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Abstract & Commentary
By Lin H. Chen, MD Dr. Chen is Assistant Clinical Professor, Harvard Medical School; Director, Travel Medicine Center, Mt. Auburn Hospital, Cambridge, MA.
Dr. Chen reports no financial relationships relevant to this field of study.
Synopsis: Dengue virus infections in the United States are commonly associated with travel to the Caribbean, but local transmission without travel has occurred in Key West, FL, in 2009-2010. Accurate travel history including domestic travel is critical in the evaluation of patients with fever, headache, myalgia, and rash.
Sources: Centers for Disease Control. Travel-associated dengue surveillance United States, 2006-2008. MMWR 2010;59(23):715-9.
Centers for Disease Control. Locally acquired dengue Key West, Florida, 2009-2010. MMWR 2010:59(19):577-581.
A number of reports on dengue have been published recently in the Morbidity and Mortality Weekly Report. The CDC described dengue surveillance in the United States using two sources of data: 1) specimens tested at the CDC Dengue Branch (CDCDB); and 2) the ArboNET surveillance system of the CDC Arboviral Diseases Branch. Probable cases are defined by a positive immunoglobulin M (IgM), and laboratory-confirmed cases are defined by a positive polymerase chain reaction (PCR) or by viral isolation. During 2006-2008, 1,125 reports were submitted to either ArboNET or CDCDB. Among 596 reports to ArboNET, 468 were considered probable (79%) and 128 (21%) were considered confirmed, with the highest number of cases reported from New York (178; 30%), Florida (99; 17%), and Texas (61; 10%).
During the same period, CDCDB tested 529 specimens, of which 136 (26%) were positive for dengue. One hundred six of the 136 (78%) were probable recent dengue infections with positive IgM, and 30 (22%) were confirmed acute dengue infections with positive viral isolation. Serotype data available for 30 cases showed: 14 DENV-1, 7 DENV-2, 6 DENV-3, and 3 DENV-4. A large number (31%) of tests were indeterminate because specimens were not collected within specified time frames. The states with the highest number of dengue-positive specimens were New York (42; 31%), Massachusetts (17; 13%), Arizona (10; 7%), and Georgia (10; 7%).
Among the confirmed and probable cases from ArboNET and CDCDB combined (n = 732) whose travel history included countries visited (n = 613), the most common region of exposure was the Caribbean (43%), followed by Mexico, Central and South America (34%), Asia and the Pacific (21%), and Africa (2%). The most common specific countries for reported dengue exposure were Dominican Republic (20%), Mexico (9%), and India (7%).
The clinical symptoms, when available, were commonly classified as dengue fever (59-72%), and less commonly as dengue hemorrhagic fever (7-16%). During 2006-2008, an average of 244 confirmed or probable travel-associated dengue cases were reported to CDCDB or ArboNET annually. In comparison, the annual average during 1990-2005 was 33.5 cases. The reporting through ArboNET started in 2003, which likely contributed many additional cases. Previously, only CDCDB had data on dengue infections diagnosed in the United States. Additionally, dengue became a nationally notifiable disease in the United States in 2010, which may lead to improved estimates of dengue infection in the United States.
Another report was on a series of dengue infections acquired in Key West, FL. The first identified case was a 34-year-old resident of New York state diagnosed in August 2009 following a one-week trip to Key West. Her sera and cerebral spinal fluid were confirmed at the CDC by positive dengue IgM and PCR analysis. Subsequent cases in Key West residents without travel were also confirmed in August and September 2009, and most recently in April 2010.
The Florida Department of Public Health (FDOH) collected and tested adult female Aedes aegypti mosquitoes throughout Key West, with positive results for DENV-1 in two mosquito pools. A serological survey performed by FDOH and CDC in September 2009 found that 13/240 households (5.4%) had evidence of recent dengue infection. Among 21 patients with symptoms compatible with dengue, 42.9% tested positive for dengue by PCR, by detection of the presence of dengue-specific nonstructural protein 1 (NS-1) in a serum specimen or by an IgM assay.
A total of 27 cases of dengue were identified in Key West in 2009 and one so far in 2010. The patient ages ranged from 15-73 years (median = 47 years). All reported fever. They also frequently reported headache, myalgia, arthralgia, eye pain, and rash, and six reported bleeding (including hematuria, epistaxis, gingival bleeding, and vaginal bleeding).
Dengue is one of the most important mosquito-borne infections in travelers. An analysis of data from GeoSentinel clinics located on six continents on travel-related illnesses found that dengue was the most common specific infection in travelers returning from southeast Asia, and one of the top three diagnoses in travelers returning from all other regions except sub-Saharan Africa and Central America.1 Dengue followed malaria as the most common infection diagnosed in travelers seen in these clinics.2 Furthermore, dengue occurred in 21/1000 ill patients presenting to the GeoSentinel surveillance network, and the rate was even higher for travelers to the Caribbean.3
Dengue virus is in the family Flavivirus and is transmitted through the bite of Aedes mosquitoes. The infection may be subclinical or symptomatic following 3-14 days of incubation. Clinical presentations typically include fever, headache, myalgia, retro-orbital pain and rash; typical laboratory findings include leukopenia and thrombocytopenia.4
A series of dengue infections among U.S. travelers returning from the Dominican Republic in 2008 illustrates precisely the surveillance findings.5 The CDC had identified a cluster of specimens with positive dengue IgM antibodies from Iowa subsequently found to be from a group of U.S. missionaries who had returned from the Dominican Republic. Among 33 missionaries from Iowa and Minnesota, 12 were confirmed serologically and at least 14 (42%) met the case definition.
The group traveled to assist with post-hurricane reconstruction for one week and stayed in urban Santiago in a "tropical style" house. The patients' age range was 12-76 years (median = 53 years). All cases reported weakness and fever, and 12 of 13 patients who were interviewed noted chills and pains; several had bleeding. Of note, only 2/13 persons sought pre-travel evaluation; 3 persons used repellent; none used insecticide; none considered mosquitoes to be a health threat. Only 3 persons had ever heard of dengue.
This dengue cluster among short-term missionaries returning from the Dominican Republic illustrates a high attack rate (≥ 42%), that the travelers lacked knowledge regarding dengue virus, that they took little precaution, and that their accommodations and activities were risky. Effective dissemination of information about dengue virus and its prevention should include methods to reach missionary and volunteer organizations.
Local transmission of dengue has occurred in the continental United States primarily along the Texas-Mexico border. As the CDC reports note, the dengue outbreak in Key West is the first such outbreak outside Texas-Mexico in several decades and the first local outbreak in Florida since 1934. Additional concern arises regarding potential nosocomial transmission, which may occur through blood transfusions, needle sticks, and other health care or laboratory accidents.6,7
Finally, Aedes aegypti is the most efficient and most common mosquito vector for dengue virus. Another vector, Aedes albopictus, was introduced into the United States in 1985, and has established itself in more than 30 states, mainly in the southern part of the United States. The presence of Aedes aegypti in Florida potentiates the local transmission of dengue virus. Aedes albopictus was the vector in the 2001 dengue outbreak in Hawaii that originated from a viremic traveler who returned from the South Pacific. Moreover, Florida mosquitoes, both Aedes aegypti and Aedes albopictus, have been shown experimentally to transmit chikungunya virus.8 Therefore, Florida is vulnerable to both dengue and chikungunya virus outbreaks if the viruses are introduced to the region and established in the local mosquitoes.