Gina T. Mootrey

An overview of the vaccine adverse event reporting system (VAERS) as a surveillance system

We evaluated the Vaccine Adverse Event Reporting System (VAERS), the spontaneous reporting system for vaccine-associated adverse events in the United States, as a public health surveillance system, using evaluation guidelines from the Centers for Disease Control and Prevention. We found that VAERS is simple for reporters to use, flexible by design and its data are available in a timely fashion. The predictive value positive for one severe event is known to be high, but for most events is unknown. The acceptability, sensitivity and representativeness of VAERS are unknown. The study of vaccine safety is complicated by underreporting, erroneous reporting, frequent multiple exposures and multiple outcomes.

Anaphylaxis from yellow fever vaccine

BACKGROUND There are very few reports of anaphylactic reactions to yellow fever (YF) vaccine in the literature, and these date from the 1940s. OBJECTIVE We sought to estimate the rate of YF vaccine-related anaphylaxis. METHODS All reports of adverse reactions to YF vaccine submitted to the Vaccine Adverse Event Reporting System between 1990 and 1997 were reviewed for those meeting criteria for probable or possible anaphylactic reactions. RESULTS Of 243 reports submitted, 40 describe probable or possible anaphylactic reactions. In 22 of these 40, YF vaccine was the only vaccine administered. There were 5,236,820 doses of YF vaccine distributed in the United States during this period. By using all 40 cases, the rate of YF vaccine-related anaphylaxis would be 40 in 5, 236,820 or about 1 in 131,000. In 35 of the reports, information was provided on whether previous doses of YF vaccine had been given. In 34 of these 35, the reaction occurred after the first dose of YF vaccine, suggesting that vaccine constituents other than the viral proteins may have been the allergens. The vaccine is grown in chicken embryos and contains gelatin as a stabilizer. CONCLUSION YF vaccine can cause anaphylactic reactions. Persons presenting for YF vaccine should be asked if they have had adverse reactions to previous doses of this or other vaccines and if they are allergic to eggs, chicken, or gelatin. Health care workers administering YF vaccine should be prepared to recognize and treat anaphylactic reactions should they occur.

Adverse event reports following vaccination for Lyme disease: December 1998–July 2000

CONTEXT The vaccine adverse event reporting system (VAERS) monitors vaccine safety post-licensure. Although events reported to VAERS are not necessarily causally associated with vaccination, VAERS reports can be used to identify possible safety concerns that occur at too low a rate to have been identified prior to licensure. OBJECTIVE To evaluate adverse events following Lyme disease vaccination reported to VAERS during the first 19 months of the vaccines licensure. DESIGN, SETTING, AND PARTICIPANTS Analysis of all VAERS reports of adverse events following vaccination for Lyme disease in the US from 28 December 1998 to 31 July 2000. MAIN OUTCOME MEASURE We evaluated reported adverse events for unexpected patterns in age, gender, time to onset, dose number, and clinical characteristics and compared them to adverse events observed in clinical trials of this vaccine. RESULTS Over 1,400,000 doses were distributed and 905 adverse events were reported to VAERS, 440 in men and 404 in women, with ages ranging from 10 to 82 years. The majority (56%) of adverse events occurred after administration of the first dose. The most frequently reported adverse events were arthralgia (250), myalgia (195), and pain (157). There were 59 reports coded as arthritis, 34 as arthrosis, 9 as rheumatoid arthritis, and 12 as facial paralysis. Sixty-six (7.4%) events were classified as serious, involving life-threatening illness, hospitalization, prolongation of hospitalization, persistent or significant disability/incapacity, or death. Twenty-two hypersensitivity reactions were reported. CONCLUSION Based on reporting to VAERS, we did not detect unexpected or unusual patterns of reported adverse events following Lyme disease vaccine administration, other than hypersensitivity reactions, compared with adverse events observed in clinical trials.

