MEETING REPORT
review
Human Vaccines 6:2, 169-177; February 2010; © 2010 Landes Bioscience
Updates from the 19th National Immunisation Conference for Health Care Workers Manchester conference Centre, December 2008 Victor Adebowale,1 Carol Baxter,2 David Elliman, 3 Andy Green,4 Martin J. Guppy, 5 Andrew Hall,6 Paul Heath,7 Tony Heagerty,8 Keith Lindley,9 Elizabeth Miller,10 David N. Baxter, 5,* 4
1 Standon House; London UK; 2NHS Employees, Leeds, UK; 3Islington PCT & Great Ormond Street Hospital; Great Ormond Steet Hospital for Children; London, UK; Surgeon General’s Department; Army Medical Directorate; Ministry of Defence; London, UK; 5Clinical Epidemiology and Public Health Unit; School of Translational Medicine; Manchester University Medical School; Manchester, UK; 6 London School of Hygiene & Tropical Medicine; London, UK; 7Child Health and Vaccine Institute, St. George’s; University of London; London, UK; 8Division of Cardiovascular and Endocrine Sciences in the School of Medicine; University of Manchester; Manchester, UK; 9Institute of Child Health and Great Ormond Street Hospital; London, UK; 10Communicable Disease Surveillance Centre’s Immunisation Department; Health Protection Agency; London, UK
Key words: immunization, vaccines, health care workers
Introduction The annual National Immunisation Conference (NIC) for Health Care Workers (HCW), first held in 1989, provides updates on current vaccine issues and new developments for any health worker involved with immunization. The conference has grown each year and continues to be of particular interest to Clinical Medical Officers, General Practitioners, Health Visitors, Practice Nurses, Occupational Health Practitioners, Paediatricians, Microbiologists, School Nurses and District Immunization Co-ordinators. Invited speakers are nationally and internationally renowned experts in their fields and there are usually around 150 delegates, mainly from the UK. The conference is organized by the University of Manchester Medical School and administration is carried out by the Stockport Foundation Trust Post-graduate Medical Department. Although the conference scientific program is largely concentrated on the use of vaccines as prophylactic agents, presentations around therapeutic immunization have also been made recognising that this is an area of growing interest and potential. The conference format combines presentations with extended periods of open discussion. The conclusions reached over the course of the conference are summarized here whilst conference video material for the past three conferences is freely available online as a learning resource (medicine.manchester.ac.uk). Immunizing People with HIV and Chronic Hepatitis B Dr. Ed Wilkins, Consultant and Clinical Director of Infectious Diseases at North Manchester General Hospital. Immunization is an important measure to protect HIV-infected adults and children against vaccine preventable diseases as such individuals are *Correspondence to: David N. Baxter; Email:
[email protected] Submitted: 08/13/09; Accepted: 08/19/09 Previously published online: www.landesbioscience.com/journals/vaccines/article/9871
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at greater risk of certain co-infections. For example, the Hepatitis B co-infection rate in people with HIV is about 9–10% across Europe, more than expected in a mono-infected group. As the impact on mortality is much greater in co-infected individuals,1 it is important to protect HIV-infected people against Hepatitis B. Several complicating factors are apparent. The antibody response, which is associated with the level of CD4 + T cell count, can be impaired by HIV-infection.2 Furthermore, certain vaccines can enhance virus replication and transiently increase HIV viral load. Vaccination should ideally be given before the immune status of the patients is suppressed. The “Green Book”3 states that live vaccines (for example BCG) can, in some situations, cause severe or fatal infections in immunosuppressed individuals due to extensive replication of the vaccine strain. For this reason, severely immunosuppressed individuals are generally not given any live vaccines, and vaccination in immunosuppressed individuals should only be conducted in consultation with an appropriate specialist. Inactivated/subunit/toxoid vaccines cannot replicate and so may be administered to immunosuppressed individuals, although they may elicit a lower response than in immunocompetent individuals.3 Hepatitis B, influenza and pneumococcal vaccine are recommended for all patients with HIV, irrespective of their CD4 count. A further consideration is travel vaccination. Current HIV treatment strategies, including highly-active antiretroviral therapy (HAART), increase patients’ CD4 count such that they are generally healthier and more willing or able to travel abroad.4 It is important not to give an individual with symptomatic HIV who has a CD4 count of 500, then you can regard them as effectively without HIV with respect to the majority of vaccines. Patients with higher CD4 counts are able to receive the yellow fever vaccine (see below). HIV-infected migrants to the UK may not have received a full immunization course as a child and such individuals are also more likely to develop varicella-zoster as adults. So it’s important to test for varicella-zoster IgG antibody in HIV-infected
