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Combined typhoid fever and hepatitis A vaccine: comparison of immunogenicity and safety to concomitant monovalent vaccine over 3 years.

BACKGROUND: The safety and immunogenicity of Viatim, a combined hepatitis A (HA) and typhoid fever (Vi) vaccine, were compared with the monovalent component vaccines up to and 1 month after a booster dose at 3 years. METHODS: Healthy, adult volunteers were randomized to receive Viatim (group A, n = 179) or separate HA and Vi vaccines (group B, n = 181); subgroups were boosted after 3 years with Viatim (groups C and D, n = 56 and 46, respectively). Local and systemic reactions were recorded for 28 days postvaccination. Seroconversion and seroprotection rates and geometric mean antibody concentrations were measured at 14 and 28 days, 1, 2, and 3 years postvaccination, and 28 days after the booster dose. RESULTS: Local and systemic safety profiles were equivalent between the two groups. Immediate local reactions were infrequent (1 in group A and 2 in group B). Local reactions, consisting mostly of mild or moderate pain, were least frequent with monovalent HA. Antibody concentrations to both antigens were similar in groups A and B, in which HA seroprotection rates (> or = 20 mIU/mL) were respectively, 98.7% and 100% at day 28, and 99.1% and 99.0% after 3 years, achieving 100% after the booster. Vi seroprotection rates (> or = 1 microg/mL) of 85.2% and 84.9% after 28 days fell to 32.1% and 35.6% after 3 years, increasing to 67.3% and 69.8% after the booster dose. CONCLUSIONS: The combined HA/Vi vaccine, Viatim, had equivalent tolerability and safety and was as rapidly immunogenic as its component monovalent vaccines when given concurrently. A booster dose after 3 years significantly increased antibody levels with some evidence of relative hyporesponsiveness of the typhoid response.

Adolescent↗

[Immunological indices in the digestive tract secretions in subcutaneous and oral vaccination against typhoid fever].

Volunteers were vaccinated subcutaneously and orally against typhoid fever; a determination was made of immunological reactions in the digestive tract secretions. Oral vaccination caused a much greater production of the secretory IgA than the subcutaneous one. Immunoglobulins of classes G and M were revealed in the intestinal contents only in a few volunteers. In studying the coprofiltrates obtained before the vaccination there was shown for the first time the presence of normal coproantibodies to typhoid fever, dysentery, tetanus, diphteria, botulism and gas gangrene; in the majority of the cases there was found a correlation between the presence of normal serum and secretory antibodies. Subcutaneous and oral vaccination caused an increase of coproantibodies specific for the vaccines used. Besides, the same vaccines stimulated the nonspecific response expressed in a rise of the level of other species of antibodies. Specificity of coproantibodies in the inhibitary passive hemagglutination reaction was demonstrated in the majority of the coprofiltrates examined.

Administration, Oral↗

[Further research on an experimental justification for the emergency prophylaxis of typhoid].

Experiments were conducted on mice. A possibility was demonstrated of express prophylaxis of typhoid fever by subcutanoues injection of the vaccine and by oral administration of sodium nucleinate, of lowering the dose by half and replacement of revaccination by sodium nucleinate alone. An increase in the titre of typhoid agglutinins and of preventive activity of the blood serum was revealed on volunteers.

Administration, Oral↗

Efficacy of purified Vi polysaccharide typhoid vaccine.

This experiment was conducted to assess the efficacy of typhoid vaccine newly produced by purifying Vi antigen of Salmonella typhi. With Karber method, LD50 of challenging organism (S. typhi ty2) was determined as 6.31 CFU/mouse, and then the organism was used for the study. With Probits method, ED50 of the vaccine was determined as 0.016 microg / 0.5 ml / mouse. The ELISA titer (0.5097+/-0.0606) was 4 times in the group treated with high dose (0.25 microg/0.5ml) as in control (0.1113+/-0.0110). Six major protein bands of 66, 55, 35, 33, 18, and 9 kd were detected in Western blot analysis with serum of a vaccine treated mouse, whereas only one weak band of about 35 kd was detected with serum of a control mouse. We concluded that typhoid vaccine produced by purifying Vi antigen of S. typhi very effectively prevent S. typhi infection in mice.

Animals↗

Laboratory diagnosis of typhoid fever with notes on treatment.

As indicated by a study of 41 cases of typhoid fever treated in three years, blood culture alone is often sufficient for the diagnosis of the disease if a large (30 cc.) specimen is used. Demonstration of the organism is the only completely diagnostic measure, but this was also achieved by the Widal reaction, by fecal or urine culture, or by aspirated bile culture, which in one case gave the only positive response. Chloramphenicol is the drug of choice in treating typhoid fever. Since only 25 per cent of patients develop immunity, immunizing injections should be started a week after therapy is discontinued.

Adult↗

Laboratory tests of typhoid vaccines used in a controlled field study.

