Zika outbreak in Cuba

Zika outbreak in Cuba

Summary: Using local and travel-associated case reporting from American and European public health systems, we identified an unreported Zika outbreak in Cuba during 2017. Virus sequencing from travelers revealed that the Zika outbreak in Cuba was sparked by multiple introductions of the virus from elsewhere in the Caribbean and Central America during 2016 that persisted into 2017.

The recent Zika virus epidemic strained our public health systems due to its surprising severity and scale. It also revealed weaknesses in our surveillance networks as it circulated for more than a year in the Americas without detection. These weaknesses, some due to overlapping symptomology with other viruses and a lack of easy and inexpensive diagnostics, are also impeding our ability to determine the true scale of the epidemic, and importantly, when the epidemic can be declared over. Accurate and standardized reporting is key to fully understanding the burden of the Zika epidemic.

There are two primary ways in which active Zika virus transmission is reported. 1) Local reporting by countries engaging in clinical Zika virus surveillance (usually suspected and confirmed cases), in which the data is submitted to the Pan American Health Organization (PAHO) for open dissemination. These data provide the most comprehensive picture of local transmission, but due to large discrepancies in public health capabilities and reporting structures, comparing Zika incidence rates among different countries and territories will be skewed by several local biases. 2) Imported, or travel, infections are also reported by several agencies in regions with high travel volumes to regions with active Zika transmission, like the Florida Department of Health (DOH), US Centers for Disease Control and Prevention (CDC), and the European CDC (ECDC). The advantage of using imported cases detected through sentinel surveillance is that they can be utilized to understand outbreak dynamics in regions without local reporting.

We compared the temporal distribution of reported local and travel Zika cases to see if the trends overlap and if the travel cases are revealing evidence for transmission not captured locally (Figure 1A). We obtained local cases from individual countries and territories provided on the PAHO website (we converted bar graphs to spreadsheet: data here). We worked directly with the Florida DOH to obtain monthly travel cases (based on symptoms onset) by country of origin (data here), and requested similar data from the ECDC. The last local cases reported by PAHO from South America, Central America (+ Mexico), and the Caribbean were during August of 2017. For South America and Central America (+ Mexico), this also corresponded with the last travel cases from individuals visiting those regions, suggesting that the epidemic ended in 2017. For the Caribbean, however, travel cases were reported until February of 2018 and revealed a sudden spike in cases in the summer of 2017 (not captured by the local PAHO data). When we further sorted the Florida DOH and ECDC travel cases by the country of origin, we found that almost all of the Zika positive travelers recently visited Cuba (Figure 1B), suggesting that there was a local outbreak that went undetected.

Figure 1. Travel cases reveal missing Zika virus outbreak in Cuba during 2017. (A) Local Zika cases reported to PAHO (left axis) and travel cases reported by the Florida DOH and the ECDC (right axis) were sorted by region. The ECDC data only extends to the end of 2017, while the Florida DOH data extends to June of 2018. (B) The Caribbean Zika travel reported by the Florida DOH and ECDC were sorted by the five most common and “other” origins.

To determine if travel cases can accurately reconstruct local Zika virus transmission, we compared the local incidence rates (local cases/100,000 population, from PAHO data) to travel incidence rates (travel cases/100,000 travelers per month) for each country of origin (Figure 2). We separated the ECDC travel data by the reporting country (United Kingdom, Spain, Italy, France, and The Netherlands) and show data for each origin-destination pair with at least 20 reported travel cases. We obtained air passenger travel volumes from the US Department of Transportation and the International Air Transport Association to calculate the travel incidence rates. For each country reporting local cases (all shown in Figure 2, except for Cuba), the travel incidence rates strongly correlate with local incidence (mean Spearman r = 0.747 [range = 0.577-0.884]). This suggests that surveillance of international travelers for infectious disease can be used when local disease reporting is not available. Importantly for this exercise, it also suggests that Cuba experienced a small Zika outbreak in 2016 followed by a large outbreak in 2017. By comparing the travel incidence rates to other countries, the 2017 Zika outbreak in Cuba appears to be as large as what was reported in 2016 for other Caribbean Islands, like the Dominican Republic, Jamaica, and Puerto Rico. If this is correct, based on the surrounding local standards, we could have expected 10,000 to 40,000 cases reported from Cuba during 2016-2017; the actual number of cases reported from Cuba were 187 in 2016 and none in 2017. We are actively developing a model to estimate the temporal distribution of cases that should have been reported and would love feedback on best methods to use, as well as ideas how best to tackle such questions.

