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Emergency Department Evaluation of Fever in the Returning Traveler. Dr. Aric Storck October 31, 2002. Objectives. Approach to the febrile traveler History Travel history Vaccinations Chemoprophylaxis Laboratory studies Treatment overview of common imported diseases. Background.

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emergency department evaluation of fever in the returning traveler

Emergency Department Evaluation of Fever in the Returning Traveler

Dr. Aric Storck

October 31, 2002

objectives
Objectives
  • Approach to the febrile traveler
    • History
      • Travel history
      • Vaccinations
      • Chemoprophylaxis
    • Laboratory studies
    • Treatment
  • overview of common imported diseases
background
Background
  • >500,000,000 people cross international boundaries each year
  • >12,000,000 North Americans travel to developing countries each year
  •  international travel =  importation of exotic infectious diseases

Suh, K, et al. Evaluation of Fever in the Returned Traveler. Medical Clinics of North America 1999:83(4)997-1018.

slide4

Travelers get sick ….

  • 20-70% of travelers report health problems while traveling
  • 1-5% seek medical attention abroad
  • 0.01-0.1% require emergency medical evacuation
  • 1 in 100,000 dies

Kain K, Ryan E. Health Advice and Immunization for Travelers. NEJM 2000;342(23)1716-1725.

low awareness of traveler s health issues
Low awareness of traveler’s health issues
  • Many travelers do not seek predeparture medical consultation
    • Poor understanding of risks
    • Not covered by health insurance
    • Shortage of physicians with travel medicine expertise
for example
For example …
  • Study of 353 North American passengers boarding international flights to regions where Hepatitis A is endemic
    • 72% did not obtain immunizations
    • 78% did not know the route of transmission of hepatitis A
    • 95% unable to identify fever, abdominal pain, jaundice as symptoms
    • 88% of flight crew were not immunized
  • Quoted in: Thanassi M, Thanassi W. EMR 1998;9(22)239-246
the result
The result ….
  • 1-2% of unimmunized travelers visiting a developing country for >1 month will develop hepatitis A
          • Steffen R. Risk of hepatitis A in travelers: the European experience. Journal of Infectious Disease 1995;171:S24-28.
  • 300 / 100,000 travelers / month in tourist areas of developing countries
  • 5-7 x increased risk for “backpackers”
          • Quoted in:Kain K, Ryan E. Health Advice and Immunization for Travelers. NEJM 2000;342(23)1716-1725.
after the holiday
After the holiday …
  • Swiss study
    • 4% of travelers to developing countries for >3 weeks develop fever
    • 61-71% remained febrile upon return

Steffen R, et al. Health problems after travel to developing countries. J Infect Dis 1987;156:84-91.

  • 5% of travelers consult MD upon return

Thanassi M, Thanassi W. EMR 1998;9(22)239-246

ed evaluation of the febrile traveler
ED evaluation of the febrile traveler
  • What infections are possible given the patient’s travel history
  • What infections are probable given the patient’s medical history and presentation
  • What infections are life-threatening or contagious or both
slide11

General Medical History

  • Immunocompromise
    • Increased risk of all infectious diseases
  • Decreased gastric acidity (achlorhydria, H2 blockers, PPI)
    • Increased risk of enteric illness (eg: cholera, typhoid)
  • Chronic respiratory disease
    • Increased risk of respiratory infections
slide12
Asplenia
    • Encapsulated organisms
  • Sickle Cell Trait / G6PD deficiency
    • Confer protection against malaria
pre travel history
Pre-travel History
  • ? pre-departure medical consultation
  • Vaccination status
    • Which vaccines
    • When
  • Chemoprophylaxis
    • Which specific medication
    • Dosing schedule
    • Patient compliance
slide15
Vaccination against the following makes diagnosis unlikely:
    • Yellow fever
    • Hepatitis A
    • Hepatitis B
  • Vaccinations for following are not very effective
    • Typhoid
    • Cholera
travel history
Travel History
  • Precise dates of travel
    • Arrival & departure from endemic regions
  • Countries and regions visited
    • Urban
    • Rural
  • Type of accommodation
    •  hotel
    • Bamboo hut
slide17
Infection prophylaxis
    • Insect repellants
    • Mosquito nets
    • Bottled water
  • Activities
    • Freshwater exposure (rafting, swimming...)
    • Trekking
    • Contact with animals
    • Drug use
sexual contacts
Sexual contacts
  • 66% of 213 Australians going to Thailand reported plans to have sex
  • 25% of Swedish women on charter holidays reported a sexual encounter with an unknown partner
  • 18.6% of 757 patients at Hospital for Tropical Diseases in London reported new sexual partner during last trip
    • Only 36% regularly used condoms

