Information about yellow fever disease, vaccines and recommendations for vaccination from the Australian Immunisation Handbook
Guidance on international travel requirements for yellow fever vaccination has been updated, including the details required on the International Certificate of Vaccination or Prophylaxis (ICVP).
Yellow fever is a viral disease that is transmitted by infected mosquitoes. Complications from yellow fever can be severe and can cause death.
Yellow fever vaccine is recommended for:
- people who work in laboratories with the yellow fever virus
- people aged ≥9 months who are travelling to an area with a risk of yellow fever virus transmission
Yellow fever vaccine is recommended for laboratory workers who work with the yellow fever virus. Workers should have their antibody titres measured if their last vaccine dose was 10 years ago or more to check that they still have protective antibody levels.
Yellow fever vaccine is recommended for people ≥9 months of age who are travelling to an area with a risk of yellow fever virus transmission.
The following travellers are recommended to receive a booster dose if their last vaccine dose was 10 years ago or more:
- women who were pregnant (in any trimester) when they received their 1st dose of yellow fever vaccine
- people who had HIV when they received their 1st dose of yellow fever vaccine
- people who will be staying in a high-risk location for an extended period of time
- people travelling to an area with ongoing outbreaks
People who have had a haematopoietic stem cell transplant after a dose of yellow fever vaccine are recommended to receive an extra vaccine dose if they will be in an area with a risk of yellow fever virus transmission.
Yellow fever virus is endemic in tropical and subtropical regions of Africa and South America where it causes significant illness and death. Vaccination prevents international spread of the disease and some countries require documented evidence of yellow fever vaccination as a condition for entry.
Laboratory workers who may be exposed to yellow fever virus are recommended to receive yellow fever vaccine
1 dose of yellow fever vaccine is recommended for people who work in laboratories with the yellow fever virus.
Laboratory workers with ongoing exposure to yellow fever virus should have their neutralising antibody titres measured if their last vaccine dose was 10 years ago or more. This is to check that they have maintained protective antibody levels.
If antibody titres cannot be measured, laboratory workers are recommended to receive a booster dose every 10 years.
People aged ≥9 months travelling to an area with a risk of yellow fever virus transmission are recommended to receive yellow fever vaccine
1 dose of yellow fever vaccine is recommended for people ≥9 months of age who are travelling to an area with a risk of yellow fever virus transmission. This includes expatriates and people who are visiting friends and relatives.
Travellers should seek up-to-date information about yellow fever virus activity and risk of yellow fever in their travel destinations from reputable sources, such as:
- the World Health Organization web page on international travel and health1
- the Centers for Disease Control and Prevention web page on on travellers’ health2
Some travellers may need yellow fever vaccination to meet a country’s vaccination requirements for travel. This might happen even if they are not travelling to an area with a risk of yellow fever virus transmission. See International travel requirements.
People who do not respond optimally to yellow fever vaccination are recommended to receive a booster dose if their last vaccine dose was 10 years ago or more. This includes:
- women who were pregnant (in any trimester) when they received their 1st dose of yellow fever vaccine
- people who had HIV when they received their 1st dose of yellow fever vaccine, regardless of their level of immunocompromise at the time
Travellers whose last vaccine dose was 10 years ago or more are recommended to receive a booster dose under certain circumstances. This might be:
- because they have a higher risk of yellow fever virus infection, such as people who will be staying in a high-risk location for an extended period of time
- because they are travelling to an area with ongoing outbreaks
The mosquitoes that carry yellow fever usually bite during the day. All people travelling to countries with a risk of yellow fever virus transmission should be told this.
Even vaccinated people should be told about the importance of avoiding mosquitoes. Ways to avoid mosquitoes include:
- using insect repellents containing at least 30% DEET
- using mosquito nets (preferably insecticide-treated nets)
- minimising outdoor exposure at dusk and dawn
- wearing clothing that leaves a minimum of exposed skin
International travel requirements
Under the International Health Regulations (2005), many countries require travellers arriving from countries with a risk of yellow fever virus transmission to provide either:
- a valid International Certificate of Vaccination or Prophylaxis (ICVP) against yellow fever, or
- a valid letter of exemption
Travellers must provide this before entering those countries.
