Recommended UK paediatric and adult travel immunisation schedules
There are a number of national and international organisations that publish travel immunisation guidelines. Guidelines may vary due to conflicting medical evidence, differing expert opinions, and different national licensing standards, marketing arrangements and availability of vaccines. This can cause confusion for both the traveller and the travel clinician [2, 3]. The recommended travel immunisations for an individual traveller will be determined by a detailed medical and travel consultation.
This section reviews in detail the current recommended paediatric and adult national guidelines of the UK for routine immunisations in the context of travellers, specific travel immunisations and mandatory travel immunisations. Reference is made to any major differences with the World Health Organization (WHO) international guidelines. The post concludes with two sections comparing the main differences between these guidelines and the national guidelines of the United States, Canada, Australia and New Zealand. The post thus aims to provide a comprehensive guide to travel immunisation for a travel clinician working in any part of the world.
Recommended UK paediatric and adult travel immunisation schedules
The WHO’s International Travel and Health Book http:// www.who.int/ith/en/ provides international travel immunisation guidelines that may be used by any country, including those that do not have their own national regulatory organisation and travel immunisation guidelines. Individual countries with their own travel immunisation guidelines may incorporate some but not all of the WHO guidelines where appropriate. The Department of Health in the UK publishes national travel immunisation guidelines in the Immunisation Against Infectious Disease Green Book www. dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/ Greenbook/DH_4097254 [1,2].
The minimum age in the table does not apply for all listed vaccine brands and it is important to refer to each vaccine brand’s Summary of Product Characteristics for the specific minimum age, licensed schedules, vaccine components and excipients, side effects and contraindications.
Indication Vaccination against anthrax should only be considered for adult travellers going to work with or handle infected animals or their products (such as wool, skin, bones and carcasses), for example farmers, veterinary surgeons, butchers, tanners and laboratory personnel. Anthrax is more common in Africa, Asia, Central and South America, and southern and eastern Europe ,
Vaccine In the UK, the inactivated anthrax vaccine is manufactured by the Health Protection Agency (HPA Anthrax) , Side effects may include localised pain, swelling and erythema (10%), headaches and myalgia (20%), fever (5%), nausea (5%) and anaphylaxis (< 1:100,000) ,
Schedule The primary schedule for adults consists of four doses over a 6-month period, with the first dose administered at day 0, the second dose 3 weeks after the first dose, the third dose 3 weeks after the second dose and the fourth dose at least 6 months after the third dose, with annual boosters for travellers at continued risk of exposure [2, 3].
Efficacy Clinical trials with anthrax vaccines used in the 1950s and with Biothrax Anthrax vaccine indicate that the vaccines maybe more than 90% effective in preventing all types of anthrax infection for up to 1 year after completion of the primary schedule [4,24],
Indication The risk of cholera infection to travellers is extremely low and is estimated to be 1 in 500,000 travellers [25, 26]. Vaccination against cholera is only recommended for healthcare, humanitarian and laboratory personnel travelling to work in regions with a confirmed Vibrio cholerae serogroup 01 outbreak, such as refugee camps. It can also be considered for travellers to remote parts of Africa, Asia, the Indian subcontinent, and South and Central America where there is confirmed V. cholerae serogroup 01 and extremely limited healthcare resources [1, 2], It is likely that due to surveillance difficulties and for fear of social and economic repercussions, morbidity and mortality data for V. cholerae are greatly underestimated . However, strict food and water hygiene precautions remain the key to prevention of cholera infection in travellers. Cholera vaccination certification is no longer a WHO international health requirement for individuals travelling from infected areas, although an official document reiterating this fact may sometimes be helpful at some remote border areas [2, 28].
Vaccine In the UK and more than 60 countries, the oral inactivated whole-cell monovalent cholera vaccine Dukoral, prepared in a sodium hydrogen carbonate solution, is licensed for administration in travellers. It consists of four strains of V. cholerae serotype 01 representing the biotypes Classical and El Tor, and the subtypes Inaba and Ogawa of El Tor, with a recombinant cholera toxin subunit B but not the enterotoxin subunit A, which is responsible for the disease. Side effects can include mild gastrointestinal and flu-like symptoms [2, 3]. It does not provide protection against V. cholerae serotype 0139, which has started to spread through parts of South Asia, Southeast Asia and China. In Southeast Asia, two biovalent vaccines, Shanchol and mORCVAX, provide protection against both V. cholerae serotypes 01 and 0139 .
Schedule The primary schedule for travellers aged 2-6 years consists of three doses with boosters every 6 months. For older travellers the primary schedule consists of two doses with boosters thereafter every 2 years for ongoing protection. If longer than 6 weeks has elapsed between doses in the primary schedule or longer than the recommended interval for booster doses, it will be necessary to restart the primary schedule from the beginning [2,28].
Efficacy The vaccination schedule should be completed at least 1 week and preferably 3 weeks before travel or potential exposure to V. cholerae 01 [ 1 ]. Studies suggest that the vaccine provides between 50% and 86% protection against V. cholerae 01 for up to 3 years [3, 25, 27, 29-33]. This protection can wane quickly, within 6 months in young children [3,33].
The cholera toxin subunit B is antigenically similar to the heat-labile toxin of Enterotoxigenic Escherichia coli (ETEC). Dukoral thus also provides 50-67% cross-protection against ETEC infection, a more common cause of travellers’ diarrhoea [7, 32, 34, 35]. Shanchol and mORCVAX do not contain cholera toxin subunit B and so do not provide crossprotection against ETEC .
Indication The incidence of hepatitis A infection is approximately 1.4 million cases per annum worldwide and it is one of the most common vaccine-preventable diseases in travellers [36, 37]. Hepatitis A vaccination is recommended for
travellers aged >1 year to regions of intermediate to high prevalence of hepatitis A for prolonged periods, especially if food hygiene and sanitation is poor. This includes travel to most regions outside western and northern Europe, Canada, the US, Japan, Australia and New Zealand, but particularly to the Indian subcontinent and Southeast Asia [2, 38]. Particular consideration with regard to the potential risk of exposure to infection with hepatitis A include travellers with underlying medical conditions, such as those with chronic renal or chronic liver disease including chronic hepatitis B or C, who may be at increased risk of severe hepatitis A infection , It is recommended that a pre-vaccination IgG hepatitis A serology test is undertaken for those travellers born before 1945 or who are over the age of 40 and have lived in a hepatitis A-endemic area or have a history of jaundice, as they may have natural immunity to hepatitis A and not require hepatitis A vaccination , Although the risk of hepatitis A infection in infants and young children who travel may be low, with subdinical infection occurring mostly, severe infection can occur with transmission to others. Hepatitis A vaccines combined with hepatitis B or typhoid vaccines can be used when protection against both of these infections is recommended ,
Vaccine Several inactivated monovalent hepatitis A vaccines are licensed in the UK, including a hepatitis A and B combined vaccine and hepatitis A and typhoid combined vaccines , Combined hepatitis A and B vaccines consist of inactivated hepatitis A virus combined with recombinant hepatitis B surface antigen, together with an aluminium salt adjuvant , Combined hepatitis A and typhoid vaccines consist of inactivated hepatitis A virus combined with inactivated purified Vi capsular polysaccharide typhoid vaccine and an aluminium hydroxide adjuvant , Hepatitis A vaccines are very safe and well tolerated, with the more common side effects including localised pain and headache. The monovalent hepatitis A vaccine Epaxal contains influenza virus haemagglutinin and is thus contraindicated in travellers who are allergic to eggs or chicken protein ,
Schedule The primary immunisation schedule for hepatitis A depends on the type administered, age of the traveller and whether combined protection with hepatitis B or typhoid is required. Some of the different hepatitis A vaccines contain different concentrations of antigen, and although the different vaccines may be used interchangeably during courses and for boosters, this is only to be recommended when the original vaccine used is unavailable .
