Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14-15 years.

Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark). Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20µg) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5µg). The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children. Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence. The adolescent study was registered at ClinicalTrials.gov on 26 March 2009 (NCT00870350).

Analysis of Bordetella pertussis clinical isolates circulating in European countries during the period 1998-2012.

Despite more than 50 years of vaccination, pertussis is still an endemic disease, with regular epidemic outbreaks. With the exception of Poland, European countries have replaced whole-cell vaccines (WCVs) by acellular vaccines (ACVs) in the 1990s. Worldwide, antigenic divergence in vaccine antigens has been found between vaccine strains and circulating strains. In this work, 466 Bordetella pertussis isolates collected in the period 1998-2012 from 13 European countries were characterised by multi-locus antigen sequence typing (MAST) of the pertussis toxin promoter (ptxP) and of the genes coding for proteins used in the ACVs: pertussis toxin (Ptx), pertactin (Prn), type 2 fimbriae (Fim2) and type 3 fimbriae (Fim3). Isolates were further characterised by fimbrial serotyping, multi-locus variable-number tandem repeat analysis (MLVA) and pulsed-field gel electrophoresis (PFGE). The results showed a very similar B. pertussis population for 12 countries using ACVs, while Poland, which uses a WCV, was quite distinct, suggesting that ACVs and WCVs select for different B. pertussis populations. This study forms a baseline for future studies on the effect of vaccination programmes on B. pertussis populations.

Investigations into the emergence of pertactin-deficient Bordetella pertussis isolates in six European countries, 1996 to 2012.

Pathogen adaptation has been proposed to contribute to the resurgence of pertussis. A striking recent example is the emergence of isolates deficient in the vaccine component pertactin (Prn). This study explores the emergence of such Prn-deficient isolates in six European countries. During 2007 to 2009, 0/83 isolates from the Netherlands, 0/18 from the United Kingdom, 0/17 Finland, 0/23 Denmark, 4/99 Sweden and 5/20 from Norway of the isolates collected were Prn-deficient. In the Netherlands and Sweden, respectively 4/146 and 1/8 were observed in a later period (2010­12). The Prn-deficient isolates were genetically diverse and different mutations were found to inactivate the prn gene. These are indications that Prn-deficiency is subject to positive selective pressure. We hypothesise that the switch from whole cell to acellular pertussis vaccines has affected the balance between 'costs and benefits' of Prn production by Bordetella pertussis to the extent that isolates that do not produce Prn are able to expand. The absence of Prn-deficient isolates in some countries may point to ways to prevent or delay the spread of Prn-deficient strains. In order to substantiate this hypothesis, trends in the European B. pertussis population should be monitored continuously.

Analysis of Swedish Bordetella pertussis isolates with three typing methods: characterization of an epidemic lineage.

Three Bordetella pertussis typing methods, pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and multi-locus variable number tandem repeat analysis (MLVA) were compared using a collection of Swedish strains. Of the three typing methods used, PFGE was found to be the most discriminatory. MLVA and MLST were less discriminatory, but may be valuable for strain discrimination when culture is not possible as they are based on PCR. The combination of MLVA/MLST was found to be equally discriminatory as PFGE and should therefore also be considered. The relationship between predominant lineages in Sweden and The Netherlands, characterized by the PFGE type BpSR11 and the allele for the pertussis toxin promoter ptxP3, respectively, was investigated. Linkage was found between the PFGE type BpSR11 and ptxP3 in that all BpSR11 strains carried ptxP3. On the other hand ptxP3 was found in several other PFGE-types. The presence of the ptxP3 allele in different genetic backgrounds may indicate horizontal gene transfer within B. pertussis or homoplasy. Alternatively, this observation may be due to convergence of PFGE types.

Analysis of Bordetella pertussis populations in European countries with different vaccination policies.

