Vaccines against norovirus: state of the art trials in children and adults.

Noroviruses (NoVs), a group of nonenveloped, single-stranded RNA viruses belonging to the Caliciviridae family, are the leading cause worldwide of acute infectious gastroenteritis. Serious and eventual fatal outcomes may be observed in at-risk populations such as the very young or older adults, especially in those with underlying diseases. NoVs are highly infectious, with a low number of virus particles causing infection, and they are highly resistant to environmental conditions. NoVs have multiple routes of transmission including faecal-oral, aerosolized vomitus, person to person and via contaminated surfaces or food and water. NoVs can cause frequent and dramatic outbreaks where people congregate in close quarters such as hospitals, long-term care facilities, cruise liners and military barracks and ships. Of the seven NoV genogroups, human disease is most frequently caused by genogroups I and II, although genogroup IV has also been associated with illness. The absence of reliable, high-yield cell culture systems or animal models has steered the development of vaccines towards nonreplicating recombinant capsid proteins including viruslike particles and the sub-virus-sized P particles. Takeda Vaccines is developing a candidate NoV vaccine formulation based on adjuvanted viruslike particles from the GI.1 genotype and a consensus GII.4 sequence derived from three natural GII.4 variants. Early clinical trial results show good tolerability and robust immune responses to both components. This approach is designed to induce broad protective immune responses in adults and children.

Assessment of nine candidate DTP-vaccines with reduced amount of antigen and/or without adjuvant as a fourth (booster-) dose in the second year of life.

BACKGROUND: The incidence of local reactions to diphtheria-, tetanus and acellular pertussis (DTaP-) vaccines in infants and toddlers increases with each subsequent dose, and entire thigh swellings (ETS) have been reported. Lowering the amount of antigen or of adjuvant may decrease the reactogenicity of DTaP while maintaining a protective immune response. OBJECTIVES: Following priming with three doses of a DTaP vaccine during infancy, the safety, reactogenicity and immunogenicity of nine different candidate DTaP-vaccines with reduced amounts of antigen and/or adjuvant given as fourth (booster) dose were evaluated. METHODS: Study participants were healthy infants aged 15-27 months at the time of booster vaccination. Each participant had received three doses of a DTaP vaccine (Infanrixtrade mark, GlaxoSmithKline, Rixensart, Belgium; "reference DTaP") at age 3, 4, and 5 months as part of a previous clinical trial. More than 20,000 children were eligible for participation in the current study protocol at the time. In a first phase at a University hospital-based vaccination study center, nine sequential cohorts of 63-119 study subjects received one of nine different candidate vaccines. Patients and study personal were blinded with regard to which vaccine was currently in use. Reactogenicity was solicited from parents using diary cards. Blood was drawn prior to and 4 weeks after vaccination and immediately centrifuged. The serum was stored at -20 degrees C until serology was performed by ELISA tests. As soon as the first candidate vaccine with adequate reactogenicity and immunogenicity profile was identified in the first study phase, a second study phase was initiated in parallel, to evaluate the safety and reactogenicity of the respective candidate vaccine in private practices in large cohorts (1613-2095 study subjects per group). RESULTS: In the first study phase, DTaP with no aluminum induced the highest frequency of ETS and fever. All other candidate vaccines caused lower rates of local and general reactions than the reference DTaP. As a general rule, vaccines with less antigen induced fewer reactions, although there was no strict dose-response effect and the difference, e.g. between a one-tenth and a one-fifth DTaP dose (DTaP 1/5; DTaP 1/10) was not clinically relevant. Separate injections of Td and aP caused fewer general reactions than the respective TdaP combination and local reactions were higher at the aP than at the Td injection site. Again, as a general rule, reduced amounts of antigen induced lower antibody concentrations, although all vaccines induced "protective" anti-tetanus and anti-diphtheria antibody responses. A total of 92-100% of children showed seroresponses to pertussis antigens even when vaccinated with reduced amounts of the respective pertussis antigen. Elimination of aluminum from DTaP vaccine induced higher anti-tetanus-antibody concentrations and so did a reduction of the amount of diphtheria antigen. Additional examples for antigen interaction were increased antibody concentrations, observed with injection of Td and aP into different limbs. In the second study phase, all three vaccines evaluated (one with a reduced amount of diphtheria antigen, TdaP; one with reduced amounts of all antigens, tdap; and one with a fifth dose of the reference vaccine (DTaP 1/5)) were safe and had an acceptable reactogenicity profile in a total of 4871 study subjects. CONCLUSIONS: Local reactions due to DTaP booster doses in the second year of life can be reduced by reducing the amount of antigen in the respective vaccine while an adequate immunogenicity is maintained. Aluminum-free vaccines induced ETS and fever most commonly. Any changes in vaccine composition should lead to a full evaluation of the new product.

