Safety and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine after one or two doses given to infants and toddlers.

With the emergence of multiple meningococcal serogroups in different geographic areas, broad vaccine protection from infancy is desirable. One hundred and seventy-five infants received either two doses of a meningococcal quadrivalent (A, C, W-135, Y) conjugate vaccine (MenACWY-CRM) at 6 and 12 months, one dose of MenACWY-CRM at 12 months, or MenC at 12 months and MenACWY-CRM at 18 months. Bactericidal antibody titers using human complement were measured before and 1 month after each dose. Injection-site reactions were reported by 22-45% of participants following MenACWY-CRM given at 6 or 12 months. Similar proportions of subjects had injection-site reactions following two doses of MenACWY-CRM (32-41%) or one dose of MenC (26-44%). The incidence of systemic adverse events was comparable between groups. After two doses of MenACWY-CRM, the percentages of participants reporting hSBA titers >or=8 were 100% for C, W-135, and Y, and 84% for A. Serogroup C titers were more than 10-fold higher after two doses of MenACWY-CRM than after one dose of MenC or MenACWY-CRM at 12 months. Serogroup C titers were comparable following a single dose of MenACWY-CRM or MenC at 12 months. MenACWY-CRM is well tolerated and immunogenic given at 12 months, or two doses at 6 and 12 months of age.

Myopia in secondary school students in Mwanza City, Tanzania: the need for a national screening programme.

BACKGROUND/AIMS: The prevalence of significant refractive errors and other eye diseases was measured in 2511 secondary school students aged 11-27 years in Mwanza City, Tanzania. Risk factors for myopia were explored. METHODS: A questionnaire assessed the students' socioeconomic background and exposure to near work followed by visual acuity assessment and a full eye examination. Non-cycloplegic objective and subjective refraction was done on all participants with visual acuity of worse than 6/12 in either eye without an obvious cause. RESULTS: 154 (6.1%) students had significant refractive errors. Myopia was the leading refractive error (5.6%). Amblyopia (0.4%), strabismus (0.2%), and other treatable eye disorders were uncommon. Only 30.3% of students with significant refractive errors wore spectacles before the survey. Age, sex, ethnicity, father's educational status, and a family history of siblings with spectacles were significant independent risk factors for myopia. CONCLUSION: The prevalence of uncorrected significant refractive errors is high enough to justify a regular school eye screening programme in secondary schools in Tanzania. Risk factors for myopia are similar to those reported in European, North-American, and Asian populations.

Predicting the accrual rate in a vaccine clinical trial: an a posteriori evaluation of the feasibility study.

To estimate the expected accrual rate in a double blinded controlled randomized trial of the absolute clinical efficacy of three anti-pertussis vaccines in infants, we performed a series of surveys among mothers and physicians in the areas to be considered for participation in the trial. In this paper, we compared the predicted enrollment with the actual enrollment achieved at the end of the recruitment phase of the trial. The predicted enrollment rate was 27%, while the observed rate was 26%. Results from the feasibility study were highly predictive of actual enrollment rate. In the local health units (USL) where such assessments were carried out, the accrual rate, was higher than those not participating in the feasibility phase.

[Epidemiology of invasive infections with Haemophilus influenzae type b in the world and in Italy]. / Epidemiologia delle infezioni invasive da Haemophilus influenzae di tipo b nel mondo e in Italia.

The incidence of Haemophilus influenzae type b (Hib) disease in the 0-5 years age group has been studied in many countries. In the United States, before the introduction of mass vaccination, the incidence of invasive Hib disease ranged from 7 per 100,000 in the 4-5 years age group to 452 pert 100,000 in the 6-11 months age group. In Europe, the incidence of this disease has been estimated to range from 21 to 60 per 100,000 per year in the 0-5 years age group. Hib infection is mainly transmitted by the respiratory route. Risk factors of the disease include: attending a day-care center, a high number of household members, low socio-economic level, age less than two years, and belonging to certain ethnic groups. Accurate estimates of the incidence of invasive Hib disease do not exist in Italy. Among the 15,601 children participating in the "Progetto Pertosse", a clinical trial for the evaluation of antipertussis vaccines, there occurred six cases of Hib meningitis, one of Hib sepsis, and one of Hib cellulitis. These episodes yield an incidence density of 28.7 per 100,000 person-years in the 2-30 month age group. Incidence data will also need to be collected for children in the 30 months-5 years age group before attempting a cost-benefit analysis with the aim of planning a mass vaccination.

