The medical letter on drugs and therapeutics november 24 2014

HEPATITIS A Hepatitis A vaccine, which is part of routine childhood immunization in the US, is recommended for all unvaccinated travelers going to countries with intermediate or high he

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IN THIS ISSUE

ISSUE

1433

Volume 56

Published by The Medical Letter, Inc • A Nonprofi t Organization

ISSUE No

1456 Vaccines for Travelers p 115

on Drugs and Therapeutics Objective Drug Reviews Since 1959

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on Drugs and Therapeutics Objective Drug Reviews Since 1959

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IN THIS ISSUE

ISSUE

1433

area in <2 weeks, a 0.02-mL/kg IM dose of immune globulin should be given in addition to the initial dose

of vaccine Children <1 year of age and travelers who elect not to receive the vaccine should receive immune globulin 0.02 mL/kg IM if they will be traveling for up

to 3 months and 0.06 mL/kg IM if they plan to travel for >3 months.The dose should be repeated in those traveling for >5 months.5

HEPATITIS B

Hepatitis B vaccine, which is part of routine childhood immunization in the US, is recommended for all travelers going to intermediate- or high-risk areas (see Table 1 for low-risk areas) In addition, travelers who may engage in behaviors that increase the risk of transmission, such as injection drug use, unprotected sexual contact with new partners, dental treatment, skin perforation practices (tattoos, acupuncture, ear piercing), or medical tourism involving invasive medical treatment (injections, stitching), should be immunized against hepatitis B regardless of their destination.6

A series started with one hepatitis B vaccine may be completed with another An interrupted series can be completed without being restarted

Patients planning to travel to other countries should be

up to date on routine immunizations and, depending

on their destination, duration of travel, and planned

activities, may also need to receive certain

travel-specifi c vaccines Common travel vaccines are listed in

Table 2 on page 117 More detailed advice for travelers

is available from the Centers for Disease Control and

Prevention (CDC) at www.cdc.gov/travel Guidelines

for routine adult immunization are discussed in a

separate issue.1

Immunocompromised or pregnant patients should

generally not receive live vaccines, although the

benefi t might outweigh the risk in some situations.2

Injectable or intranasal live vaccines not administered

simultaneously should be administered  ≥4 weeks apart

HEPATITIS A

Hepatitis A vaccine, which is part of routine childhood

immunization in the US, is recommended for all

unvaccinated travelers going to countries with

intermediate or high hepatitis A endemicity (see Table

1 for low-risk areas).3

Monovalent hepatitis A vaccines are usually

administered in two IM doses at least 6 months apart

Antibodies reach protective levels 2-4 weeks after the

fi rst dose Even when exposure to the virus occurs

sooner than 4 weeks after vaccination, the traveler

is usually protected because of the relatively long

incubation period (average 28 days) of hepatitis A A

series started with one monovalent hepatitis A vaccine

may be completed with the other Second doses

given up to 8 years after the fi rst dose have produced

protective antibody levels.4

For adults >40 years old, immunosuppressed patients,

and those with chronic liver disease or other chronic

medical conditions who will be traveling to an endemic

Table 1 Low-Risk Areas for Hepatitis A & B*

Asia Pacifi c (includes Japan, Tropical Latin America South Korea, Singapore) (includes Brazil, East Asia (includes China) Colombia, Paraguay, Southeast Asia (includes Indonesia, Venezuela) Philippines, Vietnam) Central Latin America Australasia (includes Australia, (includes Costa Rica, New Zealand) Guatemala, Honduras,

* All other areas are intermediate to high risk; vaccination is indicated.

1 Regions with a low or very low level of hepatitis A endemicity (KH Jacobsen and ST Wiersma Vaccine 2010; 28:6653).

2 Countries with a low prevalence (<2%) of hepatitis B surface antigen in adults 19-49 years old (JJ Ott et al Vaccine 2012; 30:2212).

Two vaccines are FDA-approved (JE-Vax; Ixiaro), but only Ixiaro, a Vero cell culture-derived formulation,

is available.12 Previously recommended only for use

in persons ≥17 years old, Ixiaro is now approved by

the FDA, and recommended by the ACIP, for use in children ≥2 months old In a randomized clinical trial

of Ixiaro in 385 children 2 months to 17 years old, the

seroprotection rate was 100% 28 days after completing

a 2-dose primary series of the vaccine At 6 months, 88% of children 2 months to 2 years old and 95% of those 3-17 years old had protective neutralizing antibodies.13 A single dose of Ixiaro has been shown to

effectively boost antibody levels in persons previously

vaccinated with JE-Vax, but the duration of protection

is unknown; until more data become available, the ACIP recommends that persons previously vaccinated

with JE-Vax who require continued protection receive

a 2-dose primary series of Ixiaro.

