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Trials Aug 2023Typhoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Typhoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions, typhoid conjugate vaccines (TCVs) are recommended by the World Health Organization (WHO). We present here the protocol of a cluster randomised vaccine trial to assess the impact of introducing TyphiBEV® vaccine to those between 1 and 30 years of age in a high-burden setting.
METHODS
The primary objective is to determine the relative and absolute rate reduction of symptomatic, blood-culture-confirmed S. Typhi infection among participants vaccinated with TyphiBEV® in vaccine clusters compared with the unvaccinated participants in non-vaccine clusters. The study population is residents of 30 wards of Vellore (a South Indian city) with participants between the ages of 1 and 30 years who provide informed consent. The wards will be divided into 60 contiguous clusters and 30 will be randomly selected for its participants to receive TyphiBEV® at the start of the study. No placebo/control is planned for the non-intervention clusters, which will receive the vaccine at the end of the trial. Participants will not be blinded to their intervention. Episodes of typhoid fever among participants will be captured via stimulated, passive fever surveillance in the area for 2 years after vaccination, which will include the most utilised healthcare facilities. Observers blinded to the participants' intervention statuses will record illness details. Relative and absolute rate reductions will be calculated at the end of this surveillance and used to estimate vaccine effectiveness.
DISCUSSION
The results from our trial will allow countries to make better-informed decisions regarding the TCV that they will roll-out and may improve the global supplies and affordability of the vaccines.
TRIAL REGISTRATION
Clinical Trials Registry of India (CTRI) CTRI/2022/03/041314. Prospectively registered on 23 March 2022 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62548&EncHid=&userName=vellore%20typhoid ). CTRI collects the full WHO Trial Registration Data Set.
Topics: Humans; Infant; Child, Preschool; Child; Adolescent; Young Adult; Adult; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Vaccination; India
PubMed: 37537677
DOI: 10.1186/s13063-023-07555-y -
Journal of Clinical Laboratory Analysis Jul 2023Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor...
BACKGROUND
Acute febrile illness (AFI) is a prevalent disease in developing countries that is difficult to diagnose due to the diversity of infectious organisms and the poor quality of clinical diagnosis. TaqMan array card (TAC) can detect up to 35 AFI-associated organisms in 1.5 h, addressing diagnostic demands. In this study, we aimed to evaluate the role of TAC in determining the causative organisms in hospitalized AFI patients.
METHODS
The study had a cross-sectional design and enrolled 120 admitted patients with persistent fever for three or more days from the medicine ward of Chittagong Medical College Hospital (CMCH) and Bangladesh Institute of Tropical and Infectious Diseases Hospital (BITID). Blood samples were collected and then subjected to automated BacT/Alert blood culture, microbial culture, TAC assay, and typhoid/paratyphoid test.
RESULTS
The total number of study participants was 120, among them 48 (40%) samples showed a positive result in TAC card, 29 (24.16%) were TP positive and nine (7.51%) were culture positive. The number of organisms detected by the TAC card was 13 bacteria, three viruses, one protozoan, and one fungus. The sensitivity and specificity of the TAC assay for different bacterial pathogen compared to blood culture was 44.44%, and 90.99%, respectively. In contrast, the TP test had a sensitivity and specificity of 100% and 80%, respectively, compared to the blood culture test.
CONCLUSION
TAC can be a handful tool for detecting multiple organisms in AFI with high specificity which can facilitate early diagnosis of different pathogens contributing to AFI.
Topics: Humans; Cross-Sectional Studies; Bangladesh; Bacteria; Fever; Typhoid Fever
PubMed: 37496432
DOI: 10.1002/jcla.24948 -
Vaccine Aug 2023This study aimed to evaluate the parental acceptance of Typhoid Conjugate Vaccine (TCV) and to determine the predictors of TCV vaccination status among children in an...
