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10
Diphtheria Toxoid–, Tetanus
Toxoid–, and Acellular Pertussis–
Containing Vaccines
INTRODUCTION
Diphtheria Toxoid
Diphtheria is an acute upper respiratory illness caused by Corynebac-
terium diphtheriae. C. diphtheriae is a minimally invasive gram-positive
bacillus that is resistant to environmental change and whose virulence
is mostly confined to the secretion of an exotoxin that inhibits protein
synthesis in mammalian cells (MacGregor, 2010). C. diphtheriae is spread
through direct contact with infected respiratory secretions and cutaneous
lesions (MacGregor, 2010).
Following an incubation period of 1 to 5 days, diphtheria presents most
commonly as local invasion of the respiratory tract including the back of
the mouth and upper pharynx (Vitek and Wharton, 2008). Early symptoms
may include low-grade fever (less than 101.3°F), malaise, and sore throat
(Vitek and Wharton, 2008). Approximately 24 hours after disease onset,
small patches of exudate are visible, and within 2 to 3 days a glossy, white
membrane covers one or both tonsils and other oral structures including
the tonsillar pillars, uvula, soft palate, oropharynx, and nasopharynx (Vitek
and Wharton, 2008). The magnitude of the membrane is an indication of
disease severity. Localized disease is often mild; however, the involvement
of posterior structures like the soft palate and periglottal areas generally
suggests the development of more substantial disease (Vitek and Wharton,
2008). In such cases, local lymph node enlargement also occurs due to
525
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526 ADVERSE EFFECTS OF VACCINES: EVIDENCE AND CAUSALITY
swelling and inflammation, and the individual may present with a “bulk
neck” appearance (Vitek and Wharton, 2008).
While diphtheria in the respiratory tract is the most common manifesta-
tion, aural, conjunctival, cutaneous, and vaginal diphtheria can also occur
and taken together account for approximately 2 percent of diphtheria cases
(Vitek and Wharton, 2008).
The obvious consequences of diphtheria are manifested in the com-
plications that arise from the presence and subsequent shedding of the
membrane. In severe cases, the membrane may extend into the tracheo-
bronchial tree causing pneumonia and expiratory respiratory obstruction
and membrane aspiration (Vitek and Wharton, 2008). Other complica-
tions are caused by the effect of the absorbed diphtheria toxin on organs
and organ systems proportional to the severity of the disease (Vitek and
Wharton, 2008). Evidence of myocarditis has been found in up to 66
percent of patients with 10 to 25 percent developing clinically significant
cardiac dysfunction (MacGregor, 2010). Neuropathy occurs rarely in mild
disease but occurs in up to 75 percent of patients with severe diphtheria
(MacGregor, 2010). Hypotension, pneumonia, and renal failure are also
common in severe cases, while encephalitis and cerebral infarction has been
described in rare cases (MacGregor, 2010). Death occurs most frequently
within 3 to 4 days from disease onset and is most often caused by asphyxia
or myocarditis (MacGregor, 2010).
Immunization with diphtheria toxoid has dramatically altered the epi-
demiology of diphtheria in the United States and data obtained from the
1988–1994 National Health and Nutrition Examination Survey (NHANES)
III serosurvey indicated that 80 percent of persons age 12 to 19 years were
immune to diphtheria (McQuillan et al., 2002).
The first vaccine against diphtheria was developed in the early 1800s
and was widely used in the United States as early as 1914 (Vitek and
Wharton, 2008). The vaccine consisted of a toxin-antitoxin formulation
and was found to be 85 percent effective in preventing diphtheria (Vitek
and Wharton, 2008). In the 1920s, Ramon found that by treating the
toxin with formalin and creating the toxoid, the toxicity of the prepara-
tion could be reduced while maintaining the immunogenic properties (Vitek
and Wharton, 2008). In 1926, Glenny and his associates discovered that
alum-precipitated toxoid was even more effective, and by the mid-1940s
diphtheria toxoid was being combined with tetanus toxoid and whole-cell
pertussis vaccine to create the diphtheria-tetanus-pertussis (DTP) vaccine
(Vitek and Wharton, 2008). Soon after, the DTP combination vaccine was
adsorbed onto an aluminum salt and researchers noted the enhanced immu-
nogenicity of the diphtheria and tetanus toxoid in the presence of pertussis
vaccine and the aluminum salt (Vitek and Wharton, 2008).
