DTP Vaccine Research Articles

Metabolic and Hematologic Effects and Immune Complex Formation Related to Pertussis Immunization

Selected metabolic, hematologic, and immunologic functions were evaluated in 3- to 6-mo-old Finnish infants who received whole-cell pertussis-component diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) vaccine, and in 4- to 6-y-old Los Angeles children who received either a licensed DTP vaccine or an acellular pertussis component DTP vaccine. One d after immunization, there was an increase in total leukocytes and neutrophils and a decrease in lymphocytes in all vaccinees. In 4- to 6-y-old children the leukocytosis and neutrophilia were greater in recipients who received the standard DTP vaccine than in vaccinees who received an acellular pertussis component DTP vaccine. In infants there was an increase in the mean plasma insulin concentration but no change in the glucose concentration 24 h after immunization; no increase in the mean plasma insulin was noted in the 4- to 6-y-old children. Three 4- to 6-y-old vaccinees had higher circulating immune complex concentrations after immunization and two of these children had high clinical reaction scores. The etiology of adverse reactions after DTP immunization is multifactorial. In contrast with findings in animals, our findings do not demonstrate a clinically significant effect due to lymphocytosis-promoting factor on glucose metabolism in vaccinated children. Neutrophilia in vaccinees is probably due to endotoxin, and some reactions may be due to circulating immune complexes.

Longitudinal Study of Adverse Reactions Following Diphtheria-Tetanus-Pertussis Vaccine in Infancy

A prospective study of immunogenicity and adverse effects of 1553 doses of diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP) was performed in 538 children observed longitudinally from 2 months to 20 months of age. Subjects were randomized to the standard four-dose immunization schedule or to a three-dose schedule (with a saline injection substituted for DTP at 6 months of age). The three-dose schedule could not be recommended on the basis of serologic data. Compliance for completing a clinical observation form in the 48 hours following injections was greater than 99%. Fever, local reactions, or adverse behavioral effects were described in association with 96% of DTP doses and 36% of placebo injections. Contraindications to DTP immunization developed in 3% of study children. No convulsion, hypotonic hyporesponsive episode, encephalopathy, or temperature greater than 40.5 degrees C occurred. Behavioral and local inflammatory effects occurred maximally in the first 6 hours following vaccine but fever peaked later. There was no interrelationship between occurrence of local reaction and fever. Data suggest that age has more effect on the type and rate of adverse clinical events than does vaccine dose number. Existing antibody levels to vaccine components, lot of vaccine, breast-feeding, or gestational age did not affect rate or type of clinical reactions. Neither occurrence of reactions nor the use of acetaminophen affected antibody response to vaccine.

Comparison of Acellular and Whole-Cell Pertussis-Component DTP Vaccines

An acellular pertussis-component combined diphtheria and tetanus toxoids, and pertussis (APDT) vaccine adsorbed was compared with a licensed whole-cell pertussis-component combined diphtheria and tetanus toxoids, and pertussis (DTP) vaccine adsorbed for reactogenicity and immunogenicity when given as the fifth DTP immunization to eighty-two 4- to 6-year-old children. The reaction rates with both vaccines were low; APDT vaccine recipients had significantly less pain and warmth at the injection site than did DTP vaccine recipients. Antibody responses to pertussis antigens (lymphocytosis-promoting factor, filamentous hemagglutinin, and agglutinogens) and to diphtheria and tetanus toxoids were all brisk. The APDT vaccine recipients had a more marked response in antibodies to filamentous hemagglutinin and a less marked response in agglutinins than whole-cell vaccine recipients. On the day after immunization, both APDT and DTP vaccine recipients had an increase in mean leukocyte and neutrophil counts. This APDT vaccine is immunogenic and less reactogenic than a DTP vaccine with a whole-cell pertussis component when administered as a booster to 4- to 6-year-old children.

