Yellow Fever Vaccine

Class: Vaccines
ATC Class: J07B101
VA Class: IM100
Brands: YF-VAX

Introduction

Live, attenuated virus vaccine.102 106 107 Yellow fever vaccine commercially available in the US contains organisms of the 17D-204 strain of yellow fever virus and is used to stimulate active immunity to infection by the virus.106 Different yellow fever vaccines may be available in other countries.107

Uses for Yellow Fever Vaccine

Prevention of Yellow Fever Virus Infection

Prevention of yellow fever virus infection in adults, adolescents, and children ≥9 months of age at high risk of exposure to yellow fever virus.101 106 107

Yellow fever is an acute viral illness caused by a flavivirus transmitted to humans by mosquito vectors.101 106 107 Yellow fever virus occurs only in sub-Saharan Africa and South America where it is endemic and intermittently epidemic.101 106 107 WHO estimates that about 200,000 cases of yellow fever occur annually worldwide and the fatality rate is approximately 20%.101 106 107 Fatalities associated with yellow fever have occurred in recent years (at least 6 during 1996–2002) in unvaccinated American and European tourists visiting rural areas within the yellow fever endemic zone.101 106 107

USPHS Advisory Committee on Immunization Practices (ACIP) and AAP recommend vaccination for adults, adolescents, and children ≥9 months of age residing or traveling in countries within the yellow fever-endemic zone or where an International Certificate of Vaccination or Prophylaxis (ICVP) showing vaccination against yellow fever is required as a condition for entry.101 106 107

Preexposure Vaccination Against Yellow Fever Virus Infection in High-risk Groups

Preexposure vaccination in adults, adolescents, and children ≥9 months of age who are or will be at high risk of exposure to yellow fever virus.106 107

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Travelers to areas within the yellow fever endemic zone are at risk of exposure to the disease and ACIP, AAP, and WHO recommend preexposure vaccination against yellow fever for such individuals.101 106 107

Actual areas of yellow fever virus activity far exceed the zones where the disease is officially reported.101 107 Therefore, vaccination is recommended for individuals traveling to or living in all areas where yellow fever is officially reported and also is recommended for those traveling in areas of countries that do not officially report the disease, but that lie within the yellow fever endemic zone.101 106 107

Yellow fever endemic zone includes countries in sub-Saharan Africa (e.g., Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Congo, Ethiopia, Gabon, Ghana, Guinea, Kenya, Liberia, Niger, Nigeria, Rwanda, Sierra Leone, Somalia, Sudan, Uganda) and certain countries in South America (e.g., Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Panama, Paraguay, Peru, Suriname, Trinidad and Tobago, Venezuela).101 Current information regarding which countries are in the yellow fever endemic zone and/or have vaccination requirements for entry is available at the CDC website ().101

International Health Regulations require that yellow fever vaccines produced worldwide must be approved by the WHO and administered at an approved yellow fever vaccination center.101 107 In the US, yellow fever vaccine is supplied to and can be administered only at certain sites authorized to issue valid ICVP certificates.106 107 Consult local or state public health departments or the CDC for information regarding locations of these vaccination centers.101 107

Vaccinees should receive a completed ICVP form that is signed and validated with the center’s stamp where the vaccine was given.101 107 These certificates are valid for 10 years beginning 10 days after immunization.101 106 As of December 2007, only the most recent version of the ICVP will be accepted for international travel, although individuals vaccinated prior to that date who have an older certificate may use it until it expires.101 c

A number of countries (outside the endemic zone) require an ICVP showing vaccination against yellow fever from travelers arriving from infected areas or from countries with infected areas.101 111 Some countries in Africa require evidence of immunization against yellow fever from all entering travelers; others may waive requirements for travelers coming from noninfected areas and staying <2 weeks.101 106 107 Some countries require all individuals, even if only in transit (e.g., from Africa or South America to Asia), to have evidence of immunization if they have been in areas either known or suspected to harbor yellow fever virus.101 106 107

In addition to vaccination, individuals traveling to areas with yellow fever should take precautions to avoid exposure to mosquitoes (e.g., stay in air-conditioned or well-screened quarters, wear long-sleeved shirts and long pants to cover the body, use appropriate insect repellents, use mosquito nets between dusk and dawn).101 Although yellow fever transmission is unusual in urban areas and only occurs during an epidemic, travelers to rural areas of South America and Africa may be exposed to mosquitoes transmitting the disease and other mosquito-borne disease.101

Laboratory personnel with potential exposure to virulent yellow fever virus or to concentrated preparations of yellow fever vaccine virus by direct or indirect aerosol contact should receive yellow fever vaccine.106 107

HIV-infected individuals are potentially at greater risk for complications after vaccination with a live viral vaccine, and these vaccines generally are avoided in HIV-infected individuals.105 (See Individuals with Altered Immunocompetence under Cautions.) The manufacturer, ACIP, CDC, and the USPHS/IDSA Prevention of Opportunistic Infections Working Group suggest that yellow fever vaccine be offered to travelers with asymptomatic HIV infection who cannot avoid potential exposure to yellow fever.101 105 106 107 However, ACIP states the vaccine should not be used in HIV-infected individuals who are symptomatic or have acquired immunodeficiency syndrome (AIDS).107 If an HIV-infected individual must travel to an area with yellow fever and the vaccine is not administered, they should be advised about the risk of disease, instructed in methods of avoiding bites of vector mosquitoes, and a waiver of the requirement for an ICVP should be obtained.101 105 106 107 (See Vaccination Waiver under Cautions.)

