COVID-19 vaccine safety inquiries to the centers for disease control and prevention immunization safety office.

BACKGROUND: Following the authorization and recommendations for use of the U.S. COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC)'s Immunization Safety Office (ISO) responded to inquiries and questions from public health officials, healthcare providers, and the general public on COVID-19 vaccine safety. METHODS: We describe COVID-19 vaccine safety inquiries, by topic, received and addressed by ISO from December 1, 2020-August 31, 2022. RESULTS: Of the 1978 COVID-19 vaccine-related inquiries received, 1655 specifically involved vaccine safety topics. The most frequently asked-about topics included deaths following vaccination, myocarditis, pregnancy, and reproductive health outcomes, understanding or interpreting data from the Vaccine Adverse Event Reporting System (VAERS), and thrombosis with thrombocytopenia syndrome. CONCLUSIONS: Inquiries about vaccine safety generally reflect issues that receive media attention. ISO will continue to monitor vaccine safety inquiries and provide accurate and timely information to healthcare providers, public health officials, and the general public.

The reporting sensitivity of the Vaccine Adverse Event Reporting System (VAERS) for anaphylaxis and for Guillain-Barré syndrome.

BACKGROUND: Underreporting is a limitation common to passive surveillance systems, including the Vaccine Adverse Event Reporting System (VAERS) that monitors the safety of U.S.-licensed vaccines. Nonetheless, previous reports demonstrate substantial case capture for clinically severe adverse events (AEs), including 47% of intussusception cases after rotavirus vaccine, and 68% of vaccine associated paralytic polio after oral polio vaccine. OBJECTIVES: To determine the sensitivity of VAERS in capturing AE reports of anaphylaxis and Guillain-Barré syndrome (GBS) following vaccination and whether this is consistent with previous estimates for other severe AEs. METHODS: We estimated VAERS reporting rates following vaccination for anaphylaxis and GBS. We used data from VAERS safety reviews as the numerator, and estimated incidence rates of anaphylaxis and GBS following vaccination from the Vaccine Safety Datalink (VSD) studies as the denominator. We defined reporting sensitivity as the VAERS reporting rate divided by the VSD incidence rate. Sensitivity was reported as either a single value, or a range if data were available from >1 study. RESULTS: VAERS sensitivity for capturing anaphylaxis after seven different vaccines ranged from 13 to 76%; sensitivity for capturing GBS after three different vaccines ranged from 12 to 64%. For anaphylaxis, VAERS captured 13-27% of cases after the pneumococcal polysaccharide vaccine, 13% of cases after influenza vaccine, 21% of cases after varicella vaccine, 24% of cases after both the live attenuated zoster and quadrivalent human papillomavirus (4vHPV) vaccines, 25% of cases after the combined measles, mumps and rubella (MMR) vaccine, and 76% of cases after the 2009 H1N1 inactivated pandemic influenza vaccine. For GBS, VAERS captured 12% of cases after the 2012-13 inactivated seasonal influenza vaccine, 15-55% of cases after the 2009 H1N1 inactivated pandemic influenza vaccine, and 64% of cases after 4vHPV vaccine. CONCLUSIONS: For anaphylaxis and GBS, VAERS sensitivity is comparable to previous estimates for detecting important AEs following vaccination.

Adverse events following adenovirus type 4 and type 7 vaccine, live, oral in the Vaccine Adverse Event Reporting System (VAERS), United States, October 2011-July 2018.

BACKGROUND: In March 2011, the U.S. Food and Drug Administration licensed adenovirus type 4 and type 7 vaccine, live, oral (Barr Labs, Inc.) (adenovirus vaccine) for use in military personnel 17 through 50 years of age. The vaccine was first universally administered to U.S. military recruits in October 2011. We investigated adverse event (AE) reports following the adenovirus vaccine submitted to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We searched the VAERS database for U.S. reports among persons who received adenovirus vaccine during October 2011 through July 2018 including participants in a military observational study. We reviewed all serious reports and accompanying medical records. We compared the proportion of serious reports in a proxy military recruit population and reviewed all reports of suspected allergic reactions following adenovirus vaccination. RESULTS: During the analytic period, VAERS received 100 reports following adenovirus vaccination; 39 (39%) were classified as serious and of these, 17 (44%) were from the observational study. One death was reported. Males accounted for 72% of reports. Median age of vaccinees was 19 years (range 17-32). The most frequently reported serious AEs were Guillain Barré syndrome (GBS) (n = 12) and anaphylaxis (n = 8); of these, two GBS and all the anaphylaxis reports were reported in the observational study. Reports documented concurrent receipt of multiple other vaccines (95%) and penicillin G (IM Pen G) or other antibiotics (50%). CONCLUSIONS: The reporting rate for serious AEs was higher than with other vaccines administered in the comparison military recruit population (39% vs 18%); however, we identified no unexpected or concerning pattern of adenovirus vaccine AEs. Co-administration of vaccines and IM Pen G was commonly reported in this military population. These exposures may have contributed to the GBS and anaphylaxis outcomes observed with the adenovirus vaccine. Future adenovirus vaccine safety studies in a population without these co-administrations would be helpful in clarifying the vaccine's safety profile.

Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2012-2016.

BACKGROUND: In March 2009, the U.S. Food and Drug Administration licensed an inactivated Vero cell culture-derived Japanese encephalitis vaccine (JE-VC [IXIARO®]) for use in persons aged ≥17 years. In 2013, licensure was extended to include children aged ≥2 months. A previous analysis reviewed adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from May 2009 through April 2012. METHODS: We reviewed adverse events reported to VAERS following JE-VC administered from May 1, 2012 through April 30, 2016. Adverse event reporting rates were calculated using 802,229 doses distributed. RESULTS: During the 4-year period, 119 adverse event reports were received for a reporting rate of 14.8 per 100,000 doses distributed. Nine (8%) adverse events were classified as serious for a reporting rate of 1.1 per 100,000 distributed. The most commonly reported event was hypersensitivity (n = 24; 20%) for a rate of 3.0 per 100,000 doses distributed; 1 anaphylaxis event was reported. Ten (8%) neurologic events were reported for a rate of 1.2 per 100,000 doses distributed; 2 events were classified as seizures. Sixty-three (53%) adverse events occurred after a first dose of JE-VC. Eighty (67%) adverse events occurred after administration of JE-VC with other vaccines. Eleven (9%) adverse events were reported in children; 1 was considered serious. CONCLUSIONS: These data continue to support the generally favorable safety profile of JE-VC. Reporting rates of adverse events were similar to those of the previous analysis. Although reporting rates of adverse events in children could not be calculated, there were low numbers of reported events in this age group. Post-licensure adverse event surveillance for this relatively new vaccine continues to be important to monitor adverse event reporting rates and identify possible rare serious events.

Post-licensure safety surveillance of zoster vaccine live (Zostavax®) in the United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.

BACKGROUND: Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. METHODS: We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. RESULTS: VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. CONCLUSIONS: Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently reported to VAERS following ZVL. Overall, our results are reassuring regarding the safety of ZVL.

Cognitive testing to evaluate revisions to the Vaccine Adverse Event Reporting System (VAERS) reporting form.

INTRODUCTION: The Vaccine Adverse Event Reporting System (VAERS) is the spontaneous (passive) reporting system CDC and FDA use to monitor vaccine safety. We used cognitive testing to evaluate proposed revisions to the current VAERS form. METHODS: We conducted in-person cognitive interviews with 22 volunteers to evaluate proposed revisions in a prototype VAERS 2.0 form (new VAERS form). We analyzed data using thematic analysis. RESULTS: Repeating themes included preferences for: brevity, simplicity and clarity; features to minimize time requirements and facilitate ease of completion; logical ordering of questions by topic and importance; and visual cues like color-coded highlighting. Interviews identified instances of discordance between the intended meaning questions (from the perspective of CDC and FDA) and interpretation by volunteers. CONCLUSIONS: Cognitive testing yielded useful information to guide further revisions of the VAERS form. Cognitive testing can be an effective tool for public health programs interested in developing surveys and reporting forms.

Adverse event reports following yellow fever vaccination, 2007-13.

BACKGROUND: Yellow fever (YF) vaccines have been available since the 1930s and are generally considered safe and effective. However, rare reports of serious adverse events (SAE) following vaccination have prompted the Advisory Committee for Immunization Practices to periodically expand the list of conditions considered contraindications and precautions to vaccination. METHODS: We describe adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2007 through 2013 and calculate age- and sex-specific reporting rates of all SAE, anaphylaxis, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). RESULTS: There were 938 adverse events following YF vaccination reported to VAERS from 2007 through 2013. Of these, 84 (9%) were classified as SAEs for a rate of 3.8 per 100 000 doses distributed. Reporting rates of SAEs increased with increasing age with a rate of 6.5 per 100 000 in persons aged 60-69 years and 10.3 for ≥70 years. The reporting rate for anaphylaxis was 1.3 per 100 000 doses distributed and was highest in persons ≤18 years (2.7 per 100 000). Reporting rates of YEL-AND and YEL-AVD were 0.8 and 0.3 per 100 000 doses distributed, respectively; both rates increased with increasing age. CONCLUSIONS: These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of continued physician and traveller education regarding the risks and benefits of YF vaccination, particularly for older travellers.

