Outbreak overload: fever in the returning traveller

Dr. Alissa Wright (biography and disclosures)
Disclosures: Merck – single Advisory Board, Gilead – co-investigator in a clinical trial, Sunovion and Pfizer – grants funded post-grad training. Mitigating Potential Bias: recommendations are consistent with current practice patterns and treatments/recommendations in this article are unrelated to products/services/treatments involved in disclosure statements.

What have I noticed with regards to this condition?

The outbreak of Ebola in West Africa has made us all aware that our mobile society comes with the threat of spreading infectious disease. With Ebola, MERS, Chikungunya, and avian influenza, the list of new and emerging travel-related infections is growing at an alarming pace; it leaves clinicians feeling overwhelmed and uncertain in their approach to patients with fever after travel.

What does the literature say on this topic?

Canadians travel a lot and are increasingly traveling to more exotic and remote destinations. Unfortunately, travel does carry certain risks with respect to infection; it is estimated that 20-70% of travellers from developed to developing countries become ill.(1) Approximately 8% of these travellers seek medical care either during or after their trip.(2) Many of these illnesses are entirely preventable, but a significant proportion of Canadian travellers do not receive any pre-travel advice before leaving the country.(3) They are missing the chance to get new immunizations and update their existing immunizations and they do not receive appropriate malaria and other chemoprophylaxis.

Travellers who present to medical attention upon their return can harbour serious infections. Potentially life-threatening infections include malaria, typhoid or paratyphoid fever (enteric fever), and dengue fever. In Canadians with fever and no other localizing signs or symptoms, these were also the most frequent diagnoses reported to CanTravNet from 2009-2011.(3) CanTravNet is composed of a small number of outpatient Canadian travel clinics from major urban cities which contribute anonymous surveillance data on travel-related illness to the world-wide GeoSentinel data network. Although limited to those patients who present to those specific sites for assessment, these data are still considered a fair representation of patients seen in the outpatient setting. Therefore, it is entirely possible that the febrile traveller who presents to an outpatient clinic for assessment has one of these three infections.

Consequently, post-travel assessment of a febrile patient must be comprehensive, but completed in a timely manner so that patients get the care they need. This assessment should consider new and emerging infections but it must not ignore the more common, life-threatening, travel related illnesses. The Ebola epidemic has most clearly demonstrated the need for both a rapid workup and also a broad differential. Febrile travellers from the affected regions need to be appropriately isolated and tested for Ebola. However, isolation and testing has resulted in delays in care for some patients, most of whom have not had Ebola.(4) Moreover, patients can have more than one reason for being ill even if they do have rare diagnosis like Ebola.(5) In the years just prior to the Ebola outbreak, malaria was the most common diagnosis among all returning travellers to Canada – except immigrants – from the three countries in West Africa affected.(6) Ten percent of these patients were critically ill with life threatening manifestations such as cerebral malaria. Therefore, always ensure the common infections like malaria have been looked for and ruled out – even if you think something else may be the culprit.

Finally, travellers who visit friends and relatives (VFRs) may be at particularly high risk of serious travel-related disease. These travellers are typically immigrants returning to their country of origin and, therefore, can be blind to the dangers of travel. They also are less likely to seek pre-travel advice, often because they are returning to a destination they know.(3) Consequently, infections such as malaria are not identified as life-threatening because individuals who live in these areas have naturally acquired immunity with milder presentations.(7) However, malaria immunity wanes when these individuals move to non-endemic areas and VFRs are therefore more susceptible to this infection than they remember. These patients actually end up at greater risk of malaria and typhoid fever as a result and they make up the majority of cases in non-endemic countries.(8) Therefore, special attention should be paid to the traveller from an endemic region who returns ill after a trip home to visit family and friends.

What I recommend (practice tip)

1. Don’t forget about the basics! Despite the press, diagnoses such as malaria and enteric fever are still common causes of fever in a returning traveller, even those who travel to areas of risk for emerging infections. Malaria is an emergency and this should be presumed to be the diagnosis in a febrile patient until proven otherwise. At least three blood smears for malaria should be done separated by 12-24 hours each regardless of whether another cause for the fever is found. Initial smears can be negative due to low parasite burden which is the reason for the repeated testing.
2. Travel-related risk of infection can change over time and you will need up to date information to evaluate your patient. After you have considered malaria and ordered appropriate testing, ensure that your differential diagnosis is complete by consulting governmental websites for updated travel advisories. http://travel.gc.ca/travelling/advisories or http://wwwnc.cdc.gov/travel/notices.
3. Don’t forget to protect yourself and other patients. Patients who return with febrile illnesses can harbour transmissible infections. They may require special isolation precautions such as droplet or airborne precautions for patients with fever and respiratory illnesses that are undiagnosed.
4. Ask for help if needed. Patients can be sent to the Emergency Department for malaria testing and clinicians should have a low threshold to do so for febrile, unwell patients who have recently been in a malaria endemic region. Not only is malarial testing available at all hours, but also the treatment may only be available through the hospital if a serious infection is confirmed. Similarly, your local Infectious Disease physician is also happy to answer travel-related questions over the phone should you need additional information.
5. Canadians are missing opportunities to prevent illness. If you see a patient who has plans to travel and cannot give advice, recommend they seek the advice of a local travel clinic before they go. It could save their life.

References

1. Ryan ET, Wilson ME, Kain KC. Illness after international travel. N Engl J Med. 2002 Aug 15;347(7):505-16. (Request with CPSBC or view UBC) DOI:10.1056/NEJMra020118
2. Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med. 2006 Jan 12;354(2):119-30. (View summary or the full article with UBC) DOI:10.1056/NEJMoa051331
3. Boggild AK, Geduld J, Libman M, Ward BJ, McCarthy AE, Doyle PW, et al. Travel-acquired infections and illnesses in Canadians: surveillance report from CanTravNet surveillance data, 2009-2011. Open Med. 2014 Feb 11;8(1):e20-32. (View)
4. Karwowski MP, Meites E, Fullerton KE, Stroher U, Lowe L, Rayfield M, et al. Clinical inquiries regarding Ebola virus disease received by CDC–United States, July 9-November 15, 2014. MMWR Morb Mortal Wkly Rep. 2014 Dec 12;63(49):1175-9. (View)
5. Kratz T, Roddy P, Tshomba Oloma A, Jeffs B, Pou Ciruelo D, de la Rosa O, et al. Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes. PLoS One. 2015 Jun 24;10(6):e0129333. (View)
6. Boggild AK, Esposito DH, Kozarsky PE, Ansdell V, Beeching NJ, Campion D, et al. Differential diagnosis of illness in travelers arriving from Sierra Leone, Liberia, or Guinea: a cross-sectional study from the GeoSentinel Surveillance Network. Ann Intern Med. 2015 Jun 2;162(11):757-64. (View)
7. Doolan DL, Dobano C, Baird JK. Acquired immunity to malaria. Clin Microbiol Rev. 2009 Jan;22(1):13,36, Table of Contents. (View)
8. Public Health Agency of Canada. Statement on international travellers who intend to visit friends and relatives. [Internet]. 2015 [cited October 2, 2015.]. (View)

Resources:

1. http://travel.gc.ca/travelling/advisories
2. http://wwwnc.cdc.gov/travel/notices
3. http://www.istm.org/cantravnet

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Outbreak overload: fever in the returning traveller

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