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Background Next-generation sequencing has considerably increased the number of genomes available in the public domain. However, efforts to use these genomes for surveillance of antimicrobial resistance have thus far been limited and geographically heterogeneous. We inferred global resistance trends in Escherichia coli in food animals using genomes from public databases. Methods We retrieved 7632 E. coli genomes from public databases (NCBI, PATRIC and EnteroBase) and screened for antimicrobial resistance genes (ARGs) using ResFinder. Selection bias towards resistance, virulence or specific strains was accounted for by screening BioProject descriptions. Temporal trends for MDR, resistance to antimicrobial classes and ARG prevalence were inferred using generalized linear models for all genomes, including those not subjected to selection bias. Results MDR increased by 1.6 times between 1980 and 2018, as genomes carried, on average, ARGs conferring resistance to 2.65 antimicrobials in swine, 2.22 in poultry and 1.58 in bovines. Highest resistance levels were observed for tetracyclines (42.2%–69.1%), penicillins (19.4%–47.5%) and streptomycin (28.6%–56.6%). Resistance trends were consistent after accounting for selection bias, although lower mean absolute resistance estimates were associated with genomes not subjected to selection bias (difference of 3.16%±3.58% across years, hosts and antimicrobial classes). We observed an increase in extended-spectrum cephalosporin ARG blaCMY-2 and a progressive substitution of tetB by tetA. Estimates of resistance prevalence inferred from genomes in the public domain were in good agreement with reports from systematic phenotypic surveillance. Conclusions Our analysis illustrates the potential of using the growing volume of genomes in public databases to track AMR trends globally.

In May this year, the long-awaited final report from the Review on Antimicrobial Resistance was published. 1 The report estimates that the 700 000 annual deaths currently attributable to infections by drug-resistant pathogens will increase, if unchecked, to 10 million by 2050, running up a bill of US$100 trillion in terms of lost global production between now and then. The reported numbers are somewhat apocalyptic, as they are based on crude projections of current trends and presume the failure of anti-malarial drugs and antiretroviral therapy as well as antibiotics. Nor do they account for the possible entry of new drugs onto the market. There is huge uncertainty associated with the human burden of antimicrobial resistance (AMR) in general and antibiotic resistance in particular (for the purpose of this article the widely used term antimicrobial resistance [AMR] is retained, though the emphasis here is on antibiotic resistance). The precision of the estimates does not really matter much: the point is that the problem is already immense and is growing rapidly. We have been squandering our antibiotic resources for far too long and immediate action is needed on a very large scale if we are to reverse current trends., Transactions of the Royal Society of Tropical Medicine and Hygiene, 110 (7), ISSN:0035-9203

Antimicrobial resistance (AMR) is a serious global threat driven by the overuse of drugs in humans, animals, as well as the contamination of natural environments with antimicrobial residues. In rec...

In Switzerland, the COVID-19 epidemic is progressively slowing down owing to “social distancing” measures introduced by the Federal Council on 16 March 2020. However, the gradual ease of these measures may initiate a second epidemic wave, the length and intensity of which are difficult to anticipate. In this context, hospitals must prepare for a potential increase in intensive care unit (ICU) admissions of patients with acute respiratory distress syndrome. Here, we introduce icumonitoring.ch, a platform providing hospital-level projections for ICU occupancy. We combined current data on the number of beds and ventilators with canton-level projections of COVID-19 cases from two S-E-I-R models. We disaggregated epidemic projection in each hospital in Switzerland for the number of COVID-19 cases, hospitalisations, hospitalisations in ICU, and ventilators in use. The platform is updated every 3-4 days and can incorporate projections from other modelling teams to inform decision makers with a range of epidemic scenarios for future hospital occupancy. ISSN:1424-7860 ISSN:1424-3997

Understanding the patterns and drivers of antibiotic use in livestock is crucial for tailoring efficient incentives for responsible use of antibiotics. Here we compared routines for antibiotic use between pig farms of two different levels of intensification in Khon Kaen province in Thailand. Among the 113 family-owned small-scale farms (up to 50 sows) interviewed did 76% get advice from the pharmacy about how to use the antibiotics and 84% used it primarily for treating disease. Among the 51 medium-scale-farms (100–500 sows) belonging to two companies did 100% get advice about antibiotic use from the company’s veterinarian (P, PLoS ONE, 15 (12 December), ISSN:1932-6203

