Trypanosomes

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Trypanosomes

• We will discuss two groups.
• African group (transmitted by tsetse flies
  belonging to the genus Glossina)
• New World (transmitted by bugs)

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African Sleeping Sickness

• The Trypanosoma brucei group.
• T. brucei brucei
• T. brucei gambiense
• T. brucei rhodesiense

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T. b. brucei

• Occurs in the circulatory system of most native
  antelopes, ruminants, and other wildlife in
  Africa.

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T. b. brucei

• Occurs in the circulatory system of most native
  antelopes, ruminants, and other wildlife in
  Africa.
• Non-pathogenic to these animals (does not kill
  them!).

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T. b. brucei

• Occurs in the circulatory system of most native
  antelopes, ruminants, and other wildlife in
  Africa.
• Non-pathogenic to these animals (does not kill
  them!).
• However, it is fatal to introduced livestock like
  cattle, causing a wasting disease called Nagana.

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Nagana caused by T. b. brucei
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Resistant Breeds of Cattle
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T. b. gambiense Chronic or Gambian Sleeping
Sickness

• Occurs in people.

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T. b. gambiense Chronic or Gambian Sleeping
Sickness

• Occurs in people.
• Fatal if not treated.

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T. b. gambiense Chronic or Gambian Sleeping
Sickness

• Occurs in people.
• Fatal if not treated.
• Chronic infections (low-level infection that last
  a long time).

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T. b. gambiense Chronic or Gambian Sleeping
Sickness

• Occurs in people.
• Fatal if not treated.
• Chronic infections (low-level infection that last
  a long time).
• Does not occur in either native animals or
  livestock.

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T. b. gambiense Chronic or Gambian Sleeping
Sickness

• Occurs in people.
• Fatal if not treated.
• Chronic infections (low-level infection that last
  a long time).
• Does not occur in either native animals or
  livestock.
• It is transmitted from person to person by the
  Tsetse fly.

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T. b. rhodesiense Acute or Rhodesian Sleeping
Sickness

• Causes acute infections in people.

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T. b. rhodesiense Acute or Rhodesian Sleeping
Sickness

• Causes acute infections in people.
• Usually fatal within a year.

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T. b. rhodesiense Acute or Rhodesian Sleeping
Sickness

• Causes acute infections in people.
• Usually fatal within a year.
• Occurs in native animals but it is not fatal in
  these animals.

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T. b. rhodesiense Acute or Rhodesian Sleeping
Sickness

• Causes acute infections in people.
• Usually fatal within a year.
• Occurs in native animals but it is not fatal in
  these animals.
• Transmission by Tsetse fly.

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T. b. rhodesiense Acute or Rhodesian Sleeping
Sickness

• A more recent colonizer of people and therefore
  does not do well in people and kills them.

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T. b. rhodesiense Acute or Rhodesian Sleeping
Sickness

• A more recent colonizer of people and therefore
  does not do well in people and kills them.
• It has not been around long enough to have
  adapted to its host (humans).

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The Vector Glossina
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The Vector Glossina
Biology of Glossina spp.
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The Vector Glossina

• Host seeking behavior
• Visual sense used to search for animal or human
  to feed on.
• Spend most of their time resting on vegetation
  waiting in ambush for their prey to come into
  range.

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Stimulate feeding by uric acid, leucine, valine
and lactic acid (Human Sweat).
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The Vector Glossina

• The genus is divided into 23 species (three
  species groups).

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The Vector Glossina

• The genus is divided into 23 species (three
  species groups).
• Most of these can transmit Trypanosomes.

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The Vector Glossina

• The genus is divided into 23 species (three
  species groups).
• Most of these can transmit Trypanosomes.
• However two species are important in the
  transmission to people, Glossina palpalis (T. b.
  gambiense) and Glossina morsitans (T. b.
  rhodesiense).

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Glossina spp. have different host preference!
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The G. morsitans group tends to feed on suids
(mainly warthogs), and bovids (buffalo), less so
on people.
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The G. palpalis group tends to feed on reptiles,
and loves to feed on people.
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G. morsitans is a savanna species.
G. palpalis is associated with rivers and lakes.
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Life Cycle

• Only 2 stages in life cycle Epimastigote and
  Trypomastigote.

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Trypanosoma brucei life cycle
  1. Uninfected tsetse fly (Glossina) bites an
infected vertebrate host and ingests
trypomastigote circulating in the bloodstream.  
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Trypanosoma brucei life cycle
  1. Uninfected tsetse fly (Glossina) bites an
infected vertebrate host and ingests
trypomastigote circulating in the
bloodstream.   2. Trypomastigotes multiply by
longitudinal binary fission in fly gut. 
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Trypanosoma brucei life cycle
3. Trypomastigotes migrate to the salivary
glands and transform into epimastigotes and
multiply for several generation.  
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Trypanosoma brucei life cycle
3. Trypomastigotes migrate to the salivary
glands and transform into epimastigotes and
multiply for several generation.   4.
Epimastigotes transform back into Metacyclic
Trypomastigotes (short stumpy forms) in the
salivary glands. These form the infective
stage.
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Trypanosoma brucei life cycle
3. Trypomastigotes migrate to the salivary
glands and transform into epimastigotes and
multiply for several generation.   4.
Epimastigotes transform back into Metacyclic
Trypomastigotes (short stumpy forms) in the
salivary glands. These form the infective
stage. 5. Tsetse fly bites a human or ruminant
host and inoculates metacyclic trypomastigotes
into bloodstream.
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Trypanosoma brucei life cycle
3. Trypomastigotes migrate to the salivary
glands and transform into epimastigotes and
multiply for several generation.   4.
Epimastigotes transform back into Metacyclic
Trypomastigotes (short stumpy forms) in the
salivary glands. These form the infective
stage. 5. Tsetse fly bites a human or ruminant
host and inoculates metacyclic trypomastigotes
into bloodstream. 6. Trypomastigotes live and
multiply in the blood and lymph. In some cases,
trypomastigotes migrate to the central nervous
system.
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Trypanosoma brucei life cycle

• For our purposes we will consider only two life
  cycle stages trypomastigotes in vertebrate host
  and epimastigote in Glossina which will be
  transmitted anterior station or salivarian
  transmission to the vertebrate host.

