National Academies Press: OpenBook
« Previous: 9 Haemophilus influenzae Type b Vaccines
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

10
Death

The Vaccine Safety Committee was charged with assessing a causal relation between all of the vaccines that it reviewed and death. The myriad possible causes of death made this a difficult task. To facilitate review of this serious adverse event, the committee used a categorization scheme, which is discussed below. Because the vast majority of reports of death following vaccination reside in passive surveillance systems, the committee used the scheme to analyze data from a currently operating one, the Vaccine Adverse Event Reporting System (VAERS). A description of the system is included in this chapter, and the results of this analysis are also discussed. All evidence reviewed by the committee (published literature and reports from the passive surveillance systems of the Centers for Disease Control and Prevention [CDC] and U.S. Food and Drug Administration [FDA]) regarding deaths in association with immunization is discussed later in this chapter.

To answer the question "Can any deaths be attributed to the use of the vaccines discussed in this review?," the committee categorized reports of death following immunization into seven categories:

  • deaths for which the available data were insufficient to allow a judgment of cause;

  • deaths associated with vaccine administration but attributable to inappropriate handling, contamination, production error, or error of medical care;

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
  • deaths temporally associated with vaccine administration but clearly caused by something other than the vaccine;

  • deaths classified as sudden infant death syndrome (SIDS);

  • deaths that are a consequence of vaccine-strain viral infection (applies to measles, mumps, or oral polio vaccine [OPV] for this report);

  • deaths that are a consequence of an adverse event that itself is causally related to a vaccine reviewed in this report; and

  • deaths temporally associated with vaccine administration and the cause of death is other than those listed above.

EXAMPLES

Deaths for Which the Available Data Were Insufficient to Allow a Judgment of Cause

The reports from passive surveillance systems accessed by the committee vary in the quantity and quality of the information that they contain. Many of the reports contained phrases such as "died" or "found dead at baby-sitter's." Reports with more information frequently had no additional documentation submitted with them, so assessment of the diagnosis was not possible. The information in VAERS is discussed below in great detail. The published literature contains reports of deaths following immunization that lack sufficient information for a causality assessment as well. This is most common in uncontrolled observational studies intended to give a broad picture of the results of immunization campaigns.

Deaths Associated With Vaccine Administration but Attributable to Inappropriate Handling, Contamination, Production Error, or Error of Medical Care

This category includes a wide range of contamination or handling problems; vaccines, like any other pharmaceutical agent, are subject to mishandling that might, in extreme cases, lead to death. The Cutter incident is a well-known example of vaccine contamination caused by errors in quality control by the manufacturer and lack of clear guidelines from a regulatory agency; 60 vaccine recipients and 89 contacts of recipients contracted polio as a result of contamination of two production pools of inactivated polio vaccine (IPV) with live virus in 1955 (Nathanson and Langmuir, 1963). Contamination can occur at a more local level. Sokhey (1991) reported several deaths following administration of measles vaccine in India. The report lists the cause of death as "toxic shock syndrome" and notes that contamination was likely because syringes and needles were reused and the sterilization procedures were unsatisfactory. Staphylococcus aureus was

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

isolated from a few available implicated vials. That report is discussed later in this chapter.

Deaths Temporally Associated with Vaccine Administration but Clearly Caused by Something Other Than the Vaccine

Passive surveillance systems contain many reports that fall into this category. Reports to the manufacturer or to the government regarding the death of a vaccine recipient in temporal relation to vaccination can be made before a cause of death is established. Once an autopsy is performed, it is sometimes clear that the death was temporally but not causally related to vaccination. An example of such a death is one that was reported to VAERS. This report describes the death of a 5-year-old 10 days after receipt of diphtheria and tetanus toxoids and pertussis vaccine (DPT), OPV, and measles-mumps-rubella vaccine (MMR). The cause of death was Haemophilus influenzae type b meningitis, which did not appear to be vaccine related.

Deaths Classified as SIDS

For many years, the standard immunization schedule in the first year of life (the period in which most cases of SIDS occur) included only DPT and polio vaccine. Use of hepatitis B and H. influenzae type b vaccines during the first year of life is increasing rapidly. Although the scientific question of interest is, "Does vaccination increase an infant's probability of dying of SIDS," the research has focused on the role of DPT, even though polio vaccine is often given with DPT. The previous Institute of Medicine report on rubella and pertussis vaccines (Institute of Medicine, 1991) concluded that the evidence favors rejection of a causal relation between DPT and SIDS. "Studies showing a temporal relation between these events are consistent with the expected occurrence of SIDS over the age range in which DPT immunization typically occurs" (Institute of Medicine, 1991, p. 141). A few studies that primarily investigated the role of DPT in SIDS also examined the role of polio vaccine (Bouvier-Colle et al., 1989; Hoffman et al., 1987; Taylor and Emery, 1982; Walker et al., 1987). Only Hoffman and colleagues (1987) report odds ratio estimates of the relative risk of a SIDS case infant being immunized with OPV (0.57 for age-matched controls and 0.61 for age-, race-, and low-birth-weight-matched controls). These odds ratios were very similar to those obtained for the relative risk from DPT immunization. The committee's evaluation of the causal relation between diphtheria and tetanus toxoids for pediatric use (DT) and SIDS is discussed later in this chapter.

Passive surveillance systems such as the Monitoring System for Adverse Events Following Immunization (MSAEFI) and VAERS contain many

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

reports of SIDS that occurred within 24 or 48 hours following vaccination, but these case reports often contain inadequate information to substantiate the diagnosis, and they are not necessarily evidence of a causal relation, because cases will occur in the 24- to 48-hour period following vaccination by chance alone. The licensure and recommendations for administration in the first year of life of vaccines to prevent hepatitis B and H. influenzae type b infections would suggest that studies of a possible role of vaccines in SIDS will continue. There are no controlled studies of a relation between either of these two newer vaccines and SIDS. MMR is customarily given after the first year of life in the United States; therefore, a relation between MMR and SIDS has not been investigated.

Deaths That Are a Consequence of Vaccine-Strain Vital Infection

Measles and mumps vaccines and OPV are made up of live attenuated viruses. It is plausible that administration of a live viral vaccine could cause a systemic infection in the recipient that could, in certain circumstances, be fatal. The committee identified a few such reports; they are discussed later in this chapter.

Deaths That Are a Consequence of an Adverse Event That Itself Is Causally Related to a Vaccine Reviewed in This Report

Several of the adverse events studied by the committee can lead to death. If the adverse event was caused by the vaccine and led to death, then one may say that the vaccine caused the death. An example would be a patient who suffers fatal anaphylaxis associated with vaccine administration.

If the evidence favors the acceptance of (or establishes) a causal relation between a vaccine and an adverse event and that adverse event can be fatal, then in the committee's judgment the evidence favors the acceptance of (or establishes) a causal relation between the vaccine and death from that adverse event. The case fatality rate for adverse events associated with vaccines (other than, possibly, the live viral vaccines) should not be different from that for adverse events associated with all other causes. For example, anaphylaxis caused by a vaccine should be no more or less likely to result in death than anaphylaxis precipitated by any other antigen. It is plausible, however, that some adverse events caused by an attenuated viral vaccine might be milder than that same adverse event caused by the wild-type virus. In later sections of this chapter, the committee discusses the data regarding death from adverse events that are causally related to vaccines. If the evidence is inadequate to accept or reject a causal relation between a vaccine and an adverse event, then in the committee's judgment

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

the evidence is inadequate to accept or reject a causal relation between the vaccine and death resulting from that adverse event.

Deaths Temporally Associated with Vaccine Administration and the Cause of Death Is Other Than Those Listed above

The committee explored the possibility that vaccines may cause death by mechanisms other than vaccine-strain viral infection or an adverse event that itself is causally related to vaccine administration. The committee considered whether it might have overlooked possible vaccine-related mechanisms or pathways that could lead to death. The committee was unable to hypothesize such causes. However, had the committee identified reports of death following vaccination that did not fall into any of the other six categories, de facto those reports would have been placed into this category and causality would have been assessed for those reports. The committee found no reports of death that could be placed in this category, either in theory or by exclusion from the other causes listed above.

