scholarly journals Aggressive or moderate drug therapy for infectious diseases? Trade-offs between different treatment goals at the individual and population levels

2019 ◽  
Vol 15 (8) ◽  
pp. e1007223
Author(s):  
Jérémie Scire ◽  
Nathanaël Hozé ◽  
Hildegard Uecker
2018 ◽  
Author(s):  
Jérémie Scire ◽  
Nathanaël Hozé ◽  
Hildegard Uecker

AbstractAntimicrobial resistance is one of the major public health threats of the 21st century. There is a pressing need to adopt more efficient treatment strategies in order to prevent the emergence and spread of resistant strains. The common approach is to treat patients with high drug doses, both to clear the infection quickly and to reduce the risk of de novo resistance. Recently, several studies have argued that, at least in some cases, low-dose treatments could be more suitable to reduce the within-host emergence of antimicrobial resistance. However, the choice of a drug dose may have consequences at the population level, which has received little attention so far.Here, we study the influence of the drug dose on resistance and disease management at the host and population levels. We develop a nested two-strain model and unravel trade-offs in treatment benefits between an individual and the community. We use several measures to evaluate the benefits of any dose choice. Two measures focus on the emergence of resistance, at the host level and at the population level. The other two focus on the overall treatment success: the outbreak probability and the disease burden. We find that different measures can suggest different dosing strategies. In particular, we identify situations where low doses minimize the risk of emergence of resistance at the individual level, while high or intermediate doses prove most beneficial to improve the treatment efficiency or even to reduce the risk of resistance in the population.Author summaryThe obvious goals of antimicrobial drug therapy are rapid patient recovery and low disease prevalence in the population. However, achieving these goals is complicated by the rapid evolution and spread of antimicrobial resistance. A sustainable treatment strategy needs to account for the risk of resistance and keep it in check. One parameter of treatment is the drug dosage, which can vary within certain limits. It has been proposed that lower doses may, in some cases, be more suitable than higher doses to reduce the risk of resistance evolution in any one patient. However, if lower doses prolong the period of infectiousness, such a strategy has consequences for the pathogen dynamics of both strains at the population level. Here, we set up a nested model of within-host and between-host dynamics for an acute self-limiting infection. We explore the consequences of drug dosing on several measures of treatment success: the risk of resistance at the individual and population levels and the outbreak probability and the disease burden of an epidemic. Our analysis shows that trade-offs may exist between optimal treatments under these various criteria. The criterion given most weight in the decision process ultimately depends on the disease and population under consideration.


2020 ◽  
pp. 81-85
Author(s):  
E. P. Popova ◽  
O. T. Bogova ◽  
S. N. Puzin ◽  
D. A. Sychyov ◽  
V. P. Fisenko

Spectral analysis of heart rate variability gives an idea of the role of the autonomic nervous system in the regulation of chronotropic heart function. This method can be used to evaluate the effectiveness of drug therapy. Drug therapy should be carried out taking into account the individual clinical form of atrial fibrillation. Information about the vegetative status of the patient will undoubtedly increase the effectiveness of treatment. In this study, spectral parameters were studied in patients with newly diagnosed atrial fibrillation. The effect of antiarrhythmic drug class III amiodarone on the spectral parameters of heart rate variability was studied.


Author(s):  
N.V. Rudakov ◽  
N.A. Penyevskaya ◽  
D.A. Saveliev ◽  
S.A. Rudakova ◽  
C.V. Shtrek ◽  
...  

Research objective. Differentiation of natural focal areas of Western Siberia by integral incidence rates of tick-borne infectious diseases for determination of the strategy and tactics of their comprehensive prevention. Materials and methods. A retrospective analysis of official statistics for the period 2002-2018 for eight sub-federal units in the context of administrative territories was carried out. The criteria of differentiation were determined by means of three evaluation scales, including long-term mean rates of tick-borne encephalitis, tick-borne borreliosis, and Siberian tick-borne typhus. As a scale gradation tool, we used the number of sample elements between the confidence boundaries of the median. The integral assessment was carried out by the sum of points corresponding to the incidence rates for each of the analyzed infections. Results. The areas of low, medium, above average, high and very high risk of tick-borne infectious diseases were determined. Recommendations on the choice of prevention strategy and tactics were given. In areas of very high and high incidence rates, a combination of population-based and individual prevention strategies is preferable while in other areas a combination of high-risk and individual strategies is recommended. Discussion. Epidemiologic zoning should be the basis of a risk-based approach to determining optimal volumes and directions of preventive measures against natural focal infections. It is necessary to improve the means and methods of determining the individual risk of getting infected and developing tick-borne infectious diseases in case of bites, in view of mixed infection of vectors, as well as methods of post-exposure disease prevention (preventive therapy).


