Pertussis Vaccine Testing for Freedom-from-Toxicity

The results of 9.5 years of official testing of vaccines containing pertussis vaccine, plain or adsorbed with alum, Al(OH)₃, or AlPO₄, are reported. Toxicity was evaluated by weight changes in mice at 3 and 7 days after injection and intercurrent deaths. Toxicity was encountered during the early use of AlPO₄ in pertussis vaccine products, with a special product and quadruple-antigen vaccines. Throughout the study Al(OH)₃ products, few in number, were the least reactive of the adsorbed products. The slopes of regression lines of graded-dose responses reflected variations in reactivity of “nontoxic” vaccines. The U.S.-prescribed test is discussed relative to the (i) reactivity in children, (ii) causes of toxicity, (iii) other assays for pertussis vaccine toxicity, and (iv) the use of a reference vaccine in the toxicity test.     

Vaccines beyond antibodies: Spurred by pandemic research,are T‐cell vaccines moving closer to reality?

Lessons learned from the vaccines against SARS‐CoV‐2 has encouraged research and vaccine development aimed at mustering strong T cell responses against the pathogen. Subject Categories: Microbiology, Virology & Host Pathogen Interaction, Pharmacology & Drug Discovery

The new vaccines against SARS‐CoV‐2 elicited strong antibody responses in initial trials, which encouraged optimism amongst immunologists and public health experts who expected good efficacy. “With viral infections, it is almost unheard of to have a prophylactic vaccine that doesn’t work ultimately by generating neutralising antibody responses”, explained immunologist Kingston Mills at Trinity College Dublin in Ireland. However, the antibody response is not the whole story. “Efforts to explain how immunity is working against viruses to the general public has forced everyone to try to make things so simple that now what is left is a ridiculous oversimplified picture of the vertebrate immune system”, commented Antonio Bertoletti, infectious disease scientist at Duke‐National University of Singapore. In fact, there is increasing research focus on the role of T cells in mediating the cellular response to infections and how to stimulate these cells through vaccines.Antibodies work by recognising and attaching to surface structures of a virus or bacterium, which prevents the pathogen from infecting its target cells and mark it for destruction by other immune cells. However, pathogens can escape the antibody response via mutations that decrease the efficiency of antibodies from infection or vaccination. “You will still potentially get infected if you’re vaccinated, because the antibody response is not as strong as it was”, explained immunologist Luke O’Neill at Trinity College Dublin, Ireland. “But then the T cells will kick in and stop the virus when it is inside cells”. Simply put, antibodies tend to prevent infection, while T cells combat infection and illness. Specifically, CD4 helper T cells primarily encourage B cells to generate antibodies whereas CD8 “killer” T cells eliminate cancerous and virally infected cells.     

Whole-cell Bordetella pertussis vaccine component modulates the mouse immune response to an unrelated soluble antigen

Several factors are involved in the selective activation of Th1 or Th2 cells, such as different physical characteristics of antigens and the type of antigen-presenting cells involved in the immune response, among others. To study the influence of a particulate antigen on Th1/Th2 cell differentiation during the immune response to another antigen, we analysed the immune response to tetanus toxoid (soluble antigen) in BALB/c mice immunized with one of the three following vaccines: tetanus and diphtheria toxoids (DT), or DT associated with whole-cell Bordetella pertussis or its soluble antigens (DTPw and DTPa, respectively). Similar total antibody levels were observed for all vaccines. DT vaccine showed a higher IgG1/IgG2a ratio than the similar values observed for DTPw and DTPa vaccines. DT- and DTPa-primed spleen cells showed a Th2 (IL-5) profile while a Th1/Th2 (IFN gamma, IL-5) profile was observed for DTPw. IL-6 was only produced by DTPw-primed cells. Besides, IL-12 levels induced by DTPw were three times higher than the ones induced by both DT and DTPa. Our findings indicate that whole-cell B. pertussis priming modifies the tetanus immune response from Th2 to Th1/Th2 type probably via inflammatory mechanisms. In addition, in the light of conflicting reports regarding the mechanisms of protection induced by DTP vaccines, we studied the pertussis immune response. Only DTPw immunization generated memory T cells capable of proliferating with B. pertussis as an in vitro stimulus. Results might indicate that these cells may not play a key role in protecting against B. pertussis when the host is vaccinated with DTPa.     

