DÄ internationalArchive7/2011Vaccination Coverage in Immunosuppressed Patients

Original article

Vaccination Coverage in Immunosuppressed Patients

Results of a Regional Health Services Research Study

Dtsch Arztebl Int 2011; 108(7): 105-11; DOI: 10.3238/arztebl.2011.0105

Teich, N; Klugmann, T; Tiedemann, A; Holler, B; Mössner, J; Liebetrau, A; Schiefke, I

Background: Patients with chronic inflammatory diseases are at elevated risk of infections that can be prevented by vaccination. This elevated risk is due not just to these patients’ primary illnesses, but also to the immunosuppressive treatment that they often receive. We studied the vaccination rate in a random sample of patients with two types of inflammatory bowel disease (IBD), namely, Crohn’s disease and ulcerative colitis. In particular, we asked unvaccinated patients why they had re-fused the vaccine.

Methods: From April to September 2009, we gave a 38-item questionnaire to 203 consecutive patients with IBD (57% with Crohn’s disease, 63% female, median age 36 years) who had not received vaccination counseling for at least one year, and inspected the patients’ vaccination cards. We compared the findings to the current recommendations of the German Federal Standing Committee on Vaccination (Ständige Impfkommission).

Results: 83% of the patients had a vaccination card. Substantial deficiencies in vaccination were found. Only 67% of the patients had been immunized against tetanus in the previous 10 years, and only 21% against pertussis. Only 28% were vaccinated against seasonal influenza in 2008, and only 9% had ever received anti-pneumococcal vaccine. A subgroup analysis in which we compared 39 patients taking TNF-blockers to 67 patients who never had any type of immunosuppressive treatment revealed no difference in vaccination rates. 80% of all patients said they were willing to receive all of the officially recommended vaccinations. 22% of all patients said they avoided vaccinations for fear of side effects, while 15% said they did so because their immune system was supposedly “not intact”, and 9% because they feared vaccination would worsen their IBD.

Conclusion: In this random sample, the vaccination rate fell far behind the recommendations. In particular, there was a marked discrepancy between patients’ willingness to be vaccinated and the actual provision of vaccination. These findings imply that physicians need to be more aware of the possibly inadequate vaccination state of their immunosuppressed patients.

LNSLNS

The treatment concepts for patients with chronic inflammatory bowel disease (IBD), which is subdivided into Crohn’s disease (CD) and ulcerative colitis (UC), have changed markedly in recent decades. Currently, many patients are started early on long-term treatment with classic immunosuppressive agents or anti-TNF-alpha antibodies (TNF-blockers). TNF-blockers have also been approved for a wide range of rheumatological and dermatological indications and are now the best-selling single preparations in Germany (1, 2). The “classic” immune suppressants azathioprine and methotrexate are being used more commonly as well: in 2009, the overall expenditures for these two drugs in Germany were higher than in 2008 by 4% and 10%, respectively (1). These figures imply that an increasing number of patients are being treated with potent immune suppressants.

Impaired defenses against infection are both a potential sequela of a chronic inflammatory disease and a potential side effect of immunosuppressive treatment (3, 4). There have been reports of infections that could have been prevented by vaccination, including infection with the hepatitis B virus, the human papilloma virus, the varicella-zoster virus, and the influenza virus, among patients with IBD being treated with either the “classic” immune suppressants or TNF-blockers (58). In the case of pneumococcal infection, the intensity of immunosuppressive treatment appears to be associated with the severity of infection, which ranges to the life-threatening Waterhouse-Friderichsen syndrome (912).

A IBD patient’s risk of developing an infectious disease is elevated even in the absence of immunosuppresive treatment. A recent study showed that IBD patients are 57% more likely to develop herpes zoster than normal controls, with an absolute risk of 0.89% per year, as determined from data on more than 22 000 patients (13). Consensus papers have, therefore, been issued both by the European Crohn’s and Colitis Organisation and by the German Society of Digestive and Metabolic Diseases (Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten) recommending the determination of vaccination status in IBD patients, followed by the administration of all vaccinations that have not been given or are not up to date, if applicable.

The authors, however, have gained the impression from everyday clinical practice that IBD patients often have a deficient vaccination status. The purpose of this exploratory study is to assess the vaccination status of IBD patients and, in particular, to determine what reservations, if any, the patients had against the vaccinations recommended by the The German Standing Vaccination Committee (Ständige Impfkommission, STIKO) (Table 1 gif ppt). We present our findings here and suggest that they may be relevant to patients with other types of chronic inflammatory disease as well.

