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group_2_presentation_1_-_chagas_disease [2018/02/02 23:54] yousifcr |
group_2_presentation_1_-_chagas_disease [2018/02/03 00:45] (current) babadim |
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| + | {{:group_2-_presentation_1-chagas_disease.pdf|}} | ||
| ======History====== | ======History====== | ||
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| - | <box 35% round left| >{{:chagas1.png?400 |}}</box|Figure 2. Map indicating parts of the world with their respective prevalence of chagas disease> | + | <box 35% round left| >{{:chagas1.png?400 |}}</box|Figure 2. Map indicating parts of the world with their respective prevalence of chagas disease (Bern, 2015)> |
| - | Chagas disease is predominantly in continental part of Latin America (World Health Organization, 2017). It has recently also been detected in the United States, Canada and many European countries due to travelling between these regions. It is estimated that Chagas disease infects 8 million people living in Latin American countries, 30-40% of which develop cardiomyopathy or digestive mega syndromes, or both (Rassi & Marin-Neto, 2010). Chagas disease is getting more attention as it is starting to become a global health concern since WHO recognized it to be the world’s 13th most neglected tropical disease in 2010 (Rassi & Marin-Neto, 2010). It has been estimated that more than 400,000 people have been infected with Chagas disease outside of Latin America with the US being the most affected (Steverding, 2014). //T. cruzi// infection rate is less than 1% per year, with the highest being 4% per year in hyperendemic Bolivian Chaco (Bern, 2015). It is encouraging for the scientific community to know that their efforts to decrease the occurrence rate has paid off since T. cruzi infection rate has decreased from 18 million in 1991 to 5.7 million in 2010(Bern, 2015). | + | Chagas disease is predominantly in continental part of Latin America (World Health Organization, 2017). It has recently also been detected in the United States, Canada and many European countries due to travelling between these regions. It is estimated that Chagas disease infects 8 million people living in Latin American countries, 30-40% of which develop cardiomyopathy or digestive mega syndromes, or both (Rassi & Marin-Neto, 2010). Chagas disease is getting more attention as it is starting to become a global health concern since WHO recognized it to be the world’s 13th most neglected tropical disease in 2010 (Rassi & Marin-Neto, 2010). It has been estimated that more than 400,000 people have been infected with Chagas disease outside of Latin America with the US being the most affected (Steverding, 2014). //T. cruzi// infection rate is less than 1% per year, with the highest being 4% per year in hyperendemic Bolivian Chaco (Bern, 2015). It is encouraging for the scientific community to know that their efforts to decrease the occurrence rate has paid off since T. cruzi infection rate has decreased from 18 million in 1991 to 5.7 million in 2010 (Bern, 2015). |
| ======Symptoms====== | ======Symptoms====== | ||
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| Symptoms of the Chagas disease vary between phases of the disease. About 95% of the cases with Chagas Disease do not show any symptoms in the acute phase (Teixeira, 2006). If the case does present any symptoms, they may show the following: | Symptoms of the Chagas disease vary between phases of the disease. About 95% of the cases with Chagas Disease do not show any symptoms in the acute phase (Teixeira, 2006). If the case does present any symptoms, they may show the following: | ||
| Swelling or redness at the skin infection site | Swelling or redness at the skin infection site | ||
| - | <box 50% round right|>{{ :chagas2.png?360|}}</box|Figure 3. The swelling of the left eyelid after child being bitten by T. Cruzi bug (MayoClinic, 2017)> | ||
| - | |||
| - | <box 50% round right|>{{:chagas3.png?360|}}</box|Figure 4. The swelling at the bite site near the elbow, after T. Cruzi bit it (MayoClinic, 2017)> | ||
| * Skin rash | * Skin rash | ||
| * Swollen lymph nodes | * Swollen lymph nodes | ||
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| * Cyanosis | * Cyanosis | ||
| * Coma | * Coma | ||
| + | <box 35% round|>{{ :chagas2.png?360|}}</box|Figure 3. The swelling of the left eyelid after child being bitten by T. Cruzi bug (MayoClinic, 2017)> | ||
| - | + | <box 35% round|>{{:chagas3.png?360|}}</box|Figure 4. The swelling at the bite site near the elbow, after T. cruzi bit it (MayoClinic, 2017)> | |