Factors associated with uptake of measles,mumps, and rubella vaccine (MMR) and use of single antigen vaccines in a contemporary UK cohort: prospective cohort study

Objectives To estimate uptake of the combined measles, mumps, and rubella vaccine (MMR) and single antigen vaccines and explore factors associated with uptake and reasons for not using MMR.Design Nationally representative cohort study.Setting Children born in the UK, 2000-2.Participants 14 578 children for whom data on immunisation were available.Main outcome measures Immunisation status at 3 years defined as “immunised with MMR,” “immunised with at least one single antigen vaccine,” and “unimmunised.”Results 88.6% (13 013) were immunised with MMR and 5.2% (634) had received at least one single antigen vaccine. Children were more likely to be unimmunised if they lived in a household with other children (risk ratio 1.74, 95% confidence interval 1.35 to 2.25, for those living with three or more) or a lone parent (1.31, 1.07 to 1.60) or if their mother was under 20 (1.41, 1.08 to 1.85) or over 34 at cohort child’s birth (reaching 2.34, 1.20 to 3.23, for ≥40), more highly educated (1.41, 1.05 to 1.89, for a degree), not employed (1.43, 1.12 to 1.82), or self employed (1.71, 1.18 to 2.47). Use of single vaccines increased with household income (reaching 2.98, 2.05 to 4.32, for incomes of ≥£52 000 (€69 750, $102 190)), maternal age (reaching 3.04, 2.05 to 4.50, for ≥40), and education (reaching 3.15, 1.78 to 5.58, for a degree). Children were less likely to have received single vaccines if they lived with other children (reaching 0.14, 0.07 to 0.29, for three or more), had mothers who were Indian (0.50, 0.25 to 0.99), Pakistani or Bangladeshi (0.13, 0.04 to 0.39), or black (0.31, 0.14 to 0.64), or aged under 25 (reaching 0.14, 0.05 to 0.36, for 14-19). Nearly three quarters (74.4%, 1110) of parents who did not immunise with MMR made a “conscious decision” not to immunise. Conclusions Although MMR uptake in this cohort is high, a substantial proportion of children remain susceptible to avoidable infection, largely because parents consciously decide not to immunise. Social differentials in uptake could be used to inform targeted interventions to promote uptake.     

Habilitation of Patients with Congenital Malformations Associated with Thalidomide: Surgery of Limb Defects

The deformities commonly seen in “thalidomide babies” are described. These vary from relatively uncomplicated radial-ray defects to complete phocomelia of all four extremities. It is suggested that the care of these children is best carried out in a clinic accustomed to dealing with juvenile amputee problems. A plea is made for very early fitting of upper-extremity prostheses (at approximately three months of age) in cases of unilateral upper-limb deficiencies. A “bucket” for sitting should be supplied for children with quadrilateral phocomelia to sit in when they reach seven or eight months of age. Children with severe upper-limb malformations will be candidates for some form of externally powered prostheses.     

Uptake of infant and preschool immunisations in Scotland and England during the COVID-19 pandemic: An observational study of routinely collected data

