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Background: Enterotoxigenic Escherichia coli (ETEC) and enteropathogenic Escherichia coli (EPEC) are important causes of diarrhoea in young children and are associated with significant mortality rates. Passive immunization with antibodies from immunized cows has previously been shown to be effective as prophylaxis against E. coli-induced diarrhoea and therapeutically against rotavirus and cryptosporidia-induced diarrhoea. Methods: We tested the therapeutic efficacy of an oral bovine immunoglobulin milk concentrate (BIC) from cows hyperimmunized with ETEC and EPEC strains, in a randomized, placebo-controlled study in children with E. coli-induced diarrhoea. Eighty-six children between 4-24 months of age attending the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR, B) with E. coli-induced diarrhoea (63 EPEC/ETEC and 23 with other diarrhoeagenic E. coli) were randomly assigned to receive orally administered BIC (20 g) containing anti-ETEC/EPEC antibodies or a placebo preparation daily for 4 consecutive days. Daily stool output, intake of oral rehydration solution (ORS), stool frequency, and presence of diarrhoeagenic E. coli strains in the stool were monitored for 4 days. Results: Children in the treatment group tolerated the BIC with no side effects. There were no significant differences between the two groups with regard to ORS intake, stool output, frequency of diarrhoea, or clearance of pathogen. Nor was there any significant alteration in the duration of diarrhoea. Conclusions: In contrast to the prophylactic efficacy of anti-E. coli BIC and the therapeutic efficacy of a similarly prepared anti-rotavirus BIC, antibodies from hyperimmunized cows appear to have no significant therapeutic benefit in the treatment of acute diarrhoea due to EPEC/ETEC. [ABSTRACT FROM AUTHOR]

Abstract Background Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti – rotavirus antibodies in a mouse model of rotavirus diarrhea. Results Of the six probiotic bacteria tested, Lactobacillus rhamnosus strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines. Conclusion The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used.

The Global Burden of Disease report of 2019 estimated 14 million infection-related deaths, making it the second leading cause of death after ischaemic heart disease. Bacterial pathogens accounted for 7.7 million deaths and deaths attributable to bacterial antibiotic resistance amounted to 1.3 million, describing a clear demand for novel antibiotics. Antibiotic development had its golden age in 1930-1960. Following failures in the screening of chemical libraries for novel antibiotics at the beginning of this century, the high cost of launching new antibiotics (estimated at US$ 1.4 billion per registered drug) and difficulties in achieving a return of investment for novel antibiotics, pharmaceutical industry has mostly left the field. The current Lilliput review analyses the question whether scientific or economic hurdles prevented the registration of new antibiotics. Scientifically, substantial progress has been achieved over recent years to define the chemical properties needed to overcome the permeation barrier in Gram-negative pathogens; in extending the chemical space of antibiotic candidates by full modular synthesis of suitable molecules; by extending bioprospecting to previously 'unculturable' bacteria or unusual bacteria; by attacking bacterial targets on the outer bacterial membrane; and by looking for support from structural biology, genomics, molecular genetics, phylogenetic analyses and deep machine learning approaches. However, these research activities were mostly conducted by academic researchers and biotech companies with limited financial resources. It thus seems that the development of new antibiotics, frequently described as the drying of the pipeline, is less limited by lack of scientific insight than by lack of the mobilization of the monetary resources needed to bring these discoveries to the market despite recent financial push and pull efforts of the public sector., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