Demand for poultry meat is rising in low- and middle-countries, driving the expansion of large commercial farms where antimicrobials are used as surrogates for hygiene, good nutrition. This routine use of antimicrobials in animal production facilitates the emergence and spread of antibiotic-resistant pathogens. Despite potentially serious consequences for the animal industry, few studies have documented trends in antimicrobial use (AMU) at the farm-level in low- and middle-income countries. The objective of this study was to estimate AMU in a broiler chicken farm in Pakistan over a five-year period and to extrapolate national AMU in commercial broiler farming. Between 2013 and 2017, we monitored AMU in 30 flocks from a commercial broiler farm in Punjab, the most populous province of Pakistan. The amount of antimicrobials administered was calculated in milligram/population unit of the final flock weight (mg/fPU) and in used daily dose (UDD). The annual on-farm antimicrobial use was 250.84 mg of active ingredient per kilogram of the final flock weight. This consumption intensity exceeds the amount of antimicrobial used per kilogram of chicken of all countries in the world except China. Measured in mg per kg of final flock weight or population unit (fPU), medically important drugs such as colistin (31.39 mg/fPU), tylosin (41.71 mg/fPU), doxycycline (81.81 mg/fPU), and enrofloxacin (26.19 mg/fPU) were the most frequently used antimicrobials for prophylactic or therapeutic use. Lincomycin was the most frequently used antimicrobial used in-feed (29.09 mg/fPU). Our findings suggest that the annual consumption of antimicrobials in the broiler sector in Pakistan could be as high as 568 tons. This alarmingly high consumption estimate is the first baseline study on antimicrobial use in animals in Pakistan. Our findings call for immediate actions to reduce antimicrobial use in Pakistan, and countries with comparable farming practices., Global Health Action, 12 (s1)

The global scale-up in demand for animal protein is the most notable dietary trend of our time. Antimicrobial consumption in animals is threefold that of humans and has enabled large-scale animal protein production. The consequences for the development of antimicrobial resistance in animals have received comparatively less attention than in humans. We analyzed 901 point prevalence surveys of pathogens in developing countries to map resistance in animals. China and India represented the largest hotspots of resistance, with new hotspots emerging in Brazil and Kenya. From 2000 to 2018, the proportion of antimicrobials showing resistance above 50% increased from 0.15 to 0.41 in chickens and from 0.13 to 0.34 in pigs. Escalating resistance in animals is anticipated to have important consequences for animal health and, eventually, for human health., SCOPUS: ar.j, info:eu-repo/semantics/published

BackgroundRising antimicrobial resistance (AMR) is a threat to modern medicine, and increasing international mobility facilitates the spread of AMR. Infections with resistant organisms have higher morbidity and mortality, are costlier to treat, result in longer hospital stays and place a greater burden on health systems than infections caused by susceptible organisms. Here we review the role of travel in the international dissemination of AMR and consider actions at the levels of travelers, travel medicine practitioners and policymakers that would mitigate this threat.ResultsResistant pathogens do not recognize international borders; travelers to areas with high AMR prevalence are likely to be exposed to resistant bacteria and return to their home countries colonized. Medical tourists go between health facilities with drastically different rates of AMR, potentially transmitting highly resistant strains.Drug-resistant bacteria have been found in every continent; however, differences between countries in the prevalence of AMR depend on multiple factors. These include levels of antibiotic consumption (including inappropriate use), access to clean water, adequate sanitation, vaccination coverage, the availability of quality healthcare and access to high-quality medical products.ConclusionsTravelers to areas with high levels of AMR should have vaccines up to date, be aware of ways of treating and preventing travelers’ diarrhea (other than antibiotic use) and be informed on safe sexual practices. The healthcare systems of low- and middle-income countries require investment to reduce the transmission of resistant strains by improving access to clean water, sanitation facilities and vaccines. Efforts are needed to curb inappropriate antibiotic use worldwide. In addition, more surveillance is needed to understand the role of the movement of humans, livestock and food products in resistance transmission. The travel medicine community has a key role to play in advocating for the recognition of AMR as a priority on the international health agenda.Key policy recommendationsAMR is a threat to modern medicine, and international travel plays a key role in the spread of highly resistant strains. It is essential that this is addressed at multiple levels. Individual travelers can reduce antibiotic consumption and the likelihood of infection. Travelers should have up-to-date vaccines and be informed on methods of preventing and treating travelers’ diarrhea, other than use of antibiotics and on safe sexual practices, such as condom use. Healthcare facilities need to be aware of the travel history of patients to provide appropriate treatment to those who are at high risk of exposure and to prevent further spread. Internationally, in countries without reliable and universal access to clean water, sanitation and hygiene, investment is needed to reduce the emergence and spread of resistance and ensure the antimicrobials available are of assured quality. High-income countries must ensure their use of antimicrobials is appropriate to reduce selection for AMR. Surveillance across all countries is needed to monitor and respond to this emerging threat.

