Adverse reactions of diphtheria-tetanus pertussis vaccine

Currently, the vaccines used to prevent diphtheria, pertussis, and tetanus in infants and young children contain the following active ingredients (Mortimer Jr et al., 1999; Wasilak, 1999; Edwards et al., 1999):

Diphtheria and tetanus Cold toxoid.

Vaccine to prevent one of two types of pertussis;

Inactivated Bordetella pertussis whole-cell vaccine;

Acellular vaccine, containing 1-5 Units of pure Bacillus protein.

Preservatives (such as thimerosal or phenoxyethanol), stabilizers (such as gelatin or polysorbate 80) and adjuvants such as aluminum hydroxide or aluminum phosphate.

Vaccines against diphtheria, whooping cough and tetanus (DPT) are mixed so that children can receive one dose. The vaccines used for adults are usually only the combined diphtheria and tetanus vaccine. Low-concentration diphtheria toxoid (Td) or tetanus toxoid (TT) is only used in pregnant women to control neonatal tetanus.

a) Diphtheria toxoid

Diphtheria toxoid is an inactivated preparation of diphtheria toxin. Typically, it is provided as a formulation that absorbs aluminum hydroxide or aluminum phosphate and is combined with other toxins or vaccines. Toxoid content is measured in flocculent particles (Lf), and immunity is measured in International Units (IU) per serving (these standards are measured differently and cannot be directly converted). Recommendations from the World Health Organization stipulate that the efficacy of each vaccine for children under 7 years of age should not be less than 40 international units.

Mild Adverse Events

50 years ago, efforts to protect children and adults from diphtheria infection resulted in unacceptable local and systemic reactions. Generally, these reactions are type IV delayed allergic reactions to diphtheria proteins. Purifying the toxoid, adsorbing it on aluminum hydroxide and reducing its concentration (Mortimer Jr et al., 1990) greatly reduces the frequency of such reactions.

Adsorbed diphtheria toxoid is more likely to react in people who have received a booster dose (Edsall et al., 1954). Their frequency varies with the concentration of the toxin and the level of diphtheria toxin antibodies in the blood before vaccination.

Mild reactions include:

Local reactions, mild to moderate: redness, pain, and hardness at the vaccination site (11-38).

General reactions: transient fever (1), discomfort, pain, flushing.

Serious Adverse Events

Generalized urticaria or pruritus has been reported, and rare allergic reactions have also been reported. There are few recent data on single adverse effects of diphtheria toxoid because it is commonly used with tetanus toxoid in adults and pertussis vaccine in children under 7 years of age.

b) Tetanus toxoid

Tetanus toxoid is an inactivated toxin preparation. Toxoids are used alone or in combination with other toxoids or vaccines in simple (unadsorbed) form or adsorbed to aluminum phosphate or aluminum hydroxide. The potency of tetanus toxoid, expressed in international units, can vary greatly depending on preparation methods and manufacturers, but the World Health Organization stipulates that each dose should not be less than 60 international units. The frequency and severity of local reactions to tetanus vaccine increase with dose and age (Myers et al., 1982). The risk of local reactions and sterile abscesses increases when adsorbent vaccine injections bring the seasoning into contact with subcutaneous tissue (EPI, 1982; Marks, 1999). This is particularly important for the prevention of neonatal tetanus through maternal immunization in developing countries.

Mild adverse events

The most common are mild local reactions such as pain and erythema, with incidence rates ranging from 25 to 85 (Mortimer Jr et al. 1999). In some cases, nodules form at the site of vaccination and persist for several weeks. There are 6-10 cases of sterile abscess per million doses of vaccine administered.

Systemic reactions occurred in 0.5-10 cases of booster injections; these reactions included fever, malaise, tremors, generalized pain, and headache.

Serious adverse events

Allergic reactions

Generalized urticaria and allergic reactions are rare (1-6 cases/10,000 doses).

Artus-type anaphylaxis (high susceptibility to immune syndromes) and severe local reactions may occur in hyperimmune people who have high values ??of anti-tetanus antibodies before vaccination.

