Fever in the Returning Traveler
Steven Callens, MD PhD
Ghent University Hospital
Scope of the problem
• 10% of travelers need medical care during of
after travel
• Potentially mortal or severe infections need to be
excluded first by stepwise diagnostic strategy
– Step 1: “First exclude malaria!”
– Step 2: Exclude diseases of public health importance
(eg tuberculosis, meningococcal disease, Lassa fever...)
Main causes of imported fever (%)
ITMA, n=2071
GeoSentinel, n=6957
Bottieau et al. Medicine 2007
Wilson et al. Clin Infect Dis 2007
Malaria
27
21
Respiratory illness
10
14
Bacterial enteritis
6
8
Skin/soft tissue infection
4
4
Genito-urinary infection
3
4
Dengue
3
6
Enteric fever
1
2
Unknown etiology
23
22
4
Top tropical conditions, ITMA 2000-2006
Africa
(n=1401)
Asia
(n=381)
P.falciparum malaria
(30%)
Dengue
(13%)
Non-falc. malaria
(5%)
Non-falc. malaria
(9%)
Dengue
(9%)
Rickettsial infection
(4%)
Enteric fever
(3%)
Non-falc. malaria
(4%)
Katayama
(2%)
P.falciparum malaria
(2%)
Protoz. enteritis
(2%)
Bottieau et al. Arch Intern Med 2006; Medicine 2007
America
(n=146)
Top tropical conditions, GeoSentinel 2007-2011
Evolving epidemiology
Leder K et al. Ann Intern Med 2013
Bottieau, E., Clerinx, J., Van Gompel, A., Van Esbroeck, M., Wocjiechowski, A., & J., V. den E. (2005). PostravelFever in children ISTM05. In
ISTM.
Etiology and Outcome of Imported
Fevers in Children
Bottieau, E., Clerinx, J., Van Gompel, A., Van Esbroeck, M., Wocjiechowski, A., & J., V. den E. (2005). PostravelFever in children ISTM05. In
ISTM.
Travel-Related Morbidity in Children:
A Prospective Observational Study
van Rijn, S. F., Driessen, G., Overbosch, D., & van Genderen, P. J. J. (2012). Travel-related morbidity in children: a prospective
observational study. Journal of Travel Medicine, 19(3), 144–149. http://doi.org/10.1111/j.1708-8305.2011.00551.x
First evaluation
• Severity related: exclude malaria!
• Disease related
– Region of exposure
– Latency period (time after travel)
• Traveler related
– Type of traveler (tourist, expat, VFR)
– Vaccination & Malaria prophylaxis status
– Exposure status (type of travel, bathing in fresh water, bat
exposure, rafting or canoeing in rivers, tick bites, tse tse
flies)
– Sexual history (the best protection against an STD is to
bring your partner along – although not absolute!)
Malaria: presenting symptoms
Malaria diagnosis
• Gold standard is Thick and Thin Smear
• Rapid tests
– Plasmodium histidine-rich protein 2 (HRP-2), pan-LDH,
aldolase:
• P. falciparum
• 80-96% sensitivity and 99% specificity
– Sensitivity drops rapidly at low parasite count
• Not quantitative: response can not be followed, positive till
28 after treatment
• No detection of P. vivax, ovale, malariae, knowlesi
– One negative rapid test does not rule out malaria!!
Mandell
Treatment – Severe malaria
Treatment
Alternatieve behandeling
voor ernstige malaria met
alarmtekenen!!
Voorkeursbehandeling of
tijdens eerste trimester
zwangerschap
Artesunate met Doxycycline of Clindamycin (zwangeren en
kinderen)
Quininedihydrochloride intraveneus met Doxycycline of
Clindamycine , van zodra mogelijk: Quininesulfaat
Treatment – Non severe malaria
Malaria soort en species identificatie
Geen definitieve identificatie en geen
gebruik van Malarone profylaxie
Geen definitive identificatie en wel
gebruik van Malarone profylaxie
P. vivax, ovale or malariae (met
uitzondering van Zuid Oost Azië)
P. falciparum – geen gebruik van
Malarone profylaxis
Behandeling en Caveats
Malarone
Riamet, Eurartesim
Nivaquine, nabehandeling met
Primaquine of Malarone
Malarone
Dengue - Chikungunya
First cases of autochthonous
dengue (France + Croatia)
chikungunya fever (Italy):
from bad dream to reality!
Flavivirus related to yellow fever, dengue,
West Nile virus and Japanse encephalitis virus
2007 outbreak: Federated States of Micrones
One US student viraemic traveled to US
Hayes. EID. 15(9): 1347 – 1350; Duffy. NEJM. 2009;360:2536-2543
Diagnosis
• Ask for previous episodes of dengue episodes
(severe DF!!)
• PCR exists, but not readily available
• Serology
– ELISA
– Indirect immunofluorescence
– Four fold change in titers
Treatment and Prevention
• No specific treatment exists: avoid aspirin!
