A Travel Medicine CaseA Travel Medicine Case

Thomas Miller MDThomas Miller MD

Case #1Case #1

Jack called from San Francisco at 7:30 Jack called from San Francisco at 7:30 pm.pm.

“ “Dad I am leaving for Indonesia in 2 Dad I am leaving for Indonesia in 2 days. Do I need any shots before I days. Do I need any shots before I go. What about Malaria prevention?”go. What about Malaria prevention?”

The travel consultationThe travel consultation Travelers’ diarrheaTravelers’ diarrhea ImmunizationsImmunizations Malaria prophylaxisMalaria prophylaxis ComplicationsComplications

Topics of DiscussionTopics of Discussion

The Travel Consultation The Travel Consultation

Risk assessmentRisk assessment Risk reductionRisk reduction Shared decisionsShared decisions ResourcesResources

• www.cdc.gov/travelwww.cdc.gov/travel• TravaxTravax• Yellow book Yellow book

Ideally conducted 4 weeks prior to Ideally conducted 4 weeks prior to departure, but 2 weeks will dodeparture, but 2 weeks will do

Risk assessmentRisk assessment

• Medical historyMedical history Chronic illnessesChronic illnesses Immune statusImmune status Vaccination historyVaccination history

• Travel itineraryTravel itinerary DestinationDestination Style of travelStyle of travel DurationDuration Planned activitiesPlanned activities

Medical historyMedical history• Healthy 24 year oldHealthy 24 year old• Complete childhood immunizationsComplete childhood immunizations• Hepatitis A and B vaccines given in Hepatitis A and B vaccines given in

schoolschool• Before collegeBefore college

MeningococcusMeningococcus Updated MMRUpdated MMR

Mentawai Islands, Sumatra Mentawai Islands, Sumatra IndonesiaIndonesia

Destination: IndonesiaDestination: IndonesiaBali and Mentawai IslandsBali and Mentawai Islands

CDC Traveler’s HealthCDC Traveler’s Health• ImmunizationsImmunizations

RoutineRoutine Hepatitis AHepatitis A Hepatitis BHepatitis B TyphoidTyphoid RabiesRabies Japanese encephalitisJapanese encephalitis

• Malaria preventionMalaria prevention Other than chloroquineOther than chloroquine

• Medicine for diarrheaMedicine for diarrhea

Other considerationsOther considerations• Style of travel Style of travel

Hostel styleHostel style• Not airconditionedNot airconditioned• Not usual tourist destinationNot usual tourist destination

• Duration – 1 monthDuration – 1 month• Planned activitiesPlanned activities

Travelers’ DiarrheaTravelers’ Diarrhea

EpidemiologyEpidemiology• Most common illness in travelers to resource Most common illness in travelers to resource

poor areaspoor areas• 90% of travelers will make an error in what 90% of travelers will make an error in what

they eat or drink within several daysthey eat or drink within several days• 50% of travelers will experience illness over 50% of travelers will experience illness over

the course of a 2-3 week vacationthe course of a 2-3 week vacation The illnessThe illness

• >2 loose stools over 24 hrs>2 loose stools over 24 hrs• Fever, nausea, vomiting, crampingFever, nausea, vomiting, cramping• Duration 3-5 daysDuration 3-5 days

CauseCause• Bacteriologic enteropathogens – 90%Bacteriologic enteropathogens – 90%

Enterotoxigenic E. ColiEnterotoxigenic E. Coli Others: Camphylobacter, Salmonella, ShigellaOthers: Camphylobacter, Salmonella, Shigella

• Viruses: rotavirus and noravirusViruses: rotavirus and noravirus• Parasites: giardia, crytosporidium, Parasites: giardia, crytosporidium,

cyclosporacyclospora

Food contamination more common that Food contamination more common that waterwater

PreventionPrevention• Standard food safety measuresStandard food safety measures

““Boil it; cook it; peel it or forget it.”Boil it; cook it; peel it or forget it.” Bottled beveragesBottled beverages Restaurant hygiene a bigger factorRestaurant hygiene a bigger factor

• ChemoprophylaxisChemoprophylaxis Peptobismol: 2 tabs qidPeptobismol: 2 tabs qid Fluoroquinolones – Ciprofloxacin 500mg qdFluoroquinolones – Ciprofloxacin 500mg qd Infection rates reduced from 50% to 5%Infection rates reduced from 50% to 5%