百日咳コンポーネントワクチンの百日咳感染防禦能

An outbreak of pertussis occurred in one room of a residential facility where 19 children aged 5 to 36 months were residing. They were prospectively surveyed to estimate the efficacy of acellular pertussis vaccine. Among the 19 residents, 9 were immunized with acellular pertussis vaccine. Among the 19 residents, 9 were immunized with acellular DTP vaccine and 10 were unimmunized. The spread of pertussis was surveyed bacteriologically and serologically for 2 months. Among the 9 immunized, 7 children acquired the laboratory-confirmed pertussis and 1 of the 7 developed the typical symptoms (whooping or paroxysmal coughing attack lasting for 14 days or more). Among the 10 unimmunized, 7 children acquired the laboratory-confirmed pertussis and 6 of the 7 developed the typical symptoms. There was no difference in the rate of secondary infection (7/9:7/10), but there was a significant difference in the rate of development of the typical symptoms (1/7:6/7 p less than 0.05). The point estimate of protective efficacy of the acellular DTP vaccine against typical pertussis was (6/10 - 1/9)/(6/10) x 100 = 81%. It was concluded from these findings that acellular DTP vaccine could not prevent the infection of Bordetella pertussis, but could prevent the development of the typical symptoms.

VACCINATION COVERAGE IN PRESCHOOL CHILDREN OF BUENOS AIRES

Vaccination coverage was studied in August, 1988 on five years old preschool children from county school of Buenos Aires. 768 children were selected by randomization (unit=school districts) and data was colected by preschool teachers previously instructed. The following data were registered on each child: age, sex, n9 of dosis of DTP, Sabin, BCG and Measles vaccine; level of instruction, age and occupation of the mother (or guardian); number of siblings; occupation and work stability of father and condition of housing. In addition, school district was taken into account (it was classified according to social status); school shift and parent's opinion about the importance of vaccination. 72% of children had a complete immunization, 90% coverage for BCG, 85.2% for Sabin, 84.5% for DTP and 81.9% for Measles. The following variables were considered as risk factors: a) offspring of analphabetic or with uncompleted primary instruction mother; b) three or more siblings in the family, group; c) doormen's children living in a “villa” or hotel; d) children of workmen or family workmen; e) children attending school on a eight hour schedule. These were also risk factor for Sabin, DTP and Measles vaccine but not for BCG. There was no relation between immunization and mother age, mothers working time, fathers work stability or school district social status. 74.9% of families considered that vaccines prevent diseases; the 7.2% considered that they attenuate them; 3.7% considered that they were obligated to vaccinate the children and 7.9% look up to the vaccine as a health vehicule with magical feelings, These differences do not have influence over the coverage. This data allow to review the immunization program for preschool children of Buenos Aires in order to achive a better coverage.

Durability of immunity to diphtheria, tetanus and poliomyelitis after a three dose immunization schedule completed in the first eight months of life

Blood samples were obtained from school entrants whose primary immunization schedule had consisted of three doses of DT or DTP vaccine and three doses of OPV all given before the age of 8 months. The sera were separated and assayed for diphtheria antitoxin, tetanus antitoxin and antibodies to the three serotypes of poliovirus. The results of the assays showed that the abbreviated three dose schedule induced satisfactory immunity to all five infections until school entry and that a reinforcing dose at 18 months was unnecessary

Permanent brain damage and pertussis vaccination: is the end of the saga in sight?

The development and widespread uptake of a safe and efficacious aluminium adsorbed diphtheria-tetanus-pertussis vaccine (DTP) in the United States between 1933 and 1944 led to a gradual decline in whooping cough morbidity and instilled confidence in a vaccination programme which has been effectively maintained for over 40 years. T his contrasts with the turbulent history of pertussis vaccination in the United Kingdom where doubts as to the efficacy of available vaccines delayed their active national promotion until 1957, after which various reports resulted in further doubts over efficacy and safety. In 1974, the mass media became involved in the safety issue when the National Hospital for Sick Children case series of neurological events, which had occurred after DTP vaccination was made core material for a television documentary. The Department of Health and Social Security (DHSS) responded by establishing two retrospective studies of case records of post vaccination adverse events and two prospective studies. One of the latter, the National Childhood Encephalopathy Study (NCES) was regarded as the definitive case control study. A claim for damages, Loveday v Renton and The Wellcome Foundation, heard in the High Court of Justice in London, from early October 1987 until late February 1988 dealt with the general issue of whether, on the balance of probabilities, pertussis vaccine could cause permanent brain damage. The cornerstone of the claim that pertussis vaccine can cause permanent brain damage has always been the apparent clustering of onset of neurological disorders within the first 24-48 h after vaccination. One of the main finds of the NCES, however, which was not divulged in any published report but emerged in the course of the hearing, was that permanent brain damage did not occur within 48 h of DTP vaccination in any child in England, Scotland and Wales from mid-1976 to mid-1979 when 2 million doses of vaccine were used. The NCES, in this respect, completely undermined the evidence provided by various published case series. After a 61 day hearing, High Court judgment was given to the effect that the judge was not satisfied on balance of probability that pertussis vaccine can cause permanent brain damage in young children. Were it not for the fact that The Wellcome Foundation intervened in the action and obtained a court order giving access to the NCES cases records, some crucial information collected by the NCES might not have been brought to light.(ABSTRACT TRUNCATED AT 400 WORDS)

