Fever in the Returning
Traveler
NIRAJ PATEL, MD, MS
INFECTIOUS DISEASES AND IMMUNOLOGY
THIS PRESENTATION
IS ON THE G: DRIVE,
“PRESENTATIONS”
65
60
55
50
Year
*ITA, includes travel to Canada and Mexico
20
05
20
04
20
03
20
02
20
01
20
00
19
99
19
98
19
97
19
96
45
19
95
Number of Travelers (millions)
U.S. Residents Traveling Abroad*
Where Do U.S. Residents Travel?
Of the 17% who traveled outside the U.S. . . .
40
%
30
20
10
0
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Source: HealthStyles Survey 2005
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Infectious Disease Risks to
the Traveler
 Malaria
 Diarrhea
 Leishmaniasis
 Rabies
 Dengue Fever
 Typhoid Fever
 Ebola
 Schistosomiasis
 Tuberculosis
 Leptospirosis
 Polio
 Yellow Fever
 Measles
 JEV
ETC.
Travelers’ Health Risks
Of 100,000 travelers to a developing country
for 1 month:
– 50,000 will develop some health problem
– 8,000 will see a physician
– 5,000 will be confined to bed
– 1,100 will be incapacitated in their work
– 300 will be admitted to hospital
– 50 will be air evacuated
– 1 will die
Steffen R et al. J Infect Dis 1987; 156:84-91
OBJECTIVES
Recognize common signs and
symptoms in a returning traveler
Know differential diagnosis of fever in a
returning traveler
Know methods of diagnosis and
treatment of infections acquired abroad
Potential life threatening tropical
infections
 Viral
- Hemorrhagic Fever (region dependant)
- Prodrome Viral hepatitis A,B & E
- HIV
- Other viral infections (Avian & H1N1)
 Bacterial
- Typhoid Fever
- TB
 Parasites
- Malaria
- Katayama fever
- Trypanosomiasis
 Rickettsia
- Rickettsia Africae
COMPREHENSIVE ASSESMENT
History (including: Travel Questionnaire)
Thorough Physical examination
Baseline laboratories plus clinically
guided additional tests
Associated symptoms in the
returning febrile traveler
Incubation periods of travel related
infections in febrile travelers
Med Clin of N America. Vol 83, Number 4, July 1999: 997-1017.
Fever in a returning traveler
2-3% of people who travel to developing
countries*
Diarrhea and respiratory tract infections
are the most common illnesses (25-60%)
in returning travelers*
Malaria is the next most common cause of
fever in returning travelers
* Hill, DR. Health problems in a large cohort of Americans traveling to developing countries.
J Travel Med 2000; 7:259.
622 patients returning from the tropics¥
450
400
350
300
250
54
200
392
150
100
230
203
All Tropical Diseases
Malaria in Febrile
Patients
50
0
Non-related Travel
Illness
EXCLUDE MALARIA FIRST
¥ Ansart S, Perez L, Vergely O, et al. Illness in travellers returning from the tropics: a prospective study of 622 patients. J of Travel Med;2007;12:312-318.
Malaria: Basics
Plasmodium – RBC parasite
falciparum, vivax, ovale, malariae
Vector: Anopheles spp
Drug resistance varies by region
chloroquine, mefloquine, doxycycline,
atovaquone/proguanil
Malaria Fever Characteristics
 80-90% of Malaria associated with fever1,2
 Malaria naïve traveler – fever at lower parasitic count
 Partial immunity (repeat infections) fever at higher
threshold parasitic count (flu like symptoms + d &
v1,2)
 Fever as lead symptom is often irregular at onset ,
particularly in P. falciparum malaria1
EXCEPTIONS
-if patient taken chemoprophylaxis
-if P. vivax & P. ovale
1. Grobusch M, Kremsner P. Uncomplicated Malaria.Curr Topics Microbiol Immunol 2005; 295:83-104.
2. Jelinek T, Schulte C, Behrens R,et al. Imported Falciparum malaria in Europe. Clin Infect diseases 2002; 34:572-576.
Malaria: High Risk Groups
1.Children < 5yrs
Not always protected (Chemical & Physical)
Non specific symptoms – fever, lethargy,
malaise
Risk of fever complications / severe malaria /
cerebral malaria1,2
2.Pregnant woman
3.Elderly
4.Immunocompromised
5.Inhabitants of Endemic Areas whom emigrate,
lose their immunity within 6mo after absence of
re-exposure3
1. Boggild A, Kain K. Malaria: Clinical features, management and prevention. International encyclopedia of public health. Vol.5: Academic Press; 2008.p371-382.
