WILLIAM SCHAFFNER, MD Chairman, Department of Preventive Medicine, and Professor of Medicine, Department of Medicine, Vanderbilt University School
of Medicine, Nashville, Tenn.
TIMOTHY F. JONES, MD Deputy State Epidemiologist, Communicable and Environmental Disease Services, Tennessee Department of Health, Nashville,
Tenn.
The dramatic decline in the occurrence of both tetanus and diphtheria in the United States during the second half of the 20th
century is attributable mainly to the widespread institution of routine childhood vaccinations. The risk for developing these
preventable infections, however, persists among those who have not been adequately immunized with tetanus and diphtheria (Td)
vaccine. Results from the Third National Health and Nutrition Examination Survey (NHANES III) showed that many Americans—most
prominently older adults—have antibody levels that are not considered to be protective against tetanus and diphtheria.1 Approximately 30% of the more than 25 million Americans older than 69 are optimally protected against both diseases.1,2 Further, in 1995 only 36% of people 65 or older reported that they had received a tetanus vaccination within the previous
10 years.3
Immunization with Td vaccine is particularly important for the more than 45 million American adults who are older than 60
since
- The highest rate of tetanus and tetanus-related deaths from 1998 through 2000 was among adults older than 59 years.4
- Persons born in the United States before the 1940s—when childhood immunization against diphtheria, tetanus, and pertussis
became routine—may never have received a primary series of Td vaccinations.
- Tetanus can develop as a consequence of seemingly simple wounds, such as the small cuts and scrapes from everyday activities.
- The immune response diminishes with age, particularly in the presence of chronic conditions.
Protecting older patients against tetanus and diphtheria requires awareness of their immunization status and administering
primary and booster vaccination as appropriate. A routine and comprehensive office-based vaccination program should be in
place so that immunization practices are applied consistently to all patients.
Tetanus Tetanus is an acute, potentially fatal disease that is responsible for an estimated 300,000 neonatal deaths and 50,000 maternal
deaths worldwide each year. In the United States, the disease occurs infrequently: Only 25 cases were reported in 2003, and
an average of 43 cases were reported annually from 1998 through 2000.4-6 Death due to tetanus occurs most often in persons aged 70 and older.4
Tetanus is caused by tetanospasmin, a toxin produced when spores of Clostridium tetani germinate. C tetani, commonly found in soil and animal feces, is a normal intestinal resident of humans and other mammals and is extremely hardy.
It can enter the body through a wound—typically a puncture, laceration, or abrasion—or even with a simple splinter or scratched
cornea. Such wounds may often go unrecognized or untreated by older adults. Tetanus can also occur through injection drug
use, tattooing or body piercing, minor surgical procedures, or dental work.7 Diabetic vascular insufficiency ulcers, which are more common among older adults, are also susceptible to C tetani infection. Of 130 reported cases of tetanus during 1998 to 2000, 16 (12%) occurred in diabetic patients with a median age
of 72.4
Symptoms of tetanus may appear from 3 to 21 days after exposure; generally the incubation period is longer when the anatomic
location of the injury is distant from the CNS. A shorter incubation period correlates with a higher risk of death. Among
the initial symptoms of tetanus is jaw muscle rigidity (lockjaw), which is then followed by neck stiffness; difficulty swallowing,
chewing, and speaking; and abdominal muscle rigidity. The temperature may rise several degrees above normal and may be accompanied
by sweating, elevated BP, and rapid heart rate. Muscle spasms that last several minutes may be so severe that they cause fractures
of the long bones or spinal vertebrae.7 Laryngeal muscle spasm leads to respiratory compromise and consequent nosocomial pneumonia (see "A rare case of tetanus").
Patients with tetanus are likely to need weeks in an intensive care unit and to incur high health care costs. In addition
to an often long and difficult physical recovery, these patients may experience psychological problems, such as depression,
associated with recovery from a long illness.
Although the incidence of tetanus in the United States is low, preventive immunization is key to further reducing its occurrence.
