Original Article
The Efficacy of a Salmonella typhi Vi Conjugate Vaccine in Two-to-Five-Year-Old Children
N Engl J Med 2001; 344:1263-1269April 26, 2001
- Abstract
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, randomized 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°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 percent; 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.
Media in This Article
Table 1
Characteristics of the Children in the Vaccine and Placebo Groups.Table 2
Local Reactions and Fever after the Injections of Vi-rEPA Conjugate Vaccine and Saline Placebo.Article Activity
- Article
In developing countries, typhoid fever is common, serious, and increasingly difficult to treat because of the increasing resistance of Salmonella typhi to antibiotics.1-5 Typhoid fever was once thought to occur primarily in older children and young adults. In children younger than five years of age, typhoid fever was often unrecognized, because of atypical clinical symptoms, difficulties in drawing blood, and the use of culture mediums that were less than optimal.6-8 In a population-based study of three communes in Dong Thap Province in Vietnam, the annual attack rate for typhoid fever was highest among children younger than 15 years of age: it was 413 cases per 100,000 in this age group, and 358 per 100,000 among children 2 to 4 years old.9 Similar findings have been reported in other parts of Southeast Asia.10-12
Unfortunately, it is unlikely that the drinking water and foodstuffs in many developing countries, especially in rural areas, will become safe in the near future.1,5,13 No program to control the spread of typhoid fever by routine vaccination has been adopted, because of the limitations of the three licensed vaccines (parenteral inactivated whole-cell vaccines, oral attenuated S. typhi Ty21a vaccine, and parenteral Vi polysaccharide vaccine). These vaccines confer only about 70 percent protection in older children and adults and do not protect young children.1,14-17
The capsular polysaccharide of S. typhi, Vi, is both an essential virulence factor and a protective antigen.18,19 Like most polysaccharide vaccines, the Vi vaccine does not induce either protective levels of antibodies in young children or a booster response.19-21 To overcome the limitations of the age-related and T-cell–independent immunogenicity of the vaccine, the same strategy was used as for the Haemophilus influenzae type b polysaccharide vaccine.22,23 Vi was bound to a nontoxic recombinant protein that is antigenically identical to Pseudomonas aeruginosa exotoxin A (rEPA).24-28 In initial trials, the resultant conjugate (Vi-rEPA) both enhanced the immunogenicity of Vi and gave it T-cell–dependent properties.27,28 Vi-rEPA elicited a booster response in children 2 to 4 years old, whose levels of IgG Vi antibody were approximately three times as high as those elicited by Vi in children 5 to 14 years old.28 None of the vaccinated children had a temperature higher than 38.5°C or an area of swelling that was more than 2.5 cm in diameter after receiving an injection. On the basis of these results, we initiated a double-blind, randomized trial to determine the efficacy of Vi-rEPA in Vietnamese children two to five years old — an age group for which there is not yet an effective typhoid vaccine.
Methods
Study Design
The study protocol was approved by the institutional review boards of the U.S. National Institute of Child Health and Human Development, National Institutes of Health, the Ministry of Health in Vietnam, and the Center for Biologics Evaluation and Research of the U.S. Food and Drug Administration, and the study was assigned a Single Project Assurance Number by the Office for Human Research Protections of the U.S. Department of Health and Human Services.
In November 1997, a census of 16 communes in the Cao Lânh District of Dong Thap Province in the Mekong Delta of Vietnam identified 14,285 children who were two to five years old. Almost all the households in the district rely on rivers and rain as their sources of water. Approximately 95 percent of the population of the district is engaged in agricultural activities. Cao Lânh District is served by the Dong Thap Provincial Hospital, and each commune (with a population of 5000 to 20,000) has a health center with a physician, assistant physicians, nurses, and approximately 20 community health workers.
Enrollment of Children
Informed consent for the enrollment of 13,776 children (96.4 percent of the two-to-five-year-old children in the district) was obtained from their parents or guardians during group meetings or home visits conducted by the health workers. Children with illnesses that required ongoing medical care were excluded. A unique seven-digit identification number was assigned to each enrolled child.
Vaccine
Vi-rEPA was prepared with Vi (lot 126A, Aventis Pasteur, Lyons, France) and rEPA and characterized as described previously.27-29 Each dose of Vi-rEPA conjugate contained 22.5 μg of Vi and 22 μg of rEPA in 0.5 ml of phosphate-buffered saline containing 0.01 percent thimerosal; its appearance was indistinguishable from that of the saline placebo. The five-dose vials, each containing 2.8 ml of Vi-rEPA or placebo, were labeled on a random basis with a number from 0 through 9, packaged 10 per box, and stored at 4°C. The code, kept by the Department of Pharmacy of the National Institutes of Health Clinical Center and by the chairman of the safety monitoring committee in Ho Chi Minh City, was broken on June 23, 2000.
Injection Protocol
Two rounds of injections were conducted in 1998, the first from February 21 through March 8 and the second from April 4 through April 20. The injections were administered by 64 teams. Each child was injected twice approximately six weeks apart, each time with 0.5 ml from a vial with a number identical to the last digit of his or her identification number. Before receiving the injection, the children were examined by the health staff, and their axillary temperatures were measured. Those with no fever (a temperature of less than 37.5°C) received injections in the left deltoid muscle, and the vial number was recorded. The children were observed for 20 minutes; 6, 24, and 48 hours after the injection, a community health worker measured body temperature and inspected the injection site.
Detection of Cases
The diagnosis of typhoid fever was made only when S. typhi was isolated from a blood culture. Children were visited weekly by a community health worker, at which time their history was taken and their axillary temperature was measured. Children who had a fever (a temperature of 37.5°C or higher) for at least three days were referred to the health station, and 6 ml of blood was drawn; 5 ml of this blood was transferred to a blood-culture bottle (DIFCO, Detroit), and 1 ml was used for serologic testing. Blood cultures were maintained at 37°C, and the clotted blood was maintained at refrigerator temperature (4° to 8°C); the samples were brought to the provincial hospital on the day they were obtained. Cultures were checked after one, two, and seven days, and S. typhi was identified by established biochemical and serologic assays at the microbiology laboratory of the provincial hospital and at the Clinical Microbiology Department of the National Institutes of Health. All isolates were also verified for Vi by the antiserum agar technique at the National Institute of Child Health and Human Development. There were no discrepancies in the results from the three laboratories.30
To detect any additional cases of typhoid fever, we reviewed the bacteriologic records of the provincial hospital and the district hospital, which is located just south of the Cao Lânh District; no additional cases were found. The study ended on May 31, 2000, 27 months after the first injection had been administered.
