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PubMed2007

Trial participation and vaccine desirability for Vi polysaccharide typhoid fever vaccine in Hue City, Viet Nam.

OBJECTIVES: To identify demand for Vi typhoid fever vaccine for school-age children; obstacles and enabling factors for vaccine delivery; and socio-behavioural factors associated with trial participation and possible predictors of future vaccine acceptance, in Hue City, Viet Nam. METHODS: Pre- and post-trial surveys of randomly selected households with children aged 6-17 years. Simple multinomial logistic analyses for ratios of relative risks (RRR) and significance on trial participation by demographics and variables related to typhoid fever, vaccination, and pre-trial experiences with information and consents. Multiple logistic regressions to assess differences in participation based on child's characteristics. RESULTS: As many as 62.6% of households let all school age children participate, 10.2% let some participate, and 26.8% let none of their children participate in the trial. Factors associated with all children participating included past use of healthcare facilities (RRR, 0.45; 95% CI, 0.24-0.83), knowledge of vaccines (RRR, 0.17; 95% CI, 0.03-0.86), and perceived causes of typhoid fever (RRR, 0.90; 95% CI, 0.81-0.99). Factors associated with some children participating included utilization of healthcare facilities (RRR, 0.08; 95% CI, 0.01-0.66) and perceived severity of typhoid fever (RRR, 0.64; 95% CI 0.46-0.88). Participation was associated with satisfaction regarding pre-vaccination information and consent procedures. Children and adolescents were active decision-makers. Only 14 of 461 (2.2%) respondents would not use the Vi vaccine in the future for their child(ren). CONCLUSIONS: Inter-related factors contribute to participation in a clinical vaccine trial, which may differ from desire to participate in a public health campaign. Educational campaigns need to be targeted to children and adolescents, and consideration for assent procedures for minors. Obtaining informed consent may affect trial participation within a social and political system unaccustomed to these procedures.

Adolescent↗
PubMed1999

Considerations regarding mass vaccination against typhoid fever as an adjunct to sanitation and public health measures: potential use in an epidemic in Tajikistan.

We report on the ongoing epidemic of typhoid fever in Tajikistan that started in 1996. It has involved more than 24,000 cases to date, and is characterized by multiple point sources, overflow of sewage, contaminated municipal water, and person-to-person spread. Of the Salmonella typhi isolates available for testing in western laboratories, more than 90% are multidrug-resistant (MDR). Most recently, 28 (82%) of 34 isolates are resistant to ciprofloxacin, representing the first reported epidemic of quinolone-resistant typhoid fever. In the past, mass immunization during typhoid fever epidemics has been discouraged. A review of this policy is recommended in light of the alarming emergence of quinolone-resistant strains of S. typhi, the availability of improved vaccines, and the ongoing epidemic in Tajikistan. Mass immunization may be a useful measure for the control of prolonged MDR typhoid fever epidemics, as an adjunct to correction of municipal infrastructure and public health intervention.

Anti-Infective Agents↗
PubMed1962

A controlled field trial of the typhoid component of polyvalent enteric vaccine (NIISI polyvaccine).

At the request of the Ministry of Health of the USSR, a controlled field trial of a polyvaccine containing typhoid, paratyphoid and dysentery antigens and a purified tetanus toxoid was undertaken in 1958. The main object of this trial, which was carried out over a 10-month period simultaneously in four localities, was to determine the efficacy of the typhoid component of the polyvaccine.The study population comprised over 90 000 individuals of 16-60 years of age. These were divided into two approximately equal groups, one of which received an injection of the polyvaccine under test and the other an injection of a preparation containing only the purified tetanus toxoid.The difference between the incidence of typhoid fever in the test group and that in the control group during the study period was statistically significant, and it was therefore concluded that a single injection of the polyvaccine afforded some protection against typhoid.

Humans↗
PubMed2004

Rapid diagnosis of typhoid fever by enzyme-linked immunosorbent assay detection of Salmonella serotype typhi antigens in urine.

