What uses for the acellular pertussis vaccine?

The acellular pertussis vaccine offers a better tolerance as compared with the whole cell pertussis vaccine. It has also a good protective effect against whooping cough. However given as a combined pentavalent vaccine for the primary immunization of infants, it appears to introduce an immune interference leading to a diminished response to the Haemophilus type b or poliomyelitis valence according to the type of vaccine. Thus it is recommended that immunization against whooping cough in France in the coming years uses whole cell pertussis combined vaccine for the primary immunization of infants at 2, 3 and 4 months, the acellular pertussis vaccine being used for the booster injections at 18 months and 10-11 years.     

Substance P- and calcitonin gene-related peptide-containing nerve fibers in the nasal mucosa of chronically hypoxic rats

Changes made in 1997 and 1998 in the U.S. childhood immunization schedule are discussed, with a focus on the use of poliovirus, pertussis, and combination vaccines. Oral poliovirus vaccine (OPV), the vaccine of choice for all four doses in the polio immunization series since 1962, can cause vaccine-associated paralytic poliomyelitis (VAPP). The inactivated poliovirus vaccine (IPV) has not been associated with VAPP but must be administered by injection and provides inferior intestinal immunity. With the reduced threat of poliovirus importation into the United States, the risk of VAPP, although low, has become less acceptable. The Centers for Disease Control and Prevention accordingly recommended a shift from OPV to IPV in the childhood immunization schedule for the United States, effective January 1997. A sequential OPV and IPV series is recommended, but the schedule includes an OPV-only option, which may be preferred in order to avoid the required injections, and an IPV-only option, which is recommended for immunocompromised persons and their contacts. Concern over local and systemic reactions associated with whole-cell pertussis vaccines, in addition to controversy over a possible relationship between the whole-cell vaccine and neurologic damage, has led to the development of new diphtheria and tetanus toxoids and acellular pertussis vaccine products for use in the diphtheria and tetanus toxoids and pertussis immunization series. Several combination products were licensed in 1997, and more are on the way. This will mean fewer inoculations for children. Increased use of IPV and acellular pertussis products could reduce the frequency of VAPP due to OPV and the local and systemic reactions associated with whole-cell pertussis vaccine.     

Access to a three-dimensional measure of vertebral axial rotation

BACKGROUND: A combined diphtheria-tetanus-whole cell pertussis-hepatitis B (DTPwHB) vaccine might facilitate the achievement of universal vaccination of infants against hepatitis B. METHODS: A double blind, randomized, two-armed, single center study was undertaken to evaluate the immunogenicity and reactogenicity of combined tetravalent DTPwHB vaccine, with two dosages of hepatitis B component (10 microg and 5 microg). The combined vaccine was tested in the context of a simplified vaccination schedule at 1.5, 3.5 and 6 months of age, to 120 healthy infants born to hepatitis B surface antigen-negative mothers after priming with one dose of hepatitis B vaccine (10 microg) at birth. Antibodies to each antigenic component were measured from blood samples collected immediately after birth, pre- and postvaccination blood samples. RESULTS: The reactogenicity profiles were similar in the two groups. No serious adverse events were reported. One month after completion of the four-dose vaccination schedule, all subjects except one in Group 1 (10 microg) had protective titers of anti-HBs (10 mIU/ml). At this time the geometric mean titer in Group 1 (10 microg) was higher than that observed in Group 2 (5 microg), 696 vs. 488 mIU/ml (P = 0.19). One month after three doses all subjects in both groups had protective antidiphtheria titers and antitetanus titers. The vaccine response rate to the Bordetella pertussis component of the vaccine was 88.0% in Group 1 and 96.2% in Group 2 (P = 0.86). CONCLUSION: Both combined tetravalent vaccines are safe and immunogenic when administered to infants born to a hepatitis B surface antigen-negative mother, with a 10-microg dose of priming hepatitis B vaccine at birth. This combined tetravalent DTPwHB vaccine may play an important role to promote integration of HB vaccine into the Expanded Program of Immunization in hepatitis B-endemic areas.     

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.     

