by trypanasomes in animals
- characterized by fever, lethargy, edema
- affects animals
28
How do you control Naga?
- intermediate host (what is it??)
- DDT (chemicals)
- remove brush
- destruction of reservoir hosts
- breed resistant cattle
29
How does the body respond to trypanasomes?
- body can respond well at first
- then the VSG can change its protein outer coat (DNA) and the body can no longer respond
30
What does VSG stand for?
Variable surface glycoprotein
31
How does the parasite avoid host immune response?
1. VSG coat trypomastigote plasma membrane
2. Tsetse fly injects clone (all with same VSG)
3. trypomastigote changes to expression of new VSG when attacked by host antibodies
32
Look at graph on slide 16
getting successive clones with different VSGs
33
What is the bait and switch strategy?
(like putting cheese out to catch a mouse on a trap)
- the organism that enters the body enters the bloodstream in a different form
- it gets the body to go after one form & not the other to distract it
- then the body can not respond
(coaddaptation going on between host and parasite)
34
Is trypanosomiasis increasing or decreasing in Africa?
- increasing in central africa (not multiple hosts though)
35
What is prevalence of a disease?
the number of cases at any given time
36
What is the incidence of a disease?
fresh/new cases —> acute
37
What is the prevalence of trypanosomiasis in Africa?
> 300,000
38
What is the incidence of trypanosomiasis in Africa?
30,000 and increasing
39
What is the pathogenicity of T.b. gambiense (West Africa — riverine)?
CNS involvement in months/years (“sleeping sickness”)
40
What is the resevoir host of T. b. gambiense?
None
41
What is the immediate host of T. b. gambiense?
- Glossina palpalis
- Glossina tachinoides
42
What is the pathogenicity of T.b. rhodesiense (east africa — savannah)?
death in several months (before CNS involvement)
43
What is the resevoir host of T.Bl. rhodesiense?
impala, warthog, domestic animals (pig)
44
What are the immediate hosts of T.b. rhodesiense?
- glossina pallipides
- glossina swvnnertoni
45
Look at slide 20 and know the CDC life cycle in entirely extracellular in human
(both mammalian stages and tsetse fly stages)
- look at slender/thick forms?? (idk mentioned in class)
46
What are symptoms of T.b.gambiense?
- headache
- diarrhea
- nausea
- fever
- chancre (very large — bigger then lyme)
- rash
- lymphadenopathy (Winterbottom’s sign — pic on slide 22)
- progressive wasting
- neurological symptoms: insomnia, depression, mood disorders, mental deterioration, coma
***feeds off of glucose, which is why you are tired and sleepy
47
How is T. b. gambinese diagnosed?
- puncture cerebral spinal fluid
- trypomastigotes in blood, lymph node, aspirate, SDP, new card test
48
What are treatments of T. b. gambinese?
- supra in (can have negative side affects, no longer drug of choice)
- melarsoprol — now drug of choice, affective in areas without resistance. if resistance then eflornithine is used
- drug needs to be administered within 48 hours or the patient will die
(drugs are outdated, toxic, and expensive to use)
49
How to prevent T.b.gambinese?
no chemoprophylaxis or vaccine
50
What is the prevalence of trypanosoma cruzi?
- 16-18+ million cases
- 45,000 deaths per year
51
What causes Chagas’ disease? Where is it?
trypanosoma cruzi
(in central and south america, NOT Africa — starting to increase in the state of texas)
52
What transmits trypanosoma cruzi?
kissing bug (family reduviidae, subfamily triatominae)
- called kissing bug because bites peoples faces
- also called reduviidae bug
- also called triatominae bug
53
How does an infective metacyclic trypomastigotes passed into human through kissing bug?
deposited through posterior station development through feces (enters human in trypomastigote stage)
- look where the different parts of the bacteria is in the kissing bug
54
Where are the different parts of bacteria in kissing bug and in which form?
1. trypomastigote in anterior station
2. epimastigote in mid-gut
3. metacyclic trymastigote in posterior station (sent to human)
55
What is the epidemiology of trypanasoma cruzi?
- victims often live in mud-walled, thatched roofed houses (bugs can come in at night)
- feces deposited on skin by bug (or rains) from roof — traps rubbed into wound or eye
- other (blood, transplacental (enters bloodstream), eating bugs)
- resevoir hosts (dogs, cats, cattle, raccoons, rodents)
*** can help people by giving good roof, education, teaching to not eat bugs
56
What are some resevoir hosts of trypanasoma cruzi?