We developed and evaluated an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies to capture somatic antigen 9 (O9), flagellar antigen d (Hd), and the Vi capsular polysaccharide antigen (Vi) from the urine of persons with and without typhoid fever. Sequential urine samples were collected from 44 patients with blood culture-confirmed typhoid fever and from two control groups. The first control group included patients with brucellosis (n = 12) and those with clinically diagnosed, non-typhoid, acute, febrile illness (n = 27). The second control group was a sample of healthy volunteer laboratory workers (n = 11). When assessed relative to date of fever onset, sensitivity was highest during the first week for all three antigens: Vi was detected in the urine of nine (100%) patients, O9 in 4 (44%) patients, and Hd in 4 (44%) patients. Sequential testing of two urine samples from the same patient improved test sensitivity. Combined testing for Vi with O9 and Hd produced a trend towards increased sensitivity without compromising specificity. The specificity for Vi exceeded 90% when assessed among both febrile and healthy control subjects, but was only 25% when assessed among patients with brucellosis. Detection of urinary Vi antigen with this ELISA shows promise for the diagnosis of typhoid fever, particularly when used within the first week after fever onset. However, positive reactions for Vi antigen in patients with brucellosis must be understood before urinary Vi antigen detection can be developed further as a useful rapid diagnostic test.

Antigens, Bacterial↗
PubMed2004

A cost-benefit analysis of typhoid fever immunization programmes in an Indian urban slum community.

Many economic analyses of immunization programmes focus on the benefits in terms of public-sector cost savings, but do not incorporate estimates of the private cost savings that individuals receive from vaccination. This paper considers the implications of Bahl et al.'s cost-of-illness estimates for typhoid immunization policy by examining how community-level incidence estimates and information on distribution of costs of illness among patients and the public-health sector can be used in the economic analysis of vaccination-programme options. The findings illustrate why typhoid vaccination programmes may often appear to be unattractive to public-health officials who adopt a public budgetary perspective. Under many plausible sets of assumptions, public-sector expenditure on typhoid vaccination does not yield comparable public-sector cost savings. If public-health officials adopt a societal perspective on the economic benefits of vaccination, there are many situations in which different vaccination programmes will make economic sense. The findings show that this is especially true when public decision-makers recognize that (a) the incidence of typhoid fever is underestimated by blood culture-positive cases and (b) avoided costs of illness represent a significant underestimate of the actual economic benefits to individuals of vaccination.

Adolescent↗
PubMed2006

The feasibility of a school-based VI polysaccharide vaccine mass immunization campaign in Hue City, central Vietnam: streamlining a typhoid fever preventive strategy.

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-randomized evaluation-blinded controlled trial was designed where 68 schools (cluster) were randomly 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 resources 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 practices 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.

Adolescent↗
PubMed1971

Studies of immunity in typhoid fever. Protection induced by killed oral antigens or by primary infection.

Adult male volunteers were orally vaccinated with two "killed" antityphoid preparations. The recommended doses of both vaccines resulted in serum antibody development in only a few of the subjects. When the dose of the monovalent preparation (Taboral) was doubled, serological responses occurred more frequently, with a rise in O agglutinins in nearly one-fifth of the subjects, in H agglutinins in approximately one-fourth, and in Vi antibodies in nearly half.When vaccinated volunteers were fed virulent typhoid organisms, disease occurred less frequently among those men vaccinated with Taboral at twice the recommended dose (38%) than among those not vaccinated (54%). This preparation did not confer protection at the recommended dose.Volunteers who had previously recovered from an induced typhoid infection received a further challenge with virulent organisms. These persons developed typhoid fever less frequently (23%) than individuals without prior typhoid exposure (30%).

Administration, Oral↗
PubMed1971

Epidemiological model of typhoid fever and its use in the planning and evaluation of antityphoid immunization and sanitation programmes.

An epidemiological model has been constructed for typhoid fever in a stable population in order to study the transmission of infection at different levels of endemicity. It involves a number of parameters representing the proportions of epidemiological subgroups in the population-such as the susceptible, the infected, and the immune-and rates of transition between the groups. Numerical values based on available evidence were assigned to the parameters, to provide a realistic simulation of stable endemicity.Changes were then introduced in the values of some of the parameters in order to study the consequences of mass vaccination and improvements in general health conditions and sanitation, in particular on the incidence of disease.The model shows that a single mass vaccination reduces the incidence of disease considerably, but the gain is largely lost after a few years. Repeated vaccinations at 5-year intervals will produce further decreases in incidence, though the additional gain becomes smaller at each consecutive vaccination.The model was also used to estimate the possible effect of improvements in sanitation. The incidence decreases to a new level of stability when the transmission of the infection is reduced because of improved sanitation. The effect of sanitation is long-lasting and in this respect gives better results than vaccination.The simultaneous application of mass vaccination and sanitation gives a cumulative effect, which in some cases tends to be close to the effect of sanitation alone.The model was used to forecast the probable effect of preventive measures against typhoid fever, such as mass immunization and sanitation programmes, on a selected population in terms of prevention of disease, as well as in terms of relative costs and benefits. It provides a useful guide for the rational use of funds and the facilities to be set aside for typhoid fever control purposes.Other possible uses of the model are briefly discussed.The need to adjust the model in relation to specific conditions in the community is stressed, as is the need to readjust it to take into account changes in the pattern of life and the natural history of typhoid fever.

