The Dangers of Tetanus and Diphtheria Don't Overlook Them

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The Dangers of Tetanus and Diphtheria - Don't
Overlook Them
Susan Rehm, M.D. President, National Foundation
for Infectious Diseases
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Agenda

• Immunity to Tetanus Diphtheria Why the
  Concern?
• What is Tetanus?
• What is Diphtheria?
• Tetanus Diphtheria
• Medical Management
• Populations At Risk
• Vaccine Introduction
• ACIP Recommendations
• Adverse Reactions
• Contraindications Precautions
• Special Considerations
• Tetanus Diphtheria Case Studies
• Td Vaccine Shortage 2000-2002
• Conclusions

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Immunity to Tetanus and Diphtheria Why the
Concern?

• 72 of persons six years of age protected
  against tetanus and 60 protected against
  diphtheria
• Only 47 of persons 20 years of age protected
  against tetanus and diphtheria
• Tetanus immunity much lower in women (64) than
  in men (81)
• By 70 years of age, only 45 of men and 21 of
  women protected against tetanus

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Immunity to Tetanus and Diphtheria Why the
Concern?

• Men better protected against diphtheria, but
  diphtheria immunity decreases in all adults with
  age
• Low income, previous military service have lower
  diphtheria protection previous military service
  associated with increased tetanus protection
• People with good access to medical care less
  likely to be protected against both infections

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Immunity to Tetanus and Diphtheria Why the
Concern?

• Revaccination against diphtheria and tetanus is
  performed less frequently than recommended by the
  U.S. Advisory Committee on Immunization Practices
  (ACIP)
• Although diphtheria infections and tetanus are
  rare in U.S., both are highly fatal

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What is Tetanus?Pathogenesis Clinical Features

• Clostridium tetani (C. tetani)
• Anaerobic gram-positive, spore-forming bacteria
• Spores found in soil, dust and animal feces, and
  may persist for years
• While C. tetani organism is sensitive to heat and
  cannot survive in presence of oxygen, C. tetani
  spores are very resistant to heat and usual
  antiseptics
• C. tetani enters the body through a wound
• Infection takes hold in deep or large wounds
  (e.g., punctures, scrapes, burns)
• Average incubation period lasts 8 days (range, 3
  to 21 days)
• Multiple toxins, including tetanospasmin, are
  produced with growth of bacteria and disseminated
  via blood and lymphatics

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What is Tetanus?Pathogenesis Clinical Features

• Toxin binds within the central nervous system
• Blocks normal release of inhibitory
  neurotransmitters and results in unopposed muscle
  contraction and spasm

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What is Tetanus?Pathogenesis Clinical Features

• Generalized Tetanus (Most Common)
• Accounts for about 81 of all cases
• Symptoms usually proceed in a descending pattern
• Trismus, also known as lockjaw
• Stiffness of neck
• Difficulty swallowing
• Rigidity of abdominal muscles
• Other symptoms include elevated temperature and
  blood pressure, sweating, and episodes of rapid
  heart rate
• Spasms occur frequently and last for several
  minutes
• Acute illness may continue for 3-4 weeks full
  recovery may take several months

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What is Tetanus?Pathogenesis Clinical Features

• Local Tetanus (Uncommon)
• Persistent contraction of muscles in same
  anatomic area of injury
• Accounts for 13 of cases
• Cephalic Tetanus (Rare)
• Occasionally occurs with otitis media in which C.
  tetani is present in flora of middle ear, or
  following injuries to the head
• Accounts for 8 of cases
• Neonatal Tetanus (Rare in United States)
• Form of generalized tetanus that occurs in
  newborn infants
• Occurs in infants without passive immunity
  because mother is not immune
• Estimated 270,000 deaths worldwide per year

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What is Tetanus?Tetanus Complications

• Tetanus Complications
• Laryngospasm
• Fractures of spine or long bones
• Hypertension
• Abnormal hearth rhythm
• Nonsocomial infections
• Pulmonary embolism
• Aspiration pneumonia
• Death

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What is Tetanus?Overview Risk Factors

• Tetanus is not contagious from person-to-person
• The only vaccine-preventable disease that is
  infectious, but not contagious
• Tetanus toxoid first widely used during World War
  II
• Cases have been reported following surgical
  procedures such as hemorrhoid banding, insertion
  of a spinal implant, and knee surgery
• Tetanus associated with injection drug use
  increased threefold over a seven year period
• Among acute injuries, the disease has been linked
  to self body piercing and tattooing

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What is Tetanus?U.S. Statistics to Date

