Addressing the vaccine confidence gap.

Vaccines--often lauded as one of the greatest public health interventions--are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk-benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines.

Immunogenicity and safety of four different doses of Haemophilus influenzae type b-tetanus toxoid conjugated vaccine, combined with diphtheria-tetanus-pertussis vaccine (DTP-Hib), in Indonesian infants.

Widespread use of Haemophilus influenzae type b (Hib) conjugated vaccine in industrialized countries has resulted in a dramatic decline in the incidence of invasive Hib diseases, but the vaccine's cost has prevented its inclusion in basic immunization programs in developing countries. To overcome this problem, combination with diphtheria-tetanus-pertussis (DTP) vaccine or reduction in the dose of Hib vaccine has been proposed. To evaluate the immunogenicity and adverse reactions from lower doses of Hib-polyribosylphosphate (PRP) conjugated with tetanus toxoid (PRP-T), a double-blind study was conducted in Jakarta, Indonesia, and its suburbs. A total of 1048 infants 6 weeks to 6 months of age received three doses of DTP vaccine combined with the usual 10 microg dose or with a reduced dose of 5, 2.5 or 1.25 microg of PRP-T at two-monthly intervals. Antibodies were measured prior to the first dose and 4-6 weeks following the third dose. Adverse reactions were similar among all four groups. The only significant difference was a higher rate of irritability (p<0.02) and of temperature elevation >38 degrees C (p<0.009) after doses 1 and 2 in the lowest dose group (1.25 microg PRP-T) compared to the other groups. All participants tested had a 4-fold increase in antibodies against all DTP antigens. In addition, after a fourth booster dose of Hib, 99.6% of infants produced >or=0.15 microg/ml of antibody to Hib-PRP, and 96.4% showed levels >or=1.0 microg/ml after primary immunization, level that correlate with short- and long-term immunity, respectively. Antibody titers to the PRP antigen showed no significant differences among dosage groups with the exception of the 5.0 microg group, which had a significantly higher GMC than the 1.25 microg group (p<0.012). This study demonstrates that primary vaccination with half, one-fourth, or one-eighth of the usual dose of PRP-T, combined with DTP vaccine, produces protective immune responses, and has side effects that are comparable to DTP vaccination alone. In these lower dosages, PRP-T conjugate vaccine can lower vaccine costs to a level that is affordable for infant immunization programs in developing countries.

[Episodic disseminated inflammation of the central nervous system. Case mix review over a 13 year period]. / Inflamacion diseminada episodica del sistema nervioso central en niños. Revision casuistica de un periodo de 13 años.

INTRODUCTION: Episodic disseminated inflammation of the central nervous system (CNS) presents in processes that are difficult to differentiate, such as acute disseminated encephalomyelitis (ADE) and its multiphasic variants, and multiple sclerosis (MS). Magnetic resonance imaging allows these problems to be identified more frequently than in the past. PATIENTS AND METHODS: We carried out a retrospective study of the cases of episodic disseminated inflammation of the CNS, according to clinical features and compatible neuroimaging, at the Neuropaediatric Unit of the Hospital Infantil Miguel Servet, between May 1990 and August 2003. RESULTS: Of the 6777 children evaluated over this period, 10 met the eligibility criteria, with a minimum age at onset of 2 years and 2 months. In four cases there was a history of an infectious process or vaccination. Clinical involvement was multisymptomatic, the most frequent being ataxia, dysmetry, tremor, drowsiness, paresis and cranial nerve involvement. Six of them had cerebrospinal fluid disorders and only two presented disorders in the fundus oculi. Five of them were given corticoid treatment. Progress was favourable, except in two cases: one due to the persistence of a corticoid dependent optical neuropathy and the other because of dyskinesia in the right hand. DISCUSSION: Diagnosis of ADE is established by signs of multifocal clinical involvement and neuroimaging, and depends on a compatible progression. Prognosis is generally good and corticoids seem to be effective, at least in shortening the time the clinical features last. It is not possible to completely differentiate it from MS, especially in recurring forms. Clinical and magnetic resonance controls must be carried out.

Vaccinations and risk of central nervous system demyelinating diseases in adults.

BACKGROUND: Several case reports of the onset or exacerbation of multiple sclerosis or other demyelinating conditions shortly after vaccination have suggested that vaccines may increase the risk of demyelinating diseases. OBJECTIVE: To evaluate the association between vaccination and onset of multiple sclerosis or optic neuritis. DESIGN: Case-control study involving cases of multiple sclerosis or optic neuritis among adults 18 to 49 years of age. Data on vaccinations and other risk factors were obtained from computerized and paper medical records and from telephone interviews. SETTING: Three health maintenance organizations. PARTICIPANTS: Four hundred forty case subjects and 950 control subjects matched on health maintenance organization, sex, and date of birth. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Onset of first symptoms of demyelinating disease at any time after vaccination and during specified intervals after vaccination (<1 year, 1-5 years, and >5 years). RESULTS: Cases and controls had similar vaccination histories. The odds ratios (95% confidence intervals), adjusted for potential confounding variables, of the associations between ever having been vaccinated and risk of demyelinating disease (multiple sclerosis and optic neuritis combined) were 0.9 (0.6-1.5) for hepatitis B vaccine; 0.6 (0.4-0.8) for tetanus vaccination; 0.8 (0.6-1.2) for influenza vaccine; 0.8 (0.5-1.5) for measles, mumps, rubella vaccine; 0.9 (0.5-1.4) for measles vaccine; and 0.7 (0.4-1.0) for rubella vaccine. The results were similar when multiple sclerosis and optic neuritis were analyzed separately. There was no increased risk according to timing of vaccination. CONCLUSION: Vaccination against hepatitis B, influenza, tetanus, measles, or rubella is not associated with an increased risk of multiple sclerosis or optic neuritis.

