brian s. schwartz, md ucsf, division of infectious diseases medicine... · 2018. 2. 13. ·...

2/7/2018

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Brian S. Schwartz, MD

UCSF, Division of Infectious Diseases

Update in Travel Medicine

Lecture outline1. Why should you know about travel medicine?

2. Who needs pre-travel care?

3. The pre-travel visit

4. Post-travel evaluation

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International travelers• ~1 billion travelers cross international boarders

each year

• 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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Reason for travel and 2 most frequent destinations

Business15%

VFR11%

Research/Education9%

Service Work15%

•India•S. Africa/Thailand

•India•S. Africa/Thailand

•India•Ghana•India•Ghana

•India•China•India•China

•China•India•China•India

•Haiti•Kenya•Haiti•Kenya

N=13,235Larocque R. Clin Infect Dis. 2011

Leisure50%





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What is the magnitude of travel related morbidity/mortality?

Hill DR. CID. 2006

• 20-70% report some illness

• 1-5% seek medical attention

• 0.05% evacuation

Who should seek pre-travel care?

• Travelers to resource poor settings

• Travelers with significant medical issues

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Pre-travel consultation

1. Assessing the health of the traveler

2. Assessing the risk of travel

3. Education

4. Vaccination

5. Prescribing prophylactic/self-treatment

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3. Education

4. Vaccination


Exacerbation of comorbidities is the predominant cause of death in US Travelers:

Cardiovascular Disease

49%

Injury22%

Infection1%

Other/Unknown6%

Cancer6%

Suicide/Homicide3% Medical

14%

Hargarten SW. Annals of Emergency Medicine.1991

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3. Education

4. Vaccination


Assessing the risk of travel

• Destination(s)

• Season

• Duration of stay

• Planned activities

• Accommodations

• Purpose of travel

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3. Education

4. Vaccination


Educational topics• Insect avoidance

• Injury prevention

• Safe food and water

• Altitude

• Safe sex

• Animal avoidance

• Evacuation insurance/access to med care

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Educational topics• Insect avoidance• Injury prevention• Safe food and water• Altitude• Safe sex• Animal avoidance• Evacuation insurance/access to medical care

Insect avoidance• Vector-borne diseases are common

travel-associated infection

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Mosquitos

• Viruses– Dengue fever

– Chikungunya fever

– Zika virus

– Jap. encephalitis

– Yellow fever

– WNV

• Protozoa– Malaria

• Helminths– Filariasis

• Insects– Botfly

Dengue fever• 50-100 million infections/year

• Mosquito vector (daytime)

• Urban and rural

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Dengue fever: worldwide distribution

http://www.healthmap.org/dengue/index.php

Dengue fever: clinical disease• Incubation: Short (4-7 days)

• Clinical Manifestations:– Fever, headache, joint and muscle aches– Nausea and vomiting– Rash

• Lab abnormalities: – leukopenia, thrombocytopenia, transaminitis

• Dengue Hemorrhagic Fever/Shock– Occurs 3-7 days into illness, often w/ end of fever

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Dengue rash

1-2 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

IgM

IgG

Vira

l loa

d de

tect

ed b

y RT

-PCR

Ant

ibod

ies qu

antifie

d by

ELI

SA

Viraemia

Acute illness Days0 4 6 14 21 50

NS1

Guzman MG. Nature Reviews Micro.2010

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Dengue on the Big Island (Hawaii) 2015-16 Outbreak!

http://health.hawaii.gov/docd/dengue-outbreak-2015/

Chikungunya fever in the Americas!

• Came to Caribbean in 2013 C America S America– 1.7 million cases

• 679 cases reported in US in 2015

http://www.cdc.gov/chikungunya/geo/united-states.html

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Chikungunya fever• Transmitted by Aedes mosquitos

• Incubation period 2-4 days (1-14)• Clinical manifestations (resolved within 7d)

– Fever + Polyarthralgias 2-4 days later– Rash: ~ 50%, maculopapular

• Labs: – Lymphopenia, thrombocytopenia, transaminitis

• Severe complications/deaths in elderly

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Lab features of Chikungunya vs. Dengue

Chikungunya Dengue

Lymphopenia +++ ++

Neutropenia + +++

Thrombocytopenia + +++

Hemoconcentration - ++

Diagnosis and Treatment Chikungunya

• Lab diagnosis with IgM/PCR: – CDC and DPH of CA, NY, FL– Focus labs

• Treatment:– Supportive– Avoid NSAIDs or aspirin until Dengue excluded

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Zika virus

• Transmitted by Aedes mosquitos

• Incubation period 2-4 days (1-14)

