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Guideline Summary
Guideline Title
Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP).
Bibliographic Source(s)
Staples JE, Gershman M, Fischer M, Centers for Disease Control and Prevention (CDC). Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Jul 30;59(RR-7):1-27. [157 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

This guideline updates a previously released version: Cetron MS, Marfin AA, Julian KG, Gubler DJ, Sharp DJ, Barwick RS, Weld LH, Chen R, Clover RD, Deseda-Tous J, Marchessault V, Offit PA, Monath TP. Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. MMWR Recomm Rep 2002 Nov 8;51(RR-17):1-11. [57 references]

Scope

Disease/Condition(s)

Yellow fever virus, including three transmission cycles:

  • Jungle (sylvatic)
  • Intermediate (savannah)
  • Urban
Guideline Category
Prevention
Risk Assessment
Clinical Specialty
Allergy and Immunology
Family Practice
Infectious Diseases
Internal Medicine
Preventive Medicine
Intended Users
Advanced Practice Nurses
Clinical Laboratory Personnel
Health Care Providers
Health Plans
Physician Assistants
Physicians
Public Health Departments
Guideline Objective(s)
  • To summarize the current epidemiology of yellow fever (YF), describe immunogenicity and safety data for the yellow fever vaccine, and provide recommendations for the use of yellow fever vaccine among travelers and laboratory workers
  • To update Centers for Disease Control and Prevention (CDC) recommendations for using YF vaccine
Target Population

Travelers and laboratory workers

Interventions and Practices Considered
  1. Primary vaccination and booster doses of yellow fever vaccination made from the 17D, including two substrain vaccines:
    • 17DD
    • 17D-204 YF
  2. Monitoring for adverse effects of vaccination
Major Outcomes Considered
  • Incidence of yellow fever
  • Relative efficacy and safety of the yellow fever vaccine
  • Vaccination related side effects or adverse events, including risk and incidence of vaccine-associated disease

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Searches of Unpublished Data
Description of Methods Used to Collect/Select the Evidence

The Advisory Committee for Immunization Practices (ACIP) Work Group reviewed and considered issues that included yellow fever (YF) epidemiology; incidence of and risk factors for travel-associated YF disease; measures available to prevent YF disease; and YF vaccine immunogenicity, safety, and incidence of vaccine adverse events. Further consideration was given to potential contraindications and precautions to the use of YF vaccine and International Health Regulations (IHRs) for the vaccine. Published, peer-reviewed studies were the primary source of data used. Articles were identified through searches of the PubMed, Global Health, and EMBASE databases; review of relevant bibliographies; and consultation with subject-matter experts. When relevant to issues under discussion, unpublished data available at the Centers for Disease Control and Prevention (CDC) also were considered.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Not stated
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Review
Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The Advisory Committee on Immunization Practices (ACIP) Yellow Fever Vaccine Work Group (the ACIP Work Group) first met in September 2008 to review available information on the risk for yellow fever (YF) for travelers and to revise recommendations for the use of the vaccine. In addition to ACIP members, the ACIP Work Group included participants from the American Academy of Family Physicians, the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense, the U.S. Department of State, the Food and Drug Administration (FDA), the Infectious Diseases Society of America, the International Society of Travel Medicine, the Public Health Agency of Canada (PHAC), Boston Medical Center, and the Harvard School of Public Health.

The ACIP Work Group held monthly conference calls until May 2009. Recommendation options were developed and discussed by the Work Group. When evidence from clinical trials or other research studies was lacking, the recommendations incorporated expert opinion of the ACIP Work Group members. A short overview presentation was made to ACIP at the June 2009 meeting. Proposed recommendations and a draft statement were presented to ACIP and approved at the October 2009 meeting.

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
Peer Review
Description of Method of Guideline Validation

The recommendations were approved at the October 2009 meeting of the Advisory Committee on Immunization Practices (ACIP).

Recommendations

Major Recommendations

Recommendations for the Use of Yellow Fever (YF) Vaccine in Laboratory Workers

YF vaccine is recommended for laboratory personnel who might be exposed to virulent yellow fever virus (YFV) or to concentrated preparations of YF vaccine virus strains by direct or indirect contact or by aerosols.

Recommendations for Prevention of YF Among Travelers

All travelers to countries in which YF is endemic should be advised of the risks for the disease and available methods to prevent it, including personal protective measures and vaccine.

Personal Protective Measures

All travelers should take precautions to avoid mosquito bites to reduce the risk for YF and other vector-borne infectious diseases. These precautions include using insect repellent, wearing permethrin-impregnated clothing, and staying in accommodations with screened or air-conditioned rooms.

Additional information on protection against mosquitoes and other arthropods is available at http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/protection-against-mosquitoes-ticks-insects-arthropods.aspx External Web Site Policy.

Recommendations for the Use of YF Vaccine in Travelers

YF vaccine is recommended for persons aged ≥9 months who are traveling to or living in areas at risk for YFV transmission in South America and Africa. Countries with risk for YFV transmission have been listed (Table 1 in the original guideline). For many of these countries, only a portion of the country is at risk for YFV transmission (Figure 2 in the original guideline). Given that changes in the designation of endemic regions can occur, travelers and health-care providers should obtain updated information from the Centers for Disease Control and Prevention (CDC), available at http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/yellow-fever.aspx External Web Site Policy.