Despite the widespread use of pertussis vaccines during the last decades, pertussis has remained an endemic disease with frequent epidemic outbreaks. Currently two types of vaccines are used: whole-cell vaccines (WCVs) and recently developed acellular vaccines (ACVs). The long-term aim of our studies is to assess the effect of different vaccination policies on the population structure of Bordetella pertussis and ultimately on the disease burden in Europe. In the present study, a total of 102 B. pertussis isolates from the period 1998 to 2001 from five European countries (Finland, Sweden, Germany, The Netherlands, and France) were characterized. The isolates were analyzed by typing based on variable number of tandem repeats (VNTR); by sequencing of polymorphic genes encoding the surface proteins pertussis toxin S1 and S3 subunits (ptxA and ptxC), pertactin (prn), and tracheal colonization factor (tcfA); and by fimbrial serotyping. The results reveal a relationship between geographic location and VNTR types, the frequency of the ptxC alleles, and serotypes. We have not observed a relationship between the strain characteristics we studied and vaccination programs. Our results provide a baseline which can be used to reveal changes in the B. pertussis population in Europe in the coming years.

Calibrated serological techniques demonstrate significant different serum response rates to an oral killed cholera vaccine between Swedish and Nicaraguan children.

Serum responses to oral cholera vaccines were assessed in three paediatric vaccine trials, two in León, Nicaragua and one in Stockholm, Sweden. A calibrated anti-cholera toxin B subunit (CTB) IgA ELISA was used together with an assay for vibriocidal antibodies. Swedish children had lower pre-vaccination levels of antibody, but serum responses were more pronounced in Swedish children than in Nicaraguan children. Post-vaccination levels of anti-toxin antibody were generally above those found after natural infections with enterotoxigenic Escherichia coli, that cross-reacts serologically with Vibrio cholerae. Adverse events seen after vaccination were generally mild and of little clinical significance.

How to make sense of pertussis immunogenicity data.

Studies on serologic correlates to protection in pertussis were reviewed. Trials in the 1950s showed that agglutinogen titers correlated to protection of whole-cell vaccines, but postvaccination antibodies against pertussis toxin (PT) and against filamentous hemagglutinin did not in a later trial of acellular vaccines. However, in household studies nested in 2 recent trials, preexposure antibody levels against pertactin and against fimbriae correlated with protection against typical and mild pertussis, and anti-PT correlated only with protection against typical pertussis. These findings could be used by regulatory agencies to license pertussis vaccines. A reference laboratory for pertussis should distribute panels to control interlaboratory variation in recommended assays, and a minimal response should be set for each pertussis antigen. We conclude that 2 studies have shown correlates between measurable anti-pertactin, anti-fimbriae, and anti-PT antibody levels at exposure and individual protection against pertussis. We suggest that postvaccination response rates may be used as surrogate markers of protection.

The sero-epidemiology of diphtheria in Western Europe. ESEN Project. European Sero-Epidemiology Network.

Seven countries in Western Europe collected large, representative serum banks across the entire age range and tested them for diphtheria anti-toxin (sample size ranged from 2991 to 7715). Although a variety of assays were used, the results were all standardized to those of a reference laboratory and expressed in international units. The standardization process, and the availability of similar, large data sets allowed comparative analyses to be performed in which a high degree of confidence could be ascribed to observed epidemiological differences. The results showed that there were large differences in the proportion of adults with insufficient levels of protection amongst different countries. For instance, roughly 35% of 50- to 60-year-olds were found to be seronegative (titre < or = 0.01 IU/ml) in Finland compared with 70-75% in the United Kingdom. Furthermore, the proportion of seronegative adults would be expected to increase in some countries, notably Italy and the western part of Germany. In those countries with vaccination of military recruits there was a marked sex-related difference in the proportion of seropositive individuals. All countries have high levels of infant vaccine coverage (> 90%) but the accelerated schedule in the United Kingdom appears to result in lower anti-toxin titres than elsewhere. In Sweden, booster doses are not offered until 10 years of age which results in large numbers of children with inadequate levels of protection. Although the United Kingdom and Sweden both have higher proportions of seronegative children than elsewhere the likelihood of a resurgence of diphtheria in these countries seems remote.

Towards European urinalysis guidelines. Introduction of a project under European Confederation of Laboratory Medicine.

