Vaccine-preventable diseases: From paediatric to adult targets

Vaccine-preventable diseases: From paediatric to adult targets

EJINME-02642; No of Pages 10 European Journal of Internal Medicine xxx (2013) xxx–xxx Contents lists available at ScienceDirect European Journal of ...

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EJINME-02642; No of Pages 10 European Journal of Internal Medicine xxx (2013) xxx–xxx

Contents lists available at ScienceDirect

European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim

Review Article

Vaccine-preventable diseases: From paediatric to adult targets Susanna Esposito a,⁎, Paolo Durando b, Samantha Bosis a, Filippo Ansaldi b, Claudia Tagliabue a, Giancarlo Icardi b, for the ESCMID Vaccine Study Group (EVASG) a Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy b Hygiene Unit, Department of Health Science, University of Genoa, IRCCS AOU San Martino-IST, Genoa, Italy

a r t i c l e

i n f o

Article history: Received 26 October 2013 Received in revised form 11 December 2013 Accepted 16 December 2013 Available online xxxx Keywords: Adults The elderly Infectious diseases Prevention Vaccine Vaccination

a b s t r a c t The morbidity and mortality related to many communicable infectious diseases have significantly decreased in Western countries largely because of the use of antibiotics, and the implementation of well-planned vaccination strategies and national immunisation schedules specifically aimed at infants and children. However, although immunisation has proved to be highly effective for public health, more effort is needed to improve the currently sub-optimal rates of vaccination against various diseases among adults who may be at risk because of their age, medical condition or occupation. The vaccines currently licenced in Western countries are safe, immunogenic and effective against many infectious diseases and their complications, but the availability of newer vaccines or vaccines with new indications, the evolving ecology and epidemiology of many infections, population ageing, and other demographic changes (i.e. the increasing prevalence of chronic comorbidities and immunodeficiencies, mass migration, new working relationships, and widespread international tourism) require changes in the approach to immunisation. There is now a need for appropriate preventive measures for adults and the elderly aimed at protecting people at risk by using every possible catch-up opportunity and recommending specific age-related schedules on the basis of local epidemiology. © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

1. Introduction The morbidity and mortality associated with many communicable infectious diseases have significantly decreased in Western countries largely because of the use of antibiotics, and the implementation of well-planned vaccination strategies and national immunisation schedules specifically aimed at infants and children [1,2]. Children's health has improved, and both the quality and length of life has increased in the population as a whole [3]. However, although immunisation has proved to be highly effective for public health [4], more effort is needed to improve the currently sub-optimal rates of vaccination against various diseases among adults who may be at risk because of their age, medical condition or occupation [5–9]. There is no doubt that rapid population ageing, which is mainly due to the decrease in age-specific mortality during the fourth decade of life, is a major challenge in areas such as the United States, Canada and most European countries [10,11]. It has also led to an increase in the number

⁎ Corresponding author at: Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122 Milano, Italy. Tel.: +39 02 55032498; fax: +39 02 50320206. E-mail address: [email protected] (S. Esposito).

of N 80-year-olds, which is expected to triple over the next 50 years [12] and make them the largest at-risk category of adults for whom vaccines are currently recommended throughout the world. Together with poor immune responses and the sub-optimal efficacy of some conventional/ plain vaccines, progressive ageing is therefore a key factor in the developing public health priority of improving vaccination strategies. It is also expected that the near future will see an increase in a number of age-related disorders and conditions, such as cancer, cardiovascular diseases, diabetes, obesity and dementia [13–15], all of which are well-known risk factors for the occurrence of various vaccinepreventable diseases (i.e., influenza as well as invasive pneumococcal disease). Improving vaccination strategies specifically aimed at adults and the elderly can therefore also reduce the burden of these chronic conditions by reducing hospital admissions, health costs and mortality rates, and improving the quality of life [16]. The demographic changes taking place in developed countries have also been due to the recent effects of globalisation: mass migration, changing working relationships, and more widespread international tourism have not only had an impact on social and cultural values, but also on the epidemiology of vaccine-preventable diseases such as influenza, pneumococcal infections, hepatitis A virus [HAV] infection, typhoid fever and meningococcal disease [17,18]. The aim of this review is to summarise the results obtained by vaccination programmes for adults and the elderly over the last ten years,

0953-6205/$ – see front matter © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejim.2013.12.004

Please cite this article as: Esposito S, et al, Vaccine-preventable diseases: From paediatric to adult targets, Eur J Intern Med (2013), http:// dx.doi.org/10.1016/j.ejim.2013.12.004

