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Organisms have evolved diverse strategies to manage parasite infections. Broadly, hosts may avoid infection by altering behaviour, resist infection by targeting parasites or tolerate infection by repairing associated damage. The effectiveness of a strategy depends on interactions between, for example, resource availability, parasite traits (virulence, life-history) and the host itself (nutritional status, immunopathology). To understand how these factors shape host parasite-mitigation strategies, we developed a mathematical model of within-host, parasite-immune dynamics in the context of helminth infections. The model incorporated host nutrition and resource allocation to different mechanisms of immune response: larval parasite prevention; adult parasite clearance; damage repair (tolerance). We also considered a non-immune strategy: avoidance via anorexia, reducing intake of infective stages. Resources not allocated to immune processes promoted host condition, whereas harm due to parasites and immunopathology diminished it. Maximising condition (a proxy for fitness), we determined optimal host investment for each parasite-mitigation strategy, singly and combined, across different environmental resource levels and parasite trait values. Which strategy was optimal varied with scenario. Tolerance generally performed well, especially with high resources. Success of the different resistance strategies (larval prevention or adult clearance) tracked relative virulence of larval and adult parasites: slowly maturing, highly damaging larvae favoured prevention; rapidly maturing, less harmful larvae favoured clearance. Anorexia was viable only in the short term, due to reduced host nutrition. Combined strategies always outperformed any lone strategy: these were dominated by tolerance, with some investment in resistance. Choice of parasite mitigation strategy has profound consequences for hosts, impacting their condition, survival and reproductive success. We show that the efficacy of different strategies is highly dependent on timescale, parasite traits and resource availability. Models that integrate such factors can inform the collection and interpretation of empirical data, to understand how those drivers interact to shape host immune responses in natural systems.
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Within-host interactions among coinfecting parasites can have major consequences for individual infection risk and disease severity. However, the impact of these within-host interactions on between-host parasite transmission, and the spatial scales over which they occur, remain unknown. We developed and apply a novel spatially explicit analysis to parasite infection data from a wild wood mouse (Apodemus sylvaticus) population. We previously demonstrated a strong within-host negative interaction between two wood mouse gastrointestinal parasites, the nematode Heligmosomoides polygyrus and the coccidian Eimeria hungaryensis, using drug-treatment experiments. Here, we show this negative within-host interaction can significantly alter the between-host transmission dynamics of E. hungaryensis, but only within spatially restricted neighbourhoods around each host. However, for the closely related species E. apionodes, which experiments show does not interact strongly with H. polygyrus, we did not find any effect on transmission over any spatial scale. Our results demonstrate that the effects of within-host coinfection interactions can ripple out beyond each host to alter the transmission dynamics of the parasites, but only over local scales that likely reflect the spatial dimension of transmission. Hence there may be knock-on consequences of drug treatments impacting the transmission of non-target parasites, altering infection risks even for non-treated individuals in the wider neighbourhood.
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Coinfecção , Eimeria , Enteropatias Parasitárias , Parasitos , Animais , Camundongos , Interações Hospedeiro-Parasita , Murinae/parasitologia , Suscetibilidade a DoençasRESUMO
Vector-borne pathogens, many of which cause major suffering worldwide, often circulate in diverse wildlife communities comprising multiple reservoir host and/or vector species. However, the complexities of these systems make it challenging to determine the contributions these different species make to transmission. We experimentally manipulated transmission within a natural multihost-multipathogen-multivector system, by blocking flea-borne pathogen transmission from either of two co-occurring host species (bank voles and wood mice). Through genetic analysis of the resulting infections in the hosts and vectors, we show that both host species likely act together to maintain the overall flea community, but cross-species pathogen transmission is relatively rare-most pathogens were predominantly found in only one host species, and there were few cases where targeted treatment affected pathogens in the other host species. However, we do provide experimental evidence of some reservoir-spillover dynamics whereby reductions of some infections in one host species are achieved by blocking transmission from the other host species. Overall, despite the apparent complexity of such systems, we show there can be 'covert simplicity', whereby pathogen transmission is primarily dominated by single host species, potentially facilitating the targeting of key hosts for control, even in diverse ecological communities.
