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Vaccine May 2023A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis... (Randomized Controlled Trial)
Randomized Controlled Trial
A cluster-randomized trial of Vi-TT was conducted in Dhaka, Bangladesh, using JE vaccine as the control. A subset of 1,500 children were randomly selected on 2:1 basis (Vi-TT vs JE) to assess immune response. Blood was collected before vaccination, and on days 28, 545 and 730 post-vaccination and plasma anti-Vi-IgG response was measured. A robust, persistent antibody response was induced after single dose of Vi-TT, even after 2 years of vaccination. While there is no accepted serological antibody threshold of protection, analyzing the antibodies of children who received Vi-TT provides evidence that may later be useful in predicting population protection.
Topics: Humans; Child; Typhoid Fever; Tetanus Toxoid; Salmonella typhi; Vaccines, Conjugate; Bangladesh; Immunoglobulin G; Typhoid-Paratyphoid Vaccines; Antibodies, Bacterial; Vaccination; Antibody Formation
PubMed: 37061369
DOI: 10.1016/j.vaccine.2023.04.014 -
Frontiers in Immunology 2023Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Typhi infections. TCVs offer better...
Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses.
INTRODUCTION
Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood.
METHODS AND RESULTS
Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV.
DISCUSSION
Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as . Typhi.
Topics: Animals; Mice; Salmonella typhi; Vaccines, Conjugate; Typhoid Fever; Polysaccharides, Bacterial; Immunoglobulin G; Antibody Formation; Typhoid-Paratyphoid Vaccines; Immunoglobulin M
PubMed: 37033932
DOI: 10.3389/fimmu.2023.1139329 -
Microbial Genomics Mar 2023In early 2020, the Medical Biology Laboratory of the Pasteur Institute of Cambodia isolated an unusually high number of fluoroquinolone-resistant subspecies serovar...
In early 2020, the Medical Biology Laboratory of the Pasteur Institute of Cambodia isolated an unusually high number of fluoroquinolone-resistant subspecies serovar Paratyphi A strains during its routine bacteriological surveillance activities in Phnom Penh, Cambodia. A public-health investigation was supported by genome sequencing of these Paratyphi A strains to gain insights into the genetic diversity and population structure of a potential outbreak of fluoroquinolone-resistant paratyphoid fever. Comparative genomic and phylodynamic analyses revealed the 2020 strains were descended from a previously described 2013-2015 outbreak of Paratyphi A infections. Our analysis showed sub-lineage 2.3.1 had remained largely susceptible to fluoroquinolone drugs until 2015, but acquired chromosomal resistance to these drugs during six separate events between late 2012 and 2015. The emergence of fluoroquinolone resistance was rapidly followed by the replacement of the original susceptible Paratyphi A population, which led to a dramatic increase of fluoroquinolone-resistant blood-culture-confirmed cases in subsequent years (2016-2020). The rapid acquisition of resistance-conferring mutations in the Paratyphi A population over a 3 year period is suggestive of a strong selective pressure on that population, likely linked with fluoroquinolone use. In turn, emergence of fluoroquinolone resistance has led to increased use of extended-spectrum cephalosporins like ceftriaxone that are becoming the drug of choice for empirical treatment of paratyphoid fever in Cambodia.
Topics: Humans; Salmonella paratyphi A; Paratyphoid Fever; Fluoroquinolones; Anti-Bacterial Agents; Serogroup; Cambodia; Phylogeny; Drug Resistance, Bacterial; Disease Outbreaks
PubMed: 36961484
DOI: 10.1099/mgen.0.000972 -
Clinical Infectious Diseases : An... Jul 2023The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The World Health Organization recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018, the Navi Mumbai Municipal Corporation (NMMC) implemented a typhoid conjugate vaccine (TCV) campaign. The campaign targeted all children aged 9 months through 14 years within NMMC boundaries (approximately 320 000 children) over 2 vaccination phases. The phase 1 campaign occurred from 14 July 2018 through 25 August 2018 (71% coverage, approximately 113 420 children). We evaluated the phase 1 campaign's programmatic effectiveness in reducing typhoid cases at the community level.
METHODS
We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai and offered blood cultures to children who presented with fever ≥3 days. We used a cluster-randomized (by administrative boundary) test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched test-positive, culture-confirmed typhoid cases with up to 3 test-negative, culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression.
RESULTS
Between 1 September 2018 and 31 March 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (programmatic effectiveness, 56%; 95% confidence interval [CI], 25% to 74%; P = .002). Cases aged ≥5 years were 0.37 times as likely (95% CI, .19 to .70; P = .002) and cases during the first year of surveillance were 0.30 times as likely (95% CI, .14 to .64; P = .002) to live in vaccine campaign communities.
