Original article 249

A ‘cocoon immunization strategy’ among patients with inflammatory bowel disease Karolina Waszczuka, Ewa Waszczukb, Agata Mulakb, Leszek Szenborna and Leszek Paradowskib Background and aims A ‘cocoon strategy’ is defined as the strategy of protecting vulnerable patients from infectious diseases by vaccinating those in close contact with them. In our study, we evaluate the vaccination status among children living with patients with inflammatory bowel disease (IBD) to determine the realization of the cocoon strategy and to identify characteristics associated with pediatric vaccine refusal. Patients and methods A self-completed survey was conducted on 136 hospitalized patients with IBD. The survey comprised questions about household child vaccination coverage, the reasons for vaccine refusal, and the history of infectious diseases among the patients. Results Fifty-six patients reported living with children. Forty percent of children were vaccinated with at least one of the recommended vaccines. Most frequently, children received pneumococcal (26%) and rotaviruses (22%) vaccines. The most common reason for nonimmunization was patients’ opinion that immunizations are not necessary for them (52%). There was a statistically significant association between the nonreimbursed vaccines coverage and the educational level of the patients (P < 0.0001). Despite the fact that 28% of the patients could not definitively recall

varicella infection, none of them and none of the children in their household had been vaccinated against chickenpox. Conclusion The use of nonmandatory vaccines recommended in family members of patients with IBD is insufficient. Further vaccine promotion and education of patients as well as their healthcare providers is required. A particular concern is associated with the pneumococcal, influenza, rotaviruses, and varicella infections. Nonimmunized and varicella-zoster virus-seronegative patients should be vaccinated, and in case of immunosuppression, vaccination of children in the household is required. Eur J Gastroenterol Hepatol 27:249–253 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. European Journal of Gastroenterology & Hepatology 2015, 27:249–253 Keywords: household children, immunization, infectious diseases, inflammatory bowel disease Departments of aPediatrics and Infectious Diseases and bGastroenterology and Hepatology, Wroclaw Medical University, Wroclaw, Poland Correspondence to Karolina Waszczuk, MD, Department of Pediatrics and Infectious Diseases, Wroclaw Medical University, Bujwida 44, 50-345 Wroclaw, Poland Tel: + 71 770 31 51; fax: + 71 770 31 52; e-mail: [email protected] Received 12 October 2014 Accepted 8 December 2014

Introduction Patients with inflammatory bowel disease (IBD) are at a higher risk of infections and their severe or fatal outcomes than the general population [1,2]. Predominantly, it is associated with immunosuppressive treatment, which involves corticosteroids, immunomodulators, or biologic therapy, and it is also related to malnutrition caused by the disease itself [3,4]. As some of the infectious diseases are vaccine preventable, specific immunization guidelines have been established for this group of patients [5–7]. The European Crohn’s and Colitis Organisation (ECCO) and the Polish Society of Gastroenterology emphasize the major role of hepatitis B, pneumococcal, and seasonal influenza vaccination [5,6,8]. In case of a varicella-zoster virus (VZV)-naive or measles virusnaive individual, a specific live vaccine is recommended before the initiation of immunosuppression therapy. However, vaccination coverage in IBD patients is very poor, mainly because neither gastroenterologists nor their patients are aware Part of the work has been accepted for presentation at the 22th United European Gastroenterology Week; Vienna; 18–22 October 2014. 0954-691X Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

of any existing recommendations [9–11]. Furthermore, although vaccine immunogenicity, measured as the postvaccination antibody level, is well investigated and reasonably good, there are still questions on vaccine effectiveness in chronically ill patients, especially those vaccinated on combined immunosuppressive therapy [12–17]. In addition, there is a special concern in terms of live vaccines, which are contraindicated in an immunocompromised host [3,18]. An optional method to protect a vulnerable person from developing infections is known as a ‘cocoon strategy’. Originally, it resulted from the use of the pertussis vaccine to protect infants who are at a high risk of severe complications caused by Bordetella pertussis [19]. Its main focus is close-contact immunization, which could reduce the possibility of bacterial transmission. In a broad sense, the vaccination of the general population for other immunizations is effective and provides a herd immunity effect. Recent studies have reported the beneficial effects of pneumococcal and influenza vaccination [20]. Similar results were obtained for a rotavirus vaccine-infant DOI: 10.1097/MEG.0000000000000280