REPORTS OF DEATH IDENTIFIED FROM VAERS

The preponderance of data concerning death as an adverse consequence of vaccination comes from passive surveillance systems. The committee made a concerted effort to evaluate these data. The number of reports in VAERS of death in temporal association with vaccination has been the topic of presentations to the Advisory Commission on Childhood Vaccines (ACCV), the Advisory Committee on Immunization Practices, an FDA-sponsored workshop on contraindications to vaccination, a public session regarding changes to the Vaccine Injury Table, and the Vaccine Safety Committee of the Institute of Medicine. Because of this interest, because VAERS has a number of advantages over its predecessor data bases (the Spontaneous Reporting System [SRS], which was run by the FDA, and MSAEFI, which was run by the CDC), and because VAERS contains reports of reactions to hepatitis B vaccine (particularly in infants and children) and H. influenzae type b vaccine (which would be scarce in MSAEFI and SRS because of the recent licensure of these vaccines), the committee focused its investigations of reports to the U.S. government-run passive surveillance systems of death after vaccination on the information contained in VAERS. A description of VAERS and a discussion of its strengths and weaknesses will help in the analysis of the data that follow.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

History and Background

VAERS was established by the National Childhood Vaccine Injury Act of 1986 (P.L. 99-660) to collect reports of adverse reactions following vaccination. The database is managed by a contractor under the aegises of both the CDC and the FDA. Reporting forms are available in drugstores and elsewhere, and anyone may file a report. A blank form appears in Appendix B (Figure B-1). A toll-free phone number (800-822-7967) can be used instead of the form. Physicians and nurses may report an adverse event, as may the parents, relatives, or neighbors of a patient. Health care providers are obligated to report specific adverse reactions to vaccines covered by the National Vaccine Injury Compensation Program (see box entitled The Vaccine Injury Table; see Chapter 1 for more information on the compensation program); however, reports can be made regarding any reaction to any vaccine.

Several people may submit reports about one patient. The person reporting the adverse event may supply additional information, but no supporting information is required. The form asks for the following items: the patient's initials, age, and sex; the time of event onset; description of events; general assessment of condition (dead, hospitalized, disabled, etc.); relevant diagnostic tests or laboratory data; date of vaccination; and the vaccines that were given. Once submitted to the contractor, the data are entered into a computerized database. The narrative regarding the description of the adverse event is used to determine the index terms used to categorize the adverse reaction. Up to eight terms can be assigned to each report. The indexing system used is the Coding Symbol for Thesaurus of Adverse Reaction Terms (COSTART) system.

VAERS began operation in November 1990. By July 31, 1992, there were over 17,000 reports in VAERS, almost 11,000 of which concerned vaccines covered by the National Vaccine Injury Compensation Program. Of the total number of reports, just over 2,500 of them were considered to be "serious," which is defined as the following: the patient died, suffered a life-threatening illness, or suffered a reaction that resulted in, or prolonged, hospitalization or that resulted in permanent disability.

Strengths and Weaknesses

The ease and accessibility of the reporting system might be useful in allowing VAERS to cast a large net, bringing attention to any possible adverse event. The negative aspect of this open system is that data may be inaccurate, poorly documented, or incomplete and that records may be duplicated. Although VAERS may be useful as a monitor for detecting ad-

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

THE VACCINE INJURY TABLE

Vaccine/Toxoid

Event

Interval from Immunization

DPT, pertussis vaccine

A. Anaphylaxis or anaphylactic shock

24 hours

DPT/poliovirus combined

 

 

 

B. Encephalopathy (encephalitis)a

3 days

 

C. Shock-collapse or hypotonic-hyporesponsive collapseb

3 days

 

D. Residual seizure disorderc

3 days

 

E. Any acute complication or sequela (including death) of above event which arose within the time period prescribed

No limit

Measles, mumps, and rubella; DT, Td, tetanus toxoid

A. Anaphylaxis or anaphylactic shock

24 hours

 

B. Encephalopathy (or encephalitis)a

15 days for measles, mumps and rubella vaccines; 3 days for DT, Td and tetanus toxoids

 

C. Residual seizure disorderc

15 days for measles, mumps and rubella vaccines; 3 days for DT, Td and tetanus toxoids

 

D. Any acute complication or sequela (including death) of above event which arose within the time period prescribed

No limit

Oral poliovirus vaccine

A. Paralytic poliomyelitis

 

 

—in a nonimmunodeficient recipient

30 days

 

—in an immunodeficient recipient

6 months

 

—in a vaccine-associated community case

Not applicable

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

 

B. Any acute complication or sequela (including death) of above event which arose within the time period prescribed

No limit

Inactivated poliovirus vaccine

A. Anaphylaxis or anaphylactic shock

24 hours

 

B. Any acute complication or sequela (including death) of above event which arose within the time period prescribed

No limit

NOTE: Events listed are required by law to be reported by health care providers to the U.S. Department of Health and Human Services; however, VAERS will accept all reports of suspected adverse events after the administration of any vaccine. Aids to interpretation follow as footnotes.

a Encephalopathy means any substantial acquired abnormality of, injury to, or impairment of brain function. Among the frequent manifestations of encephalopathy are focal and diffuse neurologic signs, increased intracranial pressure, or changes lasting ≥6 hours in level of consciousness, with or without convulsions. The neurologic signs and symptoms of encephalopathy may be temporary with complete recovery, or they may result in various degrees of permanent impairment. Signs and symptoms such as high-pitched and unusual screaming, persistent uncontrollable crying, and bulging fontanel are compatible with an encephalopathy, but in and of themselves are not conclusive evidence of encephalopathy. Encephalopathy usually can be documented by slow wave activity on an electroencephalogram.

b Shock-collapse or hypotonic-hyporesponsive collapse may be evidenced by signs or symptoms such as decrease in or loss of muscle tone, paralysis (partial or complete), hemiplegia, hemiparesis, loss of color or change of color to pale white or blue, unresponsiveness to environmental stimuli, depression of or loss of consciousness, prolonged sleeping with difficulty arousing, or cardiovascular or respiratory arrest.

c Residual seizure disorder may be considered to have occurred if no other seizure or convulsion unaccompanied by fever or accompanied by a fever of <102ºF occurred before the first seizure or convulsion after the administration of the vaccine involved, AND, if in the case of measles-, mumps-, or rubella-containing vaccines, the first seizure or convulsion occurred within 15 days after vaccination OR in the case of any other vaccine, the first seizure or convulsion occurred within 3 days after the vaccination, AND, if two or more seizures or convulsions unaccompanied by fever or accompanied by a fever of <102ºF occurred within 1 year after vaccination. The terms seizure and convulsion include grand mal, petit mal, absence, myoclonic, tonic-clonic, and focal motor seizures and signs.

SOURCE: Adapted from Public Law 99-660.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

verse events, it is less useful for scientific analysis and assessments of causality (Chen et al., submitted for publication).

Two issues, data quality and record duplication, limit the usefulness of the VAERS data set for analysis. Under the category of data quality are the concerns of validity, documentation, and completeness of information. Because the forms can be submitted by medical and nonmedical personnel, there is bound to be variability in the quality (and availability) of information. Even among health care providers there can be great variation in the use of diagnostic terms. Although this variation in diagnosis may be random (and not biased by the reporter's concern about the contributory effect of the vaccine), death is such a serious outcome that one would like to have information that confirms or clarifies the VAERS reports. Linkage to hospital records, autopsy reports, laboratory files, and death certificates could help validate the information. Besides accurate data regarding the cause of death, one would wish to confirm the validity of key variables such as the age of the patient at the time of vaccination, type of vaccination, calendar date (and perhaps time of day) of vaccination, date of onset of adverse event, and date of death. These would be minimal data requirements for a preliminary analysis of the overall pattern of deaths following vaccination.

Table 10-1 illustrates some of the problems associated with VAERS reports. The committee assembled a table of 28 samples of VAERS reports of deaths. The sample was not necessarily random or representative, but examples were chosen to illustrate the problem of data quality. In the majority of cases, the cause of death was not stated, and there was no information to indicate whether an autopsy was performed. The VAERS data by themselves frequently do not supply enough information to allow informative data analysis.

Some VAERS reports contain enough reliable information that the report can be evaluated and weighed as one would a published case report. For example, one specific report was filed by a nurse, the cause of death was stated to be H. influenzae type b meningitis, and laboratory tests were performed. The death occurred 10 days following immunization with DPT, OPV, and MMR. Such VAERS reports were often very useful to the committee in its assessments of all adverse reactions reviewed, not just the reports of death.

