What Is Yellow Fever

Overview

Yellow fever (YF) is a serious viral infection transmitted by certain species of mosquitoes, such as the Haemagogus, Sabethes, or Aedes aegypti mosquitoes.¹ These species of mosquito and the yellow fever virus (YFV) are found in certain areas of Africa and South America. Most people infected with the YFV will experience mild flu-like symptoms such as body aches and fever, but in some instances, it can be more severe, leading to organ failure and even death. There is a safe and effective vaccine available to prevent infection, and people travelling to at-risk regions should get a YF vaccine prior to travelling.

Background

It is believed that YF originated in Africa and was introduced to the Americas through the slave trade in the 16^th century. Due to favourable sub-tropical climate conditions and the presence of relevant mosquito species, the YFV rapidly spread to Central America and to more populated areas such as the coastal cities of the eastern United States.² During the 18^th and 19^th centuries, there were at least 25 major outbreaks which killed hundreds of thousands in America. The 1793 outbreak in Philadelphia killed 9% of the city’s population (approximately 5,000 deaths).² During the Spanish-American War in Cuba in 1898, more soldiers died from YF than on the battlefield. During the construction of the Panama Canal between 1904 and 1914, thousands were also killed due to YF, leading to delays in the completion. Identification of mosquitoes as the vector and gaining a greater understanding of transmission led to the development of mosquito control programs and the eradication of urban YF in the U.S. and several Central and South American countries.² 

The development of an effective vaccine in the first half of the 20^th century and the subsequent mass vaccination campaigns led to YF going from a major threat to a relatively neglected disease.²

Epidemiology

YF transmission has been reported in 44 countries, resulting in nearly one billion people being at risk of infection. Each year, there are about 200,000 infections and 30,000 deaths from yellow fever, with 90% of these occurring in the African continent.³ YF can be found across West, East and Central Africa, with the majority of cases and deaths taking place in sub-Saharan Africa. It can also be found in South America, mainly in the Amazon basin.³ YF outbreaks usually occur during the rainy season when the mosquito populations are at their highest.

The last urban infections in Brazil occurred in the Sena Madureira, state of Acre, in 1942. Since then, all reported cases have been due to individuals becoming infected in forested areas, where the virus circulates in animals. In recent years, these epizootic areas have spread to the mid-south and southeast of the country near densely populated areas, increasing the risk of urban reintroduction of the disease.4 There was an outbreak of YF in Brazil between 2017 and 2019, transmitted by Hemagogus spp., with cases identified in large urban centres in the coastal areas of the states of Sao Paulo, Minas Gerais, and Rio de Janeiro. There were more than 2000 cases and nearly 700 deaths. Hemagogus spp. Mosquitoes normally reside in the rainforest canopy, where they feed upon non-human primates. However, due to the expansion of human settlements into rainforest areas, the outbreak was able to spread to urban areas.⁴

Most YFV infections have no or only mild flu-like symptoms, and most patients recover 3 to 4 days after the onset of symptoms. However, some patients will then relapse after the recovery, with severe symptoms such as jaundice, bleeding, liver and kidney failure. The prognosis in such cases is poor, and the fatality rate is between 20 to 50%.³ In  South America, the mortality rate among symptomatic infections is 40–60% compared with 20% in West Africa. The lower mortality rate in West Africa is thought to be due to cross-protection (where a previous infection with a different virus provides immunity against a new viral infection)by immunity to heterologous flaviviruses.³

The continuous threat of yellow fever

YF remains a major public health threat, especially due to international travel, global migration, and geographic expansion, as there is a risk of it being introduced into new areas. It is, therefore, important that vaccination strategies are targeted at those countries where YF is endemic (where a disease regularly occurs). Travellers visiting at-risk countries should also be targeted by these programs to avoid the risk of YF being introduced into new areas by travellers becoming infected during their travels and spreading it in their home country or to other regions they visit. 

According to the World Health Organisation (WHO), a single dose of the YF vaccine provides life-long protection against the disease in most individuals.⁵ However, some people may require an additional dose, such as young children who received their initial dose at a young age, women who received their first dose during pregnancy, those with HIV infection, and persons with immunodeficiency disorders.⁴

Causes

YF is caused by a virus belonging to a group of viruses called Flaviviruses. Flaviviruses are predominantly transmitted by arthropods and include some of the most important human pathogens such as dengue, West Nile and Zika viruses.⁶ 

YF is transmitted to humans by different and overlapping transmission cycles involving mosquito vectors and non-human primates. There are several different transmission cycles identified in YF infections, including the enzootic, savannah, urban and sylvatic cycles. The dominant transmission cycle tends to change depending on geographic location. In sub-Saharan Africa and South America, YF is transmitted among non-human primates through enzootic cycles. If an unvaccinated traveller visits an at-risk area in South America, they may become infected through the bite of Hemagogus spp, which has previously bitten an infected non-human primate.

In some African countries, there is an intermediate (savannah) cycle in which humans may acquire the infection from mosquitoes that bite infected monkeys or infected humans living or working in the areas bordering the rainforest or the African savannah. In the Americas, most transmission occurs via the urban cycle, involving only humans, and is perpetuated by the mosquito Aedes aegypti, which resides in urban areas. Recently, the sylvatic cycle has become an important form of transmission in Latin America due to the increase in humans going into densely forested areas for housing or work, where mosquitoes such as Hemagogus spp. and Sabethes spp transmit the virus.⁴

To prevent infection with the YFV, it is therefore important that people entering areas of yellow fever transmission take the proper precautions to prevent mosquito bites, such as using insect repellant and mosquito nets and also get the yellow fever vaccine to prevent infection if they are bitten.