Protection against six childhood diseases with a hexavalent vaccine

Background There is an urgent call for combined vaccines, containing multiple antigens, to ensure compliance by physicians and parents with the increasing number of vaccines recommended for children. To address this need, GlaxoSmithKline (GSK) Biologicals has developed a range of acellular pertussis-based diphtheria, tetanus, pertussis (DTPa) combination vaccines, the cornerstone of which is Infanrix™ (DTPa-GSK). These combination vaccines allow for flexibility and variations in schedules and recommendations in different countries. GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib) covers six main diseases against which vaccination is recommended in many countries: diphtheria, tetanus, pertussis, hepatitis B, polio and Haemophilus influenzae type b. Clinical development In extensive clinical trials, the hexavalent GSK vaccine was well-tolerated and induced protective antibody levels against diphtheria, tetanus, hepatitis B and polio. Decreased levels of antibody against H. influenzae type b were not considered clinically relevant mainly because they were compensated for by the induction of immune memory. The three pertussis antigens (PT, FHA and PRN) produced levels of antibodies that were equivalent to those specifically generated in efficacy trials with DTPa-GSK vaccine. Further support for the protective capacity of the hexavalent vaccine against pertussis came from mouse model data and post-marketing effectiveness studies. Conclusions This manuscript provides an overview of the clinical characteristics, immunogenicity, efficacy and reactogenicity of the hexavalent GSK vaccine. The safety and effectiveness of this combination will permit vaccination against six diseases with single injections, minimize the distress to infants and children, improve cost-effectiveness, and extend vaccine coverage. In addition, the hexavalent combination lends itself as the vaccine of choice for parents and healthcare providers for childhood vaccination schedules (AU)

No disponible

Spatial interactions during bimanual coordination patterns: the effect of directional compatibility.

Whereas previous bimanual coordination research has predominantly focused on the constraining role of timing, the present study addressed the role of spatial (i.e., directional) constraints during the simultaneous production of equilateral triangles with both upper limbs. In addition to coordination modes in which mirror-image and isodirectional movements were performed (compatible patterns), new modes were tested in which the left limb lagged with respect to the right by one triangle side (non-compatible patterns). This resulted in the experimental manipulation of directional compatibility between the limbs. In addition, triangles with either horizontal or vertical orientations were to be drawn in order to assess the role of static images on movement production. Results supported the important role of directional constraints in bimanual coordination. Furthermore, triangles in vertical orientations (with a vertical symmetry axis, i.e., one apex pointing up) were drawn more successfully than those in horizontal orientations (with a horizontal symmetry axis, i.e., one apex pointing left or right), suggesting that the static aspects of a geometric form may affect movement dynamics. Finally, evidence suggested that cognitive processes related to integration of the submovements into a unified plan mediate the performance of new coordination patterns. The implications of the present finding for clinical populations are discussed

The synchronization of human arm movements to external events.