Correlation between serum bactericidal activity against Neisseria meningitidis serogroups A, C, W-135 and Y measured using human versus rabbit serum as the complement source.

The surrogate of protection against invasive meningococcal disease is the presence of serum bactericidal activity (SBA) at a titer ≥4 in an assay using human serum as the complement source (hSBA). However, for various practical and logistical reasons, many meningococcal vaccines in use today were licensed based on a modified SBA assay that used baby rabbit serum as the complement source (rSBA). To assess the strength of correlation between the two assay systems for serogroups A, C, W-135 and Y, we analyzed a subset of samples from adolescent subjects enrolled in a Phase II study of Novartis' MenACWY-CRM conjugate vaccine vs. an ACWY polysaccharide vaccine; samples were analyzed in parallel using hSBA and rSBA. We compared geometric mean titers (GMTs), calculated Pearson correlation coefficients between paired hSBA and rSBA results, and calculated sensitivity/specificity and likelihood ratios for an rSBA ≥8 or ≥128 for classifying hSBA ≥4, taking hSBA as the 'gold standard'. Correlations between hSBA and rSBA ranged from 0.46 to 0.78 for serogroup C, but were weaker for serogroups A, W-135 and Y (range -0.15 to 0.57). In post vaccination samples, nearly all subjects had rSBA titers ≥8, though up to 15% remained seronegative by hSBA. In post vaccination settings, rSBA titers at ≥8 or ≥128 was highly sensitive for an hSBA titer ≥4, but non-specific. In conclusion, results generated by rSBA did not accurately classify serostatus according to hSBA for serogroups A, W-135 and Y.

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity.

Differences by antigen in seroconversion: sensitivity, specificity and bias in the serological confirmation of pertussis.

Vaccine efficacy of the most efficacious acellular pertussis vaccines in the three recent placebo-controlled clinical trials, when estimated using the primary clinical case criterion, does not change substantially with the inclusion of serological confirmation in addition to culture confirmation. In the Italy trial, because of relatively high anti-PT antibody levels at the time of the acute-phase specimen in episodes of 21 or more days of paroxysmal cough, significant increases in antibody to PT are less likely to be seen in the acellular vaccine groups when evaluating children with bacterial isolation. However, the effect of this decreased sensitivity appears to be compensated by significant antibody increases in the FHA assay. When projecting a maximally sensitive criterion for serological assessment using the observed decreases in IgG antibody to PT over time following primary vaccination stratified by vaccine group, and comparing the expected antibody level with the observed level in the convalescent-phase specimen, the effect on estimated vaccine efficacy is minimal.

Reactogenicity of a three-dose pertussis acellular vaccine catch-up in children 21-40 months of age.

The reactogenicity of a three-dose catch-up acellular pertussis (aP) immunization of children at 21-40 months of age was evaluated. Vaccination was well-tolerated: fever > or = 38 degrees C was reported after 5% of administered doses and local reactions after 14-15%. The onset of adverse events was not associated with age at vaccination, interval between doses or previous presence of antibodies against pertussis, whereas injection in sites other than the buttock and presence of the same symptom after a previous dose were associated with higher reactogenicity. Because of the good safety profile of primary aP immunization in children > 1 year of age, catch-up vaccination campaigns could be considered in areas where pertussis whole-cell vaccination uptake has been low and where the number of susceptible children should be reduced to control pertussis circulation.

Bordetella parapertussis infection in children: epidemiology, clinical symptoms, and molecular characteristics of isolates.

