Original Article
A Placebo-Controlled Trial of a Pertussis-Toxoid Vaccine
N Engl J Med 1995; 333:1045-1050October 19, 1995
- Abstract
Background
Although many whole-cell vaccines have been effective in preventing pertussis, these vaccines are difficult to standardize and can produce side effects. In Sweden, pertussis became endemic during the 1970s despite vaccination. Because of its limited efficacy, the Swedish-made whole-cell vaccine was withdrawn in 1979.
Methods
To evaluate the efficacy of an acellular vaccine consisting of pertussis toxin inactivated by hydrogen peroxide (pertussis toxoid), we conducted a randomized, double-blind, placebo-controlled trial in Sweden. Infants were vaccinated with either diphtheria and tetanus toxoids alone (DT toxoids, 1726 infants) or diphtheria, tetanus, and pertussis toxoids (DTP toxoids, 1724 infants) at 3, 5, and 12 months of age.
Results
There were no serious reactions. With the pertussis vaccine there were slightly more local reactions than with the DT toxoids alone, but the rates of postvaccination fever were the same. The main period of surveillance, which began 30 days after the third vaccination, continued for a median of 17.5 months. There were 312 cases of pertussis (72 in the DTP-toxoids group and 240 in the DT-toxoids group) that met the clinical criterion (paroxysmal cough lasting >21 days) and laboratory criteria for pertussis as defined by the World Health Organization. The efficacy of this acellular vaccine was 71 percent (95 percent confidence interval, 63 to 78 percent). The recipients of DTP toxoids who had pertussis had cough of shorter duration than the recipients of DT toxoids, and fewer had whooping and vomiting. The vaccine efficacy after two doses was 55 percent (95 percent confidence interval, 12 to 78 percent), on the basis of 14 cases in the DTP-toxoids group and 31 in the DT-toxoids group that met the definition of the World Health Organization.
Conclusions
A pharmacologically inert, acellular pertussis-toxoid vaccine that is easily standardized is safe and confers substantial protection against pertussis.
Media in This Article
Table 1
Categories of Coughing Episodes in the Göteborg Classification.Table 2
Major and Minor Criteria for Pertussis in the Göteborg Classification.Article Activity
- Article
Vaccines consisting of inactivated Bordetella pertussis induce protection against pertussis, but estimates of their efficacy vary from 40 to 90 percent.1 There is no consensus about what the protective moieties are in whole-cell vaccines or what mechanism induces protection. The potency of whole-cell vaccines is estimated by the mouse protection test, which has considerable variability.2,3 Local reactions and fever are frequent after the administration of whole-cell vaccines, which are also associated with hypotonic–hyporesponsive events, persistent crying, and convulsions.4 These limitations of whole-cell vaccines have stimulated the development of vaccines made with purified antigens, which should have fewer side effects and be easier to standardize. All acellular vaccines contain detoxified pertussis toxin; some also contain filamentous hemagglutinin, pertactin, and fimbriae.5
Because every vaccine component has the potential for causing side effects, we evaluated the safety and efficacy of a single-component, pharmacologically inert pertussis toxoid. Pertussis toxin is a protein with a central role in the pathogenesis of pertussis.2,6 Open studies and a double-blind study indicate that pertussis toxoids induce protection.7-9 The present trial was performed in Sweden, where pertussis has been endemic since the early 1970s, when changes in production made the Swedish-made whole-cell vaccine ineffective.10 When the incidence of pertussis increased despite vaccination rates of about 90 percent, the recommended infant vaccine was withdrawn in 1979. Since then, Sweden has had no licensed pertussis vaccine. Accordingly, it was possible to perform a placebo-controlled study. Inclusion of a whole-cell vaccine was considered undesirable because renewed licensure of a whole-cell vaccine in Sweden was highly unlikely.
Methods
Study Design
The study was double-blind and placebo-controlled. Infants were randomly assigned to be vaccinated with diphtheria and tetanus toxoids (DT toxoids) or to receive the same DT toxoids with pertussis toxoid (DTP toxoids). Vaccines were injected subcutaneously in the anterolateral part of the thigh at 3, 5, and 12 months of age, as is recommended for DT toxoids in Sweden.
The study protocol was reviewed by the institutional review board of the National Institute of Child Health and Human Development; the Food and Drug Administration (FDA); the Medical Products Agency, Uppsala, Sweden; and the Ethics Committee, Göteborg University. All parents gave written consent after receiving oral and written information.
Vaccines
The pertussis toxoid inactivated by hydrogen peroxide was developed at the National Institute of Child Health and Human Development and manufactured by Amvax (Beltsville, Md.). The vaccine elicits serum antibodies that neutralize pertussis toxin.8,11 The DT toxoids were manufactured by Statens Seruminstitut (Copenhagen, Denmark). One 0.5-ml dose (DT-toxoids lot K36, DTP-toxoids lot K36-567) consisted of 25 flocculation units of diphtheria toxoid and 7 flocculation units of tetanus toxoid adsorbed onto 0.5 mg of aluminum hydroxide with 0.01 percent thimerosal, with or without 40 μg of pertussis toxoid. The purity of pertussis toxin was demonstrated by sodium dodecyl sulfate–polyacrylamide-gel electrophoresis. The inactivation of pertussis toxin was verified by tests for histamine sensitization, toxicity in Chinese-hamster-ovary cells, and hemagglutinating activity. The DTP-toxoids vaccine passed the rabbit pyrogenicity and general-safety assays of the FDA. The DT toxoids and DTP toxoids were identical in appearance. Vials were filled and coded in sets of three, one set for each child, according to a computer-based randomization list. No other vaccine was given with the study vaccines.
Recruitment and Study Cohort
Full-term, healthy infants in the Göteborg area were eligible for the study if the family had a telephone and if a parent spoke Swedish. About 99 percent of Swedish children visit publicly financed child health centers, where the first information about the study was given to parents. Vaccinations and follow-up were performed by project nurses at five study sites.
During the recruitment period, 7040 newborns were registered at 96 child health centers in the area. The parents of 3450 of 5964 eligible children (58 percent) agreed to participate. Of those, 1724 were randomly assigned to receive DTP toxoids, and 1726 to receive DT toxoids. The 1750 boys and 1700 girls were evenly distributed between the two groups. There were 817 recipients of DTP toxoids and 850 recipients of DT toxoids with one or more older siblings. At 13 months, 8 percent of the DTP-toxoids group attended day-care centers, as compared with 7 percent of the DT-toxoids group; at 27 months, the respective figures were 55 and 51 percent. The first vaccination was given to the 3450 participants between September 1991 and September 1992. The second was given to 3425 children and the third to 3379 between May 1992 and July 1993.
Fifty-two children (1.5 percent; 30 in the DTP-toxoids group and 22 in the DT-toxoids group) were withdrawn from the study, 27 before and 25 after the third vaccination. Twenty-three moved, contraindicating diseases developed in 2, 1 had pertussis before the first vaccination, 1 died, and the parents of 25 declined further participation.