2 Suh K, Kain K, Keystone J. Malaria. CMAJ 2004;170:1693-702.
3 Mascarello M, Allegranzi B, Angheben A, et al. Imported malaria in adults & children: epidemiological & clinical characteristics of 380 consecutive case observed in
Verona, Italy. J Travel Med 2008;15:229-36.
Diagnosis depends on identification
of organisms on blood smear
Malaria diagnosis6
 CLINICAL GOLD STD
Giemsa stained thick & thin
smear
REPEAT x3; 12h’ly X
24/48h11,12
 PCR – limited availability
 Serology – not helpful
 Clinical Clues:
 Platelets (rare bleeding
unless complicated malaria,
ex. DIC)
 Spleen size
11. Grobusch M, Burchard G. Diagnosis of malaria in returned travellers. Traveller’s Malaria. 2 nd ed.2008:284-299.
12. Newman R, Parise M, Barber A, et al. Malaria related deaths amongst US travellers, 1963-2001. Ann Int Med 2004;141:547-55.
Why parasites are not detected at times
in peripheral smear ?
a. partially treated patients
b. prophylactic antimalarial treatment
c. inexperienced microscopist
d. poor quality stain
e. sequestration in deep vascular bed
Malaria
algorithm
www.cdc.gov
MALARIA (UNCOMPLICATED)
Fever and any of the following:
Headache
Myalgias, arthralgias
Chills
Loss of appetite, abdominal pain
Nausea, vomiting, diarrhea
Splenomegaly
Severe Malaria (1 or more)
 Parasitemia > 5% RBC
 Hypotension
 Hypoglycemia
 Disseminated
intravascular coagulation
 Impaired
consciousness/coma
 Spontaneous bleeding
 Severe normocytic
anemia [hemoglobin < 7]
 Acidosis
 Renal failure
 Jaundice
 Acute respiratory distress
syndrome
 Repeated generalized
convulsions
 Hemoglobinuria
http://www.cdc.gov/malaria/diagnosis_treatment/clinicians2.html
Current world situation regarding malaria
and drug resistance
Malaria algorithm
TREATMENT
CASE: Fever in Returning Traveler
8 yo Indian female, stayed in northern
India for one month
At end of her stay, developed bloody loose
stools, treated with metronidazole
2 days after returning to US, developed
daily fever and fatigue
Few mosquito bites, disagreement about
street food
August 2012
CASE: Fever in Returning Traveler
Hospitalized one week later with chills,
cough with fever
No prophylaxis medications taken prior to
travel
PE: T 101.4 P144 BP 106/52 R24
Gen: flat affect; Lung: decreased BS on
left; GI: occasional abdominal pain with
palpation, otherwise normal PE
CASE: Fever in Returning Traveler
Ceftriaxone was started
Fever defervesced
Stool culture negative
Malaria smears negative
PPD negative
Blood culture grew GNR
Typhoid Fever
 Caused by the bacterium Salmonella typhi and less
commonly by Salmonella paratyphi
 Acute generalized infection of the reticuloendothelial
system, intestinal lymphoid tissue, and the gall bladder
 Always comes from another human, either ill person or
asymptomatic carrier
 The bacterium is passed on with water and foods and
can withstand both drying and refrigeration
Typhoid Fever
♦ strongly endemic
♦ endemic
♦ sporadic cases
Typhoid Fever: Causes
 Ingestion of contaminated food
 Contact with acute case of typhoid fever
 Contaminated water where inadequate sewage
systems and poor sanitation exist
 Contact with chronic asymptomatic carrier
 Eating food or drinking beverages that handled by
an infected person
Time frame




Occurs gradually over a few weeks after exposure.