BACKGROUND
This study aimed to evaluate the parental acceptance of Typhoid Conjugate Vaccine (TCV) and to determine the predictors of TCV vaccination status among children in an outbreak setting of extensively drug resistant (XDR) typhoid fever in Karachi, Pakistan.
METHODS
A cross-sectional survey using the WHO recommended rapid vaccine coverage assessment technique was conducted. Out of 11, four union councils (UCs) in Lyari Town were randomly selected. A parent or primary caretaker from the eligible household was interviewed. Data were collected using a locally validated vaccine attitudes scale (VAS). Sum of scores was calculated for VAS. A higher score denoted negative attitudes and perceptions regarding TCV and vice versa. Multivariable logistic regression was performed to determine the predictors of TCV vaccination status.
RESULTS
Based on the 14-item parental VAS, 78.0 % of the parents had a score between 0 to <40 and 22 % had a score ≥40. VAS score of <40 was significantly associated with higher odds of receiving TCV during the campaign setting (adjusted Odds Ratio (aOR): 1.30; 95 % Confidence Interval (CI): 1.02, 1.66). The odds of receiving TCV vaccination were higher among children whose parents were aware of the ongoing vaccination campaign in the area (aOR: 4.57; 95 % CI: 2.93, 7.12) and expressed willingness to get their child vaccinated against typhoid fever (aOR: 2.54; 95 % CI: 1.82, 3.55).
CONCLUSION
Parental awareness of the ongoing vaccination campaign, positive perception and attitudes towards vaccine were found to be significantly associated with TCV vaccination among children. Appropriately structured pre-vaccination awareness campaigns focused on childhood vaccination targeted towards parents are necessary to improve parental awareness, attitude and behavior towards vaccination.
Topics: Humans; Child; Typhoid Fever; Vaccines, Conjugate; Typhoid-Paratyphoid Vaccines; Pakistan; Cross-Sectional Studies; Vaccination; Parents; Disease Outbreaks
PubMed: 37463829
DOI: 10.1016/j.vaccine.2023.07.003 -
Frontiers in Immunology 2023, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, causes typhoid or gastroenteritis and is a major public health concern....
, a Gram-negative pathogen, has over 2500 serovars that infect a wide range of hosts. In humans, causes typhoid or gastroenteritis and is a major public health concern. In this study, SseB (the tip protein of the pathogenicity island 2 type III secretion system) was fused with the LTA1 subunit of labile-toxin from enterotoxigenic to make the self-adjuvanting antigen L-SseB. Two unique nanoparticle formulations were developed to allow multimeric presentation of L-SseB. Mice were vaccinated with these formulations and protective efficacy determined challenging the mice with serovars. The polysaccharide (chitosan) formulation was found to elicit better protection when compared to the squalene nanoemulsion. When the polysaccharide formulation was used to vaccinate rabbits, protection from challenge was elicited. In summary, L-SseB in a particulate polysaccharide formulation appears to be an attractive candidate vaccine capable of broad protection against
Topics: Humans; Mice; Animals; Rabbits; Escherichia coli; Salmonella Infections; Typhoid Fever; Salmonella enterica; Typhoid-Paratyphoid Vaccines
PubMed: 37457702
DOI: 10.3389/fimmu.2023.1208848 -
Human Vaccines & Immunotherapeutics Aug 2023Vaccination stands as one of the most important scientific discoveries and public health achievements in the fight against diseases. For over a century, millions of... (Review)
Review
Vaccination stands as one of the most important scientific discoveries and public health achievements in the fight against diseases. For over a century, millions of early childhood deaths have been averted through routine immunizations. However, to prevent the morbidity and mortality associated with vaccine-preventable diseases and their complications and optimize the control of vaccine-preventable diseases in communities, high uptake rates must be achieved. Mass immunization campaigns (MICs) have globally been used to introduce new vaccines for major infectious diseases and improve coverage of routine vaccines through catch-up campaigns. Malawi recently undertook such a campaign to introduce a highly efficacious typhoid conjugate vaccine and provides a catch-up to measles, rubella, and polio. Such campaigns are associated with multiple benefits. However, the MICs are associated with multiple challenges to be successfully administered. In this review, we highlight recent MIC, vaccine coverage, and potential challenges and benefits and offer recommendation for future preventive campaigns.
