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Yellow fever symptoms, causes, treatment – Yellow fever

Yellow fever is a severe disease spread by mosquitoes. It causes a yellow coloring of the skin and eyes that gives it its name.

Yellow fever is a severe and potentially deathly mosquito-transmitted disease. It is more frequent in tropical areas in Africa and South America. Disease severity varies from patient to patient. Some patients present only with mild flu-like symptoms, while others have severe viral hepatitis (liver swelling) and hemorrhagic fever (severe bleeding with the fever).

This disease is due to viral infection by the yellow fever virus of the flavivirus family, spreading through an infected mosquito’s bite. Mosquitoes get infected by biting an infected human or an infected monkey, thus creating a vicious circle.

The disease is sporadic in developed countries; in fact, the only cases in these countries are patients with a history of recent travel to an endemic area, where there currently is spreading of the infection.

There are only nine reported cases in the United States between 1970 and 2002, all of them from travelers. Of these 9 cases, seven turned out to be fatal. However, several experts predict the disease may resurface in the United States because of inadequate sanitary measures that have led to the reappearance of Aedes aegypti (the mosquito responsible for yellow fever virus transmission) in some parts of Texas and Hawaii.

The recent outbreaks of dengue fever (transmitted by the same mosquito) in Texas have raised the alarms and fear for a yellow fever outbreak.

Where does yellow fever occur?

According to statistics from the world health organization (WHO), around 90% of all cases occur in Africa, particularly in Sub-Saharan Africa. In that region, there are about 170.000 cases a year and 60.000 deaths from yellow fever. 34 countries in Africa are considered endemic areas (places where this disease is typical to appear and affect people) for yellow fever. 

In South- America, yellow fever transmission is lower than in Africa. However, due to deforestation, the frequency of yellow fever outbreaks has risen in the last few decades.

Is yellow fever still around?

Yellow fever outbreaks are still relatively frequent in South America and Africa. Human infections in South America occur mostly in persons that go into sylvatic areas either for work or recreation. Urban outbreaks in the region are extremely rare nowadays. Still, one of the lastest major outbreaks was in Brazil in the year 2016 and 2018. In 2018, some cases came from places where yellow fever was not common, which worried health officials.

How does yellow fever spread?

Yellow fever transmission occurs through a mosquito bite. Aedes aegypti is a mosquito famous for spreading several viral fevers, including Dengue fever, Chikungunya fever, Zika fever, Mayaro fever, and of course, Yellow fever.

File:Aedes aegypti mosquito.jpg
Aedes aegypti mosquito

Aedes aegypti is originally from Africa but nowadays is found in many other tropical and subtropical regions, including South America, Florida, Texas, Mediterranean countries, and South East Asia.

The mosquito is easily recognizable because of its white marks on its legs. In some South American countries, it is commonly called the white legged mosquito among the general population. The mosquito thrives in densely populated areas with inadequate sanitation measures and a deficient water supply. 

Unfortunately, Aedes is one of the most widespread mosquito species globally, and some populations have adapted to survive in colder climates. A recent study identified one of these populations in Washington, D.C (not famous for its tropical climate). 

What measures prevent the reproduction of Aedes aegypti?

The best environmental management strategy is eliminating excessive water containing habitats such as plastic bottles, jars, cans, tires, and buckets. Mosquitoes lay their eggs in the water; therefore, eliminating these water sources goes a long way in preventing mosquito reproduction and, thus, virus transmission. It is no wonder that the disease is more frequent in poor water supply areas where the local population has to store water in buckets and other containers. 

What is the incubation period for yellow fever?

The incubation period is the period between infection (mosquito bite) and the appearance of symptoms. In yellow fever, the incubation fever lasts for 3-6 days; after that, the patient begins with flu-like symptoms representing the disease’s first stage. 

Yellow fever has several stages, each with different symptoms. Not every patient reaches the three stages.