Previous research revealed the existence of coupling mechanisms (e.g. iso-directionality) at the level of perception and action. The present experiment investigated how the strength of the perception-action coupling affected synchronization performance. Arm movements were to be synchronized with a moving light that traveled back and forth from the left to the right side of a runway. Four experimental conditions were administered representing the orthogonal combination of two viewing conditions (intermittent vs. continuous) and two synchronization modes (in-phase, i.e. arm moving in the same direction as the light vs. anti-phase, i.e. arm moving in the opposite direction). Performance outcome measures, movement kinematics, and relative phase were used to examine the data. The results revealed a better synchronization performance when the arm and light traveled in the same direction (iso-directionality) during the continuous viewing condition. Apparently, the strength of the perception-action coupling has a severe impact on the quality of the synchronization of an arm movement to an external event.

The identification of coordination constraints across planes of motion.

Two dominant coordination constraints have been identified during isofrequency conditions in previous work: the egocentric constraint, i.e., simultaneous activation of homologous muscle groups, and the allocentric constraint, i.e., moving the segments in the same direction in extrinsic space. To verify their generalization, bimanual drawing movements were performed in different planes of motion (transverse, frontal, sagittal, frontal-transverse) according to the in-phase and anti-phase mode along the X- and Y-axes. Convergent findings were obtained across the transverse, frontal, and frontal-transverse planes. The in-phase mode along both axes was performed most accurately/consistently, whereas the anti-phase mode resulted in a deterioration of the coordination pattern and this effect was most pronounced when the latter mode was introduced with respect to both dimensions. For sagittal plane motions, the in-phase mode was again superior but the second most optimal configuration was the anti-phase mode along both axes. This finding was hypothesized to result from the familiarity with the pattern since it resembles cycling behavior. It illustrates how cognitive mapping is superimposed onto the dynamics of interlimb coordination. Overall, these results support the presence of both the egocentric and allocentric constraint during bimanual movement production.

Evaluation of a single-sample serological technique for diagnosing pertussis in unvaccinated children.

This study was performed to evaluate the sensitivity of immunoglobulin (Ig)G and IgA antibodies to pertussis toxin and filamentous hemagglutinin in diagnosing pertussis from a single serum sample. The pertussis group was defined according to the World Health Organization pertussis case definition. The control group coughed for 21 days or more but had no microbiological or serological evidence of Bordetella infection. Both cohorts were divided into infants (< 12 months of age), toddlers (1-4 years) and school children (5-10 years). There were 525 subjects in the pertussis group and 321 in the control group, with an even distribution of genders. IgG and IgA antibodies to pertussis toxin and filamentous hemagglutinin were measured in a standardized enzyme immunoassay. Antibody levels beyond the 95 percentile of the control cohort were regarded as indicative of recent contact, setting the specificity level at 0.95. Acute serum samples drawn between 1 week and 3 weeks after the onset of coughing showed a low sensitivity (2-19%) for diagnosing pertussis. In convalescent samples taken 5-10 weeks after the onset of symptoms, detection of IgG anti-pertussis toxin was the best single test, with a sensitivity of 61%, 65%, and 74% in infants, toddlers and school children, respectively. A combination of IgG anti-pertussis toxin and IgA anti-filamentous hemagglutinin using age-specific reference values had a sensitivity of 81-89% in diagnosing pertussis from a single serum sample taken 5-10 weeks after the beginning of symptoms.

A serologic study of organisms possibly associated with pertussis-like coughing.