Brachial neuritis

This symptom is defined as a dysfunction of the upper extremity nerve plexus that does not involve other peripheral or central nervous system structures (AAP, 1997), and this reaction occurs in It has been reported after vaccination with tetanus toxoid (relative risk 5-10; 0.5-1 per 654.38 million doses (Committee on Vaccine Safety, 1994)). Often associated with multiple vaccinations (Rutledge and Carter, 1986).

Guillermo-Barrett Syndrome

Occurs within 6 weeks of vaccination and is linked to components of the tetanus vaccine. A US survey examined 306 cases in adults. and syndrome in children, and it is thought that this association, if it exists, is very rare (Tuttle et al., 1997)

c) Combined diphtheria and tetanus toxoid vaccine

The combined diphtheria and tetanus vaccine has a reduced diphtheria component and is used in children over 7 years of age. The intensity and frequency of local and systemic reactions increase with age, inoculated copy number, and toxoid concentration (Myers et al., 1982; Centers for Disease Control and Prevention, 1996; NCCI, 1998). Therefore, as the content of the diphtheria vaccine decreases, the number of reactions and Severity also decreased. Available data suggest that diphtheria and tetanus toxoids may produce adverse effects.

Mild adverse events

Diphtheria toxoid vaccine produced local reactions, with pain, swelling, and erythema accounting for 10-75%. Some vaccine recipients develop small nodules at the injection site that last for several weeks. There are 6-10 cases of sterile abscess per million vaccinations. Fever and other systemic reactions (muscle pain, headache) accounted for 10%.

Serious Adverse Events

The allergic reactions to tetanus, brachial neuritis, and Guillain-Barre syndrome described in the above sections also apply to diphtheria toxoid vaccine.

d) Pertussis vaccine

There are two types of pertussis vaccines currently in use: whole-cell vaccine and acellular vaccine.

Whole cell vaccine is a suspension of dead pertussis microorganisms at a concentration greater than 4 international units.

Acellular vaccines consist of pure pertussis antigens. All current vaccines contain pertussis toxoid (3.2-40 micrograms per vial), and most contain filamentous lectins (2.5-34.4 micrograms per vial). Other antigens in the vaccine may include pertactin (1.6-23.4 μg), pilus 2 (0.8-5 μg), and pilus 3 (5 μg) (CDC, 1997).

The following two chapters list the adverse reactions after vaccination with pertussis combined with diphtheria and tetanus toxoid.

e) The DPT vaccine contains whole-cell pertussis vaccine.

Mild Adverse Events

The whole-cell component of pertussis is primarily, but not exclusively, responsible for reactions to DPT vaccine (Cody, 1981; Scheifele, 1994; Gupta, 1991 ; Cherry, 1996). A comparative study of triple immunity against diphtheria, tetanus, and diphtheria-tetanus in children under 6 years of age showed that the incidence of allergic reactions, redness, swelling, edema, fever, lethargy, skin inflammation, vomiting, loss of appetite, and persistent crying was significant. lower (Cody, 1981).

In another study, 6-month-old infants who had received two previous doses of DPT vaccine were compared with a placebo control (Long, 1990). Diphtheria-tetanus-pertussis vaccine production vaccine: edema 5 cm, fever above 39.4°C, and various reactions other than screaming increased significantly.

40-80% of people vaccinated with DTP vaccine experienced mild adverse reactions such as pain, edema, and erythema. Rarely, some people develop small nodules at the site of vaccination that last for several weeks. There are 6-10 cases of sterile abscess per 100 vaccines.

Mild systemic reactions include fever above 38°C and skin inflammation (40--75), lethargy (33-62), loss of appetite (20-35), and vomiting (6-13).

The frequency of local reactions increases with the number of vaccinations, while systemic reactions (Cody, 1981; Canadian Infectious Diseases, 1992), with the exception of fever (Cherry, 1996), all increase with subsequent vaccinations. And disappear. When the aluminum salt is injected into the subcutaneous tissue during intramuscular injection, the local reaction is more intense (Ipp, 1989)

Serious adverse events

The specific serious adverse reactions are summarized below. :

Cried for more than 3 hours (mainly because of pain, 1)

Body temperature exceeded 40.5℃ (0.3)

Abnormal screaming (0.1). ).