BackgroundIn 2020, the SARS-CoV-2 (COVID-19) pandemic and lockdown control measures threatened to disrupt routine childhood immunisation programmes with early reports suggesting uptake would fall. In response, public health bodies in Scotland and England collected national data for childhood immunisations on a weekly or monthly basis to allow for rapid analysis of trends. The aim of this study was to use these data to assess the impact of different phases of the pandemic on infant and preschool immunisation uptake rates.Methods and findingsWe conducted an observational study using routinely collected data for the year prior to the pandemic (2019) and immediately before (22 January to March 2020), during (23 March to 26 July), and after (27 July to 4 October) the first UK “lockdown”. Data were obtained for Scotland from the Public Health Scotland “COVID19 wider impacts on the health care system” dashboard and for England from ImmForm.Five vaccinations delivered at different ages were evaluated; 3 doses of “6-in-1” diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, and hepatitis B vaccine (DTaP/IPV/Hib/HepB) and 2 doses of measles, mumps, and rubella (MMR) vaccine. This represented 439,754 invitations to be vaccinated in Scotland and 4.1 million for England. Uptake during the 2020 periods was compared to the previous year (2019) using binary logistic regression analysis. For Scotland, uptake within 4 weeks of a child becoming eligible by age was analysed along with geographical region and indices of deprivation. For Scotland and England, we assessed whether immunisations were up-to-date at approximately 6 months (all doses 6-in-1) and 16 to 18 months (first MMR) of age.We found that uptake within 4 weeks of eligibility in Scotland for all the 5 vaccines was higher during lockdown than in 2019. Differences ranged from 1.3% for first dose 6-in-1 vaccine (95.3 versus 94%, odds ratio [OR] compared to 2019 1.28, 95% confidence intervals [CIs] 1.18 to 1.39) to 14.3% for second MMR dose (66.1 versus 51.8%, OR compared to 2019 1.8, 95% CI 1.74 to 1.87). Significant increases in uptake were seen across all deprivation levels.In England, fewer children due to receive their immunisations during the lockdown period were up to date at 6 months (6-in-1) or 18 months (first dose MMR). The fall in percentage uptake ranged from 0.5% for first 6-in-1 (95.8 versus 96.3%, OR compared to 2019 0.89, 95% CI 0.86– to 0.91) to 2.1% for third 6-in-1 (86.6 versus 88.7%, OR compared to 2019 0.82, 95% CI 0.81 to 0.83).The use of routinely collected data used in this study was a limiting factor as detailed information on potential confounding factors were not available and we were unable to eliminate the possibility of seasonal trends in immunisation uptake.ConclusionsIn this study, we observed that the national lockdown in Scotland was associated with an increase in timely childhood immunisation uptake; however, in England, uptake fell slightly. Reasons for the improved uptake in Scotland may include active measures taken to promote immunisation at local and national levels during this period and should be explored further. Promoting immunisation uptake and addressing potential vaccine hesitancy is particularly important given the ongoing pandemic and COVID-19 vaccination campaigns.

Fiona McQuaid and colleagues assess the uptake of infant and pre-school immunisations in Scotland and England during the COVID-19 pandemic.     

Role of whole-cell pertussis vaccine in severe local reactions to the preschool (fifth) dose of diphtheria-pertussis-tetanus vaccine.

OBJECTIVE: To estimate the contribution of whole-cell pertussis vaccine to severe local reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine. DESIGN: Double-blind randomized controlled trial. SETTING: Urban community. PARTICIPANTS: Volunteer sample of 200 healthy children 4 to 6 years old who were eligible for the fifth dose of DPT vaccine. INTERVENTIONS: Children received, in both arms, either diphtheria toxoid-tetanus toxoid (DT) and monovalent pertussis vaccines (group A, 99 children) or DPT and meningococcal vaccines (group B, 101 children). All were licensed products from single lots. The children were assessed 24 hours later by a trained observer. Serum samples obtained before vaccination were tested for antibodies to tetanus and diphtheria toxins and five pertussis antigens by means of enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of severe local reactions (an area of redness or swelling or both of 50 mm or greater) 24 hours after vaccination. Relation between serum antibody levels before vaccination and rates of severe local reactions to corresponding vaccines. RESULTS: All of the subjects were followed up 24 hours after vaccination. Severe redness was present in 38% given DPT vaccine, 29% given intramuscular pertussis vaccine and 9% given DT vaccine (p < or = 0.002, three-way comparison). Severe swelling was common after vaccination with all three products. After intramuscular pertussis vaccination a relation was evident between the prevaccination levels of antibody to whole-cell pertussis bacteria and the rates of redness (p < 0.02) but not between the prevaccination subcellular antibody levels and the rates of redness. CONCLUSION: That pertussis vaccine resembled the DPT vaccine in causing severe redness suggests that it is the principal cause of such reactions after DPT vaccination. The DT vaccine was also reactogenic; thus, cumulative sensitization to one or more of its constituents may be a factor.     

Cost-Effectiveness of Tdap Vaccination of Adults Aged ≥65 Years in the Prevention of Pertussis in the US: A Dynamic Model of Disease Transmission

Objectives

In February 2012, the Advisory Committee on Immunization Practices (ACIP) advised that all adults aged ≥65 years receive a single dose of reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap), expanding on a 2010 recommendation for adults >65 that was limited to those with close contact with infants. We evaluated clinical and economic outcomes of adding Tdap booster of adults aged ≥65 to “baseline” practice [full-strength DTaP administered from 2 months to 4–6 years, and one dose of Tdap at 11–64 years replacing decennial Td booster], using a dynamic model.