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individuals although vaccination of those who are negative is not always required. Whilst there are very few data on vaccinating HIV-infected adults with varicella-zoster vaccine, with perhaps more data on children, it is currently recommended that both adults and children are vaccinated if their CD4 counts are greater than 400. Despite these guidelines/recommendations the use of pneumococcal vaccine and varicella-zoster vaccine is controversial in HIV-positive people, with many healthcare professionals reluctant to give the pneumococcal vaccine to HIV-infected people based on doubts of benefits over risks. Similarly, healthcare professionals may be reluctant to give the varicella-zoster vaccine due to lack of familiarity with its use in HIV-positive people. Bacille Calmette-Guérin (BCG) is one of the most widely given vaccines globally and is safe in immunocompetent individuals. While, theoretically, individuals with asymptomatic HIV infection may be at greater risk of complications from BCG vaccines, the available data are inconclusive in this respect.6 Recent evidence shows, however, that HIV-infected infants who were routinely vaccinated with BCG at birth, i.e., when asymptomatic, and who later developed AIDS, were at higher risk of developing disseminated BCG disease (estimated incidence 407–1,300 per 100,000).7 Furthermore, there have been case reports of very severe BCG disseminated disease as a result of immunization. Complications of BCG vaccination have been reported in immunocompetent as well as in immunocompromised individuals.8 Therefore, it is recommended that BCG shouldn’t be given to HIV-infected individuals. Yellow fever is a live vaccine and there is inherent fear of using a live vaccine in an individual with a T-cell immune deficiency. However, patients with raised CD4 counts respond very well. Acute viscerotropic disease is a rare but serious complication of vaccination with 17D yellow fever vaccine.9 Both the American and the British guidelines are now happy to recommend yellow fever vaccine if the CD4 count is above 200. Similarly, HIVpositive individuals should be given MMR vaccine according to national recommendations unless they have evidence of severe immunosuppression (CD4 count < 200) because of the few cases of MMR vaccine related disease.3 For rabies, the concern is that if an HIV-infected individual is bitten by a rabid dog in an endemic region then such individuals are not going to build up sufficient immunity following the postexposure vaccination course. It is therefore recommended that the rabies vaccine is given as a pre-exposure program to all HIVinfected individuals prior to travel to a rabies endemic area.3 Further guidance on this issues is provided by the Royal College of Paediatrics and Child Health (www.rcpch.ac.uk), the British HIV Association (BHIVA) Immunization guidelines for HIV-infected adults (BHIVA, 2006),10 and the Children’s HIV Association of UK and Ireland (CHIVA) immunization guidelines (www.bhiva.org/chiva). The Role of the JCVI in National Vaccination Policy Professor Andrew Hall, Chairman of Joint Committee on Vaccine and Immunisation, JCVI. The remit of JCVI is to
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provide advice to the Secretaries of State for Health, the Scottish Ministers, the Northern Ireland Ministers responsible for health and the National Assembly for Wales on matters relating to communicable diseases, preventable and potentially preventable through immunization. This refers to both active and passive vaccination including the use of monoclonal antibodies. The JCVI, which is a non-governmental body appointed through the NHS appointments commission, meets to make key decisions three times a year on additional work done through separate sub-committees. Various specialised sub-committees review evidence and define what further evidence is needed. It is largely the Health Protection Agency (HPA) and Health Protection Scotland who produce that evidence. The sub-committees are tasked with making recommendations to the full committee. The membership of the committee is designed to represent all relevant disciplines – epidemiology, public health, general practice, infectious diseases, virology, and bacteriology - and a health economist will be soon included. The main meetings are frequently attended by international observers and this is useful as they provide another perspective on the issues under consideration. One of the main activities of the committee is “horizon scanning”—looking at what new vaccines may become available over the next five years with a view to conducting surveillance to find out in advance what are the current/ expected disease levels: the committee will also initiate other analyses including economic modeling. The JCVI is also required to consider how a new vaccine program will be implemented and whether it can be recommended. The implications of changes to the immunization schedules are also considered together with changes to vaccine indications and changes in the management and the treatment of various vaccine preventable conditions. Pandemic flu is currently a government priority and this is something that has occupied the JCVI a great deal. Clearly this is highly topical and there have been, and will be, some difficult decisions to be made over the next few years in terms of preparing for and managing a pandemic. The fact that JCVI meetings are closed