ARCHIVED - Canada Communicable Disease Report
Table of Contents
- Epidemiology of fever in the returning traveller
- Evaluation of fever in the returning traveller
- Appendix I. Specific tests to rule-out common travel-acquired infections that can cause feve
- Appendix II. Additional resources for guidance on fever in the returning traveller
The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada (PHAC) with ongoing and timely medical, scientific, and public health advice relating to tropical infectious diseases and health risks associated with international travel. PHAC acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.
Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.
Fever in the international traveller is a common syndrome seen in the post-travel setting, and may herald serious and life-threatening illness, the most important of which is malaria. All febrile patients or patients complaining of fever should therefore be asked about recent travel. While fever in the returning traveller may be due to benign self-limited infections, such as common agents of travellers’ diarrhea, or typical cosmopolitan causes unrelated to travel, it must be initially construed as a medical emergency, and warrants prompt and thorough evaluation. Accurate diagnosis and appropriate management necessitate a comprehensive travel history, including details about travel itinerary (destination, arrival and departure dates), the style of travel, pre-travel preparations, as well as potential exposures or medical treatment or care received abroad and a complete physical examination, with particular attention paid to systems with localizing symptoms or signs. The judicious use of laboratory testing should follow, with minimal essential tests outlined in the stepwise algorithm below.
This document is designed to:
- Guide front-line clinicians, including those working in the emergency room, walk-in clinics, and primary care practices, in the initial evaluation and management of fever in the returning traveller;
- Provide front-line clinicians without ready access to inpatient, internal medicine, or infectious diseases support with guidance in the evaluation and management of fever in the returning traveller beyond the initial phase.
Fever in the returning traveller may be due to tropical infections or illnesses that have more of a cosmopolitan distribution globally. Numerous large series of illness after international travel have repeatedly identified malaria (20-30%) 1, acute travellers’ diarrhea (10-20%), and respiratory tract infections (10-15%) as the top causes of fever in travellers 2–11 (Table 1). Other common causes of fever in the returning traveller include dengue (5%), enteric fever due to Salmonella enterica serovar Typhi or Paratyphi (2-7%), skin and soft tissue infections (2-11%), rickettsioses (3%), urinary tract and sexually transmitted infections (2-3%), viral hepatitis (3%), and non-specific viral or mononucleosis-like syndrome (4-25%) 2–11. In febrile returning pediatric travellers, malaria (35%), viral syndromes (28%), unspecified febrile illnesses (11%), dengue (6%), and enteric fever (6%) are the most well-represented etiologies 12. Fever after international travel may be due to non-infectious causes as well, and include diverse etiologies such as drug reactions, pulmonary emboli, inflammatory conditions such as inflammatory bowel disease (IBD), malignancy, and hyperthyroidism.
Destination-specific analysis is helpful for establishing the epidemiology of travel-acquired illness 13 (Table 2). A history of travel to the Indian sub-continent in a febrile returned traveller should raise the suspicion of enteric fever: of 416 cases of imported typhoid in the United Kingdom over a three year period, 70% were imported from India and Pakistan 14. Malaria, on the other hand, illustrates a very different epidemiology among imported cases, with relative risks highest among travellers in sub-Saharan Africa 15. Unlike malaria, dengue fever is more likely to be acquired from South Asia, Southeast Asia and Latin America, rather than from Africa 13.
Purpose of travel is another useful piece of the travel history. People who travel for the purpose of visiting friends and relatives (VFR), including VFR children, constitute a particular risk group for acquisition of travel-related infections 12, particularly malaria 16 and enteric fever 4, and in the case of VFR children, acute viral hepatitis 17.
A thorough travel history with an understanding of what illnesses are possible based on dates and style of travel, geographic risks, and specific travel itinerary including activities and behaviors is essential to narrowing the differential diagnosis and ruling out life-threatening travel-acquired infections. Incubation period, defined as the time from initial exposure and infection to manifestation of symptoms, is also useful in refining the differential diagnosis. For instance, travel-acquired illnesses with short incubation periods including dengue, chikungunya, and travellers’ diarrhea, can be reliably excluded if symptoms do not manifest until >2 weeks after leaving the endemic area. Similarly, travel-acquired illnesses with long incubation periods such as tuberculosis (TB), hepatitis B (HBV), or visceral leishmaniasis can be discounted as travel-related if symptoms occur within days of returning from a one-week trip abroad. It is important to consider the earliest and latest possible dates of exposure in ill returned short- and long-term travellers to better inform the use of the incubation period in formulating a differential diagnosis. The following step-wise algorithm is designed to guide the clinician through his or her initial assessment of a returned traveller with fever, and in rare cases, to provide further guidance when inpatient support or specialist consultation is delayed or unavailable.
