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What is the history of Diphtheria in America and other countries?

The earliest accounts of diphtheria date back to Hippocrates in the 4th century B.C. with epidemics of the disease first noted by Aetius in the 6th century A.D. Monks in A.D. 856, 1004, and 1039 also described the epidemics, but the first descriptions of the diphtheria membrane did not occur until French physician Guillaume de Baillou recorded them in 1576. Additional documentation on diphtheria was recorded in the 17th and 18th centuries. 

The disease was formally named and described in detail in 1821 by French physician Pierre Bretonneau. Its name was derived from the Greek word Diphthera, meaning leather hide, and after the characteristic pseudomembrane found in the back of the throat of those affected by the disease. 

The bacteria responsible for diphtheria, Corynebacterium diphtheriae, was first identified in 1883 by Klebs. In 1884, Loeffler discovered that this bacterium could be cultured from the back of the throat.  In 1888, Emile Roux and Alexandre Yersin demonstrated that a component of C. diphtheriae, the diphtheria toxin, caused symptoms of diphtheria in animals. In the early 1890’s, Emil Behring and Shibasaburo Kitasato reported that serum taken from animals immunized against diphtheria toxin could be used to prevent and treat diphtheria. Behring went on to develop the first diphtheria antitoxin; however, his initial serum formulation was unsuccessful. The antitoxin became more effective once researchers began using horses to produce it. In 1897, Paul Erhlich developed a standardized unit of measurement for the diphtheria antitoxin.    While reportedly effective at treating diphtheria, horse-derived antitoxin was also associated with anaphylaxis and serum sickness.    

The use of the diphtheria antitoxin was questioned by certain physicians at the time, who expressed concerns that it was not necessarily safe or even effective. In 1907, Boston physician Dr. Charles E. Page reported that injecting disease to prevent disease was likely not the solution to treating diphtheria and other diseases. Page believed that improvements in cleanliness and sanitation would ultimately be more effective. 

Proper sanitation was also mentioned as a way to prevent diphtheria in an article published in the Journal of the American Medical Association in 1922. Dr. James Gordon Cumming noted that in the past 30 years, the mortality rate from diphtheria had decreased, but the incidence rate of the disease had not. 

When diphtheria was a common disease, approximately 40 percent of cases occurred in children under age five, and 70 percent among children under age 15.

In 1920, there were 147,991 reported cases of diphtheria in the U.S.  Rates, however, were declining and according to public health officials: 

“The simultaneous decline in diphtheria morbidity and mortality rates in all age groups of individual States located in different sections of the country, which began after a cyclic increase in incidence between 1915 and 1925, suggests the operation or influence of other factors besides, or in addition to, artificially induced immunity.”

In 1930, government officials reported that while widespread vaccination programs were occurring in some areas, while other areas had few programs. Yet after 1925, diphtheria morbidity and mortality rates decreased in all U.S. states simultaneously.  Public health officials reviewing the decline in diphtheria morbidity and mortality reported that:

“The great decline in mortality, the early date at which it was manifested, and the widespread area over which it has been experienced, all go to indicate that it is attributable largely to causes other than specific treatment and immunization. The remarkable reduction in morbidity and mortality since 1927, if viewed as a separate phenomenon, might be attributed in part at least to artificial immunization. That this has been a major factor, however, would seem to be quite improbable, as the recent acceleration of the decline has likewise been experienced over a wide area and, even in many cities in which immunization has been most extensively practised, the reduction has been far greater than can be satisfactorily explained by the numbers of persons immunized. Viewing all the available facts, the conclusion seems inevitable that other factors have played a major role.” 

During this time in Europe, outbreaks of a severe form of diphtheria were increasing. In 1926, Germany reported approximately 50,000 cases. That number significantly increased to 150,000 by 1936. By this time, researchers had confirmed the presence of at least 3 types of Corynebacterium diphtheriae – Mitis, gravis, and intermedius. Additionally, in some areas of Europe, strains of an atypical diphtheria bacteria were also noted but were reported as being milder and not usually associated with severe illness. 

Mitis strains in infants were associated with high mortality rates due to airway obstruction and lung involvement. Gravis and intermedius strains were associated with paralysis and heart issues, and these strains were considered more severe. 

The diphtheria antitoxin continued to be the treatment of choice; however, published research at the time questioned its effectiveness, and researchers stated that: 

“Not only are there these numerous records of unusually severe diphtheria, but there is no doubt that in many of these outbreaks the results of serum treatment have been singularly disappointing notwithstanding the great advances in the potency of antitoxic serum. So much is this the case that a considerable controversy has gone on in the European medical press on the value of anti-diphtheritic serum.”

