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Uncovering a Hidden Zika Outbreak in Cuba

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Zika Virus in Cuba
Credit: Sharon Isern, steampunkphage.com.

When Brazilian health officials discovered four years ago that the mosquito-borne Zika virus could cause severe birth defects and other serious health problems, it prompted a major effort across the Americas to curb the infection by controlling mosquitoes and issuing travel advisories. By mid-2017, the hard work seemed to have paid off, and reports of new Zika infections had nearly stopped.

But it turns out Zika may be tougher to control than once thought. New research shows that a large, previously hidden outbreak of Zika virus disease occurred in Cuba, just when it looked like the worst of the epidemic was over. The finding suggests that the Zika virus can linger over long periods, and that mosquito control efforts alone may slow, but not necessarily stop, the march of this potentially devastating infectious disease.

When combating global epidemics, it’s critical to track the spread of dangerous viruses from one place to the next. But some viruses can be tougher to monitor than others, and that certainly has been the case with Zika in the Americas. Though the virus can harm unborn children, many people infected with Zika never feel lousy enough to go to the doctor. Those who do often have symptoms that overlap with other prevalent tropical diseases, such as dengue and chikungunya fever, making it hard to recognize Zika.

That’s why in Brazil, where Zika arrived in the Americas by early 2014, this unexpected viral intruder went undetected for well over a year. By then, it had spread unnoticed to Honduras, circulating rapidly to other Central American nations and Mexico—likely by late 2014 and into 2015.

In the United States, even with close monitoring, a small local outbreak of Zika virus in Florida also went undetected for about three months in 2016 [1]. Then, in 2017, Florida officials began noticing something strange: new cases of Zika infection in people who had traveled to Cuba.

This came as a real surprise because Cuba, unlike most other Caribbean islands, was thought to have avoided an outbreak. What’s more, by then the Zika epidemic in the Americas had slowed to a trickle, prompting the World Health Organization to delist it as a global public health emergency of international concern.

Given the Cuban observation, some wondered whether the Zika epidemic in the Americas was really over. Among them was an NIH-supported research team, including Nathan Grubaugh, Yale School of Public Health, New Haven, CT; Sharon Isern and Scott Michael, Florida Gulf Coast University, Fort Myers; and Kristian Andersen, The Scripps Research Institute, La Jolla, CA, who worked closely with the Florida Department of Health, including Andrea Morrison.

As published in Cell, the team was able to document a previously unreported outbreak in Cuba after the epidemic had seemingly ended [2]. Interestingly, another research group in Spain also recently made a similar observation about Zika in Cuba [3].

In the Cell paper, the researchers show that between June 2017 and October 2018, all but two of 155 cases—a whopping 98 percent of travel-associated Zika infections—traced back to Cuba. Further analysis suggests that the outbreak in Cuba was likely of similar magnitude to outbreaks that occurred in other Caribbean nations.

Their estimates suggest there were likely many thousands of Zika cases in Cuba, and more than 5,000 likely should have been diagnosed and reported in 2017. The only difference was the timing. The Cuban outbreak of Zika virus occurred about a year after infections subsided elsewhere in the Caribbean.

To fill in more of the blanks, the researchers relied on Zika virus genomes from nine infected Florida travelers who returned from Cuba in 2017 and 2018. The sequencing data support multiple introductions of Zika virus to Cuba from other Caribbean islands in the summer of 2016.

The outbreak peaked about a year after the virus made its way to Cuba, similar to what happened in other places. But the Cuban outbreak was likely delayed by a year thanks to an effective mosquito control campaign by local authorities, following detection of the Brazilian outbreak. While information is lacking, including whether Zika infections had caused birth defects, it’s likely those efforts were relaxed once the emergency appeared to be over elsewhere in the Caribbean, and the virus took hold.