MEASLES

Travel continues to be a cause of measles cases and

is associated with importation of the virus from other countries and the occurrence of outbreaks in the US.14 The measles vaccine is available as a live attenuated vaccine in combination with mumps and rubella (MMR) or with mumps, rubella, and varicella (MMRV; approved only for children 12 months to 12 years old) A 2-dose series of MMR, with the fi rst dose given between 12 and 15 months of age, is part of routine childhood immunization in the US

Before traveling outside the US, previously un-vaccinated children ≥12 months old should receive

2 doses of a measles-containing vaccine at least 28 days apart Children 6-11 months old should receive one dose before traveling, but will still need two more doses for routine immunization, one at ≥12 months of age and another at least 28 days later Unvaccinated adolescents and adults (born in 1957 or later [1970 in Canada]) who do not have other evidence of measles immunity should receive 2 doses of a measles-containing vaccine at least 28 days apart.15

MENINGOCOCCAL

Meningococcal vaccine is recommended for travelers going anywhere in the “meningitis belt” (semi-arid areas of sub-Saharan Africa extending from Senegal and Guinea eastward to Ethiopia) from December to June and should also be considered for areas where

epidemics of Neisseria meningitidis are occurring,

particularly for travelers who will have prolonged contact with the local population, such as those living

in a dormitory, military institution, or refugee camp, or

INFLUENZA

Influenza may be a risk in the tropics year-round,

in temperate areas of the Southern Hemisphere

from April to September, and in temperate areas of

the Northern Hemisphere from October to March

Outbreaks have occurred on cruise ships and on

organized group tours in any latitude or season.7

The US Advisory Committee on Immunization

Practices (ACIP) recommends routine annual

influenza vaccination for everyone ≥6 months old who

does not have a specifi c contraindication, including

pregnant women.8 Travelersshouldconsider being

vaccinated before going to the Southern Hemisphere

during influenza season or to the tropics in any

season, or when traveling in a group with persons

from the Southern Hemisphere during their influenza

season.9

Northern Hemisphere influenza vaccine is usually

available in the US from August until the end of

June In some years, the vaccine formulations are

the same in both hemispheres If they are different,

high-risk patients from the Northern Hemisphere

who travel to the Southern Hemisphere during

that region’s influenza season could also consider

being vaccinated on arrival because the Southern

Hemisphere influenza vaccine is rarely available in

the Northern Hemisphere

JAPANESE ENCEPHALITIS

Japanese encephalitis is an uncommon but potentially

fatal mosquito-borne viral disease that occurs in rural

Asia, especially near pig farms and rice paddies It is

usually seasonal (May-October), but may occur

year-round in tropical regions The attack rate in travelers

has been very low.10

Vaccination is recommended for travelers who expect

a long stay (≥1 month) in endemic areas or heavy

exposure to mosquitoes (such as adventure travelers)

during the transmission season Vaccination should

also be considered for travelers spending <1 month

in endemic areas during the transmission season if

they will be sleeping without air conditioning, screens,

or bed nets, or spending considerable time outside in

rural or agricultural areas, especially in the evening or

at night.11 Some expert clinicians suggest that, given

the rarity of the disease in US residents, compulsive

use of insect repellents and judicious avoidance of

exposure to mosquitoes between dusk and dawn

might be reasonable alternatives to vaccination for

short-term travelers

Table 2 Some Vaccines for Travel

Vaccines Adult Dose Pediatric Age/Dose Schedule of Protection

Hepatitis A

Havrix (GSK) 1 mL IM (1440 EU) 1-18 yrs: 0.5 mL IM (720 EU) 0 and 6-12 mos Probably lifelong after

Vaqta (Merck) 1 mL IM (50 U) 1-18 yrs: 0.5 mL IM (25 U) 0 and 6-18 mos pletion of primary series 1

Hepatitis B

Engerix-B (GSK) 1 mL IM (20 mcg) Birth-19 yrs: 0.5 mL IM (10 mcg) 0, 1, and 6 mos 2,3 Probably lifelong after

