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PubMed2004

Fluroquinolone resistance in typhoidal Salmonella and its detection by nalidixic acid disc diffusion.

OBJECTIVE: To determine the presence of fluoroquinolone resistance in Typhoidal salmonellae at Rawalpindi and the role of nalidixic acid in predicting the resistance against fluoroquinolones in Microbiology Laboratory, Department of Pathology, Army Medical College, Rawalpindi. METHODS: One hundred consecutive clinical isolates of Typhoidal salmonellae isolated from blood culture samples were studied. The organisms were identified biochemically and serologically by standard technique. Sensitivity testing was carried out against nalidixic acid and ciprofloxacin by modified Kirby bauer disc diffusion method and minimum inhibitory concentration (MICs) were determined by E-test. RESULTS: Seventeen percent of the isolates were resistant to nalidixic acid. Nalidixic acid disc diffusion and MIC estimation by E-test were 100% comparable. All isolates were sensitive to ciprofloxacin but the isolates which were resistant to nalidixic acid had raised MIC values against ciprofloxacin. CONCLUSION: Typhoidal salmonellae have not shown an overt in vitro resistance against fluoroquinolones in our set up but a significant population has emerged with raised MIC values. Nalidixic acid susceptibility test can be used an indirect evidence of resistance to quinolones.

Anti-Infective Agents↗
PubMedDate not supplied

[Hepatotoxicity of the lipid components of the lipopolyysaccharides from typhoid bacteria].

Distinct increase in amount of total lipids occurred in mice liver tissue after intraperitoneal administration of typhoid lipids A and B (the latter was nonhydrolytically isolated from typhoid lipopolysaccharides). The alteration referred primarily to neutral lipids, especially to triacyl glycerides, content of which exceeded 3- and more-fold the initial one to the end of a day. The similarity was observed in alteration of triacyl glycerides, phospho- and glycolipids in presence of both lipid preparations. These lipid components resembled intact lipopolysaccharide from typhoid bacteria in their effect on content of lipids in liver tissue. In treatment with these lipid preparations concentration of NEFA was either unaltered or distinctly decreased.

Animals↗
PubMed1982

[Biological effects of gamma rays on Salmonella gallinarum and their use in controlling fowl typhoid].

The results are given of following up some biologic effects produced by gamma-rays on Salmonella gallinarum with a view of disclosing the possibilities of their use in the control of fowl typhoid. Used were strains of Salmonella gallinarum isolated from birds affected with acute typhoid. The possibility is stated of the detoxication of an endotoxin of Salmonella gallinarum parallel to the growing intensity of the gamma-rays (1 to 10 Mrad). It was found that the process of detoxication was better expressed in the irradiation of the bacterial cell in vivo. Rates of 20 Mrad were said to substantially modify the endotoxin, rendering it slightly toxic, it retaining its antigenic properties and haptene activity. The same modification could successfully be used as an allergen in the diagnosis of typhoid of birds when alive. It was also established that the use of sublethal rates of gamma-rays from 30 to 80 krad induced various morphologic and biochemical changes in Salmonella gallinarum. Of interest were likewise the studies of the R-strains and a histidine-dependent strain of Salmonella gallinarum which had retained their immunogenic properties.

Animals↗
PubMed2000

Vaccines for preventing typhoid fever.

BACKGROUND: Whole cell vaccines, consisting of relatively crude preparations of Salmonella typhi administered parenterally, are effective but have a high incidence of adverse effects. Two vaccines have been developed more recently. Ty21a (an attenuated strain of S. typhi administered orally) and Vi (the purified bacterial capsule, given parenterally), have appeared less toxic than the older whole cell vaccines and are thought to be equally effective. OBJECTIVES: The objective of this review was to assess the effects of typhoid fever vaccines. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Index Medicus, Embase and reference lists of articles. SELECTION CRITERIA: Randomised trials comparing typhoid vaccines to other types of vaccine or placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Seventeen studies, involving nearly two million people, were included. For the whole cell vaccines single dose regimens provided significant protection for the first two years. Two dose regimens provided significant protection for five years. For the Ty21a vaccine, both two and three dose regimens provided statistically significant protection for two years. The three dose regimen provided protection in the third and fourth years, but protection was not statistically significant in the fifth year. The Vi vaccine provided protection for two years, but the protection in the third year was not significant. The three year cumulative efficacy of two doses of whole cell vaccines was 73% (95% confidence interval 65-80), three doses of Ty21a was 51%, (95% confidence interval 35 to 63) and one dose of Vi was 55% (95% confidence interval 30 to 71). Data on adverse effects were limited, but indicate that whole cell vaccines are more toxic than the newer Ty21a and Vi vaccines. REVIEWER'S CONCLUSIONS: The whole cell vaccines provided more prolonged protection than either the Ty21a vaccine or the Vi vaccine. However whole cell vaccines are associated with higher toxicity.

