Travel Vaccines

Overview
Discuss vaccines available today for managing
travellers risks
Understand that travel vaccines can be
prioritised based on an individual risk
assessment
Consider some practical aspect about advising
travellers about their vaccine requirements
Discuss the travel vaccines
Travel Vaccine Principle
We should try to have vaccines against
travellers diseases
We should prioritise those, by importance to
travellers (common or high impact)
We need low adverse events
We require high consumer acceptability (easy,
safe, and affordable)
Risk of Vaccine Preventable Diseases
Risk will vary with specific Influenza 1 : 100
itinerary and activity, Hep-A 1 : 5000
season etc Typhoid 1 : 8000

Acceptance of risk is also Hep-B 1 : 15000

qualified by potential Animal bite 1 : 400
outcome of disease, ETEC TD 1 : 10
possible adverse events JE 1 : 1000000
of vaccine, and costs Meningitis 1 : 3000000

List is estimated average Cholera 1 : 500000

risk to traveller per Polio 1 : 5000000

month travel in risk area YF West Africa 1 : 1000
Sth America 1 : 10000
Classifying vaccine priorities
1. Routine background vaccines (everybody should be
protected) tetanus/diphteria/pertussis, polio, MMRV,
influenza
2. Required
Yellow fever subject to country specific arrangements,
sanctioned by WHO
Meningitis/Polio/Pandemic influenza for Hajj
3. Recommended
Common Travel vaccines (more common disease, easily
affordable) hepatitis A, typhoid, hepatitis B, ETEC
Special Travel vaccines (spesific situations or expensive)
rabies, Yellow Fever, cholera, JE, meningitis, TBE, BCG
Routine vaccines
Routine vaccination is now provided in all developing countries
against measles, polio, tetanus, diphteria, pertussis, and
tuberculosis
To this basic package have come new vaccines : Hepatitis B is
offered in 147 countries routinely. Hib is recommended in 89
countries, and yellow fever is offered in about 30 of the 45 endemic
countries. Rubella is routine in 111 countries
Developed countries have a wider range of vaccines including
mumps, influenza, pnemococcus, rotavirus, meningitis C and target
infants, children or adolescents depending on disease.
Since the WHO Expanded Programme on Immunisation (EPI) 1974,
DTP3 coverage has reached 78% in 2003 (up from 20% in 1980),
with larger gaps in Sub-Saharan Africa and South Asia
Estimated 2.1 million persons die from disease preventable by
widely used vaccines 2002 (WHO)
Tetanus/Diphteria/Pertussis
Not very common disease of travellers, but the disease
are still present and resurgent
We want to assume that all travellers are in-date
with recommended primary program of immunisation
But for tetanus, we also would prefer that if an injury
occurred, a traveller does not need to have a booster
vaccine in situ, ie, already has adequateimmunity
So, we can ask,Have you had a booster of tetanus
within the last 10 years?
If yes, no booster required,
If no, then give a booster dTpa preferred
Measles, Mumps, Rubella
More severe disease in adults than children
Most children covered by national programs
Disease remain prevalent in developing countries
Adults in Western world born before 1957
immune, but those born later may not be
immune
Good immunity requires 2 does of vaccine
Live vaccine, made in eggs
Vaccine indicated for longterm travellers with
unclear immune status
Polio Vaccination for travellers
Travellers to polio-endemic countries or areas who
have received >3 doses of OPV or IPV should be offered
another dose of polio vaccine as a once-only dose
before departure
Non-immunised individuals intending to travel to polio-
endemic destinations should complete a primary
schedule using either OPV or IPV
For frequent travellers to polio-endemic areas but who
stay for brief periods, a one-time only additional dose
of polio vaccine after the primary series should be
sufficient to prevent disease
WHO WER 23, 4 June 2010
Polio
Primary Vaccination should be:
IPV IPV IPV
OPV OPV OPV
IPV OPV OPV
IPV IPV OPV OPV

IPV should be given IM (or S/C)

