District health information system (DHIS2) as integrated antimicrobial resistance surveillance platform: An exploratory qualitative investigation of the one health stakeholders' viewpoints in Ethiopia.

INTRODUCTION: There is an unmet need for One Health (OH) surveillance and reporting systems for antimicrobial resistance (AMR) in resource poor settings. District health information system, version 2 (DHIS2), is a globally recognized digital surveillance platform which has not been widely utilized for AMR data yet. Our study aimed to understand the local stakeholders' viewpoints on DHIS2 as OH-AMR surveillance platform in Jimma, Ethiopia which will aid its further context specific establishment. METHODS: We performed an exploratory qualitative study using semi-structured key informant interviews (KIIs) in Jimma Zone at Southwest Ethiopia. We interviewed 42 OH professionals between November 2020 and February 2021. Following verbatim transcription of the audio recordings of KIIs, we conducted thematic analysis. RESULTS: We identified five major themes which are important for understanding the trajectory of OH-AMR surveillance in DHIS2 platform. The themes were: (1) Stakeholders' current knowledge on digital surveillance platforms including DHIS2. (2) Stakeholders' perception on digital surveillance platform including DHIS2. (3) Features suggested by stakeholders to be included in the surveillance platform. (4) Comments from stakeholders on system implementation challenges. (5) Stakeholders' perceived role in the process of implementation. Despite several barriers and challenges, most of the participants perceived and suggested DHIS2 as a suitable OH-AMR surveillance platform and were willing to contribute at their current professional roles. CONCLUSIONS: Our study demonstrates the potential of the DHIS2 as a user friendly and acceptable interoperable platform for OH-AMR surveillance if the technology designers accommodate the stakeholders' concerns. Piloting at local level and using performance appraisal tool in all OH disciplines should be the next step before proceeding to workable format.

The comparison of antioxidant properties and nutrigenomic redox-related activities of vitamin C, C-vitamers, and other common ascorbic acid derivatives.

The term 'vitamin C' describes a group of compounds with antiscorbutic activity of l-ascorbic acid (AA). Despite AA's omnipresence in plant-derived foods, its derivatives have also been successfully implemented in the food industry as antioxidants, including the D-isomers, which lack vitamin C activity. This study aimed to determine the relationship between redox-related activities for five derivatives of AA using electrochemical, chemical, and biological approaches. Here we report that AA, C-vitamers, and other commonly consumed AA derivatives differ in their redox-related activities. As long as the physiological range of concentrations was maintained, there was no simple relationship between their redox properties and biological activity. Clear distinctions in antioxidant activity were observed mostly at high concentrations, which were strongly correlated with electrochemical and kinetic parameters describing redox-related properties of the studied compounds. Despite obvious similarities in chemical structures and antioxidant activity, we showed that C-vitamers may exhibit different nutrigenomic effects. Together, our findings provide a deeper insight into so far underinvestigated area combining chemical properties with biological activities of commonly applied AA derivatives.

Correction: Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

[This corrects the article DOI: 10.1371/journal.ppat.1010952.].

Preventive knowledge, attitude, and vaccination challenges for COVID-19 among Myanmar refugees and irregular migrants in Malaysia.

Access to vaccinations is crucial for everyone in the fight against the COVID-19 pandemic, regardless of migration or refugee status. This study explored COVID-19 prevention knowledge, attitudes, and vaccination challenges among refugees and irregular migrants from Myanmar in Malaysia. This study employed a descriptive mixed-method approach. Convenience sampling was used to conduct an online survey of 174 participants and two focus groups (N = 14). The majority (51.7 %) were refugees, and 48% were irregular migrant workers. In this study, 90.9% of the participants used social networks and social media chats to obtain information about COVID-19, 84.1% understood and found the vaccination campaign helpful, and 44.2% were aware of it. Although 70% of the participants considered vaccination crucial, 95% said that they would not take it because of fear of arrest and deportation, even though they considered vaccination necessary. Approximately 21.2% of the workers reported that their employers did not provide masks or hand sanitisers. Most of the participants (39.7 %) lived in dormitories provided by their employers. This puts them at a higher risk of infection because of the difficulty in practising social distancing. As part of COVID-19 prevention, the government should grant an amnesty period and work with migrant civil society organisations to administer vaccinations and effective measures for all immigrant populations in Malaysia.

