Yellow Fever Vaccine: What You Should Know

Introduction 

Yellow fever, a mosquito-borne viral illness, has been a significant public health concern for centuries.¹ With the potential for severe outbreaks in specific regions, understanding and preventing the spread of the virus is crucial. This article aims to provide an insight into both the illness itself and its vaccine, highlighting the importance of vaccination - particularly for  those living in or travelling to high-risk areas. Whether you’re planning a journey abroad or looking to improve your knowledge of infectious diseases, this guide will equip you with all the information you need on yellow fever prevention.

The history of yellow fever

The first probable case of yellow fever was recorded in Mexico,1648, and it posed a major threat to human health throughout the 18-20th centuries.¹ In the 1900s, it was discovered that mosquitoes were the vector through which the virus spread  and efforts to control the activity of mosquitoes drastically reduced the number of cases of yellow fever.² While it is now a much less devastating disease than it was 100 years ago, it is still estimated to be the cause of around 30,000 deaths every year. Furthermore, with more than 200,000 infections reported annually, it is far from being fully controlled.³

Importance of vaccination

Vaccination is an incredibly important tool in the control of yellow fever infection. This was highlighted by the development and wide application of yellow fever vaccines in the 1930s, which caused a sharp decline in cases. Since its creation, over 500 million vaccine doses have been administered.⁴ In areas where yellow fever is endemic (restricted to a specific area) and  lacking in routine immunisation programmes, there are regular outbreaks of the disease. So, despite an effective vaccine being available for over 80 years, yellow fever remains a threat to residents of endemic areas and tourists travelling there.² 

Yellow fever overview

Transmission 

The yellow fever virus, a flavivirus, is transmitted to humans through the bites of infected mosquitoes, with the Aedes and Haemagogus species of mosquitoes being the main carriers. It can be transmitted between humans and non-human primates, like monkeys, when mosquitoes feed. The virus primarily targets the liver, resulting in liver failure  and a buildup of bilirubin, a yellow pigment formed during the breakdown of red blood cells.¹ This pigment is responsible for the characteristic yellowing of the skin and is where yellow fever gets its name from.¹

There are several different strains of the virus.³ Between the strains, the  same disease-associated symptoms and severity of disease occur. However, the diversity of the strains highlights how long yellow fever has been around, due to  the amount of genetic mutations between them.

Infection and symptoms 

Around 90% of symptomatic cases of yellow fever are considered mild (oligosymptomatic).⁵ Most of these cases are seen in young children with a vaccinated mother, as the protective antibodies were passed along the placenta during foetal development. It is also seen in indigenous people who have acquired immunity through infection with other viruses. Usually, it takes around two days to make a full recovery with no lasting issues as the symptoms are not severe.

These symptoms include:⁵ 

• Mild weakness
• Headache
• Fever 

These mild symptoms often correspond with other common diseases, which can cause  frequent underreporting of yellow fever  cases outside of endemic areas.⁵ This is because a diagnosis of yellow fever is made with specific laboratory tests, thus in areas where yellow fever is not so prevalent, the oligosymptomatic person may be diagnosed with another infection common to their region.

In moderate cases, there are a few additional symptoms:⁵

• Nausea
• Body pain 
• Joint pain, which does not affect movement
• At least one of the classic symptoms of yellow fever (discussed in the severe cases section below)

Recovery may take a few extra days, but patients usually recover fully and do not experience long-lasting issues.⁵

Severe cases

Severe cases are much more dangerous, causing death in around 50% of instances. It is characterised by the three classic symptoms of yellow fever:⁵ 

• Vomiting blood (haematemesis) 
• Yellowing of the skin and eyes (jaundice) 
• Decreased urine output below 400 ml/day, often leading to no urine output at all (oliguria/anuria) 

Severe yellow fever has two phases, with a period in between where the patient improves before deteriorating.⁵  

Phase 1: prodromal period (infectious phase)

This is characterised by:⁵  

• High fever, reaching up to 40℃
• A headache felt around the entire head (holocranial) 
• Muscle aches and pains over the body (generalised myalgia) 

The patient can be infected for up to 14 days before the abrupt onset of symptoms.⁵ This initial infectious phase tends to improve after 2-3 days from showing symptoms. 

Phase 2: period of intoxication 

This phase is characterised by the drastic deterioration of the patient as the virus leaves the bloodstream and begins to cause organ damage, particularly to the liver and spleen.¹ At this stage, the virus also infects  the heart, lymph nodes, and other major organs. All of the previous symptoms above will return and get markedly worse, accompanied by new symptoms, such as: 

• Physical weakness (asthenia) 
• Reddening of the whites of the eyes 
• Slow heart rate (bradycardia) 
• Extreme myalgia, often focused in the back 
• Enlargement of the liver (hepatomegaly) 
• Bleeding from the eyes, gums, nostrils and anus

The kidneys fail after around a week, which leads to a total lack of urine output due to damage to the kidney tubule cells. The majority of deaths will occur in this period.¹ 

The more severe the jaundice is (measured by the amount of bilirubin in the patient's blood serum), the higher the chance the patient will experience brain damage, resulting in a poor chance of recovery at this stage.¹ However, most patients will die of combined liver or kidney failure, or bleeding caused by high fever.  

