Yellow Fever Vaccine

Suspected adverse events after administration of any vaccine may be reported to Vaccine Adverse Events Reporting System (VAERS), 1-800-822-7967

1-10%

Headache (5-10%)

Chills (5-10%)

Low-grade fever (5-10%)

Myalgia (5-10%)

Frequency Not Defined

Meningoencephalitis

Seizures

Rash

Urticaria

Pain

Warmth

Erythema

Guillain-Barre syndrome

Prior to administration of YF-VAX, ask potential vaccinees or their parents or guardians about their recent health status and history of yellow fever vaccination. Inform potential vaccinees or their parents or guardians about the benefits and risks of immunization and potential for adverse reactions to YFVAX administration. Instruct vaccinees or their parents or guardians to report to their health-care providers all serious adverse events that occur up to 30 days post-vaccination.

All travelers should seek information regarding vaccination requirements by consulting with their health care providers. Such requirements may be strictly enforced for entry into certain countries, particularly for persons traveling from Africa or South America to Asia. Additional information is available from local health departments, the Centers for Disease Control and Prevention (CDC), and WHO. Travel agencies, international airlines, and/or shipping lines may also have up-to-date information. The vaccination center should complete, sign, and stamp an International Certificate of Vaccination and provide the certificate to the vaccinee. The immunization record should contain the date, lot number and manufacturer of the vaccine administered. Inform vaccinees that vaccination certificates are valid commencing 10 days after vaccination. (14)

REFERENCES

14 Recommendations of the Advisory Committee on Immunization Practices (ACIP). Yellow Fever Vaccine. MMWR 2010;59(RR-7):1-32.

Do not receive another "live" vaccine for at least 4 weeks after you have received the yellow fever vaccine. Live vaccines may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine.

Yellow fever is a serious disease caused by a virus that is spread through the bite of an infected mosquito. Yellow fever can cause fever and flu-like illness, jaundice (yellowing of the eyes and skin), liver failure, lung failure, kidney failure, vomiting of blood, and possibly death.

Yellow fever vaccine is recommended for people who plan to live in or travel to areas where yellow fever is known to exist, or those who are otherwise at high risk of coming into contact with the virus.

This vaccine is used to help prevent yellow fever in adults and children who are at least 9 months old. The vaccine works by exposing you to a small dose of the virus, which causes the body to develop immunity to the disease. This vaccine will not treat an active infection that has already developed in the body.

You should receive the vaccine at least 10 days prior to your arrival in an area where you may be exposed to the virus.

This vaccine is also recommended for people who work in a research laboratory and may be exposed to yellow fever virus through needle-stick accidents or inhalation of viral droplets in the air.

Like any vaccine, the yellow fever vaccine may not provide protection from disease in every person.

Prevention of Disease Caused by Yellow Fever Virus

Prevention of disease caused by yellow fever virus in adults, adolescents, and children ≥9 months of age residing or traveling in areas of Africa or South America where yellow fever is endemic or officially reported or where an International Certificate of Vaccination or Prophylaxis (ICVP) against yellow fever is required as a condition for entry.106 115

Prevention of disease caused by yellow fever virus in laboratory personnel who might be exposed by direct or indirect contact or by aerosols to virulent yellow fever virus or to concentrated preparations of the yellow fever vaccine strain.100 106

Yellow fever virus, a Flavivirus100 105 106 115 closely related to Dengue, Japanese encephalitis virus, St. Louis encephalitis viruses, and West Nile virus (WNV),100 105 is transmitted to humans through the bite of infected mosquitoes that acquired the virus by biting infected humans or nonhuman primates (monkeys).100 101 106 115

Disease caused by yellow fever virus ranges from mild, nonspecific febrile illness to severe disease with jaundice, hemorrhagic symptoms, and eventually shock and multisystem organ failure;100 104 115 case fatality rate for severe disease is 20–50%.100 104 WHO estimates that about 200,000 cases of yellow fever and 30,000 fatalities related to the disease occur annually worldwide.100 101

Travelers to areas of sub-Saharan Africa and tropical South America where yellow fever virus is endemic and intermittently epidemic are at high risk of disease caused by yellow fever virus.100 101 104 115 Risk depends on several factors, including vaccination status, use of personal protective measures against mosquito bites, travel locations, season, duration of exposure, occupational and recreational activities while traveling, and local rate of yellow fever virus transmission at the time of travel.100 101 104 115

For US travelers, the US Public Health Service Advisory Committee on Immunization Practices (ACIP) and CDC recommend primary immunization with yellow fever vaccine in adults, adolescents, and children ≥9 months of age who will be traveling to or living in yellow fever endemic or epidemic areas of Africa and South America.100 115 However, because serious adverse effects have been reported with yellow fever vaccine (see Cautions), base vaccination decisions on careful consideration of the individual's overall risk for travel-associated yellow fever, the high mortality rate reported for yellow fever, international regulations regarding yellow fever vaccination for countries on the travel itinerary, and all known precautions and contraindications for the vaccine.100 115