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Sifonápteros , Animais , Camundongos , Arvicolinae , Especificidade de Hospedeiro , Animais Selvagens , Insetos VetoresRESUMO
Host-parasite interactions exert strong selection pressures on the genomes of both host and parasite. These interactions can lead to negative frequency-dependent selection, a form of balancing selection that is hypothesised to explain the high levels of polymorphism seen in many host immune and parasite antigen loci. Here, we sequence the genomes of several individuals of Heligmosomoides bakeri, a model parasite of house mice, and Heligmosomoides polygyrus, a closely related parasite of wood mice. Although H. bakeri is commonly referred to as H. polygyrus in the literature, their genomes show levels of divergence that are consistent with at least a million years of independent evolution. The genomes of both species contain hyper-divergent haplotypes that are enriched for proteins that interact with the host immune response. Many of these haplotypes originated prior to the divergence between H. bakeri and H. polygyrus, suggesting that they have been maintained by long-term balancing selection. Together, our results suggest that the selection pressures exerted by the host immune response have played a key role in shaping patterns of genetic diversity in the genomes of parasitic nematodes.
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Nematospiroides dubius , Trichostrongyloidea , Camundongos , Animais , Interações Hospedeiro-Parasita/fisiologia , Nematospiroides dubius/genéticaRESUMO
The World Health Organization (WHO) recently proposed a new operational definition which designates communities with ≥10% prevalence of Schistosoma spp. infection as a persistent hotspot, when, after at least two rounds of high-coverage annual preventive chemotherapy, there is a lack of appropriate reduction. However, inconsistencies and challenges from both biological and operational perspectives remain, making the prescriptive use of this definition difficult. Here, we present a comprehensive analysis of the use of the term 'hotspot' across schistosomiasis research over time, including both literature searches and opinions from a range of stakeholders, to assess the utility and generalisability of the new WHO definition of a persistent hotspot. Importantly, we propose an updated definition based on our analyses.
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Anti-Helmínticos , Esquistossomose , Animais , Praziquantel/uso terapêutico , Anti-Helmínticos/uso terapêutico , Schistosoma haematobium , Esquistossomose/epidemiologia , Esquistossomose/prevenção & controle , Esquistossomose/tratamento farmacológico , Schistosoma mansoniRESUMO
BACKGROUND: Livestock systems have been proposed as a reservoir for antimicrobial-resistant (AMR) bacteria and AMR genetic determinants that may infect or colonise humans, yet quantitative evidence regarding their epidemiological role remains lacking. Here, we used a combination of genomics, epidemiology and ecology to investigate patterns of AMR gene carriage in Escherichia coli, regarded as a sentinel organism. METHODS: We conducted a structured epidemiological survey of 99 households across Nairobi, Kenya, and whole genome sequenced E. coli isolates from 311 human, 606 livestock and 399 wildlife faecal samples. We used statistical models to investigate the prevalence of AMR carriage and characterise AMR gene diversity and structure of AMR genes in different host populations across the city. We also investigated household-level risk factors for the exchange of AMR genes between sympatric humans and livestock. RESULTS: We detected 56 unique acquired genes along with 13 point mutations present in variable proportions in human and animal isolates, known to confer resistance to nine antibiotic classes. We find that AMR gene community composition is not associated with host species, but AMR genes were frequently co-located, potentially enabling the acquisition and dispersal of multi-drug resistance in a single step. We find that whilst keeping livestock had no influence on human AMR gene carriage, the potential for AMR transmission across human-livestock interfaces is greatest when manure is poorly disposed of and in larger households. CONCLUSIONS: Findings of widespread carriage of AMR bacteria in human and animal populations, including in long-distance wildlife species, in community settings highlight the value of evidence-based surveillance to address antimicrobial resistance on a global scale. Our genomic analysis provided an in-depth understanding of AMR determinants at the interfaces of One Health sectors that will inform AMR prevention and control.