Methods

We asked 203 consecutive patients with IBD to bring all of the vaccination documents that they possessed to their next outpatient appointment. The documents were copied, and the data in them were electronically entered into an anonymous database, as were the patients’ responses to a questionnaire containing 38 questions (eSupplement, available in German). The disease-specific data that were obtained included the duration of disease, all operations that were performed to treat IBD, and a precise and detailed medication history, particularly with respect to immune suppressants. Patients who had been counselled about vaccinations by a doctor within the past year were not included in the study, in order to avoid distortion of the data through varying degrees of prior patient education.

The study began in all three of the participating institutions on 1 April 2009. We decided to terminate it on 30 September 2009, because of concern that the initial media reports of a possible “swine flu” pandemic might alter patients’ perceptions of their own vaccination status and thereby skew the findings of the study.

Findings concerning the categorical variables were expressed as frequencies (in percent). The statistical analysis was performed with the chi-squared test. If the predicted cell frequency was less than 5, Fisher’s exact test was used. Groups were compared with the Mann-Whitney U test. P-values below 0.05 were considered statistically significant.

Results

Patient characteristics

The patients’ median age was 36 years (interquartile ranks [IQR, i.e., 25th and 75th percentiles], 26 and 47 years). 127 (63 %) of the 203 participants were female. 116 (57%) had Crohn’s disease (CD), 84 (41%) had ulcerative colitis (UC), and 3 (2%) had a IBD of undetermined type. The median duration of illness was 7 years (IQR 2 years / 12 years), while the maximum duration of illnes was 34 years. 180 patients were being treated by gastroenterologists in private practice and 23 in the outpatient clinic of a university hospital. 52 (25.6%) had undergone at least one operation related to their IBD, while 162 (80%) already required 20 mg or more of prednisolone daily. Their remaining medications are summarized in Table 2 (gif ppt) . In the remainder of this article, we will refer to azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate as the “classic” immune suppressants.

Most of the study participants had spent their childhood up to age 10 in the State of Saxony (136 patients) or another state of the former East Germany (49 patients). Nearly all of the participants currently resided in Saxony (182 patients) or another eastern German state (18 patients). 40% of them had completed secondary education at least up to university-entrance level, 46% had finished 10th grade, and the remaining 14% had terminated their schooling earlier.

Documentation of vaccination and assessment of vaccination status

168 (83%) of the patients were able to produce a vaccination certificate. Most of the remaining 35 patients felt sure that they possessed such a certificate but could not find it even after an extensive search (sometimes in their parents’ house as well). 54% of the patients felt sure that they were completely vaccinated, 23% thought they were incompletely vaccinated, and the rest were unsure whether they were adequately vaccinated or not.

125 patients (62%) asked their family doctor to check their vaccination status, 34 (17%) checked their vaccination status themselves, and 15 (7%) asked their gastroenterologist. Four patients asked their occupational health physician, two asked a physician in the government health department, and one each asked a gynecologist and a rheumatologist (some sought information from multiple sources). 44 (22%) never checked their vaccination status and could not remember that it had ever been checked.

Patients’ willingness to be vaccinated and their reasons for not being vaccinated

163 patients (80.3%) responded “yes” to the question, “Would you be willing to have all of the officially recommended vaccinations?” The authors also gave the patients a list of potential arguments against vaccination and asked them to state which of these arguments applied in their case (Table 3 gif ppt). 22.2 % agreed with at least one of these arguments. Four patients said they would be willing to have all of the officially recommended vaccinations but also stated that they were afraid of side effects.

The patients also had the opportunity to write down any other reasons they had not to be vaccinated. Nine patients did so, stating that they avoided vaccinations because vaccinations are ineffective (1), questionably effective (2), or possibly unnecessary (1), or because they forgot to be vaccinated (1), have no time for it (1), prefer alternative medicine (1), are reckless with their health (1), or fear developing yet another autoimmune disease (1). 108 patients (53.2%) agreed with none of the proffered arguments and supplied no others of their own.

Evaluation of vaccination certificates

Evaluation of the vaccination certificates revealed that only two-thirds of the patients had been vaccinated against tetanus and diphtheria in the preceding 10 years; this is the STIKO’s minimal recommendation for all persons living in Germany (Table 4 gif ppt). Only 56 patients (33%) had received the seasonal influenza vaccine in 2008. The patients’ status with respect to all vaccinations recommended by the STIKO is shown in Table 5 (gif ppt).