Factors affecting access to healthcare for young people in the informal sector in developing countries: a systematic review.

Background: Young people are increasingly seeking employment in the informal sector due to increasing global unemployment. However, the precarious nature of work in the informal sectors, coupled with the high risk of occupational hazards, calls for a greater need for effective healthcare for informal sector workers, particularly young people. In addressing the health vulnerabilities of informal workers, systematic data on the determinants of health is a persistent challenge. Therefore, the objective of this systematic review was to identify and summarise the existing factors that affect access to healthcare among young people from the informal sector. Methods: We searched six data databases (PubMed, Web of Science, Scopus, ProQuest, Crossref, and Google Scholar), which was followed by hand searching. Then we screened the identified literature using review-specific inclusion/exclusion criteria, extracted data from the included studies and assessed study quality. Then we presented the results in narrative form, though meta-analysis was not possible due to heterogeneity in the study design. Results: After the screening, we retrieved 14 studies. The majority were cross-sectional surveys and were conducted in Asia (n = 9); four were conducted in Africa, and one in South America. Samples ranged in size from 120 to 2,726. The synthesised results demonstrate that problems of affordability, availability, accessibility, and acceptability of healthcare were barriers to young informal workers seeking healthcare. We found social networks and health insurance as facilitators of access for this group of people. Conclusion: To date, this is the most comprehensive review of the evidence on access to healthcare for young people in the informal sector. Our study finding highlights the key gaps in knowledge where future research could further illuminate the mechanisms through which social networks and the determinants of access to healthcare could influence the health and well-being of young people and thus inform policy development.

Use of antibiotics in poultry and poultry farmers- a cross-sectional survey in Pakistan.

Background: Antimicrobial resistance (AMR) which has been ascribed to be due to community carriage of antibiotic-resistant bacteria is highly prevalent in the WHO South-East Asia region. One of the major reasons for this is the misuse of antibiotics in animal farming practices and at the community level, which threatens both human and animal health. However, this problem of antibiotic misuse in poultry farms and in respective farmers is not well studied in countries like Pakistan. Methods: We conducted a cross-sectional study in rural Punjab to explore the current practices of antibiotic use in poultry and poultry farmers, associated factors, their healthcare-seeking behavior and biosecurity practices. Results: In the context of antibiotic use for poultry, 60% comprised of Colistin sulfate and Amoxicillin trihydrate whereas Colistin is considered as the last resort antibiotic. In addition, the significant consumption of antibiotics in poultry farms (60%) and poultry farmers (50%) was without prescription by either human health physicians or veterinarians. Most of the farms (85%) had no wastewater drainage system, which resulted in the direct shedding of poultry waste and antibiotic residue into the surrounding environment. The lack of farmers' education, professional farm training and farming experience were the most significant factors associated with antibiotic use and knowledge of AMR. Conclusion: Our study findings show that it is necessary for an integrated AMR policy with the inclusion of all poultry farmers to be educated, a mass awareness program to be undertaken and that strict antibiotic usage guidelines be available to them. Such initiatives are also important to ensure food safety and farm biosecurity practices.

Users' perception of the OH-EpiCap evaluation tool based on its application to nine national antimicrobial resistance surveillance systems.

Introduction: Antimicrobial resistance (AMR) is a One Health (OH) challenge. To achieve or maintain an effective and efficient AMR surveillance system, it is crucial to evaluate its performance in meeting the proposed objectives, while complying with resource restrictions. The OH-EpiCap tool was created to evaluate the degree of compliance of hazard surveillance activities with essential OH concepts across the following dimensions: organization, operational activities, and impact of the surveillance system. We present feedback on the application of the OH-EpiCap tool from a user's perspective, based on the use of the tool to evaluate nine national AMR surveillance systems, each with different contexts and objectives. Methods: The OH-EpiCap was assessed using the updated CoEvalAMR methodology. This methodology allows the evaluation of the content themes and functional aspects of the tool and captures the user's subjective experiences via a strengths, weaknesses, opportunities, and threats (SWOT) approach. Results and Discussion: The results of the evaluation of the OH-EpiCap are presented and discussed. The OH-EpiCap is an easy-to-use tool, which can facilitate a fast macro-overview of the application of the OH concept to AMR surveillance. When used by specialists in the matter, an evaluation using OH-EpiCap can serve as a basis for the discussion of possible adaptations of AMR surveillance activities or targeting areas that may be further investigated using other evaluation tools.