Improved standardized performance is needed because urinalysis continues to be one of the most frequently requested laboratory tests. Since 1997, the European Confederation of Laboratory Medicine (ECLM) has been supporting an interdisciplinary project aiming to produce European urinalysis guidelines. More than seventy clinical chemists, microbiologists and ward-based clinicians, as well as representatives of manufacturers are taking part. These guidelines aim to improve the quality and consistency of chemical urinalysis, particle counting and bacterial culture by suggesting optimal investigative processes that could be applied in Europe. The approach is based on medical needs for urinalysis. The importance of the pre-analytical stage for total quality is stressed by detailed illustrative advice for specimen collection. Attention is also given to emerging automated technology. For cost containment reasons, both optimum (ideal) procedures and minimum analytical approaches are suggested. Since urinalysis mostly lacks genuine reference methods (primary reference measurement procedures; Level 4), a novel classification of the methods is proposed: comparison measurement procedures (Level 3), quantitative routine procedures (Level 2), and ordinal scale examinations (Level 1). Stepwise strategies are suggested to save costs, applying different rules for general and specific patient populations. New analytical quality specifications have been created. After a consultation period, the final written text will be published in full as a separate document.

Diphtheria antitoxin response to DTP vaccines used in Swedish pertussis vaccine trials, persistence and projection for timing of booster.

Data from two Swedish pertussis vaccine trials with various combination vaccines were used to compare anti-diphtheria antitoxin concentrations over time between different vaccines, vaccine lots and vaccine schedules. The immune responses were measured with a validated ELISA method.Results are given for 1326 children, born 1992, that were recruited to the placebo (DT)-controlled Trial I which used a 2, 4, 6 month schedule. Two DTP acellular and one DTP whole cell vaccine were used. No DT boosters were given until 5 years of age. Trial II recruited children born 1993-94 and compared three DTP acellular vaccines with one DTP whole cell vaccine. Results are given for 306 children in a 2, 4, 6 month schedule and for 531 children in a 3, 5, 12 month schedule. The latter schedule gave significantly higher diphtheria antitoxin concentrations post third dose. The various DTP acellular vaccines and an inefficacious DTP whole cell vaccine gave lower antitoxin concentrations than both an efficacious DTP whole cell vaccine and the DT vaccine. The larger differences in antigen response between vaccines was reduced in the course of time. Generally, an initial rapid decline of antitoxin concentration was followed by a slower decline; the change typically occurring when the antitoxin concentration reached 0.13-0.16 EU/ml. The time needed to reach this level was between 6 and 10 months based on the initial vaccine response.A "best-fit" combined exponential regression model was used to predict the optimal timing for booster vaccinations against diphtheria.Our data support a 3, 5, 12 month schedule followed by a fourth dose 4-5 years after the third dose, depending upon the vaccine used.

Bordetella pertussis, Bordetella parapertussis, Mycoplasma pneumoniae, Chlamydia pneumoniae and persistent cough in children.

Material collected during a prospective pertussis vaccine trial in 1992-95 was examined for Bordetella pertussis (culture and serology), Bordetella parapertussis (culture), Mycoplasma pneumoniae and Chlamydia pneumoniae (PCR). From 64% (99/155) of episodes with cough for less than 100 d, 115 aetiological agents were identified in one southern and one northern subset of DT-recipients. The most common single agent was B. pertussis, representing 56%(64/115), with a median cough period of 51 d, followed by M. pneumoniae 26%(30/115), 23 d, C. pneumoniae 17% (19/115), 26 d, and B. parapertussis 2% (2/115). For co-infections, the median duration of cough was about 60 d. Spasmodic cough for 21 d or more (clinical WHO criteria for pertussis) was present in 82% (41/50) of infections with B. pertussis as single agent, 38% (17/45) with B. parapertussis, 38% (5/13) with C. pneumoniae, 26% (5/19) with M. pneumoniae and 30%(17/56) in cases where no aetiology was found. In children with cough for more than 100 d (n = 78) using all vaccine arms, B. pertussis was responsible in 83% (65/78), in 21%(16/78) together with other agents. Acellular vaccines were more efficient against serious disease than whole cell vaccine. Antibiotic treatment was more common at the southern (34%) study site than at the northern one (12%). The findings indicate that diagnosis should rely on laboratory confirmation, both for rational treatment of an individual case and for monitoring outbreaks.