Coughing episodes starting between the first vaccination and July 24, 1994, were included in the study analysis. On that day the median age of the children was 30.5 months (range, 26 to 37). The surveillance period was divided into two parts: from the first vaccination until 29 days after the third, and from 30 days after the third vaccination until July 24, 1994 (the main period of follow-up). The median duration of follow-up during the main period was 17.5 months (range, 13 to 24). The randomization code was broken on November 18, 1994.
Side Effects
Parents measured the children's rectal temperatures 6, 24, and 48 hours after each vaccination and inspected the injection site daily for seven days, after which time they were interviewed about their children's temperatures, local reactions, and such events as convulsions, symptoms of the hypotonic–hyporesponsive syndrome, and persistent crying. During the study, the parents were contacted monthly by telephone. Visits to doctors and hospitalizations were noted. Between August 1 and November 18, 1994, a final interview was conducted with parents of 3413 of the 3450 children originally enrolled (99 percent).
Coughing Episodes
Parents were instructed to contact the study nurse if anyone in the family coughed for seven or more days. A nasopharyngeal sample for culture and polymerase-chain-reaction (PCR) analysis and a serum sample were obtained. A serum sample was also obtained during convalescence, at least four weeks later. The duration of cough, paroxysms, whooping, vomiting, fever, and rhinitis and the use of antibiotics were recorded. Follow-up continued for at least 60 days or until the cough ended.
We followed the guidelines of the Swedish Board of Health and Welfare, which recommend prophylaxis with erythromycin for infants under 6 months of age and early treatment for infants 6 to 11 months old and for siblings of infants under 12 months old. All prescriptions of macrolides were documented.
Laboratory Assays
Secretions obtained with nasopharyngeal swabs were cultured on Regan–Lowe medium12 and in an enrichment medium (Regan–Lowe with 50 percent charcoal agar), and PCR was used to detect B. pertussis and B. parapertussis.13,14 Colonies of B. pertussis and B. parapertussis were verified by Gram's staining, agglutination, and biochemical tests.
Antibodies against pertussis toxin and filamentous hemagglutinin were measured by enzyme-linked immunosorbent assay15,16 in duplicate in eight threefold dilutions starting from 1:10 for IgG and 1:100 for IgM and IgA. The pertussis toxin was obtained from Amvax, and the filamentous hemagglutinin from the Institut Pasteur Mérieux, (Marcy l'Etoile, France). The reference was pertussis antiserum lot 3 from the FDA. Titers were defined as the reciprocal serum dilution corresponding to an absorbance of 0.2 above the background level. On the basis of intraassay variation and variation in individual subjects, threefold increases were considered statistically significant if the titer in the serum sample obtained during convalescence was >200. On the basis of a pilot study, titers of >6000 for IgG antibodies against pertussis toxin and filamentous hemagglutinin concurrently in a single convalescence serum sample were considered a sign of pertussis (data not shown).
Serum was obtained from 3361 children at least four weeks after the third vaccination. IgG antibodies against pertussis toxin and toxin-neutralizing antibodies17 were measured.
Case Definitions
Coughing episodes were classified according to the criteria of the World Health Organization (WHO)18 and according to the Göteborg classification (Table 1Table 1
Categories of Coughing Episodes in the Göteborg Classification. and Table 2Table 2Major and Minor Criteria for Pertussis in the Göteborg Classification.) developed by the authors. The WHO definition of pertussis includes a paroxysmal cough lasting 21 days or more and at least one of the following: a positive culture, a positive culture in a family member with onset of pertussis within 28 days before or after the onset of the episode studied, and a statistically significant increase in IgG antibodies against pertussis toxin or filamentous hemagglutinin.The Göteborg classification was developed because the WHO definition accepts only household contact confirmed by culture as a criterion and because an acute-phase serum sample, necessary for the detection of an increase in antibodies, is not always obtained. Moreover, increases in filamentous-hemagglutinin antibodies can be seen in both pertussis and parapertussis and these antibodies cross-react with outer-membrane proteins of nonencapsulated Haemophilus influenzae.19
Children with confirmed, probable, or unverified pertussis (categories 1, 2, and 3 in Table 1) were considered at risk for pertussis until the first day of cough. Children with parapertussis (category 4) were considered to be still at risk for pertussis.20
Statistical Analysis
The efficacy of the pertussis vaccine was estimated as 1 - R, where R is the ratio of incidence rates (the number of cases divided by the total time at risk) in recipients of DTP toxoids and DT toxoids. Ninety-five percent confidence intervals for efficacy were estimated by exact calculation21 based on the conditional binomial distribution that follows from the assumption of a Poisson distribution for cases in each group.22 Proportions were compared with a two-sided Fisher's exact test, and continuous variables with the two-sided permutation t-test. P values of less than 0.05 were considered to indicate statistical significance.
Results
Safety
There were no serious reactions to the vaccines. No child was withdrawn because of an adverse reaction. The frequency of fever within 48 hours of vaccination did not differ between the groups. Redness and swelling increased with the number of vaccinations and were somewhat more common among recipients of DTP toxoids (Table 3Table 3
Occurrence of Fever within 48 Hours and Local Reactions within 7 Days in Children Vaccinated with DTP Toxoids or with DT Toxoids.). Irritability and feeding and sleeping problems were equally frequent in the two groups. No child had the hypotonic–hyporesponsive syndrome, persistent or high-pitched crying, or afebrile convulsions. Two recipients of DTP toxoids had febrile convulsions within 48 hours after the third vaccination; both had respiratory tract infections. The one child who died was a DTP-toxoids recipient who had pneumococcal endocarditis. Four children, all recipients of DT toxoids, had invasive bacterial infections with favorable outcomes. Malignant diseases developed in five children (two in the DTP-toxoids group and three in the DT-toxoids group). The frequency of other serious diseases was similar in the two groups.Bordetella Infections
There were 2037 coughing episodes lasting at least seven days with onset before July 25, 1994, in children in the study. Of those, 465 (160 in the DTP-toxoids group and 305 in the DT-toxoids group) met the criteria for confirmed or probable pertussis (categories 1 and 2, Table 1), including 368 (92 in the DTP-toxoids group and 276 in the DT-toxoids group) that met the WHO definition. Another 14 children (4 in the DTP-toxoids group and 10 in the DT-toxoids group) had clinical pertussis without laboratory confirmation (category 3). Twelve children (seven in the DTP-toxoids group and five in the DT-toxoids group) had confirmed parapertussis. None of the 491 children with bordetella infections were hospitalized.
In family members, 336 of 917 coughing episodes met the WHO definition. Another 98 family members had confirmed or probable pertussis according to the Göteborg classification. Twenty-two episodes met the criteria for category 3. Four family members had confirmed parapertussis.