The primary schedule for the monovalent hepatitis A vaccines for travellers greater than 1 year of age includes the administration of a single dose on day 0 with a booster dose at 6-12 months. National guidelines in the UK currently recommend further boosters every 20 years, although the WHO does not recommend any further boosters after that at 6-12 months [1,2, 39],
The primary immunisation schedule for the combined hepatitis A and B vaccine consists of three doses for Twinrix Adult and Twinrix Paediatric over a 6-month period. An accelerated schedule over 3 weeks with Twinrix Adult provides rapid protection against hepatitis A and B. The primary immunisation schedule for travellers aged 1-15 years with Ambirix consists of just two doses, on day 0 and at 6-12 months as it contains double the concentration of both hepatitis A and B antigens as contained in Twinrix Paediatric. The first dose of Ambirix provides sufficient protection against hepatitis A and the second dose is required to provide sufficient protection against hepatitis B. Monovalent hepatitis A vaccines or Ambirix (for children less than 15 years old) are recommended when rapid single-dose protection against hepatitis A is required, rather than Twinrix Paediatric or Twinrix Adult. Booster doses with monovalent hepatitis A and monovalent hepatitis B vaccines are then recommended after completing the primary schedule with a combined hepatitis A and B vaccine , The primary immunisation schedule for the combined hepatitis A and typhoid vaccines for travellers aged >15 years includes the administration of a single dose of the combination vaccine followed by booster doses of monovalent hepatitis A and monovalent typhoid vaccine as appropriate for ongoing protection ,
Efficacy A single dose of hepatitis A vaccine provides at least 95% protection for up to 1 year. The booster dose at 6-12 months provides nearly 100% protection for at least 25 years and probably for life [1, 3, 39-42], The combined Twinrix Paediatric or Twinrix Adult vaccines administered as three doses, on day 0, 1 month and 6 months, provide after each respective dose 94%, 99% and 100% protection against hepatitis A, and 71%, 97% and 99% protection against hepatitis B [3, 43-46]. The accelerated schedule with Twinrix Adult on day 0, 7, 21 and at 12 months provides at 1 month, 12 months and 13 months 99%, 96% and 100% protection against hepatitis A, and 82%, 94% and 100% protection against hepatitis B respectively [47-50].
Human normal immunoglobulin (HNIG) is no longer recommended for administration as hepatitis A pre-exposure prophylaxis due to the extremely immunogenic properties of the hepatitis A vaccine and the relatively long incubation time of hepatitis A ,
Post-exposure prophylaxis Unimmunised travellers exposed to a potential source of hepatitis A should receive a single dose of monovalent hepatitis A vaccine within 1 week of the onset of jaundice or other symptoms in the index case. If longer than 1 week has elapsed, such travellers should receive a dose of HNIG containing a hepatitis A antibody level >100IU/ml. The dose of HNIG for travellers aged <10 years is 250 mg and >10 years 500 mg. HNIG provides 85% protection if administered within 2 weeks of exposure and it is likely to modify the severity of hepatitis A infection .
Indication It has been estimated that worldwide, 2 billion people are infected with hepatitis B with more than 350 million carriers of the disease . The risk of infection to travellers has been estimated to be 80-240 cases per 100,000 travellers per month of stay for long-term travellers and 2-10 times lower among short-term travellers. Hepatitis B is an important vaccine-preventable disease in travellers [2, 51].
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Hepatitis B vaccine is a routine childhood vaccination in more than 90 countries worldwide but currently is not part of the UK routine childhood immunisation programme. Hepatitis B vaccination is recommended for travellers to areas of intermediate (2-8%) to high (>8%) prevalence of hepatitis B as based on the local population hepatitis B surface antigen prevalence [1,2], This includes travel to sub- Saharan Africa, most of Asia and the Pacific, the Indian subcontinent, Middle East, the Amazon region of South America, Honduras, Guatemala, Haiti, Dominican Republic, and parts of eastern, central and southern Europe. Travellers to these regions at particularly high risk include those who plan to remain in areas of high or intermediate prevalence for long periods of time; young children who may be in contact with other young children in an endemic area; children and others who may require medical care while travelling to visit families or relatives in high or moderate- endemicity countries; travellers with medical conditions who may require blood product transfusions, dialysis or other medical or dental treatment and who may be exposed to infection through unsterile injections or unscreened blood or blood products; travellers with chronic liver disease; and those travelling for medical care. Other indications include for those travellers who engage in lifestyle behaviours that may expose them to a risk of hepatitis B, including sexual activity, intravenous drug use, acupuncture, piercing,tattooing and participation in contact sports. Occupational exposure should also be considered for healthcare workers and laboratory personnel. Combined hepatitis A and B vaccines can be used when protection against both hepatitis A and hepatitis B infection is desired ,
Vaccine Several inactivated monovalent hepatitis B vaccines are licensed for use, including a combined hepatitis A and B vaccine (see section on Hepatitis A vaccine) . The vaccines are very safe with few experiencing mild side effects, including localised pain and a mild fever [2, 3].
Schedule The primary immunisation schedule for hepatitis B depends on the type of vaccine administered, the age of the traveller, how quickly protection is required and whether combined protection with hepatitis A is required. Different hepatitis B vaccines may contain different concentrations of antigen and although the different vaccines may be used interchangeably during courses and for boosters, this is only to be recommended when the original vaccine used is unavailable [2, 52],
The primary schedule of most monovalent hepatitis B vaccines consists of three doses administered over a 6-month period, at day 0,1 month and 6 months. Some vaccines may also be given as a three-dose schedule over 2 months, at day 0, 1 and 2 months with a booster at 12 months [2, 53]. For travellers aged >18 years departing within 1 month, Engerix B may be administered according to an accelerated schedule over 3 weeks with a fourth booster dose administered at 12 months [2,53-57] It can also be administered in those 16-18 years where it is important to provide rapid protection and to maximise compliance.
For travellers aged <16 years, Engerix B may be given as a 0.5 ml (10 (J.g) dose according to a three-dose accelerated schedule, at day 0, 1 and 6 months and for travellers aged 11-15 years, Engerix B may be administered as a 1.0 ml (20 (J.g) adult dose according to a two-dose schedule over 6 months when the risk of infection with hepatitis B is considered to be low and to aid compliance. Consideration should be given to the administration of a single booster dose of hepatitis B vaccine at 5 years for travellers at ongoing risk of hepatitis B infection ,
Efficacy A complete course of hepatitis B immunisation is likely to be at least 80% effective in preventing infection. More than 80% of adult travellers develop adequate antibody protection after two doses of hepatitis B vaccine (this is higher in younger children). Between 90% and 100% of travellers develop an adequate antibody response after three doses of hepatitis B vaccine [58-60]. Rates of protection are slightly lower in older travellers and in travellers with certain medical conditions, including immunosuppression, those requiring dialysis and those who are obese . Although antibody levels decline over time, immunological memory and protection against hepatitis B infection persists for more than 20 years and probably for life .
The accelerated course of hepatitis B vaccine using Engerix B with three doses administered over 3 weeks provides 65% seroprotection within 1 week of completing the course and 98% within 1 month after the fourth booster dose at 12 months [50, 53]. This course of hepatitis B vaccine is to be recommended for those travelling imminently and when there is insufficient time to complete a three-dose course over a period of 6 months.
For infants and young children who have received a primary course of hepatitis B vaccine, a single booster of hepatitis B vaccine is recommended at 5 years of age, which provides protection for at least 15 years and probably for life, although there is much individual variability [1,61]. Further booster doses of hepatitis B vaccine are not routinely recommended thereafter.
Non-response to hepatitis B vaccine occurs in approximately 10-15% of adult vaccinees and is associated with several factors, including incorrect administration, gender (male), age over 40 years, obesity, smoking, alcoholism, renal insufficiency and immunosuppression. Research into the mechanisms associated with non-response has demonstrated immunogenetic mechanisms, including specific haplotype associations , Serological testing is recommended for the older traveller in order to demonstrate that protection has been afforded, travellers who are to be deployed as healthcare workers, for those with underlying medical conditions and those who may be at continued risk of exposure by virtue of travel. Such travellers may require additional booster doses of hepatitis B vaccine if they fail to mount an adequate antibody response, and the administration of a course of a combined hepatitis A and B vaccine may be considered as there is evidence to suggest that the combined hepatitis A and B vaccine may circumvent non-response to hepatitis B vaccine. Importantly, in the event of a potential exposure to infection with hepatitis B, consideration should be given to the administration of post-exposure prophylaxis in the form of hepatitis B immunoglobulin and booster doses of hepatitis B vaccine for non-responders and if hepatitis B surface antibody levels are <10mIU/mL ,
Post-exposure prophylaxis Unimmunised travellers exposed to potential infection with hepatitis B should receive three doses of hepatitis B vaccine administered on day 0,1 month and 2 months, with a booster at 12 months. If the risk of infection is considered significant, e.g. the source is confirmed as HBsAg positive, unimmunised travellers should also receive a dose of hepatitis B specific immunoglobulin (HBIG) preferably within 48 hours but up to 7 days following exposure. Immunised and partially immunised travellers should receive a booster dose of hepatitis B vaccine and complete the course as necessary [2, 3].
