This presentation, intended for emergency medicine residents, covers the evaluation and management of four common causes of fever in the international traveler: malaria, typhoid, dengue and chikungunya.

1. Fever in the International Traveler
Resident Conference
Joseph M Reardon, MD

2. Disclosure Statement
• No financial conflicts of interest to disclose.
Special Thanks
• Paul Lantos, MD

4. Your best friend for travel medicine:

5. Color Codes
•Red = Core EM Content
•Black = All the fun stuff

6. Background: Travel Medicine
• 100,000 international travelers per year
• 50,000 have a health problem while traveling
• 8,000 will see a physician
• 1,100 will be incapacitated (i.e., our patients)
ISTM

7. Case
• PWR
• 45y M
• No PMH
• 3d fever to 102F, chills, sweats
• Mild generalized HA
• NBNB emesis x1
• Malaise
• ROS otherwise negative
collider.com

8. Travel Screening
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

11. Guinea-Bissau: 0 cases
Guinea: 2,871 cases

12. Approach to Febrile Traveler
• Travel History
• Countries
• Dates
• Setting (urban vs rural)
• Contacts
• Vaccination Status
• S/Sx
• ROS
PLOS Neglected Tropical Diseases

13. Differential Diagnosis

14. Malaria

15. Malaria: Location
300-500 million infections/yr; 2.5 million deaths/yr

16. Malaria: Life Cycle

17. Malaria: Causative agent
CDC

18. Malaria: Risk Factors
ISTM
• Travel to Africa:
• 2.4% risk per month in West Africa
• 1.5% risk per month in East Africa
• Mosquito exposure (Anopheles gambiae vs Anopheles
quadrangulatus)
• Day biting (Haiti, much of Latin America) vs
• Night biting (Africa)
• 90% of reported cases in travelers had symptom onset after return to
North America

19. Malaria: Symptoms
• Cyclical fever / chills / sweats
• (often absent for falciparum, variable for others)
• Tachycardia, tachypnea
• Headache
• Cough
• Nausea / vomiting / abdominal pain / diarrhea / anorexia
• Arthralgias / myalgias
• Initial symptoms are often misleading!
WHO

20. • Vitals
• Skin:
• Jaundice
• +/- anemia
• Splenomegaly (more common after several days)
• Hepatomegaly
Malaria: Physical Exam

21. • CBC: normochromic, normocytic anemia, thrombocytopenia
• CMP: hypoglycemia, mild transaminitis
• Coags
• T&S
• Rapid test
• Giemsa Stain: thick and thin smears
• UA
• CXR
• CT Abd if splenic infarct is suspected
• NOTE: RPR and VDRL may be falsely positive!
Malaria: Diagnostic Testing
Binax

22. Malaria: Treatment
• By region:
• Chloroquine-sensitive regions (including Mexico): chloroquine
• Nonendemic areas (i.e., short-term travelers): atovaquone-proguanil
(Malarone) or mefloquine (contraindicated in Long QT)
• Alternative: primaquine (but must test for G6PD first to avoid fatal hemolysis!!)
• Endemic areas (i.e., long-term travelers / native residents): Artemisinin
combination therapy (ex: Artemether-lumefantrine [Coartem])
• Supportive care (fluids, antipyretics, antiemetics)
• Consider exchange transfusion if signs of end-organ damage
First Aid

23. • Diagnoses of complicated malaria must be admitted to ICU
• AMS, seizures
• Respiratory / circulatory collapse
• Metabolic acidosis
• Renal failure, hemoglobinuria, jaundice (blackwater fever)
• Hepatic failure
• Coagulopathy, DIC
• Severe anemia (>5% of RBCs with parasites, OR >100,000 parasites / mcL)
• Hypoglycemia
• Pregnant patient: high risk for placental malaria
Malaria: Critical Actions

24. Typhoid

25. Typhoid: Location
Frontiersoftravel.com

26. Typhoid: Life Cycle
Causes:
• Salmonella typhi
Typhoid
• Salmonella paratyphi 
Paratyphoid (types A, B &
C)
• A & B are indistinguishable
from typhoid
• C has different
symptomatology