Efficacy during the Main Period of Follow-up
Thirty days after the third vaccination, 1670 recipients of DTP toxoids and 1665 recipients of DT toxoids remained at risk. The incidence of pertussis, according to the WHO definition, was 2.96 cases per 100 person-years among the recipients of DTP toxoids and 10.32 cases per 100 person-years among the recipients of DT toxoids, respectively. The efficacy of the pertussis vaccine was 71 percent (Table 4Table 4
Cases of Pertussis and Efficacy of the Pertussis Vaccine during the Main Period of Follow-up (from 30 Days after the Third Vaccination until the End of the Study).).Nine children who had paroxysmal cough for 21 days or more (three in the DTP-toxoids group and six in the DT-toxoids group) did not meet the WHO definition but had confirmed or probable pertussis according to the Göteborg classification. Seven had elevated titers of IgG antibodies against both pertussis toxin (7156 to 65,610) and filamentous hemagglutinin (8620 to 21,870) in serum samples obtained during convalescence. Two had household contacts with serologically confirmed pertussis.
Sixty-two children (50 in the DTP-toxoids group and 12 in the DT-toxoids group) received diagnoses of confirmed or probable pertussis with paroxysmal cough lasting less than 21 days. The incidence of pertussis including all children with cough lasting at least seven days was 5.13 cases per 100 person-years among the recipients of DTP toxoids and 11.09 cases per 100 person-years among the recipients of DT toxoids (efficacy of the pertussis vaccine, 54 percent) (Table 4).
Periods of cough, vomiting, and whooping were significantly shorter in children with pertussis in the DTP-toxoids group than in those in the DT-toxoids group (Table 5Table 5
Comparison of Clinical Symptoms among Recipients of DTP Toxoids and of DT Toxoids during the Main Period of Follow-up, According to the Classification of Pertussis.). There were no significant differences in efficacy between boys and girls or among the five study sites and no decreasing efficacy with time after the third vaccination.Possible Sources of Bias
Nine children (two in the DTP-toxoids group and seven in the DT-toxoids group), who were not included in efficacy estimates, had clinical pertussis without laboratory confirmation (category 3). Eight (four of whom were positive for B. pertussis by PCR) had high values for IgG antibodies against pertussis toxin and filamentous hemagglutinin in both the initial and convalescence serum samples but did not have significant increases or titers of >6000 for both antibodies. Their first serum samples were obtained more than 10 days after the onset of cough. No serum samples were available from one child who was positive by PCR.
Three cases of pertussis in recipients of DT toxoids with onset 30 to 60 days after the third vaccination were not included in efficacy estimates because of the timing of serum collection (Table 2). Two patients had increases in IgG antibodies against pertussis toxin, and one had titers of IgG antibodies against pertussis toxin and filamentous hemagglutinin above 6000. Erythromycin was given to 5 of 125 recipients of DTP toxoids with pertussis (4 percent) and to 17 of 258 recipients of DT toxoids with pertussis (7 percent) within 14 days after onset of cough. The parents of 25 of the 52 children withdrawn from the study were interviewed during the autumn of 1994 before the randomization code was broken. Three children (two in the DTP-toxoids group and one in the DT-toxoids group) had culture-confirmed pertussis after leaving the study.
Comparison of Diagnostic Assays
Cultures were performed for 357 of 383 children with confirmed or probable pertussis. The proportion of positive cultures was lower in DTP-toxoids recipients than in DT-toxoids recipients (49 percent [56 of 115] vs. 64 percent [154 of 242], P<0.01). Results of the PCR were similar: 55 of 108 DTP-toxoids recipients with pertussis (51 percent) and 155 of 225 DT-toxoids recipients with pertussis (69 percent) were positive (P<0.01).
Paired serum samples were available for 345 of 383 children with confirmed or probable pertussis. Significant increases in IgG antibodies against pertussis toxin were less common in recipients of DTP toxoids than in recipients of DT toxoids (31 percent [33 of 107] vs. 89 percent [201 of 226], P<0.001) because 80 percent of DTP-toxoids recipients had values above 1000 for these antibodies in the acute-phase serum samples, as compared with 20 percent of DT-toxoids recipients. Significant increases in IgG antibodies against filamentous hemagglutinin were seen in 94 percent of the DTP-toxoids recipients (104 of 111) and 92 percent of the DT-toxoids recipients (216 of 234).
A significant increase in IgG antibodies against filamentous hemagglutinin was the only criterion met in 29 cases of pertussis (22 in the DTP-toxoids group and 7 in the DT-toxoids group). In all cases there was a clinical picture of bordetella infection, with known exposure, paroxysmal cough, and little or no rhinitis or fever. Nineteen cases (15 in the DTP-toxoids group and 4 in the DT-toxoids group) met the WHO definition of at least 21 days of paroxysmal cough. Seventeen involved whooping or vomiting. Four of seven DT-toxoids recipients with increases only in IgG antibodies against filamentous hemagglutinin did not have IgG, IgM, or IgA antibodies against pertussis toxin in their acute-phase and convalescence serum samples, suggesting parapertussis rather than pertussis. The other three DT-toxoids recipients had IgG antibodies against pertussis toxin in both serum samples, indicating pertussis. The 22 recipients of the DTP toxoids had IgG antibodies against pertussis toxin in both serum samples.
Efficacy before the Main Period of Follow-up
From the first vaccination to 29 days after the second, 13 children (7 in the DTP-toxoids group and 6 in the DT-toxoids group) had confirmed or probable pertussis with cough lasting at least 7 days. Eleven of these cases met the WHO definition.
From 30 days after the second vaccination to 29 days after the third, there were 69 cases with cough lasting at least 7 days (28 in the DTP-toxoids group and 41 in the DT-toxoids group; efficacy of pertussis vaccine, 31 percent; 95 percent confidence interval, -14 to 59 percent). Of the 69 cases, 45 met the WHO definition (14 in the DTP-toxoids group and 31 in the DT-toxoids group; efficacy of the pertussis vaccine, 55 percent; 95 percent confidence interval, 12 to 78 percent).
Serologic Responses
Geometric mean antibody titers were determined at least four weeks after the third vaccination in 71 DTP-toxoids recipients who later had pertussis according to the WHO definition. The values were 5407 for IgG antibodies against pertussis toxin (range, 881 to 77,990) and 200 for neutralizing antibodies (range, 40 to >640). Corresponding titers for 433 randomly selected children in whom pertussis did not develop were 7801 (528 to 65,610) and 244 (40 to >640).
Discussion
This study shows the safety of the acellular pertussis-toxoid vaccine. Apart from slight increases in local reactions in recipients of DTP toxoids as compared with recipients of DT toxoids, no adverse reactions were observed.
Pertussis is endemic in Sweden, with epidemic peaks about every third year. A peak occurred during the winter of 1993–1994. Seventeen percent of DT-toxoids recipients had pertussis during the trial. After three injections, the efficacy of the acellular vaccine against pertussis with at least 21 days of paroxysmal cough was 71 to 77 percent, depending on the case definition, and 54 percent when all cases with cough lasting at least 7 days were included. The disease had a shorter duration and lower frequency of whooping and vomiting in vaccinated children than in unvaccinated ones.
The evaluation of coughing episodes that resemble pertussis but do not meet laboratory criteria because of suboptimal diagnostic sampling indicated no overestimation of efficacy due to missed cases. The nine cases in category 3 had the same distribution among vaccine groups as cases that met the WHO definition (two in the DTP-toxoids group and seven in the DT-toxoids group). Two other potential causes of bias — erythromycin use and pertussis among children who were withdrawn from the study — were ruled out. The rate of erythromycin use was low (6 percent) and similar in the two groups, and the withdrawal rate was only 1.5 percent.
