Fever in the Returning Traveler

Aka: Fever in the Returning Traveler, Febrile Ilness in Recent Travelers, History from the Ill Returning Traveler, Fever in Returned Travelers

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II. Indications

  1. Recent travel in the last 3-4 weeks

III. Risk Factors

  1. Longer trips
  2. Lack of Pretravel Consultation (esp. lack of travel Vaccination, Malaria Chemoprophylaxis)
  3. Underlying comorbidity
  4. Pregnant women and children
  5. Travel to rural regions
  6. Outdoor activities (e.g. hiking, water activities)

IV. Precautions: Malaria and Other Important Infections

  1. Fever in a returning traveler from Malaria endemic area is Falciparum Malaria until proven otherwise
    1. Stat blood smear with direct communication with reading pathologist
    2. Especially consider Malaria with Leukopenia and Left Shift, Thrombocytopenia
    3. Up to 50% of Malaria cases are misdiagnosed on the first visit
    4. Initial presentations are often mild and non-specific (fever, chills, malaise, myalgia, Headache)
    5. This is an emergent evaluation
  2. Other common causes in the differential of Malaria
    1. Viral Hepatitis
    2. Typhoid Fever
    3. Dengue Fever
    4. Chikungunya
    5. Zika Virus
  3. Other important travel-related infectious disease to consider
    1. Leptospirosis
    2. Trypanosomiasis
    3. Schistosomiasis
    4. Rickettsial Disease (e.g. Typhus, Rocky Mountain Spotted Fever and other Tick Borne Illness)
  4. Consider Bacterial infectious conditions unrelated to travel
    1. Pneumonia
    2. Urinary Tract Infection
    3. Meningitis

V. Causes: Fever with other organ involvement

  1. See Cutaneous Conditions in Febrile Returning Traveler
  2. See GI Conditions in Febrile Returning Traveler
  3. See Altered Mental Status in Febrile Returning Traveler
  4. See Lymphadenopathy in the Febrile Returning Traveler

VI. Causes: By frequency in febrile travelers returning to developed countries

  1. Malaria (21%)
  2. Febrile Diarrhea (15%)
  3. Febrile respiratory infections (14%)
  4. Dengue Fever (6%)
  5. Non-Diarrheal, febrile gastrointestinal illness (5%)
  6. Fever with rash (4%)
  7. Genitourinary infections with fever (4%)
  8. Ricckettsia (2%)
  9. Typhoid Fever or Paratyphoid Fever (2%)
  10. Wilson (2007) Clin Infect Dis 44(12): 1560-8 [PubMed]

VII. Causes: Geographic regions

  1. Caribbean
    1. Chikungunya
    2. Malaria (Haiti)
    3. Dengue Fever
    4. Zika Virus
    5. Acute Histoplasmosis
    6. Leptospirosis
  2. Central America and South America
    1. Malaria (primarily Plasmodium Vivax)
    2. Dengue Fever
    3. Yellow Fever
    4. Enteric Fever
    5. Zika Virus
    6. Leptospirosis
    7. Leishmaniasis
    8. Chagas Disease
    9. Histoplasmosis
    10. Coccidioidomycosis
    11. Bartonellosis
  3. South Central Asia
    1. Malaria (typically NOT Plasmodium Falciparum)
    2. Dengue Fever
    3. Enteric Fever (Salmonella typhi and paratyphi)
    4. Severe Acute Respiratory Syndrome (SARS)
    5. Chikungunya virus
  4. Southeast Asia
    1. Malaria (typically NOT Plasmodium Falciparum)
    2. Dengue Fever
    3. Severe Acute Respiratory Syndrome (SARS)
    4. Enteric Fever
    5. Chikungunya virus
    6. Leptospirosis
    7. Japanese Encephalitis
    8. Leishmaniasis
  5. Sub-Saharan Africa
    1. Malaria (mostly Plasmodium Falciparum)
    2. Tick-borne Rickettsiae
    3. Acute Schistosomiasis
    4. Filariasis
    5. Yellow Fever
    6. Leishmaniasis
    7. Hemorrhagic fever
    8. African trypanosomiasis
    9. Enteric Fever
  6. West Africa (Liberia, Sierra Leone, Guinea)
    1. Ebola (as of 2014)
  7. Worldwide conditions
    1. Human Immundeficiency Virus (HIV)
    2. Hepatitis A (common) , Hepatitis E, and other Viral Hepatitis
    3. Malaria
    4. Tuberculosis
    5. COVID-19
  8. References
    1. See CDC Yellow Book resource below

