The use of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine mixed with diphtheria-tetanus-pertussis vaccine in Gambian infants

In preparation for an efficacy trial of PRP-T Haemophilus influenzae type b conjugate vaccine, 251 Gambian infants were randomized to receive three doses of PRP-T and diphtheria-tetanus-pertussis (DTP) vaccines at 2, 3 and 4 months of age, either by separate injections, or combined in the same syringe. One month after the third dose, there was no difference between anti-PRP levels in those infants who received the vaccines separately (GMT 5.83 micrograms ml-1), and those who received the vaccines combined (GMT 5.57 micrograms ml-1). The proportions achieving levels of 1.0 microgram ml-1 were 89% and 92% in the "separate" and "combined" vaccine groups, respectively. There were no significant differences between groups in levels of antibody to diphtheria or tetanus. Geometric mean titres of antibody directed against pertussis antigens in the "separate" and "combined" groups were as follows: pertussis toxin 14.2 and 13.1 ELISA units (EU) ml-1; filamentous haemagglutinin 12.2 and 9.7 EU ml-1; pertactin 17.2 and 9.0 EU ml-1 (P < 0.05), fimbrial 2/3 antigens 449 and 364 EU ml-1. The combination of PRP-T and DTP in the syringe prior to administration is safe and immunogenic. The lower levels of anti-pertussis antibody are of unknown clinical significance.     

Two primary doses of diphtheria-tetanus-acellular pertussis vaccine induce immunological responses to Bordetella pertussis as strong as those induced by three primary doses

Pertussis vaccinations are administered worldwide under various conditions and schedules with diphtheria-tetanus-pertussis (DTP). In Japan, a general vaccination with three primary doses of diphtheria-tetanus-acellular pertussis (DTaP) at 4-week intervals and one booster dose 12 months after the primary series have been used since 1981. Decreasing the number of doses of the vaccination would lessen the physical and economic costs. To compare the immunological response to two versus three primary doses, we assessed antibody and cellular immune responses in health children. The anti-filamentous hemagglutinin (anti-FHA) and anti-pertussis toxin (anti-PT) antibody responses to two primary doses of DTaP before a booster were significantly lower than the responses to three primary doses. Although these antibody levels were low in children who received two primary doses, the FHA-induced DNA synthesis was equal to that of the children who received three doses. The anti-FHA and anti-PT antibody levels 4 weeks after the booster following two doses were similar to the levels following three doses, and high antibody titers were maintained over a long period. In areas where contact with bacteria is expected, two primary doses of DTaP may be adequate to induce the necessary level of immunological responses.     

Simple, speedy, sensitive, and specific serodiagnosis of pertussis by using a particle agglutination test

We developed a particle agglutination test (KPA) with poly(gamma-methyl L-glutamate) as the solid particle for measurement of pertussis toxin (PT) antibody. In this study, KPA was assessed as a means of serodiagnosing pertussis, and the results were compared with those of indirect enzyme-linked immunosorbent assay (indirect ELISA) and the microagglutination test. First, four serum samples were collected from each of 21 healthy children: before and 4 weeks after receiving three primary doses of acellular pertussis vaccines and before and 4 weeks after receiving a booster dose. In all 21 vaccinees, a significant rise in PT antibody titers was observed by KPA after each vaccination, and among all 84 serum samples collected, an excellent correlation was demonstrated between the values obtained by indirect ELISA and those obtained by KPA (r = 0.92). Second, paired serum samples were collected at intervals of approximately 2 weeks from 51 patients with culture-confirmed pertussis. A significant increase in titer (fourfold or more) was observed in 39 (76%) patients by KPA, 34 (67%) patients by indirect ELISA, and 23 (45%) patients by the microagglutination test. In acute- and convalescent-phase sera collected from 20 nonpertussis patients, there were no changes in titers by KPA. The KPA procedure was as simple as that of the microagglutination test, and the reaction time was only 2 h (or overnight). In this study, KPA was demonstrated to be a simple, speedy, sensitive, and specific serodiagnostic method for pertussis.     

