Obituaries

Although tetanus is now rare, vaccination is currently recommended for the entire population. Most elderly North Americans have never received tetanus vaccination. We evaluated the expected cost-effectiveness of using mailed reminders from family physicians to increase primary tetanus vaccination coverage among elderly Canadians. We estimated that over 10 years the program would prevent five cases of tetanus and one death from tetanus, resulting in a gain of 13 life-years. There would be 16,700 adverse reactions to tetanus toxoid, 17% in people already immune to tetanus. The net cost of the program (in 1984 Canadian dollars) would be $1.9 million per case of tetanus prevented, $7.1 million per death prevented and $810,000 per life-year gained. These high cost-effectiveness ratios are largely attributable to the very low risk of tetanus, even among nonimmune elderly people. Tetanus toxoid and physicians'' services for vaccination would account for 86% of the program costs. Because the mailed reminders would be responsible for only 13% of the program costs, other possible programs to increase primary tetanus vaccination coverage could not be expected to have substantially lower cost-effectiveness ratios. We conclude that efforts to increase primary tetanus vaccination coverage among elderly Canadians would be a questionable use of health care resources.     

Use of reminders to increase compliance with tetanus booster vaccination.

OBJECTIVE: To assess the effect of three computerized reminder systems on compliance with tetanus vaccination. DESIGN: Prospective randomized controlled trial. SETTING: Ottawa Civic Hospital Family Medicine Centre. PARTICIPANTS: Of 8069 patients 20 years of age or more who were not in a hospital or institution 5589 were randomly assigned, by family, to a control group, a physician reminder group, a telephone reminder group or a letter reminder group. The remaining 2480 patients were not included in the randomized portion of the study but were monitored. Results are presented for the 5242 randomized patients and the 2369 nonrandomized patients for whom there was no up-to-date record of tetanus vaccination at the start of the trial. INTERVENTIONS: For the patients in the physician reminder group the physician was reminded at an office visit to assess the patient''s tetanus vaccination status and to recommend vaccination; those in the other two reminder groups received a telephone call or letter enquiring about their tetanus vaccination status and recommending a booster dose. MAIN OUTCOME MEASURE: Proportion of patients who received tetanus toxoid during the study year or who had a claim of vaccination in the previous 10 years. MAIN RESULTS: The rate of recorded tetanus vaccination in the randomized control group was 3.2%. The difference between that rate and those for the three reminder groups was 19.6% in the physician reminder group (95% confidence interval [CI] 17.1% to 22.2%, p less than 0.00001), 20.8% in the telephone reminder group (95% CI 18.3% to 23.5%, p less than 0.00001) and 27.4% in the letter reminder group (95% CI 24.8% to 30.2%, p less than 0.00001)). The letter reminders were more effective than either the telephone reminders (p = 0.00013) or the physician reminders (p less than 0.00001) in improving compliance. The cost to the practice per additional vaccination recorded was 43 for the physician reminders, $5.43 for the telephone reminders and $6.05 for the letter reminders. CONCLUSIONS: Although all three reminder systems increased the rate of recorded tetanus vaccination they fell far short of achieving complete population coverage. More intensive interventions would be required to approach that goal. However, such interventions do not appear to be justified given the rarity of tetanus.     

Causes of fatal childhood accidents involving head injury in northern region, 1979-86.

OBJECTIVE--To examine the causes and circumstances surrounding fatal accidents involving head injuries in children in the Northern region. DESIGN--Retrospective review of the hospital case notes, necropsy reports, and records of the coroners'' inquests. SETTING--Northern Regional Health Authority. PATIENTS--All 255 children aged less than 16 years who died with a head injury during 1979-86. MAIN OUTCOME MEASURES--Cause of injury and circumstances of accident according to reports of inquests; injury severity score; number of fatal accidents and mortality per 100,000 children in 10 groups of local authority wards ranked according to their score on the overall deprivation index; and distance of site of accident from child''s home. RESULTS--Of the 255 children who died after a head injury, 136 (53%) children were playing at the time of the accident. 195 (76%) children sustained the head injury in road traffic accidents, 135 as pedestrians, 35 as cyclists, and 25 as passengers in a vehicle. In 120 accidents in child pedestrians the primary cause of accident was the unsafe behaviour of the child. 172 (67%) accidents occurred within one to two km of the child''s home and 153 (63%) between 3 pm and 9 pm. The mortality was significantly related to social deprivation; excluding eight children injured while on holiday in the region, 15-fold decrease in mortality was recorded between the local authority wards that ranked highest on the overall deprivation index and those that ranked lowest (14.0/100,000 children, group 10 v 0.9/100,000, group 1 respectively, p less than 0.00001). CONCLUSIONS--The finding that most accidents occurred in children living in deprived areas who were playing unsupervised near their home suggests that childhood mortality might be appreciably reduced if children at play were protected from traffic, particularly in socially deprived areas.     