The Highly Pathogenic Avian Influenza (HPAI) subtype H5N1 virus persists in many countries and has been circulating in poultry, wild birds. In addition, the virus has emerged in other species and frequent zoonotic spillover events indicate that there remains a significant risk to human health. It is crucial to understand the dynamics of the disease in the poultry industry to develop a more comprehensive knowledge of the risks of transmission and to establish a better distribution of resources when implementing control. In this paper, we develop a set of mathematical models that simulate the spread of HPAI H5N1 in the poultry industry in Thailand, utilising data from the 2004 epidemic. The model that incorporates the intensity of duck farming when assessing transmision risk provides the best fit to the spatiotemporal characteristics of the observed outbreak, implying that intensive duck farming drives transmission of HPAI in Thailand. We also extend our models using a sequential model fitting approach to explore the ability of the models to be used in “real time” during novel disease outbreaks. We conclude that, whilst predictions of epidemic size are estimated poorly in the early stages of disease outbreaks, the model can infer the preferred control policy that should be deployed to minimise the impact of the disease., SCOPUS: ar.j, info:eu-repo/semantics/published

Global data sets on the geographic distribution of livestock are essential for diverse applications in agricultural socio-economics, food security, environmental impact assessment and epidemiology. We present a new version of the Gridded Livestock of the World (GLW 3) database, reflecting the most recently compiled and harmonized subnational livestock distribution data for 2010. GLW 3 provides global population densities of cattle, buffaloes, horses, sheep, goats, pigs, chickens and ducks in each land pixel at a spatial resolution of 0.083333 decimal degrees (approximately 10 km at the equator). They are accompanied by detailed metadata on the year, spatial resolution and source of the input census data. Two versions of each species distribution are produced. In the first version, livestock numbers are disaggregated within census polygons according to weights established by statistical models using high resolution spatial covariates (dasymetric weighting). In the second version, animal numbers are distributed homogeneously with equal densities within their census polygons (areal weighting) to provide spatial data layers free of any assumptions linking them to other spatial variables., SCOPUS: ar.j, info:eu-repo/semantics/published

Over the years, the emergence of novel H5 and H7 highly pathogenic avian influenza viruses (HPAI) has been taking place through two main mechanisms: first, the conversion of a low pathogenic into a highly pathogenic virus, and second, the reassortment between different genetic segments of low and highly pathogenic viruses already in circulation. We investigated and summarized the literature on emerging HPAI H5 and H7 viruses with the aim of building a spatio-temporal database of all these recorded conversions and reassortments events. We subsequently mapped the spatio-temporal distribution of known emergence events, as well as the species and production systems that they were associated with, the aim being to establish their main characteristics. From 1959 onwards, we identified a total of 39 independent H7 and H5 LPAI to HPAI conversion events. All but two of these events were reported in commercial poultry production systems, and a majority of these events took place in high-income countries. In contrast, a total of 127 reassortments have been reported from 1983 to 2015, which predominantly took place in countries with poultry production systems transitioning from backyard to intensive production systems. Those systems are characterized by several co-circulating viruses, multiple host species, regular contact points in live bird markets, limited biosecurity within value chains, and frequent vaccination campaigns that impose selection pressures for emergence of novel reassortants. We conclude that novel HPAI emergences by these two mechanisms occur in different ecological niches, with different viral, environmental and host associated factors, which has implications in early detection and management and mitigation of the risk of emergence of novel HPAI viruses., SCOPUS: ar.j, info:eu-repo/semantics/published