Indication All female travellers aged 12-18 years should receive the human papillomavirus (HPV) vaccine. This includes females who are already sexually active, as they may not have been exposed to the high-risk HPV 16 and 18 types which the vaccine protects against. Although there is no evidence that HPV vaccination causes harm during pregnancy, it should generally be postponed until after pregnancy unless high-risk sexual activity is continuing during the pregnancy . HPV vaccination is an opportunity to reduce the risk of acquiring HPV while travelling, particularly in young women travelling abroad during a gap year . Consideration should be given to the administration of HPV vaccine to men who may be at risk of genital warts and HPV- related cancers.
Vaccine Cervarix is a bivalent HPV vaccine protecting against HPV types 16 and 18, which are associated with 50% and 15% respectively of cervical cancers . Gardasil is a quadrivalent HPV vaccine protecting against HPV type 6, 11,16 and 18 with HPV types 6 and 11 being associated with 90% of genital warts .
Schedule Cervarix is currently part of the routine immunisation schedule for adolescent girls in the UK and is administered at day 0,1 month and 6 months . Gardasil provides additional protection against genital warts and so may be preferential for some female adolescent travellers.
Efficacy Both vaccines are >99% effective in protecting women against pre-cancerous anogenital lesions associated with HPV 16 and 18 for at least 6 years and probably much longer . The vaccines also provide some cross-protection against some other high-risk HPV types with similar structures. Gardasil provides 99% protection against genital warts associated with HPV types 6 and 11 . Alongside vaccination, advice about safe sex should be given and the importance of attending routine cervical screening must also be stressed ,
Indication In the UK, influenza vaccination is recommended for travellers >6 months. [2, 4, 8, 67]
Vaccine Influenza is present year round in the tropics, peaks between November and March in the northern hemisphere, and between April and September in the southern hemisphere [2, 3]. The principal strains of influenza circulating in the northern and southern hemispheres may vary significantly from one other. The WHO monitors globally the seasonal antigenic drift and periodic antigenic shift in influenza A haemagglutinin (H) and neuraminidase (N) surface antigens. Antigenic drift is due to point mutations and antigenic shift is due to genetic recombination. Influenza B has less antigenic drift and influenza C is only responsible for a very small portion of clinical illness. Intramuscular inactivated influenza vaccines are trivalent and consist of two subtypes of influenza A (H3N2 and H1N1) and one subtype of influenza B [1, 2, 68]. There are three main types of influenza vaccine: split virion (whole virus strains), surface antigen and surface antigen virosomes [2, 57].
The WHO provides recommendations 6 months in advance of the annual influenza season occurring in each hemisphere regarding which virus strains should be included in the influenza vaccines for the forthcoming winter season. In years when the strains of influenza in the northern and southern hemispheres are different, the influenza vaccines available in each hemisphere will also be different. Those travelling from one hemisphere to the other during that hemisphere’s influenza season should be vaccinated at least
1 weeks before departure, with an influenza vaccine specific for that hemisphere. If such an influenza vaccine is not available before travel, the traveller should be vaccinated with an influenza vaccine specific to that hemisphere as soon as possible after arriving in a country within that hemisphere [1,3].
All three different types of influenza vaccine have similar side effects, which may include mild flu-like symptoms and very rarely neuralgia, paraesthesiae, seizures, vasculitis, thrombocytopenia, neuritis and encephalomyelitis. There is a possible association with Guillain-Barre Syndrome of <1 per million doses. Split virion vaccines are slightly less reactogenic and are preferred in younger children, and influenza vaccine is contraindicated in travellers with a previous anaphylactic reaction to the vaccine or to egg products ,
Schedule The primary immunisation schedule for children aged 6 months to 13 years and for all immunocompromised children and adults includes two doses, administered on day
0 and at 4-6 weeks. For immunocompetent adults and children aged >13 years, the primary schedule consists of a single dose only. Annual single dose boosters for all ages are then recommended for ongoing protection due to the antigenic drift and shift of influenza A. Influenza vaccine in the UK is normally administered between September and November, just before the start of the flu season.
Efficacy All of the different types of influenza vaccine provide a similar protection of 70-80% against infection with influenza strains contained within the vaccine for up to 1 year [69,70]. They are much less effective in travellers aged >65 years in whom they may provide protection for only 4 months, although at present booster doses within the same year are not recommended [14, 71].
Indication Influenza A(HlNl)v vaccination is currently recommended for travellers aged >6 months who are at increased risk of influenza A(HlNl)v or severe illness. This includes healthcare workers, pregnant women, children with neurodevelopmental disorders and travellers with chronic medical conditions such as diabetes, chronic pulmonary disease, immunosuppression, asplenia or splenic dysfunction among others [2, 72], Vaccination is not currently routinely recommended in travellers aged >65 years as they seem to have some immunity to influenza A(H1N1) virus due to exposure to similar viruses in the past .
Vaccine Influenza pandemics occur when a new influenza virus emerges and spreads through a population in which there is little or no immunity. There have been three pandemics in the previous century and they have tended to be associated with high mortality as individuals have little or no immunity to the emerging virus. The most recent influenza pandemic began in 2009 and was associated with A(HlNl)v 2009 virus (swine flu). This new influenza subtype consisted of gene segments from human influenza A, pigs and bird viruses. There have also been sporadic outbreaks of avian influenza caused by the avian influenza A(H5N1) virus particularly in some countries in Southeast Asia. Inactivated H5N1 vaccines are available in some countries, although they are not generally available and their effectiveness is not known ,
The side effects are likely to be similar to those experienced with seasonal influenza vaccine. Pandemrix is contraindicated in travellers with a previous anaphylactic reaction to egg products, but Celvapan is propagated in Vero cells and so may be administered as an alternative , A swine flu vaccine used in 1976 in the US was associated with a very slight increase in the risk of Guillain-Barr£ Syndrome (GBS) . However, there is no evidence to suggest that the current influenza A(HlNl)v vaccines are associated with an increased risk of GBS.
Schedule Pandemrix is the preferred vaccine for children and pregnant women as it provides rapid protection following administration of a single dose, and there are limited data on the use of Celvapan in children. The primary schedule with Celvapan is the administration of two doses, separated by an interval of at least 3 weeks, while Pandemrix is administered as a single dose. The two vaccines are not interchangeable ,
Indication This risk of infection with Japanese encephalitis for travellers to endemic countries is very low, <1 per million travellers, rising to 1 per 5,000 per month for the local population in endemic rural areas . Japanese encephalitis is endemic in the tropical regions of Southeast Asia, southern India and Sri Lanka, occurring throughout the year and especially during their rainy seasons. In the more subtropical regions of northern Southeast Asia, northern India and Nepal, Japanese encephalitis typically occurs in epidemics during the rainy season from April to October [1, 2], Japanese encephalitis vaccination is recommended for travel to endemic areas of the Indian subcontinent, Southeast Asia and the Western Pacific for longer than
1 month [2, 3]. However, cases do occur in travellers to endemic regions for shorter durations . Vaccination is also recommended for travel of any duration to endemic areas during and just after the rainy season, and to rural areas where rice and pig farming coexist. Japanese encephalitis is not found in Africa, the Americas or Europe [2, 76].
Vaccine Two Japanese encephalitis vaccines are available in the UK: Japanese encephalitis Green Cross vaccine (GC vaccine) is currently unlicensed in the UK and is supplied on a named patient basis, and IXIARO. JE-VAX (Biken) is an inactivated vaccine derived from mouse brain cells and is no longer manufactured or available [2,21, 77].
