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 .
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 .
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 . 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
- 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
- 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)*
*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 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 )
† 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/ 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 .
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 .
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.
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.
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
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.
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 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 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).
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").
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").
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 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 .
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.