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What’s New in Travel Medicine?

What’s New in Travel Medicine?. Gregory Juckett, MD, MPH Professor of Family Medicine Director, WVU International Travel Clinic West Virginia University gjuckett@hsc.wvu.edu. Resources/Recommendations. New Travel Programs and Web Support New CDC Yellow Book 2010 Edition

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What’s New in Travel Medicine?

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  1. What’s New in Travel Medicine? Gregory Juckett, MD, MPH Professor of Family Medicine Director, WVU International Travel Clinic West Virginia University gjuckett@hsc.wvu.edu

  2. Resources/Recommendations • New Travel Programs and Web Support • New CDC Yellow Book 2010 Edition • Special Case Travelers: VFR • New Approaches to Traveler’s Diarrhea • New Recommendations for Malaria Prevention • New Travel Vaccines: Tdap, Menactra (meningitis), Ixiaro (Japanese encephalitis), H1N1 (“Swine” flu)

  3. Free Web Travel Information Sources Full Listing CDC Yellow Book Appendix B • www.cdc.gov/travel CDC Travel Info (best) • www.tripprep.comShoreland’s Travel Health Online • www.mdtravelhealth.com/ MD Travel Health • www.who.int/ith/en World Health Organization Int’l Travel • www.astmh.org American Society of Trop. Medicine • www.travel.state.gov U.S. State Dept. (202-647-5222) • www.iamat.org Int. Assoc. Med. Assist. To Travelers • www.promedmail.org Pro-MED program for monitoring emerging disease • www.healthmap.org/en Health Map --Global Disease Alert • www.medletter.com Medical Letter (Travel Health Summary) • www.fallingrain.com Altitude Finder • www.odci.gov/cia/publications/pubs.html CIA (select World Fact Book) Travel Subscription Services e.g.Shoreland TRAVAX Encompass, CultureGrams, SOS Travel Care, and Gideon are even more useful but entail an annual fee

  4. CDC Health Information for International Travel 2010www.cdc.gov/travel/index.htmU.S. Government Printing Office New, Improved! Now has popular destination-specific recommendations. “The Yellow Book”

  5. New CDC Yellow Book Features • Pre-Travel Consultation: risk assessment, risk communication, risk management • Post-Travel Consultation • Select Destinations /Travel Itineraries • Infectious Diseases Related to Travel • Yellow Fever /Malaria Tables • Special Traveler Populations: Children, Special Needs, Immigrants/Refugees • Appendices: • A. Practice of Travel medicine • B. Electronic Resources • C. Travel Vaccine Summary Table

  6. Contacting the CDC • CDC-INFO Contact Center 800-CDC-INFO or cdcinfo@cdc.gov • CDC Malaria Hotline 770-488-7788 or 770-488-7100 (after hours) • Travel Notices: cdc.gov/travel/notices (public health focus) • CDC Malaria Risk Map www.cdc.gov/malaria/features/risk_map.htm

  7. CDC Malaria Interactive Mapwww.cdc.gov/malaria/features/risk_map.htm Search Feature: Country and City

  8. Computer Travel Information Services(all entail an annual fee) • SOS Travel Carewww.internationalsos.com • Shoreland TRAVAXwww.shoreland.com and Shoreland TRAVAX Encompass (online) www.travax.com • Exodus Software www.exodus.ie • Tropimedwww.tropimed.com • Travel Medicine Advisor (online) www.ahcmedia.com or orders@ahcmedia.com

  9. Other Subscription Sites ( fee) • Gideon (for diagnosing the ill returning traveler) www.gideononline.com • CultureGrams (concise 4 page cultural summary by country) www.culturegrams.com • VaxisEHR from Travis Medical(electronic health record)www.vaxisehr.com/travel

  10. Watch Out For “VFR” Travelers • VFR =Visiting Friends and Relatives • VFRs often spent childhood at destination so more comfortable with perceived risk (unfortunately, often a false sense of security) • Partial immunity to malaria and travelers diarrhea is quickly lost with residence in a developed country • VFRs as likely to get sick as a non-native—illness perhaps even more likely due to absence of precautions • VFR Travelers are unlikely to seek travel consultation, take malaria meds or use as much care with food selection • Much of the imported malaria in the U.S. is due to visits back home (may fail to take prophylaxis especially since malaria may have been less of an issue in their childhood).