VIII. Causes: Exposure Related Febrile Illnesses

  1. Sexually Transmitted Disease
    1. Gonorrhea
    2. Human Immunodeficiency Virus (HIV)
    3. Syphilis
    4. Hepatitis B Virus
    5. Chancroid
    6. Herpes Simplex Virus
  2. Vector Contact
    1. See Vector Borne Disease
    2. Mosquitoes
      1. Malaria
      2. Dengue Fever
      3. Yellow Fever
      4. Chikungunya
    3. Ticks
      1. Rickettsioses
      2. Tularemia
    4. Reduviid Bugs
      1. American Trypanosomiasis
    5. Tsetse Flies
      1. African Trypanosomiasis
  3. Animal Contact
    1. See Pet-Borne Parasitic Zoonoses
    2. Rabies
    3. Q Fever
    4. Tularemia
    5. Brucellosis
    6. Echinococcosis
    7. Plague
    8. Psittacosis (Bird exposure)
  4. Infected Person Contact
    1. Viral Hemorrhagic Fever
    2. Enteric Fever (Salmonella typhi and paratyphi)
    3. Meningococcal infection
    4. Tuberculosis
    5. Severe Acute Respiratory Syndrome
  5. Raw or undercooked meat or fish
    1. See Foodborne Illness
    2. Enteric Infections
    3. Cestodiasis
    4. Trichinosis
    5. Typhoid Fever
    6. Cholera
    7. Salmonellosis
  6. Untreated water or unpasteurized dairy products
    1. See Waterborne Illness
    2. Salmonellosis
    3. Shigellosis
    4. Hepatitis A
    5. Amebiasis
    6. Cholera
    7. Brucellosis (dairy exposure)
    8. Tuberculosis (dairy exposure)
  7. Freshwater Exposure
    1. Acute Schistosomiasis (Katayama Fever)
    2. Leptospirosis
    3. Campylobacter
  8. Barefoot Exposure
    1. Strongyloidiasis
    2. Cutaneous Larva Migrans
  9. Infected soil exposure or cave exploring
    1. Histoplasmosis
    2. Rabies
    3. Marburg Hemorrhagic Fever
    4. Leptospirosis
    5. Tick-Borne Relapsing Fever
    6. Tetanus

IX. Causes: Incubation Periods

  1. Incubation <7-10 days
    1. Traveler's Diarrhea
    2. Dengue Fever (common)
    3. Yellow Fever
    4. Spotted Fever (Rickettsiae)
    5. Meningococcemia
    6. Chikungunya
    7. Zika Virus
    8. Severe Acute Respiratory Syndrome (SARS)
  2. Incubation 7-21 days
    1. Leptospirosis
    2. Viral Hemorrhagic Fevers (including Ebola)
    3. Japanese Encephalitis
    4. Malaria (common)
    5. Enteric Fevers
      1. Typhoid Fever (common)
      2. Paratyphoid
    6. Typhus
    7. East African Trypanosomiasis
    8. Q Fever
  3. Incubation >21 days
    1. Human Immundeficiency Virus (HIV)
    2. Hepatitis A (common) , Hepatitis E, and other Viral Hepatitis
    3. Malaria (common, symptoms may be delayed months)
    4. Tuberculosis (common, symptoms may be delayed years)
    5. Amebic Liver Abscess
    6. West African Trypanosomiasis
    7. Borreliosis
    8. Brucellosis
    9. Visceral Leishmaniasis
    10. Systemic Schistosomiasis (Katayama)
    11. Leishmaniasis
  4. Months
    1. Chagas Disease
    2. Tuberculosis