Min age is 8 weeks

WHO
 Safety of Polio vaccines
OPV can cause vaccine-associated paralytic
poliomyelitis (VAAP); in the US the overall risk
was 1 case of VAAP/2.4 million doses OPV; the
rate after the fisrt was 1 VAAP/750 000 doses; the
relatively highest rates have been reported from
immunocompromised persons
Due to the risk of VAAP following OPV, contries
polio free for long (and not anymore confronted
with wild poliomyelitis but VAAP) decided to
change the immunization policy from OPV to an
all-IPV or sequential schedule
Influenza vaccine
In healthy adults, 70-90% protection when a
good match between vaccine antigen and
circulating viruses
Both inactivated and live-attenuated vaccines
are available
WHO recommends a combination of 2 A
subtypes (H3N2, H1N1) and 1 B type, ie
trivalent influenza vaccine (TIV)
TIVs can be whole virus, split virus, subunit
Influenza TIVs
Generally safe, variable reactogenicity
For whole-cell TIV, 15-20% (esp young
children) local reactions for 1-2 days
Occasional slight increase in Guillain-Barre
syndrome in adults (additional 1 case to
background 20/106)
Adults, children > 9yrs 1 dose annually
Children 3-9 yrs 2 doses, 4 weeks apart
Children 6 mo 3 yrs 2 x doses, 4 weeks apart
Influenza live attenuated (LAV)
In Russia cold-adapted variants of H2N2
resorted with H1N1 and H3N2
Safe and efficacious for all over 3 yrs
In USA, CAIV-T uses genes from 3 strain and
CA strain
5-49 yrs only (reactive in < 5 yrs)
CI-allergy to eggs, immunosuppression, PH
GBS, 1st trim pregnancy, children on aspirin
Required Vaccine
IHR indicates that proof of vaccination before
entry may be applied by country public health
authorities-only applies to Yellow Fever
Some countries may not grant visas for entry
for specific purposes unless proof of certain
vaccines, eg Haj pilgrims required to have 4V-
meningitis, polio and influenza
YF
YF transmission occurs in 32 countries in
Africa and 13 in South America
Transmission can be urban or sylvatic, and can
be sporadic and epidemic
Under IHR, vaccination is required for entry by
20 countries, and many others seek evidence
for travellers from endemic countries
Yellow Fever Vaccine
The 17 strains (17DD and 17D204) are the only
commercial vaccines based on a wild virus
isolated in Ghana in 1927, and attenuated in
chicken embryo
Protective levels of Abs are found in 90%
recipients within 10 days and in 99% in 30 days.
Antibodies last for > 35 yrs
Safety : > 400 million doses have been given
CI : < 6 mo, immuno-deficiency, severe egg allergy
YF Vaccine Adverse Events
Mild systemic events in 30% recipients
Hypersensitivity reactions : very low rate,
relates to egg protein allergy, and rarely
sensitivity to gelatin, 1.8/105
Recent concerns over emergent severe
adverse events: VR neurotropic disease and
VR viscerotropic disease
YFV related neurotropic disease
Rare, > 26 cases reported since 1945
Rarely fatal, 2 deaths in 26
Hiatorically seen in infants, but more recently reported
in all ages
0.5-4/1000 in infants < 9 mo (c/w 1 per 8 mill > 9mo)
In adults :
Overall (YEL-AND) rate in US data about 8/mill
60-69 yrs, 16/mill
>70 yrs, 23/mill

CDC Yellow Book 2010

YFV related viscerotropic disease
> 40 cases reported, all after first ever dose of YF
Average onset 3.5 days (1-8)
Case fatality rate is 53%

US rates (YEL-AVD) CDC published data

Overall 4/mill
60-69 yrs 10/mill
>70 yrs 23/mill

CDC Yellow Book 2010

Risk Assessment
Risk of YF in 2 Risk of YEL-AVD
Week stay
Average age
1 in 250,000
W Africa: 60-69 yr
1 in 2000 1 in 100,000
By 70 yr
1 in 45,000
South America: >75 yr
1 in 20,000 1 in 4000
Neisseria Meningitidis
Humans are the only natural reservoir
Many infected people are asymptomatic carriers
source of infection for others
Asymptomatic respiratory tract carriage is present in
up to 20% of the population
Prevalence is higher when crowding occurs (eg. amy
barracks, boarding schools, camps etc.)
Serogroups A, B, C are responsible for most disease
Serogroup Y and W135 have emerged recently
Epidemic disease outbreaks, esp sub-Saharan Africa,
esp serogroup A, incident rates of 1000/100.000
Epidemiological pattern of invasive
meningococal disease