Post-licensure safety surveillance of 23-valent pneumococcal polysaccharide vaccine in the Vaccine Adverse Event Reporting System (VAERS), 1990-2013.

BACKGROUND: 23-Valent pneumococcal polysaccharide vaccine, trade name Pneumovax(®)23 (PPSV23), has been used for decades in the Unites States and has an extensive clinical record. However, limited post-licensure safety assessment has been conducted. OBJECTIVE: To analyze reports submitted to the Vaccine Adverse Event Reporting System (VAERS) following PPSV23 from 1990 to 2013 in order to characterize its safety profile. METHODS: We searched the VAERS database for US reports following PPSV23 for persons vaccinated from 1990 to 2013. We assessed safety through: automated analysis of VAERS data, crude adverse event (AE) reporting rates based on PPSV23 doses distributed in the US market, clinical review of death reports and reports involving vaccine administered to pregnant women, and empirical Bayesian data mining to assess for disproportional reporting. RESULTS: During the study period, VAERS received 25,168 PPSV23 reports; 92% were non-serious, 67% were in females and 86% were in adults aged ≥19 years. When PPSV23 was administered alone, fever (43%), injection site erythema (28%) and injection site pain (25%) were the most commonly reported non-serious AEs in children. Injection site erythema (32%), injection site pain (27%) and injection site swelling (23%) were the most commonly reported non-serious AEs in adults. Of serious reports (2129, 8% of total), fever was most commonly reported in both children (69%) and adults (39%). There were 66 reports of death, four in children and 62 in adults. Clinical review of death reports did not reveal any concerning patterns that would suggest a causal association with PPSV23. No disproportional reporting of unexpected AEs was observed in empirical Bayesian data mining. CONCLUSIONS: We did not identify any new or unexpected safety concerns for PPSV23. The VAERS data are consistent with safety data from pre-licensure clinical trials and other post-licensure studies.

Notes from the Field: Administration Error Involving a Meningococcal Conjugate Vaccine--United States, March 1, 2010-September 22, 2015.

Menveo (GlaxoSmithKline, previously Novartis AG) is a conjugate vaccine that was recommended in October 2010 for routine use in adolescents (preferably aged 11 or 12 years, with a booster at 16 years), and among persons aged 2 through 54 years with certain immunosuppressive conditions, to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y, and W-135 (1). These recommendations have since been updated (2). Menveo is supplied in two vials that must be combined before administration. The MenA lyophilized (freeze-dried) component must be reconstituted with the MenCYW-135 liquid component (Figure). To administer the vaccine, the liquid component is drawn into a syringe, and used to reconstitute the lyophilized component. The resulting solution is administered by intramuscular injection. Failure to prepare Menveo as directed by the manufacturer's instructions can lead to lack of protection against the intended pathogens (N. meningitidis serogroups A, C, Y, and/or W-135) (3). Recently, an immunization provider administered only the lyophilized component of Menveo, subsequently administered a properly prepared dose of Menveo to the same patient, and asked CDC if this practice was safe. This question prompted CDC to search the Vaccine Adverse Event Reporting System (VAERS) database for reports during March 1, 2010-September 22, 2015, of only one component of Menveo being administered. Additionally, to more broadly identify disproportional reporting of adverse events in general following Menveo immunization compared with other vaccines in VAERS (including errors in vaccine preparation and administration), the Food and Drug Administration performed data mining with empiric Bayesian methods (4).

Deaths following vaccination: What does the evidence show?

Vaccines are rigorously tested and monitored and are among the safest medical products we use. Millions of vaccinations are given to children and adults in the United States each year. Serious adverse reactions are rare. However, because of the high volume of use, coincidental adverse events including deaths, that are temporally associated with vaccination, do occur. When death occurs shortly following vaccination, loved ones and others might naturally question whether it was related to vaccination. A large body of evidence supports the safety of vaccines, and multiple studies and scientific reviews have found no association between vaccination and deaths except in rare cases. During the US multi-state measles outbreak of 2014-2015, unsubstantiated claims of deaths caused by measles, mumps, and rubella (MMR) vaccine began circulating on the Internet, prompting responses by public health officials to address common misinterpretations and misuses of vaccine safety surveillance data, particularly around spontaneous reports submitted to the US Vaccine Adverse Event Reporting System (VAERS). We summarize epidemiologic data on deaths following vaccination, including examples where reasonable scientific evidence exists to support that vaccination caused or contributed to deaths. Rare cases where a known or plausible theoretical risk of death following vaccination exists include anaphylaxis, vaccine-strain systemic infection after administration of live vaccines to severely immunocompromised persons, intussusception after rotavirus vaccine, Guillain-Barré syndrome after inactivated influenza vaccine, fall-related injuries associated with syncope after vaccination, yellow fever vaccine-associated viscerotropic disease or associated neurologic disease, serious complications from smallpox vaccine including eczema vaccinatum, progressive vaccinia, postvaccinal encephalitis, myocarditis, and dilated cardiomyopathy, and vaccine-associated paralytic poliomyelitis from oral poliovirus vaccine. However, making general assumptions and drawing conclusions about vaccinations causing deaths based on spontaneous reports to VAERS - some of which might be anecdotal or second-hand - or from case reports in the media, is not a scientifically valid practice.