The large and expanding use of antimicrobials in livestock, a consequence of growing global demand for animal protein, is of considerable concern in light of the threat of antimicrobial resistance (AMR). Use of antimicrobials in animals has been linked to drug-resistant infections in animals (1) and humans (2). In September 2016, the United Nations (UN) General Assembly recognized the inappropriate use of antimicrobials in animals as a leading cause of rising AMR. In September 2018, the interagency group established by the UN Secretary General will report on progress in the global response to AMR, including antimicrobial consumption in animals. We provide a baseline to monitor efforts to reduce antimicrobial use and assess how three global policies might curb antimicrobial consumption in food animal production: (i) enforcing global regulations to cap antimicrobial use, (ii) adherence to nutritional guidelines leading to reduced meat consumption, and (iii) imposing a global user fee on veterinary antimicrobial use., Science, 357 (6358), ISSN:0036-8075, ISSN:1095-9203

Background: A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations. The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009. Methodology: The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (, SCOPUS: ar.j, info:eu-repo/semantics/published

Background Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by serotypes of the Enterovirus A species in the genus Enterovirus of the Picornaviridae family. The disease has had a substantial burden throughout East and Southeast Asia over the past 15 y. China reported 9 million cases of HFMD between 2008 and 2013, with the two serotypes Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) being responsible for the majority of these cases. Three recent phase 3 clinical trials showed that inactivated monovalent EV-A71 vaccines manufactured in China were highly efficacious against HFMD associated with EV-A71, but offered no protection against HFMD caused by CV-A16. To better inform vaccination policy, we used mathematical models to evaluate the effect of prospective vaccination against EV-A71-associated HFMD and the potential risk of serotype replacement by CV-A16. We also extended the model to address the co-circulation, and implications for vaccination, of additional non-EV-A71, non-CV-A16 serotypes of enterovirus. Methods and Findings Weekly reports of HFMD incidence from 31 provinces in Mainland China from 1 January 2009 to 31 December 2013 were used to fit multi-serotype time series susceptible–infected–recovered (TSIR) epidemic models. We obtained good model fit for the two-serotype TSIR with cross-protection, capturing the seasonality and geographic heterogeneity of province-level transmission, with strong correlation between the observed and simulated epidemic series. The national estimate of the basic reproduction number, R 0, weighted by provincial population size, was 26.63 for EV-A71 (interquartile range [IQR]: 23.14, 30.40) and 27.13 for CV-A16 (IQR: 23.15, 31.34), with considerable variation between provinces (however, predictions about the overall impact of vaccination were robust to this variation). EV-A71 incidence was projected to decrease monotonically with higher coverage rates of EV-A71 vaccination. Across provinces, CV-A16 incidence in the post-EV-A71-vaccination period remained either comparable to or only slightly increased from levels prior to vaccination. The duration and strength of cross-protection following infection with EV-A71 or CV-A16 was estimated to be 9.95 wk (95% confidence interval [CI]: 3.31, 23.40) in 68% of the population (95% CI: 37%, 96%). Our predictions are limited by the necessarily short and under-sampled time series and the possible circulation of unidentified serotypes, but, nonetheless, sensitivity analyses indicate that our results are robust in predicting that the vaccine should drastically reduce incidence of EV-A71 without a substantial competitive release of CV-A16. Conclusions The ability of our models to capture the observed epidemic cycles suggests that herd immunity is driving the epidemic dynamics caused by the multiple serotypes of enterovirus. Our results predict that the EV-A71 and CV-A16 serotypes provide a temporary immunizing effect against each other. Achieving high coverage rates of EV-A71 vaccination would be necessary to eliminate the ongoing transmission of EV-A71, but serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the corresponding reduction in the burden of EV-A71-associated HFMD. Therefore, a mass EV-A71 vaccination program of infants and young children should provide significant benefits in terms of a reduction in overall HFMD burden., Using time series susceptible–infected–recovered (TSIR) epidemic models, Saki Takahashi and colleagues investigate hand, foot, and mouth disease dynamics and the projected effect of vaccination in China., Editors' Summary Background Hand, foot, and mouth disease (HFMD)—a common ailment that mainly affects young children—is caused by a group of enteroviruses (Enterovirus A species), which are close relatives of polioviruses (Enterovirus C species). Enteroviruses are divided into various viral serotypes (variants defined by molecules on their surface that are recognized by the immune system), and the most common serotypes that cause HFMD are Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16). Enteroviruses spread from person to person through contact with the mucus or saliva produced when an infected individual coughs or sneezes, with the feces or the fluid from vesicles of an infected individual, and through contact with contaminated surfaces. Frequent handwashing and good hygiene practices can reduce the spread of HFMD. Symptoms of HFMD include fever, sore throat, a non-itchy red rash with small blisters on the hands and feet, and painful mouth ulcers. HFMD is usually a self-limiting illness, and most children recover within 7–10 days. A small proportion of patients infected with EV-A71 develop severe complications such as meningitis (infection of the membranes around the brain and spinal cord) or encephalitis (infection of the brain). Currently, there is no specific treatment for HFMD, and vaccines are not yet available for routine use. Why Was This Study Done? HFMD is increasingly common in East and Southeast Asia. China, for example, reported 9 million cases of HFMD between 2008 and 2013. Vaccination is a specific and effective way to reduce the burden of HFMD in China. In three clinical trials, inactivated monovalent EV-A71 vaccines made in China were highly efficacious against EV-A71-associated HFMD but provided no protection against CV-A16-associated HFMD (an inactivated monovalent vaccine contains a single virus strain that is unable to replicate; exposure to the vaccine “primes” the immune system to respond quickly when challenged with live virus, thereby preventing infection with that virus). So, before these vaccines can be used for routine vaccination of infants, it is important to know whether vaccination with EV-A71 will alter the burden of HFMD caused by other enterovirus serotypes. In particular, it is important to know whether infection with EV-A71 provides cross-protection against CV-A16 and whether infections with CV-A16 or other serotypes might increase following vaccination against EV-A71 because of increased circulation of these viruses in the population (serotype replacement). Here, the researchers use mathematical models to assess the effect of vaccination against EV-A71-associated HFMD in China and the potential risk of serotype replacement by CV-A16. What Did the Researchers Do and Find? The researchers used weekly data on HFMD incidence collected in 31 Chinese provinces between 2009 and 2013 to develop a two-serotype time series susceptible–infected–recovered epidemic model (a model in which individuals are born, become susceptible to a disease, become infected and infectious with the disease, and recover). The model accurately simulated the epidemic cycles of EV-A71- and CV-A16-associated HFMD for the 31 provinces and the seasonal transmission patterns in both northern and southern Chinese provinces. It provided an estimate of cross-protection following infection with EV-A71 or CV-A16 of ten weeks in 68% of the population (an average duration of cross-protection of 6.77 weeks). The estimated basic reproduction number (the average number of additional cases one case of an infectious disease generates in an otherwise uninfected population) across China for both serotypes was 25, which means that vaccination coverage levels of above 96% are required to achieve population-level immunity. Finally, the model predicted a decrease in EV-A71-associated HFMD incidence with higher rates of EV-A71 vaccination and suggested that CV-A16 incidence following EV-A71 vaccination would be comparable to or only slightly higher than its incidence before vaccination. What Do These Findings Mean? These findings suggest that herd immunity (indirect protection from infectious disease that occurs when most of a population has become immune to an infection, thereby providing some protection for the rare individuals who are not immune) is driving the dynamics of the HFMD epidemic caused by multiple enterovirus serotypes in China. Moreover, they suggest that the infection with EV-A71 or CV-A16 serotype can provide temporary immunity against each the other serotype and that serotype replacement by CV-A16 following EV-A71 vaccination is likely to be transient and minor compared to the reduction in the burden of EV-A71-associated HFMD produced by vaccination. The accuracy of these findings depends on the assumptions included in the model and the quality and quantity of data used to run the models. However, the researchers suggest that a mass EV-A71 vaccination campaign targeted at infants and young children should greatly reduce the burden of HFMD in China, provided a high vaccination uptake level is achieved. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001958. The US Centers for Disease Control and Prevention provide information on hand, foot, and mouth disease (in English and Spanish), including a podcast on the condition The UK National Health Service Choices website provides detailed information on hand, foot, and mouth disease Further information about hand, foot, and mouth disease is provided by the World Health Organization (including up-to-date HFMD surveillance reports from China), the Nemours Foundation (in English and Spanish), and MedlinePlus (in English and Spanish) The Government of the Hong Kong Special Administrative Region Department of Health Centre for Health Protection provides information on hand, foot, and mouth disease