Half-Dose Immunization for Diphtheria, Tetanus, Pertussis: Response of Preterm Infants

The American Academy of Pediatrics currently recommends administering full-dose diphtheria, tetanus, pertussis, (DTP) vaccine to preterm infants, beginning at 2 months' chronologic age. Many physicians, however, continue to administer DTP vaccine at a reduced dosage in an attempt to lessen side effects. This study was designed to quantitate the immune response of 20 preterm infants immunized with half-dose DTP vaccine and to determine the nature and extent of side effects. Control subjects were 25 preterm infants immunized with full-dose vaccine. Although 96% of infants who received a full dose were able to mount a serologic response to pertussis after a second dose of DTP, 45% of infants who received a half dose were unable to mount a similar immune response to pertussis even after a third dose of DTP and required a full-dose (fourth dose of DTP) vaccine to better ensure protection. Serologic responses to diphtheria and tetanus were similar in the two groups. The incidence of side effects in preterm infants receiving both full-dose and half-dose DTP was less than that seen in a full-term population. Thus, the physician caring for the preterm infant should adhere to the American Academy of Pediatrics' recommendation for the immunization of preterm infants and offer full-dose DTP vaccine at the routine time intervals of 2, 4, 6, and 15 or 18 months' chronologic age to ensure adequate protection.

Preterm Infants Should Receive Full Dose DTP Vaccination

Preterm Infants Should Receive Full Dose DTP Vaccination

DOES PERTUSSIS VACCINE CAUSE PERMANENT BRAIN DAMAGE? UNITED KINGDOM COURT RULES

1. The preliminary issue to be determined by the court is, can pertussis vaccine cause permanent brain damage in young children? The question relates to pertussis vaccine manufactured in the United Kingdom and applies to all children whether or not they were neurologically normal before vaccination. The burden of proof rests on the Plaintiff and the standard of proof is that of the balance of probability. It must be shown that it is more likely than not that the vaccine can cause permanent brain damage. 2. The medical and expert opinion is deeply divided on the issue. 3. The question is not answered by showing that there is a respectable and responsible body of medical opinion that the vaccine can, albeit rarely, cause permanent brain damage, or that this view is/may be more widely held than the contrary. 4. Similarly the advice contained in the contra-indications against pertussis vaccination . . . cannot be relied upon as though it were evidence . . . that the vaccine in fact causes permanent brain damage. 5. Reports of . . . encephalopathy resulting in . . . brain damage or death where the onset occurs shortly after DTP vaccination, raises the hypothesis that the vaccine may cause brain damage or death. It does not prove the hypothesis. Such reports do not take account of events occurring by chance, for which no explanation can be found. What they do establish is that encephalopathy resulting occasionally in permanent brain damage or death does sometimes occur in close temporal proximity to pertussis vaccination. 6. I have reviewed the evidence and reasoning of the Plaintiffs and Defendants' expert witnesses . . . . I have found myself more impressed both by the cogency and quality of the evidence and reasoning of the experts called on behalf of the Defendants. 7. When I embarked on consideration of the preliminary issue, I was impressed by the case reports and what was evidently a widely held belief that the vaccination could, albeit rarely, cause permanent brain damage. I was ready to accept that this belief was well founded. But over the weeks that I have listened to and examined the evidence and arguments, I have become more and more doubtful that this is so. I have now come to the clear conclusion that the Plaintiff fails to satisfy me on the balance of probability that pertussis vaccine can cause permanent brain damage in young children. It is possible it does, the contrary cannot be proved. But in the result the Plaintiff's claim must fail.