Immunogenicity and Persistence of Vaccine-Induced IgG Vi Antibodies
Paired serum samples were obtained from 76 children before the first injection and four weeks after the second injection. To evaluate the duration of vaccine-induced Vi antibodies, a 2-ml blood sample was obtained from four randomly selected vaccinated children in each commune each month after the second injection. Serum IgG Vi antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) and expressed in ELISA units relative to a standard arbitrarily assigned a value of 100 units.28
Statistical Analysis
The efficacy of the vaccine was calculated with the following equation: (1 – [attack rate in the vaccine group ÷ attack rate in the placebo group]) ×100 percent. Confidence limits were calculated by the method of Miettinen and Nurminen.31 The chi-square test or, when appropriate, Fisher's exact test was used for the comparison of categorical variables. Logarithms of the antibody concentrations were used in all calculations. Antibody levels were expressed as geometric means, with 25th and 75th percentiles. Comparisons of geometric means were performed with the unpaired or paired t-test.
Results
Characteristics of the Study Participants
A total of 12,008 children received at least one injection (Table 1Table 1
Characteristics of the Children in the Vaccine and Placebo Groups.); 11,091 (92.4 percent) received two injections from vials that were correctly labeled (5525 in the vaccine group and 5566 in the placebo group); 771 (6.4 percent) received one injection (388 in the vaccine group and 383 in the placebo group); and 146 (1.2 percent) were injected from a vial with an incorrect code (78 in the vaccine group and 68 in the placebo group). The sex, age at vaccination, household composition and size, and interval between the two injections were similar in the vaccine group and the placebo group. The interval between the two injections ranged from 28 to 57 days (median, 42).Adverse Reactions
No serious adverse reactions were noted (Table 2Table 2
Local Reactions and Fever after the Injections of Vi-rEPA Conjugate Vaccine and Saline Placebo.). The highest temperature and maximal local reaction recorded for each participant (from the values recorded at 6, 24, and 48 hours) were used for analysis. After the first injection, 113 children had a temperature of 37.5°C or higher — 81 in the vaccine group and 32 in the placebo group (P<0.001). Of the children with a temperature of 39.0°C or higher, 17 were in the vaccine group and 5 were in the placebo group (P=0.01). None of the children had erythema or swelling at the infection site of 5 cm or more in diameter.After the second injection, a temperature of 37.5°C or higher was recorded for 109 children in the vaccine group and 25 children in the placebo group (P<0.001). One child in the vaccine group and one in the placebo group had a temperature of 39.0°C or higher. Swelling of more than 5 cm in diameter was noted in 20 children in the vaccine group, as compared with 1 in the placebo group (P<0.001). Erythema of 5 cm or more without swelling was noted in two children in the vaccine group and none in the placebo group. None of these reactions persisted for more than 48 hours after the injection.
Vaccine Efficacy
During the surveillance period (March 8, 1998, through May 31, 2000), 2335 blood cultures were obtained — 1121 from children in the vaccine group and 1214 from children in the placebo group. S. typhi was isolated from 61 children (34 boys and 27 girls) representing all the communes (Table 3Table 3
Efficacy of Vi-rEPA Conjugate Vaccine.). The number of cases of typhoid fever in each commune ranged from one to nine (median, four).Among the 11,091 children who received two injections from vials with correct codes, there were 4 cases of typhoid fever in children in the vaccine group and 47 in children in the placebo group (efficacy, 91.5 percent; 95 percent confidence interval, 77.1 to 96.6). In the placebo group, one additional child had typhoid fever after receiving two injections of placebo from incorrectly labeled vials.
Of the 771 children who received only one correctly labeled injection each, 1 child had typhoid fever 42 days after injection with Vi-rEPA and 8 children in the placebo group had typhoid fever at various times during the study period (vaccine efficacy, 87.7 percent). In total, there were 5 cases of typhoid fever in the vaccine group and 56 in the placebo group (efficacy, 91.1 percent; 95 percent confidence interval, 78.6 to 96.5). The cases in both groups were distributed evenly across the range of ages. Among the children in the vaccine group, there were two cases of typhoid fever during the first year after the second injection and three cases during the second year.
Among the 61 children with typhoid fever, 21 children (34.4 percent) were hospitalized for an average of 13 days (median, 12; range, 7 to 24); all of the hospitalized children were in the placebo group (21 of 56, vs. 0 of 5 in the vaccine group; P=0.22).
A total of 339 children (165 in the vaccine group and 174 in the placebo group) were lost to follow-up (3.1 percent): 308 moved out of the study area, 2 withdrew from the study, and 29 (12 in the vaccine group and 17 in the placebo group) died from drowning (19 children), dengue fever (3), pneumonia (2), the Stevens–Johnson syndrome (2), burns (1), a foreign body in the airway (1), or leukemia (1). No death was attributed to the vaccine or to typhoid fever. There were four isolates of Salmonella paratyphi A — one from a child in the vaccine group and three from children in the placebo group.