Not routinely recommendedNot routinely recommended• Mild disease that responds to treatmentMild disease that responds to treatment

Last for 24-36 hours with improvement Last for 24-36 hours with improvement within 6-12hrwithin 6-12hr

• Usual side effectsUsual side effects• C difC dif• Promotion of resistant bacteriaPromotion of resistant bacteria

Special PopulationsSpecial Populations• VIP’sVIP’s• Vulnerable hostsVulnerable hosts

Immune incompetentImmune incompetent• HIV, transplant, chemotherapyHIV, transplant, chemotherapy

Inflammatory bowel diseaseInflammatory bowel disease Renal insufficiencyRenal insufficiency Diabetes Diabetes

TreatmentTreatment• Loperamide (imodium): antisecretoryLoperamide (imodium): antisecretory• FluoroquinolonesFluoroquinolones

Ciprofloxacin 500bid x 1 dayCiprofloxacin 500bid x 1 day Can be extended for 3 days if neededCan be extended for 3 days if needed Shortens the course of illness by 1.5 daysShortens the course of illness by 1.5 days Improvement noted with 6-12hrImprovement noted with 6-12hr

• Oral rehydrationOral rehydration Sodas and brothSodas and broth Oral rehydration therapyOral rehydration therapy

RifaximinRifaximin• New nonabsorbable antibioticNew nonabsorbable antibiotic• A rifamycinA rifamycin• Broad spectrum of activity against gram Broad spectrum of activity against gram

pos. and neg. organismspos. and neg. organisms• Approved for the treatment of Approved for the treatment of

uncomplicated travelers’ diarrheauncomplicated travelers’ diarrhea• Little effect on gut floraLittle effect on gut flora

Tested in Central America, Tested in Central America, Caribbean, KenyaCaribbean, Kenya• Dose: 200mg tidDose: 200mg tid• Comparable to fluoroquinolones in effectComparable to fluoroquinolones in effect• TLUS cut from 60hr to 30hrTLUS cut from 60hr to 30hr• Side effects similar to placeboSide effects similar to placebo

Prophylactic useProphylactic use• Dose: 200mg qdDose: 200mg qd• 75% effective75% effective

DisadvantagesDisadvantages• Not effective for invasive disease - Not effective for invasive disease -

dysenterydysentery FeverFever Systemic toxicity Systemic toxicity Bloody diarrheaBloody diarrhea

• Cost – $3.80/pillCost – $3.80/pill

A Vaccine for TD?A Vaccine for TD?

BackgroundBackground• Enterotoxigenic E coli causes most TDEnterotoxigenic E coli causes most TD• Heat-labile enterotoxin (LT) is found in 2/3 of Heat-labile enterotoxin (LT) is found in 2/3 of

ETECETEC• Natural immunity to LT occurs and provides Natural immunity to LT occurs and provides

protectionprotection• Oral cholera vaccine cross reacts with LT and Oral cholera vaccine cross reacts with LT and

protects against TDprotects against TD• LT is strongly antigenicLT is strongly antigenic

Too toxic for oral, nasal and parenteral routesToo toxic for oral, nasal and parenteral routes

Transdermal immunization (Patch)Transdermal immunization (Patch)• Tested in a small feasibility studyTested in a small feasibility study• No difference in occurrence of TDNo difference in occurrence of TD• Reduced the incidence of severe Reduced the incidence of severe

diarrheadiarrhea• Vaccine recipients experienced a milder Vaccine recipients experienced a milder

illnessillness• Skin reactions occurred at the site of Skin reactions occurred at the site of

applicationapplication

My patientMy patient• Standard precautionsStandard precautions• Not a VIPNot a VIP• No chronic diseasesNo chronic diseases• LoperamideLoperamide• Ciprofloxacin 500 bid x 3 days maxCiprofloxacin 500 bid x 3 days max

ImmunizationsImmunizations

RoutineRoutine Hepatitis AHepatitis A Hepatitis BHepatitis B TyphoidTyphoid RabiesRabies Japanese encephalitisJapanese encephalitis