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527
DT–, TT–, AND aP–CONTAINING VACCINES
Tetanus Toxoid
Unique among the vaccine-preventable diseases, tetanus is not transmis-
sible from person to person (Wassilak et al., 2008). The disease is caused
by the gram-positive spore forming bacillus Clostridium tetani, which is
widespread throughout the environment, particularly in the soil (Wassilak
et al., 2008). C. tetani spores are introduced into the body through direct
contact with compromised tissues, where they germinate and produce a
plasmid-encoded exotoxin that binds to gangliosides at the myoneural
junction of skeletal muscle and on neuronal membranes in the spinal cord,
blocking inhibitory impulses to motor neurons (AAP, 2009; Wassilak et al.,
2008). “The action of tetanus toxin on the brain and sympathetic nervous
system is less well documented” (AAP, 2009).
The incubation period for tetanus can range from 1 day to several
months but generally lasts 3 to 21 days (Weinstein, 1973). Shorter incu-
bation periods are associated with more severe disease, while incubation
periods of 10 or more days generally result in milder disease (Adams, 1968;
Bruce, 1920; Garcia-Palmieri and Ramirez, 1957; LaForce et al., 1969).
There are three clinical descriptions of C. tetani infection: generalized,
localized, and cephalic. Generalized tetanus occurs in more than 80 percent
of all tetanus cases (Wassilak et al., 2008). Trismus (lockjaw) caused by
spasm of the facial muscles is the most common manifestation of general-
ized tetanus (Newton-John, 1984; Pratt, 1945; Weinstein, 1973). Trismus
may be followed by muscle spasms in other parts of the body including the
neck, back, and abdomen (Wassilak et al., 2008). Tetanospasm, also known
as generalized tonic tetanic seizure-like activity, is a sudden contraction of
all the muscle groups and can occur in the presence of mild external stimuli
such as sudden noise (Wassilak et al., 2008). In addition to these spasms,
those with severe tetanus are at risk of developing severe autonomic nervous
system abnormalities including diaphoresis, high or low blood pressure,
flushing, and cardiac complications (Hollow and Clarke, 1975; Kanarek
et al., 1973; Kerr et al., 1968). Tetanus neonatorum is the most com-
mon manifestation of generalized tetanus and occurs when the bacterium
infects the umbilical stump (Wassilak et al., 2008). Typically manifesting
3 to 14 days after birth, tetanus neonatorum begins with excessive crying
and decreased sucking capability, and is followed by trismus, difficulty
swallowing, and tetanic spasm (Wassilak et al., 2008). Infants who survive
this disease may experience neurologic damage and may also develop in-
tellectual and behavioral abnormalities (Anlar et al., 1989; Barlow et al.,
2001; Okan et al., 1997; Teknetzi et al., 1983). Localized tetanus is rare in
humans and involves muscle spasms confined to areas. These spasms may
last several months before subsiding or developing to generalized tetanus
(Millard, 1954). Cephalic tetanus is associated with lesions on the head or
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528 ADVERSE EFFECTS OF VACCINES: EVIDENCE AND CAUSALITY
face in line with the facial nerve and orbits (Weinstein, 1973). Considered
a form of localized tetanus, incubation is complete in 1 to 2 days after the
initial insult, which is most often a head wound (Weinstein, 1973).
