Travel Medicine Challenges

Transcription

1 Travel Medicine Challenges David G. Graham, MD, MPH Stony Brook University Medical Center October 2016 Objectives Discuss vaccines specifically indicated for travel Highlight updated recommendations on travel immunizations Discuss cases on vaccinating travelers Travel and pathogens volume of travel: 2016 ITA billion duration to reach destinations Massive jets, cruise ships, mass gatherings More ill persons traveling Pathogens spread rapidly and widely

2 Vaccinations for Travel Steffen R, et al. Vaccine preventable travel health risks: what is the evidence what are the gaps? JTM 2015 High Intermed Low/ very low 580 VPD among 37,542 ill returned travelers : Enteric fever (n =276; S. typhi=160, S. paratyphi=88, unspec=28) Acute viral hepatitis (n =148; A=97, B=51) Influenza (n = 70) Varicella (n = 37) Measles (n = 12), pertussis (n = 10), bacterial meningitis (n = 10) Associated factors: S. typhi VFR travel (p < 0.016) to SC Asia (p < 0.001) Business travel influenza (p < 0.001) Longer travel hepatitis A (p = 0.02) 3 deaths one each due to pneumococcal meningitis, S. typhi, rabies.

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4 Vaccine Updates for Travel Yellow fever: ACIP update Japanese Encep Vero cell derived inactivated vaccine Hepatitis A: recent epi, duration of protection Hepatitis B: screen for chronic HBV Typhoid, Tetanus, Influenza, Zika Polio: updated risk countries Meningococcal (conjugate); meningococcal B vaccine Rabies: animal injury risk high Other vaccines available in European Union/Canada: Tick borne encephalitis Cholera Yellow fever cases/outbreaks CDC. WHO. Flavivirus Yellow Fever Viral hemorrhagic fever transmitted by mosquitoes (Aedes aegypti) Clinical: asymptomatic to fatal Distribution: West Africa and Central Africa (90% of cases), and South America Amazon Resurgence of disease on both continents affects local populations and travelers Vector mosquitoes are present in US

5 Yellow Fever and Travelers : 9 cases, 8 fatal Risk of YF for unimmunized travelers for 2 wk stay: Rural West Africa, inter epidemic period: Illness: 1/1,200; Death: 1/10,000 South America: Illness: 1/20,000; Death: 1/100,000 Risk determined by location, disease activity, exposure to mosquitoes; reported cases may be misleading (immunized population; activity not detected by surveillance) Monath, Cetron. CID 2002;35: Yellow Fever Vaccine Live attenuated vaccine derived from the 17D virus strain and produced in eggs Adverse Effects: Minor: Headache, fever, backache, pain at injection site (25%) Major Severe allergic reactions (1/131,000); hypersensitivity to eggs or gelatin Neurologic/neurotropic disease Viscerotropic disease ACIP 2010 recommendations: YF vaccine MMWR 2010;59(RR07):1 27.

6 ACIP 2010 recommendations: Yellow Fever vaccine Contraindications Precautions - Allergy to components - Age 6 9 months - Age < 6 months - Age > 60 years - Symptomatic HIV infection - Asymptomatic HIV - Thymus disorder - Pregnancy - Primary immunodeficiency - Breastfeeding - Malignancies - Transplants - Immuncompromised MMWR 2010;59(RR07):

7 A traveler with myasthenia gravis plans to go on a safari trip to Kenya and Tanzania for 2 weeks. Which of the following vaccines would be most appropriate to consider? A. Hepatitis A, typhoid polysaccharide, meningococcal, and varicella B. YF, typhoid polysaccharide, hepatitis A, and polio C. Polio, hepatitis A, typhoid polysaccharide, and a waiver for YF vaccine D. Typhoid polysaccharide, hepatitis A, YF, and meningococcal vaccine Answer C