It is difficult to make detailed comparisons of the efficacy of this pertussis vaccine and that of others. Randomized, placebo-controlled trials of whole-cell vaccines have not been performed since the 1950s, when diagnostic methods were different.23 A review of 39 open studies of whole-cell vaccines found efficacy estimates of 40 to 90 percent.1 Several factors influence the estimates, including case definitions and rates of pertussis in the population studied. Efficacy estimates were higher when only cases of long duration were included, when laboratory confirmation was required, or when the attack rate in the unvaccinated population was relatively low. Furthermore, the amount of pertussis toxoid varies among whole-cell vaccines.24,25 During the 1980s, a double-blind, placebo-controlled efficacy trial was performed in Sweden with a one-component pertussis toxoid and a two-component vaccine composed of pertussis toxoid and filamentous hemagglutinin.9 Both vaccines reduced the incidence and severity of pertussis. Since only two doses were given and the children were 6 to 11 months of age when admitted to the trial, valid comparisons with the pertussis toxoid used in our study are not possible.
Because of cross-reactivity between outer-membrane proteins of nonencapsulated H. influenzae and filamentous hemagglutinin,19 there is a risk of overdiagnosing bordetella infections with serologic tests for filamentous-hemagglutinin antibodies. A clinical analysis of all patients with an increase in IgG antibodies against filamentous hemagglutinin as the only positive laboratory finding indicated, however, that all of them had an infection with bordetella rather than H. influenzae. Thus, cases with an increase in filamentous-hemagglutinin antibodies as the only laboratory evidence of bordetella infection should be included in calculations of vaccine efficacy, even though a few parapertussis cases could be falsely diagnosed as pertussis. If an increase in IgG antibodies against filamentous hemagglutinin alone had not been accepted as diagnostic in our study, the efficacy of the pertussis toxoid against pertussis with at least 21 days of paroxysmal cough would have been 78 percent instead of 71 percent.
This study reveals an important diagnostic difficulty that occurs when antibodies against a vaccine component are assayed for serologic diagnosis. Pertussis-toxin serologic testing had much lower sensitivity in recipients of DTP toxoids than in recipients of DT toxoids, because the DTP-toxoids recipients already had high values for IgG antibodies against pertussis toxin in the acute-phase serum samples. It was therefore of great value to measure antibodies against an antigen (filamentous hemagglutinin) that was not included in the vaccine. In trials of vaccines containing both pertussis toxin and filamentous hemagglutinin, the serologic diagnosis will be even more difficult. Furthermore, cultures and the PCR were less sensitive in vaccinated children than in unvaccinated ones.
In conclusion, a pertussis-toxoid vaccine was safe and immunogenic and reduced the incidence and severity of pertussis. Furthermore, recovery of the organism was reduced. We propose that pertussis toxoid is both essential and sufficient for the vaccination of children and adults. It is the simplest and thus theoretically the safest vaccine for pertussis. We are now investigating whether mass vaccination of children with pertussis toxoid will eliminate pertussis, as happened in the case of diphtheria, another noninvasive, toxin-mediated respiratory disease. Mass vaccination with diphtheria toxoid eliminated diphtheria even though the toxoid confers incomplete individual protection under endemic or epidemic conditions.26,27
Supported by a contract (NO1-HD-9-2905) with the National Institute of Child Health and Human Development. Polymerase-chain-reaction analyses were financed by Göteborg University.
We are indebted to head nurse Nina Knutsson and all the study nurses, laboratory technicians, and data clerks for their excellent work; to Dr. Kjell Tullus for an independent review of all cases of pertussis; to Professor Hans Wedel for reviewing the statistical calculations; and to Drs. Rachel Schneerson and Duane Alexander, Dolores Bryla, M.P.H., and Professor Ingemar Kjellmer for valuable support during the entire project.
Source Information
From the Departments of Pediatrics (B.T., J.T.), Medical Microbiology and Immunology (T.L.), Clinical Bacteriology (L.L., G.Z.), and Geriatric Medicine (V.S.), Göteborg University, Göteborg, Sweden; and the National Institute of Child Health and Human Development (C.U.L., J.B.R.) and the National Institute of Allergy and Infectious Diseases (W.B.), National Institutes of Health, Bethesda, Md.
Address reprint requests to Dr. Trollfors at the Göteborg Pertussis Vaccine Trial, St. Paulig 6, S-416 60 Göteborg, Sweden.
- References
References
1
Fine PEM ,Clarkson JA . Reflections on the efficacy of pertussis vaccines. Rev Infect Dis 1987;9:866-883
CrossRef | Medline2
Robbins JB ,Pittman M ,Trollfors B ,Lagergard TA ,Taranger J ,Schneerson R . Primum non nocere: a pharmacologically inert pertussis toxoid alone should be the next pertussis vaccine. Pediatr Infect Dis J 1993;12:795-807
CrossRef | Web of Science | Medline3
Robinson A ,Funnell SGP . Potency testing of acellular pertussis vaccines. Vaccine 1992;10:139-141
CrossRef | Web of Science | Medline4
Cody CL ,Baraff LJ ,Cherry JD ,Marcy SM ,Manclark CR . Nature and rates of adverse reactions with DTP and DT immunizations in infants and children. Pediatrics 1981;68:650-660
Web of Science | Medline5
Schmitt HJ ,Wagner S . Pertussis vaccines -- 1993. Eur J Pediatr 1993;152:462-466
CrossRef | Web of Science | Medline6
Pittman M . The concept of pertussis as a toxin-mediated disease. Pediatr Infect Dis J 1984;3:467-486
CrossRef | Web of Science7
Blennow M ,Hedenskog S ,Granstrom M . Protective effect of acellular pertussis vaccines. Eur J Clin Microbiol Infect Dis 1988;7:381-383
CrossRef | Web of Science | Medline8
Isacson J ,Trollfors B ,Taranger J , et al. Safety, immunogenicity and an open, retrospective study of efficacy of a monocomponent pertussis toxoid vaccine in infants. Pediatr Infect Dis J 1994;13:22-27
CrossRef | Web of Science | Medline9
Ad Hoc Group for the Study of Pertussis Vaccines
Web of Science | Medline10
Krantz I ,Taranger J ,Trollfors B . Estimating incidence of whooping cough over time: a cross-sectional recall study of four Swedish birth cohorts. Int J Epidemiol 1989;18:959-963
CrossRef | Web of Science | Medline11
Sekura RD ,Zhang YL ,Roberson R , et al. Clinical, metabolic, and antibody responses of adult volunteers to an investigational vaccine composed of pertussis toxin inactivated by hydrogen peroxide. J Pediatr 1988;113:806-813
CrossRef | Web of Science | Medline12
Regan J ,Lowe F . Enrichment medium for the isolation of Bordetella. J Clin Microbiol 1977;6:303-309
Web of Science | Medline13
Houard S ,Hackel C ,Herzog A ,Bollen A . Specific identification of Bordetella pertussis by the polymerase chain reaction. Res Microbiol 1989;140:477-487
CrossRef | Web of Science | Medline14
van der Zee A ,Agterberg C ,van Agterveld M ,Peeters M ,Mooi FR . Characterization of IS1001, an insertion sequency element of Bordetella parapertussis. J Bacteriol 1993;175:141-147
Web of Science | Medline15
Zackrisson G ,Krantz I ,Lagergard T , et al. Antibody response to pertussis toxin in patients with clinical pertussis measured by enzyme-linked immunosorbent assay. Eur J Clin Microbiol Infect Dis 1988;7:149-154
CrossRef | Web of Science | Medline16
Zackrisson G ,Arminjon F ,Krantz I , et al. Serum antibody response to filamentous hemagglutinin in patients with clinical pertussis measured by an enzyme-linked immunosorbent assay. Eur J Clin Microbiol Infect Dis 1988;7:764-770
CrossRef | Web of Science | Medline17
Trollfors B ,Krantz I ,Sigurs N ,Taranger J ,Zackrisson G ,Roberson R . Toxin-neutralizing antibodies in patients with pertussis, as determined by an assay using Chinese hamster ovary cells. J Infect Dis 1988;158:991-995
CrossRef | Web of Science | Medline18
WHO meeting on case definition of pertussis, Geneva, January 10–11, 1991. MIM/EPI/PERT/91.1. Geneva: World Health Organization, 1991.
