Vi Vaccine Research Articles

Immune Responses to Vi Capsular Polysaccharide Typhoid Vaccine in Children 2 to 16 Years Old in Karachi, Pakistan, and Kolkata, India

The geometric mean concentration (GMC) and the proportion maintaining a protective level (150 enzyme-linked immunosorbent assay (ELISA) units [ELU]/ml) 2 years following a single dose of 25 μg of injectable Vi capsular polysaccharide typhoid vaccine was measured against that of the control hepatitis A vaccine in children 2 to 16 years old in cluster randomized trials in Karachi and Kolkata. The GMC for the Vi group (1,428 ELU/ml) was statistically significantly different from the GMC of the control hepatitis A vaccine group (86 ELU/ml) after 6 weeks. A total of 117 children (95.1%) in the Vi group and 9 (7.5%) in the hepatitis A group showed a 4-fold rise in Vi IgG antibody concentrations at 6 weeks (P < 0.01). Protective antibody levels remained significantly different between the two groups at 2 years (38% in the Vi vaccine groups and 6% in the hepatitis A group [P < 0.01]). A very small proportion of younger children (2 to 5 years old) maintained protective Vi IgG antibody levels at 2 years, a result that was not statistically significantly different compared to that for the hepatitis A group (38.1% versus 10.5%). The GMCs of the Vi IgG antibody after 2 years were 133 ELU/ml for children 2 to <5 years old and 349 ELU/ml for children 5 to 16 years old. In conclusion, Vi capsular polysaccharide typhoid vaccine is immunogenic in children in settings of South Asia where typhoid is highly endemic. The antibody levels in children who received this vaccine remained higher than those in children who received the control vaccine but were significantly reduced at 2 years of follow-up.

Cross‐Reactive Immune Response Induced by the Vi Capsular Polysaccharide Typhoid Vaccine Against Salmonella Paratyphi Strains

There are no vaccines in clinical use against paratyphoid fever, caused by Salmonella Paratyphi A and B or, rarely, C. Oral Salmonella Typhi Ty21a typhoid vaccine elicits a significant cross-reactive immune response against S. Paratyphi A and B, and some reports suggest cross-protective efficacy against the disease. These findings are ascribed to the O-12 antigen shared between the strains. The Vi capsular polysaccharide vaccine has been shown to elicit antibodies reactive with O-9,12. Twenty-five volunteers immunized with the parenteral Vi vaccine (Typherix(®) ) were explored for plasmablasts cross-reactive with paratyphoid strains; the responses were compared to those in 25 age- and gender-matched volunteers immunized with Ty21a (Vivotif(®) ). Before vaccination, 48/50 vaccinees had no plasmablasts reactive with the antigens. Seven days after vaccination, 15/25 and 22/25 Vi- and Ty21a-vaccinated volunteers had circulating plasmablasts producing antibodies cross-reactive with S. Paratyphi A, 18/25 and 23/25 with S. Paratyphi B and 16/25 and 9/25 with Paratyphi C, respectively. Compared to the Ty21a group, the Vi group showed significantly lower responses to S. Paratyphi A and B and higher to S. Paratyphi C. To conclude, the Vi vaccine elicited a cross-reactive plasmablast response to S. Paratyphi C (Vi antigen in common) and less marked responses to S. Paratyphi A and B than the Ty21a preparation. S. Paratyphi A and B both being Vi-negative, the result can be explained by trace amounts of bacterial cell wall O-12 antigen in the Vi preparation, despite purification. The clinical significance of this finding remains to be determined.

