Blood and Tissue Flagellates Chapter 5

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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)
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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
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Four Morphological Forms
1. _______________________________
(Leishman-Donovan L-D body) - intracellular
form - ovoid 3 - 4 µm in size -
_____________________________ ___________________
___________
Flagellum Kinetosome Kinetoplast Nucleus
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Four Morphological Forms
2. ______________________________ - elongate
form - 15 - 30 µm long -
____________________________ -
____________________________ ____________________
_________
anterior
Flagellum Kinetosome Kinetoplast Nucleus
posterior
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Four Morphological Forms

• ______________________________
• - elongate form
• - ______________________________
• ______________________________
• - _______________________________
• ______________________________

anterior
Undulating membrane
posterior
Flagellated forms are adapted for movement
through fluids of their hosts.
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Four Morphological Forms

• ______________________________
• - elongate form
• - _______________________________
• ______________________________
• - _______________________________
• ______________________________
• - _______________________________
• ______________________________
• - 10 to 30 µm in length

anterior
Undulating membrane
posterior
Flagellated forms are adapted for movement
through fluids of their hosts.
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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
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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
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Leishmania
Similarities 1. 2. Species are differentiated
by 1. 2. 3. 4. 5.
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Life Cycle of Leishmania spp.
Amastigotes in lesions in skin cartilage of the
ear causing CHICLERO ULCER

• Sandfly bites infected vertebrate (human or
  reservoir host) and _______________
• __________________________________________________
  _______in the blood meal.
• 2. In sandfly midgut, amastigotes transform into
  ______________________________ that multiply by
  binary fission.
• 3. Promastigotes move to esophagus and pharynx
  of sandfly and are inoculated into vertebrate
  when sandfly takes another blood meal.

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Life Cycle of Leishmania spp.
Amastigotes in lesions in skin cartilage of the
ear causing CHICLERO ULCER

• 4. In human, promastigotes transform into
  ___________________________________ that are then
  ___________________________________
• Instead of being killed by the macrophage, the
  _____________________________ ____________________
  ____________________ and multiply by binary
  fission.
• 6. Amastigotes rupture out of macrophage,
  destroying it, and are phagocytized by new
  macrophages. Cycle is repeated for many
  generations.

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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
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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.  
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Leishmania tropica and Leishmania major pathology

• 1. L. tropica and L. major are parasites in the
  _____________ of humans
• Promastigotes are inoculated into the skin
  during a sandfly bite and transform into
  amastigotes which are engulfed by skin
  macrophages.
• These skin cells are eventually destroyed by
  the multiplying amastigotes which then invade new
  macrophages, repeating to produce a
  __________________
• _____________________________________
• other regions involved?

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Leishmania tropica Leishmania major pathology
L. major lesion bleeds quickly and is of short
duration.
L. tropica lesion is dry

and persists for months. In both
species, the lesion eventually dries up to
produce a depressed, depigmented
scar. Immunity?  
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Leishmania tropica pathology

• 2. Recent finding of a mild "viscerotropic"
  form of L. tropica during Desert
  Storm in 1991 in Middle East
• - pathology? ____________________________________
  __
• _________________________________________________
• it is a mild disease but little else is known of
  its pathology
• difficult to diagnose because there are no skin
  leasions
• - only 12 cases reported in U.S. personnel 

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Leishmania tropica and Leishmania major

• DIAGNOSIS - _____________________________________
  in skin scrapings from edge of the lesion.
• Skin smear is stained with Wright or Giemsa
  blood stain.
• TREATMENT - Antimony compound called Pentostam
• (sodium stibogluconate) is given intravenously.
• Done only when lesion is on exposed body region
  where
  it may cause disfigurement.
• Treatment not necessary due
  
  to complete natural immunity
  
  after one exposure.

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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.
Soldier in Afghanistan with Leishmania tropica on
hand
Officer holding Iraqi child with Leishmania
tropica on face
A soldier with hundreds of sandfly bites received
in one night.
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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
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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  
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Leishmania mexicana
PATHOLOGY 1. 2. If sandfly bites the
________________, amastigotes cause
__________________________________________________
_______________________________. Ear lesions
may last for many years.
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Leishmania mexicana
DIAGNOSIS AND TREATMENT Identify
______________________ in smears from
____________________________. ____________________
_________are used to treat skin sores
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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 - ______________________
________________
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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.
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Leishmania braziliensis pathology

• Amastigotes metastasize and spread from the skin
  lesion to the_____________________________________
  _______
• - secondary lesion involves the
  _________________________________________________
•  

- amastigotes are thought to be carried in
bloodstream but little known how metastasis occurs
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  - 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 ______________________________________
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Leishmania braziliensis pathology

• DIAGNOSIS AND TREATMENT - identify
  ___________________________ in
  smears from lesion.
• Antimony compounds are used to treat skin sores,
  but are not as effective against mucocutaneous
  lesions.
• 2. New oral drug Miltefosine (Impavido) -
  Recent studies from Boliva show a high cure rate
  for mucocutaneous leishmaniasis .
• Vaccine? ________________________________________
  ______

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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.