A subgroup analysis was performed to compare the vaccination status of patients taking TNF-blockers to that of patients who had never been treated with a “classic” immune suppressant. No significant difference was found (Table 6 gif ppt).

Univariate analysis revealed no significant differences regarding vaccination status between patients in the 1st and 4th age quartiles, or regarding the duration of IBD or the total population of the patient’s birthplace or educational level (below 10th grade vs. high school graduate). In the absence of such differences, no multivariate analysis was performed.

Discussion

The vaccination status of this group of patients with chronic inflammatory bowel disease was markedly inferior to the standard set by the STIKO recommendations. Only two-thirds of the participants complied with the disease-independent recommendations to boost their tetanus and diphtheria immunizations every 10 years. Two-thirds or more of them were not adequately immunized against diseases that can be especially severe in patients with IBD and that are preventable by vaccination (hepatitis B, influenza, and diseases caused by the varicella-zoster virus, pneumococci, and human papilloma viruses).

In a similar study in Los Angeles, 169 IBD patients were asked whether they had been vaccinated against tetanus in the past 10 years, and only 45% answered “yes.” This percentage is even lower than the figure of 67% obtained in the present study. On the other hand, the Los Angeles patients were vaccinated against seasonal influenza at about the same rate as our patients (28% vs. 33%), and the same was true of antipneumococcal vaccination (9% vs. 11 %). In the Los Angeles study, too, 18% of patients gave the fear of side effects as a major reason for not being vaccinated—a figure comparable with the 22% seen in our study (14). In other studies, the same fear was found to be patients’ major reason not to be vaccinated against other types of disease as well (15, 16).

The problem of inadequate vaccination of immunosuppressed patients has been found in other patient groups (1719): in one study, for example, among 46 children who had undergone renal transplantation, only 2 (4%) were fully vaccinated in accordance with the relevant disease-specific recommendations (19).

A study of the vaccination status of 715 patients with juvenile idiopathic arthritis (JIA) revealed lower rates of vaccination against tetanus and diphtheria in patients aged 7 to 11 than in healthy control children; the discrepancy was even more marked among patients aged 12 to 17. No overall statistical link was found between pharmacotherapy and the vaccination rate , but a significant correlation was found between the intensity of pharmacotherapy among the JIA patients and their non-receipt of the MMR vaccine. Every third JIA patient was inadequately immunized: the main reason was that a doctor had advised against vaccination (79%), while the parents’ refusal to vaccinate was merely a secondary reason (10%) (20).

In the present study, however, we found no difference in the rates of vaccination with the non-live tetanus/diphtheria vaccine and the live MMR vaccine (Tables 4 and 5). One obvious reason for this is that the STIKO recommends MMR vaccination in early childhood, and most of the study participants had not yet developed IBD at that age. The patients were in markedly worse compliance with the vaccination recommendations that apply only to patients receiving immunosuppressive treatment—specifically, vaccination against varicella, meningococci, and pneumococci (Table 5). Among the adults involved in the present study, unlike the children in the study mentioned above (20), no patient expressed a general aversion to vaccination, and only 8.4% had avoided vaccination on the advice of a physician. Our data, however, might not be representative of Germany as a whole: more than 90% of our patients grew up in the former East Germany, and vaccination rates in the former West Germany generally tend to be lower than in the East (20, 21).

One limitation of this study is that we could not compare our patients’ vaccination rates with those of the healthy general population. A representative study of a healthy control group with respect to all generally recommended vaccinations would not have been feasible, because such people rarely, if ever, consult a physician. Data on the vaccination status of children are collected at the start of each school year and are published annually by the Robert Koch Institute (RKI), but comparable data on adolescents and adults are lacking (22, 23). As part of its nationwide health monitoring project, the RKI is currently collecting data on the vaccination status of adults via telephone survey (Telephone Health Survey, GEDA; German Adult Health Study [Studie zur Gesundheit Erwachsener in Deutschland], DEGS), but the findings have not yet been published and are thus not available for comparison with our data. One can obtain further information on the content and methods of these studies on the Robert Koch Institute’s website, http://www.rki.de (select “English” at top right, then proceed to the link “Health Reporting” and to the subsequent link “Health Surveys”).