has attracted a certain degree of criticism. In generating recommendations, the JCVI looks at the available evidence including both published and unpublished data. One of the main reasons for having closed meetings is that a lot of the information under review has not been made public and some is commercially sensitive. As a result we have now got an agreement to publish all minutes within six weeks of the meeting (the minutes of committees and sub-committees are available online; dh.gov.uk/ab/JCVI/index.htm). In addition, for every decision that is taken and each recommendation that is made, we plan to provide the reasoning behind the decision and the evidence on which decisions were based. The JCVI has also been criticized because of a perception that some members have a conflict of interest with regard to vaccine manufacturers. However, one of the problems in recruiting suitably qualified experts is that inevitably their research has been funded partly by vaccine companies. The JCVI has a very strict register of interest and declarations are required whenever a vaccine is discussed at the meeting in addition to annual declarations;
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a distinction is made between having research funded and receiving personal funding. If a member receives personal funding in relation to a vaccine under discussion then that person cannot participate in the discussion and decision-making. The JCVI is very careful to enforce this principle to ensure that decisions are not inappropriately influenced. The vaccine manufacturing companies have complained that they have no opportunities to speak to the committee. To address this concern the JCVI has invited the companies to present evidence to the relevant sub-committees to ensure that the committee members fully understand the evidence that the recommendation will be based on. There are also regular meetings between the Department of Health (DH) and the vaccine companies and these are reported to the JCVI. Both mathematical modeling and qualitative study data are frequently used to help the JCVI decide whether or not a vaccine is cost effective from the NHS perspective. The committee itself has no budget for commissioning and is entirely dependent on good will, an arrangement between the DH and the HPA, or the DH commissioning work on behalf of the JCVI. Regarding recent JCVI activities, in 2007 the rotavirus subcommittee reviewed whether a rotavirus vaccine program should be developed and implemented. The subcommittee judged that from a societal prospective, taking into account the cost to the family and the caregiver, this was clearly a cost effective vaccine. However, from an NHS perspective it was not found to be cost effective and so the JCVI on behalf of the subcommittee concluded that a rotavirus vaccine program should not be developed. A further example concerns the varicella-zoster vaccine. There are two different strategies for the use of varicella-zoster vaccine: give it in childhood to prevent chicken pox or give it in adult life in order to prevent shingles. But what is the cost effectiveness of each of those strategies and how important is chicken pox versus shingles? These represent a number of quite difficult decisions that are currently being modeled and analysed. A sub-committee is currently looking at pneumococcal vaccine and they also have to make some difficult decisions. There are two new pneumococcal conjugate combinations, which will probably be licensed in the next year or two, a 10-valent and a 13-valent conjugate vaccine. The pneumococcal sub-committee is looking at the evidence supporting their respective use. Clearly this is an interesting and difficult issue because a conjugate vaccine is already being used; so a key question is whether the additional serotypes add to the cost effectiveness or not and therefore, should the JCVI recommend it or not. Meningitis B Vaccines Professor Elizabeth Miller, Head of the Communicable Disease Surveillance Centre’s Immunisation Department at the Health Protection Agency. Bacterial meningitis remains a serious threat to global health, accounting for an estimated annual 170,000 deaths worldwide, with all countries affected. In 2000/2001, levels of meningococcal B disease reached the highest ever on record with 1,686 cases reported in England. As the greatest burden of
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group B disease is in children under five years of age, the development of an effective group B vaccine for use in infants is a major priority. Following a decade long hiatus, group B vaccine trials are now underway. Meningococcal group B vaccine research has focused mainly on cell-surface protein antigens contained in outer-membrane vesicles (OMV). The best studied OMV vaccines were produced in response to national outbreaks in New Zealand, Norway and Cuba.11 Although they demonstrated 47–83% efficacy, they offered only poor protection to infants and the immune response was of short duration. The OMV vaccines also proved to be strain-specific, useful against clonal disease outbreaks but not for the prevention of sporadic disease caused by diverse strains.12-14 In New Zealand, the decision to stop using this vaccine took into account a range of factors, including epidemiology, vaccine effectiveness and duration of immunity, vaccine coverage, concomitant use with other vaccinations being added to