Multiple reports relating to the same adverse event in a given patient are an obvious disadvantage of analyzing the VAERS database. Many duplicates can be found by going through the VAERS reports by hand, but one cannot be certain that all duplicate reports have been identified. Verification of data quality would probably help to eliminate more duplicate records.

There are other problematic aspects of VAERS, most notably, the problem of underreporting. The accessibility of VAERS should encourage re-

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

porting, but underreporting of events may still occur. The possible incompleteness of the data hampers any attempt to analyze the data. VAERS is a passive reporting system that could serve as a sentinel for as yet unsuspected adverse events that occur following immunization. If linked to other detailed and accurate information, such a surveillance system could be a database for scientific analysis.

Follow-up of Reports of Death to VAERS

The FDA followed up all reports of death following immunization submitted to VAERS during the time period July 1, 1990, to September 30, 1991 (R. P. Wise, FDA, presentation to the ACCV, December 1992). Of 235 reports, 29 were duplicates, leaving 206 unduplicated reports. The submitted data were considered to be adequate for 78 of those reports. Complete follow-up was achieved for an additional 81 reports. Thus, the number of reports with completed assessments was 159. Follow-up was done by FDA staff. Most queries were by telephone, and a few were by mail. There were 3.5 calls per clarified report and 2.5 completed calls per clarified report. The typical succession of calls was first to the reporting physician's office and then one or more referrals to the hospital medical records department, the coroner or medical examiner's office, and occasionally, the county recorder or state public health vaccination department.

As a result, for 159 VAERS reports the diagnosis was confirmed or clarified by the FDA. Before analyzing the reports, the committee excluded 17 VAERS reports because for 16 reports the deaths followed administration of a vaccine or vaccines not under consideration by the present committee and one report concerned a miscarriage, which the committee classified as an adverse event in temporal relation to vaccination experienced by the woman who was vaccinated.

All of the 90 cases of SIDS reported to VAERS during this 15-month period occurred within 28 days of vaccination, and 78 occurred within 7 days of vaccination. There have been no changes in the incidence of SIDS over recent years; each year, on the order of 5,000 deaths in the United States are classified as SIDS (Little and Peterson, 1990). The committee calculated the number of SIDS deaths that might be expected to occur within 7 days of vaccination if vaccination had no effect on the incidence of SIDS. Assuming that all infants receive three separate immunizations during the first year of life, there are three 7-day periods when a SIDS death would occur within 7 days of vaccination by chance alone. Of the SIDS deaths in a 1-year period, 288 deaths (21/365 of the total 5,000 SIDS deaths in 1 year) would occur within 7 days following a vaccination. If it is assumed that only half of all children receive their immunizations (a low estimate), one might expect 144 SIDS deaths in the 7 days following vaccination.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

TABLE 10-1 Quality and Quantity of Data in a Sample of VAERS Reports of Death Following Immunization

Report No.

Was Vaccine Suspected?

Is Report by an MD or RN?

Is Cause of Death Stated?

Was an Autopsy Performed?

1

No information

No

No information

No information

2

No

No

Yes, meningitis

No

3

No information

Yes—MD

No

No information

4

No information

Yes—RN

No

No information

5

No information

No information

No

No information

6

No information

No information

No

No information

7

No information

Yes—MD

No

No information

8

No information

Yes—RN

No

No information

9

No information

No information

No

No information

10

No

No information

No

Yes

11

No information

Yes—MD

No

No information

12

No information

Yes—MD

No

No information

13

No information

Yes—RN

No

No information

14

No information

No information

No

No information

15

No information

Yes—RN

No

No information

16

No information

Yes—RN

No

No information

17

No information

Yes—MD

No

No information

18

No information

Yes—RN

Yes, H. influenzae type b meningitis

No information

19

No information

No information

No

No information

20

No information

Yes—MD

No

Yes

21

No information

No information

No

No information

22

No information

Yes—RN

No

No information

23

No information; drug company summary

Yes

No

No information

24

Not sure; drug company report

No information

No

Yes

25

No; drug company report

No

No

No information

26

No information; drug company report

No

No

No information

27

No information

No information

Yes, meningitis

No information

28

No; drug company duplicate reports

No information

No

No information

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

Report No.

Were Lab Tests Done?

Which Vaccines Were Given?

Age at the Time of Death?

Time Since Receipt of Vaccine (days)

1

No information

DPT, Hib, polio

19 mo

2

2

Yes

MMR, Hib

16 mo

4

3

No information

IPV, Hib, hepatitis B

4 mo

30

4

No

DPT Hib, OPV

5.5 mo

1

5

No

DPT OPV

3 mo

1

6

No

DPT OPV, Hib

2.5 mo

8

7

No

DPT OPV, Hib

2 mo

3

8

No

DPT OPV, Pedivax 129

2.5 mo

17

9

No

OPV. DPT, Hib

2 mo

1

10

No information

DPT OPV, Hib

4 mo

3

11

No information

DPT polio, Hib

1.5 mo

2

12

No information

DPT OPV, Hib

2.5 mo

1

13

No information

DPT OPV, Hib

2.5 mo

1

14

No information

DPT OPV, Hib

3 mo

1

15

No

DPT OPV, Hib

2 mo

3

16

No information

DPT OPV, Hib

4 mo

23

17

No information

DPT OPV, Hib

2 mo

1

18

Yes

DPT OPV, MMR

5 yr

10

19

No information

DT, MMR, OPV

5 yr

Same day

20

No information

DPT, polio, MMR

18 mo

9

21

No

MMR, OPV, DPT

15 mo

12

22

No information

Polio, DPT, MMR

5 yr

Same day

23

No information

MMR

11 yr

15

24

No information

MMR, DPT, polio

18 mo

Same day

25

No information

MMR

15 yr

19

26

No information

Orimune

No information

4 mo

27

No information

Hib

2 yr

1 yr

28

No information

Hepatitis B

No information

No information

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

This may be an underestimate because SIDS is not distributed evenly over the first year of life—it peaks at about 12 weeks and tapers off toward 12 months (Little and Peterson, 1990). Over a 15-month period comparable to the FDA survey period, 180 cases of SIDS would be expected to occur in the 7-day period following vaccination. Only 78 such deaths were reported to VAERS, suggesting not only that VAERS does not contain an excessive number of reports of SIDS following immunization but also that it does not pick up all cases of SIDS that occur within 7 days of vaccination.

The remaining 52 VAERS reports of deaths following vaccinations were reviewed individually by members of the Vaccine Safety Committee and were classified into the categories discussed at the beginning of the chapter. The committee received all supporting documentation (e.g., autopsy reports or letters sent by the attending physician in response to requests for follow-up information) submitted to VAERS for these reports as well as the cause of death determination made by the FDA on the basis of the follow-up described earlier in this section. After the independent reviews, the results were compared and discussed until a consensus was reached for each death.

For 10 reports, details about the cause of death were inadequate, and the review panel could not judge whether the vaccine was causally related to the death. No deaths in this group were caused by manufacturing or handling errors. Forty deaths were considered to be not caused by the vaccine. These included cases in which there were unequivocal explanations of the cause of death such as neuroblastoma of the adrenal, congenital heart disease, viral pneumonia, and asphyxiation from a foreign body, and the review panel determined that the relation between vaccine and death was not causal. One death was considered to be a result of SIDS by the committee's review panel; FDA had left the diagnosis unclear for that case, resulting in a total of 91 SIDS deaths in the data set reviewed by the committee. One death resulted from an adverse event possibly caused by a vaccine. This was a case in which a 28-year-old woman died of common complications of Guillain-Barré syndrome (GBS) that developed after receiving diphtheria and tetanus toxoids for adult use (Td). The committee determined that the evidence favors acceptance of a causal relation between Td and GBS (see Chapter 5). There were no reports for which the committee thought the cause of death was plausibly related to vaccine or that did not clearly fall into one of the other six categories.

The committee's assessment of data in VAERS is similar to those of both the FDA (R. P. Wise, FDA, presentation to ACCV, December 1992) and the CDC (R. T. Chen, presentation to ACCV, March 1993), both of which concluded that the vast majority of deaths reported to VAERS are temporally but not causally related to vaccination.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

VACCINE-SPECIFIC DATA CONCERNING DEATH AFTER IMMUNIZATION

The preceding discussion sets the stage for discussion of the evidence regarding the causal relation between the vaccines reviewed in this report and death. The discussion will focus on deaths that are classified as SIDS and deaths that are a consequence of vaccine-strain vital infection. However, reports of death from all other causes (particularly from passive surveillance systems such as MSAEFI and VAERS) will be summarized for completeness. The committee evaluated VAERS reports submitted between November 1990 and July 1992.