Efficacy of a two-component acellular pertussis vaccine in infants

OBJECTIVE: This case-control study investigated the protective efficacy against pertussis of three doses of a two-component acellular pertussis vaccine (manufactured by Biken in Japan) combined with diphtheria and tetanus toxoids (manufactured by Connaught Laboratories in the US) in infants. METHODS: A case-control study was performed in 63 pediatric practices in Germany. Prospective recruitment of 16,780 infants ages 6 to 17 weeks took place between February, 1993, and July, 1994. According to parental choice infants received either Biken acellular pertussis vaccine combined with diphtheria and tetanus toxoids (DTacP) (74.6%) at approximately 2, 4 and 6 months of age, or a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine (10.9%), diphtheria-tetanus toxoids vaccine (12.5%) or no vaccine (2.0%). Prospective surveillance of pertussis cases between February, 1993, and May, 1995, was accomplished by culturing all infants < or =2 years of age presenting with cough > or = 7 days. A pertussis case was defined as any cough of 21 days or longer plus a positive Bordetella pertussis culture or household contact exposure. RESULTS: We identified 241 pertussis cases prospectively by 11,017 B. pertussis cultures and 949 controls matched for age were selected from the same pediatric practices. Medical history and demographic and vaccine status data were collected from each case and for four controls. Data were analyzed through conditional logistic regression taking into account individual matching and adjusting for potential confounding variables. DTacP combined with diphtheria and tetanus toxoids vaccine was 82% protective (95% confidence interval, 68 to 90), diphtheria-tetanus toxoids-whole cell pertussis vaccine was 96% protective (95% confidence interval, 78 to 99). Protection against typical B. pertussis infection characterized by paroxysmal cough lasting > or =21 days was 96% (95% confidence interval, 87 to 99) for DTacP and was 97% (95% confidence interval, 79 to 100) for diphtheria-tetanus toxoids-whole cell pertussis vaccine. Adjustment for potentially confounding variables did not change the results significantly. CONCLUSIONS: Three doses of the two-component acellular pertussis vaccine protected infants against pertussis disease during the period before the recommended booster vaccination. For typical pertussis disease as defined by the WHO efficacy was high and similar to that of a licensed German diphtheria-tetanus toxoids-whole cell pertussis vaccine.     

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Hepatitis B recombinant vaccine immunoresponsiveness was studied in 427 preadolescents vaccinated with a 0, 1 and 6 months vaccination schedule. AntiHBs postvaccination titres (measured one month after the last dose) were related to the following variables: sex; weight; height; and Quetelet index. The antiHBs postvaccination titres were used to predict the length of protection induced by the vaccine. All preadolescents developed antiHBs titres 10 IU l-1 and no statistically significant differences could be found between sexes. The relation study between antiHBs postvaccination levels and Quetelet index showed a statistically significant inverse correlation. According to the antiHBs postvaccination titres, the central 50% of the sample distribution would be protected during a period between 7.5 and 10.5 years. In pre-teenagers, the hepatitis B recombinant vaccine has proven to be highly immunogenic, obesity is a predictor of poor immunoresponse and this response is not influenced by sex. According to our results, we would propose the administration of a single booster dose 10 years after primary vaccination and thus protect these subjects during the period of greatest risk.     

Reflections on the effectiveness of the new combined vaccines]

The combination vaccines are very useful to reduce the number of contacts required to immunize a child fully and to improve the vaccine coverage. Recently the new combinations between Haemophilus Influenzae vaccine (PRP-T) and pertussis vaccines in D-T-P (IVP) combined vaccines have suggested interferences with immunogenicity for PRP-T vaccines. The interference for pertussis antibodies is not significative. The depression of antiPRP antibodies is shown with the whole-cell pertussis vaccine, but the level of antibodies is related to a good protective efficacy. Inversely, when PRP-T vaccine is combined with acellular pertussis vaccines, the antibodies levels are lower, especially the number of children with a level higher than 1 mcg/ml. At the present time, these combinations between PRP-T vaccines and acellular pertussis vaccines are not recommended for primary immunization in infants in France. Such constations emphasize the necessity to perform wide comparative trials to test immunogenicity for all the next combinations between old and new vaccines. A decrease in immunogenicity of combination vaccines is acceptable as long as protective efficacy is preserved. It is possible that the growing number of new vaccines to combine will be limited to keep a clinical efficacy.     

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age

METHODS: In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections. RESULTS: There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.     

Antibody and cell-mediated immune responses to booster immunization with a new acellular pertussis vaccine in school children

235 healthy 10-12 years old school children were randomly immunized with either a booster dose of diphtheria-tetanus-acellular pertussis (dTap) or diphtheria-tetanus (dT) vaccine. For this booster immunization designed for school children and adults, the quantities of Bordetella pertussis antigens in the dTap vaccine had been reduced to one third of those of the Infanrix vaccine (SmithKline Beecham) commonly used for infants. IgG antibodies and cell-mediated immune (CMI) responses to pertussis toxin (PT), pertactin (PRN) and filamentous hemagglutinin (FHA) were assessed by an enzyme immunosorbent assay and in vitro proliferation of peripheral blood mononuclear cells, respectively. Before immunization, 55%, 80% and 99% of children had detectable serum IgG antibodies to PT, PRN and FHA, whereas CMI response was found in 35%, 27% and 50% of children, respectively. After immunization, a 20-30-fold increase in geometric mean level (GML) of antibodies to the pertussis antigens occurred and CMI response to PT, PRN and FHA was seen in 88%, 94% and 100% of children, respectively. Adverse reactions following the immunization were rare. The results show that booster immunization with an acellular pertussis vaccine with reduced concentrations of antigens induces both antibody and CMI responses and support further studies of this pertussis vaccine in school children.     