• Prevention
• Vaccination
Ricketsial Diseases
Rickettsia species
causing disease in humans
Described prior to 1984
• R. rickettsi
• R. prowazekii (TG, epi)
• R. conorii (fièvre bout.)
• R. sibrica
• R. akari
• R. typhii (TG, murine)
• R. australis
Emerging species (since 1984)
•
•
•
•
•
•
•
•
•
•
R. japonica
R. africae
R. honei
R. slovacae
R. hoifongifangensis
R. aeshlimannii
R. felis
R. parkeri
R. massiliae
R. momacensis
R. conorii (fièvre bout.)
R. africae (African tick bite fever)
Vectors
Orientia tsutsugamushi
Scrub typhus
R. akari
Rickettsial pox
R. prowazekii
Epidemic typhus
R. typhii
R. felis
Endemic typhus
Brill Zinser disease
Clinical Presentation
Mandell
Diagnosis
• Eschar with rash...
• Thrombopenia, leucopenia, slight elevation
liver function tests, decreased creatinine
clearance
• Serology (of retrospective use)
– Microimmunofluorescence assay
– IgG and IgM
Treatment and Prevention
• Treatment
– Early antibiotitic intervention is recommended to prevent
severe vascular endothelial damage
• In turns prevents complications and failure of various organ
systems
• Doxycycline, tetracycline and chloramphenical are the drugs of
choice
• Prevention
– Use of repellents and protective clothing to avoid or
reduce contact with ticks
– Careful inspection & quick removal of ticks
– Keep domestic areas free of animals ectoparasites and
perform a regular control of domestic animals hygiene
Schistosomiasis
Epidemiology
•
Schistosoma mansoni
– distributed throughout Africa: There is risk of infection in freshwater in southern and subSaharan Africa–including the great lakes and rivers as well as smaller bodies of water.
Transmission also occurs in the Nile River valley in Sudan and Egypt
– South America: including Brazil, Suriname, Venezuela
– Caribbean (risk is low): Antigua, Dominican Republic, Guadeloupe, Martinique, Montserrat,
and Saint Lucia.
•
S. haematobium
– distributed throughout Africa: There is risk of infection in freshwater in southern and subSaharan Africa–including the great lakes and rivers as well as smaller bodies of water.
Transmission also occurs in the Nile River valley in Egypt and the Mahgreb region of North
Africa.
– found in areas of the Middle East
•
S. japonicum
– found in Indonesia and parts of China and Southeast Asia
•
S. mekongi
– found in Cambodia and Laos
•
S. intercalatum
– found in parts of Central and West Africa.
http://www.cdc.gov/parasites/schistosomiasis/epi.html
Epidemiology
Life cycle
Clinical Signs
• Prepatent period
– Dermatitis lasting 3 to 5 days
www.medicinenet.com
Clinical signs
• Acute phaze: Katayama fever
– Migrating shistosomules in the body
– Lasts several weeks
•
•
•
•
•
Fever
Cough
Arthralgia
Urticaria and oedema
Hypereosoinophilia
Clinical signs
• Chronic stage: 3 to 6 months post-infestation
– S. haematobium
• Urinary signs: pollakisuria, dysuria, hematurie
• Calcification of the bladder, hydronefrosis
• Genital: epididymitis
– S. mansoni
• Diarrhea, rectal pain, tenesmus
• Hepatosplenic complications
– S. intercalatum
• Diarrhea, rectal pain, tenesmus
Diagnosis
• Diagnosis
– Serology may develop weeks after first symptoms
– Eggs in stool or urine may appear weeks after fist
symptoms
– Clinical suspicion, hypereosinophilia and exposure
history
• Treament: Steroids give prompt relief
Invasive Amoebiasis
• Entamoeba histolytica
Invasieve Amoebiasis
Invasive Amoebiasis
• Leukocytosis will be high.
• Ultrasound and serology (ELISA, Latex
agglutination) confirm the diagnosis
• Aspiration: dark brownish red colour (“anchovy "
or "chocolate" pus), no offensive odour, unlike
most bacterial (anaerobic) abscesses
• In case of doubt a trial therapy quickly produces
a spectacular improvement
• Fewer than 20 % of people with a hepatic
abscess have Entamoeba histolytica in the faeces.
Invasive Amoebiasis
• Metronidazole for 10 days (often initially IV),
followed by diloxanide furoate for 10 days.
• The latter is to destroy any amoebae in the lumen
of the intestines.
• Aspiration is only carried out for very large
abscesses or if there is a risk of breakthrough.
• Surgery is indicated if the abscess ruptures (e.g.
into the peritoneum).
• If a relapse of the abscess occurs this will usually
happen within two months.
In conclusion
• Step 1: exclude severe life threathening diseases
• Step 2: think of “public health” sensitive diseases
• Step 3: deal with severly ill patient with or without
localising symptoms
– Clinical exam: exanthem, eschar
– Blood exam: leucopenia, thrombocytopenia, liver function
and kidney function
– Hemoculture (Salmonella) (bone marrow...)
– CSF (...)
– Echography liver
• Step 4: only after failing to see the horse (cosmopolitan
infections), think zebra...