The Febrile Returned Traveler and Dengue Fever AM Report Sept. 25, 2009

The Traveler Health problems are common in the traveler –Self-reported rate of 22-64% of people who travel to developing countries The major categories are: –Systemic febrile illness w/o localizing findings –Diarrhea –Dermatologic disorders –Non-diarrheal GI disorders

GeoSentinal Surveillance effort made up of the CDC and International Society of Travel Medicine Stretches out over six continents and collects data on ill travelers Large study of almost 25,000 ill travelers between (all-comers) –Non-specific fever was the chief complaint in 28%

Febrile Illness For returned travelers presenting with an acute fever Malaria was the #1 cause, Dengue Fever #2 –21%, 6% respectively, although it is thought that Dengue is widely underrecognized and underdiagnosed secondary to lack of knowledge on the part of health care providers –In travelers to SouthEast Asia, Dengue is the #1 cause of febrile illness –In the Caribbean and South/Central America, they are roughly even Numbers 3-5 are mononucleosis (EBV or CMV), Rickettsial infection, and typhoid/paratyphoid fever

Dengue Fever – What is it? Mosquito-born virus –Four, actually. DENV-1 through DENV-4 –Flavivirus genus –Single strand RNA viruses –Exposure to one serotype provides almost no cross-protection to re-infection from other 3 types 50 million infections occur yearly throughout the world

Symptoms Typically start 4-7 days after the bite –Incubation period of 3-14 days Spectrum, from asx infection to self-limited fever to hemorrhagic fever Age is a big predictor for response – children under the age of 15 tend to have more asx infections (>50%)

Classic Presentation “Break-Bone Fever” Acute febrile illness –Typically lasts 5-7 days –Once fever disappears, prolonged fatigue (days to week) is common Muscle/joint pain Headache/retroorbital pain Varied rashes common in primary infection –Macular of maculopapular GI sx common in secondary infection Rarely (<10%), can have hematologic sx –Purpura, spontaneous bleed, melena, metorrhagia, epistaxis

Lab Findings Thrombocytopenia (<100K) Leukopenia Elevated AST (2-5x upper limit of nl)

More serious presentation – Dengue Hemorrhagic Fever Four cardinal features, per the WHO –“Plasma Leakage Syndrome” Increased vascular permeability defined by either hemoconcentration (>20% rise above baseline crit), presence of pleural effusion or ascites –Thrombocytopenia (<100K) –Fever lasting 2-7 days –Spontaneous bleeding or a “hemorrhagic tendency” (ie positive tourniquet test) Inflate BP cuff on arm to midway between systolic and diastolic pressure, wait five minutes If >20 petechiae/sq inch on skin below the cuff, test is positive ** If all four of these signs/sx plus shock  Dengue Shock Syndrome (DSS)

Epi Dengue was the cause of about 10.4% of post-travel systemic febrile illnesses among travelers returning from Southeast Asia –Second only to malaria Most frequently identified cause of systemic febrile illness among travelers returning from Southeast Asia (32%), Caribbean (24%), South Central Asia (14%), South America (14%). Second to malaria in Central America (12%)

Diagnosis Other than specific WHO criteria for Dengue Hemorrhagic Fever, classic DF has no clear criteria Mostly clinical, based on signs/sx Epidemiological studies define it differently - has been a problem for research efforts Hemagglutination Inhibition Assay is the gold standard In developed countries, can do PCR, Ag testing, or IgM/IgG immunoassay

Prevention Tx is pretty much all supportive, so focus on prevention –Particularly those traveling to Asia, Central and South America, and the Caribbean Tetravalent vaccines in development (animal testing phase)

Mosquito Control (Aedes Aegypti) –Insecticides not very effective, as they breed inside houses –Community education to reduce breeding site (tires, other containers with standing water) –Standard methods to prevent mosquito bites (long sleeves, DEET, etc) –Place a water bug, Mesocyclops, in containers

References Freedman, DO, Weld, LH, Kozarsky, PE, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med 2006; 354:119. Up-To-Date. Clinical presentation and diagnosis of dengue virus infections. Updated January, 2009 Steffen, R, deBernardis, C, Banos, A. Travel epidemiology--a global perspective. Int J Antimicrob Agents 2003; 21:89. World Health Organization Public Website – “Dengue and Dengue Haemorrhagic Fever” Wilson, ME, Weld, LH, Boggild, A, et al. Fever in returned travelers: Results from the GeoSentinel Surveillance Network. Clin Infect Dis 2007; 44:1560.