[Efficacy and side effects following immunization with Salmonella typhi Vi capsular polysaccharide vaccine]. The feasibility of a school-based VI polysaccharide vaccine mass immunization campaign in Hue City, central Vietnam: streamlining a typhoid fever preventive strategy. Ineffectiveness of an oral killed typhoid vaccine in a field trial. A seven-year field trial of two typhoid vaccines in Guyana. Controlled field trial of a high-dose oral killed typhoid vaccine in India. Typhoid VI: A Less Reactogenic Vaccine Efficacy of a locally produced, Chinese Vi polysaccharide typhoid fever vaccine during six years of follow-up. Controlled field trials of three different oral killed typhoid vaccines in India. Phase 2 Clinical Trial of AttenuatedSalmonella enterica Serovar Typhi Oral Live Vector Vaccine CVD 908-htrA in U.S. Volunteers Safety and immunogenicity of live recombinant Salmonella enterica serovar Typhi Ty21a expressing urease A and B from Helicobacter pylori in human volunteers. LARGE-SCALE FIELD TRIAL OF TY21A LIVE ORAL TYPHOID VACCINE IN ENTERIC-COATED CAPSULE FORMULATION Evaluation of a New Vi Polysaccharide Typhoid Vaccine in Children Aged 2-5 Years The efficacy of a Salmonella typhi Vi conjugate vaccine in two-to-five-year-old children. PROTECTIVE ACTIVITY OF VI CAPSULAR POLYSACCHARIDE VACCINE AGAINST TYPHOID FEVER Effectiveness of oral killed typhoid vaccine. phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers. Efficacy of one or two doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a controlled field trial. Chilean Typhoid Committee. Safety and immunogenicity of a live oral bivalent typhoid fever (Salmonella typhi Ty21a)-cholera (Vibrio cholerae CVD 103-HgR) vaccine in healthy adults.
Efficacy and side effects following the immunization with Salmonella typhi Vi capsular polysaccharide vaccine ( Vi ) were assessed . The diluted solution ( DS ) of Vi was used as placebo .  A total number of 777 children and adults were observed for side effect response . Mild and moderate fever appeared 16.93 % and 0.05 % in Vi group , 15.01 % and 0.03 % in DS group , respectively ( statistically significant ) . Two cases with mild local reaction were observed in Vi group . A total number of 81,506 vaccinees were investigated on the efficacy of Vi vaccine , using positive blood culture of Salmonolla typhi as a diagnostic criterion . The protective rate and index of vaccine were 71.35 % and 3.49 % respectively . If 2 cases of positive Widal 's test were included in , the protective rate would come up to 78.17 % with a protective index 4.85 . Clinical data showed that fever seen in the cases in Vi group was much lower than that of DS group . The systematic and local reaction of Vi vaccine were mild . The vaccine is safe and has high protective rate . It can also decrease the degree of fever with only one single dose as primary immunization . We believe Vi vaccine may serve as a vaccine of new generation to be promoted We report the coverage , safety , and logistics of a school-based typhoid fever immunization campaign that took place in Hue City , central Vietnam ; a typhoid fever endemic area . A cluster-r and omized evaluation-blinded controlled trial was design ed where 68 schools ( cluster ) were r and omly allocated the single dose Vi polysaccharide vaccine ( Typherix ) or the active control hepatitis A vaccine ( Havrix ) . A safety surveillance system was implemented . A total of 32,267 children were immunized with a coverage of 57.5 % . Strong predictors for vaccination were attending primary schools , peri-urban location of the school , and low family income . Human re sources were mainly schoolteachers and the campaign was completed in about 1 month . Most adverse events reported were mild . Safe injection and safe sharp-waste disposal practice s were followed . A typhoid fever school-based immunization campaign was safe and logistically possible . Coverage was moderate and can be interpreted as the minimum that could have been achievable because individual written informed consent procedures were sought for the first time in Hue City and the trial nature of the campaign . The lessons learned , together with cost-effectiveness results to be obtained by the end of follow-up period , will hopefully accelerate the introduction of Vi typhoid fever vaccine in Vietnam A field trial was carried out with a vaccine containing 300x10(9 ) killed S. typhi ( strain Ty58 ) per tablet . A total of 12 564 children aged 1 - 15 years were given 3 tablets of the vaccine or a placebo at the rate of one tablet on each of 3 consecutive days . The results indicated that the vaccine , in its present form and at this dosage , gives no protection Abstract In 1960 about 72,000 Guyanese schoolchildren , aged five to fifteen years , were divided into three similar groups , one of which acted as a control and was given tetanus toxoid , the second was given an acetone-killed typhoid vaccine , and the third a heat-killed-phenolised typhoid vaccine . Two subcutaneous doses of 0.5 ml . of reconstituted vaccines were given