Green Cross vaccine is highly reactogenic and contains inactivated Japanese encephalitis virus cultured in mouse brain cells. It should be administered at least 10 days prior to departure to monitor for potential side effects, which
indude fever, headache, myalgia, abdominal pain, vomiting, dizziness, angioedema and, very rarely, severe neurological side effects [2, 3]. IXIARO is manufactured from Japanese encephalitis virus produced from Vero cells and the main side effects are myalgia and headache [2, 21, 77]. Japanese encephalitis vaccination is not recommended in travellers with unstable neurological conditions, including those who have had convulsions in the previous year or who have conditions such as multiple sclerosis ,
Schedule The primary immunisation schedule for Green Cross vaccine consists of three doses administered over 1 month to those aged 1 year and over. An accelerated schedule for travellers leaving imminently consists of two or three doses administered over a 2-week period. An additional booster dose is recommended 1 month after completing the primary course for travellers aged >60 years and a booster dose is then recommended at 1 year with further boosters every 3 years ,
The primary immunisation schedule for IXIARO vaccine for travellers consists of two doses administered over 1 month for those aged 18 years and over (IXIARO is the only Japanese encephalitis vaccine available in North America and is only licensed for persons aged >17 years). The need for booster doses is currently under evaluation. There no evidence for the interchangeability of different vaccines during a schedule and so at present this is not recommended ,
Efficacy The rate of seroconversion following administration of the first dose of IXIARO is approximately 30% rising to 97% 1 week after the second dose and completion of the primary schedule [8, 78]. The duration of protection provided with IXIARO is currently unknown and under evaluation . The protective efficacy of the Green Cross vaccine is approximately 80% after completion of the primary schedule .
Measles, mumps and rubella
Indication MMR vaccination is part of the UK routine childhood immunisation programme. Measles, mumps and rubella are more common in many developing countries, especially where routine childhood immunisation programmes are not in place or where vaccination coverage is low. All travellers aged >6 months to countries where measles, mumps and/or rubella are endemic should be vaccinated with MMR. Children aged <6 months are likely to be protected by maternal antibody . Travellers from the UK born before 1970 may be considered naturally immune to measles, mumps and rubella due to the high incidence of natural exposure before this time, although they may wish to be immunised on request. Older travellers who have received inactivated monovalent measles vaccine may paradoxically be at risk of more severe measles infection due to sensitisation to measles antigen and so should be revaccinated with MMR . It is particularly important that women travellers of childbearing age have been vaccinated with MMR or have serological evidence of rubella antibodies ,
Vaccine In the UK, MMR vaccines are only available in combination, consisting of live strains of measles, mumps and rubella attenuated viruses , A common side effect (3%) occurring 1 week post-vaccination is a rash, fever and malaise lasting for 2-3 days. Rarely this may be associated with febrile convulsions, although the risk is higher with natural measles infection. A transient arthralgia may occur 1-3 weeks post vaccination especially in post-pubertal women (25%) due to the rubella component of the vaccine. Parotid swelling may occur typically in the third week Rarely (1 per 32,000 doses), idiopathic thrombocytopenic purpura (ITP) may occur within 6 weeks of vaccination, which spontaneously resolves. This risk is much less than the risk of ITP associated with wild measles or rubella virus infection , If ITP occurs within 6 weeks after the first dose of MMR, serological testing should be performed and the second dose of MMR only administered if there is incomplete seroconversion to measles, mumps and rubella. MMR is contraindicated in pregnant women and immuocompromised travellers and it should only be administered, and with extreme caution, in a hospital setting to travellers with a previous severe allergic reaction to egg products. There is overwhelming evidence that MMR is not associated with an increased risk of autism, inflammatory bowel disorders and Guillain- Barr£ Syndrome as some studies have suggested in the past [2, 80,81].
Schedule MMR is recommended when protection against measles, mumps and/or rubella is required. The primary immunisation schedule consists of two doses administered
1 weeks apart after 12 months of age. Maternal antibodies may persist and inhibit the MMR vaccine up to 18 months of age, leading to the primary failure of the immune response to the first MMR dose. Therefore, any dose administered before 12 months of age should effectively be discounted and the second dose in the schedule should ideally be administered after 18 months of age [2, 82],
Travellers born before 1996 when the two-dose MMR schedule was introduced, may incorrectly believe they are adequately immunised, but they may have had only a single dose of MMR (available since 1988), MR (used in a catch-up programme in 1994), monovalent measles vaccine (available from 1968) or monovalent rubella vaccine (available from 1970) .
Efficacy A single dose of MMR provides approximately 90% protection against measles, 61-91% protection against mumps and 95-100% protection against rubella [3, 83, 84], A second dose of MMR targets those individuals who may not have seroconverted following the first dose of MMR, and approximately 90% of travellers who do not respond to the first dose of MMR should respond to the second dose ,
Post-exposure prophylaxis Unimmunised or partially immunised travellers >6 months of age exposed to measles may be offered a dose of MMR vaccine, ideally within 3 days of the exposure as vaccine-induced measles antibody develops faster than that following natural infection. A dose of HNIG should be considered for travellers who are immunocompromised, pregnant and unimmunised on serological testing, or aged <9 months within 6 days of exposure to a confirmed or highly suspected case of measles ,
Indication In the UK, meningococcal serogroups B and C are the most common cause of meningococcal infection ,
All travellers aged 3 months to 25 years should be up to date with the routine meningococcal C conjugate vaccine immunisation schedule. Vaccination is also recommended for all unvaccinated individuals studying at school or university in the UK. Meningococcal C conjugate vaccination is recommended for all travellers aged >3 months with asplenia or splenic dysfunction because they are at increased risk from meningococcal infection ,
Meningococcal disease occurs worldwide, with certain serogroups being more prevalent in some regions. The meningococcal quadrivalent vaccine is the preferred vaccine for travellers as it provides protection against serogroups A, C, W135 and Y. It is recommended for travellers aged >3 months to regions where meningococcal serogroups A, W135 or Y are circulating and where epidemics are prevalent. Epidemics of meningococcal serogroups A and W135 occur during the annual Hajj pilgrimage to Mecca in Saudi Arabia and meningococcal quadrivalent vaccination is a mandatory visa entry requirement for Hajj and Umrah. Quadrivalent vaccination is also recommended for travel to the meningitis belt of sub-Saharan Africa during the dry season (December-June), when significant epidemics of
meningococcal serogroup A (and more recently serogroup W135 as well) occur. This is particularly important for backpackers and travellers going to live or work in close proximity within local communities for long periods of time during the dry season [3, 85]. Quadrivalent vaccination is recommended for all travellers going to study at institutions abroad and may constitute a mandatory entry requirement in order to study at universities in the United States ,
Vaccine Three types of inactivated meningococcal vaccine are licensed in the UK: the routine childhood MenC conjugate vaccine, the meningococcal quadrivalent (A, C, W135 and Y) polysaccharide vaccine and the meningococcal quadrivalent (A, C, W135 andY) conjugate vaccine (Menveo) for travellers ,
For many years the only available quadrivalent meningococcal travel vaccine in the UK was a capsular polysaccharide vaccine (ACWY Vax), which as a T cell-independent vaccine is both poorly immunogenic in children aged <2 years and provides a relatively shorter duration of protection. The conjugate meningococcal quadrivalent travel vaccine has been available in Europe and the UK (Menveo) since March 2010, with the most common side effects being localised pain, swelling, erythema, mild fever, headaches, myalgia and nausea [2, 21],
Schedule The meningococcal quadrivalent conjugate vaccine is licensed and recommended for travellers aged >11 years old. In April 2010, the Joint Committee on Vaccines and Immunisation of the Department of Health, UK, recommended that conjugate ACWY meningococcal vaccine should be used in preference to the polysaccharide ACWY meningococcal vaccine, as the conjugated quadrivalent vaccine is more immunogenic and less likely to be associated with hyporesponsiveness. The conjugated ACWY vaccine may be administered as two doses separated by one month in infants under one year with a single booster dose after 12 months of age. For children over 1 year of age and adults, a single dose may be administered. The meningococcal quadrivalent polysaccharide vaccine is no longer recommended in infants and young children but may be used in travellers aged >5 years old. Where an infant has already received the monovalent MenC conjugate vaccine previously and meningococcal quadrivalent conjugate vaccine is indicated because of travel, it is recommended than an interval of 2 weeks is observed before administration of the conjugate quadrivalent vaccine ,
Efficacy The meningococcal quadrivalent polysaccharide vaccine is more than 80% effective in providing short-term (<3 years) protection against meningococcal serogroups A, C, W135 and Y in travellers aged >3 months [2, 21], In travellers aged <2 years it is only sufficiently immunogenic for the polysaccharide serogroup A and protection quickly wanes . Studies suggest that Menveo is at least as immunogenic and in some cases more immunogenic against all four meningococcal serogroups in adolescents and adults compared with other meningococcal vaccines [21,87]. There is good evidence that being a conjugate vaccine it is likely to be more immunogenic in children aged <2 years and to elicit longer-lasting immune protection [88, 89], The meningococcal C conjugate vaccine is approximately 87-98% effective in preventing meningococcal serotype C infection in infants and young children for a relatively long duration of time [7, 90].
