Generic Name: yellow fever vaccine

Brand Names: YF-Vax

Uses

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.

Yellow fever is an acute viral illness caused by a flavivirus transmitted to humans by mosquito vectors. Yellow fever virus occurs only in sub-Saharan Africa and South America where it is endemic and intermittently epidemic. WHO estimates that about 200,000 cases of yellow fever occur annually worldwide and the fatality rate is approximately 20%. 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.

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.

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.

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.

Actual areas of yellow fever virus activity far exceed the zones where the disease is officially reported. 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.

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). 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 (http://wwwn.cdc.gov/travel).

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. In the US, yellow fever vaccine is supplied to and can be administered only at certain sites authorized to issue valid ICVP certificates. Consult local or state public health departments or the CDC for information regarding locations of these vaccination centers.

Vaccinees should receive a completed ICVP form that is signed and validated with the center’s stamp where the vaccine was given. These certificates are valid for 10 years beginning 10 days after immunization. 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.

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. 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. 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.

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). 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.

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.

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. (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. However, ACIP states the vaccine should not be used in HIV-infected individuals who are symptomatic or have acquired immunodeficiency syndrome (AIDS). 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. (See Vaccination Waiver under Cautions.)

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. (See Uses.)
• Prior to administration, evaluate patient for history of previous sensitivity to egg or chicken protein. (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. (See Sensitivity Testing and Desensitization under Cautions.)

Administration

Sub-Q Injection

Administer by sub-Q injection.

Do not administer IV or IM.

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

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

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

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

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. Use only the diluent supplied by the manufacturer.

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

Administer within 1 hour following reconstitution.

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.

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

Duration of immunity and need for revaccination or additional (booster) doses not fully determined. 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. (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.

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

Duration of immunity and need for revaccination or additional (booster) doses not fully determined. 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. (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. (See Geriatric Use under Cautions.)

Cautions

Contraindications

• Hypersensitivity to any ingredient in the formulation, including gelatin. (See Sensitivity Reactions under Cautions.)
• History of acute hypersensitivity to eggs, egg products, or chicken protein. (See Allergy to Egg-related Antigens under Cautions.)
• Immunosuppression. (See Individuals with Altered Immunocompetence under Cautions.)
• Immunosuppressive therapy. (See Specific Drugs and Laboratory Tests under Interactions.)
• Acute or febrile illness. (See Concomitant Illness under Cautions.)
• Children <9 months of age. (See Pediatric Use under Cautions.)
• Nursing mothers, particularly when nursing infants are <9 months of age. (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.

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

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

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

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.

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. Additional information is available from CDC at http://www.cdc.gov/ncidod/dvbid/yellowfever/index.htm and http://wwwn.cdc.gov/travel and at 970-221-6400 or 404-498-1600.

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. All cases reported to date occurred after primary vaccination.

Vaccine-associated viscerotropic disease resembles fulminant yellow fever caused by wild-type yellow fever virus. 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. Has been reported with various yellow fever vaccines; appears to occur because of undefined host factors rather than intrinsic virulence of the vaccine virus.

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. Incidence may be higher in vaccinees ≥60–65 years of age. (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.

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. Additional information is available from CDC at http://www.cdc.gov/ncidod/dvbid/yellowfever/index.htm and http://wwwn.cdc.gov/travel and by telephone at 970-221-6400 and 404-498-1600.

Sensitivity Reactions

Hypersensitivity Reactions

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

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

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

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. Less severe or localized manifestations of allergy to eggs or to feathers are not considered contraindications.

Prior to administration of yellow fever vaccine, obtain a history for evidence of previous sensitivity to egg or chicken protein. 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.

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. Less severe or localized manifestations of allergy to eggs or to feathers usually do not warrant skin testing with the vaccine. If vaccination is considered essential despite a positive skin test, desensitization can be considered. (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. (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.

For the scratch test, use a 1:10 dilution of yellow fever vaccine in 0.9% sodium chloride. 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. Read scratch test after 15–20 minutes. 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. The histamine control must be positive for valid interpretation. If scratch test is negative, perform an intradermal test.

For the intradermal skin test, use 0.02 mL of a 1:100 dilution of yellow fever vaccine in 0.9% sodium chloride injection. Give intradermally on the volar surface of the forearm. Positive and negative controls should be administered intradermally concurrently at separate sites. 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. If intradermal skin test is negative, the vaccine may be given.

If use of yellow fever vaccine is considered essential despite a positive skin test, desensitization can be considered. 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. Desensitization should only be performed under the direct supervision of a clinician experienced in management of anaphylaxis and with necessary emergency equipment immediately available.

