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Home , Bartonellosis, Leptospirosis, Typhoid fever, Viral hemorrhagic fever

Fever in the Returned Traveler VINCENT LO RE III, M.D., and STEPHEN J. GLUCKMAN, M.D. University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

With the rising popularity of international travel to exotic locations, family physicians are encountering more febrile patients who recently have visited tropical countries. In the majority of cases, the is caused by a common illness such as tracheobronchitis, pneu- monia, or urinary tract . However, fever in returned travelers always should raise suspicion for a severe or potentially life-threatening tropical infection. In addition to the usual medical history, physicians should obtain a careful travel history, a description of accommodations, information about pretravel or chemoprophylaxis dur- ing travel, a sexual history, and a list of exposures and risk factors. The extent and type of are important diagnostic clues. Altered mental status with fever is an alarm symptom and requires urgent evaluation and treatment. must be con- sidered in patients who traveled even briefly within an area. Enteric fever is treated with fluoroquinolones, with supportive measures only, leptospiro- sis with or , and rickettsial with doxycycline. (Am Fam Physician 2003;68:1343-50. Copyright© 2003 American Academy of Family Physicians.)

See page 1241 for stimates indicate that 15 to that the trip may be temporally, but not definitions of strength- 37 percent of short-term travelers causally, related to a fever. In rare instances, of-evidence levels. experience a health problem dur- noninfectious such as malignancies ing an international trip, and up or collagen vascular diseases present coinci- to 11 percent of returned travelers dentally during travel. Ehave a febrile illness.1 The majority of travelers with fever have infections that are common in Approach to the Diagnosis nontravelers, such as upper respiratory tract A systematic approach to the evaluation of infection, urinary tract infection, or commu- fever in the returned traveler includes identifi- nity-acquired .2,3 cation of special risk factors, exposures, or Once routine infections have been consid- physical findings that will help focus the ered, the should be work-up (Table 1).Consultation with an expanded to include travel-related infections. infectious diseases subspecialist may assist in The most serious cause of fever in travelers arriving at a diagnosis. returning from the tropics is Plasmodium falciparum malaria, which can be rapidly PRETRAVEL PREPARATION fatal.2,3 Other important causes of fever in Pretravel immunizations and chemopro- returned travelers include typhoidal and non- phylaxis taken during travel must be deter- typhoidal , dengue fever, viral mined, because these will influence the proba- , and rickettsial infections.2,3 bility of acquiring infections.4,5 Proper The family physician also should consider administration of against , , and effectively rules out these infections.6 However, immune glob- Immune globulin as a preventive for hepatitis A and vaccines ulin as a preventive for hepatitis A and vaccines against are only about 70 percent against typhoid fever are only about 70 percent effective; effective; therefore, hepatitis A and typhoid therefore, hepatitis A and typhoid fever still should be con- fever still should be considered in patients who sidered in patients with fever who have been immunized have been immunized with these agents.4 with these agents. Childhood against diseases such as , diphtheria, or measles may not