Recombivax-HB 1 mL IM (10 mcg) Birth-19 yrs: 0.5 mL IM (5 mcg) 0, 1, and 6 mos 3,4 pletion of primary series (Merck)

Hepatitis A/B

Twinrix (GSK)5 1 mL IM Not approved 0, 1, and 6 mos Booster recommended at

(720 EU/20 mcg) for <18 yrs (alternative: 0, 7, and 12 mos with accelerated

21-30 days) schedule; otherwise proba-

bly lifelong after completion

of primary series

Japanese encephalitis

Ixiaro (Novartis) 0.5 mL IM 2 mos-<3 yrs: 0.25 mL IM 0 and 28 days 6 A single booster >1 yr after

series if ongoing risk is recommended for those

≥17 yrs old 7

Meningococcal

Menomune 0.5 mL SC ≥2 yrs: 0.5 mL SC Single dose Repeat every 5 yrs 8 with (Sanofi Pasteur) (50 mcg of each (50 mcg of each Menactra or Menveo if on-

Menveo (Novartis) 0.5 mL IM (10 mcg sero- ≥2 mos: 0.5 mL IM (10 mcg 2 mos: 2, 4, 6, and 12 mos Repeat every 5 yrs 8 if

group A, 5 mcg sero- serogroup A, 5 mcg sero- 7-23 mos: 0 and 3 mos 9 going risk group C, Y, W135) group C, Y, W135) 2-55 yrs: single dose 10

Menactra 0.5 mL IM (4 mcg of ≥9 mos: 0.5 mL IM 9-23 mos: 0 and 3 mos 11 Repeat every 5 yrs 8 if (Sanofi Pasteur) each antigen) (4 mcg of each antigen) 2-55 yrs: single dose going risk

Rabies

Imovax 1 mL IM ≥Birth: 1 mL IM 0, 7, and 21 Routine boosters not nec- (Sanofi Pasteur) (≥2.5 IU of rabies (≥2.5 IU of rabies antigen) or 28 days 12 essary; for those engaging

RabAvert (Novartis) 1 mL IM ≥Birth: 1 mL IM 0, 7, and 21 ties (cavers, veterinarians,

(≥2.5 IU of rabies (≥2.5 IU of rabies antigen) or 28 days 12 laboratory workers),

every 2 yrs with booster doses if low levels 13

Typhoid

Vivotif 1 cap PO (contains ≥6 yrs: 1 cap PO (contains 1 cap every other Repeat every 5 yrs if (Crucell) 2-6x10 9 viable CFU 2-6x10 9 viable CFU of day x 4 doses going risk

of S Typhi Ty21a) S Typhi Ty21a) Typhim Vi 0.5 mL IM ≥2 yrs: 0.5 mL IM (25 mcg) Single dose Repeat every 2 yrs (3 yrs in

Yellow Fever

YF-Vax 0.5 mL SC (4.74 log10 ≥9 mos: 0.5 mL SC (4.74 log10 Single dose Booster dose every 10 yrs (Sanofi Pasteur) plaque forming units plaque forming units of if ongoing risk

of 17D204 attenuated 17D204 attenuated YF virus)

YF virus)

1 Protection likely lasts at least 12 months after a single dose.

2 An alternate schedule is 3 doses given at 0, 1, and 2 months, followed by a fourth dose at 12 months.

3 An accelerated schedule (0, 7, and 21-30 days followed by a booster dose at 12 months) that is FDA-approved for use with Twinrix may also be used, if

necessary, with hepatitis B vaccine Also, a retrospective study found that a two-visit vaccination schedule consisting of a double dose of hepatitis B vaccine

at day 0 and a single dose 4-12 months later was effective in 83% of adults (J Wong et al J Travel Med 2014; 21:260); it is not FDA-approved.

4 An alternate schedule for adolescents 11-15 years old is 0 and 4-6 months.

5 Contains the same antigenic components as pediatric Havrix (hepatitis A) and Engerix-B (hepatitis B) It can be used to complete an immunization series

started with monovalent hepatitis A and B vaccines.

6 For last-minute travelers, one double dose of the vaccine (not FDA-approved) has been shown to produce 60% protection for at least one month (E Schuller et

al Vaccine 2009; 27:2188).

