scholarly journals Evolutionary emergence of infectious diseases in heterogeneous host populations

2018 ◽  
Author(s):  
Hélène Chabas ◽  
Sébastien Lion ◽  
Antoine Nicot ◽  
Sean Meaden ◽  
Stineke van Houte ◽  
...  

AbstractEmergence and re-emergence of pathogens are notoriously difficult to predict. The erratic nature of those events is reinforced by the stochastic nature of pathogen evolution during the early phase of an epidemic. For instance, mutations allowing pathogens to escape host resistance may boost pathogen spread and promote emergence. Yet, the ecological factors that govern such evolutionary emergence remain elusive both because of the lack of ecological realism of current theoretical frameworks and the difficulty of experimentally testing their predictions. Here we develop a theoretical model to explore the effects of the heterogeneity of the host population on the probability of pathogen emergence, with or without pathogen evolution. We show that evolutionary emergence and the spread of escape mutations in the pathogen population is more likely to occur when the host population contains an intermediate proportion of resistant hosts. We also show that lower pathogen inoculum size and higher diversity of host resistance decrease the probability of evolutionary emergence. Crucially, we present experimental confirmations of these predictions using lytic bacteriophages infecting their bacterial hosts containing diverse CRISPR-Cas immune defenses. We discuss the implications of these results for cross-species spillover and for the management of emerging infectious diseases.Significance statementCan we predict the emergence of infectious diseases? The probability that an epidemic breaks out is highly dependent on the ability of the pathogen to acquire new adaptive mutations and to induce evolutionary emergence. Forecasting pathogen emergence thus requires a good understanding of the interplay between epidemiology and evolution taking place at the onset of an outbreak. Here, we provide a comprehensive theoretical framework to analyze the impact of host population heterogeneity on the probability of pathogen evolutionary emergence. We use this model to predict the impact of the fraction of susceptible hosts, the inoculum size of the pathogen and the diversity of host resistance on pathogen emergence. Our experiments using lytic bacteriophages and CRISPR-resistant bacteria support our theoretical predictions.

2019 ◽  
Vol 16 (155) ◽  
pp. 20190165 ◽  
Author(s):  
Mary Bushman ◽  
Rustom Antia

Theoretical models suggest that mixed-strain infections, or co-infections, are an important driver of pathogen evolution. However, the within-host dynamics of co-infections vary enormously, which complicates efforts to develop a general understanding of how co-infections affect evolution. Here, we develop a general framework which condenses the within-host dynamics of co-infections into a few key outcomes, the most important of which is the overall R 0 of the co-infection. Similar to how fitness is determined by two different alleles in a heterozygote, the R 0 of a co-infection is a product of the R 0 values of the co-infecting strains, shaped by the interaction of those strains at the within-host level. Extending the analogy, we propose that the overall R 0 reflects the dominance of the co-infecting strains, and that the ability of a mutant strain to invade a population is a function of its dominance in co-infections. To illustrate the utility of these concepts, we use a within-host model to show how dominance arises from the within-host dynamics of a co-infection, and then use an epidemiological model to demonstrate that dominance is a robust predictor of the ability of a mutant strain to save a maladapted wild-type strain from extinction (evolutionary emergence).


2020 ◽  
Vol 87 ◽  
Author(s):  
Luís Eduardo de Souza Gazal ◽  
Kelly Cristina Tagliari de Brito ◽  
Renata Katsuko Takayama Kobayashi ◽  
Gerson Nakazato ◽  
Lissandra Souto Cavalli ◽  
...  