The clinical trial conducted in Italy to evaluate the efficacy of acellular pertussis vaccines provided an opportunity to estimate the frequency of clinical infections with Bordetella parapertussis and to compare the clinical characteristics of children suffering from Bordetella pertussis illness with those of children with B. parapertussis illness. This study dealt with 76 B. parapertussis infections diagnosed from a population of 15,601 children participating in the follow-up of suspected cases of pertussis. An overall incidence of 2.1 cases of laboratory-confirmed parapertussis per 1,000 person-years was observed. Children affected by B. parapertussis infections showed a less severe clinical picture both in the duration of symptoms and in the percentage of patients affected, even when compared with vaccinated children with pertussis. To characterize the isolated strains, we performed assays for susceptibility to erythromycin and sulfamethoxazole-trimethoprim, and we examined the genomic DNAs by pulsed-field gel electrophoresis. The results showed a high degree of genetic stability among B. parapertussis strains regardless of time of collection and geographical distribution.

Reactogenicity and immunogenicity at preschool age of a booster dose of two three-component diphtheria-tetanus-acellular pertussis vaccines in children primed in infancy with acellular vaccines.

OBJECTIVES: To determine the reactogenicity and immunogenicity of a fourth dose of 2 three-component acellular pertussis vaccines combined with diphtheria-tetanus-acellular pertussis (DTaP) when administered at preschool age to children primed in infancy with 3 doses of the same DTaP and who had received a diphtheria-tetanus (DT) dose at the age of 12 months. SETTING: Local health units of 4 Italian regions. STUDY DESIGN: Three thousand five hundred twenty-two children, who had been randomized in the first year of life to be immunized with a DTaP vaccine by either SmithKline Beecham or Chiron Biocine, were offered a booster of the same vaccine or, if refusing, a DT vaccine at the age of 5 to 6 years. Families of children were aware of the vaccine administered. The occurrence of adverse events was compared between the children who received a DTaP booster and those boosted with a DT only. Antibody titers to pertussis vaccine components (pertussis toxin, filamentous hemoagglutinin, and pertactin) were determined on 558 paired sera taken before and 30 days after the DTaP booster administration. RESULTS: Four episodes of temperature >/=39.5 degrees C, 2 in each DTaP group, were recorded. Fever >/=38 degrees C occurred infrequently in both DTaP and DT recipients (DTaP range: 2.5%-2.8%; DT range: 0%-4.8%), as did irritability (DTaP range: 10.1%-11.7%; DT range: 7.4%-12.6%). The frequency of local reactions was significantly higher for DTaP recipients (range: 44.0%-52.8%), with respect to DT recipients (range: 29.5%-44.4%). Extensive local reactions were observed in 1.2% of DTaP recipients and in.5% of DT recipients. Both DTaP vaccines induced high antibody titers against pertussis toxin, filamentous hemoagglutinin, and pertactin, with an increase of >10 times the prebooster geometric mean titers. CONCLUSIONS: A booster dose of DTaP at preschool age in children primed with the same acellular pertussis vaccine is safe and immunogenic. However, the frequency of local reactions is higher compared with that following primary immunization and with that following booster with DT only, and parents should be informed of the potential for these reactions to occur.

Sustained efficacy during the first 6 years of life of 3-component acellular pertussis vaccines administered in infancy: the Italian experience.