Inadvertent administration of DTP and DT after age six as recorded in the Vaccine Adverse Event Reporting System

OBJECTIVE: Diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTP) and pediatric diphtheria and tetanus toxoids (DT) are not recommended for individuals > or = 7 years of age due to increased adverse reactions and the low pertussis case-fatality rate. Our objective was to determine if reactions to DTP and DT in individuals > or = 7 years of age were due to administration of pediatric DTP or DT instead of adult tetanus and diphtheria toxoids (Td), after adjusting for database inaccuracies. METHODS: We analyzed data from the Vaccine Adverse Event Reporting System (VAERS) reported from July 1, 1990 through March 31, 1992. Vaccine manufacturers were contacted to verify whether lot numbers indicated DTP or DT. RESULTS: According to VAERS's data, among individuals 7 years of age or older, 26 received DTP and 77 received DT. When lot numbers were compared with manufacturers' records, 8 of the 77 DT doses were confirmed; 11 had incorrect or missing lot numbers; one was a duplicate; 56 were Td; and one was neither DT nor Td. Alleged adverse reactions included fever, headache, and convulsions. CONCLUSION: Individuals > or = 7 years of age are inadvertently receiving DTP or DT and may be unnecessarily experiencing adverse reactions. The 1992 VAERS database offers opportunities to investigate hypotheses but should be interpreted with caution due to inaccuracies in reporting and duplicate entries.     

Unrecognized pertussis infection in adolescents

Little information is available regarding the level of immunity to Bordetella pertussis among adolescents. We measured serum antibodies in 156 healthy adolescents to the following pertussis antigens: pertussis toxin, filamentous hemagglutinin, and 69-kd outer membrane protein. In an attempt to identify intercurrent pertussis infections, we also obtained a total of 43 repeated samples during the following 5 years. Using a 50% or greater rise in IgG enzyme-linked immunosorbent assay titers to define seroconversion, we found an annual incidence of 6.1%; by alternative definitions of seropositivity, the predicted annual incidence of infection ranged from 1.2% to 8.2%. These data suggest that infection with B pertussis is common in the adolescent population.     

Pertussis in Missouri: evaluation of nasopharyngeal culture, direct fluorescent antibody testing, and clinical case definitions in the diagnosis of pertussis

No diagnostic test for pertussis in routine use in the United States has both high sensitivity and high specificity. During a statewide increase in the incidence of pertussis in Missouri, we studied the clinical features of 153 patients with suspected pertussis in the Greater St. Louis area from whom a specimen for pertussis culture had been taken between 15 May and 19 September 1989. In this cross-sectional study, nasopharyngeal cultures were more likely to be positive for persons whose specimens were collected < 21 days after cough onset (adjusted rate ratio [RRa] and 95% confidence interval = 3.4; 1.5-8.0) and who were not receiving erythromycin/sulfamethoxazole prior to the culture [RRa = 5.8; 0.8-40.6], who had received fewer than three prior doses of pertussis vaccine [RRa = 1.8; 0.8-4.2], and whose specimen was in transit to the laboratory for < 4 days [RRa = 2.0; 0.8-5.5]. Among children < 5 years of age, spasmodic cough plus a lymphocytosis of > 10,000/mm3 was the acute symptom complex associated with the highest predictive value for a positive culture result (67%). Cough for > or = 14 days plus whoop was sensitive (81%) and specific (58%) for identifying children with culture-confirmed pertussis. Direct fluorescent antibody staining performed well as a screening test for pertussis but requires substantial commitment of personnel and resources. In the absence of a positive culture result, clinical case definitions should be used for decision making (e.g., initiation of antimicrobial therapy and routine case reporting).     