Vaccination errors reported to the Vaccine Adverse Event Reporting System, (VAERS) United States, 2000-2013.

IMPORTANCE: Vaccination errors are preventable events. Errors can have impacts including inadequate immunological protection, possible injury, cost, inconvenience, and reduced confidence in the healthcare delivery system. OBJECTIVES: To describe vaccination error reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and identify opportunities for prevention. METHODS: We conducted descriptive analyses using data from VAERS, the U.S. spontaneous surveillance system for adverse events following immunization. The VAERS database was searched from 2000 through 2013 for U.S. reports describing vaccination errors and reports were categorized into 11 error groups. We analyzed numbers and types of vaccination error reports, vaccines involved, reporting trends over time, and descriptions of errors for selected reports. RESULTS: We identified 20,585 vaccination error reports documenting 21,843 errors. Annual reports increased from 10 in 2000 to 4324 in 2013. The most common error group was "Inappropriate Schedule" (5947; 27%); human papillomavirus (quadrivalent) (1516) and rotavirus (880) vaccines were most frequently involved. "Storage and Dispensing" errors (4983; 23%) included mostly expired vaccine administered (2746) and incorrect storage of vaccine (2202). "Wrong Vaccine Administered" errors (3372; 15%) included mix-ups between vaccines with similar antigens such as varicella/herpes zoster (shingles), DTaP/Tdap, and pneumococcal conjugate/polysaccharide. For error reports with an adverse health event (5204; 25% of total), 92% were classified as non-serious. We also identified 936 vaccination error clusters (i.e., same error, multiple patients, in a common setting) involving over 6141 patients. The most common error in clusters was incorrect storage of vaccine (582 clusters and more than 1715 patients). CONCLUSIONS: Vaccination error reports to VAERS have increased substantially. Contributing factors might include changes in reporting practices, increasing complexity of the immunization schedule, availability of products with similar sounding names or acronyms, and increased attention to storage and temperature lapses. Prevention strategies should be considered.

Adverse events following vaccination with an inactivated, Vero cell culture-derived Japanese encephalitis vaccine in the United States, 2009-2012.

BACKGROUND: In March 2009, the U.S. Food and Drug Administration licensed an inactivated, Vero cell culture-derived Japanese encephalitis vaccine (JE-VC [Ixiaro]) for use in adults. The vaccine was licensed based on clinical trial safety data in 3558 JE-VC recipients. It is essential to monitor post-licensure surveillance data to evaluate the safety of JE-VC because rare adverse events may not be detected until the vaccine is administered to a larger population. METHODS: We reviewed adverse events reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) for adults (≥17 years) who received JE-VC from May 2009 through April 2012. Adverse event reporting rates were calculated using 275,848 JE-VC doses distributed. RESULTS: Over the 3 year period, 42 adverse events following vaccination with JE-VC were reported to VAERS for an overall reporting rate of 15.2 adverse events per 100,000 doses distributed. Of the 42 total reports, 5 (12%) were classified as serious for a reporting rate of 1.8 per 100,000 doses distributed; there were no deaths. Hypersensitivity reactions (N=12) were the most commonly reported type of adverse event, with a rate of 4.4 per 100,000 doses distributed; no cases of anaphylaxis were reported. Three adverse events of the central nervous system were reported (one case of encephalitis and two seizures) for a rate of 1.1 per 100,000; all occurred after receipt of JE-VC with other vaccines. CONCLUSIONS: These post-marketing surveillance data suggest a good safety profile for JE-VC consistent with findings from pre-licensure clinical trials. Post-licensure safety data should continue to be monitored for any evidence of rare serious or neurologic adverse events.

Notes from the field: rotavirus vaccine administration errors--United States, 2006-2013.