Another limitation of this study is that some patients could not produce any documentation of their vaccination status. We considered this the equivalent of non-vaccination, and thus our reported findings may be worse than is actually the case. Our procedure does, however, correspond to the STIKO recommendations themselves (24). Yet another possible limitation of the patient cohort in the present study derives from our primary exclusion of all patients who had been counseled by a physician about vaccinations within the past year. Our aim was to avoid any additional bias due to variable patient education. Use of this exclusion criterion might, however, have made the findings worse than they would have been in a non-preselected patient group, because patients receiving good medical care were preferentially excluded a priori.

It seems out of keeping with the mostly inadequate vaccination status of the patients in our study that more than half of them expressed no reservations whatsoever about vaccinations, and that more than 80% said they were willing to have all of the recommended vaccinations. This discrepancy may well have been due to inadequate knowledge among the patients themselves and among their physicians, not just of the generally recommended vaccinations, but also of the vaccinations that are specifically recommended for patients with IBD. This apparent effect of physicians’ faulty knowledge on the implementation of recommendations to vaccinate is parallelled in the findings of a recently published rheumatological study. The Vaccination Committee of the German Society for Pediatric and Adolescent Rheumatology (Deutsche Gesellschaft für Kinder- und Jugendrheumatologie) surveyed its members with respect to vaccination practices and found major differences of attitude toward the use of live vaccines: for example, half of the rheumatologists surveyed said that MMR vaccination was permissible in patients receiving methotrexate, and half said that it was not. Lesser differences were found with respect to the use of non-live vaccines: most (58-100%) of the rheumatologists were willing to give the recommended vaccinations of this type to patients receiving a variety of drug combinations (21).

Most patients named their family physician or general practitioner as the most important person to whom they would turn to check their vaccination status. Fewer than 10% of them asked their gastroenterologist for help in checking their vaccination status. Nevertheless, in our opinion, the primary prescriber of immunosuppressive drugs bears the responsibility to check that the patient has actually received all of the vaccinations that are recommended when such drugs are given.

We think the findings of this study indicate deficiencies in the medical care of the patients whom we surveyed. We have, therefore, worked with the President of the Vaccination Committee for the State of Saxony (Sächsische Impfkommission, SIKO) to produce a quality management instrument that incorporates the IBD-related recommendations of both the STIKO and the SIKO. The SIKO recommendations are the most suitable ones for implementation in the region where we practice (Table 1). Updated recommendations of the STIKO can be found at http://www.rki.de, and the SIKO recommendations can be found at http://www.lua.sachsen.de. In rare cases, as when a patient lives in Saxony but is insured in a different German state, the differences between these two sets of recommendations may create difficulties in their reimbursable implementation; we recommend discussing any such problems directly with the local health department, or with the insurance carrier.

Drawing a further conclusion from the findings of this study, we recommend the serologic measurement of antibody titers against measles, mumps, rubella, varicella, and hepatitis B, as well as a tuberculosis test, for all patients with IBD, often as early as the initial consultation. This is reasonable, as it provides a means of detecting any potential need for immunization with a live vaccine (e.g., against measles, mumps, rubella, or varicella) before immunosuppressive treatment becomes necessary.

A number of opportunistic infections that are more common in immunocompromised patients cannot be prevented by vaccination: these include infection with Clostridium difficile, cytomegalovirus, and Epstein-Barr virus as well as tuberculosis, histoplasmosis, and Pneumocystis jirovecii pneumonia. Patients taking multiple immunosuppressive drugs should be given trimethoprim and sulfamethoxazole as prophylaxis against Pneumocystis pneumonia (7). The consensus until recently was that this form of prophylaxis should only be provided when three different immunosuppressive drugs are given simultaneously, but the new ulcerative colitis guidelines contain a recommendation for it when two immunosuppressive drugs are given. Patients must also be educated about further, non-pharmacological preventive measures, including proper hand-washing and food preparation. Highly practical advice on the last point can be found in a current publication of the Robert Koch Institute’s Committee on Hospital Hygiene and Infectious Disease Prevention (25).

In summary, the findings of this study allow us to conclude that

  • the vaccination status of the patients included in this study was inadequate,
  • there was a marked discrepancy between the patients’ expressed willingness to be vaccinated and their actual vaccination status, and
  • the most common reason patients gave for not being vaccinated was the fear of side effects.
  • Above all, our findings imply that physicians need to be more aware of the potentially deficient vaccination status among their patients who are taking immunosuppressive drugs.