Diphtheria and Tetanus Toxoids

Deaths Classified as SIDS

The relation between DPT and SIDS was examined by a previous Institute of Medicine committee in its investigation of the adverse effects of pertussis vaccine (Institute of Medicine, 1991). That committee concluded that the evidence favors rejection of a causal relation between DPT and SIDS. ''Studies showing a temporal relation between these events are consistent with the expected occurrence of SIDS over the age range in which DPT immunization typically occurs'' (Institute of Medicine, 1991, p. 141). Since both diphtheria and tetanus toxoids are components of DPT, it is likely that these toxoids are not causally associated with SIDS, although it is theoretically possible that pertussis vaccine could protect children from an effect of DT immunization on SIDS. Only one study (Pollock et al., 1984) compared the incidence of SIDS in cohorts of children who were immunized with DPT (13,917 doses) and DT (10,601 doses). Seven cases of SIDS occurred within 6 weeks of immunization, three (2.2 cases per 100,000 doses) in the DPT group and four (3.8 cases per 100,000 doses) in the DT group. The relative risk of SIDS after receipt of DPT versus that after receipt of DT was 0.6, with a 95 percent confidence interval (CI) of 0.1 to 2.3; thus, the relative risk was not significantly different from 1.0 (Institute of Medicine, 1991).

In a 7-year survey of vaccine reactions in the North West Thames region conducted by Pollock and Morris (1983), two deaths attributed to SIDS occurred among 133,500 children who received a primary series of DT (three doses). No deaths occurred among 221,000 children who received booster immunizations with DT.

A small case-control study conducted by Taylor and Emery (1982) concluded that infants who had received DT and polio vaccine were not more likely to have died "unexpectedly" than age-matched controls.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Deaths That Are a Consequence of an Adverse Event That Itself Is Causally Related to a Vaccine Reviewed in This Report

The evidence favors acceptance of a causal relation between Td and GBS. The evidence establishes a causal relation between tetanus toxoid and anaphylaxis (see Chapter 5). A VAERS report described a 28-year-old woman who received a Td booster following laceration of her foot, developed GBS, and required mechanical ventilation. After initial improvement, she developed interstitial pneumonitis and progressive ventilatory failure, and she died 20 days after immunization. Postmortem examination revealed massive interstitial pneumonitis and no inflammatory infiltrates in the nervous system.

A study by Kovalskaya (1967) demonstrated that it is possible to sensitize mice to fatal anaphylactic reactions to DPT. Only two cases of death associated with the administration of tetanus toxoid given as a single antigen have been described, one by Regamey in 1965 and one by Staak and Wirth in 1973. In both cases, anaphylaxis was thought to be the cause of death.

Other Reports of Death Following Immunization

Available Data Were Insufficient to Allow a Judgment of Cause Three deaths associated with DT or Td were reported to VAERS between November 1990 and September 1992. One patient received DT, MMR, and OPV at 60 months of age and died 1 day after immunization; no further clinical details were provided, and a cause of death was not indicated. The other two reports are discussed in other sections in this chapter.

Deaths Associated with Vaccine Administration but Attributable to Inappropriate Handling, Contamination, Production Error, or Error of Medical Care Early reports of death associated with toxin-antitoxin mixtures of diphtheria toxin and diphtheria toxoid were shown to be related to inadequate inactivation of toxin (see Background and History in Chapter 5); modern techniques of toxoid preparation and testing have eliminated this problem.

Deaths Temporally Associated with Vaccine Administration and the Cause of Death Is Other Than Those Listed Above Korger and colleagues (1986) reported data collected over 15 years (1970-1984) in Marburg, Germany, regarding the adverse effects of the tetanus toxoid produced by Behring. Reports were made by practicing physicians, the Drug Commission of the German Medical Association, the Paul-Ehrlich-Institut, druggists, and patients from 1970 to 1984. Data were stored on computer, and the physi-

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

cians and the manufacturer tried to determine the details of the reactions with a questionnaire. Five deaths were reported during a period when about 100 million doses were administered. When analyzed by those investigators, none of the deaths appeared to be causally related to the administration of tetanus toxoid, although one case was reported as "circulatory collapse in a patient with bronchial asthma." Clinical details of this case were not provided in the report.

In one of the three deaths associated with DT or Td reported to VAERS between November 1990 and September 1992, the cause of death in a 9-month-old child who received DT was reported as "Wilms tumor with nephrotic syndrome." The other two reports are discussed in the sections on deaths that are a consequence of an adverse event that is itself causally related to a vaccine reviewed in this report and on deaths for which the available data were insufficient to allow a judgment of cause.

In the hospital activity analysis of acute neurologic disease in the North West Thames region of England (this study is discussed in detail in Chapter 5), one case of fatal encephalopathy occurred 28 days after DT immunization (Pollock and Morris, 1983).

The National Childhood Encephalopathy Study described in the encephalopathy section of Chapter 6 was a large case-control study carried out between July 1976 and June 1979 to address the relation between vaccine administration and acute neurologic events (Alderslade et al., 1981). As part of that study, outcome data were collected, including any deaths that occurred in the children who experienced neurologic events. Of the 20 children with onset of a neurologic event within 7 days after immunization with DT, 4 died. Two children who had been normal prior to immunization developed encephalopathy or encephalitis. One child died on the same day after receiving the first DT immunization, and the other child died after 20 days. A third, previously normal child who died was originally thought to have Reye syndrome, but endocardial fibroelastosis was found at autopsy. The fourth child who died after DT immunization had a preceding neurologic abnormality, developed acute infantile hemiplegia after immunization, and died at 2.5 years of age. In the committee's judgment the evidence favors rejection of a causal relation between DT and encephalopathy (see Chapter 5).

Causality Argument

The evidence favors rejection of a causal relation between DPT and SIDS (Institute of Medicine, 1991). Pollock et al. (1984) presented data suggesting that the relative risk of SIDS after DPT versus that after DT is not significantly different from 1. In the committee's judgment the evidence favors rejection of a causal relation between DT and SIDS.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

The evidence favors acceptance of a causal relation between DT, Td, and tetanus toxoid and GBS. The evidence establishes a causal relation between DT, Td, and tetanus toxoid and anaphylaxis (see Chapter 5). Both GBS and anaphylaxis can be fatal. The only well-documented cases of death causally related to immunization with tetanus toxoid, DT, or Td are attributable to anaphylaxis; the evidence regarding death as a consequence of GBS that temporally followed administration of one of these toxoids is limited (one case report). In the committee's judgment DT, Td, or tetanus toxoid may rarely cause fatal GBS or anaphylaxis. There is no evidence or reason to believe that the case fatality rate from vaccine-associated GBS or anaphylaxis would differ from the case fatality rate for these adverse events associated with any other cause.

Reports of death from all other causes are not clearly linked to the preceding immunization. No cases of death were reported by Christensen (1972) in Denmark between 1952 and 1970, a time during which 2.5 million doses of monovalent tetanus toxoid, 2.67 million doses of DT, and 1.1 million doses of Td were given. No cases of death associated with tetanus toxoid, DT, or Td were reported through MSAEFI between 1979 and 1990. During that time, approximately 1.3 million doses of DT and 29 million doses of Td were distributed.

Conclusion

The evidence establishes a causal relation between DT, Td, and tetanus toxoid and death from anaphylaxis. Although this conclusion is based on direct evidence, it is not based on controlled studies and no relative risk can be calculated. However, the risk of death from anaphylaxis following receipt of DT, Td, or tetanus toxoid would appear to be extraordinarily low.

The evidence favors acceptance of a causal relation between DT, Td, and tetanus toxoid and death from GBS. This conclusion is not based on controlled studies and no relative risk can be calculated. However, the risk of death from GBS following receipt of DT, Td, or tetanus toxoid would seem to be extraordinarily low.

The evidence favors rejection of a causal relation between DT and SIDS.

