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Long-term immunity in cats vaccinated with an inactivated trivalent vaccine.

OBJECTIVE: To evaluate duration of immunity in cats vaccinated with an inactivated vaccine of feline panleukopenia virus (FPV), feline herpesvirus (FHV), and feline calicivirus (FCV). ANIMALS: 17 cats. PROCEDURE: Immunity of 9 vaccinated and 8 unvaccinated cats (of an original 15 vaccinated and 17 unvaccinated cats) was challenged 7.5 years after vaccination. Specific-pathogen-free (SPF) cats were vaccinated at 8 and 12 weeks old and housed in isolation facilities. Offspring of vaccinated cats served as unvaccinated contact control cats. Virus neutralization tests were used to determine antibody titers yearly. Clinical responses were recorded, and titers were determined weekly after viral challenge. RESULTS: Control cats remained free of antibodies against FPV, FHV, and FCV and did not have infection before viral challenge. Vaccinated cats had high FPV titers throughout the study and solid protection against virulent FPV 7.5 years after vaccination. Vaccinated cats were seropositive against FHV and FCV for 3 to 4 years after vaccination, with gradually declining titers. Vaccinated cats were protected partially against viral challenge with virulent FHV. Relative efficacy of the vaccine, on the basis of reduction of clinical signs of disease, was 52%. Results were similar after FCV challenge, with relative efficacy of 63%. Vaccination did not prevent local mild infection or shedding of FHV or FCV. CONCLUSIONS: Duration of immunity after vaccination with an inactivated, adjuvanted vaccine was > 7 years. Protection against FPV was better than for FHV and FCV. CLINICAL IMPLICATIONS: Persistence of antibody titers against all 3 viruses for > 3 years supports recommendations that cats may be revaccinated against FPV-FHV-FCV at 3-year intervals.

Animals↗

Mass vaccination with a two-dose oral cholera vaccine in a refugee camp.

In refugee settings, the use of cholera vaccines is controversial since a mass vaccination campaign might disrupt other priority interventions. We therefore conducted a study to assess the feasibility of such a campaign using a two-dose oral cholera vaccine in a refugee camp. The campaign, using killed whole-cell/recombinant B-subunit cholera vaccine, was carried out in October 1997 among 44,000 south Sudanese refugees in Uganda. Outcome variables included the number of doses administered, the drop-out rate between the two rounds, the proportion of vaccine wasted, the speed of administration, the cost of the campaign, and the vaccine coverage. Overall, 63,220 doses of vaccine were administered. At best, 200 vaccine doses were administered per vaccination site and per hour. The direct cost of the campaign amounted to US$ 14,655, not including the vaccine itself. Vaccine coverage, based on vaccination cards, was 83.0% and 75.9% for the first and second rounds, respectively. Mass vaccination of a large refugee population with an oral cholera vaccine therefore proved to be feasible. A pre-emptive vaccination strategy could be considered in stable refugee settings and in urban slums in high-risk areas. However, the potential cost of the vaccine and the absence of quickly accessible stockpiles are major drawbacks for its large-scale use.

Administration, Oral↗

Rapid onset of protection following vaccination of calves with multivalent vaccines containing modified-live or modified-live and killed BHV-1 is associated with virus-specific interferon gamma production.