Communicable Disease Control↗
PubMed1983

[Typhoid vaccination yesterday and today].

Despite the early attempts to produce resistance against typhoid fever with parenteral vaccination by Pfeiffer and Kolle in 1896, and with oral vaccines by Carroll in 1904, it was not until the 1950s when typhoid vaccine efficacy was prospectively evaluated in both well-controlled field trials and human volunteer studies. Among the parenteral whole cell preparations the acetone-inactivated and heat-phenol-killed vaccines, respectively, demonstrating an efficacy of 60-90% for 3-5 years, have received most attention. Oral killed typhoid vaccines have enjoyed popularity for many years, but their effectiveness has never been proven under statistically and epidemiologically controlled conditions. More encouraging results were obtained with live oral vaccines produced from genetically defective, avirulent mutants. Investigations with streptomycin-dependent strains of Salmonella typhi were followed by studies of so-called galE mutants. One of such vaccine strains, labelled Ty 21a, proved to be more effective in volunteer studies than all previous vaccines, and promoted 95% resistance to clinical illness for three years in a field trial in Egypt. It has to be borne in mind, however, that immunity to typhoid fever is never absolute but depends on the dose of infection. This is important to be known by the vaccinee in order to avoid a wrong feeling of security which might result in negligence of personal and food hygiene.

Administration, Oral↗
PubMed1980

A controlled field trial of liver oral typhoid vaccine Ty21a.

A controlled field trial of a live oral typhoid vaccine was carried out in Alexandria, Egypt, in 1978-79. A total of 32 388 children were included in the study. They were divided in two comparable groups, one given 3 doses of the vaccine and the other 3 doses of the placebo. Each active dose contained 1 x 10(9)-8 x 10(9) live Ty21a bacteria. From March 1978 to March 1979, the population studied was followed up and suspected typhoid cases were investigated bacteriologically and serologically. The effectiveness of the vaccine was assessed by analysis of the incidence of typhoid fever in the two groups. The results of the follow-up indicate that, in the dosage schedule used, the Ty21a mutant strain, found previously to be stable and safe, is protective against typhoid fever for at least one year.

Child↗
PubMed1989

Humoral and cellular immune responses to Salmonella typhi in patients with typhoid fever.

Humoral and cellular immune responses to Salmonella typhi have been studied in nine children with typhoid fever. By using dot immunobinding assay, anti-O-polysaccharide chain and antilipid A antibody titers have been evaluated during the course of the disease. Anti-O-polysaccharide chain antibody titers are lower at the first week and increase up to the third week of the infection. On the other hand, antilipid A antibody levels, which are already higher at the beginning of the disease, progressively augment during the following weeks. Concerning cellular immunity to S. typhi, antibacterial activity mediated by typhoid peripheral mononuclear cells has been determined. Results show this function to be depressed in the initial phase of typhoid, increasing with the time. Together, these data bring new insight on immunity in typhoid patients.

Antibodies, Bacterial↗
PubMed1996

A semi-quantitative reverse transcriptase polymerase chain reaction method for measurement of MRNA for TNF-alpha and IL-1 beta in whole blood cultures: its application in typhoid fever and exentric exercise.