• Widespread vaccine use since 1940s has markedly
  reduced U.S. cases
• 95 decrease in tetanus cases from 1947 to 2000
• 130 cases reported from 1998-2000 (average of 43
  cases per year)
• Case-fatality ratio declined from 91 in 1947 to
  18 during 1998-2000
• Acute injuries or wounds preceded tetanus in
  nearly three-quarters (73) of cases
• Most frequent wound types include puncture wounds
  (50), lacerations (33) and abrasions (9)
• In 2002, splinters accounted for two tetanus
  cases, one of which resulted in death
• No deaths have occurred among persons who
  previously had received three or more doses of a
  tetanus vaccine

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What is Tetanus?CDC Surveillance

• CDC surveillance records causes of exposure,
  places of injury and fatality
• Wounds caused by
• Punctures
• Self-performed body piercing or tattooing
• Animal bites
• Splinters
• Lacerations and abrasions
• Injection-drug use
• Acute injury related to surgery
• Injuries occurred in several settings
• Home (24)
• Indoors, other than home (15)
• Farming/gardening activities (39)
• Other outdoor activities (22)

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What is Diphtheria?Pathogenesis Clinical
Features

• Corynebacterium diphtheriae (C. diphtheriae)
• Aerobic gram-positive bacillus
• Toxin production occurs only when C. diphtheriae
  is itself infected by a virus carrying the
  genetic information for the toxin
• Only toxigenic strains can cause severe disease
• If isolated, must be distinguished from other
  Corynebacterium species that normally inhabit the
  nasopharynx and skin (e.g., diphtheroids)
• Toxigenic bacilli typically acquired through the
  nasopharynx
• Average incubation period lasts 2-5 days (range,
  1-10 days)

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What is Diphtheria?Clinical Features

• Diphtheria may involve any mucous membrane
  classified by site of disease
• Anterior nasal
• Pharyngeal and tonsillar (most common)
• Laryngeal
• Cutaneous
• Ocular (conjunctiva)
• Genital

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What is Diphtheria?Effects Complications

• Local effects of toxins
• Inhibition of protein synthesis
• Tissue destruction
• Membrane formation
• Systemic effects of toxins
• After absorption through the bloodstream, toxins
  are distributed throughout the body
• Most frequent complications are myocarditis and
  neuritis
• Severity of disease and complications generally
  related to extent of local disease
• Case-fatality ratio is 5-10, with higher death
  rates (up to 20) in persons less than 5 years
  and greater than 40 years of age

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What is Diphtheria?Worldwide Prevalence

• World Health Organization countries at risk for
  diphtheria
• Africa Algeria, Egypt and sub-Saharan Africa
• Americas Brazil, Dominican Republic, Ecuador,
  Haiti
• Asia/Oceania Afghanistan, Bangladesh, Cambodia,
  China, India, Indonesia, Iran, Iraq, Laos,
  Mongolia, Myanmar, Nepal, Pakistan, Philippines,
  Syria, Thailand, Turkey, Vietnam, Yemen
• Europe Albania and all countries of the former
  Soviet Union

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What is Diphtheria?U.S. Statistics to Date

• Only 51 cases of diphtheria reported in the U.S.
  between 1980 and 2000
• 55 in people gt20 years
• 43 in people gt40 years
• No cases reported in 1993 and 1995, 1 case
  reported each year in 1998, 1999, and 2000

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Tetanus DiphtheriaMedical Management

• Cost per case of tetanus or diphtheria at least
  150,000
• Diphtheria
• Diphtheria antitoxin administered
• Treatment with antibiotics (e.g., erythromycin,
  procaine penicillin) for 14 days
• Patient placed in isolation
• Respiratory support and airway maintenance
  administered as needed
• Tetanus
• Tetanus immune globulin administered
• If tetanic spasms occur, supportive therapy and
  maintenance of adequate airway are critical

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Tetanus DiphtheriaPopulations At Risk

• Under-immunized, lapsed boosters
• Older adults
• Agriculture, landscaping trades
• Construction trades
• Rescue, firefighters
• Active sports participants
• Travelers to diphtheria-endemic countries

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Tetanus DiphtheriaVaccine Introduction

• Tetanus Toxoid
• First produced in 1924
• Two types of toxoid available adsorbed
  (aluminum salt precipitated) toxoid and fluid
  toxoid
• Adsorbed toxoid preferred because antitoxin
  response reaches higher titers and is longer
  lasting than fluid toxoid
• Diphtheria Toxoid
• Developed around 1921, but not widely used until
  1930s
• Entered routine use following incorporation with
  tetanus toxoid and pertussis vaccine in 1940s
• New ACIP guidelines for administering the
  tetanus-diphtheria (Td) vaccine include a primary
  series of three properly spaced doses in persons
  seven years of age and a booster dose every decade