Targeting SARS-CoV-2 non-structural protein 13 via helicase-inhibitor-repurposing and non-structural protein 16 through pharmacophore-based screening.

Novel drug compound hunting was carried out for SARS-CoV-2 proteins with low mutation susceptibility. The probability of escape mutation and drug resistance is lower if conserved microbial proteins are targeted by therapeutic drugs. Mutation rate of all SARS-CoV-2 proteins were analyzed via multiple sequence alignment Non-Structural Protein 13 and Non-Structural Protein 16 were selected for the current study due to low mutation rate among viral strains and significant functionality. Cross-species mutation rate analysis for NSP13 and NSP16 showed these are well-conserved proteins among four coronaviral species. Viral helicase inhibitors, identified using literature-mining, were docked against NSP13. Pharmacophore-based screening of 11,375 natural compounds was conducted for NSP16. Stabilities of top compounds inside human body were confirmed via molecular dynamic simulation. ADME properties and LD50 values of the helicase inhibitors and Ambinter natural compounds were analyzed. Compounds against NSP13 showed binding affinities between -10 and -5.9 kcal/mol whereby ivermectin and scutellarein showed highest binding energies of -10 and -9.9 kcal/mol. Docking of 18 hit compounds against NSP16 yielded binding affinities between -8.9 and -4.1 kcal/mol. Hamamelitannin and deacyltunicamycin were the top compounds with binding affinities of -8.9 kcal/mol and -8.4 kcal/mol. The top compounds showed stable ligand-protein interactions in molecular dynamics simulation. The analyses revealed two hit compounds against each targeted protein displaying stable behavior, high binding affinity and molecular interactions. Conversion of these compounds into drugs after in vitro experimentation can become better treatment options to elevate COVID management.

Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

Antibiotic resistance is a leading cause of hospitalization and death worldwide. Heavy metals such as arsenic have been shown to drive co-selection of antibiotic resistance, suggesting arsenic-contaminated drinking water is a risk factor for antibiotic resistance carriage. This study aimed to determine the prevalence and abundance of antibiotic-resistant Escherichia coli (AR-Ec) among people and drinking water in high (Hajiganj, >100 µg/L) and low arsenic-contaminated (Matlab, <20 µg/L) areas in Bangladesh. Drinking water and stool from mothers and their children (<1 year) were collected from 50 households per area. AR-Ec was detected via selective culture plating and isolates were tested for antibiotic resistance, arsenic resistance, and diarrheagenic genes by PCR. Whole-genome sequencing (WGS) analysis was done for 30 E. coli isolates from 10 households. Prevalence of AR-Ec was significantly higher in water in Hajiganj (48%) compared to water in Matlab (22%, p <0.05) and among children in Hajiganj (94%) compared to children in Matlab (76%, p <0.05), but not among mothers. A significantly higher proportion of E. coli isolates from Hajiganj were multidrug-resistant (83%) compared to isolates from Matlab (71%, p <0.05). Co-resistance to arsenic and multiple antibiotics (MAR index >0.2) was observed in a higher proportion of water (78%) and child stool (100%) isolates in Hajiganj than in water (57%) and children (89%) in Matlab (p <0.05). The odds of arsenic-resistant bacteria being resistant to third-generation cephalosporin antibiotics were higher compared to arsenic-sensitive bacteria (odds ratios, OR 1.2-7.0, p <0.01). WGS-based phylogenetic analysis of E. coli isolates did not reveal any clustering based on arsenic exposure and no significant difference in resistome was found among the isolates between the two areas. The positive association detected between arsenic exposure and antibiotic resistance carriage among children in arsenic-affected areas in Bangladesh is an important public health concern that warrants redoubling efforts to reduce arsenic exposure.