Signs and symptoms

Some people with YF suffer only very mild symptoms or even no symptoms at all. Symptoms usually start 3 to 6 days after being bitten by an infected mosquito. 

Less severe symptoms include the following:

• Fever¹
• Headache¹
• Body aches³
• Fatigue⁵ 
• Nausea and vomiting¹

Most people recover after several days. However, in some cases, after the initial recovery, the patient relapses with severe symptoms. 

In more severe cases, symptoms can include the following:

• Very high fever¹
• Jaundice (yellowing of the skin and the whites of the eyes)²
• Haemorrhage (bleeding from your eyes, nose, mouth or stomach)²,³
• Shock³
• Liver failure²
• Kidney failure²
• Death²

Diagnosis

YF is difficult to diagnose, especially during the early stages, as symptoms can be confused with other mosquito-borne viruses. If your healthcare provider suspects YF, he will first take your medical history and ask about your symptoms and travel history. You may then be given a blood test to confirm the diagnosis by detecting the presence of the virus in the blood.¹ Polymerase chain reaction can be used to detect the virus in the blood if testing is done early in the illness. In the later stages of the disease (day 5 onwards), testing for the presence of virus-specific antibodies is done.¹ Management and treatment

Currently there is no specific treatment available for yellow fever, treatment is only supportive such as painkillers, hydration and plenty of rest. Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) (due to the risk of bleeding) and paracetamol (due to liver toxicity) should not be used.¹

Patients with severe symptoms require hospitalisation. They will likely be given intravenous fluids to keep them hydrated. In severe cases and in cases of respiratory distress, endotracheal intubation and mechanical ventilation may be needed. Dialysis is often necessary. In cases of bleeding, transfusions with fresh frozen plasma may also be required.¹

There is no cure for YF, therefore it is important to get vaccinated if you live in or are travelling to an area where there is a risk of contracting YF. It is also a good idea to take the following precautions to prevent mosquito bites:

• Use an EPA-registered insect repellent⁷
• Wear long-sleeved shirts and pants⁷
• Treat clothing and gear with permethrin⁷ 
• Use mosquito screens on windows and doors⁷
• Sleep under a mosquito net⁷

FAQs

What happens if I get yellow fever?

Some people with yellow fever may experience no or only very mild symptoms. For those who experience symptoms, it takes 3-6 days to develop after being bitten. Mild symptoms are usually flu-like, such as aches and pains, fever, nausea and vomiting. Some people go on to develop serious symptoms such as jaundice, bleeding, organ failure and death. In case of serious symptoms, medical attention should be sought immediately.

Can yellow fever be cured?

There is no definitive cure for yellow fever, but typically, only supportive treatment is required, such as getting plenty of rest, staying hydrated and taking painkillers (not aspirin or non-steroidal anti-inflammatory drugs, which can cause bleeding) if necessary. If you are travelling to an area where there is a risk of yellow fever transmission, it is important to get the yellow fever vaccine and to take precautions to prevent mosquito bites.

Do most people survive yellow fever?

Most people who develop yellow fever will recover after about 4 days. However, between 20-60% of patients will relapse with severe symptoms such as bleeding, jaundice, liver and kidney failure.² The prognosis in these cases is poor, with a fatality rate between 20-50%.³

How likely is it to get yellow fever?

Yellow fever is common in certain countries in Africa and South America. The CDC has published a list of countries where yellow fever vaccination is required or recommended. Travellers or people living in these countries should get the yellow fever vaccine.

Does the yellow fever vaccine last for life?

In most individuals, a single dose of the yellow fever vaccine lasts a lifetime. However, some individuals may require a subsequent booster dose, including young children who received their initial dose at a young age, women who received the vaccine during pregnancy, those with HIV infection, and persons with immunodeficiency disorders.⁴

Which countries need the yellow fever vaccine?

There are several countries in Africa and South America where the yellow fever vaccine is currently required, such as Angola, Cameroon, Ghana and French Guiana. According to the CDC, in addition to the list of required countries, there are also many countries in Africa and South America where the vaccine is recommended, such as Brazil, Guyana, Venezuela and Colombia. 

Summary

Yellow fever is a virus spread by the bite of specific species of mosquitoes in regions of Africa and South America. Symptoms range from asymptomatic or mild flu-like symptoms to severe symptoms, including bleeding, jaundice, organ failure and death. In the past, there have been serious outbreaks with a significant amount of cases and high mortality rates. Yellow fever infection can be prevented by taking precautions against mosquito bites and by vaccination. The yellow fever vaccine is effective, and in most cases, a single dose provides life-long immunity. As there is no specific treatment or cure for patients infected with yellow fever, treatment is only supportive, such as painkillers, plenty of fluids and rest.

Currently, yellow fever transmission occurs in 44 countries, putting nearly one billion people at risk of infection. Despite a successful vaccine, yellow fever remains a significant threat due to the rapid urbanisation across South America and Africa, international travel, and the global migration of yellow fever, as there is the risk of it being introduced into new areas with low immunity and low vaccination rates.