the infant schedule, vaccine supply and cost-benefit criteria.15 Disease rates in indigenous New Zealand communities remain very high. The more recent application of reverse vaccinology (based on sequencing the meningococcal genome) identified 600 potential meningococcal antigens, 350 of which have been successfully expressed as recombinant proteins in E. coli, purified, and tested for the induction of bactericidal activity in the mouse. This approach revealed 91 novel surface-exposed proteins and led to the discovery of 28 novel proteins with immunological potential for the development of new broad specificity group B vaccines.16 Of these, three front-running potential vaccine antigens—factor H binding protein, NadA and genome-derived Neisserial antigen (GNA) 2132, have each generated serum bactericidal activity (SBA) in animal models. Encouraging responses have also been observed in a clinical study conducted jointly by the Health Protection Agency and the Oxford Vaccine group involving a candidate vaccine using the three recombinant proteins with and without the OMV vaccine. Early findings indicate that these recombinant antigens will produce SBA responses to strains other than just through the OMV component.17 A further candidate universal meningococcal B vaccine is the 5CVMB recombinant vaccine (developed by Novartis), which contains three components (two fusion proteins and one single antigen). In preclinical studies, 5CVMB covered 78% of strains tested in the basic formulation and this was increased to >95% of strains using other adjuvants.18 This vaccine induced SBAs that are cross-reactive against strains of each of the factor H binding proteins regardless of the Por A sera subtype. Following a promising phase I dosing study the vaccine is now being tested in phase II trials. Vaccine licensure should be based on a correlate of protection and there also needs to be a very thorough evaluation of potential immunogenicity against a panel of strains in order to predict effectiveness. There is a further need for carriage studies to assess the potential for herd immunity. Overall, these very promising areas of active research suggest that the global elimination of bacterial meningitis may well be an achievable target. We are perhaps just 3–4 years away from the launch of an efficacious group B vaccine. However, the important matter of vaccine cost-effective remains to be determined.
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Improving Vaccine Access and Uptake: Some Paediatric Issues Dr. David Elliman, Great Ormond Street Hospital, London; Dr. Helen Bedford, Institute of Child Health, London. Current levels of vaccine uptake in England and Wales is generally good, in excess of 90% for primary vaccines, while the uptake of MMR continues to improve.19 However, even in areas of high uptake there are particular groups of children who experience poor uptake. These can broadly be divided into two groups— the totally unimmunized children, whose parents are often active rejecters, deciding not to have their children immunized; and the passive defaulters, children who are partially immunized, who have often not completed an immunization course. The latter are often from the most disadvantaged groups and have difficulty accessing services. Vulnerable children have poorer uptake. Babies who are premature or have a low birth weight also have poor uptake as well as children who have chronic or disabling conditions. Premature infants have an increased susceptibility to infection because their immune system is less mature and they may have poorer respiratory function. The risk of infection is also increased for low birth weight babies. All these groups can be a source of infection to other vulnerable adults and children, particularly in hospitals. There are very few contraindications, apart from immunosuppression (or anaphylaxis), for live vaccines, so most of these children could be immunized. Many of these children are also likely to need additional vaccines such as the polysaccharide pneumococcal vaccine—rarely do these children have a valid contraindication. It is important that these children are protected as some are at particularly high risk of severe disease or death. In an Australian study, parents were asked hypothetically whether they would accept immunization in an accident or an emergency for overdue children who were well enough to be immunized. The majority said they would accept vaccine had they been offered it at the time. In another study in Manchester, 40/56 overdue children were successfully immunized before discharge from hospital. An audit was recently conducted at Great Ormond Street hospital to determine the proportion of children admitted to a paediatric tertiary hospital who were not fully immunized. The audit also explored practice regarding how healthcare professionals determined immunization status on admission and whether unimmunized children were offered missing immunizations. A case note review was undertaken and children aged three months or older and admitted at least for an overnight stay were included. Three hundred sequential admissions were taken in two separate time points in 2004, from January and June to exclude any seasonal issues. Case notes were obtained to determine immunization status on admission along with action, if any, taken to facilitate immunization. Semi-structured in-depth interviews were also conducted with 30 staff, who were chosen to represent all the different professional backgrounds and grades within the hospital. Overall, 213 sets of case notes out of the 600 children identified from medical records were reviewed. The median age of admission was 6 years 2 months; 54% were male and 55%
