Dengue in the U.S.
By Philip R. Fischer, MD, DTM&H
Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN.
Dr. Fischer reports no financial relationships in this field of study.
SYNOPSIS: In a Boston-based survey of travelers, 19% of individuals who were born in, had lived in, or traveled to dengue-endemic countries showed serologic evidence of previous dengue infection. Even without travel, however, dengue infection occurs in the continental United States. In 2012, a woman from Texas died of dengue-associated hemophagocytic lymphohistiocytosis, the third person to die of locally-acquired dengue in the US during the past ten years.
SOURCES: Sanchez-Vegas C, et al. Prevalence of dengue virus infection in US travelers who have lived in or traveled to dengue-endemic countries. J Travel Med 2013;20(6):352-360.
Sharp TM, et al. Fatal hemophagocytic lymphohistiocytosis associated with locally acquired dengue virus infection New Mexico and Texas, 2012. MMWR 2014;63(3):49-54.
Dengue virus is transmitted by Aedes mosquitoes and causes up to 100 million infections, 500,000 hospitalizations, and 22,000 deaths each year. The incidence of dengue has increased 30-fold in the past five decades, and it is expanding to include broader geographic regions.
Travelers are at particular risk of dengue infection. To better understand specific risks, a network of five travel clinics in the Boston area evaluated 600 travelers in 2008-2009. Overall, 19% had serologic evidence of previous dengue infection by ELISA testing. Of the 140 study participants born in dengue-endemic countries, 51% were seropositive; longer residence in the endemic country was associated with a greater likelihood of seropositivity. Of the 30 who had been born in a non-endemic country but who had lived in a dengue-endemic country for more than a year, 40% were seropositive. Of the 421 who had not lived in a dengue-endemic country but who traveled to a dengue-endemic country for two to 52 weeks, 7% were seropositive.
It is generally believed that dengue fever is more severe in individuals who have previously been infected with a dengue virus. Only 3% of the travelers in the Boston study reported a history of having had dengue fever even though 19% had serologic evidence of previous infection. Thus, many people who have spent time in dengue-endemic areas have been infected without knowing it; these individuals are presumably at risk of more severe infection.
As sadly illustrated by the Texas woman reported in MMWR, however, severe dengue disease can happen without international travel and without evidence of a previous infection. A 63-year-old on mercaptopurine and mesalamine for inflammatory bowel disease presented for care with fatigue, anorexia, headache, hematuria, and leg pain. The symptoms had started while visiting New Mexico and prompted her return home for care in Texas. She subsequently became febrile, hypotensive, hypoxic, and jaundiced. A liver biopsy showed fulminant hepatitis. The kidneys failed, and hemodialysis was initiated. The patient became encephalopathic and then died one month after her initial presentation. Retrospective review confirmed that she met diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). A bone marrow aspirate was subsequently tested and found to be positive for dengue virus type 3 RNA. No other etiologic agent was identified that correlated with the disease (despite West Nile Virus testing initially being weakly positive). Inflammatory bowel disease and immunosuppression have been linked to an increased risk of HLH and might have contributed to the fatal outcome in this dengue-infected woman.
COMMENTARY
While often asymptomatic, dengue can cause symptomatic disease, and the severe pains with the acute febrile illness have prompted the disease's nickname "breakbone fever." After the initial illness, approximately 1-3% of infected individuals progress to dengue shock syndrome or dengue hemorrhagic fever. These severe forms of dengue carry a 1-5% mortality rate; infants and children in endemic areas are most at risk of poor outcomes.1 There is no specific treatment available, and management depends on supportive care.
While locally-acquired cases of dengue fever have occurred in Texas, the illness has also re-emerged in Key West, Florida.2 In Key West, infection among residents was associated with having a bird bath in the yard and with leaving windows open most of the time. Applying insect repellant, using air conditioning, and regular emptying of outdoor water containers were associated with less risk of infection.2
Dengue vaccines are under study, and some candidate vaccines are currently being used in clinical trials.1 For now, however, prevention of dengue infection depends on avoiding mosquito bites during travel and while living in parts of the southern United States (such as Texas and Florida) where dengue is endemic. Protection from dengue-transmitting Aedes mosquitoes must continue inside and during daytime hours. Insect repellants DEET (N,N-diethyl-3-methylbenzamide) and icaridin offer similar protective efficacy against Aedes with topical application.3
References
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Ratman I et al. Dengue fever and international travel. J Travel Med 2013;20(6):384-393.
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Radke EG et al. Dengue outbreak in Key West, Florida, USA, 2009. Emerg Infect Dis 2012;18(1):135-137.
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Lupi E et al. The efficacy of repellents against Aedes, Anopheles, Culex, and Ixodes spp. a literature review. Travel Med Infect Dis 2013;11(6):374-411.
