Yellow Fever Research Paper

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Flavivirus
Trey Burke
Grosse Pointe North High School

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Abstract
There are many diseases that flood our world today. One disease in particular that has been here since early exploration has left many dead and that is the yellow fever virus.
Once
yellow fever enters your system its like a bull ride. Once you get on you better hold on for dear life because surviving yellow fever is a rough road to endure. What makes this disease so mysterious that it can cause so much destruction yet ironically it start out with just a simple bite from a mosquito.

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Introduction
Yellow fever, “ an acute viral haemorrhagic disease transmitted by infected mosquitoes.
The "yellow" in the name refers to the jaundice that affects some patients.” (World Health
Organization, 2014) Several parts of the world have suffered from this virus. Yellow fever resides mostly in the tropical and warm climate areas of the world.
The majority of people who are infected with the disease are poor and can’t afford to pay for treatment so they eventually perish. According to World Health Organization, 50% of people who are infected with yellow fever and never get treated die. Yellow fever, although not a current major issue, has left a mark on the world and has taken millions of lives in its reign of terror.
History/Geography
Throughout history yellow fever has had multiple outbreaks across the world. The very first outbreak of yellow fever was recorded in 1648 in the Yucatan Peninsula of Mexico (Yellow
Fever, 2004). “In response to epidemics of yellow fever in Barbados, Cuba, and the Yucatan, a strict quarantine was established in Boston, Massachusetts, for all ships arriving from the West
Indies.” (The College of Physicians of Philadelphia, 2015). Sadly this did not stop the nation­wide spread of yellow fever in America. The disease first struck Philadelphia in 1793 and lasted for about four months. “
This outbreak killed about 10% of the city 's population, and thousands more fled, including an infected Alexander Hamilton and his wife. Dr.
Benjamin
Rush, who stayed, issued guidelines for avoiding infection and helped set up a "fever hospital" for victims.” (PBS, 2006) Moving forward in time the climax of the yellow fever in the United
States was in the Mississippi Valley. Between May 1878 and October 1878 approximately
20,000 people died to yellow fever (PBS, 2006). “Starting in New Orleans, this epidemic spread

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up the Mississippi Valley to Memphis.
More than half of the 47,000 residents of Memphis fled the city; more than 5,000 died that summer of yellow fever.” (PBS, 2006)
The first person to discover yellow was scientist Carlos Juan Finlay. The “
Cuban
epidemiologist who discovered that yellow fever is transmitted from infected to healthy humans by a mosquito .” (
The Editors of Encyclopædia Britannica
, 2014) Even though he made the discovery his ideas were ignored for 20 years. His ideas were finally brought to attention by a
American physician named Walter Reed. Through many experiments Finlay’s discoveries were finally proven to be correct. This discovery led to “ William Gorgas’ eradication of the disease in Cuba and
Panama
followed. Finlay was appointed chief sanitation officer of Cuba (1902–09), and after his death the Finlay Institute for Investigations in Tropical Medicine was created in his honour by the Cuban government.” (
The Editors of Encyclopædia Britannica
, 2014)
Yellow started off small but then gradually grew larger through time. Places where it is warm and tropical climate are common places where yellow fever is found. Africa is the
most common place to contract yellow fever. “The vast majority of cases and deaths take place in sub­Saharan Africa, where yellow fever is a major public health problem occurring in epidemic patterns.” (World Health Organization[WHO], 2015) Yellow fever is also a threat to multiple parts of Latin America. Countries such are Bolivia and Brazil are considered at the greatest risk of yellow fever. With no immunization coverage the infected mosquitoes can easily spread the disease to humans causing multiple deaths in populated urban areas. (World Health
Organization[WHO], 2015) The geography of yellow fever is not a coincidence yellow fever is found in the countries with many economical problems in society today.

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Moving forward there’s no evidence that proves yellow fever has a relation to a certain gender or ethnicity everyone is fair game to a mosquito bite.
Effects on Humans
Sylvatic yellow fever, also known as jungle fever, is when a monkey that carries the disease gets bitten by mosquito which then mosquitos transfer the disease to humans. Next we have Intermediate yellow fever. Intermediate yellow fever is when there are semi­domestic mosquitoes present in very populated area that contain the disease. This is different from sylvatic because the semi­domestic mosquito already carries the disease it does not contract it from monkeys it actually infects the monkeys as well as humans. (World Health Organization,
2014) The epidemic becomes more severe when this type of mosquito comes in contact with humans that don’t have the vaccine in a very populated area.
Finally we have urban yellow fever, the most devastating form. This is caused by the mosquito ,
Aedes aegypti, which found in the tropical areas such as South America, Africa, and the Caribbean. These mosquitoes are usually found in the jungle so when a person goes into jungle and gets bitten by one of the infected mosquitoes it’s dangerous.` This is because when the person comes back to the village he/she brings the virus over and now if the mosquitos the area bite the infected human they also carry the disease. Urban yellow fever can have a detrimental long term effect on cities and most populated areas. When a human being contracts yellow fever the likelihood of the development of symptoms is 5­20%(Yellow Fever, 2004).
According to The Gale Encyclopedia of Science, most of the symptoms of yellow are subclinical. (Yellow Fever, 2004) Therefore its very difficult to diagnose yellow fever. So in