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| Patients who have above acute-phase symptoms, have them resolved in about 3-8 weeks spontaneously (Teixeira et al, 2006). If the person’s immune system is weakened, then occasionally the acute infections show chronic symptoms. Less than 5% of patients with the above presented symptoms die in the acute phase. The cause of death in the acute phase would be due to myocarditis or meningoencephalitis along with some complications like bronchopneumonia. | Patients who have above acute-phase symptoms, have them resolved in about 3-8 weeks spontaneously (Teixeira et al, 2006). If the person’s immune system is weakened, then occasionally the acute infections show chronic symptoms. Less than 5% of patients with the above presented symptoms die in the acute phase. The cause of death in the acute phase would be due to myocarditis or meningoencephalitis along with some complications like bronchopneumonia. | ||
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| ======Clinical Presentation of Chronic Chagas Heart Disease====== | ======Clinical Presentation of Chronic Chagas Heart Disease====== | ||
| - | <box 60% round |>{{:chagas4.png|}}</box |Figure 5. Image of Normal ECG)Figure: Normal ECG (Rassi, 2014)> | + | <box 43% round |>{{:chagas4.png?520|}}</box |Figure 5. Image of Normal ECG)Figure: Normal ECG (Rassi, 2014)> |
| - | <box 60% round |>{{:chagas5.png|}}</box|Figure 6. Image of Abnormal ECG: | + | <box 43% round |>{{:chagas5.png?520|}}</box|Figure 6. Image of Abnormal ECG: |
| Abnormal ECG: Abnormal Q waves; AV blocks; low QRS voltage; SSS (Sick SInus Syndrome)-malfunctioning sinus node; PVCs (extra heartbeats)(Rassi, 2014)> | Abnormal ECG: Abnormal Q waves; AV blocks; low QRS voltage; SSS (Sick SInus Syndrome)-malfunctioning sinus node; PVCs (extra heartbeats)(Rassi, 2014)> | ||
| - | <box 60% round |>{{:chagas6.png|}}</box|Figure 7. Image of Tachycardia ECG> | + | <box 43% round |>{{:chagas6.png?520|}}</box|Figure 7. Image of Tachycardia ECG (Rassi, 2014)> |
| - | <box 60% round |>{{:chagas7.png|}}</box|Figure 8. Image of Bradyarrhythmia ECG> | + | <box 43% round |>{{:chagas7.png?520|}}</box|Figure 8. Image of Bradyarrhythmia ECG (Rassi, 2014)> |
| - | <box 60% round |>{{:chagas8.png?400|}}</box|Figure 9. Segmental/Global Dilated Cardiomyopathy> | + | <box 43% round |>{{:chagas8.png?520|}}</box|Figure 9. Segmental/Global Dilated Cardiomyopathy (Rassi, 2014)> |
| - | <box 60% round |>{{:chagas9.png?400|}}</box|Figure 10. Associated megaesophagus and megacolon> | + | <box 43% round |>{{:chagas9.png?520|}}</box|Figure 10. Associated megaesophagus and megacolon (Rassi, 2014)> |
| **In Summary:** | **In Summary:** | ||
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| - | =====Risk Factors===== | + | ======Risk Factors====== |
| Chagas disease originated in Latin America but due to low mobility in and out of these countries, the disease is not as predominant in North America. However, as travelling capabilities start to increase and more individual’s visit South America, the disease is beginning to spread north. | Chagas disease originated in Latin America but due to low mobility in and out of these countries, the disease is not as predominant in North America. However, as travelling capabilities start to increase and more individual’s visit South America, the disease is beginning to spread north. | ||
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| - | <box 45% round right|>{{ :chagas10.png?300|}}</box|Figure 11. Illustrates the size of potential vectors of //T. cruzi// http://www.wrdw.com/home/headlines/Health-officials-Deadly-kissing-bug-reported-in-Georgia-353134901.html> | + | <box 35% round right|>{{ :chagas10.png?420|}}</box|Figure 11. Illustrates the size of potential vectors of T. cruzi (http://www.wrdw.com/home/headlines/Health-officials-Deadly-kissing-bug-reported-in-Georgia-353134901.html)> |
| //T. cruzi// is transmitted through contact of faeces of infected insects of the Triatominae (kissing bugs or conenose bugs) subfamily. They are often called “kissing bugs” because they have the tendency to bite individual’s faces. When they bite, they also defecate, leaving their feces free to enter the bite site to transmit the parasite. | //T. cruzi// is transmitted through contact of faeces of infected insects of the Triatominae (kissing bugs or conenose bugs) subfamily. They are often called “kissing bugs” because they have the tendency to bite individual’s faces. When they bite, they also defecate, leaving their feces free to enter the bite site to transmit the parasite. | ||
| Some of the most well known vectors of the disease include //Triatoma infestans// (kissing bugs), as well as //Rhodnius proxlius// and //Panstrongylus megistus// (Steverding, 2014). | Some of the most well known vectors of the disease include //Triatoma infestans// (kissing bugs), as well as //Rhodnius proxlius// and //Panstrongylus megistus// (Steverding, 2014). | ||