Following the widespread use of tetanus toxoid–containing vaccines,
tetanus infections have become an uncommon occurrence in the United
States. In 1947, the incidence of reported cases was 0.39 per 100,000 in the
United States (Wassilak et al., 2008). This number dropped dramatically,
and from 1998 to 2000, the average incidence was approximately 0.16
cases per 1,000,000 representing a 96 percent decrease in the incidence
rate (CDC, 2003).
Tetanus infections peak in midsummer and are more common in warm,
damp climates. This is likely due to soil conditions and increased expo-
sure to spores as well as increased injuries that occur during the summer
months (Axnick and Alexander, 1957; Bytchenko, 1966; Heath et al., 1964;
LaForce et al., 1969).
Although described by the ancient Egyptians and Greeks, the origin
of tetanus disease was not described until 1884 when Carle and Rattone
showed that tetanus symptoms could be induced in rabbits when inoculated
with pustular fluid from a fatal case of human tetanus (Wassilak et al.,
2008). In the late 1800s, C. tetani spores were shown to survive heating
and germinate in anaerobic environments, and the repeated inoculation
with small quantities of toxin led to antibody production that was able to
neutralize the effects of tetanus toxin (Wassilak et al., 2008). In 1924, the
tetanus toxoid created by chemically inactivating the tetanus toxin was
shown to induce active immunity to tetanus disease prior to exposure to
the pathogen (Wassilak et al., 2008).
Currently, commercial tetanus toxoid is produced by culturing C. tet-
ani in liquid medium and transforming the purified toxin with 40 percent
formaldehyde at 37°C (Wassilak et al., 2008). In the United States, tetanus
toxoid vaccines are available as a single tetanus toxoid vaccine (TT) (Sanofi
Pasteur) and in combination with diphtheria toxoid as DT/Td, acellular
pertussis as DTaP/Tdap, and as DTaP with other antigens such as Hae-
mophilus influenzae B (HiB) conjugate (Wassilak et al., 2008).
Pertussis Antigen
Pertussis (whooping cough) is an upper respiratory infection caused by
Bordetella pertussis, a gram-negative, pleomorphic bacillus that attaches to
cells lining the respiratory tract (Edwards and Decker, 2008). B. pertussis is
not a particularly invasive bacterium and typically does not penetrate sub-
mucosal cells or the bloodstream, although toxins secreted by the bacteria
may produce systemic effects (Edwards and Decker, 2008).
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529
DT–, TT–, AND aP–CONTAINING VACCINES
The incubation period lasts 7 to 10 days, and pertussis disease is trans-
mitted by large respiratory droplets (Waters and Halperin, 2010). B. per-
tussis infections range from asymptomatic to severe. Symptomatic disease
is characterized by three phases: catarrhal, paroxysmal, and convalescent
(Gordon and Hood, 1951). The catarrhal phase lasts 1–2 weeks; symp-
toms of this phase may include nasal discharge, eye redness, and frequent
coughing and sneezing (Gordon and Hood, 1951; Waters and Halperin,
2010). The paroxysmal phase is characterized by periods of intense cough-
ing (paroxysms) that may lead to choking, vomiting, and an inspiratory
whoop (Gordon and Hood, 1951; Waters and Halperin, 2010). This phase
may last 2–6 weeks, as does the convalescent phase during which the symp-
toms decline. Fever is rare in pertussis infection and usually results from a
secondary infection or co-infection (Gordon and Hood, 1951; Waters and
Halperin, 2010).
According to Cortese and her colleagues (2008), apnea and respira-
tory arrest was the most common complication of pertussis followed by
pneumonia and gastroesophageal reflux. Pneumonia is the most common
complication in hospitalized patients (Cortese et al., 2008). Encephalopathy
is a rare complication and occurs most often in younger patients (Waters
and Halperin, 2010). B. pertussis antibodies have been found in the ce-
rebrospinal fluid (CSF) of patients with pertussis encephalopathy (Grant
et al., 1998). Other complications include seizures, ataxia, aphasia, blind-
ness, deafness, subconjunctival hemorrhages, syncope, and rib fractures
(Waters and Halperin, 2010). Pertussis is most serious in infants less than
12 months of age, and the risk of death is highest among infants less than 6
months old (Cortese et al., 2008; Tanaka et al., 2003; Vincent et al., 1991;
Vitek et al., 2003).