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order to know if yellow fever is present you have to go to your doctor and take blood tests to find the viral infection. When you have yellow fever you grow five brutal stages. The first stage is the called the incubation stage. In the first three to six days is when the virus develops no symptoms are present in this stage. Next stage is called the period of invasion. In this stage the infected can experience fevers, chills, nausea, muscle ache, and extreme exhaustion (Lerner, 2004). Also “ the patient 's tongue shows a characteristic white furry coating in the center, surrounded by beefy red margins.”
(Yellow Fever, 2004) “While most other infections that cause an elevation in temperature also cause an increase in heart rate, yellow fever produces an unusual symptom, called Faget 's sign—the simultaneous occurrence of a high fever with a slowed heart rate.
Throughout the period of invasion, there are still viruses circulating in the patient 's blood stream, so continued viral transmission through mosquito vectors is possible.” (Yellow Fever, 2004)
According to World Health Organization, “
The majority of infections occur in young men working in the forest
.” (World Health Organization, 2014). The third period of yellow is called remission. In this stage the fever starts to die and symptoms begin to disappear. This sign can mean two things. One is that the fever is gone and the patient is cured. On the other hand, this could mean that this was just the beginning of the clinical course of the fever and the patient will experience the last two stages of yellow fever. The fourth stage of the disease is known as the intoxication. According to Lerner “ During this time, lasting three to nine days, a type of degeneration, or tissue breakdown, of the internal organs—specifically the kidneys,liver, and heart—occurs.” Also in this stage a person can also contract jaundice disease. This is when person has damage to the liver causing their skin and the whites of their eyes to tint yellow.

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When the liver is damaged it causes bleeding. When this happens it creates another symptom called black vomit. Black vomit is when you regurgitate blood. After this grotesque period we finally hit the final stage of convalescence which is the recovering period. This is when the infected become immune the virus and never can have it again.
Treatment/Cure
Yellow fever, unfortunately, has no cure however there are vaccines and treatments that help in fighting against the disease. To relieve some of the symptoms it is recommended to use acetaminophen. Avoid using products such as ibuprofen or aspirin these products can actually complicate the problem and make matters worse than what they already are. People who experience kidney failure during the stages of yellow fever usually are treated with dialysis. “
The
required management consists of vasoactive medications, fluid resuscitation, ventilator management, and treatment of disseminated intravascular coagulation, hemorrhage, secondary infections, and renal and hepatic dysfunction.
” (Busowski, 2014). Staying hydrated is key to fighting off yellow fever. “Dehydration, due to fluid loss both from fever and bleeding, must be carefully avoided. The risk of bleeding into the stomach can be decreased through the administration of antacids and other medications.” (Yellow Fever, 2004) Victims of yellows fever in the process can acquire hemorrhages. “
Hemorrhages may require blood transfusions, and kidney failure may require dialysis, a process that allows the work of the kidneys in clearing the blood of potentially toxic substances to be taken over by a machine that is outside of the body.” (Yellow Fever, 2004) It is recommended that “travelers should also take precautions against mosquito bites when in areas with yellow fever transmission. Travelers should get vaccinated for yellow fever before visiting areas where yellow fever is found.” (CDC, 2014)

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There is a vaccine available for the yellow fever. However there a few side effects that can occur after taking the vaccine. For example, common side effects would include aches, soreness, redness, and sometimes a fever. There are also severe conditions that can occur after taking the vaccine. According to CDC, allergic reactions, organ failure, and nervous system reactions can happen but they are extremely rare side effects so most of the time taking the yellow vaccine is completely reasonable and safe to use. According to the Gale Article on
Yellow Fever, 95% of patients who take the yellow fever vaccine are immune against the yellow fever and are able to live long prosperous lives.
Morphology/Pathology
Yellow fever is caused by the microbe flavivirus . The prefix “flavi” means yellow in latin so this is why yellow fever is called yellow due to the fact that the flavivirus causes skin to turn yellow. The flavivirus derives from the family of the
Flaviviridae
. The only way to contract this microbe is through being bitten by a mosquito or tick According to Encyclopedia
Britannica, the flavivirus is extremely small it has a diameter between 40 and 60 nanometers which is completely normal for a virus.
“The genome consists of nonsegmented single­stranded positive sense RNA.”
(Britannica, 2013) When a virus has positive sense genome it has ability to act as mRNA soon as it reaches the host cell. Therefore the virus it has the ability to spread rapidly than a negative sense genome. The process of yellow fever replication starts out with the vector invades the living host membrane. The capsid lands on the host cell membrane and deposits its single stranded positive sense RNA into the cytoplasm of the host cell The RNA attaches to the ribosomes which then creates RNA polymerase which is a type of protein. The RNA polymerase