Simultaneous Immunization with B.C.G., Diphtheria-tetanus,and Oral Poliomyelitis Vaccines in Children Aged 13-14

The simultaneous administration of B.C.G. vaccine, diphtheria-tetanus toxoid aluminium hydroxide adsorbed vaccine, and oral poliovaccine was studied in 628 children aged 13-14 years between 1966 and 1969 in Newham, London. The efficacy of these vaccines was unaffected by administering them at the same time; routine simultaneous administration is considered justified when organizational difficulties prevent the attainment of high immunization rates with the vaccines given separately. No adverse reactions to B.C.G. or oral poliomyelitis vaccines took place, but 8% of children had moderately severe local reactions after diphtheria-tetanus aluminium hydroxide adsorbed vaccine, which were attributed to diphtheria toxoid.Serological studies showed the need for immunization against diphtheria, tetanus, and poliomyelitis at 13-14 years of age. Because of the adverse reactions to diphtheria toxoid, however, simultaneous administration of tetanus toxoid aluminium hydroxide adsorbed, oral poliomyelitis, and B.C.G. vaccines only is recommended at present.An “adult type” diphtheria-tetanus toxoid might overcome the problem of reactions, though in two to three years'' time most children aged 13-14 years will have received diphtheria-tetanus-pertussis vaccine in infancy and reinforcement might then be accomplished by a small intradermal dose of the currently available fluid diphtheria-tetanus vaccine.Continued serological studies of diphtheria and tetanus antitoxins and polio antibody are necessary to determine the future need for reinforcement of immunity; such studies should become an essential part of the surveillance of the community immunization programme.     

Booster vaccination against tetanus and diphtheria: insufficient protection against diphtheria in young and elderly adults

We have recently demonstrated that single shot vaccinations against tetanus and diphtheria do not lead to long-lasting immunity against diphtheria in elderly persons despite administration at 5 year intervals. In the present study we have immunized a group of young adults against tetanus and diphtheria to compare the pre- and 28 days post-vaccination immune responses in the young group with results of the same vaccination performed in an elderly group of a previous study. We also studied protection in both groups 5 years after vaccination. We compared antibody titers at all three time points and also analyzed the T cell responses in both age groups 5 years after vaccination.Before vaccination 9 % of the elderly persons were not protected against tetanus, and 48 % did not have protection against diphtheria. In the young group all participants were protected against tetanus, but 52 % were also unprotected against diphtheria before vaccination. 28 days after vaccination 100 % of all participants had protective antibody concentrations against tetanus and only a small percentage in each age group (<10 %) was unprotected against diphtheria. 5 years later, 100 % of both cohorts were still protected against tetanus, but 24 % of the young and 54 % of the elderly group were unprotected against diphtheria. Antibody concentrations against diphtheria measured by ELISA correlated well with their neutralizing capacity. T cell responses to tetanus and diphtheria did not differ between young and old persons. We conclude that booster vaccinations against tetanus and diphtheria according to present recommendations provide long-lasting protection only against tetanus, but not against diphtheria, independently of age. In elderly persons, the level of protection is even lower, probably due to intrinsic age-related changes within the immune system and/or insufficient vaccination earlier in life.     

Antibody status to poliomyelitis,measles, rubella,diphtheria and tetanus,Ontario, 1969-70: deficiencies discovered and remedies required.