X. History

  1. Travel itinerary (establish a travel and exposure timeline)
    1. Who did you see (family, wildlife, farm animals)?
    2. Where did you travel (what region and countries, what environments, what living conditions)?
    3. When did you travel and for how long?
    4. What did you do (wilderness travel, mission work, farm work, construction)?
    5. Did you seek medical care while traveling?
  2. Exposures
    1. Insects (e.g. ticks, Mosquitos)
      1. See Vector Borne Disease
    2. Animal exposures (including farm animals)
      1. See Pet-Borne Infection
      2. See Animal Bite
      3. See Marine Injury
    3. Skin Trauma
      1. See Cellulitis for specific exposures
    4. Contagious contacts (in travel country or home country)
    5. Sexually Transmitted Infection risk or exposure while traveling
    6. Food sources of infection
      1. See Foodborne Illness
    7. Water sources of infection (ingestion, fresh water swimming)
      1. See Waterborne Illness
  3. Medications
    1. New medications (especially immune compromising medications)
    2. Medications purchased in local pharmacies while traveling
    3. Pretravel Immunizations (and other Immunization status)
    4. Pretravel antibiotic prophylaxis (e.g. Mefloquine for Malaria Prophylaxis)
      1. Assess compliance with medication regimen (as low as 6% in some Malaria studies)
      2. Even with compliant use of prophylaxis, Malaria may still occur

XI. Symptoms: General

  1. Fever Pattern and course
    1. See Fever
  2. Cough and other Respiratory Symptoms
    1. Often due to common Upper Respiratory Infections
    2. Influenza or Pneumonia (Close contact with local population)
    3. Q Fever (Farm exposure to cattle, goats, sheep or unpasteurized milk)
    4. Legionellosis
    5. Leptospirosis
    6. Acute Schistosomiasis or Katayama Fever
      1. Associated with boating or swimming in sub-saharan africa or southeast asia
    7. Coronavirus
      1. Corona Virus 19 (SARS-CoV2, Covid19)
      2. Severe Acute Respiratory Syndrome (SARS)
      3. Middle East Respiratory Syndrome (MERS)
        1. Travel to arabian peninsula in last 14 days (or exposure to traveler)
  3. Rash
    1. See Febrile Traveler with Rash
    2. Dengue Fever
    3. Chikungunya
    4. Zika Virus
    5. Typhus
    6. Enteric Fever
    7. Meningococcus
    8. Uncommon with Malaria (aside from Petechiae in severe Falciparum Malaria with DIC)
  4. Lymphadenopathy
    1. See Lymphadenitis in the Febrile Returning Traveler
  5. Myalgia
    1. Malaria (mild to moderate Muscle pain and tenderness)
    2. Dengue Fever (severe Muscle pain)
    3. Leptospirosis (severe tenderness)
    4. Typhus (severe tenderness)

XII. Symptoms: Gastrointestinal

  1. See Gastrointestinal Disease in Returning Traveler
  2. Abdominal Pain
    1. Red flag findings include Jaundice, Hepatomegaly, Splenomegaly or bloody Diarrhea
    2. Rash, Abdominal Pain and fever seen in Viral Hemorrhagic Fever, Brucellosis, Enteric Fever
    3. Eosinophilia, respiratory symptoms, adominal pain and fever seen in Helminth infection (e.g. Hookworm)
  3. Diarrhea
    1. See Traveler's Diarrhea
    2. See Acute Inflammatory Diarrhea (bloody Diarrhea, Dysentery)
    3. See Infectious Diarrhea Causes
    4. See Foodborne Disease
    5. See Waterborne Illness
    6. Febrile Seizures and Diarrhea seen in Shigellosis
    7. Covid19 presents with Diarrhea in one third of patients (half have Nausea or Vomiting)
  4. Jaundice
    1. Acute Hepatitis
    2. Severe Malaria
    3. Leptospirosis
    4. Yellow Fever
    5. Dengue Fever
    6. Viral Hemorrhagic Fever
  5. Hepatosplenomegaly
    1. Acute Hepatitis (including Viral Hepatitis)
    2. Malaria
    3. Leishmaniasis
    4. Amoebiasis with abscess (Entamoeba histolytica)
    5. Enteric Fever
    6. Brucellosis
    7. Schistosomiasis