YF vaccine may be required for entry into certain countries. A list of country-specific requirements is available at http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-2/yellow-fever-vaccine-requirements-and-recommendations.aspx External Web Site Policy. Requirements are mandatory and are intended primarily to prevent importation into and transmission of YFV within a given country. However, International Health Regulations (IHRs) stipulate that a medical provider may issue a waiver of YF vaccination to a traveler to fulfill these requirements if the provider judges that YF vaccination is medically contraindicated.

Because of the risk for serious adverse events that can occur following YF vaccine administration, health-care providers should vaccinate only persons who are at risk for exposure to YF virus or require proof of vaccination for country entry. To minimize further the risk for serious adverse events, health-care providers should observe the contraindications carefully and consider the precautions to vaccination before administration of YF vaccine and provide a medical waiver when needed (see Table below).

Table. Contraindications and Precautions to Yellow Fever Vaccine Administration

Contraindications Precautions
  • Allergy to vaccine component
  • Age less than 6 months
  • Symptomatic human immunodeficiency virus (HIV) infection or CD4+ T-lymphocytes <200/mm3 (or <15% of total in children aged <6 years)*
  • Thymus disorder associated with abnormal immune function†
  • Primary immunodeficiencies
  • Malignant neoplasms
  • Transplantation
  • Immunosuppressive and immunomodulatory therapies†
  • Age 6–8 months
  • Age ≥60 years†
  • Asymptomatic HIV infection and CD4+ T-lymphocytes 200–499/mm3 (or 15%–24% of total in children aged <6 years)*
  • Pregnancy
  • Breastfeeding

*Symptoms of HIV have been classified (Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents; US Department of Health and Human Services; 2008. Available at http://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=7&ClassID=1 External Web Site Policy Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection; 2009. Available at http://www.aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?GuidelineID=8&ClassID=1 External Web Site Policy)

† New contraindication or precaution since the ACIP's recommendations for the use of yellow fever vaccine were published in 2002 (CDC. Yellow fever vaccine: recommendations of the Advisory Committee on Immunizations Practices: MMWR 2002;51[No. RR-17]).

Requirements for Vaccination before International Travel

Certain countries require evidence of vaccination from all entering travelers, which includes direct travel from the United States. Travelers who arrive in a country with a YF vaccination entry requirement without proof of vaccination may be quarantined for up to 6 days.

Country-entry requirements for proof of YF vaccination under IHRs are different from the Advisory Committee on Immunization Practices (ACIP) or CDC recommendations. Requirements are mandatory and are intended primarily to prevent importation into and transmission of YFV within a given country. CDC's recommendations are public health advice provided to travelers on the basis of the best available epidemiologic data to prevent YFV infection among travelers visiting countries with a risk for YFV transmission.

For purposes of international travel, YF vaccines must be administered at an approved YF vaccination center. In the United States, state and territorial health departments have the authority to designate nonfederal vaccination centers and to issue YF vaccination stamps to those centers. A list of designated vaccine centers is available from CDC at http://wwwnc.cdc.gov/travel/ External Web Site Policy or can be obtained from state or local health departments.

As proof of receipt of YF vaccine, all vaccinees should possess a completed International Certificate of Vaccination or Prophylaxis (ICVP), validated with the provider's signature and official YF vaccination center stamp (Figure 3 in the original guideline). An ICVP must be complete in every detail; if it is incomplete or inaccurate, it is not valid. Failure to secure validations can cause a traveler to be quarantined, denied entry, or possibly revaccinated at the point of entry to a country. Some countries do not require an ICVP for infants younger than a certain age (e.g. aged <6 months, <9 months, or <1 year, depending on the country). Information on age requirements for vaccination by individual countries is available at http://wwwnc.cdc.gov/travel External Web Site Policy.

The certificate of vaccination is valid beginning 10 days after the date of vaccination and extending for a period of 10 years. When a booster dose of the vaccine is administered within this 10-year period, the certificate is considered valid from the day of the most recent vaccination.

IHRs stipulate that a medical provider may issue a waiver of YF vaccination to a traveler if the provider judges that YF vaccination is medically contraindicated (see Contraindications and Precautions). In this case, the physician should fill out and sign the "Medical Contraindications to Vaccination" section of the ICVP (Figure 4 in the original guideline), provide a signed and dated letter on letterhead stationery clearly stating the contraindication, and bearing that center's official YF vaccination stamp. The provider should inform the traveler of any increased risk for YF infection associated with nonvaccination and how to minimize this risk. Reasons other than medical contraindications are not acceptable for exemption from vaccination. The traveler also should be advised of the possibility that the medical waiver might not be accepted by the destination country.

Because requirements and recommendations might change, all travelers should seek up-to-date information before travel from health departments, CDC, and the World Health Organization (WHO). Travel agencies, international airlines, or shipping lines also might have up-to-date information. Updated information on requirements and recommendations for vaccination are available at http://wwwnc.cdc.gov/travel External Web Site Policy.