ACIP states that primary immunization with a single dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers, but revaccination is recommended for certain travelers who will be visiting countries with a risk of yellow fever virus transmission (e.g., women who received primary immunization during pregnancy, individuals who received a hematopoietic stem cell transplant after receiving primary immunization, individuals who had HIV infection when they received their last dose of yellow fever vaccine).104 ACIP also states revaccination (booster dose) may be given to travelers who received their last dose of yellow fever vaccine at least 10 years previously and who will be in higher-risk settings based on location, season, activities, and duration of travel.104 This includes travelers who plan to spend prolonged periods in endemic areas or those traveling to highly endemic areas (e.g., rural West Africa during peak transmission season) or to areas with an ongoing outbreak of yellow fever.104

International health regulations (IHR) of the World Health Organization (WHO) allow countries to require proof of yellow fever vaccination documented on a validated ICVP as a condition of entry for travelers arriving from infected areas or from countries with infected areas, even if only in transit.100 115 Some countries require evidence of yellow fever vaccination from all entering travelers, including those traveling directly from the US.100 115 Travelers who have a specific contraindication to yellow fever vaccine and who cannot avoid travel to a country requiring vaccination should obtain a medical waiver before embarking on travel (see Medical Waivers under Cautions).100 115 Requirements regarding ICVPs may be strictly enforced and travelers arriving without a valid ICVP or medical waiver may be quarantined for up to 6 days, denied entry, or possibly vaccinated or revaccinated at the point of entry.100 115

Vaccinees should receive a completed yellow fever vaccine ICVP that is signed and validated with the official uniform stamp of the yellow fever vaccination center where the vaccine was given.100 106 115 These certificates are valid for 10 years beginning 10 days after vaccination with yellow fever vaccine.100 106 115 As of July 2016, WHO no longer requires revaccination (booster dose) of yellow fever vaccine every 10 years and states that a completed ICVP is considered valid for the lifetime of the vaccinee.115 However, it is uncertain when or if all countries with entry requirements for yellow fever vaccination will adopt this change.115

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).115 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 diseases.115

The most recent information regarding geographic areas associated with risk of yellow fever, information on country-specific requirements for yellow fever vaccination for travelers, and information on regulations regarding ICVPs and medical waivers is available from CDC at and .115

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 primary immunization with yellow fever vaccine.106 ACIP states that laboratory workers who routinely handle wild-type yellow fever virus and are at continued high risk of exposure to the virus should be tested for yellow fever virus-specific neutralizing antibody titers at least every 10 years after primary immunization to determine whether revaccination (booster dose) of the vaccine is indicated.104 (See Duration of Immunity under Cautions.)

General

• Because of risk of 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.100 106 115 (See Uses.)

• Prior to administration, evaluate patient for history of sensitivity to egg or chicken protein.106 (See Allergy to Egg-related Antigens under Cautions.) If the vaccine is considered essential in an individual with history of hypersensitivity to eggs or egg products, perform sensitivity test.100 106 115 (See Sensitivity Testing and Desensitization under Cautions.)

• In the US, yellow fever vaccine can only be administered at certain sites authorized to issue valid ICVPs.100 106 115 Vaccinees should receive a completed ICVP that is signed and validated with the official uniform stamp of the yellow fever vaccination center.100 106 115 Consult CDC or local or state public health departments for information regarding locations of these vaccination centers.115 (See Restricted Distribution under Preparations.)

Administration

Administer by sub-Q injection.106

Do not administer IM.100 However, if inadvertently given IM, ACIP states that a repeat dose given sub-Q is unnecessary since immunologic response probably not affected.100

After vaccination, observe vaccinee for at least 15 minutes for signs and symptoms of allergic reaction.100 (See Sensitivity Reactions under Cautions.)

Syncope (vasovagal or vasodepressor reaction; fainting) may occur following vaccination;134 such reactions occur most frequently in adolescents and young adults.134 Syncope and secondary injuries may be averted if vaccinees sit or lie down during and for 15 minutes after vaccination.134 If syncope occurs, observe patient until symptoms resolve.134

If multiple parenteral vaccines are administered during a single health-care visit, give each vaccine using different syringe and at a different injection site.134 Separate injection sites by at least 1 inch (if anatomically feasible) to allow appropriate attribution of any local adverse effects that may occur.134

Sub-Q Injection

In infants <12 months of age, administer sub-Q preferably into anterolateral thigh.134

In adults, adolescents, and children ≥12 months of age, administer sub-Q into upper-outer triceps area.134

To ensure appropriate delivery, make sub-Q injections at a 45° angle using a 5/8-inch, 23- to 25-gauge needle.106 134

Before withdrawing dose, carefully swirl reconstituted vaccine until a uniform suspension is obtained;106 avoid vigorous shaking to prevent foaming.106

