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Edits to pages
https://en.wikipedia.org/wiki/Malaria#Other_methods In the case of Thalassemia, the disorder is due to a reduction in the production of hemoglobin caused by multiple mutations. That defect in the hemoglobin make a malformed red blood cell unable to carry oxygen properly. The defected cells are destroyed along with the parasite by the immune system. In the case of thalassemia, both homozygous and heterozygous individuals gain benefits from the mutation.

Final draft starts here
Each year, approximately one million of deaths and over three hundred millions of cases are reported around the globe due to malaria, a disease caused by Plasmodium. Today, the illness is endemic to more than ninety countries, but scientific reports state that thousands of years ago, it might have been endemic to almost the whole planet. Records of the disease have been found in manuscripts of ancient civilizations such as Greek, Chinese and Egyptians. Knowing that other old pathogens as deadly as the malaria one had affected the human race, but at the end were eradicated, the question of how malaria has managed to stay so long constantly resurfaces. The evolutionary impact of that question is to have a better view of the relationship between humans and plasmodium and a better understanding of how they co-evolved for so long despite the impacts they have on each other. Therefore, let’s first try to understand the phenomenon of parallel evolution between plasmodium and human on the historical and physical level and then, try to understand it at a more genetic level.

Plasmodium is the genus of the protozoan parasite at the origin of the disease called malaria. Different species in this genus include: Plasmodium falciparum, Plasmodium ovale, Plasmodium knowlesi and Plasmodium vivax. The discovery of the parasite was made in 1898 by Alphonse Laveran, and has helped us track back the parasite in history. Experiments conducted on some chimpanzees and bonobos of Africa have shown that the most dangerous Plasmodium affecting humans, Plasmodium falciparum, came from bonobos ( Krief et al., 2010). This led to an understanding of how Plasmodium made its entry into the human lineage, knowing that humans branched out of apes according to the evolutionary tree. We can then conclude that the theory stating that individuals of related species are affected similarly by the same pathogen, is right. More historical studies have shown that the variations of species of Plasmodium we have today were either due to the location of the individual they affected, climate, and species of mosquito ( the vector of the parasite) they used. Studies have shown a huge genetic diversity among P. Vivax in America only (Taylor et al., 2013). We were more able to record the presence of Plasmodium Vivax in the northern occidental part of the earth ( Europe and America) while Plasmodium falciparum seems restricted to the tropical and subtropical regions. The change in climate those last years, has restructured the distribution of the parasite species, moving it from colder and dry regions to more humid and hot regions. The shift in the distribution can be correlated to the mosquitoes that transport the parasites, requiring some standing water to reproduce. Studies conducted all over Africa, showed that variance between rainfalls and human population growth was directly related to an increase in malaria incidence (Mouchet et al., 1998). That supports the reason why malaria is more recorded in extremely populated countries that are in humid regions. Most of those countries are underdeveloped with lack of education, infrastructures, proper hygienic habits. Due to those factors, there is always the perfect nest around people’s houses for mosquitoes to reproduce. Those nests can be from as ordinary as water standing in holes on roads after a rain or water in a buckets around houses to something as large as ponds or lakes. Due to the lack of education and sometime ignorance, people exposed to those risky factors fail to properly protect themselves or ever underestimate the consequences on their healths. However, despite that risky way of living, it has been noticed that people living in malaria endemic regions don’t realize the virulence of the pathogen and neither do they get terribly affected by the disease. How does that happen? Result of the frequent interaction between human and Plasmodium has lead to one of the consequences of evolution: resistance. Resistance has been so far one of the best explanation of the co-evolution of both species for so long. Resistance has been seen from the human side as much as from the parasite side. Every population have a genetic variation. Depending on the impact, the stress or the factor the individuals of the population are exposed to, some genes allow them to handle situations better than others. Over time, the favored gene have a greater frequency among the population and that is where the topic about natural selection takes form. Studies on populations of regions where malaria is endemic have shown a greater presence of red blood cell recessive disorders( hemoglubinopathy) that are assumed to make individuals less prone to the disease. Those disorders are genetic and are: Sickle-cell trait, Thalassemia and the absence of the Duffy protein. In order to understand how those disorders give immunity to malaria, it is necessary to give a background of their biological descriptions. Researches in Uganda, a malaria endemic region of East Africa, have shown up to half of the population being sickle cell carriers compared to America where only 8% of the population are carriers (Gong et all., 2013). Sickle-cell anemia is a genetic recessive red blood cell disorder in which cells have a sickle shape instead of the normal doughnut shape. It is the result of a single mutation amino acid mutation ( Glutamine to Valine) at the sixth position of the beta globin gene of the hemoglobin. The mutation leads to an abnormal hemoglobin structure which then leads to the malformed ( sickle ) shape of the red blood cell. Because of that abnormal shape, erythrocytes are not able to move easily through blood vessels and cannot assume their roles of oxygen transporters in the body. They mostly get stuck, agglutinate and block blood flow. The homozygote (HbS) individuals for the malformation have a short life expectancy due to organs damage while the heterozygous ( HbAS) gain some type of protection against blood infections such as malaria. The protection is first due to the tendency of the body to detect any malformed erythrocyte and destroy it, destroying the parasite at the same time. But also, the malformed shape of the cell doesn’t allow it to hold properly onto its nutrients so, due to nutrients leakage, the parasite die of starvation even in cases where it successfully enter the cell’s cytoplasm. However, as stated before Sickle-cell disease is not the only response to selection that the human kind have developed. Thalassemia is another genetic recessive red blood cell disorder. It is the result of the reduced production of hemoglobin protein in red blood cells. Hemoglobin is made from four subcomponents. These components are: two alpha globins and two beta globins. Different genes located on chromosome 11 and 16 are responsible for the production of the right subcomponents of hemoglobin. Unlike sickle cell disorder where the abnormality is due to a single mutation, Thalassemia is due to a mutation in one or many of the genes. Just like in the case of sickle cell, the parasite is destroyed through the process of the body destroying abnormal cells or through starvation due to the cell leaking its nutrients. In a study made on residents in 13 villages at different altitudes in Tanzania, it was observed that the lower the altitude, the higher was the carriage rate of thalassemia ( Eneyold et al., 2007). Knowing that mosquitoes, the vector of plasmodium, are more prevalent in lower altitudes than higher altitudes, the results obtained gives a good explanation of the association of thalassemia to malaria. Meanwhile, means of resistance other than the abnormalities of hemoglobin has been detected. In order to invade the red blood cell, malarial parasites bind to multiple receptors on the erythrocyte’s surface. The Duffy protein is a cell receptor protein involved in the invasion of red blood cell by Plasmodium vivax. In over 95% of the West African population, it has been found that individuals were negative for the gene coding for the protein ( Langhi et al., 2006); this was correlated to the eradication of P. vivax from the population as well. While humans have developed some effective ways to resist the Plasmodium parasite, the parasite itself has evolved ways to be less affected and be more effective in its invasion. Many drugs have been developed in order to fight malaria. Quinine was the first developed drug against the parasite. Most of the different species of Plasmodium have since developed resistance against quinine, but it remains the leading protection in the war against the disease. In the case of the virulent P. falciparum, the resistance has been related to the presence of some vacuoles on in the parasite membrane, allowing the parasite to reject the drug as fast as it enters its intracellular environment (Le Bras et al., 2003). According to an experiment in Ethiopia, P. falciparum and P vivax were still observed in patients treated with malarial drug chloroquine and sulfadoxine-pyrimethamine. Greater analysis of the parasites revealed the presence of Pfmdr1, Pfcg2 and Pfcrt genes that are involved in the resistance pathway (Schunk et al., 2006). As much as humans, those parasites seem to be able to generate resistance and their short life cycle might be a great advantage to help them with that. Also, it needs to be accentuate that within each species of Plasmodium, there is a big genetic variation making them having different effect on their hosts. Humans and plasmodium have evolved together for thousands of years. Since then, malaria has been ruling out billions of human lives while humans have been trying their best to fight back. With the help of climate change, evolution and research, humans have developed physical, biological and genetical protection against the disease. Part of those protections are drugs and red blood cells disorders such as: thalassemia and sickle cell gene. In parallel, the parasite has been able to develop resistance to the drugs it has been exposed to, but no records of resistance to the human genetic mutation have been found yet. The interaction between the two species is a good example of evolution through natural selection and its consequence on gene’s frequency due to exposure to certain conditions. However, the results of the interaction between humans and plasmodium do not seem to be over and might lead in the future to new inquiries in case plasmodium evolves resistance to the genetic barrier of the humans. �

References for paper
1- Krief, Sabrina, Ananias A. Escalante, M. Andreina Pacheco, Lawrence Mugisha, Claudine André, Michel Halbwax, Anne Fischer, Jean-Michel Krief, John M. Kasenene, Mike Crandfield, Omar E. Cornejo, Jean-Marc Chavatte, Clara Lin, Franck Letourneur, Anne Charlotte Grüner, Thomas F. McCutchan, Laurent Rénia, and Georges Snounou. "On the Diversity of Malaria Parasites in African Apes and the Origin of Plasmodium Falciparum from Bonobos." PLoS Pathog 6.2 (2010): n. pag. National Center for Biotechnology Information. U.S. National Library of Medicine, 12 Feb. 2010. Web. 29 Oct. 2014.

2- Anders Enevold, Michael Alifrangis, Juan J. Sanchez, Ilona Carneiro, Cally Roper, Claus Børsting, John Lusingu, Lasse S. Vestergaard, Martha M. Lemnge, Niels Morling, Eleanor Riley, and Chris J. Drakeley. “Associations between α+-Thalassemia and Plasmodium falciparum Malarial Infection in Northeastern Tanzania.” J Infect Dis. (2007) 196 (3): 451-459. Oxford Journals. Web. 21 Oct. 2014.

3- Gong, Lauren, Sunil Parikh, and Bryan Greenhouse. "Biochemical and Immunological Mechanisms by Which Sickle Cell Trait Protects against Malaria." Malaria Journal 12.317 (2013): n. pag. Malaria Journal. 11 Sept. 2013. Web. 29 Oct. 2014.