Serum IgG Vi Antibodies before the First Injection and Four Weeks after the Second Injection
A total of 76 paired serum samples were obtained from children before their first injection and four weeks after their second injection. There was no significant difference between the levels of IgG Vi antibodies before the first injection in the two groups, nor was there a significant difference between the level before the first injection and the level four weeks after the second injection in the placebo group (Table 4Table 4
Serum IgG Vi Antibody Levels before the First Injection and Four Weeks after the Second Injection.). In the group that received Vi-rEPA, in contrast, the level of IgG Vi antibodies increased by a factor of more than 575 (P<0.001); in 100 percent of the children in the vaccine group the level increased by a factor of at least 10.Persistence of Vaccine-Induced IgG Vi Antibodies
Blood samples were obtained each month from four randomly selected children in each commune; only those obtained before the first injection and six months, one year, and two years after the second injection are represented in Table 5Table 5
Persistence of Serum IgG Vi Antibodies in Children Who Received Two Injections, According to Age at the Time of Injections.. The levels of IgG Vi antibodies before the first injection were similar in the vaccine group and the placebo group. Six months after the second injection, the IgG Vi antibody level in the children in the vaccine group was 22.5 ELISA units, or approximately 35 times as high as that in the children in the placebo group (P< 0.001). The level of vaccine-induced IgG Vi antibodies decreased from 22.5 ELISA units at six months to 10.7 ELISA units at two years; this level was approximately 19 times as high as that among the children in the placebo group (10.7 vs. 0.57, P<0.001). Over the two-year period, the IgG Vi antibody level in the placebo group increased from 0.15 to 0.57 ELISA unit (P<0.001).A tendency toward age-related immunogenicity and the persistence of IgG Vi antibodies was observed when the vaccinated children were stratified into two age groups — two to three years old and four to five years old. The children four to five years old had a higher level of IgG Vi antibodies at all three time points after immunization, but these differences were not statistically significant. There was a smaller decline in the level of IgG Vi antibodies between six months and two years among the children four to five years old (26.7 percent) than among the children two to three years old (59.1 percent) (P=0.32).
Levels of Serum IgG Vi Antibodies in Vaccinated Patients
Only three serum samples collected at the time of blood culture were available from the four fully vaccinated children with typhoid; the levels of IgG Vi antibodies in the three samples were 4.76, 14.6, and 40.3 ELISA units. There were 37 serum samples from children with typhoid in the placebo group; in these samples, the levels of IgG Vi antibodies ranged from 0.05 ELISA unit to 3.7 ELISA units in 36 samples (geometric mean, 0.41 ELISA unit); one child had a level of 85.8 ELISA units.
Discussion
In this trial the efficacy of Vi-rEPA (91.5 percent) was the highest reported for any typhoid vaccine. The results of this trial also show the efficacy of a typhoid vaccine in young children, for whom no effective vaccine was previously available. The high degree of efficacy was predicted by the immunogenicity of Vi-rEPA in children 2 to 4 years old as compared with that of Vi in adults and in children 5 to 14 years old.28 Since it is the level of serum IgG Vi antibodies induced by a Vi-based vaccine that determines its efficacy, we predict that Vi-rEPA will be at least as protective in older children and adults.32 We are conducting passive surveillance of the participants for another two years to evaluate the duration of protection and the persistence of IgG Vi antibodies induced by Vi-rEPA.
Vi-rEPA was safe. For each type of adverse reaction, we subtracted the number of reactions among children in the placebo group from that in the vaccine group to estimate the rate of adverse reactions attributable to the vaccine. After the first injection, 0.8 percent of the children had a temperature of 37.5°C or higher, and 0.2 percent had a temperature of 39.0°C or higher; these high temperatures were attributable to the vaccine. After the second injection, fever attributable to Vi-rEPA occurred in 1.5 percent of the children, with a temperature of 37.5°C or higher, but none had a temperature of 39.0°C or higher. An area of swelling of 5 cm or more in diameter at the injection site was observed after the second injection in 20 children in the vaccine group, as compared with 1 child in the placebo group. This high degree of safety was also observed in our phase 1 and phase 2 studies of another lot of Vi-rEPA. Both lots of conjugates met the safety requirements of the World Health Organization for Vi polysaccharide vaccine.28,29 These specifications should therefore serve as minimal requirements for future lots of Vi-rEPA.
Our results suggest that the course of illness in the 5 children who received one or two injections of Vi-rEPA and in whom typhoid developed was milder than that in the 56 children with typhoid in the placebo group, because 21 of the latter (37.5 percent) were hospitalized, as compared with none of the former. The higher levels of IgG Vi antibody in the children with typhoid who had been vaccinated with Vi-rEPA, as compared with those in the children who had been injected with placebo, may explain this milder course of disease.
Similar numbers of blood cultures were obtained from children in the vaccine group (1121) and children in the placebo group (1214). Children in the placebo group from whom S. typhi was isolated (from 56 of the 1214 cultures) represent 4.6 percent of the children who had fever for three or more days. But the diagnosis of typhoid on the basis of the results of a single blood culture is not efficient.33-35 Only about 50 percent of typhoid cases identified by culture of the bone marrow are identified by blood culture. The yield of S. typhi from blood cultures is related to the duration of fever: the proportion of children with positive cultures of blood samples obtained after three days of fever was 4.6 percent, as compared with 17.1 percent after seven or more days of fever.9
The unusual structure, molecular size, and physicochemical properties of Vi made the development of Vi-rEPA difficult.24-28,32,36,37 Both the safety and the immunogenicity of Vi-rEPA in this trial were similar to those of a similar product evaluated in phase 1 and phase 2 studies in Vietnam, indicating a consistency in the production of this new vaccine.28 Vi-rEPA-induced levels of IgG Vi antibody declined by a factor of approximately two over two years, but there was no change in the efficacy of the vaccine. On the basis of the antibody level in children two to three years of age two years after vaccination, we estimate that the protective level of Vi-rEPA-induced IgG Vi antibodies is 7 ELISA units or lower. It is likely that Vi-rEPA will be at least 92 percent protective for persons older than five years of age, including military personnel and travelers to areas in which typhoid is endemic.4 Should Vi-rEPA elicit levels of Vi antibody in infants similar to those in children two to five years of age, this typhoid vaccine could be administered as part of the WHO Expanded Program on Immunization.1
Supported in part by a contract with the National Institute of Child Health and Human Development (N01-HD-3269) and by Aventis Pasteur, Lyons, France.
We are indebted to the parents and local leaders of Cao Lânh District, Dong Thap Province, for their support of the program; to Robert Austrian, Robert Chanock, Joan D. Robbins, and Robert Tauxe for their helpful suggestions and comments on the manuscript; to Vee Gill, M.D., of the Clinical Microbiology Department of the National Institutes of Health for help with microbiologic testing; and to the following contributors to this study: Arthur Karpas, Ph.D., Jian Ping Li, Ph.D., Patricia Moyer, B.S., James Trundle, Ph.D., Mya Hlaing, A.B., National Institute of Child Health and Human Development; Luisa Gravelin, George Grimes, Pharmacy Development Branch, Clinical Center, National Institutes of Health; Martha C. Anderson, Center for Biologics Evaluation and Research, Food and Drug Administration; Doan Van Hong, M.D., Director, Health Services of Dong Thap Province; Dong Phi, M.D., Cao Lânh District Health Center; the health staff of the 16 commune health centers, Cao Lânh District Health Center, and Dong Thap Provincial Hospital; and Nguyen Thi Minh Phuong, M.D., and Nguyen Thi My Thanh, Pasteur Institute, Ho Chi Minh City, Vietnam.