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were white British. Most children were in hospital for at least two days. It was found that immunization status was recorded for at least 71% of admissions and nurses were better at recording it than doctors. But most of the histories documented simply said that immunization was ‘up-to-date’, which is ambiguous because, given the age ranges of these children it is not possible to know if they have had all the vaccines required. Contraindications were not documented. Only one child had a full history of their immunization taken and was fully immunized; 57% were recorded as being fully immunized (bearing in mind that this is likely to be inaccurate). Status was not established in 29% of the population studied. It was estimated that, overall, 20% of the hospital patients were eligible for vaccination. Interviews with healthcare professionals revealed no staff training was received regarding immunization and no leaflets were made available. Staff were unaware of the current schedule. There were many different views expressed about the hospital’s role in immunising in-patient children. Most felt that more should be done to facilitate immunizations, although a number of barriers were identified. It is likely that opportunities to immunise the 20% of inpatients in this tertiary hospital who were eligible for vaccinations had already been missed. It is thought that these children were less likely to have had contact with routine primary care services. Yet we have a duty of care to these patients and there are national guidelines that should be followed and revised immunization policies have now been established at Great Ormond Street Hospital. There has been a rolling program of staff training, acting as information cascades on immunization. Department of Health leaflets are now available on the ward and each ward has a copy of the “Green Book”. An immunization history form has now been designed enabling workers to record a full immunization history. These forms will be updated as schedules change. A repeat audit is planned and consideration is being given to rolling it out more widely, working with the Health Protection Agency to look at the most effective way of raising awareness of hospital-based opportunistic immunization. Vaccination of hospital staff also needs to be considered. It is recommended that all staff with direct patient care should be up to date with immunizations, which includes MMR, hepatitis B, influenza and varicella. Improving Vaccine Access and Uptake: an Adult Perspective Lord Victor Adebowale, Turning Point; Professor Carol Baxter, Department of Health; Human Resources Directorate. For healthcare organizations, the Darzi report specifically acknowledges that more needs to be done to personalize services for people who find services inaccessible, or who find themselves discriminated against in some way.20 Vaccination programs that specifically address the needs of individuals designated as “underserved” because of their lifestyles and individual circumstances—principally the homeless, injecting drug users and female commercial sex workers—are important as such individuals have a substantially increased risk of various physical illnesses including serious infections.3 Department of Health policy is that additional vaccinations should also be considered for any adult who is at
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higher risk because of their lifestyle,3 yet many health campaigns, including immunization programs, only target those already in the system rather than those on the outside. The key health service response must be to work collaboratively with organizations that are already engaged and trusted by the target groups and involve them in the development and delivery of immunization programs. Such an approach should enhance trust and create a demand for the service. It is important that, once established, such collaborations should be properly resourced to ensure long term stability and prevent a failure of expectation for all involved. The following examples demonstrate how such collaborative partnerships can work. Turning Point’s Connected Care Model is a new approach to service delivery, providing a co-ordinated range of services which directly reflects and responds to the needs of individuals and communities they serve, and which integrates health, housing and social care services. Individuals with a range of needs often fall out of the system with frustration as they struggle to navigate between different services only catering for singular need. The hardest to reach adults are those with more than one neatly defined problem. For services to be effective and reach these individuals they need to take account of the whole person, not just one disease entity. In Turning Point’s report Meeting Complex Needs: The Future of Social Care, it was found that people with the most complex needs are failed by existing provision of health and social care services. It concluded that services need to “address the whole person’’, meeting their complex needs in terms of breadth (range of need) and