Interactions between seasonal temperature variation and temporal synchrony drive increased arbovirus co-infection incidence.

Though instances of arthropod-borne (arbo)virus co-infection have been documented clinically, the overall incidence of arbovirus co-infection and its drivers are not well understood. Now that dengue, Zika and chikungunya viruses are all in circulation across tropical and subtropical regions of the Americas, it is important to understand the environmental and biological conditions that make co-infections more likely to occur. To understand this, we developed a mathematical model of co-circulation of two arboviruses, with transmission parameters approximating dengue, Zika and/or chikungunya viruses, and co-infection possible in both humans and mosquitoes. We examined the influence of seasonal timing of arbovirus co-circulation on the extent of co-infection. By undertaking a sensitivity analysis of this model, we examined how biological factors interact with seasonality to determine arbovirus co-infection transmission and prevalence. We found that temporal synchrony of the co-infecting viruses and average temperature were the most influential drivers of co-infection incidence. Our model highlights the synergistic effect of co-transmission from mosquitoes, which leads to more than double the number of co-infections than would be expected in a scenario without co-transmission. Our results suggest that appreciable numbers of co-infections are unlikely to occur except in tropical climates when the viruses co-occur in time and space.

Impacts of K-12 school reopening on the COVID-19 epidemic in Indiana, USA.

In the United States, schools closed in March 2020 due to COVID-19 and began reopening in August 2020, despite continuing transmission of SARS-CoV-2. In states where in-person instruction resumed at that time, two major unknowns were the capacity at which schools would operate, which depended on the proportion of families opting for remote instruction, and adherence to face-mask requirements in schools, which depended on cooperation from students and enforcement by schools. To determine the impact of these conditions on the statewide burden of COVID-19 in Indiana, we used an agent-based model calibrated to and validated against multiple data types. Using this model, we quantified the burden of COVID-19 on K-12 students, teachers, their families, and the general population under alternative scenarios spanning three levels of school operating capacity (50 %, 75 %, and 100 %) and three levels of face-mask adherence in schools (50 %, 75 %, and 100 %). Under a scenario in which schools operated remotely, we projected 45,579 (95 % CrI: 14,109-132,546) infections and 790 (95 % CrI: 176-1680) deaths statewide between August 24 and December 31. Reopening at 100 % capacity with 50 % face-mask adherence in schools resulted in a proportional increase of 42.9 (95 % CrI: 41.3-44.3) and 9.2 (95 % CrI: 8.9-9.5) times that number of infections and deaths, respectively. In contrast, our results showed that at 50 % capacity with 100 % face-mask adherence, the number of infections and deaths were 22 % (95 % CrI: 16 %-28 %) and 11 % (95 % CrI: 5 %-18 %) higher than the scenario in which schools operated remotely. Within this range of possibilities, we found that high levels of school operating capacity (80-95 %) and intermediate levels of face-mask adherence (40-70 %) resulted in model behavior most consistent with observed data. Together, these results underscore the importance of precautions taken in schools for the benefit of their communities.

Air Passenger Travel and International Surveillance Data Predict Spatiotemporal Variation in Measles Importations to the United States.

Measles incidence in the United States has grown dramatically, as vaccination rates are declining and transmission internationally is on the rise. Because imported cases are necessary drivers of outbreaks in non-endemic settings, predicting measles outbreaks in the US depends on predicting imported cases. To assess the predictability of imported measles cases, we performed a regression of imported measles cases in the US against an inflow variable that combines air travel data with international measles surveillance data. To understand the contribution of each data type to these predictions, we repeated the regression analysis with alternative versions of the inflow variable that replaced each data type with averaged values and with versions of the inflow variable that used modeled inputs. We assessed the performance of these regression models using correlation, coverage probability, and area under the curve statistics, including with resampling and cross-validation. Our regression model had good predictive ability with respect to the presence or absence of imported cases in a given state in a given year (area under the curve of the receiver operating characteristic curve (AUC) = 0.78) and the magnitude of imported cases (Pearson correlation = 0.84). By comparing alternative versions of the inflow variable averaging over different inputs, we found that both air travel data and international surveillance data contribute to the model's ability to predict numbers of imported cases and individually contribute to its ability to predict the presence or absence of imported cases. Predicted sources of imported measles cases varied considerably across years and US states, depending on which countries had high measles activity in a given year. Our results emphasize the importance of the relationship between global connectedness and the spread of measles. This study provides a framework for predicting and understanding imported case dynamics that could inform future studies and outbreak prevention efforts.

Estimating unobserved SARS-CoV-2 infections in the United States.

By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections during its initial invasion of the United States remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the United States through 12 March, we estimated that 108,689 (95% posterior predictive interval [95% PPI]: 1,023 to 14,182,310) infections occurred in the United States by this date. By comparing the model's predictions of symptomatic infections with local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between 24 February and 12 March, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.98; 95% PPI: 0.66 to 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the United States.