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describe the rationale underlying them, and highlight the barriers to vaccination. 1.1. Rationale for adult immunisation Adults can protect themselves and the people living with them by keeping their vaccinations up to date. Every year, scientific and medical experts review and update the recommended adult immunisation schedules on the basis of the latest research into controlling vaccinepreventable diseases [7]. Recent reports indicate a high incidence of vaccine-preventable diseases that lead to approximately 45,000 deaths each year in the United States, the majority due to influenza [19]. An estimated 44,000 cases of invasive pneumococcal disease were reported in 2008, with most of the approximately 4500 deaths involving people aged N 35 years [19]. Furthermore, in 2009, an estimated 4070 deaths were caused by infection, with HPV strains causing the majority of cervical cancers even though they can be prevented by HPV vaccine and routine Papanicolaou smears [19]. Various vaccines are recommended for adults on the basis of age, vaccination history, current state of health, lifestyle, occupation, use of immunosuppressive drugs and travelling activities, but vaccination coverage is low [7]. Healthcare workers (HCWs) should be aware of the importance of systematically assessing patients' vaccination histories and recommending and providing the appropriate vaccines because, like the implementation of reminder/recall systems and standing orders, a strong recommendation from an HCW is associated with increased vaccine use [7]. Table 1 shows the vaccinations recommended for adults on the basis of their clinical status, whereas Table 2 summarises contraindications, precautions and the most frequent averse events to adult vaccines. 1.2. Tetanus/diphtheria/acellular pertussis vaccine Tetanus/diphtheria toxoid vaccine is recommended for all unvaccinated adults, with boosters being administered every ten years to those who have previously been vaccinated [20]. However, patients presenting with a dirty or major wound more than five years after their last injection should be revaccinated, and adults aged b65 years should receive a single dose of tetanus/diphtheria/acellular pertussis vaccine instead of the tetanus/diphtheria booster [7]. Given the reemergence of pertussis in developed countries [21], the targeted populations for pertussis-containing vaccine include HCWs and anyone exposed to infants aged less than 12 months [7,21]. 1.3. Measles/mumps/rubella vaccine One of the goals of the World Health Organisation is the global eradication of measles and rubella by 2015 [22], but there have been a

number of recent measles outbreaks in Europe [23]. The very large number of adult cases therefore means that it is important to remember that measles/mumps/rubella vaccination is recommended for all previously unvaccinated adults without a clinical history of measles or rubella, and for adults who have received only a single dose of the vaccine [7,22].

1.4. Varicella vaccine Because of the high risk of varicella-associated complications in adulthood [24], a single-antigen two-dose varicella vaccination is recommended for healthy adults without a clinical history of varicella, particularly HCWs, the household contacts of immunocompromised subjects, non-pregnant women of childbearing age, people frequently exposed to children, and international travellers [7].

1.5. Human papillomavirus (HPV) vaccine Women up to the age of 26 years who have not been vaccinated against HPV should receive three doses of HPV vaccine the second and third respectively 1–2 and 6–12 months after the first [7]. In some countries, the quadrivalent HPV vaccine is recommended for similarly aged males [25].

1.6. Influenza vaccination Annual seasonal vaccinations against influenza are recommended for all adults in the United States (including healthy adults) but, in other countries, they are only recommended for adults with underlying conditions that increase the risk of influenza-related complications [7,26]. All European countries recommend influenza vaccinations for patients with chronic pulmonary or cardiovascular diseases; renal diseases, immune system disorders, and hematological or metabolic diseases are considered eligibility factors in N90% of European countries; hepatic diseases in 58%; and neurological conditions that may impair respiratory function in 44%. Only about 50% of countries recommend vaccinating the household contacts of the people for whom the vaccination is recommended [26]. Interestingly, in a recent meta-analysis of randomised controlled trials, the use of influenza vaccine was associated with a lower risk of major adverse cardiovascular events [27]. The greatest treatment effect was seen among the highest-risk patients with more active coronary disease, highlighting that a large, adequately powered, multicenter trial is warranted to address these findings and assess individual cardiovascular end points.

Table 1 Recommended vaccinations for adults depending on their clinical status. Vaccine

Populations

Tetanus/diphtheria toxoid vaccine

All unvaccinated adults; as a 10-yearly booster in previously vaccinated adults; patients presenting with a dirty or major wound more than 5 years after their last injection. A single dose of tetanus/diphtheria/acellular pertussis vaccine should be given in place of the tetanus/diphtheria booster in adults aged b65 years HCWs; adults exposed to infants aged less than 12 months All previously unvaccinated adults with a negative clinical history of measles or rubella; all adults who received a single dose of measles/mumps/rubella vaccine Healthy adults with a negative clinical history of varicella (particularly HCWs, the household contacts of immuno-compromised subjects, non-pregnant women of childbearing age, people with frequent contacts with children, and international travellers) Women up to the age of 26 years; in some countries, also males up to the age of 26 years Significant differences in recommendations across countries Significant difference in recommendations across countries Patients with terminal complement component deficiencies or asplenia; previously unvaccinated college freshmen; military recruits; travellers to endemic regions In the United States: adults aged ≥60 years regardless of history of herpes zoster

Pertussis vaccine Measles/mumps/rubella vaccine Varicella vaccine Human papillomavirus vaccine Seasonal influenza vaccine Pneumococcal vaccine Quadrivalent meningococcal conjugate vaccine Herpes zoster vaccine HCWs: healthcare workers.