CONCLUSIONS
Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Incidence; India; Prospective Studies; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Attenuated; Vaccines, Conjugate
PubMed: 36947143
DOI: 10.1093/cid/ciad132 -
Clinical Infectious Diseases : An... Jul 2023
Topics: Child; Humans; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Public Sector; India
PubMed: 36947122
DOI: 10.1093/cid/ciad134 -
BMC Infectious Diseases Mar 2023Several prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant...
BACKGROUND
Several prolonged typhoid fever epidemics have been reported since 2010 throughout eastern and southern Africa, including Malawi, caused by multidrug-resistant Salmonella Typhi. The World Health Organization recommends the use of typhoid conjugate vaccines (TCVs) in outbreak settings; however, current data are limited on how and when TCVs might be introduced in response to outbreaks.
METHODOLOGY
We developed a stochastic model of typhoid transmission fitted to data from Queen Elizabeth Central Hospital in Blantyre, Malawi from January 1996 to February 2015. We used the model to evaluate the cost-effectiveness of vaccination strategies over a 10-year time horizon in three scenarios: (1) when an outbreak is likely to occur; (2) when an outbreak is unlikely to occur within the next ten years; and (3) when an outbreak has already occurred and is unlikely to occur again. We considered three vaccination strategies compared to the status quo of no vaccination: (a) preventative routine vaccination at 9 months of age; (b) preventative routine vaccination plus a catch-up campaign to 15 years of age; and (c) reactive vaccination with a catch-up campaign to age 15 (for Scenario 1). We also explored variations in outbreak definitions, delays in implementation of reactive vaccination, and the timing of preventive vaccination relative to the outbreak.
RESULTS
Assuming an outbreak occurs within 10 years, we estimated that the various vaccination strategies would prevent a median of 15-60% of disability-adjusted life-years (DALYs). Reactive vaccination was the preferred strategy for WTP values of $0-300 per DALY averted. For WTP values > $300, introduction of preventative routine TCV immunization with a catch-up campaign was the preferred strategy. Routine vaccination with a catch-up campaign was cost-effective for WTP values above $890 per DALY averted if no outbreak occurs and > $140 per DALY averted if implemented after the outbreak has already occurred.
CONCLUSIONS
Countries for which the spread of antimicrobial resistance is likely to lead to outbreaks of typhoid fever should consider TCV introduction. Reactive vaccination can be a cost-effective strategy, but only if delays in vaccine deployment are minimal; otherwise, introduction of preventive routine immunization with a catch-up campaign is the preferred strategy.
Topics: Humans; Adolescent; Typhoid Fever; Cost-Effectiveness Analysis; Typhoid-Paratyphoid Vaccines; Vaccines, Conjugate; Cost-Benefit Analysis
PubMed: 36890448
DOI: 10.1186/s12879-023-08105-2 -
Pediatrics and Neonatology Sep 2023Typhoid fever is a serious concern precisely in developing nations. Still investigators are exploring a better conjugate partner for Vi-polysaccharide to develop a more...
Typhoid fever is a serious concern precisely in developing nations. Still investigators are exploring a better conjugate partner for Vi-polysaccharide to develop a more effective vaccine for typhoid fever. Here, we cloned and expressed S. Typhi outer membrane protein A (OmpA). The conjugation of Vi-polysaccharide with OmpA was carried out by the carbodiimide (EDAC) method employing ADH as a linker. Total Ig and IgG generated against OmpA, and Vi polysaccharide was quantified by ELISA. Vi polysaccharide alone induced very low levels of Vi polysaccharide antibody. Vi-OmpA conjugate (Vi-conjugate) elicited a robust immune response compared to Vi polysaccharide alone and showed booster response. Further, IgG was only evoked by Vi-OmpA conjugate, not with Vi polysaccharide alone. OmpA antibody induction in both the Vi-OmpA conjugate and OmpA were similar level. Taken together, we show that OmpA as a carrier protein conjugated to Vi polysaccharide is immunogenic. We predict OmpA antibodies will contribute protection along with antibodies generated by Vi-polysaccharide. Past and current literature supports that OmpA is highly conserved protein not only among Salmonellae but entire Enterobacteriacea family with 96-100% identity.
Topics: Animals; Mice; Typhoid Fever; Salmonella typhi; Polysaccharides, Bacterial; Typhoid-Paratyphoid Vaccines; Antibodies, Bacterial; Immunoglobulin G; Immunity; Vaccines, Conjugate
PubMed: 36868948
DOI: 10.1016/j.pedneo.2022.12.011 -
Microbial Genomics Feb 2023Paratyphi B infections in England are the least common imported typhoidal infection but can still cause invasive disease. Sentinel surveillance at the reference...
Paratyphi B infections in England are the least common imported typhoidal infection but can still cause invasive disease. Sentinel surveillance at the reference laboratory detected an outbreak from Iraq due to reported travel history, enabling enhanced PCR testing for a quick diagnosis.