XIII. Symptoms: Neurologic

  1. Altered Mental Status
    1. Cerebral Malaria
    2. Viral Encephalitis
    3. Tick-borne Encephalitis (esp. Eastern European Outdoor Exposure)
    4. Bacterial Meningitis (esp. Sub-Saharan African Meningitis belt)
      1. Neisseria Meningitidis
      2. Cryptococcal Meningitis (Immunocompromised)
      3. Tuberculous Meningitis (Immunocompromised)
  2. Febrile Seizures
    1. Shigellosis (Diarrheal illness)
    2. Japanese Encephalitis (Mosquito-Borne Illness in Southeast Asia, Western Pacific)
    3. Dengue Hemorrhagic Fever
    4. Cerebral Malaria
    5. Chronic Parasitic Infections cause Seizures (however these do not present in the short-term traveler)
      1. Neurocysticercosis
      2. Schistosomiasis

XIV. Exam: Focal areas

  1. Vital Signs
    1. See Pulse-Temperature Dissociation
    2. Pulse slower than normal for fever degree (pulse fails to increase with fever spike)
      1. Seen with Typhoid Fever, Rickettsial infection
  2. Eye Exam
    1. Ocular Larva Migrans
    2. Leptospirosis (Conjunctivitis)
  3. Lymph Node Exam
    1. See Lymphadenopathy in the Febrile Returning Traveler
  4. Cardiopulmonary Exam
    1. Subacute Bacterial Endocarditis
  5. Abdominal Exam
    1. See GI Conditions in Febrile Returning Traveler
  6. Neurologic Exam
    1. See Neurologic Findings in the Febrile Returning Traveler
    2. Altered Mental Status in Febrile Returning Traveler (medical emergency)
    3. Seizures in Febrile Returning Traveler
  7. Skin Exam
    1. See Cutaneous Conditions in Febrile Returning Traveler

XV. Labs

  1. Complete Blood Count (CBC) with differential
    1. Observe for Eosinophilia (non-specific)
      1. Typically positive with Helminth infection, but not for protozoa
    2. Manual differential (standard with Wright stain)
      1. Test Sensitivity for Malaria approaching that of thin smear (Giemsa stain)
  2. Serum Electrolytes with Glucose
  3. Renal Function tests including Blood Urea Nitrogen
  4. Liver Function Tests
  5. Urinalysis
  6. Urine Pregnancy Test (if indicated)
  7. Malaria thick and thin smears (Giemsa stain) x3, 12 hours apart
  8. Serologies as indicated
  9. Serum sample spun and saved for later Antibody titers
  10. Consider Dengue Fever IgM, IgG and virus detection
    1. Diagnose and start treatment based on clinical findings if suspected
    2. Use labs only for confirmation
  11. Cultures
    1. Urine Culture
    2. Blood Culture
  12. Stool Testing (consider if Diarrhea)
    1. Stool Culture or NAAT testing (including Salmonella typhi)
    2. Stool Ova and Parasite studies
    3. Stool Occult Blood
  13. Cerebrospinal Fluid Examination
    1. Indicated in Altered Mental Status and fever
    2. Exclude Meningitis and Encephalitis

XVI. Management

  1. Consider Infectious Disease Consultation
  2. CDC and local public health mandate reporting of many of the febrile infections in returning travelers
  3. Consider empiric antibiotic coverage until diagnosis
    1. Example: Doxycycline 100 mg PO qd

XVII. Prevention

  1. See Travel Preparation

XVIII. Resources

  1. CDC Yellow Book
    1. https://wwwnc.cdc.gov/travel/yellowbook/2018/post-travel-evaluation/fever-in-returned-travelers
  2. CDC National Notifiable Diseases (2018)
    1. https://wwwn.cdc.gov/nndss/conditions/notifiable/2018/
  3. CDC Current Outbreak List
    1. https://www.cdc.gov/outbreaks/index.html

XIX. References

  1. Anderson (2014) Crit Dec Emerg Med 28(7): 11-9
  2. Black, Martin, DeVos (2018) Crit Dec Emerg Med 32(8): 3-12
  3. Mason and Marsh in Herbert (2019) EM:Rap 19(5): 12-3
  4. Nordurft-Froman and DeVos (2022) Crit Dec Emerg Med 36(4): 4-15
  5. Walker (2001) HP Primary Care Medicine Lecture
  6. Feder (2013) Am Fam Physician 88(8): 524-30 [PubMed]
  7. Lo Re (2003) Am Fam Physician 68(7):1343-50 [PubMed]
  8. Suh (1999) Med Clin North Am 83(4):997-1017 [PubMed]

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