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made a template of the virus and the template is create as negative sense. Now that the virus has a negative sense template it is now ready to replicate positive sense RNA, the original genome of the virus. These positive sense RNA are now coded for the capsid of the flavivirus and this process just keeps going on until the host is completely infected. This process is extremely fast so once a person is infected with the flavivirus it won’t take long for it to spread therefore it is extremely difficult to treat for it. The replication of this microbe is also the life cycle as well.
The flavivirus works on the lytic cycle. The lytic cycle is “the process in which a virus overtakes a cell and uses the cellular machinery of its host cell to reproduce. Copies of the virus fill the cell to bursting, killing the cell and releasing the viruses to infect more cells.” (Cox, 2000)
The shape of the flavivirus is icosahedral.
“An icosahedral virus is a virus consisting of identical subunits that make up equilateral triangles that are, in turn, arranged in a symmetrical fashion.” (Chepresov, 2015) This is popular of the virus shape because its the optimal capsid for a virus. This is because of the complexity of the shape provides the virus stability making it hard for the living host break/destroy the capsid so therefore its very hard to destroy the virus because of its shape. Within in the capsid we have the virus which is a very single stranded piece of
RNA. Ironically the genome itself is not stable as the capsid which is travels in. Single stranded
RNA can easily mutate into different forms of the flavivirus . So when the virus passes the living host cell membrane its almost near to impossible to for the immune system to fight/adapt to the virus because of the rapid mutations making it hard to code for a remedy to fight off the virus.
Issues and Solutions
Yellow fever . The origin of yellow derives from mosquitos. Mosquitoes, as you can see, are all over the place and very tiny so eradicating them is a hopeless cause. Therefore,

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attempting to eliminate yellow fever off the planet is impossible. However, “t he FDA is considering whether to approve the experimental use of genetically modified mosquitoes in the
Florida Keys to help stop the spread of dengue fever and other diseases.” (Allen, 2015) The dengue fever stems from the same microbe as the yellow fever, the flavivirus. They developed this idea when the
Aedes Aegypti started to became immune to the pesticides. The United States wasn’t the first ones to think of this idea of genetically modified mosquitoes.
“Experiments
already conducted in Malaysia, Brazil and the Cayman Islands have found that releasing bioengineered male mosquitoes can reduce the
A. Aegypti population by 90 percent.” (Allen,
2015) So with the arise of a new weapon against a similar disease to yellow fever we can assume that there will new remedies and treatments against yellow in the near future.
Third world countries, sad as it is, can’t recover because of diseases such as yellow running ramped. It is very discouraging to trade or to have any affiliations with a country that has multiple diseases. Not only do viruses like yellow isolate a country but also it destroys the financial stability of third world countries. People in places like Africa, South America, and the
Caribbean die in dozens everyday from yellow fever and the multiple other diseases which then decreases labor. With a decrease in labor it is really hard to revive the economy from a never­ending spiral of depression.
“Nearly all major urban centres in the American tropics have been reinfested with
Aedes aegypti and most urban dwellers are vulnerable because of low immunization coverage .” (World Health Organization, 2015) In a way, it’s like these countries were never meant to be successful. The majority of the diseases and viruses of the world, including yellow fever, originate from these areas of the world and they have been here for many centuries now. So it just makes a person wonder are there parts of the world that aren’t meant to

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be successful? Yellow has left a trail of knots that been here for centuries and now these countries have to unravel the knots all by themselves.
Conclusion
Currently there are no major outbreaks of yellow fever but that doesn’t mean this disease is dead it’s still out there. Yellow fever has left countries in ruin, killed millions, and there’s nothing we can really do about it. Like all other viruses, yellow fever is considered non­living which means it can’t be killed. We can only hope for a better future and in that future there will be a cure someday for this disease. For now all we can do to fight against this disease is to take the vaccine and stay hydrated. With simple things like that you can easily avoid the yellow fever virus and as well as keep the other people safe as well. Essentially I hope moving forward, people in the future start to become aware that third world countries aren’t just naturally primitive but more as though trapped. Trapped by the diseases that were already there before civilization occurred. None of these countries had a chance to thrived like the United States or the United Kingdom. Our world is evolving and now its time to revive these countries and enter a new world of civilization, united.

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References
Allen, G. (2015, January 28). Florida Health Officials Hope To Test GMO Mosquitoes This
Spring. Retrieved March 9, 2015, from NPR website: http://www.npr.org/blogs/health/2015/01/28/382168407/florida­health­officials­hope­to­t est­gmo­mosquitoes­this­spring
Busowski, M. T., & Robertson, J. L. (2014, May 2). Yellow Fever Treatment & Management
(M. R. Wallace, Ed.). Retrieved March 9, 2015, from Medscape website: http://emedicine.medscape.com/article/232244­treatment Carlos J. Finlay. (2014, May 28). Retrieved March 9, 2015, from Encyclopaedia of Britannica website: http://www.britannica.com/EBchecked/topic/207556/Carlos­J­Finlay
Authors are the editors of britannica
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