Efficacy of a two-component acellular pertussis vaccine in infants

OBJECTIVE: This case-control study investigated the protective efficacy against pertussis of three doses of a two-component acellular pertussis vaccine (manufactured by Biken in Japan) combined with diphtheria and tetanus toxoids (manufactured by Connaught Laboratories in the US) in infants. METHODS: A case-control study was performed in 63 pediatric practices in Germany. Prospective recruitment of 16,780 infants ages 6 to 17 weeks took place between February, 1993, and July, 1994. According to parental choice infants received either Biken acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTacP) (74.6%) at approximately 2, 4 and 6 months of age, or a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine (10.9%), diphtheria-tetanus toxoids vaccine (12.5%) or no vaccine (2.0%). Prospective surveillance of pertussis cases between February, 1993, and May, 1995, was accomplished by culturing all infants < or =2 years of age presenting with cough > or = 7 days. A pertussis case was defined as any cough of 21 days or longer plus a positive Bordetella pertussis culture or household contact exposure. RESULTS: We identified 241 pertussis cases prospectively by 11,017 B. pertussis cultures and 949 controls matched for age were selected from the same pediatric practices. Medical history and demographic and vaccine status data were collected from each case and for four controls. Data were analyzed through conditional logistic regression taking into account individual matching and adjusting for potential confounding variables. DTacP combined with diphtheria and tetanus toxoids vaccine was 82% protective (95% confidence interval, 68 to 90), diphtheria-tetanus toxoids-whole cell pertussis vaccine was 96% protective (95% confidence interval, 78 to 99). Protection against typical B. pertussis infection characterized by paroxysmal cough lasting > or =21 days was 96% (95% confidence interval, 87 to 99) for DTacP and was 97% (95% confidence interval, 79 to 100) for diphtheria-tetanus toxoids-whole cell pertussis vaccine. Adjustment for potentially confounding variables did not change the results significantly. CONCLUSIONS: Three doses of the two-component acellular pertussis vaccine protected infants against pertussis disease during the period before the recommended booster vaccination. For typical pertussis disease as defined by the WHO efficacy was high and similar to that of a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine.     

Monitoring of a whooping cough epidemic 1994/95 in Switzerland using the sentinel notification system. Sentinella Registry

Since June 1991 pertussis cases have been reported in the Swiss Sentinel Network (Sentinella). A total of 150-200 general practitioners, physicians specialized in internal medicine, and pediatricians participate in this system on a voluntary basis. Of the three specialties involved, this non-randomized sample represents 3.0%-3.5% of all physicians registered in Switzerland. The objective of this surveillance system is to monitor clinical pertussis over time. The case definition included all patients with a cough illness lasting at least 14 days with one of the following: paroxysms of cough, inspiratory "whoop", post-tussive vomiting (sporadic cases), or an epidemiological link to a pertussis case (epidemic cases). A laboratory diagnosis based on the polymerase chain reaction technique (PCR) was available for 82.7% of cases reported in 1994 and 1995. Of these, 27.7% had a positive PCR result. Reports of epidemic pertussis tested for Bordetella pertussis by PCR were confirmed by the laboratory in 46.5% of cases. The laboratory confirmation rate was more than twice as high among epidemic cases than among sporadic cases (20.7%). The crude incidence rate of whooping cough was 70 cases per 100,000 population per year in 1992 and 1993. Compared to previous years, pertussis incidence was significantly higher in 1994 and 1995 (370 cases per 100,000 population and 280 cases per 100,000 population respectively). The increase in reports was especially marked between July and October 1994 and whooping cough became epidemic in the third trimester of 1994 and at the beginning of 1995. In these 2 years, Switzerland experienced an estimated 40,000 clinical pertussis cases. Based on the proportion of PCR-positive pertussis cases in the sentinel sample, 12,500 of these would have been laboratory-confirmed. Most cases were observed in infants and in children up to 6 years of age. Assuming a vaccination coverage of 90%, the global efficacy of vaccination (3 or more doses versus less than 3) for 1994 and 1995 among children aged 12 to 47 months and not born before 1991 was 0.74 (0.59 and 0.88 for a vaccination coverage of 85% and 95% respectively). Vaccine efficacy was higher in PCR-positive cases (0.87; 0.79; 0.94) than in PCR-negative cases (0.54; 0.27; 0.78). Vaccination efficacy estimates on the basis of surveillance data are certainly less precise than those inferred from clinical trials. However, our results indicate that the efficacy of vaccination in children significantly declined with increasing age. Whooping cough still has the potential to cause epidemics in Switzerland in spite of a high vaccination coverage. With the introduction of acellular pertussis vaccines and new vaccination schemes in Switzerland, the Swiss Sentinel Network fulfills an important task as a monitoring system and contributes to the evaluation of new vaccination strategies.     