five weeks apart . An additional 10,000 children received one dose only . The incidence of typhoid fever , diagnosed by the bacteriological isolation of Salmonella typhi , was followed for seven years after vaccination . In those given two doses , 146 cases of typhoid occurred in the control group and 16 and 49 in the acetone and heat-phenol typhoid vaccine groups , showing protection-rates of 88 % and 65 % , respectively . In those given one dose of vaccine the protection was somewhat greater , 22 cases occurring in the control group and 1 and 4 in the groups given the acetone and heat-phenol vaccines , respectively . Protection showed little diminution until the fifth year after vaccination 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 A typhoid vaccine derived from the purified Vi capsular polysaccharide ( CPS ) antigen of Salmonella typhi was compared with a heat-killed whole-cell typhoid vaccine in 637 healthy male volunteers . The individuals were placed in three groups : group 1 received two doses of heat-killed whole-cell typhoid vaccine , at an interval of 28 days ; group 2 received a single dose of typhoid Vi CPS vaccine followed after 28 days by water for injection ; and group 3 received water for injection on the first occasion and a single dose of typhoid Vi CPS vaccine 28 days later . Local and systemic adverse reactions were recorded for 5 days following each injection . Subjects receiving the typhoid Vi CPS vaccine complained of fewer local adverse reactions on each of the first 3 days following immunization : on day 1 , 18.6 % of subjects given typhoid Vi CPS vaccine reported local reactions compared with 59.7 % of those receiving heat-killed whole-cell vaccine ( P < 0.001 ) . The percentage of subjects receiving the heat-killed whole-cell vaccine who complained of systemic reactions was more than twice that of subjects receiving the Vi CPS vaccine ( 7.9 % and 3.4 % , respectively , on day 1 ; P < 0.01 ) A locally produced Vi polysaccharide vaccine against typhoid fever was licensed in China following two placebo-controlled , efficacy trials conducted in the early 1990s in Baoying , Jiangsu Province , and Quan-zhou , Guangxi Province . The two trials each enrolled over 80,000 participants and followed participants for 12 and 19 months post-vaccination , respectively . To define the long-term efficacy of this vaccine , we retrospectively assessed the occurrence of typhoid fever , diagnosed with clinical and serological criteria , in the two study population s for 6 years following vaccination . During the second year following vaccination , vaccine efficacy was 100 % ( 95 % CI : 17 % , 100 % ) in Baoying and 85 % ( 95 % CI : 49 % , 96 % ) in Quan-zhou . There was suggestive protection ( 51 % ; PE : -95 % , 88 % ) during the third year in Baoying , nearly identical to the level observed in the third year of an earlier trial in South Africa . These results confirm that this vaccine protects for at least 2 years , and are consistent with the assertion that the vaccine protects for at least 3 years Three vaccination trials against typhoid fever were carried out in 1968/69 , 1970/71 and 1974 in New Dehli . The vaccine was generally administered in tablet form on three consecutive days . Each new trial consisted of a larger number of killed bacteria : 100.10(9 ) , then 300.10(9 ) and finally 400.10(9 ) killed S. typhi . The placebo and vaccinated groups were composed of 6,000 to 7,000 persons , sometimes only children from 6 to 17 years . The number of typhoid fever cases which appeared under normal conditions of infection did not show significant difference between the vaccinated and non-vaccinated subjects during the 18 month period of observation ABSTRACT Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens . We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA  in a double-blind , placebo-controlled , crossover study . There were no differences in the rates of side effects among volunteers who received high-dose vaccine ( 4.5 × 108 CFU ) , lower-dose vaccine ( 5 × 107 CFU ) , or placebo in the 21 days after vaccination , although recipients of high-dose vaccine ( 8 % ) had more frequent diarrhea than placebo recipients ( 0 % ) in the first 7 days . Seventy-seven percent and 46 % of recipients of high- and lower-dose vaccines , respectively , briefly excreted vaccine organisms in their stools . All blood cultures were negative . Antibody-secreting cells producing antilipopolysaccharide ( LPS ) immunoglobulin A ( IgA ) were detected in 100 and 92 % of recipients of high- and lower-dose vaccines , respectively . Almost half the volunteers developed serum anti-LPS IgG. Lymphocyte proliferation and gamma interferon production against serovar Typhi antigens occurred in a significant proportion of vaccinees . This phase 2 study supports the further development of CVD 908-htrA as a single-dose vaccine against typhoid fever and as a possible live vector for oral delivery of other vaccine antigens Helicobacter pylori urease was expressed in the common live typhoid vaccine Ty21a yielding Ty21a(pDB1 ) . Nine volunteers received Ty21a(pDB1 ) and three control volunteers received Ty21a .  