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Yellow Fever

TEM micrograph: Multiple yellow fever virions ...
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Definition:
Yellow fever (also called yellow jack, black vomit or sometimes American Plague) is an acute viral disease. It is an important cause of hemorrhagic illness in many African and South American countries despite existence of an effective vaccine. The yellow refers to the jaundice symptoms that affect some patients.It is a viral infection transmitted by mosquitoes.

Yellow fever is a viral hemorrhagic fever caused by the yellow fever virus. The yellow fever virus is a single-stranded enveloped virus that belongs to the flavivirus group. The disease can result in mild symptoms or severe illness and death (mortality rate 5-70%). Yellow fever derives its name from the yellowing of the skin and whites of the eyes (jaundice) that occur in some people infected with the virus. Jaundice is caused by the presence of bile pigment (bilirubin) in the bloodstream and results from damage to liver cells (hepatocytes) during severe infection.…click & see

The yellow fever virus infects mainly monkeys and humans: monkeys are the animal reservoir. Infection is transmitted from human to human, monkey to monkey, monkey to human, and human to monkey by daytime-biting mosquitos. Several species of Aedes and Haemoagogus mosquitos can serve as vectors, transmitting the virus during a blood meal.

Three types of transmission cycles exist for yellow fever: sylvatic (jungle), intermediate and urban. Although all three transmission cycles occur in Africa, only sylvatic and urban transmission cycles occur in South America.

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Sylvatic yellow fever (monkey to human)

* Occurs in monkeys infected by wild mosquitos in tropical rainforests

* Infected monkeys pass the virus to mosquitos during feeding
* Infected wild mosquitos bite humans entering the rainforest (accidental infection)

Intermediate yellow fever (monkey to human; human to monkey)
* Small-scale epidemics that occur in humid or semi-humid grasslands of Africa
* Separate villages experience simultaneous infections transmitted by semi-domestic mosquitos that infect both monkey and human hosts
* Most common type of outbreak in Africa

Urban yellow fever (human to human)

* Large epidemics occurring when the virus is introduced into high human population areas by migrants
* Domestic mosquitos of one species (Aedes aegypti) transmit the virus from person to person
* Monkeys are not involved in transmission
* Outbreaks spread from one source to cover a wide area

Yellow fever has been a source of several devastating epidemics. Yellow fever epidemics broke out in the 1700s in Italy, France, Spain, and England. 300,000 people are believed to have died from yellow fever in Spain during the 19th century. French soldiers were attacked by yellow fever during the 1802 Haitian Revolution; more than half of the army perished from the disease. Outbreaks followed by thousands of deaths occurred periodically in other Western Hemisphere locations until research, which included human volunteers (some of whom died), led to an understanding of the method of transmission to humans (primarily by mosquitos) and development of a vaccine and other preventive efforts in the early 20th century.

Despite the costly and sacrificial breakthrough research by Cuban physician Carlos Finlay, American physician Walter Reed, and many others over 100 years ago, unvaccinated populations in many developing nations in Africa and Central and South America continue to be at risk. As of 2001, the World Health Organization (WHO) estimates that yellow fever causes 200,000 illnesses and 30,000 deaths every year in unvaccinated populations.

Causes :-
Yellow fever is caused by a small virus that is spread by the bite of mosquitoes. This disease is common in South America and in sub-Saharan Africa.

……………You may click to see pictures of  mosquitoes  causing yellow fever.….

Anyone can get yellow fever, but the elderly have a higher risk of severe infection. If a person is bitten by an infected mosquito, symptoms usually develop 3 – 6 days later.

Yellow fever has three stages:
1.Early stage: Headache, muscle aches, fever, loss of appetite, vomiting, and jaundice are common. After approximately 3 – 4 days, often symptoms go away briefly (remission).

2.Period of remission: After 3 – 4 days, fever and other symptoms go away. Most people will recover at this stage, but others may move onto the third, most dangerous stage (intoxication stage) within 24 hours.

3.Period of intoxication: Multi-organ dysfunction occurs. This includes liver and kidney failure, bleeding disorders/hemorrhage, and brain dysfunction including delirium, seizures, coma, shock, and death.

Symptoms :-
*Arrhythmias, heart dysfunction
*Bleeding (may progress to hemorrhage)
*Coma
*Decreased urination
*Delirium
*Fever
*Headache
*Jaundice
*Muscle aches (myalgia)
*Red eyes, face, tongue
*Seizures
*Vomiting
*Vomiting blood

Although viral replication begins in cells at the site of the mosquito bite, symptoms of infection are not usually noted for a period of three to six days when the acute phase of infection presents. Acute yellow fever infection is characterized by high fever, muscle pain, backache, headache, shivers, loss of appetite, nausea and/or vomiting. Most people infected improve after three to four days.

However, within 24 hours of the disappearance of symptoms, up to 15% of those infected enter a toxic phase during which fever resumes, and the yellow fever virus quickly spreads to the kidneys, lymph nodes, spleen, bone marrow and liver. Liver invasion of one of the last stages to occur: as the liver is increasingly damaged, patients develop jaundice as bilirubin is released from damaged liver cells, experience abdominal pain and vomiting, and develop coagulopathies (inability of the blood to clot) characterized by bleeding from the mouth, nose, eyes and stomach, and presence of blood in vomit and stool. Up to 50% of people who enter the toxic phase die within two weeks of infection.

Diagnosis:-
Yellow fever may be difficult to diagnose, especially during the early stages, and may be confused with malaria, typhoid, other hemorrhagic fevers (dengue, Rift Valley, Venezuelan, Bolivian, Argentine, Lassa, Crimean-Congo, Marburg and Ebola), rickettsial infection, leptospirosis, viral hepatitis, other causes of liver failure and toxic hepatitis (e.g. carbon-tetrachloride poisoning).

