Diagnoses for Consideration in a Returning Traveler with Fever

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If illness presentation is not consistent with malaria or malaria has been ruled out, other diagnoses based on specific clinical presentation and travel itinerary/place of possible exposure should be considered. Travelers can have non-travel related reasons for fever, too.

Diagnoses Considerations Based on Specific Clinical Presentation
Common Clinical Findings Infections to Consider after Travel
Fever and rash Dengue, chikungunya, Zika, spotted fever or typhus group rickettsioses,typhoid fever (skin lesions may be sparse or absent), acute HIV infection, measles, varicella, mononucleosis, parvovirus B19, meningococcemia (lesions usually sparse)
Fever and abdominal pain Typhoid fever, hepatitis, other viral syndrome, travelers’ diarrhea, amebic liver abscess
Undifferentiated fever and normal or low white blood cell count Dengue, rickettsial infections (scrub typhus, spotted fevers without rash), typhoid fever, chikungunya, Zika, acute HIV infection, early stage viral hemorrhagic fevers, other viral infections
Fever and hemorrhage Viral hemorrhagic fevers (dengue and others), leptospirosis, rickettsial infections, meningococcemia
Fever and eosinophilia Acute schistosomiasis, drug hypersensitivity reaction, fascioliasis, and other parasitic infections (rare)
Fever and respiratory symptoms Acute schistosomiasis, Q fever, leptospirosis, pneumonic plague, tularemia, Middle East Respiratory Syndrome (MERS), endemic mycoses (histoplasmosis, blastomycosis, coccidioidomycosis, etc), other viral pneumonias, influenza, bacterial pneumonia, legionellosis
Fever and altered mental status Scrub typhus, viral or bacterial meningoencephalitis (including meningococcal meningitis and arboviral encephalitis), East African trypanosomiasis, eosinophilic meningitis (Angiostrongyliasis), rabies
Mononucleosis syndrome Epstein–Barr virus infection, cytomegalovirus infection, toxoplasmosis, acute HIV infection
Fever persisting >2 weeks Typhoid fever, acute schistosomiasis, Q fever, Epstein-Barr virus infection, cytomegalovirus infection, toxoplasmosis, acute HIV infection, brucellosis, tuberculosis, , visceral leishmaniasis (rare)
Fever with onset >6 weeks after travel Plasmodium vivax or ovale malaria, acute hepatitis (B, C, or E), tuberculosis, amebic liver abscess, visceral leishmaniasis
Dengue
  • Clinical Presentation: three phases
    • Febrile phase (4-7 days after exposure)
      • Headache, eye pain, nausea/vomiting, myalgias, arthralgias, macular rash
    • Critical phase (may develop following resolution of febrile phase, lasts 24-48 hours)
      • Shock, hemorrhage, organ failure, ARDS
    • Recovery phase
      • Clinical stabilization, may develop confluent rash
  •  Diagnosis
    • Initial diagnosis may be established by clinical suspicion
    • Laboratory testing
      • Serum RT-PCR or viral antigen testing within first week of illness
  • Management
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Typhoid
  • Clinical Presentation
    • Early clinical signs (weeks 1-2): fever, abdominal pain, “rose spots” rash overlying abdomen
    • Severe/late clinical signs (week 3): hepatosplenomegaly, hematochezia, intestinal perforation, septic shock
  • Diagnosis
    • Initial diagnosis may be established by clinical suspicion
    • Blood culture remains gold standard
    • Stool culture, serology, and rapid diagnostic tests have more limited utility
  • Treatment
    • Parenteral antibiotics for severe disease should be given in ER
      • Ceftriaxone or fluoroquinolone if low risk of fluoroquinolone resistance (travelers outside of South/Southeast Asia where resistance is >80%)
      • Ceftriaxone for travelers from South/Southeast Asia
    • Oral antibiotics for uncomplicated disease
      • Fluoroquinolone
      • Azithromycin
  • See Traveler’s Health Typhoid & Paratyphoid Fever
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Schistosomiasis
  • Acute presentation: fever, urticaria, angioedema, eosinophilia
    • Katayama Fever (acute schistosomiasis syndrome): acute onset of urticaria, angioedema, eosinophilia due to hypersensitivity reaction to schistosome antigens
  • Severe disease: can involve liver, spleen, neurological involvement but typically seen after chronic infection
  • Diagnosis: serology preferred
  • Management
    • Corticosteroids (prednisolone 20 to 40 mg) initially, followed by praziquantel after resolution of acute symptoms to avoid aggravation of symptoms
    • Neuroschistosomiasis requires immediate corticosteroid treatment, followed by praziquantel after a few days
  • See Travelers’ Health Schistosomiasis
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Leptospirosis
  • Initial presentation: fevers, rigors, myalgias, headache, conjunctival suffusion
  • Severe complications: renal failure, pulmonary hemorrhage, ARDS, myocarditis, uveitis, optic neuritis
  • Diagnosis: serology preferred; microscopic agglutination test is considered gold standard
  • Management
    • Mild disease: doxycycline or azithromycin
      • Pregnancy: azithromycin or amoxicillin
