An Overview of Yellow Fever

Yellow fever is a flu-like illness that usually resolves without treatment. For about 10-15 percent of those infected, it can become serious. It is spread by mosquitos and caused by a virus called flavovirus.. Yellow fever is endemic in Africa and South America, particularly in areas with dense forests or jungles.

History and Impact of of Yellow Fever

Over the years, yellow fever has been better controlled than it was in the past, largely because there is a vaccine.

But, every year many people are infected with yellow fever. Cases are reported everywhere from Peru, Brazil, the DRC, to Cote d'Ivoire.

Worldwide Impact

The WHO estimates that approximately 84 to 170 thousand people become infected with yellow fever each year. It is believed that many cases are not detected, so the full extent of the disease's impact is unclear. As many as 29,000 to 78,000 people die of the illness per year worldwide. 

Recent Outbreak

In 2016, there was an outbreak in the capital of Angola, where over 200 people died of the infection. The virus spread in the capital and in most provinces in the country. While it is not considered endemic in Asia, travelers and workers have returned home to China from Angola with the virus. 

History

The virus used to extend much further geographically than it does now. It first reached the U.S. at the end of the 1600s. It is believed to have been brought by human trafficking between Africa and the Americas, when mosquitoes and the virus were carried along with people who had lived in endemic areas.

 

It reached as far north as Boston, New York, and Philadelphia, and remaining in southern cities until the late 1800s. The virus was also spread by trade to European ports, as far north as Cardiff and Dublin, though countries like Greece were at most risk.

Countries Where Yellow Fever Occurs

Yellow fever is present in geographic regions where the virus and mosquito can survive.

This is largely dependent on the climate and the presence of a jungle environment.

South America and Nearby Regions

In most of South America the virus does not cause outbreaks in cities. It is found only in very specific regions, typically in remote jungle or forest areas, where the virus spreads in animals. 

In the South American region, it is centered in the Amazon, mainly in Brazil, reaching Peru, Ecuador, Bolivia, Colombia, Venezuela, and Argentina. Countries at risk also include Panama, Trinidad and Tobago, French Guiana, Guyana, Paraguay, Suriname. 

Africa

About 90 percent of yellow fever is thought to occur in Africa, where most deaths from the infection occur. It is found in West and Central Africa, as well as in some parts of East Africa. 

Countries for which there is a risk of yellow fever in Africa include: Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Republic of Congo, Cote d’Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Ethiopia, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Kenya, Liberia, Mali, Mauritania, Niger, Nigeria, Rwanda, Senegal, Sierra Leone, Sudan, South Sudan, Togo, Uganda.

Symptoms

For most people, yellow fever causes a mild illness, or may be unnoticed.

It usually takes about 3-6 days between being exposed to the virus through a mosquito bite and becoming sick. If you have mild disease and never become very ill, you are expected to make a full recovery. For some people, however, yellow fever can be deadly, with fevers, chills, aches, bleeding, yellow eyes and skin, nausea, vomiting, confusion, shock, and organ failure.

For people who do experience symptoms of yellow fever, there are 3 stages of illness:

Early Infection: 3-6 days after exposure, infection occurs. You may experience fever, muscle aches, nausea, vomiting, dizziness, fatigue.

Remission: 2-3 days later, remission occurs.

The fever drops, and symptoms improve. This may last for 24-48 hours. Most people recover at this point. About 15 percent of people infected with the virus go on to have more severe disease.

Severe Disease: Fever, nausea, and vomiting return if you experience severe disease. New symptoms emerge in serious infections.

  • Many people who have severe disease become jaundiced, which is the reason for the name yellow fever. Jaundice can be seen when the skin becomes yellow (including the palms and soles), the whites of the eyes become yellow, and the skin under the tongue becomes yellow.
  • Some people begin to bruise easily, or to have bleeding from multiple places in the body. You may notice bleeding from your nose or other mucus membranes, you may notice blood if you vomited, or you may bleed from an intravenous site. 
  • White blood cell counts may be low, meaning there will be fewer immune cells during an infection.
  • Blood tests may show that the liver is damaged, which can be detected by the presence of elevated liver enzymes in the blood. This may occur before jaundice develops. 
  • If your infection improves, your liver enzymes are expected to rise until the 2nd week of your illness, and then begin to drop towards normal. 
  • Those who recover make antibodies that fight against the virus as the virus disappears. The virus lasts in the blood longer in those who get very sick. 
  • Serious disease may cause symptoms of confusion, and ultimately, organ failure.
  • Those who go on to have severe disease can die. About 1 in 5 to 1 in 2 of those with severe disease may die. 

Causes

Yellow fever is caused by a flavivirus, a single-stranded RNA virus, spread by the Aedes aegypti mosquito. This mosquito, which also causes Zika and Dengue is, in fact, called the yellow fever mosquito. The yellow fever virus can also be spread by other mosquitoes, the Aedes africans in Africa or Haemagogus and Sabethes mosquitoes in South America. 

The mosquitoes transmit the virus by feeding on the blood of an infected person or other primate, such as a monkey, and then biting another person or other primate. A mosquitoe can pick up the virus if it feeds on infected blood right before the human or animal develops a fever and up to 5 days after the fever develops. 

Transmission Cycles

Yellow fever that spreads in a city is very different than yellow fever in a forest or jungle. The virus has 3 different transmission cycles: jungle (sylvatic), inter­mediate (savannah), and urban. It's the urban type that's the most worrisome.

