2018‐03‐03 1 Faculty/Presenter Disclosure • Faculty/Presenter: Dr. Rudy Zimmer • Relationships with commercial interests: Grants/Research Support: Not Applicable Speakers Bureau/Honoraria: Not Applicable Consulting Fees: Not applicable Other: This presentation has received support from the Alberta College of Family Physicians in the form of a speaker fee and/or expenses. Travel Hepatitis Vaccines ACFP 63 rd ASA Disclosure of Commercial Support This program has received financial support in the form of sponsorship from: • Potential for conflict(s) of interest: Those speakers/faculty who have made COI disclosure are noted in the 63rd ASA Program and on the Salon A/B slide scroll. Travel Hepatitis Vaccines
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Transcript
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Faculty/Presenter Disclosure
• Faculty/Presenter: Dr. Rudy Zimmer
• Relationships with commercial interests:
Grants/Research Support: Not Applicable
Speakers Bureau/Honoraria: Not Applicable
Consulting Fees: Not applicable
Other: This presentation has received support from the Alberta College of Family Physicians in the form of a speaker fee and/or expenses.
Travel Hepatitis Vaccines
ACFP 63rd ASADisclosure of Commercial Support
This program has received financial support in the form of sponsorship from:
• Potential for conflict(s) of interest: Those speakers/faculty who have made COI disclosure are noted in the 63rd ASA Program and on the Salon A/B slide scroll.
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Mitigating Potential Bias• ACFP:
The ACFP’s Sponsorship Guidelines apply to ASA Sponsorship. The ACFP abides by the College of Family Physicians of Canada’s Understanding Mainpro+ Certification Guidelines, the Canadian Medical Association’s Policy Guidelines for Physicians in Interactions With Industry and the Innovative Medicines Canada Code of Ethical Practices (2016). As a non‐profit organization, the ACFP complies with Canada Revenue Agency regulations. When deliberating acceptance of sponsorship, the ACFP considers and accepts sponsorship only from those whose products, services, policies, and values align with the ACFP vision, values, goals, and strategies priorities.
• ASA Planning Committee: Consideration was given by the 63rd ASA Planning Committee to identify when Planning
Committee members’ and speakers’ personal or professional interests may compete with or have actual, potential, or apparent influence over program content.
Material/Learning Objectives and/or session description were developed and reviewed by a Planning Committee composed of experts/family physicians responsible for overseeing the program’s needs assessment and subsequent content development to ensure accuracy and fair balance.
The 63rd ASA Planning Committee reviewed Sponsorship Agreements to identify any actual, potential or apparent influence over the program.
Information/recommendations in the program are evidence‐ and/or guidelines‐based, and opinions of the independent speakers will be identified as such.
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Odyssey Travel + Tropical Medicine ClinicTravel Medicine Consultant, AHS Calgary Zone
Clinical Assistant ProfessorDepartment of Community Health Services
The University of Calgary
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Non‐responders and hypo‐responders to Hepatitis B: usually older persons, and VFR immigrant travellers.
New indications for Hepatitis A vaccine for children between 6 and 12‐months‐of‐age.
Effect of direct‐to‐consumer advertising (DTCA) on physician behaviour providing combination Hepatitis A + B vaccine (e.g., revaccinating teens already vaccinated with Hepatitis B vaccine through school programs – and not checking Netcare or hard copy records)
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HAV is positive‐sense, single‐stranded linear RNA virus (only 1 serotype)
Figure 1 ‐ Current estimates on vaccine‐preventable disease incidence among Western travelers to tropical and subtropical destinationsReference: J Travel Med. 2014;22(1):1‐12. doi:10.1111/jtm.12171
Hepatitis B
Hepatitis A
Typhoid
Antibiotics
Influenza
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Not recommended unless one has not had a completed vaccine series …
… or a lab confirmed case of Hepatitis A infection in the past history.
Targets for testing:
Immigrantswith no previous test positive (e.g., look on Netcare).
History of jaundice with no documented test positive (also HBV).
Unreliable or undocumented HAV vaccine series in past.
Four possibilities: false positive core test recovery from asymptomatic acute infection distant cleared infection with waning immunity chronic infection with undetectable HBsAg*
* Use alternate testing (HBeAg, anti‐HBe, HBV DNA detection)
A positive immunity test is measured arbitrarily ≥ 10 ml/mL of anti‐HBs.
This is a surrogate marker for protection against future HBV infection.