Acknowledgement
We thank Dr. Dietmar Beier (President of the Vaccination Committee of the State of Saxony) for his kind advice.

Conflict of interest statement
Niels Teich is a scientific consultant to the Abbott and Essex companies and receives scientific project support from Novartis as well as lecture honoraria from the Abbott, Essex, Falk, Ferring, Merckle-Recordati, Siemens, Shire, and Vifor companies.

Babett Holler received lecture honoraria from the Abbott and Falk companies.

Joachim Mössner was a scientific consultant to the Astra-Zeneca and Shire companies and has received lecture honoraria from the Axcan and Falk companies.

Ingolf Schiefke is a scientific consultant to the Abbott, Essex, Fresenius, Merckle-Recordati, and Olympus companies and has received lecture honoraria from the Abbott, BMS, Essex, Falk, Nycomed, Roche, and Vifor companies.

Astrid Tiedemann, Tobias Klugmann, and Anke Liebetrau declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

Manuscript received on 11 May 2010, revised version accepted on 16 July 2010.

Translated from the original German by Ethan Taub, M.D.

Corresponding author
PD Dr. med. Niels Teich
Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten
Funkenburgstr. 19
D-04105 Leipzig, Germany
teich@igvs.de

@eSupplement available at:
www.aerzteblatt-international.de/11m0105

1.
Glaeske G, Schicktanz C, Janhsen K: Barmer GEK-Arzneimittelreport 2010. Schriftenreihe zur Gesundheitsanalyse. St. Augustin: Asgard Verlag 2010; 181: 69.
2.
Rote Liste 2010. Frankfurt Main: Verlag Rote Liste Service GmbH 2010; 51–102; 51–104.
3.
Viget N, Vernier-Massouille G, Salmon-Ceron D, Yazdanpanah Y, Colombel JF: Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis. Gut 2008; 57: 549–58. MEDLINE
4.
Toruner M, Loftus EV Jr, Harmsen WS, et al.: Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134: 929–36. MEDLINE
5.
Deutsch DE, Olson AD, Kraker S, Dickinson CJ: Overwhelming varicella pneumonia in a patient with Crohn’s disease treated with 6-mercaptopurine. J Pediatr Gastroenterol Nutr 1995; 20: 351–3. MEDLINE
6.
Leung VS, Nguyen MT, Bush TM: Disseminated primary varicella
after initiation of infliximab for Crohn’s disease. Am J Gastroenterol 2004; 99: 2503–4. MEDLINE
7.
Lu Y, Jacobson D, Bousvaros A: Immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis 2009; 15: 1417–23. MEDLINE
8.
Kane S, Khatibi B, Reddy D: Higher incidence of abnormal Pap
smears in women with inflammatory bowel disease.
Am J Gastroenterol 2008; 103: 631–6. MEDLINE
9.
Foster KJ, Devitt N, Gallagher PJ, Abbott RM: Overwhelming
pneumococcal septicaemia in a patient with ulcerative colitis and splenic atrophy. Gut 1982; 23: 630–2. MEDLINE
10.
van der Hoeven JG, de Koning J, Masclee AM, Meinders AE: Fatal pneumococcal septic shock in a patient with ulcerative colitis. Clin Infect Dis 1996; 22: 860–1. MEDLINE
11.
Ritz MA, Jost R: Severe pneumococcal pneumonia following
treatment with infliximab for Crohn’s disease. Inflamm Bowel Dis 2001; 7: 327. MEDLINE
12.
Damergis JA, Chee K, Amitai A: Otogenic pneumococcal meningitis with pneumocephalus. J Emerg Med 2010; 39: e109–12. MEDLINE
13.
Marehbian J, Arrighi HM, Hass S, Tian H, Sandborn WJ: Adverse events associated with common therapy regimens for moderate-
to-severe Crohn’s disease. Am J Gastroenterol 2009; 104: 2524–33. MEDLINE
14.
Melmed GY, Ippoliti AF, Papadakis KA, et al.: Patients with
inflammatory bowel disease are at risk for vaccine-preventable
illnesses. Am J Gastroenterol 2006; 101: 1834–40. MEDLINE
15.
