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4/16/2014
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Ill returning traveler Brian S. Schwartz, MD
UCSF, Division of Infectious Diseases
• I have no disclosures
International travel in 2010
• 940 million travelers crossed international boarders
• 60 million traveled from the US internationally
– Almost half traveled to a developing country
UNWTO World Tourism Barometer. World Tourism Organization; 2011.Office of Travel and Tourism Industries 2010 Outbound Analysis, US Dept of Commerce 2011
Travelers crossing international borders
Keystone. Travel Medicine. 2008
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What is the magnitude of travel related morbidity/mortality
• 20‐70% report some illness
• 1‐5% seek medical attention
• 3% report fevers
• 0.1‐0.01% require medical evacuation
• 1/100,000 – deathHill DR. CID. 2006
Cardiovascular Disease49%
Injury22%
Infection1%
Other/Unknown6%
Cancer6%
Suicide/Homicide3%
Medical14%
Exacerbation of comorbidities is the predominant cause of death in US Travelers:
Hargarten SW. Annals of Emergency Medicine.1991
Preventable causes of death in US travelers 2008‐2010
Air accident, 82
Disaster, 131
Drowning, 329
Drug‐related, 67
Execution, 13
Homicide, 533
Maritime accident, 31
Accident other, 332
Suicide, 357
Terrorist, 52
Vehicle accident, 735
http://travel.state.gov/law/family_issues/death accessed 01.10.2012
Illness in returned travelers: 2007‐2011
GI37%
Febrile25%
Derm21%
Resp12%
GU/STI3%
Neuro2%
Leder K. Ann Intern Med. 2013
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Top 5 complaints in returning travelers leading to MD visit
• Fever without localizing findings
• Acute diarrhea
• Dermatological disorders
• Chronic diarrhea
• Nondiarrheal gastrointestinal disorders
Freedman DO. NEJM. 2006.
Fever
• 2‐3% of American/European travelers to developing countries
– 39% fever when abroad
– 37% fevers abroad and home
– 24% fevers at home only
• Medical emergency
Hill DR. J Trav Med. 2000
How to determine etiology of fever in returned traveler?
• Destination
• Incubation period
• Exposures
• Exam findings/labs
• Prophylaxis/immunizations
0
100
200
300
400
500
600
700
800
900
1000
Carribean C. America S. America Sub‐SaharanAfrica
SouthCentral Asia
SE Asia
Cases
Freedm
an DO
. NE
JM. 2006.
Destination: Etiology of fever according to region traveled
Dengue
Unknown
EBV/CMV
Malaria
Rickettsia
Typhoid
Dengue
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0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0‐7 7‐14 14‐21 21‐28 28‐35 35‐42 >42
Proportion of Diagn
oses
Days post‐travel
7
Incubation period: Etiology of fever according to interval after travel
Wilson ME. CID. 2007.
Rickettsia
P. falciparum
P. vivax
CMV/EBV
DengueTyphoid
Other
Malaria Other
7 14 21 28 35 42 490
Exposures?
• Insect or animal exposures?
• Fresh water exposure?
• What did they eat/drink?
• Other ill travelers?
• Sexual activity?
Specific symptoms or exam findings?
• Symptoms
– Abdominal pain
– Arthralgias
• Exam findings
– Rash
– Jaundice
– Ocular changes
What kind of prevention measures were used?
• Vaccinations?
– Which ones?
– Timing of vaccinations?
• Malaria prophylaxis?
– Appropriate agents?
– Taken appropriately?
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Case 1
29 year‐old paleontologist returned 3 days ago from a 3 week research trip to southern Bangladesh complaining of fever.
He complains of high fevers and now diffuse myalgias.
Initial testing?
Initial testing?