27. Typhoid: History and Physical Exam
• Week 1: (in unvaccinated)
• Gradually rising (“stepwise”) fever, chills, without rigors
• Relative bradycardia
• Diarrhea OR constipation
• Headache
• Week 2:
• Abd pain
• “Rose spots” (faint salmon-colored macules on trunk & abdomen)
• Week 3:
• Intestinal bleeding
• Intestinal perforation, sepsis, peritonitis
• Septic shock (15% of cases)
• AMS (17% of cases)
• DIC, pneumonia, meningitis, myocarditis, renal failure
Lisa See

28. Typhoid: Diagnostic Testing
• CBC
• CMP
• Coags
• Stool culture (30% sensitive but very specific)
• Blood cultures x2 (70% sensitive but very specific)
• The floor may obtain bone marrow culture (gold standard) or ELISA

29. Typhoid: Treatment
• Patients from Asia: azithro
• Rest of the world: Cipro
• Alternative: ceftriaxone 2g IV/IM x 2 wks
• Recognize need for blood transfusion
HippoEM

30. Typhoid: Critical Actions
• Recognize life-threatening complications:
• Typhoid encephalopathy: AMS (17% of pts)
• Treatment: dexamethasone
• Intestinal perforation (more common in small bowel)
(10-25% of pts)
• DIC
Tintinalli

31. Dengue
Virology.wisc.edu

32. Dengue: Location
WHO
100 million infections/yr; 25,000 deaths/yr

33. Dengue: Life Cycle
Oxitec.com
Singapore MOH
Four serotypes
Arbovirus
(=Arthropod-borne virus)

34. Dengue: Symptoms
• “breakbone fever” x 5-7d
• sometimes biphasic fever with a second 1-2d period
• Myalgias, arthralgias
• Retroorbital HA
• N/V (1/2 of pts), diarrhea (1/3 of pts)
• Dry cough, sore throat, congestion (1/3 of pts)
• More likely asymptomatic in children
First Aid

35. Dengue: Physical Exam
• “Dengue facies” with facial edema
• Fever
• Nonspecific exam
• Pale, morbilliform rash in ½ of pts
• Spreads from trunk outward to extremities/face
• Up to ½ of pts with:
• Conjunctival injection
• Pharyngeal erythema
• Lymphadenopathy
• Hepatomegaly
UTD

36. Dengue: Diagnostic Testing
• Dengue ELISA
• CBC
• Leukopenia is specific to the diagnosis
• Thrombocytopenia <100k in most pts
• CMP
• Mild AST elevation (2-5 times upper limit of normal)
• T&S
• Fibrinogen

37. Dengue: Critical Actions
• Diagnosing Dengue Hemorrhagic Fever
• Typically an autoimmune-mediated phenomenon in patients with
prior dengue infection
• Four cardinal features:
• Hemoconcentration (Hct >20% above baseline)
• Plt <100k
• Fever x2-7d
• Hemorrhage
• Positive tourniquet test
• Spontaneous bleeding
• Require ICU admission
• Shock of septic & hemorrhagic origin
• 50% mortality without care; <5% mortality with care
First Aid

38. Tourniquet Test
• 6:27-6:37
• Inflate BP cuff to MAP x 5 mins
• Inspect for petechiae
CDC

39. Dengue: Treatment
• Fever management with APAP
• Avoid aspirin and NSAIDs due to bleeding
risk
• DIC Management
• Aggressive fluid resuscitation for
vascular permeability
• No indication for steroids, antivirals,
etc.
Williams’ Hematology

40. …AND??? …AND???
Fever + Headache in a traveler =
Malaria, dengue, meningitis…

41. Chikungunya Virus
CDC

42. Chiku-what???

44. Chikungunya: Location
NYTimes.com
2nd most common arbovirus in travelers, after Dengue

45. Chikungunya: Life Cycle
PLOS Neglected Tropical Diseases

46. • High fever x3-5d
• Symmetrical (70%) polyarthralgia, primarily distal (60%)
• Occasionally, meningoencephalitis
• Rarely, ascending paralysis & Guillain-Barré
Chikungunya: Symptoms
Tintinalli

47. Chikungunya: Physical Exam
• Periarticular edema
• Rash starting after 3d starting peripherally
Intl Congress on Infectious Diseases