Valproic acid in prophylactic treatment of migraine

AIM: To determine whether an oral tetravalent rotavirus vaccine (RV-TV) can be safely coadministered with a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP/Hib) and oral poliovirus vaccine (OPV) to healthy infants without interfering with the immune responses to any of the component antigens. METHODS: Two hundred sixty-seven infants ages 2 to 3 months were randomly assigned in a double blind fashion to receive three doses of either placebo or RV-TV, each containing 4 x 10(5) plaque-forming units, concurrently with DTP/ Hib (Tetramune) and OPV at approximately 2, 4 and 6 months of age. Infants were followed for 5 days after each dose for the occurrence of adverse events and subsequently until 3 to 6 weeks after the third dose of RV-TV or placebo. Immune responses were assessed by measuring the postvaccination serum antibody titers to each component of DTP/ Hib and OPV at 3 to 6 weeks after the third dose. RESULTS: The percentage of infants who attained protective antibody titers and the distribution of antibody titers against diphtheria toxoid, tetanus toxoid and H. influenzae type b were not statistically different between RV-TV and placebo recipients. The distribution of antibody titers against different antigens of Bordetella pertussis (agglutinins, pertussis toxoid, filamentous hemagglutinin, fimbriae antigens and the 69-kDa outer membrane protein) was compared and no significant differences were found. The percentage of infants with detectable neutralizing antibodies against the three serotypes of poliovirus and the distribution of antibody titers was not statistically different between RV-TV and placebo recipients. There were no clinically meaningful differences in postvaccination reactions between RV-TV and placebo recipients. CONCLUSIONS: Three doses of RV-TV can be safely coadministered with three doses of DTP/ Hib and OPV without diminishing an infant's serum antibody responses to each component of these vaccines. Therefore RV-TV can be given at the standard childhood visits at 2, 4 and 6 months of age.     

Incidence and hospitalization patterns of insulin-dependent diabetes mellitus

Data from a statewide insulin-dependent diabetes mellitus (IDDM) registry in Rhode Island show that IDDM affects young adults (20-29 yr) as frequently as adolescents and teenagers (10-19 yr). Overall incidence less than 30 yr was 14/100,000 population. Peak incidence occurred at 10-14 yr (19/100,000 population). Poor diabetic control and infection accounted for 46-62% of hospitalizations among 275 known diabetic persons. Despite a 10-yr mean duration of diabetes, only 31% of hospitalized diabetic persons less than 30 yr of age reported ever having received outpatient diabetes education of two or more hours. Readmissions 1 yr after initial registration were more frequent for known (43%) than new-onset (18%) IDDM cases. Increased risk of readmission for both groups was associated with a poverty socioeconomic status. Total direct hospitalization costs for IDDM in persons under 30 yr of age in Rhode Island was $530,000 per year of $2,245 per patient.     

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.     

