Yellow Fever

Yellow fever is a potentially deadly viral disease spread by mosquitoes in tropical regions of Africa and South America, causing symptoms ranging from fever and body aches to severe liver damage and bleeding, but it can be prevented with a single dose of vaccine that provides lifelong protection.

Table of contents

• What is yellow fever?
• Where yellow fever occurs
• How the disease spreads
• Signs and symptoms
• Diagnosing yellow fever
• Treatment and care
• Prevention and vaccination
• Disease burden and outcomes

What is yellow fever?

Yellow fever is a serious viral disease transmitted through the bite of infected mosquitoes^[1]. The name comes from one of its most striking symptoms: the yellowing of the skin and eyes, called jaundice, which occurs when the virus damages the liver^[2]. This condition affects the skin’s color because the damaged liver cannot properly process certain substances in the blood.

The disease is caused by the yellow fever virus, which belongs to a group of viruses called flaviviruses^[4]. While many people infected with yellow fever experience mild symptoms or none at all, the disease can become life-threatening in a significant number of cases. Yellow fever has been recognized as a major health threat for centuries, and despite the availability of an effective vaccine, it continues to cause thousands of deaths each year^[1].

Where yellow fever occurs

Yellow fever is found only in specific parts of the world. Twenty-seven African countries and 13 Latin American countries are classified as high-risk areas for yellow fever outbreaks^[1]. The disease occurs in tropical and subtropical regions of Africa, particularly in areas below the Sahara desert, and in Central and South America^[2].

In South America, the disease is found in countries including Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Panama, Paraguay, Peru, Suriname, Trinidad and Tobago, and Venezuela^[3]. Since 1970, yellow fever has re-emerged as a public health threat in the Americas, and in 2014, the virus spread beyond the Amazon basin^[3]. Recent outbreaks have been reported in and around major cities in Brazil, showing that the disease is not limited to jungle areas^[5].

Yellow fever is not found in the United Kingdom, Europe, Asia, Australia, New Zealand, or the Pacific Islands^[16]. The potential for international spread to unaffected regions remains a global health security concern^[1].

How the disease spreads

Yellow fever spreads when infected mosquitoes bite people^[1]. The mosquitoes that carry the virus include several species: Aedes, Haemagogus, and Sabethes^[1]. These mosquitoes breed in different environments, including domestic settings, forests, and semi-domestic areas. The mosquitoes that carry yellow fever bite during both day and night^[17].

The yellow fever virus has three distinct ways of spreading, known as transmission cycles. The jungle cycle involves transmission between monkeys and mosquitoes in forest areas. The intermediate cycle occurs in African savannah regions and involves humans who live or work near jungle borders, with transmission happening between monkeys and humans or between humans through mosquito bites. The urban cycle involves a person with the virus in their blood who returns to an urban area, where mosquitoes can then spread the virus to other people^[5].

Unlike some other diseases, infected humans can pass yellow fever to mosquitoes during periods when the virus is in their blood, making them part of the transmission cycle^[5]. However, the disease is not spread directly from person to person through contact, coughing, or other means without mosquito involvement^[6].

Signs and symptoms

After being bitten by an infected mosquito, it takes 3 to 6 days for symptoms to appear. This waiting period is called the incubation period^[1]. Many people infected with yellow fever virus will have no symptoms at all or only mild symptoms^[10].

The initial symptoms of yellow fever include fever, headache, general body aches, nausea, vomiting, and weakness^[1]. Some people also experience chills, severe headache, back pain, loss of appetite, and fatigue^[10]. These symptoms typically disappear within 3 to 4 days^[1]. For most people who develop symptoms, the illness improves within one week^[10].

About 15% of people infected with yellow fever will develop severe infection^[1]. In these cases, after feeling better for a brief time that may last only a few hours or a day, more serious symptoms develop^[10]. This severe phase includes the recurrence of high fever, jaundice (yellowing of the skin and eyes), vomiting, bleeding from the mouth, nose, eyes, or stomach, organ failure, and shock^[1]. People may vomit blood or have blood in their stool, and their urine may become dark^[3]. About 50% of patients who enter this severe phase die within 7 to 10 days^[1].

Among those who develop severe disease, 30% to 60% will die^[10]. For people who recover from the infection, weakness and fatigue might last several months^[10]. Once a person has been infected and recovers, they are likely protected against future infections for life^[10].

Diagnosing yellow fever

Diagnosing yellow fever is challenging, especially in the early stages when symptoms are not specific to this disease^[1]. The early symptoms of yellow fever can resemble many other common viral infections^[5]. Severe cases may look like other diseases such as malaria, leptospirosis, viral hepatitis, other bleeding fevers such as dengue, and poisoning^[1].