1. dogs (common in texas)
2. cats
3. cattle
4. raccoons
5. rodents
57
look at lifecycle on slide 28 (more important then other life cycle because its in our country and is spreading — chagas’ disease)(in texas, closest case to us in roanoke)
look at it on power point, weird on goodnotes
- Know infective and diagnostic stages
58
What is the diagnostic stage of trypanasoma cruzi?
the amastigotes in muscle tissue
59
What is a pathological mechanism of amastigotes? (more acute response)
- heart disease
- destroy cells —> esp. cardiac myofibers, motor neurons, etc.
60
Slide 31 — evasion of immune response
61
What is chagoma?
swelling at infection site, called Romana’s sign if at eye
61
How long is the acute stage of Chagas’ disease? What are its symptoms?
- 2-4 months
- Chagoma
- lymphadenopathy (swollen lymph notes)
- hepatosplenomegaly
- fever
- 5% fatality in children’s (most vulnerable)
62
What is the best way to diagnose?
DNA PCR — can look similar to other organisms (cousin) under microscope)
63
What characterizes chronic disease of chaga’s?
- can be 2ish years (acute symptoms can disappear, then chronic stage pops up)
- Immunodiagnosis though Elisa can be used (but trypomastigotes are rare in blood)
-
64
How can a parasite be diagnosed if it is not shown well in blood? What is it called?
- Xenodiagnosis
- take a germ free bug and allow it to bite a person
- if the person has the bacteria, then the big will get it
65
What is the best way to treat Chaga’s?
- Acute: 2 nearly 100% effective drugs given but most acute infections are not detected (only take when necessary because toxic)
- Chronic: no fully effective treatment
- Control: eliminate intermediate hosts, screen the blood
66
What is Leishmania?W
- “white leprosy”
- 3 types (have to use PCR to tell them apart)
- have indistinguishable morphology
- transmitted by sand fly (small)
- have many mammal reservoirs (dogs, rodents)
- Prevalence: 12 million, incidence 2 million/yr
67
What are the three types of Leishmania?
- cutaneous (L. tropics, L.major, L. mexicana)
- mucocutaneous (L. braziliansis — from first chapter ruining septum)
- Visceral (L. donovan i — enters spleen, liver, etc)
68
What is the old/new world sand fly?
- old: Phlebotomus
- new: lutzomyia
69
What is the pathological mechanism?
destruction of macrophages (mf) resultin in tissue damage
70
How does Leishmania evade immune responses?
1. privileged site
2. suppression of intracellular killing by ROI
3. manipulation of TH2 immune response
- if TH2 (antibody) response —> amastigotes survive
- if TH1 response —> mf activation—> amastigotes killed
71
What does the type of disease stand for?
depend on whether amastigotes spread from bite site
72
What is Cutaneous Leishmaniasis?
- stay at bite site
- old world
- Jereco buttons: in Mediterranean, middle east, Africa, India
- Phlebotomus spp. vector
73
What is Leishmaniannis mexicana?
- White Leprosy
- Rising in numbers
- in N, C, and S America
- Vector = Lutzomyia spp.
- Ulcer forms at bite site a few days to several months after, heals spontaneously, leaving a scar
74
What is diffuse cutaneous leishmaniasis?
1. due to defective T cell immunity
2. Responds very poorly to drugs
75
What is Mucocutaneous leishmaniasis (espundia)?
- Amastigotes spread to mouth/nose
- ulcer at initial bite site
- secondary lesions months to years later
- untreated —> massive tissue loss
- grows at cooler temps
76
What is visceral leishmaniasis (kala azar)?
- amastigotes disseminate to internal organs
- advanced forms
- organs targeted: spleen & liver (also bone marrow???)
- mf all over body become infected
77
What are symptoms of visceral leishmaniasis (kala azar)?
- fever
- hepatosplenomegaly
- examine smear for amastigotes
78
What drug can treat leishmaniasis?
- Pentavalent Antimony (periodic element)
1. is very toxic — only for L. brazilians is and L. donovani
2. possible complications: post kalaazar dermal lesions, treatable (unlike DCL)
79
How to control for
New Normal Microbiota Enhancement
1. best method is insecticide spraying
2. end of malaria eradication program in Mediterranean —> resurgence of Leishmaniasis
80
What is an endemic?
The constant amount of a specific disease that is usually present in a geographic location, like a state or county
81
What is an epidemic?
similar to an outbreak, but with a larger number of cases or occurring over a greater area or both
82
What is a pandemic?
disease on multiple continents, or global
83