• Complete blood count
• Liver function tests
• Blood cultures
• Thick and thin blood smears (malaria)
• Urinalysis
• Chest x‐ray
• Additional testing based on history/exam
Skin and Labs• 2.1>37<67
• Cr: 0.8
• AST: 78
• ALT: 93
• AP: 88
• Bili: 0.7
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Your DDx? Dengue fever
• 50‐100 million infections/year
• Mosquito vector (daytime)
• Urban and rural
Dengue fever: worldwide distribution
http://www.healthmap.org/dengue/index.php
Dengue fever: clinical disease
• Incubation: 4‐7 days
• Clinical Manifestations:– Severe headache, joint and muscle aches
– Nausea and vomiting
– Rash
• Dengue Hemorrhagic Fever/Shock Syndrome– Occurs 3‐7 days into illness, often w/ end of fever
• Labs: leukopenia, thrombocytopenia, LFTs
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Dengue rash1‐2 days post onset of symptoms
Flushing erythema
3‐5 days
Morbilliform eruptionw/ petechiae and islands of sparing
Pincus LB. J Am Acad Dermatol. 2008
Dengue diagnostics
Guzman MG. Nature Reviews Micro.2010
Dengue fever: treatment and prevention
• Treatment: supportive
• Prevention of mosquito exposure
– Avoid endemic areas
– DEET
– Permethrin
Dengue in Hawaii!!
• In 2001‐2002 > 1,000 infected on 3 islands
• No Aedes aegypti were found
• Aedes albopictus was able to transmit dengue
• Returning traveler to Hawaii infected with dengue after visiting French Polynesia
Dengue Fever Hawaii 2001-2002. Emerging Infect Dis.2005
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Chikungunya fever
http://www.cdc.gov/chikungunya/
Chikungunya in the Caribbean!
476
116
3643
Chikungunya fever
• Incubation period 2‐4 days (1‐14)
• Clinical manifestations
– Fever
– Polyarthralgias 2‐4 days later: Hands/ankles
– Rash ~ 50%, maculopapular, hyperpigmentation
• Labs: Lymphopenia, thrombocytopenia, LFTs
• Severe complications/deaths in elderly
Chikungunya: diagnostic testing
• Serological testing (IgM/IgG) available via CDC and Quest Diagnostics (via Focus Labs)
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Case 2
• 63 year‐old male with no PMH returned from a 10 day vacation to South Africa with complaints of fever, myalgias, and rash.
History cont.
July0 2110 122 13 19
To South Africa
In South Africa
Return to USA
15
Noticed lesion on right waist‐band area, non‐tender
Fevers (Tm‐101), myalgias, fatigue
Developed “red spots” on chest, arms
UCSF ED
Physical Exam
• VS: 38.5, 76, 128/70, 16, 99% RA
• Lymph:
– 1 cm R inguinal LAD, mild tenderness
• Skin:
– right waistband region, 1.5 x 1 cm ulcer w/ mild surrounding erythema non‐painful
– ~20, 0.2‐0.3 cm papulo‐vesicular lesions on trunk, flank, back, forehead, extremities
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Labs and Microbiology
Hematology
\ /5.4 ‐‐‐‐‐‐‐‐ 214
/ 47 \
DiffPoly ‐ 31%Lymph ‐ 51%Mono ‐ 15%Eos ‐ 2%Baso ‐ 1%
Chemistry
Chem 7 ‐ wnl
LFTS – wnl; UA ‐ wnl
Micro
7/18 ‐ Bld Cx X 2 – NGTD
7/18 – thin/thick ‐ neg
Your DDx?
African Tick Bite Fever
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African Tick Bite Fever
• Rickettsia africae
Jensenius, Lancet ID 2003
Clinical Presentation
• Fever
• Headache
• Muscle aches
• Inoculation eschar, often multiple
• Regional lymph node swelling
• Rash
Jensenius M. African Tick Bite Fever. Lancet Infect Dis 2003; 3: 557–64. Rauolt D. Rickettsia Africae, A Tick-borne Pathogen In Travelers To Sub-Saharan Africa. N Engl J Med 2001, 344 (20)
African tick‐bite fever
“Tache noire”
Treatment
• Doxycycline 100 mg BID x 7 days or until 48h after defervescence
• Symptoms often improve 24‐48h after initiation of treatment
Rolain JM. In Vitro Susceptibilities of 27 Rickettsiae to 13 Antimicrobials. Antimicrobial Agents and Chemotherapy. 1998. 1537–41
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Case 3• 28 year‐old male returned 3 weeks ago from a trip to Kenya
• Last week developed fever (up to 103), occasional hives, and occasional cough/wheezing
Physical Exam
• T‐101, VSS
• HEENT: oropharynx clear
• CHEST: clear
• CV: RRR no M
• ABD: soft, no HSM
• EXT: WWP
• DERM: faint diffuse maculopapular rash
Labs
• CXR ‐ clear• 8>40<320
• Eos: 6.0
• AST‐55, ALT‐63, AP & Bili‐wnl
• Cr‐0.9
Exposures
• Swam in a fresh water lake
– After swimming in lake he developed an “itchy rash” which resolved in a few days
• No uncooked food/unfiltered water
• Denies exposure to sick contacts
• Sexually active with girlfriend
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Fever and Eosinophilia?