19
Barenkamp SJ ,Leininger E . Cloning, expression, and DNA sequence analysis of genes encoding nontypeable Haemophilus influenzae high-molecular-weight surface-exposed proteins related to filamentous hemagglutinin of Bordetella pertussis. Infect Immun 1992;60:1302-1313
Web of Science | Medline20
Taranger J ,Trollfors B ,Lagergard T ,Zackrisson G . Parapertussis infection followed by pertussis infection. Lancet 1994;344:1703-1703
CrossRef | Web of Science | Medline21
Clopper CJ ,Pearson ES . The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 1934;26:404-413
CrossRef | Web of Science22
Breslow NE, Day NE. Statistical methods in cancer research: Vol. 2. The design and analysis of cohort studies. Lyon, France: International Agency for Research on Cancer, 1987. (IARC scientific publications no. 82.)
23
The prevention of whooping-cough by vaccination: a Medical Research Council investigation
CrossRef | Web of Science24
Edwards KM ,Decker MD ,Halsey NA , et al. Differences in antibody response to whole-cell pertussis vaccines. Pediatrics 1991;88:1019-1023
Web of Science | Medline25
Baker JD ,Halperin SA ,Edwards K ,Miller B ,Decker M ,Stephens D . Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines. J Pediatr 1992;121:523-527
CrossRef | Web of Science | Medline26
Diphtheria and other diseases due to corynebacteria. In: Wilson GS, Miles AA. Topley and Wilson's principles of bacteriology and immunity. 5th ed. Vol. 2. Baltimore: Williams & Wilkins, 1964:1668-710.
27
Pappenheimer AM Jr. Diphtheria. In: Germanier R, ed. Bacterial vaccines. New York: Academic Press, 1984:1-36.
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Lennart Nilsson, Tiia Lepp, Kerstin von Segebaden, Hans Hallander, Lennart Gustafsson. (2011) Pertussis vaccination in infancy lowers the incidence of pertussis disease and the rate of hospitalisation after one and two doses: Analyses of 10 years of pertussis surveillance. Vaccine
CrossRef2
Abdolreza Advani, Lennart Gustafsson, Christina Åhrén, Frits R. Mooi, Hans O Hallander. (2011) Appearance of Fim3 and ptxP3-Bordetella pertussis strains, in two regions of Sweden with different vaccination programs. Vaccine 29:18, 3438-3442
CrossRef3
Nicole Guiso, Carl-Heinz Wirsing von König, Kevin Forsyth, Tina Tan, Stanley A. Plotkin. (2011) The Global Pertussis Initiative: Report from a Round Table Meeting to discuss the epidemiology and detection of pertussis, Paris, France, 11–12 January 2010. Vaccine 29:6, 1115-1121
CrossRef4
Linjie Zhang, Sílvio OM Prietsch, Inge Axelsson, Scott A Halperin, Linjie Zhang. 2011. Acellular vaccines for preventing whooping cough in children. .
CrossRef5
Michael A. Stevner. (2010) Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish Children—a comment. European Journal of Pediatrics 169:11, 1431-1432
CrossRef6
Marie-Louise Linstow, Peter Lotko Pontoppidan, Carl-Heinz Wirsing König, James D. Cherry, Birthe Hogh. (2010) Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children. European Journal of Pediatrics 169:9, 1119-1122
CrossRef7
Nicholas H Carbonetti. (2010) Pertussis toxin and adenylate cyclase toxin: key virulence factors of Bordetella pertussis and cell biology tools. Future Microbiology 5:3, 455-469
CrossRef8
Ulrich Heininger. (2010) Update on pertussis in children. Expert Review of Anti-infective Therapy 8:2, 163-173
CrossRef9
Hans O Hallander, Lennart Gustafsson. (2009) Efficacy and effectiveness of acellular pertussis vaccines: a 20-year Swedish experience. Expert Review of Vaccines 8:10, 1303-1307
CrossRef10
John B. Robbins, Rachel Schneerson, Jerry M. Keith, Mark A. Miller, Joanna Kubler-Kielb, Birger Trollfors. (2009) Pertussis Vaccine. The Pediatric Infectious Disease Journal 28:3, 237-241
CrossRef11
Jacek J. Pietrzyk, Jacek Wysocki, Jerzy Pejcz, Andrzej Galaj, Ewa Majda-Stanislawska, Helena Käyhty, Birgit Thierry-Carstensen, Anders Mørup Jensen. (2008) Safety and immunogenicity of a DTaP-IPVVero (serum-free) combination vaccine in comparison to DTaP-IPVMkc when administered simultaneously with Haemophilus influenzae type b conjugate vaccine (PRP-T) in children at 2, 3.5, 5 and 16 months of age. Vaccine 26:41, 5296-5303
CrossRef12
Linjie Zhang, Sílvio OM Prietsch, Inge Axelsson, Scott A Halperin, Linjie Zhang. 2008. Acellular vaccines for preventing whooping cough in children. .