Adolescent↗
PubMed1989

An epidemiological model for direct and indirect transmission of typhoid fever.

The modified SIS epidemiological model considers the usual direct transmission (short cycle) and indirect transmission (long cycle) of typhoid fever. Thresholds are determined, and the equilibrium points are shown to be globally stable. Local stability of the equilibrium points is shown in the corresponding model with vaccines. After estimating parameters using current statistical data for typhoid fever in Chile, computer simulations are used to obtain the numerical behavior of this disease and to estimate the effect of several control policies.

Computer Simulation↗
PubMed1990

Efficacy of one or two doses of Ty21a Salmonella typhi vaccine in enteric-coated capsules in a controlled field trial. Chilean Typhoid Committee.

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 randomly 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.

Administration, Oral↗
PubMed2005

Efficacy of a locally produced, Chinese Vi polysaccharide typhoid fever vaccine during six years of follow-up.

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 populations 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.

Antigens, Bacterial↗
PubMed1977

Antibodies and the Aberdeen typhoid outbreak of 1964. II. Coombs', complement fixation and fimbrial agglutination tests.

In a previous paper (Brodie, 1977) the value of the Widal test in the diagnosis of typhoid fever was shown to be limited. Evaluation of possible alternative tests showed that: (1) the sensitivity of the anti-human globulin (Coombs') test appeared greater than that of the agglutination test but the length of time (48 h) before results were available rendered it of little value in rapid diagnosis: (2) the complement fixation test offered no particular help towards diagnosis; (3) immunized and non-immunized typhoid fever patients developed fimbrial antibodies, as also did immunized healthy individuals. In this latter group, however, those immunized with alcoholized TAB vaccine had higher antibody titres to fimbrial antigen than those immunized with heat-killed phenolized vaccine.

Agglutination Tests↗
PubMed1992

Epidemiology and control of an outbreak of typhoid in a psychiatric institution.

An outbreak of typhoid caused by Salmonella typhi of the same Vi-phage type (D1) and of the same antibiogram was reported in a large psychiatric institution in Singapore. A total of 95 (4.8%) of the 1965 inmates were infected, 47 with symptoms and 48 asymptomatic. Transmission was through close person-to-person contact and not through contaminated food or water. The source of infection could not be established. The outbreak was brought under control by maintaining a high standard of environmental sanitation, active search for fever and diarrhoeal cases, identification of asymptomatic cases by rectal swabbing, and isolation of those found to be infected. Mass immunization with two doses of heat-phenol inactivated typhoid vaccine was also carried out concurrently. The vaccine was found to have an efficacy of 65.8% in preventing clinical illness.

Adult↗
PubMed1987

Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals.

The Vi has proven to be a protective antigen in two double masked, controlled clinical trials in areas with high rates of typhoid fever (approximately 1% per annum). In both studies the protective efficacy of the Vi was approximately 70%. Approximately 75% of subjects in these areas responded with a fourfold or greater rise of serum Vi antibodies. In contrast, the Vi elicited a fourfold or greater rise in 95-100% of young adults in France and the United States. Methods were devised, therefore, to synthesize Vi-protein conjugates in order to both enhance the antibody response and confer T-dependent properties to the Vi (and theoretically increase its protective action in populations at high risk for typhoid fever). We settled on a method that used the heterobifunctional crosslinking reagent, N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP), to bind thiol derivatives of the Vi to proteins. This synthetic scheme was reproducible, provided high yields of Vi-protein conjugates, and was applicable to several medically relevant proteins such as diphtheria and tetanus toxoids. The resultant conjugates were more immunogenic in mice and juvenile Rhesus monkeys than the Vi alone. In contrast to the T-independent properties of the Vi, conjugates of this polysaccharide with several medically relevant proteins induced booster responses in mice and in juvenile Rhesus monkeys. Clinical studies with Vi-protein conjugates are planned. This scheme is also applicable to synthesize protein conjugates with other polysaccharides that have carboxyl functions.

Animals↗
PubMed2005

The novel oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in 2 vaccine presentations.