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.     

Pertussis vaccines: past, present and future in Australia

In August 1997, a workshop was convened by the National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases to consider current issues in the use of pertussis vaccines and implications for the Australian immunisation schedule. Topics covered included the history, efficacy and reactogenicity of whole-cell and acellular vaccines and vaccine schedules. Acellular pertussis vaccine is preferred by the National Health and Medical Research Council for the primary course as well as the 18 month and 4-5 year old childhood doses. At the time of the workshop, a 3-component acellular vaccine (DTPa) had been approved (licensed) in Australia for all doses in the childhood schedule. It was the first vaccine subject to a cost-effectiveness evaluation under the new vaccine funding arrangements. Issues considered in the evaluation of the cost-effectiveness of the vaccine were discussed. These included comparative efficacy, adverse events and compliance, and the question of community as well as individual benefit from the use of the vaccine.     

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.     

Parental knowledge and choice regarding live and inactivated poliovirus vaccines

BACKGROUND: Concern about the 8 to 10 cases per year of vaccine-associated paralytic poliomyelitis caused by the live oral poliovirus vaccine (OPV) has led to revised guidelines for immunization of children in the United States. The use of inactivated poliovirus vaccine (IPV) at 2 and 4 months of age could require administration of 3 injections per visit until combination products are available. OBJECTIVE: To determine parents' knowledge of poliovirus vaccines and the choices they would make between IPV and OPV. METHODS: Parents of 240 children aged 2 weeks to 18 months under the care of 10 private pediatricians in the Baltimore, Md, metropolitan area were interviewed prior to the announcement of revised advisory committee guidelines. RESULTS: The majority (62.5%) of respondents were not aware that 2 poliovirus vaccines are available. After reviewing standardized information about the vaccines and 2 alternate schedules, most (75%) parents would consult someone (primarily their physician) before making a final choice of a vaccine schedule. If parents made the choice without consulting anyone else, 61.3% would choose to have their child receive IPV and 3 injections per visit as compared with an all-OPV schedule and 2 injections per visit. Inactivated poliovirus vaccine was preferred by most parents because it would reduce the risk for vaccine-associated paralytic poliomyelitis. Oral poliovirus vaccine was preferred by 37.9% of parents primarily because it was given orally. If the number of injections at each visit was the same for both vaccines, 76.3% of parents would choose the IPV schedule, and if the number of injections was reduced to 2 by combining IPV with another vaccine, 87.9% of parents would choose IPV. CONCLUSION: The number of injections per visit is an important issue, but a majority of parents would choose to have their children receive extra injections to prevent the low risk for vaccine-associated paralytic poliomyelitis.     

Randomized comparison of early and late vaccination with inactivated poliovirus vaccine after allogeneic BMT

Forty-five adult HLA-matched sibling BMT recipients were randomized to receive inactivated poliovirus vaccine (IPV) at 6, 8 and 14 months (early group, n = 23) or at 18, 20 and 26 months after BMT (late group, n = 22). Ninety-five percent of the early group patients had protective antibody titres of > or = 4 to poliovirus type 1 (PV1), poliovirus type 2 (PV2) and poliovirus type 3 (PV3) by a microneutralization assay prior to the first vaccination, at 6 months after BMT. The corresponding proportion for the late group patients was only 67% at 18 months. The antibody responses 1 month after each of the three IPV doses were similar in the two vaccination groups, except that four-fold responses occurred more frequently after the first dose to PV2 and PV3 in the late group. All patients had a protective antibody titre to all poliovirus serotypes 1 and 22 months after the third vaccine dose, except one patient in the early group who lacked antibodies to PV3 at 22 months. Acute GVHD accelerated the decrease of poliovirus antibody titres prior to vaccination but had no influence on vaccination response. Chronic GVHD neither influenced the patient's ability to retain poliovirus antibodies prior to vaccination nor impaired responses to vaccinations. A vaccination schedule consisting of three IPV doses was equally immunogenic when started at 6 or 18 months after allogeneic BMT.     