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| An infected vector is one that has trypomastigotes in their hindgut. Upon taking a blood meal from humans, they leave their feces on the skin and this is how trypomastigotes enter from kissing bugs to humans. Once they are in the human body, they lose their flagella and transform in the ideal. This is the ideal life cycle for them to reproduce exponentially within the cells. Once they have fully infected the cell, they transform back into trypomastigotes and burst out of the cell and enter the bloodstream. Once in the bloodstream, they can access other organs and once again transform into amastigotes inside the cell to replicate and infect the organ. Keep in mind that if a non-infected T.cruzi takes a blood meal from an infected human, they will become infected as well (Center of Disease Control and Prevention, 2015). | An infected vector is one that has trypomastigotes in their hindgut. Upon taking a blood meal from humans, they leave their feces on the skin and this is how trypomastigotes enter from kissing bugs to humans. Once they are in the human body, they lose their flagella and transform in the ideal. This is the ideal life cycle for them to reproduce exponentially within the cells. Once they have fully infected the cell, they transform back into trypomastigotes and burst out of the cell and enter the bloodstream. Once in the bloodstream, they can access other organs and once again transform into amastigotes inside the cell to replicate and infect the organ. Keep in mind that if a non-infected T.cruzi takes a blood meal from an infected human, they will become infected as well (Center of Disease Control and Prevention, 2015). | ||
| - | <box 70% round |>{{ :chagas_18.png?500|}}</box|Figure 12. Image of the vector's life cycle (Center of Disease Control and Prevention, 2015)> | + | <box 50% round |>{{ :chagas_18.png?600|}}</box|Figure 12. Image of the vector's life cycle (Center of Disease Control and Prevention, 2015)> |
| ======Mechanism====== | ======Mechanism====== | ||
| - | **RECOGNITION OF IMMUNE CELLS SPECIFICALLY MACROPHAGES** | + | **Recognition of Immune Cells Specifically Macrophages** |
| Once the infective trypomastigote enters the host, it binds to a complimentary immune cell such as a macrophage. The macrophages are recruited to the bite site because the parasite creates an open wound that requires a response from the immune system. The vector also releases histamine which causes the itchiness of the skin. The binding of the parasite to the macrophage initiates the internalization process using phagocytosis, forming pseudopods and the parasitophoros vacuole (Calvet et. al, 2012). In turn, this causes the recruitment of the host cell’s lysosomes to try and destroy the parasite. The lysosomes contain degrading enzymes. However, they are not successful. Once it is internalized, the trypomastigote transforms into the replicating amastigote and continues to multiply (Teixeira et. al, 2006). Once it has successfully completed cell division, it transforms back into the trypomastigote in order to initiate movement and infect the rest of the host cells. The parasite can only facilitate movement in the trypomastigote form. Eventually, the host cell will burst due to the increase in parasite density and the trypomastigotes gain access to the bloodstream and continues their infective routine to cells such as cardiomyocytes (Calvet et. al, 2012). | Once the infective trypomastigote enters the host, it binds to a complimentary immune cell such as a macrophage. The macrophages are recruited to the bite site because the parasite creates an open wound that requires a response from the immune system. The vector also releases histamine which causes the itchiness of the skin. The binding of the parasite to the macrophage initiates the internalization process using phagocytosis, forming pseudopods and the parasitophoros vacuole (Calvet et. al, 2012). In turn, this causes the recruitment of the host cell’s lysosomes to try and destroy the parasite. The lysosomes contain degrading enzymes. However, they are not successful. Once it is internalized, the trypomastigote transforms into the replicating amastigote and continues to multiply (Teixeira et. al, 2006). Once it has successfully completed cell division, it transforms back into the trypomastigote in order to initiate movement and infect the rest of the host cells. The parasite can only facilitate movement in the trypomastigote form. Eventually, the host cell will burst due to the increase in parasite density and the trypomastigotes gain access to the bloodstream and continues their infective routine to cells such as cardiomyocytes (Calvet et. al, 2012). | ||