Convulsions (usually accompanied by fever, 1 case in 12,500 vaccines) (Farrington et al., 1995)

Low responsiveness and hypotonia (1 case in 1,750 vaccines). (Cody, 1981).

Anaphylaxis is rare (2 cases vaccinated with 654.38 million vaccines) (Edwards et al., 654.38 0999; Centers for Disease Control, 1996).

History of convulsions ( Children who have a relative risk of 6.4) or have a family history of convulsions (relative risk of 2.4) are more likely to develop convulsions (Edwards et al., 1999; Livengood, 1989). Relative risk of convulsions within three days after vaccination with DPT vaccine There is an increase (Farrington, 1995).

Fever and subsequent local reactions may be reduced by taking acetaminophen or any appropriate antipyretic drug at the time of vaccination and 4 hours and 8 hours after vaccination (AAP, 1997). It may also be beneficial for people with a personal or family history of convulsions (Ipp et al., 1987; U.S. Centers for Disease Control, 1987.)

The U.S. Committee on Vaccine Safety concluded in 1994 that the pertussis vaccine may cause permanent brain damage There is insufficient evidence (Edwarda et al., 1999). In addition, experts deny a causal relationship between DPT vaccine and autism, infantile spasms, Reye syndrome and sudden infant death syndrome.

f). DTP Triple Vaccine Containing Acellular Pertussis Vaccine

Mild Adverse Events

In general, vaccines containing acellular pertussis components have the same side effects, but less frequently than those containing whole-body pertussis. Vaccines with cellular pertussis components (Edwards et al., 1999; Centers for Disease Control, 1997). Studies have increasingly shown that the frequency of reactions to vaccines with acellular pertussis components is no greater than with vaccines that do not contain pertussis (DT or Td vaccines). The frequency after vaccination is high (Gustafsson, 1996). Some studies have shown that children who received the first dose of vaccine (2, 4, and 6 months old) have great differences in all mild and moderate reactions except vomiting (see Table 4) ( Mills et al., 1998; Decker et al., 1995; Decker & Edwards, 1996).

Table 4: Within 24 hours after vaccination with DTP vaccine.

Percentage of mild to moderate reactions

Counter-effects

Acellular vaccines a)

Whole cell vaccines b)

Range

Average

Red 1-19mm

15.1-44.0

31.4

56.3

Redness more than 20 mm

1.4-5.9

3.3

16.4

Edema 1-19mm

7.5-28.6

20.1

38.5

Edema exceeding 20 mm

0.8-8.0

4.2

22.4

Desire

1.6-13.2

6.9

40.2

Body temperature 37.8℃-38.3℃

16.0-29.2

20.8

44.5

Body temperature above 38.4℃

1.6-5.9

3.7

15.9

Skin inflammation

12.6-24.4

17.1

41.5

Feeling tired and sleepy

29.4-59.2

42.7

62.0

Loss of appetite

17.7-27.2

21.7

35.0

Vomiting

7.4-21.6

12.6

13.7

a) All 13 different acellular pertussis vaccines combined with diphtheria and tetanus toxoids, each containing 1-4 species antigen.

b) Whole cell pertussis vaccine combined with Lederle diphtheria and tetanus toxoid.

Source: Decker et al. (1995).

Serious Adverse Events

Studies estimating the frequency of serious and rare adverse reactions are ongoing. Even if convulsions, persistent crying, body temperature exceeding 40°C, hypoosmosis, and hyporeaction occur after vaccination with acellular vaccines, mild and severe reactions are reduced by more than half after vaccination with whole-cell vaccines (Edwards et al., 1999).

Several studies have demonstrated the safety of substituting whole-cell-containing vaccines for acellular pertussis-containing vaccines as boosters in children starting the vaccination program (Pichichero et al., 1997; Halperin et al. , 1996; Feldman et al., 1992). In particular, children who started receiving a booster (fourth dose) of acellular pertussis vaccine developed more local reactions than their initial whole-cell vaccine. However, although the frequency of local and systemic reactions associated with acellular vaccines increases with increasing copy number vaccinated, such reactions are less frequent than with whole-cell vaccines.

The parents of a 4-year-old boy in Kaifeng who had an adverse reaction to vaccination claimed a compensation of 30,000 yuan.