(CATMAT statements are available at http://www.phac-aspc.gc.ca/tmp-pmv/catmat-ccmtmv/index-eng.php)
Objective: Exclusion of life-threatening, highly communicable, or treatable illness
|A. Pre-travel preparations||Pre-travel consultation: date, location, contact details|
|Immunizations received and dates; oral versus injectable formulation if applicable; completion of full vaccination series for travel and for routine childhood immunizations|
|Malaria prophylaxis: drug, dose, schedule, adherence, duration, side effects|
|Other prophylaxis: drug, dose, schedule, adherence, duration, side effects|
|Other personal protective measures: standby treatment of malaria / travellers’ diarrhea; bednets; clothing; insecticide use|
|Air transportation preparations: deep vein thrombosis (DVT) prophylaxis, medications for jet lag|
|Environmental risk preparations: sun, extreme heat, altitude|
|B. Specific travel itinerary||Dates of travel (approximation of incubation period)|
|Season of travel: rainy, dry|
|Specific destinations: regions; urban, rural; proximity to fresh water; jungle, desert|
|Reason for travel: tourism, business, visiting friends and relatives (VFR), other|
|Style of travel: accommodation; off typical tourist routes; camping, trekking|
|Local population: possible TB contacts, outbreaks, illnesses|
|Transportation: crowding; use of animals such as camels, elephants|
|C. Exposure history*||Street foods / Local water (enteric fever, travellers’ diarrhea)|
|Arthropod bites (malaria, dengue, chikungunya, arboviruses, Rickettsia, African trypanosomiasis)|
|Uncooked meat / unpasteurized dairy (trichinosis, brucellosis, toxoplasmosis)|
|Blood and body fluid exposure: sexual encounters, tattoos, piercings, injections including immunizations, intravenous (IV) drug use, and rabies post-exposure prophylaxis (PEP) (human immunodeficiency virus [HIV], HBV, hepatitis C virus [HCV], herpes simplex virus [HSV], syphilis, gonorrhea (gonococcus) / Chlamydia trachomatis [GC/CT])|
Fresh water activities: swimming, kayaking, rafting (schistosomiasis, leptospirosis)
Animal exposures (Q-fever, brucellosis, tularemia, anthrax, rabies, Crimean-Congo hemorrhagic fever)
Safari (rickettsioses, African trypanosomiasis)
*For epidemiology of specific diseases, please refer to websites of the WHO (World Health Organization) (http://www.who.int/topics/en/), or the Public Health Agency of Canada (PHAC) (http://www.phac-aspc.gc.ca/tmp-pmv/info/index-eng.php), the U.S. Centers for Disease Control and Prevention (CDC) (http://wwwnc.cdc.gov/travel/content/diseases.aspx
|A. Fever pattern||Daily / Continuous||Common: malaria, travellers’ diarrhea, RTI, enteric fever|
|Rare: HIV, Q-fever, brucellosis, TB|
|Saddleback (biphasic)||Common: malaria, dengue|
|Rare: yellow fever, arbovirus|
|Relapsing||Common: malaria, enteric fever|
|Uncommon: amoebic liver abscess, leptospirosis|
|Rare: HIV, Q-fever, brucellosis, TB, endemic mycoses, borreliosis|
|B. Incubation period (Definition: time from exposure / infection to disease manifestation)||<2 weeks||Common: malaria, travellers’ diarrhea, dengue, RTI, influenza|
|Uncommon: rickettsioses, meningitis|
|Rare: yellow fever, arbovirus, viral hemorrhagic fever|
|2-6 weeks||Common: malaria, enteric fever|
|Uncommon: hepatitis A virus (HAV), katayama fever, amoebic liver abscess, hepatitis E virus|
|Rare: HIV, Q-fever, brucellosis, East African trypanosomiasis|
|>6 weeks||Common: malaria|
|Uncommon: HBV, amoebic liver abscess, TB|
|Rare: HIV, visceral leishmaniasis, endemic mycoses, West African trypanosomiasis, HCV|
|C. Fever duration at visit||<7 days||Common: malaria, travellers’ diarrhea, dengue, enteric fever, RTI|
|Uncommon: rickettsioses, leptospirosis, meningitis|
|Rare: yellow fever, arbovirus|
|7-21 days||Common: malaria, enteric fever|
|Uncommon: rickettsioses, viral hepatitis, leptospirosis|
|Rare: HIV, Q-fever, brucellosis|
|>21 days||Common: malaria, enteric fever|
|Uncommon: TB, HBV, bacterial endocarditis|
|Rare: HIV, Q-fever, brucellosis|
Arbovirus: includes other mosquito-borne viruses such as chikungunya, mayaro, O’nyong-nyong, Ross River, sindbis, equine encephalitis, WNV, La Crosse, Oropouche, Rift Valley fever, and tick-borne viruses such as Kyasanur Forest, Omsk, and Crimean-Congo hemorrhagic fever
