Travel Medicine for the Disclosures Disclaimers … Jagannathan Travel Me… · Travel Medicine for the ... – Epidemiology of infections in returning travelers – A couple of cases

4/14/2016

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Travel Medicine for the Community Provider

Advances in ID ‐ 2016

Prasanna Jagannathan, MD

Assistant Professor

Division of HIV, Infectious Diseases, and Global Medicine

San Francisco General Hospital, UCSF

Disclosures and Disclaimers• No Financial Disclosures

• Not meant to be an exhaustive reference

http://wwwnc.cdc.gov/travel/yellowbook/2016/table-of-contents(Free)

$9.99 (Google Play or App store)$49.95 (Oxford Press)

Goals

1. Preparing for travel

– Assessing/Managing Risk

• Current guidance on Zika and other arboviral infections

• Immunizations

• Meds (prophylactic, self‐treatment)

2. Returning travelers

– Epidemiology of infections in a returning travelers

– Approach to diagnosis

Case 1: Getting ready to travel

• 29 yo female comes to primary care clinic planning to go to El Salvador to visit family

– Last visited El Salvador 3 years previously

– G2P2, youngest child is 2 years of age

– Sexually active with husband

– No other medical problems

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What travel risk are you most worried about in this patient?

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17% 1) Zika virus infection

2) Dengue virus infection

3) Malaria

4) Diarrheal illness

5) Injury

6) Something else?

Goals




• Immunizations



– Epidemiology of infections in returning travelers


Age

Gender

Underlying Conditions

Pregnancy

Breastfeeding

Immunocompromised

Seizure Disorder

Psychiatric

Recent surgery

Recent cardiopulmonary or cerebrovascular event

Vaccination history

PMH Meds

Experience with malaria prophylaxis

Illnesses related to prior travel

Prior travel hx

Vaccines, Eggs, Latex

All

Assessing Individual Risk

Drug interactions

Itinerary Countries and specific

regions

Rural or urban

Timing Duration, season

Time to departure

Reason for Travel Tourism

Business

Visiting friends and relatives

Volunteer, missionary, aid work, education

Adventure

Assessing Risk of Travel Travel style Package tour or

independent

Special activities High altitude/climbing

Diving

Cruise ship

Rafting

Extreme sports

Animal contact

Sex

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29 yo female, otherwise healthy

G2P2, not breastfeeding

Sexually active with husband

Healthy, no medical conditions

Childhood vaccinations up to date

No medications

Mild shellfish allergy

PMH Would like to leave in one month

Visiting family in San Salvador (the capital) for one month, no plans on travelling to rural area, contact with animals

Travel plans

Case 1 Managing risk: Educational topics

• Insect avoidance

• Safe sex and pregnancy

• Injury prevention

• Safe food and water

• Altitude

• Animal avoidance

• Evacuation insurance/access to medical care overseas

Managing risk: Educational topics





• Altitude



Which insect repellant would you not advise your patient to

use?

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17% 1) DEET‐containing repellant

2) Picardin‐containing repellant

3) Lemon‐eucalyptus containing repellant

4) Citronella‐containing repellant

5) IR‐3535 –containing repellant

6) I have no idea!

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Insect avoidance

• Vector‐borne diseases are some of the most common travel‐associated infection

– Mosquitos

– Flies

– Ticks

Mosquitos

• Aedes, culex, anopheles

• Transmit several vectors

– Flaviviruses:

• Zika virus, Dengue fever

• Jap. encephalitis, Yellow fever, WNV

– Alphaviruses

• Chikungunya fever

– Protozoa and helminths

• Malaria

• Lymphatic filariasis

Aedes aegypti

Anopheles

Zika Virus: Updated Epi Dengue fever

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

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Chikungunya cases as of Oct 30, 2015

http://www.cdc.gov/chikungunya/geo/

Flies

• Protozoa

– Leishmaniasis

• Helminths

– Loa lao

Phlebotomus sp

L. panamensis via Costa Rica, courtesy of Brian Schwartz

Ticks

• African tick‐bite fever (Rickettsia africae)

• Lyme disease (Borrelia afzelii and garinii)

• Tick‐borne encephalitis (TBEV)

“Tache noire”

How to prevent insect exposure?• Avoid outbreaks

• Avoid high risk periods

– Keep indoor from dusk to dawn (anopheles)

– Aedesmost commonly feed at dusk and dawn, indoors, and shady areas, but they can “bite and and spread infection all year long and at ay time of day”

• Physical barriers

– Proper clothing (long sleeved clothing, skirts)

– Permethrin –treated insecticide bed nets

– Insect Repellants: which ones?