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Leishmania donovani

• DISTRIBUTION - Mediterranean coast, Middle East,
  India Pakistan into China. Also found in parts
  of Central and South America.
• Of major concern during Desert Storm in Middle
  East in 1990-91 but few cases have been reported
  in US soldiers
• Concern now? ____________________________________
  ____

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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.
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Leishmania donovani

• PATHOLOGY
• 1.
• 2. Promastigotes inoculated into human skin
  transform into _________________ that are
  phagocytized by _____________________________
• Amastigotes multiply in macrophage, eventually
  rupturing the cell
• Free amastigotes then invade the circulatory
  system.

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• 3. Invasion of __________________________________
  __________
• Free amastigotes in bloodstream are phagocytized
  by cells of the reticulo-endothelial system (RE
  system). These cells are then destroyed by the
  multiplying amastigotes.
• RE system is a system of phagocytic cells in the
  __________________________________________________
  ________ which cleanses foreign materials from
  the bloodstream and provides natural immunity to
  many diseases.
• Destruction of cells of the RE system by the
  amastigotes results in____________________________
  _____to many diseases and death by secondary
  infections.

RE cell Rbc liver cell RE cell
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Leishmania donovani
Symptoms - _____________________________________
(if bone marrow invaded), and ____________________
________________ - death occurs in 6 to 12 mo.
after infection in untreated cases (75-95
mortality rate)
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Leishmania donovani
4. A secondary condition called
_________________________________ ________________
_________________ commonly occurs in
India. Involves formation of reddish skin
nodules on the face. Cause?
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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
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Prevention for all species of Leishmania
1. 2. 3.
4.  
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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.  
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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.
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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.

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SECTION SALIVARIA - Trypanosoma brucei
Identified by ___________________________________.
He also identified the __________________________
___________

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SECTION SALIVARIA - Trypanosoma brucei
All utilize the _________________________________a
s the vector. ID by ___________________________
______ in wing.

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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 _______________________________________
___________ 
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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
_________________________________ ________________
_________________
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Trypanosoma brucei brucei

• Causative agent of a disease called
  _______________________________ in Africa
• Trypomastigotes are parasitic in the bloodstream
  of __________________ ____________________________
  _______________________________
•  parasites cause little pathology in these hosts
  indicating a long term host-parasite association
• Trypomastigotes also infect ___________
  
  ______________________(sheep, goats,
  cattle,
  horses, pigs, and dogs may also
  be
  infected but cattle most important)

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Trypanosoma brucei brucei
Pathology is severe ___________________________
occur in bloodstream and cerebrospinal
fluid cattle become emaciated and
uncoordinated cattle
die in a few weeks
to months

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Trypanosoma brucei brucei

• Although the parasite ____________________________
  _____________________, it makes 4.5 million
  square miles of central Africa an area where it
  is impractical to have domestic animals
• this region is called the tsetse fly belt
• nagana is associated with _____________________
  _____________________, as source of nutrition
  (milk, beef) and beasts of burden
  cannot survive
•  

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Trypanosoma brucei brucei
Diagnosis ID _________________________ in cow
blood smear Treatment drugs are available but
these are expensive Most common one used is
Berenil
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Trypanosoma brucei gambiense
Infects humans only causing ______________________
______________ ___________________________________
_________________________ VECTOR - Glossina
palpalis RESERVOIR HOSTS? DISTRIBUTION -
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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
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Trypanosoma brucei gambiense

• 2. Trypomastigotes multiply in the
  ______________________ seen in blood 1-2 weeks
  after infection
• Symptoms?
• ID?

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Trypanosoma brucei gambiense

• Trypomastigotes invade the _______________________
  ___________ - cause swelling.
• Symptoms are Winterbottom's sign
• 4. Trypomastigotes invade ________________ and
  initiate the chronic sleeping sickness stage.
• Symptoms -

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Trypanosoma brucei gambiense

• Cause of pathogenesis
•  damage to capillaries of brain called
  _______________________________________
• ______________________________due to
  overproduction of immunoglobulins by host in
  response to the trypomastigotes
• normal physiological processes are disrupted,
  and death may result from ________________________
  ______________
• ________________________________

DIAGNOSIS - identify _____________________ _______
____________________- must be done early in the
infection prognosis is poor once CNS is
involved.
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Trypanosoma brucei gambiense
TREATMENT - a number of drugs are useful most
common used are __________________________________
__________________________ but they have severe
side effects
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Trypanosoma brucei rhodesiense

