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Measles outbreak in western Sydney. Vaccine failure or failure to vaccinate?

OBJECTIVES: To determine the effectiveness of measles vaccine during a measles outbreak, and to assess whether age at vaccination was a risk factor for measles vaccine failure. DESIGN: A matched case-control study. SETTING: The five primary schools in western Sydney with the largest number of measles cases during the June to December 1993 outbreak. SUBJECTS: Seventy-nine children aged 5-9 years with an illness consistent with a clinical definition for measles. Two controls per case were selected from children in the same classroom. MAIN OUTCOME MEASURES: Estimated measles vaccine effectiveness by age of the child at vaccination and vaccination status: "unvaccinated"; "parental recall" (parents stated the child was vaccinated but no record could be found); and "record" (record including date of vaccination available). RESULTS: The estimated vaccine effectiveness was 94% (95% confidence interval [CI], 83%-98%) in the "record" group, and 81% (95% CI, 46%-93%) in the "parental recall" group. Vaccine effectiveness did not differ significantly with age at vaccination (under 12 months of age 96% [64%-99%]; 12-14 months 95% [81%-99%]; and 15 months and over 93% [80%-98%]). CONCLUSION: Vaccination records should be used to calculate a vaccine's effectiveness as parental recall may not be sufficiently accurate. The high vaccine effectiveness in the "record" group (94%) makes it unlikely that low vaccine effectiveness was the cause of the outbreak. More effort is needed to increase vaccine coverage to at least 95% in all population subgroups.

Age Factors↗

Are vaccination rates higher if providers receive free vaccines and follow contraindication guidelines?

BACKGROUND AND OBJECTIVES: Economics has been suggested as a barrier to vaccination, but data that link clinician reports to actual immunization rates are limited. This study examined the relationship between clinicians' self-report regarding likelihood of vaccinating and actual age at vaccination from a registry of children seen by the clinicians. METHODS: Standardized telephone survey results of 29 providers were compared to the immunization records of children seeing these providers, using analysis of contingency tables (on time versus late) and conditional hierarchical linear models with log age at diphtheria-tetanus-pertussis (DTP)#3, DTP#4, and measles-mumps-rubella (MMR)#1 as the dependent variables. RESULTS: Children seeing providers likely to refer an uninsured child for immunization were vaccinated at a later log age at DTP#4 but not for DTP#3 or MMR#1 than children seeing providers unlikely to refer. Vaccination rates were higher for MMR#1 (77% versus 48%), DTP#3 (84% versus 71%), and DTP#4 (82% versus 66%) among providers who received free vaccine, compared with children seen by providers who did not receive free vaccine. These results remained significant in the hierarchical analyses. Providers likely to vaccinate an 18-month-old with watery diarrhea had higher vaccination rates than those unlikely to vaccinate for MMR#1, DTP#3, and DTP#4; the results were also significant in the hierarchical analyses. CONCLUSION: Children are vaccinated later in the practices of providers who are likely to refer uninsured children to a public vaccine clinic for vaccination, who do not receive free vaccine supplies, or who overinterpret contraindications.

Age Factors↗

Vaccination of calves against bovine herpesvirus-1: assessment of the protective value of eight vaccines.

Eight separate, but related experiments, were carried out in which groups of six calves were vaccinated with one of eight commercial vaccines. In each experiment the vaccinated calves were subsequently exposed to three calves infected with virulent bovine herpesvirus-1 (BHV-1). In each experiment, all infected donor calves developed a typical severe infectious bovine rhinotracheitis (IBR) infection and excreted virus in their nasal secretions of up to 10(8.00) TCID50/0.1 ml. One live BHV-1 gE-negative vaccine (A) and three modified live vaccines (B, C, D), administered intranasally, all protected against clinical disease. The calves vaccinated with one vaccine (C) also did not excrete virus in the nasal secretions, whereas the calves protected by vaccines A, B and D excreted virus in their nasal secretions but at low titres (10(0.66)-10(1.24) TCID50/0.1 ml). A fourth modified live vaccine (E), given intramuscularly, failed to prevent mild clinical disease in the calves which also excreted virus in the nasal secretions at titre of 10(1.00) TCID50/0.1 ml. An analogous result was given by the calves vaccinated with either of the two inactivated vaccines (F and G) or with a BHV-1 subunit vaccine (H). All calves developed mild clinical signs and excreted virus at titres of 10(2.20)-10(3.12) TCID50/0.1 ml. Calves vaccinated with C vaccine were subsequently given dexamethasone, following which virus was recovered from their nasal secretions. The virus isolates did not cause disease when calves were infected and appeared to be closely related to the vaccine strain.