Typhoid VaccineTyphoid Vaccine

Typhoid feverTyphoid fever• Caused by Salmonella entericaCaused by Salmonella enterica• Source: contaminated food or waterSource: contaminated food or water• Risk in South Asia highestRisk in South Asia highest• Fever, headache, malaise, not diarrheaFever, headache, malaise, not diarrhea• 400 cases per year in US travelers400 cases per year in US travelers• Second most common cause of fever in Second most common cause of fever in

return travelersreturn travelers

Typhoid vaccine – 50-80% effectiveTyphoid vaccine – 50-80% effective• Oral live attenuated virusOral live attenuated virus

Every other day for 4 dosesEvery other day for 4 doses Must be refrigeratedMust be refrigerated Completed one week before exposureCompleted one week before exposure Headache and fever occur rarelyHeadache and fever occur rarely Boost after 5 yearsBoost after 5 years $30-40$30-40

• IM: capsular polysaccharideIM: capsular polysaccharide Single doseSingle dose Complete 2 weeks prior to exposureComplete 2 weeks prior to exposure Local erythema and indration rarelyLocal erythema and indration rarely Boost at 2 yearsBoost at 2 years $30-40 $30-40

My patientMy patient• Leaves in 2 days, but stays for a monthLeaves in 2 days, but stays for a month• RefrigerationRefrigeration• $$$ and convenience$$$ and convenience

The shared decisionThe shared decision• Oral Typhoid vaccine called to a San Oral Typhoid vaccine called to a San

Francisco pharmacyFrancisco pharmacy• A nice stewardessA nice stewardess• Cold packCold pack

RabiesRabies• Don’t pet the dogsDon’t pet the dogs• Time is on our sideTime is on our side

Japanese EncephalitisJapanese Encephalitis

Malaria PreventionMalaria Prevention

MalariaMalaria• Fever, headache, back pain, myalgiasFever, headache, back pain, myalgias• 1500 cases per year reported to CDC1500 cases per year reported to CDC

Can be fatalCan be fatal

• Accounts for 21% of fever in returned travelersAccounts for 21% of fever in returned travelers• Conveyed by Anopheles mosquitoConveyed by Anopheles mosquito

Feeds from dusk until dawnFeeds from dusk until dawn

• No risk in urban areas outside of sub-Saharan No risk in urban areas outside of sub-Saharan Africa and India – business travelAfrica and India – business travel

• Risk varies significantly from locale to localeRisk varies significantly from locale to locale

Freedman D. N Engl J Med 2008;359:603-612

Relative Risk of Malaria among Travelers, 2000 through 2002

Source of Cases over 10 YearsSource of Cases over 10 Years

Sub-Saharan Africa 60%Sub-Saharan Africa 60%

Asia 14%Asia 14%

Caribbean, Central and Caribbean, Central and

South America 13%South America 13%

Oceana .03%Oceana .03%

Visiting Friends and Relatives (VFR Visiting Friends and Relatives (VFR Travelers)Travelers)• Born in endemic regions and moved away and Born in endemic regions and moved away and

subsequent generationssubsequent generations• At greatest risk for MalariaAt greatest risk for Malaria

More than 50% of casesMore than 50% of cases

• Explanation for riskExplanation for risk High risk conditions living with familyHigh risk conditions living with family Don’t use chemoprophylaxisDon’t use chemoprophylaxis

• Misperceptions about immunityMisperceptions about immunity• Peer pressurePeer pressure• CostCost

PreventionPrevention• AvoidanceAvoidance• ChemoprophylaxisChemoprophylaxis

AvoidanceAvoidance• Limit night time outingsLimit night time outings• Clothing: long sleeves and pantsClothing: long sleeves and pants• Screened or air conditioned roomsScreened or air conditioned rooms• Mosquito nettingMosquito netting• Permethrin coated clothesPermethrin coated clothes• 30% DEET – effective for 4-8 hours30% DEET – effective for 4-8 hours

NEJM-2002 Comparative Study of NEJM-2002 Comparative Study of Insect RepellentsInsect Repellents

15 Volunteers inserted their arms 15 Volunteers inserted their arms into a cage with 10 hungry into a cage with 10 hungry mosquitoesmosquitoes• Pretested with untreated armPretested with untreated arm• Tested 16 different productsTested 16 different products• Time to first bite recordedTime to first bite recorded