Figure 2. Travel Zika incidence is correlated with the reported local incidence when data is available. The travel Zika cases were sorted by country/territory of origin and for the ECDC data, the reporting European country. Travel data is shown for all origin-destination combinations with at least 20 Zika cases. The local and travel incidence rates were correlated (mean Spearman r = 0.747; range = 0.577 [Mexico-Florida travel] – 0.884 [Puerto Rico-Florida travel]), except for Cuba that did not report temporal local cases. Monthly air passenger volumes between each route was used to calculate the travel incidence.

We sequenced Zika virus from eight infected Florida travelers arriving from Cuba during 2017 (data here) and obtained one Zika virus genome from a Cuban pregnant traveler diagnosed in Spain to determine the origins of the outbreak in Cuba (Figure 3A). Using these nine Cuban Zika virus genomes, plus other available data from French Polynesia and the Americas, we constructed a time-resolved maximum clade-credibility phylogenetic tree with BEAST. Based on the placement of the Cuban Zika virus genomes, we detected at least three separate introductions into Cuba (though clade 3 could be two separate introductions) coming from both Central America (perhaps Honduras) and the Caribbean (perhaps the Dominican Republic). It appears that most of these “successful” introductions occurred during 2016, corresponding to peak transmission elsewhere in the Caribbean and Central America and peak predicted Aedes aegypti abundance in Cuba (Figure 3B). Thus, the 2017 outbreak was sparked by long-living Zika virus transmission chains, persisting through low mosquito abundance during the dry season. The travel incidence data for Cuba in 2016 provides a rare look at transmission patterns, suggesting that large Ae. aegypti-borne virus outbreaks may be caused by “stuttered” transmission chains that persist from the season prior.

Figure 3. Multiple Zika virus introductions into Cuba during 2016 sparked the 2017 outbreak. (A) A maximum clade-credibility phylogenetic tree was constructed using 9 Zika virus genomes from Cuban travelers (8 that we sequenced) and available Zika virus genomes from French Polynesia and the Americas (analysis of the entire protein coding sequence). Insets zoom in on the the Cuba genomes. (B) The mean (with standard deviation) of the Zika virus travel incidence rates (cases/100,000 travelers) measured from Florida (USA), Spain, and Italy and predicted Ae. aegypti abundance.

The point of releasing our data and preliminary analyses now was to make the public aware of the Zika virus outbreak in Cuba, to receive feedback on our approaches, and to promote new research directions. Please let us know if you have any questions, concerns, advice, or complementary data/analyses. We are also in the process of making the travel data available, upon permission from the Florida DOH and the ECDC. A preprint of our completed analyses, including data from chikungunya and dengue viruses, will be available within a couple months.

Nathan D. Grubaugh (Yale School of Public Health), on behalf of:

Sharada Saraf, Karthik Gangavarapu, Glenn Oliveira, Nathaniel L. Matteson, Kristian G. Andersen: The Scripps Research Institute

Amanda L. Tan, Sharon Isern, Scott F. Michael: Florida Gulf Coast University

Andrea Morrison, Danielle Stanek, Blake Scott, Vanessa Landis, Stephen White, Leah Gillis, Ian Stryker, Marshall Cone, Edgar Kopp, Andrew Cannons, Lea Heberlein-Larson: Florida Department of Health

Alexander Watts, Deepit Bhatia, Kamran Khan: St. Michael’s Hospital, University of Toronto

Jason T. Ladner:  Northern Arizona University

Lauren Gardner: University of New South Wales

Moritz U.G. Kraemer: University of Oxford & Harvard University

Michael Wiley, Karla Prieto, Gustavo Palacios: US Army Medical Research Institute of Infectious Diseases

This was also posted on Virological.