Downloaded from the American Family Physician Web site at www.aafp.org/afp. Copyright© 2003 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the Web site. All other rights reserved. chemoprophylaxis were used.4,6 Although TABLE 1 these measures clearly decrease the risk of Guidelines for the Evaluation of Nonfocal Fever acquiring malaria, no antimalarial chemopro- in the Returned Traveler phylactic regimen is completely protective. Poor adherence with antimalarial drug regi- 1. Always consider mundane causes such as urinary tract and upper respiratory mens is documented in travelers who tract infections. contract malaria.4 2. Do not forget to consider nontravel-related causes: the fever may have noth- The health of the patient before travel also is ing to do with the trip. important. The presence of underlying med- 3. If the appears to be short (less than 21 days), the majority of patients will have malaria, typhoid fever, or dengue fever. Rickettsial ical conditions (e.g., cardiopulmonary dis- diseases (also a short incubation period) are becoming more frequent causes ease, immunosuppression, asplenia) may of fever in returned travelers. increase susceptibility to various infections. 4. If the incubation period appears to be long (more than 21 days), the Furthermore, medications taken for treat- majority of patients will have malaria or tuberculosis. In addition, consider ment of an underlying condition may alter the hepatitis A in unimmunized patients. presentation of certain diseases. 5. Consult with an infectious diseases subspecialist early if the patient is particularly ill or has altered mental status. Although meningococcemia and viral hemorrhagic are highly uncommon, consider these diagnoses, TRAVEL HISTORY because they are medical emergencies. Questions about the travel history should 6. If attention to these guidelines still does not establish the diagnosis, consider focus on the patient’s exact itinerary, reason uncommon causes. In this situation, consult with an infectious diseases for travel, and accommodations. subspecialist. Travel Itinerary. The risk of acquiring a travel-related infection depends on the precise geographic location and the length of stay at provide adequate protection in adults unless a each destination.4,5 Specific regions visited booster dose has been administered or natural within each country should be determined, has been reported.6 Immigrants from because some infections are focally transmit- developing countries may not have received ted, and risk is only present when traveling in routine immunizations. endemic areas.4,6 For example, malaria may be If a patient recently has traveled to an area a risk only in rural areas of a country. The Cen- where malaria is endemic, the physician ters for Disease Control and Prevention (CDC) should determine whether personal protective publishes a reference, Health Information for measures (e.g., insect repellents, bed nets) and International Travel, 2003-2004,7 detailing spe- cific infections that are found in different loca- tions. A more up-to-date version of this refer- ence is available on the CDC Web site (www. The Authors cdc.gov/travel). Infections can be acquired en VINCENT LO RE III, M.D., is a clinical and research fellow in the Division of Infectious route, so layovers and intermediate stops Diseases at the University of Pennsylvania School of Medicine, Philadelphia, where he should be identified. The type of transporta- earned his medical degree. Dr. Lo Re completed a residency in internal medicine at the Hospital of the University of Pennsylvania, where he was chief resident. tion also is relevant, because outbreaks of many types of infections have been linked specifically STEPHEN J. GLUCKMAN, M.D., is professor of medicine and chief of the Infectious Dis- eases Clinical Services in the Division of Infectious Diseases at the University of Penn- to airplanes, trains, and cruise ships. sylvania School of Medicine. Dr. Gluckman earned his medical degree at Columbia Purpose of Travel. Determining the reason University College of Physicians and Surgeons, New York . He has also received a for travel can assist in assessing the risk for cer- certificate of expertise in international and travel medicine from the American Society of Tropical Medicine and Hygiene. tain infections. The purpose of the trip may affect the duration of travel, the likelihood of Address correspondence to Vincent Lo Re III, M.D., University of Pennsylvania School of Medicine, Division of Infectious Diseases, 502 Johnson Pavilion, Philadelphia, PA 19104 travel in isolated or rural areas, and the likeli- (e-mail: vincent.@uphs.upenn.edu). Reprints are not available from the authors. hood of sexual contact with local inhabitants.8

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Accommodations. Travelers who stay in modern hotels in major urban centers gener- Fever and altered mental status in the returned traveler ally have fewer exposures than backpackers or represent a medical emergency. volunteer workers who spend significant time in rural settings with the local population.9 Persons who visit family and friends while abroad also are at increased risk of becoming begin within 10 days of exposure.4,6 Typhoid ill because they often stay in homes away from fever may present up to 21 days after expo- usual tourist routes.10 sure to contaminated food or drink. The usual incubation period for P. falciparum EXPOSURE HISTORY malaria ranges from eight to 40 days, but The risk of acquiring a tropical infection is infection with the other three Plasmodium affected by the patient’s activities during species that cause malaria (i.e., Plasmodium travel.11 Because many tropical illnesses have vivax, Plasmodium ovale, and Plasmodium nonspecific , identifica- malariae) may not become clinically appar- tion of a unique exposure may provide the ent for several months or even years after only clue to the correct diagnosis. Activities in exposure. In addition, the usual incubation remote areas increase the chance of exposure period for malaria can be lengthened if the to insect vectors and fresh-water lakes and patient has taken antimalarial medications.13 streams that may harbor schistosomes or lep- [Evidence level B, observational study] The tospires.5 In addition, eating certain foods increases the risk for food-borne illnesses. Sexual contact with new partners can occur TABLE 2 during travel and has been reported by up to Specific Exposures for Various Tropical Infectious Diseases one half of young persons who visit tropical regions.12 This contact can result in exposure to Exposure Diseases sexually transmitted diseases (STDs). Although STDs usually present with genital lesions, occa- Undercooked food , nontyphoidal salmonellosis, trichinosis, sionally only fever and nonspecific systemic typhoid fever symptoms may be noted.4,5 The sexual history Untreated water Cholera, hepatitis A, nontyphoidal salmonellosis, typhoid fever should include the number of partners, types Unpasteurized dairy , tuberculosis of sexual activities, and protection used. products A patient’s awareness of illnesses among fel- Fresh water contact , schistosomiasis low travelers or exposures to sick contacts also Sexual contact , , hepatitis B, human 9 may provide a diagnostic clue. Specific expo- immunodeficiency infection, sures for a number of tropical infections are Animals Brucellosis, , , , 4 listed in Table 2. Insects Mosquitoes Dengue fever, malaria INCUBATION PERIOD Ticks Rickettsial diseases, tularemia The physician may be able to estimate the Reduviids American trypanosomiasis incubation period for a patient’s illness Tsetse flies African trypanosomiasis based on the sequence of symptoms, travel Sick contacts , tuberculosis, viral hemorrhagic history, and exposures. This step can help fevers narrow the differential diagnosis by prompt- ing consideration or elimination of certain Adapted with permission from Suh KN, Kozarsky PE, Keystone JE. Evaluation of infections. Symptoms of dengue fever, fever in the returned traveler. Med Clin North Am 1999;83:1000. , and viral hemorrhagic fever usually

