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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). African Sleeping Sickness. The Trypanosoma brucei group. T. brucei brucei T. brucei gambiense T. brucei rhodesiense. T. b. brucei.

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Trypanosomes
Trypanosomes

  • We will discuss two groups.

    • African group (transmitted by tsetse flies belonging to the genus Glossina)

    • New World (transmitted by bugs)


African sleeping sickness
African Sleeping Sickness

  • The Trypanosoma brucei group.

    • T. brucei brucei

    • T. brucei gambiense

    • T. brucei rhodesiense


T b brucei
T. b. brucei

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


T b brucei1
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!).


T b brucei2
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.


Nagana caused by t b brucei
Nagana caused by T. b. brucei



T b gambiense chronic or gambian sleeping sickness
T. b. gambiense:Chronic or Gambian Sleeping Sickness

  • Occurs in people.


T b gambiense chronic or gambian sleeping sickness1
T. b. gambiense:Chronic or Gambian Sleeping Sickness

  • Occurs in people.

  • Fatal if not treated.


T b gambiense chronic or gambian sleeping sickness2
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).


T b gambiense chronic or gambian sleeping sickness3
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.


T b gambiense chronic or gambian sleeping sickness4
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.


T b rhodesiense acute or rhodesian sleeping sickness
T. b. rhodesiense: Acute or Rhodesian Sleeping Sickness

  • Causes acute infections in people.


T b rhodesiense acute or rhodesian sleeping sickness1
T. b. rhodesiense: Acute or Rhodesian Sleeping Sickness

  • Causes acute infections in people.

  • Usually fatal within a year.


T b rhodesiense acute or rhodesian sleeping sickness2
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.


T b rhodesiense acute or rhodesian sleeping sickness3
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.


T b rhodesiense acute or rhodesian sleeping sickness4
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.


T b rhodesiense acute or rhodesian sleeping sickness5
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).


The vector glossina
The Vector Glossina


The vector glossina1
The Vector Glossina

Biology of Glossina spp.


The vector glossina2
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.



The vector glossina3
The Vector acid (Human Sweat).Glossina

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


The vector glossina4
The Vector acid (Human Sweat).Glossina

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

  • Most of these can transmit Trypanosomes.


The vector glossina5
The Vector acid (Human Sweat).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).


Glossina acid (Human Sweat). spp. have different “host” preference!


The acid (Human Sweat).G. morsitans group tends to feed on suids (mainly warthogs), and bovids (buffalo), less so on people.


The acid (Human Sweat).G. palpalis group tends to feed on reptiles, and loves to feed on people.


G. morsitans acid (Human Sweat). is a savanna species.

G. palpalis is associated with rivers and lakes.


Life cycle
Life Cycle acid (Human Sweat).

  • Only 2 stages in life cycle – Epimastigote and Trypomastigote.


Trypanosoma brucei life cycle
Trypanosoma brucei acid (Human Sweat).life cycle

1. Uninfected tsetse fly (Glossina) bites an infected vertebrate host and ingests trypomastigote circulating in the bloodstream.


Trypanosoma brucei life cycle1
Trypanosoma brucei acid (Human Sweat).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. 


Trypanosoma brucei life cycle2
Trypanosoma brucei acid (Human Sweat).life cycle

3. Trypomastigotes migrate to the salivary glands and transform into epimastigotes and multiply for several generation.


Trypanosoma brucei life cycle3
Trypanosoma brucei acid (Human Sweat).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.


Trypanosoma brucei life cycle4
Trypanosoma brucei acid (Human Sweat).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.


Trypanosoma brucei life cycle5
Trypanosoma brucei acid (Human Sweat).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.


Trypanosoma brucei life cycle6
Trypanosoma brucei acid (Human Sweat).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.


African trypanosomiasis course of infection
African Trypanosomiasis Course of Infection acid (Human Sweat).

  • There are four phases.

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


African trypanosomiasis course of infection1
African Trypanosomiasis Course of Infection acid (Human Sweat).

  • 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.


African trypanosomiasis course of infection2
African Trypanosomiasis Course of Infection acid (Human Sweat).

  • Phase II: Trypomastigotes enter circulation.

    • Fever

    • Headache

    • Skin rash

    • Duration is variable


African trypanosomiasis course of infection3
African Trypanosomiasis Course of Infection acid (Human Sweat).

  • 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


Phase iii
Phase III acid (Human Sweat).

Enlargement of lymph nodes in cervical triangle (on back of neck) Winterbottom’s Sign one of the cardinal signs of African Trypanosomiasis.


African trypanosomiasis course of infection4
African Trypanosomiasis Course of Infection acid (Human Sweat).

  • 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


African trypanosomiasis course of infection5
African Trypanosomiasis Course of Infection acid (Human Sweat).

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


African trypanosomiasis course of infection6
African Trypanosomiasis Course of Infection acid (Human Sweat).

  • 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.


African trypanosomiasis course of infection7
African Trypanosomiasis Course of Infection acid (Human Sweat).

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

    • Duration variable with T. b. gambiense; usually does not occur with T. b. rhodesiense.


Pathology
Pathology acid (Human Sweat).

1) Parasites themselves are toxic.

-Their byproducts are toxic and end up circulating in the blood steam.


Pathology1
Pathology acid (Human Sweat).

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.


Pathology2
Pathology acid (Human Sweat).

3) Host lyses its own erythrocytes (RBCs).

-This is why anemia is a symptom of this disease.

So why does this happen?


Diagnosis
Diagnosis acid (Human Sweat).

  • Can find Trypanosomes in plasma.

  • Concentrated in lymph nodes.

    • Treatment differs if there has been invasion of CNS

  • If questionable do a lumbar puncture.


Treatment
Treatment acid (Human Sweat).

  • Drug of choice  Suramin (Bayer 205)

    • Not affected against CNS forms!


Treatment1
Treatment acid (Human Sweat).

  • 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.


Treatment2
Treatment acid (Human Sweat).

  • 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!


Distribution
Distribution acid (Human Sweat).

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


Distribution1
Distribution acid (Human Sweat).

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

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


So what is the big deal
So What is the Big Deal! acid (Human Sweat).

  • No Leishmaniasis in the US!

  • No African Trypanosomiasis in the US!


The big 3 tropical fevers to be feared
The Big 3 Tropical Fevers To Be Feared! acid (Human Sweat).

  • (3) Kala-azar

  • (2) African Trypanosomiasis

  • (1) Malaria


Negative effects of african trypanosomiasis
Negative Effects of African Trypanosomiasis acid (Human Sweat).

  • (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


Negative effects of african trypanosomiasis1
Negative Effects of African Trypanosomiasis acid (Human Sweat).

  • (2) Agriculture


African land
African Land acid (Human Sweat).


Negative effects of african trypanosomiasis2
Negative Effects of African Trypanosomiasis acid (Human Sweat).

  • (3) Other:

    • Presence of tsetse flies have affected the environment.

      • Pesticides!


Negative effects of african trypanosomiasis3
Negative Effects of African Trypanosomiasis acid (Human Sweat).

  • (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.


Negative effects of african trypanosomiasis4
Negative Effects of African Trypanosomiasis acid (Human Sweat).

  • (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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