No serious adverse effects were observed in any of the volunteers . Ten out of 12 volunteers developed humoral immune responses to the Salmonella carrier as detected by antigen-specific antibody-secreting cells but only two volunteers seroconverted . A total of five volunteers showed responses in one or two out of three assays for cellular responses to the carrier ( proliferation , IFN-gamma-secretion , IFN-gamma-ELISPOT ) . Three of the volunteers that had received Ty21a(pDB1 ) showed a weak but significant T-cell response to Helicobacter urease , while no volunteer had detectable humoral responses to urease . Ty21a(pDB1 ) is a suitable prototype to optimize Salmonella-based vaccination for efficient cellular responses that could mediate protective immunity against Helicobacter Three doses , given within one week , of Ty21a attenuated Salmonella typhi oral vaccine in an enteric-coated formulation provided 67 % efficacy for at least 3 years in a r and omised , placebo-controlled field trial involving 109,000 schoolchildren in Santiago , Chile . Increasing the interval between doses to twenty-one days did not enhance protection . Significantly less protection followed administration of vaccine in gelatin capsules with sodium bicarbonate . Ty21a provides the same level of protection as the heat/phenol-inactivated whole cell parenteral vaccine but differs in not causing adverse reactions .  Ty21a may now be regarded as a practical public health tool Typhoid fever is a major cause of morbidity and mortality in many parts of the world . In view of the increasing resistance of Salmonella typhi against antibiotics and the high costs associated with improving sanitation conditions , vaccination programs would be of great benefit . We report on the evaluation of a new c and i date VI ( sic ) polysaccharide typhoid vaccine ( TypheriX ™ (sic),2 SmithKline Beecham Biologicals ) tested in Filipino children aged 2 - 5 years where the profile was compared with that of a  competitor-vaccine ( Typhim ™ (sic ) , Pasteur Merieux Connaught).Vaccination with the new c and i date vaccine was followed by fewer general symptoms ( 2.9 % ) than with the competitor vaccine ( 14.1 % ) , particularly with lower incidence of fever . The new c and i date vaccine is also highly immunogenic : > 99 % of the vaccinees were immune 28 days post vaccination with comparable GMTs of 3597 EL.U/ml for TypheriX ™ (sic ) and 3365 EL.U/ml for Typhim ™ (sic).This trial shows that the available VI ( sic ) polysaccharide vaccines provide a reliable means in preventing a disease responsible for a significant morbidity and placing a heavy burden on health budgets BACKGROUND Typhoid fever is common in developing countries . The licensed typhoid vaccines confer only about 70 percent immunity , do not protect young children , and are not used for routine vaccination . A newly devised conjugate of the capsular polysaccharide of Salmonella typhi , Vi , bound to nontoxic recombinant Pseudomonas aeruginosa exotoxin A ( rEPA ) , has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old . METHODS In a double-blind , r and omized trial , we evaluated the safety , immunogenicity , and efficacy of the Vi-rEPA vaccine in children two to five years old in 16 communes in Dong Thap Province , Vietnam . Each of the 11,091 children received two injections six weeks apart of either Vi-rEPA or a saline placebo . Cases of typhoid , diagnosed by the isolation of S. typhi from blood cultures after 3 or more days of fever ( a temperature of 37.5 degrees C or higher ) , were identified by active surveillance over a period of 27 months . We estimated efficacy by comparing the attack rate of typhoid in the vaccine group with that in the placebo group . RESULTS S. typhi was isolated from 4 of the 5525 children who were fully vaccinated with Vi-rEPA and from 47 of the 5566 children who received both injections of placebo ( efficacy , 91.5 percent ; 95 percent confidence interval , 77.1 to 96.6 ; P<0.001 ) . Among the 771 children who received only one injection , there was 1 case of typhoid in the vaccine group and 8 cases in the placebo group . Cases were distributed evenly among all age groups and throughout the study period . No serious adverse reactions were observed . In all 36 children studied four weeks after the second injection of the vaccine , levels of serum IgG Vi antibodies had increased by a factor of 10 or more . CONCLUSIONS The Vi-rEPA conjugate typhoid vaccine is safe and immunogenic and has more than 90 percent efficacy in children two to five years old . The antibody responses and the efficacy suggest that this vaccine should be at least as protective in persons who are more than five years old The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide ( CPS ) was assessed in a r and omised double-blind controlled trial . Vaccination of 11,384 children was followed by 21 months ' surveillance . 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine  and 19 cases in those vaccinated with Vi CPS .  