OBJECTIVE: To assess the frequency of serologic evidence for an infection with microorganisms other than Bordetella pertussis in children with pertussis-like coughs. METHODS: The study was performed within a protective efficacy trial of an acellular pertussis vaccine. Children who coughed for >7 days and had no laboratory evidence of recent infection with B. pertussis were eligible for the present study. Antibodies to Mycoplasma, Chlamydia, respiratory syncytial virus and influenza viruses A and B were measured by complement fixation, and antibodies to adenovirus and parainfluenza viruses 1, 2 and 3 were measured by enzyme-linked immunosorbent assay (ELISA) in acute and convalescent serum samples. Significant titer rises (4-fold titer rise in complement fixation, 100% increase of units in ELISA) and concentrations of antibodies beyond age-specific reference values were regarded as indicative of recent infection. In some children IgM antibodies to Epstein-Barr virus and to cytomegalovirus were also measured by ELISA. RESULTS: A total of 149 of 1179 (12.6%) children had no laboratory evidence of B. pertussis infection. Serologic evidence for other infections were found in 56% (83 of 149). Adenovirus (33), parainfluenza viruses 1, 2 and 3 (18), Mycoplasma pneumoniae (15) and respiratory syncytial virus (14) were most common. Of this group 48% had been vaccinated against pertussis. CONCLUSION: We present data that a proportion of pertussis-like coughs in children may be caused by adenovirus, parainfluenza viruses, respiratory syncytial virus and Mycoplasma. The differential diagnosis of pertussis-like coughs by laboratory methods should include these infections, especially in vaccinated children.

Factors influencing the spread of pertussis in households.

UNLABELLED: The objective of this study was to compare the spread of pertussis in children and adults being secondary contacts after household exposure. The study was nested in an efficacy trial of an acellular pertussis vaccine. The spread of the disease was also monitored with respect to gender and antibiotic therapy. A total of 453 index cases, of which 133 were monitored for adult disease, fulfilled the WHO definition of pertussis. They had contacts to 173 unvaccinated children aged 6-47 months, and a total of 101 adults with pertussis were followed. Detection of the bacteria, or a significant increase of specific antibodies confirmed the diagnosis. Secondary spread of the disease was assumed, when a household member coughed for 7 days or more and had laboratory evidence for pertussis. Crude attack rates (AR) were 69% in children and 31% in adults (P < 0.05). AR in children were independent of gender but more women than men (P=0.02) were affected in those households where the index case was a child. Erythromycin treatment of the index case reduced the AR in exposed toddlers from 80% to 57% (P=0.06), and in exposed adults from 40% to 21% (P=0.2). Erythromycin therapy in contacts did not alter the clinical course of the disease significantly. CONCLUSIONS: In a household study of pertussis, 69% of children and 31% of adults (more women than men) contracted the disease. Erythromycin reduced the number of infections in household contacts, but did not alter the clinical course in those who contracted pertussis.

Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations.

UNLABELLED: With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative, multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available Haemophilus influenzae type b (Hib) vaccine concomitantly with diphtheria-, tetanus- acellular pertussis (DTaP) vaccine. Study subjects were randomly allocated to one of the following groups: (1) separate, or (2) mixed injection of DTaP and candidate Hib vaccine, or (3) separate injection of DTaP and commercial Hib vaccine. One year later the first 189 study subjects received either separate or mixed injections of the same Hib and DTaP vaccines as booster doses. Evaluation of reactogenicity was based on diary cards completed by parents. Immunogenicity was documented by measuring IgG antibody concentrations in serum samples taken before and 4 weeks after primary and booster vaccination. No serious adverse events occurred and most local and systemic reactions were mild to moderate. Booster doses were more reactogenic than primary doses with all groups. Antibody concentrations against pertussis antigens were similar to those seen with DTaP alone. All but one subject had protective antibody concentrations against diphtheria and tetanus. Primary immune response to the Hib vaccine was significantly lower in the group receiving the mixed Hib-DTaP vaccine, however, > or = 95% of vaccinees had anti-Hib antibody concentrations > or = 0.15 microg/ml and there was a marked booster response (> 100-fold) in all groups. CONCLUSIONS: Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity.

Reactogenicity and immunogenicity of a booster dose of a combined diphtheria, tetanus, and tricomponent acellular pertussis vaccine at fourteen to twenty-eight months of age.