ABSTRACT: The use of antimicrobials in fish farming is a reflection of the fast aquaculture development worldwide. The intensification of aquaculture to achieve market demands could lead to an increase in infectious diseases by pathogenic bacteria. Consequently, antimicrobials act as controls for emerging infectious diseases, but their use must follow the rules and regulations of the country where the activity is performed. Although the regulations impose limits to the use of antimicrobials in fish farming, many studies show that resistant bacteria are isolated from this system. The selection of resistant bacteria is not limited only to the use of antimicrobials, but also to co-selection of resistance genes or even with cross-resistance processes. Resistant bacteria from fish farming are a serious concern because they can be acquired by humans with handling or food chain, which may represent a public health problem. In the present review, we present an overview of antimicrobials use in aquaculture, the antimicrobial resistance and the impact of antimicrobial and bacterial resistance from a public health perspective.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ekaterina Avershina ◽  
Valeria Shapovalova ◽  
German Shipulin

Rising antibiotic resistance is a global threat that is projected to cause more deaths than all cancers combined by 2050. In this review, we set to summarize the current state of antibiotic resistance, and to give an overview of the emerging technologies aimed to escape the pre-antibiotic era recurrence. We conducted a comprehensive literature survey of >150 original research and review articles indexed in the Web of Science using “antimicrobial resistance,” “diagnostics,” “therapeutics,” “disinfection,” “nosocomial infections,” “ESKAPE pathogens” as key words. We discuss the impact of nosocomial infections on the spread of multi-drug resistant bacteria, give an overview over existing and developing strategies for faster diagnostics of infectious diseases, review current and novel approaches in therapy of infectious diseases, and finally discuss strategies for hospital disinfection to prevent MDR bacteria spread.


2009 ◽  
Vol 53 (11) ◽  
pp. 4740-4748 ◽  
Author(s):  
Anne-Sylvie Kesteman ◽  
Aude A. Ferran ◽  
Agnès Perrin-Guyomard ◽  
Michel Laurentie ◽  
Pascal Sanders ◽  
...  

ABSTRACT We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after infection with a low (105 CFU) or a high (109 CFU) inoculum of Klebsiella pneumoniae. For daily fractionated doses of marbofloxacin, prevention of resistance occurred for an area-under-the-concentration-time-curve (AUC)/MIC ratio of 189 h for the low inoculum, whereas for the high inoculum, resistant-subpopulation enrichment occurred for AUC/MIC ratios up to 756 h. For the high-inoculum-infected rats, the AUC/MIC ratio, C max/MIC ratio, and time within the mutant selection window (T MSW) were not found to be effective predictors of resistance prevention upon comparison of fractionated and single administrations. An index corresponding to the ratio of the time that the drug concentrations were above the mutant prevention concentration (MPC) over the time that the drug concentrations were within the MSW (T > MPC/T MSW) was the best predictor of the emergence of resistance: a T > MPC/T MSW ratio of 0.54 was associated with prevention of resistance for both fractionated and single administrations. These results suggest that the enrichment of resistant bacteria depends heavily on the inoculum size at the start of an antimicrobial treatment and that classical PK/PD parameters cannot adequately describe the impact of different dosage regimens on enrichment of resistant bacteria. We propose an original index, the T > MPC/T MSW ratio, which reflects the ratio of the time that the less susceptible bacterial subpopulation is killed over the time that it is selected, as a potentially powerful indicator of prevention of enrichment of resistant bacteria. This ratio is valid only if plasma concentrations achieve the MPC.


2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1026-1033
Author(s):  
Nivedha Valliammai Mahalingam ◽  
Abilasha R ◽  
Kavitha S

Enormous successes have been obtained against the control of major epidemic diseases, such as SARS, MERS, Ebola, Swine Flu in the past. Dynamic interplay of biological, socio-cultural and ecological factors, together with novel aspects of human-animal interphase, pose additional challenges with respect to the emergence of infectious diseases. The important challenges faced in the control and prevention of emerging and re-emerging infectious diseases range from understanding the impact of factors that are necessary for the emergence, to development of strengthened surveillance systems that can mitigate human suffering and death. The aim of the current study is to assess the awareness of symptomatic differences between viral diseases like COVID-19, SARS, Swine flu and common cold among dental students that support the prevention of emergence or re-emergence. Cross-sectional type of study conducted among the undergraduate students comprising 100 Subjects. A questionnaire comprising 15 questions in total were framed, and responses were collected in Google forms in SPSS Software statistical analysis. The study has concluded that dental students have an awareness of the symptomatic differences between infectious viral disease. The study concluded that the awareness of symptomatic differences between viral diseases like COVID-19, SARS, Swine flu, Common cold is good among the dental students who would pave the way for early diagnosis and avoid spreading of such diseases. A further awareness can be created by regular webinars, seminars and brainstorming sessions among these healthcare professionals.