depth (severity of need). Connecting services, having person-centred staff and flexible ways of working should be at the centre of any strategy developed to reach those most in need. Outreach services, whether by GP or Nurses (using Patient Group Directives3) are a positive way to engage with hard to reach communities in a way that works with them, instead of expecting the individual to adapt to the restrictions of the service —for example around opening hours. Through a more integrated structure, healthcare professionals with an interest in immunization can work in an inclusive manner to address the needs of the most diverse communities. Services and how healthcare staff are trained, need to be ambitious to ensure immunization and health and social care services in general address the gaps in current service provision. Mobile van services are particularly effective at engaging with the hardest to reach communities. Needle exchange services, for example, based at a drop-in service, through a mobile van unit or outreach in pharmacies, are an essential and successful model of providing vaccines to those not accessing the health service. At Turning Point’s needle exchange service in Sheffield, a nurse attends three days a week offering hepatitis A and B vaccines along with hepatitis C and HIV testing. Due to the sometimes chaotic nature of the individuals accessing this service a fasttrack system has been introduced so that a combined hepatitis A and B vaccine is provided over three weeks rather than the more usual six-month program. This increases the likelihood of the course being completed and protects against both HAV and HBV simultaneously.
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Vaccination of the Immunocompromised Host Dr. Paul Heath, St. George’s Hospital, University of London; London UK. Vaccines are a powerful tool for preventing serious and life-threatening diseases in all children, including those who are immunocompromised. Underlying conditions may increase susceptibility to, or complications from vaccine-preventable diseases and may also offer the safety and efficacy of vaccines. Children at risk include HIV-infected children, children postleukaemia and post-bone marrow transplant and children born prematurely. Vaccine coverage in these groups is currently very poor. Pneumococcal disease in HIV-infected children and adults is a significant infection with very high rates of disease.21 In order to best vaccinate children in the UK, data are gathered using a cohort of HIV-infected individuals through the Collaborative HIV Paediatric Study (CHIPS; chipscohort.ac.uk) database. The incidence rate for hospitalization from this database is about 34-fold higher than the background rate for similarly aged children who are not infected with HIV. Although the pneumococcal conjugate vaccine (PCV) is effective in infants with HIV disease,22 the precise role and value of a booster remains to be studied. Two doses of conjugate followed by a dose of polysaccharide vaccine is recommended for HIV-infected children in the UK. Using 0.35 μg/ml correlate of protection, with two doses of conjugate vaccine, nearly all have protective concentrations. When infants receive the dose of 23-valent polysaccharide vaccine, it does very little to their antibody responses. This schedule is immunogenically safe and protective concentrations are achieved in the majority with maximum benefit seen after two doses of PCV. The burden of disease was calculated using the CHIPS cohort in terms of hospitalizations due to varicella and herpes zoster. Varicella-zoster virus was the cause of 3% of deaths in 20012008. There were five deaths due to varicella and one of them was in a HIV-infected individual. The risk of hospitalization due to varicella is about 240-fold higher that of the background UK population. In terms of zoster shingles, it is 800-fold higher than the background population. In the US the varicella-zoster vaccine is now a part of the routine child immunization schedule. Studies have shown there to be a significant reduction in the burden of varicella-zoster disease between the end of 1999–2006, which coincided with the introduction of the vaccine in the routine population and with the introduction of HAART in all children. The main effect, however, is due to herd immunity as a result of widespread varicella-zoster vaccination.23 In the UK, the vaccine is not used routinely so there is no herd immunity benefit for these children. HIV-infected women and men have a higher risk of Human Papilloma Virus (HPV) complications in terms of persistent HPV infection, and cervical intraepithelial neoplasia in women.24,25 The HPV vaccine is therefore welcomed in this population and HIV-infected women will be getting it as part of their routine program. There are as yet no data in the HIV-infected population where the question will be how effective it is and if additional doses will be required. There may also be a preference for