The first stage is the infection stage in which the patient experiences symptoms such as:

  • Fever
  • Low-back pain
  • Nausea
  • Dizziness
  • Fever
  • Red eyes
  • Facial flushing 
  • Muscle aches 
  • Headache

In some cases, these initial symptoms are so mild that the patient in question dismisses them like the common cold and does not pay any attention to them or seek medical assistance. 

The next stage is the period of remission. During this stage, body temperature goes down, and the patient feels better for 24 hours. From this point on, the patient can either be completely cured, go on with regular activities, or progress to the third and more severe stage.

In 15% to 25% of patients, the remission stage is followed by the intoxication period. In this stage, the virus is completely cleared from the body by the immune system. What follows is a consequence of an uncontrolled cellular immune response.

Symptoms in this stage include:

  • High fever
  • Vomiting 
  • Abdominal pain
  • Hemorrhages [expressed by small red spots throughout your body, bleeding from the nose, gums, genitals, and intravenous (IV) lines]
  • Blood vomiting
  • Urinating less often and less urine
  • Yellow coloration of the skin and eyeballs

Why is yellow fever called yellow fever?

Yellow fever receives its name because of the yellow coloring of skin and eyes (jaundice) patients acquire during the intoxication period. Jaundice is a consequence of liver failure, which causes an increase in total serum Bilirubin, which is responsible for the characteristic yellow coloration during this phase.

File:Scleral Icterus.jpg
Scleral Icterus

The liver is also responsible for producing blood clotting factors. When the liver fails, these factors disappear, causing coagulopathy and bleeding. Liver failure often comes with renal failure, which leads to a decreased urine output (less urination) and the accumulation of waste products like creatinine in the blood. 

Although the liver and the kidneys receive the worst part of the disease, they are not the only organs that suffer. Yellow fever in its last stage can produce multiple organ failure. The brain fills up with fluid causing seizures and decreased consciousness. There is also fatty infiltration of the heart, which leads to dangerous heart rhythm abnormalities. And the damage to the stomach mucosa leads to upper intestinal hemorrhage (bleeding).

What is the mortality rate of yellow fever?

Of all infected individuals, only 15% to 25% develop a severe disease that enters the intoxication phase. According to recent outbreaks, the number of patients who die when they reach the intoxication stage is around 20% to 50%. Death occurs approximately 7 to 10 days after the onset of jaundice. And those who recover can experience weakness and fatigue for months. 

The chance of suffering from severe symptoms is greater in travelers than in native individuals of endemic regions. Other important risk factors that increase the likelihood of suffering from the severe form of the disease include people over fifty or under two years. Apparently, fatality rates are higher in South America than in Africa; the exact reasons behind this remain unknown.

How is yellow fever diagnosed?

There are several methods to detect the virus and antibodies against the virus in the blood. The most reliable way is testing for the viral RNA (its genetic material) using an RT-PCR assay. The best time for collecting a blood sample for PCR in a suspicious case is in the first 3 to 4, four days after the beginning of symptoms. After that time, the viral load becomes undetectable in the blood. Only very specialized labs in the United States perform these tests. It might take a few days for the results to come back.

Serologic tests detect antibodies against the yellow fever flavivirus. The best time for collecting a blood sample for a serologic test is within 7 to 10 days after the illness begins. Collecting a blood sample for serology before that increases the chance of having a false negative. The problem with serologic tests is that, in endemic areas, there is significant cross-reactivity with other types of flavivirus. Other viral infections that can cause a false positive in a serologic test include the Nile fever virus, dengue fever virus, St. Luis encephalitis virus, and Zika virus, among others.

A confirmed yellow fever case is one in which there is at least a positive serologic test in an individual without a history of vaccination against yellow fever and when cross-reactivity with other flavivirus is excluded. 

What other tests are required for yellow fever?

