Meeting 3

Meeting 3 - African Trypanosome Sleeping Sickness Question...

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Unformatted text preview: African Trypanosome - Sleeping Sickness Question from discussion: Who was the first to find out there could be another vector for disease, Manson or Bruci? Trypanosomes in fish or frogs are very beautiful but not well studied because we can't culture them. Griffith Evans: found trypanosomes in the blood of horses. It is found in cammels, mules, and bhorses. It doesn't folloow equatorial African which is where sleeping sickness covers. Nagana: reminder, there were people trying to grow cattle and they all died. The only ones that survived were native ones N'Darma. David Bruce was sent to investigate. He saw trypanosomes and went on to show Koch's postulates. He noticed the geographical distribution followd the distribution of a tsetse fly. He killed animals and looked at their blood and found trypanosomes. These are the sourse of the infection. Tsetse fly are really ancient. This is a fossil. 34 to 56 million years old. If you look at the distribution of tsetse and the distribution of cattle. It's outside the tsetse belt. The only place people can grow cattle is outside the region of tsetse. That mans, this whole region, you can't grow cattle. you can't use them for agriculture. If they could knock out all the tsetse, they would increase in cattle, but what would happen? Desertification is caused by overgrazing by domestic grazing. Wild animals are restricted by the tsetse fly region. You'd probably kill all the wild animals. Tsetse is infecting about 50% of the wild game. "The fly who would be king." It is protecting wild life in Africa. The disease in humans. They saw it way back in 1375. It's called the sleepy distemper where they went into a coma. They called this swelling of the cervical lymph nodes. It is a first sign of an infection. They came down with a fever. Some guy looked at this blood and saw trypanosomes. There was an epidemic ain Gambia. They commisioned Bruce. Winterbottom's sign corresponded with the disease. They looked at cerbrospinal fluid from these coma people. It's very difficult for anything to get into the brain. BRuce looked at the tsetse range and the sleeping sickness. Maybe the tsetse are also vector. There was a patient in Rhodesia (Zimbabwe) and found someonw with sleeping sickness. However, the vector wasn't there. Bruce took blood samples from the animals and 1/3 of them had trypanosome but didn't kill the animals.The abundant tsetse was morsitans. Definition: In S. America where the trypanosome go out the feces of the tsetse and we rub it in, that's ...... When it infects via mouth it is called salivarian? They started to use insecticide and it went down. Some of their control methods are strange. But it came back in the 60s. The colonials left and the nations became independent. There was no insecticide spraying and it came back. Let's compare morbidity and motality of 3 different diseases. Ascariasis is a worm disease. African sleeping sickness is one of the top diseases in WHO but malaria is the main scourge. Blue is gambiense and yellow is rhodesiense. Where do they occur. West Africa is rivery. The species is glosina palpalis. This is an anthroponosias: transmitted from man to man. Death is slow. Rhodesiense live on the savannah in east Africa. Zoonosis, mainly an animal disease. When it gets into man as an accidental host, death can occur in weeks. Only newly hatched tsetse flies can transmit and it's actually a poor vector. Computer analysis of tsetse fly range. These are predicted areas of savannah tsetse can live by using what is needed for where tsetse fly can live. Morsitans group. Red and purple is field data. Very good correlation. this is important because the fly causes the disease.There was one where they slaughtered all the wild animals. Slash and burn the lands, leading to deforestation. They put the insecticide on the cattle. You have to keep at it. Trapping. They made artificial cows in Zimbabwe and they like the color blue. Or sterile male for screw worms. Put gamma radiated males. They become sterile, female tsetse flies only mate once. So if they meet a sterile male, they wouldn't come back. Zanzibar (islands) is the best: They used a lot o pesticides. Killed 95%. Released sterile males. Summary: T. gambiense causes sleeping disease and it's very slow. T. rhodesiense that is in east africa with early cns involvement. Life cycle. We're starting at q. The twetwe bites an infected person. They trypanosomes go to midgut. They start dividing procyclic trypomastigote. Then the trypanosomes migrate through the fly and go to the sailvary glands. As they're doing this, they differentiate to epimastigote. Finally, they become non-dividing and they are the only form that is infective for the vertebrate host and they're called metacyclic. This is just likei n T. Cruzi. in life cycles, you usually have this "pre-adaptation" where it "knows" or is evolved to know it will go to a vertebrate houst. then it becomes long-slender trypomastigotes