YF-VAX

Generic Name: Yellow Fever Vaccine
Class: Vaccines
ATC Class: J07B101
VA Class: IM100

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 YF-VAX

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}

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.)

YF-VAX 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 YF-VAX

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 administered^{100 101 102 107} 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 YF-VAX

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 fev