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This is Hallie's sandbox. Final Draft Starts Here The Evolution and Spread of Chikungunya Chikungunya virus is a mosquito transmitted disease that is clinically similar to dengue fever (Pialoux 2007). The name chikungunya is derived from a word in the Kimakonde language meaning “to become contorted”. This word describes the appearance of people who are infected with the disease. The evolution of chikungunya is very complex and dates farther back than research originally shows. It is an RNA virus that is in the alpha virus genus of the Togaviridae family. Chikungunya is one of three arboviruses that have evolved to escape enzooticity to become a human disease that can be spread in a mosquito to human to mosquito cycle (Morens 2014). Chikungunya has a single-stranded RNA genome around 12 kb (Chen 2013). Chikungunya may be a third-world disease as of now, but it is gaining speed across the world. The importance of tracing the evolution and adaptation of this virus is especially important right now because it could soon be detrimental to the world. Analysis of phylogenies suggest that the current strain of chikungunya forms three geographic lineages. These are the West African lineage, the East, Central and South African lineage and the Asian lineage. The most recent common ancestor of the Asian lineage is believed to have occurred early in the 1950s, though it is not certain when the lineage was introduced from Africa to Asia. It is also not clear if the mutations and structures that occurred in the Asian lineage happened before or after being introduced from Africa (Morens 2014). The epidemiology of chikungunya is related to mosquitoes, their environments and human behavior. The adaptation of mosquitoes to the changing climate of North Africa around 5,000 years ago made them seek out environments where humans stored water. Human habitation and the mosquitos’ environments were then very closely connected (Pialoux 2007). During periods of epidemics humans are the reservoir of the virus. During other times, monkey, birds and other vertebrates have served as reservoirs (Pialoux 2007). Usually, chikungunya begins as a fever accompanied by muscle and joint pains, swollen lymph nodes and occasionally a rash. Relapsing and devastating arthritis is the stamp of a case of chikungunya. The symptoms may continue for up to several months (Pialoux 2007). A diagnosis based on isolation of the virus is very sensitive. It can only be detected during the viraemic phase. This phase occurs within forty eight hours but then disappears within four days. Reverse transcriptase polymerase chain reaction is the most sensitive and efficient means of detection that is currently available (Jain 2008). The understanding of chikungunya and its evolution is very important due to the current epidemic of the disease that has the great potential to spread. Europeans became involved in the West African slave trade that began 500 years ago and spread the mosquitoes that carried chikungunya at the time, Ae. aegypti, across the world. Chikungunya has caused periodic epidemics in tropical regions over the past several decades. The phylogenetic evidence supports the idea that chikungunya started and evolved in Africa, and then developed into related West African and South African clades. It is believed that chikungunya showed up in Asia and the Americas more than two centuries ago. Three genotypes of Chikungunya are defined. These are the West African, East/Central/South African also called the ECSA, and Asian genotypes. Analysis of phylogenies has showed that the ECSA genotype was responsible for the epidemics on the islands in the Indian Ocean (Morrison 2014). In the 1820s, an illness with symptoms resembling those of chikungunya occurred in Africa, the Caribbean and India. It was thought that this disease had originated in Africa and spread to India though slaves. In the city now known as Kolkatta in India, 95% of their population was affected by this disease. Then, in the 1850s 75% of Kolkatta’s population was affected with the same symptoms (Ching 2010). For a third time, in 1923, India reported yet another outbreak of the same symptoms. At the time of the outbreaks it was believed to be dengue fever because little was known about chikungunya. This changed in the 1950s when the emergence of chikungunya became clear (Morens 2014). The first outbreak, that was called chikungunya, occurred in 1952 in Tanzania. After this case, many other cases were reported in numerous countries in western, central and southern Africa, south Asia and Southeast Asia. The largest pandemic is the current spread from east Africa to Southeast Asia that started in 2004 (Ching 2010). During the epidemics in Africa and Asia it was known that the virus was spread by mosquitos. The virus was usually maintained in a cycle that involved primates, rodents, and forest mosquitos. It was then introduced into urban areas where domestic mosquitos reside. In Africa, the cycles are mostly sustained by Ae. africanus