Two-dose Immunization Research Articles

Measles immunization: early two-doses policy experience.

Before the implementation of the two-dose measles immunization policy in Saudi Arabia, 50 per cent of measles cases in children below the age of one year were reported for the age group 6-8 months. In 1991 two doses of measles vaccine, at 6 months and 12 months, the second dose incorporated with MMR, were integrated into the expanded programme of immunization (EPI). Since 1993, vaccination coverage for the second dose has been above 90 per cent. While measles incidence remains stable in infants below 6 months of age, the incidence in children 9-11 months of age dropped by 50 per cent. The greatest impact was seen in the 6-8-month age group where the incidence dropped by more than 75 per cent. Moreover this two-dose strategy resulted in a situation in which 80 per cent of the measles cases were in children above the age of 5 years, mostly those who had not had two doses of measles vaccine. Further control measures should include non-selective vaccination of school children against measles. The two-dose measles vaccination policy is visualized as a necessity if the goal of measles elimination is to be achieved. Routine monthly reports validated by surveys using the WHO standard 30 cluster technique was used for the study.

Responses to acellular pertussis vaccines and component antigens in a coughing-rat model of pertussis

Two acellular pertussis vaccines (SmithKline Beecham 3-component and Connaught 5-component), and a whole-cell pertussis vaccine (Evans), were similarly protective against paroxysmal coughing and leukocytosis in a coughing-rat model of pertussis. A two-dose immunization schedule was followed by sublethal intrabronchial challenge with Bordetella pertussis strain 18–323, encased in fine agarose beads, and the coughing monitored by sound-activated tape recorders. Pertussis toxoid by itself gave some protection against coughing, but lower than that afforded by the vaccines, despite inducing a higher serum anti-PT titre. The other component antigens, given individually, failed to protect against coughing although inducing antibodies. Immunization with the whole-cell and acellular vaccines and with their component antigens, as well as challenge with B. pertussis, caused significant elevation of total serum IgE antibodies. Antigen-specific IgG and IgA were detected in tracheobronchial washings from rats recovering from B. pertussis challenge, but vaccination prior to challenge had little influence on these antibody levels. The coughing-rat model of pertussis may be useful for the comparative testing of different formulations of pertussis vaccines before trials in human infants.

A benefit-cost analysis of two-dose measles immunization in Canada

In 1992, because of the limitations of the one-dose measles immunization program, the National Advisory Committee on Immunization (NACI) recommended a two-dose measles immunization program to eliminate measles. More recently, NACI recommended also a special catch-up program to prevent predicted measles outbreaks and to achieve an earlier elimination of measles. The objective of this study was to complete a benefit-cost analysis of a two-dose immunization program with and without a mass catch-up compaign compared with the current one-dose program. The resulting benefit:cost ratios vary between 2.61:1 and 4.31:1 depending on the strategy used and the age of the children targeted. Given the parameters established for this analysis, the benefits of a second-dose vaccination program against measles far outweigh the costs of such a program under all scenarios.

Immunity to mumps before and after MMR vaccination at 12 years of age in the first generation offered the two-dose immunization programme

Sweden was the first country in the world to introduce a two-dose programme of vaccination against measles, mumps and rubella with a combined vaccine (MMR). It was commenced in 1982 and the vaccination was carried out at the ages of 18 months and 12 years. In 1992–1993 the first age-group vaccinated at 18 months reached the age of 12 and accordingly received a second dose of MMR. A total of 382 children participated in the present study. Sero-immunity against mumps was studied by testing neutralizing antibodies using serial dilutions inoculated into cell cultures before and after the 12-year vaccination. Of the 229 children earlier vaccinated (group A), 27% lacked demonstrable antibodies before the booster. Of those without documented vaccination records (group B), 56% were seronegative before vaccination. After vaccination, 93% of group A and 86% of group B were seropositive (titre ⩾2). In the seronegative children, whether vaccinated earlier or not, the seroconversion was ca 75%. Previously unvaccinated children positive before vaccination and thus likely to be naturally immune had a higher mean-titre both before and after vaccination than the seropositive chlidren earlier vaccinated. So far, the two-dose programme has proceeded as expected.

Failure to Reach the Goal of Measles Elimination

Measles is the most transmissible disease known to man. During the 1980s, the number of measles cases in the United States rose dramatically. Surprisingly, 20% to 40% of these cases occurred in persons who had been appropriately immunized against measles. In response, the United States adopted a two-dose universal measles immunization program. We critically examine the effect of vaccine failure in measles occurring in immunized persons. We performed a computerized bibliographic literature search (National Library of Medicine) for all English-language articles dealing with measles outbreaks. We limited our search to reports of US and Canadian school-based outbreaks of measles, and we spoke with experts to get estimates of vaccine failure rates. In addition, we devised a hypothetical model of a school where measles immunization rates could be varied, vaccine failure rates could be calculated, and the percentage of measles cases occurring in immunized students could be determined. We found 18 reports of measles outbreaks in very highly immunized school populations where 71% to 99.8% of students were immunized against measles. Despite these high rates of immunization, 30% to 100% (mean, 77%) of all measles cases in these outbreaks occurred in previously immunized students. In our hypothetical school model, after more than 95% of schoolchildren are immunized against measles, the majority of measles cases occur in appropriately immunized children. The apparent paradox is that as measles immunization rates rise to high levels in a population, measles becomes a disease of immunized persons. Because of the failure rate of the vaccine and the unique transmissibility of the measles virus, the currently available measles vaccine, used in a single-dose strategy, is unlikely to completely eliminate measles. The long-term success of a two-dose strategy to eliminate measles remains to be determined.