Microbiological and serological diagnosis of pertussis.

Swedish vaccine trials have been used to examine sensitivity and specificity of diagnostic procedures for Bordetella pertussis infection. The proportions of cases diagnosed by culture and serology were 55% and 45%, respectively, when both methods were optimized. The culture method included nasopharyngeal aspiration, direct inoculation on plates, enrichment, and repeated collection of samples. An enzyme-linked immunosorbent assay for IgG antibodies to pertussis toxin (PT) and to filamentous hemagglutinin, with paired sera, was used for serology. Preexposure sera other than the acute serum increased the sensitivity of serology by 10%. A serology quality-assurance program to control imprecision and allow comparability over time and between laboratories is described. The direct fluorescent antibody technique had a sensitivity of 38% and a specificity of 99.6% in comparison with culture. A nested polymerase chain reaction (PCR) with the PT promoter region as target was 95% sensitive in comparison with culture if a cation-exchange resin was used to reduce inhibition. PCR enabled us to identify 83 positive samples in addition to 215 culture-positive ones-an increase of 38%--all with other indicators of pertussis infection.

Marked decline in pertussis followed reintroduction of pertussis vaccination in Sweden.

Immunisation against pertussis with an acellular pertussis vaccine for children at 3, 5, and 12 months was included in the Swedish vaccination programme in January 1996, 17 years after the withdrawal of whole cell vaccine in 1979. Within months coverage r

Measuring protection; a case study of pertussis vaccines--Swedish Trial II: secondary non-randomized comparisons between two schedules of infant vaccination.

In a double-blind trial two-, three- and five-component acellular vaccines were compared to a British whole-cell vaccine: in areas using three doses at three, five and 12 months of age (3-5-12 schedule), 72,698 children and in areas using a two, four and six months schedule (2-4-6 schedule), 10,194 children were evenly randomized to the four groups. The background incidence of pertussis was higher in the 3-5-12 schedule areas than in the 2-4-6 schedule areas; in spite of this, the point estimates of the relative risks for the 3-5-12 schedule versus the 2-4-6 schedule were close to or below one for the multicomponent acellular and the whole-cell vaccine groups, indicating a lower overall risk of pertussis when the third dose was delayed. The risk of whooping cough according to parents was lowest for the five-component and whole-cell vaccine groups in both schedules. The delayed third dose elicited booster responses for filamentous haemagglutinin but not for the other pertussis antigens. For highly efficacious pertussis vaccines two doses in infancy followed by a third dose in the second year of life may be recommended.

Levels of anti-pertussis antibodies related to protection after household exposure to Bordetella pertussis.

Vaccine efficacies against typical pertussis after household exposure to Bordetella pertussis were estimated to be 75.4% for an acellular five-component vaccine, 42.4% for an acellular two-component vaccine, and 28.5%, for a licensed US whole cell vaccine, compared to placebo. Logistic regression analyses demonstrated statistically significant correlations between clinical protection and the presence of IgG antibodies against pertactin, fimbriae 2/3 and pertussis toxin in pre-exposure sera. Multicomponent pertussis vaccines of proven high efficacy in recent Swedish NIAID-sponsored efficacy trials induced higher antibody levels against pertactin and fimbriae 2/3 than less efficacious vaccines. Anti-pertactin, anti-fimbriae 2/3, and anti-PT may be used as surrogate markers of protection for multicomponent acellular and whole-cell vaccines against pertussis.

Catch-up primary vaccination with acellular pertussis vaccines in 3-4-year-old children--reactogenicity and serological response.

In order to evaluate the optimum number of doses for catch-up primary vaccination against pertussis, 248 Swedish children 3-4 years of age were randomized to receive either two or three doses of a three-component or a five-component acellular pertussis vaccine. Adverse reactions were mild, but increased with increasing number of doses, especially in a subgroup of 17 children with serological signs of earlier pertussis. There were no clinically significant differences between the two vaccines. Antibody levels against pertussis were higher after two doses in this age group than after three doses in infancy. A primary vaccination program for older children can use two instead of three doses.

Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine. Ad Hoc Group for the Study of Pertussis Vaccines.

BACKGROUND: Trials in Italy and Sweden showed high efficacy for three-component and five-component pertussis vaccines, and poor efficacy for a whole-cell vaccine licensed in the USA and a two-component vaccine. We compared the efficacy of three acellular vaccines with a UK whole-cell vaccine. METHODS: We enrolled 82,892 babies aged 2-3 months. Babies were vaccinated at age 3 months, 5 months, and 12 months, or age 2 months, 4 months, and 6 months. They were randomly assigned a two-component acellular diphtheria-tetanus-pertussis (DTP) vaccine (n = 20,697), a three-component acellular DTP vaccine (n = 20,728), a five-component acellular DTP vaccine (n = 20,747), or a UK whole-cell DTP vaccine (n = 20,720). We collected data for all reported cases of culture-confirmed pertussis during 3 years of follow-up. The treatment status of the two-component-vaccine group had to be made known midway through the trial for boosting because of poor efficacy. We included data for the two-component vaccine in the analysis of safety and immunogenicity, and data up its unmasking in secondary analyses of relative efficacy. Analyses were by intention to treat. FINDINGS: During follow-up from the third dose (mean 22 months), in the 3 months, 5 months, 12 months schedule, there were 15 cases of culture-confirmed pertussis with at least 21 days of paroxysmal cough in the whole-cell group, relative risk 1.00, compared with 13 in the five-component group (0.85 [95% CI 0.41-1.79]), and 21 in the three-component group (1.38 [0.71-2.69]). For culture-confirmed pertussis, with or without cough, there were 19 cases in the whole-cell group (1.00). 27 in the five-component group (1.40 [0.78-2.52]), and 49 in the three-component group (2.55 [1.50-4.33]). In the intention-to-treat analyses, from the first dose in the 3 months, 5 months, 12 months schedule the whole-cell vaccine was significantly more protective than the three-component vaccine against typical pertussis. Between the second and the third doses, culture-confirmed pertussis with any cough and with at least 21 days of paroxysmal cough was significantly more frequent in the two-component group than in the three-component group, and in the three-component group than in the five-component and the whole-cell groups, respectively. The serological response of the acellular vaccines in the 2 months, 4 months, 6 months schedule were similar to those previously reported. The whole-cell vaccine was highly immunogenic for fimbriae, pertactin, and filamentous haemagglutinin, but had a low antipertussis toxin response. Hypotonic hyporesponsiveness occurred significantly more frequently in the whole-cell group (p < 0.05) and was more frequent in the acellular groups than previously reported. High fever and seizures occurred more frequently after whole-cell vaccine than after any of the acellular vaccines (p < 0.001). INTERPRETATIONS: The efficacy of the UK whole-cell vaccine and the five-component and three-component vaccines was similar against culture-confirmed pertussis with at least 21 days of paroxysmal cough. The lower efficacy of the three-component vaccine against mild disease suggests that fimbriae have a role in protection against infection. The efficacy of acellular vaccines depends on the number of components, and different whole-cell vaccines have variable efficacies.

Diagnostic pertussis serology in the recent clinical efficacy studies of acellular vaccines.

The laboratory routine used and the criteria applied for serological case confirmation in vaccine efficacy trials have a direct influence on the identification of cases, which consequently may also affect the estimation of vaccine efficacy (VE). Some differences in the application of serological confirmation criteria among the recent clinical studies of pertussis vaccines include the level of increase in titre and use of single specimen diagnostics. Additionally, the use of pre-exposure serum specimen collections increases the sensitivity of serological confirmation. In the 1992-95 Stockholm trial, a regimen to collect serum samples systematically was introduced; using acute- and convalescent-phase sera from the cough episodes, the proportion of all cases which were serologically confirmed was 25%. When pre-exposure sera were also available, the proportion was 35%; the increased sensitivity was differential by vaccine group and affected the estimated VE to some extent. Therefore, with the different application of serological methods among the various efficacy studies, direct comparisons between studies should be made with great caution.