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Product Active Ingredient Complete Protection Time

OFF Deep Woods DEET (24%) 302 minutes

Sawyer Controlled Release DEET (20%) 234 minutes

OFF Skintastic DEET (8%) 112 minutes

OFF Skintastic for kids DEET (4.75%) 88 minutes

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

Avon Skin So Soft Bug Guard Plus IR3535

IR3535 (7.5%) 22.9 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?

Rodriguez et al Journal of Insect Science Oct 2015Image from Katie Park/NPR (Jan 2016)

What about Lemon Eucalyptus?






• Altitude



What travel advice would you not give this patient?

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2) If you are going to El Salvador, don’t get pregnant until 2018.

3) After you return from El Salvador, you should avoid getting pregnant for at least 8 weeks

4) If your husband develops symptoms consistent with Zika on your trip: don’t try to get pregnant for at least 6 months

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CDC guidance re: ZIKA, travel, pregnancy and sexual transmission

• Pregnant women should not travel to areas of ongoing Zika virus transmission


• Non‐pregnant women traveling to Zika‐infected areas: There is no evidence that Zika virus will cause congenital infection in pregnancies conceived after the resolution of maternal viremia.

– After sx onset, Zika viremia may range from a few days to 1 week• Longest duration of viremia in the published literature was 11 days

– Women with symptomatic Zika should wait at least 8 weeks before attempting conception

– Women with asymptomatic Zika should also wait at least 8 weeksfrom last exposure before attempting conception


• CDC has reported 6 cases of sexual transmission from male‐> female– All from men with symptoms, and occurred within 3 weeks of symptom onset.

– Virus isolated from semen possibly up to 10 weeks after symptom onset.

• Based on these data, previously infected men and their female partners should wait >6 months after sx onset before attempting conception

• Although no reported cases of sexual transmission from asymptomatic men, men with possible Zika virus exposure without sx should wait at least 8 weeks after possible exposure before attempting conception.






• Altitude



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Leading causes of injury death for US citizens in foreign countries, 2011‐2013

US citizens 10 times more likely to die as the result of an injury than from an infectious disease

Data from travel.state.gov






• Altitude



Prevention of food‐borne disease• Many common travel‐related infections are transmitted by contaminated food/water

– Traveler’s diarrhea, typhoid, Hep A, Hep E, parasitic infections

• Safe options?

– Bottled water, even for brushing teeth!

– Carbonated soft‐drinks

– Hot foods, packaged, peeled, dry goods

• Watch out for buffets, foods left out for long periods

• Antibiotic prophylaxis: not routinely recommended, could consider in high‐risk hosts






• Altitude (see extra slides)



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Goals




• Immunizations



– Epidemiology of infections in returning travelers

– A couple of cases

Case 2

• 23 yo female research assistant needs travel advice prior to going to Uganda for work

– Leaving in 6 weeks

23 yo female

Healthy, no medical conditions

Childhood vaccinations up to date

Hep A, B

Meningococcus at age 15

No medications

No allergies

PMH Going to Uganda for 4 weeks for

research study

Rural area with ongoing malaria transmission

Planned weekend trips:

Safari

Gorilla trek in the bush

White water rafting in the Nile River

Travel plans

Case 2 After educating her about insect avoidance, injury prevention, and safe water practices, what

vaccine would you not consider for this patient?

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2) Rabies

3) Polio

4) Yellow Fever

5) Meningococcus

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Vaccine preventable diseases

• Routine vaccination should be up to date

• Travel‐related vaccines

– Includes vaccines required by some countries

– All commonly used vaccines can safely and

effectively be given simultaneously

Travel‐related vaccines• Typhoid fever

• Yellow fever

• Rabies vaccine

• Meningococcus

• Hepatitis A and B*

• Japanese encephalitis**

• Polio vaccine**

*If not yet vaccinated as a child or adolescent

** If traveling to endemic area with ongoing transmission

Typhoid Fever• Transmission:

– food/water

• > 400 cases annually US

– Travel #1 risk factor

• 2 vaccines (50‐80% protective)