Administration of Yellow Fever Vaccine

Dosage and Administration

For persons of all ages for whom vaccination is indicated, a single subcutaneous injection of 0.5 mL of reconstituted vaccine is used. According to the package insert, the vaccine needs to be administered within 1 hour of reconstitution. Once reconstituted, a multidose vial should be maintained at 35°F–46°F (2°C–8°C), and the remaining doses should be used or discarded within 1 hour.

Although limited data suggest YF vaccine might retain its potency following the expiration date, the package insert states that the vaccine should not be used after its expiration date. According to ACIP's General Recommendations on Immunization, a dose of an expired vaccine should not be counted as valid, and the dose should be repeated with a nonexpired vaccine following a 28-day interval. For more guidance on the inadvertent administration of an expired vaccine, health-care providers should contact the vaccine manufacturer.

If the vaccine is administered inadvertently via the intramuscular route, the response to vaccine probably will not be affected. Repeating doses of vaccine administered by the intramuscular route rather than by the subcutaneous route is not necessary.

Anaphylaxis has been reported to occur in persons with no history of reactions to the components of the vaccine. Given this, all persons should be observed for at least 15 minutes following the administration of the vaccine, and epinephrine injection (1:1,000) should be readily available in case of a serious allergic reaction. Furthermore, because reactions have been delayed up to several hours following YF vaccine, all patients should be advised of signs and symptoms of an allergic reaction (e.g., urticaria, angioedema, rash, dyspnea, bronchospasm, pharyngeal edema, wheezing, and throat tightness). In addition, vaccinated persons should be advised to seek immediate medical care if any symptoms of an allergic reaction develop following vaccination.

Transfusion-related transmission of yellow fever vaccine virus has been documented among persons receiving blood products that were collected from recently vaccinated persons. Blood donation centers should screen blood donors to determine if they received a yellow fever vaccine within the preceding 2 weeks and defer these donors. However, practices vary between blood collection centers, and questions about vaccination history might not be asked routinely. Therefore, health-care providers should advise persons to defer blood donation for 2 weeks after receiving YF vaccine.

Booster Doses

IHRs require revaccination at intervals of 10 years to boost antibody titer. Evidence from multiple studies demonstrates that YF vaccine immunity persists for many decades and might provide life-long protection.

To minimize the occurrence of adverse events and optimize the immune response, efforts should be taken to observe a 10-year interval between YF vaccine doses. However, limited data suggest that revaccination occurring <10 years after the previous dose does not increase the risk for adverse events, particularly as serious adverse events occur primarily after the initial vaccination of YF vaccine. Although the level of YFV-specific antibodies formed following revaccination appears to be correlated inversely to the amount of preexisting antibodies, no data suggest that earlier revaccination will have a negative impact on seroprotection. If the date of the most recent vaccination cannot be ascertained, and the patient requires vaccination, a booster dose should be administered.

Simultaneous Administration of Other Vaccines or Drugs

Determination of whether to administer YF vaccine and other immunobiologics simultaneously (i.e., administration on the same day but at a different injection site) should be made on the basis of convenience to the traveler in completing the desired vaccinations before travel and on information regarding possible immune interference.

No evidence exists that inactivated vaccines and YF vaccine interfere with the immune response to the vaccine. Therefore, inactivated vaccines can be administered either simultaneously or at any time before or after YF vaccination. YF vaccine should be administered either simultaneously or 30 days apart from other live viral vaccines because the immune response to one live virus vaccine might be impaired if administered within 30 days of another live-virus vaccine. Limited data suggest that the serologic response to YF vaccine is not inhibited by administration of measles vaccine nonsimultaneously within 30 days of YF vaccine administration. However, the serologic response to measles vaccine was not assessed in this study. Oral Ty21a typhoid vaccine can be administered simultaneously or at any interval before or after YF vaccine attributable to the different routes of administration.

Vaccines that have been administered simultaneously with YF vaccine without interfering in the immune response to the vaccines or resulting in unusual safety profiles include Bacillius Calmette-Guerin, diphtheria, hepatitis A, hepatitis B, influenza, measles, meningococcal (Menomune), pertussis, polio , smallpox, tetanus, and typhoid (both injectable and oral). No data exist regarding possible interference between YF vaccine and rabies, human papillomavirus, Japanese encephalitis, live attenuated influenza, or varicella virus vaccines.

Studies of persons administered YF vaccine and immune globulin simultaneously found no alteration of the immunologic response to YF vaccine when compared with controls (i.e., YF vaccine alone). Although chloroquine inhibits replication of YFV in vitro, it does not affect antibody responses to YF vaccine adversely among persons receiving antimalarial prophylaxis.

No data exist for YF vaccine and the potential suppression of the tuberculin skin test (TST) response. However, because the use of live attenuated measles vaccine theoretically can suppress TST reactivity resulting in a false-negative reaction, ACIP's General Recommendations on Immunization suggest that TST should be administered at the same time as YF vaccine or 4 weeks after receipt of YF vaccine. Alternatively, TST screening can be performed and read before administering YF vaccine. However, if YF vaccine has been administered recently, TST screening should be delayed for at least 4 weeks after vaccination.

