Trypanosomiasis

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Trypanosomiasis

• By Simon Shum and Eric Lee

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Facts About Trypanosomiasis

• 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.

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Symptoms

• Neurological damage is irreversible when
  treatment is delayed until the second stage.

• Early stage (in blood)
• Recurrent fever
• Headache
• Pain in joints
• Itching

• 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

• 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.
• 1970s

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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.
• The illness was practically eliminated by 1960
  because of active population screening.
• 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.
• 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.

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Important Structures in Trypanosomes

• Subpellicular microtubules
• Glycoproteins on plasma membrane
• The flagellum and flagellar pocket

Length of Cell Approx. 20 nanometers.
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Look At How They Move
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The Life Cycle of the Trypanosomes
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Why Should We Care About This Disease Anyway?

• 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.

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Treatments

• West African Trypanosomiasis
• Stage 1
• First line - Pentamidine
• Second line - Eflornithine or Melarsoprol
• Stage 2
• First line - Melarsoprol
• Second line - Eflornithine
• East African Trypanosomiasis
• Stage 1
• First line - Suramine
• Second line - Melarsoprol
• Stage 2
• First line - Melarsoprol
• Second line Melarsoprol/Nifurtimox

• These drugs, however, are in limited
  availability, have severe side effects, and are
  ineffective in the late stages of the disease.

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Recent Research and Experiments

• Taxol and its derivatives have been tested to
  inhibit microtubule growth.
• Many other drugs tested were also known to have
  different effects
• Herbicidal
• Pesticidal
• Antiprotozal
• Antibacterial
• Antitumor
• One experiment that was recently conducted
• The effect of these drugs on trypanosome growth.

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List of Compounds That Showed Inhibitory Effects
on Trypanosomes
Compounds Tested Concentration Needed for Inhibition (Nanomoles)
Taxol 9.13 x 10-3
Vinbalastine 0.184
Dequalinium Chloride 8.8 x 10-2
Prodiamine 1.14
H.C. Toxin 3.44
Trichostatin A 6.61
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Experiment Conclusion

• 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.

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Other Issues Currently Unknown

• 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?