Sometimes children suddenly become sick.
First-Stage: high fever, fatigue, weakness, headache,
sore throat, diarrhea, constipation, stomach pain, skin
rash on chest and abdominal area. Adults most likely to
experience constipation, children usually experience
diarrhea.
Second Stage: weight loss, high fever, severe diarrhea
and severe constipation, abdominal distension
Typhoid state: When typhoid fever continues untreated
for more than two to three weeks, the affected individual
may be delirious or unable to stand and move, and the
eyes may be partially open during this time. Fatal
complications such as intestinal perforation may occur.
Rose spots
Aches and pains
High fever
Diarrhea
Chest congestion
Typhoid Meningitis
Typhoid Fever: Diagnosis
 Clinical history, physical exam
 Cultures: stool, blood, urine, bone
marrow
 Serology lacks specificity
 Sensitivity of blood culture is 60%,
bone marrow is 90%
Food and Water Precautions
Bottled water
Selection of foods
well-cooked and hot
Avoidance of
salads, raw vegetables
unpasteurized dairy
products
street vendors
ice
Salmonella typhi: Treatment€
Gastroenteritis
ampicillin, amoxicillin, TMP-SMX for 10-14 d
ceftriaxone, cefotaxime, azithromycin,
flouroquinolones*
Bacteremia, osteo, meningitis, abscess
cefotaxime, ceftriaxone for 4 weeks
Dexamethasone
Delirium, obtundation, stupor, coma, shock
(Note: Relapse in 15% requiring retreatment)
€Red Book 2012
*Areas of amipicillin, TMP-SMX resistance
Cooke et al, Travel Medicine and Infectious Disease, 2004. 2:67–74.
 The best known carrier
was "Typhoid Mary”;
Mary Mallon was a cook
in Oyster Bay, New York
in 1906 who is known to
have infected 53 people,
5 of whom died.
 Later returned with false
name but detained and
quarantined after another
typhoid outbreak.
 She died of pneumonia
after 26 years in
quarantine.
Basics
Dengue
Viral infection
“Breakbone fever”
Almost always symptomatic
Repeat infection may present as VHF
Vector: Aedes spp.
Dengue Fever
 Dengue fever and dengue hemorrhagic fever are the
most common mosquito-borne viral diseases in the world
 Only the female mosquito feeds on blood because it
needs protein found in blood to produce eggs. Male
mosquitoes feed only on plant nectar
 Mosquito is attracted by body odors, carbon dioxide and
heat emitted from animal or humans
 Aedes are most active during dawn and dusk
 Short incubation period (<2 weeks)
Diagnosis confirmed by:
Dengue IgG or IgM
sero-conversion (>4)
False positive:
Yellow Fever
Japanese
Encephalitis
Dengue Fever
Vector
Precautions
 Covering exposed skin
 Insect repellent containing DEET 25 – 50%
 Treatment of outer clothing with permethrin
 Use of permethrin-impregnated bed net
 Use of insect screens over open windows
 Air conditioned rooms
 Use of aerosol insecticide indoors
 Use of pyrethroid coils outdoors
 Inspection for ticks
African Trypanosomiasis: African
Sleeping Sickness
 West Africa (T. brucei gambiense),
East Africa (T. brucei rhodesiense)
 Aggressive tsetse fly bite
 1° Chancre, 2° febrile illness, nodes, 3°
CNS disease
 Diagnosis – Blood, CSF or lymph
node trypanosomes (Notify lab –
scattered therefore easily missed)
 Treatment: pentamidine
(gambiense) and suramin
(rhodesiense), eflornathine (CNS)
YELLOW FEVER
Viral infection (Flavivirus)
Transmission: mosquito (Aedes or
Haemogogus)
Sub-saharan Africa and Central/South
America
.