B. pertussis was first isolated and grown in culture by Jules Bordet
and Octave Genou in 1906, and the first whole-cell pertussis vaccines were
licensed in the United States in 1914 (Edwards and Decker, 2008). These
vaccines were suspensions of killed bacteria and were improved upon by
Kendrick and her colleagues before being combined with diphtheria and
tetanus toxoids to produce DTP vaccine (Edwards and Decker, 2008). Ow-
ing to the reactogenicity of whole-cell vaccines, alternative vaccines were
sought, and the first acellular vaccine was developed in Japan (Edwards
and Decker, 2008). These vaccines were composed of purified filamentous
hemagglutin (FHA) and leukocytosis-promoting factor hemagglutin (Sato
et al., 1984) and were widely used in Japan starting in 1981. In 1996, acel-
lular pertussis vaccines were licensed in the United States. Currently, the
acellular pertussis vaccine is only available in combination with diphtheria
and tetanus in the United States.
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530 ADVERSE EFFECTS OF VACCINES: EVIDENCE AND CAUSALITY
Diphtheria Toxoid–, Tetanus Toxoid–, and
Pertussis Antigen–Containing Vaccines
Vaccines to prevent diphtheria, tetanus, and pertussis are available in
various formulations and are given in 0.5 mL doses (see Table 10-1). The
four most common combination vaccines are DTaP, Tdap, DT, and Td. Of
these vaccines, two (DTaP and DT) are given to children younger than 7
years of age, and two (Tdap and Td) are given to individuals 7 years or
older.1 The Advisory Committee on Immunization Practices (ACIP), the
American Academy of Pediatrics (AAP), and the American Academy of
Family Physicians recommend that children routinely receive a five-dose
series of vaccine against diphtheria, tetanus, and pertussis before age 7
years. ACIP recommends that the first four doses be administered at ages 2,
4, 6, and 15–18 months and the fifth dose at age 4–6 years (CDC, 1997).
Because the immunity provided by childhood diphtheria, tetanus,
and pertussis-containing vaccines is not lifelong, booster vaccinations are
needed to maintain disease immunity. These booster vaccinations of either
Td or Tdap, which in 2006 was recommended by the ACIP as a single-dose
booster for those who previously had not been vaccinated with Tdap, are
given every 10 years or after a tetanus exposure under certain circumstances
(CDC, 2008).
According to the National Immunization Survey from 2005 through
2009 more than 95 percent of children age 19 to 35 months had received
at least three doses of the DTP, DT, or DTaP vaccine and approximately
85 percent had received four doses (CDC, 2010b). In 2009, the National
Immunization Survey estimated that 76.2 percent of adolescents between
13 and 17 years of age had received at least one dose of the Td or Tdap
vaccines (CDC, 2010a).
One of the challenges the committee faced in assessing the safety of
diphtheria toxoid–, tetanus toxoid–, and acellular pertussis–containing
vaccines is that these particular antigens are often combined with other
antigens in a number of different formulations (see Table 10-1). This variety
at times made comparisons difficult. The committee was not charged with
reviewing the evidence regarding whole cell pertussis vaccine. When the
committee uses the phrase “diphtheria toxoid–, tetanus toxoid–, or acel-
lular pertussis–containing vaccine,” it is limiting the assessment to these
antigens.
1 Upper-case letters denote full-strength doses of diphtheria (D) and tetanus (T) toxoids and
pertussis (P) vaccines. Lower-case (d) and (p) denote reduced doses of diphtheria and pertussis
used in the adolescent/adult formulations. The (a) in DTaP and Tdap stands for “acellular,”
meaning that the pertussis component contains only a part of the pertussis organism (CDC,
1997).
