Yellow fever vaccination

Indication

Risk of yellow fever

The risk of yellow fever, country requirements and individual risk factors should be taken into account prior to vaccination. Countries and regions where vaccination is recommended are coloured in red in the Yellow fever vaccination map.

Travel in endemic areas
Vaccination is recommended in countries where there is a risk of yellow fever, either due to a potential risk because of the presence of the mosquitos and the animal reservoir or because of currently reported cases. Not all yellow fever-endemic countries require proof of vaccination, so the administrative requirements do not necessary reflect the actual risk. 

Travel to a country with certain regions at risk
Vaccination is usually advised, unless travellers are certain they will not visit endemic areas and if there is no administrative obligation, e.g., such as when crossing certain borders. 

Travel to a country or area with low potential of exposure
In accordance with the WHO guidelines, vaccination is no longer recommended when visiting a country or an area with low potential of yellow fever exposure. Examples of such countries are Tanzania and Rwanda. When travelling from a non-endemic country, a vaccination certificate or waiver is not required. 

Future travellers
It might be beneficial to vaccinate people pre-emptively who travel frequently on short notice. 
Young people without active travel plans but who might require immune modulating medication in the near future (ex. Crohn’s disease, kidney transplant,…)  could be vaccinated prior to starting treatment. It’s advised to respect a four-week waiting period between administering the vaccine and initiating immunosuppressive medication.   

Mandatory vaccination proof
In accordance with the International Health Regulations (2005) some countries require a proof of vaccination documented in an International Certificate of Vaccination or Prophylaxis at least 10 days prior to arrival. This includes countries with a yellow fever risk and countries concerned about the introduction of the virus. Proof of vaccination is typically required for individuals aged 1 year or older but sometimes from 9 months or exceptionally at 6 months. 
Vaccination may be required if a traveller has visited an endemic country within 6 days before arrival, exceptionally 10 days. 
Some countries require vaccination after a stopover in an airport in an endemic country of more than 12 hours, although this threshold can vary between 4 to 24 hours. While a traveller staying less than 12 hours in an airport would generally not need to provide proof of vaccination, some countries have very strict entry policies and may require it, even if the traveller never leaves the plane.

In particular cases where vaccination is contra-indicated, a waiver with end date should be issued in the ICVP stating “vaccination is contra-indicated for medical reasons”.

More details on the regions where yellow fever vaccination is recommended and on the entry requirements can be found on the yellow fever vaccination map and in the country specific pages. This information is based on the WHO international travel health publication and feedback from travellers. The entry requirements are subjects to change without notice. Therefor ITM cannot guarantee that the information on the website or app correspondents with the latest requirements. Please contact us whenever you experience that the entry requirements have changed. 

Side- effects

Up to 20% will have a short period (<24hrs) with mild flu-like symptoms, this usually presents between day five and ten and is self-limiting. Less than 1% will temporarily be unable to go into work. 

Anaphylaxis 
It's estimated in five to twenty per one million patients (1/50 000 – 1/200 000). This is most likely due to an allergy to egg or gelatine components. The tip caps of the prefilled syringes contain a natural rubber latex derivative, which may cause allergic reactions in latex sensitive individuals.

Yellow fever vaccine- associated neurologic disease (YEL-AND)
YEL-AND is rare with an overall risk of 0.8 per 100 000 vaccinations according to CDC, 2/3 of the cases occurred in children younger than 6 months. It consists of different neurological complications (e.g., meningoencephalitis, Guillain-Barré syndrome, acute disseminated encephalomyelitis, cranial nerve palsies) due to an immunological reaction or due to invasion of the vaccine virus in neurological tissue. This complication is seen 2 to 56 days after vaccination.

Yellow fever vaccine- associated viscerotropic diseases (YEL-AVD)
YEL-AVD is a syndrome of fever with multi- organ failure that resembles severe yellow fever disease. It was first described in 2001 and over a hundred confirmed cases have been reported worldwide, death has occurred in more than 60% of reported cases. It has only been seen with people receiving their first vaccination and develops 3 to 5 days (range 1 to 18 days) following administration.
YEL-AVD has been estimated to be reported in 0.3 cases per 100 000 doses distributed according to CDC. The rates increase with increasing age: from 1 per 100 000 vaccines in people aged 60-70 year up to 2.3 per 100 000 vaccines when older than 70 years. Risk factors for developing YEL-AVD are increasing age and thymus disorders, which can be present in conditions like myasthenia gravis. Case series have also shown that individuals with documented interferon 1 deficiency (INF-1) have an increased risk.

In case a patient would present with a clinical picture suggestive of YEL-AND or YEL-AVD (at least 38,5°C for more than 24hr) further laboratory investigations are required to confirm the diagnosis. It’s advised to contact the medical team of Institute of Tropical Medicine to discuss this further.  The federal agency for medicines and Health Products (FAGG) should be notified and this can be done through their website. 

Contraindications

Absolute contraindications

• Severe allergy (anaphylaxis) to eggs or latex or any other component
• Child under the age of 6 months
• Thymus dysfunction with abnormal immune cell function, including myasthenia gravis
• HIV with CD4 < 200 cells/µl 

• Immunosuppressive or immunomodulatory therapies

• Primary immunodeficiencies

• INF-1 deficiency (due to genetic defect or auto-antibodies)

• Transplant patient (Hematopoietic stem cell, solid organ)  

Allergy to egg products (anaphylaxis) 
The vaccine often can be administered after a small test dose (percutaneous or intradermal). This should be done in a hospital setting where adequate resuscitation support is readily available.