Reconstituted vaccine should appear as a slightly pink-brown suspension;106 discard if it appears discolored or contains extraneous particulates.106

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

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 into 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 Avoid vigorous shaking to prevent foaming.106

Must be administered within 1 hour following reconstitution.106

Dosage

Pediatric Patients

Primary immunization consists of a single dose of 0.5 mL.100 106

Administer at least 10 days prior to potential exposure to yellow fever virus.100 106 115

Manufacturer recommends revaccination with a single 0.5-mL dose every 10 years in individuals at risk of exposure to yellow fever virus.106 ACIP states revaccination no longer considered necessary for most travelers, but is recommended in certain individuals (see Uses).104 WHO states revaccination every 10 years no longer considered necessary, but uncertain whether all countries with entry requirements for yellow fever vaccination will adopt this change.115 (See Duration of Immunity under Cautions.)

Adults

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

Administer at least 10 days prior to potential exposure to yellow fever virus.100 106 115

Manufacturer recommends revaccination with a single 0.5-mL dose every 10 years in individuals at risk of exposure to yellow fever virus.106 ACIP states revaccination no longer considered necessary for most US travelers, but is recommended in certain individuals (see Uses).104 WHO states revaccination every 10 years no longer considered necessary, but uncertain whether all countries with entry requirements for yellow fever vaccination will adopt this change.115 (See Duration of Immunity under Cautions.)

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

To determine need for revaccination (booster dose) in those at continued high risk of exposure, ACIP recommends measuring yellow fever virus-specific neutralizing antibody titers at least every 10 years after primary immunization.104 If neutralizing antibody titers cannot be measured,104 ACIP recommends giving a vaccine dose every 10 years as long as laboratory worker remains at risk.104

Special Populations

Geriatric Patients

No specific dosage recommendations.106 Use with caution and consider possibility of increased risk for adverse systemic effects in this age group.100 106 115 (See Geriatric Use under Cautions.)

(YEL oh FEE ver vak SEEN)

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, powder for reconstitution [17D-204 strain]:

Stamaril: ≥1000 units per 0.5 mL dose [produced in chicken embryos; packaged with diluent]

YF-VAX: ≥4.74 log10 plaque-forming units (PFU) per 0.5 mL dose [single-dose or 5-dose vial; produced in chicken embryos; contains gelatin; packaged with diluent]

Primary immunization: SubQ: One dose (0.5 mL) ≥10 days before travel

Booster: Based on currently available data, the World Health Organization (WHO) and CDC/ACIP have determined that vaccine failure is rare and booster doses are generally not needed. A single dose of the vaccine is adequate for most travelers. The World Health Assembly removed the 10-year booster dose requirement from the International Health Regulations in July 2016 (WHO 2016). However, booster dose(s) are recommended for certain patient populations with conditions at the time of their initial dose that may limit immune response (eg, pregnant women, hematopoietic stem cell transplant recipients, HIV patients). A booster dose may also be given (≥10 years after last dose) to those who may be at increased risk for yellow fever disease (eg, certain laboratory workers [depending on antibody titers] and travelers to endemic locations for prolonged periods) (CDC/ACIP [Staples 2015]; WHO 2013).

AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Consider therapy modification

Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Canadian labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. U.S. labeling does not mention this. Consider therapy modification

Dupilumab: May enhance the adverse/toxic effect of Vaccines (Live). Avoid combination

Fingolimod: May enhance the adverse/toxic effect of Vaccines (Live). Vaccinal infections may develop. Fingolimod may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Immunosuppressants: May enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: AzaTHIOprine; Beclomethasone (Oral Inhalation); Betamethasone (Systemic); Budesonide (Systemic); Corticotropin; Cortisone; Cytarabine (Liposomal); Deflazacort; Dexamethasone (Systemic); Fludrocortisone; Fluticasone (Oral Inhalation); Hydrocortisone (Systemic); Leflunomide; Mercaptopurine; Methotrexate; MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE; Triamcinolone (Systemic). Avoid combination

Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Consider therapy modification

Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Consider therapy modification

Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses of methotrexate should be avoided. Consider therapy modification

Ocrelizumab: May enhance the adverse/toxic effect of Vaccines (Live). Ocrelizumab may diminish the therapeutic effect of Vaccines (Live). Avoid combination

Rabies Immune Globulin (Human): May diminish the therapeutic effect of Vaccines (Live). Management: Avoid administering the measles vaccine within 4 months after administration of rabies immune globulin. Avoid administering other live vaccines within 3 months after administration of rabies immune globulin. Consider therapy modification

Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. Consider therapy modification

Vaccines (Live): May diminish the therapeutic effect of other Vaccines (Live). Management: Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 28 days (ie, 4 weeks). If not, the vaccine administered second should be repeated at least 4 week later. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Rotavirus Vaccine. Monitor therapy

Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Avoid combination