Preparing the Traveler Stephen Thomas, MD Director, Viral Diseases Branch Walter Reed Army Institute of Research August 2013 Paul Keiser, MD, Feb 2014 UNCLASSIFIED
Outline • Introduction: the dynamics of tropical disease • Preparing the traveler • Ask the right questions • Resources for doctor and patient • Specific advice and preventive measures • Vaccination • Prevention and self-treatment of traveler’s diarrhea • Chemoprophylaxis of malaria • Vector avoidance • Other • Conclusion
Understand the Dynamics of Tropical Diseases Demographics, special populations Temperature, rainfall, cultural & agricultural practices, etc. HOST VECTORS THREATS Circulating animal and human pathogens Mosquitoes, ticks, bats, birds, dogs, cats, etc. Ecology / Environment
Example - Nipah Virus • Highly pathogenic paramyxovirus • Isolated from CSF • Sungai Nipah village • Natural hosts are fruit bats • Causes severe febrile encephalitis • Outbreaks • Peninsular Malaysia and Singapore (1998 – 1999) • Bangladesh: 2001, 2003, 2004, 2005, 2007 and 2008 • India: 2001 and 2007
Nipah Transmission Dynamics • Pigs crowded in pens • Pens near fruit trees • Fruit bat home destroyed • Fruit bats relocate to fruit trees • Bat fluids contain Nipah • Aerosolized virus infects pigs • Pigs infect handlers
Asking the Right QuestionsWho, Where, When, Why and What? • Who is the host / traveler? • Immunologic background, medical problems, etc. • Where are they going? • Geographic region, known threats. • When are they going? • Seasonal variations in disease threat epidemiology • Why are they going there and what will they do? • Defines likely exposure risks • Defines required prophylaxis / PPMs • Know what you do not know. Look it up. Seek consultation.
Giving the Right Advice • Vaccine preventable illness. • Malaria prophylaxis. • Traveler’s diarrhea prevention. • Insect avoidance. • Personal safety. • Behavior and sexual health. • Environmental illness. • Motion sickness and jet lag. • Access to medical care.
Practice Evidenced Based Medicine http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Travel%20Medicine.pdf
Travel Medicine Resources • U.S. Department of State • www.travel.state.gov • MILVAX • www.vaccines.mil/QuickReference • CIA Factbook • www.cia.gov/cia/publications/factbook • National Center for Medical Intelligence • www.intelink.gov/my.policy • Travax: AMEDD Virtual Library • https://medlinet.amedd.army.mil • International Society of Travel Medicine website) • http://www.istm.org/
US CDC • http://wwwnc.cdc.gov/travel/ • http://wwwnc.cdc.gov/travel/yellowbook/2014/table-of-contents
DoD On-Line Infectious Diseases Consults • firstname.lastname@example.org • Infect.email@example.com • firstname.lastname@example.org • email@example.com • Began in January 2005 • 839 teleconsultations thru July 2013 • 35 teleconsultations received January – July 2013 • 6 teleconsultations received in July 2013 • First teleconsultation received from Niger • 7.4% of all teleconsultations received in the AKO Program
Key Elements of the Consult • Patient History • When did it start • Patient symptoms now? • Getting better? Worse? Staying the same? Spreading? • Previous treatments and outcomes? • Laboratory tests results (if any)? • Your Dx / DDx • Your question • Limitations you have in managing the patient
Locations Submitting Teleconsultations http://www.cia.gov/cia/publications/factbook/reference_maps/pdf/time_zones.pdf Afghanistan Chili Honduras Japan Niger Solomon Islands US, Canadian & Australian Navy afloat Albania Congo Germany Jordan Okinawa Spain Supported Facility Bahrain Continental US Ghana Kenya Pakistan Sudan Nepal Bangladesh Djibouti Guam Kuwait Papua New Guinea Thailand Belgium Ecuador Guatemala Kyrgyzstan Peru Turkey Belize Egypt – MFO Sinai Guinea Laos Philippines Turkmenistan Bosnia El Salvador Hurricane Katrina Mali Qatar Ukraine Botswana Ethiopia Iraq Mauritania Saudi Arabia United Arab Emirates Chad Haiti Relief Italy - Sicily Morocco Senegal Yemen
Key Elements of the Consult • Patient Demographics • Age • Gender • Branch of service (if not MIL, state their nationality) • Identify if contractor, detainee, foreign military, etc. • Include digital images if appropriate • PDFs of EKGs • JPEGs of radiographs • Copies of laboratory and pathology reports • Do not send any patient identifying info(HIPAA applies)
Vaccination • Confirm up-to-date routine vaccinations for adults • Countries that do not routinely vaccinate may have higher incidences of vaccine-preventable diseases. • Confirm past travel related vaccination history • Calculate risk: benefit ratio • Disease threat versus vaccine adverse event. • Pre-existing immunity • Consider special populations • Pregnant, immunosuppressed, history of adverse vaccine reactions
Vaccine Preventable Diseases (Routine) http://www.cdc.gov/vaccines/schedules/downloads/adult/mmwr-adult-schedule.pdf
Vaccine preventable diseases for which a marker for protection exists. Kelso JM, et al. Adverse reactions to vaccines practice parameter 2012 update. J Allergy ClinImmunol. 2012 Jul;130(1):25-43.