'I Doubt Myself and Am Losing Everything I Have since COVID Came'-A Case Study of Mental Health and Coping Strategies among Undocumented Myanmar Migrant Workers in Thailand.

Migrant populations have always been vulnerable to a high burden of social exclusion, mental disorders, physical illnesses, and economic crises. The current COVID-19 pandemic has further created a frantic plight among them, particularly for undocumented migrant workers in the global south. We have conducted a mixed method study among the undocumented Myanmar migrant workers (UMMWs) in Thailand to explore how the COVID-19 disruption has impacted their mental health and what coping strategies they have adopted. Following the onset of COVID-19 and the recent coup d'état in Myanmar, our current study is the first attempt to understand the mental health status and predicament of this neglected migrant group. A total of 398 UMMWs were included in the online survey, of which 23 participated in qualitative interviews. The major mental health issues reported by the study participants were depression, generalized anxiety disorder, frustration, stress, and panic disorders, while loss of employment, worries about the pandemic, social stigma, lack of access to healthcare, lockdown, and fear of detention were the predominant contributing factors. In response, we identified two key coping mechanisms: coping at a personal level (listening to music, playing online game, praying, and self-motivation) and coping at a social level (chatting with family and friends and visiting religious institutions). These findings point to the importance of policy and intervention programs aimed at upholding mental health at such humanitarian conditions. Sustainable institutional mental health care support and social integration for the migrant workers, irrespective of their legal status, should be ensured.

Prevalence, etiology and antibiotic resistance patterns of community-acquired urinary tract infections in Dhaka, Bangladesh.

Urinary tract infection (UTI) accounts for a significant morbidity and mortality across the world and is a leading cause for antibiotic prescriptions in the community especially in developing countries. Empirical choice of antibiotics for treatment of UTI is often discordant with the drug susceptibility of the etiologic agent. This study aimed to estimate the prevalence of community-acquired UTI caused by antibiotic resistant organisms. This was a cross-sectional study where urine samples were prospectively collected from 4,500 patients at the icddr,b diagnostic clinic in Dhaka, Bangladesh during 2016-2018. Urine samples were analyzed by standard culture method and the isolated bacteria were tested for antibiotic susceptibility by using disc diffusion method and VITEK-2. Descriptive statistics were used to estimate the prevalence of community acquired UTI (CA-UTI) by different age groups, sex, and etiology of infection. Relationship between the etiology of CA-UTI and age and sex of patients was analyzed using binary logistic regression analysis. Seasonal trends in the prevalence of CA-UTI, multi-drug resistant (MDR) pathogens and MDR Escherichia coli were also analyzed. Around 81% of patients were adults (≥18y). Of 3,200 (71%) urine samples with bacterial growth, 920 (29%) had a bacterial count of ≥1.0x105 CFU/ml indicating UTI. Women were more likely to have UTI compared to males (OR: 1.48, CI: 1.24-1.76). E. coli (51.6%) was the predominant causative pathogen followed by Streptococcus spp. (15.7%), Klebsiella spp. (12.1%), Enterococcus spp. (6.4%), Pseudomonas spp. (4.4%), coagulase-negative Staphylococcus spp. (2.0%), and other pathogens (7.8%). Both E. coli and Klebsiella spp. were predominantly resistant to penicillin (85%, 95%, respectively) followed by macrolide (70%, 76%), third-generation cephalosporins (69%, 58%), fluoroquinolones (69%, 53%) and carbapenem (5%, 9%). Around 65% of patients tested positive for multi-drug resistant (MDR) uropathogens. A higher number of male patients tested positive for MDR pathogens compared to the female patients (p = 0.015). Overall, 71% of Gram-negative and 46% of Gram-positive bacteria were MDR. The burden of community-acquired UTI caused by MDR organisms was high among the study population. The findings of the study will guide clinicians to be more selective about their antibiotic choice for empirical treatment of UTI and alleviate misuse/overuse of antibiotics in the community.