Please cite this article as: Esposito S, et al, Vaccine-preventable diseases: From paediatric to adult targets, Eur J Intern Med (2013), http:// dx.doi.org/10.1016/j.ejim.2013.12.004

Vaccine

Contraindications

Precautions

Most frequent adverse events

Tetanus/diphtheria/pertussis vaccine

Severe allergic reaction (i.e., anaphylaxis) after a previous dose or to a vaccine component. For pertussis-containing vaccines: encephalopathy (i.e., coma, decreased level of consciousness, or prolonged seizures) not attributable to another identifiable cause within 7 days of administration of a previous dose of vaccine

Pain where the shot was given (about 2 in 3 adults); redness or swelling where the shot was given (about 1 person in 5); mild fever of at least 100.4 °F (up to 1 in 100 adults); headache (about 3 or 4 people in 10); tiredness (about 1 person in 3 or 4); nausea, vomiting, diarrhoea, stomach ache (up to 1 in 10 adults)

Measles/mumps/rubella vaccine

Severe allergic reaction (i.e., anaphylaxis) after a previous dose or to a vaccine component. Known severe immunodeficiency (i.e., from hematologic and solid tumours, receipt of chemotherapy, congenital immunodeficiency, or long-term immunosuppressive therapy or patients with HIV infection who are severely immunocompromised). Pregnancy. Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component. Known severe immunodeficiency (i.e., from hematologic and solid tumours, receipt of chemotherapy, congenital immunodeficiency, or long-term immunosuppressive therapy or patients with human immunodeficiency virus infection who are severely immunocompromised). Pregnancy. Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component.

Moderate or severe acute illness with or without fever. Guillain–Barrè syndrome within 6 weeks after a previous dose of tetanus toxoid–containing vaccine. History of arthus-type hypersensitivity reactions after a previous dose of tetanus or diphtheria toxoid–containing vaccine; defer vaccination until at least 10 years have elapsed since the last tetanus toxoid-containing vaccine. For pertussis-containing vaccines: progressive or unstable neurologic disorder, uncontrolled seizures, or progressive encephalopathy until a treatment regimen has been established and the condition has stabilised. Moderate or severe acute illness with or without fever. Recent (within 11 months) receipt of antibody-containing blood product (specific interval depends on product). History of thrombocytopenia or thrombocytopenic purpura. Need for tuberculin skin testing Recent (within 11 months) receipt of antibody-containing blood product (specific interval depends on product). Moderate or severe acute illness with or without fever. Receipt of specific antivirals (i.e., acyclovir, famciclovir, or valacyclovir) 24 h before vaccination; avoid use of these antiviral drugs for 14 days after vaccination

Soreness or swelling where the shot was given (up to 1 out of 3 adults); fever (1 person out of 10, or less); mild rash, up to a month after vaccination (1 person out of 25).

Moderate or severe acute illness with or without fever. Pregnancy.

Pain (about 9 people in 10); redness or swelling (about 1 person in 2); fever of 99.5 or higher degrees Fahrenheit (about 1 person in 8); headache or fatigue (about 1 person in 2); nausea, vomiting, diarrhoea, or abdominal pain (about 1 person in 4); muscle or joint pain (up to 1 person in 2) Soreness, redness, or swelling where the shot was given (about 1 person in 5); hoarseness, sore, red or itchy eyes, cough, fever, aches, headache, itching, fatigue (about 1 person in 10) About 1 out of 3 had swelling where the shot was given. About 1 out of 3 had a mild fever. Up to about 8 out of 10 became fussy or irritable. As many as half the people who get meningococcal vaccines have mild side effects, such as redness or pain where the shot was given. Redness, soreness, swelling, or itching at the site of the injection (about 1 person in 3). Headache (about 1 person in 70).

Varicella vaccine

Human papillomavirus vaccine

Seasonal influenza vaccine

Severe allergic reaction (i.e., anaphylaxis) after previous dose of any influenza vaccine or to a vaccine component, including egg protein. Severe allergic reaction (i.e., anaphylaxis) after a previous dose or to a vaccine component.

Moderate or severe acute illness with or without fever. History of Guillain–Barré syndrome within 6 weeks of previous influenza vaccination. Moderate or severe acute illness with or without fever.

Quadrivalent meningococcal conjugate vaccine

Severe allergic reaction (i.e., anaphylaxis) after a previous dose or to a vaccine component.

Moderate or severe acute illness with or without fever.

Herpes zoster vaccine

Severe allergic reaction (e.g., anaphylaxis) to a vaccine component. Known severe immunodeficiency (i.e., from haematologic and solid tumours, receipt of chemotherapy, or long-term immunosuppressive therapy or patients with HIV infection who are severely immunocompromised) Pregnancy.

Moderate or severe acute illness with or without fever. Receipt of specific antivirals (i.e., acyclovir, famciclovir, or valacyclovir) 24 h before vaccination; avoid use of these antiviral drugs for 14 days after vaccination.

Pneumococcal vaccine

Fever (up to 1 person out of 6); mild rash (about 1 person out of 20); swelling of glands in the cheeks or neck (about 1 person out of 75). They occur less often after the second dose.

S. Esposito et al. / European Journal of Internal Medicine xxx (2013) xxx–xxx

Please cite this article as: Esposito S, et al, Vaccine-preventable diseases: From paediatric to adult targets, Eur J Intern Med (2013), http:// dx.doi.org/10.1016/j.ejim.2013.12.004

Table 2 Contraindications, precautions and most frequent adverse events to commonly used vaccines in adults.