Hepatitis A • A cell culture–adapted virus, inactivated with formalin, and adsorbed to an aluminum hydroxide adjuvant. • Protective antibody levels develops within 4 weeks of the first dose in 95%; a second dose given >6 months later confers lasting immunity in >99%. • Licensed in 1995; part of the routine childhood vaccination schedule in the US since 2005. • Available in pediatric (0.5 mL) and adult (1.0 mL) formulations.
Hepatitis A • Concomitant IMIG should be considered for: • Unvaccinated adults > 40 years of age, immuno-compromised persons and those with chronic liver disease planning to travel in < 2 weeks. • Travelers who choose not to receive the vaccine. • IMIG (0.02 mL/kg) provides protection against HAV infection for up to 3 months. • Persons traveling > 2 months should get 0.06 mL/kg. • Repeat dose after 5 months for prolonged travel.
Japanese Encephalitis • An inactivated Vero cell culture–derived vaccine. • The two dose IM series (days 0 and 28) should be completed ≥1 week before travel. • Vaccination is only recommended for long-term travelers or those at increased risk of exposure to mosquitoes in rural areas. • A booster should be given if recurrent risky travel occurs >1 year after the primary series.
Japanese Encephalitis • Headache, myalgia, fatigue, and an influenza-like illness were each reported at a rate of >10%. • Approved in 2009 for adults and in 2013 for children down to age 2 months • Dose is based on age: • 2 months to 2 years old get 0.25mL • > 2 years old get 0.5mL.
THE ASSISTANT SECRETARY OF DEFENSE 1200 DEFENSE PENTAGON WASHINGTON, DC 20301-1200 HEALTH AFFAIRS MAY 07 2013 “3. We advise recommendation of JE vaccine for the following Service members and beneficiaries: • Short-term (<1 month) travelers to endemic areas during the JE transmission season if they plan to travel outside of an urban area and have an increased risk for JE exposure. 1. spending substantial time outdoors in rural or agricultural areas, especially during the evening or night; 2. participating in extensive outdoor activities (e.g., camping, hiking, trekking, biking, fishing, hunting, or farming); and 3. staying in accommodations without A/C, screens, bed nets. • Travelers to an area with an ongoing JE outbreak; • Travelers to endemic areas who are uncertain of specific destinations, activities, or duration of travel; and • Laboratory workers with potential exposure to infectious JE virus.”
Meningococcus • Purified capsular polysaccharides from four disease-causing serogroups: A, C, W, Y. • Protein-conjugated (MCV4) formulations available for ages 2 months to 55 years, given IM. • Unconjugated (MPSV4) vaccine is given SC. • The surrogate marker for protection (bactericidal antibody titer) is not commercially available. • Titers can be ordered in CHCS, but this is not a bactericidal assay. • These titers are used to evaluate antibody deficiencies, not to indicate immunity to meningococcal disease. • Licensed in 1978; a routine childhood vaccine since 2005.
Meningococcus • The risk to travelers varies by location and season • Group A predominates in sub-Saharan Africa. • Risk is highest during the dry season (Dec-June). • Other epidemics are reported through various travel resources including http://wwwnc.cdc.gov/travel/. • The Saudi government requires Hajj/Umrah visitors to present proof of vaccination: • Tetravalent vaccination for ages >2 years. • Vaccination must be within last 3 years. • Group A vaccination for ages 3 mos to <2 years. • Visitors coming from the African meningitis belt will also be administered chemoprophylaxis.
Polio • Oral polio vaccine is not available in the US. • Live virus is shed in the stool. • May lead to secondary immunization, which can be advantageous in austere environments where 100% vaccination coverage is difficult. • May also lead to vaccine associated paralytic polio (1-2 cases / million first-time vaccine recipients). • Discontinued in the US in 2000.
Polio • Trivalent inactivated polio vaccine is available in the US. • Covers all three serotypes • Grown in Vero cells, inactivated with formaldehyde. • Recommended doses: • Unvaccinated adults: 3 doses, months 0,1 6-12. • Adults completely vaccinated as children: 1 dose. • Incompletely vaccinated adults: finish the 3-dose series.
Rabies • Pre-exposure vaccination may be considered for travelers to enzootic areas with limited access to healthcare. • Two inactivated vaccines are available. • human diploid cell rabies vaccine (HDCV) • purified chick embryo cell (PCECV) vaccine • Pre-exposure regimen is 3 doses, days 0, 7, 21 or 28. • Given IM: • Not in the buttock. • ID formulation not available in the US, but in use and shown to be effective elsewhere.