BACKGROUND: M01ZH09 (Salmonella enterica serovar Typhi [Ty2 aroC(-) ssaV(-)] ZH9) is a live oral-dose typhoid vaccine candidate. M01ZH09 was rationally modified with 2 independently attenuating mutations, including a novel mutation in Salmonella pathogenicity island (SPI)-2. We demonstrate that M01ZH09, in a single oral dose, is well tolerated and prompts broad immune responses, regardless of whether prevaccination with a bicarbonate buffer is given. METHODS: Thirty-two healthy adult subjects were randomized and given 5x109 cfu of M01ZH09, with (presentation 1) or without (presentation 2) prevaccination with a bicarbonate buffer. Immunogenicity data included Salmonella Typhi lipopolysaccharide (LPS)-specific immunoglobulin (Ig) A antibody-secreting cells (enzyme-linked immunospot [ELISPOT] assay), IgG serologic responses to Salmonella Typhi LPS, lymphocyte proliferation, and interferon (IFN)- gamma production. RESULTS: The vaccine was well tolerated; adverse events after vaccination were mild. No fever or prolonged vaccine shedding occurred. Immunogenicity data demonstrated that 88% and 93% of subjects who received presentation 1 and presentation 2, respectively, had a positive response by ELISPOT assay; 81% of subjects in both groups underwent IgG seroconversion on day 14. Both groups had similar cellular immune responses to presentation 1 and presentation 2; lymphocyte proliferation to Salmonella Typhi flagellin occurred in 63% and 67% of subjects, respectively, and 69% and 73% of subjects, respectively, had an increase in IFN- gamma production. CONCLUSION: The oral typhoid vaccine M01ZH09 is well tolerated and highly immunogenic in a single oral dose, with and without prevaccination with a bicarbonate buffer. Field studies to demonstrate protective efficacy are planned.

Administration, Oral↗
PubMedDate not supplied

Progress in vaccines against typhoid fever.

The widely available heat-phenol-inactivated whole cell typhoid vaccine, which provides approximately 65% protection, has limited usefulness because of the adverse reactions it evokes. In contrast, several new typhoid vaccines promise protection without reactogenicity. Attenuated oral vaccine Ty21a has been evaluated in three field trials of efficacy in Santiago, Chile, involving 530,000 schoolchildren. Three doses of Ty21a in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Fewer doses conferred less protection, while adding a fourth dose significantly enhanced protection; increasing the interval between doses did not improve protection. Large-scale vaccination with Ty21a appeared to cause a herd-immunity effect. Ty21a has reached the stage of being a practical tool for public health. With respect to other vaccines, the safety and immunogenicity of an auxotrophic (Aro-,Pur-) Salmonella typhi mutant (strain 541Ty) has recently been evaluated. Lastly, parenteral purified Vi polysaccharide of S. typhi was safe and immunogenic and provided 64%-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.

Chile↗
PubMed2001

Typhoid fever in Bangladesh: implications for vaccination policy.

OBJECTIVE: To describe the age-specific distribution of typhoid fever including the degree of Salmonella typhi bacteremia among patients evaluated at a large private diagnostic center in Bangladesh, a highly endemic area. METHODS: We conducted a prospective-, passive- and laboratory-based study to identify patients with S. typhi bacteremia. Subjects (n = 4,650) from whom blood cultures were obtained during 16-month period were enrolled from private clinics and hospitals throughout Dhaka. Isolation and quantification of S. typhi from blood cultures were performed by the lysis direct plating/ centrifugation method. RESULTS: Bacterial pathogens were recovered from blood of 538 of 4,650 patients (11.6%) evaluated. S. typhi was the single most common pathogen recovered, comprising nearly three-fourths of isolates (72.7%; 391 of 538). Isolation rate of S. typhi was highest in monsoon and summer seasons and lowest in winter months. The majority (54.5%; 213 of 391) of S. typhi isolates were from children who were younger than 5 years, and 27% (105 of 391) were from children in the first 2 years of life. The isolation rate was highest (17.4%, 68 of 486) in the second year of life. The number of bacteria in blood on the basis of colony-forming units per ml of blood by age group was inversely related to age. CONCLUSIONS: Detection of S. typhi bacteremia in young children in Dhaka, Bangladesh, was considerably higher than previously appreciated, with a peak detection rate in children < or =2 years of age, indicating the need to reassess the age-specific burden of typhoid fever in the community on a regional basis. Contrary to current recommendations this study suggests that development of new vaccines should target infants and young children.

Adolescent↗
PubMed2005

A multi-country cluster randomized controlled effectiveness evaluation to accelerate the introduction of Vi polysaccharide typhoid vaccine in developing countries in Asia: rationale and design.

Phase-III vaccine efficacy trials typically employ individually randomized designs intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects. As a result, decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes, due to the combination of direct plus indirect vaccine protective effects. Vaccine total protection can be better evaluated with cluster randomized trials. Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide (PS) vaccine in Asia by the Diseases of the Most Impoverished (DOMI) typhoid fever programme. The DOMI's programme multi-country study is one of the largest cluster randomized vaccine trials ever mounted in Asia, which includes approximately 200,000 individuals. Its main objective is to determine the effectiveness of a licensed Vi PS vaccine. The rationale and design of this study are discussed. Preliminary results are presented that determined the final planning of the trial before immunization. Important methodological and practical issues regarding vaccine cluster randomized designs are illustrated.