Indication All travellers aged 2 months to 2 years should be up to date with pneumococcal vaccination following the routine childhood immunisation programme. Immunisation of travellers aged 2-65 years is only recommended for those with chronic medical conditions and at increased risk of severe pneumococcal infection, including travellers with diabetes, splenic dysfunction, immunosuppression and chronic respiratory disease ,
Vaccine Two types of pneumococcal vaccine are licensed in the UK, both of which are very well tolerated. The pneumococcal polysaccharide vaccine (PPV) contains polysaccharide antigens from 23 different capsular types of pneumococcus, which are responsible for the majority of serious pneumococcal infections in the UK. The pneumococcal conjugate vaccine (PCV) contains polysaccharide antigens from the 13 most prevalent capsular types of streptococcus pneumonia in the US conjugated to a diphtheria CRM197 toxin protein adjuvant, making it more immunogenic, especially in children aged less than 2 years , In 2010, Prevenar-13 was approved in the UK to replace Prevenar-7, which contained only seven streptococcus pneumonia capsular serotype antigens.
Schedule For infants under 1 year of age, the recommended primary course of PCV vaccination includes two doses administered at an interval of 2 months between each dose. The recommended age for vaccination is between 2 and 4 months.
For children from 1 year to under 2 years of age, it is recommended that the primary course of PCV consists of one dose. If the primary course in children under one year is not completed, then a single booster dose of PCV should be given at least 1 month after the last dose to complete the course.
A booster dose of PCV is recommended at between 12 and 13 months of age (i.e. within a month of the first birthday) for children who have received a complete primary course of two PCVs. This vaccine is given at the same time as Hib/ MenC and MMR vaccines.
For adults 65 years or over, it is recommended that a single dose of pneumococcal polysaccharide vaccine (PPV) should be administered ,
Efficacy The 23 serotypes contained within the PPV vaccine are responsible for approximately 96% of serious pneumococcal infections in the UK. More than 80% of adults produce a significant antibody response 3 weeks post PPV vaccination, providing between 50% and 70% protection against pneumococcal bacteraemia, pneumonia and meningitis, but not against other types of infection such as otitis media, chronic bronchitis and pneumonia without bacteraemia [ 91,92 ]. The length of protection provided may vary between the capsular types in the vaccine but typically lasts for up to
1 years. The immune response and protection provided is less effective in travellers aged less than 2 years or with immunosupression, splenic dysfunction or nephritic syndrome ,
The seven serotypes contained within the PCV vaccine are responsible for approximately 89% of serious invasive pneumococcal infections in the US. PCV vaccine is approximately 97% effective in preventing infection against the seven serotypes, including against pneumococcal pneumonia, meningitis, bacteraemia and otitis media . The vaccine has led to a significant reduction in invasive pneumococcal disease overall and it provides significant herd immunity against these seven serotypes, although there has been a slight increase in invasive pneumococcal disease from other serotypes not included in the vaccine. Trials suggest that the PCV Prevenar-13 vaccine is equally as effective as Prevenar-7 in protecting against invasive pneumococcal disease for the shared serotypes and provides additional protection against the additional six serotypes contained in the vaccine responsible for the majority of the pneumococcal infections not covered by Prevenar-7 [4, 87]. Children who began their immunisation schedule with Prevenar-7 should complete it with Prevenar-13.
Indication Travellers should be up to date with the routine polio immunisation schedule in the UK; a booster dose is recommended at 10-yearly intervals for continued protection. A booster of polio vaccine should also be considered for those travelling to or from regions where poliomyelitis is endemic (Nigeria, Pakistan and Afghanistan), and to where there are epidemics, see http://www.polioeradication.org/ casecount.asp [1, 2], This is particularly the case for travellers who are going to be working in local communities, including healthcare workers and laboratory personnel who may be at increased risk of exposure to poliomyelitis. Saudi Arabia is one country that requires proof of polio immunisation for travellers arriving from polio-endemic countries [1,2].
Vaccine Two types of polio vaccine, inactivated polio vaccine (IPV) and live oral polio vaccine (OPV), are licensed and since 2004, only IPV is recommended for administration as part of the routine childhood immunisation programme and as a travel vaccination, with OPV being reserved for administration during outbreaks of poliomyelitis .
OPV contains live attenuated polio virus serotypes 1, 2 and 3, which replicate in the gastrointestinal tract inducing local mucosal immunity, which reduces the risk of asymptomatic poliomyelitis infection. WHO thus recommends OPV for everyone living in polio-endemic regions, with an additional dose of OPV being administered 1 to 12 months prior to travel to a polio-free country to reduce the risk of transmission through asymptomatic carriage . OPV is shed in the stool for up to 6 weeks, inducing protection in unvaccinated contacts leading to community through herd immunity as well as individual protection. Care must be taken to avoid contact with immunocompromised people during this period. Very rarely, through back-mutations, the live attenuated OPV may cause paralytic poliomyelitis (1.4-3.4 per million doses) .
In the UK, IPV is only available in combination with tetanus, diphtheria, pertussis and/or Hib-containing vaccines and it contains inactivated polio virus serotypes 1, 2 and 3. IPV provides very good individual protection against poliomyelitis without the risk of live oral vaccine-associated paralytic poliomyelitis. Although IPV does not provide the enhanced herd immunity and concomitant community protection afforded by OPV, the risk of importation of wild-type poliovirus is now so low that this benefit is less significant than the potential very rare but severe side effects associated with OPV. Localised pain, swelling, erythema and a mild fever are common side effects with IPV vaccination ,
Schedule The routine immunisation schedule in the UK for IPV consists of three primary doses administered at monthly intervals followed by booster doses every 10 years for travellers to epidemic or endemic areas of polio. In the UK, recommended 10-yearly booster doses of tetanus (Td/IPV) also provide a booster for polio and diphtheria. Travellers who commenced their schedule with OPV can complete the course with IPV .
Efficacy IPV is 95-100% effective in inducing antibodies and providing protection against polio infection for many years. Booster doses every 10 years are then only recommended for travellers living in or travelling to endemic areas [2, 3].
Indication More than 50,000 deaths from rabies occur annually worldwide . Classical rabies is enzootic (high risk), especially in wild dogs and bats, in much of Asia, Africa, and Central and South America. Rabies also remains prevalent in much of eastern Europe. Most other countries, including most of western and central Europe, are considered low or no risk (rabies-free). A classification of no risk does not include the potential risk arising from bats and so rabies infection may still occur. An updated list of rabies risk by country can be find on the WHO’s Rabies Bulletin Europe (www.who-rabies-bulletin.org), Rabnet (www.who.int/rabies/rabnet) or the epidemiology website of the Centers for Disease Control and Prevention (CDC), US (www.cdc.gov/ncidod/dvrd/rabies/epidemiology/ epidemiology.htm) [1-3].
In the UK, rabies vaccination is recommended for all travellers aged >1 month travelling to rabies-enzootic regions for durations longer than 1 month, where satisfactory postexposure medical care is more than 24 hours away, who are likely to engage in outdoor activities, and/or for child travellers. Human rabies immunoglobulin is in scarce supply in many developing countries, and so may be supplies of rabies vaccine. Vaccination is also recommended for travellers working with animals in both high- and low-risk rabies areas, such as veterinary surgeons, zoologists, bat workers and cavers ,
Vaccine Two inactivated rabies vaccine are licensed in the UK , Common side effects indude localised pain and swelling (50%), headache, nausea and abdominal pain (540%) , Guillain-Barr£ Syndrome and other neurological conditions have been reported extremely rarely following rabies vaccination but no causal association has been established.
