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diphtheria

diphtheria

Introduction

  • an potentially life threatening infection caused by the bacterium Corynebacterium diphtheriae which produces the diphtheria toxin that causes the main symptoms
  • thanks to widespread vaccination of children with diphtheria vaccines (combined with tetanus and pertussis (whooping cough)), diphtheria has largely been eradicated from most developed countries although no region is completely free of it, and areas with low immunization coverage with the diphtheria toxoid-containing vaccine allow the bacteria to circulate, increasing the likelihood of outbreaks and putting all unvaccinated and under vaccinated individuals at risk
  • resurgences tend to occur any time immunization coverage becomes low
  • can affect anyone but was most common in unvaccinated children
  • The three main types of C. diphtheriae cause different severities of disease

Historical progress and epidemiology

  • 1st described in the 5th century BC by Hippocrates
  • 1613, Spain experienced an epidemic of diphtheria. The year is known as El Año de los Garrotillos (The Year of Strangulations) in the history of Spain
  • 1735, New England epidemic
  • 1826, French epidemic which spread to England
  • 1826, Pierre Bretonneau gave the disease the name diphthérite (from Greek διφθέρα, diphthera 'leather') describing the appearance of pseudomembrane in the throat
  • the illness was referred to as “diphtheritic croup”, “true croup”, or sometimes simply as “croup”
    • given it is now rare, the term croup is now reserved for the common viral condition of croup
  • 1856, epidemic in California
  • 1878, Queen Victoria's daughter Princess Alice and her family became infected with diphtheria, causing two deaths, Princess Marie of Hesse and by Rhine and Princess Alice herself.
  • 1882, the bacterium was identified by Edwin Klebs and named it Klebs–Loeffler bacterium.
  • 1884, Friedrich Loeffler was the first person to cultivate C. diphtheriae and used Koch's postulates to prove association between C. diphtheriae and diphtheria, and showed that the bacillus produces an exotoxin.
  • 1885, Joseph P. O'Dwyer introduced the O'Dwyer tube for laryngeal intubation in patients with an obstructed larynx, replacing tracheostomy as the emergency treatment
  • 1888, Roux and Yersin showed that a substance produced by C. diphtheriae caused symptoms of diphtheria in animals
  • 1890, Shibasaburo Kitasato and Emil von Behring immunized guinea pigs with heat-treated diphtheria toxin and showed that an “antitoxin” made from serum of immunized animals could cure the disease in non-immunized animals.
  • 1894, successful treatment of human patients with horse-derived antitoxin began after production and quantification of antitoxin had been optimized.
  • 1897, Paul Ehrlich developed a standardized unit of measure for diphtheria antitoxin.
  • 1901, 10 of 11 inoculated St. Louis children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of tetanus. This played an important part in initiating US federal regulation of biologic products.
  • 1904, Ruth Cleveland died of diphtheria at the age of 12 years in Princeton, New Jersey. Ruth was the eldest daughter of former President Grover Cleveland
  • 1906, Clemens Pirquet and Béla Schick described serum sickness in children receiving large quantities of horse-derived antitoxin.
  • 1911, Béla Schick developed the Schick test to detect pre-existing immunity to diphtheria in an exposed person. Only those who had not been exposed to diphtheria were vaccinated.
  • 1919, in Dallas, Texas, 10 children were killed and 60 others made seriously ill by toxic antitoxin which had passed the tests of the New York State Health Department
  • In the 1920s, each year an estimated 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths occurred in the United States.
  • 1930's, widespread vaccination pushed cases in the United States down from 4.4 per 100,000 inhabitants in 1932 to 2.0 in 1937
  • 1974, the WHO included DPT vaccine in their immunisation schedules
  • 2015, 4,500 cases were officially reported worldwide with 2100 deaths, down from 8000 deaths in 1990, and down from nearly 100,000 reported cases in 1980.
  • prior to 1980 there were approx. a million cases a year
  • 2017, an outbreak of occurred in Indonesia with more than 600 cases found and 38 fatalities
  • 2022, largest diphtheria epidemic in Western Europe for 70 years with 362 notified cases that year (98% male, median age 18, 96% were recent migrants who appeared to have picked it up en route, 77% were cutaneous, 15% were more severe resp. forms) and in 2023 spread to other vulnerable populations in several European countries. This strain had genetic links to an epidemic that occurred in Germany in 2025. By June 2025, there had been a total of 536 cases, including at least three deaths, reported in Europe.1)
  • July 2022, there were 2 cases in children in northern NSW - the 1st cases in NSW this century
  • post-Covid-19 globally decreased immunization uptake rates pose further epidemic risks
  • see vaccines for history of vaccine development

Prevention

  • vaccination:
    • in Australia, the recommendation is:
      • that children receive diphtheria vaccines at the ages of two, four, six and 18 months and boosters at four and 15 years.
      • that adults get the combined diphtheria, tetanus and pertussis vaccine every 10 years and during pregnancy.
    • in Australia in 2020:
      • 95% of children aged one and five across the country have received all their recommended vaccines and 93% of two-year-olds are fully vaccinated
  • close contacts of a case:
    • ensure vaccinated
    • prophylactic antibiotics such as 14 day course of either erythromycin, metronidazole or procaine penicillin IM
  • previous infection may not protect against infection

Transmission

  • The disease is contagious and can be spread through coughing, sneezing and occasionally through contact with contaminated surfaces
  • People who don’t receive treatment can remain infectious for up to four weeks after they start showing symptoms
  • Some are asymptomatic carriers

Incubation period

  • Symptoms usually start up to 10 days after exposure, mostly within 2-5 days of exposure

Clinical features

  • most infections are asymptomatic or have a mild clinical course of sore throat, loss of appetite and mild fever
  • in severe cases, this is followed by a greyish-white membrane forming over the throat and tonsils that makes it hard to breathe and swallow.
  • can also cause:
    • brassy or barking croup-like cough
    • stridor
    • massive swelling in the neck “bull neck” due to lymphadenopathy
    • myocarditis which can cause rhythm disturbances and weeks later, cardiac failure
    • inflammation of nerves causing paralysis of eye, neck, throat or respiratory muscles
    • renal issues
  • overall 5-10% mortality rate for treated cases
    • 40-50% mortality in untreated cases
    • treated mortality in those under 5yrs or those over 40yrs may bas as high as 20%

Treatment

  • manage airway as needed - severe cases may require a surgical airway
  • IV antibiotics
  • EARLY diphtheria antitoxin
    • as this does not neutralize toxin that is already bound to tissues, delaying its administration increases risk of death.
    • thus, the decision to administer diphtheria antitoxin is based on clinical diagnosis, and should not await laboratory confirmation
diphtheria.txt · Last modified: 2025/06/10 05:29 by gary1

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