Yellow Fever Vaccine Dosage and Administration

General

  • Because of the risk for serious adverse effects in vaccine recipients (see Cautions), administer yellow fever vaccine only when clearly indicated for individuals truly at risk for exposure to yellow fever virus.107 108 (See Uses.)

  • Prior to administration, evaluate patient for history of previous sensitivity to egg or chicken protein.106 b (See Allergy to Egg-related Antigens under Cautions.) If the vaccine is considered necessary in an individual with possible history of acute hypersensitivity to eggs or egg products, perform a skin test.101 102 107 (See Sensitivity Testing and Desensitization under Cautions.)

Administration

Sub-Q Injection

Administer by sub-Q injection.101 106 107

Do not administer IV or IM.106

Depending on patient age, administer sub-Q into the deltoid muscle or anterolateral thigh.100 For infants <1 year of age, sub-Q injections should preferably be administered into the anterolateral thigh;100 sub-Q injections can also be administered into the upper-outer triceps of an infant, if necessary.100 For adults, adolescents, and children ≥1 year of age, the deltoid muscle is preferred.100

To ensure appropriate delivery, sub-Q injections should be made at a 45° angle using a 5/8-inch, 23- to 25-gauge needle.100 106

Before withdrawing each dose, swirl reconstituted vaccine until a uniform suspension is obtained; avoid vigorous shaking to prevent foaming.106 Discard vaccine if it contains particulates, appears discolored, or cannot be resuspended with swirling.106

After administering vaccine, carefully dispose of vial and any unused vaccine (e.g., sterilize, discard as medical waste).106

Reconstitution

To reconstitute, withdraw volume of diluent specified by the manufacturer from the vial containing diluent (0.9% sodium chloride injection) using a syringe and slowly inject it into the vial of lyophilized vaccine.106 Use only the diluent supplied by the manufacturer.106

Allow reconstituted vaccine to stand for 1–2 minutes, then carefully swirl until a uniform suspension is obtained.106 Reconstituted suspension is slightly opalescent and light orange in color.106

Administer within 1 hour following reconstitution.106

Dosage

Pediatric Patients

Prevention of Yellow Fever Virus Infection
Children and Adolescents 9 Months to 18 Years of Age
Sub-Q

Primary immunization consists of a single dose of 0.5 mL.101 106 107

Those who receive the dose 10–14 days prior to an exposure probably will be protected.106

Duration of immunity and need for revaccination or additional (booster) doses not fully determined.106 107 Revaccination every 10 years is recommended for those at continuing risk of exposure to yellow fever virus and is required by International Health Regulations for travelers.106 107 (See Duration of Immunity under Cautions.)

Adults

Prevention of Yellow Fever Virus Infection
Adults ≥19 Years of Age
Sub-Q

Primary immunization consists of a single dose of 0.5 mL.101 106 107

Those who receive the dose 10–14 days prior to an exposure probably will be protected.106

Duration of immunity and need for revaccination or additional (booster) doses not fully determined.106 107 Revaccination every 10 years is recommended for those at continuing risk of exposure to yellow fever virus and is required by International Health Regulations for travelers.106 107 (See Duration of Immunity under Cautions.)

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations. Consider possibility of increased risk for adverse systemic effects in this age group.101 102 106 107 (See Geriatric Use under Cautions.)

Cautions for Yellow Fever Vaccine

Contraindications

  • Hypersensitivity to any ingredient in the formulation, including gelatin.106 (See Sensitivity Reactions under Cautions.)

  • History of acute hypersensitivity to eggs, egg products, or chicken protein.102 106 107 (See Allergy to Egg-related Antigens under Cautions.)

  • Immunosuppression.106 (See Individuals with Altered Immunocompetence under Cautions.)

  • Immunosuppressive therapy.106 (See Specific Drugs and Laboratory Tests under Interactions.)

  • Acute or febrile illness.106 (See Concomitant Illness under Cautions.)

  • Children <9 months of age.106 107 (See Pediatric Use under Cautions.)

  • Nursing mothers, particularly when nursing infants are <9 months of age.106 (See Lactation under Cautions.)