• Strongyloides
• Acute schistosomiasis (Katayama fever)
• Visceral larva migrans (toxocariasis)
• Hookworm
• Ascariasis
• Cutaneous larva migrans
• Filariasis
• Trichinosis
Eosinophilia in returning travelers
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
SE Asia Ind.subcont.
Mid East Asiaother
S. & C.America
Sub‐sah.Africa
Oceania
% of cases
Non‐schisto eos Schistosomiasis
Meltzer E. AJTMH. 08.
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Diagnostics
• Bld cx x 2 – NGTD
• Thick/thin smear – negative
• Schisto IgG ‐ positive
Schistosomiasis
Gryseels B. Lancet ‘06
“Swimmer’s itch”(12-24 hrs)
Katayama Fever(2-6 wks)Chronic Infx
-Gut-Urine-Liver-Other (months-yrs)
Diagnosis
• Micro
– Stool O&P
– Urine O&P
• Serology
• Histology
Gryseels B. Lancet ‘06
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Treatment
• Praziquantil is the treatment of choice
– Not active against immature forms
– Katayama fever, repeat 6‐8 weeks later (+/‐steroids)
Case 4
• 45 year‐old Russian business man presents to urgent care with fever and rash for several days. He also complains of cough, nasal congestion, and itchy eyes
• He has been in San Francisco for 1 week for a conference. He otherwise has no past medical history
http://children.webmd.com/
Morbilliform eruption and fever in returning traveler
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Measles cases in US 2001‐2013
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6236a2.htm
Case 5
• 34 y/o M presents with fever
• Returned 2 wks ago from a 3 wk trip to Ghana
• Received hep A, typhoid, yellow fever vaccines•
• Drank bottled water, cooked his food paying close attention to preparation
• Used treated bed net, no malaria prophylaxis
Exam
• T‐102.3, 110, 123/67, 20, 99% RA
• HEENT: oropharynx clear
• CHEST: clear
• CV: RRR no M
• ABD: soft, no HSM
• EXT: WWP
• DERM: clear
Labs
• WBC: 8
• HCT: 35
• PLT: 90
• AST‐33, ALT‐36, Alk Phos 67, TBili: 1.9
• Cr‐0.9
• CXR ‐ clear
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http://www.cdc.gov/dpdx/malaria/gallery.html#pfalmaurerclefts http://www.cdc.gov/dpdx/malaria/gallery.html#pfalmaurerclefts
Malaria
Freeman DO. NEJM 2008
Malaria in the US ‐ 2011
0
500
1000
1500
2000
2500
2008 2009 2010 2011
Malaria Cases
Undetermined
Mixed
Other species
P. vivax
P. falciparum
CDC. Malaria Surveillance — United States, 2011. 2013
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Clinical signs and symptoms
• Fever/Chills/Sweats
• Headaches
• Nausea/vomiting
• Body aches
• General malaise
• Enlarged spleen/Mild jaundice
• Enlargement of the liver
Severe malaria
• Impaired consciousness/coma/seizure
• Severe normocytic anemia
• Renal failure
• Pulmonary edema/ARDS
• Hemaglobinuria
• Jaundice
• Parasitemia of > 5%
Treatment of uncomplicated P. falciparum
• Atovaquone‐proguanil (Malarone™)
– 4 adult tabs po qd x 3 days
• Artemether‐lumefantrine (Coartem™)
– 3‐day (total of 6 oral doses): initial dose, second dose 8 hrs later, 1 dose po bid x 2 days
• Quinine + (Doxy or Tetra or Clinda) x 7 days
• Mefloquine (Lariam™)
– 750 mg salt, then 500 mg salt 6‐12 hours later
http://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf
Treatment of complicated P. falciparum
• Artesunate (plus second agent)
– Malaria Hotline: 770‐488‐7788 (M‐F, 8am‐4:30pm, eastern time) or after hours, 770‐488‐7100
• Quinidine plus (doxy, tetra, or clinda)
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Malaria prevention