OBJECTIVES: The primary objective was to assess the nature and incidence of adverse events after a fourth dose of a tricomponent acellular pertussis-diphtheriatetanus vaccine given in the second year of life after primary vaccination with the same vaccine at 3, 4, and 5 months of age. A secondary objective was to analyze the immunogeniecity of the booster vaccination. DESIGN: Of the 5361 children enrolled (aged 14 to 28 months), adverse reactions were specifically solicited from the first 1863 enrollees for the first 4 days after vaccination and then were unsolicited for the remainder of the 4 weeks of follow-up (group 1). In the next 3498 subjects, safety and reactogenicify were entirely unsolicited for this 4-week period (group 2). Immunogenicity was analyzed by means of prebooster and postbooster serum antibody titers for all vaccine components in a random subgroup of 197 children from group 1. RESULTS: Soliciting symptoms elicited reports of at least one symptom in 1314 of 1809 children in group 1 (72.6%), including 993 (54.9%) with local and 885 (48.9%) with general symptoms during the first 4 days after vaccination. When symptoms were gathered in an unsolicited fashion, only 580 of 3498 children in group 2 (16.6%) had a reported symptom during this time, consisting of 344 (9.8%) local and 319 (9.1%) general symptoms, respectively. An unsolicited symptom, areactive edematous swelling of the whole thigh, occurred in 62 children (1.1%), with 45 and 17 reports in groups 1 and 2, respectively. The vast majority of all reported symptoms were mild to moderate, and all children recovered without sequelae. Fourteen serious adverse events were reported, but none was considered to be related to the vaccination. Immunogenicity analysis showed a vaccine response to pertussis toxin in 99.5% of subjects, to filamentous hemagglutinin in 98.5%, and to pertactin (69 kd outer membrane protein) in 99%. All subjects had postvaccination antibody titers of 0.1 IU/ml or greater against diphtheria and tetanus toxoids.

Evidence for induction of polysaccharide specific B-cell-memory in the 1st year of life: plain Haemophilus influenzae type b-PRP (Hib) boosters children primed with a tetanus-conjugate Hib-DTPa-HBV combined vaccine.

UNLABELLED: The lack of an adequate immune response to the major polysaccharide of the Haemophilus influenzae type b (Hib) capsule (polyribosyl ribitol phosphate) (PRP) in very young infants (< 18 months) can be overcome by conjugating PRP to a T-cell dependent carrier protein. We studied whether administration of a tetanus-PRP conjugate vaccine reconstituted with a diphtheria-tetanus-acellular pertussis-hepatitis B (DTPa-HBV) vaccine as a three dose primary course at 3, 4 and 5 months of age induced PRP-specific immunological memory, by examining the anti-PRP response to a dose of unconjugated PRP given with the DTPa-HBV booster approximately 1 year later. The unconjugated PRP elicited protective anti-PRP antibody levels (> or = 0.15 microgram/ml) in all but 3 of the 369 vaccinees, including 13 infants who failed to demonstrate a measurable immune response after the primary course. In a sub-cohort of 54 subjects all had anti-PRP levels > or = 0.5 microgram/ml within 7-14 days of the booster showing a rapid anamnestic type response. Both primary and booster responses were predominantly IgGl indicating a T-cell dependent response. The DTPa-HBV components elicited protective anti-diphtheria, anti-tetanus and anti-HBs antibody levels in > or = 98.5% of vaccinees, and immune responses to each of the acellular pertussis vaccine components in 92.3%-97.3% of subjects. CONCLUSION: The tetanus-PRP conjugate vaccine not only elicited a good primary humoral response, but also induced immunological memory so that the infants were able to mount a large and rapid immune response to subsequent exposure to plain PRP, indicating that protection against circulating wild-type Hib had been generated. Successful induction of immunological memory occurred even when there was no measurable humoral anti-PRP response to the primary course. Tetanus-PRP conjugate vaccine can be used in combination with DTPa-HBV vaccine, when administered separately or as a single injection in the same syringe, in primary immunisation schedules at 3, 4 and 5 months of age.