7 One study found that a single dose of Ixiaro effectively boosted immunity in travelers previously vaccinated with JE-Vax (EO Erra et al Vaccine 2013; 32:119), but until more data become available, the ACIP recommends that adults previously vaccinated with JE-Vax receive a primary series of Ixiaro (MMWR Morb

Mortal Wkly Rep 2011; 60:661).

8 Repeat after three years for children vaccinated at <7 years of age.

9 The second dose should be given at age ≥12 months and ≥3 months after the fi rst.

10 For children 2-5 years old at continued high risk, a second dose may be administered 2 months after the fi rst.

11 The second dose can be administered 8 weeks after the fi rst if required before travel.

12 Regimen for pre-exposure vaccination If a previously vaccinated traveler is exposed to a potentially rabid animal, post-exposure prophylaxis with 2 additional vaccine doses separated by 3 days should be initiated as soon as possible.

13 Minimal acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fl uorescent focus inhibition test.

working in a healthcare setting.16 Saudi Arabia requires

a certifi cate of immunization (within 3 years before

travel) for pilgrims during Hajj or Umrah

Three quadrivalent vaccines are available against

N meningitidis serogroups A, C, Y, and W-135:

Menomune, which contains meningococcal capsular

polysaccharides, and Menactra and Menveo,17,18 which

contain capsular polysaccharides conjugated to a

protein carrier Menactra and Menveo are preferred for

use in persons ≤55 years old Menomune is preferred

for meningococcal vaccine-naive travelers ≥56 years

old who anticipate requiring only a single dose.16 The

FDA recently approved a vaccine (Trumenba) active

against four N meningitidis serogroup B strains

prevalent in the US for use in adolescents and young

adults 10-25 years old.19 It has not been recommended

for travelers Group B infections are rare in

sub-Saharan Africa

POLIO

All travelers to countries with wild poliovirus

circulation during the last 12 months (Table 3)

should complete a primary series of inactivated

polio vaccine (IPV; IPOL) before departure from the

US Adults who have not previously been immunized

against polio should receive a 3-dose primary

series of IPV (2 doses 4-8 weeks apart; third dose

6-12 months after the second) If protection is

needed sooner, 2 or 3 doses can be given ≥4 weeks

apart; if <4 weeks are available before protection

is needed, a single dose is recommended Adults

who previously completed a primary series and

have never had a booster should receive a single

booster dose of IPV Previously unimmunized

children should receive a 4-dose primary series of

IPV The first dose can be given at age ≥6 weeks; the

minimum interval is 4 weeks between doses 1 and

2 and 2 and 3, and 6 months between doses 3 and

4 A child who received 4 doses before age 4 should

be given a fifth dose

Travelers planning to stay for >4 weeks in a country

with recent wild poliovirus circulation may be required

to present proof of polio vaccination when departing

that country All polio vaccine administration for

travelers should be documented on an International Certifi cate of Vaccination or Prophylaxis (“yellow card”) Children and adults who will be in a polio-infected country for >4 weeks, and whose last dose

of polio vaccine was administered >12 months before the date they will be leaving that country, should receive an additional dose of IPV before leaving the

US Those who plan to reside in a polio-infected country for >12 months may be required to receive

a dose of the polio vaccine that is available in that country (either IPV or oral polio vaccine) between 4 weeks and 12 months before their departure from the polio-infected country.20

RABIES

Rabies is highly endemic in many parts of Africa, Asia (particularly India, Pakistan, Bangladesh, and Bali, Indonesia), and Central and South America, but the risk to travelers is generally low.21 Pre-exposure vaccination against rabies is recommended for travelers with an occupational risk of exposure, for those (especially children) visiting endemic areas where immediate access to medical treatment, particularly rabies immune globulin, tends to be limited, and for outdoor-adventure travelers.22 The

2 vaccines available in the US (Imovax; RabAvert)

are similar

After exposure to a potentially rabid animal, patients who received pre-exposure vaccination should promptly receive 2 additional doses of vaccine Without pre-exposure vaccination, the ACIP recommends human rabies immune globulin (RIG) plus 4 doses of vaccine given over 14 days; immunosuppressed patients should receive 5 doses of vaccine (over 28 days).23 One retrospective study found that some patients did not develop adequate antibody levels after 4 doses of vaccine.24

According to the CDC, cell culture rabies vaccines available outside the US are acceptable alternatives

to FDA-approved vaccines; neural tissue vaccines have high rates of serious adverse effects and should

be avoided RIG is a blood product, and its purity and potency may be less reliable, if it is available at all, in developing countries Purifi ed equine rabies immune globulin is available in some developing countries and has been used effectively, with a low incidence of adverse reactions

