This study highlights good compliance with routine childhood immunizations, with the 90% up-to date status equivalent to the coverage rates of 93.6% at seen in Victoria, Australia overall. The uptake of recommended additional vaccines such as annual influenza vaccination and pneumococcal vaccine boosters was low.
There are very few published studies on compliance guidelines on immunizations in IBD patients[2, 21]. In a United States immunization status survey of 169 adolescents and adults diagnosed with IBD, 86% were using immunosuppressive therapies. On immunization status recall only 28% had received influenza and 13% pneumococcal vaccination. This compares with this study of influenza vaccination confirmed in 10% and additional pneumococcal vaccination 5%. When reviewing other special risk groups' compliance with recommended additional vaccines, a Victorian study of childhood cancer survivors found 47% had 'ever' had an influenza vaccine. This compared to 27% of children < 7 years diagnosed with cystic fibrosis and managed at RCH who had received an annual influenza vaccine and 37% the additional recommended pneumococcal vaccine. In addition in a study of preterm infants at two Victorian tertiary neonatal units, only 20% of infants with chronic lung disease had received an influenza vaccine.
The increased risk of morbidity and mortality from influenza infection in those with a chronic illness such as IBD is well described and confirmed in the 2009-10 HINI influenza epidemic[26, 27]. The response to influenza vaccine in patients receiving immunomodulatory therapy is variable, but usually satisfactory, as seen in an influenza vaccine sero-response study in 146 IBD patients, including those who were immunosuppressed. The safety of influenza vaccine in IBD patients has been reviewed in a cohort of adult IBD patients following H1N1 influenza vaccination . Four weeks after immunization, absence of a disease flare was observed in 96.7% patients with Crohn's disease and 95.6% with ulcerative colitis. The importance of physician recommendation for uptake of influenza vaccine, has been highlighted in a parental survey of children with a chronic illness.
Invasive pneumococcal disease (IPD) is also increased in those with an underlying chronic illness and on immunosuppressive therapies. It is hence important to protect IBD patients from these VPD. Australia introduced a 7-valent conjugate pneumococcal vaccine (PCV7) on 1 Jan 2005, and the special risk guidelines current in 2007 recommended additional 7vPCV if under 10 years and 23 valent polysaccharide vaccine 23vPPV if > 10 years of age. The response in adults to 23vPPV is variable and IBD patients on biologic therapies such as infliximab achieve lower protective titres. Newer pneumococcal conjugate vaccines with increasing numbers of serotypes are becoming available internationally  and the 13 valent conjugate vaccine (PCV13) introduced into a number of countries including the United States and soon in Australia[34, 35]. Importantly the PCV13 vaccine is also being studied in adults > 50 years, and early results from phase III immunogenicity studies found an equivalent or better response than the 23vPPV. Studies are also in progress to determine the efficacy of this vaccine in preventing community acquired pneumonia in adults > 65 years. Studies of these newer PCV are required in special risk populations to assess both their safety and immunogenicity and help determine the best schedule to optimise IPD protection.
The risk of reactivation of diseases such as hepatitis B by these anti-TNFα antibody therapies, has led to recommendations of additional screening before commencing therapy[38, 39]. In this study 20% of participants had been treated with infliximab and other biologic therapies may be used in the future. Reassuringly, 93% (39/42) of those with comprehensive immunization records had documented evidence of hepatitis B vaccination. However, serological testing confirming a negative Hepatitis B infection status was conducted in only four patients. It is possible this is an underestimate as serology samples may have been sent to external laboratories. Another limitation of this serological evaluation was that it was conducted at only one of the two sites (RCH), but included 94% of subjects.
Live vaccines need to be considered with caution in patients who are immunosuppressed, due to the risk of vaccine associated morbidity such as seen with measles vaccine. Varicella vaccine was introduced into Australian on 1 November 2005 for all children aged 18 months with a catch-up program at age 12-13 years. In this study 9% (4/42) were found to not have a history of clinical infection or immunization against varicella placing them at risk, similar to the 10% found in the United States IBD survey. The morbidity of varicella in immunosuppressed patients has led to studies challenging the general recommendation that this live attenuated vaccines not be administered. A case series of six young people with IBD safely receiving varicella vaccination whilst on infliximab therapy. Despite small numbers of patients, it highlights the need to discuss the risk versus benefits of live attenuated vaccines on a case-by-case basis. Another approach is to review the immunization status at diagnosis and give all recommended vaccines (e.g. varicella, hepatitis B) before commencing immunosuppressive therapy. This, however, is becoming a smaller window of opportunity with the earlier use of immunomodulatory therapy in IBD.
A limitation of the study is the retrospective nature of the review in a state based IBD population. It was a representative sample of the database, but some IBD patients may have been excluded if seeing a private and/or adult gastroenterologist and not placed on the register. One major difficulty in conducting the study was uptake of 'opt in' consent, reflected by only 53% of adolescent and young adult patients being contactable. These are common issues in retrospective health related research and a number of surveys have explored the importance of exploring meaningful non-consent and considering 'opt out' consent[43, 44]. The study was powered for 100 audit participants, but the results were affected by the low recruitment for the telephone immunization status review. The reported proportions of participants receiving the additional pneumococcal and influenza vaccines may not reflect the actual immunization status due to this incomplete record obtainment. The study was also underpowered to detect differences in the characteristics of those who received influenza vaccine. Another limitation is that the ACIR only routinely captures and maintains immunization records in children < 7 years of age, so added little information in this predominantly adolescent population. Whilst ACIR can include additional vaccines (e.g. influenza and pneumococcal), this information is not always captured.
Suboptimal compliance with annual influenza vaccination and other additional vaccines recommended could be due to lack of awareness or acceptance of immunization guidelines for IBD patients. Engagement with subspecialists like pediatric gastroenterologists managing these complex patients is important. As the primary source of healthcare related advice for IBD patients, surveying their opinions regarding immunization would be helpful and lack of this information is a study limitation. An Australian survey of adult gastroenterologists found hepatitis B, influenza and pneumococcal vaccines were recommended infrequently and the window before significant immunosuppressive therapies commenced not always being utilised.
Strategies to optimise protection from VPD include education of both patients and their parents/carers, as highlighted by the reasons given for influenza vaccination not being received. Education itself needs to be supported by system changes and this may include immunization reminders, which in the form of cards, telephone and electronic, have all been shown to be effective[46, 47]. Protecting IBD patients through "cocooning", by ensuring parents and siblings are protected against VPD (e.g. influenza, pertussis and varicella), is also recommended.