Adolescent↗
PubMed1975

Vi antigen from Salmonella typhosa and immunity against typhoid fever. 11. Safety and antigenicity in humans.

Safety and antigenicity of a purified preparation of Salmonella typhosa Vi antigen was evaluated in human volunteers. Dosages of Vi antigen at 25, 50, and 100 mug were less toxic than U.S. standard typhoid vaccine (lot 6A) containing 5 X 10(8) bacteria per dosage. Vi antigen in comparison with the standard typhoid vaccine induced higher hemagglutinating antibody but lower bactericidal antibody responses.

Antibody Formation↗
PubMed1977

Assessment of typhoid vaccines by using the intraperitoneal route of challenge.

Present laboratory tests for human typhoid vaccines use an intraperitoneal route of challenge given 7 days after injection of increasing doses of standard and test vaccines by the same route. In studies reported here, groups of B6D2 mice were vaccinated intraperitoneally with 2 x 10(8) acetone-killed Salmonella typhi Ty2, with the Vi antigen-free variant O-901, or with Yersinia enterocolitica and Serratia marcescens suspensions. Other groups of mice received 200 mug of purified S. typhi or S. marcescens endotoxin, or their corresponding purified lipid A components. All of the vaccinated mice (except for saline- or thioglycolate-injected controls) exhibited increased protection against the lethal intraperitoneal challenge with S. typhi Ty2. Serial quantitative bacterial counts carried out on peritoneal washouts and on homogenates of the draining mediastinal lymph nodes indicated the development of an antibacterial response by the vaccinated host which was not observed in the control animals. Mice receiving purified endotoxin (lipopolysaccharide) exhibited varying degrees of protection, both in terms of increased host survival and the amount of inactivation of the challenge population in vivo. The response seen when the antigenically unrelated S. marcescens lipopolysaccharide was injected was little different from that seen when the acetone-killed S. typhi Ty2 whole-cell vaccine was used. This suggests that nonspecific inactivation of the intraperitoneal challenge contributes substantially to the immune response seen in mice vaccinated intraperitoneally with specific typhoid antigens.

Animals↗
PubMed1998

Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity.

OBJECTIVE: To estimate the efficacy and toxicity of typhoid fever vaccines. DESIGN: Meta-analysis of randomised efficacy trials and both randomised and non-randomised toxicity studies of the parenteral whole cell, oral Ty21a, and parenteral Vi vaccines. SUBJECTS: 1,866,951 subjects in 17 efficacy trials; 11,204 subjects in 20 toxicity studies. MAIN OUTCOME MEASURES: Pooled estimates of three year cumulative efficacy, year specific efficacy, and incidence of adverse events. RESULTS: Three year cumulative efficacy was 73% (95% confidence interval 65% to 80%) for two doses of whole cell vaccines (based on seven trials); 51% (35% to 63%) for three doses of Ty21a vaccine (four trials); and 55% (30% to 71%) for one dose of Vi vaccine (one trial). For whole cell and Ty21a vaccines, regimens of fewer doses were less effective. Efficacy was shown to be significant for five years for whole cell vaccines, four years for Ty21a vaccine, and two years for Vi vaccine. Neither the age of vaccine recipient nor the incidence of typhoid fever in the control group (varying from 6 to 810 cases per 100,000 person years) affected the efficacy of the whole cell or Ty21a vaccines. After vaccination, fever occurred in 15.7% (11.5% to 21.2%) of whole cell vaccine recipients, 2.0% (0.7% to 5.3%) of Ty21a vaccine recipients, and 1.1% (0.1% to 12.3%) of Vi vaccine recipients. CONCLUSIONS: Whole cell vaccines are more effective than the Ty21a and Vi vaccines but are more frequently associated with adverse events. Whether the added efficacy of the whole cell vaccines outweighs their toxicity will depend on the setting in which vaccination is used.

Administration, Oral↗
PubMed1985

Management of typhoid.

Typhoid fever is still a major problem in developing Third World countries where socioeconomic conditions and standards of hygiene are still well below standard. Prophylaxis is far from satisfactory. However, recent developments using live oral vaccines are encouraging. Specific treatment for the disease consists of chloramphenicol or co-trimoxazole; amoxycillin and ampicillin are inferior agents but are of value in several situations because their potential toxic effects are less marked. Most other agents also have drawbacks or are relatively ineffective. In the severely toxic patient, corticosteroids seem to affect prognosis favourably. Of the many other acute complications of typhoid fever, ileal perforation is the most serious; there is still controversy concerning the respective roles of conservative and surgical management, but it is clear that individual cases must be assessed on their merit. Amoxycillin, because it is very rapidly absorbed and produces very high blood concentrations, is probably the best antibiotic for the carrier state.

Adrenal Cortex Hormones↗