Topics: Child, Preschool; Humans; Typhoid Fever; Malawi; Vaccine-Preventable Diseases; Vaccination; Immunization; Rubella; Measles; Typhoid-Paratyphoid Vaccines; Poliomyelitis
PubMed: 37431661
DOI: 10.1080/21645515.2023.2233397 -
The Journal of Clinical Investigation Aug 2023BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have... (Clinical Trial)
Clinical Trial
BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have been developed based on the surface Vi-capsular polysaccharide of S. Typhi; these include a plain-polysaccharide-based vaccine, ViPS, and a glycoconjugate vaccine, ViTT. To understand immune responses to these vaccines and their vaccine-induced immunological protection, molecular signatures were analyzed using bioinformatic approaches.METHODSBulk RNA-Seq data were generated from blood samples obtained from adult human volunteers enrolled in a vaccine trial, who were then challenged with S. Typhi in a controlled human infection model (CHIM). These data were used to conduct differential gene expression analyses, gene set and modular analyses, B cell repertoire analyses, and time-course analyses at various post-vaccination and post-challenge time points between participants receiving ViTT, ViPS, or a control meningococcal vaccine.RESULTSTranscriptomic responses revealed strong differential molecular signatures between the 2 typhoid vaccines, mostly driven by the upregulation in humoral immune signatures, including selective usage of immunoglobulin heavy chain variable region (IGHV) genes and more polarized clonal expansions. We describe several molecular correlates of protection against S. Typhi infection, including clusters of B cell receptor (BCR) clonotypes associated with protection, with known binders of Vi-polysaccharide among these.CONCLUSIONThe study reports a series of contemporary analyses that reveal the transcriptomic signatures after vaccination and infectious challenge, while identifying molecular correlates of protection that may inform future vaccine design and assessment.TRIAL REGISTRATIONClinicalTrials.gov NCT02324751.
Topics: Adult; Humans; Polysaccharides, Bacterial; Receptors, Antigen, B-Cell; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination
PubMed: 37402153
DOI: 10.1172/JCI169676 -
Frontiers in Public Health 2023Typhoid fever, a common enteric disease in Pakistan, caused by , is becoming an extended drug-resistant organism and is preventable through the typhoid conjugate vaccine...
Typhoid fever, a common enteric disease in Pakistan, caused by , is becoming an extended drug-resistant organism and is preventable through the typhoid conjugate vaccine (TCV). Public adherence to preventive measures is influenced by knowledge and attitude toward the vaccine. This study investigates the knowledge, attitudes, and practices of the general population of Pakistan toward TCV. The differences in mean scores and factors associated with typhoid conjugate vaccine knowledge, attitudes, and practices were investigated. A total of 918 responses were received with a mean age of 25.9 ± 9.6, 51% were women, and 59.6% had graduation-level education. The majority of them responded that vaccines prevent illness (85.3%) and decrease mortality and disability (92.6%), and typhoid could be prevented by vaccination (86.7%). In total, 77.7 and 80.8% considered TCV safe and effective, respectively. Of 389 participants with children, 53.47% had vaccinated children, according to the extended program on immunization (EPI). Higher family income has a higher odds ratio (OR) for willingness toward booster dose of TCV [crude odds ratio (COR) = 4.920, -value <0.01; adjusted odds ratio (aOR) = 2.853, <0.001], and negative attitude regarding the protective effect of TCV has less willingness toward the booster dose with statistical significance (COR = 0.388, = 0.017; aOR = 0.198, = 0.011). The general population of Pakistan had a good level of knowledge about the benefits of TCV, and attitude and practices are in favor of the usage of TCV. However, a few religious misconceptions are prevalent in public requiring the efforts to overcome them to promote the usage of vaccines to prevent the disease and antibiotic resistance.