Infant Immunization With Acellular Pertussis Vaccines in the United States: Assessment of the First Two Years' Data From the Vaccine Adverse Event Reporting System (VAERS)

Objective. To evaluate the safety of infant immunization with acellular pertussis vaccines in the United States. Background. The US Food and Drug Administration approved the first acellular pertussis vaccine for use in infants in the United States on July 31, 1996. Outcome Measures. Adverse events in the United States after infant immunization with pertussis-containing vaccines, representing temporal (but not necessarily causal) associations between vaccinations and adverse events. Data Source. Reports to the Vaccine Adverse Event Reporting System (VAERS), a passive national surveillance system. Design. Reports concerning infant immunization against pertussis between January 1, 1995 (when whole-cell vaccine was in exclusive use) and June 30, 1998 (when acellular vaccine was in predominant use) were analyzed, if the reports were entered into the VAERS database by November 30, 1998. Results. During the study, there were 285 reports involving death, 971 nonfatal serious reports, and 4514 less serious reports after immunization with any pertussis-containing vaccine. For 1995 there were 2071 reports; in 1996 there were 1894 reports; in 1997 there were 1314 reports, and in the first half of 1998 there were 491 reports. Diphtheria-tetanus-pertussis vaccine (DTP) was cited in 1939 reports, diphtheria–tetanus–whole-cell pertussis–Haemophilus influenzae type b vaccine (DTPH) in 2918 reports, and diphtheria-tetanus-acellular pertussis vaccine (DTaP) in 913 reports. The annual number of deaths during the study was 85 in 1995, 82 in 1996, 77 in 1997, and 41 in the first half of 1998. The annual number of reported events categorized as nonfatal serious (defined as events involving initial hospitalization, prolongation of hospitalization, life-threatening illness, or permanent disability) to VAERS for all pertussis-containing vaccines declined: 334 in 1995, 311 in 1996, 233 in 1997, and 93 in the first half of 1998. Similarly, the annual number of less serious reports to VAERS for pertussis-containing vaccines declined: 1652 in 1995, 1501 in 1996, 1004 in 1997, and 357 in the first half of 1998. A comparison of the adverse event profiles (proportional distributions) for DTaP, DTP, and DTPH, as well as an analysis of specific adverse events considered in a 1991 Institute of Medicine report on the safety of diphtheria-tetanus-pertussis vaccine, did not identify any new, clear safety concerns. Conclusions. These findings reflect the administration of millions of doses of acellular pertussis vaccine and are reassuring with regard to the safety of marketed acellular pertussis vaccines. VAERS data, although subject to the limitations of passive surveillance, support the prelicensure data with regard to the safety of the US-licensed acellular pertussis vaccines that we evaluated.

Challenges and controversies in immunization safety.

No vaccine is perfectly safe or effective. As diseases such as diphtheria and polio fade, vaccine safety concerns, especially alleged links between vaccinations and several chronic illnesses, have become increasingly prominent in the media and to the public. This article reviews the current scientific evidence on several recent vaccine safety controversies. It also provides information on how various safety research is conducted, some of the concurrent challenges, and finally, some guidance on communicating with patients on vaccine risks.

Recommended adult immunization schedule: United States, October 2007-September 2008