Factors influencing the analysis of secondary prevention of pertussis.

The aim of this study was to evaluate factors that influenced the spread of pertussis in secondary contacts after household exposure. The data were acquired during a prospective household-contact study into the efficacy of an acellular vaccine. The spread of the disease was monitored with respect to various case definitions of pertussis, socio-economic factors, household composition, and antibiotic therapy. A total of 453 index cases had contact with 173 unvaccinated children aged from 6 to 47 months. Depending on the clinical case definition, the attack rates (AR) in children with a laboratory-confirmed Bordetella infection increased from 55% for the WHO definition to 69%, when a less stringent definition was used. AR in children were independent of age and gender. The social status of the family had no significant influence on the AR in children. Erythromycin treatment of the index case reduced the AR from 64% to 51% (p = 0.08). These factors should be taken into consideration when studies into the secondary prevention of pertussis by acellular vaccines are initiated.

Overview of the clinical development of a diphtheria-tetanus--acellular pertussis vaccine.

A tricomponent acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, and pertactin combined with diphtheria and tetanus toxoids (DTPa) was developed as a less reactogenic alternative to the traditional whole cell pertussis (DTPw) vaccine. In studies of DTPa as a primary vaccination and as a booster dose in DTPa- or DTPw-primed children, the vaccine was safe, well-tolerated, and highly immunogenic; it was less reactogenic than DTPw but at least as immunogenic. A three-dose primary vaccination sequence with DTPa vaccine in the first 6 months of life protects against pertussis under conditions of high infectious pressure. These results support the licensing of the vaccine for primary and booster vaccination in a growing number of countries. Combined DTPa-based pediatric vaccines are in clinical development.

Acellular pertussis vaccines: the rationale for an efficacy trial in Germany.

After concern about the safety of diphtheria-tetanus toxoid-whole cell pertussis vaccines (DTPw), the recommendation to vaccinate children with DTPw was withdrawn in 1974 in the former West Germany. This led pertussis cases to increase to an estimated 100,000 annually. Despite renewal of the vaccination recommendation in 1991, vaccine use remained low. The German health care structure assures regular contact between most children and pediatricians. This enabled the conduct of a large efficacy trial with a diphtheria-tetanus toxoid-acellular pertussis (DTPa) vaccine. Because a placebo-controlled trial was not ethically possible, a prospective household contact study with a blinded clinical follow-up was done. Possible study participants were screened by their pediatrician, who also initiated diagnostic procedures. Clinical follow-up was done by another locally based but independent and blinded physician. Vaccine efficacy was calculated to be 89% (95% confidence interval, 76.6%-94.6%). None of the identified confounding factors biased results in favor of the DTPa vaccine.

Immunogenicity and safety of a live attenuated varicella vaccine (Oka/SB Bio) in healthy children.

An Oka strain varicella vaccine developed by SmithKline Beecham Biologicals in the early 1980s is registered for immunization of high-risk groups in nine European countries. Because the preparation must be stored at -20 degrees C, it was reformulated to facilitate its use for general vaccination in healthy children with storage at 2-8 degrees C for 2 years. Studies using production lots of the reformulated vaccine in approximately 1400 healthy children are summarized. During the 42-day follow-up, no vaccine-related serious adverse events were reported. Unsolicited reactogenicity rates were low: 14.2% in children ages 9-36 months (the main target age group for the vaccine). Seroconversion rates were 98.6% after a single dose. Consistent reactogenicity and immunogenicity were observed across vaccine lots. After efficacy is demonstrated in other studies, widespread use of this vaccine will prevent a common and potentially serious childhood illness.

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants.

