 |
|
Measles-Mumps-Rubella and Other Measles-Containing Vaccines Do Not Increase the Risk for Inflammatory Bowel Disease
A Case-Control Study From the Vaccine Safety Datalink Project
Robert L. Davis, MD, MPH;
Piotr Kramarz, MD;
Kari Bohlke, ScD;
Patti Benson, MPH;
Robert S. Thompson, MD;
John Mullooly, PhD;
Steve Black, MD;
Henry Shinefield, MD;
Edwin Lewis, MPH;
Joel Ward, MD;
S. Michael Marcy, MD;
Eileen Eriksen, MPH;
Frank Destefano, MD, MPH;
Robert Chen, MD;
for the Vaccine Safety Datalink Team
Arch Pediatr Adolesc Med. 2001;155:354-359.
ABSTRACT
| |
Context A link between measles virus–containing vaccines and inflammatory
bowel disease (IBD) has been suggested by recent studies.
Objective To address whether receipt or timing of measles-containing vaccine (MCV)
increases risk for IBD.
Design A case-control study.
Setting Four large health maintenance organizations (HMOs) that are part of
the Centers for Disease Control and Prevention's Vaccine Safety Datalink project.
Patients or Other Participants A total of 155 persons with codes from International
Classification of Diseases, Ninth Revision specific for IBD, born between
1958 and 1989 and enrolled from birth to the onset of disease, were identified.
Up to 5 controls were matched by sex, HMO, and birth year.
Intervention None.
Main Outcome Measures Risk for IBD, Crohn's disease, and ulcerative colitis.
Results Past vaccination was not associated with an increased risk for Crohn's
disease (odds ratio [OR] for measles-mumps-rubella vaccine [MMR], 0.4; 95%
confidence interval [CI], 0.08-2.0), ulcerative colitis (OR, 0.8; 95% CI,
0.18-3.56), or IBD (OR, 0.59; 95% CI, 0.21-1.68). Risk for IBD was not increased
among children vaccinated who were younger than 12 months (OR for MMR, 0.61;
95% CI, 0.15-2.45) or aged 12 to 18 months (OR, 0.86; 95% CI, 0.28-2.59) relative
to unvaccinated children. Children vaccinated with MMR who were older than
18 months were at significantly decreased risk for IBD (OR, 0.16; 95% CI,
0.04-0.68). Neither past vaccination nor age at vaccination with other MCV
was associated with increased risk for Crohn's disease, ulcerative colitis,
or IBD. Risk for Crohn's disease, ulcerative colitis, or IBD was not elevated
in the time immediately following vaccination with either vaccine.
Conclusions Vaccination with MMR or other MCV, or the timing of vaccination early
in life, did not increase the risk for IBD.
INTRODUCTION
CONCERN about a possible link between measles virus–containing
vaccines and inflammatory bowel disease (IBD) was brought to the forefront
in 1995 when a study in the United Kingdom by Thompson et al1
suggested that measles virus–containing vaccine recipients had an up
to 3-fold increased risk for subsequently developing Crohn's disease and ulcerative
colitis. This concern was further heightened when Wakefield et al2 published a case series report of 12 children with
nonspecific colitis, ileal-lymphoid nodular hyperplasia, and developmental
disorders in whom symptoms were reported to have begun shortly after receipt
of measles-containing vaccine (MCV).
While these studies have been questioned on methodological grounds,
there has been considerable public interest and media attention focused on
the safety of measles-mumps-rubella vaccine (MMR).3, 4
Following these early reports, vaccination coverage rates for MMR dropped
in the United Kingdom, raising concern about the potential for future outbreaks
of these vaccine-preventable diseases.5, 6
We studied whether MMR or other MCVs increase the risk for IBD using
data from the Vaccine Safety Datalink (VSD) project, a collaborative project
coordinated by the Centers for Disease Control and Prevention, Atlanta, Ga.
The VSD incorporates data from 4 large health maintenance organizations (HMOs)
in the United States and captures approximately 2% of all children in the
US population younger than age 7 years. Our study focused on a series of questions:
Was the age of first vaccination with MMR or other MCV, or receipt of vaccination
itself, associated with an increased risk for Crohn's disease or ulcerative
colitis later in life? Was receipt of MMR or other MCV associated with the
acute onset of disease shortly following vaccination?