Schedule The primary immunisation schedule consists of three intramuscular 1.0 ml doses administered on day 0, 7
and 28, or an accelerated schedule over 21 days with a booster dose at 1 year for those at regular and continuous risk, and then further boosters every 3-5 years. Those travellers who are at intermittent risk or revisiting infected areas are recommended to receive a booster dose administered 2 years following a full primary course , WHO also recommends a more economically efficient schedule for those residing in developing countries consisting of three intradermal 0.1ml doses administered on days 0, 7 and 28. Chloroquine may inhibit the immune response to intradermal rabies vaccination and so this schedule should be avoided in travellers taking such malaria prophylaxis .
Efficacy The overall failure rate for cell culture rabies vaccines is estimated to be <1 case per 80,000 treatments, but this does not circumvent the need for the post-exposure administration of rabies vaccine , A course of preexposure rabies vaccination, however, provides a significant level of protection and may modify the post-exposure management such that rabies-specific immunoglobulin may not need to be administered and fewer doses of post-exposure rabies vaccine may be required. Intramuscular vaccination is slightly more immunogenic than administration using the intradermal route. Rabies vaccines containing classical rabies virus provide a varying degree of cross-protection against rabies-related lyssaviruses .
Post-exposure prophylaxis Following a potential risk of exposure to infection with rabies, a risk assessment based on the local incidence of rabies, behaviour characteristics of the animal involved and nature of the exposure should be undertaken. Rabies is more common in certain mammals such as dogs, cats, bats, foxes and raccoons than others such as rats, squirrels and cattle. Rabies infection is more likely in unprovoked attacks from animals with frantic or paralysed behaviour. If possible the animal should be tested for rabies or observed for behavioural changes (for 10 days in the case of dogs and cats), although this should not delay the start of post-exposure prophylaxis . A traveller who wakes up in a room with a bat should seek local medical advice regarding an assessment for the risk of rabies, depending on the local bat epidemiology, as a bat bite or scratch may go unnoticed and may not be visible. Bites and proximal wounds such as those on the hands and face where there is a high density of nerve endings are a higher risk for infection than scratches, mucous membrane contact and more distal wounds ,
Rabies virus travels to the brain via nerves and not in the bloodstream. Prevention of the virus reaching the brain in travellers exposed to a potential source of rabies may therefore be achieved by thorough wound or mucous membrane cleaning, rabies vaccination and/or wound infiltration with human rabies immunoglobulin. Post-exposure prophylaxis should begin immediately within 24 hours of exposure, but if delayed can be commenced any time after exposure since the incubation time of rabies infection maybe days to years. There are no contraindications to post-exposure prophylaxis since the risk of rabies outweighs any potential vaccine adverse effects [2, 3].
Fully vaccinated travellers should receive only two further doses of rabies vaccine on day 0 and day 3 for both low- and high-risk exposures , Unvaccinated and partially vaccinated travellers exposed to a low risk of rabies infection should receive five intramuscular doses of rabies vaccine on days 0, 3, 7, 14 and 28 (Essen regimen). The WHO recommends four doses, with two on day 0 (one in each deltoid muscle), and a single dose on day 7 and 21 (Zagreb regimen). If the risk of exposure is high, they should also receive 20IU/ kg of human rabies immunoglobulin (HRIG) infiltrated into and around the wound on day 0. For small wounds, any remaining HRIG should be administered intramuscularly. For large wounds the HRIG should be diluted with normal saline to ensure that the entire wound is infiltrated. HRIG can be administered up to 7 days after receiving rabies vaccination and provides rapid protection until an adequate immune response has been induced through vaccination .
WHO also recommends a more economically efficient schedule for those residing in developing countries consisting of the intradermal administration of 0.1ml doses of rabies vaccine. Such post exposure intradermal regimens consist of either 8 or 14 doses depending on the type of rabies vaccine used. The 8 dose regimen consists of two doses in each deltoid on days 0, 3, 7 and 28. The 14 dose regimen consists of 8 doses on day 0 (each deltoid, each suprascapular region, each anterolateral thigh, and the left and right lower abdominal quadrants), 4 doses on day 7 (each deltoid and each anterolateral thigh), a single dose on day 30, and a single dose on day 90 .
Rabies vaccines prepared in animal brain tissue and consisting of 5 ml/dose are still available in some developing countries and should be avoided for post-exposure prophylaxis. If HRIG is not available in a developing country, equine rabies immunoglobulin may be used ,
Tetanus, diphtheria and pertussis
Indication All travellers aged >2 months should be up to date with the routine childhood immunisation programme for tetanus, diphtheria and pertussis, and tetanus boosters are routinely recommended every 10 years. Indeed, all travellers should be up to date, especially those travelling to regions with limited medical facilities in case human tetanus immunoglobulin is not available following a tetanus-prone wound .
Unimmunised travellers bom before 1940 may be considered naturally immune to diphtheria. Adult travellers whose last dose of diphtheria vaccine was more than 10 years ago should have a booster dose if they are travelling to regions where diphtheria is endemic or there is an epidemic. This includes travel to Africa, the Indian subcontinent, Southeast Asia and South America. Healthcare workers, laboratory personnel and other travellers living and working within local communities in such regions are at particularly increased risk of exposure to diphtheria , Pertussis vaccination is not routinely recommended in the UK for children aged >10 years or adults who are travelling, and monovalent pertussis vaccine is not available in the UK. In many other countries, such as Australia, the US and Canada, pertussis vaccination is administered as a booster dose as part of the national vaccination schedule and may be considered for adolescents and adults travelling to developing countries where there is a risk of exposure to infection [1, 4],
Vaccine In the UK, intramuscular tetanus, diphtheria and pertussis vaccines are only available in combination for infants and children as Pediacel (DTaP/IPV/Hib), Repevax (dTaP/IPV), Infanrix-IPV (DTap/IPV), and for adults as Revaxis (Td/IPV) , Two strengths of the diphtheria and pertussis components exist, a stronger more immunogenic dose ‘D’ (>/30IU diphtheria toxoid) and ‘aP’ (five pertussis antigen components) for the primary immunisation of travellers aged 6 weeks to 10 years, and a smaller dose ‘d’ (2 IU diphtheria toxoid) and ‘ap’ (three pertussis antigen components) for travellers aged >10 years. The lower-strength diphtheria and pertussis vaccines have less risk of inducing vaccine-associated adverse reactions while remaining sufficiently immunogenic in the older age group (but not in younger travellers) , The choice of combination vaccine will also depend on the need to provide protection against the other component vaccines.
Side effects may include localised pain, swelling and erythema (25%), unilateral limb swelling (3%), vomiting (2%), persistent crying (1:1,000), seizures (1:14,000), high fever (1:16,000) and anaphylaxis (< 1:1,000,000) , A very rare side effect of tetanus-containing vaccines is brachial neuritis post tetanus vaccination (5-10 per million doses) .
Schedule The primary immunisation schedule for tetanus consists of three doses administered at 3-monthly intervals followed by a booster dose at 1-3 years and a second booster dose at 5-10 years. Subsequent booster doses should then be given routinely every 10 years. After the age of 10 years, booster doses are normally given with Revaxis (Td/IPV). Repevax (dTaP/IPV), which contains diphtheria, tetanus, pertussis and polio, is licensed for use in the UK but is not administered routinely as a booster dose for adolescents or adults.
Efficacy The diphtheria, acellular pertussis and tetanus components are approximately 97%, 92% and 100% effective respectively in preventing infection [3, 96-98].
Post-exposure tetanus prophylaxis Travellers are considered fully immunised against tetanus if they have received a primary course of tetanus vaccine with a booster dose within the previous 10 years [1, 2], For travellers to areas where medical attention may not be accessible and whose last dose of a tetanus-containing vaccine was more than 10 years previously, a booster dose should be given prior to travelling, even if the individual has received five doses of tetanus vaccine previously. This is a precautionary measure in case immunoglobulin is not available to the individual should a tetanus-prone injury occur.