Besides positive PCR and positive antibodies, there are other important abnormalities in blood tests that help doctors see. These abnormalities are not only useful for aiding in the diagnosis. They also help the healthcare provider assess your situation’s severity and decide on specific therapeutic measures. Here are some useful tests in the context of yellow fever:

  • Complete blood count: Normally, a low white blood cell count evolves to a high blood cell count during the intoxication phase. Low platelets (during the intoxication phase). Increased hemoglobin and hematocrit (dehydration causes them to overconcentrate).
  • Coagulation studies: During the intoxication phase, coagulation studies are likely to reveal increased PT and PTT times as well as reduced fibrinogen and coagulation factors. All of this consistent with a coagulopathy (blood clot problems)
  • Blood chemistry: In cases of kidney failure, it will show elevated creatinine and blood urea nitrogen as well as metabolic acidosis. Hypoglycemia (low blood sugar levels) is secondary to liver failure.
  • Urine exam: The most important finding is the presence of a protein called albumin in the urine. This helps differentiate yellow fever from other forms of liver swelling (hepatitis). 
  • Imaging studies: A chest x-ray can help in severe cases where the lungs begin to fill up with fluid. A CT scan helps to detect brain hemorrhages (bleeding) due to coagulopathy. 
  • Electrocardiogram (ECG): Detects arrhythmias in patients with other severe symptoms during the intoxication phase. 
  • Liver function tests: Abnormalities in these values often precede the skin’s yellow coloration (jaundice) onset; performing them in the early phases helps predict the possible outcomes for the patient and the likelihood of entering the intoxication phase. They include liver enzymes (ALT and AST) that typically exceed 1000 IU in severe cases, bilirubin levels (levels over 2.5 cause jaundice), and albumin (it decreases in liver failure).

What is the treatment for yellow fever?

Currently, there isn’t any specific treatment for yellow fever. There is no way to eliminate the virus or modulate the inappropriate immune response that causes the intoxication phase. Treatment is mostly symptomatic and supportive, basically doing everything to increase survival rates while the intoxication phase settles down on its own. 

Some basic measure to improve the possibility of survival include the following: 

  • Using antipyretics like acetaminophen as well as cooling blankets and wet sponges reduces body temperature, which decreases oxygen consumption and improves the prognosis. In cases where there is no fever but hypothermia, warming blankets also help.
  • Glucose infusions to prevent hypoglycemia.
  • Gastric protection with drugs like omeprazole, esomeprazole, and ranitidine protect the stomach and prevent upper intestinal hemorrhage. 
  • Dialysis for patients with severe kidney failure.
  • Replacement of red blood cells, platelets, and clotting components prevent severe hemorrhages and hypovolemic shock.
  • Fluid and electrolyte replacement prevent shock, arrhythmias, metabolic acidosis, and other deadly complications.
  • In severe hypotension cases, vasoactive drugs like dopamine, norepinephrine, or adrenaline help maintain stable blood pressure. 
  • Patients with severe respiratory failure may require intubation and sedation.

How can I prevent yellow fever?

Yellow fever is an easily preventable disease through vaccination. Remember is always better to prevent a disease than to treat it. The yellow fever vaccine available today offers nearly lifelong immunity and is 99% effective.

Besides vaccination, other measures do not only prevent yellow fever, but other mosquito-transmitted diseases like dengue fever, and include the following:

  • When traveling to endemic areas, try sleeping in air-conditioned facilities
  • Wearing protective clothing in endemic areas such as shirts with long sleeves and long pants
  • Using insect repellent spray containing N, diethyl – meta- toluamide (DEET)
  • Use mosquito nets for sleeping.

Who is a candidate for yellow fever vaccination?

Everyone over the age of 9 months planning to travel to an endemic area such as Sub-Saharan Africa or the Amazonic region should get the vaccine. As a matter of fact, yellow fever vaccination is a requirement to enter certain countries endemic countries. Other countries such as Belize and Bahamas require visitants from endemic countries to have a vaccination certificate before entering.

For some countries, yellow fever vaccination is only required to enter certain areas; for example, in Venezuela, the yellow fever vaccine certificate is only necessary to enter the country’s Amazonic part.

Who should not get the yellow fever vaccine?