The objective of this study was to determine the effect of vaccination with commercially-available multivalent vaccines containing either modified-live (MLV) bovine herpesvirus-1 (BHV-1) (Bovishield) or MLV plus killed (MLV + K) BHV-1 (Reliant Plus) on protection against challenge at 5 days after a single vaccination. An additional objective was to determine whether cell-mediated immunity as measured by virus-specific interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) was associated with any early protection induced by vaccination. Clinical signs, serum neutralizing (SN) titers, and nasal virus isolation (VI) titers were also measured. The 12-16-week-old dairy cross-calves seronegative for antibodies to BHV-1 were vaccinated with a multivalent vaccine containing MLV BHV-1 (n = 19), a multivalent vaccine containing MLV + K BHV-1 (n = 19), or a control multivalent vaccine not containing BHV-1 (n = 10) on day 0 and challenged intranasally on day 5. PBMC were isolated on days 0, 3, 5, 8, 10, 14 and 19. PBMC were incubated in vitro with spent media, live BHV-1, or heat-inactivated BHV-1 for 72 h. Supernatants were assayed for bovine IFN-gamma by ELISA. Bovine herpesvirus-1-specific IFN-gamma production was expressed as percent of the kit positive control, with value for spent media subtracted. Clinical signs were monitored daily. Serum VN titers were measured on days 0-5 and 19. Nasal VI titer was measured every other day from days 5 to 19. Interferon gamma production was higher on day 5, and was significantly increased post-challenge, in both vaccine groups compared to controls. There was no difference between vaccine groups on any day. There was no significant difference in SN titer among groups on any day. Virus isolation titer was significantly higher in controls on days 6 and 8 compared to both vaccine groups. Temperatures were significantly higher and nasal discharge was present more often post-challenge in controls compared to vaccine groups. Vaccination 5 days prior to challenge with commercially-available vaccine containing MLV or MLV + K BHV-1 was associated with increased BHV-1-specific IFN-gamma production, decreased viral shedding, lower temperatures and less nasal discharge post-challenge. Cell mediated immune responses as measured by IFN-gamma production are stimulated rapidly following BHV-1 vaccination of calves.

Animals↗

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

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

Antibodies, Bacterial↗

A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America.

OBJECTIVES: In 1998 the World Health Organization (WHO) recommended the inclusion of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization programs, whenever in accordance with national priorities. GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPw-HB/Hib) vaccine containing 5 microg of polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant injections. METHODS: We performed a randomized, double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine given as a single injection, compared with the reference regimen. RESULTS: Both vaccination regimens elicited excellent immune responses, with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination. The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components. Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups, and a marked increase of all antibody concentrations was observed after the booster dose. Both vaccine regimens were similar in terms of their overall reactogenicity profiles. CONCLUSIONS: Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis.

Child, Preschool↗

Varicella vaccines and measles, mumps, rubella, and varicella vaccine.

OBJECTIVES: To present an up-to-date review of studies investigating the efficacy, adverse events and vaccination regimens of the varicella vaccine and the new presentation combined with the vaccine for measles, mumps and rubella. SOURCES OF DATA: Bibliographic review of the MEDLINE and LILACS databases covering the period 1999 to 2006. SUMMARY OF THE FINDINGS: The varicella vaccine protects 70 to 90% of immunized children against any form of varicella zoster infection, but the efficacy against severe forms is higher (95 to 98%). This is a well-tolerated vaccine that causes few reactions. Since the vaccine was licensed, there have been three confirmed cases of transmission of the vaccine virus by domestic contacts to previously healthy people, who went on to develop mild disease. Despite evidence that the protection offered by this vaccine can wane over a number of years, it is not yet possible to state that a second dose is warranted, bearing in mind exposure to wild virus. After universal vaccination the chances of natural stimulation should drop and it is very probable that booster doses will become necessary. A measles, mumps, rubella, and varicella vaccine has recently been licensed that combines vaccines for measles, mumps, rubella and varicella in a single product with high rates of seroconversion. CONCLUSIONS: The Brazilian Society of Pediatrics recommends the varicella vaccine for children from 1 year on. We hope that the measles, mumps, rubella, and varicella vaccine will soon be available in Brazil, since combined vaccines facilitate wider vaccination coverage.

Brazil↗

Pneumococcal vaccination in pennsylvania nursing homes: factors associated with vaccination level.