Quoted in: Matteelli A, Carosi G. Sexually Transmitted Diseases in Travelers. Clinical Infectious Diseases 2001;32:1063-1067.

sex and the long term traveler
Sex and the long-term traveler
  • 60% of 1080 Peace Corps had sexual encounter with new partner
    • 40% with local partner
    • 1/3 used condoms
  • 50% of Belgian expatriates in Central Africa reported extramarital sex
    • 1/3 with commercial sex workers

Quoted in: Matteelli A, Carosi G. Sexually Transmitted Diseases in Travelers. Clinical Infectious Diseases 2001;32:1063-1067.

commonest causes of fever
Commonest causes of fever (%)

sources: O’Brien D, et al.Clinical Infectious Diseases 2001;33:603-9. Suh, K, et al. Medical Clinics of North America 1999:83(4)997-1018.

incubation periods
Incubation Periods
  • Short (<1 week)
    • GI bacterial pathogens
    • Dengue Fever
    • Yellow Fever
  • Medium (1-2 weeks)
    • Malaria
    • Typhoid
    • Trypanosomiasis
incubation periods1
Incubation Periods
  • Long (>3 weeks)
    • Viral hepatitis
    • Malaria
    • Schistosomiasis
    • Tuberculosis
    • Amoebic liver abscess
    • Rabies
frequency of presenting symptoms in febrile returned travelers
Frequency of presenting symptoms in febrile returned travelers

O’Brien D, et al. Fever in Returned Travelers. Clinical Infectious Diseases 2001;33:603-9

diarrhea
Diarrhea
  • Traveler’s Diarrhea (e. coli)
    • Most common travel related illness
    • Only 15% febrile
  • Dysentery (bloody diarrhea)
    • Campylobacter, Salmonella, Shigella
  • Typhoid
    • 30-50% c/o diarrhea
  • Viral, protozoal, helminth
  • Malaria
jaundice
Jaundice
  • Hepatitis A
    • Most common cause
  • Yellow fever
  • Hemorrhagic fevers
  • Leptosporosis
  • Malaria
    • 20% jaundiced secondary to hemolysis
respiratory complaints
Respiratory complaints
  • The usual suspects
    • CAP, influenza
  • Tuberculosis
    • Usually due to reactivation
    • Suspect in immigrants, not in travelers
  • P.falciparum
    • ARDS (often fatal)
  • Helminths
    • Strongyloides, schistosoma, ascaris
  • Protozoa
    • Entamoeba histolytica, trypanosoma
dermatologic complaints
Dermatologic complaints
  • Rose spots - Typhoid
    • faint pink macules/papules on trunk
  • Maculopapular exanthem
    • Dengue fever
    • Viral hemorrhagic fevers
  • Petechiae / ecchymotic lesions
    • Meningococcemia
    • Dengue
    • Viral hemorrhagic fevers
neurologic complaints
Neurologic complaints
  • Meningitis
    • Meningococcal
    • Aseptic (enterovirus, rickettsiae, typhoid...)
  • Encephalitis
    • Arbovirus (eg: Japanese encephalitis)
  • Cerebral malaria (P.falciparum)
    • Looks like toxic coma
    • Consider empiric antimalarial therapy if neurologic SSx and diagnosis uncertain
splenomegaly
Splenomegaly
  • Common and non-specific
  • Malaria
    • OR 7.9; 95% CI 2.4-27.3; P<0.001