The evidence is inadequate to accept or reject a causal relation between tetanus toxoid, DT, or Td and death from causes other than those listed above.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

Measles and Mumps Vaccines

Deaths Classified as SIDS

Measles and mumps vaccines are not administered in the United States to the age group in which most cases of SIDS occur (under age 6 months). There are scattered reports of sudden death in temporal relation to measles vaccine (Hirayama, 1983; Miller, 1982; Nader and Warren, 1968), but insufficient information was provided to classify these as SIDS.

Deaths That Are a Consequence of Vaccine-Strain Viral Infection

Several articles have reported the death from measles infection of immunocompromised children following administration of live attenuated measles vaccine. Hong and colleagues (1985) reported the death of a 4-month-old boy with Omenn's disease following immunization with an unspecified strain of live attenuated measles vaccine. He was first seen at 4 months of age because of a skin eruption and fever following immunization with live attenuated measles vaccine. Attempts to culture measles virus from throat, skin, lymph node, and stool specimens were not successful. His skin rash persisted for several weeks, and he experienced unexplained high fevers and chronic diarrhea and cough. He was readmitted to the hospital at 15 months of age and died soon thereafter. The autopsy showed lymphoma and measles virus antigen in his bone marrow and lymphoid tissue. There was no evidence of subacute sclerosing panencephalitis. It thus appears that because of the patient's T-cell deficiency, the measles virus was not contained, suggesting a chronic measles infection following vaccination.

Bellini and colleagues reported on two cases of fatal measles following vaccination of two children with severe combined immunodeficiency syndrome (Bellini et al., 1992; Coffin et al., 1993). In both cases, RNA-templated nucleotide sequencing showed that the gene sequences of the RNAs isolated from the children's tissues were identical to the gene sequences of the RNA of the vaccine strain. Two other case reports link measles vaccine and the subsequent development of measles that led to death in immunocompromised children. One child each suffered from dysgammaglobulinemia (Mawhinney et al., 1971) and acute leukemia (Mitus et al., 1962). The technology used by Bellini and colleagues described above was not available at the time of the latter two studies, so the findings do not permit as confident an inference of a causal association.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Deaths That Are a Consequence of an Adverse Event That Itself Is Causally Related to a Vaccine Reviewed in This Report

The evidence favors acceptance of a causal relation between measles vaccine and anaphylaxis. The evidence establishes a causal relation between MMR and thrombocytopenia anaphylaxis (see Chapter 6). The committee identified no reports of death from these adverse events that occurred in temporal relation to vaccination.

Other Reports of Death Following Immunization

The committee does not consider the apparent increased relative risk of death following administration of high-titer Edmonston-Zagreb or Schwarz strain measles vaccine such as has been seen in clinical trials conducted in Senegal (Garenne et al., 1991) to be relevant to the United States because these high-titer vaccines are not licensed for use in the United States. The cause of the increased mortality such as that seen in Senegal is not known.

Available Data Were Insufficient to Allow a Judgment of Cause Starke and colleagues (1970) described three deaths that occurred during a mass measles immunization campaign in the former East Germany from 1967 to 1969. One child died of toxic circulatory collapse 6 days after immunization. The article stated that virologic examinations showed no proof of a pathogenic agent, but it is not clear how rigorously this was pursued. Another child died 3 days after measles vaccination. Autopsy results report cerebral edema as the cause of death. Another child died approximately 6 weeks after immunization. Autopsy results showed encephalitis as the cause of death. Haun and Ehrhardt (1973) described an 11-month-old child who developed clonic seizures and encephalitis within 12 days of receiving measles vaccine (Leningrad-16 SSW) and who died soon thereafter of probable disseminated intravascular coagulation. The authors were unsure whether vaccine-strain virus was responsible. Nader and Warren (1968) described 23 cases of neurologic disease following measles vaccination reported to the U.S. Communicable Disease Center (now CDC) between 1965 and 1967. Two deaths were reported 7 and 13 days following vaccination. Measles antibody was not detectable in either patient. One of the cases was diagnosed as encephalitis (herpes simplex virus was isolated from brain, but there were no detectable antibodies against this virus in serum) and the other was diagnosed as a sudden death. Landrigan and Witte (1973) reported on 84 cases of neurologic disorders reported to the CDC between 1963 and 1971 and diagnosed within 1 month following administration of measles vaccine. Five of these patients had extensive neurologic disorders that were ultimately fatal. They also reported five fatalities in which the

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

clinical course was consistent with overwhelming bacterial or viral infection. Culturing was inadequate, and no cause of death was established. Hirayama (1983) described complications from measles vaccine reported as part of a compensation system established by the Preventive Vaccination Law in Japan in 1976. During the time period covered by the article (1978 to approximately 1982), 2.15 million individuals were inoculated with the Schwarz measles vaccine and 1.39 million individuals were inoculated with the Biken-CAM live attenuated measles vaccine. The authors estimated that during the 18 days following administration of the vaccine in children younger than 1 year of age, the combined risk of acute neurologic disease and sudden death was 9.8 per 100,000 doses per year. The annual background incidence of acute neurologic disease and sudden deaths was 200 per 100,000 infants younger than 1 year.

The evidence is inadequate to accept or reject a causal relation between measles vaccine and encephalitis, encephalopathy, or residual seizure disorder (see Chapter 6). In the committee's judgment the evidence is inadequate to accept or reject a causal relation between measles vaccine and death from encephalitis, encephalopathy, and residual seizure disorder.

Summary statistics from MSAEFI from 1979 to 1990 showed 3 deaths after administration of measles vaccine, 16 deaths after administration of MMR alone, and 8 deaths after administration of MMR in conjunction with DPT and OPV. No other data regarding deaths were obtained from MSAEFI. The committee identified 32 reports in VAERS (submitted between November 1990 and July 1992) of death in association with administration of measles and mumps vaccines. One of these was in association with measles vaccine, one with mumps vaccine, one with measles-mumps vaccine, and nine with MMR. Twenty reports were of MMR administered in conjunction with other vaccines. The vaccinees ranged in age from 2 months to 15 years, and the interval from the time of vaccination to death ranged from 1 day to at least 56 days. Missing data from some VAERS reports precludes the listing of more precise information concerning the age of the child or the interval from the time of vaccination to death.

Deaths Associated with Vaccine Administration but Attributable to Inappropriate Handling, Contamination, Production Error, or Error of Medical Care Sokhey (1991) reported the results of a monitoring effort following immunization in India for the year 1990. The monitoring effort covered a number of childhood vaccines, although only the events possibly associated with measles vaccines are described here. There were apparently five separate locations where children received the measles vaccine, and 9 of 54 children died after receiving the vaccine. The authors attributed the deaths of eight children to toxic shock syndrome (TSS). In one incident, 6 of the 12 immunized children died within 24 hours of receiving the vaccine (the

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

vaccine strain was unidentified). Apparently, all 12 children had adverse reactions and 6 survived. The ages of those who died ranged from 9 to 18 months. This extraordinary mortality rate was attributed by the author to TSS and, specifically, the use of unhygienic conditions in administering the vaccine. A second incident involved the death of the only child (age 8 months) immunized at a particular location. Death occurred within 24 hours of vaccine administration and was attributed to TSS. In a third incident, 1 of 33 immunized children died following measles vaccination. This child was 23 months old and died of TSS 17 hours after immunization. A fourth incident involved the death of one of seven immunized children. The 16-month-old child became semiconscious within 30 minutes of receiving the vaccine and died approximately 40 hours later. The death was attributed to underlying hemorrhagic diathesis.

Deaths Temporally Associated with Vaccine Administration, and the Cause of Death Is Other Than Those Listed Above Miller (1982) described a case series of 10,035 children who were vaccinated between 1970 and 1980 in Oxford, England, with the Beckenham 31 and Schwarz measles vaccine strains. One 12-month-old child died 36 hours after the vaccination. The report indicated that the coroner's death certificate stated "sudden death in infancy and acute bronchiolitis" (Miller, 1982, p. 535).

Causality Argument

The data relating death and measles or mumps vaccine are from case reports and case series. The largest series comes from India, but TSS caused by the unhygienic conditions involved in the immunization program was the apparent cause of death reported for eight of nine patients. Evidence based on RNA sequencing techniques has linked measles vaccine and measles infection to subsequent death in some severely immunocompromised children. In contrast, studies of the immunogenic response to measles vaccine in children infected with human immunodeficiency virus (HIV), which causes acquired immune deficiency syndrome (AIDS), have not recorded any deaths from measles vaccine-strain viral infection.