A country may require this documentation even for travellers who are only in transit through that country (in general this will only be requested for over 12 hours of airport transit time). This is because, if an infected traveller brought the virus into the country, the virus could be introduced and established in local Aedes aegypti mosquitoes.
In 2016, the World Health Organization extended the validity of the ICVP from 10 years to the life of the vaccinated person. This decision was based on evidence that a single dose of yellow fever vaccine protects most people for many decades.3-5 (See Duration of immunity.)
Travellers should check the yellow fever vaccination entry requirements for the countries they intend to enter or transit through before they leave Australia. Travellers can contact the country’s foreign embassy or consulate in Australia.
Australia’s travel requirements
Australia strongly recommends that travellers >1 year of age have a valid ICVP with proof of valid yellow fever vaccination if they:
- are entering Australia within 6 days of leaving a country that is on Australia’s list of yellow fever–declared places
- stayed in the at-risk area overnight or longer
- name of the vaccinated person
- date of the vaccination (day–month–year sequence, with the month written in letters)
- vaccine the person received
- manufacturer and batch number of vaccine or prophylaxis
- signature and professional status of the authorised health professional
- official stamp of the administering centre (provided by the state or territory health authority)
- signature of the vaccinated person (or guardian)
As of 16 June 2016, Australia considers an ICVP to be valid for the life of the vaccinated person. The certificate becomes valid 10 days after vaccination.
Travellers arriving in Australia who do not have a valid ICVP receive information about yellow fever. They are advised to promptly seek medical assessment if they develop relevant symptoms within 6 days of leaving a yellow fever–declared place.
A list of yellow fever–declared places is available from the Australian Government Department of Health’s yellow fever fact sheet.6
Exemptions to vaccination
People with a true contraindication to yellow fever vaccine (see Contraindications and precautions) can still travel to countries with a risk of yellow fever virus transmission. They should have a dated and signed letter on letterhead stationery from an accredited Yellow Fever Vaccination Centre. The letter should:
- state that the yellow fever vaccine is contraindicated on medical grounds
- display the centre’s official stamp provided by the state or territory health authority
Medical exemption letters should be written for the current trip only. If the person needs exemption for yellow fever vaccination for another trip, they need a new medical exemption letter. The immunisation provider must also complete, stamp and sign the Medical Contraindications to Vaccination section of the ICVP.
Travellers arriving in Australia who have a medical exemption letter for yellow fever vaccination receive information about yellow fever. They are advised to promptly seek medical assessment if they develop relevant symptoms within 6 days of leaving a yellow fever–declared place.
Contraindicated travellers to other countries that need an exemption for yellow fever vaccination should contact the country’s foreign embassy or consulate in Australia. The mission can advise which language(s) the letter needs to be written in.
Vaccines, dosage and administration
Yellow fever vaccine available in Australia
Registered for use in people aged ≥9 months.
Live attenuated yellow fever vaccine
Lyophilised powder in a monodose vial with a pre-filled diluent syringe.
Each 0.5 mL reconstituted dose contains:
- ≥1000 IU of yellow fever virus (17D strain)
- 16.0 mg lactose
- 8.0 mg sorbitol
- 833 µg L-histidine hydrochloride
May contain traces of egg proteins.
Dose and route of administration
The dose of yellow fever vaccine in children and adults is 0.5 mL given by either intramuscular or subcutaneous injection.
Only Yellow Fever Vaccination Centres can provide yellow fever vaccination. These centres must be approved by the relevant state or territory health authorities. See International travel requirements.
Co-administration with other vaccines
Children and adults can receive yellow fever vaccine at any time before or after, or with, inactivated vaccines and oral live vaccines relevant to travel (such as cholera and typhoid).
Children and adults can receive yellow fever vaccine and most other parenteral live vaccines either:
- on the same day, or
- at least 4 weeks apart
If a person receives yellow fever vaccine at the same time as other live vaccines, this does not affect their immune response to any of the vaccine antigens. This includes co-administration with:
- Japanese encephalitis vaccine7
BCG (bacille Calmette–Guérin) vaccine
One Brazilian study suggested that co-administration of yellow fever and MMR vaccines on the same day resulted in lower seroconversion rates to the vaccine antigens than when the vaccines were given at least 4 weeks apart.8 More studies are needed to determine the clinical significance of this finding. See Immunogenicity in children in Vaccine information.