Vaccines for preventing typhoid fever

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development. To evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever. In June 2013, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2013 and scanned the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease). Two review authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella typhi in blood. We calculated risk ratios (RRs) and efficacy (1-RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs were included in this review; 12 evaluated efficacy (Ty21a: five trials; Vi polysaccharide: six trials; Vi-rEPA: one trial), and 11 reported on adverse events. Ty21a vaccine (oral vaccine, three doses) A three-dose schedule of Ty21a vaccine prevents around one-third to one-half of typhoid cases in the first two years after vaccination (Year 1: 35%, 95% CI 8% to 54%; Year 2: 58%, 95% CI 40% to 71%; one trial, 20,543 participants; moderate quality evidence; data taken from a single trial conducted in Indonesia in the 1980s). No benefit was detected in the third year after vaccination. Four additional cluster-RCTs have been conducted, but the study authors did not adjust for clustering.Compared with placebo, this vaccine was not associated with more participants with vomiting, diarrhoea, nausea or abdominal pain (four trials, 2066 participants; moderate quality evidence) headache, or rash (two trials, 1190 participants; moderate quality evidence); however, fever (four trials, 2066 participants; moderate quality evidence) was more common in the vaccine group. Vi polysaccharide vaccine (injection, one dose) A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (Year 1: 69%, 95% CI 63% to 74%; three trials, 99,979 participants; high quality evidence). In Year 2, the trial results were more variable, with the vaccine preventing between 45% and 69% of typhoid cases (Year 2: 59%, 95% CI 45% to 69%; four trials, 194,969 participants; moderate quality evidence). The three-year cumulative efficacy of the vaccine is around 55% (95% CI 30% to 70%; 11,384 participants, one trial; moderate quality evidence). These data are taken from a single trial in South Africa in the 1980s.Compared with placebo, this vaccine was not associated with more participants with fever (four trials, 133,038 participants; moderate quality evidence) or erythema (three trials, 132,261 participants; low quality evidence); however, swelling (three trials, 1767 participants; moderate quality evidence) and pain at the injection site (one trial, 667 participants; moderate quality evidence) were more common in the vaccine group. Vi-rEPA vaccine (two doses) Administration of two doses of the Vi-rEPA vaccine prevents between 50% and 96% of typhoid cases during the first two years after vaccination (Year 1: 94%, 95% CI 75% to 99%; Year 2: 87%, 95% CI 56% to 96%; one trial, 12,008 participants; moderate quality evidence). These data are taken from a single trial with children 2 to 5 years of age conducted in Vietnam.Compared with placebo, the first and second doses of this vaccine were not associated with increased risk of adverse events. The first dose of this vaccine was not associated with fever (2 studies, 12,209 participants; low quality evidence), erythema (two trials, 12,209 participants; moderate quality evidence) or swelling at the injection site (two trials, 12,209 participants; moderate quality evidence). The second dose of this vaccine was not associated with fever (two trials, 11,286 participants; low quality evidence), erythema (two trials, 11,286 participants; moderate quality evidence) and swelling at the injection site (two trials, 11,286 participants; moderate quality evidence). The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.

Cross-reactive immune response elicited by parenteral Vi polysaccharide typhoid vaccine against non-typhoid Salmonellae

BackgroundDespite 155000 deaths and over 90 million cases – and the current emergence of antimicrobial resistance – no vaccines are available against non-typhoid Salmonellae (NTS). We recently presented immunological arguments for using the oral Salmonella Typhi Ty21a as surrogate vaccine against NTS strains: Ty21a elicits intestinal antibodies against typhoidal O-9,12 antigen, and numerous NTS strains share one or both of these structures with S. Typhi. The Vi polysaccharide vaccine can, presumably because of contaminating typhoidal lipopolysaccharide, also elicit a humoral response to O-9,12, although a lower one in magnitude than the Ty21a. In this study, the Vi vaccine was explored for cross-reactive immune response to various NTS strains, and compared to that elicited by the Ty21a vaccine. Materials and methodsVolunteers immunized with the Vi polysaccharide (Typherix®; n=25) were investigated for circulating plasmablasts secreting antibodies reactive with six NTS serotypes. The results were compared to those for 25 age- and gender-matched volunteers vaccinated with Ty21a (Vivotif®), as partly presented in our previous study. The cross-reactive plasmablasts elicited by the Vi vaccine were also analyzed for homing receptor expressions. Results49 out of 50 vaccinees showed a cross-reactive plasmablast response against S. Enteritidis sharing both O-9 and O-12 antigens with S. Typhi (mean: 95%CI 37: 19–55 and 363: 234–493 plasmablasts/106 PBMC in the Vi and the Ty21a group, respectively). The response against strains only sharing O-12 was weaker (22: 8–38 and 222: 105–338 against S. Typhimurium). Strains without typhoidal O-antigens generated no significant reactivity. The cross-reactive plasmablasts elicited by the Vi vaccine had systemic homing properties. ConclusionsThe Vi vaccine elicited an immune response cross-reactive with several NTS strains. This response was lower than that in Ty21a-vaccinated volunteers. The clinical significance of these responses deserves further research with respect to both gastrointestinal and invasive NTS (iNTS) disease.