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Gado , Saúde Única , Humanos , Animais , Escherichia coli/genética , Antibacterianos/farmacologia , Quênia/epidemiologia , Farmacorresistência Bacteriana/genéticaRESUMO
Monitoring the prevalence and abundance of parasites over time is important for addressing their potential impact on host life histories, immunological profiles and their influence as a selective force. Only long-term ecological studies have the potential to shed light on both the temporal trends in infection prevalence and abundance and the drivers of such trends, because of their ability to dissect drivers that may be confounded over shorter time scales. Despite this, only a relatively small number of such studies exist. Here, we analysed changes in the prevalence and abundance of gastrointestinal parasites in the wild Soay sheep population of St. Kilda across 31 years. The host population density (PD) has increased across the study, and PD is known to increase parasite transmission, but we found that PD and year explained temporal variation in parasite prevalence and abundance independently. Prevalence of both strongyle nematodes and coccidian microparasites increased during the study, and this effect varied between lambs, yearlings and adults. Meanwhile, abundance of strongyles was more strongly linked to host PD than to temporal (yearly) dynamics, while abundance of coccidia showed a strong temporal trend without any influence of PD. Strikingly, coccidian abundance increased 3-fold across the course of the study in lambs, while increases in yearlings and adults were negligible. Our decades-long, intensive, individual-based study will enable the role of environmental change and selection pressures in driving these dynamics to be determined, potentially providing unparalleled insight into the drivers of temporal variation in parasite dynamics in the wild.
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Coccídios , Doenças Transmissíveis , Gastroenteropatias , Enteropatias Parasitárias , Nematoides , Parasitos , Ovinos , Animais , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/veterinária , Enteropatias Parasitárias/parasitologia , Carneiro Doméstico , Gastroenteropatias/epidemiologia , Gastroenteropatias/veterináriaRESUMO
Anthropogenic activities and natural events such as periodic tree masting can alter resource provisioning in the environment, directly affecting animals, and potentially impacting the spread of infectious diseases in wildlife. The impact of these additional resources on infectious diseases can manifest through different pathways, affecting host susceptibility, contact rate and host demography. To date however, empirical research has tended to examine these different pathways in isolation, for example by quantifying the effects of provisioning on host behaviour in the wild or changes in immune responses in controlled laboratory studies. Furthermore, while theory has investigated the interactions between these pathways, this work has focussed on a narrow subset of pathogen types, typically directly transmitted microparasites. Given the diverse ways that provisioning can affect host susceptibility, contact patterns or host demography, we may expect the epidemiological consequences of provisioning to vary among different parasite types, dependent on key aspects of parasite life history, such as the duration of infection and transmission mode. Focusing on an exemplar empirical system, the wood mouse Apodemus sylvaticus, and its diverse parasite community, we developed a suite of epidemiological models to compare how resource provisioning alters responses for a range of these parasites that vary in their biology (microparasite and macroparasite), transmission mode (direct, environmental and vector transmitted) and duration of infection (acute, latent and chronic) within the same host population. We show there are common epidemiological responses to host resource provisioning across all parasite types examined. In particular, the epidemiological impact of provisioning could be driven in opposite directions, depending on which host pathways (contact rate, susceptibility or host demography) are most altered by the addition of resources to the environment. Broadly, these responses were qualitatively consistent across all parasite types, emphasising the importance of identifying general trade-offs between provisioning-altered parameters. Despite the qualitative consistency in responses to provisioning across parasite types, we predicted notable quantitative differences between parasites, with directly transmitted parasites (those conforming to SIR and SIS frameworks) predicted to show the strongest responses to provisioning among those examined, whereas the vector-borne parasites showed negligible responses to provisioning. As such, these analyses suggest that different parasites may show different scales of response to the same provisioning scenario, even within the same host population. This highlights the importance of knowing key aspects of host-parasite biology, to understand and predict epidemiological responses to provisioning for any specific host-parasite system.