O’Brien D, et al. Fever in Returned Travelers. Clinical Infectious Diseases 2001;33:603-9

  • Trypanosomiasis
  • Dengue
hepatomegaly
Hepatomegaly
  • Malaria
    • OR 4.0; 95%CI 1.3-12.5; P=0.006

O’Brien D, et al. Fever in Returned Travelers. Clinical Infectious Diseases 2001;33:603-9

lymphadenopathy
Lymphadenopathy
  • EBV
  • HIV
  • Dengue
  • NOT in malaria
typhoid fever
Typhoid Fever

Salmonella typhi

typhoid fever1
Typhoid Fever
  • Gram negative bacilli
    • Salmonella typhi
    • Salmonella paratyphi
  • Fecal-oral route
    • Contaminated food or water
  • Incubation period 5-21 days
typhoid fever2
Typhoid Fever
  • Endemic in almost all developing countries
  • 16,000,000 clinically significant cases annually (WHO)
  • Many more subclinical cases
  • 600,000 deaths annually
classical presentation
Classical Presentation
  • Week 1
    • Fever
    • Bacteremia
  • Week 2
    • Abdominal pain
    • Rash (Rose spots)
  • Week 3
    • Hepatosplenomegaly
    • Intestinal perforation / hemorrhage
diagnosis
diagnosis
  • Laboratory
    • Anemia
    • Leukocytosis / leukopenia
    • Abnormal LFTs
  • Isolation of bacteria
    • Blood culture – positive in 40-80%
    • Stool culture – positive in 30-40%
    • Bone marrow – positive in 98%
treatment
Treatment
  • Fluoroquinolone
    • Ciprofloxacin 500 mg bid
    • Ofloxacin 400 mg bid
  • Plus 3rd generation cephalosporin
    • High levels of resistance in some strains
    • Continue while sensitivities pending
    • Ceftriaxone 2-3 g od
typhoid mary
Typhoid Mary …
  • 2-5% of hosts become asymptomatic carriers
    • Very high risk of transmitting disease to others if involved in food preparation
    • Mary Mallon – responsible for 54 cases of typhoid and 3 deaths in New York
hepatitis a
Hepatitis A
  • Most common vaccine-preventable illness in travelers
  • Fecal-oral transmission via food and water
  • Risk as high as 2 cases / 100 travellers / 4 week stay
    • 10-100x more common than typhoid
    • 1000x more common than cholera
  • Thanassi M, Thanassi W. EMR 1998;9(22)239-246
hepatitis a1
Hepatitis A
  • Incubation period 15 – 30 days
  • Fever in pre-icteric phase
  • Often asymptomatic in children
  • Jaundice by age group
    • <6 = <10%
    • 6-14 = 40-50%
    • >14 = 70-80%
hepatitis a complications
Hepatitis AComplications
  • Fulminant hepatitis
  • Cholestatic hepatitis
  • Relapsing hepatitis
  • No chronic sequelae
  • Overall mortality 1:1000 cases (varies widely according to age)
hepatitis a3
Hepatitis A