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TABLE 10-1 Diphtheria Toxoid–, Tetanus Toxoid–, and Acellular Pertussis–Containing Vaccines Licensed and
Available in the United States
Trade Dose Age
Vaccine Name Manufacturer (Presentation) Antigen Concentration Preservative Group Doses Route
DT No Trade Sanofi Pasteur, Inc 0.5 mL (single- 6.7 LF diphtheria toxoid; 6 weeks– 3 or 4* Intramuscular
≤ 0.3 µg
Name dose vials) 5 LF tetanus toxoid Hg/0.5 mL 6 years
dose
DT No Trade Sanofi Pasteur, Inc 0.5 mL (single- 25 LF diphtheria toxoid; 0 6 weeks– 5 Intramuscular
Name dose vials) 5 LF tetanus toxoid 6 years
DTaP Tripedia Sanofi Pasteur, Inc 0.5 mL (single- 6.7 LF diphtheria toxoid; 6 weeks– 5 Intramuscular
≤ 0.3 µg
dose vials) 5 LF tetanus toxoid; Hg/ 6 years
23.4 µg PT; 0.5 mL
23.4 µg FHA dose
DTaP Infanrix GlaxoSmithKline 0.5 mL (single- 25 LF diphtheria toxoid; 0 6 weeks– 5 Intramuscular
Biologicals dose vials and 10 LF tetanus toxoid; 6 years
syringes) 25 mg pertussis toxin;
25 mg FHA;
8.0 mg pertactin
DTaP DAPTACEL Sanofi Pasteur, Ltd 0.5 mL (single- 15 LF diphtheria toxoid; 0 6 weeks– 5 Intramuscular
dose vials) 5 LF tetanus toxoid; 6 years
10 mg pertussis toxin;
5 mg FHA;
3 mg PRN;
5 mg FIM
531
continued
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TABLE 10-1 Continued
532
Trade Dose Age
Vaccine Name Manufacturer (Presentation) Antigen Concentration Preservative Group Doses Route
DTaP- Pediarix GlaxoSmithKline 0.5 mL (single- 25 LF diphtheria toxoid 0 6 weeks– 3 Intramuscular
IPV-Hep Biologicals dose vials and 10 LF tetanus toxoid; 6 years
B syringes) 25 µg pertussis toxin;
25 µg FHA;
8 µg pertactin;
10 µg HBsAg;
40 DU type 1 poliovirus;
8 DU type 2 poliovirus;
32 DU type 3 poliovirus
DTaP-IPV KINRIX GlaxoSmithKline 0.5 mL (single- 25 LF diphtheria toxoid 0 4–6 years Booster Intramuscular
Biologicals dose vials and 10 LF tetanus toxoid;
syringes) 25 µg pertussis toxin;
25 µg FHA;
8 µg pertactin;
40 DU type 1 poliovirus;
8 DU type 2 poliovirus;
32 DU type 3 poliovirus
DTaP- Pentacel Sanofi Pasteur 0.5 mL 15 LF diphtheria toxoid; 0 6 weeks– 4 Intramuscular
IPV-Hib Limited (two vials: 5 LF tetanus toxoid; 4 years
combination 20 µg PT;
of DTaP- 20 µg FHA;
IPV vaccine 3 µg PRN;
and ActHIB 5 µg FIM;
vaccine) 40 DU type 1 poliovirus;
8 DU type 2 poliovirus;
32 DU type 3 poliovirus;
10 mg PRP of HiB bound
to 24 mg tetanus toxoid
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Td No Trade MassBiologics 0.5 mL (single- 2 LF tetanus toxoid; 3 and/ Intramuscular
≤ 0.3 µg ≥ 7 years
Name dose vials) 2 LF diphtheria toxoid Hg/0.5 mL or
dose booster
Td DECAVAC Sanofi Pasteur, Inc 0.5 mL (single- 5 LF tetanus toxoid; 3 and/ Intramuscular
≤ 0.3 µg ≥ 7 years
dose vials and 2 LF diphtheria toxoid Hg/0.5 mL or
syringes) dose booster
TT No Trade Sanofi Pasteur, Inc 0.5 mL (7.5 4 LF tetanus toxoid 25 µg Booster Intramuscular
≥ 7 years
Name mL 15 dose Hg/0.5 mL or Subcutaneous
vials) dose
Tdap Adacel Sanofi Pasteur, Ltd 0.5 mL (single- 5 LF tetanus toxoid; 0 11–64 Booster Intramuscular
dose syringes) 2 LF diphtheria toxoid; years
2.5 µg PT;
5 µg FHA;
5 µg FIM;
3 µg PRN
Tdap Boostrix GlaxoSmithKline 0.5 mL (single- 5 LF tetanus toxoid; 0 Booster Intramuscular
≥ 10
Biologicals dose vials and 2.5 LF diphtheria toxoid; years
syringes) 8 µg PT;
8 µg FHA;
2.5 µg PRN