This Lilliput article provides a literature overview on ecological effects of the plant microbiome with a focus on practical application in forestry, agriculture and urban greenspace under the spectre of climate change. After an overview of the mostly bacterial microbiome of the model plant Arabidopsis thaliana, worldwide data from forests reveal ecological differentiation with respect to major guilds of predominantly fungal plant root symbionts. The plant-microbiome association forms a new holobiont, an integrated unit for ecological adaptation and evolutionary selection. Researchers explored the impact of the microbiome on the capacity of plants to adapt to changing climate conditions. They investigated the impact of the microbiome in reforestation programs, after wildfire, drought, salination and pollution events in forestry, grasslands and agriculture. With increasing temperatures plant populations migrate to higher latitudes and higher altitudes. Ecological studies compared the dispersal capacity of plant seeds with that of soil microbes and the response of soil and root microbes to experimental heating of soils. These studies described a succession of microbiome associations and the kinetics of a release of stored soil carbon into the atmosphere enhancing global warming. Scientists explored the impact of synthetic microbial communities (SynComs) on rice productivity or tea quality; of whole soil addition in grassland restoration; or single fungal inoculation in maize fields. Meta-analyses of fungal inoculation showed overall a positive effect, but also a wide variation in effect sizes. Climate change will be particularly prominent in urban areas ("urban heat islands") where more than half of the world population is living. Urban landscape architecture will thus have an important impact on human health and studies started to explore the contribution of the microbiome from urban greenspace to ecosystem services., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

With three major viral pandemics over the last 100 years, namely the Spanish flu, AIDS and COVID-19 each claiming many millions of lives, pandemic preparedness has become an important issue for public health. The economic, social and political consequences of the upheaval caused by such pandemics also represent a major challenge for governments with respect to sustainable development goals. The field of pandemic preparedness is vast and the current article can only address selected aspects. The article looks first backwards and addresses the question of the efficacy of non-pharmaceutical interventions (NPI) on the trajectory of the COVID-19 pandemic. The article looks then forward by asking to what extent viral candidates for future pandemics can be predicted by virome analyses from metagenome and transcriptome sequencing, by focusing on the virome from specific animal species and using ecological and epidemiological data about spillover viral infections in veterinary and human medicine. As a comprehensive overview on pandemic preparedness is beyond the capacity of a single reviewer, only selected topics will be discussed using recent key scientific publications. Since COVID-19 has not run its course, a computational program able to predict the future evolution of SARS-CoV-2 is mentioned that could assist proactive mRNA vaccine developments against possible future variants of concern. Ending the COVID-19 epidemic necessitates mucosal vaccines that can suppress the transmission of SARS-CoV-2 and therefore this article closes by discussing a promising and versatile protein nanoparticle experimental vaccine approach for inhalation that does not depend on needles nor a cold chain for distribution., (© 2024 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd.)

Pandemic preparedness starts with an early warning system of viruses with a pandemic potential. Based on information collected in a multitude of surveys, hazard models were developed identifying influenza viruses presenting a pandemic threat. Scores are attributed for 10 viral traits by expert panels which identified avian influenza viruses (AIV) belonging to subtypes H7N9 and H5N1 as representing the greatest pandemic risk. In 2013, more than 100 human cases infected with AIV H7N9 were observed in China. Case fatality rate (CFR) was high (27%), but the human-to-human transmission rate was low and by serological evidence H7N9 did not spread widely. Nevertheless, until 2019 more than 1500 H7N9 patients were identified characterized by a high CFR of 39%. Serology demonstrated that mild infections with H7N9 were widespread. In 2003, more than 400 people experienced AIV H7N7 cross-infection causing mainly conjunctivitis during a large poultry epidemic in The Netherlands. Between 1996 and 2019, a total of 881 human infections with avian H5N1 viruses were documented showing a CFR of 52%. Outbreaks were centred on South East Asia and showed close associations with epizootics in poultry. Mutations predisposing to human cross-infections were identified in the haemagglutinin (HA) and the RNA polymerase subunit PB2 of human H7N9 isolates. Human H5N1 isolates showed mutations in the receptor binding domain of HA and transmission in mammals could be obtained by as few as four additional aa changes introduced experimentally. Researchers have defined viral point mutations in HA, PB2 and the nucleoprotein NP that allowed AIV to cross the species barrier to mammals with respect to receptor recognition, RNA replication and escape from innate immunity respectively. Based on this insight a sequence-based early warning system for AIV preadapted to human transmission could be envisioned. Mink farms and live poultry markets are prime targets for such sequencing efforts., (© 2024 The Authors. Microbial Biotechnology published by Applied Microbiology International and John Wiley & Sons Ltd.)