Fever 10.7, rash 3.5, this is the probability of "adverse reactions" after vaccination.

Many people may not know that vaccines have side effects. Zhu Mingyue, a young mother in Kaifeng, is one of them, but neither the epidemic prevention station nor the kindergarten told her about this. Her child was "caught" like this: she had a fever, talked nonsense, and cried loudly for more than 10 days.

Doctors remind that "adverse reactions" such as fever mostly occur after vaccination. Children should pay close attention to their condition after being vaccinated. If there are any abnormalities, they should be sent to the hospital immediately.

Children are vaccinated in the "middle"

Zhou Runtong, a 4-year-old student in Class 2 of Huakai Kindergarten in Kaifeng City, received a notice from the school on February 27 this year that the Shunhe District Health and Epidemic Prevention Station Come to the kindergarten to vaccinate all the children.

After paying 58 yuan, Xiaoruntong received a vaccine called "measles".

"That night, the child developed symptoms such as fever, gibbering, and crying." Zhu Mingyue, Xiaoruntong's mother, said that on the morning of March 3, she took her child to Shunhe District for health and epidemic prevention I asked at the station and was told that it was a normal reaction and I was advised to drink an antiviral oral solution. But her condition never eased and developed into a high fever, rashes all over her body, blisters all over her mouth, and large ulcers in her mouth. She was unable to eat normally and cried day and night.

Subsequently, Xiao Runtong was sent to Kaifeng First People's Hospital by Zhu Mingyue for hospitalization, and was diagnosed with vaccine reaction and oral ulcers. Hospitalized for 10 days.

Since both the Uni-President Kindergarten and the Heshun District Health and Epidemic Prevention Station said they were not responsible for the incident, the family members sued him in court, claiming more than 30,000 yuan in medical expenses and mental damages. On October 9, 2018, the case was heard in the Shunhe District Court of Kaifeng. Both parties held different opinions and the court did not pronounce a verdict in court.

The defendant believed that he was not at fault.

"It has been more than six months. The child will suddenly wake up from his dream at night and cry incessantly." Zhu Mingyue said, and there are also terrible "sequelae": every two days, he will He will tell his mother that his little butt is not clean, but in fact there is nothing there. You can still see a white mark around the child's mouth, which is the pain left by the vaccine, so the compensation for mental damage of 30,000 yuan is also Reasonable.

During the trial, the defendant’s attorney insisted that “the vaccination procedure is legal, there is no fault, and he should not be held responsible” and provided a piece of evidence: “Measles, mumps, and rubella combined attenuated virus "Vaccine" instructions, which states that "one-time fever and scattered rash may occur, which can resolve spontaneously within 2 days. The incidence of adverse reactions is fever 10.7% and rash 3.5%." In this regard, Zhang, a lawyer at Henan Tianzhiquan Law Firm, the plaintiff's lawyer. It is believed that parents did not know that vaccines still have side effects, and kindergartens and epidemic prevention stations failed to fulfill their obligation to inform them and did not ask whether their children were suitable for vaccination. There were obvious omissions and they should bear corresponding legal responsibility.

Nearly half of the young parents don’t know that the vaccine has side effects.

Zhu Mingyue has been blaming herself for 10 days after her child suffered the disease because the couple did not know that the vaccine would have side effects. Director of the Third Affiliated Hospital of Zhengzhou University. Physician Tian conducted a survey in May this year. The respondents were parents aged between 25 and 35. Among them, 48 did not know that the vaccine would have side effects, and less than 20 were fully aware of the side effects of the vaccine itself. It is a virus that reduces its activity. After vaccination, there will inevitably be certain side effects, most of which will include fever and other symptoms. This is inevitable, but with good care, the side effects will be less harmful to the baby. "Tian suggested that after a child is vaccinated, you must pay close attention to his condition. It is best not to take a bath within 4 hours, and apply a thin layer of potato chips on the needle hole. Once it becomes 3.5 in the unfortunate event, children with unknown symptoms such as fever Send to the hospital for treatment immediately

“Side effects of vaccination are common and there is no need to talk about them. "Tian reminded that young mothers must inquire in detail about the possible side effects of the vaccine before vaccination, and let the doctor know the child's medical history to determine whether the child is suitable for vaccination.