Planetary Health Education and Capacity Building for Healthcare Professionals in a Global Context: Current Opportunities, Gaps and Future Directions.

The emerging concept of planetary health needs to be discussed in a more organized and sustainable way within the global public health and healthcare disciplines. Therefore, planetary health should be considered a cardinal component of the global academic framework for healthcare professionals. The availability of related curricula and courses is crucial to equip health professionals in this relatively new discipline of planetary health. In this review article, we aimed to explore published articles and online databases of courses to summarize the available planetary health education opportunities and discussions for health professionals, to identify the gaps in resource allocation and to suggest future recommendations. We observed a visible resource inequity in the global south with the lack of a universal planetary health module for healthcare professionals. Additionally, there is minimal inclusion of allied health disciplines in this learning process. We therefore recommend a dedicated network of motivated healthcare professionals and regional hubs with an agenda to ensure a comprehensive, uniform, and inclusive planetary health education curriculum and practice.

Iron Overload and Breast Cancer: Iron Chelation as a Potential Therapeutic Approach.

Breast cancer has historically been one of the leading causes of death for women worldwide. As of 2020, breast cancer was reported to have overtaken lung cancer as the most common type of cancer globally, representing an estimated 11.3% of all cancer diagnoses. A multidisciplinary approach is taken for the diagnosis and treatment of breast cancer that includes conventional and targeted treatments. However, current therapeutic approaches to treating breast cancer have limitations, necessitating the search for new treatment options. Cancer cells require adequate iron for their continuous and rapid proliferation. Excess iron saturates the iron-binding capacity of transferrin, resulting in non-transferrin-bound iron (NTBI) that can catalyze free-radical reactions and may lead to oxidant-mediated breast carcinogenesis. Moreover, excess iron and the disruption of iron metabolism by local estrogen in the breast leads to the generation of reactive oxygen species (ROS). Therefore, iron concentration reduction using an iron chelator can be a novel therapeutic strategy for countering breast cancer development and progression. This review focuses on the use of iron chelators to deplete iron levels in tumor cells, specifically in the breast, thereby preventing the generation of free radicals. The inhibition of DNA synthesis and promotion of cancer cell apoptosis are the targets of breast cancer treatment, which can be achieved by restricting the iron environment in the body. We hypothesize that the usage of iron chelators has the therapeutic potential to control intracellular iron levels and inhibit the breast tumor growth. In clinical settings, iron chelators can be used to reduce cancer cell growth and thus reduce the morbidity and mortality in breast cancer patients.

Changes in life expectancy and disease burden in Norway, 1990-2019: an analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Geographical differences in health outcomes are reported in many countries. Norway has led an active policy aiming for regional balance since the 1970s. Using data from the Global Burden of Disease Study (GBD) 2019, we examined regional differences in development and current state of health across Norwegian counties. METHODS: Data for life expectancy, healthy life expectancy (HALE), years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) in Norway and its 11 counties from 1990 to 2019 were extracted from GBD 2019. County-specific contributors to changes in life expectancy were compared. Inequality in disease burden was examined by use of the Gini coefficient. FINDINGS: Life expectancy and HALE improved in all Norwegian counties from 1990 to 2019. Improvements in life expectancy and HALE were greatest in the two counties with the lowest values in 1990: Oslo, in which life expectancy and HALE increased from 71·9 years (95% uncertainty interval 71·4-72·4) and 63·0 years (60·5-65·4) in 1990 to 81·3 years (80·0-82·7) and 70·6 years (67·4-73·6) in 2019, respectively; and Troms og Finnmark, in which life expectancy and HALE increased from 71·9 years (71·5-72·4) and 63·5 years (60·9-65·6) in 1990 to 80·3 years (79·4-81·2) and 70·0 years (66·8-72·2) in 2019, respectively. Increased life expectancy was mainly due to reductions in cardiovascular disease, neoplasms, and respiratory infections. No significant differences between the national YLD or DALY rates and the corresponding age-standardised rates were reported in any of the counties in 2019; however, Troms og Finnmark had a higher age-standardised YLL rate than the national rate (8394 per 100 000 [95% UI 7801-8944] vs 7536 per 100 000 [7391-7691]). Low inequality between counties was shown for life expectancy, HALE, all level-1 causes of DALYs, and exposure to level-1 risk factors. INTERPRETATION: Over the past 30 years, Norway has reduced inequality in disease burden between counties. However, inequalities still exist at a within-county level and along other sociodemographic gradients. Because of insufficient Norwegian primary data, there remains substantial uncertainty associated with regional estimates for non-fatal disease burden and exposure to risk factors. FUNDING: Bill & Melinda Gates Foundation, Research Council of Norway, and Norwegian Institute of Public Health.