OCTOBER 1, 2003 / VOLUME 68, NUMBER 7 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1345 TABLE 3 Typical Incubation Periods for Infectious Diseases in the Returned Traveler

Fewer than 21 days More than 21 days incubation periods for various tropical dis- East African trypanosomiasis human immunodeficiency virus infection eases are provided in Table 3.4 Dengue fever Acute systemic schistosomiasis (Katayama fever) Japanese Amebic PHYSICAL FINDINGS Leptospirosis Borreliosis () A thorough physical examination of the Malaria Brucellosis patient can help guide the physician Meningococcemia Leishmaniasis toward the correct diagnosis. Key findings Nontyphoidal salmonellosis Malaria (especially after ineffective prophylaxis) and their implications for the returned Plague Rabies Typhoid fever Tuberculosis traveler with fever are summarized in Table 4-6,9 Typhus (A, B, C, D, E) 4. The presence of localized or general- Viral hemorrhagic fevers West African trypanosomiasis ized lymphadenopathy is especially helpful Yellow fever diagnostically (Table 5).6 Fever and altered mental status in the returned traveler rep- Adapted with permission from Suh KN, Kozarsky PE, Keystone JE. Evaluation of resent a medical emergency and should be fever in the returned traveler. Med Clin North Am 1999;83:999. managed in consultation with an infec- tious diseases subspecialist (Table 6).6

TABLE 4 Physical Examination of the Returned Traveler with Fever

Area of physical examination Diagnostic value

Vital signs A rate that is slow for the degree of fever (pulse-temperature dissociation) may suggest typhoid fever or a rickettsial disease. Skin A maculopapular rash may be present in many travel-related infections, notably dengue fever, leptospirosis, and typhus, as well as in acute human immunodeficiency virus infection and acute hepatitis B.4,6 Drug eruption also should be considered. Rose spots (evanescent crops of pink macules, 2 to 3 mm in diameter, on the chest or abdomen) suggest typhoid fever. An eschar (black necrotic ulcer with erythematous margins) may be present in many rickettsial diseases. Patients with dengue fever, meningococcemia, and viral hemorrhagic fevers may present with petechiae, ecchymoses, or hemorrhagic lesions. Eyes The eyes should be examined for evidence of (leptospirosis). Sinuses, ears, Sinuses, ears, and teeth are common sites of occult infection (sinusitis, otitis media, tooth teeth abscess); attention to these areas can help avoid unnecessary testing for travel-related causes of infections.9 Heart, lungs Auscultation of the lungs should focus on the detection of inspiratory crackles and wheezes, whereas auscultation of the heart should focus on detection of a murmur (subacute bacterial ).5 Abdomen is associated with mononucleosis, malaria, visceral leishmaniasis, typhoid fever, and brucellosis. Lymph nodes The presence of localized or generalized lymphadenopathy may be diagnostically helpful (see Table 5). Neurologic Fever and altered mental status in the returned traveler represent a medical emergency system (see Table 6).

Information from references 4 through 6 and 9.

