Diphtheria

Diphtheria, like tetanus, is also a rather dangerous disease, but what is the probability of getting sick with diphtheria today, and how effective is the vaccine?

Diphtheria is caused by the bacterium called Corynebacterium diphtheria, which itself is fairy harmless. However, if this bacterium is infected with a specific virus (bacteriophage), it begins to produce and secrete a strong toxin. This toxin is responsible for the severe symptoms of diphtheria. Diphtheria toxin destroys the throat tissue and forms a pseudomembrane in it, whereas without the toxin this bacterium can only cause pharyngitis. If this toxin enters the circulatory system, the complications could lead to myocarditis and temporary paralysis. The fatality rate is 5-10%.
The disease is mostly transmitted through respiratory droplets, but it can also be transmitted through contaminated objects.
Most people infected with diphtheria bacterium do not get sick, but simply become the bacteria reservoirs and carriers.
During the epidemics, most children happen to be carriers, but they do not get sick. The highest incidence of diphtheria is during winter and spring (one can already guess why).

Diphtheria vaccine is not produced separately. It is always combined with tetanus (DT, Td) and usually with pertussis (DTaP/DTP). Same as tetanus vaccine, this vaccine is a toxoid, i.e. formalin-inactivated toxin.
Antibiotics and diphtheria immunoglobulin are used as treatment. However, since diphtheria is an extremely rare disease, human immunoglobulin is not produced for it, and horse immunoglobulin is used instead, even in the developed countries..

The concept of allergies was unknown until 1906. It was invented by an Austrian pediatrician and used to describe the strange symptoms he observed in those who received the diphtheria immunoglobulin.
The concept of anaphylactic shock also did not exist until 1902.

In 1926, Glenny and his group experimented with the diphtheria vaccine and tried to improve its effectiveness. They accidentally found that adding aluminum to the vaccine triggers a stronger immune response. Since then, aluminum is added to most inactivated vaccines.
Glenny was not interested in the safety of having aluminum in a vaccine 90 years ago, nor does it interest anyone today.

• Diphtheria was always considered a childhood disease, but in mid 20th century adults also began to get sick with it. In 1960, 21% of the disease cases were in adults (over 15 years of age). In 1964, there were already 36% of adults, and it 1970s – 48%. The mortality ratio has also changed. In the 1960s, 70% of those who died of diphtheria in Canada were children, in in the 1970s, 73% of those who died were adults.
  
• In the 1960s, the Indians suffered from diphtheria 20 times more often than white people, and 3 times more often black people. The reason is considered to be in the lack of proper hygiene due to the Indians’ poverty.
  
• In the late 1960s, there were diphtheria outbreaks in Austin (88 cases) and San Antonio (196 cases). Diphtheria was mainly observed in the city districts with a low socioeconomic status.
  
• One of the forms of diphtheria is cutaneous (skin) diphtheria. It is commonly found in homeless people, and is much less dangerous.
  Cutaneous diphtheria is associated mostly with the poorer population, living in crowded conditions with low hygienic standards. By 1975, 67% of diphtheria cases were of the cutaneous type, and it was mostly Indians who got sick.
  In an overwhelming majority of cases the cutaneous diphtheria infection is also accompanied by staphylococcus and streptococcus. It seems that a skin infection of streptococcus and staphylococcus predisposes to secondary infection with diphtheria, and the low level of hygiene is a main contributing factor.
  
• In the 1970s, there was a diphtheria outbreak in Seattle. Of the 558 cases, 334 were from Skid Road (i.e. homeless). 3 people died. 74% suffered from cutaneous diphtheria. 70% were heavy alcoholics.
  
• In 1971, there was a diphtheria outbreak in Vancouver (44 cases). Most of the cases were poor alcoholics.
  
• In 1973, there was an outbreak among the Indian children. 4 children with cutaneous diphtheria were the source.
  
