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group_2_presentation_3_-_malaria [2016/12/02 17:35]
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  ​====== Malaria ======  ​====== Malaria ======
  
-Malaria ​has been known for many thousand ​years. Around 7,​000-12,​000 years ago with increase in temperatures in Africarise in humidity creating new water sources ​and the start of agriculture ​in the Middle East and North East Africa ​there were many water bodies and pools of water [11]. This led to a favourable climate and area for breeding and transmission of malaria parasites and its carrier, the mosquito.+Malaria ​and malaria-causing parasites have been known to mankind ​for thousands of years. Around 7,​000-12,​000 years ago the increasing ​temperatures in Africa ​caused a rise in humidity, thus creating ​many new water bodies ​and allowing for agricultural development ​in the Middle East and North East Africa ​to occur (Srinivas, 2016). This led to the formulation of  favourable climate and area for breeding and transmission of malaria parasites and its carrier, the mosquito.
  
 +PowerPoint Presentation:​ {{:​malaria_-_final_.pdf|}}
  
 {{:​africa_malaria.gif|}} {{:​africa_malaria.gif|}}
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 ==== Discovery of the Malaria Parasite (1880) ==== ==== Discovery of the Malaria Parasite (1880) ====
  
-Charles Louis Alphonse Laveran, a French army surgeon stationed in Constantine,​ Algeria, was the first to notice parasites in the blood of a patient suffering from malaria. This occurred on the 6th of November 1880. For his discovery, Laveran was awarded the Nobel Prize in 1907 [7].+Charles Louis Alphonse Laveran, a French army surgeon stationed in Constantine,​ Algeria, was the first to notice parasites in the blood of a patient suffering from malaria. This occurred on the 6th of November 1880. For his discovery, Laveran was awarded the Nobel Prize in 1907 (Lambert, 2016).
  
 ==== Differentiation of Species of Malaria (1886) ==== ==== Differentiation of Species of Malaria (1886) ====
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-Camillo Golgi, an Italian neurophysiologist,​ established that there were at least two forms of the disease, one with tertian periodicity (fever every other day) and one with quartan periodicity (fever every third day). He also observed that the forms produced differing numbers of merozoites (new parasites) upon maturity and that fever coincided with the rupture and release of merozoites into the blood stream. He was awarded a Nobel Prize in Medicine for his discoveries in neurophysiology in 1906 [5].+Camillo Golgi, an Italian neurophysiologist,​ established that there were at least two forms of the disease, one with tertian periodicity (fever every other day) and one with quartan periodicity (fever every third day). He also observed that the forms produced differing numbers of merozoites (new parasites) upon maturity and that fever coincided with the rupture and release of merozoites into the blood stream. He was awarded a Nobel Prize in Medicine for his discoveries in neurophysiology in 1906 (Fagan, 2016).
  
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-The Italian investigators Giovanni Batista Grassi and Raimondo Filetti first introduced the names Plasmodium vivax and P. malariae for two of the malaria parasites that affect humans in 1890 [9]. Laveran had believed that there was only one species, Oscillaria malariae. An American, William H. Welch, reviewed the subject and, in 1897, he named the malignant tertian malaria parasite P. falciparum.+The Italian investigators Giovanni Batista Grassi and Raimondo Filetti first introduced the names Plasmodium vivax and P. malariae for two of the malaria parasites that affect humans in 1890 (Mandal, 2016). Laveran had believed that there was only one species, Oscillaria malariae. An American, William H. Welch, reviewed the subject and, in 1897, he named the malignant tertian malaria parasite P. falciparum.
  
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-On August 20th, 1897, Ronald Ross, a British officer in the Indian Medical Service, was the first to demonstrate that malaria parasites could be transmitted from infected patients to mosquitoes ​[7].  For his discovery, Ross was awarded the Nobel Prize in 1902.+On August 20th, 1897, Ronald Ross, a British officer in the Indian Medical Service, was the first to demonstrate that malaria parasites could be transmitted from infected patients to mosquitoes ​(Lambert, 2016).  For his discovery, Ross was awarded the Nobel Prize in 1902.
  