Full and Preterm Infants Respond Similarly to DTP Vaccine

Full and Preterm Infants Respond Similarly to DTP Vaccine

DTP immunization status and tetanus antitoxin titers of Mexican American children ages six months through eleven years.

Data from the Mexican American portion of the Hispanic Health and Nutrition Examination Survey (HHANES), conducted in 1982-83, were analyzed for the number of diphtheria, tetanus, and pertussis (DTP) immunizations reported for Mexican American children 6 months-11 years of age and for levels of tetanus antitoxin titers in Mexican American children 4-11 years of age. In Mexican American children 6 months-11 years, 98.2 per cent had one or more DTP immunizations reported (95 per cent CI: 97.5, 98.9%); 85.1 per cent had three or more DTP immunizations reported (95 per cent CI: 83.2, 87.0%). The reported immunization coverage in Mexican American children was corroborated by the tetanus antitoxin titers which were above the minimum protective level (greater than or equal to 0.01 IU/ml) in 99.6 per cent of the 4-11 year olds. Using the American Academy of Pediatrics' (AAP) recommendations for the number of DTP immunizations, 61.1 per cent of the children 6 months-11 years of age had the age-appropriate number of immunizations (95 per cent CI: 58.5, 63.7%). AAP immunization completion rates were higher for children who: had a source of care reported (62.1 vs 44.3%; 95% CI of the difference: 7.1, 28.5); had insurance coverage (63.5 vs 56.1%; 95% CI of the difference: 2, 12.8); lived in a standard metropolitan statistical area (SMSA)-not central city as compared to SMSA-central city or not SMSA (66.6 vs 57.1%; 95% CI of the difference: 4.3, 14.7); and had 12 or more completed years of education for the head of the household (65.4 vs 58.3%; 95% CI of the difference: 1.8, 12.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Risk of sudden infant death syndrome after immunization with the diphtheria-tetanus-pertussis vaccine.

To evaluate recent immunization against diphtheria, tetanus, and pertussis (DTP) as a possible risk factor for sudden infant death syndrome (SIDS), we studied the rates of SIDS after the administration of DTP vaccine in a cohort of 129,834 children who were born in four urban Tennessee counties during the period from 1974 through 1984. All the children received at least one DTP immunization in the first year of life at county health-department clinics or from Medicaid providers. Computerized immunization records from these sources were linked with Tennessee birth and death certificates to establish the cohort, ascertain the timing of immunization, and identify cases of SIDS. These children represented 42 percent of the births in the four counties. Among these children, 204 deaths occurred at the ages of 29 to 365 days; 109 deaths were classified as due to SIDS. We estimated the risk of SIDS according to the length of time, up to 30 days, since DTP immunization and compared it with the risk 31 days or more after immunization to calculate the relative risk. With control for age, the relative risk from 0 to 3 days after DTP immunization was 0.18 (95 percent confidence interval, 0.04 to 0.8); from 4 to 7 days, 0.17 (95 percent confidence interval, 0.04 to 0.7); from 8 to 14 days, 0.75 (95 percent confidence interval, 0.4 to 1.5); and from 15 to 30 days, 1.0 (95 percent confidence interval, 0.6 to 1.6). A multivariate analysis in which we controlled for age, sex, race, year, birth weight, and Medicaid enrollment, produced similar results. We conclude that in this large population of children there was no increase in the risk of SIDS after immunization with the DTP vaccine.

What Is `Significant' and DTP Reactions

To the Editor.— I read with interest the article by Hoffman et al.1 The authors conclude from this study that DTP immunization is not a significant factor in the occurrence of SIDS because only five (1.8%) of the case infants died within 24 hours of receiving the DTP vaccine. Their data are welcomed and provide convincing evidence that the DTP vaccine does not contain a potent toxin contributing to infant sudden death. However, if one assumes that the adverse reaction to the DTP vaccine may result from an immunologic intravascular complexing of particulate antigen (whole-cell or disrupted pertussis organisms) with specific antibody to produce a Jarisch-Herxheimer reaction,2,3 then the adverse reaction may not occur within 24 hours of inoculation.