• Cutaneous diphtheria was recognized as an infection reservoir in 1969 in Louisiana and Alabama. The bacterium was isolated in 30% of healthy people. Vaccinated and unvaccinated people were equally infected.
  
• Since the 1980s, diphtheria is almost never found in North America.

• The protective level of antibodies of diphtheria is considered to be from 0.01 to 0.1 IU/ml. The exact value cannot be determined.
  
• Not a single case of diphtheria has been recorded in Sweden from the late 1950s to 1984. 3 outbreaks were observed in 1984 (17 cases, 3 deaths). Almost all patients were chronic alcoholics. Most patients had the level of antibodies below 0.01 IU/ml.
  
• Researchers measured the level of antibodies in children. 48% of those who received 3 doses of the vaccine in infancy had the antibodies level below 0.01 IU/ml. Among the 6-year-olds 15% had such results. Among the 16-year-olds, who have received booster vaccines in addition to being vaccinated in infancy, 24% had the antibodies level below 0.01 IU/ml.
  It is possible that the low level of antibodies in Sweden could be due to the fact that the pertussis component has been excluded from the vaccine in the 1970s. Since the pertussis toxin is an adjuvant itself, its exclusion makes the diphtheria vaccine less effective.
  
• The immune response to booster vaccines among 16-year-olds was much worse than that of 6-year-olds, even despite the fact that 16-year-olds received a 2.5 times bigger doses. The authors do not have an explanation for this phenomenon.
  
• It is believed that antibodies level above 1 IU/ml provides protection for over 10 years. Only 50% of 16-year-olds and 22% of 10-year-olds had such level of antibodies after vaccination.
  
• The level of antibodies falls by 20-30% in a year. It decreases even faster in children. While 94% of children at the age of 15 months had the level of antibodies above 1 IU/ml, 4 years later the average level of for them was only 0.062 IU/ml.

The authors measured antibodies level of 2,400 people in Sweden. 19% of people of the age of 20 and under did not have immunity against diphtheria. Among people over 40 years of age, only 15% had sufficient level of antibodies. Among the elderly, 81% of women and 56% of men did not have the immunity. On average, 70% of adult women and 50% of adult men had antibodies level below 0.01 IU/ml.

84% of men and 89% of women in Minnesota had diphtheria antibodies level below 0.01 IU/ml.

40% of Americans do not have sufficient immunity to diphtheria (below 0.1 IU/ml).

A decrease in the incidence of diphtheria in the 1970s occurred despite the lack of immunity among adults.
Recent diphtheria outbreaks occur only among alcoholics and homeless.

More than half of the population in different countries does not have the protective level of antibodies against diphtheria.

Recommendations for getting booster vaccines against diphtheria and tetanus every ten years are based on serological studies, according to which, the elderly have lower level of antibodies. However, the goal of the vaccination is to prevent disease, not the production of antibodies. In Canada, the incidence of diphtheria does not increase with age; neither does the tetanus mortality rate increase.
The authors conclude that the benefit from booster vaccines against diphtheria and tetanus in adults, does not justify neither the risks, nor the cost.

Adults in Belgium got revaccinated against diphtheria. 24% of them did not get their antibodies above the ‘protective’ level. Among those, whose antibodies level was initially low it remained insufficient in 42% of the cases. The authors conclude that one booster dose for adults is not enough.

Diphtheria outbreak in a British school in 1946 (18 cases). All but two (or three) children have been vaccinated (which is probably the reason why no one died, the authors believe).
Among the 23 unvaccinated children, 13% got sick. Among the 299 vaccinated children, 5% got sick.
One of the unvaccinated children has actually been vaccinated, but more than ten years ago. If he is excluded, then the percentage of sick children among the unvaccinated goes down to 9%.
If the vaccinated children are divided into two groups: those who were vaccinated less than 5 years ago, and those who were vaccinated more than 5 years ago – the incidence rate is the same for both groups. Nonetheless, for those who were recently vaccinated the disease was milder than for those vaccinated a long time ago or those unvaccinated.
The authors conclude that the vaccine is not very effective without the subsequent booster shots and urge to get booster vaccines every three years, in addition to being vaccinated in infancy.

