Study: 99% of travelers with complicated dengue showed warning signs

Key takeaways:

• Only 2% of dengue cases reported to the GeoSentinel Network were complicated.
• Warning signs include abdominal pain, fluid accumulation, lethargy, liver enlargement, mucosal bleeding and persistent vomiting.

Although rare in travelers, nearly all complicated cases of dengue showed warning signs, highlighting the importance of monitoring patients with dengue to prevent severe disease, according to researchers.

Ralph Huits, MD, PhD, a clinical research associate in the department of infectious tropical diseases and microbiology at IRCCS Sacro Cuore Don Calabria Hospital in Italy, and colleagues wrote in Annals of Internal Medicine that dengue is the most widely occurring arboviral infection globally, with 50 to 100 million symptomatic infections reported each year. However, classifying the virus’ severity and predicting outcomes “can be challenging,” they added.

“The objective of this analysis was to describe the epidemiology, clinical manifestations, and outcomes of a large cohort of international travelers with severe dengue and dengue with warning signs,” they wrote. “Warning signs in a patient with dengue include abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, and increasing hematocrit with decreasing platelets.”

The researchers evaluated 2007 to 2022 data from the GeoSentinel network surveillance platform, a surveillance system with 71 international sites that monitor infectious diseases and other adverse health effects. They identified 5,958 travelers who were diagnosed with dengue, 95 of whom (2%) met the criteria for complicated dengue. Patients with complicated dengue had a mean age of 34 years and 56% were women. All the travelers were returning to Europe from continents other than Africa. Most of those who had complicated dengue traveled to the Caribbean (31%) and Southeast Asia (24%).

Of the 86 patients who had completed a supplemental questionnaire, 99% had warning signs for complicated dengue. Meanwhile, 31% met the 2009 WHO criteria for severe dengue, or dengue with plasma leakage leading to shock, organ failure or severe hemorrhage.

According to the researchers, common warning signs among the patients with complicated dengue included:

• thrombocytopenia (78%);
• elevated aminotransferase (62%);
• bleeding (52%); and
• plasma leakage (20%).

Additionally, 25% of patients had comorbidities, whereas 91% were hospitalized. Those with comorbidities were more likely to be admitted to the ICU.

“It is likely that comorbidities themselves contribute to the development of severe disease, but analogous to other viral infections, dengue may also exacerbate comorbidities and lead to ICU admissions,” Huits and colleagues wrote.

Among severe cases, the researchers observed incidences of ophthalmologic pathology (n = 3), severe liver disease (n = 3), myocarditis (n = 2) and neurologic symptoms (n = 2).

They explained that after diagnosis and identification of warning signs, “supportive treatment greatly reduces the risk for poor outcomes among patients with dengue.”

“Therefore, clinicians should consider admitting travelers with dengue and warning signs and monitor them closely for laboratory findings and signs that may indicate progression

to severe disease,” they wrote. “The application of systematic grading of dengue disease using clinical trial metrics may aid in the management of dengue patients in nonendemic areas.”

The best strategy to reduce poor outcomes is to prevent infection, according to Huits and colleagues.

“Travelers should be encouraged to adhere to mosquito bite precautions during travel and be advised to seek care at the onset of any clinical symptoms of dengue,” they wrote.

The Dengvaxia (Sanofi Pasteur) vaccine is recommended only for seropositive individuals in endemic areas because of a risk for severe dengue and hospitalization following vaccination, the researchers noted. The vaccine is currently approved in the United States for children aged 9 to 16 years who have laboratory-confirmed previous dengue infection. It is the only FDA-approved dengue vaccine in the U.S.

Qdenga (Takeda) has demonstrated serostatus-independent efficacy and long-term protection against hospitalization in youth with virologically confirmed dengue, according to Huits and colleagues. However, “although this vaccine was recently approved by the European Medicines Agency for use in persons aged 4 years or older, efficacy and effectiveness at preventing complicated dengue in travelers remains to be evaluated,” they wrote.