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Claire Panosian Dunavan, MD, DTM&HClaire Panosian Dunavan, MD, DTM&H

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TRAVEL MEDICINETRAVEL MEDICINEMade PracticalMade Practical

Current Clinical Issues in Primary CarePri-Med West, Anaheim, CA, April 28-30, 2011

Made PracticalMade Practical

Claire Claire PanosianPanosian, MD, DTM&H (London), MD, DTM&H (London)Division of Infectious Diseases Division of Infectious Diseases

David Geffen School of Medicine at UCLADavid Geffen School of Medicine at UCLA

Once upon a time …Once upon a time …

Travel to exotic Travel to exotic destinations was a destinations was a rare privilegerare privilegerare privilege …rare privilege …

and (sometimes)and (sometimes)a definite hazarda definite hazard

American Express Travel Poster circa 1920s

Today … the world is smaller and more accessible, but medical hazards still exist.

View of Earth from Apollo 11

Global Tourism TodayGlobal Tourism Today

A leading leisure activity A leading leisure activity A vital source of employment and incomeA vital source of employment and income

In 2007:In 2007:900 million international tourist arrivals900 million international tourist arrivals

(6.6 % (6.6 % ↑↑ over previous year)over previous year)USD 856 billion in monetary receiptsUSD 856 billion in monetary receipts

““

“ It is better not to “ It is better not to fall ill ... fall ill ... than to be cured.”than to be cured.”

Giovanni Maria Giovanni Maria LancisioLancisio(1654(1654--1720)1720)

UCLA brochure, 1987 (available online at www.cdc.gov)

Preparation for TravelPreparation for TravelThe BasicsThe Basics

Medical / Dental CheckMedical / Dental Check--UpUp

Medical “Dossier”Medical “Dossier”

Overseas Health CareOverseas Health Care

Traveler’s Medical KitTraveler’s Medical Kit

Preparation for TravelPreparation for TravelThe Six “I’s”The Six “I’s”

INSECTSINSECTS repellents, nets, medicationrepellents, nets, medication

INGESTIONSINGESTIONS food and water safetyfood and water safety

INDISCRETIONSINDISCRETIONS HIV, STIsHIV, STIs

INJURIES INJURIES personal safety, accidents personal safety, accidents

IMMERSIONIMMERSION schistoschisto, , leptospirosisleptospirosis

INSURANCEINSURANCE coverage, access to carecoverage, access to care

Preparation for TravelPreparation for TravelAnticipation of Special HazardsAnticipation of Special Hazards

Jet LagJet Lag

Motion SicknessMotion Sickness

Altitude SicknessAltitude Sickness

Sun ExposureSun ExposureSun ExposureSun Exposure

Allergic ReactionsAllergic Reactions

Water exposureWater exposure

SnakebiteSnakebite

HIV risk or testing requirementsHIV risk or testing requirements

Political terrorismPolitical terrorism

In the Clinic:In the Clinic:3 Main Topics of Discussion3 Main Topics of Discussion

Vaccinations for TravelVaccinations for Travel

Traveler’s DiarrheaTraveler’s Diarrhea

VectorVector--borne Infection, borne Infection, egeg malariamalaria

Immunizations for TravelImmunizations for Travel

Routine Childhood and Adult VaccinesRoutine Childhood and Adult Vaccines

TetanusTetanus--diphtheria or diphtheria or TDaPTDaPppPolioPolio

MeaslesMeasles--MumpsMumps--RubellaRubellaVaricellaVaricella

Hepatitis BHepatitis B

InfluenzaInfluenzaPneumococcalPneumococcal

Immunizations for TravelImmunizations for Travel

Vaccines for Special Settings or RisksVaccines for Special Settings or Risks

Yellow Fever*Yellow Fever*Hepatitis A / Hepatitis BHepatitis A / Hepatitis B

TyphoidTyphoidMeningococcal*Meningococcal*

RabiesRabiesJapanese encephalitisJapanese encephalitis

Immunizations for TravelImmunizations for Travel

Vaccines rarely if ever usedVaccines rarely if ever used

SmallpoxSmallpoxppCholeraCholera

BCGBCGTyphusTyphusAnthraxAnthrax

Variola major (last natural infection acquired Somalia, 1977) Tetanus--San Lazaro Hospital, Manila. 1987

Pharyngeal membrane of diphtheria

Polio with and without rehabilitation

PolioPolio——New Problems on the New Problems on the Road to EradicationRoad to Eradication

Independent Outbreaks Independent Outbreaks Vaccine Associated Vaccine Associated Paralytic Polio (VAPP)Paralytic Polio (VAPP)