9 Responses

  1. CanadaCuba says:

    Dr. Grubaugh, do you know of resources for non-academics to access to determine where in Cuba current transmitted cases are? We would like to travel to Cuba to visit family, but cannot find documentation of which provinces/cities are Zika-free, or whether its the whole island at risk. Thank you

    • Nathan Grubaugh says:

      Hi – the primary issue is that there isn’t much for resources or information regarding Zika and other virus transmission in Cuba. The link below shows where they documented some transmission in 2016, though it’s likely not comprehensive. Good news is, while there still is some evidence for Zika virus transmission in Cuba, it is decreasing fast and will be mostly absent very soon. I cannot provide any direct advice on when to travel, but it seems like the risk is diminishing.

      – Best, Nate


  2. Was it possible to determine what is the influence of the hurricane Nate in october 2017?

    I believe cuban policy for vector control (mainly done because of Dengue virus) and case control (isolation) to reduce the burden and the risk of outbreak is quite efficient.

    The hurricane most probably was not only a cause of flood and peak in Aedes spp, but also the cause of a probable collapse in the vector control program.
    Thank you in advance

    • Nathan Grubaugh says:

      Hi Giles – great question. Honestly, we really don’t have the data to directly assess, especially local data about mosquito abundance. The timing of the hurricane occurred while Zika virus activity and estimated Ae. aegypti abundance were already decreasing due to seasonal changes. Because of that, my guess is that it had little effect (transmission peak was Aug-Sep).

      We looked at this a bit in Miami during their 2016 Zika outbreak after Hurricane Matthew hit in October. By measuring Ae. aegypti abundance (mosquitoes/trap/night), we saw an initial decrease in abundance following the hurricane – likely because mosquitoes and breeding sites were blown away and flooded out – but not a population boom after that some predicted. Sorry, can’t imbed images, see tweet: https://twitter.com/NathanGrubaugh/status/909972336077664256.

      In my opinion, because hurricanes in the Caribbean mostly occur in the Fall when the conditions for mosquitoes are waning, I think they mostly decrease mosquito-borne transmission. More research is definately needed.



  3. H says:

    Hi Nathan, based on the mosquito population graph, does it seem that feb is a good time to go to Cuba to minimize risk? Trying to make an expensive decision on whether or not to keep a vacation to Cuba in Feb while considering pregnancy.

    • Nathan Grubaugh says:

      Hi H. First, I cannot provide advice about important personal decisions. For some, any risk of Zika while family planning is too much. I can say that 1) Zika virus transmission in Cuba is decreasing and 2) mosquito abundance in Cuba should be low in Feb. That means that Zika risk will be relatively low, but it doesn’t mean that risk is zero. I hope that helps.


  4. Rebecca MacLachlan says:

    We are planning a family vacation in Cuba, we all fly into Santa Clara on Jan. 15. Our group of 7 includes ages 4 to 67. This is not our first time to Cuba and are aware of health precautions to take. But I am more concerned now that our children & grandchildren will be included this time. Is this a highly affected area for mosquito (Zika) and time of year?

    • Nathan Grubaugh says:

      Our data does not tell us which parts of Cuba had Zika virus outbreaks, so I cannot help you there (sorry). Good news is that we (the Florida Department of Health) has not detected a travel-associated Zika virus case from Cuba in the last month or so, and transmission is only going to decrease in January. Overall, it looks like the Zika outbreak in Cuba is waning, however, there may still be some residual transmission during that time. My biggest worry would be pregnant women (or women who may become pregnant) and their partners. There is less overall concern for children who were not infected as fetuses.

      That said – there is a large dengue virus outbreak currently happening in Cuba. Please read this article carefully: https://www.miamiherald.com/news/nation-world/world/americas/cuba/article222627955.html

      My cousin just had dengue fever after returning from Haiti. It isn’t fun. So please protect yourself from mosquitoes!



  5. Followgram says:

    “Our results therefore suggest that the 2017 Zika outbreak in Cuba was similar in size to the known 2016 outbreaks in countries with similar population sizes,” the authors write. They declined to comment on the work because it is under review for publication in a journal.

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