International travelers and genomics uncover a ‘hidden’ Zika outbreak

Nathan D. Grubaugh; Sharada Saraf; Karthik Gangavarapu; Alexander Watts; Amanda L. Tan; Rachel J. Oidtman; Jason T. Ladner; Glenn Oliveira; Nathaniel L. Matteson; Moritz U.G. Kraemer; Chantal B.F. Vogels; Aaron Hentoff; Deepit Bhatia; Danielle Stanek; Blake Scott; Vanessa Landis; Ian Stryker; Marshall R. Cone; Edgar W. Kopp; Andrew C. Cannons; Lea Heberlein-Larson; Stephen White; Leah D. Gillis; Michael J. Ricciardi; Jaclyn Kwal; Paola K. Lichtenberger; Diogo M. Magnani; David I. Watkins; Gustavo Palacios; Davidson H. Hamer; Lauren M. Gardner; T. Alex Perkins; Guy Baele; Kamran Khan; Andrea Morrison; Sharon Isern; Scott F. Michael; Kristian G. Andersen

We previously demonstrated that mosquito control campaigns can reduce Ae. aegypti populations and human Zika virus infections . Cuba has a long history of successful Ae. aegypti control (Gubler, 1989; Toledo et al., 2007) , and following the detection of the Zika outbreak in Brazil, the country implemented a "National Zika Action Plan" for aggressive Ae. aegypti mosquito surveillance and control (Gorry, 2016; Reardon, 2016) . To investigate if mosquito control may have played a role in delaying the Zika outbreak in Cuba, we compared the reported start of the mosquito control campaign to Zika and dengue virus transmission (based on travel incidence rates) in Cuba (Fig. 4B) . We found that following the implementation of mosquito control in February, 2016, travel incidence data showed minimal transmission of both dengue and Zika viruses throughout the year (Fig. 4B) . By searching news articles for Zika and dengue in Cuba from 2015-2018, we found that Cuban officials reported that the mosquito control program was successful, based on a near elimination of dengue and very few Zika cases (see Supplemental File 3 for a timeline of selected news articles). However, no information was reported on the overall length of the campaign, and importantly, if it was still ongoing when the Zika outbreak intensified in 2017. The timing of the mosquito control campaign, followed by a decrease in both dengue and Zika cases (Fig. 4B ) -despite high transmission potential (Fig. 4B ) -suggests that mosquito control efforts may have been responsible for delaying the Zika outbreak in Cuba. The outbreak the following year was likely preceded by a resurgence in Ae. aegypti populations, leading to an increase in transmission of Zika virus lineages that were introduced in 2016 (Fig. 3) .