A serologic survey was made in 15 health unit areas, testing some 5000 individuals in the age groups 4 to 6, 11 to 13, 15 to 17 and 23 to 45 years. Two types of serious deficiency were found. Only 65% of children 4 to 6 years old had antibodies to all three types of poliovirus, the antibodies being due almost entirely to immunization with Salk vaccine. Even in children who had had six or more doses only 74% had antibodies to the three types. The high percentage of students 11 to 13 and 15 to 17 years old with poliovirus antibodies can be attributed largely to natural infection and to Sabin vaccine in the mass campaign of 1962, as well as to Salk vaccine. In children who had received Sabin vaccine as well as Salk vaccine a very high level of immunity was found. The immunity of the school-age population will decline to an insufficient level unless Sabin vaccine is used after immunization with Salk vaccine. Of children 4 to 6 years old 18% had no diphtheria antitoxin and 6% had no tetanus antitoxin. Even in those who had had six or more doses of the antigens 5% had no diphtheria antitoxin and 1 to 2% had no tetanus antitoxin. This apparently refractory state is probably due to the use of unadsorbed toxoids, and it is clear that adsorbed toxoids should be used. In the adults, diphtheria antitoxin was found in only 55% and tetanus antitoxin in only 38%.     

Epidemiological and immunological monitoring of tetanus in Georgia (Republic)

During the period of 1961-1990 the regular immunological and epidemiological monitoring of tetanus was carried out. At the prevaccination period (1937-1960) 140 cases of tetanus were registered, 77 patients died (morbidity rate being 0.97-0.11 per 100,000 of the population with mortality rate equal to 55.6%). At the period of mass vaccinal prophylaxis (1960-1990) 56 cases were registered and 27 patients died (the corresponding values: 0.09-0.11 with 48.2% mortality). In 1981-1990 altogether 53,213 vaccinees were examined. 4,864 vaccinees (8.9%) proved to be seronegative and 43,615 vaccinees (81.9%) were found to have protective antibody titers. 4,220 pregnant women were examined; 476 women (11.2%) proved to be seronegative and 3,576 women (84.3%) were found to have protective antibody titers. Timely specific prophylaxis proved to be the only way for decreasing tetanus morbidity.     

Significance of circulating toxin and antitoxin in unimmunized tetanus cases of neonates and infants

The level of circulating tetanus toxin, antitoxin and their individual influence on the outcome of tetanus cases were determined in unimmunized 125 neonatal and 39 infant cases of tetanus. PHA (passive haemagglutination) test showed 40% positive cases for toxin while its absence in the remaining cases indicated of either toxin fixation to the central nervous system (CNS) or it got neutralized by antitoxin. TN (toxin neutralization) and PHA test carried out in 46 sera samples revealed a strong positive correlation (r = 0.9) showing that 35/46 (76%) and 38/46 (82.6%) samples were positive for antitoxin, respectively. 25.4% of the neonate and infant cases and 34% of the control group had a protective serum tetanus antitoxin level. 42.5% of the paired sera from unimmunized mothers and their neonates showing nonprotective antitoxin levels suggested that a high level of antitoxin is needed for transplacental transfer, although transfer may not play a decisive role in the resistance against the disease. The presence of toxin or antitoxin in the clinical cases did not affect the outcome of the disease, although in neonates, presence of toxin was found to be a bad prognostic sign. This study explicitly advocates for the need to improve the vaccination coverage strategy.     

TETANUS IN CALIFORNIA—Epidemiology and a Review of 232 Cases

A study was made of records of the 232 reported cases of tetanus in California, from 1953 through 1958. Cases occurred in 30 of California''s 58 counties. Two-thirds of the patients lived in suburban and urban areas. Two-thirds of the cases occurred in persons over the age of 20 years. The incidence was twice as high in males as in females. Forty-seven per cent of the patients died, with the highest death rates being in persons over the age of 40 years.Sixty-three per cent of the injuries associated with these 232 cases occurred in the home environment and 17 per cent at the place of employment.Ninety-one per cent of the patients had never been immunized with tetanus toxoid, or if they had been immunized, had not received the booster injections necessary to maintain effective immunity. Nine per cent gave a history of having had one or more injections of tetanus toxoid within five years.     

