Unexpected Souvenirs: The Latest in Fever in the Returning Traveller

The Travel History

When assessing a febrile returning traveler, epidemiologic context is everything. Start with open-ended questions, then narrow in on symptom onset, duration, and associated complaints. When time permits, use a structured approach to gather key travel details across the following domains:

1. Specific Travel Itinerary

• Dates of travel and destinations (cities, countries)

• Urban vs. rural settings

• Purpose of travel (e.g., tourism, work, visiting friends or relatives)

2. Pre-travel Preparation

• Vaccinations — cover the 3 R’s:

  • Routine (e.g., MMR, Tdap)

  • Recommended (e.g., Hepatitis A, typhoid)

  • Required (e.g., yellow fever for entry)

• Malaria prophylaxis: drug used, adherence, and timing

3. Exposures During Travel

• Food and water sources (raw or unclean consumption)

• Animal or insect bites

• Freshwater contact (risk of schistosomiasis)

• Sexual activity, tattoos, or medical/dental procedures

4. Healthcare Encounters Abroad

• Any hospitalizations, injections, or blood transfusions

5. Host Factors

• Immunocompromised state, chronic illnesses, or pregnancy

6. Contacts and Outbreaks

• Sick contacts during or after travel

• Illness in travel companions

• Known outbreaks in visited regions

   

Mnemonic: TRAVEL

A helpful way to structure your history:

• Time, place, and purpose

• Routine and risky exposures

• Adherence to prophylaxis

• Vaccinations (Routine, Recommended, Required)

• Epidemiologic context

• Local outbreaks and sick contacts

The Physical Exam

In the emergency department, a focused yet thorough physical exam is essential for identifying subtle but critical diagnostic clues in the febrile traveler. These findings often help narrow the differential and guide early management.

Vital Signs

• Watch for relative bradycardia, which can suggest typhoid fever

• Keep in mind that antipyretics may obscure a fever, so take the medication history seriously

Neurologic Exam

• Assess mental status

• Screen for meningismus

• Look for focal neurologic deficits

Skin Findings

Skin clues are often diagnostic. Look for:

• Rose spots – suggestive of typhoid

• Eschar – seen in rickettsial infections

• Petechiae or jaundice – may indicate dengue, leptospirosis, or viral hepatitis

• Dengue rash – classically described as “islands of white in a sea of red”

Cardiopulmonary

• Listen for crackles, wheezes, or new murmurs, which may indicate systemic involvement such as endocarditis or pulmonary infection

Abdominal Exam

• Check for tenderness, hepatosplenomegaly, or a positive Murphy’s sign

• Don’t overlook lymphadenopathy, which may suggest viral infections, HIV, or parasitic causes

Though often subtle, these physical findings can be invaluable in guiding diagnostic testing and timely interventions for returning travelers in the ED.

Diagnostic Testing

Use your initial assessment, HPI, and physical exam to guide your differential and targeted diagnostics. At minimum, the following labs should be considered:

Core Workup

• CBC with differential: Look for anemia, lymphopenia, thrombocytopenia, and eosinophilia (which may suggest parasitic infection)
• LFTs & bilirubin: Elevations may point to malaria, viral hepatitis, or typhoid
• Metabolic Panel & creatinine: Assess end-organ function
• Urinalysis + urine culture
• Pregnancy test: Always order in women of childbearing potential
• Blood cultures (x2): Especially if fever persists or systemic illness is suspected

Additional Testing Based on Presentation

• Malaria testing:
  • Rapid test (if available), plus
  • Thick & thin blood smears q12h until 3 negative smears
  • Parasitemia can be cyclical – don’t rule out malaria prematurely
• Dengue serology: Consider in appropriate regions/symptoms
• Stool studies: If diarrhea is present
• CXR: For respiratory symptoms or abnormal lung exam
• Other tests PRN: Viral serologies, sputum C&S, AFB, amylase, or targeted imaging

Consult your local infectious disease or travel medicine specialist – may include ID, EM, GIM, or Micro – for guidance on uncommon pathogens or complex cases.

Differential Diagnosis

In the ED, a detailed travel history is often your most powerful diagnostic tool. When a patient presents with fever after travel, start with the basics:

Where did they go? When did they return? What did they do? How long were they there?

These questions lay the foundation. A focused history, combined with the clinical picture and timing of symptoms, can rapidly narrow your differential.

Use the following three-part framework to guide your diagnostic approach:

1. Geographic Risk

Start by using the patient’s destination(s) to shape your initial differential. Many travel-related diseases are geographically clustered. For example:

(Adapted from Wrynn et al., 2023)

2. Timing & Incubation Period

Understanding when symptoms began in relation to the return date helps you rule in—or rule out—specific pathogens. For example:

• Malaria can present weeks after return

• Dengue typically appears within 4–7 days

• Viral hepatitis has a longer incubation (2–6 weeks)

A timeline-based approach keeps your differential focused.