From:http://www.worldwidevaccines.com/public/diseas/hepa23.asp

diagnosis treatment
Diagnosis & Treatment
  • Clinical
    • Fever
    • Jaundice
    • RUQ pain
  • Laboratory
    • Transaminitis
    • Cholestatis
    • Hepatitis serology
  • Treatment
    • Supportive
dengue virus
Dengue virus
  • Causes both
    • Dengue Fever – benign self limited illness
    • Dengue Hemorrhagic Fever (DHF) – life threatening
  • Flavivirus composed of single-stranded RNA
  • Arbovirus transmitted by the Aedes aegypti mosquito
  • No vaccination, no chemoprophylaxis, no specific treatment
slide52
Four serotypes (DEN 1,2,3,4)
    • No cross immunity
  • Prior infection with different serotype, co-infection with >1 serotype increases risk of DHF
  • Incubation period 4-7 days
    • Do not include in DDx if >14 days from exposure
  • Symptoms persist 3-10 days (avg =5)
aedes aegypti
Aedes aegypti
  • Bite during day
  • Urban dwellers
slide55

Distribution of Aedes aegypti in 1970 (end of mosquito eradication program), and in 1997

Source: CDC

slide56
American countries with laboratory-confirmed hemorrhagic fever (red shaded areas), prior to 1981 and from 1981 to 1997

Source: CDC

the epidemic
The epidemic…
  • Declining vector control
  • Poor water supply systems
  • Increasing use of non-biodegradable containers
  • Increased air travel
  • Increased urban population density
dengue fever clinical features
Dengue FeverClinical Features
  • High Fever
  • Severe headache – retro-ocular
  • Bony pains (aka. break-bone fever)
  • Nausea and vomiting
  • Blanching macular rash
  • Hemorrhagic manifestations
  • Altered LOC
hemorrhagic manifestations
Hemorrhagic Manifestations
  • Mild
    • Petechiae, ecchymosis
    • Gingival bleeding
    • Epistaxis
    • GI bleed
  • Severe
    • Hemorrhagic shock
diagnosis1
Diagnosis
  • History
    • Travel to endemic area within past 2 weeks
  • Clinical
    • Evidence of increased vascular permeability (pleural effusions, ascites)
    • Hemorrhage
    • Tourniquet test
tourniquet test
Tourniquet Test
  • Inflate BP cuff to MAP x 5 minutes.
  • >20 petechiae / square inch suggests dengue
diagnosis2
Diagnosis
  • Laboratory Diagnosis
    • Routine Blood Work
      • Generally neutropenic and thrombocytopenic
    • Dengue serology (definitive)
      • Viral culture – only within 5 days of onset of symptoms
      • IgM ELISA – after 5 days of symptoms
treatment1
Treatment
  • Outpatient
    • Well hydrated
    • No hemorrhagic manifestations
  • Outpatient observation
    • Mild hemorrhagic manifestations
    • Dehydration
  • Hospitalization
    • Severe hemorrhage
    • Shock
treatment2
Treatment
  • Supportive
  • Educate outpatients about danger signs
  • Close follow-up needed
    • HPTP
    • Odyssey Travel Clinic
malaria
Malaria

Merozoite of p. falciparum

malaria what is it
Malaria, what is it?
  • Protozoal infection caused by
    • Plasmodium falciparum
      • Africa, East Asia, Oceania, Haiti
      • 50% of all cases
      • 95% of all deaths
    • Plasmodium vivax
      • Central America, Middle East, India, SE Asia
    • Plasmodium ovale
    • Plasmodium malariae
  • NB: Mixed infections common
malaria the vector
Malariathe vector

Anopheles mosquito

  • Also maternal-fetal, blood transfusions, dirty needles, etc.
malaria epidemiology
MalariaEpidemiology
  • >2 billion people (41% of the world population) live in malaria-risk areas
  • Endemic to >100 countries
  • Every year
    • 300-500 million people get malaria
    • 1.5-2.7 million people die from malaria
      • 90% in rural, sub-Saharan Africa
      • Disproportionately in children <5
slide70

Malaria, not hard to get …..