Warnings/Precautions

Warnings

Vaccine-associated Neurotropic Disease

Yellow fever vaccine-associated neurotropic disease (previously known as postvaccinal encephalitis) occurs rarely following administration of yellow fever vaccine.101 102 106 107 108

Reported frequency of vaccine-associated neurotropic disease ranges from 4–6 cases per 1 million doses distributed in the US.101 Known risk factors are age <9 months and immunosuppression.101 106

Most cases have occurred in children <9 months of age,101 102 106 107 although several cases of encephalitis were reported in adult vaccinees in recent years.101 108 Adult cases occurred in first-time vaccine recipients and onset of illness occurred 4–23 days after vaccination.101 108

Other adverse neurologic effects (e.g., Guillain-Barré syndrome [GBS], seizures, focal neurologic deficits) reported rarely.106

Because of risk for serious adverse effects in vaccine recipients, yellow fever vaccine should be administered only to individuals truly at risk for exposure to yellow fever virus.107 108

CDC states clinicians are encouraged to report promptly to Vaccine Adverse Event Reporting System (VAERS) any patients with symptoms suggestive of neurotropic illness or any patients with fever ≥38.5°C for >24 hours and illness onset <30 days following a dose of yellow fever vaccine.107 108 Additional information is available from CDC at and and at 970-221-6400 or 404-498-1600.107 108

Vaccine-associated Viscerotropic Disease

Yellow fever vaccine-associated viscerotropic disease (previously known as febrile multiple organ system failure) reported rarely following administration of yellow fever vaccine.101 106 107 108 110 All cases reported to date occurred after primary vaccination.101

Vaccine-associated viscerotropic disease resembles fulminant yellow fever caused by wild-type yellow fever virus.106 Case analysis indicates this serious adverse reaction probably occurs as a clinical spectrum of disease, varying in severity from moderate illness with focal organ dysfunction to fatal disease with overt multiple organ system failure and death.101 107 Has been reported with various yellow fever vaccines;101 106 107 108 110 appears to occur because of undefined host factors rather than intrinsic virulence of the vaccine virus.106

Although determination of an accurate incidence rate is precluded by lack of prospective data, CDC estimates a reported incidence of vaccine-associated viscerotropic disease of 3–4 cases per 1 million doses distributed in the US.101 107 Incidence may be higher in vaccinees ≥60–65 years of age.101 107 (See Geriatric Use under Cautions.)

Because recent enhanced surveillance for serious adverse effects in recipients of yellow fever vaccine has identified cases consistent with yellow fever vaccine-associated viscerotropic disease, the vaccine should be administered only to individuals truly at risk for exposure to yellow fever virus.106 107 108

CDC states clinicians are encouraged to report promptly to VAERS any patients with symptoms suggestive of viscerotropic illness or any patients with fever ≥ 38.5°C for >24 hours and illness onset <30 days following a dose of yellow fever vaccine.107 108 Additional information is available from CDC at and and by telephone at 970-221-6400 and 404-498-1600.107 108

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and/or anaphylactic shock or other hypersensitivity reactions (e.g., rash, urticaria, asthma) reported rarely with yellow fever vaccine.106 107

Consider possibility that anaphylaxis may occur if yellow fever vaccine is administered to individuals hypersensitive to egg-related antigens or any other vaccine components.102 106 107 Anaphylaxis may occur even in individuals with no prior history of hypersensitivity to the vaccine components.106

Epinephrine and other appropriate agents should be readily available in case anaphylaxis or other serious allergic reaction occurs.106

Allergy to Egg-related Antigens

Because yellow fever vaccine is produced in chick embryos, it is contraindicated in individuals with a history of acute hypersensitivity to eggs, egg products, or chicken protein.102 106 107 Less severe or localized manifestations of allergy to eggs or to feathers are not considered contraindications.102 106

Prior to administration of yellow fever vaccine, obtain a history for evidence of previous sensitivity to egg or chicken protein.106 b Asking individuals whether they can eat eggs without adverse effects is a reasonable screening method since individuals who are able to eat eggs or egg products generally can receive the vaccine safely.100 101 106 107

If yellow fever vaccine is considered necessary in an individual with a possible history of acute hypersensitivity to eggs or egg products, perform a skin test for hypersensitivity prior to administration of the vaccine.101 102 107 Less severe or localized manifestations of allergy to eggs or to feathers usually do not warrant skin testing with the vaccine.106 If vaccination is considered essential despite a positive skin test, desensitization can be considered.106 (See Sensitivity Testing and Desensitization under Cautions.)

If international travel regulations are the only reason to vaccinate an individual hypersensitive to egg or chicken protein, efforts should be made to obtain a waiver.101 102 107 (See Vaccination Waiver under Cautions.)

Sensitivity Testing and Desensitization

In individuals hypersensitive to eggs or chicken protein, perform a scratch and intradermal skin test prior to administration of the vaccine.102 106 107

For the scratch test, use a 1:10 dilution of yellow fever vaccine in 0.9% sodium chloride.102 106 Place a drop of the 1:10 dilution of vaccine on a superficial scratch, prick, or puncture on the volar surface of the forearm; also use positive (histamine) and negative (0.9% sodium chloride) controls.102 106 Read scratch test after 15–20 minutes.102 106 A positive scratch test consists of a wheal with a diameter that is 3 mm larger than that of the 0.9% sodium chloride negative control, usually with surrounding erythema.102 106 The histamine control must be positive for valid interpretation.102 106 If scratch test is negative, perform an intradermal test.102 106

For the intradermal skin test, use 0.02 mL of a 1:100 dilution of yellow fever vaccine in 0.9% sodium chloride injection.102 106 Give intradermally on the volar surface of the forearm.102 106 Positive and negative controls should be administered intradermally concurrently at separate sites.102 106 A positive intradermal skin test reaction consists of a wheal that has a diameter that is at least 5 mm larger than that of the negative control and with surrounding erythema.102 106 If intradermal skin test is negative, the vaccine may be given.102