that are dividing and they go in cycles. when it goes down due to immune system. They go to intermediate blood form and stop dividing and now it can infect insects. Another species in probscis. They stick to the walls via receptors. A is food cannal. B is hypopharynx. When salivary comes out you get a whole bunch of them. The blood stream infection are very interesting. They don't have active mitochondria. And it allows cells to live in oxygen. When a cell has mitochondria, then it's very pro____. The procyclics and epis have it, but the meta and cyclic don't have cristi (inner membrane chain) in the mitochondria. They survive on glucose. They're VERY aerobic but the oxygen goes through an alternate pathway but does nothing. Biological phenomenon: there's no cristae. But when it becomes short-stumpy, they're starting to develop mitochondrial enzyme. Once they're back in the tsetse, they have a complete mitochondrion and Kreb cycle. This is good in biological research and see how mitochondrion are made. An example of the use of a parasitic lifecycle. the patient usually has a relapse in fevers. During 3 and 4, the immune system kills them due to a single antigen. They have long-slenders and short-stumpy. They have all their glycolygtic enzyme in an enclosed organelle. Why? Because they only live on glycolysis for a while so maybe this is more efficient. Oxidase, same one found in plants. Tells us something about evolution. Lateral gene transfer? Plant to parasite? Glucose is limiting so then they use AA very effectively. Disease- Winterbottoms lymphnodes. Primary stage: subcutaneous infection. Winterbottom. They usually take an aspirate of the lymph node. Chancre Blood stage: Fever or aka malaise. headache and poains in the joints. Then you get trypanosomes in the blood. Gambiense is acute. There's more trypanosomes than blood cells. They also enter lymphatics. Now there's an influx of B cells. They lyse the trypanosomes but they release toxins that stimulate macrophages to release TNF and produce cachexia. Then there's this cyclic fever for 7-10 days. Late stage: Rhodesian you get invasion of th eCNS or could get heart problem before heart. Gambienses you get personality changes, insomina or iititabilityor invasion of the CNS. Death occcurs from secondary infection such as pneumonia. Summary Let's compare African and American American - feces, unilateral swelling, lymphnodesk, blood, intermediate stage, chronic stage, and then mycarditis or mega syndrome. African - chancre, blood, fever, lymphatics, etc. death Cure? They don't like to work on tropical diseases. Because they don't get money for it because the people don't have money for it. A lot of stuff injected and you get horrible side effects and sometimes death. The only way new drugs are being made is because WHO are interested in working on these diseases. They give people small research grants. They have partnerships in the industry. It's not major like Merck. There are a slew of other trypanosomal diseases. T. Congolense is much like the others. T. lewisi is flea to rat. Very lethal for certain strains of mouth. Cocktail Moment Christmas Island. They collected rats. The island had phophate and brough mining. They found black rats had been introduced. All these native rats had disappeared. Why had black rats taken over the island? When they had specifmens, the t. lewisi came from black rats and exterminated all the native rats. It's a parasitic disease that caused an ecological change. T. evansi (that Evans guy) introduced to the new world. It is transmitted by a horse fly tabanid. The range of the disease is widespread. There's also vampire bats. if you look at these carfeully. There's nothing here. Some lack DNA. They live quite well. In the fly, they're not a vector. It's mechanical transmission. It's like a dirty siringe. It survives for 10-15 minutes in the fly. There is no development in the fly. The kinetoplast DNA is mitochondral DNA. You have about 1000 Mito in your liver cells and there's molecules. About 10-20 genes. They produce the units needed for the respiration chain. Mitochondrial DNA is the ultimate parasite. It's lost all it's genes except for 10-20 and only hydrophobic proteins. but if you don't have those proteins, you can't perspire. Even though the mito DNA is different in trypanosome. What about the Evans wihtout the DNA? Long-slender form trypomastigotes with no mitochondria. Why can T. evansi continue to live without it? It can live glycolytically. T equiperdum. some of them dont' have kDNA. Some have actually mutated. This is a horse disease. We have 3 species. Even the ones that have kDNA have lost some of it. Brucei and rhodesinese are pretty much the same. Differ by one gene. Called the SRA gene. It allows them to live in humans. Some diverged to become gambiense. They live in blood but via a different mechanism. ...
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This note was uploaded on 12/31/2009 for the course MIMG 168 taught by Professor Staff during the Fall '08 term at UCLA.

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