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Antimicrobial susceptibility testing was performed on 3627 isolates ofEscherichia coliand 180 isolates ofShigellaspp. collected in rural locations from 875 Egyptian children with diarrhoea between 1995 and 2000. The cumulative rates of resistance forE. coliandShigellaspp. were high (respectively, 68.2% and 54.8% for ampicillin, 24.2% and 23.5% for ampicillin–sulbactam, 57.2% and 42.5% for trimethoprim–sulphamethoxazole, and 50.9% and 75.4% for tetracycline). Non-enterotoxigenicE. coli(NETEC) isolates had a consistently higher level of antimicrobial resistance than did enterotoxigenicE. coli(ETEC) isolates. Trend testing showed significant decreases in resistance to ampicillin, ampicillin–sulbactam and tetracycline among allE. coliisolates. Increasing rates of resistance were observed for trimethoprim–sulphamethoxazole in ETEC isolates andShigellaspp., but not in NETEC isolates. Low levels of resistance were observed for all other antimicrobial agents tested. Overall, high levels, but decreasing trends, of resistance to commonly used antimicrobial agents were detected among isolates ofE. coliandShigellaspp. from children in rural Egypt. [ABSTRACT FROM AUTHOR]

Background: . Oral administration of bovine antibodies active against enterotoxigenic Escherichia coli (ETEC) have demonstrated safety and efficacy against diarrhea in human challenge trials. The efficacy of bovine serum immunoglobulins (BSIgG) against recombinant colonization factor CS6 or whole cell ETEC strain B7A was assessed against challenge with the CS6-expressing B7A., Methods: . This was a randomized, double-blind, placebo-controlled trial in which healthy adults received oral hyperimmune BSIgG anti-CS6, anti-B7A whole cell killed or non-hyperimmune BSIgG (placebo) in a 1:1:1 ratio then challenged with ETEC B7A. Two days pre-challenge, volunteers began a thrice daily, seven day course of immunoprophylaxis. On day 3, subjects received 1 × 10 10 CFUs of B7A. Subjects were observed for safety and the primary endpoint of moderate-severe diarrhea (MSD)., Results: . A total of 59 volunteers received product and underwent ETEC challenge. The BSIgG products were well-tolerated across all subjects. Upon challenge, 14/20 (70%) placebo recipients developed MSD, compared to 12/19 (63%; p = .74) receiving anti-CS6 BSIgG and 7/20 (35%; p = .06) receiving anti-B7A BSIgG. Immune responses to the ETEC infection were modest across all groups., Conclusions: . Bovine-derived serum antibodies appear safe and well tolerated. Antibodies derived from cattle immunized with whole cell B7A provided 50% protection against MSD following B7A challenge; however, no protection was observed in subjects receiving serum antibodies targeting CS6. The lack of observed efficacy in this group may be due to low CS6 surface expression on B7A, the high dose challenge inoculum and/or the use of serum derived antibodies versus colostrum-derived antibodies.

Investment in vaccine product development should be guided by up-to-date and transparent global burden of disease estimates, which are also fundamental to policy recommendation and vaccine introduction decisions. For low- and middle-income countries (LMICs), vaccine prioritization is primarily driven by the number of deaths caused by different pathogens. Enteric diseases are known to be a major cause of death in LMICs. The two main modelling groups providing mortality estimates for enteric diseases are the Institute for Health Metrics and Evaluation (IHME) at the University of Washington, Seattle and the Maternal Child Epidemiology Estimation (MCEE) group, led by Johns Hopkins Bloomberg School of Public Health. Whilst previous global diarrhoea mortality estimates for under five-year-olds from these two groups were closely aligned, more recent estimates for 2016 have diverged, particularly with respect to numbers of deaths attributable to different enteric pathogens. This has impacted prioritization and investment decisions for vaccines in the development pipeline. The mission of the Product Development for Vaccines Advisory Committee (PDVAC) at the World Health Organisation (WHO) is to accelerate product development of vaccines and technologies that are urgently needed and ensure they are appropriately targeted for use in LMICs. At their 2018 meeting, PDVAC recommended the formation of an independent working group of subject matter experts to explore the reasons for the difference between the IHME and MCEE estimates, and to assess the respective strengths and limitations of the estimation approaches adopted, including a review of the data on which the estimates are based. Here, we report on the proceedings and recommendations from a consultation with the working group of experts, the IHME and MCEE modelling groups, and other key stakeholders. We briefly review the methodological approaches of both groups and provide a series of proposals for investigating the drivers for the differences in enteric disease burden estimates., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Acute diarrhoeal disease caused by viral, bacterial and parasitic infections is a major global health problem; in low- and middle-income countries (LMICs) it is associated with substantial mortality and morbidity in children under 5. Some of these infections also impact large segments of populations in high-income countries (HICs), as well as individuals who travel overseas for work, business or pleasure., Aims: The aim of this review is to describe the current landscape of licensed enteric vaccines, potential new vaccines on the horizon, and the challenges of development and utilization of vaccines against enteric pathogens., Sources: Relevant data from the literature, as well as clinical trials described in European and US registries, were examined in the conduct of this review., Content: The review involves discussion of current licensed vaccines against rotavirus, cholera and typhoid, as well as potential second- and third-generation vaccines against these pathogens currently in the development pipeline. In addition, novel vaccines against enterotoxigenic Escherichia coli, shigellosis and norovirus in advanced development are described. Challenges to the development and utilization of global vaccines are discussed., Implications: Despite advances in population health, food security, improved sanitation and water quality, and the reduction in poverty, acute enteric infections continue to plague global populations. Advancing utilization of current enteric vaccines is of critical public health importance, as is the development of new vaccines, particularly for enteric pathogens where none currently exist., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: Vaccine development for enterotoxigenic Escherichia coli (ETEC) is dependent on in-depth understanding of toxin and colonization factor (CF) distribution. We sought to describe ETEC epidemiology across regions and populations, focusing on CF and toxin prevalence., Methods: We conducted a systematic review of the published literature, including studies reporting data on ETEC CF and toxin distributions among those with ETEC infection. Point estimates and confidence intervals were calculated using random effects models., Results: Data on 17,205 ETEC isolates were abstracted from 136 included studies. Approximately half of the studies (49%) involved endemic populations, and an additional 17% involved only travel populations. Globally, 60% of isolates expressed LT either alone (27%) or in combination with ST (33%). CFA/I-expressing strains were common in all regions (17%), as were ETEC expressing CFA/II (9%) and IV (18%). Marked variation in toxins and CFs across regions and populations was observed., Discussion/conclusions: These results demonstrate the relative importance of specific CFs in achieving target product profiles for a future ETEC vaccine. However, heterogeneity across time, population, and region, confounded by variability in CF and toxin detection methodologies, obfuscates rational estimates for valency requirements., (Published by Elsevier Ltd.)