Fever After a Stay in the Tropics Diagnostic Predictors of the Leading Tropical Conditions Emmanuel Bottieau, MD, Jan Clerinx, MD, Erwin Van den Enden, MD, Marjan Van Esbroeck, MD, Robert Colebunders, MD, PhD, Alfons Van Gompel, MD, and Jef Van den Ende, MD, PhD Abstract: Differential diagnosis of fever in travelers returning from the tropics is extremely diverse. Apart from the travel destination, other diagnostic predictors of tropical infections are poorly documented in returning travelers. From April 2000 to December 2005, we prospectively enrolled all patients presenting at our referral centers with fever within 1 year after visiting a tropical or subtropical area. For clinical relevance, the diagnostic predictors of the leading tropical conditions were particularly investigated in the febrile episodes occurring during travel or within 1 month after return (defined as early-onset fever). In total, 2071 fever episodes were included, occurring in 1962 patients. Most patients were western travelers (60%) or expatriates (15%). Regions of exposure were mainly sub-Saharan Africa (68%) and southern Asia/Pacific (14%). Early-onset fever accounted for 1619 episodes (78%). Most tropical infections were related to specific travel destinations. Malaria (mainly Plasmodium falcipa- rum) was strongly predicted by the following features: enlarged spleen, thrombocytopenia (platelet count <150  10 3 /mL), fever without localizing symptoms, and hyperbilirubinemia (total biliru- bin level 1.3 mg/dL). When malaria had been ruled out, main predictors were skin rash and skin ulcer for rickettsial infection (mainly African tick bite fever); skin rash, thrombocytopenia, and leukopenia (leukocyte count <4  10 3 /mL) for dengue; eosinophil count 0.5  10 3 /mL for acute schistosomiasis; and enlarged spleen and elevated alanine aminotransferase level (70 IU/L) for enteric fever. The initial clinical and laboratory assessment can help in selecting appropriate investigations and empiric treatments for patients with imported fever. (Medicine 2007;86:18–25) INTRODUCTION The differential diagnosis of fever in travelers return- ing from the tropics remains a challenge, particularly for physicians less familiar with exotic pathology. Clinicians face patients possibly exposed to various tropical pathogens, and must consider many cosmopolitan infections as well (infections with worldwide distribution) 10 . Most tropical infections have a nonspecific presentation, and some may evolve rapidly into severe disease if not adequately treated 16 . Therefore, optimal management should aim at recognizing promptly the most serious conditions, while minimizing unnecessary workup and treatment for milder diseases 7 . Morbidity profiles in international travelers vary significantly according to the region of exposure 10 . In a recent 5-year study 2 investigating the etiology of fever after a stay in the tropics in 1842 returning travelers or migrants, we demonstrated that the clinical spectrum depended not only on the geographic risk, but also on other factors such as the type of traveler and the lapse between exposure and onset of fever. Since the epidemiology of imported fever considerably overlaps, additional elements of the initial assessment are necessary to steer the diagnostic and therapeutic strategy. Diagnostic predictors of several tropical diseases have been investigated in endemic settings 5 , but only incompletely in returning travelers, except for ma- laria 3,8,9,21 . We conducted the current study to identify in febrile travelers and migrants the clinical and lab- oratory features that could help in diagnosing the most frequent tropical conditions, and to quantify their predictive contribution. PATIENTS AND METHODS Study Setting and Patients From April 2000 to December 2005 we prospectively recruited all consecutive patients attending the Institute of Tropical Medicine (outpatient travel clinic, national refer- ence center) and the University Hospital (emergency ward and inpatient Unit of Tropical Diseases, tertiary-care hospital) of Antwerp, Belgium, if they presented with fever within 1 year after visiting a tropical or subtropical area. The epidemiology and the etiologic spectrum of the first 1842 febrile episodes (from April 2000 to March 2005) have been recently reported 2 . Abbreviations: LR = likelihood ratio; OR = odds ratio. 18 Medicine  Volume 86, Number 1, January 2007 From Department of Clinical Sciences (EB, JC, EVdE, MVE, RC, AVG, JVdE), Institute of Tropical Medicine, Antwerp; Unit of Tropical Medicine (RC, JVdE), University Hospital Antwerp; and Faculty of Medicine (RC), University of Antwerp; Antwerp, Belgium. Address reprint requests to: Dr. Emmanuel Bottieau, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerp, Belgium. Fax: 32(0)3/ 247.64.52; e-mail: EBottieau@itg.be. Copyright n 2007 by Lippincott Williams & Wilkins ISSN: 0025-7974/07/8601-0018 DOI: 10.1097/MD.0b013e3180305c48 Copyr ight © Lippincott Williams & Wilkins. Unauthor iz ed reproduction of this article is prohibited.