Host Range and Emerging and Reemerging Pathogens

Emerging and reemerging species of human pathogens are associated with a broad range of nonhuman hosts

Predictors of human-infective RNA virus discovery in the United States, China, and Africa, an ecological study

BACKGROUND: The variation in the pathogen type as well as the spatial heterogeneity of predictors make the generality of any associations with pathogen discovery debatable. Our previous work confirmed that the association of a group of predictors differed across different types of RNA viruses, yet there have been no previous comparisons of the specific predictors for RNA virus discovery in different regions. The aim of the current study was to close the gap by investigating whether predictors of discovery rates within three regions—the United States, China, and Africa—differ from one another and from those at the global level. METHODS: Based on a comprehensive list of human-infective RNA viruses, we collated published data on first discovery of each species in each region. We used a Poisson boosted regression tree (BRT) model to examine the relationship between virus discovery and 33 predictors representing climate, socio-economics, land use, and biodiversity across each region separately. The discovery probability in three regions in 2010–2019 was mapped using the fitted models and historical predictors. RESULTS: The numbers of human-infective virus species discovered in the United States, China, and Africa up to 2019 were 95, 80, and 107 respectively, with China lagging behind the other two regions. In each region, discoveries were clustered in hotspots. BRT modelling suggested that in all three regions RNA virus discovery was better predicted by land use and socio-economic variables than climatic variables and biodiversity, although the relative importance of these predictors varied by region. Map of virus discovery probability in 2010–2019 indicated several new hotspots outside historical high-risk areas. Most new virus species since 2010 in each region (6/6 in the United States, 19/19 in China, 12/19 in Africa) were discovered in high-risk areas as predicted by our model. CONCLUSIONS: The drivers of spatiotemporal variation in virus discovery rates vary in different regions of the world. Within regions virus discovery is driven mainly by land-use and socio-economic variables; climate and biodiversity variables are consistently less important predictors than at a global scale. Potential new discovery hotspots in 2010–2019 are identified. Results from the study could guide active surveillance for new human-infective viruses in local high-risk areas. FUNDING: FFZ is funded by the Darwin Trust of Edinburgh (https://darwintrust.bio.ed.ac.uk/). MEJW has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 874735 (VEO) (https://www.veo-europe.eu/)

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

A Meta-Analysis of Experimental Studies of Attenuated Schistosoma mansoni Vaccines in the Mouse Model.

Schistosomiasis is a water-borne, parasitic disease of major public health importance. There has been considerable effort for several decades toward the development of a vaccine against the disease. Numerous mouse experimental studies using attenuated Schistosoma mansoni parasites for vaccination have been published since 1960s. However, to date, there has been no systematic review or meta-analysis of these data. The aim of this study is to identify measurable experimental conditions that affect the level of protection against re-infection with S. mansoni in mice vaccinated with radiation attenuated cercariae. Following a systematic review, a total of 755 observations were extracted from 105 articles (published 1963-2007) meeting the searching criteria. Random effects meta-regression models were used to identify the influential predictors. Three predictors were found to have statistically significant effects on the level of protection from vaccination: increasing numbers of immunizing parasites had a positive effect on fraction of protection whereas increasing radiation dose and time to challenge infection had negative effects. Models showed that the irradiated cercariae vaccine has the potential to achieve protection as high as 78% with a single dose vaccination. This declines slowly over time but remains high for at least 8 months after the last immunization. These findings provide insights into the optimal delivery of attenuated parasite vaccination and into the nature and development of protective vaccine induced immunity against schistosomiasis, which may inform the formulation of human vaccines and the predicted duration of protection and thus frequency of booster vaccines

Epidemiology of antimicrobial-resistant Escherichia coli carriage in sympatric humans and livestock in a rapidly urbanizing city

There are substantial limitations in understanding of the distribution of antimicrobial resistance (AMR) in humans and livestock in developing countries. This papers present the results of an epidemiological study examining patterns of AMR in Escherichia coli isolates circulating in sympatric human (n = 321) and livestock (n = 633) samples from 99 households across Nairobi, Kenya. E. coli isolates were tested for susceptibility to 13 antimicrobial drugs representing nine antibiotic classes. High rates of AMR were detected, with 47.6% and 21.1% of isolates displaying resistance to three or more and five or more antibiotic classes, respectively. Human isolates showed higher levels of resistance to sulfonamides, trimethoprim, aminoglycosides and penicillins compared with livestock (P0.05). These findings revealed a high prevalence of AMR E. coli circulating in healthy humans and livestock in Nairobi, with no evidence to suggest that keeping livestock, when treated as a single risk factor, contributed significantly to the burden of AMR in humans, although the presence of livestock waste was significant. These results provide an understanding of the broader epidemiology of AMR in complex and interconnected urban environments