Challenges of traction in critical care: a case study

PROBLEM/CONDITIONS: Despite widespread availability of a safe and effective vaccine against tetanus, 124 cases of the disease were reported during 1995-1997. Only 13% of patients reported having received a primary series of tetanus toxoid (TT) before disease onset. Of patients with known illness outcome, the case-fatality ratio was 11%. REPORTING PERIOD COVERED: 1995-1997. DESCRIPTION OF SYSTEM: Physician-diagnosed cases of tetanus are reported by state and local health departments to CDC's National Notifiable Diseases Surveillance System. In addition, since 1965, supplemental clinical and epidemiologic information for cases has been provided to CDC's National Immunization Program. RESULTS: From 1995 through 1997, a total of 124 cases of tetanus were reported from 33 states and the District of Columbia, accounting for an average annual incidence of 0.15 cases per 1,000,000 population. Sixty percent of patients were aged 20-59 years; 35% were aged > or =60 years; and 5% were aged <20 years, including one case of neonatal tetanus. For adults aged > or =60 years, the increased risk for tetanus was nearly sevenfold that for persons aged 5-19 years and twofold that for persons aged 20-59 years. The case-fatality ratio varied from 2.3% for persons aged 20-39 years to 16% for persons aged 40-59 years and to 18% for persons aged > or =60 years. Only 13% of patients reported having received a primary series of TT before disease onset. Previous vaccination status was directly related to severity of disease, with the case-fatality ratio ranging from 6% for patients who had received one to two doses to 15% for patients who were unvaccinated. No deaths occurred among the 16 patients who previously had received three or more doses. Tetanus occurred following an acute injury in 77% of patients, but only 41% sought medical care for their injury. All patients who sought care were eligible for TT as part of wound prophylaxis, but only 39% received it. Tetanus in injecting-drug users (IDUs) with no known acute injury comprised 11% of all cases, compared with 3.6% during 1991-1994. None of the IDU-associated tetanus cases occurred among persons who were known to have been vaccinated. Sixty-nine percent of IDU-associated tetanus cases were reported from California, and 77% of these cases occurred in heroin users. INTERPRETATION: Tetanus remains a severe disease that primarily affects unvaccinated or inadequately vaccinated persons. Adults aged > or =60 years continue to be at highest risk for tetanus and for severe disease. However, the overall incidence of tetanus has decreased slightly since the late 1980s and early 1990s, from 0.20 to 0.15, a result primarily of a decreased incidence among persons aged > or =60 and <20 years. ACTIONS TAKEN: Tetanus is preventable through both routine vaccination and appropriate wound management. In addition to decennial booster doses of diphtheria and tetanus toxoids during adult life, the Advisory Committee on Immunization Practices (ACIP) recommends vaccination visits for adolescents at age 11-12 years and for adults at age 50 years to enable health-care providers to review vaccination histories and administer any needed vaccine. Every contact with the health-care system, particularly among older adults and IDUs, should be used to review and update vaccination status as needed.     

Relationship between structure and neutralizing activity of rabbit tetanus antibodies elicited by acellular and whole-cell pertussis DTP vaccines

Symmetric and asymmetric IgGs having different neutralizing capacity are synthesized in variable proportions by the same clones during the course of immune response. The neutralizing activity of tetanus antibodies was studied in rabbits vaccinated with acellular (DTPa) or whole-cell pertussis (DTPw) vaccines. Symmetric and asymmetric F(ab)'2 fragments from the IgG fraction of the peak serum pools from each group of rabbits were purified by concanavalin A chromatography and measured by ELISA. After the third vaccine dose the asymmetric antibody percentage for DTPw (40%) was twice that for DTPa (20%). The neutralizing activity of asymmetric antibodies was roughly sixfold lower than symmetric ones. When antibody values titrated by ELISA approach minimal protective level, the proportion of symmetric antibodies with high toxin neutralizing activity acquires crucial importance.     

Epidemiological features of cholera outbreak in Delhi in 1988

During 1988 a large scale outbreak of cholera occurred in Delhi giving rise to a total of 1708 bacteriologically proved El Tor cholera cases, the highest number recorded in a single year in Delhi, following its first detection in 1965. Civil lines and Shahdara zones were the worst affected areas recording 85.7 and 55.7 cases per 100,000 population respectively. The highest incidence rate was observed in the age group of 1-4 years (77 per 100,000). Males and females were equally affected. The data of moving average show the endemicity of cholera in Delhi with an increasing trend. The risk factors identified are lower socioeconomic status, poor personal hygiene, drinking water and food storage practices.     