This measurement is only meaningful done 1‐2 months after provocation*
* Following a full primary series (e.g., 0, 1 and 6 ‐12 months)* Following a booster shot in a person with a distant primary series* Following exposure to HBV infection in an immunized person
Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018 Jan 12; 67(1): 1–31. Available: https://www.cdc.gov/mmwr/volumes/67/rr/rr6701a1.htm
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Testing if done several years after a primary HBV series or infection:
Only helpful if anti‐HBs titres are still ≥ 10 ml/ml (slow waning)
Meaningless if < 10 ml/ml due to normal waning antibodies with time
If testing distant vaccine series, boost first and test 1‐2 month later
Routine testing of anti‐HBs is not recommended, if an individual has had a confirmed completed vaccine series
Vaccine immunity is considered to last > 30 years or “life time”, regardless of waning antibodies in an otherwise healthy person.
Reference: Van Der Meeren O, Crasta P, et al. Characterization of an age‐response relationship to GSK's recombinant hepatitis B vaccine in healthy adults: An integrated analysis. Hum Vaccin Immunother. 2015;11(7):1726‐9. Available:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514334/ (accessed 2018 Feb 04).
80% seroconversion at 60 years old
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There is no clear guidance on this issue with great variance of opinions.
NACI recommends a second full normal dose series, 50‐70% will respond. NACI then recommends “giving up” and assuming non‐response – we disagree.
The problem with non‐response is lack of antigen “noise”, thus our experience over 16 years is more doses of normal “noise” does not work, we crank the noise.
We recommend only using 20ug anti‐HBs vaccine (Engerix®‐B) for adults.
If there is no‐low response to primary series, then boost 20ug x 2 as a trial, but test anti‐HBs with HBsAg and anti‐HBc 1‐2 m later, if not done already.
Recombivax HB®‐Adult dialysis (40ug) is not usually available in community, whereas Recombivax HB® only contains 10ug which is insufficient > 30‐40 years.
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Medical literature also suggests other approaches, some still experimental:
Twinrix® (combined HAV + HBV) vaccine using HAV as adjuvant – we disagree
Our experience with Twinrix® is similar to Engerix® regarding vaccine failures
Intradermal HBV vaccine administration shows promise in other travel clinics
It requires expertise in ID administration and could lead to vaccine waste
Formulated vaccine adjuvants added to the monovalent HBV vaccine
There are no currently licensed adjuvanted HBV vaccines in Canada
Reference: Leroux‐Roels G. Old and new adjuvants for hepatitis B vaccines. Med Microbiol Immunol. 2015 Feb;204(1):69‐78.
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Studies estimate 44 ‐ 55% of reported HA cases in Canada are linked to travel.
Low‐budget travellers, volunteer humanitarian workers, and Canadian‐born children of new Canadians returning to their country of origin to visit friends and relatives, may be at increased risk.
The risk of HA for susceptible travellers to developing countries is estimated to range from 0.1/1,000 to 1/1,000 per month.
Update on the Recommended use of Hepatitis A Vaccine. An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI). May 2016. Available: https://www.canada.ca/en/public‐health/services/publications/healthy‐living/update‐recommended‐use‐hepatitis‐vaccine.html
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Canada has several licensed HAV‐containing vaccines, all with similar safety and protective efficacy:
AVAXIM® (adult formulation) and AVAXIM®‐Pediatric (paediatric formulation) (inactivated hepatitis A vaccine), Sanofi Pasteur SA (manufacturer), Sanofi Pasteur Ltd. (distributor) (HA)
HAVRIX® 1440 (adult formulation) and HAVRIX® 720 Junior (paediatric formulation) (inactivated hepatitis A vaccine), GlaxoSmithKline Inc. (HA)
TWINRIX® (adult formulation) and TWINRIX® Junior (paediatric formulation) (combined hepatitis A and hepatitis B [HB ] vaccine), GlaxoSmithKline Inc.