Contraindications

Allergy to Vaccine Components

YF vaccine is contraindicated for persons with a history of hypersensitivity to any of the vaccine components, including eggs, egg products, chicken proteins, or gelatin. The stopper used in vials of vaccine also contains dry latex rubber, which might cause an allergic reaction.

According to the manufacturer, persons who are able to eat eggs or egg products may receive the vaccine. However, potential hypersensitivity reactions might occur in persons with a history of minor reactions to eggs. For egg-sensitive persons, a scratch test or intradermal test can be performed before administering the vaccine to check for reactivity. If a person has a severe egg-sensitivity or has a positive skin test to the vaccine, but the vaccination is recommended because of their travel destination-specific risk, desensitization can be performed under direct supervision of a physician experienced in the management of anaphylaxis. The desensitization procedure is detailed in the product insert.

Given the risk for anaphylaxis, even among persons with no history of reactions to components of the vaccine, all persons should be observed for at least 15 minutes following the administration of the vaccine, and epinephrine (1:1,000) should be readily available in case of a serious allergic reaction. Vaccinated persons should be advised of symptoms of an allergic reaction and should be advised to seek immediate medical care if any symptoms of an allergic reaction develop following vaccination.

Infants Aged <6 Months

YF vaccine is contraindicated for infants aged <6 months. This contraindication was instituted in the late 1960s in response to a high rate of yellow fever vaccine-associated neurotropic disease (YEL-AND) documented in vaccinated young infants. The mechanism of increased neurovirulence in infants is unknown but might be attributable to the immaturity of the blood-brain barrier, higher or more prolonged viremia, or immune system immaturity.

Altered Immune Status

Thymus Disorder

YF vaccine is contraindicated for persons with a thymus disorder that is associated with abnormal immune cell function (e.g., thymoma or myasthenia gravis). Four (17%) of the initial 23 yellow fever vaccine-associated viscerotropic disease (YEL-AVD) reported cases were noted to occur in persons who had had thymectomies performed for thymomas. In 2003, thymus disorder was added to the YF vaccine package insert as a contraindication. To date, no evidence has been identified of immune dysfunction or increased risk for YF vaccine-associated serious adverse events in persons who have undergone incidental surgical removal of their thymus or have had indirect radiation therapy in the distant past. Therefore, YF vaccine can be administered, if indicated based on their destination-specific YF risk, in persons who underwent incidental surgical removal of the thymus or have a remote history of radiation therapy to the thymus.

AIDS and HIV Infection with Severe Immune Suppression

YF vaccine is contraindicated for persons with acquired immunodeficiency syndrome (AIDS) or other clinical manifestations of HIV, including persons with CD4 counts <200 per mm3 or <15% of total lymphocytes for children aged <6 years. This recommendation is based on a theoretic increased risk for encephalitis in this population. One fatal YEL-AND case has been reported in a person with a previously undiagnosed HIV infection and a CD4 count of 108 cells/mm3 who was vaccinated with YF vaccine. No large prospective, randomized trials have been performed to address the safety and efficacy of YF vaccine among this group adequately. Several retrospective and prospective studies that included a total of approximately 450 HIV-infected persons who received YF vaccine reported no additional serious adverse events. However, these studies included a limited subset of adults (n = 10) with a CD4 counts <200 per mm3.

If travel to an area in which YF is endemic cannot be avoided in a person with severe immune suppression based on CD4 counts (<200 per mm3 or <15% total) or symptomatic HIV, a medical waiver should be provided, and counseling on protective measures against mosquito bites should be emphasized. (See Precautions for other HIV-infected persons not meeting these criteria.)

Immunodeficiencies Other than Thymus Disorder or HIV Infection

YF vaccine is contraindicated for persons with primary immunodeficiencies, malignant neoplasms, and transplantation. Although no data exist on the use of YF vaccine in these persons, they are presumed to have an increased risk for YF vaccine-associated serious adverse events. More specific information on primary immunodeficiencies for which the use of live viral vaccines, such as YF vaccine, is contraindicated will be published. In general, solid organ transplant or hematopoietic stem cell transplant recipients within 2 years of transplantation, or persons whose transplants occurred >2 years ago but who are still taking immunosuppressive drugs, are considered to be immunosuppressed. Live viral vaccines should be deferred in persons with a history of malignant neoplasm or transplantation until immune function has improved substantially. This is best determined by a physician who is familiar with the patient and the patient's underlying medical condition and treatments in consultation with a YF vaccination center. If a person with an immunodeficiency cannot avoid travel to an area in which YF is endemic, a medical waiver should be provided, and counseling on protective measures against mosquito bites should be emphasized.

Immunosuppressive and Immunomodulatory Therapies

YF vaccine is contraindicated for person whose immunologic response is either suppressed or modulated by current or recent radiation therapies or drugs. Drugs with known immunosuppressive or immunomodulatory properties include high-dose systemic corticosteroids, alkylating drugs, antimetabolites, tumor necrosis fact (TNF)-alpha inhibitors (e.g., etanercept), interleukin (IL)-1 blocking agent (e.g., anakinra), and other monoclonal antibodies targeting immune cells (e.g., rituximab, alemtuzumab). No specific data exist on the use of YF vaccine in persons receiving these therapies. However, these persons are presumed to be at an increased risk for YF vaccine-associated serious adverse events, and the use of live attenuated vaccines in these persons is contraindicated according to the package insert for most of these therapies.