Ogura and Powers: "Functional restitution of traumatic stenosis of the larynx and pharynx." (Laryngoscope 1964;74: 1081-1110)

The objective of this study was to evaluate the immune response and reactogenicity of a combined hepatitis B, diphtheria, tetanus and whole-cell Bordetella pertussis (DTPw-HBV) vaccine administered to healthy infants at 2, 4 and 6 months of age. A total of 179 infants (6-12 weeks of age) received three doses of DTPw-HBV vaccine. Blood samples for antibody determinations were taken before vaccination, 2 months after the second dose and 1 month after the third dose. Solicited and unsolicited symptoms were recorded by parents in a diary card. All vaccinees had protective levels of anti-HBs [geometric mean titre (GMT): 1526 mIU.ml-1], anti-diphtheria and anti-tetanus antibodies, 1 month after the third dose. Ninety-two percent of the subjects exhibited a response to the B. pertussis component. Most (99.4%) solicited reactions occurred within the first 48 h and the majority were mild or moderate. The safety, immunogenicity of this tetravalent vaccine was demonstrated when it was administered in infants following the 0, 2, 4-month dosing schedule.     

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.     

Mapplet: a CORBA-based genome map viewer

BACKGROUND: Pertussis vaccination in infancy has been suggested to increase the risk for development of asthma and allergy. OBJECTIVE: To assess sensitization rates and development of atopic diseases in a prospective randomized controlled trial of pertussis vaccine. PATIENTS AND METHODS: A total of 669 children were randomized to 1 of 4 vaccine groups (2-component acellular pertussis, 5-component acellular pertussis, whole-cell pertussis vaccines, and placebo [diphtheria and tetanus toxoids]). Diphtheria and tetanus toxoids were also given to the children in the pertussis vaccine groups. The children were evaluated by means of questionnaires at age 2 months, 7 months, and 2 1/2 years; skin prick tests at age 7 months and 2 1/2 years; and blinded clinical investigation at age 2 1/2 years. The families were contacted at regular intervals to assess possible adverse effects after the vaccinations and symptoms of whooping cough. RESULTS: The cumulative incidence of atopic diseases was 30% and incidence rates were similar in the 4 groups after adjusting for family history. Exposure to environmental tobacco smoke and home dampness did not confound these results. The frequency of adverse effects did not differ appreciably between atopic and nonatopic children, with the exception that a nodule at the vaccination site was more frequent after whole-cell pertussis vaccination in the nonatopic children. Among 47 children with proven pertussis, atopic disease appeared in 19 (40%). Of these 47 children, 9 (19%) developed asthma, as compared with 58 (9%) noninfected children (P=.03). CONCLUSIONS: We found no support for a drastic increase in allergic manifestations after pertussis vaccination. There was a positive association between whooping cough and asthma by 2 1/2 years of age. There seems to be little reason to withhold pertussis vaccination from infants, irrespective of family history of allergy.     

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age

METHODS: In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections. RESULTS: There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.     