ResultsResults• DEET superior to all other productsDEET superior to all other products

Higher concentrations provided longer Higher concentrations provided longer protectionprotection

24% solution protected for 300 min24% solution protected for 300 min Controlled release formulation was no betterControlled release formulation was no better

• Skin-So-Soft worked for 23 minSkin-So-Soft worked for 23 min• Citronella worked for 20 minCitronella worked for 20 min

Medical Letter - 2005Medical Letter - 2005

CONCLUSION — The 7% picaridin CONCLUSION — The 7% picaridin formulation currently sold in the US might formulation currently sold in the US might be as effective in repelling mosquitoes as be as effective in repelling mosquitoes as low concentrations of DEET, but no data low concentrations of DEET, but no data are available. Higher strength products are available. Higher strength products sold in Europe (with 20% picaridin) protect sold in Europe (with 20% picaridin) protect against mosquitoes for up to 8 hours and against mosquitoes for up to 8 hours and against ticks for a shorter period of time. If against ticks for a shorter period of time. If higher concentrations become available in higher concentrations become available in the US, picaridin could replace DEET due the US, picaridin could replace DEET due to its superior tolerability, but its long-term to its superior tolerability, but its long-term safety is less well establishedsafety is less well established

20% Picaridin20% Picaridin• Now available in USNow available in US• As effective as DeetAs effective as Deet• No odorNo odor• Not a solventNot a solvent

ChemoprophylaxisChemoprophylaxis• Chloroquine: first choice for Mexico, much of Central Chloroquine: first choice for Mexico, much of Central

America and CaribbeanAmerica and Caribbean• Malarone (atovaquone-proguanil) Malarone (atovaquone-proguanil)

Best toleratedBest tolerated Daily dosing and continued for 1 week after returnDaily dosing and continued for 1 week after return Expensive - $300 for 30 day tripExpensive - $300 for 30 day trip

• Doxycycline 100mg qdDoxycycline 100mg qd Cheap and effectiveCheap and effective Solar sensitizer and gastrointestinal side effectsSolar sensitizer and gastrointestinal side effects Must be continued for 1 month after returnMust be continued for 1 month after return

• MefloquineMefloquine Associated with psychiatric side effectsAssociated with psychiatric side effects

• Primaquine Primaquine G6PD testing requiredG6PD testing required

Our patientOur patient• Considers cost and risk of solar Considers cost and risk of solar

sensitization sensitization • Doxycycline and sunscreenDoxycycline and sunscreen

How did we do?How did we do?

Jack’s Second CallJack’s Second Call

Dad, Robby has had diarrhea for a Dad, Robby has had diarrhea for a week, going over 10 times per day week, going over 10 times per day and getting up at night. The cipro and getting up at night. The cipro has not helped at all. He also has has not helped at all. He also has fevers and chills. He wonders fevers and chills. He wonders whether he needs to come home and whether he needs to come home and see a doctor. He is not having blood see a doctor. He is not having blood in his stool and he is not vomiting. He in his stool and he is not vomiting. He is still surfing, but it has been hard.is still surfing, but it has been hard.

• Reported first in Thailand, but now Reported first in Thailand, but now spreading throughout SE Asiaspreading throughout SE Asia

Among military personnel in Thailand Among military personnel in Thailand Camphylobacter causes 20-60% of TDCamphylobacter causes 20-60% of TD

85% are resistant to fluoroquinolone85% are resistant to fluoroquinolone

Resistant TDResistant TD

RCT: Azithromycin vs LevofloxacinRCT: Azithromycin vs Levofloxacin• 156 military personnel with TD enrolled and 156 military personnel with TD enrolled and

randomized (85% using doxycycline for malaria randomized (85% using doxycycline for malaria prophylaxis)prophylaxis)

Azithromicin 1gm onceAzithromicin 1gm once Azithromicin 500mg bid x 3 daysAzithromicin 500mg bid x 3 days Levofoxacin 500mg qd x 3 daysLevofoxacin 500mg qd x 3 days

• PathogensPathogens Bacterial pathogens identified in 81%Bacterial pathogens identified in 81%

• Camphylobacter – 64%Camphylobacter – 64% 50% levoquin resistant50% levoquin resistant 93% ciprofloxacin resistant93% ciprofloxacin resistant