Author(s):  
Nicholas Evans ◽  
Thomas Inglesby

This chapter introduces ethical issues that arise in the context of biosecurity: policies and actions intended to prevent the development or emergence, or mitigate the consequences, of serious biological threats. These threats could include deliberate biological weapon attacks (bioterrorism), pandemics, emerging infectious diseases, or major laboratory accidents. The basic values that underpin these public health concerns are first introduced. Ethical issues that arise before, during, and following a biosecurity crisis are then examined, including issues of resource allocation, dual-use research, and the possibility of quarantine. Their resolution requires trade-offs among different ethical values, including utility, fairness, and liberty.


Author(s):  
Joshua Simmons ◽  
Kristen Splinter

Physics-based numerical models play an important role in the estimation of storm erosion, particularly at beaches for which there is little historical data. However, the increasing availability of pre-and post-storm data for multiple events and at a number of beaches around the world has opened the possibility of using data-driven approaches for erosion prediction. Both physics-based and purely data-driven approaches have inherent strengths and weaknesses in their ability to predict storm-induced erosion. It is vital that coastal managers and modelers are aware of these trade-offs as well as methods to maximise the value from each modelling approach in an increasingly data-rich environment. In this study, data from approximately 40 years of coastal monitoring at Narrabeen-Collaroy Beach (SE Australia)has been used to evaluate the individual performance of the numerical erosion models SBEACH and XBeach, and a data-driven modelling technique. The models are then combined using a simple weighting technique to provide a hybrid estimate of erosion.Recorded Presentation from the vICCE (YouTube Link): https://youtu.be/v53dZiO8Y60


2021 ◽  
Vol 9 ◽  
Author(s):  
Cécile Sarabian ◽  
Raphaël Belais ◽  
Andrew J. J. MacIntosh

Intense selection pressure from parasites on free-living animals has resulted in behavioral adaptations that help potential hosts avoid sources of infection. In primates, such “behavioral immunity” is expressed in different contexts and may vary according to the ecology of the host, the nature of the infectious agent, and the individual itself. In this study, we investigated whether avoidance of contaminated food was associated with reduced parasite infection in sanctuary-housed bonobos. To do this, we used bonobos’ responses to soil- and fecally-contaminated food in behavioral experiments, and then compared the results with an estimate of protozoan infection across individuals. We found that avoidance of contaminated food correlated negatively with Balantioides coli infection, a potentially pathogenic protozoan transmitted through the fecal-oral route. The association between avoidance responses and parasitism were most evident in experiments in which subjects were offered a choice of food items falling along a gradient of fecal contamination. In the case of experiments with more limited options and a high degree of contamination, most subjects were averse to the presented food item and this may have mitigated any relationship between feeding decisions and infection. In experiments with low perceived levels of contamination, most subjects consumed previously contaminated food items, which may also have obscured such a relationship. The behavioral immunity observed may be a consequence of the direct effects of parasites (infection), reflecting the first scale of a landscape of disgust: individual responses. Indirect effects of parasites, such as modulation of feeding decisions and reduced social interactions—and their potential trade-offs with physiological immunity—are also discussed in light of individual fitness and primate evolution. This study builds on previous work by showing that avoidance behaviors may be effective in limiting exposure to a wide diversity of oro-fecally transmitted parasites.


2012 ◽  
Vol 13 (4) ◽  
pp. 178 ◽  
Author(s):  
D Besada ◽  
G Van Cutsem ◽  
E Goemaere ◽  
N Ford ◽  
H Bygrave ◽  
...  

In a previous issue of the Southern African Journal of HIV Medicine, Pillay and Black summarised the trade-offs of the safety of efavirenz use in pregnancy (Pillay P, Black V. Safety, strength and simplicity of efavirenz in pregnancy. Southern African Journal of HIV Medicine 2012;13(1):28-33.). Highlighting the benefits of the World Health Organization’s proposed options for the prevention of mother-to-child transmission (PMTCT) of HIV, the authors argued that the South African government should adopt Option B as national PMTCT policy and pilot projects implementing Option B+ as a means of assessing the individual- and population-level effect of the intervention. We echo this call and further propose that the option to remain on lifelong antiretroviral therapy, effectively adopting PMTCT Option B+, be offered to pregnant women following the cessation of breastfeeding, for their own health, following the provision of counselling on associated benefits and risks. Here we highlight the benefits of Options B and B+.