• Low risk: Insect avoidance, consider chemoprophylaxis in certain travelers
– vulnerable travelers– immigrants visiting friends/relatives– prolonged travel (> 1 mo)– unreliable access to medical care
• Moderate‐high risk: Chemoprophylaxis
sporozoites
schizont
schizont
trophozoite
merozoites
merozoites
LIVERRBC
Hepatocyte
Lifecycle of P. falciparum
7-14d after infection
MefloquineDoxycyclineChloroquine
Atovaquone/proguanil
Malaria chemoprophylaxisDrug Areas of use Directions Pro/cons
Atovaquone/ proguanil
AllDaily; 1 wk post
Pro: Minimal SEsCon: $
ChloroquineChloroquine‐susceptible
Weekly; 4 wks post
Pro: WeeklyCon: GI upset
Doxycycline AllDaily; 4 wks post
Pro: $Con: Photos; GI
Mefloquine Mefloquine‐susceptible
Weekly;4 wks post
Pro: $, ok in preg, kidsCon: Dreams, avoid psych/Seiz.
Top 5 complaints in returning travelers leading to MD visit
• Fever without localizing findings
• Acute diarrhea
• Dermatological disorders
• Chronic diarrhea
• Nondiarrheal gastrointestinal disorders
Freedman DO. NEJM. 2006.
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Travelers’ diarrhea (TD)
• #1 travel‐related illness: 30‐70% of travelers
• Pathogens:
– Bacteria 80‐90%: ETEC, campy, shigella, salmonella
– Viruses 10%: Norovirus, rotavirus
• Course:
– Bacterial and viral diarrhea lasts 3‐5 days
– Longer durations suggests other diseases
Prevention of TD
• Prevention
–Avoidance of contaminated food/water
• Prophylaxis
–Bismuth subsalicylate 2 tabs QID
–Rifaximin 200 mg PO QD‐BID (vs. placebo)
• TD: 15% vs. 54% in Mexican travelers
DuPont HL. Annals of Internal Medicine. 2005
Self‐treatment of TD
• Ciprofloxacin:
– 500 mg PO BID for 1‐3 days
• Azithromycin: SE Asia, children, pregnancy
– 500 mg PO QD x 3 days or 1000 mg PO x 1
• Rifaximin: not for invasive infections
– 200 mg PO TID x 3 days
• Loperamide: not for invasive infections
– Added benefit, use in “emergency”
Top 5 complaints in returning travelers leading to MD visit
• Fever without localizing findings
• Acute diarrhea
• Dermatological disorders
• Chronic diarrhea
• Nondiarrheal gastrointestinal disorders
Freedman DO. NEJM. 2006.
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10 top dermatological conditions in returning travelers
1. Cutaneous larva migrans
2. Bacterial SSTIs
3. Arthropod bites
4. Allergic reaction/urticaria
5. Myiasis
6. Superficial fungal infx
7. Injuries/animal bites
8. Scabies
9. Cutaneous leishmaniasis
10. Tungiasis
Cutaneous larva migrans Cutaneous larva migrans
• Treatment:
– Albendazole 400 BID x 3‐7d OR
– Ivermectin 200 mcg/kg QD x 1‐2d
• Prevention: wear shoes in risk areas
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Returning traveler from Panama Returning traveler from Costa Rica
Returning traveler from Portugal Returning traveler from Israel
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Returning traveler from Brazil
Cutaneous leishmaniais
Protozoa(single‐celled eukaryotes)
GI/GUBlood
TissueEntamoebaGiardiaCryptosporidiumTrichomonas
PlasmodiumBabesia
TrypanosomaLeishmaniaToxoplasma
Leishmaniasis: Clinical disease
Cutaneous MucosalVisceral
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Distribution of species by clinical disease
Cutaneous
Mucosal
Visceral
L major
L aethiopica
L mexicana
L panamensisL braziliensis
L infantum
L donovani
L tropica
Distribution of species by geography
Old WorldNew World
L major
L aethiopica
L mexicana
L panamensis
L braziliensis
L infantum
L donovani
L tropica
Where do you get it? Cutaneous How do you get it?