Whole blood cultures are used to study cytokine stimulation and release ex vivo. In the present study this method was compared with a more direct approach and a quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to assess mRNA expression for IL-1 beta and tumour necrosis factor alpha (TNF-alpha) and mRNA in whole blood. Stimulation of whole blood from normal donors with lipopolysaccharide (LPS) at various time intervals showed a parallel rise of immunogenic IL-1 beta and TNF-alpha as well as a rise of mRNA expression for IL-1 beta and TNF-alpha with peak levels for IL-1 beta after 4-6 h stimulation and for mRNA TNF-alpha expression after 2 h stimulation. These methods were used to explore cytokine production during the course of typhoid fever and after a 5 km run. In both conditions circulating cytokine concentrations were not influenced, but the TNF-alpha and IL-1 beta mRNA gene expression in circulating whole blood cells was increased in patients with typhoid fever. The LPS-stimulated production of TNF-alpha and IL-1 beta was decreased in both but there was no change for the mRNA content in whole blood for these cytokines. These findings demonstrate that RT-PCR is an attractive method to study the gene expression of cytokines in whole blood, an increased TNF-alpha and IL-1 beta gene expression is present in typhoid fever, and that the LPS stimulated downregulation of cytokines in exercise and typhoid fever may be mediated by post-transcriptional processes.

Cells, Cultured↗
PubMed1992

Typhoid fever in the Neapolitan area: a case-control study.

Typhoid fever is endemic in the Neapolitan area, where its yearly incidence rate largely exceeds the corresponding national figure. During the period from January to June, 1990, a matched case-control study was carried out in order to identify risk factors of the disease in this area; 51 subjects (mean age 27.2 years) with typhoid fever were compared with 102 controls matched with respect to age, sex and educational level. Consumption of raw shellfish was reported by 76.5% of the cases, as opposed to 19.6% of the controls (P < 0.01). Subjects who had eaten this food item had a 13.3-fold risk (C.I. 95% = 5.5 - 32.8) of contracting typhoid fever. In contrast, no risk was found to be associated with consumption of cooked shellfish, raw vegetables, ice-cream, non-potable water, or unpasteurized milk. The risk factor identified in this study shows that hazardous dietary habits and inadequate sewage treatment facilities, combined with lack of sanitation in the harvesting and marketing of shellfish, play a major role in the endemicity of typhoid fever in the Neapolitan area.

Case-Control Studies↗
PubMed1976

Chemotherapy of typhoid fever: a review of literature.

Until the last few years, chloramphenicol was recognized positively as the drug of choice in the treatment of acute typhoid fever. Its hematoxicity, as well as the recently observed epidemic and the present endemic occurrence of S. typhi strains with R-factor-mediated resistance to chloramphenicol in Mexico, India and South-EAst Asia, render the clinical evaluation of new antibacterial agents extremely important. By means of a literature review on controlled comparative trials, the value of thiamphenicol, ampicillin, amoxycillin, furazolidone and co-trimoxazole as alternative drugs for the treatment of acute typhoid fever is examined. Co-trimoxazole seems to be the drug of choice in the treatment of acute typhoid fever. For the treatment of the chronic typhoid carrier ampicillin is most frequently used, but amoxycillin and co-trimoxazole seem to be just as effective.

Amoxicillin↗
PubMedDate not supplied

Pefloxacin versus chloramphenicol in the therapy of typhoid fever.

An open, randomized clinical study was carried out to compare the clinical efficacy and safety of pefloxacin with that of chloramphenicol in the treatment of typhoid fever. Sixty hospitalized patients (40 men and 20 women, aged from 17 to 64 years), affected by severe proven typhoid sepsis, were randomly assigned to treatment with pefloxacin at a daily dose of 1,200 mg for 15 days (Group A) or with chloramphenicol at a daily dose of 2 g for 15 days (Group B). The two groups of patients were statistically homogeneous regarding both age and sex and all patients were followed for 30 days after the end of therapy. In Group A all the patients completely recovered from infection and all the isolated strains of Salmonella typhi were eradicated by pefloxacin treatment. In Group B two patients had a relapse, two patients became chronic enteric carriers of S. typhi and only 26 patients recovered from infection with complete eradication of the pathogen. The results indicate that pefloxacin is as active as chloramphenicol in the therapy of typhoid fever and that pefloxacin could be a valid antibacterial agent to be used together with appropriate hygienic measures for an eradication program of typhoid fever in the endemic countries.

Adolescent↗
PubMed1993

Complications of typhoid fever requiring laparotomy during childhood.