The Advisory Committee on Immunization Practices (ACIP) annually reviews the recommended Adult Immunization Schedule to ensure that the schedule reflects current recommendations for the licensed vaccines. In June 2007, ACIP approved the Adult Immunization Schedule for October 2007September 2008. This schedule has also been approved by the American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and American College of Physicians. Changes in the Schedule for October 2007September 2008 The 20072008 schedule differs from the previous schedule as follows: The yellow bar for varicella has been extended through all age groups on the age-based schedule (Figure top), indicating that varicella vaccine is recommended for all adults without evidence of immunity to varicella. Figure. Recommended Adult Immunization Schedule: United States, October 2007September 2008. 1. Tetanus, diphtheria, and acellular pertussis (Td/Tdap) vaccination Tdap should replace a single dose of Td for adults age <65 years who have not previously received a dose of Tdap (either in the primary series, as a booster, or for wound management). Only 1 of 2 Tdap products (Adacel, Sanofi Pasteur) is licensed for use in adults. Adults with uncertain histories of a complete primary vaccination series with diphtheria and tetanus toxoidcontaining vaccines should begin or complete a primary vaccination series. A primary series for adults is 3 doses: administer the first 2 doses at least 4 weeks apart and the third dose 6 to 12 months after the second dose. Administer a booster dose to adults who have completed a primary series and if the last vaccination was received 10 years previously. Tdap or Td vaccine may be used, as indicated. If the person is pregnant and received the last Td vaccination 10 years previously, administer Td during the second or third trimester; if the person received the last Td vaccination in <10 years, administer Tdap during the immediate postpartum period. A 1-time administration of 1 dose of Tdap with an interval as short as 2 years from a previous Td vaccination is recommended for postpartum women, close contacts of infants age <12 months, and all health care workers with direct patient contact. In certain situations, Td can be deferred during pregnancy and Tdap substituted in the immediate postpartum period, or Tdap can be given instead of Td to a pregnant woman after an informed discussion with the woman. Consult the ACIP statement for recommendations for administering Td as prophylaxis in wound management. 2. Human papillomavirus (HPV) vaccination Human papillomavirus vaccination is recommended for all women age 26 years who have not completed the vaccine series. History of genital warts, abnormal Papanicolaou test, or postive HPV DNA test is not evidence of prior infection with all vaccine HPV types; HPV vaccination is still recommended for these women. Ideally, vaccine should be administered before potential exposure to HPV through sexual activity; however, women who are sexually active should still be vaccinated. Sexually active women who have not been infected with any of the HPV vaccine types receive the full benefit of the vaccination. Vaccination is less beneficial for women who have already been infected with 1 or more of the HPV vaccine types. A complete series consists of 3 doses. The second dose should be administered 2 months after the first dose; the third dose should be administered 6 months after the first dose. Although HPV vaccination is not specifically recommended for females with the medical indications described in Figure (bottom), it can be administered because it is not a live-virus vaccine. However, immune response and vaccine efficacy might be less than that in persons who do not have the medical indications described or who are immunocompetent. 3. Measles, mumps, rubella (MMR) vaccination Measles component: Adults born before 1957 can be considered immune to measles. Adults born during or after 1957 should receive 1 dose of MMR unless they have a medical contraindication, documentation of 1 dose, history of measles based on health care provider diagnosis, or laboratory evidence of immunity. A second dose of MMR is recommended for adults who 1) have been recently exposed to measles or in an outbreak setting; 2) have been previously vaccinated with killed measles vaccine; 3) have been vaccinated with an unknown type of measles vaccine during 19631967; 4) are students in postsecondary educational institutions; 5) work in a health care facility; or 6) plan to travel internationally. Mumps component: Adults born before 1957 can generally be considered immune to mumps. Adults born during or after 1957 should receive 1 dose of MMR unless they have a medical contraindication, history of mumps based on health care provider diagnosis, or laboratory evidence of immunity. A second dose of MMR is recommended for adults who 1) are in an age group that is affected during a