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| An amastigote can also bind to the surface of the macrophage and become internalized via phagocytosis (Teixeira, et., al, 2006). Using a similar technique, pseudopods and a parasitophorous vacuole are formed and fused with the lysosomes. The lysosomes digest the vacuole and the amastigote is free to divide rapidly (Calvet et. al, 2012). Again, the amastigotes transform back into the trypomastigote, causing the host cell to burst, and are then released into the bloodstream (Teixeira et. al, 2006). | An amastigote can also bind to the surface of the macrophage and become internalized via phagocytosis (Teixeira, et., al, 2006). Using a similar technique, pseudopods and a parasitophorous vacuole are formed and fused with the lysosomes. The lysosomes digest the vacuole and the amastigote is free to divide rapidly (Calvet et. al, 2012). Again, the amastigotes transform back into the trypomastigote, causing the host cell to burst, and are then released into the bloodstream (Teixeira et. al, 2006). | ||
| - | <box 50% round|> {{:chagas12.png?360|}}</box|Figure 13. An amastigote internalizing itself via. Phagocytosis and then replicating. Once it has replicated it bursts the host cell, transforming into the trypomastigote form, allowing to further infect other cells while travelling through the bloodstream. (Teixeira, et., al, 2006)> | + | <box 35% round|> {{:chagas12.png?360|}}</box|Figure 13. An amastigote internalizing itself via. Phagocytosis and then replicating. Once it has replicated it bursts the host cell, transforming into the trypomastigote form, allowing to further infect other cells while travelling through the bloodstream. (Teixeira, et., al, 2006)> |
| Once T. Cruzi enters the host’s bloodstream, it needs to successfully recognize cardiomyocyte cells in order to infect the host cell. It does so using a variety of adhesion and internalization mechanisms. The trypomastigote binds to the cardiomyocyte cell in a similar way as the macrophage. Once it attaches to the surface, it forms the parasitophorous vacuole and transforms into the amastigote form to replicate. Following the rapid cell division, the parasite transforms back into the trypomastigote form and travels to the next cell to infect (Calvet, et. al, 2012). | Once T. Cruzi enters the host’s bloodstream, it needs to successfully recognize cardiomyocyte cells in order to infect the host cell. It does so using a variety of adhesion and internalization mechanisms. The trypomastigote binds to the cardiomyocyte cell in a similar way as the macrophage. Once it attaches to the surface, it forms the parasitophorous vacuole and transforms into the amastigote form to replicate. Following the rapid cell division, the parasite transforms back into the trypomastigote form and travels to the next cell to infect (Calvet, et. al, 2012). | ||
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| An third way T.Cruzi is internalized is using lipid membrane rafts. The parasitophorous vacuole on T. Cruzi binds strongly to the low density lipoprotein receptor on the cholesterol and sphingolipid areas of the raft, further allowing internalization (Calvet et. al, 2012). | An third way T.Cruzi is internalized is using lipid membrane rafts. The parasitophorous vacuole on T. Cruzi binds strongly to the low density lipoprotein receptor on the cholesterol and sphingolipid areas of the raft, further allowing internalization (Calvet et. al, 2012). | ||
| - | <box 50% round right|> {{:chagas_13.png?360|}}</box|Figure 14. A variety of different adhesion mechanisms that T. cruzi uses to recognize different types of host cells in order to infect and begin internalization. (Calvet et. al, 2012)> | + | <box 40% round right|> {{:chagas_13.png?450|}}</box|Figure 14. A variety of different adhesion mechanisms that T. cruzi uses to recognize different types of host cells in order to infect and begin internalization. (Calvet et. al, 2012)> |
| - | **INVASION/INTERNALIZATION** | + | **Invasion/Internalization** |
| Once T.Cruzi is successfully bound to the host cell, microfilaments are rearranged which encloses the parasite into the cell. The rearrangement in the cytoskeleton introduces a protrusion of the cardiomyocyte plasma membrane, creating a actin-based membrane skeleton to capture and internalize the parasite. This disturbs the structure of the cell, causing the breakdown of the cardiomyocyte fibres such as fibronectin (FN) and gap junctions that are needed to generate action potentials when the heart beats. As a result, this causes cardiac arrhythmias since the structure of the heart is compromised (Teixeira et. al, 2006). | Once T.Cruzi is successfully bound to the host cell, microfilaments are rearranged which encloses the parasite into the cell. The rearrangement in the cytoskeleton introduces a protrusion of the cardiomyocyte plasma membrane, creating a actin-based membrane skeleton to capture and internalize the parasite. This disturbs the structure of the cell, causing the breakdown of the cardiomyocyte fibres such as fibronectin (FN) and gap junctions that are needed to generate action potentials when the heart beats. As a result, this causes cardiac arrhythmias since the structure of the heart is compromised (Teixeira et. al, 2006). | ||
