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- Heterogeneity in susceptibility to infection can explain high reinfection ratesPublication . Rodrigues, P.; Margheri, A.; Rebelo, C.; Gomes, M.G.M.Heterogeneity in susceptibility and infectivity is inherent to infectious disease transmission in nature. Here we are concerned with the formulation of mathematical models that capture the essence of heterogeneity while keeping a simple structure suitable of analytical treatment. We explore the consequences of host heterogeneity in the susceptibility to infection for epidemiological models for which immunity conferred by infection is partially protective, known as susceptible-infected-recovered-infected (SIRI) models. We analyze the impact of heterogeneity on disease prevalence and contrast the susceptibility profiles of the subpopulations at risk for primary infection and reinfection. We present a systematic study in the case of two frailty groups. We predict that the average rate of reinfection may be higher than the average rate of primary infection, which may seem paradoxical given that primary infection induces life-long partial protection. Infection generates a selection mechanism whereby fit individuals remain in S and frail individuals are transferred to R. If this effect is strong enough we have a scenario where, on average, the rate of reinfection is higher than the rate of primary infection even though each individual has a risk reduction following primary infection. This mechanism may explain high rates of tuberculosis reinfection recently reported. Finally, the enhanced benefits of vaccination strategies that target the high-risk groups are quantified.
- Positive epistasis drives the acquisition of multidrug resistancePublication . Trindade, S.; Sousa, A.; Xavier, K.B.; Dionísio, F.; Ferreira, M.G.; Gordo, I.The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact--epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics. Surprisingly we find that a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds, that some double resistances entail no measurable cost, and that some allelic combinations are hotspots for rapid compensation. These results provide additional insight as to why multi-resistant bacteria are so prevalent and reveal an extra layer of complexity on epistatic patterns previously unrecognized, since it is hidden in genome-wide studies of genetic interactions using gene knockouts
- Positive Epistasis Drives the Acquisition of Multidrug ResistancePublication . Trindade, S.; Sousa, A.; Xavier, KB.; Dionisio, F.; Ferreira, MG.; Gordo, I.The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact-epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics.
- Positive Epistasis Drives the Acquisition of Multidrug ResistancePublication . Trindade, S.; Sousa, A.; Xavier, KB.; Dionisio, F.; Ferreira, MG.; Gordo, I.The evolution of multiple antibiotic resistance is an increasing global problem. Resistance mutations are known to impair fitness, and the evolution of resistance to multiple drugs depends both on their costs individually and on how they interact-epistasis. Information on the level of epistasis between antibiotic resistance mutations is of key importance to understanding epistasis amongst deleterious alleles, a key theoretical question, and to improving public health measures. Here we show that in an antibiotic-free environment the cost of multiple resistance is smaller than expected, a signature of pervasive positive epistasis among alleles that confer resistance to antibiotics. Competition assays reveal that the cost of resistance to a given antibiotic is dependent on the presence of resistance alleles for other antibiotics. Surprisingly we find that a significant fraction of resistant mutations can be beneficial in certain resistant genetic backgrounds, that some double resistances entail no measurable cost, and that some allelic combinations are hotspots for rapid compensation. These results provide additional insight as to why multi-resistant bacteria are so prevalent and reveal an extra layer of complexity on epistatic patterns previously unrecognized, since it is hidden in genome-wide studies of genetic interactions using gene knockouts.