8 36 studies & 22 reports: 12 on immunogenicity, 8 duration Seroconversion rates % Non endemic populations: Berlin 94% seropositivity yr 1, 75% after 10 yrs Elderly in travel clinics 95% seropositive at years after vaccination WWII vets 81% seropositive >30 years after vaccination ACIP YF recommendations 2015 Single dose protects life long in most travelers Consider revaccination in risk groups: Pregnant when received YF vaccine Had HSCT since prior YF vaccine HIV when received YF vaccine High risk exposures long stay, high incidence areas, recent or ongoing outbreaks Lab workers handling YF virus (measure ab if possible) A healthy 65 year old US born male will visit The Gambia and Senegal for 1 month. He had YF vaccine, gamma globulin, polio, and cholera vaccines in the 1980s when he lived in Senegal for 2 years. He recently had influenza, pneumococcal, and tetanus diphtheria pertussis vaccines. He leaves in 5 days. Which vaccines are the most appropriate recommendation at this visit: A. YF, hepatitis A, oral typhoid and meningitis ACYW135 B. YF waiver, injectable typhoid, combined hepatitis A/B, meningitis ACYW135 C. YF waiver, rabies, hepatitis A, meningitis ACYW135 D. YF, meningitis ACYW135, hepatitis A, injectable typhoid Answer D

9 Japanese encephalitis distribution wwwnc.cdc.gov/travel/yellowbook/2016/chapter 3 infectious diseases related to trav el/ japanese encephalitis Japanese encephalitis Flavivirus Culex mosquitoes Asia: Breed in farms, rice paddies Tropical year round Temperate May Oct Incubation 5 15 days Fever, HA, vomiting, MS change, neuro deficits, movement disorder Risk : Long stay (>1 month) Or Rural areas Night time, outdoors Ongoing outbreaks Japanese Encephalitis Travelers from non endemic countries: 55 cases : 17 countries Age 1 91, median = 34 years 18% died, 44% mild to severe sequelae 65% spent 1 month in endemic areas Overall risk <1 case/1 million travelers (Hills S et al. AJTMH 2010) 2 US children: Philippines, Thailand (CDC. MMWR 2010) 3 US adults: China, Taiwan, S Korea (Hills et al. JTM 2014)

10 Japanese Encephalitis Vaccine JE VC (Ixiaro; killed Vero cell vaccine SA ; Intercell/Novartis) 2 doses, day 0, 28 Licensed in 2009 for age 17 years Licensed in 2013 in US for 2 mo 16 years: 2 months to less than 3 years, 0.25 ml (half dose) 3 years and older, 0.5 ml (full dose) Past: JE MB JE vaccine How long does protection last? How much protection is achieved with 1 dose? If only 1 dose given, how do you complete series? Seroprotection (PRNT 50 1:10) Complete primary series (Day 0, 28) Month 6 Month 12 Month 18 83% 58% Month 24 48% Booster: Month 11, 15, or % 98.5% Incomplete primary series (Day 0 9% only: seroconversion 43% d28) Booster: Month 11 99% 4.3% Dubischar Kastner K et al. Vaccine 2010; Schuller et al. Vaccine 2009; Eder S et al. Vaccine JE vaccine If previously had JE MB, is there protection from 1 dose? Primed vs vaccine naïve: (Erra et al. Clin Infect Dis 2012) Primed had better response with a single dose (95 98% vs %) Primed with JE MB (2 3 doses): (Woolpert et al. Vaccine 2012) 1 dose of JE VC led to 100% seroprotection Primed with JE MB (3 doses): (Erra et al. Vaccine 2014) 1 dose of JE VC led to % seroprotection at 2 years

11 Live attenuated JE vaccine Imojev (available Australia, Sanofi) Recombinant DNA based on 17D YF vaccine virus with 2 genes replaced from JE virus, & code for PrM and E proteins Vaccine elicits neutralizing antibodies and cell mediated immunity 1 dose, age 12 months Seroprotection: 93% at 14 days, 99% at 30 days, 91% at 4 yrs A 44 year old traveler is leaving in 2 weeks to visit family in rural Philippines affected by Typhoon Haiyan, staying for 2 months. He received one dose of the inactivated Vero cell culture derived Japanese encephalitis (JE) vaccine a year ago. What s the most appropriate advice to reduce the risk of Japanese encephalitis? A. Restart JE series, and advise him to delay departure until he can complete a 2 dose series 28 days apart. B. Rely on using repellent and mosquito net only since there is insufficient time to complete the 2 doses 28 days apart. C. Administer the 2 nd dose of the series now since there will be adequate response when it is given a year after the initial dose. D. Accelerate the 2 dose series so to complete them within 2 weeks. Answer C