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-The malaria ​life cycle begins when the P. falcifarum sporozoites enter the bloodstream of the  human host from the Anopheles mosquito (Haldar, Murphy, Milner, Taylor, 2007) . The sporozoites are the stage in parasite development that is infectious to humans (“Anopheles Mosquitoes”,​ 2015), and they briefly circulate in the body upon entering the hepatocytes. ​In the hepatocytes, ​ the sporozoites undergo asexual reproduction for 10 to 12 days, after which the liver cells rupture and release merozoitestheir daughter cells (STAN) into the bloodstream (Haldar et al., 2007). These merozoites are non-motile and therefore likely interact with the erythrocytes by random collision (Wiser M.F., 2016). Although the exact mechanism of the entry into the erythrocyte is still not fully understood, it has been found that the merozoite surface proteins (MSPs), specifically MSP-1, interact with the glycoprotein band 3 on the red blood cells (Haldar et al., 2007). ​ A tight junction forms between the apical end of the merozoite and the erythrocyte,​ as the apical organelles as the apical membrane antigen-1 (AMA-1) interacts with the rhoptry neck proteins that are inserted into the host cells (Cowman, Berry, Baum 2012)+The malarial ​life cycle begins when the P. falcifarum sporozoites enter the bloodstream of the  human host from the Anopheles mosquito (Haldar, Murphy, Milner, Taylor, 2007) . The sporozoites are the stage in parasite development that is infectious to humans (“Anopheles Mosquitoes”,​ 2015), and they briefly circulate in the body upon entering the hepatocytes. ​Within ​the hepatocytes, ​ the sporozoites undergo asexual reproduction for 10 to 12 days, after which the liver cells rupture and release merozoites ​(their daughter cells) into the bloodstream (Haldar et al., 2007). These merozoites are non-motile and therefore likely interact with the erythrocytes by the occurrence of a random collision (Wiser M.F., 2016). Although the exact mechanism of the entry into the erythrocyte is still not fully understood, it has been found that the merozoite surface proteins (MSPs), specifically MSP-1, interact with the glycoprotein band 3 on the red blood cells (Haldar et al., 2007). ​ A tight junction forms between the apical end of the merozoite and the erythrocyte,​ as the apical organelles as the apical membrane antigen-1 (AMA-1) interacts with the rhoptry neck proteins that are inserted into the host cells (Cowman, Berry, Baum 2012)
 Once the merozoites have invaded the surrounding erythrocytes,​ they undergo asexual reproduction for the next two days. These merozoites then develop into ring stage trophozoites,​ the feeding or growing stage of the parasite development,​ as they feed off the host resources within this time (Haldar et al., 2007). The trophozoites then mature into schizonts, which develop into 16 to 32 daughter merozoites. These merozoites undergo another round of asexual reproduction,​ with some differentiating into female and male gametes. The gametes then can be ingested by the female mosquito, where they fuse and reproduces into infective sporozoites via sexual reproduction (Haldar et al., 2007). These sporozoites are then passed on to the next person at the female mosquitos’ next blood meal, and the cycle repeats. Once the merozoites have invaded the surrounding erythrocytes,​ they undergo asexual reproduction for the next two days. These merozoites then develop into ring stage trophozoites,​ the feeding or growing stage of the parasite development,​ as they feed off the host resources within this time (Haldar et al., 2007). The trophozoites then mature into schizonts, which develop into 16 to 32 daughter merozoites. These merozoites undergo another round of asexual reproduction,​ with some differentiating into female and male gametes. The gametes then can be ingested by the female mosquito, where they fuse and reproduces into infective sporozoites via sexual reproduction (Haldar et al., 2007). These sporozoites are then passed on to the next person at the female mosquitos’ next blood meal, and the cycle repeats.
  
 {{:​life_cycle_malaria.jpg|}} {{:​life_cycle_malaria.jpg|}}
  
-Figure 2: Life cycle of P.falciparum parasite. Retrieved from "The cellular and molecular basis for malaria+//Figure 2: Life cycle of P.falciparum parasite. Retrieved from "The cellular and molecular basis for malaria
 parasite invasion of the human red blood cell", Cowman A.F, Berry D, Baum J, 2012, //The Journal of Cell Biology//, //198//, p. 962. www.jcb.org/​cgi/​doi/​10.1083/​jcb.201206112 parasite invasion of the human red blood cell", Cowman A.F, Berry D, Baum J, 2012, //The Journal of Cell Biology//, //198//, p. 962. www.jcb.org/​cgi/​doi/​10.1083/​jcb.201206112
 +//
  