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LABORATORY TESTS Thick and thin films for malaria and blood cultures for The initial laboratory evaluation should typhoid fever are important initial tests in the evaluation of focus on diseases that are life-threatening, febrile travelers. most importantly P. falciparum malaria and typhoid fever.9,10 Thick and thin blood films for malaria and blood cultures for typhoid fever are important initial tests in the evalua- tion of febrile travelers. If the first blood films TABLE 5 are negative and malaria is still suspected, Causes of Lymphadenopathy in the Returned Traveler smears should be repeated every eight to 12 hours for several days.4-6,8,9,11 Localized lymphadenopathy Other useful screening tests include a com- Bacterial infection: (cat-scratch disease), plague, staphylococcal plete blood count with differential (paying infection, streptococcal infection, tuberculosis (scrofula), tularemia, typhus close attention to eosinophilia), blood Parasitic infection: African trypanosomiasis, American trypanosomiasis, , chemistries, liver-associated enzymes, and uri- nalysis with urine culture. Because most viral Generalized lymphadenopathy and rickettsial infections are diagnosed by Bacterial infection: brucellosis, leptospirosis, , secondary syphilis, demonstrating an response, storing tuberculosis, enteric fever a tube of drawn when a patient is first Viral infection: acute human immunodeficiency virus infection, dengue fever, evaluated (acute-phase sample) may provide hepatitis B, , measles, mononucleosis (Epstein-Barr virus, the diagnosis when a sample is obtained at a ), rubella later date (convalescent-phase sample) and Fungal infection: blastomycosis, coccidioidomycosis, histoplasmosis 4,5,9 the samples are compared. Parasitic infection: visceral leishmaniasis Major Tropical Causes of Fever Noninfectious causes: malignancy (lymphoma, melanoma, metastatic carcinoma), rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, MALARIA medications (phenytoin [Dilantin], carbamazepine [Tegretol], allopurinol Malaria should be the first consideration in [Zyloprim], sulfonamides) a febrile traveler who has returned from an endemic area. The disease is caused by a blood Information from reference 6. parasite that is transmitted by night-biting Anopheles mosquitoes. The worldwide distri- bution of malaria is shown in Figure 1. Updated information on malarious areas is TABLE 6 7 available in the CDC’s travel resource or on Life-Threatening Causes of Fever its travel Web site. Even brief exposures in and Altered Mental Status in Travelers endemic areas can put travelers at risk for malaria, as in cases of runway or airport Bacterial infection: acute bacterial , 14 malaria. enteric fever, meningococcemia Of the four Plasmodium species that cause Viral infection: , rabies, yellow malaria in humans, P. falciparum results in the fever, viral hemorrhagic fevers (, , most serious illness. Approximately 90 percent Lassa) of malaria cases originate in Africa, and up to Parasitic infection: African trypanosomiasis, 90 percent of travelers with P. falciparum Plasmodium falciparum malaria infection become ill within two months of departure from a malarious area.4 Symptoms Information from reference 6. resulting from infection with other Plasmod-

OCTOBER 1, 2003 / VOLUME 68, NUMBER 7 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1347 ium species may be delayed and can present P. falciparum malaria or any patient in whom months to years after international travel.4 identification to the species level cannot be A typical presentation consists of the abrupt obtained. Consultation with an infectious dis- onset of rigors followed by high fevers and eases subspecialist is recommended to ensure diaphoresis.15,16 The patient also may have proper antimalarial treatment. profound , severe , , and vague .15 Gastrointestinal ENTERIC FEVER symptoms of , vomiting, and Enteric fever refers to a clinical syndrome may occur in up to 25 percent of patients and caused by typhi (typhoid fever) or, potentially can result in a delay of the diagno- less commonly, Salmonella paratyphi (paraty- sis of malaria. and hepatospleno- phoid fever).11,17 Disease usually is acquired by megaly may be noted on physical examina- direct fecal-oral spread or through fecal cont- tion. , , , amination of food or water. Typhoid fever is and abnormal liver-associated enzymes often common in many developing nations, and accompany clinical illness.15 Untreated P. falci- travel to Mexico, India, the Philippines, Pak- parum infection can cause hypoglycemia, istan, El Salvador, and accounts for the renal failure, pulmonary , and neuro- majority of cases. logic deterioration, leading to death.4 Following an incubation period of five to The physician must aggressively pursue the 21 days, patients with enteric fever usually confirmation or exclusion of malaria by per- present with sustained fever, , forming serial blood smears.11 A total of three malaise, and vague abdominal discomfort. smears should be obtained eight to 12 hours Although diarrhea may occur early, it often apart over the course of two days.4,9,11 Hospi- resolves before fever develops, and constipa- tal admission is required for any patient with tion is a usual complaint on presentation.4,17 A

Malaria-Endemic Countries, 2003

No malaria Countries with malaria risk

NOTE: This map shows countries with endemic malaria. In most of these countries, malaria risk is limited to certain areas.