• Clinical manifestations (resolved within 7d)– fever, rash, joint pain, conjunctivitis

• Severe complications rare

Zika virus risk areas

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Zika virus associated microcephaly• Recommendations to pregnant women

– Avoid travel to Zika risk areas– If visited risk area

• CDC has testing

– No treatment available– No vaccine

• Sexual transmission– Men to avoid intercourse or use condoms with

pregnant partners

http://www.cdc.gov/mmwr/volumes/65/wr/mm6502e1er.htm?s cid=mm6502e1er e

Zika vs. Dengue vs. Chikungunya

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BotflyDermatobia hominis

McGraw TA. J Am Acad Dermatol. 2008

Flies

• Protozoa– Leishmaniasis

• Helminths– Loa lao

Phlebotomus sp

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Geographic distribution of cutaneous leishmaniasis

Reithinger R. Lancet ID. 2007

Old world-Dry, arid conditionsNew world

-Forested areas

Returning from Panama

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Returning from Costa Rica

Returning from Portugal

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Returning from Israel

Returning from Brazil

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Ticks• African tick-bite fever

• Lyme disease

• Tick-borne encephalitis

African Tick Bite Fever

• Rickettsia africae

• Aggressive Bont ticks live on undulates and in grassy areas

Jensenius, Lancet ID 2003

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Clinical Presentation• Fever• Headache• Muscle aches• Inoculation eschar, often multiple• Regional lymph node swelling• Rash – papular

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

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African tick-bite fever: skin findings

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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How to prevent insect exposure?• Avoid outbreaks

– www.cdc.gov/travel

• Avoid high risk periods– Keep indoor from dusk to dawn (malaria)

• Physical barriers– Proper clothing and bed nets

• Insect repellents

Product Active Ingredient Complete Protection Time

OFF Deep Woods DEET (24%) 302 minutes

Picardin 20% (Sawyer) Picardin (20%) >300 minutes

Sawyer Controlled Release DEET (20%) 234 minutes

OFF Skintastic DEET (8%) 112 minutes

OFF Skintastic for kids DEET (4.75%) 88 minutes

Avon Skin So Soft + IR3535 IR3535 (7.5%) 23 minutes

Herbal Armor Citronella (12%) 14 minutes

Fradin MS, Day JF. N Engl J Med 2002;347:13-18.Roey et al PLoS Negl Trop Dis. 2014 Dec; 8(12): e3326.

Which insect repellant to use?

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Insect repellants• Which ones are effective?

– DEET*– Picardin*– Oil of Lemon Eucalyptus– IR3535– Permethrin (not on skin)

• Which ones are not effective?– Citronella– Wristbands, candles, fans, etc.

• Order: Sunscreen repellant

Educational topics• Insect avoidance• Injury prevention• Safe food and water• Altitude• Safe sex• Animal avoidance• Evacuation insurance/access to medical care

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Preventable causes of death in US travelers Air accident,

82Disaster, 131Drowning,

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

Educational topics• Insect avoidance• Injury prevention• Safe food and water• Altitude• Safe sex• Animal avoidance• Evacuation insurance/access to medical

care

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Food and water safety• Many common travel-related infections are

transmitted by contaminated food/water

– Travelers’ Diarrhea

– Hepatitis A

– Hepatitis E

– Typhoid fever

– Parasitic infections

Prevention of food-borne disease

• Most studies failed to correlate guideline adherence to risk of travelers’ diarrhea

• Where you eat < what you eat!

• Safe options?

– Drinks: Bottled H20, soft-drinks

– Foods: Hot, processed, packaged, peeled

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Educational topics

• Insect avoidance

• Injury prevention

• Safe food and water

• Altitude

• Safe sex

• Animal avoidance

• Evacuation insurance/access to med care




3. Education

4. Vaccination

5 Prescribing prophylactic/self-treatment

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Vaccine preventable diseases

• Routine vaccination should be up to date

• Required vaccines

• Travel-related vaccines

Travel-related vaccines

• Hepatitis A*

• Typhoid fever*

• Yellow fever*

• Meningococcal infection

• Japanese encephalitis

• Polio vaccine

• Rabies vaccine

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Hepatitis A• Transmission:

– food/water

• Vaccine (inactivated)– Intramuscular: Hep A and Hep A/B (Twinrix)

– Life-long protection after 2nd dose (6 mo)