– Intramuscular (inactivated) – booster Q2 years• Give >2 wks prior to exposure

• Not for infants <2 yrs

– Oral (live attenuated) – booster Q5 years• Every other day for 4 doses

• Must be refrigerated

• Complete 1 week before exposure; not for children <6 yrs

Yellow Fever

• Transmission: mosquito

• 1970‐2013: 10 travelers– 5 West Africa, 5 South America

– 8/10 died

• YF Risk: illness (death)

•W. Africa: 50(10)/100,000

• S. America: 5(1)/100,000

• Vaccine required and regulated

• Live vaccine

• Side effects rare but significant CDC Yellow Book 2016

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Rabies

• Pre‐exposure vaccination

– Consider primary course (3 shots

at $250/shot) if travelling to areas were rabies is enzootic

and immediate access to appropriate medical care,

including PEP, is limited

• Postexposure prophylaxis

– Previously vaccinated: 2 doses of cell culture vaccine

– Unvaccinated: 1 dose rabies immunoglobulin + 4 doses

rabies vaccine

MeningoccalVaccine

– No prior vaccination: Age 2‐55 MenACWY, Age >55: MPSV4

– Previously vaccinated age 9 months to 6 years

• Additional dose of MenACWY 3 years after last

– Previously vaccinated age 7 years to 55 yo

• MenACWY 5 years after last dose

• Age >55: MPSV4 5 years after last dose

In US: 3 conjugate, 1 polysaccharaide vaccine ‐‐ For travelers to meningitis belt:

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2) Atovaquone‐proguanil

3) Chloroquine

4) Praziquantel

5) Azithromycin

6) Lactobacillus sp probiotic

After vaccinating her for typhoid, mening, and yellow fever (refused rabies due to cost), what

medication would you not prescribe this patient?

Praziquantel?

N Engl J Med 2016; 374:469 February 4, 2016

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Prophylactic/self‐treatment medications for travelers

• Travelers’ diarrhea*

• Malaria*

• Altitude illness (Acetazolamide)

• Jet lag (i.e. zolpidem at destination)

• Motion sickness (scopalamine patches)

• Common infections (UTI, SSTI, yeast infection)

Travelers’ diarrhea (TD)

• #1 travel‐related illness: 30‐70% of travelers

• Pathogens:

– Bacteria 80‐90%: ETEC, campy, shigella, salmonella

– Viruses 5‐8%: Norovirus, rotavirus

– Parasites: ~10%: giardia >> E. histolytica, cryptosporidium, cyclospora

• Course:

– Bacterial and viral diarrhea lasts 3‐5 days

– Longer durations suggests other diseases

Best approach: self‐treatment• Fluoroquinolones: best studied

– Ciprofloxacin 500 mg PO BID for 1‐3 days

– Improvement within 6‐12 hrs, shortens illness by 1.5 days

• Azithromycin: increasing resistance of campylobacter, shigella to fluroquinolones especially in SE Asia

– 500 mg PO QD x 3 days or 1000 mg PO x 1

– Also preferred for children, pregnancy

• Rifaximin: not for invasive infections

– 200 mg PO TID x 3 days

• Oral rehydration (sodas, broth, ORT)

• Bismuth salicylate (Pepto Bismol, Kayopectate)

• Loperamide: not for invasive infectionscdc-malaria.ncsa.uiuc.edu

Areas where malaria is endemic: 2015

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Malaria in U.S. travelers: 2012

• 1687 cases (1,925 cases reported in 2011)

– 79% acquired in sub‐Saharan Africa

– Only 34% had taken prophylaxis

• Of these, 11% took a medicine not CDC recommended

• Of those with adherence data (n=182), 65% reported nonadherence

• 14% cases were severe; 6 deaths

– 4/6 individuals who died did not take prophylaxis

(no data on other 2 individuals)

MMWR Surveill Summ. 2014;63(12):1

Malaria chemoprophylaxisDrug Areas of use Directions Pro/cons

Atovaquone/ proguanil

AllQD Daily; 1‐2 days pre ‐>1 wk post

Pro: Minimal SEsCon: $

Doxycycline AllBID Daily; 1‐2 days pre ‐>4 wks post

Pro: $Con: Photos; GI

Mefloquine Mefloquine‐susceptible (not SE Asia)

Weekly;2 wks pre ‐> 4 wks post

Pro: $, ok in preg, kidsCon: Dreams, avoid psych/Seizure meds

ChloroquineCarribean, Central America,

Weekly; 1‐2 wks pre ‐> 4 wks post

Pro: WeeklyCon: GI upset

Freedman DO. NEJM. 2008.

