DIPHTHERIA

At one time, diphtheria was common in the United States. More than
200,000 cases, primarily among children, were reported in 1921.
Approximately 5%-10% of cases were fatal; the highest case-fatality
ratios were recorded for the very young and the elderly. Reported
cases of diphtheria of all types declined from 306 in 1975 to 59 in
1979; most were cutaneous diphtheria reported from a single state (3).
After 1979, cutaneous diphtheria was no longer notifiable. From 1980
to 1989, only 24 cases of respiratory diphtheria were reported; two
cases were fatal, and 18 (75%) occurred among persons greater than or
equal to 20 years of age.

Diptheria is currently a rare disease in the United States primarily
because of the high level of appropriate vaccination among children
(97% of children entering school have received greater than or equal
to three doses of diphtheria and tetanus toxoids and pertussis vaccine
(DTP)) and because of an apparent reduction in the circulation of
toxigenic strains of Corynebacterium diphtheriae. Most cases occur
among unvaccinated or inadequately vaccinated persons. The age
distribution of recent cases and the results of serosurveys indicate
that many adults in the United States are not protected against
diphtheria. Limited serosurveys conducted since 1977 indicate that
22%-62% of adults 18-39 years of age and 41%-84% of those greater than
or equal to 60 years of age may lack protective levels of circulating
antitoxin against diphtheria (4-7). Thus, it appears that further
reductions in the incidence of diphtheria would require more emphasis
on adult immunization programs. Both toxigenic and nontoxigenic
strains of C. diphtheriae can cause disease, but only strains that
produce toxin cause myocarditis and neuritis. Furthermore, toxigenic
strains are more often associated with severe or fatal illness in
noncutaneous (respiratory or other mucosal surface) infections and are
more commonly recovered in association with respiratory than from
cutaneous infections.

C. diphtheriae can contaminate the skin, usually at the site of a
wound. Although a sharply demarcated lesion with a pseudomembranous
base often results, the appearance may not be distinctive, and
infection can be confirmed only by culture. Usually other bacterial
species can also be isolated. Cutaneous diphtheria has most commonly
affected indigent adults and certain groups of American Indians.

A complete vaccination series substantially reduces the risk of
developing diphtheria, and vaccinated persons who develop disease have
milder illnesses. Protection lasts at least 10 years. Vaccination does
not, however, eliminate carriage of C. diphtheriae in the pharynx or
nose or on the skin.

TETANUS

The occurrence of tetanus in the United States has decreased
dramatically from 560 reported cases in 1947, when national reporting
began, to a record low of 48 reported cases in 1987 (8). The decline
has resulted from widespread use of tetanus toxoid and improved wound
management, including use of tetanus prophylaxis in emergency rooms.

Tetanus in the United States is primarily a disease of older adults.
Of 99 tetanus patients with complete information reported to CDC
during 1987 and 1988, 68% were greater than or equal to 50 years of
age, while only six were less than 20 years of age. No cases of
neonatal tetanus were reported. Overall, the case-fatality rate was
21% (8). The age distribution of recent cases and the results of
serosurveys indicate that many U.S. adults are not protected against
tetanus. Serosurveys undertaken since 1977 indicate that 6%-11% of
adults 18-39 years of age and 49%-66% of those greater than or equal
to 60 years of age may lack protective levels of circulating tetanus
antitoxin (4-7). The disease continues to occur almost exclusively
among persons who are unvaccinated or inadequately vaccinated or whose
vaccination histories are unknown or uncertain (8).

Surveys of emergency rooms suggest that 1%-6% of all persons who
receive medical care for injuries that can lead to tetanus receive
less than the recommended prophylaxis (9,10). In 1987-1988, 58% of
tetanus patients with acute injuries did not seek medical care for
their injuries; of those who did, 81% did not receive prophylaxis as
recommended by ACIP guidelines (8).

In 4% of tetanus cases reported during 1987 and 1988, no wound or
other condition was implicated. Nonacute skin lesions such as ulcers,
or medical conditions such as abscesses were reported in association
with 14% of cases.

Neonatal tetanus occurs among infants born under unhygienic conditions
to inadequately vaccinated mothers. Vaccinated mothers confer
protection to their infants through transplacental transfer of
maternal antibody. From 1972 through 1984, 29 cases of neonatal
tetanus were reported in the United States (11). No cases of neonatal
tetanus were reported in the period 1985-1989. Spores of Clostridium
tetani are ubiquitous. Serologic tests indicate that naturally
acquired immunity to tetanus toxin does not occur in the United
States. Thus, universal primary vaccination, with subsequent
maintenance of adequate antitoxin levels by means of appropriately
timed boosters, is necessary to protect persons among all age-groups.
Tetanus toxoid is a highly effective antigen; a completed primary
series generally induces protective levels of serum antitoxin that
persist for greater than or equal to 10 years.

PERTUSSIS

Disease caused by Bordetella pertussis was once a major cause of
infant and childhood morbidity and mortality in the United States
(12,13). Pertussis became a nationally notifiable disease in 1922, and
reports reached a peak of 265,269 cases and 7,518 deaths in 1934. The
highest number of reported pertussis deaths (9,269) occurred in 1923.
The introduction and widespread use of standardized whole-cell
pertussis vaccines combined with diphtheria and tetanus toxoids (DTP)
in the late 1940s resulted in a substantial decline in pertussis
disease, a decline which continued without interruption for nearly 30
years.