The evidence favors the acceptance of a causal relation between measles vaccine and anaphylaxis. The evidence establishes a causal relation between MMR and thrombocytopenia and anaphylaxis (see Chapter 6). Anaphylaxis and thrombocytopenia can be fatal. Although there is no direct evidence of death as a consequence of measles vaccine-related anaphylaxis or of MMR-related thrombocytopenia or anaphylaxis, in the committee's judgment measles vaccine could cause fatal anaphylaxis and MMR could cause fatal thrombocytopenia or anaphylaxis. There is no evidence or reason to believe that the case fatality rate from measles vaccine-related

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

thrombocytopenia or anaphylaxis would differ from the case fatality rates for these adverse events associated with any other cause.

Conclusion

The evidence establishes a causal relation between vaccine-strain measles virus infection and death. The conclusion is based on case reports in immunocompromised individuals and not on controlled studies. No relative risk can be calculated. However, the risk of death from measles vaccine-strain infection would seem to be extraordinarily low.

The evidence establishes a causal relation between MMR and death from complications associated with severe thrombocytopenia. The evidence establishes a causal relation between MMR and death from anaphylaxis. There is no direct evidence for this; the conclusion is based on the potential of severe thrombocytopenia and anaphylaxis to be fatal. The risk would seem to be extraordinarily low.

The evidence favors acceptance of a causal relation between measles vaccine and death from anaphylaxis. There is no direct evidence for this; the conclusion is based on the potential of anaphylaxis to be fatal. The risk would seem to be extraordinarily low.

The evidence is inadequate to accept or reject a causal relation between measles and mumps vaccines and death from causes other than those listed above.

Risk-Modifying Factors

There is evidence that some severely immunocompromised children, such as those with severe combined immunodeficiency syndrome, dysgamma-globulinemia, or leukemia, are susceptible to overwhelming measles infection and subsequent death, even from attenuated measles vaccine. Infection with HIV has not been associated with death from measles vaccine-strain viral infection.

Polio Vaccines

Deaths Classified as SIDS

For many years, the standard immunization schedule in the first year of life (the period in which SIDS occurs) included only DPT and polio vaccine. The research on SIDS has focused on DPT. A few studies that primarily investigated the role of DPT in SIDS also looked at polio vaccine (Bouvier-Colle et al., 1989; Hoffman et al., 1987; Taylor and Emery, 1982; Walker et al., 1987). Only Hoffman and colleagues (1987) report odds ratio

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

estimates of the relative risk of a SIDS case infant being immunized with OPV (0.57 for age-matched controls and 0.61 for age-, race-, and low-birth-weight-matched controls). These odds ratios were very similar to those obtained for the relative risk of SIDS after DPT immunization. A small case-control study conducted by Taylor and Emery (1982) concluded that infants who had received DT and polio vaccine were not more likely to have died "unexpectedly" than age-matched controls. Mobius and colleagues (1972) described 13 deaths that occurred in the 21 days following receipt of polio vaccine over the years 1959 to 1968 in the former East Germany. Three deaths labeled sudden death followed administration of OPV and one labeled fever and sudden death followed administration of IPV.

Passive surveillance systems such as MSAEFI and VAERS contain many reports of SIDS occurring within 24 or 48 hours following vaccination, but these case reports are not necessarily evidence of an association or a causal relation, because cases will occur in the 24- to 48-hour period following vaccination by chance alone.

Deaths That Are a Consequence of Vaccine-Strain Viral Infection

One VAERS report states that molecular biologic techniques were used to identify vaccine-strain poliovirus from the myocardium of a 3.5-month-old baby who died of myocarditis 4 days after receiving his second doses of OPV and DPT. On the basis of details in the VAERS report, the committee believes this report concerns the same baby described to the committee at its May 1992 public meeting (see Appendix B).

Deaths That Are a Consequence of an Adverse Event That Itself Is Causally Related to a Vaccine Reviewed in This Report

The evidence favors acceptance of a causal relation between OPV and GBS. The evidence establishes a causal relation between OPV and paralytic poliomyelitis (see Chapter 7).

The committee identified no reports of death following GBS that occurred in temporal relation to OPV immunization. In the committee's review of over 90 papers reporting cases of vaccine-associated polio, the committee found 6 papers that described deaths among patients with vaccine-associated polio. These deaths are summarized in Table 10-2. Two papers described the same case (Davis et al., 1977; Saulsbury et al., 1975) of a female infant with immunodeficiency associated with cartilage-hair hypoplasia who contracted polio but who died of pneumonia 3 months after the diagnosis of polio. Two other deaths reported in the United States (Chang et al., 1966; Gaebler et al., 1986) also occurred in immunodeficient individuals. The sixth paper describes the first year of Peru's vaccination

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

TABLE 10-2 Deaths Among Patients with Vaccine-Associated Polio

Reference

Case Description

Davis et al., 1977

Female diagnosed with polio at age 8 mo, diagnosed with dwarfism because of cartilage-hair hypoplasia at 10 mo, died of pneumonia at age 11 mo

Gross et al., 1987

40-yr-old man receiving long-term steroid therapy; he developed polio 51 days after daughter's immunization with OPV and died of cardiac arrest I year later

Gaebler et al., 1986

Infant boy received typical course of immunizations and developed polio at age 7.5 mo; he died at age 21 mo: the authors considered boy to be immune deficient, but evidence of vaccine-associated polio was not definitive

Saulsbury et al., 1975

Same as Davis et al., 1977

Roedenbeck and Diaz. 1967

Fourteen deaths among patients with polio occurring in the first year (1966) of Peru's vaccination program

Chang et al., 1966

A 7-yr-old boy diagnosed with ''vaccine-like'' polio and then discovered to be hypogammaglobulinemic; he died of pneumococcal meningitis more than 1 yr following diagnosis of polio

program (Roedenbeck and Diaz, 1967). The authors described 14 deaths that occurred in children who were recently immunized with OPV. This was at a time when wild-type poliovirus was still circulating; the cases of polio and the deaths may therefore have been associated with wild-type strains. A third case occurred in a person who had been on long-term steroids and might have been immunocompromised (Gross et al., 1987).

The CDC reported five deaths that occurred in people with vaccine-associated polio over the years 1980 to 1991 (Division of Immunization, Centers for Disease Control, personal communication, 1993). Four of the deaths occurred in immunodeficient or immunosuppressed patients. The fifth patient was not considered to be immunosuppressed but was described in the published case report described above (Gross et al., 1987) as possibly being immunocompromised because of long-term steroid use.

There may have been other deaths among people with vaccine-associated polio, but the case reports in the literature do not always follow the patients long enough. It is interesting to note that all the deaths in the United States reported in the literature occurred in immunodeficient or immune-suppressed people. This suggests that immunodeficiency is a risk-modifying factor that increases the case fatality rate of polio. In such immunodeficient patients with polio, other infections contributed to the patients' deaths. The immunodeficient patients may therefore be at increased risk of dying compared with the risk for other people who contract vaccine-associated polio.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Death from Other Causes Following Immunization

Available Data Were Insufficient to Allow a Judgment of Cause Summary statistics from MSAEFI for the years 1979 to 1990 include 1 report of death following administration of OPV only, 1 report following IPV only, 445 reports following OPV plus other vaccines, and 1 report following IPV and other vaccines. VAERS (reports submitted between November 1990 and July 1992) contained 1 report of death following OPV only, 267 following OPV plus other vaccines, and 1 following IPV and other vaccines. Many VAERS reports contain insufficient data to assess a causal relation between polio vaccines and death.

Deaths Temporally Associated with Vaccine Administration and the Cause of Death Is Other Than Those Listed Above Ehrengut and Ehrengut-Lange (1969) reviewed the deaths in which illness started in the 4 weeks following vaccination that occurred in Bavaria, Germany, during the years 1962 to 1964. They found that 26 such deaths occurred among 702,348 children aged 0 to 3 years. In all cases, poliomyelitis or polyradiculitis was ruled out as the cause of death. The main causes of death were respiratory infections (pneumonia, bronchitis, etc.). The authors did not comment on the causes of death, but suggested that mortality following receipt of polio vaccine was similar to that following receipt of smallpox vaccine in the same years.