Are Food Animals Responsible for Transfer of Antimicrobial-Resistant Escherichia coli or Their Resistance Determinants to Human Populations?:A Systematic Review

The role of farm animals in the emergence and dissemination of both AMR bacteria and their resistance determinants to humans is poorly understood and controversial. Here, we systematically reviewed the current evidence that food animals are responsible for transfer of AMR to humans. We searched PubMed, Web of Science, and EMBASE for literature published between 1940 and 2016. Our results show that eight studies (18%) suggested evidence of transmission of AMR from food animals to humans, 25 studies (56%) suggested transmission between animals and humans with no direction specified and 12 studies (26%) did not support transmission. Quality of evidence was variable among the included studies; one study (2%) used high resolution typing tools, 36 (80%) used intermediate resolution typing tools, six (13%) relied on low resolution typing tools, and two (5%) based conclusions on co-occurrence of resistance. While some studies suggested to provide evidence that transmission of AMR from food animals to humans may occur, robust conclusions on the directionality of transmission cannot be drawn due to limitations in study methodologies. Our findings highlight the need to combine high resolution genomic data analysis with systematically collected epidemiological evidence to reconstruct patterns of AMR transmission between food animals and humans

Parasite co-infections show synergistic and antagonistic interactions on growth performance of East African zebu cattle under one year

The co-occurrence of different pathogen species and their simultaneous infection of hosts are common, and may affect host health outcomes. Co-infecting pathogens may interact synergistically (harming the host more) or antagonistically (harming the host less) compared with single infections. Here we have tested associations of infections and their co-infections with variation in growth rate using a subset of 455 animals of the Infectious Diseases of East Africa Livestock (IDEAL) cohort study surviving to one year. Data on live body weight, infections with helminth parasites and haemoparasites were collected every 5 weeks during the first year of life. Growth of zebu cattle during the first year of life was best described by a linear growth function. A large variation in daily weight gain with a range of 0·03–0·34 kg, and a mean of 0·135 kg (0·124, 0·146; 95% CI) was observed. After controlling for other significant covariates in mixed effects statistical models, the results revealed synergistic interactions (lower growth rates) with Theileria parva and Anaplasma marginale co-infections, and antagonistic interactions (relatively higher growth rates) with T. parva and Theileria mutans co-infections, compared with infections with T. parva only. Additionally, helminth infections can have a strong negative effect on the growth rates but this is burden-dependent, accounting for up to 30% decrease in growth rate in heavily infected animals. These findings present evidence of pathogen–pathogen interactions affecting host growth, and we discuss possible mechanisms that may explain observed directions of interactions as well as possible modifications to disease control strategies when co-infections are present.This work was supported by the Wellcome Trust (grant No. 079445).http://www.parasitesandvectors.com/am2014ab201

Parasite co-infections and their impact on survival of indigenous cattle

In natural populations, individuals may be infected with multiple distinct pathogens at a time. These pathogens may act independently or interact with each other and the host through various mechanisms, with resultant varying outcomes on host health and survival. To study effects of pathogens and their interactions on host survival, we followed 548 zebu cattle during their first year of life, determining their infection and clinical status every 5 weeks. Using a combination of clinical signs observed before death, laboratory diagnostic test results, gross-lesions on post-mortem examination, histo-pathology results and survival analysis statistical techniques, cause-specific aetiology for each death case were determined, and effect of co-infections in observed mortality patterns. East Coast fever (ECF) caused by protozoan parasite Theileria parva and haemonchosis were the most important diseases associated with calf mortality, together accounting for over half (52%) of all deaths due to infectious diseases. Co-infection with Trypanosoma species increased the hazard for ECF death by 6 times (1.4–25; 95% CI). In addition, the hazard for ECF death was increased in the presence of Strongyle eggs, and this was burden dependent. An increase by 1000 Strongyle eggs per gram of faeces count was associated with a 1.5 times (1.4–1.6; 95% CI) increase in the hazard for ECF mortality. Deaths due to haemonchosis were burden dependent, with a 70% increase in hazard for death for every increase in strongyle eggs per gram count of 1000. These findings have important implications for disease control strategies, suggesting a need to consider co-infections in epidemiological studies as opposed to singlepathogen focus, and benefits of an integrated approach to helminths and East Coast fever disease control.The Wellcome Trust (grant No. 079445)http://www.plosone.orgam201