Wound management is insufficient for this purpose, because many injuries that result in tetanus typically neither warrant
nor receive professional medical attention. A CDC summary of tetanus cases from 1998 through 2000 found that only 37% of patients
with acute injuries sought medical attention for the injury; of those who did, only 63% of eligible patients received tetanus
toxoid as wound prophylaxis. Many of the injuries were likely to be considered mild and had occurred in persons inadequately
immunized.4 Wound management with tetanus immune globulin and tetanus toxoid after exposure does not always prevent the onset of disease.
In addition, because C tetani is ubiquitous in the environment, a need for immunization will always exist. Few cases of tetanus have occurred in people
with a documented primary immunization series with tetanus toxoid.7
Diptheria Diphtheria is caused by a toxin produced by Corynebacterium diphtheriae, an aerobic, gram-positive bacillus. Diphtheria toxin inhibits the synthesis of cellular proteins and causes local tissue
destruction. Only toxigenic strains cause severe disease; nontoxigenic strains produce milder symptoms.8 The organism, which can invade any mucous membrane, is spread through close contact with infected persons. The sites most
commonly infected are the nasal passages and nasopharynx. A patient who has respiratory diphtheria, the most common form,
presents with a sore throat, low-grade fever, and an adherent, leathery membrane that may partly or completely obstruct the
nasopharynx. Respiratory diphtheria is associated with systemic absorption of the toxin, which spreads through the bloodstream
and can damage the heart, nervous system, and kidneys. Sequelae may include myocarditis, respiratory paralysis, coma, and
sudden death. Cutaneous diphtheria is characterized by infected skin lesions that may resemble cigarette burns.
Before the institution of routine diphtheria-tetanus-pertussis (DTP) vaccination for children in the United States in the
1940s, diphtheria was a dreaded childhood disease with an incidence of 100 to 200 cases per 100,000 population.9 The subsequent marked reduction of diphtheria in children, who often served as the transmission vectors, contributed to a
decrease in the occurrence of adult disease. Although only 53 cases of diphtheria were reported in the United States between
1980 and 2000, some strains of the organism continue to circulate in Native American communities.6 Multiple strains of C diphtheriae documented in a Northern Plains Indian community in 1996 were closely related to an outbreak between 1979 and 1983, suggesting
the continuous presence of the organism in the community despite a prolonged absence of reported cases.10
Diphtheria is still active in more than 80 countries that are just an airplane ride away, and the mortality rate for the disease
can be as high as 20%. A recent case of a US citizen who was found to have diphtheria after returning from foreign travel
illustrates the importance of maintaining protection against the disease through primary immunization and routine booster
inoculation. In October 2003, the CDC reported a case of respiratory diphtheria in a 63-year-old Pennsylvania man who had
visited Haiti, where diphtheria is still common. On returning, the man was admitted to a hospital with a severe sore throat
and respiratory distress, and he died after the diagnosis of respiratory diphtheria was made. The clinical efficacy of the
diphtheria vaccine is 97%, but this man had never been immunized.11
In the 1990s, a massive outbreak of diphtheria occurred in the former Soviet Union after the disease had been well-controlled
for decades.9,12 More than 157,000 cases and 5000 deaths were attributed to several factors, including the absence of routine adult booster
vaccinations.9,13,14 This epidemic is a compelling illustration of diphtheria's devastating effects in an industrialized society where population
immunity has faltered.15
Figure 1: Protection against tetanus and diptheria declines with age.
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The prevalence of immunity A recent study examining data from NHANES III found that only 47% of American adults older than 19 had antibody levels that
are considered to be protective against both tetanus and diphtheria (see Figure 1).1 Only 30% of those older than 69 were found to have adequate levels of antibody against both diseases.1 Yet, older adults have the highest case-fatality rate for tetanus.4The lower prevalence of tetanus and diphtheria immunity among older adults can be attributed to several factors. First, childhood
DTP immunization was not routine in the United States until the 1940s, and so many older adults today never received a primary
vaccination series as children. Second, the decline in the prevalence of tetanus and diphtheria immunity after age 60 is more
pronounced among women, who are less likely than men to have received immunization in conjunction with military service or
consequent to an injury. Finally, the 2000 census reported that approximately 11% of persons in the United States were foreign
born.16 Many of these people may have emigrated from countries that lack adequate preventive health care.