  • Studies of European / North American travelers to Kenya and Peace Corps volunteers in Africa
    • Malarial attack rate of 15/1000 per month
    • 2-4% mortality in those infected

Quoted in: Stanley J. Malaria. Emergency Medicine Clinics of North America 1997;15(1)113-155.

malaria in canada
Malaria in Canada
  • 1994 – 430 cases reported
  • 1995 – 621 cases reported
  • 1997 – 1036 cases reported
  • Per capita rate 10x as high as USA
  • 1994-1997 – tenfold increase in severe malaria requiring admission to ICU

Kain K, et al. Malaria deaths in visitors to Canada and in Canadian travellers; a case series. CMAJ 2001;164(5)656-659

malaria symptoms
Malaria Symptoms

Headache

Muscle aches

Diarrhea

Fever

Chills

Vomiting

Coughing

Abdominal pain

Malaria symptoms usually appear within 7 to 21 days of the mosquito bite, but may not appear until later

slide74
Interval between date of entry and onset of illness by plasmodium species for imported malaria cases in the United States (1992)

Adapted from MMWR 44:1-14, 1995

malaria is
Malaria is ….
  • Usually preventable
  • Almost always curable

Nobody should die of malaria!

case in point
Case in point …
  • Vietnam War
    • Mortality of US soldiers from malaria 40 times greater when treated by civilian MD vs. military MD

Stanley J. Malaria. Emergency Medicine Clinics of North America 1997;15(1)113-155.

  • 40% of malaria mortality in US is due to missed diagnosis

Stanley J. Malaria. Emergency Medicine Clinics of North America 1997;15(1)113-155.

plasmodium falciparum
Plasmodium Falciparum

Two merozoites of Plasmodium falciparum (blue and pink) in red blood cell

plasmodium falciparum1
Plasmodium Falciparum
  • Potentially fatal due to:
    • Expression of membrane proteins causing adherence of red cells to endothelial walls
      • End organ microcirculatory occlusion and tissue ischemia
      • Death usually due to brain or lung injury
  • Other species rarely fatal as they do not induce cytoadherence
plasmodium falciparum malaria
Plasmodium Falciparum Malaria
  • Renal failure
  • Hepatic failure
  • Pulmonary Edema
  • Seizures
  • Coma
  • Death (up to 7% of North American and European travelers)
    • Lobel HO, Kozansky PE. Update on prevention of malaria for travelers. JAMA. 1997; 278(21): 1767-1771.
slide81
“FEVER OCCURRING IN A TRAVELLER WITHIN 3 MONTHS OF DEPARTURE FROM A MALARIA-ENDEMIC AREA IS A MEDICAL EMERGENCY …”

Canadian recommendations for the prevention and treatment of malaria among international travellers. CATMAT, Laboratory for Disease Control. Canadian Communicable Disease Report 2000;26(Supp 2):I-vi, 1-42

malaria diagnosis
MalariaDiagnosis
  • Current Standard of Care
    • Thick film – screen for malaria
    • Thin film – species identification
  • Gold Standard
    • PCR
      • detect low levels of parasitemia and mixed infections
  • The Future
    • Dipsticks – presently being investigated
malaria diagnosis1
MalariaDiagnosis
  • Thick/Thin films often negative with low levels of parasitemia
  • A high index of suspicion requires repeat films q12h x 3 to rule out malaria
  • NB: malaria is a reportable disease in every province
malaria laboratory investigations
Malarialaboratory investigations
  • All of the following are necessary to determine severity of disease
    • CBC
    • LFTs, bilirubin
    • INR, aPTT
    • BUN, Creatinine
    • Glucose
    • Urinalysis
    • G6PD
      • prior to initiating treatment with primaquine for non-falciparum malaria
the three essential questions
The three essential questions …
  • Is this infection caused by P. falciparum?
  • Is this a severe or complicated infection?
  • Was this infection acquired in an area of known drug resistance?
malaria treatment
MalariaTreatment
  • Choice of treatment based on
    • Species of malaria
    • Level of parasitemia
    • Likelihood of drug resistance
    • Severity of infection
    • Patient specific factors (age, immunocompromise, etc.)
malaria drug resistance
Malariadrug resistance

Kain, K et al. Malaria deaths in visitors to Canada and in Canadian travellers.