12 HAV: picornavirus, non enveloped RNA virus Vaccines: Havrix (GSK), Vaqta (Merck), Transmission: fecal oral Incubation: TwinRix (GSK) 28d (15 50) Outside US: (TwinRix Jr, Canada), Risk: 1/1000 5/1000 per month stay Avaxim (Sanofi Pasteur), Epaxal (Crucell) Hepatitis A vaccine Inactivated virus vaccine 2 doses IM, >6 months apart Immunogenicity: 1 dose = >94% 2 doses = % Duration: antibody persist >17 years (Van Herck K 2012) Antibody modeling: 97 98% of vaccinees will remain seropositive 25 years after dose 1 (of 0,6m or 0, 12m series) (Hens N et al. Vaccine 2014) Delay in 2 nd dose: no need to restart 2006: incorporated into routine childhood schedule Ethelberg S, et al. Eurosurveillance 2013 Eurosurveillance 2014 Eurosurveillance 2014

13 Hepatitis A Vaccines HAVRIX (Hepatitis A) - Age Dose No. of Schedule (Yrs.) (EL.U.) Volume Doses (Months) ml 2 0 and 6-12 > ml 2 0 and 6-12 VAQTA (Hepatitis A) - Age Dose No. of Schedule (Yrs.) (EL.U.) Volume Doses (Months) ml 2 0 and 6-18 > ml 2 0 and 6-18

14 1 dose hepatitis A vaccine insufficient Administer 2 doses prior to travel, or IG if insufficient time N=53 Seroprotection % Seroprotection % at 1 mo at 6 mo 1 dose doses Hepatitis A vaccine response Immunocompromised patients showed moderate to good serologic response BUT need more time to develop immunity Garcia Garrido HM, et al. Response to Hepatitis A Vaccination in Immunocompromised Travelers. J Infect Dis Feb 3. pii: jiv060. [Epub ahead of print] Hepatitis B prevalence wwwnc.cdc.gov/travel/yellowbook/2014/chapter 3 infectious diseases related to travel/hepatitis b

15 Hepatitis B Screen for HBV in persons from countries with HBsAg prevalence 2% Colvin HM et al, eds; IOM. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C. National Academies Press Weinbaum CM et al. MMWR 2008; 57(RR 8). Vaccine indicated for travelers visiting destinations with HBsAg prevalence 2% Mast EE, et al. MMWR 2006;55(RR16). CDC. MMWR 2011;60(4). Hepatitis B Risk: Danish survey N=1090 traveled to endemic areas 7% had possible HBV exposure Voluntary risk (23%) acupuncture, cosmetic surgery, tattoos, scarification Involuntary risk (77%) medical/dental procedures, blood transfusions, medical aid Risk increased with journey length: <4 weeks (5%) 1 5 months (20%) 6 months (41%) HBV, hepatitis B virus Nielsen US, et al. J Infect. 2009;59: Hepatitis B Vaccine Recombinant vaccines 3 doses day 0, 1 mo, 6 mo Alternate schedules Day 0, 1 mo, 4 mo Day 0, 2 mo, 4 mo Accelerated Day 0, 7, 21, 12 mo Response following doses: 1= 30 55%; 2= 75%; 3= >90% Duration: 22 years McMahon et al, JID Poorolajal et al. Vaccine Jan et al. Hepatology Middleman AB. Pediatrics2014.

16 Vaccines to prevent hepatitis B VACCINE TRADE NAME AGE (Yrs) DOSE ROUTE SCHEDULE BOOSTER Hepatitis B vaccine, recombinant Engerix-B (GlaxoSmithK) 20 (primary) 20 (accelerated) 1.0 ml (20 μg HBsAg) 1.0 ml (20 μg HBsAg) IM IM 0, 1, 6 mo 0, 1, 2 mo None 12 mo Hepatitis B vaccine, recombinant Recombivax HB (Merck) 20 (primary) 1.0 ml (10 μg HBsAg) IM 0, 1, 6 mo None Combined hepatitis A and B vaccine Twinrix (GlaxoSmithK) 18 (primary) 18 (accelerated) 1.0 ml (720 ELU HAV + 20 μg HBsAg) same as above IM IM 0, 1, 6 mo 0, 7, d None 12 mo