SUBJECTS AND METHODS
STUDY SITES
This study was carried out in the 4 HMOs of the VSD: (1) Group Health
Cooperative, Seattle, Wash; (2) Kaiser Permanente of Northern California,
Oakland; (3) Kaiser Permanente Northwest, Portland, Ore; and (4) Southern
California Kaiser Permanente, Los Angeles. The VSD project was started in
1991, and the computerized medical databases at each HMO include information
on vaccinations and hospitalizations. Information on outpatient visit encounters
and emergency department visits are available for 3 of the HMOs.
CASE AND CONTROL ASCERTAINMENT
We selected potential cases for medical record review by identifying
persons with International Classification of Diseases, Ninth
Revision (ICD-9) codes specific for Crohn's disease, ulcerative colitis,
and idiopathic proctocolitis (ICD-9 codes 555 and
556) in the computerized databases. At 3 sites, we drew our study sample from
the population of HMO members born between 1958 (when membership files were
first available) and 1989. At 1 site, case and control selection was limited
to people born after 1979 since automated membership data were not available
prior to that year. At all 4 HMOs, cases were ascertained from hospital databases
covering hospital admissions. Outpatient visits, emergency department visits,
and urgent care clinic visits were ascertained from 3 HMOs; the earliest dates
of case ascertainment from these respective databases were determined by the
year the respective databases (eg, outpatient visits) were created. Because
outpatient, emergency department, and urgent care clinic databases were not
available at 1 HMO, only hospitalized cases were ascertained at this site.
To be included in our sample, cases and controls had to be enrolled
from age 6 months up to the index date (the first date of disease diagnosis
or symptoms for cases) or reference date for controls. For both cases and
controls, we allowed up to 6 months of continuous disenrollment at any time
during life to account for transient lapses in insurance coverage. For each
case, we matched up to 5 controls according to sex, HMO, and birth year. The
reference date of each control was established as the date that the disease
was diagnosed for their matched case.
EXPOSURE ASSESSMENT
To accurately capture information on exposure to first MMR or other
MCV, we limited our selection of study subjects, as described in the previous
section, to patients enrolled for the entire period between 6 months of age
and disease onset (for cases) or reference date (for controls). The entire
medical record for cases and controls was abstracted to collect information
on vaccination history with all types of MCVs. Information on vaccines administered
in all health care settings was collected. A second MMR vaccination is recommended
either at age 4 to 6 years or 10 to 12 years, but these vaccinations were
not analyzed in the current study.
MEDICAL RECORD ABSTRACTION
Trained medical record abstractors at each HMO reviewed medical records
using a standardized instrument. Cases were classified according to type of
disease (Crohn's, ulcerative colitis/proctitis, or IBD unspecified) and by
certainty of diagnosis. We defined cases of "definite IBD" as persons diagnosed
with IBD by a gastroenterologist at one of the HMOs who had at least 1 sign
or symptom compatible with IBD (such as bloody stool and/or bloody diarrhea
or severe and/or recurrent abdominal pain) recorded and a diagnostic test
result (such as biopsy with pathology specimen, colonoscopy, or sigmoidoscopy)
consistent with IBD. Cases were defined as having "probable IBD" if the diagnosis
of IBD was made by either an HMO nongastroenterologist physician or a gastroenterologist
outside the HMO, there was at least 1 sign or symptom compatible with IBD,
and there was a diagnostic test result consistent with IBD. Potential subjects
with possible or questionable IBD who did not meet these criteria were excluded
from further study.
STATISTICAL ANALYSES
We used conditional logistic regression to estimate the strength of
association between vaccination and disease, while accounting for the matching
and enrollment criteria. In all analyses we further adjusted for race, where
race was categorized as white (reference category, including Hispanics and
non-Hispanics), African American, and other/unknown.
We excluded cases categorized as "possible" or "questionable" from all
analyses. Separate analyses were performed on datasets that were limited to
definite and probable cases combined or of definite cases only. Because the
results from these analyses did not differ appreciably, we present only the
results on the larger dataset of definite and probable cases combined.
Finally, we performed analyses with 2 different onset dates. For the
analysis of whether receipt of vaccination was associated with an increased
risk for IBD, Crohn's disease, or ulcerative colitis, we used as the onset
date the first date a diagnosis was made by a physician. The analysis of whether
vaccination was associated with the acute onset of symptoms consistent with
IBD, Crohn's disease, or ulcerative colitis was dependent on using the onset
date of first symptoms rather than the date of first diagnosis (which might
lag symptom onset by months). Therefore, for this part of the analysis, we
used the patient's first reported symptoms as the onset date. This lowered
our case number by a small amount because not all cases with a known date
of first diagnosis had a specified date of symptom onset in the medical record.
