Yellow Fever

Yellow fever is an infectious disease caused by a virus belonging to the flavivirus family. It is spread by the Aedes aegypti mosquito and is prevalent in the areas of Africa and South America. The mild form of the disease is of short duration and finishes on its own after causing mild symptoms of fever, chills, malaise, headaches, body aches, nausea, poor appetite. In 15-25% of people, the disease returns after subsiding and affects the liver causing abdominal pain and jaundice (yellowish discoloration of skin and sclera). It can further deteriorate, affecting the kidneys, blood clotting system, lungs, and brain.

Once the disease takes a serious course, it can only be managed symptomatically. There is no particular medicine effective against the yellow fever virus. However, vaccination and spread control methods can help prevent infection.

Yellow fever is caused by an RNA virus belonging to the family named Flaviviridae. The virus is transmitted by mosquitos, especially the Aedes aegypti species. Other than humans, the virus infects the monkeys also. It can be transferred between monkeys, humans, or both.

The mosquito sucks up the blood of an infected person. The virus travels to the salivary glands of the mosquito. When this mosquito bites another person, it delivers the virus through the mouth into the person’s bloodstream and causes the disease.

Yellow fever is not common in the USA due to effective vaccination and mosquito control methods. Americans usually get the disease when they travel to yellow fever endemic regions. Therefore, it is vital to talk bout vaccination with your physician before planning to travel.

The regions with the highest prevalence of yellow fever are Africa and South America. In 2013, about 127,050 cases of severe yellow fever infections and 45,000 deaths were recorded worldwide, with around 90% of the cases occurring in Africa.

You may have increased chances of infection when you travel to yellow fever prevalent regions. You are unvaccinated. You do not use mosquito repellents. These mosquitos grow in the tropical wet season and early dry season. If you indulge in activities related to wet areas or trees, you can get an infection. 

The history of symptoms is divided into three stages:

1. The period of infection: It is the period when the infection signs and symptoms first appear
2. Period of remission: It is the period when the symptoms subside, the infection clears, and patients recover completely.
3. Period of intoxication: In 15-25% of people, the fever returns and results in a more severe illness

The symptoms during the period of infection are:

• General malaise
• Fever
• Chills
• Headache
• Lower back pain
• Nausea

The period of intoxication results in severe illness and is marked by the following:

• Fever
• Vomiting
• Abdominal pain
• Renal failure
• Hemorrhage
• Jaundice
• Enlarged liver
• Bleeding spots in the body
• Bruises
• Fluid overload (due to kidney failure)
• Altered consciousness (due to brain ischemia)
• Breathing problems (due to fluid buildup in lungs)

Yellow fever should be suspected in any person returning from a trip and showing symptoms of fever, jaundice, body aches. It is difficult to diagnose the illness in the initial stages. However, a history typical of traveling and symptoms can direct towards the diagnosis. Findings of the tender abdomen, scleral icterus, bruises, and bleeding spots can further help in diagnosis. The following investigations are usually advised:

• Complete blood count (CBC)
• Blood urea, creatinine, nitrogen
• Liver function tests (LFTs)
• Coagulation studies
• Urinalysis
• Specific tests for virus: Polymerase chain reaction assay (PCR), Enzyme-linked immunosorbent assay (ELISA) for antibodies detection, Immunohistochemical tissue staining to identify the yellow fever antigen.

Many other diseases can look like yellow fever:

• Dengue Hemorrhagic Fever
• Ebola Hemorrhagic Fever
• Malaria
• Typhoid Fever
• Leptospirosis
• Hepatitis E
• Acute Liver Failure

After the diagnosis, the case has to be reported to the local health authorities as outbreaks can happen if not taken care of. Yello fever has no specific treatment as per se. Once the patient is infected, he can be managed by providing supportive care. Severe cases need to be admitted to the intensive care unit, where they are under close supervision. Severe cases are managed by adapting the following protocol:

• The patient’s nutritional status has to be maintained to prevent hypoglycemia by providing food through a Nasogastric tube (NG tube).
• The Nasogastric tube may also be needed to provide suction of gastric contents in cases of gastric dilatation and to prevent aspiration of gastric contents.
• Hydration status has to be managed by providing intravenous fluids and medicines that increase the contractility of the blood vessels, thus improving blood pressure in patients with hypotension.
• Oxygen administration if the oxygen levels of patients are decreasing
• Medicines are given to reduce the release of gastric acid as it is released in larger amounts during stressful situations. For example, esomeprazole, which is a proton pump inhibitor.
• Metabolic abnormalities and acidosis are treated.
• If the patients have hemorrhagic episodes due to coagulation system abnormalities, they are given Fresh Frozen plasma, which helps prevent bleeding.
• If a patient is having renal failure and is not able to eliminate waste materials from the body and even the extra fluid by making urine, dialysis needs to be done.
• Antibiotics are administered to prevent secondary bacterial infections.
• Patients may need to be shifted to ventilator support for breathing if a respiratory failure occurs.
• Throughout the treatment, salicylates are to be avoided as they can further increase the risk of bleeding by hampering the function of platelets which helps to clot blood. 

Yellow fever can cause a mild illness or severe hemorrhagic fever. Most of the time, it’s a self-limited illness and gets clear on its own. In 15-25% of patients, a fatal infection occurs, resulting in complications like Liver failure, Renal failure, Pulmonary edema, Myocarditis, Secondary bacterial infections, Hemorrhage, disseminated intravascular coagulation, Encephalitis (rare), Shock, or death. People who are non-native to the infectious areas are more prone to severe reactions like travelers, infants, and people over 50 years have increased chances of a fatal reaction. The mortality risk is 50% for people suffering from a fatal infection. Death usually occurs after 7-10 days of the onset of the toxic phase of yellow fever. 

A milestone was achieved in 1937 by Max Theiler, who developed the live attenuated vaccine 17D to prevent yellow fever. 95% of immunity can be achieved by using currently available vaccines. It is recommended by WHO to vaccinate the people living in infection-prone areas by 9tha and 12^th months after birth. The vaccine is necessary for travelers also. Once you get an infection, you will be immune to the yellow fever virus for the rest of your life.

The other preventive method on the government level is controlling the growth of the vector, the mosquitos. It is achieved by eliminating the water accumulations to prevent the larvae which tend to develop in the stagnant water. The population of adult yellow fever mosquitoes is killed by using small amounts of pesticides.

You are advised to take the vaccine on an individual level before traveling to endemic areas. It would help if you also tried to protect yourself against the mosquitoes by adapting the following methods:

• Try to avoid unnecessary outdoor activity to reduce exposure to the mosquitoes, especially when it's the season.
• Wear an item of well-covered clothing like long-sleeved shirts and full-length pants when you intend to go into mosquito-prone areas.
• Try to stay in well-screened accommodations.
• Use nets to ward off mosquitos if the housing is not well covered.
• Use mosquito repellents. Take care of the safety precautions using repellents as they can be toxic, especially with young children. 

Our clinical experts continually monitor the health and medical content posted on CURA4U, and we update our blogs and articles when new information becomes available. Last reviewed by Dr.Saad Zia on May 10, 2023.

References

https://link.springer.com/article/10.1186/s40794-020-0101-0

https://wwwnc.cdc.gov/travel/diseases/yellow-fever#:~:text=Yellow%20fever%20is%20a%20serious,days%20after%20they%20are%20infected.