  • When yellow fever spreads in the jungle it largely spreads without humans. It spreads from a non-human primate (like a monkey) to non-human primate by mosquitoes. If people visit the jungle area (say for mining, hunting, or tourism), they can also be bitten by a mosquito and become ill.
  • In the intermediate cycle (also called the savannah cycle), yellow fever spreads regularly between monkeys and humans through mosquitoes, in areas on the edge of jungle areas. It can spread monkey to human, monkey to monkey, human to human, or human to monkey.
  • In the urban cycle, yellow fever spreads primarily between people through mosquitoes living in urban areas. It usually starts when someone who has been infected with the virus returns from a jungle area. It can lead to sudden and large outbreaks in crowded urban areas.

Diagnosis

Diagnosis of yellow fever is based on the clinical history of exposure to a mosquito bite in an endemic region, as well as a history of symptoms. There are a few tests that can support or confirm the diagnosis of yellow fever. 

  • Antibody test: There is a blood test that can detect for antibodies to the virus. This test is the most well established diagnostic test for yellow fever. Antibodies are immune proteins made by the body to fight off infections. If there are antibodies to yellow fever present in your blood, this indicates that your body has fought the infection. It may take several days for your body to make enough antibodies that they could be detected in your blood sample. Additionally, you should expect that it may take up to 2 weeks for the results of your antibody test to return from the laboratory. 
  • Viral PCR test:PCR tests can detect the genetic material of the virus in your blood. The difference between a positive PCR test and a positive antibody test is that an antibody test indicates that you are either fighting off or have effectively have fought the infection, while a PCR test indicates that you have the virus in your body. Therefore, a positive PCR test is a stronger indication of a current infection. The limitation of a PCR test in yellow fever is that the viral RNA is detectable early after infection, but is not easily detectable after several days of infection. This means that you can test negative even if you have the infection. 
  • Urine test: A relatively new test can detect the viral PCR in the urine, making the diagnosis more practical. However, this test, while promising, is not yet in common use. 

Treatment

There is no specific antiviral treatment for yellow fever. Yet, the illness can become quite severe, necessitating medical treatment for the complications of the infection. Treatment of yellow fever should take place in a hospital, with supervised medical care, and not at home. If you experience symptoms that necessitate treatment, the illness can be serious, or even fatal, and should be managed professionally. 

  • Prevention of bleeding: Because of the risk of bleeding, medications that induce bleeding, such as aspirin, ibuprofen, naproxen should generally be avoided.
  • Hydration: Maintaining hydration throughout the illness with oral or IV fluids may be necessary, particularly if you experience vomiting or low blood pressure.
  • Fever control: Generally, yellow fever is associated with low grade fevers. But if your fevers become higher than expected, you may need medication to lower your fever. 
  • Pain: If you experience muscle pain or generalized discomfort, this may be managed with oral or injected pain relievers.
  • Blood pressure support: For those who are in shock, which occurs when blood pressure is extremely low, the blood pressures can be raised with medications that constrict the blood vessels, often referred to as pressors. 
  • Management of organ failure: When yellow fever causes organ failure, those organs need to be supported while the infection improves. Methods such as assistance with breathing through a ventilator, or replacing the job of the kidneys with dialysis. may be necessary.

Prevention

Because yellow fever has been around for a while, the transmission of the virus is well understood, and there are some effective ways to prevent the infection. Additionally, if you are at risk, you might be advised to get the vaccine to prevent yourself from becoming sick.

  • Vaccination: From some people, vaccination is recommended. If you live in an endemic area, you might already be immune to the infection, and you should follow the official recommendations regarding vaccination for yourself and your children. If you are traveling to an area where yellow fever is endemic, you will likely need to have the vaccine. Usually, vaccines for travelers are not widely available, and you may need to make an appointment at a local travel clinic. It is also best to plan ahead because it is recommended that you have the vaccine at least 10 days before your trip. 
  • Mosquito precautions: If you are in an endemic area, you can protect yourself and your children against mosquitoes. While it is not always possible to completely avoid mosquito bites, you can wear layers, particularly when traveling in jungles and forests, and you can use insect spray. It is also recommended to sleep under protective nets, even if you will be in an enclosed room.  
  • Protecting others: In general, because the virus can spread from person to person through a mosquito, it is recommended that you remain under mosquito nets to avoid spreading the virus if you know that you have become infected.

A Word From Verywell

Yellow fever is an infection that is usually mild, but can can cause serious illness. It is preventable with a vaccine. If you are traveling to an area where yellow fever is endemic, you should take the recommended precautions and familiarize yourself with the common symptoms so that you can be aware of what to look for in case you become sick. 

Fortunately, you are unlikely to become infected if you take precautions in advance. And, even if you become infected with the virus, you are likely to experience a good recovery. If you have any of the symptoms, seek medical attention. Your chances of a good recovery are much higher if you get medical care before any complications occur. 

Sources:

Cui S, Pan Y, Lyu Y. Detection of yellow fever virus genomes from four imported cases in China. Int J Infect Dis. 2017 Jul;60:93-95. doi: 10.1016/j.ijid.2017.05.001. Epub 2017 Jun 13.

Hughes HR Russell BJ, Mossel EC, Kayiwa J, Lutwama J, Lambert AJ. Development of a real-time RT-PCR assay for the global differentiation of yellow fever virus vaccine adverse events from natural infections. J Clin Microbiol. 2018 Apr 11. pii: JCM.00323-18. doi: 10.1128/JCM.00323-18. [Epub ahead of print]