2021 ◽  
Vol 9 ◽  
Author(s):  
Abel Bernadou ◽  
Boris H. Kramer ◽  
Judith Korb

The evolution of eusociality in social insects, such as termites, ants, and some bees and wasps, has been regarded as a major evolutionary transition (MET). Yet, there is some debate whether all species qualify. Here, we argue that worker sterility is a decisive criterion to determine whether species have passed a MET (= superorganisms), or not. When workers are sterile, reproductive interests align among group members as individual fitness is transferred to the colony level. Division of labour among cooperating units is a major driver that favours the evolution of METs across all biological scales. Many METs are characterised by a differentiation into reproductive versus maintenance functions. In social insects, the queen specialises on reproduction while workers take over maintenance functions such as food provisioning. Such division of labour allows specialisation and it reshapes life history trade-offs among cooperating units. For instance, individuals within colonies of social insects can overcome the omnipresent fecundity/longevity trade-off, which limits reproductive success in organisms, when increased fecundity shortens lifespan. Social insect queens (particularly in superorganismal species) can reach adult lifespans of several decades and are among the most fecund terrestrial animals. The resulting enormous reproductive output may contribute to explain why some genera of social insects became so successful. Indeed, superorganismal ant lineages have more species than those that have not passed a MET. We conclude that the release from life history constraints at the individual level is a important, yet understudied, factor across METs to explain their evolutionary success.


1989 ◽  
Vol 121 (2) ◽  
pp. 304
Author(s):  
H. Schleusener ◽  
J. Schwander ◽  
C. Fischer ◽  
R. Holle ◽  
G. Holl ◽  
...  

Abstract. Graves' disease is an autoimmune disease characterized by a course of remission and relapse. Since the introduction of antithyroid drug treatment, various parameters have been tested for their ability to predict the clinical course of a patient with Graves' disease after drug withdrawal. Nearly all these studies were retrospective and often yielded conflicting results. In a prospective multicentre study with a total of 451 patients, we investigated the significance of a variety of routine laboratory and clinical parameters for predicting a patient's clinical course. Patients who had positive TSH receptor antibodies activity at the end of therapy showed a significantly higher relapse rate than those without (P < 0.001). However, the individual clinical course cannot be predicted exactly (sensitivity 0.49, specificity 0.73, N = 391). The measurement of microsomal (P = 0.99, sensitivity 0.37, specificity 0.63, N = 275) or thyroglobulin antibodies (P = 0.76, sensitivity 0.18, specificity 0.84, N = 304) at the end of antithyroid drug therapy did not show a statistically significant difference in the antibody titre between the patients of the relapse and those of the remission group. Additionally, HLA-DR typing (HLA-DR3: P = 0.37, sensitivity 0.36, specificity 0.58, N = 253) was proven to be unsuitable for predicting a patient's clinical course. Patients with abnormal suppression or an abnormal TRH test at the end of antithyroid drug therapy relapse significantly more often (P< 0.001) than patients with normal suppression or normal TRH test. Patients with a large goitre also have a significantly (P< 0.001) higher relapse rate than those with only a small enlargement. The sensitivity and specificity values of all these parameters, however, were too low to be useful for daily clinical decisions in the treatment of an individual patient. This is also true for the combinations of different parameters. Though the highest sensitivity value (0.94) was found for a combination of the suppression and the TRH test at the end of therapy, the very low specificity value (0.13) for this combination reduced its clinical usefulness.


Author(s):  
Jaeyoung Jung ◽  
Joseph Y. J. Chow

With major investments in electric taxis emerging around the world, there is a need to better understand resource allocation trade-offs in subsidizing electric vehicle taxis (e-taxis) and investing in electric charging infrastructure. This is addressed using simulation experiments conducted in New York City: 2016 taxi pickups/drop-offs, a Manhattan road network (16,782 nodes, 23,337 links), and 212 charging stations specified by a 2013 Taxi & Limousine Commission study. The simulation is based on a platform used to evaluate taxi operations in California and Seoul. Eleven scenarios are analyzed: a baseline of 7,000 non-electric taxis, five scenarios ranging from 1,000 e-taxis to 5,000 e-taxis, and another five scenarios in which the e-taxis have infinite chargers as an upper bound. The study finds that the number of charging locations recommended in the earlier study may be insufficient at some locations even under the 3,000+ e-taxi scenarios. More importantly, despite an average revenue of $260 per taxi for the 7,000 non-electric taxis and about $247 per taxi for electric taxis over the finite charger scenarios, the revenue gap between e-taxis and non-electric taxis in a mixed fleet increases significantly as the e-taxi share increases. This is because the increasing queue delay imposed on e-taxis gives non-electric taxis an increasing competitive advantage, raising their average revenue from $260 per taxi (1,000 e-taxis) up to $286 per taxi (5,000 e-taxis, 150% revenue gap increase), all other operating costs being equal. This has implications for individual versus whole-fleet policies, as the individual-oriented policies may be less effective.


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