Pertussis, pertussis vaccine, and care of exposed persons

BACKGROUND: Pertussis is a highly contagious bacterial infection caused by Bordetella pertussis. Before routine vaccination against pertussis was available, most persons were infected during childhood. After widespread vaccination, however, the incidence of pertussis in the United States dropped by more than 95 percent, though localized outbreaks continue to occur. METHODS: A multidisciplinary team developed a set of review articles as part of continuing medical education modules in the Teaching Immunization in Medical Education (TIME) Project. The team developed the materials using expert judgment and selected materials from the literature and the Centers for Disease Control and Prevention (CDC). The first step was the creation of specific learning objectives that used the spectrum of Bloom's taxonomy, when possible. After the materials were developed, they were pilot-tested and revised. Subsequently they underwent summative evaluation by field-testing the materials with 24 other primary care physicians. Then the materials were reviewed by the CDC and national vaccine experts and revised based on their comments. RESULTS AND CONCLUSIONS: The efficacy of whole-cell pertussis vaccine is about 70 to 90 percent, though local adverse events are common. Since 1990 several purified, acellular pertussis vaccines have been developed that have one quarter to one half of the common adverse events associated with whole-cell vaccine and have similar efficacy rates. The incidence of pertussis can be further reduced by increasing age-appropriate vaccination rates.     

Cloning of two putative Giardia lamblia glucosamine 6-phosphate isomerase genes only one of which is transcriptionally activated during encystment

Acellular pertussis vaccines provide protection against whooping cough with few adverse effects. Their introduction to routine immunisation programmes would be facilitated by their incorporation with other routinely administered vaccines. 262 infants were immunised with an acellular pertussis vaccine containing pertussis toxin and filamentous haemagglutinin, combined with diphtheria and tetanus toxoids. This vaccine was mixed with Haemophilus influenzae type b tetanus toxoid vaccine (PRP-T) so that infants received a single injection at age 2, 3 and 4 months. One month after the third dose the geometric mean titre of Hib IgG antibody was 0.48 microgram ml-1. Eighty-two percent of infants achieved a titre of 0.15 microgram ml-1, with only 27% achieving 1.0 microgram ml-1. This combination vaccine induced low Hib antibody responses when compared to other studies in which PRP-T was mixed with acellular or whole-cell pertussis vaccines. The combined vaccine did, however, appear to prime a subset of 35 infants for response to a fourth dose of PRP-T at 13 months of age, with a rise in GMT from 0.21 microgram ml-1 to 36.6 micrograms ml-1. These data have important implications for the introduction of combination acellular pertussis vaccines.     

The role of subunit composition on prepulse facilitation of the cardiac L-type calcium channel

The prevalence of neurocysticercosis has been well documented in rural communities in Latin America using the enzyme-linked inmmunoelectrotransfer blot (EITB) assay. We studied the prevalence of neurocysticercosis in an urban, upper-middle class population in Cuenca, Ecuador. Family members of 34 index cases with parenchymal neurocysticercosis on a computed tomography (CT) scan and family members of 14 patients who had normal CT scans after a trauma or migraine were enrolled in the study. Serum was obtained from 226 individuals, 173 (72%) from the case families and 67 (28%) from the control families. Twelve percent of the case family members and 4% of the control family members were seropositive by the EITB assay. This was a statistically significant difference (P < 0.05) when age and education were held constant by logistic regression. Seropositivity was not related to age. No neurologic symptom proved predictive of serostatus and the only demographic variable that correlated with seropositivity was increased crowding. Positive serology in index cases did correlate with CT findings as follows: 86% of patients with active lesions, 67% with transitional lesions, and only 41% of patients with inactive lesions were positive by the EITB assay. Eighteen percent of family members with a positive EITB test result had parenchymal lesions on a subsequent CT scan. This study demonstrates a high rate of seropositivity of cysticercosis among urban, middle to upper-middle class individuals in a region endemic for Taenia solium. Household contacts of patients with neurocysticercosis had a three-fold higher risk of positive serology for cysticercosis, in comparison with controls.     

An age-structured model for pertussis transmission

The vaccination program for pertussis (whooping cough) in the United States consists of giving multiple doses of pertussis vaccine to young children. A demographic model with a steady-state age distribution is used as a basis for building an epidemiologic model for the transmission of pertussis. This age-structured model includes vaccination of infants and children for pertussis with waning of both infection-acquired and vaccine-induced immunity. Computer simulations of the mathematical model between 1940 and 2040 show the changes that took place during the implementation phase of the U.S. program and predict only minor future changes in the age distribution and incidence of pertussis if the vaccination program is maintained at the 1995 level. The sensitivities of these results to changes in demographic and epidemiologic parameters, vaccine efficacy, duration of protection, and levels of vaccination coverage are investigated.     