CrossRef13
David A. Sack, Janet Shimko, Olga Torres, August L. Bourgeois, Domingo Sanchez Francia, Björn Gustafsson, Anders Kärnell, Iréne Nyquist, Ann-Mari Svennerholm. (2007) Randomised, double-blind, safety and efficacy of a killed oral vaccine for enterotoxigenic E. Coli diarrhoea of travellers to Guatemala and Mexico. Vaccine 25:22, 4392-4400
CrossRef14
John B. Robbins, Rachel Schneerson, Jerry M. Keith, Joseph Shiloach, Mark Miller, Birger Trollors. (2007) The rise in pertussis cases urges replacement of chemically-inactivated with genetically-inactivated toxoid for DTP. Vaccine 25:15, 2811-2816
CrossRef15
Zoe M. Rodriguez, Michelle G. Goveia, Jon E. Stek, Michael J. Dallas, John W. Boslego, Mark J. DiNubile, Penny M. Heaton. (2007) Concomitant Use of an Oral Live Pentavalent Human-Bovine Reassortant Rotavirus Vaccine With Licensed Parenteral Pediatric Vaccines in the United States. The Pediatric Infectious Disease Journal 26:3, 221-227
CrossRef16
Jan T Poolman, Hans O Hallander. (2007) Acellular pertussis vaccines and the role of pertactin and fimbriae. Expert Review of Vaccines 6:1, 47-56
CrossRef17
Kazunari Kamachi, Yoshichika Arakawa. (2007) Development of safer pertussis DNA vaccine expressing non-toxic C180 polypeptide of pertussis toxin S1 subunit. Vaccine 25:6, 1000-1006
CrossRef18
Claire Cameron, Joanne White, Deirdre Power, Natasha Crowcroft. (2007) Diphtheria boosters for adults: Balancing risks. Travel Medicine and Infectious Disease 5:1, 35-39
CrossRef19
Owen Tinnion, Mark Hanlon, Mark Hanlon. 2006. Acellular vaccines for preventing whooping cough in children. .
CrossRef20
Scott A. Halperin, Bruce Tapiero, Barbara Law, Francisco Diaz-Mitoma, Bernard Duval, Joanne M. Langley, Donald B. Elrick, Jeanne-Marie Jacquet. (2006) Interchangeability of two diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, Haemophilus influenzae type b conjugate vaccines as a fourth dose in 15–20-month-old toddlers. Vaccine 24:18, 4017-4023
CrossRef21
Birger Trollfors, Nina Knutsson, John Taranger, Anders Mark, Elisabet Bergfors, Valter Sundh, Teresa Lagergård. (2006) Diphtheria, tetanus and pertussis antibodies in 10-year-old children before and after a booster dose of three toxoids: implications for the timing of a booster dose. European Journal of Pediatrics 165:1, 14-18
CrossRef22
Marco A Medeiros, Geraldo R.G Armôa, Odir A Dellagostin, Douglas McIntosh. (2005) Induction of humoral immunity in response to immunization with recombinant Mycobacterium bovis BCG expressing the S1 subunit of Bordetella pertussis toxin. Canadian Journal of Microbiology 51:12, 1015-1020
CrossRef23
Janet R Casey, Michael E Pichichero. (2005) Acellular Pertussis Vaccine Safety and Efficacy in Children, Adolescents and Adults. Drugs 65:10, 1367-1389
CrossRef24
Birger Trollfors, John Taranger, Teresa Lagerg??rd, Valter Sundh. (2005) REDUCED IMMUNOGENICITY OF DIPHTHERIA AND TETANUS TOXOIDS WHEN COMBINED WITH PERTUSSIS TOXOID. The Pediatric Infectious Disease Journal 24:1, 85-86
CrossRef25
E Netterlid, M Bruze, M Hindsén, M Isaksson, P Olin. (2004) Persistent itching nodules after the fourth dose of diphtheria–tetanus toxoid vaccines without evidence of delayed hypersensitivity to aluminium. Vaccine 22:27-28, 3698-3706
CrossRef26
Anders Hviid, Michael Stellfeld, Peter Henrik Andersen, Jan Wohlfahrt, Mads Melbye. (2004) Impact of routine vaccination with a pertussis toxoid vaccine in Denmark. Vaccine 22:27-28, 3530-3534
CrossRef27
Eric Desauziers, Luc Hessel, Michael D Decker, J Jaime Caro, Johannes G Liese. (2004) Letter to the Editor. Vaccine 22:21-22, 2681-2684
CrossRef28
Herbert W Hethcote, Peter Horby, Peter McIntyre. (2004) Using computer simulations to compare pertussis vaccination strategies in Australia. Vaccine 22:17-18, 2181-2191
CrossRef29
Magda Campins-Martí, Fernando A Moraga-Llop. (2004) Acellular pertussis vaccines for use among infants and young children. Expert Opinion on Pharmacotherapy 5:4, 807-817
CrossRef30
Eric Mallet, Bernd H Belohradsky, Rosanna Lagos, Leif Gothefors, Patrice Camier, Jean-Pierre Carrière, Güler Kanra, Agnès Hoffenbach, Jacques Langue, François Undreiner, François Roussel, Philippe Reinert, Carl-Erik Flodmark, Silvia Stojanov, Johannes Liese, Myron M Levine, Alma Muñoz, Florian Schödel, Luc Hessel. (2004) A liquid hexavalent combined vaccine against diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type B and hepatitis B: review of immunogenicity and safety. Vaccine 22:11-12, 1343-1357
CrossRef31
Michael J Corbel, Dorothy K L Xing. (2004) Toxicity and potency evaluation of pertussis vaccines. Expert Review of Vaccines 3:1, 89-101
CrossRef32
A Giammanco, A Chiarini, P.A.C Maple, N Andrews, R Pebody, N Gay, R.M Ölander, F Fivet-Groyne, S Baron, A Tischer, S Swidsinski, J Schellekens, E Reizenstein. (2003) European Sero-Epidemiology Network: standardisation of the assay results for pertussis. Vaccine 22:1, 112-120
CrossRef33
Elisabet Bergfors, Birger Trollfors, Annica Inerot. (2003) Unexpectedly high incidence of persistent itching nodules and delayed hypersensitivity to aluminium in children after the use of adsorbed vaccines from a single manufacturer. Vaccine 22:1, 64-69
CrossRef34
B. Trollfors, T. Lagergard, E. Gunnarsson, J. Taranger. (2003) Determination of pertactin IgG antibodies for the diagnosis of pertussis. Clinical Microbiology and Infection 9:7, 585-589
CrossRef35
Sylvia H Yeh. (2003) Pertussis: persistent pathogen, imperfect vaccines. Expert Review of Vaccines 2:1, 113-127
CrossRef36
P. Juretzko, R. von Kries, M. Hermann, C. H. Wirsing von König, J. Weil, G. Giani. (2002) Effectiveness of Acellular Pertussis Vaccine Assessed by Hospital‐Based Active Surveillance in Germany. Clinical Infectious Diseases 35:2, 162-167
CrossRef37
C.C. Grant, J.D. Cherry. (2002) Keeping Pace with the Elusive Bordetella pertussis. Journal of Infection 44:1, 7-12
CrossRef38