    • Severe disease in adults: IV penicillin, IV doxycycline, IV ceftriaxone, or IV cefotaxime
      • Pregnancy: avoid doxycycline
    • Severe disease in children: IV azithromycin; avoid doxycycline
    • Jarisch-Herxheimer reaction (inflammation in response to spirochete clearance) can occur
  • See Travelers’ Health Leptospirosis
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Scrub Typhus and other Rickettsial infections
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Chikungunya
  • Acute infection: high-grade fever, polyarthralgia (typically bilateral/symmetric, distal>proximal joints), macular rash
  • Severe complications: meningoencephalitis, respiratory failure, renal failure, hepatitis, hemorrhagic, heart failure/cardiomyopathy
  • Diagnosis: RT-PCR or serology, consider testing for dengue and Zika as well
  • Management
    • Supportive care, fluids as appropriate
    • Avoid aspirin/NSAIDS in patients with concern for dengue until patient is afebrile for 48 hours and no additional warning signs for dengue to reduce risk of hemorrhage
  • See Travelers’ Health Chikungunya
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Zika
  • Acute infection: non-specific presentation (fever, pruritic rash, arthralgia)
  • Severe complications: Guillain-Barre syndrome, other neurologic complications including encephalitis, transverse myelitis
  • Diagnosis: RT-PCR or serology, consider testing for chikungunya and dengue as well
  • Management
    • Supportive care, fluids, acetaminophen
    • Avoid aspirin/NSAIDS in patients with concern for dengue until patient is afebrile for 48 hours and no additional warning signs for dengue to reduce risk of hemorrhage
  • See Travelers’ Health Zika
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Q Fever
  • Clinical presentation: fever, myalgias, shortness of breath, dyspnea, hepatomegaly, endocarditis
  • Diagnosis: serology
  • Management: doxycycline preferred
  • See Travelers’ Health Q Fever
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Tularemia
  • Nonspecific symptoms of fever, malaise may be accompanied by one of six additional disease forms:
    • Ulceroglandular: skin lesion with central eschar, may be accompanied by lymphadenopathy
    • Glandular: tender regional lymphadenopathy without skin lesion
    • Oculoglandular: ocular pain, photophobia, lymphadenopathy
    • Pharyngeal: severe sore throat, oropharyngeal ulcers, tonsillitis
    • Typhoidal: acute or chronic in presentation, may include abdominal pain, diarrhea, hepatosplenomegaly
    • Pneumonic: similar to community-acquired pneumonia
  • Diagnosis: serology
  • Management: streptomycin preferred, gentamicin is an alternative
  • See Tularemia For Clinicians
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Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
  • Clinical presentation: severe pneumonia, ARDS
  • Diagnosis: RT-PCR of lower respiratory tract specimens (sputum, endotracheal aspirate, or bronchoalveolar lavage)
  • Management: Immediate respiratory isolation; supportive care; no specific treatment is available
  • See Travelers’ Health Middle East Respiratory Syndrome (MERS)
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African Trypanosomiasis
  • Early infection: headache, fevers, malaise, arthralgias, lymphadenitis; trypanosomal chancre (rare);
  • Late infection: progressive meningoencephalitis and other CNS involvement
  • Diagnosis: trypanosome visualization on serum, CSF, chancre or lymph node aspirate
  • Management:
    • All patients with concern for trypanosomiasis should undergo CSF evaluation to rule out CNS involvement which can be subclinical
    • Infectious diseases clinical consult recommended to guide choice of antitrypanosomal therapy, which differs by species of trypanosome (T.b. gambiense vs. T.b. rhodesiense). Drugs include suramin, melarsoprol, eflornithine, and others under investigation.
  • See Travelers’ Health Trypanosomiasis, African (Sleeping Sickness)
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Plague
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References
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  • Taylor, Terrie E. Treatment of severe malaria. In: UpToDate, Daily, Johanna (Ed), UpToDate, Waltham, MA, 2017.
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  • Thomas, Stephen J. et al. Dengue virus infection: Clinical manifestation and diagnosis. In: UpToDate, Hirsch, Martin S. (Ed), UpToDate, Waltham, MA, 2017.
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  • Galloway, Renee L; Stoddard, Robyn A; Schafer, Ilana J. Leptospirosis. In: CDC Yellow Book 2018: Health Information for International Travel. Oxford University Press, New York, NY, 2017. Accessed online: https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/leptospirosis.
  • Centers for Disease Control and Prevention. Dengue Case Management Clinician Guide Cdc-pdf[PDF – 8 pages].
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Page last reviewed: July 13, 2018
Content source: Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP), Viral Special Pathogens Branch (VSPB)