If you have traveled to an area where yellow fever is found and develop symptoms, you should see your healthcare provider immediately^[10]. Your healthcare provider will ask about your symptoms and your travel history, including the dates and exact locations you visited^[10]. It is important to tell anyone you speak to about your recent travel and whether you were bitten by mosquitoes^[16].

To confirm yellow fever, laboratory testing is required. In the early stage of infection, diagnosis is carried out by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) testing of blood, which detects the virus’s genetic material^[1]. In the later stage of infection, diagnosis is done by detecting antibodies through tests called ELISA or plaque reduction neutralization^[1]. Your healthcare provider can order blood tests to look for yellow fever or other similar viruses^[10].

Treatment and care

There is no specific medicine that treats the yellow fever virus itself^[1]. Treatment focuses on managing symptoms and supporting the body while it fights the infection. This approach is called supportive care^[1].

For people with yellow fever, supportive care includes rest and drinking plenty of fluids to stay hydrated^[1]. Healthcare providers may give medicine to help reduce fever and relieve aching^[10]. However, certain medications should be avoided. People with yellow fever should not take aspirin or nonsteroidal anti-inflammatory drugs such as ibuprofen or naproxen, because these medicines may increase the risk of bleeding^[10].

The severity of symptoms determines where a patient receives care. Patients may be managed at home, hospitalized, or referred for emergency care depending on how serious their condition is^[1]. Jaundice is a sign of severe disease that requires hospitalization, often in an intensive care unit^[1]. People with severe symptoms should be hospitalized for close observation and supportive care^[10].

In the hospital, treatment may include managing liver and kidney failure, controlling fever, and giving antibiotics for secondary bacterial infections^[1]. Severely ill patients should be treated in an intensive care setting and may need vasoactive medications, fluid replacement, ventilator support, and treatment for bleeding problems and organ failure^[15].

Two antiviral treatments, sofosbuvir and a monoclonal antibody called TY014, are being studied, but they are currently recommended only in research settings^[1]. Clinical studies are ongoing, but no specific antiviral treatment is available for routine use^[1].

People infected with yellow fever should protect themselves from mosquito bites for up to 5 days after symptoms begin^[10]. This may mean staying indoors or under a mosquito net. This precaution helps prevent spreading the virus to other mosquitoes that could then infect other people^[10].

Prevention and vaccination

The best way to prevent yellow fever is to get vaccinated before traveling to areas where the disease occurs and to protect yourself from mosquito bites^[17]. A safe and effective vaccine against yellow fever exists and has been in use for over 60 years^[5]. The vaccine provides lifelong protection with a single dose for most situations^[1].

Vaccination is recommended for people 9 months old and older who are traveling to or living in areas at risk for yellow fever in Africa and South America^[5]. Some countries require travelers to have an International Certificate of Vaccination or Prophylaxis to prove they have been vaccinated^[1]. The vaccine must be received at least 10 days before traveling^[19]. Yellow fever vaccine is available only from registered vaccination centers^[16].

In addition to vaccination, travelers should take steps to avoid mosquito bites. This includes using insect repellent that contains DEET on exposed skin^[17]. Wearing long-sleeved shirts and long pants helps cover arms and legs, particularly during early morning and early evening when mosquitoes are most active^[16]. Treating clothing and gear with 0.5% permethrin provides additional protection^[17].

Other protective measures include closing windows and doors whenever possible, or using blinds or screens, and sleeping under a mosquito net treated with insecticide, including during the day^[16]. Travelers should choose hotels or lodging with air conditioning or screens on windows and doors^[17].

Disease burden and outcomes

Yellow fever continues to cause significant illness and death worldwide. An estimated 67,000 to 173,000 severe infections and 31,000 to 82,000 deaths occur each year in Africa and the Americas, with most of the burden being in Africa^[1]. In 2013, yellow fever was estimated to have caused 130,000 severe infections and 78,000 deaths in Africa^[4].

Approximately 90% of an estimated 200,000 cases of yellow fever per year occur in Africa^[4]. Yellow fever is a very rare cause of illness in travelers from the United States, but fatal cases in unvaccinated travelers to Africa and South America continue to be reported^[19].

For people who develop symptoms, most will recover after 3 or 4 days of mild illness^[6]. However, death occurs in up to half of those who develop severe disease^[1]. The outcome depends greatly on whether the infection progresses to the severe phase with organ damage.

Due to its high impact and potential for international spread, yellow fever poses a significant threat to global health security^[1]. Large epidemics can occur when infected people introduce the virus into heavily populated areas with high mosquito density and where most people have little or no immunity due to lack of vaccination^[3].