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250 European Journal of Gastroenterology & Hepatology 2015, Vol 27 No 3

immunization program, which resulted in a decreased morbidity rate among nonimmunized children and adults [21]. Of particular interest is a rotavirus infection in an immunosuppressed host that may have a prolonged or a disseminated course of disease [22]. An indirect way to protect these individuals is through the immunization of their young children. There are two available vaccines against rotaviruses infection: Rotarix, which is approved for use in infants from 6 to 24 weeks of age, and Rotateq, which may be administered by the age of 32 weeks [23,24]. Children are also common vectors of other easily transmitted infectious diseases, which pose a risk to a chronically ill adult living in the same household. However, to our knowledge, there are no previous studies assessing vaccination coverage among close contacts of either IBD patients or patients with other chronic conditions. Polish children follow an immunization schedule based on the Polish National Immunisation Programme. It is established annually as a directive of the Ministry of Health and includes mandatory vaccines, paid by the Ministry of Health, as well as recommended, nonreimbursed vaccines [25]. A detailed list of vaccines is shown in Table 1. Except measles, mumps, rubella and, in some cases, the VZV vaccine, all the other vaccines recommended for healthy household contacts are self-funded. In our study, we aimed to evaluate the vaccination status of children living with IBD patients to determine the realization of the cocoon strategy and to identify the characteristics associated with pediatric vaccine refusal.

Patients and methods Study group

Our cross-sectional study was carried out at the Department of Gastroenterology and Hepatology of Wroclaw Medical University. The clinic provides consultative care for patients with IBD for the entire south-west of Poland. Data were collected from November 2013 to April 2014. As a part of a larger study on the immunization of IBD patients, we enrolled 136 consecutive IBD patients admitted to the clinic for the evaluation or the treatment of IBD. Every patient received a detailed information sheet on the study and its aims. The Polish national immunization program 2014 for children aged 0–18 years (except some high-risk groups) [25]

Table 1

Mandatory vaccines Hepatitis B Tuberculosis (only at birth) Tetanus, diphtheria, pertussis (TdP/TdaP) Haemophilus influenzae B (HiB) Poliomyelitis Measles, mumps, rubella

Recommended vaccines Hepatitis A Varicella Influenza Pneumococcal Meningococcal Rotaviruses Human papilloma virus (HPV)

The study was approved by our institutional ethics committee and written informed consent was obtained from all the participants before enrollment. Study instrument

A self-completed survey on vaccination coverage among IBD patients and their household children was conducted. The survey was designed by authors on the basis of the ECCO consensus on the prevention of opportunistic infections in IBD [5,6]. Initially, patients were asked whether they had at least one child in the household (yes/no question). The survey consisted of two main parts. The first part comprised questions about the IBD patients, including their basic demographic data, IBD-related medical history, immunization history, and previous VZV infection. In the second part, we collected information on the children in the patient’s household. We asked to which age group the children belonged (0–5, 6–12, 13–18 years), their immunization coverage of mandatory and self-paid vaccines, and the reasons for recommended vaccine refusal. The immunization status was assessed on the basis of recall of vaccination against pneumococcus (ever), influenza (annually), and varicella (ever) and also, only for children, rotaviruses (ever). To carry out a statistical analysis, a child was defined as ‘vaccinated’ with a recommended, nonrefunded vaccine if he/she had received at least one of the vaccines of interest (i.e. pneumococcal, influenza, varicella or rotaviruses vaccine). Consequently, we divided the IBD patients into two groups: living with ‘vaccinated’ and ‘unvaccinated’ child/children. Then, we analyzed whether patient educational level, residency, age, or time from IBD diagnosis influenced the vaccination status of the child. Randomly, patients completed the survey with a physician present to clarify the questions if necessary. To ensure test–retest reliability, a group of 10 patients completed the survey twice. Statistical analysis

Statistical analysis was carried out using R Statistical Software (R Foundation for Statistical Computing, Vienna, Austria) [26]. We used the Fisher exact test for 3 × 2 contingency tables to check nonrandom associations between two categorical variables – that is, the educational level and child vaccination coverage as well as residency and child vaccination coverage. If a statistical difference was found, with P-value less than 0.05, we subsequently carried out a post-hoc analysis for the detection of the group responsible for the difference. For this reason, we applied the Fisher exact test for every three combinations of 2 × 2 contingency tables. We also applied the Bonferroni correction to the P-value to reduce the possibility of significance towing to chance because of multiple statistical testing, and significance was assumed only when the P-value was less than 0.017. In the analysis of IBD patients, age and time from the IBD diagnosis in the two subgroups of patients with

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A ‘cocoon strategy’ in IBD patients Waszczuk et al. 251

vaccinated and nonvaccinated children by self-funded vaccines, we used the Mann–Whitney–Wilcoxon test at a 0.05 level of significance.

