Fever in the International Traveler

Resident Conference

Joseph M Reardon, MD

Disclosure Statement

• No financial conflicts of interest to disclose.

Special Thanks• Paul Lantos, MD

Your best friend for travel medicine:

Color Codes

•Red = Core EM Content

•Black = All the fun stuff

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

Case

• PWR

• 45y M

• No PMH

• 3d fever to 102F, chills, sweats

• Mild generalized HA

• NBNB emesis x1

• Malaise

• ROS otherwise negative

collider.com

Travel Screening!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

Guinea-Bissau: 0 cases

Guinea: 2,871 cases

Approach to Febrile Traveler

• Travel History• Countries

• Dates

• Setting (urban vs rural)

• Contacts

• Vaccination Status

• S/Sx

• ROS

PLOS Neglected Tropical Diseases

Differential Diagnosis

Malariarealsimplescience.com

Malaria: Location300-500 million infections/yr; 2.5 million deaths/yr

Malaria: Life Cycle

Malaria: Causative agent

CDC

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

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

• Vitals

• Skin: • Jaundice

• +/- anemia

• Splenomegaly (more common after several days)

• Hepatomegaly

Malaria: Physical Exam

• 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

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): Artemisinincombination therapy (ex: Artemether-lumefantrine [Coartem])

• Supportive care (fluids, antipyretics, antiemetics)

• Consider exchange transfusion if signs of end-organ damage

First Aid

• 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

TyphoidTelugumd.com

Typhoid: Location

Frontiersoftravel.com

Typhoid: Life Cycle

Causes:

• Salmonella typhiTyphoid

• Salmonella paratyphiParatyphoid (types A, B & C)• A & B are indistinguishable

from typhoid

• C has different symptomatology

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

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

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

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

DengueVirology.wisc.edu

Dengue: Location

WHO

100 million infections/yr; 25,000 deaths/yr

Dengue: Life Cycle

Oxitec.comSingapore MOH

Four serotypes

Arbovirus (=Arthropod-borne virus)

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

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

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

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 careFirst Aid

Tourniquet Test

• 6:27-6:37

• Inflate BP cuff to MAP x 5 mins

• Inspect for petechiae

CDC

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

…AND??? …AND???

Fever + Headache in a traveler =

Malaria, dengue, meningitis…

Chikungunya Virus

CDC

Chiku-what???

Chikungunya: Location

NYTimes.com

2nd most common arbovirus in travelers, after Dengue

Chikungunya: Life Cycle

PLOS Neglected Tropical Diseases

• High fever x3-5d

• Symmetrical (70%) polyarthralgia, primarily distal (60%)

• Occasionally, meningoencephalitis

• Rarely, ascending paralysis & Guillain-Barré

Chikungunya: Symptoms

Tintinalli

Chikungunya: Physical Exam

•Periarticular edema

•Rash starting after 3d starting peripherally

Intl Congress on Infectious Diseases

Chikungunya: Diagnosis

• Chikungunya IgM ELISA

• PCR

• CBC

• CMP

• EKG

• Consider LP to r/o alternative cause of neurologic manifestation

• No quick diagnostic mechanism!

Tintinalli

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

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.

N. Meningitidis Serotype A

BioQuell

Neisseria meningitidis Serotype A: Location

Natl Healthcare Travel Network & Centre

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!

ComparisonAgent P. falciparum S. typhi Dengue virus Chikungunya

Location Tropics Tropics Tropics Africa,Asia,Euro,Carribbean

Key Symptoms Cyclic fever Abd pain, IBS-likesymptoms

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

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

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

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

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