(obtained from Khan, 2013)

(obtained from Khan, 2013)

3. Syndromic Presentation

Finally, categorize based on how the patient presents clinically. Consider common symptom groupings like:

• Fever + Rash: Dengue, chikungunya, rickettsial infections

• Fever + GI symptoms: Typhoid, hepatitis A, parasitic infections

• Fever + Respiratory symptoms: COVID-19, TB, influenza

This allows you to act quickly and initiate empiric management where needed

(obtained from Khan, 2013)

Malaria

When evaluating a febrile returning traveler, there’s one golden rule: Assume malaria until proven otherwise.

Malaria is a potentially fatal disease that can progress rapidly—particularly when caused by Plasmodium falciparum, the species responsible for most severe cases and the majority of imported malaria in Canada.

Transmission

Malaria is transmitted via the bite of the female Anopheles mosquito. While five Plasmodium species infect humans, your immediate priority in the ED is twofold:

1. Rule out P. falciparum

2. Identify signs of severe malaria

Early recognition is critical, as symptoms can be nonspecific. Key features include:

• Onset: Typically ≥7 days after exposure, but can present weeks to months after return

• Symptoms: Fever, chills, myalgias, headache—often mistaken for a viral illness

• Fever pattern: May appear cyclical (every 48–72 hours), but often irregular early on

• Red flags for severe disease:

  • Altered mental status

  • Respiratory distress

  • Jaundice

  • Severe anemia

  • Hypoglycemia

  • Renal failure

Bottom line: Even if the fever looks benign, never rule out malaria without appropriate testing.

From PHC: https://www.canada.ca/en/public-health/services/diseases/malaria/health-professionals-malaria.html

Timely and accurate testing is critical when malaria is on the differential. Here’s how to approach it in the ED:

Gold Standard: Thick and Thin Blood Smears

• The definitive test for malaria

• Identifies:

  • Presence of parasites

  • Plasmodium species

  • Level of parasitemia

⚠️ One negative smear does not rule out malaria.

In early disease or low parasitemia, the initial smear may be falsely negative.

If clinical suspicion remains high:

• Repeat smears every 12–24 hours

• Continue until 3 consecutive smears are negative

Management

Severe Malaria

Suspect severe malaria in patients with any of the following:

• Altered level of consciousness

• Hypotension or shock

• Severe anemia

• Respiratory distress or organ dysfunction

Treatment:

• First-line:

  • IV artesunate (available in Canada through the Canadian Malaria Network)

  • Administer as soon as possible—do not delay for confirmatory testing if clinical suspicion is high

• If artesunate is unavailable:

  • IV quinine

    • Requires cardiac monitoring due to risk of QT prolongation and hypoglycemia

Uncomplicated Malaria

For stable patients who can tolerate oral medications:

Options include:

• Atovaquone-proguanil (Malarone)

• Quinine + doxycycline

  • If doxycycline is contraindicated (e.g., pregnancy), substitute with clindamycin

💡 Don’t forget: Treatment choice may vary based on species, local resistance patterns, pregnancy status, and drug availability. Involve infectious disease if you’re unsure.

From PHC: https://www.canada.ca/en/public-health/services/diseases/malaria/health-professionals-malaria.html

Special Populations:

• Pregnant patients: Artesunate is safe in all trimesters and preferred.
• Avoid quinine and doxycycline unless necessary.

From PHC: https://www.canada.ca/en/public-health/services/diseases/malaria/health-professionals-malaria.html

**Note: Avoid steroids in severe malaria, as they may worsen complications (WHO, CDC, Canada recommendations)

Prevention

• Chemoprophylaxis (Malarone, doxycycline, mefloquine) reduces but doesn’t eliminate risk.
• Focus on mosquito avoidance: use insecticide-treated nets, stay in screened or air-conditioned rooms, wear long clothing, and apply DEET repellent.

Key Takeaways

• Suspect malaria in any febrile traveler from endemic areas.
• Early diagnosis and prompt treatment save lives.
• A single negative smear does not rule out malaria – repeat testing is essential.
• Even if prophylaxis was taken, malaria is not excluded.
• Engage ID early and access IV artesunate through Canadian Malaria Network (CMN).
• Report cases to public health where applicable.

Dengue Fever

Dengue is a viral hemorrhagic fever transmitted by Aedes mosquitoes and is endemic in over 100 countries, particularly in tropical and subtropical regions. With the rise in global travel and the effects of climate change, cases are increasing worldwide—making dengue a critical diagnosis to consider in febrile travelers.

Clinical Presentation

Dengue presents in three forms:

1. Classic Dengue: High fever, intense body aches (“breakbone pain”), headache, rash, and abdominal discomfort. Most recover fully.
2. Severe Dengue (Dengue Hemorrhagic Fever): Severe bleeding, shock, and organ dysfunction. Key signs include petechiae (classic rash pattern: “islands in a sea of red”) and plasma leakage, which can be fatal if untreated.
3. Critical Phase: After initial fever, the patient enters a critical phase with risk of hypotension and shock due to fluid leakage. Watch for persistent vomiting, severe abdominal pain, and bleeding.