A dose of human tetanus immunoglobulin is only recommended for fully immunised travellers with high-risk, heavily contaminated wounds or with extensive devitalised tissue . Travellers exposed to a tetanus-prone wound who are non-immune (either unvaccinated, incompletely vaccinated or whose boosters are not up to date) should have a dose of tetanus vaccine, complete their primary immunisation course of tetanus vaccination if still incomplete, and receive a dose of human tetanus immunoglobulin. For those travellers who are not protected against tetanus, postexposure doses of tetanus vaccine do not induce a sufficient immune response within the relatively short incubation time of tetanus infection, but will protect the traveller from future exposure , Booster tetanus vaccine doses and human tetanus immunoglobulin are not recommended for clean wounds, even in non-immune travellers. Particular care should be taken with immunocompromised travellers even if they have been fully immunised, because they might not have mounted a sufficient immune response [2, 3]. Human tetanus immunoglobulin is administered as a single 1ml (250IU) intramuscular injection. This dose is doubled to
0 ml (500 IU) for contaminated burns, high-risk wounds and if more than 24 hours has elapsed since the injury. Human tetanus immunoglobulin is also used in the treatment of suspected and confirmed cases of tetanus with a dose of 5,000-10,000 IU by intravenous infusion or multiple divided intramuscular injections ,
Indication Vaccination against tick-borne encephalitis should be considered for all travellers aged >1 year to endemic regions, especially if they are partaking in high-risk activities such as hiking, camping, farming and forestry. This includes travel to many of the forested regions of central and eastern Europe, Scandinavia, large parts of Russia and Siberia, and northern and eastern China, particularly during the spring and summer months ,
Vaccine Tick-borne encephalitis vaccine is very well tolerated and it is contraindicated in travellers with known anaphylactic reactions to egg products or other components of the vaccine ,
Schedule The primary immunisation schedule for tick- borne encephalitis vaccine consists of two doses administered over 1 month or an accelerated course over 2 weeks with booster doses administered at 3- to 5-yearly intervals. In some countries such as Austria it is part of the national immunisation schedule ,
Efficacy Tick-borne encephalitis vaccine is effective against the European and probably the Far East (but not Siberian) subtype of tick-borne encephalitis, providing up to 98% protection .
Indication In the UK, vaccination against TB is recommended for unvaccinated tuberculin skin testing-negative travellers from birth to adulthood at increased risk of exposure. This includes healthcare professionals, laboratory personnel and all those travelling for longer than 3 months to regions with a high (>40 per 100,000) annual incidence of TB. Many countries in Africa, South and Central America, Southeast Asia and the Indian subcontinent have a high annual incidence of TB. Although vaccination against TB is no longer part of the routine childhood immunisation programme in the UK, vaccination of travellers aged <16 years who may be at increased risk of exposure is important since they are at increased risk of severe TB infection. This includes children travelling to or having lived in a country or region with a high incidence of TB for longer than 3 months, or if they have a parent or grandparent who was born in such a country. This policy is in accordance with the WHO recommendations for routine immunisation of children living in countries with a high prevalence of TB and for selective immunisation of high- risk children living in low-risk countries [ 1,2,99].
A tuberculin skin test is recommended before TB vaccination in travellers aged >6 years and in travellers who have been exposed to TB ,
Vaccine In the UK, the bacillus Calmette-Gu6rin (BCG) vaccine consists of a live attenuated strain of Mycobacterium bovis. It is administered by intradermal injection into the lateral part of the left upper arm at the level of the insertion of the deltoid muscle , The normal response to BCG vaccination is slight induration at the injection site, which develops into a papule that may ulcerate and be associated with regional lymphadenopathy (<1 cm) before healing over several weeks, leaving a small scar. Rare but severe local side effects are usually due to poor administration technique, wrong dosage or inadvertently vaccinating tuberculin- positive travellers. Injection into the shoulder tip predisposes to large keloid scars, subcutaneous injection predisposes to abscess formation, and covering an oozing injection site with an impervious dressings results in delayed healing and a larger scar. Other rare side effects include regional lymphadenopathy (>lcm), suppurative lymphadenitis (100-1,000 per million doses), osteitis, osteomyelitis and disseminated BCG infection (0.19-1.56 per million doses), which may need to be treated with rifampicin and isoniazid [1,2]. Other vaccines may be given at the same time as BCG but not in the same limb for at least 3 months due to the risk of regional lymphadenitis. BCG vaccination is contraindicated in travellers who have previously had TB infection, been vaccinated with BCG, have a positive tuberculin skin test or are immunocompromised, including travellers with HIV ,
Schedule The primary schedule in newborns, children and adults is a single intradermal dose. Booster doses are not recommended ,
Efficacy The BCG vaccine is not very immunogenic and is no longer used in many countries where two-step tuberculin skin testing is preferred (see US section). It provides 70-80% protection against severe miliary TB and TB meningitis in infants and young children. It is less effective in protecting against pulmonary TB in adults and the efficacy in travellers aged >35 years is very poorly established [2,99,100]. Overall protection from tuberculosis infection is only about 51%. BCG is not usually recommended for travellers aged >45 years because most will have had some natural exposure. However, all tuberculin-negative travellers, including those aged >45 years, can be vaccinated with BCG if the risk of TB exposure is high. Protection begins within 6-8 weeks postvaccination and probably lasts 10-15 years before it begins to wane. Booster doses are not recommended as there is no evidence of significant additional protection but there is an increased risk of side effects [2, 3, 100, 101].
Tuberculin skin testing Tuberculin skin testing is recommended prior to BCG vaccination for all unvaccinated travellers aged >6 years, all travellers without a characteristic BCG scar who are uncertain whether they have had BCG vaccination, and for all travellers who have been exposed to
TB in the past or are at increased risk of previous exposure. It is not recommended post-vaccination as further booster doses of BCG are not recommended. Tuberculin skin testing is also used as a method of screening for evidence of infection in both unvaccinated and vaccinated travellers for latent or active TB post exposure. It may take up to 6 weeks following an exposure for tuberculin sensitivity to develop and so a negative result should be repeated at 6 weeks.
Tuberculin purified protein derivative (PPD) consists of protein antigens from seven strains of M. tuberculosis. The Mantoux test involves the intradermal injection of 0.1 ml of PPD into the flexor surface of the left forearm to form a 7 mm bleb. Within 48-72 hours of administration, the area of induration at the injection site is measured. A positive result is due to a type four hypersensitivity reaction due to previous exposure to mycobacteria. A positive result may be due to latent or active tuberculosis or non-tuberculosis mycobacteria infection, or previous BCG vaccination. False- negatives may occur, for example in travellers who are immunosuppressed, including with HIV, or malnourished. Results, particularly for screening for infection, should always be interpreted along with any clinical symptoms, known risk of exposure, and other test results including sputum smears and culture, a chest X-ray, histopathology and a Quantiferon blood test, which is more specific for exposure to M. tuberculosis [2, 3].
Indication Typhoid fever is present worldwide and affects an estimated 22 million people per annum, resulting in approximately 200,000 deaths , The risk of infection in unvaccinated travellers to India is estimated at 300 per 100,000 per month of stay and the importance of vaccination cannot be overemphasised, with the evidence of increasing antibiotic resistance to Salmonella typhi in South Asia , Vaccination is recommended for all travellers aged >2 years travelling to endemic areas of typhoid fever, including the Indian subcontinent, parts of Southeast Asia and the Middle East, Africa, and South and Central America, where hygiene and sanitation are poor [ 102]. Combined hepatitis A and typhoid vaccines can be used when protection against both hepatitis A and typhoid are required ,
Vaccine Both live and inactivated typhoid vaccines are licensed; the live oral typhoid vaccine consists of attenuated Ty21a strain of Salmonella typhi, and combined polysaccharide typhoid and hepatitis A vaccines are licensed similarly (see Hepatitis A section) ,
The most common side effects associated with the Ty21a vaccine are gastrointestinal upset and influenza-like symptoms. Antibiotics should be avoided 3 days before and after vaccination with Ty21a to avoid the theoretical risk of interaction. Vaccination should be postponed in travellers with diarrhoea and vomiting until recovery. Ty21a is contraindicated in travellers who are imunocompromised (including HIV) or pregnant , Side effects with the inactivated typhoid vaccines include fever, headache (20%), localised pain and erythema ,
Schedule The Ty21a vaccine is licensed for administration to travellers aged >6 years and consists of three oral capsules, the first administered on day 1, the second on day 3 and the third on day 5. Booster doses comprise of the complete course of three capsules administered over 4 days and are recommended annually for travellers travelling from nonendemic areas to endemic regions .