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Doenças Transmissíveis , Parasitos , Doenças dos Roedores , Animais , Animais Selvagens , Interações Hospedeiro-Parasita , Camundongos , MurinaeRESUMO
The gut microbiome performs many important functions in mammalian hosts, with community composition shaping its functional role. However, the factors that drive individual microbiota variation in wild animals and to what extent these are predictable or idiosyncratic across populations remains poorly understood. Here, we use a multi-population dataset from a common rodent species (the wood mouse, Apodemus sylvaticus), to test whether a consistent "core" gut microbiota is identifiable in this species, and to what extent the predictors of microbiota variation are consistent across populations. Between 2014 and 2018 we used capture-mark-recapture and 16S rRNA profiling to intensively monitor two wild wood mouse populations and their gut microbiota, as well as characterising the microbiota from a laboratory-housed colony of the same species. Although the microbiota was broadly similar at high taxonomic levels, the two wild populations did not share a single bacterial amplicon sequence variant (ASV), despite being only 50km apart. Meanwhile, the laboratory-housed colony shared many ASVs with one of the wild populations from which it is thought to have been founded decades ago. Despite not sharing any ASVs, the two wild populations shared a phylogenetically more similar microbiota than either did with the colony, and the factors predicting compositional variation in each wild population were remarkably similar. We identified a strong and consistent pattern of seasonal microbiota restructuring that occurred at both sites, in all years, and within individual mice. While the microbiota was highly individualised, some seasonal convergence occurred in late winter/early spring. These findings reveal highly repeatable seasonal gut microbiota dynamics in multiple populations of this species, despite different taxa being involved. This provides a platform for future work to understand the drivers and functional implications of such predictable seasonal microbiome restructuring, including whether it might provide the host with adaptive seasonal phenotypic plasticity.
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To date, few studies of parasite epidemiology have investigated 'who acquires infection from whom' in wildlife populations. Nonetheless, identifying routes of disease transmission within a population, and determining the key groups of individuals that drive parasite transmission and maintenance, are fundamental to understanding disease dynamics. Gammaherpesviruses are a widespread group of DNA viruses that infect many vertebrate species, and murine gammaherpesviruses (i.e. MuHV-4) are a standard lab model for studying human herpesviruses, for which much about the pathology and immune response elicited to infection is well understood. However, despite this extensive research effort, primarily in the lab, the transmission route of murine gammaherpesviruses within their natural host populations is not well understood. Here, we aimed to understand wood mouse herpesvirus (WMHV) transmission, by fitting a series of population dynamic models to field data on wood mice naturally infected with WMHV and then estimating transmission parameters within and between demographic groups of the host population. Different models accounted for different combinations of host sex (male/female), age (subadult/adult) and transmission functions (density/frequency-dependent). We found that a density-dependent transmission model incorporating explicit sex groups fitted the data better than all other proposed models. Male-to-male transmission was the highest among all possible combinations of between- and within-sex transmission classes, suggesting that male behaviour is a key factor driving WMHV transmission. Our models also suggest that transmission between sexes, although important, wasn't symmetrical, with infected males playing a significant role in infecting naïve females but not vice versa. Overall this work shows the power of coupling population dynamic models with long-term field data to elucidate otherwise unobservable transmission processes in wild disease systems.
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Herpesviridae , Roedores , Animais , Feminino , Masculino , CamundongosRESUMO
A curated murine oral microbiome database to be used as a reference for mouse-based studies has been constructed using a combination of bacterial culture, 16S rRNA gene amplicon, and whole-genome sequencing. The database comprises a collection of nearly full-length 16S rRNA gene sequences from cultured isolates and draft genomes from representative taxa collected from a range of sources, including specific-pathogen-free laboratory mice, wild Mus musculus domesticus mice, and formerly wild wood mouse Apodemus sylvaticus At present, it comprises 103 mouse oral taxa (MOT) spanning four phyla-Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes-including 12 novel undescribed species-level taxa. The key observations from this study are (i) the low diversity and predominantly culturable nature of the laboratory mouse oral microbiome and (ii) the identification of three major murine-specific oral bacterial lineages, namely, Streptococcus danieliae (MOT10), Lactobacillus murinus (MOT93), and Gemella species 2 (MOT43), which is one of the novel, still-unnamed taxa. Of these, S. danieliae is of particular interest, since it is a major component of the oral microbiome from all strains of healthy and periodontally diseased laboratory mice, as well as being present in wild mice. It is expected that this well-characterized database should be a useful resource for in vitro experimentation and mouse model studies in the field of oral microbiology.IMPORTANCE Mouse model studies are frequently used in oral microbiome research, particularly to investigate diseases such as periodontitis and caries, as well as other related systemic diseases. We have reported here the details of the development of a curated reference database to characterize the oral microbial community in laboratory and some wild mice. The genomic information and findings reported here can help improve the outcomes and accuracy of host-microbe experimental studies that use murine models to understand health and disease. Work is also under way to make the reference data sets publicly available on a web server to enable easy access and downloading for researchers across the world.