OBJECTIVES: To determine the levels of knowledge and beliefs about pneumococcal disease and the pneumococcal polysaccharide vaccine (PPV), the level of PPV use, PPV-related practices, and factors associated with PPV use in Pennsylvania's nursing homes. DESIGN/SETTING: A 68-item, cross-sectional survey of Nursing Directors at a random sample of PA nursing homes (291) was conducted between April and June 1999. Survey results and facility characteristics were used to describe vaccination practices, estimate the vaccination level and determine through bivariate analysis, associations between vaccination level and facility characteristics and practices. RESULTS: Respondents are knowledgeable about PPV and recommendations for its use but less knowledgeable about financial reimbursement. Pneumonia is believed to be a serious threat to nursing home residents; PPV is thought to be important, effective, cost-effective, and safe for use in nursing homes. The estimated PPV rate is 49%, and vaccination practices are variable. Factors associated with higher vaccination level include: knowledge of financial reimbursement, strong belief in the importance of vaccinating residents and the effectiveness of the vaccine, practices related to policies, assessment, consent and orders, and organizational factors of size, ownership, average length of stay, and identification of a staff "vaccine advocate." CONCLUSION: Staff members are knowledgeable about the vaccine and believe it should be used in nursing homes. Efforts aimed at improving vaccination rates should concentrate on examples of effective vaccination programs and practices rather than basic information about the vaccine. Development of institutional policies, which guide vaccination practice and institutionalize the use of automated patient management systems that prompt staff to assess vaccination status and order vaccination, could have considerable impact in meeting the recommendation for vaccination of nursing home residents.

Journal Article↗

Reasons for delayed compliance with the childhood vaccination schedule and some failings of computerised vaccination registers.

OBJECTIVE: To identify reasons for delay in completing the primary vaccination schedule. METHOD: Brisbane, Queensland, 1995. Telephone interviews of a random sample of parents whose children according to a computerised database were fully vaccinated (100 parents) and parents whose children had commenced but not completed vaccination (200 parents). RESULTS: The main reason for delaying vaccinations was medical advice to do so because of false contra-indications. The most significant factor in predicting timely vaccination, was the belief that giving vaccinations at the correct time was "very important", odds ratio 2.07 (95% CI 1.32-3.26). Eighty-six per cent of the children of interviewed parents from the group recorded as not fully vaccinated were in fact fully vaccinated. CONCLUSIONS: The most important predictors of vaccination behaviour are the advice provided by medical practitioners and parental beliefs. Computerised vaccination records can seriously underestimate vaccination rates. IMPLICATIONS: Vaccination providers and the public need accurate knowledge about both the need for timely vaccination and the real contraindications to vaccination. For a vaccination register to record vaccination status with accuracy, service providers need to be highly co-operative in completing and returning vaccination records, and central data entry needs to be comprehensive and accurate.

Attitude to Health↗

A follow-up study of combined vaccination with plasma-derived and recombinant hepatitis B vaccines in infants.

This study was aimed to evaluate the efficacy and immunogenicity of combined hepatitis B vaccination with plasma-derived vaccine (PDV) and recombinant vaccine (RV). A total of 329 infants was recruited, including 224 high-risk infants born to hepatitis B e antigen-positive mothers and 105 low-risk infants born to hepatitis B e antigen-negative mothers. The high-risk infants received four doses of hepatitis B vaccine at 0, 1, 2 and 12 months of age with five different schedules. Group A1 and A2 infants were vaccinated with PDV as the first dose and RV (SB vaccine for group A1, MSD vaccine for group A2) as the remaining three doses. Group B1 and group B2 infants were vaccinated with PDV as the first two doses and RV (SB vaccine for group B1, MSD vaccine for group B2) as the remaining two doses. Group C infants received four doses of PDV. Low-risk infants were vaccinated with PDV at birth, and RV at 1 and 6 months of age (group D1, using SB vaccine; group D2, using MSD vaccine). At completion of vaccination schedules, 20 of 224 high-risk infants (9%) were positive for hepatitis B surface antigen. The overall protective efficacy was 90%. Hepatitis B surface antibody (anti-HBs)-positive rate ranged between 94 and 100% among the remaining infants. The protective efficacy and immunogenicity were similar among groups except that the mean level of anti-HBs in group C, D1 and D2 infants tended to be lower than that of the other four groups. To ensure an optimal immune response, four doses of vaccine are recommended in high-risk infants when two types of vaccine are to be used in combination.