Validation of nested Bordetella PCR in pertussis vaccine trial.

A nested PCR, using a 239-bp sequence in the pertussis toxin promoter region, was developed and evaluated. The assay differentiates Bordetella pertussis, Bordetella parapertussis, and Bordetella bronchiseptica by restriction enzyme analysis of the amplified fragments. The diagnostic performance of the PCR was evaluated in a Swedish pertussis vaccine efficacy trial which took place from 1992 to 1995, including study children and household members and using culture and serology for laboratory confirmation of suspected cases. In total 2,421 nasopharyngeal aspirates were analyzed. The total diagnostic sensitivity for B. pertussis was 90.2% (194 of 215). During the study period samples were processed with and without the cation-exchange resin Chelex. The PCR diagnostic sensitivity for B. pertussis among the Chelex-treated aspirates was 94.9% (75 of 79), and that for B. pertussis among 124 aspirates in a consecutive non-Chelex-treated material was 89.5% (111 of 124). After Chelex treatment of the 13 PCR-negative samples, an additional six became PCR positive, giving a final sensitivity of 94.3%. In addition, PCR was positive for B. pertussis with 57 of 1,744 samples negative by culture but with available serological data. The specificity of PCR with these samples was supported by a significant increase in antibody levels between acute and convalescent sera in 45 cases and by epidemiological or clinical data in all but two of the remaining cases. PCR was also positive for B. pertussis with 26 of 415 aspirates from episodes lacking serology. The diagnostic sensitivity of PCR for B. parapertussis was 74.0% (37 of 50). There were an additional seven culture-negative B. parapertussis PCR findings, six from cases with significant antibody increases against filamentous hemagglutinin only and one from a case lacking serology. There were no samples positive for B. bronchiseptica. In conclusion, PCR detection of B. pertussis and/or B. parapertussis enabled us to identify 90 positive nasopharyngeal aspirates, in addition to the 262 culture-positive samples (an increase of 34%). Relating these cases to serology and clinical data indicated a PCR specificity approaching 100%.

A controlled trial of a two-component acellular, a five-component acellular, and a whole-cell pertussis vaccine.

BACKGROUND: Because of concern about safety and efficacy, no pertussis vaccine has been included in the vaccination program in Sweden since 1979. To provide data that might permit the reintroduction of a pertussis vaccine, we conducted a placebo-controlled trial of two acellular and one whole-cell pertussis vaccines. METHODS: After informed consent was obtained, 9829 children born in 1992 were randomly assigned to receive one of four vaccines: a two-component acellular diphtheria-tetanus-pertussis (DTP) vaccine (2566 children), a five-component acellular DTP vaccine (2587 children), a whole-cell DTP vaccine licensed in the United States (2102 children), or (as a control) a vaccine containing diphtheria and tetanus toxoids (DT) alone (2574 children). The vaccines were given at 2, 4, and 6 months of age, and the children were then followed for signs of pertussis for an additional 2 years (to a mean age of 21/2 years). RESULTS: The whole-cell vaccine was associated with significantly higher rates of protracted crying, cyanosis, fever, and local reactions than the other three vaccines. The rates of adverse events were similar for the acellular vaccines and the control DT vaccine. After three doses, the efficacy of the vaccines with respect to pertussis linked to a laboratory-confirmed case of pertussis or contact with an infected household member with paroxysmal cough for > or = 21 days was 58.9 percent for the two-component vaccine (95 percent confidence interval, 50.9 to 65.9 percent), 85.2 percent for the five-component vaccine (95 percent confidence interval, 80.6 to 88.8 percent), and 48.3 percent for the whole-cell vaccine (95 percent confidence interval, 37.0 to 57.6 percent). CONCLUSIONS: The five-component acellular pertussis vaccine we evaluated can be recommended for general use, since it has a favorable safety profile and confers sustained protection against pertussis. The two-component acellular vaccine and the whole-cell vaccine were less efficacious.