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Gastrointestinal (GI) helminths are common parasites of humans, wildlife, and livestock, causing chronic infections. In humans and wildlife, poor nutrition or limited resources can compromise an individual's immune response, predisposing them to higher helminth burdens. This relationship has been tested in laboratory models by investigating infection outcomes following reductions of specific nutrients. However, much less is known about how diet supplementation can impact susceptibility to infection, acquisition of immunity, and drug efficacy in natural host-helminth systems. We experimentally supplemented the diet of wood mice (Apodemus sylvaticus) with high-quality nutrition and measured resistance to the common GI nematode Heligmosomoides polygyrus. To test whether diet can enhance immunity to reinfection, we also administered anthelmintic treatment in both natural and captive populations. Supplemented wood mice were more resistant to H. polygyrus infection, cleared worms more efficiently after treatment, avoided a post-treatment infection rebound, produced stronger general and parasite-specific antibody responses, and maintained better body condition. In addition, when applied in conjunction with anthelmintic treatment, supplemented nutrition significantly reduced H. polygyrus transmission potential. These results show the rapid and extensive benefits of a well-balanced diet and have important implications for both disease control and wildlife health under changing environmental conditions.
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Nematospiroides dubius , Preparações Farmacêuticas , Animais , Suplementos Nutricionais , Interações Hospedeiro-Parasita , Camundongos , MurinaeRESUMO
Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, the impacts of such interactions on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce nematode infection and measured the effects on both nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary reservoir (Peromyscus spp.). Treatment significantly reduced nematode infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both nematodes and SNV were in better condition and survived up to four times longer than uninfected or singly infected mice. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.
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Nematoides , Parasitos , Doenças dos Roedores , Vírus Sin Nombre , Animais , Anticorpos Antivirais , Masculino , Camundongos , Peromyscus , Doenças dos Roedores/epidemiologia , Roedores , Estudos SoroepidemiológicosRESUMO
Urban areas are often considered to be a hostile environment for wildlife as they are highly fragmented and frequently disturbed. However, these same habitats can contain abundant resources, while lacking many common competitors and predators. The urban environment can have a direct impact on the species living there but can also have indirect effects on their parasites and pathogens. To date, relatively few studies have measured how fine-scale spatial heterogeneity within urban landscapes can affect parasite transmission and persistence.Here, we surveyed 237 greenspaces across the urban environment of Edinburgh (UK) to investigate how fine-scale variation in socio-economic and ecological variables can affect red fox (Vulpes vulpes) marking behavior, gastrointestinal (GI) parasite prevalence, and parasite community diversity.We found that the presence and abundance of red fox fecal markings were nonuniformly distributed across greenspaces and instead were dependent on the ecological characteristics of a site. Specifically, common foraging areas were left largely unmarked, which indicates that suitable resting and denning sites may be limiting factor in urban environments. In addition, the amount of greenspace around each site was positively correlated with overall GI parasite prevalence, species richness, and diversity, highlighting the importance of greenspace (a commonly used measure of landscape connectivity) in determining the composition of the parasite community in urban areas.Our results suggest that fine-scale variation within urban environments can be important for understanding the ecology of infectious diseases in urban wildlife and could have wider implication for the management of urban carnivores.