Recommendations for Td immunization For immunization in adults, the CDC's Advisory Committee on Immunization Practices (ACIP) recommends the use of dual antigen
(Td) vaccine over the single antigen tetanus toxoid (Tt) vaccine.17 No evidence exists that the combined preparation carries an increased risk of adverse reactions, and the monovalent Tt vaccine
no longer has a cost advantage over the combined Td preparation.
All adults should receive a Td booster vaccination every 10 years.17 Those with an unknown or uncertain immunization history should receive a primary Td vaccine series of 3 inoculations: The
first dose is followed at least 4 weeks later by the second, and the final dose is given 6 to 12 months after the second dose.
Booster vaccinations should be given every 10 years thereafter.17 The only contraindication to Td vaccination is a history of neurologic or severe hypersensitivity reaction after a previous
dose. Common local reactions at the injection site—erythema, induration, or pain—are generally self-limited and require no
treatment.7,8
Putting Td immunization into practice An immunization history should be obtained from every patient, and administration of booster doses of the Td vaccine every
10 years should be standard in every practice. Every patient visit presents an opportunity to review the immunization history
and provide protection against tetanus and diphtheria as appropriate.
Studies on improving immunization rates in clinical practice have found that the most successful of these efforts combine
enhancement of patient awareness, education of nonphysician health care staff, and easing of financial and administrative
barriers to vaccination wherever possible.18 Computer-based reminder systems have also proved effective in increasing adherence to preventive services in primary care
settings.19
The Put Prevention Into Practice (PPIP) program is disseminated by the Agency for Healthcare Research and Quality (AHRQ) to
help physicians increase patients' appropriate use of clinical preventive services, such as screening tests, immunizations,
and counseling, based on recommendations from the US Preventive Services Task Force.20 The program consists of research-based materials for providers, patients, and office staff, including flowcharts for staff
to document services rendered and personal health guides for patients. The PPIP program has been found to significantly increase
the rate of Td immunizations and other selected clinical preventive services.21 Information about the PPIP program is available on the AHRQ Web site at http:// www.ahrq.gov/clinic/ppipix.htm .
This article was contributed by Dr Schaffner and
Dr Jones and edited by Julia Muino Russell.
Dr Schaffner and Dr Jones disclose that they have no financial involvements with any companies doing business in this field.
REFERENCES 1. McQuillan GM, Kruczon-Moran D, et al. Serologic immunity to diphtheria and tetanus in the United States. Ann Intern Med. 2002;136:660-666.
2. US Census Bureau. Census 2000 Summary File 1, Matrices P13 and PCT12. Available at: http://factfinder.census.gov . Accessed September 8 2004
3.Centers for Disease Control and Prevention. Tetanus surveillance—United States, 1995-1997. MMWR Morb Mortal Wkly Rep. 1998;47(SS-2):1-13.
4. Centers for Disease Control and Prevention. Tetanus surveillance—United States, 1998-2000. MMWR Morb Mortal Wkly Rep. 2003;52(SS-3):1-8.
5. World Health Organization. Vaccines, immunization, and biologicals: tetanus toxoid vaccine. Available at: http://www.who.int/vaccines/en/ tetanus.shtm . Accessed October 10, 2003.
6. Centers for Disease Control and Prevention. Summary of provisional cases of selected notifiable diseases, United States.
MMWR Morb Mortal Wkly Rep. 2003;52:1291.
7. National Immunization Program, Centers for Disease Control and Prevention, US Dept of Health and Human Services. Tetanus.
In: Epidemiology and Prevention of Vaccine-Preventable Diseases, the Pink Book. 8th ed. Waldorf, Md: Public Health Foundation; 2003:49-57. Available at: http:// www.cdc.gov/nip/publications/pink/def_pink_full.htm . Accessed September 8, 2004.