Adapted from Reference 7.

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1.7. Pneumococcal vaccination There are also some differences between countries concerning adult pneumococcal vaccinations [28]. The 13-valent pneumococcal conjugate vaccine (PCV13) is recommended for people aged ≥ 19 years with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leaks or cochlear implants who have not previously received PCV13 or pneumococcal polysaccharide vaccine (PPSV23) [7,28]. They should receive a single dose of PCV13 followed by a dose of PPSV23 at least eight weeks later. Adults aged ≥19 years with the same conditions who have previously received one or more doses of PPSV23 should receive a dose of PCV13 one or more years after the last PPSV23 dose [7]. Other high-risk categories, including patients with chronic heart or lung disease, diabetes mellitus or chronic liver disease, and people exposed to alcoholism or cigarette smoking, should receive PPSV23, with the first dose being given no sooner than eight weeks after PCV13 and at least five years after the most recent dose of PPSV23 [7]. 1.8. Meningococcal vaccination Finally, the use of the quadrivalent meningococcal conjugate vaccine (which consists of groups A, C, Y and W135 conjugated to diphtheria toxoid) is recommended for patients with terminal complement component deficiencies or asplenia, previously unvaccinated college freshmen, military recruits, and travellers to endemic regions [7,29]. Re-vaccination is not routinely recommended, but people who remain at risk of developing meningococcal infection should receive a second dose 2–3 years after the first. 1.9. Immunisation in the elderly In Western (particularly European) countries, the proportion of people aged ≥65 years increased from 13.9% in 1990 to 17.4% in 2010, and it is estimated that the figure will reach 30% by 2060 [30]. The incidence of infections, their severity, the risk of complications, and hospitalisation and mortality rates all increase with age, and the elderly are classified as one of the highest risk groups mainly because of their reduced immune response and the high prevalence of risk factors [31]. Vaccination is certainly the most efficient means of preventing infectious diseases, although it has been established that most vaccines are less effective in the elderly. Immunosenescence (a set of age-related changes in the innate and adaptive immune systems) affects the antibody responses to vaccine components in many elderly patients, and limits the immunogenicity and efficacy of the vaccines themselves. These changes include a decrease in the number of Langerhans cells, a reduction in the capacity of dendritic cells to produce antigen, a decrease in natural killer cell cytotoxicity and cytokine production, reduced phagocytosis and superoxide production in neutrophils and monocytes/macrophages, defects in the production of toll-like receptors (TLRs), and a decrease in the production of MHC class I and II molecules [32–42]. In addition, the regression of the thymus reduces the production of mature naive T cells and hence their circulation in peripheral blood and lymphoid organs, and there is a decline in the ability of B cells to produce antibodies against novel antigens [32–42]. A number of strategies have been explored in an attempt to increase immune responses and optimise vaccine efficacy in the elderly, including the use of vaccine adjuvants or more efficient routes of vaccine delivery, the adaptation of already licenced vaccines, and the development of new vaccines [43]. 1.10. Influenza vaccination Influenza is a major cause of vaccine-preventable morbidity and mortality in the elderly, and annual vaccinations against influenza are generally recommended, although the age limits vary from country to

country [26]. A number of systematic reviews and meta-analyses have shown that influenza vaccination reduces hospitalisation and mortality: the number of hospitalisations of non-institutionalised elderly people may be as much as 25–39% and overall mortality during influenza seasons is reduced by 39–75% [44–47]. However, the real effectiveness of influenza vaccines in the elderly is still unclear because of variations in epidemiological factors such as the prevalence of the virus, the virulence of the circulating strain, and differences between it and the strains included in the vaccine. Moreover, the immunogenicity of influenza vaccines in terms of seroconversion and seroprotection rates is generally lower in the elderly than in younger adults, and decreases with increasing age. Most studies have shown that the ability of influenza vaccines to induce an effective and robust immune response is reduced in the elderly, and one recent meta-analysis found that clinical vaccine efficacy in the elderly is of 17–53% (depending on circulating viruses) in comparison to 70–90% of clinical vaccine efficacy in young adults [48]. Optimising protection against influenza among the elderly is an urgent need, and strategies explored so far are the development of new and more efficient vaccines, and the extension of vaccination to other populations in close contact with the elderly. It has been demonstrated that MF59-adjuvanted vaccines can enhance and broaden the immune response in comparison with subunit influenza vaccines, and induce higher seroprotection rates especially among subjects aged N 75 years [49–53]. The immunogenicity of virosomal-adjuvanted influenza vaccine has been widely studied in the elderly, but the results of comparative studies of virosomal, standard and MF59-adjuvanted vaccines are controversial [54–65]. Studies of the immunogenicity of the currently approved intradermal influenza vaccine in elderly subjects aged N60 years have shown that the 15 μg per strain formulations lead to higher seroprotection and seroconversion rates than conventional intramuscular vaccines and have a similar immunogenicity profile to that of MF59-adiuvanted vaccines [66–69]. Furthermore, the elderly may benefit from the immunisation of the people in their households and HCWs, particular those working in long-term care facilities [70,71]. 1.11. Pneumococcal vaccination Another vaccination recommended for the elderly is against pneumococcal infections, but there is still debate as to whether to use PPSV23 or PCV13 to prevent invasive and non-invasive pneumococcal disease. One recent meta-analysis of 22 adult studies has found that the risk of invasive pneumococcal disease (and to a lesser extent allcause pneumonia) is reduced by pneumococcal vaccination [72], but another evaluating the efficacy of PPSV23 in preventing pneumonia and acute re-exacerbations of chronic obstructive pulmonary disease (COPD) did not find any statistically significant difference between the pneumococcal vaccination and control groups [73]. Melegaro and Edmunds found that the efficacy of PPSV23 against pneumonia was not significant in healthy elderly people [74], whereas a randomised, placebo-controlled study by Maruyama et al. showed a 63.8% reduction in pneumococcal pneumonia in institutionalised subjects [75], and a 3-year cohort study by Vila-Corcoles et al. demonstrated a reduction in the incidence of all cases of bacteremic and non-bacteremic pneumococcal pneumonia in adults aged N 50 years [76]. PCV13 is now available for the immunisation of adults aged ≥50 years [77] and, although there are no published data concerning its efficacy against pneumonia and invasive pneumococcal disease, it represents a promising option. 1.12. Herpes zoster vaccine Herpes zoster or shingles, a painful vesicular rash with a dermatomal distribution caused by the reactivation of varicella zoster virus (VZV) once T cell-mediated immunity against VZV falls below a crucial level, is extremely common in the elderly [78]. In Western countries, its incidence is 1.1–2.9 per 1,000 people aged b50 years but 10.9 per 1,000 people aged N 80 years; approximately 50% of cases occur in subjects