  11. Traveler’s Diarrhea3+ unformed stools in 24 h with at least one of the following : fever, N/V, cramps, tenesmus, or bloody stools (dysentery)Occurs in up to 55% of travelers from a developed country visiting a less-developed country, usually within the first two weeks

  12. Traveler’s Diarrhea “Poo-Pak” • Loperamide hydrochloride (Imodium A/D) 2 mg Adults: one after each loose stool (max: 8 mg/d) for symptom relief but avoid with dysentery! You do not wish to slow the bowel with an invasive organism. Stop in 48h if ineffective. Reserve for older children (>6y) ADD ANTIBIOTIC (IF ILL) FOR UP TO THREE DAYS: 1. Ciprofloxacin (Cipro) 500mg one q 12h x 1-3d prn (other quinolones work as well) or 2. Azithromycin (Zithromax Tri-Pak) 500mg one q d x 1-3d (best for children/pregnancy; quinolone-resistant areas like SE Asia and India; alternative to Cipro) or 3. Rifaximin (Xifaxan) 200 mg 3x/d for 3 days Rifaximin not helpful for invasive organisms Only diarrhea with illness needs to be treated with antibiotics!

  13. Azithromycin Off Label Alternative • Zithromax 500 mg qd x 1-3 days for adults (or 1000 mg x 1 dose) • Zithromax 250 mg qd x 1-3d for older children • Zithromax 100 mg or 200mg/5ml susp. for younger children (10mg/kg/d) > 6mo. • Best for S.E. Asia (e.g. Thailand) and India • Appears safe in pregnancy (category B[m]) but transmitted to breast milk

  14. New Therapy: Rifaximin (Xifaxan) • Broad-spectrum nonabsorbableRifamycin-derivative for travelers’ diarrhea caused by non-invasive E.coli • Approved by FDA for patients 12 years of age or older (5/25/04)—marketed Autumn 2004 • Non-systemic: treats only GI tract (<.4% absorbed) so less likely to cause drug reactions, interactions • Side effects similar to that of placebo (flatulence 11%), HA (9.7%), abdominal pain (7%) , tenesmus (7%) • Safe, no clinically significant resistance • Rifaximin200mg TID x 3d • Not ideal for diarrhea w/ fever or blood in stool; discontinue if diarrhea persists > 24-48h

  15. TD Option#2: Tinidazole (Tindamax) • Good second-line diarrhea drug if antibiotics don’t work • Indications: Giardiasis, Intestinal amebiasis and amebic liver abscess • Better than metronidazole as well tolerated and shorter course (more expensive in U.S.) • Giardiasis: adult 2g single dose • Amebiasis: adult 2g qd x 3d • Like metronidazole, has the advantage of treating pseudomembranous colitis caused by Clostridium difficile(often from excessive use of antibiotics) • Available as 250 mg and 500 mg tablets • Must avoid alcohol during and 3d after use; avoid 1st TM • Potentiates oral anticoagulants, lithium, phenytoin • Side effects: GI upset, abdominal pain, metallic taste, anorexia, constipation, dizziness, HA, transient leukopenia Rare: seizures, peripheral neuropathy

  16. No pooping or smoking allowed!

  17. World Malaria Risk

  18. Insect Bite Prevention DEET containing insect repellant (35%) =6h protection N,N diethyl-m-toluamide apply to skin at dusk—not on clothes/gear Now considered safe in children > 2months or 2nd, 3rd TM pregnancy @ 35% ; apply to skin after sunscreen use if using both; avoid >50% DEET products Picaridin containing insect repellent (20%) safe, reasonable duration, not approved for children < 2 Permethrin-impregnated bed nets Long light-colored sleeves and trousers Window screens Avoid or reduce activity after dusk Mosquito coils Unproven: B vitamins (thiamine), ultrasound, wrist bands, Demal 200 (homeopathic prophylaxis) —these don’t work reliably and should not be relied upon!

  19. Global Dengue Risk Common cause of febrile illness in returning travelers: Prevention is only available strategy

  20. Malaria Prophylaxis Menu of Options G6PD testing necessary

  21. TRAVAX Costa Rica Old vs. New Malaria Maps

  22. India TRAVAX Map: risk stratification

  23. Atovaquone/Proguanil (Malarone) Malaria Prophylaxis • Newest anti-malarial drug for prophylaxis • Adult (250/100) and Pediatric (62.5/25) doses • Well-Tolerated (take w/ food) • Expensive • Best for short trips (1-4 weeks) into malarious regions • Best options for patients w/ seizure disorders • Daily prophylaxis dosing with 1 week “tail”