Understanding transmission pathways and integrated digital surveillance potential of antimicrobial resistance in Ethiopia in a One Health approach: a mixed-method study protocol.

INTRODUCTION: Antimicrobial resistance (AMR) has a critical global impact, mostly affecting low- and middle-income countries. A major knowledge gap exists in understanding the transmission pathway of the gut colonisation with AMR bacteria between healthy humans and their animals in addition to the presence of those AMR bacteria in the surrounding environment. A One Health (OH) approach is necessary to address this multisectoral problem. METHODS AND ANALYSIS: This cross-sectional, mixed-method OH study design will use both quantitative and qualitative methods of data collection. Quantitative methods will be carried out to assess the prevalence and risk factors associated with multidrug resistant Gram-negative bacteria and vancomycin-resistant enterococci in humans, animals (cattle) and the environment. The focus will be on cattle rearing as an exposure risk for AMR among humans. The assessment of AMR in the population of Jimma, Ethiopia with or without exposure to cattle will reinforce the importance of OH research to identify the impending exchange of resistance profile between humans and animals as well as its ultimate dissemination in the surrounding environment.The targeted semistructured key stakeholder interviews will aid to strengthen the OH-AMR surveillance in Ethiopia by understanding the acceptability of an integrated AMR surveillance platform based on the District Health Information Software-2 and the feasibility of its context-specific establishment. ETHICS AND DISSEMINATION: The study has been approved by the Regional Ethics Committee, Norway, and the Institutional Review Board of Jimma University, Ethiopia. The study's data will be stored on a secure server known as Services for Sensitive Data hosted by the University of Oslo. In addition, the new European Union Global Data Protection Guidelines for data sharing, storage and protection will be followed. We will publish the results in peer-reviewed journals and present the findings at national and international conferences.

Safety and efficacy of favipiravir for the management of COVID-19 patients: A preliminary randomized control trial.

Background: The novel coronavirus disease, commonly called COVID-19, has already killed millions of lives. Our study aimed to identify a safe and right drug for the management of such globally threatened COVID-19. Methods: This preliminary double-blinded randomized controlled trial was done among 57 hospitalized COVID-19 patients in the early stage of their illness. Of them, 29 patients received Favipiravir (FVP) and the remaining 28 patients received a placebo under the standard of care. Among the patients, 4 from Favipiravir (FVP) group and 3 from the placebo group were discontinued. The patients were observed regularly for a period of 10 days. Result: In our study, the FVP treated group showed accelerated viral clearance compared to the placebo-treated group. Assessment of chest X-ray showed remarkable improvement of pheumonia patient in group A compared to Group B. Hematological and Biochemical parameters such as total WBC count, neutrophil and lymphocyte counts were examined. No significant differences in the hematological parameters such as WBC count, neutrophil and lymphocyte counts in Group A and Group B patients. Liver transaminases levels were also stable in FVP treated group (average ALT ranges 39.4-46.2; AST 28.2-32.8). Conclusion: The drug Favipiravir displayed remarkable improvements in the clinical conditions and recovery of COVID-19 patients at the early stages of their infections.

Spatiotemporal distribution of antimicrobial resistant organisms in different water environments in urban and rural settings of Bangladesh.