FIGURE 1. Countries in which malaria is endemic in the year 2003. Retrieved August 2003, from: www.dpd.cdc.gov/dpdx/html/Frames/M-R/malaria/body_malaria_page2.htm.

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pulse-temperature dissociation and hepato- splenomegaly may be noted on physical LEPTOSPIROSIS examination.4 Rose spots are found in 30 to Leptospirosis, caused mainly by the spiro- 50 percent of patients, but they are subtle and chete interrogans, infects animals in fleeting and must be searched for carefully. tropical and subtropical climates; the organ- Laboratory findings are nonspecific. ism is then excreted in their urine.24 Transmis- Because current typhoid vaccines have an sion to humans occurs when leptospires enter efficacy of approximately 70 percent, enteric the body through abraded skin, mucous fever is still a possibility in patients who have membranes, or following contact been immunized.18 [Evidence level C, consen- with urine-contaminated or water.25 sus/expert guidelines] Diagnosis is achieved Exposure to the organism is occupational by isolation of the organism in cultures of (e.g., gardening, farming) or recreational blood, stool, urine, , and duode- (e.g., swimming, rafting, crossing streams).24 nal aspirates.11 Leptospirosis may occur as two clinically Resistance to (Chloro- distinguishable syndromes. In anicteric lep- mycetin), , and trimethoprim-sul- tospirosis (90 percent of cases), high fever, famethoxazole (Bactrim, Septra) is relatively headaches, and myalgias follow a usual incu- common. Multidrug-resistant Salmonella bation period of seven to 12 days. Conjunc- strains usually are found in travelers who have tivitis, a maculopapular rash, and hepato- been to the . Fluoro- splenomegaly also may be noted. Later in the quinolone are the treatment of course of the illness, immune-mediated asep- choice.17 [Evidence level C, consensus/expert tic meningitis, , or chorioretinitis may guidelines] occur.25 Icteric leptospirosis, or Weil’s syn- drome, is less common (10 percent of cases) DENGUE FEVER and much more severe. It is characterized by Dengue fever is endemic in many tropical fever, jaundice, azotemia, and . and subtropical areas, particularly Mexico, The diagnosis of leptospirosis usually is the Caribbean, and Central and South Amer- established retrospectively by serologic tests. ica.19-21 The for this flavivirus infection Blood, urine, and can be is the day-biting Aedes mosquito. obtained for culture. Empiric therapy with After an incubation period of three to penicillin or doxycycline (Vibramycin) should 10 days, patients with dengue fever typically be initiated if the diagnosis is considered.24-26 present with abrupt onset of fever, frontal Doxycycline is an effective prophylaxis for headaches, and severe myalgias.19,22,23 Retro- travelers to endemic areas who have a high orbital pain, exacerbated by movement of the risk of exposure.27 [Evidence level B, system- eyes, is a usual complaint.23 The typical rash atic review of lower quality controlled trials] associated with dengue fever is a macular or maculopapular erythroderma that blanches RICKETTSIAL INFECTIONS under light pressure.11,22,23 Leukopenia and Rickettsial diseases are vector-borne ill- mild thrombocytopenia are frequent but non- nesses usually carried by ticks, lice, , or specific findings.23 , and are widely distributed throughout The diagnosis of dengue fever is made clin- the world. The many agents that cause these ically and can be confirmed by a fourfold rise diseases produce similar syndromes. in antibody titer between acute- and convales- Mediterranean , or bouton- cent-phase serum samples obtained at least neuse fever, is the most common imported four weeks apart. Treatment consists of sup- rickettsial disease in returning travelers.28,29 portive measures. This disease is endemic in southern Europe

OCTOBER 1, 2003 / VOLUME 68, NUMBER 7 www.aafp.org/afp AMERICAN FAMILY PHYSICIAN 1349 Fever