VAQTA® (inactivated hepatitis A vaccine), Merck Canada Inc. (HA )
ViVAXIM® (combined purified Vi polysaccharide typhoid and inactivated hepatitis A vaccine), Sanofi Pasteur Ltd. (distributor) (HA‐Typh‐I)
Hepatitis A Vaccine. Canadian Immunization Guide: Part 4 ‐ Active Vaccines (evergreen). Available: https://www.canada.ca/en/public‐health/services/publications/healthy‐living/canadian‐immunization‐guide‐part‐4‐active‐vaccines/page‐6‐hepatitis‐a‐vaccine.html
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Recommendation 1: HA vaccine may be provided, beginning at six months of age, to infants who are at increased risk of infection or severe HA. (NACI recommendation Grade B)
Canadian‐born infants travelling to HA endemic countries, including children of new Canadians returning to their country of origin to visit friends and relatives
Update on the Recommended use of Hepatitis A Vaccine. An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI). May 2016. Available: https://www.canada.ca/en/public‐health/services/publications/healthy‐living/update‐recommended‐use‐hepatitis‐vaccine.html
AHS Hepatitis A Vaccine Biological Page. Revised February 2017. Available: https://www.albertahealthservices.ca/assets/info/hp/cdc/if‐hp‐cdc‐hep‐a‐vac‐bio‐pg‐07‐230.pdf
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Recommendation 3: For post‐exposure prophylaxis, unless contraindicated or unavailable, HA vaccine is recommended in preference to Ig for healthy individuals six months of age and older. (NACI recommendation Grade B)
There are a total of six new recommendations available on‐line:
Update on the Recommended use of Hepatitis A Vaccine. An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI). May 2016. Available: https://www.canada.ca/en/public‐health/services/publications/healthy‐living/update‐recommended‐use‐hepatitis‐vaccine.html
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Heywood P, Cutler J, Burrows K, et al. A community outbreak of travel‐acquired hepatitis A transmitted by an infected food handler. Can Commun Dis Rep. 2007 Nov 1;33(11):16‐22. Available:
One recurrent observation over 15 years is the provision of a single normal dose of the combined HAV + HBV vaccine in last minute travellers.
The combined vaccine contains ½ the normal antigen dose of HAV, which increases the risk of HAV vaccine non‐response.
A single normal antigen dose of HBV does not induce protective immunity in a majority of health individuals.
Focus on administering a full monovalent HAV vaccine dose, and consider separately starting a HBV series to be completed after the trip.
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Another recurrent observation over 15 years is the provision of a rapid series of the combined HAV + HBV vaccine in non‐last minute travellers.
A standard (0, 1 and 6 months) and rapid (0, 7 and 21 days) series will provide equivalent protection against HBV within 60 days, when needed *.
At 6 months, anti‐HBs was higher in a standard series (3 doses).
A rapid series needs boosting at 12 months to ensure long‐term immunity.
A rapid series simply provides a shorter window to prime (< 1 month).
* Jin H, Tan Z, Zhang X, et al. Comparison of Accelerated and Standard Hepatitis B Vaccination Schedules in High‐Risk Healthy Adults: A Meta‐Analysis of Randomized Controlled Trials. PLoS One. 2015 Jul 21;10(7):e0133464. Available:
For older children, 2 adult doses given 6‐12 month apart provides similar long‐term response compared to a standard 3 child dose series.
Limiting factor is pain due to larger injection volumes in smaller children.
Though licensed 1‐15 years, practice experience limits administration to larger‐sized children (e.g., 6 years and older – case‐by‐case).
Useful in extremely needle‐phobic children and/or anxious parents.
Data on long‐term antibody persistence or protection among adolescents for 2‐dose schedules are lacking*.
* Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018 Jan 12; 67(1): 1–31
The availability heuristic is a mental shortcut that relies on immediate examples that come to a given person's mind when evaluating a specific topic, concept, method or decision (e.g., “off the top of my head”).
Availability is a heuristic whereby people make judgments about the likelihood of an event based on how easily an example, instance, or case comes to mind.
Branding and marketing create new customers or patients,where there may be none and no medical necessity for a particular product.
Brown JL. Physician Exposure to Direct‐to‐Consumer Pharmaceutical Marketing: Potential for Creating Prescribing Bias. Am J Med. 2017 Jun;130(6):e247‐e248.
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Update on the Recommended use of Hepatitis A Vaccine. An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI). May 2016. Available: https://www.canada.ca/en/public‐health/services/publications/healthy‐living/update‐recommended‐use‐hepatitis‐vaccine.html
Pondé RA. Atypical serological profiles in hepatitis B virus infection. Eur J Clin Microbiol Infect Dis. 2013 Apr;32(4):461‐76. doi: 10.1007/s10096‐012‐1781‐9.
Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2018 Jan 12; 67(1): 1–31Available: https://www.cdc.gov/mmwr/volumes/67/rr/rr6701a1.htm
Update on the Recommended use of Hepatitis B Vaccine. An Advisory Committee Statement (ACS) National Advisory Committee on Immunization (NACI). February 2017. Available: https://www.canada.ca/en/public‐health/services/publications/healthy‐living/update‐recommended‐use‐hepatitis‐b‐vaccine.html
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Rudy Zimmer, MD, FCFP, FRCPC, CTropMed®Office Address:#142, 3715‐51 Street SWCalgary, AB T3E 6V2
Office Ph: 403‐229‐2273 or 403‐210‐4770Office Fx: 403‐246‐9688