Two “Lost Boys of Sudan” Undergo Liver Transplantation

Two “Lost Boys of Sudan” Undergo Liver Transplantation

Head-to-Head Comparison of Humoral Immune Responses to Vi Capsular Polysaccharide and Salmonella Typhi Ty21a Typhoid Vaccines–A Randomized Trial

BackgroundThe two typhoid vaccines, the parenteral Vi capsular polysaccharide and the oral live whole-cell Salmonella Typhi Ty21a vaccine, provide similar levels of protection in field trials. Sharing no antigens, they are thought to confer protection by different mechanisms. This is the first head-to-head study to compare the humoral immune responses to these two vaccines.Methods50 age- and gender-matched volunteers were immunized, 25 with the Vi and 25 with the Ty21a vaccine. Circulating plasmablasts reactive with whole-cell Salmonella Typhi or one of the typhoidal antigenic structures, Vi, O-9,12, and H-d antigens, were identified as antibody-secreting cells (ASC) with ELISPOT. Homing receptor (HR) expressions were determined. These results were compared with ASC in four patients with typhoid fever. Antibodies to S. Typhi lipopolysaccharides were assessed in cultures of ALS (antibodies in lymphocyte supernatants) and in serum with ELISA.ResultsIn 49 out of 50 vaccinees, no typhoid-specific plasmablasts were seen before vaccination. On day 7, response to Vi antigen was mounted in 24/25 volunteers in the Vi, and none in the Ty21a group; response to S. Typhi and O-9,12 was mounted in 49/50 vaccinees; and to H-d in 3/50. The numbers of typhoid-specific plasmablasts (total of ASC to Vi, O-9,12 and H-d antigens) proved equal in the vaccination groups. The HR expressions indicated a mainly systemic homing in the Vi and intestinal in the Ty21a group, the latter resembling that in natural infection. Plasmablasts proved more sensitive than serum and ALS in assessing the immune response.ConclusionsThe typhoid-specific humoral responses to Vi and Ty21a vaccines are similar in magnitude, but differ in expected localization and antigen-specificity. The unforeseen O antigen-specific response in the Vi group is probably due to lipopolysaccharide contaminating the vaccine preparation. Only the response to Ty21a vaccine was found to imitate that in natural infection.Trial RegistrationCurrent Controlled Trials Ltd. c/o BioMed Central ISRCTN68125331

137. Inflammatory effects on human Rhinal cortex glucose metabolism predict subsequent spatial memory impairment

Rodent studies implicate inflammatory mediators in both physiological and pathological hippocampus-dependent memory processes (Yirmiya, BBI, 2011). Predominant effects on encoding or consolidation are uncertain, though recent transgenic mice data with selective hippocampal IL-1beta over-expression suggest early encoding effects (Moore, Neuroscience, 2009). To investigate this in humans, twenty healthy participants (24.7 ± 6.8 yrs) underwent 18 Fluorodeoxyglucose (18FDG)– PET scanning at baseline 4 and 8 h. After session 1 and 2 they learned and recalled the spatial location of objects in two separate PC-based virtual environments, completed a non-hippocampus dependent (control) mirror-tracing task then received Typhoid (Typhim Vi) vaccination followed by Saline (control) or vice versa. After session 3 they recalled the spatial location of objects learned at sessions 1 and 2. Inflammation at 4 h was associated with a discrete reduction in resting Rhinal-cortex metabolism: interaction group × time, P F (1,17) = 5.01, P = 0.039, F (1,17) = 1.38, p = 0.26). To investigate, whether inflammatory effects on resting Rhinal-cortex metabolism predicted subsequent spatial memory impairment we performed a regression analysis of our behavioural and PET data. Strikingly, this revealed that though Rhinal-cortex metabolism prior to encoding predicted subsequent spatial memory performance (both immediate and late) in controls ( P inflammation (significant interaction with group p Rhinal-cortex metabolism may impair encoding in human spatial memory .

High-Resolution Genotyping of the Endemic Salmonella Typhi Population during a Vi (Typhoid) Vaccination Trial in Kolkata

BackgroundTyphoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas.MethodologyWe used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003–December 2006, vaccinations given December 2004).Principal FindingsA diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%), which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole). Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin). Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes.ConclusionsTyphoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period.