Causes____________________________________________
___________ ______________________________________
_____________________ HOSTS - ____________________
___________________ - antelope are important
reservoir hosts - disease is a
____________________________ VECTOR - Glossina
morsitans DISTRIBUTION -    
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Trypanosoma brucei rhodesiense

• PATHOLOGY - disease in humans is acute - two
  stages
• 1. ___________________________- small skin sore
  similar to that of gambian infection
• Trypomastigotes quickly multiply in
  ___________________________
• Toxemia due to parasites in bloodstream causes
  rapid weight loss
• Death due to
• DIAGNOSIS AND TREATMENT
• Identify _______________________________________
  _
• Melarsoprol or Suramin useful
• early diagnosis is critical if treatment is to be
  successful.

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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)  
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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.  
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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.?
 
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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  
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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

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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.
.
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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?
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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? _______________________________ _____
__________________________
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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
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Morphology of Trypanosoma cruzi in humans

• Trypomastigote
• Shape?
• important structure?  

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Morphology of Trypanosoma cruzi in humans

____________________ occurs in pockets in
cardiac ganglion cells or autonomic ganglion cells
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Morphology of Trypanosoma cruzi in bugs

__________________________ are the predominant
stage in the reduviid bug. Characteristics of
epimastigote? ____________________________ ______
______________________
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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?

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Pathology of Trypanosoma cruzi

• 3. Chronic phase - occurs in adults
• - _______________________ cause gradual
  destruction of body cells
• - 2 commonly affected areas
•  (1) ________________________
• ___________________________
• apex of heart usually becomes very thin
• impulses into ventricles are affected -
  _______________ _______________________
• death?
•  

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Pathology of Trypanosoma cruzi

• (2)_________________________________
• ___________________________________
• muscle tone and peristalsis is destroyed
• organs increase their diameters
  greatly causing _______________________________
• _______________________________
• victim may not be able to swallow
  and dies from
  starvation
• feces not formed effectively and victim
• death?
•  

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Trypanosoma cruzi

• DIAGNOSIS identify _____________________________
  ________________
• ?, S, or C shape and large kinetoplast are
  diagnostic
• ____________________________________is used to
  diagnose cases in which there are too few
  trypomastigotes in bloodstream. Procedure
  involves feeding an uninfected lab-reared
  reduviid bug on a patient bug is examined for
  epimastigotes in a 10-30 days.
• RECENT CONCERN - _________________________________
  _________
•  

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Trypanosoma cruzi

• TREATMENT - there is no effective treatment
• Why?
• Can anything be done?
• Chronic infection may last for years before
  reaching a fatal climax - Old age security
  is a minor problem in areas where Chagas' disease
  is highly endemic.
•  

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Section Stercoraria - Trypanosoma rangeli

• Common parasite in the bloodstream of
  _____________________________________
• Where? ___________________________________________
  __
• Stage in humans? _________________________________
  ___
• Pathology? _______________________________________
  ___
• Although trypomastigotes are morphologically
  distinct (small kinetoplast) from those of T.
  cruzi, parasite may cause a diagnostic problem in
  the untrained technician.
• Vector? ______________________
• importance?
•  

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Section Stercoraria - Trypanosoma lewisi

Cosmopolitan parasite of _________________________
_ (no other host can be infected) Stage?
__________________________________ Pathology?____
______________________________________ Vector? I
mportance?  
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How are Leishmania and Trypanosoma able to evade
the human immune response?

• Amastigotes of Leishmania spp. and Trypanosoma
  cruzi
• amastigotes live ________________________________
  ___
• Leishmania inside _________________________
• T. cruzi inside _________________________________
  
• the immune system cannot find parasites in these
  cells 
• amastigotes are in danger when free, but
  invade cells to hide
•  

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How are Leishmania and Trypanosoma able to evade
the human immune response?

• Trypomastigotes of Trypanosoma brucei
• trypomastigotes are able to live in the human
  bloodstream where they are in constant contact
  with immune cells.
• they are successful here due to
  __________________________________
  - the production of _________________________
  _________over time.
•  - trypomastigote possesses chemicals on its
  surface coat which are recognized by our immune
  system as __________________________.
• - a primary immune response is initiated and
  __________________________are produced in 7-10
  days to destroy these antigens.

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How are Leishmania and Trypanosoma able to evade
the human immune response?

• Trypomastigotes of Trypanosoma brucei cont
• By the time these antibodies are produced, the
  trypomastigote changes its ______________________
  ____________
• So?
• This cycle is repeated over and over (one
  trypanosome has changed its surface antigens 101
  times in lab.)
• Result?