Even if it’s not possible to proceed with the full subcutaneous dose, a fractional intradermal dose of 1 ml results in protective neutralizing antibodies, but does not meet the requirements under the IHR and proof of vaccination for international travel cannot be issued.

Children under the age of 6 months have a higher risk of YEL-AND.

Thymus dysfunction with abnormal immune cell function
Vaccination is contraindicated in patients who have a thymus disorder associated with abnormal immune cell function (e.g., thymoma, Di George, myasthenia gravis), because of increased risk YEL-AVD. There is no evidence of immunodysfunction or increased risk of yellow fever vaccine-associated serious adverse events in people who have undergone incidental thymectomy, or who have had indirect radiation therapy, so these people can be vaccinated.

Patients with primary or secondary acquired immunodeficiencies 
Due to potential serious side effects, vaccination is not recommended in patients with severe immunodeficiencies (e.g., HIV CD4< 200/µl, post-transplant, immune modulating or suppressive therapy, primary immune deficiency). The guideline of vaccination of immunocompromised patients of the Superior Health Council should be consulted for more detailed information.

INF-1 deficiencies
Individuals with INF-1 deficiencies are at higher risk of YEL-AVD. Although INF-1 deficiencies are not commonly tested for in routine screening, if an individual is known to have this deficiency, yellow fever vaccination is contraindicated.

Relative contraindications

Relative contraindications are associated with an increased risk of vaccine related side effects or a reduced effectiveness. An individualized risk-benefit assessment prior to vaccine administration is needed.

• Primo-vaccination ≥60 years of age
• Child between 6 and 9 months old
• Pregnancy
• Breastfeeding in infants under 6 months

Adults 60 years of age or older
There is an increased risk of YEL-AND and YEL-AVD in people older than 60 years of age, mainly reported in primary vaccine recipients. The rate of reported serious adverse events in people ≥60 years is 7.7 per 100 000 doses compared to 3.8 per 100 000 in the overall population. The decision to vaccinate needs to weigh the risks and benefits of the vaccination in the context of their destination-specific risk.

The risk and benefits to take into considerations for travellers over 60 years of age to a risk country are:

• Future plans to travel to yellow fever areas. 
• Visiting neighbouring countries, anticipation of problems at border crossing.
• Prolonged travel or travel with unavoidable exposure to mosquitoes.
• Serious adverse events after yellow fever vaccination in a relative (contra-indication). 

Children
The yellow fever vaccine can be administered to children starting from 9 months of age. In cases there is a high risk (e.g., visiting friends and relatives who will be spending several weeks to months in rural areas) it might be exceptional administered to children from the age of 6 months after expert advice. 

Pregnancy
Usually life attenuated vaccines are contra-indicated in pregnant women and it is recommended to delay pregnancy until 4 weeks after vaccination. In general, it is safer to avoid travel to yellow fever risk areas.

However, in two observational studies, no major congenital problems were observed in children exposed to yellow fever vaccination in early pregnancy. A slight increase in minor abnormalities (mainly naevi) was observed in one study.

Yellow fever vaccination in pregnant women results in less seroconversions, especially during third trimester. Therefore, a single revaccination is recommended when the women will be exposed again and is not pregnant.

Pregnant women who require proof of vaccination solely for administrative purposes should be granted a waiver. 

Breastfeeding
The yellow fever virus and vaccine can be transmitted into breastmilk. Transmission of the vaccine virus was demonstrated in several young infants, usually below the age of 2 months who developed YEL-AND, often without long term consequences (Drugs and lactation database NIH). Administration of yellow fever vaccine to breastfeeding woman ideally should be avoided but could be considered if exposure to yellow fever viruses is inevitable. Some experts  recommend that breastfeeding is suspended for two weeks post-vaccination. 
The vaccine derived virus transmitted by breastfeeding will not protect the infant. Infants over 9 months of age should receive the vaccine if they will be traveling to a yellow fever endemic area. Exposure to the yellow fever vaccine via breastmilk does not present an increased risk to an infant who also receives the vaccination. 

Co-administration

Non-live vaccines
The vaccine can be administered at the same time as other non-live vaccinations.

Life attenuated vaccines
Vaccination against measles is preferably given with an interval of 4 weeks because a few studies demonstrate lower vaccine response rates for yellow fever and MMR in infants. There are no data in adults. However, if separating the vaccinations is not feasible, simultaneous administration is advised, but preferable in a different limb. If this is also not possible and there is an indication for both vaccines, the yellow fever vaccine and other live-attenuated vaccines can be administered at any interval, as the risk of delaying vaccination outweighs the potential risks of shorter interval.

Yellow fever vaccine can be administered together with immunoglobulins (in non-endemic settings) and antimalaria medication.

Tuberculosis intradermal skin test (Mantoux)
The vaccine can interfere with a tuberculosis intradermal skin test, as any live virus vaccine, with a risk of a false-negative test result due to a possible suppressed immune response. Therefore the vaccine should preferably not be administered in a period of four weeks before a tuberculin skin test.

Blood donations

Blood donations should be deferred until 4 weeks after vaccination.