Author(s):  
Polina Trachuk ◽  
Vagish Hemmige ◽  
Ruth Eisenberg ◽  
Kelsie Cowman ◽  
Victor Chen ◽  
...  

Abstract Objective Infection is a leading cause of admission to intensive care units (ICU), with critically ill patients often receiving empiric broad-spectrum antibiotics. Nevertheless, a dedicated infectious diseases (ID) consultation and stewardship team is not routinely established. An ID-Critical Care Medicine (ID-CCM) pilot program was designed at a 400-bed tertiary care hospital in which an ID attending was assigned to participate in daily rounds with the ICU team, as well as provide ID consultation on select patients. We sought to evaluate the impact of this dedicated ID program on antibiotic utilization and clinical outcomes in patients admitted to the ICU. Method In this single site retrospective study, we analyzed antibiotic utilization and clinical outcomes in patients admitted to an ICU during post-intervention period from January 1, 2017 to December 31, 2017 and compared it to antibiotic utilization in the same ICUs during the pre-intervention period from January 1, 2015 to December 31, 2015. Results Our data showed a statistically significant reduction in usage of most frequently prescribed antibiotics including vancomycin, piperacillin-tazobactam and cefepime during the intervention period. When compared to pre-intervention period there was no difference in-hospital mortality, hospital length of stay and re-admission. Conclusion With this multidisciplinary intervention, we saw a decrease in the use of the most frequently prescribed broad-spectrum antibiotics without a negative impact on clinical outcomes. Our study shows that the implementation of an ID-CCM service is a feasible way to promote antibiotic stewardship in the ICU and can be used as a strategy to reduce unnecessary patient exposure to broad-spectrum agents.


Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 851
Author(s):  
Chris Hoffmann ◽  
Stephanie Wurr ◽  
Elisa Pallasch ◽  
Sabrina Bockholt ◽  
Toni Rieger ◽  
...  

Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely Mastomys natalensis (M. natalensis). In this study, we investigated the history of infection and virus transmission within the natural host population. To this end, we infected M. natalensis at different ages with MORV and measured the health status of the animals, virus load in blood and organs, the development of virus-specific antibodies, and the ability of the infected individuals to transmit the virus. To explore the impact of the lack of evolutionary virus–host adaptation, experiments were also conducted with Mobala virus (MOBV), which does not share M. natalensis as a natural host. Animals infected with MORV up to two weeks after birth developed persistent infection, seroconverted and were able to transmit the virus horizontally. Animals older than two weeks at the time of infection rapidly cleared the virus. In contrast, MOBV-infected neonates neither developed persistent infection nor were able to transmit the virus. In conclusion, we demonstrate that MORV is able to develop persistent infection in its natural host, but only after inoculation shortly after birth. A related arenavirus that is not evolutionarily adapted to M. natalensis is not able to establish persistent infection. Persistently infected animals appear to be important to maintain virus transmission within the host population.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fabian Chiong ◽  
Mohammed S. Wasef ◽  
Kwee Chin Liew ◽  
Raquel Cowan ◽  
Danny Tsai ◽  
...  

