Hidden Zika outbreak in Cuba uncovered by genomic sequencing and travel data

By Dr. Ananya Mandal, MDAug 25 2019

Researchers from the Scripps have stumbled upon evidence of a hidden outbreak of Zika virus infection in Cuba, around 300 miles from the coast of Miami. The researchers managed to detect the outbreak by some detective work that used air travel patterns as well as genome sequencing of the viral samples. The results from their research is published in a study titled, “Travel Surveillance and Genomics Uncover a Hidden Zika Outbreak during the Waning Epidemic” in the August 22nd issue of the journal Cell. The study was a collaborative effort from researchers at Scripps, Yale University, Florida Gulf Coast University, the Florida Department of Health, among other organizations.

The Andersen lab at Scripps Research uses infectious disease genomics to investigate how pathogenic viruses such as Zika cause large-scale outbreaks. Pictured here are graduate students Nate Matteson (left), Glenn Oliveira (back) and Karthik Gangavarapu (front), and principal investigator Kristian Andersen, Ph.D. (right); all contributed to the Aug. 22, 2019 study in Cell. CREDIT Scripps Research

Zika virus is mosquito borne and made its first global appearance in Brazil in 2015. By then the virus had already affected thousands and according to researchers on this study, by the time the world was aware of the virus, it had spread to nearly 40 nations. The virus that caused mild febrile illness in most adults was especially dangerous for pregnant mothers. When they contracted the infection, their babies were born with a congenital deformity called microcephaly meaning their brains and heads were smaller than normal. They went on to be severely mentally retarded. The Zika virus gained an international panic status in the late 2015. Several health agencies came together for surveillance of the infection as well as its detection and meticulous recording. The epidemic came to a decline by the end of 2016.

Kristian Andersen, PhD, lead researcher and associate professor at Scripps Research and director of Infectious Disease Genomics at the Scripps Research Translational Institute said in a statement, “Infectious diseases such as Zika are global problems, not local problems, and greater international collaboration and coordination is critical if we are to stay ahead of looming threats. Through this study, we developed a framework for a more global, more proactive way of understanding how viruses are spreading. The traditional reliance on local testing may not always be sufficient on its own.”

By the end of 2016, when the Zika outbreak was at its end, the World Health Organization (WHO) withdrew its status as the “Public Health Emergency of International Concern”. This meant that the travellers were no longer stringently tested for the virus before international movement. Andersen and his team members detected that it was around this time that Cuba was experiencing a Zika outbreak that were undetected and unreported. The outbreak remained low around the Caribbean countries due to effective mosquito control and public health awareness programmes, the study noted. Other mosquito borne disease such as Dengue incidence had also declined over this time in Cuba says the study.

The team began to work on the travel associated Zika cases in 2017 with the aim of looking at the decline of the epidemic. They were surprised to find that there was a steady number of cases of Zika infection among the travellers from and to the Carribean and there was little or no surveillance and local reporting. The team then gathered blood samples from the travellers who were infected and isolated the viruses. These viruses were then studied in details and their genomic sequences were detailed. The researchers called this form of genetic investigation “genomic epidemiology.”

First author, Karthik Gangavarapu, a graduate student in Andersen's lab explained that their isolates of the Zika virus from the travellers seemed to have come from a common ancestor and they created a familial hierarchy of the virus to trace its origins. The age of the virus could also be determined from the genetic sequences said Gangavarapu. They explained that this outbreak in Cuba was a year after the outbreaks recorded in the Caribbean. Gangavarapu concluded, “We realized there was a whole outbreak that had gone undetected.”

The authors write, “Having uncovered an unreported Zika outbreak in Cuba, we next investigated its size. We created a model using relationships between the local and travel Zika incidence rates and found that it was likely as large as Zika outbreaks on other Caribbean islands that peaked the year prior.”

Another undergraduate intern in the Andersen Lab and co-first author of the study, Sharada Saraf worked on a different angle in the investigation. She looked at the airline travel schedules and the cruise ship schedules and plans. When both the genetic data and traveller data was combined, a picture of the Zika virus outbreak emerged. Saraf explained, “Given that undetected viral outbreaks have the potential to spread globally, I hope that this study will encourage utilizing both travel surveillance and genomic data--in addition to local reporting--for future surveillance efforts.” She also gathered the health data from the passengers travelling during that time. She explained, “This data was public but often not available in formats to analyze. For example, the data might be presented in bar graphs, requiring a lot of time to extract actual numbers that we could analyze. One of the nice things that has come out of this work is that we have consolidated this data in an easily downloadable and usable format, and made it publicly available on our lab website for anyone to use as soon as it was generated.” In addition to the passenger data the team also made the viral genomic data publicly accessible.

The authors of the study highlighted the main findings of the study as, “Travel surveillance and genomics uncovered hidden Zika transmission. An unreported and 1-year delayed Zika outbreak was detected in Cuba. Mosquito control may delay, not prevent, Zika virus establishment. A surveillance framework to detect hidden outbreaks was created.” They found at least 20 travel-associated Zika infection cases. The infections were less common in cruise ship travels compared to air travel, they found. The authors wrote, “Taking the population size of Cuba into account, we estimated that 5,707 Zika cases (interquartile range: 1,071 to 22,611) likely went unreported in this country, with the majority of these cases (>99%) having occurred in 2017.” Thus they could conclude, “...results therefore suggest that the 2017 Zika outbreak in Cuba was comparable in size to the known 2016 outbreaks in countries with similar population sizes, such as Haiti (3,103 reported cases), Dominican Republic (5,305 reported cases), and Jamaica (7,165 reported cases).”

Andersen said that traveller data and health records could help detect similar outbreaks in future and also prevent international spread of the infection. He added that public health organizations as well as academic organizations need to collaborate to make sense of this data. He said, “So many serious diseases--not just Zika--are almost perfectly linked to fluctuations in mosquito populations, yet this type of data isn't being collected or made available in most places of the world. Especially as mosquito populations and other animal reservoirs of infectious diseases increase due to climate change and an expanding human population, it is becoming critically important for governments to prioritize this type of proactive monitoring.” Gangavarapu also added, “It can be applied to many countries that may not have the capacity to detect diseases or may have a reporting bias.”