Although the immunosuppressive effects of corticosteroids can vary, a dose of either ≥2 mg/kg of body weight or a total ≥20 mg/day of prednisone or its equivalent for persons who weigh >10 kg when administered for ≥2 weeks is considered sufficiently immunosuppressive to contraindicate the use of live attenuated vaccines. Corticosteroids are not a contraindication when administration is under any of the following circumstances: short-term (i.e., <2 weeks); a low-to-moderate dose (<20 mg of prednisone or its equivalent per day); long-term, alternate-day treatment with short-acting preparations; maintenance physiologic doses (replacement therapy); or administered topically (skin or eyes), inhaled, or by intra-articular, bursal, or tendon injection.

Administration of live viral vaccines should be deferred in persons who have discontinued these therapies until immune function has improved. This is best determined by a physician who is familiar with the patient's underlying medical conditions and by the patient's pharmacist, who can assist in determining the specific half-lives of the immunosuppressive drugs and the potential duration of immune suppression. If someone receiving immunosuppressive or immunomodulatory therapies cannot avoid travel to an area in which YF is endemic, a medical waiver should be provided, and counseling on protective measures against mosquito bites should be emphasized.

Precautions

Infants Aged 6–8 Months

Age 6–8 months is a precaution for YF vaccine administration. In infants aged <6 months, the rates of YEL-AND are substantially elevated (50–400 cases per 100,000 infants vaccinated). Two cases of YEL-AND have been reported among infants aged 6–8 months. By age 9 months, the risk for YEL-AND is believed to be substantially lower. In general, whenever possible, travel of children aged 6–8 months to countries in which YF is endemic should be postponed or avoided. If travel is unavoidable, the decision of whether to vaccinate these infants needs to balance the risks for YFV exposure with the risk for adverse events following vaccination.

Adults Aged ≥60 Years

Age ≥60 years is a precaution for YF vaccine administration, particularly if the first dose of the YF vaccine is to be administered. A recent analysis of adverse events reported to the Vaccine Adverse Effects Reporting System (VAERS) during 2000–2006 indicates that persons aged ≥60 years are at increased risk for any serious adverse events after vaccination, compared with younger persons. The rate of serious adverse events in persons aged ≥60 years was 8.3 events per 100,000 doses distributed compared with 4.7 events per 100,000 doses distributed for all YF vaccine recipients. This reinforces findings from VAERS data from 1990–1998 that reported the rate of serious adverse events was 7.5 times higher in persons aged ≥60 years than in the reference group (persons aged 19–29 years). The risk for YEL-AND and YEL-AVD also are increased in this age group, at 1.8 and 1.4 reported cases per 100,000 doses distributed, respectively, compared with 0.8 and 0.4 reported cases per 100,000 doses distributed for all YF vaccine recipients. Given that YEL-AND and YEL-AVD are seen almost exclusively in primary vaccine recipients, caution should be exercised with older travelers who might be receiving YF vaccine for the first time. If travel is unavoidable, the decision to vaccinate travelers aged ≥60 years needs to weigh the risks and benefits of the vaccination in the context of their destination-specific risk for exposure to YFV.

Asymptomatic HIV Infection with Moderate Immune Suppression

Asymptomatic HIV infection with moderate immune suppression (i.e., CD4 counts of 200–499 per mm3 for persons aged ≥6 years or 15%–24% of total lymphocytes for children aged <6 years) is a precaution for YF vaccine administration. Large prospective randomized trials have not been performed to address the safety and efficacy of YF vaccine adequately among this group. Several retrospective and prospective studies including approximately 450 persons infected with HIV have reported no serious adverse events among patients considered moderately immunosuppressed based on their CD4 counts.

HIV infection has been associated with a reduced immunologic response to a number of inactivated and live-attenuated vaccines, including YF vaccine. In a recent retrospective cohort study, 65 (83%) of 78 HIV-infected persons developed specific antibodies against YFV in the first year after vaccination; however, this was significantly lower than vaccinated persons without HIV infection (97%; p=0.01). Among HIV-infected infants in developing nations, only three (17%) of 18 developed YFV-specific neutralizing antibodies within 10 months of vaccination compared with 42 (74%) of 57 HIV-uninfected controls matched for age and nutritional status. The mechanisms for the diminished immune response in HIV-infected persons are uncertain but appear to be correlated with HIV RNA levels and CD4 counts. Because vaccination of asymptomatic HIV-infected persons might be less effective than that for persons not infected with HIV, measurement of their neutralizing antibody response to vaccination should be considered before travel. Health-care providers should contact the appropriate state health department or CDC (at telephone 1-970 221-6400) to discuss serologic testing further.