If use of yellow fever vaccine is considered essential despite a positive skin test, desensitization can be considered.102 106 For the desensitization procedure, give the following doses of yellow fever vaccine sub-Q at 15- to 20-minute intervals: 0.05 mL of a 1:10 dilution, 0.05 mL of undiluted vaccine, 0.1 mL of undiluted vaccine, 0.15 mL of undiluted vaccine, 0.2 mL of undiluted vaccine.102 106 Desensitization should only be performed under the direct supervision of a clinician experienced in management of anaphylaxis and with necessary emergency equipment immediately available.102 106

Gelatin Sensitivity

Contains gelatin as a stabilizer.106 Consider possibility of allergic reactions in individuals sensitive to gelatin.102 106 107

Individuals with a history of food allergy to gelatin rarely develop anaphylaxis after receiving gelatin-containing vaccines.102 Although skin testing for gelatin sensitivity before administering a gelatin-containing vaccine such as yellow fever vaccine can be considered, there currently are no specific protocols for this purpose.102 Gelatin used in vaccines manufactured in the US usually is derived from porcine sources; since food gelatin may be derived solely from bovine sources, a negative food history does not exclude the possibility of a reaction to gelatin contained in vaccines.102

Latex Sensitivity

A packaging component (i.e., vial stopper) contains dry natural latex.106

Some individuals may be hypersensitive to natural latex proteins.106 Take appropriate precautions if this preparation is administered to individuals with a history of latex sensitivity.106

General Precautions

Individuals with Altered Immunocompetence

Because yellow fever vaccine contains live, attenuated virus, viral replication and the development of infection with the vaccine virus may be potentiated by altered immune status and immunocompromised individuals may have an increased risk of encephalitis or other serious adverse effects.104 106

Contraindicated in individuals with severe underlying disease (e.g., leukemia, lymphoma, thymoma, generalized malignancy), gammaglobulin deficiency (e.g., agammaglobulinemia, hypogammaglobulinemia, dysgammaglobulinemia), or immunosuppression secondary to AIDS or other manifestations of HIV infection.101 104 106 107 Also contraindicated in individuals receiving immunosuppressive agents (e.g., corticosteroids, antimetabolites, radiation).101 104 106 (See Specific Drugs and Laboratory Tests under Interactions.)

Evidence suggests that thymic disease may be an independent risk factor for development of yellow fever vaccine-associated viscerotropic disease.106 (See Vaccine-associated Viscerotropic Disease under Cautions.) Prior to administration of yellow fever vaccine, clinicians should ask individuals about a history of thymus disease (e.g., myasthenia gravis, thymoma, prior thymectomy).106 b

Individuals with previously diagnosed asymptomatic HIV infection who cannot avoid potential exposure to yellow fever virus should be offered the choice of vaccination.101 104 107 If yellow fever vaccine is used in an HIV-infected individual, monitor for possible adverse effects; in addition, consider possibility that the immune response to the vaccine may be less pronounced than in non-HIV-infected individuals.101 104 105 106 107 (See Pre- and Postvaccination Serologic Testing under Cautions.)

If travel to a yellow fever-infected zone is necessary, immunocompromised patients who cannot receive yellow fever vaccine should be advised of the risk, instructed in methods for avoiding bites by vector mosquitoes, and supplied with vaccination waiver letters by their physician.101 104 106 107 (See Vaccination Waiver under Cautions.)

The manufacturer, ACIP, and CDC state that family members of immunosuppressed or HIV-infected individuals may receive yellow fever vaccine, provided they have no contraindications for the vaccine.101 104 106 107

Limitations of Vaccine Effectiveness

May not protect all vaccine recipients against yellow fever virus infection.106

A single dose of yellow fever vaccine given 10–14 days prior to yellow fever virus exposure probably will protect most individuals.106 No evidence of age-related differences in immunologic response to the vaccine.106

Data suggest the small percentage of immunologically healthy individuals who fail to develop an immune response to initial vaccination with yellow fever vaccine may do so following revaccination.106

Concomitant Illness

The decision whether to administer or delay administration of yellow fever vaccine in an individual with a current or recent febrile illness depends largely on the severity and etiology of the illness.100

Manufacturer states vaccination is contraindicated in individuals with acute or febrile illness, but that minor acute illness with low-grade fever generally does not preclude vaccination.106

ACIP, AAP, and American Academy of Family Physicians (AAFP) state that minor acute illness, such as mild upper respiratory infection (with or without fever) or mild diarrhea, does not preclude vaccination.100 However, vaccination of individuals with moderate or severe acute illness generally should be deferred until they have recovered from the acute phase of the illness.100

Duration of Immunity

Duration of immunity and need for revaccination or additional (booster) doses after the initial dose not fully determined.106 107

For those at continuing risk of exposure and for international travelers, additional (booster) doses of yellow fever vaccine are recommended every 10 years to boost antibody titers.106 107 However, there is clinical evidence that immunity following vaccination persists for 30–35 years and probably for life.106 107

Pre- and Postvaccination Serologic Testing

Because immunocompromised individuals may have a reduced immune response to yellow fever vaccine, postvaccination serologic testing to document seroconversion should be considered if use of the vaccine is necessary in asymptomatic HIV-infected individuals.101 106 107 (See Individuals with Altered Immunocompetence under Cautions.)