in east Africa and Ae, codellieri in South Africa. In the urban epidemics, Ae. aegypti is to blame. Ae. aegypti is also the primary vehicle of transmission in Asia (Chen 2013). During the time that it spread across the Indian Ocean it gained gene mutations that gave rise to the Indian Ocean Lineage of the disease. Distinctive molecular features were identified. In the region that codes for non-structural proteins, over ten of the amino acid changes were identified (Schuffenecker 2006). Because of these mutations another vector called Ae. albopictus, was able to transmit the virus (Morens 2014). This is now the major vector in Cameroon, Thailand and Malaysia. It is obvious that a shift in the major vehicle of transmission evolved as the virus spread from Africa across continents wildly. In a study done on the host alternation of chikungunya virus, it was found that there was a positive correlation between adaptability and genetic diversity. The most diverse mutants were the best at escaping antibodies (Coffey 2010). The strains of evolution on arboviruses are caused by the need to fulfill criteria for both the host and the vector. There is a low evolutionary rate of the virus because the two part system requires so much. These low evolutionary rates compare similarly to those of dengue fever as well as equine encephalitis virus. This two part host contrasts largely with that of the single-host viruses such as influenza (Konstantine 2013). A low mutation rate is also observed in this virus, but the gradual changes in genes has driven the change in the epidemiology of the virus. One mutation found is the E1-A226B substitution (Ching 2010). This mutation has enhanced the transmissibility of the virus. The mutation is seen in Ae. albopictus which may be the reason for a large number of outbreaks in the tropical region that started in 2004 (Ching 2010). Evolutionary convergence is rarely seen in nature (Lamballerie 2008). Since the move of Ae. albopictus from Asia to Europe and then to the Americas was the result of trading and traveling by humans, this shows how viruses can evade the impact of human interference (Lamballerie 2008). It was found that this mutation also shortens the incubation period of the virus. Combined, this is likely why the epidemic potential has continued to rise, even though the Asian lineage is not thriving as well. The Asian lineage is seen to be inferior to its ancestor in Africa. This suggests that the Asian lineage was not a result of directional selection. Instead, scientists believe that it may have come from a population bottleneck when being introduced from Africa to Asia. The introduction of this strand that had deletions led to genetic drift and mutations. It is believed that these strains that are results of the founder effect have reduced fitness and therefore limit the potential for an epidemic in Asia (Chen 2013). Adaptations to environmental factors may also be to blame for the wide urban spread of the virus. For example, in Kenya where the current pandemic started in 2004, it was seen that there were harsh drought conditions. Some scientists believed that the sporadic renewal of water supplies and the high temperature may be to blame for the increased virus transmission. They based some of this off of the fact that in countries with increased temperature change, dengue transmission grew (Ching 2010). Another study showed that Ae. aegypti larva that were shocked with heat grew into adults mosquitos that were tolerant to high temperatures. These two examples display that the increased temperatures and likelihood for mosquito breeding grounds could have easily caused the current pandemic that began in Africa (Ching 2010). What is unclear about these epidemics is why it takes around 4-5 decades between each to occur. At this time, it is not certain whether the fairly large time interval is due to the time required to build up a population that is vulnerable to the disease or if it is due to other factors that have yet to be discovered (Jain 2008). Because it is a relatively new disease to the world of research and is very complex, the patterns of chikungunya occurrence and reoccurrence are not completely understood. The expanding epidemic of the virus in populations that were not previously exposed makes it hard to be optimistic about the situation. It is not believed that the chikungunya virus was ever established in the Western Hemisphere. Because of this, it is a great possibility that it may become established in the near future (Morens 2014). The mutations and adaptions talked about before have made it much easier for reproduction in the gut of the mosquito. This greatly increases the chance of the virus being transmitted as long as the mosquito is biting. Ae. albopictus has been spreading across the world for the past twenty years (Enserink 2013). Examples of different control measures taken are given in response to an outbreak in Ravenna, Italy in 2007. A surveillance system for Ae. albopictus was set up in the region. Other control measures include