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

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

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. 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

Resistant Breeds of Cattle

N'Dama are a breed of cattle from West Africa.

T. b. gambiense: Chronic or Gambian Sleeping Sickness

• Occurs in people.

T. b. gambiense: Chronic or Gambian Sleeping Sickness

• Occurs in people.

• Fatal if not treated.

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 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 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

• Causes acute infections in people.

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 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 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 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 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

Biology of Glossina spp.

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.

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

Mystery of Zebra Stripes Solved?

The Vector Glossina

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

The Vector Glossina

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

• Most of these can transmit Trypanosomes.

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).

Glossina spp. have different “host” preference!

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

people.

The G. palpalis group tends to feed on reptiles, and loves to feed on people.

G. morsitans is a savanna species.

G. palpalis is associated with rivers and lakes.

Life Cycle

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

Trypanosoma brucei life cycle

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

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. 

Trypanosoma brucei life cycle3. Trypomastigotes migrate to the salivary glands and transform into epimastigotes and multiply for several generation. 

Trypanosoma brucei life cycle3. 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 cycle3. 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 cycle3. 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 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

• There are four phases.

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

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.

African Trypanosomiasis Course of Infection

• Phase II: Trypomastigotes enter circulation.

– Fever– Headache– Skin rash– Duration is variable

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

Phase III

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 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

African Trypanosomiasis Course of Infection

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

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.

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.

Pathology

1) Parasites themselves are toxic.

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

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.

Variable Antigenic Types

Pathology

3) Host lyses its own erythrocytes (RBCs).

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

So why does this happen?

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.

Treatment • Drug of choice Suramin (Bayer 205)

– Not affected against CNS forms!

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.

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!

Distribution

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

Distribution

• 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!

• No Leishmaniasis in the US!

• No African Trypanosomiasis in the US!

The Big 3 Tropical Fevers To Be Feared!

• (3) Kala-azar

• (2) African Trypanosomiasis

• (1) Malaria

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

Negative Effects of African Trypanosomiasis

• (2) Agriculture

African Land

Negative Effects of African Trypanosomiasis

• (3) Other:– Presence of tsetse flies have affected the

environment.• Pesticides!

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.

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?