In 1954-55, a controlled field trial of two types of typhoid vaccine-alcoholized ("vaccine A") and phenolized ("vaccine F")-prepared in Yugoslavia was carried out in the town and district of Osijek. In an attempt to correlate the protection conferred on man by these vaccines with their potency in laboratory animals, arrangements were made for laboratory tests to be performed jointly by the Central Institute of Hygiene, Zagreb, Yugoslavia; the Lister Institute of Preventive Medicine, Elstree, Herts, England; and the Walter Reed Army Institute of Research (WRAIR), Washington, D.C., USA. In this paper, the results of the WRAIR tests are presented.The potency relationship between vaccine A and vaccine F was found to vary with the type of test performed. According to active-immunization tests in mice, using either mucin or saline challenge, vaccine A was more potent than vaccine F, as it proved also in the passive immunization of mice with saline challenge and in Vi-antibody production in rabbits. As judged by the results of the passive immunization of mice with mucin challenge and of O-antibody production in rabbits, there was, however, no clear-cut difference in potency between the two vaccines. And, as indicated by H-antibody production in rabbits, vaccine F was clearly superior to vaccine A. Since vaccine F was also the more effective in man, the last-mentioned findings are of considerable interest, suggesting that the H antigen may be more, and the Vi antigen less, important in protecting man against typhoid fever than is currently considered to be the case.

Animals↗

A report on the laboratory assays carried out at the Lister Institute of Preventive Medicine on the typhoid vaccines used in the field study in Yugoslavia.

The results of the laboratory assays of the Yugoslav typhoid vaccines used in the field trials at Osijek are disappointing when compared with the results of the field trials.The tests carried out at the Lister Institute in England, the Central Institute of Hygiene in Zagreb, Yugoslavia, and the Walter Reed Army Institute of Research in the USA indicate that, except for the agglutination tests for H antigen, there is little or no demonstrable difference in the potency of the two Yugoslav vaccines in either active immunization tests or passive protection tests.Although only a relatively small number of assays were carried out using the intracerebral route of challenge, the results indicate that there is no advantage in this method over the more usual intraperitoneal route. Since there was a difference between the potency of the vaccines in the field trails, it must be concluded that the mouse is not a suitable animal for typhoid assay or that the proper way of testing the mouse has not yet been found. The great variation in detail in nominally identical tests made in different laboratories and the differences in the results emphasizes the essential importance of at least one common assay, identical in detail between collaborating laboratories, in a study of this kind.

Agglutination Tests↗

A CONTROLLED FIELD TRIAL OF ACETONE-DRIED AND INACTIVATED AND HEAT-PHENOL-INACTIVED TYPHOID VACCINES IN BRITISH GUIANA.

In 1960, some 72 000 schoolchildren in British Guiana participated in a controlled field trial of typhoid fever vaccines that was supported in part by the World Health Organization. The children were divided into three groups each receiving two doses, one of acetone-dried and inactivated vaccine, the second of heat-phenol-inactivated vaccine, and the third (control group) of tetanus toxoid. They were followed up over 3 1/2 years, during which time 99 cases of typhoid fever occurred in the control group, 6 in the acetone-dried vaccine group, and 26 in the heat-phenol vaccine group. Attack rates of the same order of magnitude were observed among 10 000 other children divided into the same three groups but given only one inoculation.The vaccines used were the same as those tested in a similar trial in Yugoslavia, and, although the attack rates in British Guiana were considerably lower in all groups than those in Yugoslavia, the findings in the two trials are in general agreement and indicate that acetone-dried vaccine confers greater protection than vaccine prepared from the same strains but inactivated by heat-phenol.

Accident Prevention↗

An unusual case of Behçet's syndrome: triggered by typhoid vaccination?

A case of Behçet's syndrome in a 32-year-old woman occurring shortly after her third vaccination against typhoid fever is described. Scleritis and pyoderma gangrenosum were unusual manifestations of BS that occurred in this case. Treatment benefit was provided by mycophenolate mofetil and etanercept. As bacterial antigens have been proposed as potential triggers for the onset of BS, it is possible that the syndrome was precipitated by typhoid vaccination in this patient.

Adult↗

[Application of cluster randomization method on typhoid Vi vaccine trails].

OBJECTIVE: To describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation. METHODS: Simple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine. RESULTS: According to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced. CONCLUSION: Confounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.

Adolescent↗

Antityphoid and antitetanic intradermal vaccination of chronic neuropsychic patients in a typhoid fever outbreak.

Intradermal immunization of 229 chronic neuropsychic patients in Gura Ocnitzei Sanatorium, Dîmbovitza County, where a typhoid fever outbreak burst, was performed with a freeze-dried typhoid vaccine, suspended in purified and concentrated tetanic anatoxin. Adverse reactions were minimal and immunologic response, evaluated by laboratory tests, was good, reaching the level of that obtained as a result of classic vaccination methods (subcutaneous antityphoid and intramuscular anti-tetanic). Both after vaccination and also booster O and H agglutinating titers increased 4-7 times and anti-S. typhi. seroprotecting effect reached and maintained a high level. Moreover, antityphoid vaccination permitted epidemic focus limiting and its complete extinguishing after booster. Antitetanic vaccination resulted in protecting titers settlement (greater than or equal to 0.01 IU/ml) in all previously non-protected persons (1/3 of all subjects) and in the increase of protecting titers, existing before vaccination in the other persons.