*This vaccine is given in a five-dose series to infants between the ages of 6 weeks and 12 months, and a three-dose series in children 1 to 6 years
of age.
SOURCE: GlaxoSmithKline, 2010a,b,c, 2011; MassBiologics, 2009; Sanofi Pasteur, Inc., 2005a,b,c, 2008, 2009, 2010a,b, 2011.
533
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534 ADVERSE EFFECTS OF VACCINES: EVIDENCE AND CAUSALITY
ENCEPHALITIS AND ENCEPHALOPATHY
Epidemiologic Evidence
The committee reviewed nine studies to evaluate the risk of encephalitis
or encephalopathy after the administration of vaccines containing diphthe-
ria toxoid, tetanus toxoid, and acellular pertussis antigens alone or in com-
bination. Seven studies (Geier and Geier, 2004; Gold et al., 1999; Isomura,
1991; Kuno-Sakai and Kimura, 2004; Rosenthal et al., 1996; Stetler et al.,
1985; Zielinski and Rosinska, 2008) were not considered in the weight of
epidemiologic evidence because they provided data from passive surveil-
lance systems and lacked unvaccinated comparison populations.
The two remaining controlled studies (Greco, 1985; Yih et al., 2009)
contributed to the weight of epidemiologic evidence and are described
below.
Greco (1985) conducted a case-control study in children (3 to 48
months of age) admitted to the Santobono Hospital in Campania, Italy,
from January 1980 through February 1983. The cases were identified
from the hospital intensive care unit register. Patients were included as an
encephalopathy case if they were admitted to the intensive care unit for the
following diagnoses, which were obtained from medical records: Reye’s
syndrome, coma due to unknown causes, convulsions due to unknown
causes, death due to unknown causes, or stupor due to unknown causes.
Two hospital controls were matched to each case on age (within 6 months),
sex, and date of admission (within 30 days), and had confirmed diagnoses
different from the cases. Two residence controls from the national birth
register were matched to each case on age (within 1 month), sex, and place
of residence (by zone or by town), and were alive during the time cases
were hospitalized. A total of 45 cases, 90 matched hospital controls, and
90 matched residence controls were included in the analysis. Vaccination
histories for the cases and controls were obtained from an extensive search
of the national immunization register. During the 1 month preceding the
hospital admission, 64 percent, 10 percent, and 13 percent of the cases,
hospital controls, and residence controls received a diphtheria and tetanus
toxoids vaccine, respectively. Oral polio vaccine was given at the same time
as the diphtheria and tetanus toxoids vaccine in 51 percent of the cases and
28 percent of the controls; however, the authors did not explicitly state that
other vaccinations were not also given. The odds ratio for encephalopathy
within 1 month of the administration of diphtheria and tetanus toxoids vac-
cine compared to the hospital controls was 291.9 (95% CI, 53.3–1,596.9)
and compared to the residence controls was 22.5 (95% CI, 8.2–62.1). The
authors observed an increased risk but concluded that the study design
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535
DT–, TT–, AND aP–CONTAINING VACCINES
was insufficient to infer a causal relationship between the administration of
diphtheria and tetanus toxoids vaccine and encephalopathy.