Source Information
From the National Institute of Child Health and Human Development (F.Y.C.L., Z.K., D.A.B., J.B.R., R.S., S.C.S.), and the National Institute of Diabetes and Digestive and Kidney Diseases (J.S.), National Institutes of Health, Bethesda, Md.; and Dong Thap Provincial Hospital, Cao Lânh (V.A.H., P.V.B.), the Pasteur Institute, Ho Chi Minh City (H.B.K., T.C.T.), and the National Institute of Hygiene and Epidemiology, Hanoi (D.D.T.) — all in Vietnam.
Address reprint requests to Dr. Lin at the National Institute of Child Health and Human Development, Rm. 7B03, 6100 Executive Blvd., Bethesda, MD 20892-7510, or at link@exchange.nih.gov.
- References
References
1
Ivanoff B ,Levine MM ,Lambert PH . Vaccination against typhoid fever: present status. Bull World Health Organ 1994;72:957-971
Web of Science | Medline2
Bhutta ZA ,Naqvi SH ,Razzaq RA ,Farooqui BJ . Multidrug-resistant typhoid in children: presentation and clinical features. Rev Infect Dis 1991;13:832-836
CrossRef | Medline3
Wain J ,Ho NT ,Chinh NT , et al. Quinolone-resistant Salmonella typhi in Viet Nam: molecular basis of resistance and clinical response to treatment. Clin Infect Dis 1997;25:1404-1410
CrossRef | Web of Science | Medline4
Mermin JH ,Townes JM ,Gerber M ,Dolan N ,Mintz ED ,Tauxe RV . Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med 1998;158:633-638
CrossRef | Web of Science | Medline5
Mermin JH ,Villar R ,Carpenter J , et al. A massive epidemic of multidrug-resistant typhoid fever in Tajikistan associated with consumption of municipal water. J Infect Dis 1999;179:1416-1422
CrossRef | Web of Science | Medline6
Rao PT ,Rao KVK . Typhoid fever in children. Indian J Pediatr 1959;26:258-264
CrossRef | Medline7
Scragg J ,Rubidge C ,Wallace HL . Typhoid fever in African and Indian children in Durban. Arch Dis Child 1969;44:18-28
CrossRef | Web of Science | Medline8
Galloway H ,Clark NS ,Blackhall M . Paediatric aspects of the Aberdeen typhoid outbreak. Arch Dis Child 1966;41:63-68
CrossRef | Web of Science | Medline9
Lin FY ,Ho VA ,Bay PV , et al. The epidemiology of typhoid fever in the Dong Thap Province, Mekong Delta region of Vietnam. Am J Trop Med Hyg 2000;62:642-64610
Thisyakorn U ,Mansuwan P ,Taylor DN . Typhoid and paratyphoid fever in 192 hospitalized children in Thailand. Am J Dis Child 1987;141:862-865
Web of Science | Medline11
Simanjuntak CH ,Paleologo FP ,Punjabi NH , et al. Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet 1991;338:1055-1059
CrossRef | Web of Science | Medline12
Sinha A ,Sazawal S ,Kumar R , et al. Typhoid fever in children aged less than 5 years. Lancet 1999;354:734-737
CrossRef | Web of Science | Medline13
Tarr PE ,Kuppens L ,Jones TC ,Ivanoff B ,Aparin PG ,Heymann DL . Considerations regarding mass vaccination against typhoid fever as an adjunct to sanitation and public health measures: potential use in an epidemic in Tajikistan. Am J Trop Med Hyg 1999;61:163-170
Web of Science | Medline14
Acharya IL ,Lowe CU ,Thapa R , et al. Prevention of typhoid fever in Nepal with the Vi capsular polysaccharide of Salmonella typhi: a preliminary report. N Engl J Med 1987;317:1101-1104
Full Text | Web of Science | Medline15
Klugman KP ,Gilbertson IT ,Koornhof HJ , et al. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet 1987;2:1165-1169
CrossRef | Web of Science | Medline16
Levine MM ,Ferreccio C ,Abrego P ,Martin OS ,Ortiz E ,Cryz S . Duration of efficacy of Ty21a, attenuated Salmonella typhi live oral vaccine. Vaccine 1999;17:Suppl 2:S22-S27
CrossRef | Web of Science | Medline17
Typhoid immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1994;43:1-7
Medline18
Felix A ,Pitt RM . A new antigen of B. typhosus. Lancet 1934;2:186-191
CrossRef | Web of Science19
Robbins JD ,Robbins JB . Re-examination of the protective role of the capsular polysaccharide (Vi antigen) of Salmonella typhi. J Infect Dis 1984;150:436-449
CrossRef | Web of Science | Medline20
Landy M . Studies on Vi antigen. VI. Immunization of human beings with purified Vi antigen. Am J Hyg 1954;60:52-62
Web of Science | Medline21
Keitel WA ,Bond NL ,Zahradnik JM ,Cramton TA ,Robbins JB . Clinical and serological responses following primary and booster immunization with Salmonella typhi Vi capsular polysaccharide vaccines. Vaccine 1994;12:195-199
CrossRef | Web of Science | Medline22
Schneerson R ,Barrera O ,Sutton A ,Robbins JB . Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. J Exp Med 1980;152:361-376
CrossRef | Web of Science | Medline23
Robbins JB ,Schneerson R ,Anderson P ,Smith DH . Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b: impact on public health and implications for other polysaccharide-based vaccines. JAMA 1996;276:1181-1185
CrossRef | Web of Science | Medline24
Szu SC ,Stone AL ,Robbins JD ,Schneerson R ,Robbins JB . Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever: preparation, characterization, and immunogenicity in laboratory animals. J Exp Med 1987;166:1510-1524
CrossRef | Web of Science | Medline25
Szu SC ,Li XR ,Schneerson R ,Vickers JH ,Bryla DA ,Robbins JB . Comparative immunogenicities of Vi polysaccharide-protein conjugates composed of cholera toxin or its B subunit as a carrier bound to high- or lower-molecular-weight Vi. Infect Immun 1989;57:3823-3827
Web of Science | Medline26
Szu SC ,Taylor DN ,Trofa AC , et al. Laboratory and preliminary clinical characterization of Vi capsular polysaccharide-protein conjugate vaccines. Infect Immun 1994;62:4440-4444
Web of Science | Medline27