Child, Preschool↗

A DNA vaccine coding for gB and gD of pseudorabies virus (suid herpes type 1) primes the immune system in the presence of maternal immunity more efficiently than conventional vaccines.

DNA vaccines are capable of priming the immune system of neonates in the presence of maternal antibodies. However, it is still not clear whether the extent of priming and protection against challenge infections induced by a DNA vaccine in maternally immune newborns is better than that induced by conventional vaccines. To study this, we used the pseudorabies virus (PRV) infection model in the natural host, the pig. We compared the efficacy of a DNA vaccine with the efficacy of a conventional modified live vaccine (MLV) and an inactivated vaccine (IV) in maternally immune newborn piglets. We measured the priming of the immune response and the degree of protection against challenge infection for all vaccine types. We vaccinated piglets with or without maternal immunity twice, at the age of 5 and 9 weeks, and we assessed protection by challenge infection with virulent PRV at the age of 15 weeks. Vaccination with DNA or conventional vaccines induced both humoral and cell-mediated immune responses in maternally immune animals. DNA vaccination seemed not to suffer from suppression by maternal immunity and resulted in similar or stronger immune responses in maternally immune piglets as compared in naïve piglets. In contrast, vaccination with conventional vaccines resulted in weaker immune responses in maternally immune piglets than in naïve piglets. Moreover, DNA vaccination provided better protection against challenge infection in maternally immune piglets than in naive piglets, whereas vaccination with conventional vaccines did not.

Animals↗

Oral vaccination of brushtail possums with BCG: Investigation into factors that may influence vaccine efficacy and determination of duration of protection.

AIMS: To determine factors that may influence the efficacy of an oral pelleted vaccine containing Mycobacterium bovis bacille Calmette-Guérin (BCG) to induce protection of brushtail possums against tuberculosis. To determine the duration of protective immunity following oral administration of BCG. METHODS: In Study 1, a group of possums (n=7) was immunised by feeding 10 pellets containing dead Pasteur BCG, followed 15 weeks later with a single pellet of live Pasteur BCG. At that time, four other groups of possums (n=7 per group) were given a single pellet of live Pasteur BCG orally, a single pellet of live Danish BCG orally, 10 pellets of live Pasteur BCG orally, or a subcutaneous injection of live Pasteur BCG. For the oral pelleted vaccines, BCG was formulated into a lipid matrix, and each pellet contained approximately 107 colony forming units (cfu) of BCG, while the vaccine injected subcutaneously contained 106 cfu of BCG. A sixth, non-vaccinated, group (n=7) served as a control. All possums were challenged by the aerosol route with a low dose of virulent M. bovis 7 weeks after vaccination, and killed 7-8 weeks after challenge. Protection against challenge with M. bovis was assessed from pathological and bacteriological findings. In Study 2, lipid-formulated live Danish BCG was administered orally to three groups of possums (10-11 per group), and these possums were challenged with virulent M. bovis 8, 29 or 54 weeks later. The possums were killed 7 weeks after challenge, to assess protection in comparison to a non-vaccinated group. RESULTS: The results from Study 1 showed that vaccine efficacy was not adversely affected by feeding dead BCG prior to live BCG. Feeding 10 vaccine pellets induced a level of protection similar to feeding a single pellet. Protection was similar when feeding possums a single pellet containing the Pasteur or Danish strains of BCG. All vaccinated groups had significantly reduced pathological changes or bacterial counts when compared to the non-vaccinated group. In Study 2, oral administration of Danish BCG induced protection against challenge with M. bovis, which persisted for at least 54 weeks after vaccination. Some protection was observed in possums challenged 54 weeks after vaccination, but this protection was significantly less than that observed in groups vaccinated 29 or 8 weeks prior to challenge. There was a strong relationship between the proportion of animals producing positive lymphocyte proliferation responses to M. bovis antigens and protection against challenge with M. bovis. CONCLUSIONS: Factors considered potentially capable of interfering with vaccination, including feeding dead BCG to possums prior to feeding live BCG, feeding multiple doses of BCG at one time, and changing strains of BCG, were shown not to interfere with the acquisition of protective immune responses in possums. Protection against tuberculosis was undiminished up to 29 weeks after vaccination with BCG administered orally. It is concluded that vaccination of possums by feeding pellets containing BCG is a robust and efficient approach to enhance the resistance of these animals to tuberculosis.