For HIV-infected persons who experience immune reconstitution in response to antiretroviral therapy, their current CD4 count and symptoms of HIV infection (if stable over 3 month time period) rather than a CD4 count nadir and a history of prior opportunistic infections/symptomatic HIV should be used to categorize their HIV status. Of note, one YEL-AVD case was reported in a person determined to have a genetic polymorphisms in chemokine receptor CCR5. Consequently, concern has been raised that despite having adequate immune function, persons with HIV infection who are receiving an antiretroviral regimen containing a CCR5-receptor antagonist could be at increased risk for adverse events after YF vaccination. Further research is needed to address this concern.

If an asymptomatic HIV-infected person with moderate immune suppression is traveling to an area in which YF is endemic, vaccination can be considered. Vaccinated persons should be monitored closely after vaccination for evidence of adverse events. If an adverse event occurs, a VAERS report should be filed, and the state health department or CDC should be notified to obtain technical support and assistance with diagnostic testing. If international travel requirements rather than an increased risk for acquiring YFV infection are the only reason to vaccinate HIV-infected persons, the person should be excused from vaccination and issued a medical waiver to fulfill health regulations. If an asymptomatic HIV-infected person has no evidence of immune suppression based on CD4 counts (CD4 count ≥500 per mm3 or ≥25% of total lymphocytes for children aged <6 years), YF vaccine can be administered, if recommended on the basis of their destination-specific YF risk. (See "Contraindications" above for other HIV-infected persons not meeting these criteria.)

Pregnancy

Pregnancy is a precaution for YF vaccine administration, compared with most other live vaccines, which are contraindicated in pregnancy. If travel is unavoidable, and the risks for YFV exposure are felt to outweigh the vaccination risks, a pregnant woman should be vaccinated. If the risks for vaccination are felt to outweigh the risks for YFV exposure, pregnant women should be issued a medical waiver to fulfill health regulations. Although no specific data are available, a woman should wait 4 weeks after receiving YF vaccine before conceiving (see "Vaccination of Women During Pregnancy and Breastfeeding" in the original guideline document).

Breastfeeding

Breastfeeding is a precaution for YF vaccine administration. Two serious adverse events have been reported in exclusively breastfed infants whose mothers were vaccinated with YF vaccine. Further research is needed to document the risk for potential vaccine exposure through breastfeeding. Until more information is available, YF vaccine should be avoided in breastfeeding women. However, when travel of nursing mothers to a YF endemic area cannot be avoided or postponed, these women should be vaccinated (see "Vaccination of Women During Pregnancy and Breastfeeding" in the original guideline document).

Special Populations

Age

YF vaccine is approved for use in persons aged ≥9 months. The vaccine is contraindicated for infants aged <6 months (see "Contraindications" for more information). Age 6–8 months and adults aged ≥60 years are precautions for YF vaccine administration (see "Precautions").

Pregnancy

Limited data are available regarding the safety and immunogenicity of YF vaccine in pregnancy. Pregnancy is a precaution for YF vaccine administration (see "Vaccination of Women During Pregnancy and Breastfeeding" and "Precautions").

Breastfeeding Women

Although no data are available on the immune response in breastfeeding mothers, no alteration to the immune response in these women are suspected. Limited data are available regarding the safety of YF vaccine in breastfed infants. Breastfeeding is a precaution for YF vaccine administration (see "Vaccination of Women During Pregnancy and Breastfeeding" and "Precautions").

Altered Immune Status

The following conditions are a contraindication for YF vaccine administration: 1) thymus disorders associated with abnormal immune cell function, 2) symptomatic HIV infection or CD4+ T-lymphocyte values <200 per mm3 or <15% of total lymphocytes for children aged <6 years, 3) primary immunodeficiencies, 4) malignant neoplasms, 5) transplantation, 6) immune suppression or modulation attributable to current or recent radiation therapies or drugs. The following condition with altered immune status is a precaution for YF vaccine administration: asymptomatic HIV infection with CD4+ T-lymphocyte values 200–499 per mm3 or 15%–24% of total lymphocytes for children aged <6 years (see "Contraindications" and "Precautions").

Complete details are not available regarding what medications the nine patients with reported YEL-AVD who had a history of autoimmune disease or diseases with potential autoimmune etiology were taking; these might have included immunosuppressive medications. Four of the nine patients were aged >60 years, including two who also had a history of thymectomy for thymoma (see "YEL-AVD" section in the original guideline document). Older age and history of thymoma are both risk factors for YEL-AVD. Nonetheless, the fact that nine (16%) of 57 persons with reported cases of YEL-AVD had a history of autoimmune disease is a concern and suggests that autoimmune disease, either by itself or in conjunction with other risk factors, including immunosuppressive medication, could increase the risk for YEL-AVD. Definitive data are lacking to guide decision-making about YF vaccination in these patients. Health-care providers should consider the possibility of diminished immune function resulting from the autoimmune disease state itself and/or the medication used in deciding whether or not to administer YF vaccine to these patients.

Reporting of Vaccine Adverse Events

Even if a causal relation to vaccination is not certain, all adverse events following receipt of vaccine that are thought to be clinically significant by health-care providers or vaccine recipients should be reported to VAERS at http://vaers.hhs.gov External Web Site Policy or by telephone at 1-800-822-7967. To promote better timeliness and quality of safety data, secure web-based reporting is available and health-care providers are encouraged to report electronically at http://vaers.hhs.gov/esub/index#Online External Web Site Policy.