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African Trypanosomiasis Course of Infection

• There are four phases.
• The first two phases of trypanosomiasis only show
  up in people of non-African decent (Europeans).

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African Trypanosomiasis Course of Infection

• Phase I Incubation Period.
• Trypomastigote in skin.
• Red lesion and chancre at site of bite, painful.
• Itching and inflammation of skin.
• Duration one to two weeks.

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African Trypanosomiasis Course of Infection

• Phase II Trypomastigotes enter circulation.
• Fever
• Headache
• Skin rash
• Duration is variable

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African Trypanosomiasis Course of Infection

• Phase III Trypomastigotes collect in lymph nodes
  and channels.
• Cells not invaded but there is proliferation of
  endothelial cells
• Infiltration of leukocytes
• Enlargement of lymph nodes

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Phase III
Enlargement of lymph nodes in cervical triangle
(on back of neck) Winterbottoms Sign one of the
cardinal signs of African Trypanosomiasis.
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African Trypanosomiasis Course of Infection

• Phase III Trypomastigotes collect in lymph nodes
  and channels.
• Fever, headache, and delayed sensation to pain
• General weakness
• Duration many years with T. b. gambiense less
  than 1 year and usually less than 4 mo for T. b.
  rhodesiense

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African Trypanosomiasis Course of Infection

• Phase IV Invasion of Central Nervous
  System-African Sleeping Sickness.

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African Trypanosomiasis Course of Infection

• Phase IV Invasion of Central Nervous
  System-African Sleeping Sickness.
• Headaches are severe
• Emaciation
• Mental dullness
• Apathy disinclination to work
• Drowsiness and coma
• Death from asthenia, heart failure, meningitis,
  severe fall, etc.

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African Trypanosomiasis Course of Infection

• Phase IV Invasion of Central Nervous
  System-African Sleeping Sickness.
• Duration variable with T. b. gambiense usually
  does not occur with T. b. rhodesiense.

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Pathology

• 1) Parasites themselves are toxic.
• -Their byproducts are toxic and end up
  circulating in the blood steam.

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Pathology

• 1) Parasites themselves are toxic.
• -Their byproducts are toxic and end up
  circulating in the blood steam.
• 2) Hyper stimulated immune system.
• -Parasite has variable antigenic types (VATs)
  which are constantly changing.
• -This compromises our immune system, and those
  infected can be susceptible to other bacteria
  and virus infections.

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Pathology

• 3) Host lyses its own erythrocytes (RBCs).
• -This is why anemia is a symptom of this
  disease.
• So why does this happen?

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Diagnosis

• Can find Trypanosomes in plasma.
• Concentrated in lymph nodes.
• Treatment differs if there has been invasion of
  CNS
• If questionable do a lumbar puncture.

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Treatment

• Drug of choice ? Suramin (Bayer 205)
• Not affected against CNS forms!

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Treatment

• Drug of choice ? Suramin (Bayer 205)
• Not affected against CNS forms!
• Melarsoprol (and arsenical toxic) is used with
  Bayer 205 to treat CNS forms.
• Vomiting, and kidney damage.
• 10 of patients will die from treatment.

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Treatment

• Drug of choice ? Suramin (Bayer 205)
• Not affected against CNS forms!
• Melarsoprol (and arsenical toxic) is used with
  Bayer 205 to treat CNS forms.
• Vomiting, and kidney damage.
• 10 of patients will die from treatment.
• Ornidyl (DFMO)? Current drug of choice.
• Tolerated well effective against CNS, but 2 week
  treatment is 150!

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Distribution

• T. b. rhodesiense ? occurs in E. Africa.

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Distribution

• T. b. rhodesiense ? occurs in E. Africa.
• T. b. gambiense ? occurs in costal W. Africa and
  in drainages of Congo and Niger Rivers.

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So What is the Big Deal!

• Few casses of Leishmaniasis in the US!
• No African Trypanosomiasis in the US!

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The Big 3 Tropical Fevers To Be Feared!

• (3) Kala-azar
• (2) African Trypanosomiasis
• (1) Malaria

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Negative Effects of African Trypanosomiasis

• (1) Depopulation
• Uganda 1901-1905.
• 30,000 ? 100,000 due to T. b. rhodesiense
  epidemic.
• Equality of life
• Lack of productivity in society
• Social stability

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Negative Effects of African Trypanosomiasis

• (2) Agriculture

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African Land
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Negative Effects of African Trypanosomiasis

• (3) Other
• Presence of tsetse flies have affected the
  environment.
• Pesticides!

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Negative Effects of African Trypanosomiasis

• (3) Other
• Presence of tsetse flies have affected the
  environment.
• Pesticides!
• Presence of tsetse flies have affected the
  climate.
• Cattle are underweight.
• Many regions have extensive over-grazing.

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Negative Effects of African Trypanosomiasis

• (3) Other
• Presence of tsetse flies have affected the
  environment.
• Pesticides!
• Presence of tsetse flies have affected the
  climate.
• Cattle are underweight.
• Many regions have extensive over-grazing.
• Aesthetics.
• How many wild animals can we live with?

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