Yellow Fever
Clinical symptoms: fever, chills,
myalgias, headache
15% progress to jaundice, shock,
hemorraghic symtoms, organ failure
Diagnosis: serology
Treatment: symptomatic
Prevention: yellow fever vaccine,
vector precautions
SUMMARY
Fever in returning traveler should prompt
evaluation for infections acquired abroad
Travel history and physical examination
are important
Malaria is the most common infection in
returning travelers, and must be excluded
Prompt diagnosis leads to improved
outcomes
Travel Health Resources
 CDC Travelers’ Health Website
– www.cdc.gov/travel
 World Health Organization
– www.who.int/int
 State Department
– travel.state.gov
 International Society of Travel Medicine
– www.istm.org
 Health Information for International Travel
– CDC “Yellow Book”
 International Travel and Health
– WHO “Green Book”
Katayama Fever
Clinical Diagnosis (negative Malaria)
Serology only positive 3/12 post exposure
Positive ova in urine only 45 days post exposure
1 day absolute risk swimming in Lake Malawi of
acquiring Shistosomiasis 52%-74%13
13. D’Acremont V, Burnard B, Ambresin A, et.al. Practice guidelines for the evaluation of fever in the returning traveler. J Travel Med 2003;10 Suppl 2:S25-S45.
Yellow fever risk areas-Africa
Nathnac.org
5. Geographical infections
Example: Loa Loa disease (African eye worm)
Location: West Africa rain forests
Vector: Crysops fly
Reservoir:
Human
Clinical: Eye & skin – calabar swelling
Diagnosis:
Microfilaria on Giemsa Stained
Blood smear & microscopy
Rickettsia Africae
 Clinical Diagnosis
 Serology only turns converts
only 7 days after exposure
 Weil-Felix – poor sensitivity &
specificity
Immunizations to Consider for Adult
Travelers
Routine
Diphtheria*
Tetanus*
Pertussis*
Measles +
Mumps+
Rubella +
Varicella
Pneumococcus
Influenza
* Td or Tdap
+ MMR
Travel related
Hepatitis A
Hepatitis B
Typhoid
Rabies
Meningococcal disease
Polio
Japanese encephalitis
Yellow Fever
Exposure and Tropical
infections
 Insect bites
– malaria, rickettsial infections, dengue,
trypanosomiasis
 Animal - Q fever, anthrax, rabies
 Human - viral haemorrhagic fever
Exposure and Tropical
infections
 Raw/undercooked foods
– enteric infections, hepatitis, trichinosis
 Fresh water swimming
– schistosomiasis, leptospirosis
Pathology and Pathogenesis of
Enteric fever
 Caused by
S. typhi
S.paratyphi
A BC
Organisms penetrate ileal mucosa reach mesentric lymph
nodes via lymphatics, multiply,
Invade Blood stream via thoracic duct
In 7 – 10 days through blood stream infect
Liver, Gall Bladder,, spleen, Kidney, Bone marrow.
After multiplication bacilli pass into blood causing
secondary and heavier bactermia
Clinical presentation
 Ingestion to onset of fever varies from 3 –
50 days. ( 2 weeks )
 Insidious start, early symptoms are vague
 Dull continuous head ache
 Abdominal tenderness discomfort may
present with constipation.
 May progress and present with step ladder
pattern temperature
 Temperature fall by crisis in 3 – 4th week
Box 1: Criteria for diagnosing severe Plasmodium Falciparum Malaria
Boggild, A. K. et al. CMAJ 2009;180:1129-1131
Copyright ©2009 Canadian Medical Association or its licensors
Visiting Friends and Relatives
Foreign-born increased 57% since 1990
from 19.8 million to 31.1 million1
20% of US population are first- or
second-generation immigrants
Comprised ~46% of US international air
travelers in 20043
1US
Census Bureau, Census 2000 Brief, The Foreign-Born Population: 2000, issued Dec 2003 (Previous: US
Census Bureau, Profile of the Born Outside the United States Population 2000, issues Dec 2003???
2 Angell & Cetron, 2005
32004 Profile of U. S. Resident Travelers Visiting Overseas Destinations Reported From: Survey of
International Air Travelers, Office of travel and tourism Industries, USDOC