Diagnostic Testing

• CBC: thrombocytopenia, leukopenia, and mild to moderate LFT elevation – often non-specific
• Severe diseases: rising hematocrit, AKI
• Coagulation panel: if bleeding is a concern
• Urinalysis: may show hematuria, proteinuria
• Dengue serology
• Imaging: CXR or bedside POCUS if respiratory symptoms or concern for third spacing

Management

• Supportive care is the cornerstone of treatment.
• Fluid resuscitation is vital in severe cases.
• Avoid NSAIDs and aspirin due to bleeding risk. Use acetaminophen for pain relief.
• If Severe Dengue (DHF) is suspected, hospitalization and close monitoring are essential, often requiring ICU care.

Prevention

• Vector control is key: advise travelers to use DEET-based repellents, wear protective clothing, and avoid mosquito-infested areas (active throughout the day)
• Dengvaxia vaccine is approved for those with a previous confirmed dengue infection in endemic areas, but it’s not for general travelers.

Key Takeaways

• Dengue should be on the radar for any febrile traveler from tropical regions.
• Watch for the classic triad: fever, rash, and severe myalgias.
• Be aware of the risk for DHF in patients with severe bleeding or shock.
• Those who have previously had dengue infection are at highest risk for DHF
• Always report confirmed or suspected cases to public health.

Early recognition, supportive care, and fluid management can prevent the progression to life-threatening complications like shock and organ failure.

Typhoid Fever

Typhoid fever, caused by Salmonella enterica serotype Typhi, is a serious systemic illness transmitted via fecally contaminated food or water. It’s common in travelers returning from South Asia, Africa, and Latin America, particularly those visiting friends and relatives. In Canada, about 140 cases are reported annually – nearly all travel-related, with rare domestic outbreaks.

Clinical Presentation

Typhoid has a gradual onset over 1-2 weeks

• Starting with low-grade fever, fatigue, headache, and abdominal discomfort.
• GI symptoms vary by age – diarrhea is more common in children, constipation in adults.
• Rose spots (faint salmon-colored rash) are classic but rare.
• Look for relative bradycardia and hepatosplenomegaly.
• In severe cases, typhoid can progress to intestinal perforation, GI hemorrhage, encephalopathy, or shock, especially if left untreated.

Diagnostic Testing

• Blood cultures (x2) are the gold standard
• Labs may show leukopenia and elevated LFTs, though non-specific
• Stool and urine cultures, and rapid tests (e.g., BioFire GI panel), can support diagnosis but are less reliable early in illness.

Given time constraints, ED diagnosis often relies on a combination of travel history and clinical judgement.

Management

• Start empiric antibiotics in the ED based on travel history:
  • Most regions: Ceftriaxone or Azithromycin are safe first-line options
  • If returning from Pakistan or Iraq (high resistance areas):
    • Uncomplicated cases: Trial of azithromycin
    • Complicated/severe disease: start a carbapenem
• Avoid fluoroquinolones unless confirmed susceptibility
• Supportive care (IV/PO fluids, antipyretics) is crucial.
• Fever may persist for several days despite therapy; after 5 days, reassess for drug resistance or occult infection

Prevention

• Typhoid is vaccine-preventable: Travelers ≥2 years old should get vaccinated before visiting high-risk areas (oral or injectable options).
• Emphasize food and water hygiene: “Boil it, cook it, peel it, or forget it.”
• No vaccine exists for paratyphoid – safe food practices are essential.
• Report confirmed or suspected cases to public health.

Key Takeaways

• Always suspect typhoid in febrile travelers from endemic regions.
• Order blood cultures early, and don’t rely on response to antimalarials.
• Start appropriate empiric antibiotics based on destination.
  • Returning from Pakistan or Iraq: Azithromycin or Carbapenem
• Reinforce travel hygiene and vaccination for prevention.
• Stay vigilant – complications can be life-threatening if missed.

Summary

When faced with a febrile traveler, your most important diagnostic tool is a good travel history. Always ask:
Where did they go? What did they do? When did they return?
This context can drastically narrow your differential and help you act quickly.

Always Rule Out Malaria First!
If there’s any travel to sub-Saharan Africa or South Asia, malaria is your top priority. It’s rapidly fatal if missed, and early recognition saves lives. Send blood smears immediately-even if symptoms are vague or intermittent.

Think Regionally:

• Tropical regions → consider arboviruses:
  • Dengue, Chikungunya, Zika – all present with fever, rash, and myalgias, but each has distinct risks and complications.
• South Asia or Latin America → consider Enteric fever (typhoid) – look for subacute fever with abdominal symptoms, and don’t forget to ask about food or water exposures.

Don’t Forget the Common Culprits:

• COVID-19, Influenza, and even MERS-CoV remain relevant in travel-related fever presentations.

Broaden the Differential:
If infectious causes don’t fit, don’t overlook non-infectious etiologies:

• PE/DVT (especially after long-haul flights)
• Drug fevers
• Hypersensitivity reactions

In a busy environment, it’s tempting to rush, but for febrile travelers, a few extra minutes spent on a detailed history can dramatically alter the trajectory of care – and possibly save a life. Plus, you’ll often hear some fascinating stories.