Socio-Psychological Factors Driving Adult Vaccination: A Qualitative Study

BackgroundWhile immunization is one of the most effective and successful public health interventions, there are still up to 30,000 deaths in major developed economies each year due to vaccine-preventable diseases, almost all in adults. In the UK, despite comparatively high vaccination rates among ≧65 s (73%) and, to a lesser extent, at-risk ≤65 s (52%) in 2013/2014, over 10,000 excess deaths were reported the previous influenza season. Adult tetanus vaccines are not routinely recommended in the UK, but may be overly administered. Social influences and risk-perceptions of diseases and vaccines are known to affect vaccine uptake. We aimed to explore the socio-psychological factors that drive adult vaccination in the UK, specifically influenza and tetanus, and to evaluate whether these factors are comparable between vaccines.Methods20 in-depth, face-to-face interviews were conducted with members of the UK public who represented a range of socio-demographic characteristics associated with vaccination uptake. We employed qualitative interviewing approaches to reach a comprehensive understanding of the factors influencing adult vaccination decisions. Thematic analysis was used to analyze the data.ResultsParticipants were classified according to their vaccination status as regular, intermittent and non-vaccinators for influenza, and preventative, injury-led, mixed (both preventative and injury-led) and as non-vaccinators for tetanus. We present our finding around five overarching themes: 1) perceived health and health behaviors; 2) knowledge; 3) vaccination influences; 4) disease appraisal; and 5) vaccination appraisal.ConclusionThe uptake of influenza and tetanus vaccines was largely driven by participants'' risk perception of these diseases. The tetanus vaccine is perceived as safe and sufficiently tested, whereas the changing composition of the influenza vaccine is a cause of uncertainty and distrust. To maximize the public health impact of adult vaccines, policy should be better translated into high vaccination rates through evidence-based implementation approaches.     

Nonfatal childhood injuries: a survey at the Children's Hospital of eastern Ontario.

OBJECTIVE: To examine the types and severity of injuries seen in the Emergency Department of the Children''s Hospital of Eastern Ontario and the circumstances surrounding the events. DESIGN: Chart review. SETTING: A tertiary care hospital that serves a child population of 600,000 in eastern Ontario and western Quebec. PARTICIPANTS: Every sixth day''s charts of children up to 17 years of age who visited the Emergency Department because of injuries between Sept. 1, 1984, and Aug. 31, 1985, were examined retrospectively. RESULTS: A total of 2886 charts were reviewed. There were more boys than girls. Most (1354 [46.9%]) of the accidents had occurred at home. Falls and sports-related accidents were the leading causes of injury (in 1088 [37.7%] and 560 [19.4%] of the cases respectively). Most of the visits were for minor injuries (bumps, swellings, cuts, bruises and scrapes), and only 114 (4.0%) of the children were admitted to the hospital. Injuries from motor vehicle accidents accounted for the highest admission rate (17.4%). Important information regarding the circumstances surrounding the events (e.g., whether a seat belt or car seat was used) was frequently missing from the charts. CONCLUSIONS: Nonfatal injuries are common, especially in or around the home, and remain a significant problem in our society in terms of radiographic and consulting fees, time off from school or work and pain. Given the difficulties in obtaining information on the circumstances surrounding the events prospective studies are needed. Factors related to the occurrence and severity of childhood injury and whether these factors can be altered remain a high priority for research.     

Evidence for familial immune defect in meningococcal meningitis.

Twenty-six patients who had recovered from group A meningococcal meningitis were vaccinated with group C meningococcal polysaccharide and tetanus toxoid. Their haemagglutinating antibody response was measured two weeks later and compared with those of 22 siblings and 39 controls. Patients and siblings had a significantly lower antibody response to the group C vaccine but not to tetanus toxoid. This suggests that patients susceptible to meningococcal disease may have an immune defect involving their response to meningococcal polysaccharides.     

Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized,open-label,parallel group study in healthy subjects

The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell-dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti-pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes.     

Preparation of affinity-purified,biotinylated tetanus toxin,and characterization and localization of cell surface binding sites on nerve growth factor-treated PC12 cells