• Salmonella – 17%Salmonella – 17%• E coli – 10%E coli – 10%

OutcomesOutcomes• 72 hour cure rate72 hour cure rate

Azithromycin 1gm 94%Azithromycin 1gm 94% Azithromycin 500mg bid 80%Azithromycin 500mg bid 80% Levofloxacin 500mg qd 70%Levofloxacin 500mg qd 70%

• TLUSTLUS Azithromycin 1gm 39hrAzithromycin 1gm 39hr Azithromycin 500mg bid 43hrAzithromycin 500mg bid 43hr Levofloxacin 500mg qd 56hrLevofloxacin 500mg qd 56hr

• Illness longest in patients with resistant Illness longest in patients with resistant organisms treated with levofloxacin – 76hrorganisms treated with levofloxacin – 76hr

Side effectsSide effects• Nausea after first doseNausea after first dose

Azithromycin 1gm 14%Azithromycin 1gm 14%• One patient vomitedOne patient vomited

Azithromycin 500mg bid 6%Azithromycin 500mg bid 6% Levofloxacin 500mg qd 2%Levofloxacin 500mg qd 2%

• Nausea for 3 daysNausea for 3 days Azithromycin 1gm 17%Azithromycin 1gm 17% Azithromycin 500mg 8%Azithromycin 500mg 8% Levofloxacin 500mg qd 6%Levofloxacin 500mg qd 6%

Treatment recommendation for Treatment recommendation for Thailand and other parts of SE AsiaThailand and other parts of SE Asia• Azithromycin 1gm qd Azithromycin 1gm qd

With a large single dose 46% of active drug With a large single dose 46% of active drug remains in the gut yielding high luminal remains in the gut yielding high luminal levelslevels

Also effective for conventional TD in other Also effective for conventional TD in other parts of the worldparts of the world

Footnote: Rifaximin is ineffective against Footnote: Rifaximin is ineffective against campylobactercampylobacter

Telephone medicine to IndonesiaTelephone medicine to Indonesia• Try to find some azithromycinTry to find some azithromycin

20-30% of drugs may be counterfeit20-30% of drugs may be counterfeit

• Clear fluids Clear fluids Sodas and brothSodas and broth Oral rehydration solutionOral rehydration solution

Happy CampersHappy Campers

The Second Complication Occurred The Second Complication Occurred Several Weeks LaterSeveral Weeks Later

Doxycycline photosensitivity Doxycycline photosensitivity • Painful erythematous eruptionPainful erythematous eruption• Mechanism poorly understoodMechanism poorly understood• Prevented by sunscreenPrevented by sunscreen

Altitude SicknessAltitude Sickness At 10,000 ft (3,000 m), the inspired PO2 is only 69% of sea-At 10,000 ft (3,000 m), the inspired PO2 is only 69% of sea-

level value. level value.

Degree of hypoxic stress depends upon altitude, rate of Degree of hypoxic stress depends upon altitude, rate of ascent, and duration of exposure. ascent, and duration of exposure.

Process of acute acclimatization to high altitude takes 3–5 Process of acute acclimatization to high altitude takes 3–5 days; Rec: acclimatizing for a few days at 8,000–9,000 ft days; Rec: acclimatizing for a few days at 8,000–9,000 ft before proceeding to higher altitude. before proceeding to higher altitude.

Inadequate acclimatization may lead to altitude illness in Inadequate acclimatization may lead to altitude illness in any traveler going to 8,000 ft (2,500 m) or higher. any traveler going to 8,000 ft (2,500 m) or higher.

It is best to average no more than 1,000 ft (300 m) ft per It is best to average no more than 1,000 ft (300 m) ft per day in altitude gain above 12,000 ft (3,660 m). day in altitude gain above 12,000 ft (3,660 m).

Clinical PresentationsClinical Presentations

Acute mountain sickness (AMS)Acute mountain sickness (AMS) 25% of people at alt>8,000 ft. Feels like hangover (HA, nausea). Develops 25% of people at alt>8,000 ft. Feels like hangover (HA, nausea). Develops

2-12 hrs after arrival, resolves after 24-72 hrs of acclimatization2-12 hrs after arrival, resolves after 24-72 hrs of acclimatization

High-altitude cerebral edema High-altitude cerebral edema (HACE)(HACE)

Severe progression of AMS (rare), usually involves pulm edema. Sx include: Severe progression of AMS (rare), usually involves pulm edema. Sx include: lethargy, ataxia, confusion. lethargy, ataxia, confusion. Life threateningLife threatening: must descend : must descend immmediately, death w/in 24 hrs of sx. immmediately, death w/in 24 hrs of sx.