A NEW LOOK AT MEASLES

Since the measles vaccine was licensed in the United States in 1963, the number of measles cases has declined by 98%. Nevertheless, measles has not been eliminated as had been hoped, and, in fact, has started to increase in incidence. The increase in the number of cases has been accompanied by a change in measles epidemiology; the highest attack rate now occurs in preschool-age children and in older school-age and college students. The latter is the basis for the adoption of a two-dose measles immunization schedule by the ACIP and AAP. In preschool-age children, however, the problem is more disturbing and reflects low rates of immunization, particularly among inner-city populations. A major public health effort must be directed to achieve and maintain high vaccination rates if measles elimination is to be accomplished. Otherwise, measles outbreaks, with their accompanying morbidity and mortality, will continue to occur.

Measles in Israel, the West Bank, and Gaza: Continuing Incidence and the Case for a New Eradication Strategy

Measles continues to occur in epidemic waves in Israel, Gaza, and the West Bank, causing morbidity and mortality. In Israel, immunization of infants against measles began in 1967, and 90% had been immunized by the mid-1980s. In Gaza and the West Bank, where immunization of infants against measles began in 1973 and 1976, respectively, the immunization rate reached 75% in the late 1970s and increased to greater than 90% in the 1980s. Measles epidemics, which previously had occurred in 5- to 7-year cycles, occurred every 2-4 years in the 1980s and affected individuals who were older than those affected in previous years. Israel's commitment to eradicating measles by 1992 will require a substantially expanded immunization program in comparison with the traditional program that requires immunization of infants alone. The benefits of several alternative immunization strategies considerably exceed their costs. A new, two-dose immunization will be needed as a minimal strategy, and a campaign for administering booster doses to school-aged children may be required as well to achieve control and eradication of measles. Measles is a serious but preventable public health problem; appropriate strategies must be devised by national and international public health officials to control the disease in developing and developed countries.

Protection against group B meningococcal disease. III. Immunogenicity of serotype 2 vaccines and specificity of protection in a guinea pig model.

Protein vaccines were prepared from the serotype antigen of group B Neisseria meningitidis strain M986. The detergents Triton X-100, Emulphogene BC-720, and deoxycholate were used to removed the toxic lipopolysaccharide (LPS) portion of the serotype antigen. The LPS was most preferentially solubilized by Emulphogene. Guinea pigs were immunized with one or two doses of vaccine given intramuscularly without adjuvants and the antibody response quantitated by an enzyme-linked immunosorbant assay. Immunization with graded doses of vaccine between 25 to 200 microgram protein indicated a wide range of effective dosage and that a two-dose immunization schedule was superior to a single immunization. The vaccines elicited peak mean serum antibody levels of approximately 30 microgram/ml with bactericidal titers of 1:1,600-1:6,400. The peak antibody levels occurred 5-6 wk after immunization and persisted above preimmune levels for several months. To evaluate the protective effects of immunization, stainless steel springs were implanted subcutaneously into the guinea pigs. The resulting chambers, in unimmunized animals, could be infected with less than 100 type 2 organisms. A single 25-50 microgram dose of vaccine protected 50% of animals from challenge by 5 X 10(5) type 2 meningococci, and as little as 1 microgram vaccine significantly reduced the severity of infection. A two-dose immunization schedule was best and provided nearly complete protection for at least 4 mo against type 2 strains of meningococcal groups B, C, and Y.

Influenza immunization in immunosuppressed children

Optimal influenza immunization of individuals with malignancy and other immunodeficient states requires and understanding of responses to currently recommended regimens. Children with acute lymphocytic leukemia and other malignancies between three and 17 years of age were immunized with bivalent influenza vaccine containing A/New Jersey/76 and A/Victoria/75. Folowing a two-dose immunization schedule, only 37% (25468) on cancer chemotherapy seroconverted to a hemagglutination inhibition titer greater than or equal to 20 for A/NJ/76; the seroconversion rate in those not on chemotherapy was 92% (68/74, P less than 0.001). The immune response to the A/Vic/75 antigen was also related to a history of recent chemotherapy. There was no correlation between the immune response and the peripheral white blood cell count except at counts less than or equal to 1,000. The optimum time to immunize children with malignancies is when they have been off chemotherapy for one month and have peripheral white blood counts greater than 1,000.

SINGLE-DOSE ANTENATAL TETANUS IMMUNISATION

A series of two-dose and one-dose antenatal tetanus immunisation schedules using various toxoids and adjuvants have been examined for their efficacy in producing levels of antitoxin protective against neonatal tetanus at the time of delivery. If a maternal antitoxin titre of 0·01 unit per ml. or more at delivery is accepted as protective, then complete protection was afforded by two doses of a 50 limit-flocculation units (Lf) adsorbed toxoid. Standard doses of commercially available tetanus vaccines do not give complete protection unless three doses are given. The best single-dose schedule tested was 100 Lf of an adsorbed toxoid containing the quaternary ammonium adjuvant 'Arquad 2HT' (the principal component of which is dioctadecyl dimethyl ammonium chloride), which achieved 83% protection. There were no adverse reactions of significance reported in any of the schedules. Transfer of antitoxin to the infant is more effective and rapid after a two-dose schedule than after a single dose. Further investigations into immunisation early in pregnancy with adsorbed toxoids in higher doses than used in this investigation (i.e., greater than 100 Lf) are required. From these promising results it is probable that an acceptable one-dose schedule in the prevention of neonatal tetanus will be achieved. Antenatal immunisation effective in protecting against neonatal tetanus does not seem to interfere with subsequent active immunisation in infancy.