All the complications requiring laparotomy among 680 children who were diagnosed as having typhoid fever between 1981 and 1990, at Hacettepe University Children's Hospital, were retrospectively analyzed. Four patients developed intestinal perforation, two gastrointestinal bleeding, and two splenic abscess, with frequencies of 0.58%, 0.29%, and 0.29%, respectively. The overall frequency was 1.17%. While the risk was 1.58% among males, it was 0.42% among females with no statistically significant difference (P > .05). The risk was higher among patients above 6 years of age (P < .05). While perforation and hemorrhagic complications developed within 10 days of initial symptoms and splenic abscess required 10 and 30 days for development, there were no clinical signs and laboratory findings predicting the occurrence of complications in the course of typhoid fever. Two patients, one with intestinal perforation and the other with gastrointestinal hemorrhage, died within 2 days following the septic postoperative courses. On the other hand, 12 patients, among those without complications requiring laparotomy, died of unremitting septic course of the disease. The mortality rate rose from 1.78% to 25% when complications occurred. The findings in this series demonstrate that typhoid fever presents a challenge to the pediatric surgeons not only because of the complications requiring laparotomy with high mortality rates, but also the absence of criteria predicting the occurrence of complications in the course of typhoid fever.

Abscess↗
PubMed2006

Evaluation of new-generation serologic tests for the diagnosis of typhoid fever: data from a community-based surveillance in Calcutta, India.

Although typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi, rapid and simple diagnostic serologic tests would be useful in developing countries. We examined the performance of Widal test in a community field site and compared it with Typhidot and Tubex tests for diagnosis of typhoid fever. Blood samples were collected from 6697 patients with fever for > or =3 days for microscopy, culture, and serologic testing and from randomly selected 172 consenting healthy individuals to assess the baseline Widal anti-Typhi O lipopolysaccharide antibody (anti-TO) and anti-Typhi H flagellar antibody (anti-TH) titers. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 3 serologic tests were calculated using culture-confirmed typhoid fever cases as "true positives" and paratyphoid fever and malaria cases as "true negatives". Comparing cutoff values for the Widal test, an anti-TO titer of 1/80 was optimal with 58% sensitivity, 85% specificity, 69% PPV, and 77% NPV. Sensitivity was increased to 67% when the Widal test was done on the 5th day of illness and thereafter. The sensitivity, specificity, PPV, and NPV of Typhidot and Tubex were not better than Widal test. There is a need for more efficient rapid diagnostic test for typhoid fever especially during the acute stage of the disease. Until then, culture remains the method of choice.

Antibodies, Bacterial↗
PubMed2005

Evaluation of Salmonella enterica serovar Typhi (Ty2 aroC-ssaV-) M01ZH09, with a defined mutation in the Salmonella pathogenicity island 2, as a live, oral typhoid vaccine in human volunteers.

Salmonella enterica serovar Typhi strains with mutations in the Salmonella pathogenicity island-2 (SPI-2) may represent an effective strategy for human vaccine development, and a vectoring system for heterologous antigens. S. Typhi (Ty2 aroC-ssaV-) M01ZH09 is an attenuated, live, oral typhoid vaccine harboring defined deletion mutations in ssaV, which encodes an integral component in the SPI-2 type III secretion system (TTSS), as well as a mutation in an aromatic biosynthetic pathway needed for bacterial growth in vivo (aroC). SPI-2 mutant vaccines have yet to be evaluated in a large, randomized human trial. A simplified or single-oral dose oral typhoid vaccine using the SPI-2 strategy would offer significant advantages over the currently licensed typhoid vaccines. We performed a double-blinded, placebo-controlled, dose-escalating clinical trial in 60 healthy adult volunteers to determine the tolerability and immunogenicity of a single dose of M01ZH09. Three groups of 20 healthy adult volunteers were enrolled; 16 in each group received a single oral dose of the freeze-dried vaccine at 5 x 10(7), 5 x 10(8) or 5 x 10(9)CFU in a bicarbonate buffer. Four volunteers in each cohort received placebo in the same buffer. Adverse events were infrequent and not statistically different between vaccine and placebo recipients, although two subjects in the mid-range dose and three subjects in the highest dose had temperature measurements >37.5 degrees C. No blood or urine cultures were positive for M01ZH09, and fecal shedding was brief. The immune response was dose-related; the highest vaccine dose (5 x 10(9)CFU) was the most immunogenic. All tested subjects receiving the highest dose had a significant ASC response (mean 118 spots/10(6) cells). A >or=4-fold increase in antibody titer for S. Typhi LPS or flagellin was detected in 75% of volunteers in the highest-dose cohort by day 28. The SPI-2 mutant vaccine, M01ZH09, is a promising typhoid vaccine candidate and deserves further study as a vectoring system for heterologous vaccine antigens.

Administration, Oral↗