Sand fly
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Clinical manifestations
• Incubation period: 1‐4 weeks
• Morphology:
– Small raised bump ulcer (months)
– May grow as large as 5 cm
• Not painful in most cases
• Often self‐resolves within 6 months
Mucocutaneous disease
• Caused by only a few species
– L. braziliensis
– L. panamensis
• Weeks to years
• Ulcerations that eventuate in mutilating destruction of the oropharynx Schwartz E. Lancet Infect Dis 2006.
Diagnosis• Skin biopsy: sterile, full‐thickness punch‐biopsy specimens at the active border of the lesion
• Aspiration for culture and PCR testing
• Coordinate testing swith CDC
– Frank Steurer (tele: 404‐718‐4175; email: [email protected]; fax: 404‐718‐4195)
http://www.cdc.gov/parasites/leishmaniasis/resources/pdf/cdc_diagnosis_guide_leishmaniasis.pdf.pdf
Treatment
• Key factors
1. species
2. extent of disease
3. comorbidities
• Options:
– No treatment
– Topical: Paromomycin
– Intralesional injections: Antimony
– Systemic: Antimony; Ampho B; Miltefosine; Azoles
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L guyanensis‐ Ambisome
L panamensis– miltefosine (FDA IND)
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L infantum – posaconazole then topical amphotericin (study)
L major – topical paromomycin
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Other skin lesions that might “bug” your patients
McGraw TA. J Am Acad Dermatol. 2008
Returning traveler after an Amazonian trek
Botfly
Returning researcher from Ethiopia
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Tungiasis Top 5 complaints in returning travelers leading to MD visit
• Fever without localizing findings
• Acute diarrhea
• Dermatological disorders
• Chronic diarrhea
• Nondiarrheal gastrointestinal disorders
Freedman DO. NEJM. 2006.
Chronic diarrhea
• Protozoal infections
– Giardia
– Cryptosporidium
– Entamoeba histolytica
– Other: Cyclospora, isospora, etc…
• Other infections
– C. difficile colitis
• Non‐infectious etiologies
Evaluation of chronic diarrhea
• Bacterial culture
• Stool O&P x 3
• Other tests
– Giardia antigen
– Stool AFB stain (cryptosporidium, isospora, etc.)
– Stool Cryptosporidium antigen
– Stool Entamoeba histolytica antigen
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Top 5 complaints in returning travelers leading to MD visit
• Fever without localizing findings
• Acute diarrhea
• Dermatological disorders
• Chronic diarrhea
• Nondiarrheal gastrointestinal disorders
Freedman DO. NEJM. 2006.
Nondiarrheal gastrointestinal disorders
• Intestinal nematode infection
– Strongyloides, schistosomiasis, ascaris
• Gastritis/PUD
• Acute hepatitis
– Hepatitis A, E, B
• Constipation
Evaluation of nondiarrhealgastrointestinal disorders
• Check LFTs
• CBC w/ differential (eos?)
• Stool O&P x 3
• Serology: Strongyloides and schistosoma IgG
• GI referral for other diagnoses
Post‐infectious irritable bowel syndrome
• 3‐10% of travelers after episode of TD
• Diagnosis of exclusion
• Last months ‐ years
Connor BA. Clin Inf Dis. 2005
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Summary
• Fever (with rash) and cutaneous diseases are very common in returning travelers
• A systematic approach to diagnosis includes a detailed travel history and for febrile patients laboratory testing is often indicated