Protective efficacy was 60 % calculated from the day of vaccination and 64 % from 6 weeks after vaccination . Surveillance also included 11,691 unvaccinated children ; 173 cases occurred in this group .  Protective efficacy in relation to the unvaccinated group was 77.4 % and 81.0 % after 21 months , calculated immediately and 6 weeks after vaccination , respectively . Vaccination was associated with minimum local side-effects , and an increase in anti-Vi antibodies occurred , as measured by radioimmunoassay and enzyme-linked immunosorbent assay . Antibody levels remained significantly raised at 6 and 12 months post vaccination . Vi CPS is thus a safe and effective means of typhoid vaccination A controlled field trial of oral killed typhoid vaccine was carried out in Delhi , India in 1968 - 69 . Altogether , 13 374 children below the age of 17 years were included in the study . Two comparable groups of children were given either placebo or vaccine . Each tablet of vaccine contained 100x10(9 ) killed Salmonella typhi , and 3 tablets of vaccine or placebo were administered to each child . The vaccinated subjects were followed up from 10 June 1968 to 31 August 1969 . The effectiveness of the vaccine was measured by comparing the incidence of typhoid fever ( based only on bacteriologically positive cases ) in the two groups . It was found that the difference in incidence of the disease in the two groups was not statistically significant . The oral killed typhoid vaccine in the dosage schedule used in the present trial was found not to be effective against the disease The phoP/phoQ virulence regulatory genes of Salmonella typhi Ty2 were deleted , and the result ant strain ( Ty800 ) was tested as a live attenuated typhoid fever vaccine in human volunteers . Groups of 2 or 3 subjects received single oral doses of 10(7 ) , 10(8 ) , 10(9 ) , or 10(10 ) cfu . Two volunteers who received the largest dose had self-limited side effects ; no bacteremias were detected . Ten of 11 subjects had evidence of intestinal immune responses to the vaccine as measured by increases in S. typhi lipopolysaccharide-specific IgA-secreting cells in peripheral blood sample s. Humoral immune responses were measured and compared with those of control vaccinees who received 4 oral doses of S. typhi Ty21a . In the most sensitive assays , 9 of 11 volunteers and 5 of 8 Ty21a control vaccinees had evidence of IgG directed against S. typhi antigens . Ty800 is safe , and single oral doses are highly immunogenic in humans Typhoid fever remains an important public health problem in many areas of the world and an effective , non-reactogenic vaccine would be useful to control this disease . An attenuated Salmonella typhi strain ( Ty21a ) , which has shown promise in previous trials , was evaluated in a controlled field trial in Santiago , Chile . In this trial , 82,543 schoolchildren were r and omly assigned to receive one or two doses of Ty21a vaccine in enteric-coated capsules or placebo . The enteric-coated vaccine formulation was well tolerated and practical for mass oral immunization . In the first two years of surveillance , 213 cases of bacteriologically-confirmed typhoid fever were found in schoolchildren participating in the trial ; annual rates in the placebo group were 139 and 227 per 100,000 . Vaccine efficacy in the first two years after vaccination was 59 % for two doses and 29 % for one dose ; no efficacy was found 3 - 5 years after vaccination . These results indicate that it will be necessary to identify a vaccine formulation and schedule for Ty21a S. typhi that is practical and provides high level protection for greater than 2 years The safety and immunogenicity of the live oral attenuated vaccine strains vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a were evaluated alone or in a combined bivalent formulation in four groups composed of 185 healthy European adults . All presentations were well tolerated . The serum anti-S. typhi lipopolysaccharide immunoglobulin G and immunoglobulin A antibody responses were comparable for all groups ( 66 to 72 % seroconversion ) . The serum vibriocidal antibody seroconversion rate ranged from 78 to 92.5 % ( P > 0.05 ) among the groups . However , the peak and geometric mean vibriocidal antibody titers were significantly higher ( P < 0.005 ) in the groups which received the bivalent formulation along with two doses of Ty21a than in the group which received CVD 103-HgR followed by two doses of killed Escherichia coli K-12 placebo . The ingestion of a placebo shortly after CVD 103-HgR may have suppressed the magnitude of the immune response . These findings demonstrate the feasibility of producing multivalent live oral attenuated vaccines
BACKGROUND Two typhoid vaccines are commercially available , Ty21a ( oral ) and Vi polysaccharide ( parenteral ) , but neither is used routinely .
Other vaccines , such as a new modified , conjugated Vi vaccine called Vi-rEPA , are in development .
OBJECTIVES To evaluate vaccines for preventing typhoid fever .