  
 ==== Transmission ==== ==== Transmission ====
  
-Malaria ​is transmitted ​through the female Anopheles mosquitoes. Anopheles mosquitoes can be identified through specific characteristics such as spotted wings, ​no buzzing sound, and when at rest it is inclined at 45 degrees to the surface. Only Anopheles mosquitoes can transmit malaria, and they must have been infected through a previous blood meal taken from an infected person. Since the malaria parasite is found in the red blood cells, malaria can also be transmitted through blood transfusions,​ organ transplants,​ or the use of shared syringes/​needles that are contaminated with blood. It can also be transmitted from a mother to her unborn baby before ​or during delivery. Malaria is not contagious, it cannot spread from casual contact from person to person and cannot be sexually transmitted. (Euroclinix,​ 2016)+Malaria ​parasites are transmitted ​to humans via female Anopheles mosquitoes. Anopheles mosquitoes can be identified through specific characteristics such as spotted wings, ​the absence of a buzzing sound, and when at rest their body is inclined at 45 degrees to the surface. Only Anopheles mosquitoes can transmit malaria, and they must have been infected through a previous blood meal taken from an infected person. Since the malaria parasite is found in the red blood cells, malaria can also be transmitted through blood transfusions,​ organ transplants,​ or the use of shared syringes/​needles that are contaminated with blood. It can also be transmitted from a mother to her unborn baby in utero or during delivery. Malaria is not contagious, ​meaning that it cannot spread from casual contact from person to person and cannot be sexually transmitted. (Euroclinix,​ 2016)
  
  
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 ==== Stages ==== ==== Stages ====
  
-There are three stages of a malarial infection: the initial cold stage, where the person feels cold and shivers; the following hot stage where the person develops a fever and may experience vomiting; and the final sweating stage, where the body temperature returns to normal and the individual experiences extreme tiredness. This entire experience lasts anywhere from 6 to 10 hours (“Malaria,​ 2015), which makes it very difficult to isolate the symptoms as a result of a malarial infection. If the infection is not treated within 24 hours, the person is at risk of their infection progressing to a severe stage, which could resul</​style>​t ​in death (“Malaria”,​ 2016).+There are three stages of a malarial infection: the initial cold stage, where the person feels cold and shivers; the following hot stage where the person develops a fever and may experience vomiting; and the final sweating stage, where the body temperature returns to normal and the individual experiences extreme tiredness. This entire experience lasts anywhere from 6 to 10 hours (“Malaria,​ 2015), which makes it very difficult to isolate the symptoms as a result of a malarial infection. If the infection is not treated within 24 hours, the person is at risk of their infection progressing to a severe stage, which could result ​in death (“Malaria”,​ 2016).
  
 ==== Severe Malaria ==== ==== Severe Malaria ====
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 ====== References ====== ====== References ======
  
