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Abstract 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.

Background Pneumococcal infections are common in children with nephrotic syndrome. Knowledge of the commonly available serotypes and antibiotic susceptibility will help in prevention and appropriate management of pneumococcal sepsis, especially in resource-limited countries. Methods Demographic, clinical, and laboratory data on children with nephrotic syndrome and pneumococcal infections were extracted from the electronic medical records. Results Sixty-three isolates of pneumococci obtained from 60 children with nephrotic syndrome, over a period of 14 years, were included in the study. This represented 18% of all pneumococcal infections occurring in children during the same period. Commonly available vaccines covered up to 58% of all the serotypes causing infection. Severe disease, with shock, intensive care admission and/or meningitis, was observed in 38% children and mortality was observed in 10%. Resistance to commonly used antibiotics was not observed, except for erythromycin. Conclusions Pneumococcal sepsis was observed to be common in children with nephrotic syndrome and results in significant morbidity and mortality. Commonly used antibiotics were observed to be effective in management of the infections., Author(s): Georgie Mathew [sup.1] , Anish Sam George [sup.1] , R. V. Deepthi [sup.1] , Winsley Rose [sup.2] , Valsan Philip Verghese [sup.2] , Rosemol Varghese [sup.3] , Balaji Veeraraghavan [...]

The emergence of multi-drug resistance in Salmonella, causing food-borne infections, is a significant issue. With over 2,600 serovars in in Salmonella sp., it is crucial to identify specific solutions for each serovar. Phage therapy serves as an alternate treatment option. In this study, vB_SalP_792 phage was obtained from sewage, forming plaques in eight out of 13 tested clinical S. enterica isolates. Transmission electron microscopy (TEM) examination revealed a T7-like morphotype. The phage was characterized by its stability, life cycle, antibiofilm, and lytic ability in food sources. The phage remains stable throughout a range of temperatures (-20 to 70°C), pH levels (3-11), and in chloroform and ether. It also exhibited lytic activity within a range of MOIs from 0.0001 to 100. The life cycle revealed that 95% of the phages attached to their host within 3 min, followed by a 5-min latent period, resulting in a 50 PFU/cell burst size. The vB_SalP_792 phage genome has a dsDNA with a length of 37,281 bp and a GC content of 51%. There are 42 coding sequences (CDS), with 24 having putative functions and no resistance or virulence-related genes. The vB_SalP_792 phage significantly reduced the bacterial load in the established biofilms and also in egg whites. Thus, vB_SalP_792 phage can serve as an effective biocontrol agent for preventing Salmonella infections in food, and its potent lytic activity against the clinical isolates of S. enterica, sets out vB_SalP_792 phage as a successful candidate for future in vivo studies and therapeutical application against drugresistant Salmonella infections. [ABSTRACT FROM AUTHOR]

The rising challenge of carbapenem-resistant Enterobacterales (CRE) infections in Indian healthcare settings calls for clear clinical guidance on the management of these infections. The Indian consensus on the management of CRE infection in critically ill patients (ICONIC-II) is a follow-up of the ICONIC-I study, which was undertaken in 2019. A modified Delphi method was used to build expert consensus on CRE management in India, involving online surveys, face-to – face expert meetings, and a literature review. A panel of 12 experts was formed to develop potential clinical consensus statements (CCSs), which were rated through two survey rounds. The CCSs were finalized in a final face-to – face discussion. The finalized CCSs were categorized as consensus, near consensus, and no consensus. The outcomes included 46 CCSs (consensus: 40; near consensus: 3; and no consensus: 3). The expert panel discussed and achieved consensus on various strategies for managing CRE infections, emphasizing the significance of existing and emerging resistance mechanisms, prompt and tailored empiric therapy, and use of combination therapies. The consensus statements based on the collective expertise of the panel can potentially assist clinicians in the management of CRE infections that lack high-level evidence. [ABSTRACT FROM AUTHOR]