By 1970, the annual reported incidence of pertussis had been reduced
by 99%. During the 1970s, the annual numbers of reported cases
stabilized at an average of approximately 2,300 cases each year.
During the 1980s, however, the annual numbers of reported cases
gradually increased from 1,730 cases in 1980 to 4,157 cases in 1989.
An average of eight pertussis-associated fatalities was reported each
year throughout the 1980s. It is not clear whether the increase in
reported pertussis reflects a true increase in the incidence of the
disease or improvement in the reporting of pertussis. However, these
data underestimate the true number of cases, because many are
unrecognized or unreported, and diagnostic tests for B. pertussis --
culture and direct-immunofluorescence assay -- may be unavailable,
difficult to perform, or incorrectly interpreted. Because direct-
fluorescent-antibody testing of nasopharyngeal secretions has been
shown in some studies to have low sensitivity and variable
specificity, it should not be relied on as a criterion for laboratory
confirmation (14,15). In addition, reporting criteria have varied
widely among the different states. Laboratory diagnosis based on
serologic testing is not widely available and is still considered
experimental (16). In 1990, to improve the accuracy of reporting, the
U.S. Council of State and Territorial Epidemiologists adopted uniform
case definitions for pertussis (17).

Before widespread use of DTP, less than 20% of cases and 50%-70% of
pertussis deaths occurred among children less than 1 year of age
(13,18). For the period 1980-1989, 47% of reported illnesses from B.
pertussis occurred among children less than 1 year of age, and 72%
occurred among children less than 5 years of age; 61 (77%) of 79
deaths reported to CDC occurred among children less than 1 year of age
(19). Infants less than 2 months of age were at highest risk of
complications, with a case-fatality rate of 1.3%. Although incidence
based on reported cases increased among all age-groups during the
1980s, the most striking increases occurred among adolescents and
adults (19). Whether this represented a true increase or more complete
recognition and reporting is not clear.

Pertussis is highly communicable (attack rates of greater than 90%
have been reported among unvaccinated household contacts) and can
cause severe disease, particularly among very young children. Of
10,749 patients less than 1 year of age reported nationally as having
pertussis nationally during the period 1980-1989, 69% were
hospitalized, 22% had pneumonia, 3.0% had greater than or equal to one
seizure, 0.9% had encephalopathy, and 0.6% died (19). The high rate of
hospitalization for infants with pertussis has been observed in
several population-based studies (20-22). Because of the substantial
risks of complications of the disease, completion of a primary series
of DTP vaccine early in life is essential.

Among older children and adults, including those previously
vaccinated, B. pertussis infection may result in symptoms of
bronchitis or upper-respiratory-tract infection. Pertussis may not be
diagnosed because classic signs, especially the inspiratory whoop, may
be absent. Older preschool children and school-age siblings who are
not fully vaccinated and who develop pertussis can be important
sources of infection for infants less than 1 year of age. Adults also
play an important role in the transmission of pertussis to
unvaccinated or incompletely vaccinated infants and young children
(23).

Controversy regarding the safety of pertussis vaccine during the 1970s
led to several studies of the benefits and risks of this vaccination
during the 1980s. These epidemiologic analyses clearly indicate that
the benefits of pertussis vaccination outweigh any risks (24-28).

PREPARATIONS USED FOR VACCINATION

Diphtheria and tetanus toxoids are prepared by formaldehyde treatment
of the respective toxins and are standardized for potency according to
the regulations of the U.S. Food and Drug Administration. The limit of
flocculation (Lf) content of each toxoid (quantity of toxoid as
assessed by flocculation) may vary among different products. The
concentration of diphtheria toxoid in preparations intended for adult
use is reduced because adverse reactions to diphtheria toxoid are
apparently directly related to the quantity of antigen and to the age
or previous vaccination history of the recipient, and because a
smaller dosage of diphtheria toxoid produces an adequate immune
response among adults.

Pertussis vaccine is a suspension of inactivated B. pertussis cells.
Potency is assayed by comparison with the U.S. standard pertussis
vaccine in the intracerebral mouse protection test. The protective
efficacy of pertussis vaccines for humans has been shown to correlate
with this measure of vaccine potency.

Diphtheria and tetanus toxoids and pertussis vaccine, as single
antigens or various combinations, are available as aluminum-salt-
adsorbed preparations. Only tetanus toxoid is available in nonabsorbed
(fluid) form. Although the rates of seroconversion are essentially
equivalent with either type of tetanus toxoid, the adsorbed toxoid
induces a more persistent level of antitoxin antibody. The following
preparations are currently available in the United States:

Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (DTP)
and Diphtheria and Tetanus Toxoids Adsorbed (DT) (for pediatric use)
are for use among infants and children less than 7 years of age. Each
0.5-mL dose is formulated to contain 6.7-12.5 Lf units of diphtheria
toxoid, 5 Lf units of tetanus toxoid, and less than or equal to 16
opacity units of pertussis vaccine. A single human immunizing dose of
DTP contains an estimated 4-12 protective units of pertussis vaccine.

Tetanus and Diphtheria Toxoids Adsorbed for Adult Use (Td) is for use
among persons greater than or equal to 7 years of age. Each 0.5-mL
dose is formulated to contain 2-10 Lf units of tetanus toxoid and less
than or equal to 2 Lf units of diphtheria toxoid.

Pertussis Vaccine Adsorbed (P), * Tetanus Toxoid (fluid), Tetanus
Toxoid Adsorbed (T), and Diphtheria Toxoid Adsorbed (D) ** (for
pediatric use), are single-antigen products for use in special
instances when combined antigen preparations are not indicated.

____________

Distributed by the Division of Biologic Products, Michigan Department
of Public Health. Contact Dr. Robert Myers, Chief, Division of
Biologic Products, Bureau of Laboratories and Epidemiological
Services, Michigan Department of Public Health, Lansing, Michigan
48909 (telephone: 517-335-8120).

http://www.cdc.gov/mmwr/preview/mmwrhtml/00041645.htm