Biotinylated derivatives of tetanus toxin were prepared and isolated by chromatofocusing and ganglioside-affinity chromatography. Biotinylation was monitored by the appearance of a 210,00 dalton complex upon SDS-polyacrylamide gel electrophoresis in the presence of avidin, and by selective binding to an avidin-Sepharose gel. At molar biotin:toxin ratios from 11 to 201 only biotinylated derivatives with low toxicity were obtained; these derivatives, however, retained 60–80% of their specific binding affinity for brain synaptosomes. A biotinylated tetanus toxin derivative purified by ganglioside-affinity chromatography was used to identify and localize tetanus toxin binding sites on PC12 cells. Electron microscopic analysis with streptavidin-gold revealed very low levels of tetanus toxin binding sites on the surface of untreated cells, and the appearance of such binding sites during the second week of nerve growth factor-induced differentiation. Examination of micrographs of the differentiated cells indicated that the tetanus toxin binding sites sites are concentrated on the neurites, with relatively few appearing on the cell bodies. Cognate studies using¹²⁵I-labeled, affinity-purified tetanus toxin revealed an increase in PC12 binding capacity from about 0.07 nmol/mg protein in untreated cells to 0.8 nmoles/mg protein in cells treated for 14 days with nerve growth factor. Cells treated in suspension for 2–3 weeks with nerve growth factor do not express tetanus toxin binding sites; upon plating, these cells required one week for the appearance of binding sites, although neurites grew much more rapidly from these primed cells. The high binding capacity of these tetanus toxin sites, as well as their sensitivity to neuraminidase, is indicative of a polysialoganglioside structure. The advantages of biotinylated tetanus toxin derivatives are discussed and the significance of nerve growth factor-differentiated PC12 cells grown as monolayers as a model for the study of the development, localization, and function of neuraminidase-sensitive tetanus toxin binding sites is presented.Abbreviations PBS phosphate-buffered saline - STS sucrose-Tris-serum solution - NGF nerve growth factor - C collagen - PL polylysine - BBG bovine brain ganglioside mixture - GM₁ gafactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide - GD_1a [N-acetylneuraminyl]-galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide - GT_1a [N-aceylneuraminyl]-galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosyl ceramide - GD_1b galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl-N-acetylneuraminyl]-galactosylglucosyl ceramide - GT_1b [N-acetylneuraminyl]-galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl-N-acetylneuraminyl] galactosylglucosyl ceramide - NANA N-acetylneuraminic acid     

Vehicle–wild vertebrate collision mortality on the highways of Tigray,Ethiopia, implications for conservation

In view of the upcoming road network improvement and expansion in Ethiopia, specifically in Tigray, it is also necessary to understand the potential impacts of road accidents with wildlife vertebrate animals. Road mortality detection surveys were conducted from March 2013 to June 2014. We surveyed around 530 km using vehicle with special emphasis given to roads surrounded by wetlands, forests, rocky areas and rivers each month. Additional information was also collected using a standardized questionnaire. A total of twenty species, 143 individuals of amphibians, reptiles, birds and mammals were recorded as road vehicular accidents in the surveyed area. Of all, mammals showed the highest species richness (80 individuals belonging to ten species) followed by birds (49 individuals belonging to eight species). The survey revealed most accidents happened during the early morning and late evening. This might be due to relatively high traffic and continued activity of wild animals at that time, besides the driver's inability to avoid accidents when it is dark. Wildlife underpasses during road construction, location of crossing structures, rules of wildlife conservation, improving driver's awareness are relevant in this context and may be the most important mitigation measures to reduce mortality of wildlife on the roads.     

Bicycle accidents in childhood.

The results of a 10 year study of bicycle fatalities and an eight year study of serious non-fatalities are reported for urban Brisbane (population 1,000,000). There were 845 serious non-fatal bicycle accidents and 46 fatalities during the study. Boys were involved in 86% of accidents. Boys have an accident rate of 134.21 per 100,000 population at risk and a fatality rate of 5.06 per 100,000 at risk. Serious bicycle accidents have increased by 50% in this decade; but considering fatal cases alone, no secular trend was evident over the 10 year period of the study. This suggests that an increase in the overall rate of bicycle accidents has been in part compensated by less serious injuries. In 70% of fatalities children had head injuries, and 87% of fatalities followed a collision between a cyclist and a motor vehicle or a train. Bicycle accidents on the roads most commonly occur to boys aged between 12 and 14 years on a straight road at "mid-block" between 3 and 5 pm in clear weather conditions and in daylight. It is concluded that injuries and fatalities after bicycle accidents can be reduced by protecting children''s heads, separating child cyclists from other road traffic, or educating and training both cyclists and other road users in safe behaviour. The compulsory use of helmets and the restriction of access to the roads by child cyclists to reduce injuries are, however, still controversial in many areas.     