9. Saxe SE, Gardner P. The returning traveler with fever. Infect Dis Clin North Am 1992;6:427-39. 10. Ryan ET, Wilson ME, Kain KC. Illness after interna- tional travel. N Engl J Med 2002;347:505-16. 11. Magill AJ. Fever in the returned traveler. Infect Dis Clin North Am 1998;12:445-69. FIGURE 2. Tâche noire (black spot) of rick- 12. Matteelli A, Carosi G. Sexually transmitted diseases ettsial disease. in travelers. Clin Infect Dis 2001;32:1063-7. 13. Reyburn H, Behrens RH, Warhurst D, Bradley D. The effect of chemoprophylaxis on the timing of and the Middle East, where it is caused by onset of falciparum malaria. Trop Med Int Health conorii.In sub-Saharan Africa, a 1998;3:281-5. similar illness, African tick typhus, is caused 14. Conlon CP, Berendt AR, Dawson K, Peto TE. Run- 4,26 way malaria. Lancet 1990;335:472-3. by . 15. Svenson JE, MacLean JD, Gyorkos TW, Keystone J. After a five- to seven-day incubation period, Imported malaria. Clinical presentation and exami- fever, headaches, and myalgias may occur. A nation of symptomatic travelers. Arch Intern Med 1995;155:861-8. maculopapular rash beginning on the trunk 16. Dorsey G, Gandhi M, Oyugi JH, Rosenthal PJ. Diffi- and spreading outward (as opposed to distal culties in the prevention, diagnosis, and treatment to proximal spread in Rocky Mountain spot- of imported malaria. Arch Intern Med 2000;160: 2505-10. ted fever, the main rickettsial disease in the 17. Mermin JH, Townes JM, Gerber M, Dolan N, Mintz ) to involve the palms, soles, and ED, Tauxe RV. Typhoid fever in the United States, face may accompany the illness. There is usu- 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern ally an eschar, called a tâche noire (black spot), Med 1998;158:633-8. at the site of the tick bite4,11,26 (Figure 2). 18. Typhoid : recommendations of the The diagnosis of rickettsial disease usually is Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1994;43 confirmed with serologic testing. Doxycycline (RR-14):1-7. is the treatment of choice. 19. Jelinek T. Dengue fever in international travelers. Clin Infect Dis 2000;31:144-7. The authors indicate that they do not have any con- 20. Jelinek T, Dobler G, Holscher M, Loscher T, Noth- flicts of interests. Sources of funding: none reported. durft HD. Prevalence of infection with among international travelers. Arch Intern Med REFERENCES 1997;157:2367-70. 21. Gubler DJ, Clark GG. Dengue/dengue hemorrhagic 1. Bruni M, Steffen R. Impact of travel-related health fever: the emergence of a global health problem. impairments. J Travel Med 1997;4(2):61-4. Emerg Infect Dis 1995;1:55-7. 2. O’Brien D, Tobin S, Brown GV, Torresi J. Fever in 22. Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, returned travelers: review of hospital admissions Sanders EJ, Vorndam AV. Dengue and dengue for a 3-year period. Clin Infect Dis 2001;33:603-9. haemorrhagic fever. Lancet 1998;352:971-7. 3. Doherty JF, Grant AD, Bryceson AD. Fever as the 23. Schwartz E, Mendelson E, Sidi Y. Dengue fever presenting complaint of travellers returning from among travelers. Am J Med 1996;101:516-20. the tropics. QJM 1995;88:277-81. 24. Van Crevel R, Speelman P, Gravekamp C, Terpstra 4. Suh KN, Kozarsky PE, Keystone JS. Evaluation of WJ. Leptospirosis in travelers. Clin Infect Dis 1994; fever in the returned traveler. Med Clin North Am 19:132-4. 1999;83:997-1017. 25. Farr RW. Leptospirosis. Clin Infect Dis 1995;21:1-6. 5. Humar A, Keystone J. Evaluating fever in travellers 26. Guidugli F, Castro AA, Atallah AN. Antibiotics for returning from tropical countries. BMJ 1996;312: preventing leptospirosis. Cochrane Database Syst 953-6. Rev 2003;(2):CD001305. 6. Strickland GT. Fever in the returned traveler. Med 27. Guidugli F, Castro AA, Atallah AN. Antibiotics for Clin North Am 1992;76:1375-92. leptospirosis. Cochrane Database Syst Rev 2003; 7. Health information for international travel, 2003- (2):CD001306. 2004. Atlanta: U.S. Dept. of Health and Human 28. McDonald JC, MacLean JD, McDade JE. Imported Services, Public Health Service, Centers for Disease rickettsial disease: clinical and epidemiologic fea- Control and Prevention, National Center for Infec- tures. Am J Med 1988;85:799-805. tious Diseases, Division of , 2003. 29. Spira AM. Assessment of travellers who return 8. Felton JM, Bryceson AD. Fever in the returning home ill. Lancet 2003;361:1459-69. traveller. Br J Hosp Med 1996;55:705-11.

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