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Novel infectious diseases continue to emerge within human populations. Predictive studies have begun to identify pathogen traits associated with emergence. However, emerging pathogens vary widely in virulence, a key determinant of their ultimate risk to public health. Here, we use structured literature searches to review the virulence of each of the 214 known human-infective RNA virus species. We then use a machine learning framework to determine whether viral virulence can be predicted by ecological traits, including human-to-human transmissibility, transmission routes, tissue tropisms, and host range. Using severity of clinical disease as a measurement of virulence, we identified potential risk factors using predictive classification tree and random forest ensemble models. The random forest approach predicted literature-assigned disease severity of test data with mean accuracy of 89.4% compared to a null accuracy of 74.2%. In addition to viral taxonomy, the ability to cause systemic infection was the strongest predictor of severe disease. Further notable predictors of severe disease included having neural and/or renal tropism, direct contact or respiratory transmission, and limited (0 < R0 ≤ 1) human-to-human transmissibility. We present a novel, to our knowledge, comparative perspective on the virulence of all currently known human RNA virus species. The risk factors identified may provide novel perspectives in understanding the evolution of virulence and elucidating molecular virulence mechanisms. These risk factors could also improve planning and preparedness in public health strategies as part of a predictive framework for novel human infections.
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Previsões/métodos , Infecções por Vírus de RNA/epidemiologia , Virulência/fisiologia , Especificidade de Hospedeiro/fisiologia , Humanos , Aprendizado de Máquina , Modelos Teóricos , Vírus de RNA/patogenicidade , Fatores de Risco , TropismoRESUMO
BACKGROUND: Antimicrobial resistance (AMR) driven by antibiotic consumption is a growing global health threat. However, data on antimicrobial consumption patterns in low- and middle-income countries (LMICs) is sparse. Here, we investigate the patterns of antibiotic sales in humans and livestock in urban Nairobi, Kenya, and evaluate the level of awareness and common behaviours related to antibiotic use and AMR amongst human and veterinary pharmacists. METHODS: A total of 40 human and 19 veterinary drug store pharmacists were interviewed in Nairobi in 2018 using a standard questionnaire. Data recorded included demographic variables, types of antibiotics sold, antibiotic customers, antibiotic prescribing practices and knowledge of antibiotic use and AMR. RESULTS: Our study shows that at the retail level, there is a considerable overlap between antibiotic classes (10/15) sold for use in both human and veterinary medicine. Whilst in our study, clinical training significantly influenced knowledge on issues related to antibiotic use and AMR and respondents had a relatively adequate level of knowledge about AMR, several inappropriate prescribing practices were identified. For example, we found that most veterinary and human drug stores (100% and 52% respectively) sold antibiotics without a prescription and noted that customer preference was an important factor when prescribing antibiotics in half of the drug stores. CONCLUSION: Although more research is needed to understand the drivers of antibiotic consumption in both human and animal populations, these findings highlight the need for immediate strategies to improve prescribing practices across the pharmacists in Nairobi and by extension other low- and middle-income country settings.
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Antibacterianos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Farmacêuticos/psicologia , Adulto , Animais , Estudos Transversais , Resistência Microbiana a Medicamentos , Feminino , Humanos , Prescrição Inadequada/estatística & dados numéricos , Quênia , Masculino , Farmacêuticos/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
The immune system represents a host's main defense against infection to parasites and pathogens. In the wild, a host's response to immune challenges can vary due to physiological condition, demography (age, sex), and coinfection by other parasites or pathogens. These sources of variation, which are intrinsic to natural populations, can significantly impact the strength and type of immune responses elicited after parasite exposure and infection. Importantly, but often neglected, a host's immune response can also vary within the individual, across tissues and between local and systemic scales. Consequently, how a host responds at each scale may impact its susceptibility to concurrent and subsequent infections. Here we analyzed how characteristics of hosts and their parasite infections drive variation in the pro-inflammatory immune response in wild wood mice (Apodemus sylvaticus) at both the local and systemic scale by experimentally manipulating within-host parasite communities through anthelmintic drug treatment. We measured concentrations of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) produced in vitro in response to a panel of toll-like receptor agonists at the local (mesenteric lymph nodes [MLNs]) and systemic (spleen) scales of individuals naturally infected with two gastrointestinal parasites, the nematode Heligmosomoides polygyrus and the protozoan Eimeria hungaryensis. Anthelmintic-treated mice had a 20-fold lower worm burden compared to control mice, as well as a four-fold higher intensity of the non-drug targeted parasite E. hungaryensis. Anthelmintic treatment differentially impacted levels of TNF-α expression in males and females at the systemic and local scales, with treated males producing higher, and treated females lower, levels of TNF-α, compared to control mice. Also, TNF-α was affected by host age, at the local scale, with MLN cells of young, treated mice producing higher levels of TNF-α than those of old, treated mice. Using complementary, but distinct, measures of inflammation measured across within-host scales allowed us to better assess the wood mouse immune response to changes in parasite infection dynamics after anthelmintic treatment. This same approach could be used to understand helminth infections and responses to parasite control measures in other systems in order to gain a broader view of how variation impacts the immune response.