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

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

Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age

This double-blind, randomised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine (DTPa-HBV) co-administered with three lots of Haemophilus influenzae type b conjugate (Hib) vaccine in one injection, as a primary vaccination course in healthy infants at 2, 4 and 6 months of age. 269 infants (8-11 weeks of age) were randomly allocated to three groups to receive DTPa-HBV/Hib vaccines, concomitantly with oral polio vaccine. Blood samples for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects. Local and general symptoms were recorded by parents on diary cards. All vaccinees had post-vaccination protective anti-D and anti-T (> or = 0.1 IU ml-1) antibodies, and 98% had protective anti-HBs antibody titres (> or = 10 mIU ml-1). There were no statistically significant differences between groups in post-vaccination anti-D, anti-T, anti-HBs antibody geometric mean titres (GMT), these being 3.49 IU ml-1, 5.92 IU ml-1 and 1109 mIU ml-1, respectively. All subjects responded to three pertussis components, i.e. pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Although statistically significant differences in GMTs of anti-PT, anti-FHA and anti-PRN were found between groups, these were not believed to be of any clinical relevance as the minimum GMTs were 60, 193 and 230 EL.U ml-1 for anti-PT, anti-FHA and anti-PRN, respectively. There were no statistically significant differences in anti-PRP antibody GMT (4.05 micrograms ml-1) between groups, 100% and 85% of subjects having titres > or = 0.15 and 1.0 microgram ml-1, respectively. No symptoms were reported for one third of the subjects. Fever (> 38 degrees C) was reported after 16% of doses, with < 1% having > 39.5 degrees C. Almost all local and general symptoms were mild or moderate, and lasted less than 48 h. No subject dropped out due to a severe adverse reaction. The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe, well-tolerated and immunogenic for all vaccine components.     

Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.     

Childhood poisoning: a population study in Trieste, Italy, 1975-1994

We describe the epidemiology of 1918 cases of childhood poisoning referred to the emergency room in Trieste, Italy, from 1975 to 1994. The incidence rate of emergency room referral and subsequent hospitalization was calculated on the basis of the distribution of children resident in Trieste by calendar year. The occurrence of childhood poisoning was described according to time trends, age and gender of the child, route of exposure, symptoms at presentation to the emergency room, role of the child or others, intention, and substance involved in the poisoning. The association between presence of symptoms and characteristics of referral, host factors and substances involved was evaluated by estimating the odds ratio in multivariate models. Possible determinants of the clinical decision to treat certain cases were evaluated using logistic regression. Despite an increasing incidence of referral (from 155 per 100,000 persons per year in 1975-79 to 352 per 100,000 in 1990-94), hospital admission rates showed a two-fold decrease. Younger children (age 0-4 years) were more likely to be asymptomatic and required treatment and hospitalization less often than older children (age > or = 10 years). Trends show a decrease in pharmaceutical poisonings due probably to the introduction of child-resistant containers and an increase in domestic poisons. We also observed a steady increase in carbon monoxide inhalation and alcohol poisonings, mostly among teenagers.     

Human (Homo sapiens) facial attractiveness and sexual selection: the role of symmetry and averageness

The current potency test for pertussis vaccines, the mouse protection test (MPT), has many disadvantages. However, no alternative is yet available. The purpose of this study is to develop a serological alternative for the MPT based on in vitro assessment of the humoral immune response against pertussis in mice. After immunization with pertussis whole cell vaccine, the MPT shows a normal primary and secondary antibody response. Moreover, the i.c. challenge has a distinct booster effect on the pertussis IgG response. The relationship between the concentration of IgG antibodies against the surface-antigens of pertussis bacteria and the survival of mice after the i.c. challenge was demonstrated in a modified MPT (R = 0.91). To this end a protecting antibody level of > or = 45 EU/ml was selected as a level at which concentration most of the mice survived. Survival of mice in the MPT could be predicted, based on the antibody concentration at the day of challenge. Potencies estimated with the predicted and actual survival corresponded well (P = 0.990). This confirmed the essential role of vaccine induced pertussis antibodies in the protection against a lethal i.c. challenge and offered a possibility to develop a pertussis potency test based on serology. We developed a model in which mice (20-24 g) are immunized (i.p.) with graded doses of vaccine and bled after four weeks. Sera are titrated in Bordetella pertussis whole cell ELISA and potency based on vaccine dose dependent antibody response is estimated by means of a parallel line analysis. The potency of vaccines tested in the Pertussis Serological Potency Test (PSPT) and MPT are significantly similar, a P-value of 0.92 was found by means of the chi 2 test. Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller 95% confidence intervals. Moreover, by using the PSPT the animal distress can be reduced to an acceptable level and the PSPT also results in a reduction of more than 25% in use of mice.     