insecticides in public and private areas. Organ and tissue donation was put on hold (Angelini 2007). Currently, treatments are given individually based on different symptoms. If arthritis persists, 250 mg of chloroquine per day has shown to be beneficial (Jain 2008). Antibody treatments along with vaccines for the chikungunya virus are in the early stages of testing (Angelini 2007). In 2010, the National Institute of Allergy and Infectious Disease tested an experimental vaccine for chikungunya on nonhuman primates. It was concluded that the vaccine protected the animals from the virus. It was later tested on 25 human volunteers. It was stated that “the candidate vaccine prompted a robust immunological response in recipients and was very well tolerated” (NIH 2014). Though this gives hope of prevention and a cure, it is a fact that officials will be challenged when deciding who to vaccinate. For this reason, the threat of an epidemic occurring now in the Western Hemisphere should not be met with the hope of a vaccine. Instead, public health and mosquito control must be put into place. In the last decade, Chikungunya has reemerged as a huge threat to public health on a global level (Morrison 2014). Together, the multiple facts shown by studies brought up in this paper are all important in understanding the evolution of Chikungunya. They showcase the significance of studying arbovirus transmission (Coffey 2010). The different molecular features that have continued to evolve and adapt in this virus shows that it has high evolutionary potential and the understanding of these allows us to understand the virulence of these outbreaks (Schuffenecker 2006). The understanding of the evolution, mutations and adaptation of the virus is crucial to the advancement of work being done to find a vaccine, antiviral compounds, and other drugs. Works Cited Angelini, R. 2007 September. An outbreak of chikungunya fever in in the province of 	Ravenna, Italy. Eurosurveillance. Retrieved 23 October 2014. Chang, LJ. 2014 August. Chikungunya Vaccine Shows Promise. NIH Research Matters. Retrieved November 12, 2014. Chen, R. 2013 August. Chikungunya Virus 3′ Untranslated Region: Adaptation to 	Mosquitoes 	and a Population Bottleneck as Major Evolutionary Forces. PLOS: Pathogens. Retrieved 	September 14, 2014. Ching, L. 2010 October. Tracing the path of Chikungunya virus-Evolution and adaptation. ScienceDirect. Retrieved September 14, 2014. Coffey, Lark. 2010 November. Host Alternation of Chikungunya Virus Increases Fitness while 	Restricting Population Diversity and Adaptability to Novel Selective Pressures. Journal of	 Virology. Retrieved November 12, 2014. Enserink, Martin. 2013 July. Chikungunya: No Longer a Third World Disease. NewsFocus. Retrieved September 14, 2014. Jain, Manisha. 2008. Chikungunya: a review. Tropical Doctor. Retrieved October 20, 2014. Konstantine, T. 2013 December. Multi-peaked adaptive landscape for chikungunya virus 	evolution predicts continued fitness optimization in Aedes albopictus mosquitoes. NatureCommunications. Retrieved September 14, 2014. Lamballerie, Xavier. 2008 February. Chikungunya virus adapts to tiger mosquito via evolutionary 	convergence: a sign of thins to come? Virology Journal. Retrieved November 12, 2014. Morens, D. 2014 September. Chikungunya at the Door - Déjà Vu All Over Again? — NEJM. Retrieved September 14, 2014. Morrison, Thomas E. 2014 July. Reemergence of Chikungunya Virus. Journal of Virology. Retrieved November 12, 2014. Pialoux, Gilles. 2007 May. Chikungunya, an epidemic arbovirus. ScienceDirect. Retrieved 	October 25, 2014. Schuffenecker, Isabelle. 2006 May. Genome Microevoluton of Chikungunya Causing the Indian Ocean Outbreak. PLOS Medicine. Retrieved November 12, 2014.

October 1st Edit https://en.wikipedia.org/wiki/Chikungunya Three suggestions for "Vaccine" and "Treatment" sections: The "Vaccine" section can be updated with new information given by The New England Journal of Medicine. The "Treatment" section is short and needs work. There are no medicines to completely abolish the virus, but there are other treatments available than what is mentioned, such as traditional herbal remedies. Though I read that some do not agree with homeopathic remedies, I believe it is worth it to add them to the page so that the information is available whether it is used or not. Also, under "Treatment" it might be wise to add the harmful effects of chloro quine since it is a treatment that is mentioned.

Sentences added to page + citation: If a vaccine becomes available, public health officials will then have to decide who should be vaccinated and under what conditions a vaccination is necessary. The unpredictable and fast moving nature of chikungunya would make it difficult to control with a vaccine alone after it has already been spread. Because of this, it is important that astute clinicians diagnose and report the disease immediately after it occurs. [55]

Morens, D. (2014, September 1). “Chikungunya at the Door - Déjà Vu All Over Again?” — 	NEJM. Retrieved September 14, 2014.