Because there is some evidence that the immune response in pregnant women may be lower than that in other healthy women, consider postvaccination serologic testing to document seroconversion if use of the vaccine is necessary in a pregnant woman.101 107 (See Pregnancy under Cautions.)

For information regarding the need for serologic testing in immunosuppressed individuals and pregnant women, contact the appropriate state health department or CDC's Division of Vector-Borne Infectious Diseases (970-221-6400) or Division of Global Migration and Quarantine (404-498-1600).101 107

Vaccination Waiver

If International Health Regulations are the only reason to vaccinate a traveler with a contraindication to yellow fever vaccine (e.g., hypersensitivity to egg or chicken protein, pregnancy, immunosuppression), a clinician’s letter clearly stating the traveler's contraindication has been accepted as a waiver by some governments.101 Ideally, the letter should be written on letterhead stationery and bear the stamp used by health department and official immunization centers to validate the ICVP.101

Under these conditions, it also is helpful for the traveler to obtain specific and authoritative advice from the country or countries to be visited (e.g., by contacting their embassies or consulates).101 Waivers of requirements obtained from embassies or consulates should be documented by appropriate letters and retained for presentation with the ICVP.101

Improper Storage and Handling

Improper storage or handling of vaccines may result in loss of vaccine potency and reduced immune response in vaccinees.100

Yellow fever vaccine is heat sensitive because it contains live viruses.100 102 Potency is substantially reduced if stored at room temperature.106 This information is important for countries or areas where there is an inadequate cold chain and where there is potential for inadvertent exposure to abnormal temperatures during shipping and/or storage of the vaccine.106

Do not administer yellow fever vaccine that has been mishandled or has not been stored at the recommended temperature (2–8°C).100 (See Storage under Stability.)

Inspect all vaccines upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.100

Specific Populations

Pregnancy

Category C.106

Limited data indicate that if yellow fever vaccine is administered during pregnancy, the vaccine virus can cross the placenta and infect the developing fetus;106 107 potential risks of such congenital infection not known.101

If international travel regulations are the only reason to vaccinate a pregnant woman, efforts should be made to obtain a waiver for the pregnant woman.101 107

Efforts should be made to postpone travel to areas where a substantial risk of exposure to yellow fever exists until after delivery when the vaccine can be administered.101 b If travel to high-risk areas is unavoidable during pregnancy and a high level of prevention against mosquito exposure is not feasible, the ACIP, CDC, and AAP state that yellow fever vaccine can be administered100 101 102 107 since the benefits of vaccination against yellow fever outweigh the theoretical risk to the fetus and mother.100 101 107

If yellow fever vaccine is given during pregnancy, administration during the second or third trimester may minimize concern over teratogenicity.a If a pregnant woman receives yellow fever vaccine, her infant should be monitored closely for evidence of congenital infection and other possible vaccine adverse effects.101 107 In addition, consider performing serologic testing to document seroconversion after vaccination.101 107 (See Pre- and Postvaccination Serologic Testing under Cautions.)

Lactation

Contraindicated in nursing women because of the theoretical risk of transmission of the vaccine virus to the infant and the increased risk of encephalitis in infants <9 months of age.106

Although transmission of yellow fever vaccine virus from nursing mothers to infants has not been reported to date, there is a theoretical risk that the virus could be distributed into milk.101 106 107

Vaccination of nursing women should be avoided whenever possible.101 106 However, if a nursing woman cannot postpone travel with their infants to areas where substantial risk of exposure to yellow fever exists, the ACIP and CDC state that nursing women may receive the vaccine.101 107

Pediatric Use

Contraindicated in children <9 months of age because of an increased risk of serious adverse reactions in this age group, especially an increased risk of yellow fever vaccine-associated neurotropic disease.106 107 (See Vaccine-associated Neurotropic Disease under Cautions.)

Individuals planning to travel with infants <9 months of age to countries in yellow fever-endemic zones or to countries experiencing an epidemic should either postpone or avoid such travel, whenever possible.101 107

Clinicians who encounter the rare circumstance when an infant <9 months of age is to travel to an area where yellow fever is endemic should consult CDC’s Division of Vector-Borne Infectious Diseases (970-221-6400) or Division of Global Migration and Quarantine (404-498-1600) for advice.101 107

ACIP and WHO state that there might be some situations in which vaccination of a child 6–8 months of age might be considered (e.g., setting of endemic or epidemic yellow fever where there is an increased likelihood of becoming infected with yellow fever virus and exposure of a child in this age group is unavoidable).107 CDC states that children 6–8 months of age should receive yellow fever vaccine only if they must travel to areas of ongoing epidemic yellow fever and a high level of protection against mosquito bites is not possible.101

ACIP states that children <6 months of age should not receive yellow fever vaccine under any circumstance.107