Scientific Reports, 6, ISSN:2045-2322

Background: Temperature is a key determinant of environmental suitability for transmission of human malaria, modulating endemicity in some regions and preventing transmission in others. The spatial modelling of malaria endemicity has become increasingly sophisticated and is now central to the global scale planning, implementation, and monitoring of disease control and regional efforts towards elimination, but existing efforts to model the constraints of temperature on the malaria landscape at these scales have been simplistic. Here, we define an analytical framework to model these constraints appropriately at fine spatial and temporal resolutions, providing a detailed dynamic description that can enhance large scale malaria cartography as a decision-support tool in public health. Results: We defined a dynamic biological model that incorporated the principal mechanisms of temperature dependency in the malaria transmission cycle and used it with fine spatial and temporal resolution temperature data to evaluate time-series of temperature suitability for transmission of Plasmodium falciparum and P. vivax throughout an average year, quantified using an index proportional to the basic reproductive number. Time-series were calculated for all 1 km resolution land pixels globally and were summarised to create high-resolution maps for each species delineating those regions where temperature precludes transmission throughout the year. Within suitable zones we mapped for each pixel the number of days in which transmission is possible and an integrated measure of the intensity of suitability across the year. The detailed evaluation of temporal suitability dynamics provided by the model is visualised in a series of accompanying animations. Conclusions: These modelled products, made available freely in the public domain, can support the refined delineation of populations at risk; enhance endemicity mapping by offering a detailed, dynamic, and biologically driven alternative to the ubiquitous empirical incorporation of raw temperature data in geospatial models; and provide a rich spatial and temporal platform for future biological modelling studies. © 2011 Gething et al; licensee BioMed Central Ltd., SCOPUS: ar.j, info:eu-repo/semantics/published

Since 1996 when Highly Pathogenic Avian Influenza type H5N1 first emerged in southern China, numerous studies sought risk factors and produced risk maps based on environmental and anthropogenic predictors. However little attention has been paid to the link between the level of intensification of poultry production and the risk of outbreak. This study revised H5N1 risk mapping in Central and Western Thailand during the second wave of the 2004 epidemic. Production structure was quantified using a disaggregation methodology based on the number of poultry per holding. Population densities of extensively- and intensively-raised ducks and chickens were derived both at the sub-district and at the village levels. LandSat images were used to derive another previously neglected potential predictor of HPAI H5N1 risk: the proportion of water in the landscape resulting from floods. We used Monte Carlo simulation of Boosted Regression Trees models of predictor variables to characterize the risk of HPAI H5N1. Maps of mean risk and uncertainty were derived both at the sub-district and the village levels. The overall accuracy of Boosted Regression Trees models was comparable to that of logistic regression approaches. The proportion of area flooded made the highest contribution to predicting the risk of outbreak, followed by the densities of intensively-raised ducks, extensively-raised ducks and human population. Our results showed that as little as 15% of flooded land in villages is sufficient to reach the maximum level of risk associated with this variable. The spatial pattern of predicted risk is similar to previous work: areas at risk are mainly located along the flood plain of the Chao Phraya river and to the south-east of Bangkok. Using high-resolution village-level poultry census data, rather than sub-district data, the spatial accuracy of predictions was enhanced to highlight local variations in risk. Such maps provide useful information to guide intervention., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published