Surveillance to monitor, characterize, and quantify YF vaccine-specific adverse outcomes are ongoing. Because current reporting mechanisms are strictly passive, detection of YEL-AVD and YEL-AND in recently vaccinated persons who experience new symptoms largely depends on health-care providers being familiar with these conditions and with reporting requirements. An education program regarding the vaccine and possible serious adverse events is being developed and will be made available to all health-care providers by fall 2010 through CDC's Travelers' Health website. State health departments are encouraged to incorporate requirements for completion of these programs into their certification and recertification processes for issuance of YF vaccination stamps to health-care providers.

Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is not specifically stated for each recommendation.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits
  • Appropriate use of yellow fever (YF) vaccine among travelers and laboratory workers
  • Prevention of yellow fever
Potential Harms

Adverse Events to Yellow Fever (YF) Vaccine

  • Mild headaches, myalgia, low-grade fevers, or other minor symptoms for 5–10 days. Localized pain, swelling, erythema, or warmth might occur at the injection site for up to a week following vaccination.
  • The majority of reported adverse events to Vaccine Adverse Event Reporting System (VAERS) are classified as nonserious (rate: 38 per 100,000 population) and include reports of fever, injection-site pain, injection-site erythema, pruritus, headache, urticaria, and rash. The majority of events occur a median of 1 day after vaccination; roughly 60% occur within the first 2 days after vaccination.
  • Three well-characterized serious adverse events occur following YF vaccine administration: 1) immediate hypersensitivity or anaphylactic reactions, 2) YF vaccine-associated neurologic disease (YEL-AND), and 3) YF vaccine-associated viscerotropic disease (YEL-AVD).

See the original guideline document for more information concerning these adverse effects.

Contraindications

Contraindications

See the "Major Recommendations" field for a full discussion of the contraindications to yellow fever vaccine.

Qualifying Statements

Qualifying Statements
  • Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
  • References to non-Centers for Disease Control and Prevention (CDC) sites on the Internet are provided as a service to MMWR readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the U.S. Department of Health and Human Services. CDC is not responsible for the content of these sites. URL addresses listed in MMWR were current as of the date of publication.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Foreign Language Translations
Patient Resources
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness
Safety

Identifying Information and Availability

Bibliographic Source(s)
Staples JE, Gershman M, Fischer M, Centers for Disease Control and Prevention (CDC). Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2010 Jul 30;59(RR-7):1-27. [157 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2002 Nov 8 (revised 2010 Jul 30)
Guideline Developer(s)
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]
Source(s) of Funding

United States Government

Guideline Committee

Yellow Fever Vaccine Work Group

Composition of Group That Authored the Guideline

Prepared by: J. Erin Staples, MD, PhD, 1Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases; Mark Gershman, MD, Division of Global Migration and Quarantine, National Center for Emerging and Zoonotic Infectious Diseases; Marc Fischer, MD, Division of Vector-Borne Diseases, National Center for Emerging and Zoonotic Infectious Diseases

Advisory Committee on Immunization Practices

Membership List, October 2009

Chair: Carol Baker, MD, Baylor College of Medicine, Houston, Texas

Executive Secretary: Larry Pickering, MD, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, Georgia

Members: Lance Chilton, MD, University of New Mexico, Albuquerque, New Mexico; Paul Cieslak, MD, Oregon Public Health Division, Portland, Oregon; Kristen Ehresmann, MPH, Minnesota Department of Health, St. Paul, Minnesota; Janet Englund, MD, University of Washington and Children’s Hospital and Regional Medical Center, Seattle, Washington; Franklyn Judson, MD, University of Colorado Health Sciences Center, Denver, Colorado; Wendy Keitel, MD, Baylor College of Medicine, Houston, Texas; Susan Lett, MD, Massachusetts Department of Public Health, Boston, Massachusetts; Michael Marcy, MD, UCLA Center for Vaccine Research, Torrance, California; Cody Meissner, MD, Tufts Medical Center, Boston, Massachusetts; Kathleen Neuzil, MD, University of Washington, Seattle, Washington; Sara Rosenbaum, JD, George Washington University, District of Columbia; Mark Sawyer, MD, University of California - San Diego, California; Ciro Valent Sumaya, MD, Texas A&M Health Science Center, College Station, Texas; Jonathan Temte, MD, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

Ex Officio Members: James E. Cheek, MD, Indian Health Service, Albuquerque, New Mexico; Wayne Hachey, DO, Department of Defense, Falls Church, Virginia; Geoffrey S. Evans, MD, Health Resources and Services Administration, Rockville, Maryland; Bruce Gellin, MD, National Vaccine Program Office, District of Columbia; Linda Murphy, Centers for Medicare and Medicaid Services, Baltimore, Maryland; George T. Curlin, MD, National Institutes of Health, Bethesda, Maryland; Norman Baylor, MD, Food and Drug Administration, Bethesda, Maryland; Linda Kinsinger, MD, Department of Veterans Affairs, Durham, North Carolina