Contraindications and precautions
However, if such travel is unavoidable, the person should receive information about avoiding mosquitoes (see Avoiding mosquitoes) and a medical exemption letter which is required for crossing borders – see Exemptions to vaccination and International travel requirements.
Anaphylaxis to vaccine components
Yellow fever vaccine is contraindicated in people who have had:
- anaphylaxis after a previous dose of any yellow fever vaccine
- anaphylaxis after any component of a yellow fever vaccine
- anaphylaxis to eggs
People with a known allergy to eggs who want to receive yellow fever vaccine should discuss this with an immunologist or allergist, or be referred to a specialised immunisation adverse events clinic.
Contact a specialist travel medicine clinic or your state or territory health authority for more details.
Routine yellow fever vaccine is generally contraindicated in infants <9 months of age. This is because of the risk of severe adverse events after vaccination (see Adverse events).
However, countries experiencing a mass outbreak of yellow fever may choose to immunise infants from as young as 6 months of age.9
People who are immunocompromised
The yellow fever vaccine is a live viral vaccine. It should generally not be given to people who are immunocompromised.
However, vaccination can be considered case by case. This needs to take into account factors such as risk of exposure and level of immunocompromise. See Vaccination for people who are immunocompromised.
People who are immunocompromised may not mount a sufficient immune response after vaccination. They may also be at risk of vaccine-related adverse events. However, few studies have assessed yellow fever vaccine immunogenicity in people who are immunocompromised (see Vaccine information).
People with thymus disorders
People with a history of any thymus disorder should not receive yellow fever vaccine. This is due to the increased risk of yellow fever vaccine–associated viscerotropic disease.10 See Adverse events.
Relevant thymus conditions include:
- myasthenia gravis
- DiGeorge syndrome
- thymic damage from chemoradiotherapy or graft-versus-host disease
Adults aged ≥60 years
Adults aged ≥60 years have a higher risk of severe adverse events after yellow fever vaccination than younger adults.11-15
Adults ≥60 years of age should receive yellow fever vaccine only if they intend to travel to endemic countries (see Recommendations). They should also receive information about the risk of developing a severe complication, even though this risk is very low.
Haematopoietic stem cell transplant recipients
People who have had a haematopoietic stem cell transplant after a dose of yellow fever vaccine are recommended to receive an extra vaccine dose if they will be in an area with a risk of yellow fever virus transmission. This is regardless of when they received their last dose.
People with HIV
People with HIV can receive a yellow fever vaccine, unless they are immunocompromised. See Vaccination for people who are immunocompromised.
Studies of yellow fever vaccine in small numbers of people with HIV suggest a reduced immune response, but vaccination is well tolerated.16,17 See Vaccine information.
There are few studies of yellow fever vaccine in people with HIV who have CD4+ counts of <200 per µL. These people should receive yellow fever vaccine only if they cannot avoid the risk of yellow fever infection. This should be considered case by case.
Women who are pregnant or breastfeeding
Yellow fever vaccine is not recommended, other than in exceptional circumstances, for:
- pregnant women
- women who are breastfeeding infants aged <9 months
Yellow fever vaccine is a live viral vaccine (see Vaccine information). Live viral vaccines are generally contraindicated in pregnant women except in extenuating circumstances. Pregnant women are not recommended to receive yellow fever vaccine unless there is a risk of exposure to the virus.
Pregnant women should be advised against travelling to an area with a risk of yellow fever virus transmission. However, if travel is unavoidable, pregnant women should receive the vaccine.18-21
Many pregnant women have received the yellow fever vaccine18,19,22 with no evidence of any adverse outcomes. This means that women who are vaccinated in early pregnancy can be reassured that there is:22
- no evidence of risk to themselves
- very low — if any — risk to the fetus
Women who are breastfeeding infants aged <9 months should avoid being vaccinated against yellow fever.