Please cite this article as: Esposito S, et al, Vaccine-preventable diseases: From paediatric to adult targets, Eur J Intern Med (2013), http:// dx.doi.org/10.1016/j.ejim.2013.12.004

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aged ≥ 60 years and its incidence is increasing partially due to prolonged life expectancy [79–81]. A live, attenuated vaccine against herpes zoster and post-herpetic neuralgia has been approved for adults aged ≥50 years in the US and EU [82–87]. It is worth noting that zoster and influenza vaccines can be injected concomitantly in different body sites without affecting the immunogenicity of either [88], whereas the concomitant administration of zoster vaccine and PPSV23 is not recommended because of the risk of reducing the immunogenicity of the former, although their simultaneous administration does not increase the risk of herpes zoster in adults [89,90]. Zoster vaccine significantly reduces the burden of herpes zoster in adults aged ≥ 50 years by reducing the incidence of herpes zoster and post-herpetic neuralgia, although it is less efficacious with increasing age: the incidence of herpes zoster have been found to be reduced by 69.8% in subjects aged 50–59 years, 63.9% in those aged 60–69 years, and 37.6% in those aged ≥ 70 years [91–93]. However, in the United States (where a single dose of zoster vaccine is recommended for adults aged ≥60 years regardless of their history of herpes zoster), the acceptance of the vaccine has generally been lower than that of others recommended for adults, such as influenza and pneumococcal vaccine [94,95]. This highlights the urgent need to overcome the barriers to zoster vaccination, especially in the elderly for whom it provides a unique opportunity to reduce the burden of the illness associated with herpes zoster.

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1.13. Vaccinations for health care workers (HCWS) Because of their continuous contacts with patients and infectious material, HCWs are at high risk of developing some vaccine-preventable diseases such as hepatitis B, influenza, measles, mumps, rubella, pertussis and varicella, and may also be a source of infection for susceptible patients or other colleagues [96]. Serious and fatal cases and costly outbreaks of pertussis, influenza, rubella, chickenpox, hepatitis A, hepatitis B, mumps, measles, chickenpox, drug-resistant tuberculosis, and invasive meningococcal disease have been documented among HCWs [96]. Furthermore, the lost working days they cause can have a negative effect on the provision of all healthcare services. The current recommendations for HCW vaccination programmes in Western countries are therefore a major infection prevention and control measure (see the US and European recommendations in Table 3). The US Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC) released updated recommendations for the immunisation of HCWs in November 2011 that included specific recommendations for vaccinations against hepatitis B, influenza, measles, mumps, rubella, varicella, tetanus, diphtheria, pertussis and meningococcus [97]. A recent survey carried out in the 27 EU Member States and Norway, Russia and Switzerland reviewed existing policies concerning the recommended and mandatory occupational vaccinations for HCWs, and found significant differences in

Table 3 US and European national policies for the vaccination of healthcare workers, by vaccine and country. Country