The findings serve as yet another reminder that the Zika virus—first identified in the Zika Forest in Uganda in 1947 and for many years considered a mostly inconsequential virus [4]—has by no means been eliminated. Indeed, such unrecognized and delayed outbreaks of Zika raise the risk of travelers innocently spreading the virus to other parts of the world.

The encouraging news is that, with travel surveillance data and genomic tools —enabled by open science—it is now possible to detect such outbreaks. By combining resources and data, it will be possible to develop even more effective and responsive surveillance frameworks to pick up on emerging health threats in the future.

In the meantime, work continues to develop a vaccine for the Zika virus, with more than a dozen clinical trials underway that pursue a variety of vaccination strategies. With the Zika pandemic resolved in the Americas, these studies can be harder to conduct, since proof of efficacy is not possible without active infections. But, as this paper shows, we must remain ready for future outbreaks of this unique and formidable virus.

References:

[1] Genomic epidemiology reveals multiple introductions of Zika virus into the United States. Grubaugh et al. Nature. 2017 Jun 15;546(7658):401-405.

[2] Travel surveillance and genomics uncover a hidden Zika outbreak during the waning epidemic. Grubaugh ND, Saraf S, Gangavarapu K, Watts A, Tan AL, Oidtman RJ, Magnani DM, Watkins DI, Palacios G, Hamer DH; GeoSentinel Surveillance Network, Gardner LM, Perkins TA, Baele G, Khan K, Morrison A, Isern S, Michael SF, Andersen .KG, et. al. Cell. 2019 Aug 22;178(5):1057-1071.e11.

[3] Mirroring the Zika epidemics in Cuba: The view from a European imported diseases clinic. Almuedo-Riera A, Rodriguez-Valero N, Camprubí D, Losada Galván I, Zamora-Martinez C, Pousibet-Puerto J, Subirà C, Martinez MJ, Pinazo MJ, Muñoz J. Travel Med Infect Dis. 2019 Jul – Aug;30:125-127.

[4] Pandemic Zika: A Formidable Challenge to Medicine and Public Health. Morens DM, Fauci AS. J Infect Dis. 2017 Dec 16;216(suppl_10):S857-S859.

Links:

Video: Uncovering Hidden Zika Outbreaks (Florida Gulf Coast University, Fort Myers)

Zika Virus (National Institute of Allergy and Infectious Diseases/NIH)

Zika Virus Vaccines (NIAID)

Zika Free Florida (Florida Department of Health, Tallahassee)

Grubaugh Lab (Yale School of Public Health, New Haven, CT)

Andersen Lab (The Scripps Research Institute, La Jolla, CA)

NIH Support: National Institute of Allergy and Infectious Diseases; National Center for Advancing Translational Sciences


Study Associates Frequent Digital Media Use in Teens with ADHD Symptoms

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Teens using smart phones

Credit: Thinkstock/monkeybusinessimages

The rise of smart phones, tablets, and other mobile technologies has put digital media, quite literally, at the fingertips of today’s youth. Most teens now have ready access to a smartphone, with about half spending the majority of their waking hours texting, checking social media sites, watching videos, or otherwise engaged online [1].

So, what does this increased access to digital media—along with the instant gratification that it provides—mean for teens’ health and wellbeing? In a two-year study of more than 2,500 high school students in Los Angeles, NIH-funded researchers found that those who consumed the most digital media were also the most likely to develop symptoms of attention-deficit/hyperactivity disorder (ADHD) [2].


NIH Family Members Giving Back: Toben Nelson

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Roseville Raiders

Caption: Toben Nelson (back row, far left) celebrates with his Roseville Raiders after winning Gopher State Tournament of Champions.
Caption: Heather Hammond Nelson

What was Toben Nelson, a University of Minnesota epidemiologist who studies the health risks of alcohol abuse and obesity, doing this summer lugging around a heavy equipment bag after work? Giving back to his community. Nelson volunteered as a coach for the Roseville Raiders, a 13-year-old-and-under traveling baseball team that just wrapped up its season by winning the prestigious Gopher State Tournament of Champions in their age group.