Mobius and colleagues (1972) described 13 deaths that occurred in the 21 days following receipt of polio vaccine over the years 1959 to 1968 in the former East Germany. Eleven deaths occurred following receipt of OPV and two occurred following receipt of IPV. The causes of death following receipt of OPV were as follows: three were "found dead," three were "sudden death," and there was one each of epiglottitis, aspiration, pneumonia, and ''unclear." One of the fatalities was in a child who died of myocarditis. The authors report that the child had been administered oral polio vaccine stains 1 and 3, however polio virus type II was isolated. The causes of death following IPV were convulsions and fever/sudden death.

Causality Argument

The evidence favors acceptance of a causal relation between OPV and GBS. The evidence establishes a causal relation between OPV and paralytic poliomyelitis in recipients or contacts (see Chapter 7). GBS and paralytic poliomyelitis can be fatal. Although there is no direct evidence of death as a consequence of OPV-induced GBS, in the committee's judgment OPV could cause fatal GBS. There are data regarding death from vaccine-strain polio infection; the data derive primarily from immunocompromised

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

individuals. There is no evidence or reason to believe that the case fatality rate for GBS or vaccine-associated poliovirus infection (including that resulting in paralytic poliomyelitis) is less than that for these adverse events associated with any other cause.

The possible causal relation between polio vaccines and SIDS has rarely been studied. The evidence is inadequate to accept or reject a causal relation between polio vaccines and SIDS.

Conclusion

The evidence establishes a causal relation between OPV and death from vaccine-strain poliovirus infection, including infection that results in paralytic poliomyelitis. The conclusion is based on case reports and not on controlled studies. No relative risk can be calculated. However, the risk of death from OPV-related polio infection would seem to be extraordinarily low.

The evidence favors acceptance of a causal relation between OPV and death from GBS. There is no direct evidence for this; the conclusion is based on the potential of GBS to be fatal. The risk would appear to be extraordinarily low.

The evidence is inadequate to accept or reject a causal relation between polio vaccines and SIDS.

The evidence is inadequate to accept or reject a causal relation between OPV and death from causes other than those listed above.

Risk-Modifying Factors

Immunodeficient individuals may be at greater risk of dying than immunocompetent persons if they contract vaccine-associated poliovirus infection.

Hepatitis B Vaccine

Deaths Classified as SIDS

Hepatitis B vaccine has only recently been used in infants under 1 year of age. A possible causal relation between hepatitis B vaccine and SIDS has not been studied. There are reports in VAERS (submitted between November 1990 and July 1992) of SIDS occurring in temporal relation to hepatitis B vaccination.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Deaths That Are a Consequence of an Adverse Event That Itself Is Causally Related to a Vaccine Reviewed in This Report

The committee did not identify any reports of fatal anaphylaxis following hepatitis B vaccination.

Death from Other Causes Following Immunization

Available Data Were Insufficient to Allow a Judgment of Cause Two deaths following hepatitis B vaccination were reported to MSAEFI for the years 1979 to 1990. Both deaths occurred in vaccinees who concurrently received DPT and OPV. No other data regarding deaths were obtained from MSAEFI.

The committee identified nine reports in VAERS (submitted between November 1990 and July 1992) of death that occurred in association with administration of hepatitis B vaccines. Six of these were associated with administration of hepatitis B vaccine only; the other three were associated with administration of hepatitis B vaccine in conjunction with other vaccines. The ages of the vaccinees ranged from 1 month to 70 years, and the interval from vaccination to death ranged from 1 to 30 days.

Causality Argument

The evidence establishes a causal relation between hepatitis B vaccine and anaphylaxis (see Chapter 8). Anaphylaxis can be fatal. Although there is no direct evidence of fatal anaphylaxis following hepatitis B vaccination, in the committee's judgment hepatitis B vaccine could cause fatal anaphylaxis. There is no evidence or reason to believe that the case fatality rate for vaccine-associated anaphylaxis would differ from the case fatality rate for anaphylaxis associated with any other cause.

Hepatitis B vaccine has only recently begun to be administered to the age group that is affected by SIDS. There are no published studies of a possible causal relation between hepatitis B vaccine and SIDS. There are reports in VAERS of SIDS following immunization with hepatitis B vaccine given in conjunction with other vaccines.

Conclusion

The evidence establishes a causal relation between hepatitis B vaccine and fatal anaphylaxis. There is no direct evidence for this; the conclusion is based on the potential for anaphylaxis to be fatal. The risk would appear to be extraordinarily low.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

The evidence is inadequate to accept or reject a causal relation between hepatitis B vaccine and SIDS.

The evidence is inadequate to accept or reject a causal relation between hepatitis B vaccine and death from any cause other than those listed above.

Haernophilus influenzae Type b Vaccine

Deaths Classified as SIDS

There are no published studies of the relation between H. influenzae type b (Hib) vaccines and SIDS. Hib vaccines are licensed for administration to children under 1 year of age. There are reports in VAERS of SIDS occurring in temporal relation to Hib vaccine administration. As part of an investigation of VAERS reports of death following administration of Hib vaccines, the CDC has preliminary data suggesting that Hib vaccines do not appear to be causally related to SIDS (R. T. Chen, presentation to ACCV, March 1993).

Deaths That Are a Consequence of an Adverse Event That Itself Is Causally Related to a Vaccine Reviewed in This Report

The committee found no reports of death caused by Hib disease that occurred within 7 days of immunization with the unconjugated (polyribosylribitol phosphate [PRP]) Hib vaccine in children over 18 months of age who receive their first Hib immunization with unconjugated PRP vaccine, although in 10 instances outcome information was not provided.

Death from Other Causes Following Immunization

Available Data Were Insufficient to Allow a Judgment of Cause The committee identified 223 reports of death in association with the administration of Hib vaccine from VAERS between November 1990 and August 1992. Of these 223 reports, 17 were of children who received Hib vaccine alone. The ages of the children in the 223 reports ranged from 2 months to at least 36 months. The interval from the time of vaccination to death ranged from 1 to 210 days. Because data were missing from some VAERS reports, more precise information about the age of the child or the time interval from vaccination to death is unavailable.

There were no reports to MSAEFI regarding death in association with Hib vaccination from 1979 to 1984. There were reports to MSAEFI of two deaths following Hib vaccination from 1985 to 1990. The recent licensure of the Hib vaccine makes this finding not surprising.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Causality Argument

The evidence favors rejection of a causal relation between conjugated Hib vaccines and early-onset Hib disease. The evidence favors acceptance of a causal relation between PRP vaccine and early-onset Hib disease in children 18 months of age or older who receive their first Hib immunization with unconjugated PRP vaccine (see Chapter 9). Hib disease can be fatal. Although there is no direct evidence of death as a consequence of early-onset Hib disease in children 18 months of age or older who receive their first Hib immunization with PRP vaccine, in the committee's judgment PRP vaccine could cause fatal Hib disease in children 18 months of age or older who receive their first Hib immunization with PRP vaccine. There is no evidence or reason to believe that the case fatality rate from PRP-associated Hib disease would differ from the case fatality rate from Hib disease not associated with PRP vaccine.

Conclusion

The evidence favors acceptance of a causal relation between PRP vaccine and death from early-onset Hib disease in children 18 months of age or older who receive their first Hib immunization with unconjugated PRP vaccine. There is no direct evidence for this; the conclusion is based on the potential for Hib disease to be fatal. The risk would appear to be extraordinarily low.

The evidence favors rejection of a causal relation between conjugated Hib vaccines and death from early-onset Hib disease.

The evidence is inadequate to accept or reject a causal relation between Hib vaccines and SIDS.

The evidence is inadequate to accept or reject a causal relation between Hib vaccine and death from causes other than those listed above.

REFERENCES

Alderslade R, Bellman MH, Rawson NS, Ross EM, Miller DL. The National Childhood Encephalopathy Study: a report on 1000 cases of serious neurological disorders in infants and young children from the NCES research team. In: Department of Health and Social Security. Whooping Cough: Reports from the Committee on the Safety of Medicines and the Joint Committee on Vaccination and Immunization. London: Her Majesty's Stationery Office; 1981.


Bellini WJ, Rota JS, Greer FW, Zaki SR. Measles vaccination death in a child with severe combined immunodeficiency: report of a case. Laboratory Investigation 1992;66:19A.

