The Enterics for Global Health (EFGH) Shigella Surveillance Study in Bangladesh.

Background: Shigella is an important cause of diarrhea in Bangladeshi children <5 years of age, with an incidence rate of 4.6 per 100 person-years. However, the report was more than a decade old, and data on Shigella consequences are similarly outdated and heterogeneously collected. Methods: Facility-based disease surveillance is planned to be carried out under the Enterics for Global Health (EFGH) Shigella Surveillance Study consortium for 2 years with aims to optimize and standardize laboratory techniques and healthcare utilization and coverage survey, clinical and anthropometric data collection, safety monitoring and responsiveness, and other related activities. The EFGH is a cohesive network of multidisciplinary experts, capable of operating in concert to conduct the study to generate data that will pave the way for potential Shigella vaccine trials in settings with high disease burden. The study will be conducted within 7 country sites in Asia, Africa, and Latin America. Conclusions: We outline the features of the Bangladesh site as part of this multisite surveillance network to determine an updated incidence rate and document the consequences of Shigella diarrhea in children aged 6-35 months, which will help inform policymakers and to implement the future vaccine trials.

Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example.

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study-a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella--associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data.

Diarrhea Case Surveillance in the Enterics for Global Health Shigella Surveillance Study: Epidemiologic Methods.

Background: Shigella is a leading cause of acute watery diarrhea, dysentery, and diarrhea-attributed linear growth faltering, a precursor to stunting and lifelong morbidity. Several promising Shigella vaccines are in development and field efficacy trials will require a consortium of potential vaccine trial sites with up-to-date Shigella diarrhea incidence data. Methods: The Enterics for Global Health (EFGH) Shigella surveillance study will employ facility-based enrollment of diarrhea cases aged 6-35 months with 3 months of follow-up to establish incidence rates and document clinical, anthropometric, and financial consequences of Shigella diarrhea at 7 country sites (Mali, Kenya, The Gambia, Malawi, Bangladesh, Pakistan, and Peru). Over a 24-month period between 2022 and 2024, the EFGH study aims to enroll 9800 children (1400 per country site) between 6 and 35 months of age who present to local health facilities with diarrhea. Shigella species (spp.) will be identified and serotyped from rectal swabs by conventional microbiologic methods and quantitative polymerase chain reaction. Shigella spp. isolates will undergo serotyping and antimicrobial susceptibility testing. Incorporating population and healthcare utilization estimates from contemporaneous household sampling in the catchment areas of enrollment facilities, we will estimate Shigella diarrhea incidence rates. Conclusions: This multicountry surveillance network will provide key incidence data needed to design Shigella vaccine trials and strengthen readiness for potential trial implementation. Data collected in EFGH will inform policy makers about the relative importance of this vaccine-preventable disease, accelerating the time to vaccine availability and uptake among children in high-burden settings.

Immune responses in children after vaccination with a typhoid Vi-tetanus toxoid conjugate vaccine in Bangladesh.

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.

Measuring the Effectiveness of COVID-19 Vaccines Used during a Surge of the Delta Variant of SARS-CoV-2 in Bangladesh: A Test-Negative Design Evaluation.

BACKGROUND: From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant. METHODS: A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days' duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose. RESULTS: In total, 313 cases were matched to 1196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: -21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines. CONCLUSIONS: Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries.

A Survey on Knowledge, Attitude, and Practices of Large-Animal Farmers towards Antimicrobial Use, Resistance, and Residues in Mymensingh Division of Bangladesh.