48. Chikungunya: Diagnosis
• Chikungunya IgM ELISA
• PCR
• CBC
• CMP
• EKG
• Consider LP to r/o alternative cause of neurologic
manifestation
• No quick diagnostic mechanism!
Tintinalli

49. Chikungunya: Treatment
• NSAIDs once dengue fever is ruled out
• Ribavirin for severe cases
• Interferon-alpha for severe cases
• Chloroquine may reduce long-term arthralgias (but is
not recommended by most recent studies)
Tintinalli

50. Chikungunya: Red Flags
• Meningoencephalitis is most common neurologic
complication
• Respiratory failure
• Myocarditis
• Shock
• 5-30% of patients will have chronic arthropathy
• Severe complications are rare.

51. N. Meningitidis Serotype A
BioQuell

52. Neisseria meningitidis Serotype A: Location
Natl Healthcare Travel Network & Centre

53. Neisseria meningitidis Serotype A: Pearls
• Slightly different serotype from N. meningitidis in the United
States, which contributes to its high transmissibility
• Is preventable with Menactra and Menveo vaccines
• A new vaccine is being developed specifically targeted for
the African strain
• Treat similarly to US-acquired meningitis:
• Ceftriaxone admit to monitored setting
• Strains generally respond to ceftriaxone and even penicillin G!

54. Comparison
Agent P. falciparum S. typhi Dengue virus Chikungunya
Location Tropics Tropics Tropics Africa,Asia,Euro,Carr
ibbean
Key Symptoms Cyclic fever Abd pain, IBS-like
symptoms
Retroorbital HA Polyarthralgias, rash
Exam Findings Splenomegaly Rose spots Petechiae Edema, rash
Diagnosis Giemsa BCx, Stool Cx Coaguloathy, ELISA Transaminitis, ELISA
Treatment Chloroquine,
atovaquone,
artemisinin
Azithro (Asia), Cipro
(everyone else)
Supportive,
transfusion
Supportive, ribavirin,
interferon
Red Flags Cerebral malaria,
Placental malaria
Encephalopathy,
intestinal perf
Dengue
Hemorrhagic Fever
Meningoencephalitis

55. Practice questions!
A 4-year-old female Brazilian immigrant presents with fatigue and
abdominal pain with temperature to 104F. She appears acutely ill. She
is tachycardic and tachypneic with hepatomegaly; there is no rash or
indication of joint pain. Test results include: Tbili 4.9, AST 236, ALT 247.
RUQ ultrasound demonstrates an enlarged liver.
• Which would confirm the diagnosis?
• Viral hepatitis panel
• Blood smear
• Leptospirosis microscopic agglutination test
• Stool O&P
Modified from PEER

56. Practice questions!
A 27-year-old male backpacker presents with diffuse macular
erythrodermal rash, blood pressure 85/37, temperature 102F. Lab tests
reveal elevated transaminases and creatinine, and Plt of 86K. He
recently returned from Guatemala and states that he developed a
persistent nosebleed while hiking 1 week ago. He still has packing in
both nostrils.
• What is the most likely causative agent?
• Rickettsia prowazekii
• Dengue virus
• Staphylococcus aureus
• Yersinia pestis
Modified from PEER

57. Practice questions!
A 24-year-old man presents with high fever to 106F, confusion, swelling
of the wrists and ankles, and weakness of the bilateral lower
extremities. He recently traveled to Democratic Republic of Congo and
received all recommended vaccinations prior to travel. Which of the
following is most likely to reduce the risk of neurologic complication?
• Ice packs and intravenous ketorolac 30mg Q6H
• Ice packs, intravenous acetaminophen, and await serologic testing
• Lumbar puncture and therapeutic CSF removal
• Intravenous piperacillin/tazobactam
• Intravenous methylprednisolone

58. Practice questions!
A 39-year-old woman presents with confusion, mild headache,
generalized myalgias, and morbiliform rash in the setting of 2 weeks of
low-grade fever. She returned from Peru last week. She has been
constipated since she returned home, which she attributes to no longer
eating vegetables from roadside stands. Which of the following is most
important to prevent serious neurologic complication?
• Intravenous azithromycin
• Intravenous ciprofloxacin and dexamethasone
• Intravenous vancomycin and piperacillin/tazobactam
• Intravenous acyclovir