The Febrile Returned Traveler and Dengue Fever

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

2. 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

3. 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 1997-2006 (all-comers) • Non-specific fever was the chief complaint in 28%

4. 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

5. 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

6. 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%)

7. 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

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

9. 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)

10. 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%)

11. 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

12. 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)

13. 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

14. 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” http://www.who.int/mediacentre/factsheets/fs117/en/ Wilson, ME, Weld, LH, Boggild, A, et al. Fever in returned travelers: Results from the GeoSentinel Surveillance Network. Clin Infect Dis 2007; 44:1560.