Yih et al. (2009) conducted a cohort study in patients (10 to 64 years
of age) enrolled in seven managed care organizations (MCOs) participat-
ing in the Vaccine Safety Datalink (VSD) from August 2005 through May
2008. The study investigated the occurrence of adverse events (reported
from outpatient, inpatient, and emergency department visits) following
Tdap vaccination. The exposed group included approximately 660,000
patients that received a Tdap vaccination. Diagnoses of encephalopathy,
encephalitis, and meningitis were obtained from the medical records and
included in the analysis if they occurred within 42 days of vaccination. The
disease incidence following Tdap vaccination was compared to the disease
incidence 1 to 42 days after Td vaccination in a historical VSD comparison
population; this could have introduced bias if coding practices or back-
ground disease incidences differed in the two cohorts. The comparison
group included approximately 890,000 patients that received a Td vac-
cine from 2000 through 2004. The observed number of encephalopathy–
encephalitis–meningitis events in the Tdap cohort (34 events) was less than
the historical Td cohort (40.33 events), which resulted in a relative risk of
0.84 (confidence interval not provided). The authors concluded that the
risk of encephalopathy–encephalitis–meningitis following Tdap vaccination
is not significantly higher than the risk following Td vaccination, which
only provides information on the safety of the acellular pertussis antigen
component.
Weight of Epidemiologic Evidence
Greco et al. (1985) investigated the association of diphtheria and teta-
nus toxoids vaccine with encephalopathy; however, 50 percent of the cases
considered had oral polio given with the diphtheria and tetanus toxoids vac -
cine, and it is not clear if any other vaccines were administered at the same
time. Additionally, the case definition included a wide range of diagnoses.
The paper by Yih et al. (2009) found no increased risk of encephalopathy–
encephalitis–meningitis after Tdap vaccination compared to historical data
on this adverse event after Td vaccination, which only provided information
on the safety of the acellular pertussis antigen component.
The committee has limited confidence in the epidemiologic evi-
dence, based on two studies that lacked validity and precision, to
assess an association between diphtheria toxoid–, tetanus toxoid–,
or acellular pertussis–containing vaccine and encephalitis or
encephalopathy.
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TABLE 10-6 Continued
588
Studies Contributing Cases Contributing
Epidemiologic to the Epidemiologic Mechanistic to the Mechanistic Causality
Vaccine Adverse Event Assessment Assessment Assessment Assessment Conclusion
DT, TT, or Arthropathy Limited 2 Lacking None Inadequate
aP containing (diphtheria toxoid
or tetanus toxoid)
Insufficient None
(acellular pertussis)
DT, TT, or Type 1 Diabetes High 5 Lacking None Favors
aP containing (null) Rejection
DT, TT, or Myocarditis Insufficient None Weak None Inadequate
aP containing (diphtheria toxoid)
Lacking None
(tetanus toxoid or
acellular pertussis)
DT, TT, or Fibromyalgia Insufficient None Lacking None Inadequate
aP containing
DT, TT, or Sudden Infant Death Insufficient None Lacking None Inadequate
aP containing Syndrome
DT, TT, or Immune Thrombocytopenic Insufficient None Lacking None Inadequate
aP containing Purpura
*Although not originally charged to the committee by the sponsor, the committee considered this adverse event in its review of the literature.
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589
DT–, TT–, AND aP–CONTAINING VACCINES
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