CMAJ (2001);164(5)654-9

criteria for severe p falciparum
Criteria for severe P.falciparum

Either

  • History of recent possible exposure and no other recognized pathology

Or

  • Asexual forms of Plasmodium falciparum on blood smear
and 1 or more of
And 1 or more of:
  • Decreased LOC
  • Severe normocytic anemia
  • Renal failure
  • Pulmonary edema
  • Hypoglycemia
  • Shock
  • Spontaneous bleeding / DIC
  • Seizures
  • Acidosis
  • Hemaglobinuria
  • >5% parasitemia in non-immune individuals
treatment of uncomplicated falciparum malaria
Treatment of uncomplicated falciparum malaria
  • Malarone 4 tabs po od x 3 days

OR

  • Quinine sulfate 350mg po tid x 7 days

AND

  • Doxycycline 100mg po bid x 7 days
uncomplicated p falciparum
Uncomplicated P. falciparum
  • Can treat as outpatient if:
    • First dose of medication given in ER and tolerated
    • Patient has reliable supply of medication
    • Patient has reliable supervision
    • Patient has close follow-up
      • Malaria smears od/bid until negative
      • Odyssey clinic
treatment of severe falciparum malaria
Treatment of severe Falciparum Malaria
  • Immediate hospitalization
    • Mortality rate >20%
  • IV quinine
    • Available 24 hours a day through pharmacy at Alberta Children’s Hospital
    • Comes with detailed instructions
  • IV quinidine
    • equally effications but more cardiotoxic
    • Requires cardiac monitoring
treatment non falciparum malaria
TreatmentNon-Falciparum Malaria
  • Chloroquine 1.5g po over 3 days
    • 300 mg po bid on days 1-2
    • 300 mg po od on day 3
  • 80% chloroquine resistance of P.vivax in Papua New Guinea and Irian Jaya
  • Reports of resistance in Indonesia, Myanmar, Guyana, Solomon Islands
prevention of relapse in non falciparum malaria
Prevention of Relapse inNon-Falciparum Malaria
  • Primaquine 15mg po od x 14 days
      • Absolute contraindication: G6PD deficiency
      • MUST CHECK G6PD LEVEL FIRST!
  • Plus one of
    • Doxycycline 100mg po bid x 7 days
    • Fansidar – single dose of 3 tabs
    • Clindamycin 10mg/kg iv loading dose followed by 5mg/kg iv q8h until blood is clear of parasites (only if unable to tolerate 1 or 2)

Canadian recommendations for the prevention and treatment of malaria among international travellers. CATMAT, Laboratory for Disease Control. Canadian Communicable Disease Report 2000;26(Supp 2):I-vi, 1-42

non falciparum malaria
Non-falciparum Malaria
  • Can treat as outpatient if:
    • First dose of medication given in ER and tolerated
    • Patient has reliable supply of medication
    • Patient has reliable supervision
    • Patient has close follow-up
      • Malaria smears od/bid until negative
      • Odyssey Clinic
slide98

The most important factors that determine the survival of patients with falciparum malaria are early diagnosis and prompt initiation of appropriate treatment.

Canadian recommendations for the prevention and treatment of malaria among international travellers. CATMAT, Laboratory for Disease Control. Canadian Communicable Disease Report 2000;26(Supp 2):I-vi, 1-42

where do i send my patients for follow up
Where do I send my patients for follow-up?

Dr. Susan Kuhn

Odyssey Travel & Tropical Medicine Clinic

208 2004 14th Street NW

Calgary, AB

T2M 3N3

Tel: (403) 210-4770

summary
Summary
  • Tropical infectious diseases are coming to an Emergency Department near you
  • Many potentially lethal diseases are easily diagnosed and treated
  • The first step to making a diagnosis is to think about it
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