Abstract Background Pseudomonas aeruginosa bacteraemia (PAB) is associated with high mortality. The benefits of infectious diseases consultation (IDC) has been demonstrated in Staphylococcal aureus bacteraemia and other complex infections. Impact of IDC in PAB is unclear. This study aimed to evaluate the impact of IDC on the management and outcomes in patients with PAB. Methods This is a retrospective cohort single-centre study from 1 November 2006 to 29 May 2019, in all adult patients admitted with first episode of PAB. Data collected included demographics, clinical management and outcomes for PAB and whether IDC occurred. In addition, 29 Pseudomonas aeruginosa (PA) stored isolates were available for Illumina whole genome sequencing to investigate if pathogen factors contributed to the mortality. Results A total of 128 cases of PAB were identified, 71% received IDC. Patients who received IDC were less likely to receive inappropriate duration of antibiotic therapy (4.4%; vs 67.6%; p < 0.01), more likely to be de-escalated to oral antibiotic in a timely manner (87.9% vs 40.5%; p < 0.01), undergo removal of infected catheter (27.5% vs 13.5%; p = 0.049) and undergo surgical intervention (20.9% vs 5.4%, p = 0.023) for source control. The overall 30-day all-cause mortality rate was 24.2% and was significantly higher in the no IDC group in both unadjusted (56.8% vs 11.0%, odds ratio [OR] = 10.63, p < 0.001) and adjusted analysis (adjusted OR = 7.84; 95% confidence interval, 2.95–20.86). The genotypic analysis did not reveal any PA genetic features associated with increased mortality between IDC versus no IDC groups. Conclusion Patients who received IDC for PAB had lower 30-day mortality, better source control and management was more compliant with guidelines. Further prospective studies are necessary to determine if these results can be validated in other settings.


Antibiotics ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 228
Author(s):  
Michaela Projahn ◽  
Jana Sachsenroeder ◽  
Guido Correia-Carreira ◽  
Evelyne Becker ◽  
Annett Martin ◽  
...  

Cefotaxime (CTX)-resistant Enterobacteriaceae are still an ongoing challenge in human and veterinary health. High prevalence of these resistant bacteria is detected in broiler chickens and the prevention of their dissemination along the production pyramid is of major concern. The impact of certain on-farm interventions on the external bacterial contamination of broiler chickens, as well as their influence on single processing steps and (cross-) contamination, have not yet been evaluated. Therefore, we investigated breast skin swab samples of broiler chickens before and during slaughter at an experimental slaughter facility. Broiler chickens were previously challenged with CTX-resistant Escherichia coli strains in a seeder-bird model and subjected to none (control group (CG)) or four different on-farm interventions: drinking water supplementation based on organic acids (DW), slow growing breed Rowan × Ranger (RR), reduced stocking density (25 kg/sqm) and competitive exclusion with Enterobacteriales strain IHIT36098(CE). Chickens of RR, 25 kg/sqm, and CE showed significant reductions of the external contamination compared to CG. The evaluation of a visual scoring system indicated that wet and dirty broiler chickens are more likely a vehicle for the dissemination of CTX-resistant and total Enterobacteriaceae into the slaughterhouses and contribute to higher rates of (cross-) contamination during processing.


Author(s):  
Gabriele Sganga ◽  
Mohamed Baguneid ◽  
Pascal Dohmen ◽  
Evangelos J. Giamarellos-Bourboulis ◽  
Emilio Romanini ◽  
...  

AbstractSurgical site infections represent a considerable burden for healthcare systems. To obtain a consensus on the impact and future clinical and economic needs regarding SSI management in an era of multidrug resistance. A modified Delphi method was used to obtain consensus among experts from five European countries. The Delphi questionnaire was assembled by a steering committee, verified by a panel of experts and administered to 90 experts in 8 different surgical specialities (Abdominal, Cancer, Cardiac, General surgery, Orthopaedic, Thoracic, Transplant and Vascular and three other specialities (infectious disease, internal medicine microbiology). Respondents (n = 52) reached consensus on 62/73 items including that resistant pathogens are an increasing matter of concern and increase both treatment complexity and the length of hospital stay. There was strong positive consensus on the cost-effectiveness of early discharge (ED) programs, improvement of quality of life with ED and association between increased length of stay and economic burden to the hospital. However, established ED protocols were not widely available in their hospitals. Respondents expressed a positive consensus on the usefulness of antibiotics that allow ED. Surgeons are aware of their responsibility in an interdisciplinary team for the treatment of SSI, and of the impact of multidrug-resistant bacteria in the context of SSI. Reducing the length of hospital stays by applying ED protocols and implementing new treatment alternatives is crucial to reduce harm to patients and costs for the hospital.


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