Kossaczka Z ,Bystricky S ,Bryla DA ,Shiloach J ,Robbins JB ,Szu SC . Synthesis and immunological properties of Vi and di-O-acetyl pectin protein conjugates with adipic acid dihydrazide as the linker. Infect Immun 1997;65:2088-2093
Web of Science | Medline28
Kossaczka Z ,Lin FY ,Ho AV , et al. Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam. Infect Immun 1999;67:5806-5810
Web of Science | Medline29
Requirements for Vi polysaccharide typhoid vaccine (requirements for biological substances no. 48). WHO Tech Rep Ser 1994;840:15-29
30
Nolan CM ,LaBorde EA ,Howell RT ,Robbins JB . Identification of Salmonella typhi in faecal specimens by an antiserum-agar method. J Med Microbiol 1980;13:373-377
CrossRef | Web of Science | Medline31
Miettinen O ,Nurminen M . Comparative analysis of two rates. Stat Med 1985;4:213-226
CrossRef | Web of Science | Medline32
Robbins JB ,Schneerson R ,Szu SC . Hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis 1995;171:1387-1398
CrossRef | Web of Science | Medline33
Gilman RH ,Terminel M ,Levine MM ,Hernandez-Mendoza P ,Hornick RB . Relative efficacy of blood, urine, rectal swab, bone-marrow, and rose-spot cultures for recovery of Salmonella typhi in typhoid fever. Lancet 1975;1:1211-1213
CrossRef | Web of Science | Medline34
Escamilla J ,Santiago LT ,Uylangco CV ,Cross JH . Evaluation of sodium polyanethanol sulfonate as a blood culture additive for recovery of Salmonella typhi and Salmonella paratyphi A. J Clin Microbiol 1983;18:380-383
Web of Science | Medline35
Farooqui BJ ,Khurshid M ,Ashfaq MK ,Khan MA . Comparative yield of Salmonella typhi from blood and bone marrow cultures in patients with fever of unknown origin. J Clin Pathol 1991;44:258-259
CrossRef | Web of Science | Medline36
Szu SC ,Li XR ,Stone AL ,Robbins JB . Relation between structure and immunologic properties of the Vi capsular polysaccharide. Infect Immun 1991;59:4555-4561
Web of Science | Medline37
Bystricky S ,Szu SC . O-acetylation affects the binding properties of the carboxyl groups on the Vi bacterial polysaccharide. Biophys Chem 1994;51:1-7
CrossRef | Web of Science | Medline
- Citing Articles (86)
Citing Articles
1
So Jung An, Yeon Kyung Yoon, Sudeep Kothari, Deok Ryun Kim, Jeong Ah Kim, Neha Kothari, Eugene Lee, Tai Hyun Park, Rodney Carbis. (2011) Immune suppression induced by Vi capsular polysaccharide is overcome by Vi-DT conjugate vaccine. Vaccine
CrossRef2
F. Micoli, S. Rondini, I. Pisoni, C. Giannelli, V. Di Cioccio, P. Costantino, A. Saul, L.B. Martin. (2011) Production of a conjugate vaccine for Salmonella enterica serovar Typhi from Citrobacter Vi. Vaccine
CrossRef3
Wilbur H. Chen, Samer S. El-Kamary. (2011) Vaccines for enteric infections. Current Opinion in Gastroenterology1
CrossRef4
Flor M. Sánchez-Vargas, Maisam A. Abu-El-Haija, Oscar G. Gómez-Duarte. (2011) Salmonella infections: An update on epidemiology, management, and prevention. Travel Medicine and Infectious Disease
CrossRef5
Piyush Kumar Paliwal, Anju Bansal, Sarada S.K. Sagi, Mustoori Sairam. (2011) Intraperitoneal immunization of recombinant HSP70 (DnaK) of Salmonella Typhi induces a predominant Th2 response and protective immunity in mice against lethal Salmonella infection. Vaccine 29:38, 6532-6539
CrossRef6
Sunil Karande. (2011) Update on Imminent Vaccines: Report of the APPA VU 2010: II. The Indian Journal of Pediatrics 78:8, 993-995
CrossRef7
Raphael Simon, Sharon M. Tennant, James E. Galen, Myron M. Levine. (2011) Mouse models to assess the efficacy of non-typhoidal Salmonella vaccines: Revisiting the role of host innate susceptibility and routes of challenge. Vaccine 29:32, 5094-5106
CrossRef8
Anna Seale, Adam Finn. (2011) What is the best way to use conjugate vaccines?. Current Opinion in Infectious Diseases 24:3, 219-224
CrossRef9
Surendra Karki, Kuldeep Kumar. (2011) Study on the possible use of Vi polysaccharide typhoid fever vaccine to control endemic typhoid fever in Nepal. Asian Pacific Journal of Tropical Disease 1:1, 76-79
CrossRef10
F. Micoli, S. Rondini, I. Pisoni, D. Proietti, F. Berti, P. Costantino, R. Rappuoli, S. Szu, A. Saul, L.B. Martin. (2011) Vi-CRM197 as a new conjugate vaccine against Salmonella Typhi. Vaccine 29:4, 712-720
CrossRef11
Dominic F. Kelly, Stephen Thorson, Mitu Maskey, Sandeep Mahat, Umesh Shrestha, Mainga Hamaluba, Eleri Williams, Sabina Dongol, Anja M. Werno, Howard Portess, Bharat K. Yadav, Neelam Adhikari, Malcolm Guiver, Kurien Thomas, David R. Murdoch, Andrew J. Pollard. (2011) The burden of vaccine-preventable invasive bacterial infections and pneumonia in children admitted to hospital in urban Nepal. International Journal of Infectious Diseases 15:1, e17-e23
CrossRef12
Yen-Lin Huang, Chung-Yi Wu. (2010) Carbohydrate-based vaccines: challenges and opportunities. Expert Review of Vaccines 9:11, 1257-1274
CrossRef13
Eyal Meltzer, Eli Schwartz. (2010) Enteric fever: a travel medicine oriented view. Current Opinion in Infectious Diseases 23:5, 432-437
CrossRef14
Buddha Basnyat. (2010) Neglected hepatitis E and typhoid vaccines. The Lancet 376:9744, 869
CrossRef15
Aatekah Owais, Shazia Sultana, Umber Zaman, Arjumand Rizvi, Anita K. M. Zaidi. (2010) Incidence of Typhoid Bacteremia in Infants and Young Children in Southern Coastal Pakistan. The Pediatric Infectious Disease Journal1
CrossRef16
M Imran Khan, R Leon Ochiai, John D Clemens. (2010) Population impact of Vi capsular polysaccharide vaccine. Expert Review of Vaccines 9:5, 485-496
CrossRef17
Rena D. Astronomo, Dennis R. Burton. (2010) Carbohydrate vaccines: developing sweet solutions to sticky situations?. Nature Reviews Drug Discovery 9:4, 308-324
CrossRef18
Giuseppe Del Giudice, Rino Rappuoli. 2010. Adjuvants and Subunit Vaccines. .