Assessment of vaccination coverage among adults 30-49 years of age following a mass diphtheria vaccination campaign: Ukraine, April 1995.

Ukraine has been experiencing epidemic diphtheria since 1991. In efforts to control this epidemic, a mass vaccination campaign was held in April 1995. Persons not vaccinated in the previous 3 years were considered eligible for vaccination with tetanus-diphtheria toxoids (Td). Two cluster sample surveys were conducted to determine vaccination coverage achieved. In the urban and rural survey areas, respectively, 628 and 618 persons 30-49 years of age were interviewed. Fifty-nine percent of urban and 58% of rural participants were eligible for vaccination. During the vaccination campaign, 58% (95% confidence interval [95% CI], 47.1-69.2) of eligible persons received Td in the urban area, compared with 92% (95% CI, 89.2-95.3) in the rural area. Apparent barriers to vaccination included misconceptions about the safety, efficacy, and need for booster doses of Td. Future vaccination campaigns should include targeted information and education messages. Mass vaccination campaigns can be successful in vaccinating large numbers of adults; however, in urban areas, additional efforts may be required to achieve levels of coverage adequate to confer herd immunity and interrupt the diphtheria epidemic.

[Epidemiologic data for tetanus prophylaxis. Assessment of the need for vaccination]. / Epidemiologische Daten zum Tetanusschutz. Zwischen Impfnotwendigkeit und Uberimpfung.

OBJECTIVE: In spite of the low morbidity secondary to tetanus, the high fatality rate (about 50%) requires effective and extensive protection of the population by vaccination. Since documentation is often lacking, booster tetanus vaccination is frequently applied in cases of minor injury. This leads to vaccination associated complications such as hyperergic reactions. The more intense the vaccination-associated side effects are, the less revaccination is possible. We investigated the tetanus immune status of a selected Austrian population. MATERIALS AND METHODS: Tetanus antitoxin antibodies were measured with ELISA (Immunozym Tetanus, Immuno AG) in serum samples from 218 subjects who were hospitalised in a dermatology unit. In addition, patient history and data concerning vaccination were collected. RESULTS: Based on the assumption that an antitoxin level of 0.1 IU/ml provides sufficient protection, 63% of the subjects were found to be adequately protected. 56% showed high antibody concentrations above 0.5 IU/ml. However, the data also revealed no protection by vaccination in 37% of the subjects. Data obtained by case history or vaccination certificates could not serve as a discrimination factor for applying revaccination or not. CONCLUSION: We strongly recommend better documentation of tetanus vaccination. In some cases, a search for tetanus antibodies before applying booster tetanus vaccination might be necessary.

[Adverse effects of the vaccines Tétracoq, IPAD/DTCP and DTCP. A French study of regional drug monitoring centers]. / Effets indésirables des vaccins Tétracoq, IPAD/DTCP et DTCP. Enquête française des centres régionaux de pharmacovigilance.

UNLABELLED: On request of the French Drug Agency, the Regional Pharmacovigilance Center (RPVC) of Tours has been in charge of the analysis of adverse events (AEs) associated with tetravalent vaccines IPAD/DTCP, DTCP and Tétracoq, and reported to the RPVC or to the pharmaceutical companies that produce them. METHODS: All AEs spontaneously reported during use of one of these vaccines to one of the French Pharmacovigilance Centers or to the responsible firms between January 1, 1986 and December 31, 1990 were take into account. An AE was noted as "serious" in accordance with the European criteria. The incidence of adverse effects was estimated by evaluating the ratio of adverse effects and the number of sales of the vaccine for the same period. RESULTS: From 1986 to 1990, 631 AEs (with 19 duplicate cases) associated with tetravalent vaccines in 606 children (75% < 1 year) were reported. The most frequent AEs were: local AEs at the site of injection (43%), neurologic disorders (12%), hyperthermia (10%) and allergic reactions (10%). Serious AEs represented 25% of all AEs and were similar to those usually described with these vaccines, particularly persistent crying (23), febrile seizures (12), apyretic seizures (14), uneasiness (28) and, rarely, shock (3). CONCLUSION: Incidences of AEs reported with pentavalent vaccines are very low, probably underestimated because of the under-notification by prescribers of AEs of vaccines licensed some time ago. It will be interesting to compare these data with AEs of penta- and hexavalent vaccines since they have replaced tetravalent vaccines.

Estimated effects of a delay in the recommended vaccination schedule for diphtheria and tetanus toxoids and pertussis vaccine.