The spatial distribution of clinically important antibiotic resistant bacteria (ARB) and associated genes is important to identify the environmental distribution of contamination and 'hotspots' of antimicrobial resistance (AMR). We conducted an integrated survey of AMR in drinking water, wastewater and surface water (rivers and ponds) in three settings in Bangladesh: rural households, rural poultry farms, and urban food markets. Spatial mapping was conducted via geographic information system (GIS) using ArcGIS software. Samples (n = 397) were analyzed for the presence of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-Ec), carbapenem-resistant E. coli (CR-Ec) and resistance genes (blaCTX-M-1,blaNDM-1). In rural households, 5% of drinking water supply samples tested positive for ESBL-Ec, and a high proportion of wastewater, pond and river water samples were positive for ESBL-Ec (90%, 76%, and 85%, respectively). In poultry farms, 10% of drinking water samples tested positive for ESBL-Ec compared to a high prevalence in wastewater, pond and river water (90%, 68%, and 85%, respectively). CR-Ec prevalence in household wastewater and pond water was relatively low (8% and 5%, respectively) compared to river water (33%). In urban areas, 38% of drinking water samples and 98% of wastewater samples from food markets tested positive for ESBL-Ec while 30% of wastewater samples tested positive for CR-Ec. Wastewaters had the highest concentrations of ESBL-Ec, CR-Ec, blaCTXM-1 and blaNDM-1 and these were significantly higher in urban compared to rural samples (p < 0.05). ESBL-Ec is ubiquitous in drinking water, wastewater and surface water bodies in both rural and urban areas of Bangladesh. CR-Ec is less widespread but found at a high prevalence in wastewater discharged from urban food markets and in rural river samples. Surveillance and monitoring of antibiotic resistant organisms and genes in waterbodies is an important first step in addressing environmental dimensions of AMR.

Evidence of Antimicrobial Resistance in Bats and Its Planetary Health Impact for Surveillance of Zoonotic Spillover Events: A Scoping Review.

As a result of the COVID-19 pandemic, as well as other outbreaks, such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread, and persistence of AMR at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wildlife has important implications for zoonotic pandemic surveillance, disease transmission, and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n = 38) that provided data on resistant bacteria in bats prior to 30 September 2022. There is substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types, and time. We found all major groups of Gram-positive and Gram-negative bacteria in bats, which are resistant to commonly used antibiotics. The most alarming issue is that recent studies have increasingly identified clinically significant multi-drug resistant bacteria such as Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing, and Colistin resistant Enterobacterales in samples from bats. This evidence of superbugs abundant in both humans and wild mammals, such as bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic preparedness as well as global AMR containment during pandemic events and beyond.

Synthesis, in vitro bioassays, and computational study of heteroaryl nitazoxanide analogs.

Antiprotozoal drug nitazoxanide (NTZ) has shown diverse pharmacological properties and has appeared in several clinical trials. Herein we present the synthesis, characterization, in vitro biological investigation, and in silico study of four hetero aryl amide analogs of NTZ. Among the synthesized molecules, compound 2 and compound 4 exhibited promising antibacterial activity against Escherichia coli (E. coli), superior to that displayed by the parent drug nitazoxanide as revealed from the in vitro antibacterial assay. Compound 2 displayed zone of inhibition of 20 mm, twice as large as the parent drug NTZ (10 mm) in their least concentration (12.5 µg/ml). Compound 1 also showed antibacterial effect similar to that of nitazoxanide. The analogs were also tested for in vitro cytotoxic activity by employing cell counting kit-8 (CCK-8) assay technique in HeLa cell line, and compound 2 was identified as a potential anticancer agent having IC50 value of 172 µg which proves it to be more potent than nitazoxanide (IC50  = 428 µg). Furthermore, the compounds were subjected to molecular docking study against various bacterial and cancer signaling proteins. The in vitro test results corroborated with the in silico docking study as compound 2 and compound 4 had comparatively stronger binding affinity against the proteins and showed a higher docking score than nitazoxanide toward human mitogen-activated protein kinase (MAPK9) and fatty acid biosynthesis enzyme (FabH) of E. coli. Moreover, the docking study demonstrated dihydrofolate reductase (DHFR) and thymidylate synthase (TS) as probable new targets for nitazoxanide and its synthetic analogs. Overall, the study suggests that nitazoxanide and its analogs can be a potential lead compound in the drug development.