Topics: Humans; Salmonella paratyphi B; Paratyphoid Fever; Sentinel Surveillance; Iraq; Mass Gatherings; Genomics; Disease Outbreaks
PubMed: 36825878
DOI: 10.1099/mgen.0.000940 -
MMWR. Morbidity and Mortality Weekly... Feb 2023Typhoid fever, an acute febrile illness caused by Salmonella enterica serovar Typhi (S. Typhi), is endemic in many low- and middle-income countries (1). In 2015, an...
Typhoid fever, an acute febrile illness caused by Salmonella enterica serovar Typhi (S. Typhi), is endemic in many low- and middle-income countries (1). In 2015, an estimated 11-21 million typhoid fever cases and 148,000-161,000 associated deaths occurred worldwide (2). Effective prevention strategies include improved access to and use of infrastructure supporting safe water, sanitation, and hygiene (WASH); health education; and vaccination (1). The World Health Organization (WHO) recommends programmatic use of typhoid conjugate vaccines for typhoid fever control and prioritization of vaccine introduction in countries with the highest typhoid fever incidence or high prevalence of antimicrobial-resistant S. Typhi (1). This report describes typhoid fever surveillance, incidence estimates, and the status of typhoid conjugate vaccine introduction during 2018-2022. Because routine surveillance for typhoid fever has low sensitivity, population-based studies have guided estimates of case counts and incidence in 10 countries since 2016 (3-6). In 2019, an updated modeling study estimated that 9.2 million (95% CI = 5.9-14.1) typhoid fever cases and 110,000 (95% CI = 53,000-191,000) deaths occurred worldwide, with the highest estimated incidence in the WHO South-East Asian (306 cases per 100,000 persons), Eastern Mediterranean (187), and African (111) regions (7). Since 2018, five countries (Liberia, Nepal, Pakistan, Samoa [based on self-assessment], and Zimbabwe) with estimated high typhoid fever incidence (≥100 cases per 100,000 population per year) (8), high antimicrobial resistance prevalence, or recent outbreaks introduced typhoid conjugate vaccines into their routine immunization programs (2). To guide vaccine introduction decisions, countries should consider all available information, including surveillance of laboratory-confirmed cases, population-based and modeling studies, and outbreak reports. Establishing and strengthening typhoid fever surveillance will be important to measure vaccine impact.
Topics: Humans; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Incidence; Anti-Infective Agents
PubMed: 36795626
DOI: 10.15585/mmwr.mm7207a2 -
Vaccine Mar 2023The typhoid conjugate vaccine (TCV) ensures a long-lasting protective immune response, requires fewer doses and is fit for children under 2 years of age. From Phase I... (Randomized Controlled Trial)
Randomized Controlled Trial
A Phase II/III, Multicenter, Observer-blinded, Randomized, Non-inferiority and Safety, study of typhoid conjugate vaccine (EuTCV) compared to Typbar-TCV® in healthy 6 Months-45 years aged participants.
The typhoid conjugate vaccine (TCV) ensures a long-lasting protective immune response, requires fewer doses and is fit for children under 2 years of age. From Phase I study, EuTCV displayed considerable immunogenicity and reliable safety, thus endorsing further examination in Phase II/III trials. Therefore, a clinical Phase II/III study (NCT04830371) was conducted to evaluate its efficacy in healthy Filipino participants aged 6 months to 45 years through administration of the test vaccine (Arm A, B, and C) or comparator vaccine Typbar-TCV® (Arm D). Sera samples were collected pre-vaccination (Visit 1) and post-vaccination (Visit 4, Day 28) to assess the immunogenicity of EuTCV and Typbar-TCV®. During the study, participants were regularly monitored through scheduled visits to the clinic to report any adverse events associated with the vaccine. For vaccine safety, the proportion of solicited and unsolicited Treatment-Emergent Adverse Events was all comparable between EuTCV and Typbar-TCV® groups. A single dose of EuTCV produced seroconversion in 99.4% of treated participants, with seroconversion rates non-inferior to that of Typbar-TCV®. Batch-to-batch consistency was concluded based on the 90% Confidence Interval of the geometric mean ratio (EuTCV Arm A, B, and C) at Week 4, lying within the equivalence margin of 0.5 to 2.0 for all batches. Results from this Phase II/III clinical trial of EuTCV in healthy volunteers show comparable safety and considerable immunogenicity, compared to Typbar-TCV®, meeting the objectives of this pivotal study. ClinicalTrials.gov registration number: NCT04830371.
Topics: Child; Humans; Infant; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccines, Conjugate; Vaccination; Smallpox Vaccine; Immunogenicity, Vaccine
PubMed: 36774331
DOI: 10.1016/j.vaccine.2022.12.007