Methods

We constructed a population-level disease transmission model to evaluate the cost-effectiveness of supplementing baseline practice by vaccinating 10% of eligible adults aged ≥65 with Tdap replacing the decennial Td booster. US population effects, including indirect benefits accrued by unvaccinated persons, were estimated during a 1-year period after disease incidence reached a new steady state, with consequences of deaths and long-term pertussis sequelae projected over remaining lifetimes. Model outputs include: cases by severity, encephalopathy, deaths, costs (of vaccination and pertussis care) and quality-adjusted life-years (QALYs) associated with each strategy. Results in terms of incremental cost/QALY gained are presented from payer and societal perspectives. Sensitivity analyses vary key parameters within plausible ranges.

Results

For the US population, the intervention is expected to prevent >97,000 cases (>4,000 severe and >5,000 among infants) of pertussis annually at steady state. Additional vaccination costs are $4.7 million. Net cost savings, including vaccination costs, are $47.7 million (societal perspective) and $44.8 million (payer perspective). From both perspectives, the intervention strategy is dominant (less costly, and more effective by >3,000 QALYs) versus baseline. Results are robust to sensitivity analyses and alternative scenarios.

Conclusions

Immunization of eligible adults aged ≥65, consistent with the current ACIP recommendation, is cost saving from both payer and societal perspectives.     

An international collaborative study of the effect of active pertussis toxin on the modified Kendrick test for acellular pertussis vaccines

Speculation that the Japanese modified intra-cerebral challenge assay, which is used in several countries for control of acellular pertussis vaccines, depends on the presence of small amounts of active pertussis toxin led to an assumption that it may not be appropriate for highly toxoided or genetically detoxified vaccines. Consequently, at the recommendation of a World Health Organisation AD Hoc Working Group on mouse protection models for testing and control of acellular pertussis vaccine, the effect of pertussis toxin on the modified intra-cerebral challenge assay (modified Kendrick, MICA) was evaluated in an international collaborative study. Results of this study showed that for genetically detoxified vaccines both with and without active pertussis toxin the MICA clearly distinguished mice vaccinated with acellular vaccines from unvaccinated mice and gave a significant dose–response relationship. However, vaccine samples containing active pertussis toxin (5 or 50 ng/single human dose) appeared to be more potent than the equivalent sample without active pertussis toxin. Similar results were also given by two respiratory infection models (intranasal and aerosol) included in the study. The results also indicated that the effect of pertussis toxin may vary depending on mouse strain.     

No receptor stands alone: IgG B-cell receptor intrinsic and extrinsic mechanisms contribute to antibody memory

Acquired immunological memory is a striking phenomenon. A lethal epidemic sweeps through a naïve population, many die but those who survive are never “attacked twice ― never at least fatally”, as the historian Thucydides observed in 430 BCE. Antibody memory is critical for protection against many human infectious diseases and is the basis for nearly all current human vaccines. Antibody memory is encoded, in part, in isotype-switched immunoglobulin (Ig)G-expressing memory B cells that are generated in the primary response to antigen and give rise to rapid, high-affinity and high-titered antibody responses upon challenge with the same antigen. How IgG-B-cell receptors (BCRs) and antigen-induced IgG-BCR signaling contribute to memory antibody responses are not fully understood. In this review, we summarize exciting new advances that are revealing the cellular and molecular mechanisms at play in antibody memory and discuss how studies using different experimental approaches will help elucidate the complex phenomenon of B-cell memory.     

Evaluation of efficacy in terms of antibody levels and cell-mediated immunity of acellular pertussis vaccines in a murine model of respiratory infection

The efficacy of six acellular pertussis vaccines, prepared by various manufacturers in Japan, was investigated in a murine model of respiratory infection (aerosol challenge model) and a murine intracerebral (i.c.) challenge model. There was a good correlation between bacterial clearance from the lungs after aerosol challenge and the potency of vaccines as determined by i.c. challenge. The levels of antibodies against filamentous hemagglutinin were higher after immunizations with all tested vaccines than the levels of antibodies against pertussis toxin and pertactin. Spleen cells from mice immunized with each individual vaccine secreted interferon gamma (IFN-gamma) in response to stimulation by pertussis toxin, filamentous hemagglutinin and fimbriae. The production of interleukin-4 in response to each of the antigens tested was detected but was lower than that of IFN-gamma. However, antibody levels and cell-mediated immune responses were not correlated with the protective effects of the vaccines after aerosol challenge and after i.c. challenge.     