4- Langhi, DM, and JO Bordin. "Duffy Blood Group and Malaria." PubMed 11.5 (2006): 389-98. National Center for Biotechnology Information. U.S. National Library of Medicine, Oct. 2006. Web. 29 Oct. 2014.

5- Le Bras, J., and R. Durand. "The Mechanisms of Resistance to Antimalarial Drugs in Plasmodium Falciparum." Fundam Clin Pharmacol 17.2 (2003): 147-53. National Center for Biotechnology Information. U.S. National Library of Medicine, Apr. 2003. Web. 25 Oct. 2014.

6- Schunk, M., K. Wondimagegn, I. Miranda, M. Osman, S. Roewer, A. Alano, T. Loscher, Ulrich Bienze, and F. Mockenhaupt. "High Prevalence of Drug-resistance Mutations in Plasmodium Falciparum and Plasmodium Vivax in Southern Ethiopia." Malaria Journal 5.54 (2006): n. pag. Malaria Journal. Web. 27 Oct. 2014.

7- Mouchet, J., S. Manguin, J. Sircoulon, S. Laventure, O. Faye, A. Onapa, P. Carnevale, J. Julvez, and D. Fontenille. "Evolution of Malaria in Africa for the past 40 Years: Impact of Climatic and Human Factors." J Am Mosq Control Assoc 14.2 (1998): 121-30. National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 29 Oct. 2014.

8- Taylor, JE, MA Pacheco, and DJ Bacon. "The Evolutionary History of Plasmodium Vivax as Inferred from Mitochondrial Genomes: Parasite Genetic Diversity in the Americas." Mol Biol Evol 30.9 (2013): n. pag. National Center for Biotechnology Information. U.S. National Library of Medicine, 30 Sept. 2013. Web. 29 Oct. 2014.

Assignment October 14th
link to response: https://en.wikipedia.org/wiki/User_talk:I_dream_of_horses#Your_message_to_me

Assignment October 1st
Link to article: https://en.wikipedia.org/wiki/Plasmodium#Evolution

--Daouda.1 (talk) 04:04, 1 October 2014 (UTC)3 suggestions--Daouda.1 (talk) 04:04, 1 October 2014 (UTC)


 * I would like to see more info on the influence of Plasmodium on the human genome. We know that humans and plasmodium have been evolving together for quite a while so, what are the resistance made by he human body to stand the illness? Some research have lead to the increase in Sickle gene in population where malaria is still endemic.
 * Another suggestion is to improve the history behind the evolution of the parasite as of: how and when each type of Plasmodium ruled out many human lives.
 * A last suggestion is to talk about the multiple attempts and weapons used to eradicate the disease ( malaria) caused by Plasmodium in humans; such as DDT and their effects.

--Daouda.1 (talk) 04:04, 1 October 2014 (UTC)1 sentence + citation--Daouda.1 (talk) 04:04, 1 October 2014 (UTC)

Sickle hemoglobin confers survival advantage to those living in area where malaria is endemic; the infection of the parasite is less harmful to them

Ferreira, Ana, Ivo Marguti, Ingo Bechmann, Viktoria Jeney, and Angelo Chora. "Sickle Hemoglobin Confers Tolerance to Plasmodium Infection." 145.3 (2011): 398-409. CellPress. 29 Apr. 2011. Web. 30 Sept. 2014.

Topics
Topic: how did humans and malaria co-evolved over centuries despite being enemies

1- Shah, Sonia. The fever: How Malaria Has Ruled Humankind For 500,000 Years. New York: Picador, 2010. Print.

Shah's book is taking us to her trip of learning about Malaria. she teleport us between the past, the preset ans sometime the future, to give a better understanding of how the parasite has evolve, got linked to human and is still making ravage.

2- Carter, Richard, and Kamini Mendis. "Evolutionary and Historical Aspects of the Burden of Malaria." American Society of Microbiology (2002): 564-94. Web. 14 Sept. 2014.

I describe the evolution and history of malaria. Being one of the oldest disease in the world, it is still rising it's victim's bar.

3- Molina-Cruz, Alvaro, and Carolina Barillas-Mury. "The Remarkable Journey of Adaptation of the Plasmodium Falciparum Malaria Parasite to New World Anopheline Mosquitoes." National Center for Biotechnology Information. U.S. National Library of Medicine, Aug. 2014. Web. 14 Sept. 2014.

4- Instituto Gulbenkian de Ciencia. "Mystery solved: How sickle hemoglobin protects against malaria." ScienceDaily. ScienceDaily, 29 April 2011. .

This article discuss of how sickle hemoglobin protects against malaria and might inspire new cure to fight the disease.

5- Kwiatkowski, Dominic P. "How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria." The American Journal of Human Genetic (2005): 171-92. National Center for Biotechnology Information. U.S. National Library of Medicine, 06 July 2005. Web. 15 Sept. 2014.

It discuss the effect of malaria on human genome, creating resistance strains.