Adult↗

[The effect of immunostimulants on the resistance of white mice to the causative agent of typhoid fever].

The influence of prodigiosan, salmosan, polyribonate and levamisole on the body nonspecific and specific resistance to S. typhi strain 4446 has been studied. Prodigiosan and salmosan have proved to be the most effective. The injection of these compounds simultaneously with typhoid vaccine (both chemical adsorbed vaccine and alcohol-treated vaccine, enriched with Vi-antigen) significantly increases the survival rate of immunized animals (by 35-45%), elevates the resistance index (1.5- to 2.3-fold) and the effectiveness index of the vaccine (17- to 32-fold) in comparison with the controls. Besides, prodigiosan and salmosan alone are capable of increasing nonspecific resistance to S. typhi strain 4446, which is manifested by an increase of the survival rate of stimulated animals by 61.87%. Proceeding from the results thus obtained, the possibility of good prospects for prodigiosan and salmosan in the prophylaxis of typhoid fever in humans may be inferred.

Adjuvants, Immunologic↗

Controlled field trial of a high-dose oral killed typhoid vaccine in India.

A controlled field trial of a modified vaccine containing Salmonella typhi, TY 2 strain, in a dose of 400 x 10(9) killed organisms per capsule, was carried out in schoolchildren aged 6-17 years. The children were followed up for 6-8 months. There were 66 cases of typhoid fever in the vaccine group (7312 children) and 54 in the control group (7292 children who had received a placebo). This difference is not statistically significant. The results confirm that, as found in earlier trials, oral typhoid vaccine, in the dosages used so far, gives no protection.

Administration, Oral↗

Reactions and serologic responses to monovalent acetone-inactivated typhoid vaccine and heat-killed TAB when given by jet injection.

Monovalent acetone-inactivated typhoid vaccine and heat-killed TAB caused local reactions in 82-88% of volunteers vaccinated by jet injection, whereas they caused local reactions in only 24% of volunteers injected by means of a conventional syringe. Both vaccines induced a high seroconversion rate to typhoid H antigen, but neither proved significantly immunogenic to antigens O and Vi. There was no increase in the occurrence of local reactions when a second jet injection was given 5 weeks after the first.

Adult↗

[Immunogenic and antigenic properties of continuously cultured typhoid bacteria].

It was shown that in continuous cultivation of typhoid bacilli, by changing the rate of dilution and the regimens of carbohydrate and oxygen supply it was possible to determine conditions under which the most highly immunogenic vaccines were obtained and the maximal synthesis of antigens was observed. The regimen optimal for obtaining the highly immunogenic typhoid vaccines (D = 0.4 h-1; So = 5 g/l; pO2 = 50%) coincided with the regimen at which the maximal O-antigen synthesis was seen, and failed to coincide with the regimens necessary for the greatest synthesis of Vi- and H-antigens.

Animals↗

[Experience with the autovaccinal treatment of chronic carriers of typhoid bacteria].

Considering bacterial carriership as a special form of typhoid infection inducing the allergic transformation of the body with the development of delayed type hypersensitivity and believing that vaccinal therapy might be the most promising method for treating the states of this kind, the authors used autovaccine, introduced by the method of epicutaneous electrophoresis in accordance with Alisov's scheme, for the treatment of chronic carriers of typhoid bacteria. The subsequent prolonged (up to 20 years) observation of the carriers revealed that the release of the infective agents became less intensive and the number of persistent carriers decreased 2.5 times as compared with the control group of carriers treated with antibiotics and roborants. The results of the study of morphological changes occurring in the mucous membrane of the small intestine of the carriers indicated that after complex treatment the inflammatory process decreased and in some carriers disappeared.

Adolescent↗

Efficacy of a live oral typhoid vaccine in human volunteers.

A live oral attenuated vaccine, lacking the enzyme epimerase, has been given with complete safety to 173 men. Two preparations of the vaccine, one with and one without galactose in the initial culture media, led to somewhat differing results. Vaccine A, prepared with galactose, was more readily identified in the stool specimens of its recipients and was more likely to provoke an O antibody response than was vaccine B. Furthermore, the clinical protection from typhoid fever was significant in the vaccine A group, whereas not so with the vaccine B counterpart. The protection afforded by vaccine A exceeds that of any of our previous candidate strains. It is perhaps not presumptuous to imagine that such a vaccine would be equally effective in an area endemic for typhoid fever, where the vaccine might act as a booster effect in a previously exposed population. Remaining questions to be answered include the duration of the protection, and the efficacy of a lyophilized preparation.

Administration, Oral↗