Hepatitis B virus infection, hepatitis B vaccine, and hepatitis B immune globulin

Hepatitis B virus (HBV) infection is a major health problem in the United States; in 1995, approximately 128,000 cases occurred. Transmission of HBV occurs primarily by blood exchange (eg, by shared needles during injection drug use) and by sexual contact. Persons infected early in life are much more likely to become chronically infected than those infected during adulthood: as many as 90% of infants infected perinatally develop chronic infection and up to 25% will die of HBV-related chronic liver disease as adults. Clinical signs of acute hepatitis occur in about 50% of infected adults but in only 5% of infected preschool-aged children. In the United States, hepatitis B vaccine is currently made by recombinant DNA technology using baker's yeast. Preexposure vaccination results in protective antibody levels in almost all infants and children (> 95%) and healthy adults younger than 40 years of age (> 90%). The most common adverse event following administration of hepatitis B vaccine is pain at the injection site, which occurs in 13% to 29% of adult and 3% to 9% of children. A comprehensive hepatitis B vaccination policy is now recommended that includes (1) routine infant vaccination; (2) catch-up vaccination of 11- to 12-year-olds who were not previously vaccinated; (3) catch-up vaccination of young children at high risk for infection; (4) vaccination of adolescents and adults based on lifestyle or environmental, medical, and occupational situations that place them at risk; and (5) prevention of perinatal HBV infection.     

Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage

OBJECTIVE: To determine the frequency of adverse reactions, particularly the occurrence of apnea, among preterm infants after immunization with diphtheria and tetanus toxoids and whole cell pertussis vaccine adsorbed (DTP) and Haemophilus influenzae type b conjugate (HibC) vaccine in the neonatal intensive care unit. STUDY DESIGN: After the occurrence of apnea in two preterm infants following immunization with DTP and HibC, a prospective surveillance of 97 preterm infants younger than 37 weeks of gestation who were immunized with DTP (94 also received HibC at the same time) in the neonatal intensive care unit was performed to assess the frequency of adverse reactions and in particular, the occurrence of apnea. For each infant, data were recorded for a 3-day period before and after receipt of the immunization. RESULTS: The majority of preterm infants tolerated immunizations with DTP and HibC without ill effects. However, 12 (12%) infants experienced a recurrence of apnea, and 11 (11%) had at least a 50% increase in the number of apneic and bradycardic episodes in the 72 hours after immunization. This occurred primarily among smaller preterm infants who were immunized at a lower weight (p = 0.01), had experienced more severe apnea of prematurity (p = 0.01), and had chronic lung disease (p = 0.03). CONCLUSION: The temporal association observed between immunization of preterm infants and a transient increase or recurrence of apnea after vaccination merits further study. Cardiorespiratory monitoring of these infants after immunization may be advisable.     

Ganciclovir resistance as a result of oral ganciclovir in a heart transplant recipient with multiple human cytomegalovirus strains in blood

The etiologic spectrum of acute encephalitis syndrome (AES) has not been well defined in Vietnam. Cohort and case-control studies were performed on all adult and pediatric AES patients admitted to the Neurology Service of Bach Mai Hospital between June 5 and August 3, 1995. Among pediatric AES patients, 31 (67%) of 46 had acute Japanese encephalitis (JE), compared with only two (6%) of 33 adult AES patients (P < 0.0001). For confirmed JE cases, serum specimens obtained 15-21 days after symptom onset had the highest mean anti-JE IgM signal-to-noise (P/N) ratios (8.08 + 1.09 SE). A serosurvey of adult household members did not reveal any cases of recent subclinical JE infection, although 26% had evidence of past JE infection. The use of bed netting was nearly universal but did not appear to reduce the risk of AES or JE. Given the high incidence of JE, particularly among children, Vietnam seems well suited for the development of a targeted JE vaccination strategy.     

What uses for the acellular pertussis vaccine?