In the fall, Nelson will gear up for hoops as the volunteer president of the Roseville Youth Basketball Association, which provides an opportunity for kids in this Minneapolis-St. Paul suburb to take part in organized sports. Nelson says volunteering grounds him as a scientist. It reminds him every single day that his NIH-supported research back at the office affects real lives and benefits real communities like his own.


Widening Gap in U.S. Life Expectancy

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Map of life expectancies

Caption: Life expectancy at birth by county, 2014. Life expectancy into 80s (blue), 70s (green, yellow, orange), 60s (red).

Americans are living longer than ever before, thanks in large part to NIH-supported research. But a new, heavily publicized study shows that recent gains in longevity aren’t being enjoyed equally in all corners of the United States. In fact, depending on where you live in this great country, life expectancy can vary more than 20 years—a surprisingly wide gap that has widened significantly in recent decades.

Researchers attribute this disturbing gap to a variety of social and economic influences, as well as differences in modifiable behavioral and lifestyle factors, such as obesity, inactivity, and tobacco use. The findings serve as a sobering reminder that, despite the considerable progress made possible by biomedical science, more research is needed to figure out better ways of addressing health disparities and improving life expectancy for all Americans.

In the new study published in JAMA Internal Medicine, a research team, partially funded by NIH, found that the average American baby born in 2014 can expect to live to about age 79 [1]. That’s up from a national average of about 73 in 1980 and around 68 in 1950. However, babies born in 2014 in remote Oglala Lakota County, SD, home to the Pine Ridge Indian Reservation, can expect to live only about 66 years. That’s in stark contrast to a child born about 400 miles away in Summit County, CO, where life expectancy at birth now exceeds age 86.


Creative Minds: Building the RNA Toolbox

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Mice

Caption: Genetically identical mice. The Agouti gene is active in the yellow mouse and inactive in the brown mouse.
Credit: Dana Dolinoy, University of Michigan, Ann Arbor, and Randy Jirtle, Duke University, Durham, NC

Step inside the lab of Dana Dolinoy at the University of Michigan, Ann Arbor, and you’re sure to hear conversations that include the rather strange word “agouti” (uh-goo-tee). In this context, it’s a name given to a strain of laboratory mice that arose decades ago from a random mutation in the Agouti gene, which is normally expressed only transiently in hair follicles. The mutation causes the gene to be turned on, or expressed, continuously in all cell types, producing mice that are yellow, obese, and unusually prone to developing diabetes and cancer. As it turns out, these mutant mice and the gene they have pointed to are more valuable than ever today because they offer Dolinoy and other researchers an excellent model for studying the rapidly emerging field of epigenomics.

The genome of the mouse, just as for the human, is the complete DNA instruction book; it contains the coding information for building the proteins that carry out a variety of functions in a cell. But modifications to the DNA determine its function, and these are collectively referred to as the epigenome. The epigenome is made up of chemical tags and proteins that can attach to the DNA and direct such actions as turning genes on or off, thereby controlling the production of proteins in particular cells. These tags have different patterns in each cell type, helping to explain, for example, why a kidney and a skin cell can behave so differently when they share the same DNA.

Some types of genes, including Agouti, are particularly vulnerable to epigenomic effects. In fact, Dolinoy has discovered that exposing normal, wild-type (brown) mice to certain chemicals and dietary factors during pregnancy can switch on the Agouti gene in their developing offspring, turning their coats yellow and their health poor. Dolinoy says these experiments raise much larger questions: If researchers discover populations of humans that have been exposed to lifestyle or environmental factors that modify their epigenomes in ways that may possibly contribute to risk for certain diseases, can the modification be passed on to their children and grandchildren (referred to as transgenerational epigenetic inheritance, a controversial topic)? If so, how can we develop the high-precision tools needed to better understand and perhaps even reduce such risks? The University of Michigan researcher received a 2015 NIH Director’s Transformative Research Award to undertake that challenge.


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