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Trypanosomiasis By Simon Shum and Eric Lee 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. 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 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. 1970’s – More History ----- It was not until the dawn of African independence that the disease was reduced to a few sporadic cases. 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. 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 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? 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 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 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. 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 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 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?