Gelatin Sensitivity

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

Individuals with a history of food allergy to gelatin rarely develop anaphylaxis after receiving gelatin-containing vaccines. 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. 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.

Latex Sensitivity

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

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

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.

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. Also contraindicated in individuals receiving immunosuppressive agents (e.g., corticosteroids, antimetabolites, radiation). (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. (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).

Individuals with previously diagnosed asymptomatic HIV infection who cannot avoid potential exposure to yellow fever virus should be offered the choice of vaccination. 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. (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. (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.

Limitations of Vaccine Effectiveness

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

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

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.

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.

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.

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. 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.

Duration of Immunity

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

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. However, there is clinical evidence that immunity following vaccination persists for 30–35 years and probably for life.

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. (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. (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).

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. 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.

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). Waivers of requirements obtained from embassies or consulates should be documented by appropriate letters and retained for presentation with the ICVP.

Improper Storage and Handling

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

Yellow fever vaccine is heat sensitive because it contains live viruses. Potency is substantially reduced if stored at room temperature. 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.

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

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

Specific Populations

Pregnancy

Category C.

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

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.

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. 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 since the benefits of vaccination against yellow fever outweigh the theoretical risk to the fetus and mother.

If yellow fever vaccine is given during pregnancy, administration during the second or third trimester may minimize concern over teratogenicity. 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. In addition, consider performing serologic testing to document seroconversion after vaccination. (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.

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.

Vaccination of nursing women should be avoided whenever possible. 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.

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. (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.

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.

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). 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.

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

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.

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.

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.

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.

Common Adverse Effects

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

Interactions

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. Only limited data are available regarding administration of yellow fever vaccine with other vaccines (see Specific Drugs and Laboratory Tests under Interactions). 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.

Yellow fever vaccine is a live, attenuated virus vaccine. 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. 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). 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.

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

Specific Drugs and Laboratory Tests

Stability

Storage

Parenteral

For Injection, for Sub-Q Use

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

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

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

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. 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).
• Yellow fever vaccine available in the US is a monovalent vaccine (YF-VAX^®). Each 0.5-mL of the vaccine contains ≥4.74 log₁₀ plaque-forming units (PFU).
• Yellow fever is transmitted by mosquito vectors. The disease has an abrupt onset after an incubation period of 3–6 days. 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. Natural infection with wild-type yellow fever virus results in lifelong immunity.
• Yellow fever vaccine stimulates active immunity to yellow fever virus infection by inducing production of yellow fever virus-specific IgM neutralizing antibodies. Immune response to the vaccine is similar to that induced by wild-type infection.
• Anti-yellow fever antibodies are detectable in most individuals within 10–14 days after a single dose of yellow fever vaccine.
• Yellow fever vaccine is highly immunogenic in most adults, adolescents, and children >9 months of age. In US studies using the currently available vaccine, the seroconversion rate was 81–100% in adults. There is no evidence of age-related differences in the immune response to the vaccine.
• A reduced immune response to yellow fever vaccine and lower antibody titers may occur in immunocompromised individuals and pregnant women. In one study, only 70% of HIV-infected adults with CD4⁺ T-cell counts >200/mm³ developed neutralizing antibody following vaccination.
• The minimum titer of anti-yellow fever antibodies conferring protection against yellow fever has not been definitely established to date. 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.

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 http://www.cdc.gov/vaccines/pubs/vis/default.htm).
• Advise patient and/or patient's parent or guardian of the risks and benefits of vaccination with yellow fever vaccine.
• 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. Importance of informing clinicians of any previous history of sensitivity to egg or chicken protein since sensitivity testing may be necessary prior to vaccination. (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).
• 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. 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 (http://wwwn.cdc.gov/travel).
• Advise patient and/or patient's parent or guardian that yellow fever vaccine may not provide protection in all vaccinees. 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).
• 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. (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. 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 http://www.vaers.hhs.gov/.
• 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. (See Pediatric Use under Cautions.)
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses. (See Concomitant Illness under Cautions.)
• Importance of women informing clinicians if they are or plan to become pregnant. 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. If travel to yellow fever endemic areas cannot be avoided during pregnancy, discuss the risks and benefits of vaccination. (See Pregnancy under Cautions.)
• Importance of women informing clinicians if they plan to breast-feed. Advise such women that the vaccine is not recommended for use in nursing women, particularly when breast-feeding infants are <9 months of age. (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. Local or state public health departments or the CDC should be consulted for information regarding the location of these vaccination centers.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions June 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.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.