No abstract

The campaign to eradicate dracunculiasis (Guinea worm [GW] disease) and its causative pathogen Dracunculus medinensis (GW) in Chad is challenged by infections in domestic dogs, which far outnumber the dwindling number of human infections. We present an agent-based simulation that models transmission of GW between a shared water source and a large population of dogs. The simulation incorporates various potential factors driving the infections including external factors and two currently used interventions, namely, tethering and larvicide water treatments. By defining and estimating infectivity parameters and seasonality factors, we test the simulation model on scenarios where seasonal patterns of dog infections could be driven by the parasite's life cycle alone or with environmental factors (e.g., temperature and rainfall) that could also affect human or dog behaviors (e.g., fishing versus farming seasons). We show that the best-fitting model includes external factors in addition to the pathogen's life cycle. From the simulation, we estimate that the basic reproductive number, R 0 , is approximately 2.0; our results also show that an infected dog can transmit the infection to 3.6 other dogs, on average, during the month of peak infectivity (April). The simulation results shed light on the transmission dynamics of GWs to dogs and lay the groundwork for reducing the number of infections and eventually interrupting transmission of GW.

In this paper we first set the stage with a brief overview of the tangled history of humility in theology and philosophy-beginning with its treatment in the Bible and ending with the more recent work that has been done in contemporary philosophy ( § §1-2).

Despite recent interest in multiobjective integer programming, few algorithms exist for solving biobjective mixed integer programs. We present such an algorithm: the Boxed Line Method. For one of its variants, we prove that the number of single-objective integer programs solved is bounded by a linear function of the number of nondominated line segments in the nondominated frontier; this is the first such complexity result. An extensive computational study demonstrates that the Box Line Method is also efficient in practice, and that it outperforms existing algorithms on a diverse set of instances.

Guinea worm disease (or dracunculiasis) is currently transmitted among dogs in Chad, which presents risks for the human population. We studied how interventions implemented at different levels might reduce the spread of Guinea worm disease (geographically and over time) and what levels of interventions might accelerate elimination. We built a multi-water-source agent-based simulation model to analyze the disease transmission among dogs in Chad, as well as in geographic district clusters, and validated it using local infection data. We considered two interventions: (i) tethering, where infected dogs are kept on a leash during periods of infectivity, and (ii) Abate, under which the water source is treated to reduce infectivity. Our results showed that elimination (0 dog infections) is most likely achieved within five years with extremely high levels of tethering (95%) and Abate (90%), when intervention levels are uniform across district clusters. We used an optimization model to determine an improved strategy, with intervention levels which minimize the number of dogs newly infected in the sixth year, under limitations on intervention levels across clusters; the number of dogs infected after five years of intervention could be reduced by approximately 220 dogs with an optimized strategy. Finally, we presented strategies that consider fairness based on intervention resource levels and outcomes. Increased tethering and Abate resources above historical levels are needed to achieve the target of Guinea worm disease elimination; optimization methods can inform how best to target limited resources and reach elimination faster.