Rationale:

• Many of the illnesses listed are associated with nonspecific constitutional symptoms. However, there are certain features, such as the blotchy rash in dengue and deeply icteric injected conjunctiva with hemorrhages in leptospirosis, that may indicate a particular illness, whereas other features, such as neck stiffness in meningitis, may suggest an alternate diagnosis.
• The pretest probability for the particular differential diagnosis is influenced by the geographic area visited (yellow fever is not prevalent in Asia), type of travel (adventure travelers to the Rift Valley are more likely to acquire schistosomiasis or leptospirosis from fresh water contact than are visitors to Nairobi, Kenya), time of travel (dengue is much less likely to be acquired during the dry season, when mosquito transmission is markedly reduced), type of food and water ingested (enteric fever is relatively unlikely in persons eating only cooked food and drinking bottled water), and the vaccination history (the efficacy of yellow fever and hepatitis A and B vaccines makes these diseases unlikely if the patient is vaccinated).

Evidence:

• A review and two clinical studies recommend that dengue always be on the list of differential diagnoses of fever in travelers or immigrants who have been in a dengue-endemic area within the previous 2 weeks (56; 83; 84).
• A prospective study included all travelers presenting at referral outpatient and inpatient centers with ongoing fever after a stay in the tropics between 2000 and 2004. Outcome was assessed by at least one follow-up consultation or telephone call within 3 months after initial contact. There were 1842 fever episodes involving 1743 patients. The main regions of exposure were sub-Saharan Africa (68%) and the Southeast Asia-Pacific region (12%). Tropical diseases accounted for 39% of all cases. Travel destination influenced the pattern of disease. Malaria (35%; mainly Plasmodium falciparum) and rickettsial infection (4%) were the leading diagnoses after a stay in Africa; dengue (12%), malaria (9%), and enteric fever (4%) were the leading diagnoses after travel to Asia; and dengue (8%) and malaria (4%) were the leading diagnoses upon return from Latin America. Hospitalization was required for 503 (27%) fever episodes. P. falciparum malaria accounted for 36% of all hospital admissions and was the only tropical disease to cause deaths in this cohort (5 of 9 patients) (85).
• A study analyzed the relative frequency of travel-associated health complaints in 622 travelers attending a travel clinic between November 2002 and May 2003. The median duration of travel was 36.9 days, and the main travel destinations were Africa (57.6%) and Asia (26.4%). The diseases diagnosed were dengue fever (2.5%), skin diseases (23.4%), gastrointestinal infections (19.1%), respiratory tract infections (11.5%), malaria (8.8%), schistosomiasis (7.2%), viral hepatitis (4.1%), urinary tract infections (3.5%), sexually transmitted infections (3.5%), tuberculosis (2.7%), and others (13.8%). Among 257 febrile travelers, the main imported tropical diseases were malaria, dengue fever, schistosomiasis, amebiasis, and gastrointestinal disorders caused by intestinal nematodes (86).
• Among 232 successive patients admitted to a tertiary care hospital in Victoria, Australia, for management of a febrile illness acquired overseas, malaria was the most common diagnosis (27% of patients), followed by respiratory tract infection (24%), gastroenteritis (14%), dengue fever (8%), and bacterial pneumonia (6%) (4).
• In a study that included 211 hospitalized patients with a history of recent travel between January 1999 and December 2003, febrile diseases accounted for 77% of the admissions. The most common diagnoses were malaria (54 patients [26%]), unidentified febrile disease (34 patients [16%]), and dengue fever (27 patients [13%]). A total of 101 patients (48%) had visited Asia, 71 patients (34%) had traveled to Africa, and 43 patients (20%) had traveled to the Americas. The main health problem in those returning from a visit to Asia was dengue fever (87).
• A study reviewed cases of infection acquired overseas in the Japanese surveillance system of imported infectious diseases between 1999 and 2008. During this period, 10,030 cases of imported infectious diseases were identified. Shigellosis was the most common, followed by amebiasis, malaria, enterohemorrhagic Escherichia coli infection, HIV, typhoid fever, dengue fever, hepatitis A, giardiasis, cholera, and paratyphoid fever (88).
• A systematic review of the literature from 1990 to 2007 was conducted to differentiate patients with dengue from those with other febrile illnesses. Of the 49 studies identified, only 15 met the criteria for inclusion (10 prospective cohort studies and 5 case-control studies). Seven studies assessed patients of all ages, 4 assessed children only, and 4 assessed adults only. Patients with dengue had significantly lower platelet, leukocyte, and neutrophil counts and a higher frequency of petechiae than patients with other febrile illnesses. Higher frequencies of myalgia, rash, hemorrhagic signs, lethargy/prostration, and arthralgia/joint pain and higher hematocrits were reported in adult patients with dengue but not in children (89).
• A prospective study of 928 adult patients with short-duration fever admitted to a hospital in Sri Lanka from February to June of 2004 randomly selected 1 in 4 patients for assessment of the severity of six clinical features: headache, body aches, vomiting, retro-orbital pain, generalized weakness (on a scale of 0 to 9), and skin erythema (grade 1 to 5). There were 148 patients with dengue fever and 54 patients without dengue fever who served as controls. All symptoms assessed (cutoff 5) and skin erythema (grade 2 or higher) had a good positive predictive value for dengue fever. Erythema had the best negative predictive value, helping to differentiate dengue fever from other short-duration fevers (90).

Comments:

• Some diseases that need to be differentiated from dengue are less likely to be considered by physicians not well acquainted with tropical diseases, are seen with appreciable frequency among travelers returning from dengue-endemic areas, can present clinically within 1 month of exposure, and may be serious or life-threatening if not treated with specific drugs.
• Rapid diagnostic tests for some diseases are often limited or not available.
• Definitive diagnosis often relies on nonroutine methods of pathogen isolation or serologic testing that relies on serologic comparisons of acute and convalescent (taken 2 to 4 weeks later) antibody titers.