John Taranger, Birger Trollfors, Elisabet Bergfors, Nina Knutsson, Valter Sundh, Teresa Lagergård, Lena Lind‐Brandberg, Gunilla Zackrisson, Jo White, Helen Cicirello, Joan Fusco, John B. Robbins. (2001) Mass Vaccination of Children with Pertussis Toxoid—Decreased Incidence in Both Vaccinated and Nonvaccinated Persons. Clinical Infectious Diseases 33:7, 1004-1010
CrossRef39
Nina Knutsson, Birger Trollfors, John Taranger, Elisabet Bergfors, Valter Sundh, Teresa Lagergård, Erik Östergaard, Helen Cicirello, Helena Käyhty. (2001) Immunogenicity and reactogenicity of diphtheria, tetanus and pertussis toxoids combined with inactivated polio vaccine, when administered concomitantly with or as a diluent for a Hib conjugate vaccine. Vaccine 19:31, 4396-4403
CrossRef40
Margaret A. Conway, Laura Madrigal-Estebas, Siobhan McClean, David J. Brayden, Kingston H.G. Mills. (2001) Protection against Bordetella pertussis infection following parenteral or oral immunization with antigens entrapped in biodegradable particles: effect of formulation and route of immunization on induction of Th1 and Th2 cells. Vaccine 19:15-16, 1940-1950
CrossRef41
STANLEY A. PLOTKIN. (2001) Immunologic correlates of protection induced by vaccination. The Pediatric Infectious Disease Journal 20:1, 63-75
CrossRef42
ERIC MALLET, PASCAL FABRE, EMMANUELLE PINES, HERV?? SALOMON, TED STAUB, FLORIAN SCH??DEL, PAUL MENDELMAN, LUC HESSEL, GEORGE CHRYSSOMALIS, EMMANUEL VIDOR, AGN??S HOFFENBACH. (2000) Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants. The Pediatric Infectious Disease Journal 19:12, 1119-1127
CrossRef43
Catpagavalli Canthaboo, Laura Williams, Dorothy K.L Xing, Michael J Corbel. (2000) Investigation of cellular and humoral immune responses to whole cell and acellular pertussis vaccines. Vaccine 19:6, 637-643
CrossRef44
R. Gylca, V. Gylca, O. Benes, A. Melnic, V. Chicu, C. Weisbecker, P. Willems, A. Kaufhold. (2000) A new DTPa-HBV-IPV vaccine co-administered with Hib, compared to a commercially available DTPw-IPV/Hib vaccine co-administered with HBV, given at 6, 10 and 14 weeks following HBV at birth. Vaccine 19:7-8, 825-833
CrossRef45
A.Dale Horne, Peter A. Lachenbruch, Karen L. Goldenthal. (2000) Intent-to-treat analysis and preventive vaccine efficacy. Vaccine 19:2-3, 319-326
CrossRef46
Mg Hanlon, R Nambiar, Am Kakakios, P McIntyre, Mv Land, Pl Devine. (2000) Pertussis antibody levels in infants immunized with an acellular pertussis component vaccine, measured using whole-cell pertussis ELISA. Immunology and Cell Biology 78:3, 254-258
CrossRef47
D. L. Klein. (2000) From Pertussis to Tuberculosis: What Can Be Learned?. Clinical Infectious Diseases 30:Supplement 3, S302-S308
CrossRef48
P.Helena Mäkelä. (2000) Vaccines, coming of age after 200 years. FEMS Microbiology Reviews 24:1, 9-20
CrossRef49
John Taranger, Birger Trollfors, Nina Knutsson, Valter Sundh, Teresa Lagergård, Erik Østergaard. (1999) Vaccination of infants with a four-dose and a three-dose vaccination schedule. Vaccine 18:9-10, 884-891
CrossRef50
Rose-Marie Carlsson, Bo A. Claesson, Teresa Lagergård, Birger Trollfors. (1999) Acquisition of serum antibodies against filamentous hemagglutinin and pertactin unrelated to Boráetella pertussis infection. Clinical Microbiology and Infection 5:11, 709-712
CrossRef51
Peter Williamson, Ruth Matthews. (1999) Development of neutralising human recombinant antibodies to pertussis toxin. FEMS Immunology & Medical Microbiology 23:4, 313-319
CrossRef52
Elisabet Bergfors, Birger Trollfors, John Taranger, Teresa Lagergård, Valter Sundh, Gunilla Zackrisson. (1999) Parapertussis and pertussis: Differences and similarities in incidence, clinical course, and antibody responses. International Journal of Infectious Diseases 3:3, 140-146
CrossRef53
Sharon Choo, Adam Finn. (1999) Pediatric combination vaccines. Current Opinion in Pediatrics 11:1, 14
CrossRef54
Hans O. Hallander, Judy Gnarpe, Håk. (1999) Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and Persistent Cough in Children. Scandinavian Journal of Infectious Diseases 31:3, 281-286
CrossRef55
E.L. Hewlett, S.A. Halperin. (1998) Serological correlates of immunity to Bordetella pertussis. Vaccine 16:20, 1899-1900
CrossRef56
James D Cherry, Jeffrey Gornbein, Ulrich Heininger, Klemens Stehr. (1998) A search for serologic correlates of immunity to Bordetella pertussis cough illnesses. Vaccine 16:20, 1901-1906
CrossRef57
ROSE-MARIE CARLSSON, BO A. CLAESSON, URBAN SELSTAM, EVA FAGERLUND, MARTA GRANSTRÖM, CHRISTINE BLONDEAU, AGNÈS HOFFENBACH. (1998) Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age. The Pediatric Infectious Disease Journal 17:11, 1026-1033
CrossRef58
Elaine Mills, Ronald Gold, John Thipphawong, Luis Barreto, Roland Guasparini, William Meekison, Les Cunning, Margaret Russell, Dana Harrison, Melody Boyd, Fang Xie. (1998) Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus b conjugate vaccine administered to infants at two, four and six months of age. Vaccine 16:6, 576-585
CrossRef59
BIRGER TROLLFORS, JOHN TARANGER, TERESA LAGERGÅRD, VALTER SUNDH, DOLORES A. BRYLA, RACHEL SCHNEERSON, JOHN B. ROBBINS. (1998) Immunization of children with pertussis toxoid decreases spread of pertussis within the family. The Pediatric Infectious Disease Journal 17:3, 196-199
CrossRef60
BETH A. HALPERIN, BRIAN J. EASTWOOD, SCOTT A. HALPERIN. (1998) Comparison of parental and health care professional preferences for the acellular or whole cell pertussis vaccine. The Pediatric Infectious Disease Journal 17:2, 103-109
CrossRef61
Alberto Eugenio Tozzi, Marta Luisa Ciofi degli Atti, Steven Gary Fite Wassilak, Stefania Salmaso, Pietro Panei, Alessandra Anemona, Stefania Luzi, Donato Greco. (1998) Predictors of adverse events after the administration of acellular and whole-cell diphtheria-tetanus-pertussis vaccines. Vaccine 16:2-3, 320-322
CrossRef62
Ryan, Murphy, Ryan, Nilsson, Shackley, Gothefors, Oymar, Miller, Storsaeter, Mills. (1998) Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines in children. Immunology 93:1, 1-10
CrossRef63