BACKGROUND: In 1992-1993, a randomized, double-blind, placebo-controlled clinical trial of two 3-component acellular pertussis vaccines was started in 4 of Italy's 20 regions. During the trial, the children had been randomized to receive 3 doses of 1 of 2 acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DT) or of a DT vaccine only, at 2, 4, and 6 months of age. Both diphtheria-tetanus-acellular pertussis (DTaP) vaccines, 1 manufactured by SmithKline Beecham (DTaP SB; Infanrix) and 1 manufactured by Chiron Biocine (DTaP CB; Triacelluvax), contain pertussis toxin (PT), filamentous hemagglutinin, and pertactin. The results of the first period of follow-up, which ended in 1994 (stage 1), showed that both vaccines had a protective efficacy of 84% in the first 2 years of life; when the trial's follow-up was extended under partial blinding until the participating children had reached 33 months of age (stage 2 of the follow-up), these high levels of efficacy had persisted. Therefore, the objective of this study was to estimate the persistence of protection from 3 to 6 years of age of the 2 3-component DTaP vaccines administered as primary immunization in infancy. METHODS: An unblinded prospective longitudinal study of vaccinated and unvaccinated children in 4 Italian regions, with active surveillance of cough, was conducted by study nurses, and Bordetella pertussis infections were confirmed laboratory. The present study (stage 3) included those children who completed stage 2 of the follow-up and were still under active surveillance as of October 1, 1995, accounting for 4217 children who had received DTaP SB (representing 94% of the vaccine's recipients in the initial phase of the trial), 4215 who had received DTaP CB (95% of the original recipients), and 266 who had received DT only (18% of the original recipients). Because the parents of most of the original DT placebo group accepted pertussis vaccination during stage 2 in 1995, an additional 856 children were recruited in the DT group at the initiation of stage 3. These additional children were identified from the census list of children born in the same period and living in the same areas as the trial participants but who had been vaccinated in infancy with DT only. Eligible children were included in stage 3 if they had no history of either pertussis or pertussis vaccination and if a serum sample obtained at the time of enrollment had undetectable immunoglobulin G (IgG) against PT. Parental consent to participate in the study was obtained. Active surveillance for pertussis was conducted in the field by 72 study nurses through monthly contact with each family in the study. A cough episode that lasted >/=7 days was considered to be a laboratory-confirmed infection by Bordetella pertussis if at least 1 of the following 5 criteria (listed in hierarchic order) was met: 1) B pertussis was obtained from nasopharyngeal culture (culture-confirmed infection); 2) the enzyme-linked immunosorbent assay (ELISA) IgG or IgA titer against PT in the convalescent-phase serum sample increased by at least 100% compared with the acute-phase sample; 3) the PT-neutralizing titers in Chinese hamster ovary assay in the convalescent-phase sample increased by at least 4-fold compared with the acute-phase sample; 4) the ELISA IgG or IgA titer against filamentous hemagglutinin in the convalescent-phase sample increased by at least 100% and the culture or the polymerase chain reaction assay on the nasopharyngeal aspirate was negative for B parapertussis; and 5) the ELISA IgG PT titer in 1 of the 2 serum samples exceeded the geometric mean titer computed on convalescent sera of the children with a culture-confirmed B pertussis infection in each study group. Incidence of laboratory-confirmed B pertussis infection, using case definitions that varied in terms of duration and type of cough, was computed and the proportion of cases prevented among DTaP recipients in comparison with DT recipients was calculated. RESULTS: A total of 391 laboratory-confirmed infections were identified in the 3-year follow-up period (138 DTaP SB, 126 DTaP CB, 127 DT recipients, respectively). The mean duration of cough in children with laboratory-confirmed infection was 48, 47, and 70 days for the DTaP SB, DTaP CB, and DT recipients, respectively; the mean duration of spasmodic cough was 15, 13, and 23 days, respectively. When using the primary case definition (ie, laboratory-confirmed B pertussis infection and >/=14 days of spasmodic cough or >/=21 days of any cough), the efficacy was 78% for the DTaP SB vaccine (95% confidence interval [CI]: 71%-83%) and 81% for the DTaP CB vaccine (95% CI: 74%-85%). When using the case definition based on a more severe clinical presentation (>/=21 days of spasmodic cough), the vaccine efficacy was 86% (95% CI: 79%-91%) for both vaccines. When using the case definition based on milder clinical presentation (any cough for >/=7 days), the efficacy was 76% (95% CI: 69%-81%) for the DTaP SB vaccine and 78% (95% CI: 72%-83%) for the DTaP CB vaccine. CONCLUSIONS: The persistence of protection through 6 years of age suggests that the fourth DTaP dose could be postponed until preschool age in children who received 3-component acellular pertussis vaccines in infancy, provided that immunity to diphtheria and tetanus is maintained. Additional booster doses could be administered at older ages to reduce reactogenicity induced by multiple administrations and to optimize the control of pertussis in adolescents and young adults.

Variations of HIV and STI prevalences within communities neighbouring new goldmines in Tanzania: importance for intervention design.