Results From the group of 136 patients surveyed, we analyzed data from 56 of those who reported having at least one child in the household (41%, 56/136). The average patient age was 36 years (range 16–60 years), 27 of these were women. Most of the patients in this group had ulcerative colitis (68%, 38/56), whereas 32% had Crohn’s disease. The mean duration of the disease was 8 years. The overall number of children living with IBD patients was 65; 34% belonged to the 0–5 years age group, 32% belonged to the 6–12 years age group, and 34% belonged to the 13–18 years age group. The vaccination status of IBD patients is presented in Table 2. In our study group, only individual patients indicated that they had received the pneumococcal or the VZV vaccine. The influenza vaccine uptake was slightly higher – 4/56 (7%) of patients reported annual immunization. Because of the very poor vaccination coverage of IBD patients, we could not statistically compare it with the immunization status of the child in their household. The varicella immunity in our study group was as follows: most of the patients (70%) reported having a previous varicella infection, but 28% could not definitively recall VZV infection and only one patient had been vaccinated against VZV. In the section on child household contact immunization, two patients reported refusal of one mandatory vaccine. They also filled the additional free space providing the reasons for this. In one case, there were concerns about the safety of the measles, mumps, rubella vaccine; in the second case, the obligatory immunization program was not performed because of medical contraindications. Table 2 presents the household child vaccination status. Forty percent of children were vaccinated with at least one of the recommended vaccines. Most frequently, the pneumococcal vaccine was chosen (26%), followed by rotaviruses (22%), VZV (14%), and influenza (12%) vaccines. A statistically significant difference was found in child vaccination coverage between patients with primary, Vaccination status of inflammatory bowel disease patients and the children in their household Table 2

N (%)

Vaccinations Pneumococcal Influenza VZV Rotaviruses

Number of vaccinated IBD patients

Number of vaccinated children

1/56 (2) 4/56 (7) 1/56 (2) –

IBD, inflammatory bowel disease; VZV, varicella-zoster virus.

17/65 8/65 9/65 14/65

(26) (12) (14) (22)

secondary, and tertiary education level. Adults with university degree-level education were more likely to have their children immunized with at least one self-funded vaccine than less-educated patients (P < 0.001) (Table 3). There was no influence of the IBD patients’ age, time from the IBD diagnosis, and place of residence on the decision of vaccination of a child. Thirty-six patients provided the reasons for the refusal of a recommended vaccination for a child (Table 4). Over half (52%) of the patients claimed that, in their opinion, recommended immunizations were not necessary, whereas 25% of the patients expressed concern over the potential side effects of the vaccine. Other answers included patients’ doubts about the efficacy of immunization (14%), the high cost of the vaccine (6%), and discouragement from medical health workers (3%).

Discussion To our knowledge, this is the first study that attempts to evaluate the level of IBD patients’ protection from some vaccine-preventable infections by the use of the ‘cocoon strategy’. There are no similar previous studies either on IBD patients or on patients with other chronic disorders. Moreover, little data exist on herd protection in the general population; when found, it is usually focused on influenza, pneumococcal, and rarely, rotavirus vaccines. Not surprisingly, we found that vaccination coverage among IBD patients is very poor, which is consistent with several previous studies carried out in Poland as well as in the USA [9,10]. The Polish study showed that healthy controls are more likely to be vaccinated against influenza than children with IBD by a factor of 2 [10]. In our study, 7% of patients reported receiving the annual influenza vaccination, whereas only 2% had been immunized against Streptococcus pneumoniae. This can be attributed to promotion of the pneumococcal vaccine, which, in Poland, is focused on children and individuals older than 65 years of age, and does not target individuals with chronic immune-mediated diseases. Factors influencing parents’ decision on administration of recommended vaccination for children

Table 3

Child vaccination status

Parent educational level Primary Secondary Tertiary Post-hoc analysis Primary vs. secondary Secondary vs. tertiary Primary vs. tertiary Residency Village Town population < 40 000 Town population > 40 000

Vaccinated

Unvaccinated

P-value

1 4 18

8 9 6

< 0.0001*

NS < 0.0001** < 0.0001** 6 10 11

14 9 6

NS

*Fisher exact test; 0.05 level of significance. **Fisher exact test with Bonferroni correction; 0.017 level of significance.