RON DAGAN, KARIM IGBARIA, LOLITA PIGLANSKY, RIMMA MELAMED, PAUL WILLEMS, ANNALISA GROSSI, ACHIM KAUFHOLD. (1997) Safety and immunogenicity of a combined pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus and Haemophilus influenzae type b-tetanus conjugate vaccine in infants, compared with a whole cell pertussis pentavalent vaccine. The Pediatric Infectious Disease Journal 16:12, 1113-1121
CrossRef64
JOHANNES G. LIESE, CARLTON K. MESCHIEVITZ, ERIKA HARZER, JAMES FROESCHLE, PHIL HOSBACH, JÖRG E. HOPPE, FRANK PORTER, SILVIA STOJANOV, KII NIINIVAARA, ALEXANDER M. WALKER, BERND H. BELOHRADSKY. (1997) Efficacy of a two-component acellular pertussis vaccine in infants. The Pediatric Infectious Disease Journal 16:11, 1038-1044
CrossRef65
Gregory A Poland. (1997) Still more questions on pertussis vaccines. The Lancet 350:9091, 1564-1565
CrossRef66
François Simondon, Marie-Pierre Preziosi, Ablaye Yam, Coumba Toure Kane, Laurence Chabirand, Isabelle Iteman, Gary Sanden, Souleymane Mboup, Agnes Hoffenbach, Kim Knudsen, Nicole Guiso, Steven Wassilak, Michel Cadoz. (1997) A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal. Vaccine 15:15, 1606-1612
CrossRef67
John Taranger, Birger Trollfors. (1997) ON OBSERVER ERRORS IN PERTUSSIS VACCINE STUDIES. The Pediatric Infectious Disease Journal 16:9, 914
CrossRef68
H. J. Schmitt, C. H. Wirsing von König, F. Zepp, J. Huff, K. Jahn, P. Schmidtke, C. Meyer, P. Habermehl, R. Uhlenbusch, P. Angersbach. (1997) Immunogenicity and reactogenicity of HbOC vaccine administered simultaneously with acellular pertussis vaccine (DTaP) into either arms or thighs of infants. Infection 25:5, 298-302
CrossRef69
STANLEY A. PLOTKIN, MICHEL CADOZ. (1997) The acellular pertussis vaccine trials: an interpretation. The Pediatric Infectious Disease Journal 16:5, 508-517
CrossRef70
Patrick Olin. (1997) Commentary: The best acellular pertussis vaccines are multicomponent. The Pediatric Infectious Disease Journal 16:5, 517-519
CrossRef71
JAMES D. CHERRY. (1997) Comparative efficacy of acellular pertussis vaccines: an analysis of recent trials. The Pediatric Infectious Disease Journal 16, S90-S96
CrossRef72
ERIK L. HEWLETT. (1997) Pertussis: current concepts of pathogenesis and prevention. The Pediatric Infectious Disease Journal 16, S78-S84
CrossRef73
Scott A. Halperin, Luis Barreto, Brian J. Eastwood, Lorna Medd, Roland Guasparini, Elaine Mills. (1997) Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine given as a single injection with Haemophilus influenzae b conjugate vaccine. Vaccine 15:3, 295-300
CrossRef74
JOHN TARANGER, BIRGER TROLLFORS, TERESA LAGERGÅRD, LENA LIND, VALTER SUNDH, GUNILLA ZACKRISSON, DOLORES A. BRYLA, JOHN B. ROBBINS. (1997) Unchanged efficacy of a pertussis toxoid vaccine throughout the two years after the third vaccination of infants. The Pediatric Infectious Disease Journal 16:2, 180-184
CrossRef75
Patrick Olin, Finn Rasmussen, Peter Gottfarb. (1997) Schedules and protection, simultaneous vaccination and safety: Experiences from recent controlled trials. International Journal of Infectious Diseases 1:3, 143-147
CrossRef76
John Taranger, Birger Trollfors, Teresa Lagergård, John B. Robbins. (1997) Protection against pertussis with a monocomponent pertussis toxoid vaccine. International Journal of Infectious Diseases 1:3, 148-151
CrossRef77
Juhani Eskola, Rose-Marie Ölander, Tapani Hovi, Leila Litmanen, Sara Peltola, Helena Käyhty. (1996) Randomised trial of the effect of co-administration with acellular pertussis DTP vaccine on immunogenicity of Haemophilus influenzae type b conjugate vaccine. The Lancet 348:9043, 1688-1692
CrossRef78
F. Simondon, A. Yam, J. Y. Gagnepain, S. Wassilak, B. Danve, M. Cadoz. (1996) Comparative safety and immunogenicity of an acellular versus whole-cell pertussis component of diphtheria-tetanus-pertussis vaccines in Senegalese infants. European Journal of Clinical Microbiology & Infectious Diseases 15:12, 927-932
CrossRef79
Rachel Schneerson, John B Robbins, John Taranger, Teresa Lagergard, Birger Trollfors. (1996) A toxoid vaccine for pertussis as well as diphtheria? Lessons to be relearned. The Lancet 348:9037, 1289-1292
CrossRef80
Q. He, K. Edelman, H. Arvilommi, J. Mertsola. (1996) Protective role of immunoglobulin G antibodies to filamentous hemagglutinin and pertactin ofBordetella pertussis inBordetella parapertussis infection. European Journal of Clinical Microbiology & Infectious Diseases 15:10, 793-798
CrossRef81
S.A. Halperin, B.J. Eastwood, L. Barreto, B. Friesen, L. Medd, W. Meekison, R. Guasparini. (1996) Adverse reactions and antibody response to four doses of acellular or whole cell pertussis vaccine combined with diphtheria and tetanus toxoids in the first 19 months of life. Vaccine 14:8, 767-772
CrossRef82
Birger Trollfors, Lars Burman, Teresa Lagergård, Maija Leinonen, John Taranger. (1996) NO CROSS-REACTIVITY WITH FILAMENTOUS HEMAGGLUTININ OF BORDETELLA PERTUSSIS IN SERA FROM PATIENTS WITH NONTYPABLE HAEMOPHILUS INFLUENZAE PNEUMONIA. The Pediatric Infectious Disease Journal 15:6, 558-559
CrossRef83
Gustafsson, Lennart, Hallander, Hans O., Olin, Patrick, Reizenstein, Elisabet, Storsaeter, Jann, . (1996) A Controlled Trial of a Two-Component Acellular, a Five-Component Acellular, and a Whole-Cell Pertussis Vaccine. New England Journal of Medicine 334:6, 349-356
Full Text84
Edwards, Kathryn M., Decker, Michael D., . (1996) Acellular Pertussis Vaccines for Infants. New England Journal of Medicine 334:6, 391-392
Full Text85
Greco, Donato, Salmaso, Stefania, Mastrantonio, Paola, Giuliano, Marina, Tozzi, Alberto E., Anemona, Alessandra, Ciofi degli Atti, Marta L., Giammanco, Anna, Panei, Pietro, Blackwelder, William C., Klein, David L., Wassilak, Steven G.F., the Progetto Pertosse Working Group. (1996) A Controlled Trial of Two Acellular Vaccines and One Whole-Cell Vaccine against Pertussis. New England Journal of Medicine 334:6, 341-349
Full Text86
GregoryA. Poland. (1996) Acellular pertussis vaccines: new vaccines for an old disease. The Lancet 347:8996, 209-210
CrossRef