OBJECTIVES: To measure the prevalence of HIV and other STIs in communities neighbouring new large scale gold mines in northern Tanzania in order to inform the design of a targeted HIV/STI intervention programme. METHODS: Cross sectional surveys were conducted in adults aged 16-54 years from different sectors of communities neighbouring two newly opened, large scale gold mines near Lake Victoria. Mine workers, men, women, and female food and recreational facility workers (FRFW) from the community were randomly selected for interview and HIV and STI testing. RESULTS: 207 male Tanzanian mine workers, 206 FRFW, 202 other male and 205 female community members were enrolled. Overall, 42% of FRFW were HIV positive, compared to 6% of male mine workers, and 16% and 18% of other community men and women respectively. HIV prevalence in FRFW was significantly associated with alcohol consumption (adjusted odds ratio (aOR) = 2.5, 95% confidence interval (CI) 1.1 to 5.5), past or present syphilis (TPPA+) (aOR = 2.7, 95% CI 1.4 to 5.1) and single status (aOR = 3.8, 95% CI 1.2 to 11.9). Among FRFW, 24% had active syphilis (RPR+, TPPA+), 9% Chlamydia trachomatis, and 4% Neisseria gonorrhoeae. Overall, 50% of FRFW and 50% of community men never used condoms during sex, and 55% mineworkers, 61% male, and 20% female community members reported receiving/giving payment for sex during the previous year. CONCLUSIONS: There is a high prevalence of HIV and other STIs in communities around new goldmines in Tanzania, especially in FRFW. HIV and STI prevalence in the mining workforce is still relatively low, but high risk sexual behaviour is reported by all adult subgroups surveyed in this study. Programmes focusing on HIV/STI prevention, with targeted interventions for high risk women such as FRFW, will be extremely important in such high transmission communities where there is substantial recent in-migration of men and women seeking work. Such programmes have recently been initiated by a private/public/NGO partnership.

Incidence of invasive Haemophilus influenzae type b disease in Italian children.

To estimate the incidence of Haemophilus influenzae type b (Hib) invasive disease in Italian infants we performed a prospective study in a cohort of newborns enrolled for a randomized trial on safety and efficacy of three pertussis vaccines and followed for onset of serious disease or pertussis. The overall cumulative incidence observed in 15,601 children was 51.3/100,000 for all invasive Hib infections and 38.4/100,000 for Hib meningitis, over 27 months of observation. The incidence density of all invasive Hib disease was 28.7/100,000 person-years, while meningitis occurred with an incidence of 21.5/100,000 person-years. Among the eight cases detected, six were meningitis, one sepsis, and one cellulitis. The child with sepsis died. The incidence and epidemiology of invasive Hib disease in Italy are comparable to those reported from other European countries. Cost-benefit analyses are needed for planning Italian vaccination policy.

Case definitions.

The definition of a case of pertussis is an essential point in evaluating and comparing the results from the seven studies on pertussis vaccines presented at the Symposium. An assessment of the impact of case definition on the evaluation of vaccine efficacy has been performed on the Italian data-set, by comparing the clinical presentation of cough illnesses which were laboratory-confirmed as B. pertussis infection with those not-confirmed, by study vaccine. The results show that the estimate of vaccine efficacy is greatly variable by the choice of case definition and dependent on the study design. The assessment of the effect of each vaccine should be performed by using various clinical endpoints and the method used in detection of suspected cases in each study should be carefully evaluated to verify comparability of results.

Persistence of protection through 33 months of age provided by immunization in infancy with two three-component acellular pertussis vaccines. Stage II Working Group.

A large, randomized, placebo-controlled clinical trial in Italy on two three-component pertussis vaccines, given as DTaP in infancy, one manufactured by SmithKline and Beecham (SB) and one by Chiron Biocine (CB), found each vaccine to be 84% efficacious through the average age of 24 months. The cohort of children enrolled in the trial was followed with unmodified case ascertainment procedures for nine additional calendar months, during which partial unblinding occurred, for the unvaccinated randomized group. For the DTaP groups, the specific vaccine assignment remained double-blinded throughout the entire additional observation period. Pertussis was defined as paroxysmal cough lasting at least 21 days and confirmed by culture or serology. In the additional 9 months the observed absolute efficacy was 78% (95% CI, 62-87%) for SB DTaP vaccine and 89% (95% CI, 79-94%) for CB DTaP. The relative risk of developing pertussis in SB DTaP recipients compared to CB DTaP vaccinees was 1.99 (95% CI, 1.13-3.51). By combining observations from the initial and additional follow-up periods, the overall observed vaccine efficacy through an average age of 33 months of SB DTaP was 80% and of CB DTaP, 85%.

