Fever in the Returning Traveler

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

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II. Epidemiology

  1. Of those travelers returning with acute life-threatening illness, 9!% present with fever
  2. Up to two thirds of international travelers develop a travel related illness
    1. Most illnesses are minor and self-limited
    2. Most common travel related illnesses are Traveler's Diarrhea and respiratory infections (e.g. Influenza)
    3. However more than 50% seek medical advice prior to travel, and may lack recommended Vaccines and chemoprophylaxis

III. Indications

  1. Recent travel in the last 3-4 weeks

IV. 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)
  7. Visit to friends and relatives
    1. Typically stay longer in more remote or rural areas, with greater exposure to local food and drink
    2. Frequently avoid pretravel medical Consultation, Immunizations, chemoprophylaxis, and overall travel prevention

V. 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)
    5. Ebola
  4. Vaccine preventable illness that are more common outside the United States
    1. Measles
    2. Rubella
    3. Varicella Zoster Virus
  5. Consider Bacterial infectious conditions unrelated to travel
    1. Pneumonia
    2. Urinary Tract Infection
    3. Meningitis

VI. 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

VII. 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]

VIII. 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. Chikungunya
    3. Dengue Fever
    4. Yellow Fever
    5. Enteric Fever
    6. Zika Virus
    7. Leptospirosis
    8. Leishmaniasis
    9. Chagas Disease
    10. Histoplasmosis
    11. Coccidioidomycosis
    12. 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 (most common fever cause in southern africa)
    3. Acute Schistosomiasis
    4. Dengue Fever
    5. Chikungunya virus
    6. Filariasis
    7. Yellow Fever
    8. Leishmaniasis
    9. Hemorrhagic fever
    10. African trypanosomiasis
    11. Enteric Fever
    12. Katayama Fever
    13. Meningococcal Meningitis
  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

IX. Causes: Vector Exposures

  1. See Vector Borne Disease
  2. Mosquitoes
    1. Malaria
    2. Dengue Fever
    3. Yellow Fever
    4. Chikungunya
    5. West Nile Virus
    6. Japanese Encephalitis
  3. Ticks
    1. Rickettsioses
    2. Tularemia
    3. Babesiosis
    4. African Tick Bite fever
    5. Lyme Disease
    6. Q Fever (Coxiella Burnetii)
  4. Fleas
    1. Murine Typhus
    2. Rickettsial infection
    3. Yersinia pestis
  5. Mites
    1. Scrub Typhus
  6. Reduviid Bugs
    1. American Trypanosomiasis (Chagas Disease)
  7. Flies
    1. African Trypanosomiasis (Tsetse Flies)
    2. Leishmaniasis (Sand Flies)
    3. Loiasis
    4. Onchocerciasis or River Blindness (Black Flies)
  8. Lice
    1. Borrelia recurrentis
    2. Rickettsial infection

X. Causes: Animal Exposures

  1. See Pet-Borne Parasitic Zoonoses
  2. See Animal Bite
  3. See Marine Injury
  4. General
    1. Rabies
      1. Bat exposure and Dog Bites in developing countries are among the highest risk of Rabies infection
    2. Q Fever
    3. Tularemia (esp. Rabbits)
    4. Brucellosis
    5. Echinococcosis
    6. Plague
    7. Tetanus
  5. Livestock
    1. Anthrax
    2. Brucellosis
    3. Cysticercosis
    4. Q Fever
    5. MERS (Camels)
  6. Cats
    1. See Pet Borne Zoonoses
    2. See Cat Bite
    3. Bartonella Henselae
    4. Capnocytophaga canimorsus (life threatening in Asplenic patients)
    5. Pasteurella multiocida
    6. Toxoplasmosis
  7. Dogs
    1. See Pet Borne Zoonoses
    2. See Dog Bite
    3. Dog Bites in developing countries is the most common cause or Rabies worldwide
    4. Cutaneous Larva Migrans (common)
    5. Helminths (e.g. Anclyostoma, Echinococcus, Toxocara)
    6. Parasites (e.g. Giardia)
    7. Bacterial Infections (Pasteurella, Leptospirosis)
  8. Bats
    1. Rabies
    2. Viral Hemorrhagic Fever
    3. Nipah Virus
    4. Histoplasmosis
    5. Respiratory Virus (SARS, SARS-CoV2, MERS)
  9. Rodents (or their urine or droppings)
    1. Hantavirus
    2. Lassa Fever
    3. Leptospirosis
    4. Plague
    5. Rat Bite Fever
    6. Rickettsioses
  10. Primates
    1. Hepatitis A
    2. MPox
    3. Tetanus
    4. Viral Hemorrhagic Fever
  11. Exotic Birds
    1. Chlamydophila psittaci
    2. Mycobacterium avium
    3. Psittacosis