Belarus (1965Belarus (1965--66)66)Canada (1966Canada (1966--68)68)Egypt (1983Egypt (1983--1993)1993)Hispaniola (2000Hispaniola (2000--2001)2001)Philippines (2002)Philippines (2002)Madagascar (2001Madagascar (2001--2002)2002)Haiti (2002)Haiti (2002)China (2006)China (2006)Cambodia (2005Cambodia (2005--2006)2006)Myanmar (2006Myanmar (2006--2007)2007)Iran (1995, 2005Iran (1995, 2005--2007)2007)

Maculo-papular facial rash – measles (rubeola)GLOBAL MEASLES DEATHS ↓ FROM 750,000 (2000) TO 200,000 (2007)

Chickenpox progressing to acute respiratory failure (pre-Acyclovir) Risk of Hepatitis A, sidewalk crab seller – Taiwan, 1983

Acute hepatitis B -- Bangkok, 1999

Hepatitis A VaccineHepatitis A Vaccine

Licensed schedules for adultsLicensed schedules for adults

Havrix (GSK)Havrix (GSK) 1 ml (1440 U) x 2 1 ml (1440 U) x 2 0, 60, 6--12 mo12 mo( )( ) ( )( ) ,,

Vaqta (Merck)Vaqta (Merck) 1 ml (50 U) x 21 ml (50 U) x 2 0, 60, 6--12 mo12 mo

Twinrix (GSK)Twinrix (GSK) 1 ml (720, 20)1 ml (720, 20) x 3x 3 0, 1, 6 mo0, 1, 6 mo

Immune Serum GlobulinImmune Serum Globulin

Is there still a role for Is there still a role for

gamma globulin shots?gamma globulin shots?

In certain patients, the answer is In certain patients, the answer is “YES”“YES”

Typhoid Fever:Typhoid Fever:Have we Forgotten ??Have we Forgotten ??

Typhoid Vaccine EfficacyTyphoid Vaccine Efficacy

ParenteralParenteral 4242--93%93%

Oral Ty21aOral Ty21a (US volunteers)(US volunteers) 87%87%(Egypt)(Egypt) 90%90%(Chile)(Chile) 67%67%

Vi capsular polysaccharideVi capsular polysaccharide 70%70%

TYPHOID FEVER: TYPHOID FEVER: A Look at Recent TrendsA Look at Recent Trends

JAMA “Typhoid Fever in the US,” 1999JAMA “Typhoid Fever in the US,” 1999--20062006

1902 patients: median age 22 yrs (11902 patients: median age 22 yrs (1--90), 90), 79% traveled overseas within 30 days of illness79% traveled overseas within 30 days of illnessyy

13% multi13% multi--drug resistant (AMP, CP, TMPdrug resistant (AMP, CP, TMP--SX)SX)

38% decreased susceptibility to Ciprofloxacin, 38% decreased susceptibility to Ciprofloxacin, increasing from 19% in 1999 to 54% in 2006increasing from 19% in 1999 to 54% in 2006

Patients with resistant infections more likely to report Patients with resistant infections more likely to report travel to Indian subcontinenttravel to Indian subcontinent

Countries Visited by TF Patients Countries Visited by TF Patients in 30 days before illnessin 30 days before illness

CountriesCountries No. of TravelersNo. of TravelersIndiaIndia 606 606 (47%)(47%)PakistanPakistan 126126 (10%)(10%)BangladeshBangladesh 124124 (10%)(10%)MexicoMexico 9090 (7%)(7%)PhilippinesPhilippines 5757 (4%)(4%)

Meningococcal Vaccination 2010Meningococcal Vaccination 2010

Yellow Fever Yellow Fever in Africa and Americasin Africa and Americas

Japanese encephalitis--Kaohsiung Med Cntr, Taiwan, 1983

Japanese EncephalitisJapanese Encephalitis

Most common epidemic viral encephalitisMost common epidemic viral encephalitis

CulexCulex vector / bird and mammal reservoirvector / bird and mammal reservoir CulexCulex vector / bird and mammal reservoirvector / bird and mammal reservoir

Up to 10Up to 10--20 cases/100,000 q yr20 cases/100,000 q yr

Subclinical disease 50Subclinical disease 50--100 : 1100 : 1

NOTE: NOT ALL RABID ANIMALS LOOK LIKE THIS !

Recovered cholera pt with IV bottles required for re-hydration Clean Water – the new “most precious” world resource ?