Hepatitis B

Influenza

United States

Recommended

Recommended

Austria

Recommended

Recommended

Belgium

hM

Recommended

Bulgaria

Recommended

Recommended

Cyprus

Recommended

Recommended

Czech Republic

Recommended

Recommended

Denmark Estonia

Measles

Mumps

Recommended Recommended spR

spR

Recommended Recommended NotR

NotR

Recommended Recommended NotR

NotR

Rubella

Varicella

Diphtheria

Tetanus

Pertussis

Recommended

Recommended

Recommended

spR

spR

spR

Recommended

Recommended

Recommended

NotR

NotR

NotR

NotR

Recommended

NotR

Recommended

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Recommended Recommended spR

spR

Recommended Recommended NotR

MenC

MenACWY

spR

spR

NotR

spR

NotR

NotR

NotR

NotR

spR

spR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Recommended

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Finland

spR

spR

Mandatory

Mandatory

Mandatory

spR

Recommended

Recommended

spR

NotR

NotR

France

spM

Recommended

spR

nR

nR

spR

Mandatory

Mandatory

spR

NotR

NotR

Germany

Recommended

Recommended

Recommended

spR

spR

spR

NotR

NotR

Recommended

spR

spR

Greece

Recommended

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Hungary

NotR

Recommended

NotR

spR

NotR

NotR

NotR

spR

NotR

Ireland

Recommended

Recommended

Recommended Recommended

Recommended

Recommended

spR

NotR

NotR

NotR

NotR

Italy

Recommended

Recommended

Recommended Recommended

Recommended

Recommended

NotR

NotR

spR

NotR

NotR

hM

Recommended

NotR

NotR

Recommended

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

Latvia Lithuania

NotR

NotR

Recommended

Recommended

Recommended Recommended

Recommended

Recommended

Recommended

Recommended

Luxemburg

hM

Recommended

Recommended Recommended

Recommended

Recommended

Recommended

Recommended Recommended

NotR

NotR

Malta

spR

Recommended

Recommended Recommended

Recommended

spR

Recommended

Recommended

NotR

NotR

NotR

Norway

Recommended

Recommended

NotR

NotR

spR

spR

NotR

NotR

spR

spR

spR

Poland

hM

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR NotR

Portugal

Recommended

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Romania

Recommended

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Russia

Recommended

Recommended

Recommended

NotR

Recommended

NotR

Recommended

Recommended

NotR

NotR

NotR NotR

Slovakia

Mandatory

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Slovenia

Mandatory

Recommended

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

NotR

Spain

Recommended

Recommended

Recommended

Recommended

Recommended

Recommended

NotR

NotR

NotR

Sweden

Recommended

NotR

NotR

Switzerland

Recommended

Recommended

The Netherlands

hM

Recommended

United Kingdom

spR

spR

Recommended Recommended NotR

NotR

Recommended Recommended NotR

NotR

Recommended Recommended

NotR

Recommended

NotR

NotR

NotR

NotR

Recommended

Recommended

Recommended

Recommended

NotR

spR

spR

NotR

NotR

NotR

Recommended

NotR

NotR

NotR

Recommended

spR

Recommended

NotR

NotR

Recommended Recommended

spR: recommended for specific groups of HCWs or healthcare settings; NotR: not recommended; spM: mandatory for specific groups of HCWs or healthcare settings; hM: mandatory for employment. Men C: Meningococcus C vaccine; MenACWY Meningococcal ACW135Y vaccine. Adapted from References 96 and 97.

Please cite this article as: Esposito S, et al, Vaccine-preventable diseases: From paediatric to adult targets, Eur J Intern Med (2013), http:// dx.doi.org/10.1016/j.ejim.2013.12.004

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the number of vaccines for which there is a specific policy, and the target HCW subgroups and healthcare settings [96]. The strategies concerning vaccination against hepatitis B and seasonal influenza were the same throughout the continent (29 of the 30 countries recommend both), but 21 countries had no specific policies regarding vaccination against pertussis, and 50% no specific policies concerning vaccinations against mumps, measles, rubella, or varicella [96]. The most recent Italian National Immunisation Plan (2012–2014) strongly recommends HCW vaccinations against hepatitis B, influenza, measles, mumps, rubella and varicella [97,98], and pertussis vaccine is recommended for the personnel of obstetric clinics [98]. However, despite these recommendations, there are few published data concerning the critical issue of vaccination coverage rates. A recent survey of 2348 HCWs conducted by the US Centers for Disease Control and Prevention (CDC) found that 66.9% received the influenza vaccination for the 2011–12 season [99]. HCW influenza vaccination coverage rates in Europe are lower than in the US, and a survey carried out during four influenza seasons (2003/2004-2006/2007) in the five countries with the largest populations (Germany, United Kingdom, Italy, France and Spain) revealed substantial differences [100]. Vaccination coverage rates ranged from 13.2% (in Italy during the 2005/2006 season) to 29.3% (in Spain during the 2003/2004 season). Furthermore, there was a continuous decrease in immunisation over the study period [100].