TETANUS, DIPHTHERIA, AND PERTUSSIS

Previously unimmunized children should receive 3 or (preferably) 4 doses of pediatric diphtheria, tetanus,

Table 3 Countries with Wild Poliovirus Circulation 1

Afghanistan Iraq Somalia

Equatorial Guinea Nigeria

Ethiopia Pakistan

1 GS Wallace et al MMWR Morb Mortal Wkly Rep 2014; 63:591.

2 Also the West Bank and Gaza.

and acellular pertussis vaccine (DTaP) before travel

An accelerated schedule can be used beginning at

age ≥6 weeks, with the second and third doses given

4 weeks after the previous dose The fourth dose is

given ≥6 months after the third; the child must be at

least 12 months old

Adults with an uncertain history of primary

vaccination should receive 3 doses of a tetanus

and diphtheria toxoid vaccine The first 2 doses

should be administered at least 4 weeks apart

and the third 6-12 months after the second One

of the 3 doses (preferably the first) should contain

protein components of acellular pertussis combined

with diphtheria and tetanus toxoids (Tdap) to also

provide protection against pertussis Two Tdap

vaccines (Adacel; Boostrix) are available and are

recommended by the ACIP for use in all adults,

including those ≥65 years old.25

A booster dose of inactivated adsorbed

(aluminum-salt-precipitated) tetanus and diphtheria toxoid (Td)

vaccine is recommended every 10 years for adults

All persons ≥11 years old who have completed a

primary childhood series and have not yet received

Tdap vaccine should receive a single dose, which can

be given regardless of the interval since the last Td to

provide pertussis protection before travel

TYPHOID

Typhoid vaccine is recommended for travelers

going to areas where there is an increased risk of

typhoid fever, especially if they expect a long stay

or will be visiting friends or relatives or traveling

outside routine tourist destinations.26,27 The risk is

highest in southern Asia Other risk areas are East

and Southeast Asia, Central and South America, the

Caribbean, and Africa

A live attenuated oral vaccine (Vivotif) is available

for adults and children ≥6 years old It is taken every

other day as a single capsule (at least 1 hour before

eating) for a total of 4 capsules, beginning no later

than 2 weeks before departure; it provides protection

for about 5 years The capsules must be refrigerated

Antibiotics should be avoided for at least 24 hours

before administration of the fi rst capsule and for 1

week after administration of the last capsule

A purifi ed capsular polysaccharide parenteral vaccine

(Typhim Vi) for adults and children ≥2 years old is

given at least 2 weeks before departure A combined

hepatitis A/typhoid vaccine (Vivaxim – Sanofi Pasteur)

is available in Canada

YELLOW FEVER

Yellow fever vaccine (YF-Vax), a single-dose live

attenuated vaccine prepared in eggs, should be given

at least 10 days before travel to endemic areas, which include tropical South America and sub-Saharan Africa.28 Some countries require an International Certifi cate of Vaccination or Prophylaxis as proof

of vaccination against yellow fever, or a physician’s waiver letter, from all entering travelers; other countries require evidence of vaccination from travelers coming from or traveling through endemic or infected areas, including brief airport transits An updated list of countries requiring proof of yellow fever vaccination is available at www.cdc.gov/travel

In the US, the vaccine is available only from providers certifi ed by state health departments According to the World Health Organization, a single dose of the vaccine

is suffi cient to confer life-long immunity, but more data documenting the duration of immunity after vaccination are needed Boosters are recommended every 10 years

by the ACIP and may be necessary for travel to countries that require a certifi cate of vaccination.29,30

Yellow fever vaccine-associated viscerotropic disease,

a severe systemic illness that can cause fatal organ failure, has been reported rarely It has occurred only

in fi rst-time recipients Vaccine-associated neurologic disease (encephalitis, Guillain-Barré syndrome, Bell’s palsy) has also occurred almost exclusively in fi rst-time recipients; the risk is increased in infants and travelers >60 years old.31,32 Caution is advised for travelers ≥60 years old who are receiving the vaccine for the fi rst time and for those with asymptomatic HIV infection and moderate immune suppression (CD4 counts 200-499 cells/mm3).A small case series study found a signifi cant increase in relapse rates among travelers with multiple sclerosis who received yellow fever vaccine.33 There have been case reports of vaccine-associated neurologic disease in breast-fed infants of recently vaccinated women.34 The vaccine

is contraindicated in infants <6 months old and should

be avoided if possible in infants 6-8 months old

VACCINES AVAILABLE OUTSIDE THE US CHOLERA — The risk of cholera in tourists is very

low Vaccination should be considered for those who plan to work in refugee camps, in outbreak settings,

or as healthcare providers in endemic areas.35 Two

oral, whole-cell killed vaccines are available Dukoral

(Crucell, the Netherlands), licensed in many European countries and in Canada, is administered in 2 doses