Freshmen in domitories
5 to 13/100.000/yr

Hajj pilgrims
25/100.000/yr

African Meningitis Belt countries

100 to 800 cases/100.000/yr
Meningitis Vaccines
Polysaccharide vaccines
Bivalent (A,C) or quadrivalent (A,C,W135,Y)
Safe, minor local reactions
Efficacious 85-100%, in > 2 yrs age, for 2-3 years
Immune-tolerance vs serogroup C occurs in children
Group B is poorly immunogenic, even when conjugated

Conjugated vaccines
Quadrivalent (A,C,W135,Y)
Safe, minor local reactions
Efficacious 90-100% in > 2 yrs, for many (?) years
Recommended Vaccines
Travel related vaccines based on likelihood of
risk
Requires detailed assessment of the travellers
health, the risk of disease at destination, the
likely exposures due to activities,
accomodation and season
Hepatitis A Vaccines
Several inactivated vaccines, including 4 in Western
markets
All safe and effective, with long-lasting protection
None are licensed for children < 1 yr
100% protection rapidly after one dose
2nd dose induces long-lasting immunity > 20 yrs
Combination vaccines available
Hep-A and Hep-B
Hep-A and typhoid Vi
Ab test is a test for natural immunity, not very helpful
for vaccine induced protection
Typhoid Fever
Travellers make up 70% of cases reported in
industrialised countries
Multi-drug resistant strains reported in Asia,
the Middle East and Latin America
Increasing recognition of S paratyphi A & B
Vaccination is recommended for travellers to
endemic areas
Typhoid Old Vaccines
Inactivated whole cell vaccine
Highly reactogenic :
Adverse systemic reactions 10-20%
Adverse local reactions 10-50%
Still available in some developing countries
Low efficacy 50-60%
Modern Typhoid vaccines
Live attenuated strain (Ty21a)
Induces Ig A against typhoid antigens, including
012 surface antigen which is shared by s thyphi
and s paratyphi A and B
Parenteral subunit vaccine targetting the Vi
(surface polysaccharide) antigen
Induces IgG response. S Paratyphi does not have
Vi antigen
Both have negligible systemic adverse reactions,
and are well tolerated
Typhoid Current vaccines
Oral
Ty21a capsule/liquid
3 or 4 doses
55-80% protection for 3-5 years, IgA
>2 yrs (6 yr for tabs), offers protection vs s paratyphi A and B also

Parenteral
Injectable Vi polysaccharide
70% protection for about 3 years, IgG
>2 yrs, protects against s Typhi only

Combination of Vi and Hep-A vaccine

? Sequential vacciantion

WHO WER 6, 8 Feb 2008

Hepatitis B
400 million carriers globally (65 million will die)
The most contagious blood-borne virus
Chronic carriage risk highest early in life; acute
disease more likely in adolescence/adulthood
Chronic HB can cause chronic hepatitis, cirrhosis
and primary hepatocellular carcinoma
HB accounts for up to 80% of liver cancer (second
only to tobacco as carcinogen)
Universal pediatric immunisation recommended
worlwide; eventually eradicable
Hepatitis B vaccines
Recombinant vaccine was introduced in 1986 and
gradually replaced plasma-derived vaccine
Protective efficacy is related to induction of Hep-BsAb
and induction of memory T cells
Hep-BsAb levels are a reliable marker of immunity
Overall 3 doses induces immunity in > 95% infants,
children and adolescents
No compelling evidence of need for boosting
Safe, well tolerated vaccine
Adverse events infrequent and mild
Non-converters can be revaccinated +/- Hep-A vaccine
Hep-B : immunisation schedules
Standard Accelerated Rapid
0, 1, 6 months 0, 1, 2, 12 months 0, 7, 21 days, 12 months