However, breastfeeding women who cannot avoid or postpone potential exposure to yellow fever virus should receive a yellow fever vaccine.20,21
Several case reports have shown that the vaccine strain of yellow fever virus can be transmitted through breast milk. This has resulted in probable vaccine-associated neurotropic disease in infants. This adverse event is extremely rare. On follow-up of these infants, their neurological development was normal.20,21 See Adverse events.
Mild adverse events
Adverse events after receiving yellow fever vaccine are generally mild, such as:
- low-grade fevers
- other minor symptoms
Symptoms usually appear in the first 5 days after vaccination, and can last up to 2 weeks.23 In clinical trials in which people were specifically asked about their symptoms:14,22,24
- up to 25% of vaccine recipients reported mild adverse events
- up to 1% restricted their regular activities
Immediate hypersensitivity reactions
Immediate hypersensitivity reactions, including anaphylaxis, after yellow fever vaccination are very rare — less than 1 in 1 million. These reactions mainly occur in people with an anaphylactic sensitivity to eggs.13,14,22
An anaphylactic sensitivity to gelatin may also trigger anaphylaxis after vaccination.25 Some yellow fever vaccines contain gelatin as a stabiliser. Stamaril does not contain gelatin.
Vaccine-associated neurotropic adverse events
Yellow fever vaccine–associated neurotropic disease (YF-AND) is a severe adverse event that can be fatal in rare cases. YF-AND has several distinct clinical syndromes, including:26,27
- meningoencephalitis (neurotropic disease)
- Guillain–Barré syndrome
- acute disseminated encephalomyelitis
- bulbar palsy
Between 1992 and 2014, more than 200 cases of neurological adverse events after yellow fever vaccination were reported worldwide.22
YF-AND is more likely to occur in very young infants and older people. Of 23 cases of meningoencephalitis reported between 1945 and 2001, 16 (70%) were infants <9 months of age. Most were <4 months of age.28
In the 1960s, recommendations against immunising infants aged <6 months led to fewer reports of encephalitis.29,30 Although YF-AND is rare in adults, adults ≥60 years of age have the highest risk.11,13,31
Vaccine-associated viscerotropic adverse events
Yellow fever vaccine–associated viscerotropic disease (YF-AVD) is a rare but severe adverse event after yellow fever vaccination. YF-AVD is characterised by multiorgan system failure. It occurs in 3–4 cases per million doses of vaccine. YF-AVD mimics naturally acquired yellow fever disease. The vaccine virus proliferates and disseminates throughout the body.32
2 risk factors have been identified for YF-AVD:
- older age
- history of thymus disease or thymectomy
A systematic review of YF-AVD among older people showed that older travellers have an increased risk of YF-AVD. However, the risk among older people in endemic populations is unknown.15 Of the initial 27 reported cases of YF-AVD worldwide, 4 occurred in people who had thymectomies performed for thymomas.10 The prevalence of thymomas in the general population is low.10,33
Several cases of YF-AVD have involved a history of autoimmune disease or diseases with potential autoimmune aetiology. However, in several of these cases, the person also had another known risk factor. More information is needed to assess the risk of YF-AVD in people with autoimmune disease.34
Nature of the disease
Yellow fever is a viral haemorrhagic fever caused by an RNA flavivirus.
The virus is transmitted by mosquitoes (mainly Aedes aegypti) through 2 zoonotic transmission cycles:
- jungle, between non-human primates and mosquitoes
- urban, between humans and mosquitoes
In Africa, an intermediate transmission cycle exists between humans or non-human primates and Aedes species mosquitoes that breed in tree holes in savanna areas. 36
Initial symptoms of yellow fever
The clinical spectrum of yellow fever varies from a non-specific febrile illness to fatal haemorrhagic fever.37 The disease begins abruptly with:
- eye congestion
The patient appears acutely ill.
