Imagine discovering that a tropical disease like dengue fever could strike in the driest corners of the world – think the scorching sands of Egypt's Sinai Peninsula. That's the shocking reality uncovered in a recent study of four Israeli travelers who fell ill after vacations in Sharm El-Sheikh during the spring and summer of 2024. But here's where it gets controversial: This desert oasis has long been deemed inhospitable for the mosquitoes that spread dengue, raising eyebrows about how the virus is adapting and spreading. Stick around as we dive into the details – and this is the part most people miss – the genetic clues pointing to far-flung origins that challenge our understanding of global health risks.
First off, a quick disclaimer for clarity: This piece draws from an early-release article, meaning it might see some tweaks before its official publication. Any updates will pop up online in the month it's finalized.
The research team hails from top Israeli institutions. Leading the charge is Sheba Medical Center in Ramat-Gan, with contributors like N.S. Zuckerman, Y. Lustig, K. Friedman, T. Kushnir, V. Indenbaum, and E. Schwartz. Tel-Aviv University in Tel Aviv adds G. Choshen, Y. Lustig, O. Halutz, and E. Schwartz to the mix. Meir Medical Center in Kfar-Saba brings G. Choshen and A. Shoykhet, while the Infectious Disease Institute at Soroka University Medical Center in Beer Sheba includes H. Azulay.
Let's set the stage: Dengue virus, or DENV, tops the list as the most widespread arbovirus on the planet – that's a virus transmitted by insects like mosquitoes. Over the last 20 years, its cases have skyrocketed tenfold, fueled by warming climates and increased travel around the world (1). While it's no stranger to Southeast Asia and the Americas, we're seeing more 'autochthonous' outbreaks – meaning locally acquired cases – popping up in places like Europe where the virus hasn't traditionally lingered.
Now, onto the heart of the story: The study details four confirmed cases of dengue fever in people flying back to Israel after trips to Sharm El-Sheikh, a bustling resort town in the South Sinai region of Egypt. This spot, tucked away in the desert, has never been on the radar as a dengue hotspot. In fact, experts thought the dry, harsh environment of the Sinai Peninsula was too tough for the main carriers, Aedes mosquitoes, which thrive in wetter, more humid areas.
For beginners, Aedes mosquitoes are tiny, winged pests that bite during the day and can spread viruses through their saliva. They're the key players here because dengue doesn't pass directly from person to person – it's all about that mosquito bite.
These four cases were completely independent; their trips didn't overlap, and they stayed in different hotels scattered 3 to 25 kilometers apart. All presented with classic dengue symptoms: high fevers, pounding headaches, aching muscles, and skin rashes. They ended up in the hospital for supportive care – think plenty of rest, fluids, and monitoring – and thankfully, they all pulled through. One patient showed signs of meningeal irritation, which is inflammation around the brain, but tests on their cerebrospinal fluid came back clear. Interestingly, though, DENV serotype 2 (DENV-2) genetic material was found via a technique called quantitative real-time PCR, with a cycle threshold of 32.5. To explain simply, PCR amplifies tiny bits of DNA or RNA to detect the virus, and the cycle threshold indicates how much virus was present – lower numbers mean more virus.
All samples were taken within a week of symptoms starting. Blood tests (serum) nailed down the diagnosis as DENV-2 using a multiplex version of real-time PCR (2), which checks for multiple things at once. Some patients also tested positive for the nonstructural protein 1 antigen (a marker of active infection) and antibodies like IgM and IgG, which show the body's immune response.
To trace where this DENV-2 might have come from, the scientists sequenced the entire virus genome. They used special primers designed for whole-genome capture (check out the Grubaugh Lab's open-science tools for more). Libraries were prepped with Nextera-XT and sequenced on the Illumina NovaSeq platform (learn more at illumina.com). Consensus sequences were built by aligning reads to the DENV-2 reference genome (GenBank accession NC_001474.2), and all were uploaded to GenBank (see the appendix table for details). The study got ethical approval from Sheba Medical Center's Institutional Review Board (SMC-6190-19).
The genomic data was robust for three of the four samples, but patient four's had lower quality, possibly due to that higher cycle threshold of 34, so it was left out. Phylogenetic analysis – basically a family tree of viruses – compared these sequences to 1,492 global DENV-2 samples. The Israeli strains clustered within the Cosmopolitan genotype, a widespread group of the virus. The three sequences formed their own tight cluster, sharing a recent common ancestor and differing by just 32 mutations from the closest global match. That nearest relative? Strains from Pakistan. The only nearby public sequence from the United Arab Emirates in 2023 fell into a different Cosmopolitan branch, alongside viruses from China, India, and Bangladesh (see the figure, panel A).