Two live rotavirus oral vaccines, RotaTeq (RV5) (Merck & Co., Inc.) and Rotarix (RV1) (GlaxoSmithKline Biologicals), are approved for prevention of rotavirus gastroenteritis and recommended at ages 2, 4 (RV5/RV1), and 6 (RV5) months by the Advisory Committee on Immunization Practices. Because most childhood vaccines are injectable, vaccination providers might have less experience administering oral vaccines. To assess that hypothesis, CDC searched for reports to the Vaccine Adverse Event Reporting System (VAERS) of rotavirus vaccine administration errors involving injection and eye splashes in the United States during the period January 1, 2006-August 1, 2013. A total of 66 reports were found.

Adverse event reports following Japanese encephalitis vaccination in the United States, 1999-2009.

We reviewed adverse events following receipt of inactivated mouse brain-derived Japanese encephalitis (JE) vaccine reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 1999 to 2009. During this period, VAERS received 300 adverse event reports following JE vaccination (24 per 100,000 doses distributed); 106 (35%) were classified as hypersensitivity reactions (8.4 per 100,000 doses) and four (1%) were classified as neurologic events (0.3 per 100,000 doses). Twenty-three (8%) reports described serious adverse events (1.8 per 100,000 doses distributed). There were no reports of encephalitis, meningitis, or Guillain-Barré syndrome. As reported previously, hypersensitivity reactions were common among persons receiving inactivated mouse brain-derived JE vaccine.

Safety assessment of recalled Haemophilus influenzae type b (Hib) conjugate vaccines--United States, 2007-2008.

PURPOSE: On 13 December 2007, Merck & Co., Inc. voluntarily recalled 1.2 million doses of Haemophilus influenzae type b (Hib) vaccines that had been distributed since April 2007 for concerns regarding potential Bacillus cereus contamination. Enhanced postrecall surveillance was conducted to detect vaccine-associated B. cereus infections. METHODS: We reviewed reports involving recalled Hib vaccines received by the Vaccine Adverse Event Reporting System (VAERS) during 1 April 2007-29 February 2008. For each reported death, autopsy review sought evidence of B. cereus infections. For each specified outcome, the proportional reporting ratios (PRRs) were calculated to compare the recalled Hib vaccines with the manufacturer's nonrecalled Hib vaccines in the VAERS databases. On 20 December 2007, we used the Epidemic Information Exchange (Epi-X) to solicit nongastrointestinal vaccine-associated B. cereus infections, and requested B. cereus isolates for genotyping to compare with the manufacturing facility isolate. RESULTS: VAERS received 75 reports involving recalled Hib vaccines; none described a confirmed B. cereus infection. Comparative analyses did not reveal disproportionate reporting of specified outcomes for recalled Hib vaccines. The Epi-X posting triggered one report of vaccine-associated B. cereus bacteremia from a child who received a nonrecalled Hib vaccine manufactured by Merck; the genotypes of isolates from the patient and the manufacturing facility differed. CONCLUSIONS: No evidence of vaccine-associated B. cereus infection had been found in recipients of recalled Hib vaccines. Conducting laboratory surveillance through Epi-X was feasible and may enhance public health response capacities for future vaccine safety emergencies.

Serum sickness-like reaction associated with inactivated influenza vaccination among Thai health care personnel: risk factors and outcomes.

Fourteen (3%) of 495 Thai health care personnel were identified as having a serum sickness-like reaction in 2008 after receipt of inactivated influenza vaccine manufactured in Thailand. These health care personnel experienced fever, myalgia, centrifugal arthralgias, and injection site erythema. A history of allergic reactions to food or drugs (adjusted odds ratio, 5.9; 95% confidence interval, 1.54-25.4) was independently associated with a serum sickness-like reaction.

Adverse event reports following yellow fever vaccination.

Yellow fever (YF) vaccine has been used for prevention of YF since 1937 with over 500 million doses administered. However, rare reports of severe adverse events following vaccination have raised concerns about the vaccine's safety. We reviewed reports of adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2000 to 2006. We used estimates of age and sex distribution of administered doses obtained from a 2006 survey of authorized vaccine providers to calculate age- and sex-specific reporting rates of all serious adverse events (SAE), anaphylaxis, YF vaccine-associated neurotropic disease, and YF vaccine-associated viscerotropic disease. Reporting rates of SAEs were substantially higher in males and in persons aged > or =60 years. These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of physician and traveler education regarding the risks and benefits of YF vaccination, particularly for travelers > or =60 years of age. Vaccination should be limited to persons traveling to areas where the risk of YF is expected to exceed the risk of serious adverse events after vaccination, or if not medically contraindicated, where national regulations require proof of vaccination to prevent introduction of YF.