Salmon DA, Moulton LH, Omer SB, DeHart MP, Stokley S, Halsey NA: Factors associated with refusal of childhood vaccines among parents of school-aged children: a case-control study. Arch Pediatr Adolesc Med 2005; 159: 470–6. MEDLINE
16.
Omer SB, Salmon DA, Orenstein WA, de Hart MP, Halsey N: Vaccine refusal, mandatory immunization, and the risks of vaccine-
preventable diseases. N Engl J Med 2009; 360: 1981–8. MEDLINE
17.
Chevaux JB, Nani A, Oussalah A, et al.: Prevalence of hepatitis B and C and risk factors for nonvaccination in inflammatory bowel disease patients in Northeast France. Inflamm Bowel Dis 2010; 16: 916–24. MEDLINE
18.
Gasink LB, Wurcell AG, Kotloff RM, Lautenbach E, Blumberg EA: Low prevalence of prior streptococcus pneumoniae vaccination among potential lung transplant candidates. Chest 2006; 130: 218–21. MEDLINE
19.
Chaves TS, Pereira LM, De Santos SS, David-Neto E, Lopes MH: Evaluation of the vaccination status in pediatric renal transplant recipients. Pediatr Transplant 2008; 12: 432–5. MEDLINE
20.
Dippelhofer A, Meyer C, Kamtsiuris P, Rasch G, Reiter S, Bergmann KE: Erste Ergebnisse zum Impfstatus aus der Pilotphase des Kinder- und Jugendgesundheitssurveys. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2002; 45: 332–7.
21.
Minden K, Niewerth M, Borte M, Singendonk W, Haas JP: Impfungen bei rheumatischen Erkrankungen des Kindes- und Jugendalters. Z Rheumatol 2007; 66: 111–20. MEDLINE
22.
Kalies H, Siedler A, Kriess R: Impfquoten in Deutschland: Überblick über Datenlage und Datenquellen. Public Health Forum 2009; 17: 4–6.
23.
Poggensee G, Reuss A, Reiter S, Siedler A: Überblick und Bewertung der verfügbaren Datenquellen zur Inzidenz impfpräventabler Krankheiten, zum Durchimpfungsgrad und zum Immunstatus in Deutschland. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2009; 52: 1019–28. MEDLINE
24.
Empfehlungen der Ständigen Impfkommission (STIKO) am Robert Koch-Institut, Stand Juli 2009, Epidemiologisches Bulletin Nr. 30/2009.
25.
Kommission für Krankenhaushygiene und Infektionsprävention beim Robert Koch-Institut: Anforderungen an die Hygiene bei der medizinischen Versorgung von immunsupprimierten Patienten. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2010; 53: 357–88. MEDLINE
Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig:
PD Dr. med. habil. Teich, Dr. med. Klugmann
Praxisverbund für die Klinische Forschung, Leipzig:
PD Dr. med. habil. Teich, Dr. med. Klugmann, Prof. Dr. med. Schiefke
Klinikum St. Georg gGmbH, Klinik für Gastroenterologie und Hepatologie, Leipzig:
PD Dr. med. habil. Teich, Dr. med. Tiedemann, Prof. Dr. med. Schiefke
Universitätsklinikum Leipzig AöR, Department für Innere Medizin und Dermatologie, Klinik für
Gastroenterologie und Rheumatologie: Dr. med. Holler, Prof. Dr. med. habil. Mössner
Gesundheitsamt der Stadt Leipzig: Dr. med. Liebetrau
Gastroenterologie und Hepatologie am Johannisplatz, Leipzig: Prof. Dr. med. Schiefke
1.Glaeske G, Schicktanz C, Janhsen K: Barmer GEK-Arzneimittelreport 2010. Schriftenreihe zur Gesundheitsanalyse. St. Augustin: Asgard Verlag 2010; 181: 69.
2.Rote Liste 2010. Frankfurt Main: Verlag Rote Liste Service GmbH 2010; 51–102; 51–104.
3.Viget N, Vernier-Massouille G, Salmon-Ceron D, Yazdanpanah Y, Colombel JF: Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis. Gut 2008; 57: 549–58. MEDLINE
4.Toruner M, Loftus EV Jr, Harmsen WS, et al.: Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 2008; 134: 929–36. MEDLINE
5.Deutsch DE, Olson AD, Kraker S, Dickinson CJ: Overwhelming varicella pneumonia in a patient with Crohn’s disease treated with 6-mercaptopurine. J Pediatr Gastroenterol Nutr 1995; 20: 351–3. MEDLINE
6.Leung VS, Nguyen MT, Bush TM: Disseminated primary varicella