Traveler’s DiarrheaTraveler’s DiarrheaThe most common afflictionThe most common affliction

Lomotil ad, circa 1985

Traveler’s DiarrheaTraveler’s Diarrhea““The Usual Suspects”The Usual Suspects”

EnterotoxigenicEnterotoxigenic E. coli (ETEC)E. coli (ETEC) Salmonella, Salmonella, ShigellaShigella, Campylobacter, Campylobacter AeromonoasAeromonoas PleisiomonasPleisiomonas VibriosVibrios AeromonoasAeromonoas, , PleisiomonasPleisiomonas, , VibriosVibrios

Rotavirus, Norwalk agent (Rotavirus, Norwalk agent (norovirusnorovirus))

Intestinal protozoaIntestinal protozoa((egeg. Cryptosporidium, . Cryptosporidium, GiardiaGiardia, , EntamoebaEntamoeba----more indolent in onset )more indolent in onset )

Treatment of Traveler’s DiarrheaTreatment of Traveler’s DiarrheaRecommended AgentsRecommended Agents

ProphylaxisProphylaxisBismuth subsalicylate (PB), Bismuth subsalicylate (PB), NorfloxacinNorfloxacin, , Ciprofloxacin, Ciprofloxacin, RifaximinRifaximin

S t ti T t tS t ti T t tSymptomatic TreatmentSymptomatic TreatmentBismuth subsalicylate (PB), Bismuth subsalicylate (PB), LoperamideLoperamide

Antibiotic treatmentAntibiotic treatmentFluoroquinolonesFluoroquinolones ( ( NorfloxacinNorfloxacin, Ciprofloxacin, , Ciprofloxacin, OfloxacinOfloxacin, , LevofloxacinLevofloxacin), ), AzithromycinAzithromycin, , RifaximinRifaximin

DO NOT FORGET ORAL REHYDRATION!DO NOT FORGET ORAL REHYDRATION!- Advertisement for RAID, circa 1987

VectorVector--borne Diseasesborne DiseasesWhat do you need to know?What do you need to know?

MALARIA, MALARIA, MALARIAMALARIA, MALARIA, MALARIA

Other MosquitoOther Mosquito borne infectionsborne infections Other MosquitoOther Mosquito--borne infectionsborne infections(eg. dengue fever, JEV)(eg. dengue fever, JEV)

PLUSPLUS

Sandflies, blackflies, ticks, tsetses … Sandflies, blackflies, ticks, tsetses … Aedes aegyptii mosquito—dengue fever vector

DENGUE FEVERDENGUE FEVER

100 MILLION CASES YEARLY100 MILLION CASES YEARLY

RNA virus: RNA virus: family Togaviridae,family Togaviridae,l i il i igenus Flavivirusgenus Flavivirus

4 ANTIGENICALLY SIMILAR SEROTYPES4 ANTIGENICALLY SIMILAR SEROTYPES

AEDES VECTOR: dayAEDES VECTOR: day--biting, biting, urbanurban--dwellingdwelling

60 yo UCLA professor post- travel to San Juan, Puerto Rico

Diffuse, blanching rash during 2nd phase of “saddleback” fever Dengue hemorrhagic fever: spontaneous bleeding from gums

Other TravelOther Travel--related related ArbovirusesArboviruses

Yellow FeverYellow Fever

Japanese encephalitisJapanese encephalitis

West Nile virusWest Nile virus

ChikungunyaChikungunya

TickTick--borne encephalitis borne encephalitis

-- Ixodid (hard-backed) tick

UCLA ER patient -- 5 days post South Africa

Dx RICKETTSIA AFRICAE – Rx DOXYCYLINE Phlebotomus (sandfly) – vector of leishmaniasis

Ulcerating nodules weeks after sandfly bites in tropical Costa Rica African Tsetse fly

Trypanosoma brucei trypamastigotes in blood Female Anopheles mosquito – vector of human malaria

Malaria worldwide distribution: past and present

4 Main Species of Human Malaria4 Main Species of Human Malaria

** ** Plasmodium falciparum Plasmodium falciparum ****

* * Plasmodium vivax Plasmodium vivax **

Plasmodium malariaePlasmodium malariae

Plasmodium ovalePlasmodium ovale

P. P. falciparumfalciparum threatens 2.4 billion people threatens 2.4 billion people ––35% of the global population 35% of the global population

Taking into account the effect of Taking into account the effect of temperature and aridity, areas were temperature and aridity, areas were defined as stable (dark red areas where defined as stable (dark red areas where P. P. falciparumfalciparum annual parasite incidence (annual parasite incidence (PfPfAPIAPI))falciparumfalciparum annual parasite incidence (annual parasite incidence (PfPfAPIAPI) ) ≥0.1/1,000 persons), unstable (pink areas where ≥0.1/1,000 persons), unstable (pink areas where PfPfAPIAPI<0.1/1,000 <0.1/1,000 persons), or no risk (light grey).(8) (citation for new map) 74% of persons), or no risk (light grey).(8) (citation for new map) 74% of P. P. falciparumfalciparum cases occur in Africa, 25% in Asia, and 1% in the Americas.(1)cases occur in Africa, 25% in Asia, and 1% in the Americas.(1)