Administration, Oral↗

The protective effect of measles vaccine under routine vaccination conditions in Dar es Salaam, Tanzania: a case-control study.

A case-control study was conducted to determine the protective effect of measles vaccine under routine vaccination conditions in Dar es Salaam, Tanzania. A total of 172 cases of measles were obtained over two six-week periods from hospitals likely to admit such cases in the city and their mothers interviewed using a questionnaire that had been developed for the purpose. In addition, each case was matched to four controls for age, sex and place of residence and their mothers were also interviewed using the same questionnaire as for the cases. Vaccination status of the cases and the controls was ascertained by asking the mothers as well as obtaining vaccination information from the Mother-and-Child or Road-to-Health (MCH) clinic cards normally issued to mothers at first vaccination of their children. The overall protective effect of measles vaccine in all age groups studied was found to be 54% (95% confidence limits (CL)36%-67%) when mothers' recall for vaccination status was used. This level of protection was considered to be low compared with the efficacy of the vaccine under experimental conditions in controlled trials previously reported. However when MCH Clinic cards were used to ascertain vaccination status the protective effect rose to as high as 96% (95% CL 83%-99%). Potential biases in the study design and their role in masking or exaggerating the vaccine efficacy are discussed. It was therefore concluded that the protective effect of measles vaccine under routine vaccination conditions prevailing in Dar es Salaam region at the time of this study was as high as observed under experimental conditions when ascertainment of vaccination status was record-based. The study therefore recommended that, whenever in doubt about vaccine efficacy, simple study designs like the case-control method should be used to quickly evaluate vaccine efficacy by utilizing record-based vaccination status ascertainment methods.

Case-Control Studies↗

Impact of the Joint Statement by the American Academy of Pediatrics/US Public Health Service on thimerosal in vaccines on hospital infant hepatitis B vaccination practices.

OBJECTIVE: To determine the impact of the American Academy of Pediatrics/US Public Health Service (AAP/USPHS) joint statement on thimerosal in vaccines on hospital infant hepatitis B vaccination policies in Wisconsin. METHODS: The nurse managers of hospital newborn nurseries (n = 110) were surveyed by mail. Nonresponders were resurveyed. Twelve hospitals no longer provided obstetric services. Of the remaining 98 hospitals, 84 (86%) responded to the initial mailing and 14 (14%) responded to the second mailing. The number of hospitals that offered hepatitis B vaccine to infants before July 1999 was compared with that in March 2000. The number of hospitals that had policies in place to vaccinate infants whose mothers' hepatitis B surface antigen status (HBsAg) was positive or unknown during the thimerosal alert (July 1999 through November 1999) was compared with that in March 2000. RESULTS: Before July 1999, 81% of the hospitals representing 84% of reported Wisconsin births routinely offered hepatitis B vaccine to all infants. By March 2000, 50% of hospitals, representing 43% of births, had resumed routine infant hepatitis B vaccination. Physician decision to use a combination Haemophilus influenzae type b hepatitis B vaccine was the most frequently given reason for not reinstituting infant hepatitis B vaccination. During the thimerosal alert, 23% of hospitals did not have policies to vaccinate infants whose mothers were HBsAg-positive and 51% did not have policies to vaccinate infants whose mothers' HBsAg status was unknown. By March 2000, 6% of hospitals still did not have policies to vaccinate infants whose mothers were HBsAg-positive and 24% did not have policies to vaccinate infants whose mothers' HBsAg status was unknown. CONCLUSION: The AAP/USPHS joint statement on thimerosal in vaccines has resulted in a 38% decrease in the number of hospitals routinely offering infants hepatitis B vaccine. Although thimerosal-free hepatitis B vaccine is now available, some hospitals still do not have appropriate policies in place for vaccinating infants whose mothers' HBsAg status is positive or unknown. In the future, policymakers should include anticipated consequences that may result from changes in immunization policy in their recommendations.