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| A second way is through a lysosome dependent mechanism. The parasite causes an increase in cytosolic calcium that leads to depolymerization of the actin and allows the recruitment of lysosomes to the parasite binding site. The lysosomes allow entry into the cell. These elevated levels of calcium are caused by a sensitivity to leupeptin leading to a release of calcium from the sarcoplasmic reticulum calcium stores, and extracellular calcium influx through cellular membrane calcium channels (Teixeira et. al, 2006). | A second way is through a lysosome dependent mechanism. The parasite causes an increase in cytosolic calcium that leads to depolymerization of the actin and allows the recruitment of lysosomes to the parasite binding site. The lysosomes allow entry into the cell. These elevated levels of calcium are caused by a sensitivity to leupeptin leading to a release of calcium from the sarcoplasmic reticulum calcium stores, and extracellular calcium influx through cellular membrane calcium channels (Teixeira et. al, 2006). | ||
| - | <box 50% round|> {{:chagas_14.png?360|}}</box| Figure 15. An image representing T. Cruzi internalized in a cardiomyocyte via phagocytosis and using the parasitophorus vacuole in order to do so (Calvet et al, 2012).> | + | <box 40% round left|> {{:chagas_14.png?450|}}</box| Figure 15. An image representing T. cruzi internalized in a cardiomyocyte via phagocytosis and using the parasitophorus vacuole in order to do so (Calvet et al, 2012).> |
| ======Pathophysiology====== | ======Pathophysiology====== | ||
| - | <box 50% round right|> {{:chagas15.png?360|}} </box|Figure 16. Image A shows a normal neural population in cardiomyocytes and image B shows a degenerative neural population in cardiomyocytes as T. cruzi infection worsens (Calvet, et. al, 2012).> | + | <box 30% round right|> {{:chagas15.png?360|}} </box|Figure 16. Image A shows a normal neural population in cardiomyocytes and image B shows a degenerative neural population in cardiomyocytes as T. cruzi infection worsens (Calvet, et. al, 2012).> |
| Once the parasite has successfully compromised the host cell, the host’s immune system starts generating a response in order to fight the infection. When the amastigotes start to divide rapidly they accumulate and damage the nerve cells and overall structure of the cell. They do so by causing necrosis of the myofibrils in the cytoskeleton and therefore, a dysfunction in the microtubule filaments, specifically fibronectin. Immune response cells are recruited to the site of damage but also end up accumulating and contributes to the enlargement of the cardiomyocytes. The cell will receive specific responses from cytokines, chemokines, and nitric oxide. Some of the genes involved in the accumulation include nitric oxide synthase 2, matrix metalloproteinase -2 (NMP-2), NMP-9, interleukin-6 (IL-6), and tumour necrosis factor-alpha. Although this is meant to be a defensive response against the parasite, it often results in cardiac fibrosis and hypertrophy due to the accumulation of cells (Chaves et al., 2016). Cardiac hypertrophy is the abnormal enlargement of the heart muscle due to an increase in cardiomyocyte cells and size (Calvet et al., 2012). Specifically, a build up of immune response cells, and the protrusion of the cardiomyocyte plasma membrane will cause the hypertrophy. Similarly, cardiac fibrosis is the abnormal thickening of the hearts valves characterised by a dense accumulation of collagen due to the over proliferation of cardiac fibroblasts that results from the disruption in the extracellular matrix (Calvet et al., 2012). | Once the parasite has successfully compromised the host cell, the host’s immune system starts generating a response in order to fight the infection. When the amastigotes start to divide rapidly they accumulate and damage the nerve cells and overall structure of the cell. They do so by causing necrosis of the myofibrils in the cytoskeleton and therefore, a dysfunction in the microtubule filaments, specifically fibronectin. Immune response cells are recruited to the site of damage but also end up accumulating and contributes to the enlargement of the cardiomyocytes. The cell will receive