Factors associated with in-hospital mortality of adult tetanus patients–a multicenter study from Bangladesh

BackgroundTetanus, a vaccine-preventable disease, is still occurring in the elderly population of low- and middle-income countries with a high case-fatality rate. The objective of the study was to elucidate the factors associated with in-hospital mortality of tetanus in Bangladesh.MethodsThis prospective observational study, conducted in two specialized infectious disease hospitals, conveniently selected adult tetanus patients (≥18 years) for inclusion. Data were collected through a preformed structured questionnaire. Kaplan Meier survival analysis and univariate and multivariable Cox regression analysis were carried out to assess factors associated with in-hospital mortality among patients. All analysis was done using Stata (version 16) and SPSS (version 26).ResultsA total of 61 tetanus cases were included, and the overall in-hospital mortality rate was 34.4% (n = 21). Patients had an average age of 46.49 ±15.65 years (SD), and the majority were male (96.7%), farmers (57.4%), and came from rural areas (93.4%). Survival analysis revealed that the probability of death was significantly higher among patients having an age of ≥ 40 years, incubation time of ≤12 days, onset time of ≤ 4 days, and having complication(s). However, on multivariable Cox regression analysis, age (adjusted hazard ratio [aHR] 4.03, 95% Confidence Interval [CI] 1.07–15.17, p = 0.039) and onset time (≤4 days) (aHR 3.33; 95% CI 1.05–10.57, p = 0.041) came as significant predictors of in-hospital mortality after adjusting for incubation period and complications.ConclusionOlder age and short onset time are the two most important determinants of in-hospital mortality of tetanus patients. Hence, these patients require enhanced emphasis and care.     

Diphtheria-tetanus overimmunization in children with no records: can it be prevented?

A pilot study was undertaken to assess the validity of two new tests for predicting the immune response of Toronto schoolchildren with no acceptable evidence of prior administration of diphtheria or tetanus toxoid to a routine booster injection of diphtheria and tetanus (DT) toxoid. The tests, an inexpensive enzyme-linked immunosorbent assay (ELISA) fingerprick test for tetanus antibodies and a modification of the Schick skin test for susceptibility to diphtheria, were administered before the booster injection. One week later the ELISA test was repeated and the result of the modified Schick test read. On both occasions a diphtheria microneutralization assay was done for "gold standard" evidence of prior exposure to diphtheria toxoid or toxin. The results were used to determine the sensitivity and specificity of a single prebooster tetanus ELISA test or a modified Schick test for predicting which children with no records could be safely protected with only one DT booster dose instead of the primary series of three or four doses usually given to such children. Only 6 of the 34 subjects (18%) were totally without prior exposure to tetanus toxoid. Two of the six (6% of 33 subjects) appeared to mount a primary immune response to diphtheria toxoid as well. An initial ELISA titre of 0.01 IU/ml or lower correctly identified all six children needing a full series of tetanus toxoid (sensitivity for a primary immune response 100%) and falsely identified only 3 of 28 immune children as needing the series (specificity for immunity 89.3%). The modified Schick test appeared to have even greater accuracy for identifying children needing a full series of diphtheria toxoid. However, its use, entailing the costs of an extra nurse visit, would have prevented only seven more children from receiving an unnecessary full series of diphtheria toxoid than use of the baseline tetanus ELISA test alone.     

GANGLIOSIDES IN NERVOUS TISSUE CULTURES AND BINDING OF 125I-LABELLED TETANUS TOXIN, A NEURONAL MARKER

Abstract— —Continuous cell lines, primary cell cultures derived from embryonic CNS, and homogenates made from adult and embryonic CNS were compared with respect to their lipid pattern and their ability to bind ¹²⁵I-labelled tetanus toxin. In parallel experiments de novo synthesis of gangliosides in the cell lines was studied, using [¹⁴C]glucosamine as precursor. Of the total lipid only gangliosides were specifically labelled by [¹⁴C]glucosamine. The patterns of the de novo synthesized gangliosides corresponded to those present in the respective cells.
Pronounced binding of ¹²⁵I-labelled toxin was only detectable in tissues containing long-chain gangliosides (ganglioside C which represents GDIb and GTI).
Accordingly, hybrid (neuroblastoma x glioma) cells, due to their lack of long-chain gangliosides, bound just-discernible amounts of labelled toxin. When previously exposed to gangliosides, their binding of tetanus toxin tremendously increased.
It was concluded that only the long-chain gangliosides in the neuronal cells are functionally involved in the binding of the tetanus toxin and that these acceptors of tetanus toxin can be transplanted.