8. National Immunization Program, Centers for Disease Control and Prevention, US Dept of Health and Human Services. Tetanus.
In: Epidemiology and Prevention of Vaccine-Preventable Diseases, the Pink Book. 8th ed. Waldorf, Md: Public Health Foundation; 2003:39-48. Available at: http:// www.cdc.gov/nip/publications/pink/def_pink_full.htm . Accessed September 8, 2004.
9. Centers for Disease Control and Prevention. Diphtheria: technical information. Available at: http://www.cdc.gov/ncidod/dbmd/diseaseinfo/diptheria_t.htm . Accessed September 8, 2004.
10. Centers for Disease Control and Prevention. Toxigenic Corynebacterium diphtheriae—Northern Plains Indian Community, August-October 1996. MMWR Morb Mortal Wkly Rep. 1997;46:506-510.
11. Centers for Disease Control and Prevention Health Alert Network. Fatal respiratory diphtheria in a US traveler to Haiti—Pennsylvania,
2003. MMWR Morb Mortal Wkly Rep. 2004:52:1285-1286.
12. Vitek CR, Wharton M. Diphtheria in the former Soviet Union: reemergence of a pandemic disease. Emerg Infect Dis. 1998;4:539-550.
13. Bisgard KM, Rhodes P, Hardy IR, et al. Diphtheria toxoid vaccine effectiveness: a case-control study in Russia. .J Infect Dis. 2000;181(suppl 1):S184-S187.
14. Galazka A. The changing epidemiology of diphtheria in the vaccine era. J Infect Dis. 2000;18(suppl 1):S2-S9.
15. Golaz A, Hardy IR, Strebel P, et al. Epidemic diphtheria in the newly independent states of the former Soviet Union:
implications for diphtheria control in the United States. J Infect Dis. 2000;181(suppl 1):S237-S243.
16. US Census Bureau. United States Census 2000 Summary File 3 (SF 3). Available at: http:// www.census.gov/Press-Release/www/2002/sumfile3.
html. Accessed September 8, 2004.
17. Centers for Disease Control and Prevention. Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other
preventive measures recommendations of the Immunization Practices Advisory Committee. .MMWR Morb Mortal Wkly Rep.1991;40(RR10):1-28.
18. Zimmerman RK. Adult vaccination, part I: vaccines indicated by age. Teaching Immunization for Medical Education (TIME)
Project. J Fam Pract. 2000;49(suppl 9):S41-S50.
19. Ornstein SM, Garr DR, Jenkins RG, et al. Computer-generated physician and patient reminders: tools to improve population
adherence to selected preventive services. J Fam Pract. 1991;32:82-90.
20. Agency for Healthcare Research and Quality. Put Prevention Into Practice. A Step-by-Step Guide to Delivering Clinical
Preventive Services: A Systems Approach. Available at: http://www.ahrq.gov/clinic/ppipix.
htmAccessed September 8, 2004.
21. Gottlieb NH, Huang PP, Blozis SA, et al. The impact of Put Prevention Into Practice on selected clinical preventive services
in five Texas sites. Am J Prev Med. 2001;21:35-40.
A rare case of tetanus A recent case of tetanus in a 76-year-old Vermont woman illustrates both the low prevalence of immunity among older patients
and the potential for misdiagnosis of the disease. The woman worked on a horse farm and had never been immunized against tetanus.
She presented to her local hospital on 3 occasions with leg, back, and jaw pain, and no obvious wounds. The disease was not
suspected until the symptoms were recognized by a physician who had grown up in Pakistan, where tetanus was common. A tracheostomy
was performed, and the patient received supportive care and antibiotic treatment. After 2 weeks of respirator support, she
spent 2 weeks in the intensive care unit, followed by 2 weeks of rehabilitation.1
1. P. Novotny, MD, Southwestern Vermont Medical Center, oral communication, October 28, 2003.