Higher antibody levels Confers rapid protection Fourth dose at 12 months

after third dose Assists compliance for long-term protection
Fourth dose at 12 months For adults at immediate
for long-term protection risk of HBV infection
Used for those st high risk
Rabies
Awareness of animals
Wash wounds and access post-exposure
treatment (PET)
In unimmunised, RIG + vaccine 0,3,7,14,28
(full course)
Consider pre-exposure vaccination, 3 x IM,
0,7,21-28
In Pre-immunised, vaccine 0,3 (boosters)
Rebies Vaccine
Several modern cell-culture vaccines : inactivated virus
HDCV : MIRV. Imovax
Rabies vaccine adsorbed : (RVA)
PCEC : Rabipur, RabAvert
PVCV : Verorab
PDEV : Lyssavac N
Considered interchangable
Given as :
Per-exposure : D 0,7,28 IM (ID) with booster on D 0,3
Post exposure : D 0,3,7,14,28 (Essen regime) in comb with RIG (or other WHO
approved regime)
Efficacy : Pre-exposure with timely Peboosters 100%
Post exposure alone failures recorded
Safety : No significant A/E recorded with modern cell-culture vaccines
Routine
Tetanus/diphtheria/pertussis, polio, MMRV,
influenza
Required
Yellow fever
(Meningitis/Polio for Hajj)
Recommended
Common Travel vaccines
hepatitis A, typhoid, hepatitis B, ETEC
Special Travel vaccines
rebies, Yellow Fever, cholera, JE, meningitis, TBE,
BCG
Japanese Encephalitis
Transmitted to humans by mosquitoes
Humans are an incidental host rather than part of the enzootic cycle
Prolific breeding of vectors (mosquitoes) in flooded rice fields of
rural areas
Pigs and birds are virus amplifying hosts
High level of transmission to humans when pigs are kept near
residental areas
Two recognised epidemiological patterns:
Epidemics during summer or wet season months-temperature or
sub-tropical regions of Asia (Northern Thailand, Nth Vietnam,
Korea, Japan, Taiwan, China, Nepal, Nth India)
Endemic, during the year-tropical regions (most of SEA, Sri Lanka,
South India)
JE Vaccines old and new
Mouse-brain derived, purified, inactivated
(Nakayama or Beijing strains) eg JE-Vax
Cell-culture derived, inactivated (Beijing or 14-
14-2 strains) eg IXIARO/JESPECT
Cell-culture derived, live attenuated (14-14-2
strain) eg CD-JEVAX
Mouse-brain derived, inactivated
Dose Booster
Adults and Children >3 yrs 3 doses 0,7,21 1 yr, then 3 yrly
Children 6mo-3 yrs 3 doses 0,7,21 1 yr, then 3 yrly

Efficacy : > 95% for 3 dose schedule

Safety : generally safe, but 20% recipients local reactions (red, swelling, tender) and
20% mild systemic effects
Acute Disseminated Encephalomyelitis , ADEM reported at 1 in 50-100.000 doses-
not formally studied-but caused withdrawal of vaccine in Japan
Hypersensitivity reported in 18-64 per 10.000 up to 12-72 hrs post vaccine
So difficult vaccine to manage, observing patients, avoid travel for several days, etc
WHO 34/35 25 Aug 2006
Cell-culture derived, inactivated
Dose Booster
Adults (>17 yrs) 2 doses, 0,28 Not clear
Children Not yet licensed

Chinese vaccine (Beijing P3 strain) made in PHK cells being replaced by live-
attenuated vaccine
European (14-14-2 strain) made in vero cells experience still growing
Japanese (Beijing strain) made in vero cells Jebik-V
Efficacy: >95%
Safety: Well tolerated
 Cell-culture derived, live attenuated
CD-JEVAX manufactured in China since 1989, in PHK cells (14-14-2
starin) and new vaccine made in vero cells
Single dose induces long lasting immunity
In China, public health programs have focussed on children at about
8-9mo , and boosters at 18-24mo ang 6 yrs
Appears to be well tolerated, no hypersensitivity or acute
neurological disease reported in small children, but not currently
used in adults due to reports of neurological events in NE China in
early 2000s
IMOJEV. Prospective Vaccine being developed as chimeric construct
based on YF 17D vaccine. Very effective, long-lasting immunity
In registration phase, licensed in several countries, but not to
market
Vibrio Cholera
More than 200 V cholerae serogroups, exist 2 (01 and
0139) cause the clinical syndrome of cholera.
Spread by contaminated food with cholera bacteria
Usually characterized by watery diarrhea, lasting one
or more days (rice water stools)
Up to 90% of people infected have mild to moderate
symptoms of watery diarrhoea, dehydration with shock
and death.
Common cause of TD in Asia, Africa and South and
Central America.
Severe disease is not a travellers disease