15 HQ McLean et al Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommenda-tions of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 2013; 62(RR-4):1.

16 AC Cohn et al Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 2013; 62(RR-2):1.

17 A new conjugate meningococcal vaccine (Menveo) Med Lett Drugs Ther 2010; 52:59.

18 JR MacNeil et al Use of MenACWY-CRM vaccine in children aged 2 through 23 months at increased risk for meningococ-cal disease: recommendations of the Advisory Committee on Immunization Practices, 2013 MMWR Morb Mortal Wkly Rep 2014; 63:527.

19 Meningococcal group B vaccine Med Lett Drugs Ther 2014 (in press).

20 GS Wallace et al Interim CDC guidance for polio vaccination for travel to and from countries affected by wild poliovirus MMWR Morb Mortal Wkly Rep 2014; 63:591.

21 C Malerczyk et al Imported human rabies cases in Europe, the United States, and Japan, 1990 to 2010 J Travel Med 2011; 18:402.

22 CE Rupprecht and RV Gibbons Clinical practice Prophylaxis against rabies N Engl J Med 2004; 351:2626.

23 CE Rupprecht et al Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recom-mendations of the Advisory Committee on Immunization Prac-tices MMWR Recomm Rep 2010; 59(RR-2):1.

24 M Uwanyiligira et al Rabies postexposure prophylaxis in rou-tine practice in view of the new Centers for Disease Control and Prevention and World Health Organization recommendations Clin Infect Dis 2012; 55:201.

25 Prevention and treatment of pertussis Med Lett Drugs Ther 2012; 54:73.

26 MF Lynch et al Typhoid fever in the United States, 1999-2006 JAMA 2009; 302:859.

27 JA Whitaker et al Rethinking typhoid fever vaccines: implica-tions for travelers and people living in highly endemic areas J Travel Med 2009; 16:46.

28 JE Staples et al Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR Recomm Rep 2010; 59(RR-7):1.

29 World Health Organization Yellow fever vaccination Weekly epidemiological record 2013; 20:208 Available at www.who.int/ wer/2013/wer8820.pdf?ua=1 Accessed November 13, 2014.

30 Collaborative group for studies on yellow fever vaccines Du-ration of post-vaccination immunity against yellow fever in adults Vaccine 2014; 32:4977.

31 RE Thomas et al How many published cases of serious adverse events after yellow fever vaccination meet Brighton Collabora-tion diagnostic criteria? Vaccine 2013; 31:6201.

32 RE Thomas et al The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review Am J Trop Med Hyg 2012; 86:359.

33 MF Farez and J Correale Yellow fever vaccination and in-creased relapse rate in travelers with multiple sclerosis Arch Neurol 2011; 68:1267.

34 S Kuhn et al Case report: probable transmission of vaccine strain of yellow fever virus to an infant via breast milk CMAJ 2011; 183:E243.

35 RC Charles and ET Ryan Cholera in the 21st century Curr Opin Infect Dis 2011; 24:472.

36 Cholera vaccines: WHO position paper Wkly Epidemiol Rec 2010; 85:117.

37 A Banzhoff et al Protection against tick-borne encephalitis (TBE) for people living in and travelling to TBE-endemic areas Travel Med Infect Dis 2008; 6:331.