mumps outbreak; 2) are students in postsecondary educational institutions; 3) work in a health care facility; or 4) plan to travel internationally. For unvaccinated health care workers born before 1957 who do not have other evidence of mumps immunity, consider giving 1 dose on a routine basis and strongly consider giving a second dose during an outbreak. Rubella component: Administer 1 dose of MMR vaccine to women whose rubella vaccination history is unreliable or who lack laboratory evidence of immunity. For women of childbearing age, regardless of birth year, routinely determine rubella immunity and counsel women regarding congenital rubella syndrome. Women who do not have evidence of immunity should receive MMR vaccine upon completion or termination of pregnancy and before discharge from the health care facility. 4. Varicella vaccination All adults without evidence of immunity to varicella should receive 2 doses of single-antigen varicella vaccine unless they have a medical contraindication. Special consideration should be given to those who 1) have close contact with persons at high risk for severe disease (e.g., health care personnel and family contacts of immunocompromised persons) or 2) are at high risk for exposure or transmission (e.g., teachers; child care employees; residents and staff members of institutional settings, including correctional institutions; college students; military personnel; adolescents and adults living in households with children; nonpregnant women of childbearing age; and international travelers). Evidence of immunity to varicella in adults includes any of the following: 1) documentation of 2 doses of varicella vaccine at least 4 weeks apart; 2) U.S.-born before 1980 (although for health care personnel and pregnant women, birth before 1980 should not be considered evidence of immunity); 3) history of varicella based on diagnosis or verification of varicella by a health care provider (for a patient reporting a history of or presenting with an atypical case, a mild case, or both, health care providers should seek either an epidemiologic link with a typical varicella case or to a laboratory confirmed case or evidence of laboratory confirmation, if it was performed at the time of acute disease); 4) history of herpes zoster based on health care provider diagnosis; or 5) laboratory evidence of immunity or laboratory confirmation of disease. Assess pregnant women for evidence of varicella immunity. Women who do not have evidence of immunity should receive dose 1 of varicella vaccine upon completion or termination of pregnancy and before discharge from the health care facility. The second dose should be administered 4 to 8 weeks after the first dose. 5. Influenza vaccination Medical indications: Chronic disorders of the cardiovascular or pulmonary systems, including asthma; chronic metabolic diseases, including diabetes mellitus; renal or hepatic dysfunction; hemoglobinopathies; immunosuppression (including immunosuppression caused by medications or HIV); any condition that compromises respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration (e.g., cognitive dysfunction, spinal cord injury, or seizure disorder or other neuromuscular disorder); and pregnancy during the influenza season. No data exist on the risk for severe or complicated influenza disease among persons with asplenia; however, influenza is a risk factor for secondary bacterial infections that can cause severe disease among persons with asplenia. Occupational indications: Health care personnel and employees of long-term care and assisted living facilities. Other indications: Residents of nursing homes and other long-term care and assisted living facilities; persons likely to transmit influenza to persons at high risk (e.g., in-home household contacts and caregivers of children age 0 to 59 months, or persons of all ages with high-risk conditions); and anyone who would like to be vaccinated. Healthy, nonpregnant adults age 49 years without high-risk medical conditions who are not contacts of severely immunocompromised persons in special care units can receive either intranasally administered influenza vaccine (FluMist, MedImmune Vaccines, Gaithersburg, Maryland) or inactivated vaccine. Other persons should receive the inactivated vaccine. 6. Pneumococcal polysaccharide vaccination Medical indications: Chronic pulmonary disease (excluding asthma); chronic cardiovascular diseases; diabetes mellitus; chronic liver diseases, including liver disease as a result of alcohol abuse (e.g., cirrhosis); chronic alcoholism, chronic renal failure, or nephrotic syndrome; functional or anatomic asplenia (e.g., sickle cell disease or splenectomy [if elective splenectomy is planned, vaccinate at least 2 weeks before surgery]); immunosuppressive conditions; and cochlear implants and cerebrospinal fluid leaks. Vaccinate as close to HIV diagnosis as possible. Other indications: Alaska Natives and c