Academies and Institutes↗

Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system.

BACKGROUND: Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants. To assess rare adverse events, postlicensure surveillance was conducted. OBJECTIVE: To describe the cases of intussusception among rotavirus vaccine recipients reported to the Vaccine Adverse Event Reporting System from October 1998 through December 1999. SETTING AND PARTICIPANTS: Infants vaccinated with rotavirus vaccine in the United States. OUTCOME MEASURES: Intussusception confirmed by radiology, surgery, or autopsy report with medical record documentation or confirmed by a primary health care provider. RESULTS: There were 98 confirmed cases of intussusception after vaccination with rotavirus vaccine reported to the Vaccine Adverse Event Reporting System; 60 of these developed intussusception within 1 week after vaccination. Based on calculations using vaccine distribution data and intussusception incidence rates from 2 separate databases, an estimated 7 to 16 cases would have been expected to occur in the week after vaccination by chance alone. CONCLUSION: Using a passive surveillance system for vaccine adverse events, we observed at least a fourfold increase over the expected number of intussusception cases occurring within 1 week of receipt of rotavirus vaccine. Other studies were initiated to further define the relationship between rotavirus vaccine and intussusception. In light of these and other data, the rotavirus vaccine manufacturer voluntarily removed its product from the market, and the recommendation for routine use of rotavirus vaccine among US infants has been withdrawn.

Adverse Drug Reaction Reporting Systems↗

Vaccinating children with a history of serious reactions after vaccination or of egg allergy.

OBJECTIVE: To describe the results of vaccinating children with a history of serious adverse reactions after vaccination or of egg allergy at a special clinic established for that purpose. DESIGN: Retrospective case series. PATIENTS: Children who attended the clinic between 1 August 1994 and 31 July 1996 after being referred by vaccine providers. SETTING: A clinic conducted in the Emergency Department of The Canberra Hospital, Australian Capital Territory. MAIN OUTCOME MEASURES: Reasons for referral; vaccinations given; and subsequent adverse vaccination events. RESULTS: 91 children received 155 vaccinations at the clinic, and only one serious event--a hypotonic/hyporesponsive episode (HHE) after diphtheria-tetanus-whole-cell pertussis (DTPw), oral polio and Haemophilus influenzae type b vaccination--was subsequently reported; this child recovered spontaneously. Fifty-three children referred because of a previous serious adverse vaccination event were revaccinated at the clinic with whole-cell pertussis vaccine (47), combined diphtheria and tetanus vaccine (4), tetanus toxoid (1), and typhoid vaccine (1). Three children (referred because of previous meningitis, subdural haemorrhage or parental suspicion of allergy to DTPw) received their first dose of pertussis vaccine at the clinic. The remaining 35 children had a history of egg allergy and were given measles-mumps-rubella vaccine. CONCLUSIONS: We successfully vaccinated children with histories of serious reactions to vaccination, including HHEs, convulsions, apnoea, high temperatures and persistent screaming, as well as those with egg allergy. We believe special clinics can improve vaccination coverage.

Adolescent↗

Skin reaction to yellow fever vaccine after immunization with rabies vaccine of chick embryo cell culture origin.

Skin reaction to yellow fever vaccine was examined after immunization with rabies vaccine. The two vaccines contained substrates from chick embryo cells (rabies vaccine) and chick whole embryo (yellow fever attenuated vaccine), as well as gelatin. A prick test with gelatin showed negative results in all vaccinees examined. An intradermal skin test revealed that the yellow fever vaccine had reacted with an anti-egg protein antibody-like substance in a case with a history of egg allergy before rabies vaccination. A case inoculated two times with the rabies vaccine revealed a positive reaction to egg-white protein as well as the yellow fever vaccine. This case had no anamnesis of egg allergy. Thus, an antibody reactive to the egg-white protein and/or the yellow fever vaccine was inducible by the rabies vaccine. The reaction of this antibody was not systemic but local at the skin test by the yellow fever vaccine. The period of the rabies vaccine sensitization reactive to the yellow fever vaccine could be estimated as longer than 14.3 +/- 9.6 days (mean +/- SD), based on a follow-up examination of the positive skin reaction in 41 of 84 cases examined. We therefore conclude that the yellow fever vaccine can be safely administered at an interval of at least four weeks after a second rabies vaccination.