  24. Chloroquine (Aralen): Central America, Haiti • 500 mg (300 mg base) once weekly starting one week prior to departure and continuing x 4 weeks after return • Reliable only in Central America, Hispaniola (Haiti), Mid-East —elsewhere varying degrees of resistance • Side effects: GI upset, itching (esp. blacks), psoriasis exacerbation, intradermal HDCRV interference, safe for retina at prophylactic doses (avoid if diseased) • Safe in pregnancy; avoid with seizures, retinopathy • Pediatric dosing based on 5mg/kg base weekly (6.3mg/kg salt) • Dangerous to children in overdose; Nivaquinesyrup 6mg/ml available outside U.S. • Resistance mostly in P. falciparum—but also P. vivax in Indonesia/PNG and increasing worldwide

  25. Mefloquine (Lariam): best long-term option • CDC’s recommendation for most areas with CRPF; resistance in SE Asia—esp. Thai border-- areas (rare resistance elsewhere) • Dose: 250 mg weekly starting one week prior to travel, weekly in area of risk and weekly x 4 weeks afterwards (half-life 21d) # = wks+5; convenient for long trips • Cost: $10/tab • Side effects: vivid dreams, insomnia, GI upset (take with water), dizziness, seizures, panic, hallucinations, cardiac conduction problems • Contraindications: avoid in seizure disorders, past history of psychosis or depression, cardiac conduction defects (avoid use w/ quinine, quinidine, halofantrine)—beta-blockers and calcium channel blockers now ok; avoid in pilots unless tolerance already “proven” • Relative Contraindications: 1st trimester pregnancy (ok 2nd, 3rd TM w/consent), airline pilots or tasks involving fine motor coordination, infants (<5 kg?) • Many refuse it out of fear of neuropsychiatric reactions!

  26. Mefloquine Resistance in SE Asia In “red” areas, use doxycycline or Malarone —not mefloquine

  27. Doxycycline: cheapest but least convenient option • Dose: 100mg daily starting 1-2 d prior to travel, daily during risk period and daily for 4 weeks (28d) after • Best cheap alternative to mefloquine for resistant malaria; Best for SE Asian areas of mefloquine-resistance • Side effects: photosensitivity (3%), esophagitis(take w/ water and keep upright), monilia, BCP interaction • Contraindications: pregnancy, children < 8 yrs, allergy Interaction: antagonized by Dilantinand seizure meds • Mechanism: ribosomal inhibition (pre- and erythrocytic phases) Safe for long-term chemoprophylaxis • No resistance reported but compliance poorer due to long post-trip regimen and side effects

  28. Malaria Self Treatment Options • If > 24h from medical care with fever 38+C, consider stand-by self-administered anti-malarial Rx (different from what is already being used as chemoprophylaxis) • Must continue prophylactic regimen (if any) and get medical care ASAP • Malarone 250/100 (atovaquone/proguanil) usual best choice!:4 tabs daily with food for 3 days (#12) $60-70 • Coartem (artemether/lumefantrine) 4 tabs @dx, then 4@8h then 4 BID x 2d (#24) Novartis sells for $69 • Chloroquine phosphate 600 mg base , 300 mg 6h later, 300 mg q d for next 2d (Central America, Haiti) • Fansidar (pyrimethamine-sulfadoxine) 3 tabs no longer reliable due to resistance • Lariam(mefloquine) 250 mg 3 tabs followed 12h later by 2 tabs or 1250 mg in 24H –frequent neuropsychiatric problems at treatment dose

  29. Coartem Self-Treatment of Malaria Now licensed in U.S. (2009) and commonly used for self-treatment in Africa • Artemether 20 mg and Lumefantrine 120 mg (Novartis) • Riamet(marketed in Europe) = Coartem • Three Day Rx: 4 tabs @dx, then @8h then BIDx2d (dose for resistant areas, non-immune patient) • >95% cure rates, no increased QT problems • Can be used in small children (5-10 kg) • Well-tolerated; good “standby” Rxfor traveler

  30. Malaria Prevention Summary • No regimen guarantees 100% protection against malaria so avoid mosquito bites • Malaria ABCsA: Be aware of malaria risk; B: Avoid being bitten; C: Take chemoprophylaxis; D: Seek diagnosis /treatment if fever develops 1 week or more after entering risk area and up to 3m (falciparum) or 1 year (other species) after departure. • Mefloquine: best for long trips and pregnancy; neuropsychiatric issues hinder its use • Malarone: best option for short-term travel; $ • Overseas, ignore advice re regimens there