XI. 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. Infected Person Contact
    1. Viral Hemorrhagic Fever
    2. Enteric Fever (Salmonella typhi and paratyphi)
    3. Meningococcal infection
    4. Tuberculosis
    5. Severe Acute Respiratory Syndrome
  3. Raw or undercooked meat or fish
    1. See Foodborne Illness
    2. Enteric Infections
    3. Cestodiasis
    4. Trichinosis
    5. Typhoid Fever
    6. Cholera
    7. Salmonellosis
  4. 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)
  5. Freshwater Exposure
    1. Acute Schistosomiasis (Katayama Fever)
    2. Leptospirosis
    3. Campylobacter
  6. Barefoot Exposure
    1. Strongyloidiasis
    2. Cutaneous Larva Migrans
  7. Infected soil exposure or cave exploring
    1. Histoplasmosis
    2. Rabies
    3. Marburg Hemorrhagic Fever
    4. Leptospirosis
    5. Tick-Borne Relapsing Fever
    6. Tetanus

XII. 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)
    9. Cuteneous Larva Migrans
    10. Plague
    11. Viral respiratory infections (Influenza, Covid19)
  2. Incubation 7-21 days
    1. Amebiasis
    2. Babesiosis
    3. Leptospirosis
    4. Viral Hemorrhagic Fevers (including Ebola)
    5. Japanese Encephalitis
    6. Plasmodium FalciparumMalaria (common)
    7. Enteric Fevers
      1. Typhoid Fever (common)
      2. Paratyphoid
    8. Typhus
    9. East African Trypanosomiasis
    10. 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. Plasmodium Vivax and Plasmodium OvaleMalaria
    10. Visceral Leishmaniasis
    11. Systemic Schistosomiasis (Katayama)
    12. Visceral Leishmaniasis
    13. Filariasis
    14. Rabies
  4. Months
    1. Chagas Disease
    2. Tuberculosis

XIII. 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?
    6. Did you take locally prescribed or recommended medications or therapies?
  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
      1. Did you use barrier protection?
      2. Drug resistant gonorrhea Prevalence is increasing world-wide
    6. Food sources of infection
      1. See Foodborne Illness
    7. Water sources of infection (ingestion, fresh water swimming)
      1. See Waterborne Illness
    8. Adventure Tourism
      1. Weather extremes (e.g. Cold Weather Injury)
      2. Rural exposures (e.g. Waterborne Illness, Vector Borne Disease)
    9. Medical Tourism (travel for less expensive surgical or medical care)
      1. Bacterial Infections acquired in travel are multi-drug resistant in up to 30% of cases
      2. ESBL Infections (esp. E. coli) are most common (esp. north africa, and southeast and southern asia)
      3. Sridhar (2021) Curr Opin Infect Dis 34(5): 423-31 [PubMed]
    10. Humanitarian Travel (e.g. medical missions)
      1. Health care workers may be at particular risk of unique infections
    11. Mass Gatherings (e.g. wedding)
      1. Higher risk for respiratory infections (e.g. Influenza, Covid19)
  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

XIV. 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. Mpox (Monkeypox)
    9. Rash is uncommon with Malaria
      1. Aside from Petechiae in severe Falciparum Malaria with DIC
    10. Most common causes
      1. Cutaneous Larva Migrans
      2. Insect Bites
      3. Skin Abscess
  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)

XV. 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. Typhoid Fever (Enteric Fever) is among the most concerning causes of fever and Abdominal Pain
    4. 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. Most Diarrhea in the returning traveler is self-limited and rarely caused by Parasites or Helminths
    7. Most common Bacterial causes include E. coli (enterotoxigenic and enteroaggregative)
    8. Febrile Seizures and Diarrhea seen in Shigellosis
    9. Covid19 presents with Diarrhea in one third of patients (half have Nausea or Vomiting)
    10. Differential diagnosis includes Hepatitis A infection and Clostridioides difficile
  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

XVI. 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

XVII. 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

XVIII. 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. Infectious disease panel (multiplex and biofilm PCR) as indicated for system involved
  11. 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
  12. Cultures
    1. Urine Culture
    2. Blood Culture
  13. Stool Testing (consider if Diarrhea)
    1. Stool Culture or NAAT testing (including Salmonella typhi)
    2. Stool Ova and Parasite studies
    3. Stool Occult Blood
  14. Cerebrospinal Fluid Examination
    1. Indicated in Altered Mental Status and fever
    2. Exclude Meningitis and Encephalitis

XIX. 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 orally twice daily

XX. Prevention

  1. See Travel Preparation
  2. Two most important, common Vaccine preventable illnesses
    1. Influenza Vaccine
    2. Hepatitis A Vaccine

XXI. Resources

  1. CDC Yellow Book
    1. https://wwwnc.cdc.gov/travel/yellowbook/2024/posttravel-evaluation/fever-in-the-returned-traveler
  2. CDC National Notifiable Diseases
    1. https://www.cdc.gov/healthywater/statistics/surveillance/notifiable.html
  3. CDC Current Outbreak List
    1. https://www.cdc.gov/outbreaks/index.html
  4. GeoSentinel
    1. https://geosentinel.org/
    2. Collaboration between CDC and the International Society of Travel Medicine (ISTM)
    3. Worldwide infectious disease surveillance (requires subscription
    4. Among the first to widely report Covid19 epidemic onset in China, late 2019

XXII. 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. Rathjen (2023) Am Fam Physician 108(4): 396-403 [PubMed]
  9. Suh (1999) Med Clin North Am 83(4):997-1017 [PubMed]

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