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the quadrivalent vaccine in this population because the other two types in the quadrivalent vaccine are more relevant in this population in terms of their burden of disease. Adolescent males with HIV might also benefit from the vaccine. In HIV-positive children, vaccines are often less immunogenic than in HIV-negative children and booster doses may be required to reach protective thresholds. The baseline risk of vaccine preventable infections is significantly higher in HIV-infected children than in HIV negative children. The value of even a moderate efficacy vaccine is therefore significantly greater in this population and vaccination can provide added benefits for other family members especially the use of pneumococcal, varicella and influenza vaccines. Children with leukaemia should avoid live vaccines during and for six months after completion of chemotherapy. During their treatment and up to six months afterwards, inactivated vaccines including influenza vaccine are appropriate. They should then have one dose of all of the conventional vaccines in the routine schedule beginning at six months after completion of therapy. A study with 50 children with leukaemia showed one dose of those vaccines was very immunogenic with protective titres achieved for the great majority of children. For children with post-bone marrow transplant, the current guidelines were formulated based only on the limited available evidence. The guidelines vary with the type of bone marrow transplant. The re-vaccination program should commence either 12 or 18 months after the transplant. The program suggested was total re-vaccination as infants would receive three doses of the routine vaccines, with MMR beginning a little bit later. Studies with this vaccine program showed that the program was safe and resulted in very high levels of protective antibody in these children. The effect of PCV was also looked at in this group, and most had two doses of PCV-7 and some had a third dose of polysaccharide vaccine. Two doses of conjugate vaccine gave high levels of protection with little additional benefit with the 23-valent vaccine. Pneumococcal disease in this group is worthy of focus because there are good data to show that the burden of invasive pneumococcal disease in children with leukaemia is significantly (10- to 50-fold) higher than that of background population. In a recent audit, nearly all oncology centres in the UK said they were following Royal College of Medicine recommendations. A third of centres are not recommending the PCV in this group and this is something that needs to be addressed. Premature infants are immunocompromised and are at increased risk of vaccine preventable infections.26 Premature infants have been shown to have an increased risk of pertussis, which can occur at six months of age and, therefore, the pertussis vaccine must be introduced as early as possible. The risk of disease for pneumococcal disease is highest within the first six months. Again, the vaccine must be used to give protection as early as possible because audits show that this group is under vaccinated. With regards to the protein vaccines, such as tetanus, as a general rule pre-term infants handle these vaccines well. The toxoid vaccines are very immunogenic and the protective concentrations that need to be achieved are very low. Premature infants do not
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respond so well to the Haemophilus influenzae Type b (Hib) vaccine. The conjugate and protein vaccines tend to behave differently in this population. In a study of the conjugate vaccines using the 2, 3, 4-month schedule comparing antibody responses in premature and full-term infants, responses were good in premature infants after three doses but below that of full-term infants. The protective antibody levels after three doses is similar in pre-term as in fullterm infants. However, titres start to fall by one year of age, which is the basis for the booster dose at 12 months. Similar conclusions can be drawn about the use of meningococcal C conjugate. Premature infants often achieve lower antibody concentrations after primary vaccination compared with full-term infants although the proportions achieving protective concentrations are often equivalent. The differences in concentrations become more evident with increasing time, so booster doses are particularly important in this group. They should receive all their vaccines on time with particular attention to booster doses. Hospitalised infants at the time of their first set of vaccines should be vaccinated in hospital before they are discharged and may be vaccinated a little earlier than 60 days if they are about to be discharged. This helps ensure that the first dose is given before they leave hospital and that their subsequent doses are given on time. The immunocompromised have a greater need for effective and safe vaccines than healthy children. They are usually under vaccinated. The evidence base for recommendations is often relatively small and further research is required in terms of burden of disease and the safety and immunogenicity of the vaccines. Cocooning strategies should be emphasized. Prospects for a Hypertension Vaccine Professor Tony Heagerty, Division of Cardiovascular and Endocrine Sciences in the School of Medicine, University of Manchester. Hypertension is the cause of 7.6 million premature deaths worldwide; 13.5% of total global deaths can be attributed to high blood pressure.27 It is estimated that by 2025, 1.56 billion people worldwide will have the disorder. High blood pressure is the single most important and reversible cause of stroke and heart disease. The British Hypertension Society (2004) set out a series of guidelines and suggested that if you have uncomplicated hypertension your blood pressure should be