Diphtheria-Tetanus-Pertussis Immunization by Intradermal Jet Injection

An intradermal jet injector was used to administer combined diphtheria, tetanus, and pertussis (D.T.P.) vaccines to infants aged 2 to 12 months. A second dose was given one month after the first and a third six months after the second. Each dose was considerably smaller than the standard intramuscular dose. Blood samples taken one month after the third dose showed a satisfactory diphtheria and tetanus antitoxin response in all but a few cases. The antibody response to the pertussis component was not examined. Reactions were insignificant. Intradermal jet injection is proposed as a cheap, extremely rapid, and effective technique for D.T.P. immunization, especially suitable for use in remote areas where trained staff and facilities are few and many children require immunization.     

Pertussis Prevalence and Its Determinants among Children with Persistent Cough in Urban Uganda

Background

We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control.

Methods

In a cross-sectional study, 449 children aged 3 months to 12 years with persistent cough lasting ≥14 days were enrolled and evaluated for pertussis using DNA polymerase chain reaction (PCR) and ELISA serology tests.

Results

Pertussis prevalence was 67 (15% (95% Confidence Interval (CI): 12–18)) and 81 (20% (95% CI: 16–24)) by PCR and ELISA, respectively among 449 participating children. The prevalence was highest in children with >59 months of age despite high vaccination coverage of 94% in this age group. Study demographic and clinical characteristics were similar between pertussis and non-pertussis cases. Of the 449 children, 133 (30%) had a coughing household member and 316 (70%) did not. Among 133 children that had a coughing household member, sex of child, sharing bed with a coughing household member and having a coughing individual in the neighborhood were factors associated with pertussis. Children that had shared a bed with a coughing household individual had seven-fold likelihood of having pertussis compared to children that did not (odds ratio (OR) 7.16 (95% CI: 1.24–41.44)). Among the 316 children that did not have a coughing household member, age <23 months, having or contact with a coughing individual in neighborhood, a residence with one room, and having a caretaker with >40 years of age were the factors associated with pertussis. Age <23months was three times more likely to be associated with pertussis compared to age 24–59 months (OR 2.97 (95% CI: 1.07–8.28)).

Conclusion

Findings suggest high prevalence of pertussis among children with persistent cough at a health facility and it was marked in children >59 months of age, suggesting the possibility of waning immunity. The factors associated with pertussis varied by presence or absence of a coughing household member.     

Myocardial Infarction and Carbohydrate Metabolism Relating to Diabetes Mellitus

Fifteen non-obese males with acute myocardial infarction and no diabetic history were evaluated for diabetes. During infarction, results of oral glucose tolerance tests were “diabetic” or “probably diabetic” in 10 of the 15 patients (67 percent). The plasma immuno-reactive insulin response in 12 patients (80 percent) was of a pattern observed in patients with maturity-onset diabetes. Six months after infarction, follow-up glucose tolerance tests in 12 surviving patients were diabetic or probably diabetic in three cases (25 percent). In seven of twelve patients (58 percent) had delay in the peaking of the plasma insulin response to an oral glucose tolerance test, a phenomenon that is observed in patients with maturity-onset diabetes.Glucose tolerance tests were abnormal in one of fourteen control subjects (7 percent). There was a delayed plasma insulin response to an oral glucose test in two of fourteen controls (14 percent).Patients with myocardial infarction have an increased incidence of diabetes mellitus.     

Tissue Matching and Early Rejection of Cadaveric-Donor Renal Allografts: The Importance of Unidentified Donor Antigens

Tissue typing has been reviewed in a series of 100 technically successful cadaveric-donor kidney grafts. The criterion of transplant failure was immunological rejection causing total loss of function within three months of operation.No significant correlation was observed between matching grade and graft failure due to early acute rejection. This is attributed to the failure to detect at least one “LA” or “4” antigen (as defined in our laboratory), representing a potential incompatibility, in 89% of the grafts, and in the remaining 11% to the lack of an available recipient with identical “LA” and “4” typing. Undetected antigens on the donor are usually incompatible, and probably these incompatibilities unfavourably influence early graft survival.If the results of cadaveric-donor renal transplantation are to equal those of transplantation from well-matched living related donors it will be necessary to type with sera which can recognize individually all HL-A antigens, including those not yet identified, and to create an international pool of over 1,000 potential recipients.     