CrossRef19
Justen H. Passwell, Shai Ashkenzi, Yonit Banet-Levi, Reut Ramon-Saraf, Nahid Farzam, Liat Lerner-Geva, Hadas Even-Nir, Baruch Yerushalmi, Chiayung Chu, Joseph Shiloach, John B. Robbins, Rachel Schneerson. (2010) Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1–4-year-old Israeli children. Vaccine 28:10, 2231-2235
CrossRef20
David K. Byers, Kyle Petersen. (2009) A Case of Salmonella enterica Serotype Typhi in a Patient Without a History of International Travel. Journal of Travel Medicine 16:3, 223-225
CrossRef21
KyungDong Bae, JunYoul Choi, YangSuk Jang, SangJeom Ahn, ByungKi Hur. (2009) Innovative vaccine production technologies: The evolution and value of vaccine production technologies. Archives of Pharmacal Research 32:4, 465-480
CrossRef22
Laila Woc-Colburn, David A. Bobak. (2009) The expanding spectrum of disease due to Salmonella: An international perspective. Current Infectious Disease Reports 11:2, 120-124
CrossRef23
Tanvir Ahmed, Ann-Mari Svennerholm, Abdullah Al Tarique, Gazi N.N. Sultana, Firdausi Qadri. (2009) Enhanced immunogenicity of an oral inactivated cholera vaccine in infants in Bangladesh obtained by zinc supplementation and by temporary withholding breast-feeding. Vaccine 27:9, 1433-1439
CrossRef24
Jennifer A. Whitaker, Carlos Franco-Paredes, Carlos del Rio, Srilatha Edupuganti. (2009) Rethinking Typhoid Fever Vaccines: Implications for Travelers and People Living in Highly Endemic Areas. Journal of Travel Medicine 16:1, 46-52
CrossRef25
Nizar Ajjan. 2009. Acquisitions récentes en matière de vaccinations et vaccins du futur. , 207-301.
CrossRef26
Jiri Mestecky, Huan Nguyen, Cecil Czerkinsky, Hiroshi Kiyono. (2008) Oral immunization: an update. Current Opinion in Gastroenterology 24:6, 713-719
CrossRef27
Gunilla Källenius, Andrzej Pawlowski, Beston Hamasur, Stefan B. Svenson. (2008) Mycobacterial glycoconjugates as vaccine candidates against tuberculosis. Trends in Microbiology 16:10, 456-462
CrossRef28
Monthida Fangtham, Henry Wilde. (2008) Emergence of Salmonella paratyphi A as a Major Cause of Enteric Fever: Need for Early Detection, Preventive Measures, and Effective Vaccines. Journal of Travel Medicine 15:5, 344-350
CrossRef29
Aliya Naheed, Pavani K. Ram, W. Abdullah Brooks, Eric D. Mintz, Md. Anowar Hossain, Michele M. Parsons, Stephen P. Luby, Robert F. Breiman. (2008) Clinical value of Tubex™ and Typhidot® rapid diagnostic tests for typhoid fever in an urban community clinic in Bangladesh. Diagnostic Microbiology and Infectious Disease 61:4, 381-386
CrossRef30
Denise DeRoeck, R Leon Ochiai, Jin Yang, Dang Duc Anh, Vibha Alag, John D Clemens. (2008) Typhoid vaccination: the Asian experience. Expert Review of Vaccines 7:5, 547-560
CrossRef31
Corryn S Greenwood, Nicholas P Greenwood, Philip R Fischer. (2008) Immunization issues in pediatric travelers. Expert Review of Vaccines 7:5, 651-661
CrossRef32
William Stauffer, John C. Christenson, Philip R. Fischer. (2008) Preparing children for international travel. Travel Medicine and Infectious Disease 6:3, 101-113
CrossRef33
J. A. CRUMP, P. K. RAM, S. K. GUPTA, M. A. MILLER, E. D. MINTZ. (2008) Part I. Analysis of data gaps pertaining to Salmonella enterica serotype Typhi infections in low and medium human development index countries, 1984–2005. Epidemiology and Infection 136:04,
CrossRef34
William A. Petri, Mark Miller, Henry J. Binder, Myron M. Levine, Rebecca Dillingham, Richard L. Guerrant. (2008) Enteric infections, diarrhea, and their impact on function and development. Journal of Clinical Investigation 118:4, 1277-1290
CrossRef35
Sebastian O. Ekenze, Anthony N. Ikefuna. (2008) Typhoid intestinal perforation under 5 years of age. Annals of Tropical Paediatrics: International Child Health 28:1, 53-58
CrossRef36
Sophie E. Moore, Fehmida Jalil, Shousun Chen Szu, Mirjana Hahn-Zoric, Andrew M. Prentice, Lars Å. Hanson. (2008) Revaccination does not improve an observed deficit in antibody responses in Pakistani adults born of a lower birth weight. Vaccine 26:2, 158-165
CrossRef37
Peter Klein Klouwenberg, Louis Bont. (2008) Neonatal and Infantile Immune Responses to Encapsulated Bacteria and Conjugate Vaccines. Clinical and Developmental Immunology 2008, 1-10
CrossRef38
Wei-Zhong Zhou, Hye-Won Koo, Xuan-Yi Wang, Jun Zhang, Jin-Kyung Park, Fengcai Zhu, Jacqueline Deen, Camilo J. Acosta, Yan Chen, Hua Wang, Claudia M. Galindo, Leon Ochiai, Taesung Park, Lorenz von Seidlein, Zhi-Yi Xu, John D. Clemens. (2007) Revaccination With Locally-Produced Vi Typhoid Polysaccharide Vaccine Among Chinese School-Aged Children. The Pediatric Infectious Disease Journal 26:11, 1001-1005
CrossRef39
Abigail Fraser, Mical Paul, Elad Goldberg, Camilo J. Acosta, Leonard Leibovici. (2007) Typhoid fever vaccines: Systematic review and meta-analysis of randomised controlled trials. Vaccine 25:45, 7848-7857
CrossRef40
Abigail Fraser, Elad Goldberg, Camilo J Acosta, Mical Paul, Leonard Leibovici, Abigail Fraser. 2007. Vaccines for preventing typhoid fever. .