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Anti-Helmínticos/farmacologia , Coccidiose/veterinária , Eimeria/fisiologia , Murinae , Nematospiroides dubius/fisiologia , Doenças dos Roedores/imunologia , Infecções por Strongylida/veterinária , Animais , Biomarcadores , Coccidiose/imunologia , Coccidiose/parasitologia , Interações Hospedeiro-Parasita , Ivermectina/farmacologia , Pamoato de Pirantel/farmacologia , Doenças dos Roedores/parasitologia , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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 (nâ¯=â¯321) and livestock (nâ¯=â¯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 (P<0.01), while poultry isolates were more resistant to tetracyclines (Pâ¯=â¯0.01) compared with humans. The most common co-resistant phenotype observed was to tetracyclines, streptomycin and trimethoprim (30.5%). At the household level, AMR carriage in humans was associated with human density (P<0.01) and the presence of livestock manure (Pâ¯=â¯0.03), but keeping livestock had no influence on human AMR carriage (P>0.05). 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.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/fisiologia , Infecções por Escherichia coli/epidemiologia , Escherichia coli/efeitos dos fármacos , Gado/microbiologia , Aves Domésticas/microbiologia , Aminoglicosídeos/farmacologia , Animais , Estudos Transversais , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Quênia/epidemiologia , Testes de Sensibilidade Microbiana , Penicilinas/farmacologia , Sulfonamidas/farmacologia , Tetraciclinas/farmacologia , Trimetoprima/farmacologiaRESUMO
The role of the host immune system in determining parasite burdens and mediating within-host parasite interactions has traditionally been studied in highly controlled laboratory conditions. This does, however, not reflect the diversity of individuals living in nature, which is often characterised by significant variation in host demography, such as host age, sex, and infection history. Whilst studies using wild hosts and parasites are beginning to give insights into the complex relationships between immunity, parasites and host demography, the cause-and-effect relationships often remain unknown due to a lack of high resolution, longitudinal data. We investigated the infection dynamics of two interacting gastrointestinal parasites of wild wood mice (Apodemus sylvaticus), the nematode Heligmosomoides polygyrus and the coccidian Eimeria hungaryensis, in order to assess the links between infection, coinfection, and the immunological dynamics of two antibodies (IgG1 and IgA). In an anthelmintic treatment experiment, mice were given a single oral dose of an anthelmintic treatment, or control dose, and then subsequently followed longitudinally over a period of 7-15 days to measure parasite burdens and antibody levels. Anthelmintic treatment successfully reduced burdens of H. polygyrus, but had no significant impact on E. hungaryensis. Treatment efficacy was driven by host age, with adult mice showing stronger reductions in burdens compared to younger mice. We also found that the relationship between H. polygyrus-specific IgG1 and nematode burden changed from positive in young mice to negative in adult mice. Our results highlight that a key host demographic factor like age could account for large parts of the variation in nematode burden and nematode-specific antibody levels observed in a naturally infected host population, possibly due to different immune responses in young vs. old animals. Given the variable success in community-wide de-worming programmes in animals and humans, accounting for the age-structure of a population could increase overall efficacy.