  31. TRAVEL VACCINATION • Safe, effective way to reduce morbidity from travel diseases • Three vaccine categories: recommended, required and routine • Contact with unvaccinated population = loss of “herd” immunity and increased disease risk • Procrastination a major problem: ideally see patients >1 month before travel • Often not covered by insurance

  32. Live Vaccines Avoid in immunocompromised patients and in pregnancy Give together or 4 weeks apart LIVE VACCINE LIST • Measles-Mumps-Rubella (MMR) • Flu-Mist (and new H1N1 live vaccine) • Oral Typhoid (Vivotif Berna) • Varicella (Varivax) • Yellow Fever

  33. Hepatitis A Vaccine • Two main options equivalent and interchangeable • Havrix, Vaqta: adult (>19) and pediatric (18 and under) doses • Available in U.S. since 1995 – essential recommended vaccine for most travelers to developing countries!!! • Single dose HAV given IM deltoid 4wks prior gives 98-100% protection (give up till departure if necessary) • Booster dose 6 -12 m later for long-term immunity • Approved for children over 1 year of age (IG public health option for younger children in daycare) • Now recommended for all U.S. children > 1 year 5/06 • Pediatric Doses: 2-18 y 720 EL.U. IM, >18y 1440 EL.U. IM

  34. Hepatitis B Vaccine • Recombinant Hepatitis B surface antigen • Recombivax, Engerix-B, Comvax(Hep B/HIB) in pediatrics • Dose: 0, 1, 6 months 0.5 ml IM deltoid 10+yr • AcceleratedEngerix-B regimens: 0, 1, 2 m w/ 12m booster or 0, 7, 21 days w/12 m booster (65% seroprotection on day 28 increasing to 99% month 13) • Pregnancy precaution but safe– noninfectious HBsAg • Indicated for long-term (6+m) or frequent travel or any anticipated sexual or body fluid exposure • Highest risk: China, Sub-Saharan Africa • Now a standard pediatric vaccination in much of the world Assume students will be sexually-active overseas!!

  35. Patpong District, Bangkok

  36. Hepatitis A+B Vaccine Combination • TwinrixHepatitis A/B Vaccine (SKB) • 3 doses: 0, 1, 6 months or 0, 1, 2 w/ 12 m booster • 1 cc IM deltoid adult dose • For adults >18 years old • Vaccine Formulation: adult Hepatitis A antigen 720 EI. U. (ped dose) HBsAg 20mcg Dose volume 1 ml Accelerated off label option: 0, 7, 21 d (83 % HBAb 1m) w/ booster in 12 m 93% Hepatitis A antibody present after 1st dose

  37. Influenza “Seasonal Flu” Vaccine • Flu occurs year round rather than seasonally in the tropics and seasons reversed in southern hemisphere (some exceptions) • Consider vaccination for elderly, ill and diabetic travelers (inactivated so cannot cause flu!) • Adult: 0.5 ml IM deltoid x 1 (give 1 month before flu season) • Pediatric: 6m-8y 2 doses 1m apart for 1st immunization then one dose/y (dose: .25 ml 6-35m, .5ml > 3y) • Avoid in egg allergy, active neurological disorder • Nasal live (cold-adapted) flu vaccine (FluMist) approved for healthy patients 5-49 yrs old

  38. H1N1 “Swine Flu” Vaccine • Still a concern for travelers; vaccine is expiring • 4 manufacturers: 3 killed and 1 live vaccine options (no adjuvant in this year’s vaccine) • May be given at same time as seasonal flu • One dose for adults and children >10years • Children <10 yneed 2 doses (21-28d apart) • Recommended for 5 target groups first: pregnant women, caregivers/contacts for children < 6 months, health care workers, everyone 6 m-24y old, 25-64 y with health problems (do not give if < 6m) • Multi-dose vials contain thimerosol (not in single dose)

  39. Japanese Encephalitis • Virus transmitted in Asia by Culex night-feeding mosquitoes • 10-15, 000 deaths/yr out of > 50,000 reported cases. Most cases sub-clinical but up to 30% fatality rate in those with clinical encephalitis. • Encephalitis survivors often have permanent neurologic sequelae • However much less common in American travelers so vaccination recommended for expatriates and longer-term(>1m) travelers.