Rabies • Need for post-exposure prophylaxis is determined by the WHO category of exposure • Category I – touching or feeding animals, licks on the skin • Category II - nibbling of uncovered skin, minor scratches or abrasions without bleeding, licks on broken skin • Category III – single or multiple transdermal bites or scratches, contamination of mucous membrane with saliva from licks; exposure to bat bites or scratches
Rabies • Post-exposure regimen for category II and III • With pre-exposure vaccination • Two boosters of a cell culture vaccine (days 0, 3). • Without pre-exposure vaccination • Four doses of cell culture vaccine (days 0,3,7,14). • For category III exposures, also inject human RIG into the wound and IM (20 IU/kg)
Typhoid • Two vaccines are available, each with 50-80% efficacy: • Oral live attenuated vaccine (from the Ty21a strain) • Four doses, taken on alternate days. • Complete at least one week before travel. • Must be kept refrigerated. • Do not administer with antibiotics (mefloquine and chloroquine are okay; proguanil is not). • Not approved for children <6. • Not for the immunocompromised. • May cause nausea, other GI symptoms. • Boost (with the same regimen) after 5 years if needed.
Typhoid • Two vaccines are available, each with 50-80% efficacy: • IM Vi capsular polysaccharide (ViCPS) • Approved down to age two. • Administer at least 2 weeks before travel. • Frequently associated with pain (>95%), headache (16-20%), malaise. • Boost after 2 years.
Yellow Fever • A live attenuated vaccine, prepared by culturing the a 17D strain of yellow fever virus in chicken embryos. • Hypersensitivity to eggs is a contraindication. • No preservative; the vaccine must be reconstituted immediately before use. • One subcutaneous dose every 10 years as needed. • Mild systemic reactions are common (10-30%). • Use with caution in the immunosuppressed. • Thymic disorders, HIV, malignancy, transplant • Immunosuppressive drugs and biologicals. • Family members of immunocompromised patients can receive the vaccine.
Yellow Fever • YF vaccine–associated neurologic disease. • Includes disseminated infection and non-infectious complications such as Guillain-Barre and Bell’s palsy. • Incidence is age-related; • 0.8/100,000 doses overall; >50/100,000 doses in infants; 2.3/100,000 for age >70. • Has occurred in breast-fed infants of vaccinated mothers. • Rarely occurs with booster doses. • YF vaccine–associated viscerotropic disease • Disseminated infection similar to wild-type disease. • 2.3/100,000 doses for age>70. • Does not occur with booster doses.
Yellow Fever • Administer 30 days apart from MMR. • No decrease in efficacy if given with IMIG. • Proof of vaccination: • May be required for entry into • Endemic countries, to prevent illness. • Non-endemic countries, to prevent importation. • Traveler’s with vaccine contraindications may require a waiver letter to be permitted entry. • Traveler’s with inadequate documentation may be quarantined, typically for six days.
Vaccination Adverse Events • Avoid live-attenuated vaccines in immunocompromised travelers. • Anaphylaxis to vaccines occurs about 1/million doses. • Patients should be monitored post-vaccination. • Epinephrine should be available. • Patients with contact allergies to vaccine components (neomycin) can generally receive parenteral vaccines.
Vaccination: General comments • Live-virus vaccines should be administered together or >4 weeks apart. • Administering a live-virus vaccine within 4 weeks after administration of another live-virus vaccine can decrease immunogenicity to the second vaccine.
Traveler’s Diarrhea (TD) • Attack rates range from 30% to 70% of travelers • Clinical syndrome from a variety of intestinal pathogens • Bacterial pathogens are the predominant risk (80%–90%) • Viruses have been isolated (5%–8%), Norovirus may > % • Protozoal pathogens (10%), longer-term travelers • Bacteria • Enterotoxigenic Escherichia coli (#1), Campylobacter jejuni, Shigella spp., and Salmonella spp. Enteroadherent and other E. coli species are also common. Aeromonas spp. and Plesiomonas spp. as well. • Viral • Norovirus, rotavirus, and astrovirus. • Protozoal • Giardia, Entamoeba histolytica and Cryptosporidium uncommon • Cyclospora (Nepal, Peru, Haiti, and Guatemala) • Dientamoeba fragilis is a low-grade but persistent pathogen
Traveler’s Diarrhea (TD) • Prevention • Food and beverage selection • Wash it, boil it ,cook it, peel it: reduces, does not eliminate risk • Non-antimicrobial drugs for prophylaxis • Bismuth subsalicylate (Pepto-Bismol) • Not in travelers w/ aspirin allergy, renal insufficiency, or gout. • Not for use with anticoagulants, probenecid, or methotrexate. • Not generally recommended for children aged <12. • Studies have not established safety for periods >3 weeks. • Prophylactic Antibiotics • Diarrhea attack rates are reduced by 90% or more • At this time, prophylactic antibiotics not recommended for most • Ease of treating diarrhea versus side effects of antibiotics