Exams and Tests
A person with advanced yellow fever may show signs of liver failure, renal failure, and shock.

If you have symptoms of yellow fever, tell your doctor if you have traveled to areas where the disease is known to thrive. Blood tests can confirm the diagnosis.

Treatment :-

There is no specific treatment for yellow fever. Treatment for symptoms can include:

*Blood products for severe bleeding
*Dialysis for kidney failure
*Fluids through a vein (intravenous fluids)

The treatment for yellow fever is supportive: control of fever, fluids to treat dehydration, and intensive support related to organ damage.

The World Health Organization estimates 200,000 cases of yellow fever per year with approximately 30,000 deaths.

CLICK TO READ ..>: Early sign of yellow fever could lead to new treatment

Prognosis: :-

Yellow fever ranges in severity. Severe infections with internal bleeding and fever (hemorrhagic fever) are deadly in up to half of cases.

Historical reports have claimed a mortality rate of between 1 in 17 (5.8%) and 1 in 3 (33%). CDC has claimed that case-fatality rates from severe disease range from 15% to more than 50%. The WHO factsheet on yellow fever, updated in 2001, states that 15% of patients enter a “toxic phase” and that half of that number die within ten to fourteen days, with the other half recovering

Possible Complications :-

*Coma
*Death
*Disseminated intravascular coagulation (DIC)
*Kidney failure
*Liver failure
*Parotitis
*Secondary bacterial infections
*Shock

Prevention :-

If you will be traveling to an area where yellow fever is common:

*Sleep in screened housing
*Use mosquito repellents
*Wear clothing that fully covers your body
*There is an effective vaccine against yellow fever. Ask your doctor at least 10 – 14 days before traveling if you should be *vaccinated against yellow fever.

In 1937, Max Theiler, working at the Rockefeller Foundation, developed a safe and highly efficacious vaccine for yellow fever that gives a ten-year or more immunity from the virus. The vaccine consists of a live, but attenuated, virus called 17D. The 17D vaccine has been used commercially since the 1950s. The mechanisms of attenuation and immunogenicity for the 17D strain are not known. However, this vaccine is very safe, with few adverse reactions having been reported and millions of doses administered, and highly effective with over 90% of vaccinees developing a measurable immune response after the first dose.

click to see the picture

Although the vaccine is considered safe, there are risks involved. The majority of adverse reactions to the 17D vaccine result from allergic reaction to the eggs in which the vaccine is grown. Persons with a known egg allergy should discuss this with their physician prior to vaccination. In addition, there is a small risk of neurologic disease and encephalitis, particularly in individuals with compromised immune systems and very young children. The 17D vaccine is contraindicated in infants, pregnant women, and anyone with a diminished immune capacity, including those taking immunosuppressant drugs.

According to the travel clinic at the University of Utah Hospital, the vaccine presents an increased risk of adverse reaction in adults aged 60 and older, with the risk increasing again after age 65, and again after age 70. The reaction is capable of producing multiple organ failure and should be evaluated carefully by a qualified health professional before being administered to the elderly.

Finally, there is a very small risk of more severe yellow fever-like disease associated with the vaccine. This reaction occurs in 1~3 vaccinees per million doses administered. This reaction, called YEL-AVD, causes a fairly severe disease closely resembling yellow fever caused by virulent strains of the virus. The risk factor/s for YEL-AVD are not known, although it has been suggested that it may be genetic. The 2`-5` oligoadenylate synthetase (OAS) component of the innate immune response has been shown to be particularly important in protection from Flavivirus infection. In at least one case of YEL-AVD, the patient was found to have an allelic mutation in a single nucleotide polymorphism (SNP) of the OAS gene. People most at risk of contracting the virus should be vaccinated. Woodcutters working in tropical areas should be particularly targeted for vaccination. Insecticides, protective clothing, and screening of houses are helpful, but not always sufficient for mosquito control; people should always use an insecticide spray while in certain areas. In affected areas, mosquito control methods have proven effective in decreasing the number of cases.

Recent studies have noted the increase in the number of areas affected by a number of mosquito-borne viral infections and have called for further research and funding for vaccines

Current research:-
In the hamster model of yellow fever, early administration of the antiviral ribavirin is an effective early treatment of many pathological features of the disease. Ribavirin treatment during the first five days after virus infection improved survival rates, reduced tissue damage in target organs (liver and spleen), prevented hepatocellular steatosis, and normalized alanine aminotransferase (a liver damage marker) levels. The results of this study suggest that ribavirin may be effective in the early treatment of yellow fever, and that its mechanism of action in reducing liver pathology in yellow fever virus infection may be similar to that observed with ribavirin in the treatment of hepatitis C, a virus related to yellow fever. Because ribavirin had failed to improve survival in a virulent primate (rhesus) model of yellow fever infection, it had been previously discounted as a possible therapy.

In 2007, the World Community Grid launched a project whereby computer modelling of the yellow fever virus (and related viruses), thousands of small molecules are screened for their potential anti-viral properties in fighting yellow fever. This is the first project to utilize computer simulations in seeking out medicines to directly attack the virus once a person is infected. This is a distributed process project similar to SETI@Home where the general public downloads the World Community Grid agent and the program (along with thousands of other users) screens thousands of molecules while their computer would be otherwise idle. If the user needs to use the computer the program sleeps. There are several different projects running, including a similar one screening for anti-AIDS drugs. The project covering yellow fever is called “Discovering Dengue Drugs – Together.” The software and information about the project can be found at: World Community Grid web site

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.
Resources:
http://en.wikipedia.org/wiki/Yellow_fever
http://www.nlm.nih.gov/medlineplus/ency/article/001365.htm
http://microbiology.suite101.com/article.cfm/yellow_fever

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