38 U Kunze Is there a need for a travel vaccination against tick-borne encephalitis? Travel Med Infect Dis 2008; 6:380.

1-6 weeks apart (3 doses in children 2-6 years old)

Shanchol (Shantha Biotechnics, India) is administered

in 2 doses 2 weeks apart to persons >1 year old.36

TICKBORNE ENCEPHALITIS (TBE) — TBE occurs in

temperate areas of Europe and Asia; the risk area

extends from eastern France to northern Japan, and

from northern Russia to Albania.37,38 The risk of infection

is greatest from April to November Humans acquire the

disease through the bite of an infected tick or, rarely,

from eating unpasteurized dairy (mostly goat) products

Immunization is recommended only for travelers who

will spend extensive time outdoors in rural areas

Two inactivated cell culture-derived vaccines are

available in Europe (Encepur – Novartis, Germany;

FSME-Immun – Baxter, Austria); they are usually given

in 3 doses over 6-15 months, but the second dose can

be administered 2 weeks after the fi rst if a rapid

im-mune response is required Encepur can also be given

over 3 weeks (0, 7, and 21 days) Two inactivated TBE

vaccines are also available in Russia (TBE-Moscow;

EnceVir); they are usually given in 2 doses 5-7 months

apart, but a rapid schedule of EnceVir at 0 and 1-2

months can be used in emergency situations ■

1 Adult immunization Treat Guidel Med Lett 2014; 12:39.

2 General recommendations on immunization -

recommenda-tions of the Advisory Committee on Immunization Practices

(ACIP) MMWR Recomm Rep 2011; 60(2):1.

3 RM Klevens et al The evolving epidemiology of hepatitis A in

the United States: incidence and molecular epidemiology from

population-based surveillance, 2005-2007 Arch Intern Med

2010; 170:1811.

4 S Iwarson et al Excellent booster response 4 to 8 years after

a single primary dose of an inactivated hepatitis A vaccine J

Travel Med 2004; 11:120.

5 Centers for Disease Control and Prevention CDC Health

Information for International Travel 2014 The Yellow Book

Chapter 3, Hepatitis A Available at: www.cdc.gov/travel/yellow

book/2014/chapter-3-infectious-diseases-related-to-travel/

hepatitis-a Accessed November 13, 2014.

6 DF Johnson et al Hepatitis B and C infection in international

travelers J Travel Med 2013; 20:194.

7 R Steffen Influenza in travelers: epidemiology, risk, prevention,

and control issues Curr Infect Dis Rep 2010; 12:181.

8 Influenza vaccine for 2014-2015 Med Lett Drugs Ther 2014;

56:97.

9 Centers for Disease Control and Prevention (CDC) Use of

north-ern hemisphere influenza vaccines by travelers to the southnorth-ern

hemisphere MMWR Morb Mortal Wkly Rep 2009; 58:312.

10 SL Hills et al Japanese encephalitis in travelers from

non-en-demic countries, 1973-2008 Am J Trop Med Hyg 2010; 82:930.

11 E Mirzaian et al Mosquito-borne illnesses in travelers: a review

of risk and prevention Pharmacotherapy 2010; 30:1031.

12 A new Japanese encephalitis vaccine (Ixiaro) Med Lett Drugs

Ther 2009; 51:66.

13 Use of Japanese encephalitis vaccine in children:

recommen-dations of the advisory committee on immunization practices,

2013 MMWR Morb Mortal Wkly Rep 2013; 62:898.

14 PA Gastañaduy et al Measles - United States, January 1-May

23, 2014 MMWR Morbid Mortal Wkly Rep 2014; 63:496.

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1 Discuss the recommendations for use of vaccines available for US travelers.

2 Determine the appropriate vaccinations for an individual patient based on their travel destination, duration of travel, and planned activities.

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DO NOT FAX OR MAIL THIS EXAM

To take CME exams and earn credit, go to:

medicalletter.org/CMEstatus Issue 1456 Questions

(Correspond to questions #101-110 in Comprehensive Exam #71, available January 2015)

6 A 7-month-old boy will be traveling to India next month with his parents Which of the following statements about measles vaccination in this patient is correct?

a vaccination is not recommended for travel to India

b he should receive 2 doses, 28 days apart, before travel

c he should receive 1 dose before travel, but will need 2 more doses for routine immunization

d he should not travel to India until he completes his routine immunization schedule

7 Which of the following vaccines are recommended for a 35-year-old man traveling to Ethiopia in January?

a Menactra

b Trumenba

c both Menactra and Trumenba

d none of the above

8 How many doses of inactivated polio vaccine are recommended for an adult planning a 3-week trip to Israel who has previously completed a primary series and never had a booster dose?

a 0

b 1

c 2

d 3

9 A 19-year-old woman is bitten by a potentially rabid dog while vacationing in Indonesia She received pre-exposure vaccination before leaving the US What treatment should she receive now?