Topics: Child; Humans; Female; Adolescent; Young Adult; Adult; Male; Typhoid Fever; Vaccines, Conjugate; Cross-Sectional Studies; Typhoid-Paratyphoid Vaccines; Pakistan; Health Knowledge, Attitudes, Practice
PubMed: 37333546
DOI: 10.3389/fpubh.2023.1151936 -
Open Forum Infectious Diseases May 2023Patients with suspected enteric (typhoid and paratyphoid) fever are predominantly managed as outpatients in endemic regions. Nonspecific clinical presentation, lack of...
Patients with suspected enteric (typhoid and paratyphoid) fever are predominantly managed as outpatients in endemic regions. Nonspecific clinical presentation, lack of accurate diagnostic tools, and widespread antimicrobial resistance makes management challenging. Resistance has been described for all antimicrobials including chloramphenicol, amoxycillin, trimethoprim-sulfamethoxazole, ciprofloxacin, ceftriaxone, and azithromycin. No significant differences have been demonstrated between these antimicrobials in their ability to treat enteric fever in systematic reviews of randomized controlled trials (RCTs). Antimicrobial choice should be guided by local resistance patterns and national guidance. Extensively drug-resistant typhoid isolates require treatment with azithromycin and/or meropenem. Combining antimicrobials that target intracellular and extracellular typhoid bacteria is a strategy being explored in the Azithromycin and Cefixime in Typhoid Fever (ACT-SA) RCT, in progress in South Asia. Alternative antimicrobials, such as the oral carbapenem, tebipenem, need clinical evaluation. There is a paucity of evidence to guide the antimicrobial management of chronic fecal carriers.
PubMed: 37274536
DOI: 10.1093/ofid/ofad179 -
Open Forum Infectious Diseases May 2023There is now a robust pipeline of licensed and World Health Organization (WHO)-prequalified typhoid conjugate vaccines with a steady progression of national...
There is now a robust pipeline of licensed and World Health Organization (WHO)-prequalified typhoid conjugate vaccines with a steady progression of national introductions. However, typhoid fever is responsible for less than half the total global burden of disease, and even less among children aged <5 years. Invasive nontyphoidal disease is the dominant clinical presentation of in Africa, and over a quarter of enteric fever in Asia is due to paratyphoid A. In this article, we explore the case for combination vaccines, review the current pipeline of these vaccines, and discuss key considerations for their development, including geographies of use, age of administration, and pathways to licensure. While a trivalent typhoid/nontyphoidal vaccine is attractive for Africa, and a bivalent enteric fever vaccine for Asia, a quadrivalent vaccine covering the 4 main disease-causing serovars of would provide a single vaccine option for global coverage.
PubMed: 37274529
DOI: 10.1093/ofid/ofad041 -
Open Forum Infectious Diseases May 2023serovar Paratyphi A, the causative agent of paratyphoid fever, is a neglected tropical disease with a high burden and mortality in low- and middle-income countries....
serovar Paratyphi A, the causative agent of paratyphoid fever, is a neglected tropical disease with a high burden and mortality in low- and middle-income countries. Limited information is available regarding its genomic diversity, especially from South Asian countries that are collectively responsible for >80% of all paratyphoid cases. At the 2021 International Conference on Typhoid and Other Salmonelloses, researchers from the around the globe presented their work on Paratyphi A genomics. Presentations described recent genomic data from South Asia and the development of , an open-access single-nucleotide polymorphism-based genotyping scheme, to segregate Paratyphi A genomes in a systematic and sustainable manner. In this review, we attempt to summarize the progress made thus far on Paratyphi A genomics and discuss the questions that remain to better understand the pathogen and develop interventions to fight it.
PubMed: 37274527
DOI: 10.1093/ofid/ofad077