Diphtheria outbreak in Halifax (Canada) in 1940. 66 cases, of which 30% were fully vaccinated.

In the early 1940s, Canada had a diphtheria epidemic (1,028 cases, 4.3% fatality rate). 24% of the patients were vaccinated (or protected). Among them, five have died (one of them was vaccinated just six months before getting sick).
Overall, those vaccinated had milder symptoms. The authors conclude that the vaccine is effective, but not 100%.

Diphtheria outbreak in Baltimore. 103 cases were recorded in 1943. 29% of the patients have been vaccinated, and another 14% claimed that they have also been vaccinated, but had no documented proof.
Consequently, they started to vaccinate more in Baltimore. In the first half of 1944, 142 cases were already recorded. 63% of them have been vaccinated.

Diphtheria in Western countries is so rare that no one even remembers what it is anymore. They barely even teach about it in medical school. In Russia and former USSR countries, however, many still fear diphtheria, because of the epidemic in the early '90s. But who was it that got sick during this epidemic?

• The role of antibacterial immunity in protection against diphtheria has not been studied since the 30s.
  
• Prior to the World War II, diphtheria was rarely observed in the countries of Western Europe. During the war, an epidemic started in Netherlands, Denmark and Norway, in the territories occupied by the Germans. It was the last diphtheria epidemic in developed European countries. The remaining isolated cases were observed mainly among the lower socioeconomic class.
  
• In the early 90s Russia, diphtheria cases among the military were observed 6 times more often that among the civilian population. In the late 80s this proportion was even higher.
  
• In the 90s epidemic in the former USSR countries, 83% of all cases were recorded in Russia. Most patients were adults.
  The patients were mainly homeless and patients of psychiatric hospitals, living in cramped quarters and poor sanitary conditions. Among the people working under normal conditions, there were very few cases of the disease.
  Children rarely got sick, but they were carriers of the disease. Economic crisis after the fall of the USSR worsened living conditions and intensified the epidemic.
  Since virtually the entire population of the USSR was vaccinated, it is hard to blame the epidemic on the lack of vaccination, but the authors succeeded. After all, the article was written by the CDC.

1,860 cases of diphtheria in the Botkin hospital in St. Petersburg. Fatality rate was 2.3%. 69% of those who died were chronic alcoholics.
Among those who suffered from the toxic form of the disease, fatality rate was 26%. 6% of vaccinated patients and 14% of unvaccinated patients suffered from the toxic form. However, only those vaccinated in the last five years were considered as vaccinated.
Overall, the diphtheria fatality rate (2.3%) was relatively low, as compared to the last known epidemics. And if alcoholics were to be excluded, the fatality rate would be about 1%. Most of those who died got to the hospital at the late stages of the disease, and were either alcoholics or very busy people.
The authors conclude that diphtheria epidemic in developed countries is unlikely to have high fatality rate in the future. Also, since there was no vaccination data for the alcoholics, the authors believe that they were unvaccinated.
Vaccination provides immunity for a relatively short time. How exactly is diphtheria transmitted from person to person is not really known.

• To get diphtheria from another person, the distance to that person should be less than 1 meter. If the distance is greater, the risk of infection is significantly reduced.
  
• 40-78% of unvaccinated children in Afghanistan, Burma and Nigeria developed natural immunity by the age of 5.
  
• Socioeconomic factors, such as cramped quarters, poverty, alcoholism and low level of hygiene contribute to the spread of diphtheria.

• Among children, elementary level education of the mother was associated with a 4 times higher risk of getting diphtheria, as compared to those, whose mothers had academic education.
  
• Among adults, people with elementary level education got sick with diphtheria 5 times more often than those, who got a university degree.
  
• Chronic illnesses were associated with a 3 times higher risk of getting diphtheria. Unemployed got sick twice as often. Taking a shower less than once a week was associated with a two times higher risk of infection.
  