What Is `Significant' and DTP Reactions

In Reply.— The two letters received in response to our article1 express a diversity of opinion regarding the inferences to be drawn from the findings regarding SIDS and DTP reported from the NICHD SIDS Cooperative Epidemiological Study. In the first instance, Dr Eden suggests that we were too cautious in our concluding statement that: "DTP immunization does not appear to be a significant factor in the occurrence of SIDS." The critical point to be made is that in any study, regardless of the number of subjects included and the care taken in study design and implementation, the most that can be claimed is a statistical result that admits a small probability of exception.

Pertussis Immunization and Convulsions

A follow-up study of 18 infants and children who suffered convulsions (9 cases) or “hypotonic-hyporesponsive“ episodes (9 cases) within 48 hours following DTP immunization was conducted in the Depts of Pediatrics, UCLA Hospital and Clinics, and the Kaiser Permanente Medical Group, Los Angeles, CA.

Influence of parental knowledge and opinions on 12-month diphtheria, tetanus, and pertussis vaccination rates.

To assess the magnitude and cause of decreasing diphtheria, tetanus toxoids, and pertussis (DTP) immunization rates, a retrospective cohort study investigated the immunization status against pertussis among 1-year-old children in Utah. Questionnaires were sent to the parents of 2975 children born in June 1985. Parents were asked about each child's DTP immunization status, including the number, type, and dates of the vaccinations, reasons for or against vaccination, and their knowledge of whooping cough and the vaccine. Children were considered adequately immunized against pertussis when they had received three DTP vaccinations by their first birthday. In Utah, the lack of pertussis immunization among young children is a serious problem: greater than 30% of 1-year-old children were not adequately protected. Accurate parental knowledge about the relative risks of vaccination and illness was associated with a greater likelihood for immunization. Although some parents chose to forego the vaccination because they were concerned about its side effects, the most common reason for incomplete immunization was illness at the time the vaccination was to be given. If immunization rates are to improve, health care professionals must not only make an effort to educate the general population regarding the vaccine, but they must also ensure immediate follow-up for immunization when the procedure is delayed.

Seizures Following DTP Immunization

The incidence of seizures following the administration of DTP vaccine at the Group Health Cooperative of Puget Sound, Seattle, has been estimated by epidemiologists at the Harvard School of Public Health, Boston, and by the Boston Collaborative Drug Surveillance Program, Waltham, Mass.

Clinical and serologic responses to acellular pertussis vaccine in infants and young children.

We administered diphtheria, tetanus, and pertussis (DTP) vaccine containing acellular (lymphocytosis promoting factor and filamentous hemagglutinin) pertussis vaccine to three groups of 20 children each (4 to 6 years, 17 to 21 months, and 5 to 9 months of age). All the children tolerated the vaccine well; no reactions occurred that contraindicated further immunization. Older children had significantly more local (redness or swelling) and systemic (fever or fretfulness) reactions than younger children. Eighty percent to 90% of the children in the two older age groups had fourfold or greater increases in antibody titers to DTP antigens one month after vaccination. The postvaccine concentrations of antibody to tetanus and diphtheria were greater than 0.01 IU/mL in all children. Serologic responses to lymphocytosis promoting factor and filamentous hemagglutinin varied with age; significantly more older children than younger children had four-fold or greater increases. Acellular pertussis DTP vaccine was antigenic in young children and was less reactogenic than standard whole cell DTP vaccine according to rates reported in previous studies.

Haemophilus influenzae type b: the search for a vaccine.

In adults Hib CPS protein conjugates are much more immunogenic than the polysaccharide alone; further studies have shown that they induce a booster response in children. The antibodies produced in response to the conjugates have the same biologic properties, isotype and IgG subclass composition as those elicited by Hib CPS alone or those present in serum after convalescence from Hib disease. More recently attempts have been made to make the conjugates compatible with DTP vaccine. In this procedure DTP is absorbed onto aluminum compounds (aluminum hydroxide or phosphate), with the effect of significantly prolonging diphtheria and tetanus antibody synthesis. Adsorption of the Hib CPS conjugate under controlled conditions does not alter the total amount of antibody elicited in infant rhesus monkeys after the third or final injection. The appearance of Hib CPS antibodies after the first injection, however, is accelerated with conjugate that has been adsorbed. This is an encouraging finding, because it means that more polysaccharide conjugates can be compatible with existing DTP vaccine.