The symptoms indicate a ‘period of infection’. During this time, there is an intense viraemia that lasts 3–4 days.37
This may be followed by the ‘period of remission’. During this time, the fever and symptoms settle over 24–48 hours, and the immune response clears the virus.37
Relapse and complications of yellow fever
Approximately 15–25% of patients relapse. This is called the ‘period of intoxication’. Symptoms and complications include:37
- high fever
- epigastric pain
- renal failure
These complications can be severe. The period of intoxication reflects the viscerotropic nature of the yellow fever virus — that is, its ability to infect the liver, heart and kidneys. The case-fatality rate varies widely. It has been reported as 14% in African countries and 48% in South American countries.22
The epidemiology of yellow fever is dynamic due to changes in:
- climate, such as rainfall patterns
- human factors, such as migration and air travel36
West Africa has the highest burden of yellow fever disease. Fewer cases occur in other regions of Africa and South America.22
In 2016, 1080 cases of yellow fever, including 171 deaths, were reported to the World Health Organization (WHO) from 6 countries:38
- Democratic Republic of the Congo
In 2006, WHO introduced the Yellow Fever Initiative, which aims to control and eliminate epidemic yellow fever in Africa. Strategies include:
- including yellow fever vaccine in routine childhood immunisation programs
- mass vaccination campaigns
In endemic areas with high vaccination coverage, yellow fever outbreaks have decreased substantially. South America has used a similar approach.39
Risk to travellers
The risk of susceptible travellers acquiring yellow fever varies considerably. It depends on:
- location of travel
- duration of travel
- use of mosquito avoidance measures
Some cases of yellow fever in unvaccinated travellers to Africa and South America have all been fatal.40,41
Travellers should seek up-to-date information about yellow fever virus activity and risk of yellow fever in their travel destinations from reputable sources, such as:
Yellow fever vaccine is a live, freeze-dried preparation of attenuated 17D strain yellow fever virus. The virus is cultured in, and harvested from, embryonated chicken eggs. The vaccine does not contain antibiotics, preservatives or gelatin.
Efficacy and immunogenicity
No studies have directly assessed the efficacy of yellow fever vaccine. Immunogenicity is used as a surrogate for protection. Thresholds for protective immunity are defined as either: 42
- log10 neutralisation index (LNI) >0.7, or
- a titre of >1:10 using plaque reduction neutralisation tests
Immunogenicity in adults
After a single dose of yellow fever vaccine, approximately 90% of healthy adult vaccine recipients develop protective levels of neutralising antibodies by day 14. Virtually all recipients develop these levels by day 28.22
Immunogenicity in children
In children, the proportion of vaccine recipients who achieve protective yellow fever antibody levels after a single dose of vaccine is similar to that in adults. 43,44
1 randomised trial suggested lower seroconversion rates (70%) against yellow fever virus in children <2 years of age. However, this was when yellow fever vaccine was co-administered with MMR vaccine.8 In comparison, 87% of children who received yellow fever and MMR vaccines seroconverted when the 2 vaccines were given at least 30 days apart. This study did not report on the proportion of participants with protective levels of neutralising antibodies on the basis of commonly applied definitions.
Immunogenicity in people with medical conditions
Immunogenicity studies in people with underlying medical conditions are limited. Some data suggest that pregnant women and people with HIV do not respond well to yellow fever vaccination.