In summary, these findings confirm four DENV-2 infections from travelers visiting Sharm El-Sheikh, an arid spot in Sinai previously thought unfit for Aedes mosquitoes and free of dengue reports. The genetic patterns suggest these cases stemmed from a single outbreak, with ties to Pakistani strains. Minus that one UAE sequence, there's a glaring lack of recent viral data from Sinai, highlighting a huge gap in disease monitoring. This echoes other reports of DENV-2 moving along the Red Sea coast and even recent flare-ups in Florence, Italy (8).
Over the past two decades, Aedes aegypti mosquito populations have been expanding in Egypt, particularly along the Red Sea shoreline (figure, panel B), often coinciding with dengue outbreaks. But Sinai lacks any entomologic data – meaning studies on insect vectors. The dry climate poses survival challenges for mosquitoes, yet the grouping of cases in one resort area hints at local adaptation, perhaps aided by man-made water sources in urban settings (9). For example, think of hotel pools or irrigation systems creating micro-oases that support mosquito breeding.
Travel plays a big role too: Airplanes and ships could repeatedly introduce Aedes aegypti and dengue viruses to the Red Sea region. But the outbreak patterns in Red Sea ports point strongly to maritime transport as the main culprit (6,7,10). Daily ferry services from Hurghada – a spot where dengue has recently emerged – to Sharm El-Sheikh stand out as a potential vector (figure, panel B). Genetic evidence from a 2019 outbreak in Jizan, Saudi Arabia, plus older strains from Saudi Arabia (1992–2014), suggest multiple introductions of a DENV-2 variant similar to those from Malaysia, Singapore, Korea, and China (6).
Further digging into Saudi Arabian strains from 1992–2014 shows tight clustering with viruses from countries sending the most Hajj and Umrah pilgrims: Indonesia, Pakistan, and India (10). Our sequences align most closely with recent Pakistani ones, but the limited data from Egypt and its neighbors makes it tricky to pinpoint exact origins, spread, or how widespread it really is. The genetic diversity observed suggests we're only seeing the tip of the iceberg, with many undetected cases lurking.
Reporting four cases over three months across different Sharm El-Sheikh locations points to ongoing DENV-2 transmission, calling for beefed-up mosquito surveillance and control measures – a wake-up call for health officials. And this is the part most people miss: The genomic insights here could fill crucial voids in regional sequencing data, shedding light on dengue's molecular evolution and roots.
Dr. N.S. Zuckerman heads the Bioinformatics and Genomics Center at Israel's Central Virology Laboratory under the Ministry of Health and is linked to Tel Aviv University's School of Public Health. Her expertise shines in genomic monitoring, molecular epidemiology, and using bioinformatics to tackle viral threats.
Now, here's a controversial twist: Some might argue that globalization and travel are inevitable boons, but are they also supercharging disease spread in unexpected places? Could human activities, like resort development in deserts, be inadvertently creating mosquito havens? And this is where it gets provocative – what if neglecting surveillance in arid areas is a bigger oversight than we think, potentially allowing viruses to mutate and surprise us? Do you agree that climate change is turning unlikely spots into hotspots, or do you see travel bans as the solution? Share your views in the comments – we'd love to hear if you've experienced similar travel scares or have thoughts on global health preparedness!
References:
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8. Newman EA, et al. Defining the roles of local precipitation and anthropogenic water sources in driving the abundance of Aedes aegypti, an emerging disease vector in urban, arid landscapes. Sci Rep. 2024;14:2058. DOI: https://doi.org/10.1038/s41598-023-50346-3
9. El-Kafrawy SA, et al. Multiple introductions of dengue 2 virus strains into Saudi Arabia from 1992 to 2014. Vector Borne Zoonotic Dis. 2016;16:391–9. DOI: https://doi.org/10.1089/vbz.2015.1911
Suggested citation: Zuckerman NS, et al. Molecular evidence of dengue virus serotype 2 in travelers returning to Israel from the Sinai Peninsula. Emerg Infect Dis. 2025 Nov [date cited]. https://doi.org/10.3201/eid3111.250991
These authors contributed equally to this article.
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