Geriatric Use

Adults ≥60–65 years of age may be at increased risk for adverse systemic effects after receiving yellow fever vaccine compared with younger adults.101 102 106 107

Postmarketing surveillance data of adverse effects reported to VAERS from 1990–1998 indicate the rate of adverse systemic effects occurring following vaccination was >2.5 times higher in those 65–74 years of age compared with adults 25–44 years of age.106

For travelers ≥60–65 years of age, CDC recommends that clinicians discuss the risks and benefits of yellow fever vaccination in the context of the destination-specific risk for exposure to yellow fever virus.101 107

If use of yellow fever vaccine is considered necessary in a geriatric individual, the manufacturer recommends that the health status of the individual be evaluated prior to vaccination and that they be carefully monitored for adverse effects for 10 days after vaccination.106

Common Adverse Effects

Low-grade fever, mild headache, myalgia, malaise, injection site reactions (edema, hypersensitivity, erythema, pain).101 106 107

Interactions for Yellow Fever Vaccine

Other Vaccines

Decisions regarding whether to administer yellow fever vaccine simultaneously with other vaccines should be based on convenience to the traveler in completing the desired vaccinations before travel and on information regarding possible interference with the other vaccines.106 107 Only limited data are available regarding administration of yellow fever vaccine with other vaccines (see Specific Drugs and Laboratory Tests under Interactions).101 106 107 The manufacturer states that when data are not available to support concurrent administration, other vaccines should be given 4 weeks before or after yellow fever vaccine.106

Yellow fever vaccine is a live, attenuated virus vaccine.102 106 107 Limited evidence suggests that immune responses and adverse effects are not affected if yellow fever vaccine is administered concurrently or within 1 month of other live, attenuated vaccines.101 106 However, there are theoretical concerns that the immune response to one parenteral live virus vaccine might be impaired if given within 28–30 days of another parenteral live virus vaccine (e.g., measles, mumps, rubella, varicella, yellow fever).100 101 ACIP, CDC, and AAFP state that, whenever possible, if another parenteral live vaccine is indicated in a patient receiving yellow fever vaccine, the vaccines should either be administered on the same day or at least 4 weeks apart.100 101

Inactivated vaccines can be administered simultaneously with or at any time before or after yellow fever vaccine.100 102 However, each vaccine should be administered using a different syringe and different injection site.100 102

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

BCG vaccine

Has been administered concomitantly with yellow fever vaccine without reduced antibody responses or increased adverse effects101 107

Blood products (e.g., whole blood, packed RBCs, plasma)

Blood products prepared in the US are unlikely to contain a substantial amount of antibody to yellow fever vaccine virus and interactions between blood products and yellow fever vaccine are unlikely 100

Although it has been recommended that administration of yellow fever vaccine be deferred until 2 months after receipt of blood or plasma transfusion,a ACIP states this precaution is unnecessary and yellow fever vaccine can be given simultaneously with or at any interval before or after blood products100

Chloroquine

Inhibits replication of yellow fever virus in vitro;101 no evidence that the drug adversely affects antibody response to yellow fever vaccine in individuals receiving antimalarial prophylaxis101 106 107

AAP states that yellow fever vaccine may be given simultaneously with chloroquine102

Hepatitis A (HepA) vaccine

Yellow fever vaccine and HepA vaccine may be given simultaneously (using different syringes and different injection sites)100 101 102 106 107

Hepatitis B (HepB) vaccine

Yellow fever vaccine and HepB vaccine can be administered simultaneously (using different syringes and different injection sites)100 101 102 106 107

Immune globulin (IGIM, IGIV) or specific immune globulin (HBIG, RIG, TIG, VZIG)

No evidence that immune globulin preparations interfere with the immune response to yellow fever vaccine100 102 106

Yellow fever vaccine may be given simultaneously with immune globulin preparations (using different syringes and different injection sites) or at any time before or after these preparations100 102

Immunosuppressive agents (e.g., alkylating agents, antimetabolites, corticosteroids, radiation)

Potential for decreased antibody response to yellow fever vaccine and an increased risk of adverse effects (e.g., encephalitis)106

Viral replication and the development of infection with yellow fever vaccine virus may be potentiateda

Short-term (<2 weeks), low- to moderate-dose (e.g., 10 mg of prednisone or equivalent) systemic corticosteroid therapy; long-term, alternate-day, systemic corticosteroid therapy using low to moderate doses of short-acting drugs; topical corticosteroid therapy (e.g., nasal, cutaneous, ophthalmic); or intra-articular, bursal, or tendon injections with corticosteroids should not be immunosuppressive100 107

Contraindicated in individuals receiving immunosuppressive therapy106

Postpone vaccination and avoid travel to yellow fever endemic areas until immunosuppressive therapy is discontinued106

Measles, mumps, and rubella vaccine (MMR)

Yellow fever vaccine has been administered simultaneously with monovalent measles vaccine without an increase in adverse effects or interference with the immune response to the vaccine100 107

Effect of nonsimultaneous administration of yellow fever vaccine and monovalent measles vaccine or MMR unknown100