after initiation of infliximab for Crohn’s disease. Am J Gastroenterol 2004; 99: 2503–4. MEDLINE
7.Lu Y, Jacobson D, Bousvaros A: Immunizations in patients with inflammatory bowel disease. Inflamm Bowel Dis 2009; 15: 1417–23. MEDLINE
8.Kane S, Khatibi B, Reddy D: Higher incidence of abnormal Pap
smears in women with inflammatory bowel disease.
Am J Gastroenterol 2008; 103: 631–6. MEDLINE
9.Foster KJ, Devitt N, Gallagher PJ, Abbott RM: Overwhelming
pneumococcal septicaemia in a patient with ulcerative colitis and splenic atrophy. Gut 1982; 23: 630–2. MEDLINE
10.van der Hoeven JG, de Koning J, Masclee AM, Meinders AE: Fatal pneumococcal septic shock in a patient with ulcerative colitis. Clin Infect Dis 1996; 22: 860–1. MEDLINE
11.Ritz MA, Jost R: Severe pneumococcal pneumonia following
treatment with infliximab for Crohn’s disease. Inflamm Bowel Dis 2001; 7: 327. MEDLINE
12.Damergis JA, Chee K, Amitai A: Otogenic pneumococcal meningitis with pneumocephalus. J Emerg Med 2010; 39: e109–12. MEDLINE
13.Marehbian J, Arrighi HM, Hass S, Tian H, Sandborn WJ: Adverse events associated with common therapy regimens for moderate-
to-severe Crohn’s disease. Am J Gastroenterol 2009; 104: 2524–33. MEDLINE
14.Melmed GY, Ippoliti AF, Papadakis KA, et al.: Patients with
inflammatory bowel disease are at risk for vaccine-preventable
illnesses. Am J Gastroenterol 2006; 101: 1834–40. MEDLINE
15.Salmon DA, Moulton LH, Omer SB, DeHart MP, Stokley S, Halsey NA: Factors associated with refusal of childhood vaccines among parents of school-aged children: a case-control study. Arch Pediatr Adolesc Med 2005; 159: 470–6. MEDLINE
16.Omer SB, Salmon DA, Orenstein WA, de Hart MP, Halsey N: Vaccine refusal, mandatory immunization, and the risks of vaccine-
preventable diseases. N Engl J Med 2009; 360: 1981–8. MEDLINE
17.Chevaux JB, Nani A, Oussalah A, et al.: Prevalence of hepatitis B and C and risk factors for nonvaccination in inflammatory bowel disease patients in Northeast France. Inflamm Bowel Dis 2010; 16: 916–24. MEDLINE
18.Gasink LB, Wurcell AG, Kotloff RM, Lautenbach E, Blumberg EA: Low prevalence of prior streptococcus pneumoniae vaccination among potential lung transplant candidates. Chest 2006; 130: 218–21. MEDLINE
19.Chaves TS, Pereira LM, De Santos SS, David-Neto E, Lopes MH: Evaluation of the vaccination status in pediatric renal transplant recipients. Pediatr Transplant 2008; 12: 432–5. MEDLINE
20.Dippelhofer A, Meyer C, Kamtsiuris P, Rasch G, Reiter S, Bergmann KE: Erste Ergebnisse zum Impfstatus aus der Pilotphase des Kinder- und Jugendgesundheitssurveys. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2002; 45: 332–7.
21.Minden K, Niewerth M, Borte M, Singendonk W, Haas JP: Impfungen bei rheumatischen Erkrankungen des Kindes- und Jugendalters. Z Rheumatol 2007; 66: 111–20. MEDLINE
22.Kalies H, Siedler A, Kriess R: Impfquoten in Deutschland: Überblick über Datenlage und Datenquellen. Public Health Forum 2009; 17: 4–6.
23.Poggensee G, Reuss A, Reiter S, Siedler A: Überblick und Bewertung der verfügbaren Datenquellen zur Inzidenz impfpräventabler Krankheiten, zum Durchimpfungsgrad und zum Immunstatus in Deutschland. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2009; 52: 1019–28. MEDLINE
24.Empfehlungen der Ständigen Impfkommission (STIKO) am Robert Koch-Institut, Stand Juli 2009, Epidemiologisches Bulletin Nr. 30/2009.
25.Kommission für Krankenhaushygiene und Infektionsprävention beim Robert Koch-Institut: Anforderungen an die Hygiene bei der medizinischen Versorgung von immunsupprimierten Patienten. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2010; 53: 357–88. MEDLINE