The occurrence of adverse events temporally associated with diphtheria and tetanus toxoids and pertussis vaccine (DTP) has led to consideration of a delay in the schedule of initial vaccination. We developed an inferential model estimating the changes in pertussis- and DTP-associated health outcomes that might occur if initial DTP administration were delayed from 2, 4, and 6 months to 8, 10, and 12 months of age. An additional 636 cases of pertussis--115 of which would be associated with complications, including two encephalopathies--were projected to occur under the proposed as compared to the current schedule. Adverse medical events attributable to the vaccine were assumed to remain unchanged following the change in schedule. We projected 353 fewer chance associations with sudden infant death syndrome but 1311 more chance associations between DTP and seizures. These estimates suggest that the current schedule of vaccinating infants at 2, 4, and 6 months of age is casually associated with less morbidity and should be continued.

Quality assessment of tetanus prophylaxis in the wounded patient.

New guidelines on tetanus prophylaxis in wound management have been prepared by the American College of Surgeons and are available in a poster format or in bulletins. The purpose of this study was to determine the impact of these educational brochures on tetanus prophylaxis in a hospital setting. The results of this study indicate that these informational brochures and posters had insignificant impact on the quality of prophylaxis against tetanus in our hospital. Innovative programs of information exchange and quality assurance are urgently needed to improve the delivery of health care.

Outbreaks of group A streptococcal abscesses following diphtheria-tetanus toxoid-pertussis vaccination.

Two outbreaks of group A streptococcal abscesses following receipt of diphtheria-tetanus toxoid-pertussis (DTP) vaccine from different manufacturers were reported to the Centers for Disease Control (CDC) in 1982. The clustering of the immunization times of cases, the isolation of the same serotype of Streptococcus from all cases in each outbreak, and the absence of reported abscesses associated with receipt of the same lots of vaccine in other regions of the country, suggest that each outbreak was probably caused by contamination of a single 15-dose vial of vaccine. The preservative thimerosal was present within acceptable limits in unopened vials from the same lot of DTP vaccine in each outbreak. Challenge studies indicate that a strain of Streptococcus from one of the patients can survive up to 15 days in DTP vaccine at 4 degrees C. Contamination of vials during manufacturing would have required survival of streptococci for a minimum of 8 months. Preservatives in multidose vaccine vials do not prevent short-term bacterial contamination. Options to prevent further clusters of streptococcal abscesses are discussed. The only feasible and cost-effective preventive measure now available is careful attention to sterile technique when administering vaccine from multidose vials.

DTP-associated reactions: an analysis by injection site, manufacturer, prior reactions, and dose.

Local and less serious systemic reactions are frequent following immunization with diphtheria-tetanus-pertussis (DTP) vaccine. The effects of injection site, manufacturer, previous reactions, and dosage reduction upon subsequent reactions to DTP immunization were investigated. Local reactions, notably pain and swelling, were less common when the immunization was given in the buttocks than in the thigh. No injection site was consistently associated with lower systemic reaction rates. There was no significant difference in the rate of more serious reactions by vaccine manufacturer. Differences in rates of less serious reactions by manufacturer were observed but seemed to be related to vaccine lot differences rather than the specific vaccines. In a subset of 772 children, in whom data regarding sequential reactions were available, it was noted that all three reactions investigated--local redness, temperature greater than or equal to 39 degrees C, and persistent crying longer than one-half hour--were two to three times more frequent on a subsequent immunization when present on a prior vaccination than if not present on a prior vaccination than if not present previously. One hundred children received a half dose of DTP vaccine because of a less serious reaction associated with prior immunization. In all instances, they had significantly less serious local reactions as well as notable differences in temperature, drowsiness, and persistent crying.

Administration and evaluation of rural health services. I. A tetanus control program in Haiti.

Tetanus has been a public health problem of major importance in rural Haiti. Energetic preventive measures by a rural Haitian hospital were successful in controlling the problem only after immunization services were made easily available to the entire population served by the hospital. This was accomplished by a program which carried the services to the market places and villages of the region. The program developed several new categories of auxiliary personnel who were recruited locally and trained on the job. These personnel were utilized in a program which incorporated preparatory publicity, timing, handling of large crowds in open surroundings, education, record keeping, follow-up and evulation as well as the technical matters concerning the giving of injections. The program sharply reduced the number of admissions to the hospital for the treatment of tetanus. Evaluated on the basis of hospitalizations avverted the program cost only 1/9 the value of the 50,000 hospital days of care for the tetanus cases it prevented.

PIP: A rural hospital in Haiti -- the Albert Schweitzer Hospital of Deschapelles -- initiated an energetic preventive program to deal with the public health problem of tetanus. The program was successful in controlling the problem only after immunization services were made easily available to the entire population served by the hospital. The program offered services in the market places and villages of the region. Several new categories of auxiliary personnel were recruited locally and trained on the job. The program incorporated preparatory publicity, timing, handling of large crowds in open surroundings, education, record keeping, follow-up and evaluation and the technical administration of the injections. The program was responsible for a marked reduction in the number of admissions to the hospital for the treatment of tetanus.