specific responses from cytokines, chemokines, and nitric oxide. Some of the genes involved in the accumulation include nitric oxide synthase 2, matrix metalloproteinase -2 (NMP-2), NMP-9, interleukin-6 (IL-6), and tumour necrosis factor-alpha. Although this is meant to be a defensive response against the parasite, it often results in cardiac fibrosis and hypertrophy due to the accumulation of cells (Chaves et al., 2016). Cardiac hypertrophy is the abnormal enlargement of the heart muscle due to an increase in cardiomyocyte cells and size (Calvet et al., 2012). Specifically, a build up of immune response cells, and the protrusion of the cardiomyocyte plasma membrane will cause the hypertrophy. Similarly, cardiac fibrosis is the abnormal thickening of the hearts valves characterised by a dense accumulation of collagen due to the over proliferation of cardiac fibroblasts that results from the disruption in the extracellular matrix (Calvet et al., 2012). | ||
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| In summary, the constant destruction of cardiac fibres, the collection of collagen leading to fibrosis to replace destroyed myocytes and the hypertrophy of the remaining cardiomyocytes in order to compensate for the loss of myocytes all lead to heart failure and cardiac arrhythmias (Calvet et al., 2012). | In summary, the constant destruction of cardiac fibres, the collection of collagen leading to fibrosis to replace destroyed myocytes and the hypertrophy of the remaining cardiomyocytes in order to compensate for the loss of myocytes all lead to heart failure and cardiac arrhythmias (Calvet et al., 2012). | ||
| - | <box 50% round left|>{{:chagas16.png?360|}}</box| Figure 17. These images are a comparison between an infected cardiomyocyte with an uninfected one. In image A, it is an uninfected cardiomyocyte. In image B, the arrow points to the T. Cruzi parasite, red represents enlarged cells, and the green represents disorganized fibronectin. Image C is an uninfected cardiomyocyte with the blue being the cell, and the red being organized and normally placed fibronectin. Image D displays enlarged cardiomyocytes in blue, with displaced and decreased amounts of fibronectin in red. The arrows point to the parasite T cruzi. Image E represents the invasion of the T. Cruzi parasite (the light blue circles where the arrow is pointing), and the green represents the disorganized and deteriorating microtubules necessary for heart contraction. (Calvet, et. al, 2012)> | + | <box 43% round left|>{{:chagas16.png?500|}}</box| Figure 17. These images are a comparison between an infected cardiomyocyte with an uninfected one. In image A, it is an uninfected cardiomyocyte. In image B, the arrow points to the T. Cruzi parasite, red represents enlarged cells, and the green represents disorganized fibronectin. Image C is an uninfected cardiomyocyte with the blue being the cell, and the red being organized and normally placed fibronectin. Image D displays enlarged cardiomyocytes in blue, with displaced and decreased amounts of fibronectin in red. The arrows point to the parasite T cruzi. Image E represents the invasion of the T. Cruzi parasite (the light blue circles where the arrow is pointing), and the green represents the disorganized and deteriorating microtubules necessary for heart contraction. (Calvet, et. al, 2012)> |
| ======Treatment====== | ======Treatment====== | ||
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| <box 60% round|>{{ :chagas17.png?300 |}}</box| Figure 18. Chemical structures of compounds used in the treatment and control of Chagas disease (Steverding, 2014)> | <box 60% round|>{{ :chagas17.png?300 |}}</box| Figure 18. Chemical structures of compounds used in the treatment and control of Chagas disease (Steverding, 2014)> | ||
| - | **BENZNIDAZOLE (Benz-nidah-zol)** | + | **Benznidazole** |
| Benznidazole is a nitroimidazole (O₂NC₃H₂N₂H.) and was developed in 1966 and was officially released in 1972 at La Roche Laboratories. It is the primary treatment for the Chagas disease, and it’s FDA approved to use for children between 2 to 12 years. Nonetheless, patients are recommended to consume lower doses of it for their safety and adverse side effects. Through many clinical trials, it was found that Benznidazole is considered somehow effective in reducing the symptoms and detect the T.cruzi parasite inside the body. It was found that this treatment reduced 60 to 85 % of the acute cases, and in more than 90% of congenitally infected infants, if treated in their first year of life. However, the efficacy of Benznidazole in the chronic stage of the Chagas disease is still questionable. Many clinical types of research have shown that Benznidazole fails to treat Chagas patients in the chronical phase. Partially