Yellow fever vaccine and MMR may be given simultaneously (using different syringes and different injection sites)100 107

If not given simultaneously, give at least 4 weeks apart100 106

Meningococcal vaccine

MCV4 (Menomune): Has been administered concomitantly with yellow fever vaccine without reduced antibody responses or increased adverse effects101 106 107

Meningococcal vaccine may be administered simultaneously (using different syringes and different injection sites) or at any interval before or after yellow fever vaccine100 102

Poliovirus vaccine inactivated (IPV)

IPV may be administered simultaneously (using different syringes and different injection sites) or at any interval before or after yellow fever vaccine100 102

Rabies vaccine

Data not available106

Since no data are available, manufacturer of yellow fever vaccine states administer 4 weeks apart106

Tuberculin

Effect of yellow fever vaccine, if any, on tuberculin testing not determined;100 another live virus vaccine (measles vaccine) has been reported to temporarily suppress tuberculin skin sensitivity100

ACIP states a tuberculin skin test can be given during the same health-care visit as yellow fever vaccine;100 if not given simultaneously, the tuberculin test should be delayed until ≥4 weeks after the vaccine dose100

Vaccination with yellow fever vaccine should not be delayed based only on a theoretical concern about a possible interaction with tuberculin skin testing100

Typhoid vaccine

Oral live typhoid vaccine (Vivotif): Specific data not available regarding simultaneous administration with yellow fever vaccine

Parenteral inactivated typhoid vaccine (Typhim Vi): Has been administered concomitantly at a different site with yellow fever vaccine with or without concomitant HepA vaccine (Vaqta) without any apparent decrease in immune responses or increase in adverse effects109

Oral live typhoid vaccine (Vivotif) or parenteral inactivated typhoid vaccine (Typhim Vi): Yellow fever vaccine can be administered simultaneously with or at any interval before or after these typhoid vaccines100 102

Varicella vaccine

Data regarding nonsimultaneous administration not available100

Yellow fever vaccine and varicella vaccine may be given simultaneously (using different syringes and different injection sites)100

If not given simultaneously, give at least 4 weeks apart, if possible100 106

Stability

Storage

Parenteral

For Injection, for Sub-Q Use

Prior to reconstitution, store at 2–8°C.106 107 Do not freeze.106

Discard reconstituted yellow fever vaccine if not used within 1 hour.106 107

Yellow fever vaccine does not contain thimerosal or any other preservatives.106

Actions

  • Yellow fever vaccine available in the US is a lyophilized preparation of live, attenuated organisms of the 17D-204 strain of yellow fever virus.106 107 The vaccine is prepared by culturing the attenuated 17D-204 strain of live yellow fever virus in living chick embryos free of avian leukosis virus (ALV).106

  • Yellow fever vaccine available in the US is a monovalent vaccine (YF-VAX).106 Each 0.5-mL of the vaccine contains ≥4.74 log10 plaque-forming units (PFU).106

  • Yellow fever is transmitted by mosquito vectors.101 106 107 The disease has an abrupt onset after an incubation period of 3–6 days.106 107 A subclinical illness and influenza-like syndrome may occur or the disease may progress to an overwhelming pansystemic disease with hepatic and renal failure and hemorrhage caused by platelet and clotting abnormalities.101 106 107 108 Natural infection with wild-type yellow fever virus results in lifelong immunity.106

  • Yellow fever vaccine stimulates active immunity to yellow fever virus infection by inducing production of yellow fever virus-specific IgM neutralizing antibodies.106 Immune response to the vaccine is similar to that induced by wild-type infection.106

  • Anti-yellow fever antibodies are detectable in most individuals within 10–14 days after a single dose of yellow fever vaccine.100 106

  • Yellow fever vaccine is highly immunogenic in most adults, adolescents, and children >9 months of age.106 In US studies using the currently available vaccine, the seroconversion rate was 81–100% in adults.106 There is no evidence of age-related differences in the immune response to the vaccine.106

  • A reduced immune response to yellow fever vaccine and lower antibody titers may occur in immunocompromised individuals and pregnant women.106 107 In one study, only 70% of HIV-infected adults with CD4+ T-cell counts >200/mm3 developed neutralizing antibody following vaccination.107

  • The minimum titer of anti-yellow fever antibodies conferring protection against yellow fever has not been definitely established to date.106 WHO considers a log10 neutralization index of ≥0.7 measured by a plaque reduction assay to be indicative of an adequate response to yellow fever vaccine and this was the level used to define seroconversion in clinical trials of the vaccine.106

Advice to Patients

  • Prior to administration of the vaccine dose, provide a copy of the appropriate CDC Vaccine Information Statement (VIS) to the patient or patient's legal representative (VISs are available at ).b

  • Advise patient and/or patient's parent or guardian of the risks and benefits of vaccination with yellow fever vaccine.106 b

  • Advise patient and/or patient's parent or guardian that yellow fever vaccine should not be used in individuals with life-threatening allergic reactions to eggs, egg products, or chicken protein, vaccine ingredients or packaging components (e.g., gelatin, latex), or a previous dose of the vaccine.106 b Importance of informing clinicians of any previous history of sensitivity to egg or chicken protein since sensitivity testing may be necessary prior to vaccination.106 b (See Sensitivity Reactions under Cautions.)