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Parents’ answers on the reasons for refusal of vaccines recommended for children (n = 36)

Table 4

N (%) I don’t think it is necessary I doubt vaccine efficacy I am afraid of vaccine side effects Vaccines are too expensive Medical health workers discouraged me from vaccination

19 5 9 2 1

(52) (14) (25) (6) (3)

Taking into account the vulnerability of immunosuppressed patients to infections, in addition to their low immunization rates, additional protection should be considered. Alarmingly, further to this, children living with IBD patients are not sufficiently vaccinated with immunizations recommended for them. Because of the lack of other studies in this field, we can compare our findings only to the general pediatric population in Poland. Ganczak et al. [27] reported low nonreimbursed vaccination uptake among Polish children. According to their study, more than half of the parents decided to opt for a combined vaccine to decrease the number of injections. We did not assess this type of vaccine as their compounds jointly enter into the mandatory immunization schedule and their selection does not alter the general herd immunity. Among immunizations of special importance for the IBD patient population, we found similar uptake of pneumococcal and influenza vaccines (26 and 12%, respectively), but there were discrepancies in VZV and rotavirus immunization (Fig. 1). The reason for this could be in a significant, and larger than in Ganczak's study, number of children aged 0–5 years in our study group, because the rotavirus vaccine is contraindicated for children over 8 months of age and older children cannot be vaccinated. Moreover, the findings of our study and those of Ganczak and colleagues on influenza coverage differ from the official data provided by the National Institute of Public Health, which reported that only 1–2% of Polish children are up to date with influenza vaccination [28]. The analysis of patients’ statements on the refusal of recommended vaccines shows that almost half of them mistakenly perceive that they are not at a high risk of severe infections. A similar observation was also reported by Melmed et al. [9]. Among the patients studied, 25% admitted that they had concerns about the side effects of the vaccine. This was the most common reason that parents provided for opting not to have the influenza vaccine [10]. In addition, patients also doubted the efficacy of vaccines. Surprisingly, in one case, the patient was advised by a medical health worker to avoid immunization. Taken together, we can conclude that patients are misinformed about immunizations. Partially, this may have resulted from the impact of growing antivaccination movements but also from misinformation from healthcare providers. Similar to previous studies, we found a relationship between educational level and self-funded vaccination

Fig. 1

40 Our study Ganczak et al.’s study

30

20

10

0 Varicella

Influenza

Pneumococcal

Rotavirus

Vaccination coverage (%) in a selected Polish population examined in the present study compared with the study of Ganczak et al. [27].

coverage [27]. In contrast, we did not find any influence of patients’ place of residence, age, and duration of IBD [27]. The European and American guidelines highlight the special concern of VZV infection in an immunocompromised host [5–7]. Among our patients, 28% could not definitively recall a previous varicella infection and none of them and none of the children in their household had been vaccinated against chickenpox. In this situation, even if a negative history of chickenpox is often unreliable, all these patients should undergo VZV serological testing to determine their immune status. In case of a naive individual, the VZV vaccine should be administered; as it is a live vaccine, it is contraindicated in an immunosuppressed host. In this situation, the main objective is prevention of VZV infection by vaccinating children living with a susceptible individual. Our study has several limitations. First of all, it is a small, single-center study group. It is based on self-reported vaccination rates, but only recommended, nonreimbursed vaccination uptake was questioned and usually patients recall what they have purchased. Moreover, to reduce respondent bias, the assistance of a medical healthcare worker was provided, if needed. We can conclude that the strategy of IBD patient closecontact immunization is not accomplished at all. Our study is the first to assess the cocooning strategy in this group of patients and provides new data on this aspect. First of all, patients are not aware either of the importance of the vaccinations or the role of ‘cocoon’ protection.

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A ‘cocoon strategy’ in IBD patients Waszczuk et al. 253

Summarizing our findings and taking into account that IBD patients may have an impaired response to pneumococcal and influenza vaccine, there are contraindications for live vaccine administration during immunosuppression therapy, and the vaccine against rotaviruses is not available for adults; children in the household should be offered, in particular, pneumococcal, influenza, varicella, and rotaviruses vaccines [12,15–17].

9

10

11

It is likely that patients would benefit from promotion programs that highlight the importance of prevention of infectious disease. Also of special importance is the education of gastroenterologists, who play a major role in the counseling of IBD patients and should keep immunizations up to date [9]. Moreover, further multicenter studies are required on close-contact immunization of patients with IBD to provide more robust evidence.

Acknowledgements K.W. conceived and designed the study, analyzed the data, and drafted the manuscript. E.W. designed and coordinated the study, performed the surveys, and revised the manuscript. A.M. carried out the study and revised the manuscript. L.S. participated in designing and coordinating the study, and revised the manuscript. L.P. participated in designing and coordinating the study, and revised the manuscript. All authors read and approved the final manuscript. Conflicts of interest

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L.S. has received grants from GlaxoSmithKline, Pfizer, and Novartis for study conduct; he has acted as a speaker for Pfizer, Novartis, Sanofi, GSK; he has received grants from Novartis and Pfizer for participation in conferences. For the remaining authors there are no conflicts of interest.

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A 'cocoon immunization strategy' among patients with inflammatory bowel disease.

A 'cocoon strategy' is defined as the strategy of protecting vulnerable patients from infectious diseases by vaccinating those in close contact with t...
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