Liaison Representatives: American Academy of Family Physicians, Doug Campos-Outcalt, MD, Phoenix, Arizona; American Academy of Pediatrics, Joseph Bocchini, MD, Shreveport, Louisiana, David Kimberlin, MD, Birmingham, Alabama; American College Health Association, James C. Turner, MD, Charlottesville, Virginia; American College of Obstetricians and Gynecologists, Stanley Gall, MD, Louisville, Kentucky; American College of Physicians, Gregory Poland, Rochester, Minnesota; American Geriatrics Society, Kenneth Schmader, MD, Durham, North Carolina; America’s Health Insurance Plans, Mark Netoskie, MD, Houston, Texas; American Medical Association, Litjen Tan, PhD, Chicago, Illinois; American Osteopathic Association, Stanley Grogg, DO, Tulsa, Oklahoma; American Pharmacists Association, Stephan L. Foster, PharmD, Memphis, Tennessee; Association for Prevention Teaching and Research, W. Paul McKinney, MD, Louisville, Kentucky; Biotechnology Industry Organization, Clement Lewin, PhD, Cambridge, Massachusetts; Canadian National Advisory Committee on Immunization, Joanne Langley, MD, Halifax, Nova Scotia, Canada; Council of State and Territorial Epidemiologists, Christine Hahn, MD, Boise, Idaho; Department of Health, United Kingdom David M. Salisbury, MD, London, United Kingdom; Healthcare Infection Control Practices Advisory Committee, Alexis Elward, MD, St Louis, Missouri; Infectious Diseases Society of America, Samuel L. Katz, MD, Durham, North Carolina; National Association of County and City Health Officials, Jeff Duchin, MD, Seattle, Washington; National Association of Pediatric Nurse Practitioners, Patricia Stinchfield, St Paul, Minnesota; National Foundation for Infectious Diseases, William Schaffner, MD, Nashville, Tennessee; National Immunization Council and Child Health Program, Mexico, Vesta Richardson, MD, Mexico City, Mexico; National Medical Association, Patricia Whitley-Williams, MD, New Brunswick, New Jersey; National Vaccine Advisory Committee, Guthrie Birkhead, MD, Albany, New York; Pharmaceutical Research and Manufacturers of America, Damian A. Braga, Swiftwater, Pennsylvania, Peter Paradiso, PhD, Collegeville, Pennsylvania; Society for Adolescent Medicine, Amy Middleman, MD, Houston, Texas; Society for Healthcare Epidemiology of America, Harry Keyserling, MD, Atlanta, Georgia

ACIP Yellow Fever Vaccine Work Group

Chair: Carol J. Baker, MD, Houston, Texas

Members: Elizabeth Barnett, MD, Boston, Massachusetts; Louisa Chapman, MD, Atlanta, Georgia; Eileen Farnon, MD, Atlanta, Georgia; Patrick Garmon, PharmD, PhD, Falls Church, Virginia; Mark D. Gershman, MD, Atlanta, Georgia; Christina Greenaway, MD, Toronto, Canada; Kristen B. Janusz, DVM, Fort Collins, Colorado; James F. Jones, MD, Atlanta, Georgia; Franklyn N. Judson, MD, Denver, Colorado; Katrin S. Kohl, MD, Atlanta, Georgia; Nina Marano, DVM, Atlanta, Georgia; Michael E. Neseman, MD, Lima, Peru; Karen O'Brien, MD, Fort Monroe, Virginia; Michele Sabourin, Ottawa, Ontario, Canada; Betsy Schroeder, MPH, Atlanta, Georgia; Barbara A. Slade, MD, Atlanta, Georgia; J. Erin Staples, MD, PhD, Fort Collins, Colorado; Andrea Sutherland, MD, Silver Springs, Maryland; Mary E. Wilson, MD, Boston, Massachusetts

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

This guideline updates a previously released version: Cetron MS, Marfin AA, Julian KG, Gubler DJ, Sharp DJ, Barwick RS, Weld LH, Chen R, Clover RD, Deseda-Tous J, Marchessault V, Offit PA, Monath TP. Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. MMWR Recomm Rep 2002 Nov 8;51(RR-17):1-11. [57 references]

Guideline Availability

Electronic copies: Available from the Centers for Disease Control and Prevention (CDC) Web site External Web Site Policy.

Print copies: Available from the Centers for Disease and Control Prevention, MMWR, Atlanta, GA 30333. Additional copies can be purchased from the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402-9325; (202) 783-3238.

Availability of Companion Documents

None available

Patient Resources

The following are available:

  • Yellow fever vaccine: what you need to know. Vaccine information statement (VIS). Atlanta (GA): Centers for Disease Control and Prevention (CDC). 2011 Mar 30. Electronic copies: Available in Chinese, Spanish, Tagalog, Vietnamese, and English from the CDC Web site External Web Site Policy.
  • Yellow fever vaccine: what you need to know. Audio. Atlanta (GA): Centers for Disease Control and Prevention (CDC). 2003 Mar 13. Electronic copies: Available from the CDC Web site External Web Site Policy.

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

NGC Status

This NGC summary was completed by ECRI on March 17, 2003. This NGC summary was updated by ECRI Institute on April 12, 2011.

Copyright Statement

No copyright restrictions apply.

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