a none because she received pre-exposure vaccination

b two additional doses of rabies vaccine

c human rabies immune globulin and 4 doses of vaccine over 14 days

d human rabies immune globulin and 5 doses of vaccine over 14 days

10 Yellow fever vaccine:

a should be given as a 3-doses series beginning 4 weeks before travel

b should be given before international travel regardless of destination

c is recommended for all infants traveling to sub-Saharan Africa

d has rarely been associated with severe systemic illness and organ failure

1 Live vaccines:

a generally should not be used in immunocompromised patients

b can be given simultaneously

c should be given at least 4 weeks apart if not given

simultaneously

d all of the above

2 A 49-year-old woman with cirrhosis is leaving next week on a

2-week trip to Africa She has not been vaccinated previously against

hepatitis A Which of the following would you recommend she receive

before her trip?

a only an initial dose of hepatitis A vaccine

b only a 0.02-mL/kg IM dose of immune globulin

c both an initial dose of hepatitis A vaccine and a 0.02-mL/kg IM

dose of immune globulin

d she doesn’t need any prophylaxis because Africa is considered

a low-risk area for hepatitis A acquisition

3 A healthy 21-year old woman is planning a one-week trip to Spain

for spring break She has not been vaccinated previously against

hepatitis A or B You should tell her:

a she should be vaccinated against hepatitis A because Spain is

a high-risk country for hepatitis A acquisition

b hepatitis B vaccination is required for all travelers to Spain

c she should consider being vaccinated against hepatitis B if

she might engage in risky behaviors such as getting a tattoo or

having unprotected sexual contact with a new partner while on

vacation

d none of the above

4 Influenza vaccination should be considered for persons traveling:

a to the tropics in any season

b to the Southern Hemisphere from April to September

c in a group with persons from the Southern Hemisphere during

their influenza season

d all of the above

5 A mother asks you whether her 4-year-old daughter should receive

Ixiaro before traveling to Hong Kong You should tell her that:

a Ixiaro is not approved for use in children <17 years old

b you would not recommend vaccination with Ixiaro because she

is not likely to be exposed to Japanese encephalitis in Hong

Kong

c you would recommend vaccination with Ixiaro because they are

planning to stay in Hong Kong for more than 2 weeks

d you would recommend JE-Vax instead

ACPE UPN: Per Issue Exam: 0379-0000-14-456-H01-P; Release: November 24, 2014, Expire: November 24, 2015 Comprehensive Exam 71: 0379-0000-15-071-H01-P; Release: January 2015, Expire: January 2016

EDITOR IN CHIEF: Mark Abramowicz, M.D.; EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School; EDITOR: Jean-Marie Pflomm, Pharm.D.; ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne Z Morrison, Pharm.D., Michael P Viscusi, Pharm.D.; CONSULTING EDITORS: Brinda M Shah, Pharm.D.,

F Peter Swanson, M.D; SENIOR ASSOCIATE EDITOR: Amy Faucard

CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons; Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical

School; Eric J Epstein, M.D., Albert Einstein College of Medicine; Jane P Gagliardi, M.D., M.H.S., F.A.C.P., Duke University School of Medicine; Jules Hirsch, M.D., Rockefeller University; David N Juurlink, BPhm, M.D., Ph.D., Sunnybrook Health Sciences Centre; Richard B Kim, M.D., University of Western Ontario; Hans Meinertz, M.D., University Hospital, Copenhagen; Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine; Dan M Roden, M.D., Vanderbilt University School of Medicine; Esperance A.K Schaefer, M.D., M.P.H., Harvard Medical School; F Estelle R Simons, M.D., University of Manitoba; Neal H Steigbigel, M.D., New York University School of Medicine; Arthur M F Yee, M.D., Ph.D., F.A.C.R.,

Weill Medical College of Cornell University

MANAGING EDITOR: Susie Wong; ASSISTANT MANAGING EDITOR: Liz Donohue; EDITORIAL ASSISTANT: Cheryl Brown

EXECUTIVE DIRECTOR OF SALES: Gene Carbona; FULFILLMENT & SYSTEMS MANAGER: Cristine Romatowski; DIRECTOR OF MARKETING COMMUNICATIONS: Joanne F Valentino; VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy

Founded in 1959 by Arthur Kallet and Harold Aaron, M.D.

Copyright and Disclaimer: The Medical Letter, Inc is an independent nonprofi t organization that provides healthcare professionals with unbiased drug prescribing recommendations The editorial

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