Bouvier-Colle MH, Flahaut A, Messiah A, Jougla E, Hatton F. Sudden infant death and immunization: an extensive epidemiological approach to the problem in France—winter 1986. International Journal of Epidemiology 1989; 18:121-126.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

Chang TW, Weinstein L, MacMahon HE. Paralytic poliomyelitis in a child with hypogamma-globulinemia: probable implication of type I vaccine strain. Pediatrics 1966;37:630-636.

Chen RT, Rastogi SC, Mullen JR, Hayes SW, Cochi SL, Donlon JA, et al. The Vaccine Adverse Event Reporting System (VAERS). Atlanta: Centers for Disease Control; submitted for publication.

Christensen PE. Side reactions to tetanus toxoid. Scientific Publication, Pan American Health Organization 1972;253:36-43.

Coffin CM, Roberts RL, Monafo WJ, Haslam DB, Bellini W J, Zaki S, et al. Disseminated measles infection following vaccination in severe combined immune deficiency syndrome. Society for Pediatric Pathology 1993; 13:102.


Davis LE, Bodian D, Price D, Butler IJ, Vickers JH. Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child. New England Journal of Medicine 1977;297:241-245.


Ehrengut W, Ehrengut-Lange J. Interkurrente todliche Erkrankungen nach Polioschluckimpfung und Pockenschutzimpfung. [Intercurrent fatal diseases after oral polio vaccination and smallpox vaccination.] Munchener Medizinische Wochenschrift 1969;111:1092-1099.


Gaebler JW, Kleiman MB, French ML, Chastain G, Barrett C, Griffin C. Neurologic complications in oral polio vaccine recipients. Journal of Pediatrics 1986;108:878-881.

Garenne M, Leroy O, Beau J-P, Sene I. Child mortality after high titre measles vaccines: prospective study in Senegal. Lancet 1991;338:903-907.

Gross TP, Khurana RK, Higgins T, Nkowane BS, Hirsch RL. Vaccine-associated poliomyelitis in a household contact with Netherton's syndrome receiving long-term steroid therapy. American Journal of Medicine 1987;83:797-800.


Haun U, Ehrhardt G. Zur problematik postvakzinaler Komplikationen nach Masernschutzimpfung. [Postvaccinal complications following protective vaccination against measles.] Deutsche Gesundheitswesen 1973;28:1306-1308.

Hirayama M. Measles vaccines used in Japan. Reviews of Infectious Diseases 1983;5:495-503.

Hoffman HJ, Hunter JC, Damus K, Pakter J, Peterson DR, van Belle G, Hasselmeyer EG. Diphtheria-tetanus-pertussis immunization and sudden infant death: results of the National Institute of Child Health and Human Development Cooperative Epidemiological Study of Sudden Infant Death Syndrome Risk Factors. Pediatrics 1987;79:598-611.

Hong R, Gilbert EF, Opitz JM. Omenn disease: termination in lymphoma. Pediatric Pathology 1985;3:143-154.


Institute of Medicine. Adverse Effects of Pertussis and Rubella Vaccines. Washington, DC: National Academy Press; 1991.


Korger G, Quast U, Dechert G. Tetanusimpfung: Vertraglichkeit und Vermeidung von Nebenreaktionen. [Tetanus vaccination: tolerance and avoidance of adverse reactions.] Klminische Wochenschrift 1986:64:767-775.

Kovalskaya SI. Anafilaktogennye svoistva adsorbipovannoi i neadsorbirovannoi kokliusnodifterino-stolbniachnoi vaktsin. [The anaphylactogenic properties of absorbed and nonabsorbed pertussis-diphtheria-tetanus vaccines.] Zhurnal Mikrobiologii, Epidemiologii, i Immunobiologii 1967;44:105-109.


Landrigan PJ, Witte JJ. Neurologic disorders following live measles-virus vaccination. Journal of the American Medical Association 1973;223:1459-1462.

Little RE, Peterson DR. Sudden infant death syndrome epidemiology: a review and update. Epidemiologic Reviews 1990:12:241-246.


Mawhinney H, Allen IV, Beare JM, Bridges JM, Connolly HH, Haire M, et al. Dysgamma-globulinaemia complicated by disseminated measles. British Medical Journal 1971;2:380-381.

Miller CL. Surveillance after measles vaccination in children. The Practitioner 1982;226:535-537.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×

Mitus A, Holloway A, Evans AE, Enders JF. Attenuated measles vaccine in children with acute leukemia. American Journal of Diseases of Children 1962;103:243-248.

Mobius G, Wiedersberg H, Wunscher W, Backer F. Pathologisch-anatomische Befunde bei Todesfallen nach Poliomyelitis- und Dreifach-Schutzimpfung. [Pathological-anatomical findings in cases of death following poliomyelitis and diphtheria-pertussis-tetanus vaccination.] Deutsche Gesundheitswesen 1972;27:1382-1386.

Nader PR, Warren RJ. Reported neurologic disorders following live measles vaccine. Pediatrics 1968;41:997-1001.

Nathanson N, Langmuir AD. The Cutter incident: poliomyelitis following formaldehyde-inactivated poliovirus vaccination in the United States during the spring of 1955. I. Background. American Journal of Hygiene 1963;78:16-28.


Pollock TM, Morris J. A 7-year survey of disorders attributed to vaccination in North West Thames region. Lancet 1983;1:753-757.

Pollock TM, Miller E, Mortimer JY, Smith G. Symptoms after primary immunization with DTP and with DT vaccine. Lancet 1984;2:146-149.


Regamey RH. Die Tetanus-Schutzimpfung. In: Herrlick A, ed. Handbuch der Schutzimpfungen. Berlin: Springer: 1965.

Roedenbeck SD, Diaz C. Poliomielitis y vacuna oral. [Poliomyelitis and oral vaccine.] Revista de Neuro-Psiquiatria 1967;30:38-56.


Saulsbury FT, Winkelstein JA, Davis LE, Hsu SH, D'Souza BJ, Gutcher GR, Butler, IJ. Combined immunodeficiency and vaccine-related poliomyelitis in a child with cartilage-hair hypoplasia. Journal of Pediatrics 1975;86:868-872.

Sokhey J. Adverse events following immunization: 1990. Indian Pediatrics 1991;28:593-607.

Staak M, Wirth E. Zur problematik anaphylaktischer Reaktionen nach aktiver Tetanus-Immunisierung. [Anaphylactic reactions following active tetanus immunization.] Deutsche Medizinische Wochenschrift 1973;98:110-111.

Starke VG, Hlinak P, Nobel B, Winkler C, Kaesler G. Masernradikation—eine Moglichkeit? Ergebnisse und Erfahrungen mit der Masernschutzimpfung 1967 bis 1969 in der DDR [Measles eradication—a possibility? Results and experiences with the measles inoculation from 1967 to 1969 in the GDR.] Deutsche Gesundheitswesen 1970;25:2384-2390.


Taylor EM, Emery JL. Immunization and cot deaths (letter). Lancet 1982;2:721.


Walker AM, Jick H, Perera DR, Thompson RJ, Knauss TA. Diphtheria-tetanus-pertussis immunization and sudden infant death syndrome. American Journal of Public Health 1987;77:945-951.

Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 274
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 275
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 276
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 277
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 278
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 279
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 280
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 281
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 282
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 283
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 284
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 285
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 286
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 287
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 288
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 289
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 290
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 291
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 292
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 293
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 294
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 295
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 296
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 297
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 298
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 299
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 300
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 301
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 302
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 303
Suggested Citation:"10 Death ." Institute of Medicine. 1994. Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality. Washington, DC: The National Academies Press. doi: 10.17226/2138.
×
Page 304
Next: 11 Need for Research and Surveillance »
Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality Get This Book
×
Buy Paperback | $120.00
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Childhood immunization is one of the major public health measures of the 20th century and is now receiving special attention from the Clinton administration. At the same time, some parents and health professionals are questioning the safety of vaccines because of the occurrence of rare adverse events after immunization.

This volume provides the most thorough literature review available about links between common childhood vaccines--tetanus, diphtheria, measles, mumps, polio, Haemophilus influenzae b, and hepatitis B--and specific types of disorders or death.

The authors discuss approaches to evidence and causality and examine the consequences--neurologic and immunologic disorders and death--linked with immunization. Discussion also includes background information on the development of the vaccines and details about the case reports, clinical trials, and other evidence associating each vaccine with specific disorders.

This comprehensive volume will be an important resource to anyone concerned about the immunization controversy: public health officials, pediatricians, attorneys, researchers, and parents.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!