1.14. Vaccinations for travellers It is widely agreed that there is a need to prevent the spread of travelrelated infections, and that this requires the adoption of appropriate awareness campaigns and specific prophylactic measures. A pre-travel consultation with an HCW specialised in preventing infectious diseases is important in order to help reduce and manage the risk of illness and injury by means of counselling, education, vaccinations and medications [101]. The risk needs to be evaluated by gathering information about the journey (i.e. the countries to be visited, urban vs rural areas, the length of the trip, its purpose, transportation, possible activities, types of accommodation) and the traveller (age, gender, vaccination history, medical history, allergies, pregnancy and breastfeeding) [101]. It is important to highlight that immune-suppressed frequent travellers should be vaccinated for travel-associated infections possibly before their therapeutic regimen has started [101]. In terms of pre-travel immunisation, three types of vaccinations should be considered: “required”, “recommended” and “routine” [101]. The first are those that a traveller needs to enter a particular country and for which an international proof of vaccination certificate is mandatory; the second type are those that are medically advisable on the basis of the disease risks of the journey, regardless of formal entry requirements; and the third are those that protect against diseases that continue to cause outbreaks in developed and developing countries. HCWs should make sure that travellers are up-todate with their routine vaccinations by referring to the current immunisation schedules. Table 4 summarises the main vaccinations for travellers. Hepatitis A virus (HAV) infection is the most frequent potentially vaccine-preventable diseases affecting international travellers. Its incidence among unprotected travellers to a developing country is

estimated to be 3-20/1,000 travellers per month, with differences between short-term travellers or businessmen staying in Western-style accommodation and travellers to locations with poor hygienic conditions [102]. A number of travel-related cases and outbreaks of HAV infection have been recently reported in Europe and the US, usually involving infections imported by asymptomatic children from abroad [103–105]. The infection is endemic throughout the developing world (mainly Asia, Africa, Central and South America) because of poor sanitary conditions and HAV vaccine should be considered for travellers to any destination [101]. However, despite the current recommendations, some authors have recently shown that vaccination coverage among adults travelling to endemic areas is as low as 27% [106]. Another common vaccination for travellers is vaccination against typhoid fever [101]. The risk of typhoid fever is highest for travellers to Southern Asia, but it is also highly endemic in other parts of Asia, Africa, the Caribbean, and Central and South America. Typhoid vaccine is recommended for all travellers to areas at risk and should be given ≥ 2 weeks before exposure [101,107]. Two vaccines are available: an oral live attenuated vaccine for immunocompetent subjects that requires a booster every five years, and an intramuscular capsular polysaccharide vaccine for immunocompromised subjects that requires a booster every two years [107]. Although the incidence of meningococcal disease in travellers is appreciably lower than that of other preventable diseases, it is very high in Africa (from Senegal in the west to Ethiopia in the east, the socalled “meningitis belt”) and the Middle East (during outbreaks among Hajj pilgrims to Mecca), where the peak incidence rates can respectively be as high as 800/100,000 and 640/100,000 inhabitanys/year [108]. There is a a real risk that new serogroups of Neisseria meningitis (i.e. serogrup A or W135) will be introduced to Europe, and this can only be faced by improving public health strategies [109] such as: i) immunising travellers to high-risk countries and regions; ii) immunising military forces; and iii) recommending the novel quadrivalent conjugate vaccine (ACYW135) in the immunisation schedules of developed countries for adolescents and young adults, such as high-school and college students. Another vaccine recommended for travellers to sub-Saharan Africa and tropical South America is yellow fever vaccine [101,110]. The risk facing travellers depends on their immunisation status, the itinerary of the trip, the season (the risk is highest during the rainy season), the type of activities, and the local rate of virus transmission at the time of the trip. The only vaccine against yellow fever is a live attenuated vaccine that is contraindicated in the presence of an allergy to any of its components, symptomatic HIV infection or a CD4 + T lymphocyte level of b200/μL, primary immunodeficiencies or thymus disorders, malignant neoplasms, transplantation and immunosuppressive or immunomodulatory therapies (the countries that require the vaccination require certification of a contraindication signed by a physician). The risk/benefit ratio of vaccination needs to be carefully evaluated in subjects aged ≥60 years, patients with asymptomatic HIV infection and CD4+ T lymphocyte levels of 200–499/μL, and pregnant or breastfeeding women [101,110]. Other vaccines that may be required of travellers include BCG and vaccines against tick-born encephalitis, Japanese encephalitis, cholera and rabies [101]. However, their use is quite uncommon and related to specific travel-related risks.

Table 4 Main vaccines for travellers. Vaccine

Population

Hepatitis A Typhoid fever Quadrivalent meningococcal conjugate vaccine

Travellers to any destination Travellers to areas at risk (Asia, Africa, the Caribbean, Central and South America) Travellers to Africa (from Senegal in the west to Ethiopia in the east, the so-called “meningitis belt”) and the Middle East (during outbreaks occurring among the Hajj pilgrims to Mecca) Travellers to selected countries in sub-Saharan Africa and tropical South America