Objective To assess the preparedness of veterinary laboratories in India to participate in an integrated antimicrobial resistance surveillance network and to address gaps in provision identified. Methods The Indian Council of Medical Research and the Indian Council of Agricultural Research collaborated: (i) to select eight nationally representative veterinary microbiology laboratories whose capacity for participating in an integrated antimicrobial resistance surveillance network would be assessed using a standardized tool; (ii) to identify gaps in provision from the assessment findings; and (iii) to develop a plan, and take the necessary steps to address these gaps in consultation with participating organizations. Findings The main gaps in provision identified were: (i) a lack of dedicated funding for antimicrobial resistance surveillance; (ii) the absence of standard guidelines for antimicrobial susceptibility testing; (iii) a shortage of reference strains for testing and quality assurance; and (iv) the absence of mechanisms for sharing data. We addressed these gaps by creating a veterinary standard operating procedure for antimicrobial susceptibility testing, by carrying out a validation exercise to identify problems with implementing the procedure and by conducting capacity-building workshops for veterinary laboratories. Conclusion Antimicrobial resistance surveillance networks depend on the availability of accurate, quality-controlled testing. The challenges identified in creating an integrated surveillance network for India can be overcome by developing a comprehensive plan for improving laboratory capacity in human, veterinary and environmental sectors that is supported by the necessary funds. The study's findings may provide guidance for other low- and middle-income countries planning to develop a similar network. Un reseau de surveillance integre pour la resistance aux antimicrobiens en Inde Objectif Evaluer le degre de preparation des laboratoires veterinaires en Inde dans l'optique d'une participation a un reseau de surveillance integre pour la resistance aux antimicrobiens, et combler les lacunes identifiees dans le systeme. Methodes Le Conseil indien de la recherche medicale et le Conseil indien de la recherche agronomique ont travaille ensemble afin de: (i) selectionner huit laboratoires de microbiologie veterinaire representatifs a l'echelle nationale, dont la capacite de participation a un tel reseau serait evaluee grace a un outil standardise; (ii) determiner quelles sont les faiblesses du systeme a partir des resultats de l'evaluation; et, enfin, (iii) developper un plan et prendre les mesures necessaires pour remedier a ces faiblesses, en concertation avec les organismes participants. Resultats Les principales lacunes observees dans le systeme etaient: (i) l'absence de fonds dedies a la surveillance de la resistance aux antimicrobiens; (ii) l'absence de directives types pour le test de sensibilite aux antimicrobiens; (iii) le manque de souches de reference pour les tests et l'assurance qualite; et, enfin, (iv) l'absence de mecanismes de partage de donnees. Nous avons comble ces lacunes en creant une procedure operationnelle standardisee a usage veterinaire pour le test de sensibilite aux antimicrobiens, en menant un exercice de validation afin d'identifier les problemes rencontres lors de la mise en oeuvre de la procedure, et en organisant des ateliers de renforcement des capacites pour les laboratoires veterinaires. Conclusion Les reseaux de surveillance pour la resistance aux antimicrobiens dependent de l'existence ou non de tests precis faisant l'objet de controles de qualite. Les defis que pose la creation d'un reseau de surveillance integre en Inde peuvent etre releves grace a l'elaboration d'un plan global d'amelioration des capacites humaines, veterinaires et environnementales des laboratoires en y injectant les fonds requis. Les resultats de cette etude peuvent servir d'orientation pour d'autres pays a faibles et moyens revenus qui prevoient d'instaurer un reseau similaire. Una red de vigilancia integrada para la resistencia antimicrobiana resistencia a los antimicrobianos, India Objetivo Evaluar la preparacion de los laboratorios veterinarios de la India para participar en una red integrada de vigilancia de la resistencia a los antimicrobianos y subsanar las deficiencias detectadas en la prestacion. Metodos El Consejo Indio de Investigacion Medica y el Consejo Indio de Investigacion Agricola colaboraron: (i) para seleccionar ocho laboratorios de microbiologia veterinaria representativos a nivel nacional cuya capacidad para participar en una red integrada de vigilancia de la resistencia a los antimicrobianos seria evaluada mediante una herramienta estandarizada; (ii) para identificar las lagunas en la prestacion a partir de los resultados de la evaluacion; y (iii) para desarrollar un plan, y tomar las medidas necesarias para abordar estas lagunas en consulta con las organizaciones participantes. Resultados Las principales lagunas identificadas son las siguientes (i) la falta de financiacion dedicada a la vigilancia de la resistencia a los antimicrobianos; (ii) la ausencia de directrices estandar para las pruebas de susceptibilidad a los antimicrobianos; (iii) la escasez de cepas de referencia para las pruebas y la garantia de calidad; asi como (iv) la ausencia de mecanismos para compartir datos. Para subsanar estas deficiencias, creamos un procedimiento operativo estandar veterinario para las pruebas de susceptibilidad a los antimicrobianos, llevamos a cabo un ejercicio de validacion para identificar los problemas de aplicacion del procedimiento y realizamos talleres de capacitacion para los laboratorios veterinarios.Conclusion Las redes de vigilancia de la resistencia a los antimicrobianos dependen de la disponibilidad de pruebas precisas y de calidad controlada. Los retos identificados en la creacion de una red de vigilancia integrada para la India pueden superarse mediante el desarrollo de un plan integral para mejorar la capacidad de los laboratorios en los sectores humano, veterinario y medioambiental que cuente con los fondos necesarios. Las conclusiones del estudio pueden servir de orientacion a otros paises de ingresos bajos y medios que se propongan crear una red similar., Introduction The misuse and overuse of antimicrobials in both humans and animals are major drivers of antimicrobial resistance. (1-3) Several clinically important antibiotics are used extensively in food-producing animals, either [...]

The profile of the intestinal microbiota is known to be altered in malnourished young children in low- and middle-income countries. However, there are limited studies longitudinally evaluating the intestinal microbiota in malnourished young children in resource-limited settings over the first two years of life. In this longitudinal pilot study, we determined the effect of age, residential location, and intervention on the composition, relative abundance, and diversity of the intestinal microbiota in a representative sample of children under 24 months of age with no diarrhea in the preceding 72 h in the urban and rural areas of Sindh, Pakistan nested within a cluster-randomized trial evaluating the effect of zinc and micronutrients on growth and morbidity (ClinicalTrials.gov Identifier: NCT00705445). The major findings were age-related with significant changes in alpha and beta diversity with increasing age. There was a significant increase in the relative abundance of the Firmicutes and Bacteroidetes phyla and a significant decrease in that of the Actinobacteria and Proteobacteria phyla (p < 0.0001). There were significant increases in the relative abundances of the major genera Bifidobacterium, Escherichia/Shigella and Streptococcus (p < 0.0001), and no significant change in the relative abundance of Lactobacillus. Using the LEfSE algorithm, differentially abundant taxa were identified between children in the first and second years of age, between those residing in rural and urban areas, and those who received different interventions at different ages from 3 to 24 months. The numbers of malnourished (underweight, wasted, stunted) or well-nourished children at each age, in each intervention arm, and at urban or rural sites were too small to determine if there were significant differences in alpha or beta diversity or differentially abundant taxa among them. Further longitudinal studies with larger numbers of well-nourished and malnourished children are required to fully characterize the intestinal microbiota of children in this region.