Animals↗

Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B vaccine during the primary immunization course?

A combined hepatitis A/B vaccine (Twinrix Adult) has been licensed in Germany since 1997. We investigated possible differences in immunogenicity and safety when changing over from vaccinations with monovalent vaccines made by different manufacturers to vaccinations with the combined hepatitis A/B vaccine in an open, randomized, multicenter trial. We therefore compared four different schemes changing over from concomitant vaccinations with monovalent vaccines against hepatitis A and B (Havrix 1440+Engerix-B or Vaqta+Gen H-B-Vax) to combined vaccination against hepatitis A+B with three injections of the combined hepatitis A/B vaccine (0, 1, and 6 month schedule). Local and general symptoms were mostly mild in all five groups. With complete three-dose course using the combined vaccine or an early changeover from monovalent vaccines to the combined vaccine, higher overall anti-HBs seroprotection rates and geometric mean concentrations (GMCs) against hepatitis B could be achieved as early as after 2 months as compared to those groups switching later to the combined vaccine. This study demonstrated for the first time that switching from monovalent hepatitis A and B vaccinations to the combined hepatitis A and B vaccination has no negative influence on the tolerability and improves the immunogenicity.

Adolescent↗

Rotavirus vaccines and vaccination in Latin America.

Worldwide, rotaviruses account for more than 125 million cases of infantile gastroenteritis and nearly 1 million deaths per year, mainly in developing countries. Rather than other control measures, vaccination is most likely to have a major impact on rotavirus disease incidence. The peak incidence of rotavirus diarrhea occurs between 6 and 24 months of age. In developing countries, however, cases are not uncommon among children younger than 6 months. G serotypes 1 to 4 are responsible for most disease, but there are indications that in Brazil that G type 5 is of emerging epidemiological importance. Both homotypic and heterotypic responses are elicited during natural rotavirus infection, and the immunological response at the intestinal mucosal surface is probably the more consistent predictor of clinical immunity. With the primary objective of protecting children against life-threatening dehydrating diarrhea, many approaches to rotavirus vaccine development have been attempted. One vaccine, the tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV), was given licensing approval in the United States of America, introduced to the market, and later withdrawn. A number of studies have found better efficacy of RRV-TV in developed countries than in developing ones. Field trials with a 4 x 10(4) plaque-forming units (PFU) preparation of RRV-TV have been carried out in two countries in Latin America, Brazil and Peru. Those trials yielded protective efficacy rates against all rotavirus diarrhea ranging from 18% to 35%. Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 x 10(5) PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be overcome by giving three doses of the rotavirus vaccine or by using a higher-titer formulation of it. Wild enteroviruses, however, may cause primary rotavirus vaccine failure in developing countries. Studies in Peru with RRV-TV have shown a trend towards higher vaccine efficacy rates against "pure" (rotavirus-only) diarrheal episodes. Economic analyses made in the United States indicate that a vaccine that costs less than US$ 9 per dose would lead to a net savings in medical costs. To date, however, cost-benefit studies have not been done in developing countries. In the future, it is possible that some Latin American countries might adapt their polio production facilities to the preparation of rotavirus vaccines for human use. A year after RRV-TV was licensed for vaccination of infants in the United States, the occurrence of intussusception as an adverse event led to the vaccine's withdrawal from the market. The implications of that action, particularly for Latin America, will be addressed in this article, including the need to explore alternative rotavirus candidate vaccines, particularly through the conduct of parallel clinical trials in both developed and developing countries.

Animals↗