Transcript Document

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