CrossRef41
R. L. Ochiai, C. J. Acosta, M. Agtini, S. K. Bhattacharya, Z. A. Bhutta, C. G. Do, B. Dong, X. Chen, B. Stanton, L. Kaljee, A. Nyamete, C. M. Galindo, L. v. Seidlein, D. DeRoeck, L. Jodar, J. D. Clemens. (2007) The Use of Typhoid Vaccines in Asia: The DOMI Experience. Clinical Infectious Diseases 45:Supplement 1, S34-S38
CrossRef42
Anoop S Pulickal, Andrew J Pollard. (2007) Vi polysaccharide–protein conjugate vaccine for the prevention of typhoid fever in children: hope or hype?. Expert Review of Vaccines 6:3, 293-295
CrossRef43
Thomas Ebensen, Claudia Link, Carlos A. Guzm
n. 2006. Human and Veterinary Classical Vaccines against Bacterial Diseases. .
CrossRef44
Zulfiqar A. Bhutta. (2006) Typhoid Fever. Infectious Diseases in Clinical Practice 14:5, 266-272
CrossRef45
A. Gupta, N.T. My Thanh, S.J. Olsen, S. Sivapalasingam, T.T. My Trinh, N.T. Phuong Lan, R.M. Hoekstra, W. Bibb, N.T. Minh, T.P. Danh, P.D. Cam, E.D. Mintz. (2006) Evaluation of community-based serologic screening for identification of chronic Salmonella Typhi carriers in Vietnam. International Journal of Infectious Diseases 10:4, 309-314
CrossRef46
Myron M. Levine. (2006) Enteric infections and the vaccines to counter them: Future directions. Vaccine 24:18, 3865-3873
CrossRef47
Christine Hale, Frances Bowe, Derek Pickard, Simon Clare, Jean-Francois Haeuw, Ultan Powers, Nathalie Menager, Pietro Mastroeni, Gordon Dougan. (2006) Evaluation of a novel Vi conjugate vaccine in a murine model of salmonellosis. Vaccine 24:20, 4312-4320
CrossRef48
Carlos A. Guzman, Stefan Borsutzky, Monika Griot-Wenk, Ian C. Metcalfe, Jon Pearman, Andre Collioud, Didier Favre, Guido Dietrich. (2006) Vaccines against typhoid fever. Vaccine 24:18, 3804-3811
CrossRef49
L. Sánchez Martínez, E. Garrido Álvarez, P. Álvarez Álvarez, M. Rodríguez Zapata. (2006) Infecciones por Salmonella. Fiebre tifoidea y salmonelosis no tifoideas. Medicine - Programa de Formación Médica Continuada Acreditado 9:53, 3439-3448
CrossRef50
C. D. Ericsson, C. Hatz, B. Basnyat, A. P. Maskey, M. D. Zimmerman, D. R. Murdoch. (2005) Enteric (Typhoid) Fever in Travelers. Clinical Infectious Diseases 41:10, 1467-1472
CrossRef51
H.H. Tran, G. Bjune, B.M. Nguyen, J.A. Rottingen, R.F. Grais, P.J. Guerin. (2005) Risk factors associated with typhoid fever in Son La province, northern Vietnam. Transactions of the Royal Society of Tropical Medicine and Hygiene 99:11, 819-826
CrossRef52
Eyal Meltzer, Chantal Sadik, Eli Schwartz. (2005) Enteric Fever in Israeli Travelers: A Nationwide Study. Journal of Travel Medicine 12:5, 275-281
CrossRef53
MK Bhan, Rajiv Bahl, Shinjini Bhatnagar. (2005) Typhoid and paratyphoid fever. The Lancet 366:9487, 749-762
CrossRef54
Rémy Michel, Eric Garnotel, André Spiegel, Marc Morillon, Pierre Saliou, Jean-Paul Boutin. (2005) Outbreak of typhoid fever in vaccinated members of the French Armed Forcesin the Ivory Coast. European Journal of Epidemiology 20:7, 635-642
CrossRef55
CJ Acosta, CM Galindo, JL Deen, RL Ochiai, HJ Lee, L von Seidlein, R Carbis, JD Clemens. (2004) Vaccines against cholera, typhoid fever and shigellosis for developing countries. Expert Opinion on Biological Therapy 4:12, 1939-1951
CrossRef56
JOHN B. ROBBINS, RACHEL SCHNEERSON. (2004) Future Vaccine Development at NICHD. Annals of the New York Academy of Sciences 1038:1, 49-59
CrossRef57
E. B. Steinberg, R. Bishop, P. Haber, A. F. Dempsey, R. M. Hoekstra, J. M. Nelson, M. Ackers, A. Calugar, E. D. Mintz. (2004) Typhoid Fever in Travelers: Who Should Be Targeted for Prevention?. Clinical Infectious Diseases 39:2, 186-191
CrossRef58
N. Q. Chanh, P. Everest, T. T. Khoa, D. House, S. Murch, C. Parry, P. Connerton, P. Van Bay, T. S. Diep, P. Mastroeni, N. J. White, T. T. Hien, V. Van Ho, G. Dougan, J. J. Farrar, J. Wain. (2004) A Clinical, Microbiological, and Pathological Study of Intestinal Perforation Associated with Typhoid Fever. Clinical Infectious Diseases 39:1, 61-67
CrossRef59
Rosa Marı́a Salazar-González, Carmen Maldonado-Bernal, Nora Elena Ramı́rez-Cruz, Nora Rios-Sarabia, Jorge Beltrán-Nava, Jorge Castañón-González, Noemı́ Castillo-Torres, José A Palma-Aguirre, Manuel Carrera-Camargo, Constantino López-Macı́as, Armando Isibasi. (2004) Induction of cellular immune response and anti-Salmonella enterica serovar typhi bactericidal antibodies in healthy volunteers by immunization with a vaccine candidate against typhoid fever. Immunology Letters 93:2-3, 115-122
CrossRef60