17 Combined hepatitis A B vaccine 3 dose series Day 0, 1 month, 6 month Accelerated: Day 0, 7, 21 days, 12 month Age 18 years Seroprotection: comparable to monovalent Reduced hepatitis A antigen content: 2 doses of HAB vaccine (Day 0, 1 month) desirable before travel; more reliable hepatitis A protection Protective duration: >17 years» Van Damme P et al. J Med Virol 2012;84. Typhoid fever Incubation: 3 60 d, (avg 1-2wks) Fever, headache, malaise Rose spots WHO 2009 Salmonella enterica serotype Typhi Transmission: food, water Epidemiology: 22 million infections/yr, 200,000 deaths/yr Risk: highest in South Asia Typhoid US cross sectional, lab surveillance (Lynch et al. JAMA 2009) : 1,902 persons with epi data Foreign travel within 30 days = 79% Indian SC 85% of MDRST Salmonella enterica serotype Paratyphi A in Asia increasing (CrumpJA, Mintz ED. CID 2010) Antimicrobial resistance to FQ, 3 rd generation cephalosporins Azithromycin effective

18 Typhoid vaccines: efficacy ~60% Vaccine Route Min. age (Yr) Vi capsular polysaccharide (Typhim Vi) Live attenuated Ty21a (Vivotif) Duration (Yr) Combined Efficacy = ~60% IM IM 16 Typhoid: hepatitis 3 = Intramuscular A/typhoid (Canada) AE IM 2 2 Local rxn 7% Oral 4 caps HA 16 20% 6 5 HA 0 5% Fever 0 5% GI <10% Same as Vi capsular polysaccharide Routine Immunizations: Polio Complete primary series for all travelers US: give 4th dose after age 4; interval between doses 3 and 4 should be 6 months CDC: One time IPV booster for certain travelers to selective countries

19 2014: WHO declared international spread of WPV a public health emergency of international concern. New temporary polio vaccine requirements: Afghanistan, Cameroon, Equatorial Guinea, Ethiopia, Iraq, Israel, Nigeria, Pakistan, Somalia, Syria. Madagascar LT travelers (>4 weeks) to the countries above may be required to show proof of polio vaccination when departing the polio infected country (4 weeks 12 months before departure from polio infected country). Cholera in the Americas: Haiti: >1 million cases, with over 10,000 deaths Started in 2010 by UN peacekeepers who discharged their wastes into the rivers. The UN finally acknowledged it this year. (NY Times 10/16/2016) Dominican Republic: 32,171 cases, 484 deaths Mexico: 14 cases (2014) Cuba 700 cases, 3 deaths

20 Cholera Vibrio cholera O1 or O139 Transmission: water or food contamination Epidemiology ,000 cases 7800 deaths Haiti >55% Africa CFR 1.3% Incub hrs. Rice water stool, nausea, vomiting, dehydration Cholera vaccines Oral killed whole cell B subunit (WC/rBS, Dukoral) 2 doses 85% protection over 6 mo May protect against ETEC for 3 mo Killed V. cholerae O1 & O139 (Shanchol): India 2009 No cholera toxin B subunit 2 doses 1 2 weeks apart, every 3 yrs Protective efficacy 68% CVD 103 HgR: vaccine candidate seeking FDA approval Single dose, oral, live attenuated vaccine

21 Meningococcal vaccines Quadrivalent: ACYW 135 CDC. MMWR 2011;60(3). Cohn et al. MMWR 2013;62(RR2). Booster Polysaccharide at 4 5 years (MPSV4; Menomune) Clinical efficacy 85% for AC Routine at age years; boost at age 16 years Does not eliminate carriage 2 dose primary series for high risk (complement deficiency, Conjugate asplenia, (MCV4; travel Menactra, to endemic Menveo); region) interchangeable Approved for 2 55 years old Menactra also approved from 9 23 months for high risk Reduce carriage serogroup C in UK decreased by 66% Meningococcal B (Trumenba, Bexsero) 2/15 ACIP US outbreaks recommends (emergency for use: previously special populations licensed in NZ, EU) Complement FDA approved deficiency, 10/2014, 1/2015 asplenia, microbiologists, outbreaks Rhabdoviridae, genus Lyssavirus Neurotropic, encephalomyelitis Animal injury risk: >1/100 personmonth of travel (PiyaphaneePLoS NTD2012)

22 Rabies exposure Any animal bite is considered a rabies exposure Strategy depends on length of stay, location, likelihood of animal exposure and availability of post-exposure treatment Short travel: Animal avoidance, don t feed them Long or frequent travel: Vaccination If bitten, wash the wound with soap and water for at least 10 minutes Seek immediate medical treatment