Myocarditis, Pericarditis, and Dilated Cardiomyopathy after Smallpox Vaccination among Civilians in the United States, January-October 2003

Myocarditis was reported after smallpox vaccination in Europe and Australia, but no association had been reported with the US vaccine. We conducted surveillance to describe and determine the frequency of myocarditis and/or pericarditis (myo/pericarditis) among civilians vaccinated during the US smallpox vaccination program between January and October 2003. We developed surveillance case definitions for myocarditis, pericarditis, and dilated cardiomyopathy after smallpox vaccination. We identified 21 myo/pericarditis cases among 37,901 vaccinees (5.5 per 10,000); 18 (86%) were revacinees, 14 (67%) were women, and the median age was 48 years (range, 25-70 years). The median time from vaccination to onset of symptoms was 11 days (range, 2-42 days). Myo/pericarditis severity was mild, with no fatalities, although 9 patients (43%) were hospitalized. Three additional vaccinees were found to have dilated cardiomyopathy, recognized within 3 months after vaccination. We describe an association between smallpox vaccination, using the US vaccinia strain, and myo/pericarditis among civilians.

Student vaccination requirements of U.S. health professional schools: a survey.

BACKGROUND Unvaccinated health care personnel are at increased risk for transmitting vaccine-preventable diseases to their patients. The Advisory Committee on Immunization Practices (ACIP) recommends that health care personnel, including students, receive measles, mumps, rubella, hepatitis B, varicella, influenza, and pertussis vaccines. Prematriculation vaccination requirements of health professional schools represent an early opportunity to ensure that health care personnel receive recommended vaccines. OBJECTIVE To examine prematriculation vaccination requirements and related policies at selected health professional schools in the United States and compare requirements with current ACIP recommendations. DESIGN Cross-sectional study using an Internet-based survey. SETTING Medical and baccalaureate nursing schools in the United States and its territories. PARTICIPANTS Deans of accredited medical schools granting MD (n = 130) and DO (n = 26) degrees and of baccalaureate nursing programs (n = 603). MEASUREMENTS Proportion of MD-granting and DO-granting schools and baccalaureate nursing programs that require that entering students receive vaccines recommended by the ACIP for health care personnel. RESULTS 563 schools (75%) responded. More than 90% of all school types required measles, mumps, rubella, and hepatitis B vaccines for entering students; varicella vaccination also was commonly required. Tetanus, diphtheria, and acellular pertussis vaccination was required by 66%, 70%, and 75% of nursing, MD-granting, and DO-granting schools, respectively. Nursing and DO-granting schools (31% and 45%, respectively) were less likely than MD-granting schools (78%) to offer students influenza vaccines free of charge. LIMITATIONS Estimates were conservative, because schools that reported that they did not require proof of immunity for a given vaccine were considered not to require that vaccine. Estimates also were restricted to schools that train physicians and nurses. CONCLUSION The majority of schools now require most ACIP-recommended vaccines for students. Medical and nursing schools should adopt policies on student vaccination and serologic testing that conform to ACIP recommendations and should encourage annual influenza vaccination by offering influenza vaccination to students at no cost. PRIMARY FUNDING SOURCE None.

Safety of Routine Childhood Vaccinations An Epidemiological Review

Immunisations have been one of the most cost-effective public health interventions in human history. Despite remarkable progress, several challenges face immunisation programs worldwide. Paradoxically, despite vaccines’ clear effectiveness in reducing risks of diseases that were previously widely prevalent and caused substantial morbidity and mortality, current vaccination policies have become increasingly controversial due to concerns about vaccine safety.Vaccines, like other pharmaceutical products, are not entirely risk-free. While most known adverse effects are minor and self-limited, some vaccines have been associated with very rare but serious adverse effects. Because such rare effects are often not evident until vaccines come into widespread use, ongoing surveillance programs to monitor vaccine safety are needed. Such monitoring will be essential if the public is to accept the increasing number of new vaccines made possible by biotechnology. The interpretation of data from vaccine safety research is complex and is associated with some uncertainty. Effectively communicating this uncertainty and continuing to improve understanding of rare risks and risk factors are essential for “mature” immunisation programs to maintain public confidence in immunisations.

Adverse event reporting rates following tetanus–diphtheria and tetanus toxoid vaccinations: data from the Vaccine Adverse Event Reporting System (VAERS), 1991–1997

Since 1966, the Advisory Committee on Immunization Practices (ACIP) has recommended tetanus-diphtheria toxoid (Td) be used instead of single antigen tetanus toxoid (TT) because, while both vaccines protect against tetanus, only Td protects against diphtheria. Despite this recommendation, approximately 2.5 million doses of TT were distributed annually from 1991 to 1997. One possible explanation for the continued use of TT is concern about the relative safety of Td. Small clinical trials found Td to be associated with a higher rate of local vaccine-associated adverse events (VAEs) than TT. To determine if the findings from the trials would hold up on a larger scale, we compared the rate of reporting to the Vaccine Adverse Event Reporting System (VAERS), a passive reporting system, after either vaccine from 1991 to 1997. There were 40 reports per million doses of Td, and 27 reports per million doses of TT, for a reporting rate ratio of 1.4. Reporting rates to VAERS are lower than the rates of VAEs identified in the clinical trials, but the magnitude of the difference in VAEs following TT versus Td is similar. While reporting rates are lower after TT than Td, rates of reported VAEs after both vaccines are low.