The risk of Yellow fever for travelers.

Travel exposes our bodies to bacteria and viruses that could pose a real threat to our health.

One of those pathogens is Yellow fever. Yellow fever is spread by mosquitos. The infection can cause severe symptoms which include a hemorrhagic fever. This can have a high mortality.

Clinically, infection with Yellow fever can cause liver dysfunction, kidney failure, bleeding, shock and possibly death.

Those travelers who are going to the tropical regions of South America and sub-Saharan Africa where the disease is endemic are at risk for infection and require immunization.

Yellow fever is a vaccine preventable disease!

Yellow fever is a member of the family Flaviviridae, a group of small, enveloped, viruses that replicate inside of the infected cells.

The Yellow fever virus is a single serotype and is antigenically conserved, this is a good thing because that means the vaccine protects against all strains of the virus.

It is possible to distinguish seven major genotypes based on geography. There are two types in West Africa, three in Central-East Africa and Angola, and two types in South America.

There was a large outbreak of Yellow fever in Africa in 2015-16 and one in Brazil from 2016 to 2018.

An infected female mosquito injects approximately 1000 to 100,000 virus particles into the skin during blood feeding.

Virus replication begins and spreads through local lymphatic channels to regional lymph nodes. Yellow fever reaches other organs using the lymphatic system and then the bloodstream.

Large amounts of virus are produced in the liver, lymph nodes, and spleen and are released into the blood. When the virus is replicating, usually days three to six, infection may be transmitted to blood-feeding mosquitoes.

How does Yellow fever cause organ damage?

Yellow fever can damage the liver, kidneys and it can cause bleeding.

Injury to the liver is due to degeneration of cells followed by cell death, which is a different mechanism than what is seen in viral hepatitis.

Kidney injury is caused by degeneration and fatty change in the kidney. This is multifactorial and is thought to be a result of both direct viral injury and changes in blood pressure due to shock, specifically low blood pressure.

Yellow fever infection can also injure the heart muscles.

The bleeding caused by Yellow fever is due to liver making less vitamin K, this vitamin is required for the body to make coagulation factors, these are the components needed by the body to allow for normal clotting.

The late phase of the disease is characterized by shock. Patients who have succumbed to yellow fever have been found to have brain swelling at autopsy on top of all the other organ damage.

Where is Yellow fever found?

Yellow fever occurs in tropical regions of sub-Saharan Africa and South America. The incidence of endemic disease is not well established.

The incidence of Yellow fever in Africa varies widely, and the disease occurs in epidemics.

Mosquito borne epidemics in Africa occur where people live in densely populated areas and there is limited access to the vaccine. The highest number of outbreaks have occurred in West Africa, but this situation is changing due to a concerted effort to undertake mass immunization campaigns in that region.

Human to human transmission in the absence of the mosquito has not been reported.

Recent outbreaks

Brazil had an outbreak in late 2016, this is still ongoing. To combat this, In March 2018, the Brazilian health ministry issued a recommendation for universal Yellow fever vaccination in Brazil.

Since January 2018, ten travel-related cases have been reported in travelers returning from Brazil. Among those, four died from complications of Yellow fever infection. None of the ten travelers had been vaccinated against Yellow fever.

Again, this is a vaccine preventable disease!

In 2018, five countries in the Americas reported confirmed cases of yellow fever: Bolivia, Brazil, Colombia, French Guiana, and Peru. As of late 2019, three countries in the Region of the Americas reported yellow fever. These include Bolivia, Brazil, and Peru.

What happens when you are infected with Yellow fever?

Three things can happen:

1- Subclinical infection - very mild symptoms

2- Nonspecific fever without liver damage

3- Life-threatening disease with fever, jaundice (yellowing of the skin), renal failure, and hemorrhage

Yellow fever affects all ages, but disease severity and mortality is highest in older adults. The onset of illness appears abruptly about 4 days after the bite of an infected mosquito.

What is the outcome after infection?

How an infected patient recovers is usually determined during the second week after onset of symptoms. At that point there is either rapid recovery or the patient succumbs to the viral illness.

Nearly half of patients who get the severe infection succumb to the disease.

Recovery may be associated with fatigue lasting for several weeks.

Complications of yellow fever include bacterial superinfections, such as pneumonia, parotitis, and sepsis.

How is Yellow fever diagnosed?

Diagnosis is made by lab tests.

How do you treat Yellow fever?

There is no specific treatment for Yellow fever.

Treatment consists of supportive care. As of the writing of this blog, there is no specific antiviral therapy available.

What can be done to prevent or minimize risk of infection?

THIS IS A VACCINE PREVENTABLE DISEASE!