  • Importance of informing clinicians if the patient has a weakened immune system (e.g., leukemia, lymphoma, HIV/AIDS, thymic disease) or is receiving treatment that may weaken the immune system (e.g., high-dose corticosteroids).b

  • Advise patient and/or patient's parent or guardian that yellow fever vaccine is given only at approved vaccination centers authorized to issue valid ICVPs and that the completed document will be needed as proof of vaccination before the individual is allowed to enter certain countries.101 106 b Current information regarding which countries are in the yellow fever endemic zone and/or have vaccination requirements for entry is available at the CDC website ().101

  • Advise patient and/or patient's parent or guardian that yellow fever vaccine may not provide protection in all vaccinees.106 b In addition to being vaccinated, importance of avoiding exposure to mosquitoes while in yellow fever endemic areas (e.g., stay in air-conditioned or well-screened areas, wear long-sleeved shirts and long pants to cover the body, use appropriate insect repellents, use mosquito nets between dusk and dawn).101 b

  • Advise individuals ≥65 years of age that they may be at increased risk for adverse effects after receiving yellow fever vaccine compared with younger adults.101 106 107 (See Geriatric Use under Cautions.)

  • Importance of informing clinicians if any adverse reactions (including allergic reactions) occur ≤30 days after vaccination with yellow fever vaccine.106 b Clinicians or individuals can report any adverse reactions that occur following vaccination to the Vaccine Adverse Event Reporting System (VAERS) at 800-822-7967 or .106 b

  • Advise patients with young children that yellow fever vaccine should not be used in infants <9 months of age and of the importance of avoiding yellow fever endemic areas if traveling with children in this age group.106 b (See Pediatric Use under Cautions.)

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.106 b (See Concomitant Illness under Cautions.)

  • Importance of women informing clinicians if they are or plan to become pregnant.106 b Advise such women that the vaccine should only be used during pregnancy in rare circumstances and that efforts should be made to postpone travel to yellow fever endemic areas until after delivery. 106 b If travel to yellow fever endemic areas cannot be avoided during pregnancy, discuss the risks and benefits of vaccination.b (See Pregnancy under Cautions.)

  • Importance of women informing clinicians if they plan to breast-feed.106 b Advise such women that the vaccine is not recommended for use in nursing women, particularly when breast-feeding infants are <9 months of age.106 (See Lactation under Cautions.)

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

For the purposes of international travel, yellow fever vaccine is supplied to and can be administered only at certain sites that are authorized to issue valid ICVP certificates.101 106 Local or state public health departments or the CDC should be consulted for information regarding the location of these vaccination centers.101

Yellow Fever Vaccine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for sub-Q use

≥4.74 log10 plaque-forming units (PFU) per 0.5 mL

YF-VAX (with gelatin and sorbitol; preservative-free; available in single- and multiple-dose vials with 0.9% sodium chloride injection diluent)

Sanofi Pasteur

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

100. Centers for Disease Control and Prevention. General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006; 51(RR-15):1-48.

101. Centers for Disease Control and Prevention. Health information for international travel, 2008. Atlanta, GA: US Department of Health and Human Services; 2008. Updates available from CDC website.

102. American Academy of Pediatrics Committee on Infectious Diseases. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006:12-18, 41-50, 71-85, 98-103, 211-217.

103. Centers for Disease Control and Prevention. Yellow fever vaccine: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. 1990; 39(RR-6):1-6.

104. Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence. MMWR Recomm Rep. 1993; 42(RR-4):1-18.

105. US Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA) Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. From website.

106. Sanofi Pasteur. YF-VAX (yellow fever vaccine) prescribing information. Swiftwater, PA; 2008 Feb.

107. Centers for Disease Control and Prevention. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2002; 51(RR-17):1-11.

108. Centers for Disease Control and Prevention. Adverse events associated with 17D-derived yellow fever vaccination—United States, 2001-2002. MMWR Morb Mortal Wkly Rep. 2002; 51:989-93. [IDIS 489906] [PubMed 12455906]

109. Jong EC, Kaplan KM, Eves KA et al. An open randomized study of inactivated hepatitis A vaccine administered concomitantly with typhoid fever and yellow fever vaccines. J Travel Med. 2002; 9:66-70. [PubMed 12044272]

110. Martin M, Tsai TF, Cropp B et al. Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases. Lancet. 2001; 358:98-104. [IDIS 467069] [PubMed 11463410]

111. Anon. Advice for travelers. Med Lett Treat Guid. 2004; 2:33-40.

a. AHFS drug information 2008. McEvoy GK, ed. Yellow fever vaccine. Bethesda, MD: American Society of Health-System Pharmacists; 2008.

b. Centers for Disease Control and Prevention. Yellow fever vaccine information statement. 2004 Nov. From CDC website. Accessed 2008 Mar 17.

c. Centers for Disease Control and Prevention. Notice to readers: requirements for use of a new international certificate of vaccination or prophylaxis for yellow fever vaccine. MMWR Morb Mortal Wkly Rep. 2008; 56:1345-6.

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