Yellow fever vaccine

The yellow fever vaccine, called YF-17D, is a type of vaccine known as live attenuated.¹ It uses the whole live virus, which has been weakened to cause a very mild form of illness. This allows the immune system to become familiar with the virus so it will be able to fight against it, if the individual is ever infected by the actual yellow fever virus. As such, the body will have immune defences prepared to specifically attack the virus and prevent symptomatic infection. The virus from the vaccine will replicate in the body, with the number of viral particles peaking after one week and returning to undetectable levels as the immune system fights the infection.¹ It will be completely eliminated within 2 weeks of the vaccination. The infection gives your body the chance to rapidly produce antibodies which can control the infection, with many of these antibodies lasting upwards of 40 years.

Who should get vaccinated? 

Travel considerations

It is highly recommended that anyone travelling to a country affected by yellow fever receives a vaccination to protect themselves, even if the country doesn’t require this for entry. Some of the most popular travel destinations where vaccination is either required or highly recommended include:

• Argentina
• Brazil
• Gabon 
• Ghana
• Kenya
• Peru
• Tanzania

Though not all of these countries are holoendemic, meaning that only parts of the country are  affected by the virus, rather than the whole country itself. So, research should be done on high tourism areas within these countries  to assess the risk of catching yellow fever.

Vaccination should be received at least 10 days before travel to allow for full immunity to the disease. On top of vaccination, travellers should further protect themselves by using mosquito repellent, netting and protective clothing to avoid being bitten by mosquitoes carrying the virus.  

Contraindications

While the yellow fever vaccine is safe and effective, there are some considerations to be aware of  as the vaccine  may not be appropriate for everyone, such as:⁴ 

• Infants under the age of 6 months, as they are more at risk of adverse neurological side effects 
• Individuals over the age of 60, as they are more susceptible to adverse systemic events 
• Anyone with a history of thymus disease or who has had their thymus removed, as they will not be able to respond to the virus in the vaccine as effectively  
• People who are pregnant, as it can be passed through the placenta to the developing foetus 
• People who are immunosuppressed, including those taking immunosuppressive drugs or chemotherapy 
• HIV infected individuals – even before the disease progresses to AIDS 
• Anyone with a hypersensitivity or allergy to eggs, as the vaccine is made using chicken eggs 

If anyone in any of these groups cannot avoid travel to affected countries, expert medical advice should be given before receiving the vaccine rather than simply avoiding the vaccine altogether.  

Vaccination process

What to expect 

The yellow fever vaccine is given as a single dose injected into the upper arm and full protection is acquired after 10 days of vaccination. However, if you are frequently travelling to or working in high-risk areas, the World Health Organisation recommends getting boosters roughly every ten years to ensure the best levels of protection.⁴ 

Vaccination takes place at a dedicated vaccination center – you can find information about how to find your closest centre here. The cost of the vaccine is around £65-80, which is not covered by the NHS. 

Side effects

Serious side effects after getting the yellow fever vaccine are rare.⁷ Common side effects affect 1 in 3 people and are similar to those of other routine vaccinations. They can last up to two weeks after the injection, but usually clear up within a couple of days. These side effects include: 

• Headache 
• Fever 
• Tenderness and muscle pain at the injection site 

Allergic reactions are rare but can cause serious complications and so should be treated by a medical professional as soon as possible. In extremely rare cases, the vaccine can potentially cause fatal issues with the brain and other organs. These cases are more likely to affect those who are older than 60 or have a weakened immune system. If you feel very unwell after receiving the vaccine, you should seek medical help immediately.

Travel and certifications 

Countries which require vaccination 

There is a lengthy list of countries which require vaccination in order to enter the country. You can find more information about this here.

Even though not all countries affected by yellow fever will require vaccination to enter the country, it is still important to consider getting vaccinated to protect yourself from the illness as well as prevent outbreaks in vulnerable communities.  

Obtaining vaccination certificates

Countries that require a yellow fever vaccination to enter will need a certificate as proof. These are known as an International Certificate of Vaccination or Prophylaxis (ICVP) and will be given to you at the same time as your vaccine appointment. It is important to keep this safe and to make a copy for your own records, as if you lose the original you can  get it replaced as long as you have the details copied. 

Summary

• Yellow fever is a condition caused by the yellow fever virus, which is spread through mosquito bites 
• It is named yellow fever due to the build-up of yellow bile products when the liver gets damaged 
• It causes fever, headaches, and body pain in mild cases 
• In severe cases, it can cause total liver and kidney failure, often leading to death 
• Yellow fever vaccination is very effective as it uses the whole, live virus 
• Immunocompromised individuals should seek medical advice before receiving the vaccine  
• Many countries require proof of vaccination before entry  
• As well as vaccination, it is important to protect yourself by preventing mosquito bites wherever possible