because the benefits of the drug in preventing cardiac and megacolon and megaesophagus manifestations are not yet clear (Gaspar et al., 2015). | Benznidazole is a nitroimidazole (O₂NC₃H₂N₂H.) and was developed in 1966 and was officially released in 1972 at La Roche Laboratories. It is the primary treatment for the Chagas disease, and it’s FDA approved to use for children between 2 to 12 years. Nonetheless, patients are recommended to consume lower doses of it for their safety and adverse side effects. Through many clinical trials, it was found that Benznidazole is considered somehow effective in reducing the symptoms and detect the T.cruzi parasite inside the body. It was found that this treatment reduced 60 to 85 % of the acute cases, and in more than 90% of congenitally infected infants, if treated in their first year of life. However, the efficacy of Benznidazole in the chronic stage of the Chagas disease is still questionable. Many clinical types of research have shown that Benznidazole fails to treat Chagas patients in the chronical phase. Partially because the benefits of the drug in preventing cardiac and megacolon and megaesophagus manifestations are not yet clear (Gaspar et al., 2015). | ||
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| * Peripheral neuropathy | * Peripheral neuropathy | ||
| - | **NIFURTIMOX (Ni-fur-ti-mix)** | + | **Nifurtimox** |
| It is a Nitrofuran derivative (C10H13N3O5S) and is the only alternative to Benznidazole for the treatment of Chagas Disease. However it is not approved by the FDA. Moreover, Nifurtimox is used also to treat second stage African trypanosomiasis caused by a different parasite (Gaspar et al., 2015). The efficacy of this drug is similar to Benznidazole. However, Nifurtimox is more critical and causes more adverse effects. The mechanism of this drug is very similar to the mechanism of Benznidazole which is using the process of nitro reduction to produce nitro radicals that will affect the parasite on a cellular level. On the other hand, this drug uses Oxygen to produce oxygen species like superoxide and hydrogen peroxide ion that are also toxic to //T.cruzi//. This parasite is proved to be sensitive to oxidative stress as it has weak detoxification mechanisms due to the absence of catalase of peroxidase activity and reduced superoxide dismutase activity. Nifurtimox is not recommended for pregnant ladies for obvious reasons. | It is a Nitrofuran derivative (C10H13N3O5S) and is the only alternative to Benznidazole for the treatment of Chagas Disease. However it is not approved by the FDA. Moreover, Nifurtimox is used also to treat second stage African trypanosomiasis caused by a different parasite (Gaspar et al., 2015). The efficacy of this drug is similar to Benznidazole. However, Nifurtimox is more critical and causes more adverse effects. The mechanism of this drug is very similar to the mechanism of Benznidazole which is using the process of nitro reduction to produce nitro radicals that will affect the parasite on a cellular level. On the other hand, this drug uses Oxygen to produce oxygen species like superoxide and hydrogen peroxide ion that are also toxic to //T.cruzi//. This parasite is proved to be sensitive to oxidative stress as it has weak detoxification mechanisms due to the absence of catalase of peroxidase activity and reduced superoxide dismutase activity. Nifurtimox is not recommended for pregnant ladies for obvious reasons. | ||
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| ======References====== | ======References====== | ||
| + | Bern, C. (2015). Chagas’ disease. New England Journal of Medicine, 373(5), 456-466. | ||
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| + | Bonney, K. M., & Engman, D. M. (2008). Chagas heart disease pathogenesis: one mechanism or many?. Current molecular medicine, 8(6), 510-518.* | ||
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| + | Calvet, C. M., Melo, T. G., Garzoni, L. R., Oliveira Jr, F. O., Neto, D. T. S., NSL, M., ... & Pereira, M. C. (2012). Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction. Frontiers in immunology, 3. | ||
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| + | Center of Disease Control and Prevention (2015). Chagas. Retrieved from https://www.cdc.gov/parasites/chagas/biology.html | ||
| + | |||
| + | Chaves, A. T., Estanislau, J. D. A. S. G., Fiuza, J. A., Carvalho, A. T., Ferreira, K. S., Fares, R. C. G., ... & da Costa Rocha, M. O. (2016). Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses. BMC infectious diseases, 16(1), 191. | ||
| + | |||
| + | Gaspar, L., B Moraes, C., H Freitas-Junior, L., Ferrari, S., Costantino, L., Paola Costi, M., ... & Cordeiro-da-Silva, A. (2015). Current and future chemotherapy for Chagas disease. Current medicinal chemistry, 22(37), 4293-4312. Retrieved from https://research-repository.standrews.ac.uk/bitstream/handle/10023/9920/Gaspar_2016_Current_CurrMedChem_4293.pdf?sequence=1 | ||