Vaccination is the primary tool for prevention of Yellow fever.

Vaccination

Available vaccines

A live-attenuated vaccine was developed in 1936 (yellow fever 17D vaccine). There are six manufacturers of yellow fever vaccine worldwide, which produce about 70 to 90 million doses annually. Of those, four are approved by the World Health Organization (WHO) and supply the vast majority of doses. In general supply does not meet demand. This is important to take into consideration when planning your trip.

The WHO maintains an emergency stockpile of six million doses. This was depleted and replenished three times in the 2016 Angolan outbreak.

Guidance for travelers

The Centers for Disease Control and Prevention (CDC), the United States Advisory Committee on Immunization Practices (ACIP), and the WHO all recommend vaccination for travelers to yellow fever-endemic areas of Africa and South America.

For all travelers regardless of age, a careful risk-benefit assessment should be undertaken. Due to the risk of serious adverse events (particularly in individuals >60 years of age), the benefit of immunization should be established based on careful review of the traveler's itinerary with respect to potential for exposure to yellow fever virus.

It is uncertain whether travelers need routine booster vaccination.

The ACIP recommends that a single primary dose of Yellow fever vaccine is adequate for most travelers.

Immunization certificates

In the US, Yellow fever vaccine is distributed only through approved vaccination centers. These include travel clinics and some health departments. These designated centers are listed in a registry at the CDC travel website.

Some countries in Yellow fever-endemic zones require a World Health Organization international certificate of vaccination as evidence of Yellow fever immunization prior to entry.

These are listed in the publications and websites of the CDC and WHO. In addition, some countries outside of yellow fever zones also require evidence of immunizations prior to entry for individuals with recent travel in endemic countries.

The WHO international certificate of immunization for international travel is valid for life.

Individuals with contraindications or precautions deemed to place the traveler at high risk of adverse events may receive a waiver letter from a physician for travel to areas where vaccination is an international travel requirement.

Does the vaccine work?

The vaccine produces high levels of protection against Yellow fever. Protective immunity occurs in 90 percent of individuals within 10 days after receiving the 0.5 mL subcutaneous dose and in nearly 100 percent of individuals within three to four weeks after vaccination.

A single dose of the vaccine may provide lifetime protection.

The WHO Strategic Advisory Group of Experts in Immunization concluded in 2013 that a single primary dose of yellow fever vaccine is sufficient to confer sustained immunity and lifelong protection against yellow fever disease, and a booster dose of the vaccine is not needed.

In May 2014, the World Health Assembly adopted the recommendation to remove the 10-year booster dose requirement from the International Health Regulations by June 2016. In 2015, the United States Advisory Committee on Immunization Practices issued recommendations stating that a single primary dose of yellow fever vaccine is adequate for most travelers.

Is the vaccine safe?

More than 700 million doses of vaccines have been administered. So yes, it is safe.

Serious adverse reactions to the vaccine are very rare and include two syndromes. These are known as Yellow fever vaccine-associated neurotropic disease (YEL-AND) and Yellow fever vaccine-associated viscerotropic disease (YEL-AVD).

In the United States, the risks of YEL-AND and YEL-AVD in civilian travelers are estimated at 0.8 and 0.4 per 100,000 respectively, although the risk is higher in older individuals.

The vaccine is contraindicated for persons with known egg allergy.

The yellow fever vaccine virus may be transmitted by transfusion of blood products. Vaccine recipients should avoid blood donation for at least two weeks.

Take away points:

This is a vaccine preventable disease.

Yellow fever is a mosquito-borne viral hemorrhagic fever with a high case-fatality rate. Travelers to tropical regions of South America and sub-Saharan Africa are at risk for acquisition of infection and require immunization.

There is no specific treatment for Yellow fever. Treatment consists of supportive care, there is no specific antiviral therapy available.

In accordance with the United States Centers for Disease Control and Prevention (CDC), the United States Advisory Committee on Immunization Practices (ACIP), and the World Health Organization (WHO), Yellow fever vaccine is recommended for travelers to yellow fever-endemic areas of Africa and South America and for residents of those areas.

Serious adverse reactions to the Yellow fever vaccine are very rare and include two syndromes. Yellow fever vaccine-associated neurotropic disease (YEL-AND) and Yellow fever vaccine-associated viscerotropic disease (YEL-AVD).

Some countries in Yellow fever-endemic zones require an international certificate of vaccination as evidence of Yellow fever immunization prior to entry.

Safe travels.

Please remember that medical information provided by us must be considered an educational service only. This blog should not be relied upon as medical judgement and does not replace your physician’s independent judgement. This is NOT medical advice. Please seek the advice of your physician.