Impact of Vi vaccination on spatial patterns of typhoid fever in the slums of Kolkata, India

A mass typhoid Vi vaccination campaign was carried out among approximately 60,000 slum residents of Kolkata, India. This study evaluated the impact of the campaign on spatial patterns of typhoid fever. Eighty contiguous residential groups of households in the study area were randomized to receive either a single dose of the Vi polysaccharide vaccine or a single dose of the inactivated hepatitis A vaccine as the control agent. Persons aged two years and older were eligible to receive the vaccine. Vaccine protection against typhoid fever was monitored for two years after vaccination at both outpatient and inpatient facilities serving the study population. Geographic analytic and mapping tools were used in the analysis. Spatial randomness of the disease was observed during the pre-vaccination period, which turned into a significant pattern after vaccination. The high-risk areas for typhoid were observed in the area dominated by the control clusters, and the low-risk areas were in the area dominated by the Vi clusters. Furthermore, the control clusters surrounded by the Vi clusters were low risk for typhoid fever. The results demonstrated the ability of mass vaccination to change the spatial patterns of disease through the creation of spatial barriers to transmission of the disease. Understanding and mapping the disease risk could be useful for designing a community-based vaccination strategy to control disease.

Oral priming with Salmonella Typhi vaccine strain CVD 909 followed by parenteral boost with the S. Typhi Vi capsular polysaccharide vaccine induces CD27+IgD− S. Typhi-specific IgA and IgG B memory cells in humans

Attenuated live oral typhoid vaccine candidate CVD 909 constitutively expresses Salmonella Typhi capsular polysaccharide antigen (Vi). A randomized, double-blind, heterologous prime-boost clinical study was conducted to determine whether immunity to licensed parenteral Vi vaccine could be enhanced by priming with CVD 909. Priming with CVD 909 elicited higher and persistent, albeit not significant, anti-Vi IgG and IgA following immunization with Vi, than placebo-primed recipients. Vi-specific IgA B memory (B(M)) cells were significantly increased in CVD 909-primed subjects. S. Typhi-specific LPS and flagella IgA B(M) cells were observed in subjects immunized with CVD 909 or with the licensed Vi-negative oral typhoid vaccine Ty21a. CVD 909-induced B(M) cells exhibited a classical B(M) phenotype (i.e., CD3(-)CD19(+)IgD(-)CD27(+)). This is the first demonstration of classical B(M) cells specific for bacterial polysaccharide or protein antigens following typhoid immunization. The persistent IgA B(M) responses demonstrate the capacity of oral typhoid vaccines to prime mucosally relevant immune memory.

Population impact of Vi capsular polysaccharide vaccine

Development of a safe and efficacious vaccine against typhoid fever has been the mainstay of enteric vaccinology since production of the first parenteral whole-cell typhoid vaccine in 1896. The new-generation Vi polysaccharide single-dose injectable typhoid vaccine developed in the 1980s is widely used in countries where it is locally produced, such as China, and in travelers from industrialized countries to typhoid-endemic settings. However, Vi vaccine use is limited to private practice at a small scale by residents of high-burden countries such as India, Pakistan and Bangladesh. Recognition of the public health importance of typhoid fever prevention has significantly increased due to the emergence of antimicrobial-resistant strains of Salmonella enterica serovar Typhi in recent years. Recent evidence of herd protection conferred by the Vi vaccine has highlighted the significance of the vaccine’s effects beyond the vaccinated population. The large-scale use of this vaccine can yield protective benefits to a larger population and can reduce the epidemiologic and economic burden of typhoid fever in endemic countries.

The Case for Investing in Typhoid Vaccines

The Case for Investing in Typhoid Vaccines

Genetic variation in response to a typhoid vaccine

Genetic variation in response to a typhoid vaccine

Vaccine desirability during an effectiveness trial of the typhoid fever polysaccharide Vi vaccine, Kolkata India

Background: High rates of typhoid fever and the emergence of multi-drug resistant strains create a need for prevention efforts including vaccines. Socio-behavioral research can provide important data for participation in future trials and public health vaccination campaigns. Design: A 3b phase clinical trial in Kolkata India including pre- and post-vaccination socio-behavioral surveys. Methods: 700 households randomly selected 503 respondents (71.85%) completing both the pre- and post- closed-ended surveys. Data analysis included descriptive statistics, Pearson’s chi-square tests, independent t-tests, and stepwise logistic regression analysis. Four open-ended questions were included in the survey. These qualitative data were coded and reviewed for common themes and patterns. Results: 47.9% of respondents were male. Ward 29 respondents included 32.4% Hindu and Ward 30 respondents were 99.0% Hindu. Lower rates of participation were found among Muslim respondents and those with post high school education. Lack of information and negative information affected participation. Joint decision-making within households increased participation rates. Conclusions: Individuals’ decisions to participate or not participate in a vaccine trial entail a balance between individual beliefs, household dynamics, and socio-political influences. Efforts prior to vaccination trials need to develop strategies which address potential underlying mediators for belief systems as well as structural factors which may reinforce individuals’ beliefs and perceptions about vaccination trials.