High-altitude pulmonary edema High-altitude pulmonary edema (HAPE)(HAPE)

May occur in conjunction with AMS or HACE or alone. Incidence is 1/10,000 May occur in conjunction with AMS or HACE or alone. Incidence is 1/10,000 skiers in Colorado and up to 1 of 100 climbers at >14,000 ft. Dyspnea with skiers in Colorado and up to 1 of 100 climbers at >14,000 ft. Dyspnea with exertion progresses to SOB at rest. Supplemental O2 or decent > 1,000 m exertion progresses to SOB at rest. Supplemental O2 or decent > 1,000 m is lifesaving. is lifesaving. May be more rapidly fatal than HACEMay be more rapidly fatal than HACE..

Tips for reducing riskTips for reducing risk Ascend gradually, if possible. Try not to go directly from low Ascend gradually, if possible. Try not to go directly from low

altitude to >9,000 ft (2,750 m) sleeping altitude in one day. altitude to >9,000 ft (2,750 m) sleeping altitude in one day.

Consider using acetazolamide (Diamox) to speed Consider using acetazolamide (Diamox) to speed acclimatization if abrupt ascent is unavoidable. acclimatization if abrupt ascent is unavoidable.

Avoid alcohol for the first 48 hours. Avoid alcohol for the first 48 hours.

Participate in only mild exercise for the first 48 hours. Participate in only mild exercise for the first 48 hours.

Having a high-altitude exposure at >9,000 ft (2,750 m), for Having a high-altitude exposure at >9,000 ft (2,750 m), for 2 nights or more within 30 days prior to the trip is useful. 2 nights or more within 30 days prior to the trip is useful.

Treat an altitude headache with simple analgesics Treat an altitude headache with simple analgesics

TreatmentsTreatments AcetozolomideAcetozolomide: Acidifies blood=> : Acidifies blood=>

Incr RRIncr RR Dose: 125 mg po bid starting one day prior to ascent and continued for 2 Dose: 125 mg po bid starting one day prior to ascent and continued for 2

days afterdays after. . Usually well tolerated. Sulfa derivative, so test dose Usually well tolerated. Sulfa derivative, so test dose recommended for people w/ hx of anaphylaxis to sulfa. recommended for people w/ hx of anaphylaxis to sulfa.

Dexamethesone:Dexamethesone: Very effective in prevention and Tx of HACE, AMS and possibly HAPEVery effective in prevention and Tx of HACE, AMS and possibly HAPE Acetozolamide is recommended for prevention of AMS, Dex for treatmentAcetozolamide is recommended for prevention of AMS, Dex for treatment Dose: 4 mg po Q 6hrsDose: 4 mg po Q 6hrs

*HAPE is always associated with pulmonary HTN:*HAPE is always associated with pulmonary HTN: Nifedipine may ameliorate/prevent at a dose of 20 mg ER Q 12 hrNifedipine may ameliorate/prevent at a dose of 20 mg ER Q 12 hr

Take Home PointsTake Home Points Know the early symptoms of altitude illness and be willing Know the early symptoms of altitude illness and be willing

to acknowledge when they are present. to acknowledge when they are present.

Never ascend to sleep at a higher altitude when Never ascend to sleep at a higher altitude when experiencing symptoms of altitude illness, no matter how experiencing symptoms of altitude illness, no matter how minor they seem. minor they seem.

Descend if the symptoms become worse while resting at Descend if the symptoms become worse while resting at the same altitude.the same altitude.

Gradual accent is the key!Gradual accent is the key! If ascent must be rapid, If ascent must be rapid, acetazolamide may be used prophylactically, and dexamethasone acetazolamide may be used prophylactically, and dexamethasone and pulmonary artery pressure-lowering drugs, such as nifedipine and pulmonary artery pressure-lowering drugs, such as nifedipine or sildenafil, may be carried for emergenciesor sildenafil, may be carried for emergencies