• Unvaccinated people got sick 19 times more often than those who have been vaccinated. However, only those who received all doses and boosters, and have been vaccinated in the last 10 years, were considered as vaccinated. The rest were considered as unvaccinated. The authors write that perhaps the patients did not remember well whether they have been vaccinated or not.
  
• Among the 181 cases: 9% were unvaccinated, 48% had a chronic illness, 21% took showers less than once a week. The authors conclude that vaccination is the most important tool in the control of diphtheria, but do not overly emphasize that people should wash themselves more often than once a week.
  Also, the authors write that diphtheria is not very contagious and that it takes a prolonged contact with a patient to contract it.
  Visiting crowded places was not a risk factor.
  Compared to the previous epidemics in Europe and USA, which occurred mainly among alcoholics, the authors did not find an increased risk in alcoholism in this study. They conclude that low socioeconomic status, and not alcoholism, is likely a risk factor.

Vaccination coverage in Ukraine is above 90% among children, and over half of adults have been vaccinated between 1991 and 1994. Nonetheless, the number of diphtheria cases is increasing.

In the 90s, due to the opening of borders, a flood of tourists poured from Finland to Russia and from Russia to Finland. 400 thousand Finns visited Russia every year, and 200 thousand Russians visited Finland. 10 million trips were made. Despite the epidemic in Russia, only 10 Finns contracted diphtheria in Russia. Almost all of them were middle-aged men; only three of them had a severe form (described below), five had a mild form, and two were only carriers.

1) A 43-year-old resident of Finland visited St. Petersburg in 1993. There he kissed his local girlfriend, and when he returned to Finland, he was diagnosed with diphtheria. He was vaccinated against diphtheria 20 years ago, and was considered as unvaccinated (antibodies level was 0.01 IU/ml). His Russian girlfriend did not get sick. Another bacterium carrier was identified, who traveled in same group with the first one. He also had intimate relations with the same “girlfriend” in St. Petersburg. It was the first case of diphtheria in Finland in 30 years.
2) 57-year-old male visited Vyborg for one day in 1993 and came back infected with diphtheria. He denied having had close contact with the locals, but his friends said that he visited prostitutes. It is unknown whether he has been vaccinated (antibodies level was 0.06 IU/ml).
3) 45-year-old male visited Vyborg for 22 hours and came back infected with diphtheria. His friends said that he also visited a prostitute. He has been vaccinated and even received a booster shot one year before the trip (antibodies level was 0.08 IU/ml). He was the only one fully vaccinated, and also the only one who died.
All three of them consumed large amounts of alcohol during the trip, and two of them were chronic alcoholics.

In 2016, 25 years after diphtheria has been fully eradicated, a diphtheria outbreak began in Venezuela. Since the vaccination coverage there was only increasing, each year, and given the humanitarian crisis currently happening there, it is hard to blame the outbreak on the lack of vaccination. However, WHO wouldn’t be WHO if they let the facts confuse them.

In November-December of 2017, diphtheria outbreaks began in Yemen and in a refugee camp in Bangladesh. This, of course, happened because of the insufficient vaccination, and not because of the civil war in Yemen, and certainly not because the refugees in Bangladesh lived in tents, 30 people in each.

Apart from humans and primates, guinea pigs are the only mammals that do not synthesize vitamin C.
Guinea pigs were injected with diphtheria toxin. Those who were on a low vitamin C diet lost more weight than those on a regular diet. Diphtheria toxin depleted vitamin C in the adrenal glands, pancreas and kidneys.

• Vitamin C deficiency causes the decreased resistance to infections and increased damages from bacterial toxins. Decreased resistance appears before the scurvy symptoms can be observed.
  