 +  - "​Anopheles Mosquitoes"​. (2015). Retrieved November 22, 2016, from https://​www.cdc.gov/​malaria/​about/​biology/​mosquitoes/​index.html
   - CDC (2016). Impact of Malaria. Centers for Disease Control and Prevention. Retrieved from https://​www.cdc.gov/​malaria/​malaria_worldwide/​impact.html   - CDC (2016). Impact of Malaria. Centers for Disease Control and Prevention. Retrieved from https://​www.cdc.gov/​malaria/​malaria_worldwide/​impact.html
   - CDC (2015). Malaria: Disease. Centers for Disease Control and Prevention. Retrieved from http://​www.cdc.gov/​Malaria/​about/​disease.html   - CDC (2015). Malaria: Disease. Centers for Disease Control and Prevention. Retrieved from http://​www.cdc.gov/​Malaria/​about/​disease.html
   - Chua, C. L., Brown, G., Hamilton, J. A., Rogerson, S., & Boeuf, P. (2013). Monocytes and macrophages in malaria: Protection or pathology?​ Trends in    Parasitology,​ 29(1),​ 26-34. doi:​10.1016/​j.pt.2012.10.002   - Chua, C. L., Brown, G., Hamilton, J. A., Rogerson, S., & Boeuf, P. (2013). Monocytes and macrophages in malaria: Protection or pathology?​ Trends in    Parasitology,​ 29(1),​ 26-34. doi:​10.1016/​j.pt.2012.10.002
 +  - Cowman, A. F., Berry, D., & Baum, J. (2012). The cellular and molecular basis for malaria parasite invasion of the human red blood cell. The Journal of Cell Biology, 198(6), 961-971. doi:​10.1083/​jcb.201206112 ​
   - Euroclinix (2016). Malaria Transmission - Malaria Life Cycle. Retrieved 23 November 2016, from https://​www.euroclinix.net/​en/​travel-health/​malaria/​transmission   - Euroclinix (2016). Malaria Transmission - Malaria Life Cycle. Retrieved 23 November 2016, from https://​www.euroclinix.net/​en/​travel-health/​malaria/​transmission
   - Fagan, T. (2016). When was malaria first discovered and by whom? How is the disease transmitted?​ What are its effects?. Scientific American. Retrieved 28 November 2016, from https://​www.scientificamerican.com/​article/​when-was-malaria-first-di/​   - Fagan, T. (2016). When was malaria first discovered and by whom? How is the disease transmitted?​ What are its effects?. Scientific American. Retrieved 28 November 2016, from https://​www.scientificamerican.com/​article/​when-was-malaria-first-di/​
   - Gaillard, T., Madamet, M., & Pradines, B. (2015). Tetracyclines in malaria. Malaria journal,​ 14(1),​ 1.   - Gaillard, T., Madamet, M., & Pradines, B. (2015). Tetracyclines in malaria. Malaria journal,​ 14(1),​ 1.
 +  - Hadjiliadis,​ D. (2015). Acute respiratory distress syndrome: MedlinePlus Medical Encyclopedia. Retrieved November 22, 2016, from https://​medlineplus.gov/​ency/​article/​000103.htm ​
 +  - Haldar, K., Murphy, S. C., Milner, D. A., & Taylor, T. E. (2007). Malaria: Mechanisms of Erythrocytic Infection and Pathological Correlates of Severe Disease. Annual Review of Pathology: Mechanisms of Disease, 2(1), 217-249. doi:​10.1146/​annurev.pathol.2.010506.091913
   - Lambert, P. (2016). Malaria - History of Malaria. Nobelprize.org. Retrieved 28 November 2016, from https://​www.nobelprize.org/​educational/​medicine/​malaria/​readmore/​history.html   - Lambert, P. (2016). Malaria - History of Malaria. Nobelprize.org. Retrieved 28 November 2016, from https://​www.nobelprize.org/​educational/​medicine/​malaria/​readmore/​history.html
   - Malarone (Atovaquone and Proguanil Hcl) Drug Information:​ Clinical Pharmacology - Prescribing Information at RxList. (2016, October 26). Retrieved November 23, 2016, from http://​www.rxlist.com/​malarone-drug/​clinical-pharmacology.htm   - Malarone (Atovaquone and Proguanil Hcl) Drug Information:​ Clinical Pharmacology - Prescribing Information at RxList. (2016, October 26). Retrieved November 23, 2016, from http://​www.rxlist.com/​malarone-drug/​clinical-pharmacology.htm
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   - Tripathi, K. D. (2013). Essentials of medical pharmacology. JP Medical Ltd.   - Tripathi, K. D. (2013). Essentials of medical pharmacology. JP Medical Ltd.
   - Hemingway, J. & Bates, I. (2003). Malaria: past problems and future prospects. EMBO Reports,​ 4(Supp1),​ S29-S31. http://​dx.doi.org/​10.1038/​sj.embor.embor841   - Hemingway, J. & Bates, I. (2003). Malaria: past problems and future prospects. EMBO Reports,​ 4(Supp1),​ S29-S31. http://​dx.doi.org/​10.1038/​sj.embor.embor841
 +  - Wiser, M. F. (2016). Cell Biology of Plasmodium. Retrieved November 21, 2016, from http://​www.tulane.edu/​~wiser/​malaria/​cmb.html
 +  - Wiser, M. F. (2016). Plasmodium Life Cycle. Retrieved November 20, 2016, from http://​www.tulane.edu/​~wiser/​protozoology/​notes/​mal_lc.html ​
   - World Health Organization. (2006). Guidelines for the treatment of malaria. World Health Organization. Fagan, T. (2016). When was malaria first discovered and by whom? How is the disease transmitted?​ What are its effects?. Scientific American. Retrieved 28 November 2016, from https://​www.scientificamerican.com/​article/​when-was-malaria-first-di/​   - World Health Organization. (2006). Guidelines for the treatment of malaria. World Health Organization. Fagan, T. (2016). When was malaria first discovered and by whom? How is the disease transmitted?​ What are its effects?. Scientific American. Retrieved 28 November 2016, from https://​www.scientificamerican.com/​article/​when-was-malaria-first-di/​
   - World Health Organization. 2016. Malaria. [Fact sheet]. Retrieved from http://​www.who.int/​mediacentre/​factsheets/​fs094/​en/ ​   - World Health Organization. 2016. Malaria. [Fact sheet]. Retrieved from http://​www.who.int/​mediacentre/​factsheets/​fs094/​en/ ​
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