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Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asuncion, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission.

The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.

Yellow fever virus is a global health threat due to its endemicity in parts of Africa and South America where human infections occur in residents and travelers. To understand yellow fever dynamics, it is critical to characterize the incubation periods of the virus in vector mosquitoes and humans. Here, we compare four statistical models of the yellow fever incubation periods fitted with historical data. The extrinsic incubation period in the urban vector Aedes aegypti was best characterized with a temperature-dependent Weibull model with a median of 10 days at 25°C (middle 95% = 2.0–37 days). The intrinsic incubation period, fitted with a log-normal model, had a median of 4.3 days (middle 95% = 2.3–8.6 days). These estimates and their associated statistical models provide a quantitative basis to assist in exposure assessments, model potential outbreaks, and evaluate the effectiveness of public health interventions.