Atovaquone-progunail onlyneeds to be given 7 days after exposure due to activity inliver stage of infection

Anti-relapse therapy: P. Vivax and P. Ovale associated with dormant hypnozoite stage

If at risk for these infections (i.e. places with >90% P vivax) -- Give primaquine for last 14 days of therapy

Goals




• Immunizations



– Epidemiology of infections in a returning travelers


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Case 3

• 60 yo male returned from trip to India visiting relatives presenting with 2 days of fever, chills, muscle aches

– Traveled to India for 2 weeks

– Previously well, no other illnesses

– Did not take malaria prophylaxis

ROS: +HA, chills, myalgia No diarrhea, abdominal pain, cough, shortness of breath

Extracurriculars:

Visiting friends and family

Stayed predominantly in cities of Bangalore and Chennai and did not travel to rural areas

Not sexually active

Reports lots of mosquito bites during stay

HPI Temp 103, HR 105, BP 120/75

Clear lungs, soft abdomen,

heart tachy without murmurs, faint rash on chest, lower extremities

PE

Case 3

Labs CBC: 8.8 < 13.5 > 85

Renal Panel: Na 138, Cr 0.9

LFTs: AST 75, ALT 76

What’s the diagnosis (best guess?)

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2) Dengue

3) Chikungunya

4) Zika

5) Ricketsial infection

6) Something else

Diagnoses in ill‐returned travelers

Gastrointestinal Diagnosis, 34%

Febrile Illness, 23.30%

Dermatologic, 19.50%

Resp/pharyngeal, 10.90%

Neuro, 1.70% GU/STI/Gyn, 2.90%

Leder K. Ann Intern Med. 2013.N=42173 Travelers

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How to determine etiology of febrile illness in returned traveler

Patients need immediate evaluation

• Destination(s)

• Incubation period

• Exposures

• Exam findings/labs

• Prophylaxis/immunizations

Etiology of illness according to region

Leder K. Ann Intern Med. 2013.

Etiology of febrile illness according to interval after travel

Wilson ME. CID. 2007.

Exposures/Prophylactics

• Insect or animal exposures?

• Fresh water exposure?

• What did they consume?

• Other ill travelers?

• Sexual activity?

• Vaccination history?

• Malaria prophylaxis?

Symptoms or exam findings?

• Symptoms

– Abdominal pain?

– Headache?

• Exam findings

– Rash?

– Lymphadenopathy?

– Arthritis?

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Initial lab testing

• CBC w/ differential

• LFTs

• Blood cultures x 2

• Thick and thin blood smear x 2

• Urinalysis

• CXR

• Additional testing based on history/exam

Patient course• Febrile for 3 days

• Platelets continued to decline to 10, admitted,

requiring daily platelet infusions

• LFTs rose up to max AST 320, ALT 315

• Blood cultures x 2 neg

• Thick and thin blood smear x 2 neg

• Urinalysis neg

• CXR: neg

• Additional testing returned:

Arboviral Serologies sent:

• Chikungunya: negative IgM, negative IgG

• Dengue: IgM 10.91 (nl <0.9); IgG 0.28 (normal <0.9)

– Were these the correct tests to order?

– Does he have dengue?

Differentiating dengue, chik, and zikaInfection Clinical

PresentationSeverity of illness Lab

abnormalities

DengueFebrile illness, rash, myalgia, arthralgia

75% asymptomatic Of symptomatic: most commonly mild; 5% can be severe hemorrhagic sx

Leukopenia, thrombocytopeniua, hyponatremia, elevated AST/ALT

ChikungunyaFebrile illness, rash, myalgia, arthralgia

~25% asymptomaticOf symptomatic: high fever and joint pains (b/l, symmetric; hands/feet)Severe disease rare

Lyphopenia, thrombocytopenia,elevated Cr, AST/ALT

ZikaFebrile illness, rash, myalgia, arthralgia

“Dengue‐light”Severe disease uncommon

Leukopenia, thrombocytopeniua, hyponatremia, elevated AST/ALT

Significant cross-reactivity between ELISAs for different flavivirusesCDC Revised testing algorithm 2/16 for Zika, dengue:RT-PCR now preferred diagnostic for patients with acute febrile illness

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How would you counsel this patient re: his future risk for dengue?