**Consider referral to a person with expertise in tropical medicine or infectious diseases (as available) if primary laboratory investigations yield no definitive diagnosis and patient is not improving, or patient is at risk of complications (e.g., pregnant women, children, underlying co-morbidities, immunocompromised, etc). Additional support, if required, may be sought through the Canadian Malaria Network (http://www.phac-aspc.gc.ca/tmp-pmv/quinine/index-eng.php)**
Consider if patient fulfills the following criteria:
|Travelled to the Indian Sub-Continent or Southeast Asia||Travelled outside the Indian Sub-Continent or Southeast Asia|
- Step 4 is not a substitute for Step 3 (Primary laboratory investigations after comprehensive physical examination), nor should empiric therapy preclude ongoing and close follow-up of the patient. Undifferentiated fever refers to fever without prominent localizing symptoms or signs, and is often the presenting complaint in many travel-acquired illnesses including malaria and enteric fever. It is essential that all febrile returned travellers to potentially malarious areas undergo malaria screening with 2-3 smears over 48 hours ± rapid antigen testing. Adult patients who have not improved substantially, either subjectively or objectively, over the previous 48-72 hours are candidates for empiric therapy as above while investigations are pending. These patients require frequent clinical reassessment (every 1-2 days) until either a diagnosis is made and definitive therapy instituted, or until subjective and objective clinical improvement is achieved. Prior to initiation of empiric therapy as above, all samples for microbiological testing should have been obtained as outlined in Step 3.
- Caution must be exercised in the evaluation and empiric therapy of fever in children, given the higher rate of complicated disease in this age group. Clinicians should have a low threshold for admission and initiation of IV therapy for presumed enteric fever, in which case a parenteral third generation cephalosporin (ceftriaxone or cefotaxime) could be considered. Similarly, use of doxycycline and ciprofloxacin is not routine in children and generally reserved for specific cases in which the benefits of these antibiotics are felt to exceed the potential risks (permanent dental staining, arthropathy). Consultation with a specialist experienced in the treatment of pediatric tropical diseases should be considered.
*3-day regimen for suspected travellers’ diarrhea; 7-10-day regimen for suspected enteric fever
**this will also cover leptospirosis
|Travel-acquired infection||Diagnostic test(s)|
|Acute travellers’ diarrhea / gastroenteritis (60-80% bacterial)||
|Enteric fever due to Salmonella enterica serovar Typhi or Paratyphi||
|Skin and soft tissue infection||
|Acute UTI / STI||
|Other potentially travel-acquired infections diagnosed by serology||
Committee to Advise on Tropical Medicine and Travel (CATMAT) Statements
Canadian Recommendations for the Prevention and Treatment of Malaria among International Travellers (2009) - http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/35s1/index-eng.php
Statement On Persistent Diarrhea In The Returned Traveller (2006) - http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/06vol32/acs-01/index-eng.php
Statement on Travellers and Sexually Transmitted Infections (2006) - http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/06vol32/acs-05/index-eng.php
Public Health Agency of Canada
Travel Health Notices website - http://www.phac-aspc.gc.ca/tmp-pmv/pub-eng.php
National Microbiology Laboratory - http://www.nml-lnm.gc.ca/index-eng.htm
United States - Centers for Disease Control and Prevention - http://www.cdc.gov/
Viral Special Pathogens Branch, NCID - http://www.cdc.gov/ncidod/dvrd/spb/mnpages/disinfo.htm
VSPB specimen submission info - http://www.cdc.gov/ncidod/dvrd/spb/mnpages/specimen.htm (phone number 404-639-2888)
World Health Organization outbreak site – www.who.int/csr/don/en
Promed – www.promedmail.org
Articles for further reading
Johnston V, Stockley JM, Dockrell D, et al. Fever in returned travellers presenting in the United Kingdom: Recommendations for investigation and initial management. J Infection 2009;59:1-18.
Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relationship to place of exposure in ill returned travellers. N Engl J Med 2006;354:119-130.
Boggild AK, Page AV, Keystone JS, Morris AM, Liles WC. Delay in diagnosis: malaria in a returning traveller. CMAJ 2009;180(11):1129-1131. Available at: http://www.cmaj.ca/cgi/content/full/180/11/1129
Rynor B. Dengue fever on the rise at tourist getaways. CMAJ 2010;182(4):E195-196. Available at: http://www.cmaj.ca/cgi/content/full/182/4/E195
Szakacs TA, McCarthy AE. An all-inclusive vacation. CMAJ 2007;177(1):29-31. Available at: http://www.cmaj.ca/cgi/content/full/177/1/29
Daneman N, Slinger R. Tache noire. CMAJ 2008;178(7):841. Available at: http://www.cmaj.ca/cgi/content/full/178/7/841
- Committee to Advice on Tropical Medicine and Travel. Canadian Recommendations for the Prevention and Treatment of Malaria Among International Travellers. CCDR 2009;34:1-45.
- Steffen R, Rickenbach M, Wilhem U, Helminger A, Schar M. Health problems after travel to developing countries. J Infect Dis 1987;156:84-91.
- Hill D. Health problems in a large cohort of Americans traveling to developing countries. J Travel Med 2000;7:259-266.
- Wilson M, Weld L, Boggild A et al. Fever in returned travelers: results from the GeoSentinel Surveillance Network. Clin Infect Dis 2007;44:1560-1568.
- Bottieau E, Clerinx J, Schrooten W et al. Etiology and outcome of fever after a stay in the tropics. Arch Intern Med 2006;166:1642-1648.
- Doherty J, Grant A, Bryceson A. Fever as the presenting complaint of travellers returning from the tropics. QJM 1995;88:277-281.
- O'Brien D, Tobin S, Brown G, Torresi J. Fever in returned travelers: review of hospital admissions for a 3-year period. Clin Infect Dis 2001;33:603-609.
- Antinori S, Galimberti L, Gianelli E et al. Prospective observational study of fever in hospitalized returning travelers and migrants from tropical areas, 1997-2001. J Travel Med 2004;11:135-142.
- Parola P, Soula G, Gazin P, Foucault C, Delmont J, Brouqui P. Fever in travelers returning from tropical areas: prospective observational study of 613 cases hospitalised in Marseilles, France, 1999-2003. Travel Med Infect Dis 2006;4:61-70.
- West N, Riordan F. Fever in returned travellers: a prospective review of hospital admissions for a 2(1/2) year period. Arch Dis Child 2003;88:432-434.
- Klein J, Millman G. Prospective, hospital based study of fever in children in the United Kingdom who had recently spent time in the tropics. BMJ 1998;316:1425-1426.
- Hagmann S, Neugebauer R, Schwartz E et al. Illness in children after international travel: analysis from the GeoSentinel Surveillance Network. Pediatrics 2010;125:e1072-e1080.
- 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;354:119-130.
- Cooke F, Day M, Wain J, Ward L, Threlfall E. Cases of typhoid fever imported into England, Scotland and Wales (2000-2003). Trans R Soc Trop Med Hyg 2007;101:398-404.
- Freedeman DO. Malaria prevention in short-term travellers. N Engl J Med 2008;359:603-612.
- Centers for Disease Control and Prevention. CDC surveillance summaries - malaria surveillance: United States 2004. MMWR 2006;55:23-37.
- Behrens R, Collins M, Botto B, Heptonstall J. Risk for British travellers of acquiring hepatitis A. BMJ 1995;311:193.
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