The widespread and indiscriminate use of antimicrobials in food animals is a key contributor to antimicrobial resistance and antimicrobial residue, which have become a growing public and animal health concern in developing countries such as Bangladesh. This study was aimed to assess the knowledge, attitude, and practices (KAP) of large-animal farmers towards antimicrobial use (AMU), antimicrobial resistance (AMR), and antimicrobial residue (AR) with their correlation. A cross-sectional survey was conducted with a structured and pretested questionnaire in the Mymensingh division of Bangladesh. A total of 212 large-animal farmers (dairy, beef fattening, buffalo, sheep, and goat farmers) were surveyed. Results showed that most of the farmers are male (85.8%) and belong to the 18-30 age group (37.3%). About 20.3% had no formal education, and nearly half of the participants (48.1%) received training regarding antibiotic use and resistance. Penicillin is the most common class of antibiotic used (61.8%) in the study area, followed by other antimicrobials. Only 37.7% of the farmers used antimicrobials on the recommendation of their veterinarian. Overall, 41.5%, 42.5%, and 21.7% of farmers possess adequate knowledge and a satisfactory attitude and perform desirable practices, respectively. Farmers in the 31-40 age group have adequate knowledge, attitude, and ability to implement desired practices compared to farmers in the 18-30 age group. Farmers having a graduate or post-graduate degree scored better in relation to knowledge, attitude, and practice than other farmers. Analysis revealed that farmers who received training on AMU and AMR had 10.014 times (OR = 10.014, 95% CIs: 5.252-19.094), 9.409 times (OR = 9.409, 95% CIs: 4.972-17.806), and 25.994 times (OR = 25.994, 95% CIs: 7.73-87.414) better knowledge, attitude, and performance, respectively, compared to their counterparts. A significant proportion of farmers (97.2%) dispose of leftover antibiotics inappropriately. The findings of the present study will be used to intervene in the education and training of the farmers, which will help to limit the indiscriminate and irrational use of antimicrobials, leading to reducing the chances of developing AMR.

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.

BACKGROUND: Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. METHODS: We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. FINDINGS: 41 344 children were vaccinated in April-May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI -12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. INTERPRETATION: Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. FUNDING: The study was funded by the Bill & Melinda Gates Foundation.

Extract of neem (Azadirachta indica) leaf exhibits bactericidal effect against multidrug resistant pathogenic bacteria of poultry.

The aim of the study was to determine the efficacy of neem leaf extract against multidrug resistant (MDR) pathogenic bacteria. Laboratory stock culture of Pasteurella multocida, Salmonella pullorum, Salmonella gallinarum and Escherichia coli was revived. Antibiogram profiles of these bacteria were determined by disc diffusion method. Ethanolic extract of neem leaf was prepared. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of neem leaf extract (112.5, 100, 50, 25, 12.5, 6.25 and 3.12 mg/ml) against MDR pathogenic bacteria of poultry were determined by double dilution method. The MIC and MBC of the neem leaf extract were 12.5 and 25 mg/ml, respectively for P. multocida, 50 and 100 mg/ml for S. pullorum and S. gallinarum, 100 and 112.5 mg/ml for E. coli. Neem leaf extracts exhibited bactericidal effect against MDR pathogenic bacteria of poultry.

Role of Different Growth Enhancers as Alternative to In-feed Antibiotics in Poultry Industry.

The poultry industry has grown so fast alongside the irrational use of antibiotics to maximize profit and make the production cost-effective during the last few decades. The rising and indiscriminate use of antibiotics might result in the deposition of residues in poultry food products and in the development of resistance to these drugs by microorganisms. Therefore, many diseases are becoming difficult to treat both in humans and animals. In addition, the use of low-dose antibiotics as growth enhancer results in antibiotic residues in food products, which have detrimental effects on human health. On the other hand, many studies have shown that antibiotics administered to poultry and livestock are poorly absorbed through the gut and usually excreted without metabolism. These excreted antibiotics eventually accumulate in the environment and enter the human food chain, resulting in the bioaccumulation of drug residues in the human body. In this regard, to find out alternatives is of paramount importance for the production of safe meat and egg. Therefore, in recent years, much research attention was disarticulated toward the exploration for alternatives to antibiotic as in-feed growth enhancers after its ban by the EU. As a result, probiotics, prebiotics, phytobiotics, spirulina, symbiotic, and their combination are being used more frequently in poultry production. Feed additives therefore gained popularity in poultry production by having many advantages but without any residues in poultry products. In addition, numerous studies demonstrating that such biological supplements compete with antimicrobial resistance have been conducted. Therefore, the purpose of this review article was to highlight the advantages of using biological products instead of antibiotics as poultry in-feed growth enhancers to enhance the production performance, reduce intestinal pathogenic bacteria, and maintain gut health, potentiating the immune response, safety, and wholesomeness of meat and eggs as evidence of consumer protection, as well as to improve the safety of poultry products for human consumption.