The acellular pertussis vaccine offers a better tolerance as compared with the whole cell pertussis vaccine. It has also a good protective effect against whooping cough. However given as a combined pentavalent vaccine for the primary immunization of infants, it appears to introduce an immune interference leading to a diminished response to the Haemophilus type b or poliomyelitis valence according to the type of vaccine. Thus it is recommended that immunization against whooping cough in France in the coming years uses whole cell pertussis combined vaccine for the primary immunization of infants at 2, 3 and 4 months, the acellular pertussis vaccine being used for the booster injections at 18 months and 10-11 years.     

Household and dwelling contact as risk factors for leprosy in northern Malawi

Data on household and dwelling contact with known leprosy cases were available on more than 80,000 initially disease-free individuals followed up during the 1980s in a rural district of northern Malawi. A total of 331 new cases of leprosy were diagnosed among them. Individuals recorded as living in household or dwelling contact with multibacillary patients at the start of follow-up were at approximately five- to eightfold increased risk of leprosy, respectively, compared with individuals not living in such households or dwellings. Individuals living in household or dwelling contact with paucibacillary cases were both at approximately twofold increased risk. The higher risk associated with multibacillary contact and the fact that dwelling contact entailed a greater risk than household contact if the association was with multibacillary, but not with paucibacillary, disease suggest that paucibacillary cases may not themselves be sources of transmission, but rather just markers that a household has had contact with some (outside) source of infection. When household contact was considered alone, the risks of disease were appreciably higher for younger than for older contacts and for male compared with female contacts. Despite the elevated risk of leprosy associated with household or dwelling contact, only 15% of all incidence cases arose among recognized household contacts. Given the dynamic nature of household membership and consequent misclassification of contact status, the true contribution to overall incidence of contact within household or dwelling settings is likely to be much higher than this, perhaps 30% or higher. Considering the predilection of males for infectious multibacillary forms of the disease, the transmission of Mycobacterium leprae at an early age, in particular to males, may be of particular importance for the persistence of leprosy in endemic communities. Although residential contact with a multibacillary case is the strongest known determinant of leprosy risk, the vast majority of such contacts never manifest disease, which indicates a crucial role for genetic and/or environmental factors in the transmission of M. leprae infection and/or the pathogenesis of clinical leprosy.     

Changing epidemiology of congenital rubella syndrome in the United States

To describe clinical presentation and epidemiology of US infants with congenital rubella syndrome (CRS) and to identify missed opportunities for maternal vaccination, data from CRS cases reported to the National Congenital Rubella Syndrome Registry (NCRSR) from 1985 through 1996 were analyzed. Missed opportunities for maternal vaccination were defined as missed postpartum, premarital, and occupational opportunities, that is, times when rubella vaccination is recommended but was not given. From 1985 through 1996, 122 CRS cases were reported to the NCRSR. The most frequent CRS-related defect was congenital heart disease. Of the reported infants with CRS, 44% were Hispanic. Of 121 known missed opportunities for rubella vaccination among 94 mothers of infants with indigenous CRS, 98 (81%) were missed postpartum opportunities. CRS continues to occur in the United States. Hispanic infants have an increased risk of CRS. Missed opportunities for postpartum rubella vaccination were identified for 52% of indigenous CRS cases.     

Humoral immune response against antigen 60 in BCG-vaccinated infants

An ELISA assay based on the A-60 antigen complex from Mycobacterium bovis BCG cytoplasm was used to detect anti-mycobacterial antibodies of different classes in the sera of 63 BCG-vaccinated infants during the 6-month post-vaccination period. The mean IgM and IgA levels increased, whereas the mean IgG level decreased after BCG vaccination. However, in a minority of cases only Ig levels were above the cut-off line: this was true for IgM in 11/63 (17%) cases and for IgA in 14/63 (22%) of cases but none of the tested infants was anti-A60 IgG ELISA positive. Fifty-two infants (83%) were tuberculin-positive eight weeks after vaccination, and no significant difference in mean antibody levels of tuberculin-positive and negative cases was observed, except for IgG (p < 0.05).     