A Cluster-Randomized Effectiveness Trial of Vi Typhoid Vaccine in India

Typhoid fever remains an important cause of illness and death in the developing world. Uncertainties about the protective effect of Vi polysaccharide vaccine in children under the age of 5 years and about the vaccine's effect under programmatic conditions have inhibited its use in developing countries. We conducted a phase 4 effectiveness trial in which slum-dwelling residents of Kolkata, India, who were 2 years of age or older were randomly assigned to receive a single dose of either Vi vaccine or inactivated hepatitis A vaccine, according to geographic clusters, with 40 clusters in each study group. The subjects were then followed for 2 years. A total of 37,673 subjects received a dose of a study vaccine. The mean rate of vaccine coverage was 61% for the Vi vaccine clusters and 60% for the hepatitis A vaccine clusters. Typhoid fever was diagnosed in 96 subjects in the hepatitis A vaccine group, as compared with 34 in the Vi vaccine group, with no subject having more than one episode. The level of protective effectiveness for the Vi vaccine was 61% (95% confidence interval [CI], 41 to 75; P<0.001 for the comparison with the hepatitis A vaccine group). Children who were vaccinated between the ages of 2 and 5 years had a level of protection of 80% (95% CI, 53 to 91). Among unvaccinated members of the Vi vaccine clusters, the level of protection was 44% (95% CI, 2 to 69). The overall level of protection among all residents of Vi vaccine clusters was 57% (95% CI, 37 to 71). No serious adverse events that were attributed to either vaccine were observed during the month after vaccination. The Vi vaccine was effective in young children and protected unvaccinated neighbors of Vi vaccinees. The potential for combined direct and indirect protection by Vi vaccine should be considered in future deliberations about introducing this vaccine in areas where typhoid fever is endemic. (ClinicalTrials.gov number, NCT00125008.)

An optimization model for reducing typhoid cases in developing countries without increasing public spending

This article considers the investment case for using the Vi polysaccharide vaccine in developing countries from two perspectives: reducing typhoid cases and limiting new health care spending. A case study is presented using data from South and Southeast Asia. The purpose of the paper, however, is to draw broad implications that may apply to developing countries in general. Typical consumer demand functions developed from stated preference household surveys in South and Southeast Asia are used to predict probabilities of adults and children purchasing typhoid vaccinations at different prices. These functions are incorporated in a formal mathematical model. Using data from the recent literature for South and Southeast Asia for typhoid incidence, Vi vaccine effectiveness, public cost of illness, and vaccination program cost, three mass vaccination policy alternatives are evaluated: charging adults and children different (optimal) prices, charging uniform prices, and providing free vaccines. Assuming differential pricing is politically feasible, different vaccine prices for children and adults would maximize the number of typhoid cases avoided from a mass vaccination program if the public sector faces a budget constraint on spending for the vaccination program. However, equal prices for children and adults produce very similar results, and they might be more readily accepted by the community. Alternatively, if vaccines are free, the number of cases is not significantly reduced compared to either pricing policy, but a large external financial contribution from government or donors would be required. A Monte Carlo simulation explores the effects of uncertain parameters on vaccination program outcomes.

The cost-effectiveness of typhoid Vi vaccination programs: Calculations for four urban sites in four Asian countries