– Ok to give up until departure in most patients

• Immune globulin

Typhoid Fever• Transmission:

– food/water

• > 400 cases annually US– Travel #1 risk factor

• 2 vaccines (50-80% protective)– Intramuscular (inactivated) – booster Q2 years

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Yellow Fever• Mosquito transmitted

• YF Risk: illness (death)• W. Africa: 50(10)/100,000

• S. America: 5(1)/100,000

• Vaccine required/regulated

• Side effects rare but significant – > risk for 60 yr CDC Yellow Book 2014

Other travel-related vaccines

• Japanese encephalitis

• Meningococcus

• Polio vaccine

• Rabies vaccine

H titi B

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3. Education

4. Vaccination

5 Prescribing prophylactic/self-treatment

Prophylactic/self-treatment medications for travelers

• Malaria*

• Travelers’ diarrhea*

• Altitude illness

• Jet lag

• Motion sickness

• Common infections (UTI, SSTI, yeast infection)

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Malaria in the US

CDC. Malaria Surveillance — United States, 2012. 2014

0

500

1000

1500

2000

2500

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Mal

aria

Cas

es

Year

Status not recordedForeign residentsU.S. civilians

Malaria in the US

• What: 70% Plasmodium falciparum

• Where: 72% cases from Africa

• Who:– 54% - “visiting friends and relatives”

– 3% - “tourists”

– 6 deaths in 2012CDC. Malaria Surveillance — United States, 2012. 2014

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Malaria

Freeman DO. NEJM 2008

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

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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.

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Treatment

http://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf

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

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Prevention of TD

• Prevention– Avoidance of contaminated food/water

• Prophylaxis– Bismuth subsalicylate 2 tabs QID

– Rifaximin 200 mg PO QD-BID (vs. placebo) 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

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Risk of ESBL colonization with travel

Kantele A. Clin Infect Dis. 2015

A new tool for you to get your patients ready for travel http://gten.travel/prep/prep

• Provide destination specific recs using CDC data

• Generates a medical note to cut and paste into EMR

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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 disordersFreedman DO. NEJM. 2006.

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• Acute diarrhea




How to determine etiology of fever in returned traveler

Patients need immediate evaluation

• Destination(s)

• Incubation period

• Exposures

• Exam findings/labs

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0

100

200

300

400

500

600

700

800

900

1000

Carribean C. America S. AmericaSub‐Saharan AfricaSouth Central AsiaSE Asia

Cases

Freedm

an DO

. NE

JM.

2006.

Destination: Etiology of fever according to region traveled

Dengue

Unknown

EBV/CMV

Malaria

Rickettsia

Typhoid

Dengue

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 Diagnoses

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

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Exposures?• Insect or animal exposures?

• Fresh water exposure?

• What did they consume?

• Other ill travelers?

• Sexual activity?

Specific symptoms or exam findings?

• Symptoms– Abdominal pain?

– Headache?

• Exam findings– Rash?

– Lymphadenopathy?

– Arthritis?

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Prophylaxis?

• Vaccinations?– Which ones?

– Timing of vaccinations?

• Malaria prophylaxis?– Appropriate agents?

– Taken appropriately?

Initial testing?

• CBC w/ differential

• LFTs

• Blood cultures x 2

• Thick and thin blood smear x 2

• Urinalysis

• CXR

• Additional testing based on history/exam

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• Acute diarrhea




Acute diarrhea

• Most likely travelers’ diarrhea

• Consider empiric treatment

– Ciprofloxacin, azithromycin, rifaximin

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• Acute diarrhea




5 most common dermatological diagnoses in returning travelers

• Cutaneous larva migrans

• Insect bite

• Skin abscess

• Superinfected insect bite

• Allergic rashLedermen ER. J Infect Dis. 2008

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• Acute diarrhea




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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

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• Acute diarrhea




Nondiarrheal gastrointestinal disorders

• Intestinal nematode infection– Strongyloides, schistosomiasis, ascaris

• Gastritis/PUD

• Acute hepatitis

– Hepatitis A, E, B

• Constipation

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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• Travel health risks are dependent on underlying

medical conditions as well as itinerary, duration of travel, purpose of travel, and planned activities

• Travelers should be up to date on routine and travel-specific vaccinations

• Travelers should be given prophylactic and self-treatment medications as appropriate

• Recommend evacuation insurance to travelers, particularly those at high-risk

• A febrile returning traveler is a medical emergency

brian s. schwartz, md ucsf, division of infectious diseases medicine... · 2018. 2. 13. ·...

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