In the U.S, the number decreased significantly and by 1943, 14,811 cases and 1,169 deaths were reported  and 8 out of 11 cases were diagnosed in adults.  A study published in 1950 reported that while diphtheria morbidity and mortality had decreased by 90 percent, cases had increased among adults. Additionally, mortality rates among all persons under the age of 20 declined nearly uniformly, but in most states, death rates of persons over the age of 20 did not significantly decrease when compared to the younger age group. The study’s author hypothesized that since diphtheria was no longer as widespread, symptoms of the disease in adults was not recognized early enough for treatment to be effective. 

An increase in the percentage of cases among adults was noted in both the U.S. and in Europe during this time, and while most public health officials attributed the shift in demographic to vaccination, historical data notes that this shift also occurred in areas that did not vaccinate. During World War II, many European countries experienced diphtheria outbreaks and it was estimated that in 1943, there were approximately one million cases, and at least 50,000 deaths. Many countries noted an increase in rates among adults. 

In the early 1940’s, Germany experienced a significant outbreak of diphtheria, and by 1943, over half the cases occurred among adults. Antitoxin treatment was found to be ineffective, even when administered early. Death rates among adults also increased, from 12 percent in 1939, to 48 percent in 1943. While some researchers suggested that vaccination of children against diphtheria was responsible for the age shift, this was not accurate, as diphtheria cases also rose significantly among children. Further, any vaccination strategies during World War II were likely very limited and would have had little to no impact on changing the age demographic of diphtheria. 

Researchers also suggested that the spike in diphtheria cases was likely due to living conditions during the war, which frequently resulted in water, food, and electricity shortages, and confinement in overcrowded bomb shelters. 

In the U.S. in 1953, there were 2,355 diphtheria cases and 156 deaths, indicating a death rate of 6.6 percent. Most cases of diphtheria were reported in the Southern U.S. States.  Cases continued to decrease until 1959, when a slight increase from one year earlier occurred. In 1959, there were 934 cases and 72 deaths, up from a total of 918 cases and 74 deaths one year earlier.  Most cases were among children ages five through nine, and most occurred in persons living in the South Central and South Atlantic States. 

Between 1960 and 1979, diphtheria continued to decrease; however, the decline was not as consistent. Sporadic outbreaks continued to occur, but the incidence rates were reported at 0.11 cases per 100,000 population. Between 1959 and 1970, most cases occurred in the Southern U.S. States, with Louisiana most impacted. Between 1971 and 1975, cases occurred more frequently in the Western states. Native Americans were most impacted and rates of diphtheria among this population were 20 times higher than rates among Caucasians, and three times higher than rates among African Americans. The higher rates among these populations were blamed on low socioeconomical status and poor hygiene. 

Cases among persons 15 years of age and older increased from 21 percent in 1960 to 48 percent between 1971 and 1981. Death rates between 1959 and 1970 were four times higher among children under five than for persons 20 years of age and older. 

In 1960, there were 918 diphtheria cases and 69 death, with 43 out of 50 states reporting cases.  By 1978, there only 76 cases and four deaths, with most cases occurring in Washington State.   

Between 1972 and 1975, an outbreak of diphtheria impacted Seattle, Washington, with most cases occurring in a poor section of the city known as “Skid Row”. This outbreak resulted in 558 cases, of which 74 percent were cutaneous diphtheria. Ninety-three percent of cases occurred in adults, with approximately 70 percent reporting frequent alcohol use. Most cases were among males (84 percent) and three deaths were reported, all among white males over the age of 47.  Of those infected who were under the age of 20, 80 percent had received the three recommended primary doses of diphtheria vaccine. 

During this outbreak, 39 percent of cases were among Native Americans and in 1973, a separate outbreak of cutaneous diphtheria occurred among Native American children residing in a rural area of Washington State. This outbreak infected 27 children, and 54 were found to be carriers of diphtheria.    

Since 1979, reporting of cutaneous diphtheria has not been consistent and in 1990, the CDC stated that cases of cutaneous diphtheria should not be reported.  There were only four reported cases of diphtheria in 1990. 

In the 1990s, the former Soviet Union experienced an outbreak of diphtheria with an estimated 115,000 cases and 3,000 deaths. Despite vaccination programs targeting diphtheria which had been ongoing since the 1950s, toxigenic strains of C. diphtheriae had continued to circulate in the environment. Many cases of diphtheria occurred among vaccinated individuals and researchers reported that a new biotype of C. diphtheriae and waning immunity were responsible for the outbreak. Additionally, they stated that vaccine supply, an adequate vaccine, and access to vaccine providers were not responsible for the outbreak. They also reported that social factors such as an increase in homelessness, crowded living conditions, and a susceptible military contributed to this outbreak. 

Between 1996 and 2017, there were 13 reported cases of respiratory diphtheria in the U.S. – five confirmed through culture and eight considered probable, as culturing was not completed. Of those cases, one fatality occurred in an international traveler who returned from an area where diphtheria is considered endemic. 

IMPORTANT NOTE: NVIC encourages you to become fully informed about Diphtheria and the Diphtheria vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.

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