The monovalent polysaccharide typhoid vaccine is licensed for administration to travellers aged >2 years and comprises of a single dose only, with booster doses administered every 3 years for continued protection. This vaccine may be considered for travellers aged 1-2 years, although polysaccharide vaccines are poorly immunogenic in travellers aged <2 years and advice regarding strict food and water hygiene is an essential adjunct to vaccination ,
Efficacy The live oral and inactivated polysaccharide typhoid vaccines provide only 55-78% protection [3,4,103-105]. It is therefore essential that travellers are advised about the importance of strict personal, food and water hygiene. Vaccination does not provide protection against Salmonella paratyphi ,
Indication Travellers who have had chickenpox or herpes zoster infection should be considered naturally immune and varicella serology should be performed to confirm non- immune status before vaccination. Varicella vaccination is not currently part of the routine childhood immunisation programme in the UK nor routinely recommended for non- immune women of child-bearing age as it is in other countries ,
Varicella zoster virus is present worldwide and in temperate climates many adults are seropositive from childhood exposure. Varicella zoster virus is more common in tropical countries, but despite this, infection occurs predominantly in adolescents and adults. Many indigenous adults in tropical countries are thus seronegative and at increased risk of severe varicella infection . Therefore varicella vaccination should be considered for all non-immune travellers, especially women of child-bearing age planning to live in close proximity with local indigenous people in tropical countries. Vaccination should also be considered for non-immune travellers and immigrants from tropical to temperate climates as they may be seronegative and at risk of infection from the indigenous population to which they migrate. Consequently, if the same group return to their country of origin for a visit, they may inadvertently transmit varicella infection to those that they visit .
Vaccine Two live varicella vaccines are licensed in the UK and their side effects may include a localised or generalised vesicular or papular rash in the first month after vaccination (10% adults, 5% children) [2, 107]. Very rarely, the vaccine virus can establish latent infection and reactivate to cause herpes zoster infection, although this risk is much lower than the risk from wild varicella virus. The vaccine is contraindicated in travellers who are pregnant, immunocompromised or who have had an anaphylactic reaction to any of the vaccines’ constituent parts ,
Schedule The primary immunisation schedule in travellers aged 1-13 years consists of a single dose and for travellers aged >13 years two doses over 1 month. Further booster doses are not recommended ,
Efficacy Seroconversion rates of 97% have been demonstrated in infants receiving one dose of vaccine, with consistently high levels of antibody present for up to 10 years following completion of the course. In recipients aged >13 years, approximately 78% seroconvert after the first dose, rising to 99% after completion of the course. The vaccine provides up to 90% protection in young children and 75% protection in adolescents and adults against chicken pox [2, 107,108]. Most of the individuals with breakthrough infections have milder clinical courses.
Post-exposure prophylaxis Immunocompromised and non- immune pregnant travellers should be offered human varicella zoster immunoglobulin within 10 days of a significant exposure to varicella zoster , Varicella vaccine alone may also be administered to non-immune individuals up to 3 days following varicella zoster virus exposure, where it may prevent chickenpox infection, although this use is not routine ,
Indication Yellow fever is endemic in certain jungle regions of Africa and South America. It has never occurred in Asia, although in many Asian countries the vector for transmission is present. During the period 1970 to 2010, there have been nine reported cases of yellow fever infection, of which eight were fatal, occurring in unvaccinated North American
and European travellers. Of these, only one reported case of yellow fever infection occurred in a traveller who was vaccinated [3,4]. Many countries where yellow fever is endemic or where there are mosquito vectors and non-human primate hosts require an International Certificate of Vaccination and Prophylaxis (ICVP) under the WHO International Health Regulations, for entry of travellers arriving from, or who have been in transit through, endemic countries. Some countries require a certificate for all travellers and others do not have any yellow fever requirements. These requirements are to limit the spread of or potential importation and introduction of yellow fever in a country. This list is updated on an annual basis on the WHO website (www.who.int/ith). The vaccine can only be administered in yellow fever- designated centres that are designated to issue such certificates .
WHO recommends yellow fever vaccination for individuals travelling to endemic areas in sub-Saharan Africa or Central and South America, especially if the risk of contracting yellow fever outweighs the rare but potentially serious adverse effects of the vaccine. Yellow fever occurs both endemically and in epidemics, when the risk of transmission is higher. In West Africa, endemic yellow fever occurs in a jungle cycle, savannah cycle and urban cyde involving mosquitoes and humans , This risk is greatest at the end of the rainy season from July to October , In South America, endemic yellow fever is primarily a jungle cyde involving non-human primates, with humans becoming infected when they enter the jungle. The risk is greatest during the rainy season between January and May , A careful risk assessment should be carried out to determine the risk of yellow fever based on the travel itinerary and the risk of adverse events associated with administration of the vaccine. The vaccine should also be considered in individuals travelling to a country where an International Yellow Fever Vaccination Certificate is a requirement. It is important to note that a traveller may be exposed to yellow fever in a country that does not require yellow fever vaccination , Also there are some regions in Africa and South America where yellow fever virus is present but there is a lack
of reported human cases either due to poor local surveillance, high immunity in the indigenous people or a low level of transmission ,
Vaccine Yellow fever vaccine is a live attenuated vaccine administered subcutaneously , Vaccine side effects are normally mild and include localised pain, fever, headache and myalgia (30%). Vaccination is contraindicated in travellers who are immunocompromised, pregnant or have had a previous anaphylactic reaction to egg. However, vaccination maybe considered in travellers who are in the third trimester of pregnancy and in travellers with HIV who have a CD4 count >200 and low viral load if the risk of yellow fever exposure is extremely high. Travellers for whom yellow fever vaccination is contraindicated should avoid travel to endemic regions or adopt a strict mosquito bite prevention strategy, particularly in the daytime. For travellers in whom yellow fever vaccination is contraindicated, a letter of exemption can be issued by the yellow fever vaccine centre for travel to countries where an International Certificate of Vaccination and Prophylaxis (ICVP) against yellow fever is required for entry [1, 2] ,
Yellow fever vaccine-associated encephalitis is a rare neurological adverse reaction that affects infants in whom the
risk is inversely proportional to age, and is known to occur rarely as part of yellow fever vaccine-associated neurological disease (YEL-AND) . Vaccination is contraindicated in travellers aged <6 months where the risk is 500-4,000 per million doses, and only recommended for travellers aged 6-9 months if the risk of yellow fever exposure is unavoidable . Yellow fever vaccine-associated neurological disease (YEL-AND) is a rare adverse reaction that affects non- immune travellers undergoing primary immunisation. It presents 3-28 days post-vaccination and symptoms/signs include fever, headache, confusion, focal neurological deficits, coma and/or Guillain-Barr£ Syndrome . This risk increases substantially in travellers aged >60 years from 4 to 17 cases per million doses. The cerebrospinal fluid (CSF) contains yellow fever virus IgM antibody, with a raised cell count and protein. There is usually complete recovery [1,2,110, 111]. Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is another rare adverse reaction that effects non-immune travellers undergoing primary immunisation [112, 113]. It presents 2-7 days post-vaccination with symptoms resembling yellow fever infection, including fever, headache, malaise, hepatitis, hypotension, multi-organ failure and death in more than 60% of cases. The risk also increases substantially in travellers aged >60 years from 3 to 20.5 cases per million doses . Travellers who have a thymus disorder or have had a thymectomy are also at increased risk of YEL-AVD and vaccination is contraindicated in such travellers , Yellow fever virus and viral antigens have been detected in patients with YEL-AVD, although there is no evidence the attenuated virus has reverted to a more virulent form ,
The risk of yellow fever infection in travellers to endemic areas generally outweighs the small risk of vaccine-associated serious adverse events. However, it is important to vaccinate only those travellers at risk of exposure to yellow fever, especially infants and elderly travellers, based on a comprehensive travel health risk assessment [3,114],
Schedule The primary immunisation schedule for travellers aged >6 months consists of a single dose with booster doses every 10 years for ongoing exposure ,
Efficacy Yellow fever vaccination provides 95-100% protection in travellers for at least 10 years and probably for life [2, 3, 115-117]. It takes approximately 10 days to mount a sufficient immune response to the vaccine and consequently, the International Yellow Fever Vaccination Certificate becomes valid 10 days post-vaccination and lasts for 10 years. The vaccine should thus be administered at least 10 days prior to departure. For subsequent re-immunisations the certificate is valid immediately if they occur within the 10-year period.