Yellow fever

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1.15. Current barriers to adult immunisation Immunisation is the cornerstone of preventive medicine and one of the most successful and cost-effective public health interventions but, ever since its introduction in the late 18th century, opponents have argued that vaccines do not work, that they are or may be dangerous, that personal hygiene is more reliable, or that mandatory vaccinations violate individual rights or religious principles [111]. The direct and indirect costs of immunisation, vaccine storage difficulties or limited availability, the lack of updated or easy-to-check immunisation records are logistical barriers faced by subjects and healthcare providers [112]. Low-income families may not be aware of the possibilities of free offer of vaccination or, in some cases, national programmes for uninsured subjects, and may face other barriers such as transportation problems or fragmented records [113]. Stringent storage requirements and vaccine shortages may hamper the work of immunisation centres and lead to temporary changes in administration guidelines [114,115]. The lack of computerised vaccine registries has been documented by various surveys and represents a significant obstruction for correct and tailored healthcare, with the potential risks of both over-immunisation and incomplete immunisation [116,117]. The barriers faced by healthcare providers include a lack of knowledge of the indications for and against immunisation, missed opportunities for needed vaccine administrations, limited routine assessments of patients' immunisation status, and insufficient time spent on communicating the risks and benefits of vaccines [118,119]. Language may also be a major barrier among vulnerable ethnic groups not only in terms of immunisation compliance, but also in terms of access to and the use of healthcare services, and can lead to less efficient care [120]. A dislike of needles and a fear that a vaccine may make a recipient ill are much less frequently mentioned as reasons for avoiding immunisation [121]. Identifying the real reasons underlying the tendency of adults to forego immunisation is a critical step in improving the approach to offering adult vaccinations, implementing vaccination strategies, and enhancing policies designed to increase adult immunisation coverage. 1.16. How to increase vaccination coverage The risk-category strategy of passively offering vaccines to patients at particular risk because of their medical condition, age or occupations have so far led to sub-optimal results [122,123]. As most of the problems that lead to low vaccination coverage depend on the lack of knowledge of vaccines of healthcare providers and persons at risk, educational programmes should be specifically aimed at each of these groups. It is also essential that all physicians providing immunisation develop approaches that acknowledge concerns and respectfully try to correct any misconceptions. The risk of non-acceptance can be further reduced by implementing systems for recording vaccine administrations, providing immunisation services in special medical homes or by integrating healthcare sites. Another means of increasing immunisation coverage could be the publication of age-based adult immunisation schedules appropriately supported by improved public education campaigns, and making some vaccines available not only in healthcare settings, but also in non-traditional places such as retail stores and work settings [124]. Other successful strategies have included the use of recall/reminder letters and text messaging for patients, and electronic medical record reminders for physicians in primary care and emergency departments, in order to identify any missed vaccination opportunities [125–127]. Clear immunisation programme objectives, easy access to vaccinations, and incentives for HCWs are other key issues that need to be considered. Finally, so-called “civil society organisations” (CSOs) [128] could play an important role in the introduction and sustainability of new vaccination programmes. CSOs can be active at national level by supporting national policy makers, and can bring innovative and effective new approaches to communicating the benefits of vaccination by

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means of public events, celebrity messages, and social media blogs. Working with experts, CSOs can be an important bridge between the scientific community and the lay public, which could provide a vital counterbalance to media hype and anti-vaccination groups—although it must also be remembered that they can be active and vocal opponents of immunisation. Although various possibilities of improving vaccination coverage have been identified, achieving the levels necessary to obtain the greatest effect is still a difficult goal that will only be reached by the combined efforts of healthcare systems and providers. 2. Conclusions The vaccines currently licenced in Western countries are safe, immunogenic and effective against a number of communicable infectious diseases and their complications. The availability of newer vaccines or vaccines with new indications (i.e. Tdap, HPV vaccine, new influenza formulations, PCV13, meningococcal conjugate quadrivalent vaccine, zoster vaccine), the evolving ecology and epidemiology of numerous infections (also due to the immune pressure caused by national immunisation policies mainly aimed at the paediatric population), demographic changes (e.g. population ageing), and the new case mix of patient populations characterised by an increasing prevalence of some chronic co-morbidities and immunodeficiencies have all led to a need to up-date and improve immunisation strategies for adults and the elderly. Although important advances have been made over the last ten years, there are still some critical issues: measles outbreaks, the re-emergence of pertussis, the continuing burden of influenza and pneumococcal diseases among the elderly, the increased risk that travellers to high-incidence countries may acquire and transmit HAV infection and meningococcal diseases are only some examples. There is no doubt that significant economic benefits can be achieved by improving healthy and active ageing. A more dynamic approach to the prevention and control of some vaccine-preventable infectious diseases among adults and the elderly may further improve general health in Western countries [129,130], although they need to take into account the economic sustainability of healthcare systems. These are all issues that pose ethical dilemmas and may require difficult decisions by public health policy makers, particularly at this time of austerity. 2.1. Learning points • The vaccines currently licenced in Western countries are safe, immunogenic and effective against a number of communicable infectious diseases and their complications. • The availability of newer vaccines or vaccines with new indications, the evolving ecology and epidemiology of numerous infections, demographic changes, and the new case mix of patient populations have all led to a need to up-date and improve immunisation strategies for adults and the elderly. • There is now a need for appropriate preventive measures for adults and the elderly aimed at protecting people at risk by using every possible catch-up opportunity and recommending specific age-related schedules on the basis of local epidemiology • Significant economic benefits can be achieved by improving healthy and active ageing. Conflicts of interests The authors have no conflict of interest to declare. Acknowledgements This review was supported by a grant from the Italian Ministry of Health (Bando Giovani Ricercatori 2009).

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Please cite this article as: Esposito S, et al, Vaccine-preventable diseases: From paediatric to adult targets, Eur J Intern Med (2013), http:// dx.doi.org/10.1016/j.ejim.2013.12.004