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3, 4, and 5 months. Serious adverse events were followed for 1 month after each vaccination, and neurologic events for 1 year or longer. Serum IgG antibodies were assayed before vaccination and 1 month after vaccination. RESULTS: After 67,000 doses, 153 serious adverse events (0.23%) were reported, 8 considered possibly related, and 5 related to vaccination, including 1 hypotonic-hyporesponsive episode. Incidence rates of sudden infant death syndrome (7; 0.01%) or acute neurologic events (20; 0.030%) were no higher than expected and not considered to be related to vaccination. Redness and swelling of 20 mm or greater occurred after 44 (0.6%) and 40 (0.6%) of the 7270 doses, respectively, and high fever (> 39.5 degrees C) in 6 (0.08%) subjects within 48 hours of vaccination. In the immunogenicity analysis of 580 infants, 98% responded to pertussis toxin, 96% to filamentous hemagglutinin, and 98% to pertactin. In an additional 5712 infants, the response rate to pertussis toxin was 99%. CONCLUSIONS: In a large cohort of 22,505 infants vaccinated, SmithKline Beecham Biologicals' tricomponent DTaP vaccine was shown to be safe, well-tolerated, and immunogenic for all component antigens.

Efficacy of acellular pertussis vaccine in early childhood after household exposure.

OBJECTIVE: To evaluate the efficacy of a three-dose primary vaccination with a diphtheria-tetanus tricomponent acellular pertussis vaccine against "typical" pertussis, defined as a spasmodic cough of 21 days or longer with confirmation of Bordetella pertussis infection by culture or serology. DESIGN: Passive monitoring for suspected first household (index) cases of typical pertussis in six areas in Germany comprising 22,505 children vaccinated with study vaccine at 3, 4, and 5 months of age. Blinded, prospective follow-up of household contacts of index cases for incidence and progression of pertussis. SETTING: Six areas in Germany with a high incidence of pertussis. SUBJECTS: Four hundred fifty-three households with index cases comprising 360 evaluable contacts eligible for analysis of vaccine efficacy. MAIN OUTCOME MEASURE: Vaccine efficacy from attack rates of pertussis in household contacts classified by vaccination status. RESULTS: Of the 173 nonvaccinated household contacts, 96 developed typical pertussis, compared with seven of 112 contacts vaccinated with acellular pertussis vaccine. Vaccine efficacy was consequently calculated to be 88.7% (95% confidence interval, 76.6% to 94.6%). Protection did not wane until at least the time recommended for booster vaccination. None of the analyzed potential confounding factors--age, socioeconomic status, erythromycin treatment, household composition, center effect, and selection bias--influenced study results in favor of the vaccine. CONCLUSIONS: Under conditions of intense household exposure, primary vaccination with acellular vaccine protected against pertussis until at least the time recommended for booster vaccination. The vaccine can be expected to be equally or more effective in settings with lower infectious pressure.

Symptoms and complications of pertussis in adults.

There is increasing evidence that pertussis occurs frequently in adults, but there is limited information on the clinical course of this disease beyond childhood. A household contact study on the efficacy of an acellular pertussis vaccine was used to study the symptoms of pertussis in adults. Among 257 patients with pertussis identified in 121 families during a two-year period in one study center with a low whole-cell pertussis-vaccine uptake, 79 (30.7%) were adults, aged 19-83 years (mean age: 36 years) with a 1:1.8 male to female ratio. Ninety-one percent of the adults suffered from coughing (mean duration: 54 days), and in 80% this cough lasted > or = 21 days. Whoops were rare (8%), whereas cough followed by vomiting and/or choking (53%) and cough disturbing sleep (52%) were common. This is the first report to describe sweating attacks as symptom of pertussis (14%). Pharyngeal symptoms (37%), influenza-like symptoms (30%), sneezing attacks (22%), hoarseness (18%), sinus pain (16%) and headaches (14%) were also observed. Various complications were seen in 23% of the patients. In order to minimize the spread of the organism, microbiological diagnostics should be vigorously applied to all symptomatic contacts of a patient with pertussis but also to all patients with long lasting cough-irrespective of age.