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Unformatted text preview: Chagas disease Trypanosome Cruzei Blood sucking bugs. They were called barbeiros becaue they bit around the mouth when they were asleep. Sometimes there's 1000s of bugs. Do these bugs transmit a disease? He found a lot of flagellates known as trypanosomes. No one knew they caused diseases. He sent them to the institutes to bite monkeys and it was found in the bodies of the monkey. It didn't have animal specificity. They were known for a long time from the missionaries. It doesn't hurt, but allergic reaction causes itching. He thought it was a vectof of a human disease but did not know what the disease was. He found the vector and parasite but no diesase. He went to a little girl that was feverish etc. Her blood had a LOT of trypanosomes. They followed her all life and died but probably not from Chagas disease. You can look in the blood and see these little guys. He drew all the little guys. The main characteristic is that it had two little blue dots. Anline makes dyes. It stains DNA one color and RNA another color. There were two things that contained DNA in these cells. It was diagnostic for these guys. He became really famous, but made a lot of enemies. For example, Cruz was passed over. He believed in eugenics. Chagas's work was rediscovered 20 years later. Morphology of T. Cruzi. They exist in 3 different forms. left is in blood. C-shaped. In the insect, they look like top left. Mastigote means flagellum. Trypo mastigote is needle. They thought the kinetoplast had to do with motility because it was at the end of the flagellum. Ginza? stain of Trypanosome in an acute infection. There are a lot of them. It's about to divide. Here's a SEM bottom left. Epimastigote is top right and bottom right. Chagas Disease It goes in chronic stage and difficult to diagnose. One of the most wide spread infectious diseases. It hurts the heart and kills young patients. Traitomine bug take a blood meal from infected human. It injests trypomastigotes (c-shaped) and stay in the midgut as epimastigotes. they multiply and become differentiation and become metacyclic that is now infectious for humans. Epimastigotes are not infectious. When the triatomine takes another blood meal and have a habit of defecating rapidly after feeding. They defecate around the bite wound. We scratch and rub the feces into the wound. They get taken up by macrophages. They are in the phagocytic lysosal and then break out to live in the cytosol. Then they multiply to become amastigotes. They go out and infect other cells primarily spleen, lymphnodes, etc but very non-specific. 1st symptom is a swelling over one eye. Usually unilateral where the bug bites. Then you get spleen and liver growing larger and larger leading to the acute stage. You get romana sign, a fever, an enlarged spleen, a large amount of T. cruzei in the blood. 10% mortality in children. Some of the drugs are as bad as the disease. Sometimes the drug is 15% mortality! >< The indeterminate years can be as long as 5 years. Then, they form these nests in the heart muscle. They cause inflammation. You can duplcate this stage in tissue culture. After 5 years, it becomes chronic. It is the most difficult phase to diagnose. You get nerve degeneration, especially the glanglia in the peristalsis. They like the heart. 80% get cardiomyopathy, enlargement, and breakage of the heart. There are two other syndromes which are called megaesophagus and megacolon where there's no peristalsis. The percentage varies with the locality. We don't know why. It could be a different host or it could be a different parasite. They have different tropism. If they do an EKG, it blocks impulses from the other side. Chagas heart is much larger (left). The muscle thins out and is called an apical aneurysm. it can thin so much it bursts. The mega syndrome, is quite devestating. they can't eat or swallow. The colon has really bad constipation. You see a huge extended colon. We have three definitions. The only vertebrate host is a human is anthroponosis. A zoonosis is where the only host is an animal. A reservoir host is when it infects animals but it can go to humans. Most of T. Cruzei was a zoonosis. When parasites have lived with animals for a long time, they've acheived an equilibrium. But when people come into the trees, they also bring domestic animals. Some triatomines that have become domesticated. They prefer living in these huts where these humans are the vector. Don't eat these bugs! There's the domestic transmission and the silvatic cycle. The Beverly Hills bugs don't defecate right away. They built better housing in Venezuela and the bugs couldn't live there anymore. It is socio-economic disease of people who can't make good housing. Reduviid vectors can get in. There are not good antiparasite drugs. There are some insectiside with low toxicity and low cost. Alternative methods of transmission. A lot of people from rural areas migrated to the cities. A lot of them had chronic Chagas disease and sold their blood. The parasites got into the blood supply. The prevalence ranges from 1.7% to 53% of the blood bank. It's become a problem in LA due to immigration. They don't screen but they do have questionnaires. how do you diagnose? Assay must be specific so that there's very few false-positives. it must have very little cross reactivity with other organisms. It should be sensitive down to the single cell or single parasite. There are two ways, indirect and direct. Indirect is to detect the andybody. It is evidence of past infection and maybe present, we cna't tell. Or there's direct. The easies way is the direct microscopy assay to see if you have T. cruzei floating around. You can take the parasites and culure them. We can grow them in eczena, in no other live organism. Youc an grow them up and study them. How do you know what percent form cultures. Remember there's very few circulating in chronic disease blood. This organism T. rangelli looks like T. cruzi and givey ou a misdiagnosis. To look at them serologically. Indirect immunofluorescence. They found that 60-90% of racoons had them in Georgia. This is an antibody against IgG. Negative control and positive. These are T. Cruzei cells. They light up because there are antibodies. This is called Xenodiagnosis. This is the "gold standard" for diagnosis. Grow up triatomines and strap the jar on one end and let them take blood meals. It was first described in 1877. You take the bug back to the lab and squish them after growing them. Look at hind gut. They are sampling a lot of blood from the patient. But problems, there are different strains of T. Cruzi. you may have picked the wrong bug for that strain. People don't want to have bugs biting them. DNA-based assays (direct) We look for genes that are only in the parasite and not in the host. You need specificity and sensitivity. Mitochondrial mincircles. One cell has thousands of these. The minicircles in Cruzi have 4 conserved regions. Any strain of T. Cruzi could be amplified and amplify the variable region. Then, now we can look at which strain because of the variable. 10-20 mLs of blood to detect a single parasite. We are better than Xenodiagnosis or the same. Workshop October 1st. On Chagas disease...
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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.
- Fall '08