74% of PF cases in Africa, 25% in Asia,

1% in the Americas

P. P. vivaxvivax threatens 2.6 billionthreatens 2.6 billion——almost 40% of world’s populationalmost 40% of world’s population

Of 130-390 million yearly PV cases: 52 % in S. and S.E. Asia,

15 % in E Mediterranean, 13% in South America

Malaria life cycle in manMalaria life cycle in man

Plasmodium falciparum blood smear

Malaria in US ResidentsMalaria in US Residents

19971997--2006: 10,745 cases reported2006: 10,745 cases reported 60% acquired in 60% acquired in subSaharansubSaharan AfricaAfrica 14% acquired in Asia14% acquired in Asia 13% acquired in Caribbean, Central and 13% acquired in Caribbean, Central and

South AmericaSouth America____________________________________________________________________During same period, 54 fatal infectionsDuring same period, 54 fatal infections——

85% PF, 71% acquired SSA85% PF, 71% acquired SSA

(available online at www.cdc.gov)

Prevention of Malaria in TravelersPrevention of Malaria in Travelers

Education Education

Mosquito avoidanceMosquito avoidance

“Prophylactic” medication“Prophylactic” medication

SelfSelf--administered empiric therapyadministered empiric therapy

PostPost--exposure prophylaxis for exposure prophylaxis for P. vivaxP. vivax

Prevention of Malaria in TravelersPrevention of Malaria in TravelersPersonal Protective MeasuresPersonal Protective Measures

Chemoprophylaxis = 75Chemoprophylaxis = 75--95% protection95% protection

Insecticides (eg. deltamethrin, permethrin): Insecticides (eg. deltamethrin, permethrin): knockknock--down sprays or impregnate clothes/netsdown sprays or impregnate clothes/nets

Repellants (eg DEET, PMD, picaridin) for skinRepellants (eg DEET, PMD, picaridin) for skin

DEET based repellantsDEET based repellants–– best evidence and longest history of usebest evidence and longest history of use–– 20% DEET safe in pregnancy20% DEET safe in pregnancy–– Now sanctioned for infants > 2 monthsNow sanctioned for infants > 2 months

Antimalarials in the 21Antimalarials in the 21stst centurycenturyProphylactic RegimensProphylactic Regimens

AtovaquoneAtovaquone--proguanil (Malarone)proguanil (Malarone)250/100 mg qd 250/100 mg qd 7d beyond7d beyond

MefloquineMefloquine 250 mg q wk250 mg q wk 4 wks beyond4 wks beyond

DoxycyclineDoxycycline 100 mg qd100 mg qd 28 days beyond28 days beyond

ChloroquineChloroquine 500 mg q wk500 mg q wk 4 wks beyond4 wks beyond

Antimalarials in the 21Antimalarials in the 21stst centurycenturyStandStand--by Emergency Selfby Emergency Self--Treatment (SBET)Treatment (SBET)

ArtemetherArtemether--lumefantrinelumefantrine ((RiametRiamet, Co, Co--ArtemArtem))Effective, rapid parasite and fever clearance, Effective, rapid parasite and fever clearance, good safety/tolerability good safety/tolerability

AtovaquoneAtovaquone--proguanilproguanil ((MalaroneMalarone))Currently effective, good safety/tolerabilityCurrently effective, good safety/tolerability–– BUTBUT–– pending pending resistance? resistance?

MefloquineMefloquine ((LariamLariam))Effective Effective --––BUTBUT---- neurotoxocityneurotoxocity aat treatment dosest treatment doses

ChloroquineChloroquine ((NivaquinNivaquin))Inexpensive , safe Inexpensive , safe ——BUTBUT—— widespread resistancewidespread resistance

-- Chen, Wilson, Schlagenhauf, JAMA, 2006

Travel MedicineTravel MedicineSpecial Cases and IssuesSpecial Cases and Issues

Global Health workersGlobal Health workers

LongLong--term travelersterm travelers

ImmunosuppressedImmunosuppressed patientspatients

Unanticipated hazards in “clean” environments Unanticipated hazards in “clean” environments ((egeg norovirusnorovirus outbreaks on cruise lines)outbreaks on cruise lines)

Emerging infectious diseasesEmerging infectious diseases

Prompt, expert evaluation of postPrompt, expert evaluation of post--travel illnesstravel illness

-- South China Sea, 1987