There are certain groups of people in which the yellow fever vaccine might pose a health hazard. There are two main groups with absolute contraindications (people that should not get the vaccine for in any situation) these are: 

  • Infants younger than six months of age (most vaccination schemes suggest not giving the vaccine before nine months of age).
  • Allergy to any component of the vaccine, including eggs, chicken proteins, and gelatin.
  • Weakening of the immune system due to cancer, corticosteroid treatment for rheumatologic diseases.
  • Thymus disorders.
  • People with AIDS

Groups with relative contraindications (can receive the vaccine in certain situations and always under the approval and supervision of a physician with expertise in the area) include:

  • Being over the age of 60
  • Infants between the ages of 6 to 8 months 
  • Breastfeeding mothers
  • Pregnant women

How many doses of yellow fever vaccine do I need?

In most people, a single dose provides life long immunity. However, certain groups might benefit from a booster dose. These groups include:

  • Travelers to endemic areas that received their last dose more than ten years ago.
  • HIV patients should receive a new dose every ten years.
  • Travelers that want to stay for a long time (months) in endemic areas or those that travel to endemic areas during peak transmission season or an area with an ongoing outbreak.
  • Laboratory workers who constantly handle the yellow fever virus (there are very few of these laboratories worldwide).

Are there adverse effects to the yellow fever vaccine?

Although relatively frequent, the vaccine’s adverse effects are mild and transitory (not lasting more than five days after vaccination). Some common symptoms after vaccination include: 

  • Mild to severe headache
  • Muscle pain
  • Low-grade fever 

Severe side effects are rare, and they include neurologic complications and allergic complications (anaphylactic reaction). Neurologic side effects affect one patient of every 125.000 they can manifest as severe headache, seizures, stiff neck, paralysis, or decreased consciousness. These complications can occur within the first 30 days after administering the vaccine. The presence of any of these symptoms should prompt you to seek medical assistance immediately. 

Where can I get the yellow fever vaccine?

The yellow fever vaccine is not available in every health center. This vaccine is under international health regulators’ regulation, and only authorized providers can administer the vaccine. A yellow fever vaccination center will frequently provide you with other vaccines and medicines necessary for traveling abroad. These centers are distributed throughout all 50 states in the United States. 

Is yellow fever going away soon?

Most experts agree that, unfortunately, yellow fever is not likely to go away soon. Deforestation in endemic regions has reintroduced the virus in areas where the virus had been inactive for years.

During the last decade, there have been several outbreaks in the regions that had been yellow fever-free for years, especially in some areas of Brazil and West Africa. Furthermore, a sylvatic life-cycle of the yellow fever virus in which disease transmission occurs between monkeys and mosquitoes makes it harder to eradicate.

The disease’s global burden is currently greater than the resources available to prevent it (proper epidemiologic surveillance, vector control, and mass vaccination in endemic areas). However, unlike in other hemorrhagic fevers like dengue fever, there is an effective vaccine to prevent it. There is also a significant risk for the virus to be used as a bioterrorist weapon in the coming years.

Do you have symptoms of this disease?

This tool is a Yellow Fever Symptoms Checker. It gathers the most important signs, symptoms, and risk factors for the infection. Therefore, the tool will tell anybody who uses it the likelihood of their symptoms because of Yellow Fever. Using the tool is free and would only take a few minutes.

What do you think?

Written by Dr. Esteban Kosak

Doctor of Medicine - MD Recently Graduated from Medical School and inspired to aid the global population during this situation. I think that we shall no longer be waiting to see a doctor when we feel sick. Several times we feel disease searches in Google drive us to a rabbit hole and come out thinking that we may die of cancer or something very serious, given that symptoms may seem to fit a wide variety of illnesses. Since I recently graduated from medical school. I have all the medical information fresh in my mind. My thorough experience as an expert researcher allows me to very-well known the different diseases and conditions that affect human bodies. Empowered by the United Nations 17 Sustainable Development Goals (SGDs). I think that we all can provide a grain of sand to help humanity. That's why we created Symptoms.Care a place where you can come and screen your symptoms and find what different illnesses can be related to them. Armed with the right information you can instantly, discretely, secure and from the comfort of your home talk with a Doctor that can Evaluate your Symptoms and help you seek the right treatment.


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