Childhood immunizations: position on the enhanced inactivated poliovirus vaccine and live attenuated oral poliovirus vaccine dilemma

Recent review of the polio vaccines (live attenuated oral poliovirus vaccine [OPV] and enhanced inactivated poliovirus vaccine [eIPV]) for children has generated much debate between infectious disease experts and public health officials. Poliomyelitis was a common medical condition in the 1940s and 1950s, and the success of OPV in eradicating poliomyelitis from the United States and even the Western hemisphere cannot be disputed. However, the adverse condition of vaccine-associated paralytic poliomyelitis (VAPP) has been reported in eight to nine cases per year as a result of exclusively using OPV in the United States. The dilemma has been how to continue the elimination of wild-type poliovirus paralytic poliomyelitis in the United States and worldwide while minimizing the occurrence of VAPP. Clinical trials have supported that eIPV and OPV provide similar protection for humoral immunity. However, OPV provides superior gastrointestinal immunity, which is a public health benefit for vulnerable populations. Recommendations among experts have concluded that the sequential eIPV/OPV is the preferred schedule, with eIPV only or OPV only as alternative equally acceptable schedules. Therefore, factors such as cost, compliance, and access to health care must be considered by parents and providers when selecting a polio vaccine regimen, especially among underserved populations.     

Bacterial ADP-ribosylating toxins: form, function, and recombinant vaccine development

No products of the biotechnology revolution will likely have a greater legacy than recombinant vaccines. Clinical efficacy trials of new acellular pertussis vaccines have recently been completed; among them, a vaccine containing a genetically modified pertussis toxin showed superior effectiveness in protection against disease caused by Bordetella pertussis. The foundations for this vaccine derive from the work of many investigators, but most notably: Japanese researchers who demonstrated the potential for subcomponents of B. pertussis, and particularly pertussis toxin, to confer protective immunity; research teams in Italy and the United States who cloned and sequenced the pertussis toxin operon; and our own group who molecularly dissected the toxin molecule to produce recombinant analogs of this heterohexameric protein that retained protective immunogenicity yet lacked the intrinsic enzyme activity that results in the adverse reactogenic effects of immunization. Another result of the research leading to this new pertussis vaccine is an intimate understanding of the relationship between form and function in the ADP-ribosylating toxins with AB5 architecture, including the structure of their catalytic domains their immunologic and adjuvant properties, characteristics and possible pathologic consequences of host cell receptor recognition, and the assembly and subunit interactions of these complex multimeric proteins.     

Southcentral Foundation--Dena A Coy: a model program for the treatment of pregnant substance-abusing women

Although in many countries pertussis had been successfully controlled by the routine mass immunization in infants and children, the disease continues to cause extensive morbidity and mortality throughout the world. Whole-cell pertussis vaccine plays an important role in the control of pertussis in the world and the vaccine proved to be very successful during nearly 50 years of its use. However, the whole-cell pertussis vaccine causes an increased rate of local and general adverse events although many of these events described as caused by vaccination are occurring co-incidentally, not being related to vaccination. Results of recent clinical and field trials in the USA, Sweden, Italy, Germany and Senegal showed that acellular pertussis vaccines are effective in preventing pertussis in children and safe in infants. However, a crucial issue in more general use of acellular pertussis vaccine is its availability and its price. It may be prove too expensive for many countries, including Poland. The cost can be expected to decrease in the future, when the production capacity and the number of doses used increase. The introduction of acellular pertussis vaccine in the immunization programme in Poland will need several organizational, technological and scientific actions.     

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.     

Pertussis, pertussis vaccine, and care of exposed persons

BACKGROUND: Pertussis is a highly contagious bacterial infection caused by Bordetella pertussis. Before routine vaccination against pertussis was available, most persons were infected during childhood. After widespread vaccination, however, the incidence of pertussis in the United States dropped by more than 95 percent, though localized outbreaks continue to occur. METHODS: A multidisciplinary team developed a set of review articles as part of continuing medical education modules in the Teaching Immunization in Medical Education (TIME) Project. The team developed the materials using expert judgment and selected materials from the literature and the Centers for Disease Control and Prevention (CDC). The first step was the creation of specific learning objectives that used the spectrum of Bloom's taxonomy, when possible. After the materials were developed, they were pilot-tested and revised. Subsequently they underwent summative evaluation by field-testing the materials with 24 other primary care physicians. Then the materials were reviewed by the CDC and national vaccine experts and revised based on their comments. RESULTS AND CONCLUSIONS: The efficacy of whole-cell pertussis vaccine is about 70 to 90 percent, though local adverse events are common. Since 1990 several purified, acellular pertussis vaccines have been developed that have one quarter to one half of the common adverse events associated with whole-cell vaccine and have similar efficacy rates. The incidence of pertussis can be further reduced by increasing age-appropriate vaccination rates.