| + | |||
| + | Loury, E. (2012). Chagas' disease can cast a silent, lifelong shadow. Los Angeles Times. Retrieved from http://articles.latimes.com/2012/jul/08/local/la-me-chagas-20120708 | ||
| + | |||
| + | Moncayo, Á. (2010). Carlos Chagas: biographical sketch. Acta tropica, 115(1), 1-4. | ||
| + | |||
| + | Montgomery, S. (2017). Heart Failure at Age 46? Centers for Disease Control and Prevention. Retrieved from https://blogs.cdc.gov/global/2017/04/14/heart-failure-at-age-46/ | ||
| + | |||
| + | Rassi, A., (2014) Chagas’ Heart Disease. World Congress of Cardiology Scientific Sessions. | ||
| + | |||
| + | Rassi, A., & Marin-Neto, J. A. (2010). Chagas disease. The Lancet, 375(9723), 1388-1402. | ||
| + | |||
| + | Rassi Jr, A., Rassi, A., & Marin-Neto, J. A. (2009). Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification. Memorias do Instituto Oswaldo Cruz, 104, 152-158. | ||
| + | |||
| + | Steverding, D. (2014). The history of Chagas disease. Parasites & vectors, 7(1), 317. | ||
| + | |||
| + | Teixeira, D. E., Benchimol, M., Crepaldi, P. H., & de Souza, W. (2012). Interactive multimedia to teach the life cycle of Trypanosoma cruzi, the causative agent of Chagas disease. PLoS neglected tropical diseases, 6(8). | ||
| + | |||
| + | Teixeira, A.R.L., Nitz, N., Guimaro, M.C., Gomes, C., & Santos-Buch, C.A. (2006). Chagas disease. Postgrad Med J, 82 (974): 788-798. | ||
| - | - Steverding, D. (2014). The history of Chagas disease. Parasites & vectors, 7(1), 317. | + | World Health Organization (2017). Chagas Disease. Retrieved from: http://www.who.int/mediacentre/factsheets/fs340/en |
| - | - Moncayo, Á. (2010). Carlos Chagas: biographical sketch. Acta tropica, 115(1), 1-4. | + | |
| - | - World Health Organization (2017). Chagas Disease. Retrieved from: http://www.who.int/mediacentre/factsheets/fs340/en/ | + | |
| - | - Rassi, A., & Marin-Neto, J. A. (2010). Chagas disease. The Lancet, 375(9723), 1388-1402. | + | |
| - | - Bonney, K. M., & Engman, D. M. (2008). Chagas heart disease pathogenesis: one mechanism or many?. Current molecular medicine, 8(6), 510-518.* | + | |
| - | - Chaves, A. T., Estanislau, J. D. A. S. G., Fiuza, J. A., Carvalho, A. T., Ferreira, K. S., Fares, R. C. G., ... & da Costa Rocha, M. O. (2016). Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses. BMC infectious diseases, 16(1), 191. | + | |
| - | - Gaspar, L., B Moraes, C., H Freitas-Junior, L., Ferrari, S., Costantino, L., Paola Costi, M., ... & Cordeiro-da-Silva, A. (2015). Current and future chemotherapy for Chagas disease. Current medicinal chemistry, 22(37), 4293-4312. Retrieved from https://research-repository.st-andrews.ac.uk/bitstream/handle/10023/9920/Gaspar_2016_Current_CurrMedChem_4293.pdf?sequence=1 | + | |
| - | - Steverding, D. (2014). The history of Chagas disease. Parasites & vectors, 7(1), 317. Retrieved from https://parasitesandvectors-biomedcentral-com.libaccess.lib.mcmaster.ca/articles/10.1186/1756-3305-7-317 | + | |
| - | - Calvet, C. M., Melo, T. G., Garzoni, L. R., Oliveira Jr, F. O., Neto, D. T. S., NSL, M., ... & Pereira, M. C. (2012). Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction. Frontiers in immunology, 3. | + | |
| - | - Teixeira, D. E., Benchimol, M., Crepaldi, P. H., & de Souza, W. (2012). Interactive multimedia to teach the life cycle of Trypanosoma cruzi, the causative agent of Chagas disease. PLoS neglected tropical diseases, 6(8). | + | |
| - | - Rassi Jr, A., Rassi, A., & Marin-Neto, J. A. (2009). Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification. Memorias do Instituto Oswaldo Cruz, 104, 152-158. | + | |
| - | - Teixeira, A.R.L., Nitz, N., Guimaro, M.C., Gomes, C., & Santos-Buch, C.A. (2006). Chagas disease. Postgrad Med J, 82 (974): 788-798. | + | |
| - | - Rassi, A., (2014) Chagas’ Heart Disease. World Congress of Cardiology Scientific Sessions. | + | |
| - | - Rassi, A., & Marin-Neto, J. A. (2010). Chagas disease. The Lancet, 375(9723), 1388-1402. | + | |
| - | - Bern, C. (2015). Chagas’ disease. New England Journal of Medicine, 373(5), 456-466. | + | |
| - | - Center of Disease Control and Prevention (2015). Chagas. Retrieved from https://www.cdc.gov/parasites/chagas/biology.html | + | |
| - | - Montgomery, S. (2017). Heart Failure at Age 46? Centers for Disease Control and Prevention. Retrieved from https://blogs.cdc.gov/global/2017/04/14/heart-failure-at-age-46/ | + | |
| - | - Loury, E. (2012). Chagas' disease can cast a silent, lifelong shadow. Los Angeles Times. Retrieved from http://articles.latimes.com/2012/jul/08/local/la-me-chagas-20120708 - Ordered List Item | + | |