The burden of typhoid fever remains high in impoverished settings, and increasing antibiotic resistance is making treatment costly. One strategy for reducing the typhoid morbidity and mortality is vaccination with the Vi polysaccharide vaccine. We use a wealth of new economic and epidemiological data to evaluate the cost-effectiveness of Vi vaccination against typhoid in sites in four Asian cities: Kolkata (India), Karachi (Pakistan), North Jakarta (Indonesia), and Hue (Vietnam). We report results from both a societal as well as a public sector financial perspective. Baseline disease burden estimates in the four areas are: 750 cases per year in two Kolkata neighborhoods (pop 185,000); 84 cases per year in the city of Hue (pop 280,000); 298 cases per year in two sub-districts in North Jakarta (pop 161,000), and 538 cases per year in three squatter settlements in Karachi (pop 102,000). We estimate that a vaccination program targeting all children (2–14.9) would prevent 456, 158, and 258 typhoid cases (and 4.6, 1.6, and 2.6 deaths), and avert 126, 44, and 72 disability-adjusted life years (DALYs) over 3 years in Kolkata, North Jakarta and Karachi, respectively. The net social costs would be US$160 and US$549, per DALY averted in Kolkata and North Jakarta, respectively. These programs, along with a similar program in Karachi, would be considered “very cost-effective” (e.g. costs per DALY averted less than per capita gross national income (GNI)) under a wide range of assumptions. Community-based vaccination programs that also target adults in Kolkata and Jakarta are less cost-effective because incidence is lower in adults than children, but are also likely to be “very cost-effective”. A program targeting school-aged children in Hue, Vietnam would prevent 21 cases, avert 6 DALYs, and not be cost-effective (US$3779 per DALY averted) because of the low typhoid incidence there.

An Optimisation Model for Use of the Vi Polysaccharide Vaccine to Prevent Typhoid in Developing Countries

This article considers the investment case for using the Vi polysaccharide vaccine (Vi) in developing countries from two perspectives: reducing typhoid cases and limiting new health care spending. Consumer demand functions that predict probabilities of adults and children purchasing typhoid vaccinations at different prices are incorporated in a formal mathematical model. This optimisation model solves for the optimal vaccine prices to charge adults and children to maximise the number of typhoid cases avoided subject to the constraint that the sum of 1) vaccination revenues, 2) the public savings from avoided cases, and 3) an external (e.g., donor) contribution (if any), is sufficient to pay for the costs of the vaccination program. Using values from the recent literature for South and Southeast Asia for typhoid incidence, Vi vaccine effectiveness, public cost of illness, and vaccination program cost, three mass vaccination policy alternatives are considered - charging adults and children different (optimal) prices, charging uniform prices, and providing free vaccines. Assuming differential pricing is politically feasible, the vaccine price for children should be zero (because their incidence is much higher than adults), and fees for adults should cover most of costs of the vaccination program (because the savings from reduced public sector treatment are small). Equal prices for children and adults produce very similar results to the optimal solution. Alternatively, if vaccines are free, the number of cases is not significantly reduced compared to either pricing policy, but a large external financial contribution would be required.

Enteric Fever in South China: Guangxi Province

Guangxi is a province of China endemic for enteric fever. Salmonella enterica serovar Paratyphi A has been found to be causing more and more enteric fever episodes in the last 10 years, evident not only from routine surveillance but also from prospective population-based surveillance. The prevalent pattern of paratyphoid seen was different from typhoid since it mainly occurred in outbreaks. Almost all strains collected from different areas and years in Guangxi were resistance to nalidixic acid, which is an indicator of reduced efficacy of ciprofloxacin treatment. The emergence of epidemic paratyphoid fever occurred after large-scale use of the typhoid Vi vaccine, but little is know about why it emerged. This is of particular concern in the post Vi vaccine era due to the emergence and worldwide spread of multi-drug resistant S. Paratyphi A strains and the lack of a vaccine.

Seroprevalence of anti Vi antibodies and immunogenicity of Typhim Vi vaccine in children

This prospective study was carried out on 250 children between 6 months to 5 years of age to determine seroprevalence of anti Vi antibodies and to measure seroresponse and percent seroconversion to TyphimVi polysaccharide vaccine in children 2-5 years of age. Fifty children each were enrolled between 6 to12 months of age (Group A), between 1- 2 years of age(Group B), between 2-3 years of age(Group C), between 3-4 years of age (Group D) and between 4-5 years of age (Group E). Anti- Vi antibody baseline titres were determined in all children. Children in Groups C to E were vaccinated with Typhim Vi vaccine. Baseline and postvaccination antibody titres were determined by ELISA. Test serum which had antibody levels >1 µg/ml were scored as seropositive. Of 250 children, 3 had base line anti-Vi antibodies >1µg/ml. Following immunization overall seroconversion rate was 77.5% with 65.3%, 78.2% and 88% children showing seroconversion in Groups C, D and E respectively. Seroconversion was significantly more in Group E children compared to Group C (p=0.0148). There were no significant adverse reactions following vaccination. The study highlights very low prevalence of baseline anti Vi antibodies in children between 6 months and less than 5 years of age and shows high immunogenicity and safety of Typhim Vi polysaccharide vaccine in children 2- 5 years of age.