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2) Be careful if you go back: you might get reallysick if you get Dengue again

3) It’s ok to travel to dengue‐endemic areas: Your risk of severe dengue is the same whether it is your first or second infection

Summary• Travel health risks are dependent on underlying medical conditions as well as itinerary, duration of travel, purpose of travel, and planned activities

• Appropriate pre‐travel visit should assess these risks and provide appropriate guidance

– Education re: risks • For insect avoidance, remember that DEET and picardin are best, ok to use lemon eucalyptus

– Assessment and provision of travel‐specific vaccinations

– Prescription of prophylactic and self‐treatment medications as appropriate

• A febrile returning traveler is a medical emergency

Thanks! Extra Slides

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International travel continues to rise

• 1.2 billion travelers crossed international boarders in 2015

– Up from 763 million in 2004

• 68 million traveled from the US internationally in 2014

– 17 million in Jan 2016 alone!

UNWTO World Tourism Barometer. World Tourism Organization; 2016.Office of Travel and Tourism Industries 2014 Outbound Analysis, US Dept of Commerce 2015

Business15%

VFR11%

Research/Education9%

Service Work15%

•India•S. Africa/Thailand

•India•Ghana

•India•China

•China•India

•Haiti•Kenya

Reason for travel and 2 most frequent destinations

N=13,235

Larocque R. Clin Infect Dis. 2012

Leisure50%

What is the magnitude of travel related morbidity/mortality

• 22‐64% report some illness

– 34% report GI illnesses

– 23‐28% report fevers

• 8% require medical care

• 1/100,000 – deathSteffen R Int J Antimicrob Agents. 2003

Freedman NEJM 2006Hill DR. CID. 2006

Zika Virus: Updated Epi

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Algorithm for pregnant women with potential Zika exposure

Altitude illness

• Many popular destination are at high‐altitude

• Kiliminjaro: 19,341 Feet! • Biggest risk: Hypoxia

• at 10,000 ft, PaO2 is 69% of sea-level

• Depends on rate of ascent, duration of exposure

• Acute mountain sickness (HA, nausea)

• High-altitude cerebral /pulmonary edema (life-threatening)

Prevention of altitude illness

• Behavioral

– Gradual ascent (allow > 1 day to get to 9K feet)

– Sleep at lower altitudes

– Minimize ETOH and exercise in first 24‐48 hours

– If symptoms develop – do not ascend further!

• If sx get worse while resting: DESCEND

• Pharmacological

– Acetazolamide 125 mg PO BID, start 2 days before ascent, during ascent, and 2 days after reaching apex

Chronic diarrhea

• Protozoal infections

– Giardia

– Cryptosporidium

– Entamoeba histolytica

– Other: Cyclospora, isospora, etc…

• Other infections

– C. difficile colitis

• Non‐infectious etiologies

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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

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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5 most common dermatological diagnoses in returning travelers

• Cutaneous larva migrans

• Insect bite

• Skin abscess

• Superinfected insect bite

• Allergic rash

Ledermen ER. J Infect Dis. 2008

Leptospirosis

• Spirochete bacteria

• Infection through skin (cuts/abrasions) or mucous membranes

– Humans infected by direct contact with water/soil contaminated by urine from infected animals

– Prior outbreaks in river rafters, Borneo EcoChallenge

• Incubation period 2 days‐3 weeks

– Acute phase (~ 7days) presents as febrile illness

– 2nd phase (Weil Disease) = severe, occurs in 5‐10% of patients ‐> renal failure, pulmonary hemorrhage

MMWR Apr 3 2015

New Guidance?Greater proportion of imported shigella infections resistant to ciprofloxacin

Travelers should be encouraged to- Use bismuth subsalicylate or

loperamide for treatment of mild to moderate TD

- Reserve antibiotics for severe cases of TD

- Consider Azithromycin for empiric treatment

Documents

Travel Medicine for the Disclosures Disclaimers … Jagannathan Travel Me… · Travel Medicine for the ... – Epidemiology of infections in returning travelers – A couple of cases