• Guinea pigs on a low vitamin C diet, who got injected with sublethal dose of diphtheria toxin, experienced a wider tissue damage, bigger weight loss, wider areas of necrosis, worse teeth development, and shorter lifespan, as compared to guinea pigs who were not restricted in vitamin C consumption.
  Most likely, a low level of vitamin C leads to systemic disorders of the whole body, and especially the endocrine system.
  The authors conclude that the level of vitamin C for detoxification from diphtheria should be significantly higher than the level of vitamin C required to prevent scurvy.

• When guinea pigs are injected with a sublethal dose of diphtheria toxin, a 30-50% decrease in the vitamin C level in tissues is observed within 24-48 hours.
  
• Children who received little vitamin C, developed scurvy during the infection. It resolved spontaneously after recovery, without increasing the amount of vitamin C in the diet.
  
• What correlated with the absence of tooth caries in children of 10-14 years of age are good nutrition and lack of diseases in infancy and childhood.
  
• Guinea pigs got injected with 0.4 and 0.8 of the minimum lethal dose of diphtheria toxin. Among those who received 0.8 mg of vitamin C daily, destruction of dental tissue was observed. Teeth of those who received 5 mg of vitamin did not decay.

Guinea pigs with limited vitamin C in the diet got injected with sublethal dose of diphtheria toxin. They developed arteriosclerosis in the lungs, liver, spleen and kidneys.

Guinea pigs with low vitamin C reserve, who got injected with lethal dose of diphtheria toxin, died faster than guinea pigs on a regular diet.
Guinea pigs that received large doses of vitamin C, survived even after being injected with several lethal doses of the toxin.

The effect of vitamin C on diphtheria has not been studied since the 40s. in 1971, Klenner reported a case of a girl being cured of diphtheria by an intravenous injection of the vitamin. Two other children, who did not get vitamin C, died. All three also received the antitoxin.

As is the case with other diseases, the decrease in diphtheria fatality rate began long before the introduction of the vaccine.

Since diphtheria vaccine is a toxoid, it cannot prevent the infection, but it can prevent complications from the disease. Thus, it would be logical to expect the diphtheria fatality rate to decrease with the introduction of the vaccine. However, that did not happen. Despite the fact that the number of diphtheria cases was continuously decreasing, fatality rate remained at approximately 10% level from 1920s to 1970s, despite increasing vaccination coverage. (data source).

Here’s some data from India, one of the last countries in the world where diphtheria still exists. Despite the increased vaccination coverage, the number of diphtheria cases has barely decreased since the 80s.

Diphtheria is an extremely rare disease nowadays. It is rarely found even in most of the third world countries.
Since 2000, only 6 cases of diphtheria have been reported in the USA. One of these patients died. He was 63 years old, and got infected in Haiti. This is such a rare disease that CDC writes up a separate report on almost every case. [1 ], [2].
At the same time, 96 people have been sick with bubonic plague in USA since 2000. 12 of them died. Their deaths have not been widely reported, since they do not vaccinate children against the plague.

Death from diphtheria in developed countries is so rare that every such case is widely reported in the media. In 2015, a boy died of diphtheria in Spain, and in 2008, a girl died in England. These seem to be the only deaths of children from diphtheria in developed countries in the last 30 years.

Since the diphtheria vaccine is always combined with tetanus/pertussis, its safety data is the same as was presented in the respective chapters.
The vaccine (without the pertussis component) causes Guillain-Barre syndrome, anaphylactic shock and brachial neuritis, lowers the level of lymphocytes, increases the risk of allergies and antiphospholipid syndrome. From 2000 to 2017, VAERS has registered 29 deaths and 181 disability cases after the diphtheria vaccine, without the pertussis component (DT/Td). During the same time, 6 people got sick with diphtheria and one died. Considering that only 1-10% of all cases get registered with VAERS, the probability of dying from the vaccine is hundreds of times higher than the probability of getting diphtheria.
The probability of getting diphtheria in developed countries is maximum of 1 in 10 millions, and usually even less. The probability of just the anaphylactic shock is at least 1 in a million, and probability of brachial neuritis is 1 in 100 thousand.