Browsing by Author "Rodrigues, P."
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- Drug resistance in tuberculosis - a reinfection modelPublication . Rodrigues, P.; Gomes, M. G. M.; Rebelo, C.There is increasing recognition that reinfection is an important component of TB transmission. Moreover, it has been shown that partial immunity has significant epidemiological consequences, particularly in what concerns disease prevalence and effectiveness of control measures. We address the problem of drug resistance as a competition between two types of strains of Mycobacterium tuberculosis: those that are sensitive to anti-tuberculosis drugs and those that are resistant. Our objective is to characterise the role of reinfection in the transmission of drug-resistant tuberculosis. The long-term behaviour of our model reflects how reinfection modifies the conditions for coexistence of sensitive and resistant strains. This sets the scene for discussing how strain prevalence is affected by different control strategies. It is shown that intervention effectiveness is highly sensitive to the baseline epidemiological setting.
- 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.
- Implications of partial immunity on the prospects for tuberculosis control by post-exposure interventionsPublication . Gomes, M. G. M.; Rodrigues, P.; Hilker, F. M.; Mantilla-Beniers, N. B.; Muehlen, M.; Paulo, A. C.; Medley, G. F.One-third of the world population (approximately 2 billion individuals) is currently infected with Mycobacterium tuberculosis, the vast majority harboring a latent infection. As the risk of reactivation is around 10% in a lifetime, it follows that 200 million of these will eventually develop active pulmonary disease. Only therapeutic or post-exposure interventions can tame this vast reservoir of infection. Treatment of latent infections can reduce the risk of reactivation, and there is accumulating evidence that combination with post-exposure vaccines can reduce the risk of reinfection. Here we develop mathematical models to explore the potential of these post-exposure interventions to control tuberculosis on a global scale. Intensive programs targeting recent infections appear generally effective, but the benefit is potentially greater in intermediate prevalence scenarios. Extending these strategies to longer-term persistent infections appears more beneficial where prevalence is low. Finally, we consider that susceptibility to reinfection is altered by therapy, and explore its epidemiological consequences. When we assume that therapy reduces susceptibility to subsequent reinfection, catastrophic dynamics are observed. Thus, a bipolar outcome is obtained, where either small or large reductions in prevalence levels result, depending on the rate of detection and treatment of latent infections. By contrast, increased susceptibility after therapy may induce an increase in disease prevalence and does not lead to catastrophic dynamics. These potential outcomes are silent unless a widespread intervention is implemented