Morad Hassani, Mahesh C Patel, Liise-anne Pirofski. (2004) Vaccines for the prevention of diseases caused by potential bioweapons. Clinical Immunology 111:1, 1-15
CrossRef61
Ann-Mari Svennerholm, Duncan Steele. (2004) Progress in enteric vaccine development. Best Practice & Research Clinical Gastroenterology 18:2, 421-445
CrossRef62
Christopher M. Parry. (2004) Typhoid fever. Current Infectious Disease Reports 6:1, 27-33
CrossRef63
Lanh, Mai Ngoc, Van Bay, Phan, Ho, Vo Anh, , Thanh, Tran Cong, , Lin, Feng Ying C., Bryla, Dolores A., Chu, Chiayung, Schiloach, Joseph, Robbins, John B., Schneerson, Rachel, Szu, Shousun C., . (2003) Persistent Efficacy of Vi Conjugate Vaccine against Typhoid Fever in Young Children. New England Journal of Medicine 349:14, 1390-1391
Full Text64
Stephen Lockhart. (2003) Conjugate vaccines. Expert Review of Vaccines 2:5, 633-648
CrossRef65
Beth D. Kirkpatrick, W Kemper Alston. (2003) Current immunizations for travel. Current Opinion in Infectious Diseases 16:5, 369-374
CrossRef66
Nancy F. Crum. (2003) Current trends in typhoid fever. Current Gastroenterology Reports 5:4, 279-286
CrossRef67
JUSTEN H. PASSWELL, SHAI ASHKENAZI, EFRAT HARLEV, DAN MIRON, REUT RAMON, NAHID FARZAM, LIAT LERNER-GEVA, YONIT LEVI, CHIAYUNG CHU, JOSEPH SHILOACH, JOHN B. ROBBINS, RACHEL SCHNEERSON. (2003) Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-r EPAsucc conjugate vaccines in one- to four-year-old children. The Pediatric Infectious Disease Journal 22:8, 701-706
CrossRef68
G. Ada. (2003) Progress towards achieving new vaccine and vaccination goals. Internal Medicine Journal 33:7, 297-304
CrossRef69
SP Kalra, N Naithani, SR Mehta, AJ Swamy. (2003) Current trends in the management of typhoid fever. Medical Journal Armed Forces India 59:2, 130-135
CrossRef70
G. Ada, D. Isaacs. (2003) Carbohydrate-protein conjugate vaccines. Clinical Microbiology and Infection 9:2, 79-85
CrossRef71
Marcela F Pasetti, Myron M Levine, Marcelo B Sztein. (2003) Animal models paving the way for clinical trials of attenuated Salmonella enterica serovar Typhi live oral vaccines and live vectors. Vaccine 21:5-6, 401-418
CrossRef72
Parry, Christopher M., Hien, Tran Tinh, Dougan, Gordon, White, Nicholas J., Farrar, Jeremy J., . (2002) Typhoid Fever. New England Journal of Medicine 347:22, 1770-1782
Full Text73
J.Wayne Conlan, Hua Shen, Ann Webb, Malcolm B Perry. (2002) Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen. Vaccine 20:29-30, 3465-3471
CrossRef74
Stephen M. Graham. (2002) Salmonellosis in children in developing and developed countries and populations. Current Opinion in Infectious Diseases 15:5, 507-512
CrossRef75
K. Christiansen, C. Carbon, O. Cars. (2002) Moving from recommendation to implementation and audit: Part 2. Review of interventions and audit. Clinical Microbiology and Infection 8, 107-128
CrossRef76
William M. Stauffer, Deepak Kamat. (2002) Traveling with Infants and Children. Part 2: Immunizations. Journal of Travel Medicine 9:2, 82-90
CrossRef77
John Wain, Deborah House, Julian Parkhill, Christopher Parry, Gordon Dougan. (2002) Unlocking the genome of the human typhoid bacillus. The Lancet Infectious Diseases 2:3, 163-170
CrossRef78
Mackay, Ian R., Rosen, Fred S., , Ada, Gordon, . (2001) Vaccines and Vaccination. New England Journal of Medicine 345:14, 1042-1053
Full Text79
Joseph M. Vinetz. (2001) Leptospirosis. Current Opinion in Infectious Diseases 14:5, 527-538
CrossRef80
(2001) A Salmonella typhi Vi Conjugate Vaccine. New England Journal of Medicine 345:7, 545-546
Full Text81
&NA;. (2001) Typhoid conjugate vaccine could be an 'exciting advance'. Inpharma Weekly &NA;:1286, 11
CrossRef82
Guerrant, Richard L., Kosek, Margaret, . (2001) Polysaccharide Conjugate Typhoid Vaccine. New England Journal of Medicine 344:17, 1322-1323
Full Text83
Arthi Ramkissoon, Prakash Jugnundan. (2001) Reactogenicity and Immunogenicity of a Single Dose of a Typhoid Vi Polysaccharide Vaccine in Adolescents. BioDrugs 15:Supplement 1, 21-26
CrossRef84
Edouard Lebacq. (2001) Comparative Tolerability and Immunogenicity of Typherix??? or Typhim Vi??? in Healthy Adults*. BioDrugs 15:Supplement 1, 5-12
CrossRef85
Jane N. Zuckerman. (2001) A Recently Developed Typhoid Vi Polysaccharide Vaccine. BioDrugs 15:Supplement 1, 1-4
CrossRef86
Helena H. Pelser. (2001) Reactogenicity and Immunogenicity of a Single Dose of Typhoid Vi Polysaccharide Vaccine in Children Aged between 4 and 14 Years. BioDrugs 15:Supplement 1, 13-19
CrossRef
