Transcript Trypanosome

Trypanosomiasis
By Simon Shum and Eric Lee
Facts About Trypanosomiasis
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Trypanosomiasis is caused by a protozoan parasite known as a
trypanosome.
Trypanosomiasis is a lethargic-like sickness in humans - “African
sleeping sickness.”
The transfer of trypanosomes is a result of the bite of tsetse
flies.
Three types of infectious African trypanosomes:
 T. Brucei causes a wasting disease in cattle (Nagana) but
does not infect humans.
 T. Brucei gambiense causes a chronic disease in humans.
 T. Rhodesiense causes an acute disease in humans.
Symptoms
Neurological
damage is
irreversible when
treatment is
delayed until the
second stage.
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Early stage (in blood):
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Recurrent fever
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Headache
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Pain in joints
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Itching
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Second Stage (in CNS):
Chronic encephalopathy
Headache and mental changes
Loss of higher mental function
Difficulty in concentration
Confusion and insomnia
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History of Trypanosomiasis
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In the 14th cent., Sultan Djata of Mali was believed to have died
of a “strange lethargic sickness”.
It was known to the slave traders, who rejected Africans with
the characteristic swollen cervical glands, because they knew
that these people would die untimely deaths.
In 1902, English scientists ford and Dutton identified the
parasite and named it Trypanosoma brucei gambiense.
The following year, David Bruce recognized the tsetse fly as the
vector of the disease.
There have been three particularly severe epidemics during the
twentieth century in Africa:
 1896 – 1906.
->
 1920 – 1929.
 1970’s –
More History
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It was not until the dawn of African independence that the disease was reduced
to a few sporadic cases.
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In many newly independent countries, the human and financial resources were
not available to keep up the indispensable effort to control and monitor the
disease.
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The illness was practically eliminated by 1960 because of active population screening.
New outbreaks which have been reported in the last 30 years in old and new locations.
In 1984, the World Health Organization launched a program to control and
prevent sleeping sickness.
Today, recent scientific and technical advances have produced new tools and
improved field control strategies.
Important Structures in Trypanosomes
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Subpellicular microtubules
Glycoproteins on plasma membrane
The flagellum and flagellar pocket
Length of Cell:
Approx. 20 nanometers.
Look At How They Move
The Life Cycle of the
Trypanosomes
Why Should We Care About This
Disease Anyway?
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Sleeping sickness is a daily threat to more than 60
million men, women and children in 36 countries of
sub-Saharan Africa.
22 of the countries are among the least developed
countries in the world that have diagnosed cases of
sleeping sickness.
The estimated number of people thought to have the
disease is between 300,000 and 500,000.
Sleeping sickness has a major economic impact on
the development of rural areas by decreasing the
labor force and hampering production and work
capacity.
Treatments
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West African Trypanosomiasis:
 Stage 1:
 First line - Pentamidine
 Second line - Eflornithine or Melarsoprol
 Stage 2:
 First line - Melarsoprol
 These drugs, however,
 Second line - Eflornithine
are in limited availability,
East African Trypanosomiasis:
have severe side effects,
 Stage 1:
and are ineffective in the
 First line - Suramine
late stages of the
 Second line - Melarsoprol
disease.
 Stage 2:
 First line - Melarsoprol
 Second line – Melarsoprol/Nifurtimox
Recent Research and Experiments
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Taxol and its derivatives have been tested to inhibit
microtubule growth.
Many other drugs tested were also known to have
different effects:
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Herbicidal
Pesticidal
Antiprotozal
Antibacterial
Antitumor
One experiment that was recently conducted:
 The effect of these drugs on trypanosome growth.
List of Compounds That Showed
Inhibitory Effects on Trypanosomes
Concentration (Nanomoles)
Concentration Needed for
Compounds
Tested
Amount of Compound Needed To Inhibit Trypanosome
6.5
6
5.5
5
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
Inhibition (Nanomoles)
6.61
Taxol
9.13 x 10-3
Vinbalastine
0.184
Dequalinium Chloride
8.8 x 10-2
Prodiamine
1.14
H.C.
Toxin
0.088
0.00913
Taxol
Dequalinium
Trichostatin
A
Chloride
3.44
1.14
0.184
Vinbalastine
Prodiamine
Compounds
3.44
H.C. Toxin
6.61
Trichostatin A
Experiment Conclusion
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Of all the compounds that were tested,
only very few showed inhibitory effects.
The results show that Taxol had the
greatest inhibitory effect.
Further experiments included testing
Taxol and its derivatives in vitro with
the trypanosomes.
Other Issues Currently Unknown
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How do the trypanosomes enter the nervous system?
How does the infection kill?
How can recent findings on drug mechanisms be
translated into useful tools in controlling the disease?
How should targets be selected from biochemical
studies against which new drugs can be designed?
How can efforts to fight the disease in Africa be
effectively combined on a local, national, and
international level?