A New Approach to Bacterial Vaccines

Immunizing antigens against only 10 bacterial diseases—cholera, diphtheria, paratyphoid, pertussis, plague, scarlet fever, staphylococcal disease, tetanus, tuberculosis and typhoid—have been licensed for sale in Canada and the United States. Convincing evidence of efficacy is available for only four of these—diphtheria and tetanus toxoids, and pertussis and typhoid vaccines.The principles which determine the efficacy of different immunizing antigens are not always the same. Toxoids, for example, stimulate the formation of antitoxin-producing mechanisms which can neutralize toxins produced by invading organisms, thereby rendering them harmless. Conversely, vaccines stimulate the formation of antibacterial mechanisms which stop the growth of organisms before they can produce disease.Use of enzyme-lysed vaccines for prevention of staphylococcal disease represents a new approach in vaccine research. Animal tests have shown lysed vaccines to be 10 to 100 times less toxic, and about eight times more effective, than whole bacterial vaccines. Studies with lysed vaccines for other diseases are now in progress.     

Pulmonary Contusion in Children due to Rubber Bullet Injuries

Three cases of pulmonary contusion occurred in children as a result of injuries from “rubber bullets.” Radiological changes were evident soon after the injury, and in one case these persisted for two months. Symptoms disappeared quickly in all three cases.     

Specificity and detection limit of a dermal temperature histamine sensitization test for absence of residual pertussis toxin in vaccines

Currently, an assay based on fatal sensitization of mice to histamine challenge is widely used for testing absence of residual pertussis toxin in acellular pertussis containing vaccines. For replacement of this lethal end-point assay, an alternative method based on body temperature measurement in mice has been presented, and in this study the specificity and detection limit of a dermal temperature-based assay were assessed. Test preparations containing pertussis toxin were prepared in aluminum-adjuvanted pertussis toxoid vaccine and injected intraperitoneally in histamine sensitive mice. Later the mice were challenged with histamine and the pertussis toxin-induced decrease in dermal temperature recorded. By comparison of mice treated with pertussis toxoid vaccine spiked with pertussis toxin with mice treated with pertussis toxoid vaccine alone, the assay gave a response that specifically could detect presence of pertussis toxin. The acellular pertussis containing vaccine did not interfere with the pertussis toxin-induced temperature response recorded. In tests for presence of pertussis toxin in the pertussis vaccine preparation, the detection limit of the assay was estimated to approximately 5 ng pertussis toxin per human dose of pertussis toxoid. The dermal temperature-based assay was found to be a valid method to be applied in routine quality control of vaccines.     

Verification of components of acellular pertussis vaccines that have been distributed solely, been in routine use for the last two decades and contributed greatly to control of pertussis in Japan.

An ideal acellular pertussis vaccine is now under investigation worldwide. We have had acellular pertussis vaccines available for the last 22 years, which contributed greatly to the control of pertussis in Japan, although it has not been known whether they are one of ideal acellular pertussis vaccines or not. Moreover, the formulations of acellular pertussis vaccines that we have been using have not been widely recognized. Serum samples were taken from recipients of the T type, B type, and two-component acellular pertussis vaccine and assayed by ELISA for anti-PT, anti-FHA, and anti-69 kD OMP antibody levels and by the agglutination test. Although it was shown that T type vaccine contained four components (PT, FHA, 69 kD OMP, agglutingen), B type vaccine contained three components (PT, FHA, 69 kD OMP) and the two-component vaccine contained PT and FHA, it was concluded that PT and FHA were essential and common antigens contained in all three acellular pertussis vaccines in Japan. The national monitoring system for adverse effects of routine immunization demonstrated low reactogenicity of DTaP in Japan. This resulted in high acceptance rates of DTaP and in virtual control of pertussis.     

A Controlled Study of Disturbances Recorded Following the Use of Oral Poliomyelitis Vaccine

A double-blind study of disturbances recorded following the administration of a live trivalent oral poliomyelitis vaccine and an identical-appearing placebo was undertaken. Seven hundred and forty-one persons, 81% of the entire population of a small town, constituted the trial group. The two feedings, with a varied feeding sequence, were eight days apart, and at the second feeding and again eight days later, the participants were investigated under controlled conditions. There were no statistically significant differences in the number, nature or timing of the disturbances reported following the administration of the two vaccines. With both vaccines, significantly fewer reactions were reported among males, among the under-5 year group, among Occupational Class I, and after the first feeding as compared with the second. The Salk vaccine immunization status of the participants made no significant difference. With both active vaccine and placebo “vaccine” 14 to 15% of the participants reported some “reaction”.