38.6% of pregnant women who received yellow fever vaccine in their 3rd trimester achieved protective levels of neutralising antibodies. In comparison, 81.5–93.7% of non-pregnant women of child-bearing age and other adults achieved protective levels of neutralising antibodies.45
A better response to the yellow fever vaccine was reported in a separate study of women who were vaccinated in their 1st trimester of pregnancy. This suggests that antibody response to vaccination in pregnant women may depend on the stage of gestation.18
People with HIV
2 studies reported lower rates of neutralising antibodies among HIV-infected people than in uninfected controls.16,17 Some observational studies have reported that seroconversion rates in people with HIV were similar to those reported in healthy adults (>90%). However, the number of participants in these studies was small and there were no healthy controls.46-49 When reported, CD4+ counts of HIV-infected participants were >200 cells per µL. Several studies found that higher antibody titres were associated with higher CD4+ counts and lower HIV RNA levels. 49,50
People who are immunocompromised
Only a few small, low-quality studies and case reports provide data on the immunogenicity of yellow fever vaccine in people who are immunocompromised, other than people with HIV.51,52
A reduced immune response to yellow fever vaccine was reported among people who received immunosuppressive therapy for rheumatoid disease.53
Duration of immunity
A single dose of yellow fever vaccine should provide lifelong immunity in most healthy adults and children. Protective levels of neutralising antibodies have been detected in 75–100% of healthy adults from endemic and non-endemic yellow fever areas when measured 10–69 years after the 1st vaccination.3-5
Although vaccinated people have contracted yellow fever disease, it has only been reported in people living in highly endemic areas. A study from Brazil showed that, among 459 people with laboratory-confirmed yellow fever who reported previous vaccination, 432 (94%) had yellow fever 10 or more years after vaccination. This suggests secondary vaccine failure due to waning immunity, although primary vaccine failure (poor initial immune response) may have contributed.54
Few studies have assessed the duration of immunity in groups who do not respond optimally to primary yellow fever vaccination. A cohort study measured levels of yellow fever neutralising antibodies in people with and without HIV. Within 1–10 years after vaccination, 23% of people with HIV lost protective antibody levels. In comparison, 12% of people without HIV lost protective antibody levels.17
A booster dose of yellow fever vaccine can produce protective levels of yellow fever neutralising antibodies in people whose response to the primary vaccine dose was low or negative. 55,56
Transporting, storing and handling vaccines
Transport according to National vaccine storage guidelines: Strive for 5.57 Store at +2°C to +8°C. Do not freeze. Protect from light.
Stamaril must be reconstituted. Add the entire contents of the diluent syringe to the vial and shake until the powder completely dissolves. Use reconstituted vaccine within 1 hour.
Public health management
Yellow fever is a notifiable and quarantinable disease in all states and territories in Australia.
State and territory public health authorities can provide advice about the public health management of yellow fever, including management of cases and their contacts.
Variations from product information
The product information for Stamaril states that pregnancy is a contraindication to receiving the vaccine. The Australian Technical Advisory Group on Immunisation recommends that pregnant women can receive the vaccine if they cannot avoid travelling to an area with a risk of yellow fever virus transmission.
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- Collaborative Group for Studies on Yellow Fever Vaccines. Duration of post-vaccination immunity against yellow fever in adults. Vaccine 2014;32:4977-84.
- Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). Grading of recommendations, assessment, development, and evaluation (GRADE) for yellow fever vaccine booster doses. 2015 (accessed May 2018).
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- Kernéis S, Launay O, Ancelle T, et al. Safety and immunogenicity of yellow fever 17D vaccine in adults receiving systemic corticosteroid therapy: an observational cohort study. Arthritis Care and Research 2013;65:1522-8.
- Scheinberg M, Guedes-Barbosa LS, Mangueira C, et al. Yellow fever revaccination during infliximab therapy. Arthritis Care and Research 2010;62:896-8.
- Oliveira AC, Mota LM, Santos-Neto LL, et al. Seroconversion in patients with rheumatic diseases treated with immunomodulators or immunosuppressants, who were inadvertently revaccinated against yellow fever. Arthritis and Rheumatology 2015;67:582-3.
- Câmara FP, de Carvalho LM, Gomes AL. Demographic profile of sylvatic yellow fever in Brazil from 1973 to 2008. Transactions of the Royal Society of Tropical Medicine and Hygiene 2013;107:324-7.
- Hepburn MJ, Kortepeter MG, Pittman PR, et al. Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine. Vaccine 2006;24:2843-9.
- Omilabu SA, Adejumo JO, Olaleye OD, Fagbami AH, Baba SS. Yellow fever haemagglutination-inhibiting, neutralising and IgM antibodies in vaccinated and unvaccinated residents of Ibadan, Nigeria. Comparative Immunology, Microbiology and Infectious Diseases 1990;13:95-100.
- National vaccine storage guidelines: Strive for 5. 3rd ed. Canberra: Australian Government Department of Health and Ageing; 2019. https://www.health.gov.au/resources/publications/national-vaccine-storage-guidelines-strive-for-5
- international units
- bacille Calmette-Guérin
- ribonucleic acid
- World Health Organization
- Japanese encephalitis
- Western Australia