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.     

Comparative reactogenicity and immunogenicity of booster doses of diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine and diphtheria-tetanus-inactivated poliovirus vaccine in preadolescents

BACKGROUND: The changing epidemiology of pertussis in France has emphasized the need for booster vaccinations in adolescents. Although not previously recommended because of the high reactogenicity of whole cell pertussis in children older than 2 years old, the development of less reactogenic acellular pertussis vaccines means that this recommendation may be reconsidered. OBJECTIVES: Assessment of the reactogenicity and immunogenicity of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus (DTPa-IPV=Group 1) vaccine administered as the fifth dose in preadolescents in comparison with a commercial diphtheria-tetanus-inactivated poliovirus (DT-IPV) (Group 2) vaccine currently recommended for this age group. MATERIALS AND METHODS: An open, randomized study involving 115 healthy subjects ages 10 to 13 years previously vaccinated with 4 doses of diphtheria-tetanus-whole cell pertussis-IPV vaccines. Reactogenicity was assessed for 4 days postvaccination using diary cards. Immunogenicity based on antibody assays in sera taken before and 1 month postvaccination was evaluated for all vaccine antigen components. RESULTS: Both vaccines showed good tolerability, local and general reactogenicity being similar. For local reactions Group 1=88.1% and Group 2=86.8%, and for general reactions Group 1=40.7% and Group 2=47.2%. Headache was the most frequent general symptom with 27.1% for DTPa-IPV and 39.6% for DT-IPV. The incidence of fever was 5.1% with DTPa-IPV and 9.4% for DT-IPV. Good immune responses were obtained against all vaccine components. CONCLUSIONS: The inclusion of acellular pertussis did not significantly increase the reactogenicity of DTPa-IPV in comparison with the currently recommended DT-IPV vaccine when given as a fifth dose in preadolescents. To prevent recent resurgence of pertussis in France, this vaccine should be preferred as the booster dose of DTPa-IPV at 11 to 13 years of age as recently approved by the National Council of Hygiene of France.     

Age-dependent Neisseria meningitidis serogroup C class-specific antibody concentrations and bactericidal titers in sera from young children from Montana immunized with a licensed polysaccharide vaccine

Neisseria meningitidis serogroup C bactericidal titers and class-specific enzyme-linked immunosorbent assay (ELISA) antibody concentrations were measured in sera from 173 children (1 to 5 years old) before and 6 weeks and 7 months following vaccination with a quadrivalent (A/C/Y/W-135) polysaccharide vaccine. The immune responses of the children were compared with those of 40 adults 6 weeks postvaccination. Both bactericidal titers and ELISA antibody concentrations were significantly higher in the adults than in the children (P < 0.05). In addition, the ratio of immunoglobulin G (IgG) to IgM was higher in the children than in the adults. With an ELISA total antibody concentration of >/=2 microg/ml used as a measure of seroconversion, >/=84% of the individuals from each age group responded to the serogroup C polysaccharide. However, with a >/=4-fold-increase in bactericidal titer used, only 18% of 1-year-olds, 32% of 2-year-olds, and 50 to 60% of 3-, 4-, and 5-year-olds seroconverted. The ELISA results suggest that >50% of all children retained >/=2 microg of total antibody per ml at 7 months postimmunization. However, the bactericidal titers suggest that <10% of children <4 years old retained a >/=4-fold increase at 7 months following vaccination. Of particular note, 59 of 79 sera (75%) from the 1- and 2-year-olds had high ELISA antibody concentrations (2 to 20 microg/ml) with no associated bactericidal titer (<1:8). Discordant results between bactericidal titers and ELISA antibody concentrations were not explained by the presence of IgA blocking antibody or relative levels of IgG and IgM. The bactericidal results show age-dependent differences in the production and retention of antibody in young children immunized with serogroup C polysaccharide; these differences are not evident with the ELISA data.