Adult↗

[Vaccination of calves with contaminated batches of bovine herpes virus 1 vaccines did not result in infection with bovine virus diarrhea virus].

The aim of the experiment was to study whether bovine herpesvirus 1 (BHV1) marker vaccine batches known to be contaminated with bovine virus diarrhoea virus (BVDV) type 1 could cause BVD in cattle. For this purpose, four groups of cattle were used. The first group (n = 4 calves, the positive control group), was vaccinated with vaccine from a batch contaminated with BVDV type 2. The second group (n = 4 calves, the negative control group), was vaccinated with vaccine from a batch that was not contaminated with BVDV. The third group (n = 39 calves), was vaccinated with a vaccine from one of four batches contaminated with BVDV type 1 (seronegative experimental group). The fourth group (n = 6 seropositive heifers), was vaccinated with a vaccine from one of three batches known to be contaminated with BVDV type 1. All cattle were vaccinated with an overdose of the BHV1 marker vaccine. At the start of the experiment, all calves except those from group 4 were seronegative for BVDV and BHV1. The calves from group 4 had antibodies against BVDV, were BVDV-free and seronegative to BHV1. After vaccination, the positive control calves became severely ill, had fever for several days, and BVDV was isolated from nasal swabs and white blood cells. In addition, these calves produced antibodies to BVDV and BHV1. No difference in clinical scores of the other groups was seen, nor were BVDV or BVDV-specific antibody responses detected in these calves; however, they did produce antibodies against BHV1. The remainder of each vaccine vial used was examined for the presence of infectious BVDV in cell culture. From none of the vials was BVDV isolated after three subsequent passages. This indicates that BVDV was either absent from the vials or was present in too low an amount to be isolated. Thus vaccination of calves with vaccines from BHV1 marker vaccine batches contaminated with BVDV type 1 did not result in BVDV infections.

Animals↗

The present status of rabies vaccine development and clinical experience with rabies vaccine.

Attempts to control human rabies have a long history: animal and human vaccines provide efficient weapons for prevention. In this presentation, we would like to consider the different rabies vaccines available for human use, and particularly the modern vaccines produced in cell culture. Rabies virus is considered as an unique virus, but in fact, 5 groups of rabies fixed strains are used throughout the world to produce human rabies vaccines: Pasteur, Beijing, Flury, Fuenzalida and SAD strains. The Pasteur-derived strains, designated PV or PM, are the most widely used for the production of traditional vaccines of the Semple or Suckling Mouse Brain (SMB) types, but also for the production of modern cell culture vaccines: Human Diploid and Purified Vero Cell vaccines (HDCV and PVRV). The different rabies vaccines should be classified according to the cell system used to cultivate the virus: animal systems are still employed to produce the old traditional vaccines-Semple and SMB-which continue to be produced in several countries; Primary cell systems, particularly Hamster Kidney and Chick embryo cells, are used; Cell lines are presently the most interesting approach for vaccine production. The use of the human diploid cell system permitted the development of the HDCV, the most widely distributed cell culture rabies vaccine, and today considered as the reference vaccine. The heteroploid VERO cell line was introduced in 1982 to the production of inactivated rabies vaccine; it retained all the advantages of the Human Diploid Cell system, while offering the possibility of the large scale industrial production of PVRV. For both HDCV and PVRV, production security is guaranteed by the existence of a master cell seed and working cell bank, with a complete history of the cell, a limited number of passages and permanent and total quality control of the cell substrate. The principal human rabies vaccines produced worldwide at present using cell culture are compared, in terms of their technical characteristics and their capacity economically to face worldwide vaccine needs. The greatest needs are today in tropical countries, where only a limited amount of modern cell culture vaccines are used.

Animals↗