23 Rabies prevention Avoid contact with animals (esp dogs, monkeys, cats, bats) Pre exposure prophylaxis (PrEP): day 0, 7, 21 or 28 Post exposure prophylaxis (PEP) Wound care Rabies immune globulin (HRIG) (unless had PrEP) Vaccine series (4 doses normal host, 5 doses if immune compromised) WHO Rabies PEP categories of exposure Categories of contact with suspect rabid animal Post exposure prophylaxis measures Category I touching or feeding animals, licks on intact skin Category II nibbling of uncovered skin, minor scratches or abrasions without bleeding Category III single or multiple transdermal bites or scratches, licks on broken skin; contamination of mucous membrane with saliva from licks, contacts with bats. None Vaccine + wound care RIG + vaccine + wound care ACIP Rabies PEP categories of exposure

24 Rabies Post Exposure Prophylaxis Immunization Vaccine/pr status oduct No PrEP RIG (not + previously Vaccine immunized) PrEP (previously immunized) Vaccine Dose 20 IU/kg 1.0 ml No. of doses 1 4 Schedule (days) 0 0,3,7, ml 2 0, 3 Meta analysis (> 1,270,000 individuals) 0.4% travelers overall experience an at risk bite per month of stay Preexposure proph Expatriates 30% Travelers 13% Rabies post exposure treatment France, Australia, New Zealand, (n=261): 11% of 170 needing RIG received abroad, 13% waited until return; 33% no RIG» Gautret P et al. JTM 2008 Liverpool, UK, (n=139): 3.8% of 78 bites needing RIG had RIG abroad, 14% had it on return» Wijaya L et al, JTM 2011 Lausanne, Switzerland, (n=90): 14% of 54 saw MD abroad/had RIG, 90% of 31 bites saw MD Switzerland/got RIG» Uwanyiligira M et al, CID 2012 Bali, Indonesia, (n=45): 5.3% of 38 with RIG indication had RIG in Bali 7.9% no RIG at all» Gautret P et al. Clin Microbiol Infect 2010

25 A traveler has had the 3 dose series of rabies pre exposure vaccine (days 0, 7, 28). You would recommend the following pre exposure boosting schedule: A. Boosters are not needed after completing preexposure prophylaxis unless new exposure occurs. B. Check titers if it has been 2 years or more since the initial series and give a booster if titers are low. C. Give a booster if it has been more than 10 years since the initial series. D. Repeat the 3 dose series if more than 10 years have elapsed since the initial series. Answer A Tick borne encephalitis Flavivirus 3 subtypes: European, Far Eastern, Siberian Transmission: Ixodes tick bite or ingestion of raw milk Small rodents are main tick hosts and man is accidental host Incubation 7 14 days Shorter after milk exposure Tick borne encephalitis Epidemiology Rural and forested Elevations <1400 meters Peak: April November Biphasic illness Viremic phase (2 4 days) Fever, malaise, anorexia, muscle aches, headache, nausea, +/ vomiting CNS phase in 20 30% of patients, after 8 d remission Meningitis, encephalitis or meningoencephalitis

26 TBE vaccines Europe: FSME IMMUN and Encepur (ages >1) Russia: TBE Moscow and EnceVir (ages > 3) China: Far Eastern virus strain WHO: immunize residents in highly endemic areas Not available in US; limited in Canada WHO. Wkly EpidemiolRec. 2011;86: Summary: vaccine updates Updated risk estimates for travelers YF: ACIP and WHO recommendations 2016 JE Vero cell derived inactivated vaccine: boost in 12 months, pediatric use licensed, JE MB can prime Hepatitis A: protective duration >25 years by modeling Hepatitis B: screen for HBsAg prevalence 2% Typhoid: rising resistance esp Indian Sub Continent Polio: risk countries updated Meningococcal (conjugate): boost in 3 5 yrs, NO menb Rabies: animal injury risk high Online resources CDC Traveler s Health. PAHO. WHO International Travel and Health. CDC Vaccines & Immunizations. ACIP recommendations. Immunization Action Coalition. Epidemiology and Prevention of Vaccine Preventable Diseases (Pink Book). State Department. ISID ProMED.

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28 So, as we get older. GETTING OLDER A distraught senior citizen phoned her doctor's office. "Is it true," she wanted to know, "that the medication you prescribed has to be taken for the rest of my life?" "'Yes, I'm afraid so,"' the doctor told her. There was a moment of silence before the senior lady replied, "I'm wondering, then, just how serious is my condition because this prescription is marked 'NO REFILLS'." 28