  40. Arboviruses of the World ARBO= Arthropod borne TBE JE YF YF Tick-Borne Encephalitis (Red) Japanese Encephalitis (Blue) Yellow Fever (Yellow))

  41. Japanese Encephalitis Map

  42. Seasonal Risk of Japanese Encephalitis Sanofi will cease manufacture of JE-Vax Summer 2005—supplies to run out 2009. New JE Vaccine is Ixiaro (Intercell)

  43. Japanese Encephalitis Vaccine (Obsolete)JE-Vax (Biken) • Consider for 1+ m travel in rural Asia (esp. May-September) Risk up to 1:5,000 per month of travel • Rare in U.S. tourists but high morbidity (50%)/mortality (30%); Recommended for long term stays • Three 1.0 ml SC doses: 0,7, 30d (0, 7, 14 d short course); formalin-inactivated mouse brain vaccine—last dose must be 10+ days before departure (delayed reactions incl. anaphylaxis) • 1ml > 3y, 0.5ml < 3y, avoid under 1 year of age • Risk of delayed urticaria (.6%), anaphalaxis, angioedema— observe for 30 min (10d access to care); Expensive • Contraindications: urticaria hx, pregnancy, < 1yr • May give booster dose after 2 years if risk indicates • Manufacture ceased 2005 (supplies to run out this year) but only JE vaccine approved for children (1-17)

  44. New Japanese Encephalitis Vaccine: Ixiaro(made by InterCell/marketed by Novartis) • Vero-cell culture inactivated vaccine to replace JE-Vax (approved March 2009) better tolerability • Adults 17+ years old (pregnancy category B); still must use JE-Vax for children • 96% seroconversion by 4 weeks (99% Ab later) • Duration and need for boosters still unknown • 2 dose 0.5 ml IM deltoid series given 28 days apart • HA, injection site pain and myalgias but apparently less risk of delayed urticaria • $195 x 2 = $390 cost; No 10d wait period to travel • No thimerosol but contains protamine sulfate

  45. Meningococcal Quadrivalent Vaccines • Menomunequadrivalent A, C, Y, W-135 polysaccharide vaccine (MPVS4) —0.5 ml SC deltoid (polysaccharide vaccines have shorter duration of protection); approved for ages >2 years (best option for > 55yrs); boost q3-5yrs • Menactraquadrivalentconjugate vaccine (MCV4, 2005) approved for ages 2-55 y 0.5 ml IM deltoid; avoid in latex allergy • Menveoquadrivalent conjugate vaccine (MCV4, 2010) approved for ages 11-55y (applying for 2-11) same dose as above • Indications • Hajj (Pilgrims to Mecca) required by Saudi Arabia • Travel to Sub-Saharan Africa meningitis belt Dec-June dry season (serogroup A outbreaks) • Incoming University Students (Dorm Residents) • Medical/mission work in developing world • Neither vaccine protects against serogroup B • Menactra and Menveo conjugate vaccines will give longer immunity (10 years) than Menomune polysaccharide vaccine

  46. Meningitis Belt African Meningitis Belt

  47. Inactivated Polio Vaccine: IPV • Wild polio eradicated in the Western Hemisphere but still a concern in Africa, India, Afganistan, Pakistan, Nepal • Current epidemic in Africa began in 2003 • IPOL Types 1, 2, 3 inactivated poliovirus 0.5 ml • Non-immunized adults: IPV 0.5 ml IM or SC three deltoid doses 1m apart or 0,1-2,6 m • Immunized adults: single IPV booster as adult(travelers to Sub-Saharan Africa, India) • Avoid in pregnancy, avoid OPV (no longer in U.S.) with live typhoid vaccine

  48. Polio Outbreak • Kano State, Nigeria refused polio vaccination: none given since 8/03 • Polio has since spread from Nigeria throughout Africa and then on to Yemen, India, and Indonesia

  49. Rabies Pre-Exposure Vaccine • Rabies Human Diploid Cell Vaccine (HDCV) = Imovax(now available again) • Rabies Purified Chick Embryo Cell Vaccine (PCEC) = RabAvert • Pre-exposure regimen: 1 ml IM deltoid on days 0, 7, 21 (or 28) or .1 ml (HDCV only) ID 0, 7, 21 (or 28) d • EXPENSIVE!!! ID ($250+) much less expensive than IM ($700+) but no longer available in U.S. • Advantages: “Peace of Mind” for expats and their children living in high risk developing countries—children should be highest priority as they play with animals and may not report an exposure.

  50. 50,000 cases rabies in world/y—over half U.S. rabies due to foreign dog exposure: DON’T PET Animals! High Risk High Risk High Risk Free World Rabies Risk Map

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