Public awareness of rabies and compliance with pet vaccination laws in Connecticut, 1993

OBJECTIVE: To determine the degree of public awareness of rabies and compliance with cat and dog vaccination laws in Connecticut in 1993. DESIGN: Monthly telephone surveys. SAMPLE POPULATION: 1,810 households. PROCEDURE: A telephone interview was conducted, using rables-related questions contained in the Behavioral Risk Factor Surveillance System, with an adult member from households randomly selected statewide by telephone number. Results of the surveys for the year were aggregated, and weighted data were analyzed. RESULTS: Ninety percent of respondents had heard about rabies during the preceding year, and 84% considered it a problem in Connecticut. Forty-seven percent of households surveyed owned dogs or cats. Ninety-three percent of dogs and 80% of cats were reported to be vaccinated against rabies. Twenty-two percent of households with cats had at least 1 cat that was not current on rabies vaccination. CLINICAL RELEVANCE: In Connecticut, an epizootic of rabies in raccoons was accompanied by a high degree of awareness of rabies and rate of reported vaccination of dogs and cats. However, vaccination of cats was less common than that of dogs. Public education efforts should emphasize the necessity to vaccinate cats and to avoid contact with unknown cats in rabies epizootic or enzootic areas. A surveillance system can be used to help evaluate public health programs.     

Mania in young children

OBJECTIVE: To establish safety and immunogenicity of a reformulated whole cell pertussis based diphtheria-tetanus-pertussis vaccine (DTPw) at the 18-month booster stage following a 2, 4, and 6-month primary immunization course. METHOD: Open trial in suburban Melbourne in 100 healthy children initially recruited through maternal and child health centres. Thirty-five subjects were bled prior to vaccination, and 4-6 weeks after vaccination. A 7-day diary card was used to record subject temperatures and other systemic and local clinical signs. RESULTS: The increase in antibody geometric mean titres (GMT) after boosting was 19.5-fold (95%ci 14.2, 27.2) for tetanus and 26.5-fold (95%ci 16.6, 42.4) for diphtheria. Pertussis antibody GMTs also all showed substantial increases following the booster, with mean fold changes in titre ranging from 7.3 (Agg2) to 31.3 (Fha). Seventeen percent of subjects (95%ci 10%, 26%) experienced axillary temperatures > or = 38 degrees C during the 24-h period following vaccination. Low rates of significant (> 25 mm) injection site redness (13%) and swelling (8%) were recorded at 24 h postvaccination. CONCLUSION: This vaccine was well tolerated by children at 18 months of age, and showed substantial boosting of antibody to all components.     

Access to a three-dimensional measure of vertebral axial rotation

BACKGROUND: A combined diphtheria-tetanus-whole cell pertussis-hepatitis B (DTPwHB) vaccine might facilitate the achievement of universal vaccination of infants against hepatitis B. METHODS: A double blind, randomized, two-armed, single center study was undertaken to evaluate the immunogenicity and reactogenicity of combined tetravalent DTPwHB vaccine, with two dosages of hepatitis B component (10 microg and 5 microg). The combined vaccine was tested in the context of a simplified vaccination schedule at 1.5, 3.5 and 6 months of age, to 120 healthy infants born to hepatitis B surface antigen-negative mothers after priming with one dose of hepatitis B vaccine (10 microg) at birth. Antibodies to each antigenic component were measured from blood samples collected immediately after birth, pre- and postvaccination blood samples. RESULTS: The reactogenicity profiles were similar in the two groups. No serious adverse events were reported. One month after completion of the four-dose vaccination schedule, all subjects except one in Group 1 (10 microg) had protective titers of anti-HBs (10 mIU/ml). At this time the geometric mean titer in Group 1 (10 microg) was higher than that observed in Group 2 (5 microg), 696 vs. 488 mIU/ml (P = 0.19). One month after three doses all subjects in both groups had protective antidiphtheria titers and antitetanus titers. The vaccine response rate to the Bordetella pertussis component of the vaccine was 88.0% in Group 1 and 96.2% in Group 2 (P = 0.86). CONCLUSION: Both combined tetravalent vaccines are safe and immunogenic when administered to infants born to a hepatitis B surface antigen-negative mother, with a 10-microg dose of priming hepatitis B vaccine at birth. This combined tetravalent DTPwHB vaccine may play an important role to promote integration of HB vaccine into the Expanded Program of Immunization in hepatitis B-endemic areas.