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Tetanus DiphtheriaACIP Recommendations

• Pediatric DTaP, DT
• 97 of pediatric patients vaccinated at school
  entry
• Adolescent Td, TT
• Some school requirements, often at age 11 years
• 91 of 6- to 11-year olds protected
• Protection decreases to 80 in 12- to 19-year
  olds
• Adult Td, TT
• Primary vaccination
• Decennial boosters
• Wound prophylaxis, non-sterile birth, travel

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Tetanus DiphtheriaACIP Recommendations

• Routine Td Schedule (7 years of age)

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Tetanus DiphtheriaTd Vaccine Adverse Reactions

• Adverse reactions following vaccination
• Local adverse events (common)
• Erythema
• Induration
• Pain at injection site
• Exaggerated local reactions (occasional)
• Arthus-type, extensive painful swelling
• Fever and systemic reactions (uncommon)
• Severe systemic reactions (rare)
• Generalized urticaria
• Anaphylaxis
• Neurologic complications

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Tetanus DiphtheriaContraindications
Precautions

• Contraindications Precautions
• Severe allergic reaction to a vaccine component
  or following a prior dose
• Acute respiratory distress or collapse
• Moderate-to-severe acute illness
• Defer routine vaccination

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Tetanus DiphtheriaSpecial Considerations

• Pregnancy
• Toxoid vaccines are considered safe in pregnancy
  and are usually administered prophylactically in
  the second or third trimester
• Newborns receive passive immunity via placental
  transport
• Since the widespread Td vaccination in the
  developing world, rates of neonatal tetanus have
  plummeted by over 90 in some countries

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Diphtheria in RussiaOutbreak of Global
Proportions

• Immunization rates in former Soviet Union were
  once equivalent to those in the United States
• Outbreak began in 1990 in Russian Federation of
  15 Newly Independent States (NIS)
• More than 157,000 cases of diphtheria reported
  and more than 5,000 deaths
• From 1990-1995, NIS accounted for 90 of all
  diphtheria cases worldwide reported to WHO
• In some NIS, as many as 80 of cases were in
  adults
• Lack of routine immunization seen as major factor
  in epidemic

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Diphtheria in the U.S.The Need for Continued
Protection

• Although rare in the U.S., C. diphtheriae
  continues to circulate in areas of country with
  previously endemic diphtheria
• In 1996, 10 isolates of C. diphtheriae obtained
  from Native American community in South Dakota
• Eight of 10 isolates toxigenic
• None of infected persons had classic diphtheria
  disease, although five had either pharyngitis or
  tonsillitis
• Case illustrates critical need for maintaining
  levels of protection against diphtheria

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Tetanus in the Elderly Missed Opportunities

• From December 2001 to April 2002, three cases of
  tetanus in Puerto Rico identified in residents
  68 years of age
• Causes were splinter (two cases) and nail
• Two deaths resulted from tetanus infection
• Patients appeared to have no prior immunization
• Mix of delayed or missed diagnosis and delayed
  treatment vaccination and TIG at time of acute
  wound care would have saved two deaths

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Tetanus in Children Philosophic Exemptions

• From 1992 to 2000, 15 cases of tetanus in
  children lt15 years of age
• Twelve boys infected
• Two cases in neonates lt10 days of age
• Thirteen cases in children between 3 and 14 years
  of age
• Median hospitalization 28 d 8 required
  ventilation
• Twelve (80) unprotected due to lack of
  vaccination
• Among all unvaccinated cases, objection to
  vaccination, either religious or philosophic, was
  reported reason for choosing not to vaccinate

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Td Vaccine Shortage 2000-2002

• October 2000
• Shortage occurs after production decreased
• Quantities dramatically reduced after one of two
  manufacturers discontinues production
• May 2001
• During 11 months necessary for corresponding
  production increases, CDC recommends that
  prophylactic boosters be temporarily deferred
• June 2002
• Supply sufficient to resume routine vaccination
• CDC lifts deferral of routine Td boosters,
  enabling physicians to provide patients with
  vaccinations

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Conclusions

• The dramatic reduction in vaccine-preventable
  diseases is a major public health triumph, but
  recent U.S. goals for eradication of tetanus and
  diphtheria have not been achieved
• Tetanus and diphtheria overwhelmingly occur in
  non-vaccinated or under-vaccinated individuals
• ACIP guidelines for administering the Td vaccine
  include a primary series of 3 doses and a booster
  dose every decade
• Universal immunization is the only strategy for
  achieving universal protection