Predictors of adverse events after the administration of acellular and whole-cell diphtheria-tetanus-pertussis vaccines.

Recurrence of adverse events, the effect of site of injection, and concurrent administration of oral polio vaccine (OPV) and hepatitis B vaccine (HBV) on reactogenicity were assessed in recipients of two acellular pertussis vaccines given in combination with diphtheria and tetanus toxoids (DTaP), one whole-cell DTP vaccine (DTPwc) and one DT vaccine during a double blind, randomized, controlled clinical trial. Local and systemic side reactions were more likely to recur after the administration of DTaP and DT compared with DTPwc. In all vaccine groups, injection in the buttock was associated with a lower rate of common adverse events compared with injection in the thigh, while simultaneous administration of OPV and/or HBV did not increase the risk of onset of side reactions.

"A bit more truthful": the validity of adolescent sexual behaviour data collected in rural northern Tanzania using five methods.

OBJECTIVE: To assess the validity of sexual behaviour data collected from African adolescents using five methods. METHODS: 9280 Tanzanian adolescents participated in a biological marker and face to face questionnaire survey and 6079 in an assisted self-completion questionnaire survey; 74 participated in in-depth interviews and 56 person weeks of participant observation were conducted. RESULTS: 38% of males and 59% of females reporting sexual activity did so in only one of the two 1998 questionnaires. Only 58% of males and 29% of females with biological markers consistently reported sexual activity in both questionnaires. Nine of 11 (82%) in-depth interview respondents who had had biological markers provided an invalid series of responses about sex in the survey and in-depth interview series. Only one of six female in-depth interview respondents with an STI reported sex in any of the four surveys, but five reported it in the in-depth interviews. CONCLUSION: In this low prevalence population, biological markers on their own revealed that a few adolescents had had sex, but in combination with in-depth interviews they may be useful in identifying risk factors for STIs. Self-reported sexual behaviour data were fraught with inconsistencies. In-depth interviews seem to be more effective than assisted self-completion questionnaires and face to face questionnaires in promoting honest responses among females with STIs. Participant observation was the most useful method for understanding the nature, complexity, and extent of sexual behaviour.

A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working Group.

BACKGROUND: Concern about both safety and efficacy has made the use of whole-cell pertussis vaccines controversial. In some European countries, including Italy, the rate of vaccination against pertussis is low. METHODS: We conducted a double-blind trial in Italy in which infants were randomly assigned to vaccination at two, four, and six months of age with an acellular pertussis vaccine together with diphtheria and tetanus toxoids (DTP); a DTP vaccine containing whole-cell pertussis (manufactured by Connaught Laboratories); or diphtheria and tetanus toxoids without pertussis (DT). The acellular DTP vaccine was either one containing filamentous hemagglutinin, pertactin, and pertussis toxin inactivated with formalin and glutaraldehyde (SmithKline Beecham) or one with filamentous hemagglutinin, pertactin, and genetically detoxified pertussis toxin (Chiron Biocine). Pertussis was defined as 21 days or more of paroxysmal cough, with infection confirmed by culture or serologic testing. RESULTS: The efficacy of each vaccine, given in three doses, against pertussis was determined for 14,751 children over an average of 17 months, with cases included in the analysis if cough began 30 days or more after the completion of immunization. For both of the acellular DTP vaccines, the efficacy was 84 percent (95 percent confidence intervals, 76 to 89 percent for Biocine DTP and 76 to 90 percent for SmithKline DTP), whereas the efficacy of the whole-cell DTP vaccine was only 36 percent (95 percent confidence interval, 14 to 52 percent). The antibody responses were greater to the acellular vaccines than to the whole-cell vaccine. Local and systemic adverse events were significantly more frequent after the administration of the whole-cell vaccine. For the acellular vaccines, the frequency of adverse events was similar to that in the control (DT) group. CONCLUSIONS: The two acellular DTP vaccines we studied were safe, immunogenic, and efficacious against pertussis, whereas the efficacy of the whole-cell DTP vaccine was unexpectedly low.