RESULTS
DESCRIPTIVE
There was a total of 155 cases of IBD. Of these 155 cases, 152 were
either definite or probable cases, while 3 were listed as possible or questionable.
After excluding the latter 3 cases, along with 7 that lacked a clearly discernible
diagnosis and symptom onset date, 2 cases of IBD unspecified, and 1 case with
a late age of vaccination (>10 years), there was a total of 142 cases for
the analysis of timing of vaccination and diagnosis of IBD.
Of these 142 cases, there were 75 cases of Crohn's disease and 67 cases
of ulcerative colitis (Table 1).
There was a slight excess of cases classified as white or African American
compared with controls. Overall, 52% of both cases and controls, respectively,
were female, and 58% of cases were diagnosed between age 11 and 19 years,
with few cases being diagnosed either after age 25 years or before age 5 years.
|
|
|
|
Table 1. General Descriptives of Cases and Controls*
|
|
|
Among all cases (n = 142), 94 (66%) had been vaccinated with MMR, 38
(27%) with other MCV, and 10 (7%) had never been vaccinated with either. Among
the controls (n = 432), 300 (69%) had been vaccinated with MMR, 109 (25%)
with other MCV, and 23 (5%) had never been vaccinated with either. There were
13 cases that did not have a clearly demarcated first date of symptoms, leaving
a total of 129 cases for the separate analysis of vaccination and acute symptom
onset.
VACCINATION AND RISK FOR IBD
There were no differences in the lag between vaccination with MMR or
other MCV and the case index date (mean and median time between vaccination
and onset of symptoms of 143.4 and 136.3 months, respectively) or the control
reference date (mean and median time between vaccination and reference date
of 143.0 and 136.7 months, respectively). As given in Table 2, cases of Crohn's disease, ulcerative colitis, or of all
IBD combined were no more likely than controls to have ever been vaccinated.
|
|
|
|
Table 2. History of Ever Being Vaccinated and Risk for Inflammatory
Bowel Disease*
|
|
|
AGE AT VACCINATION AND RISK FOR IBD
Vaccination with MMR or other MCV was most common for both cases and
controls who were 12 to 18 months old (Table 3). Cases of Crohn's disease, ulcerative colitis, or all IBD
combined were no more likely than controls to have been vaccinated while younger
than 12 months with either MMR or other MCV (Table 3). Similarly, cases of IBD, Crohn's disease, or ulcerative
colitis were no more likely than controls to have been vaccinated at age 12
to 18 months or after age 18 months. Cases of all IBD combined were less likely
to have ever been vaccinated with MMR after age 18 months than controls. This
decrease was present but not statistically significant when cases were restricted
to Crohn's disease or ulcerative colitis and analyzed separately. A significant
decrease was not found for vaccination with other MCV after age 18 months.
|
|
|
|
Table 3. Age at Vaccination and Risk for Inflammatory Bowel Disease*
|
|
|
VACCINATION AND ACUTE ONSET OF SYMPTOMS
The analysis of vaccination and the acute onset of symptoms of IBD revealed
no cases of Crohn's disease or ulcerative colitis who were vaccinated in the
2- or 4-month time period just prior to the first symptoms. One case of Crohn's
disease (1.5% of cases with defined onset of symptoms) was vaccinated with
MMR within the 6-month time window prior to first symptoms, compared with
2 of the controls (1.0%) (odds ratio [OR], 1.86; 95% confidence interval [CI],
0.09-39.4 for Crohn's disease in the 6 months following vaccination). In the
year prior to onset of symptoms, there was 1 case (the same that was exposed
within 6 months) of Crohn's disease who was vaccinated with MMR (1.5%) and
3 controls (1.4%) (OR, 0.72; 95% CI, 0.06-8.29 for Crohn's disease in the
12 months following vaccination). Overall, there were no statistically significant
elevations in risk for developing symptoms of Crohn's disease, ulcerative
colitis, or all IBD together in the 2, 4, 6, or 12 months following vaccination
with either MMR or other MCV.
COMMENT
In this population-based study of IBD at 4 large HMOs, we found no evidence
that vaccination with MMR or other MCV, or that the age of vaccination early
in life, was associated with an increased risk for development of IBD. In
addition, we did not find evidence that MMR or other MCV acutely triggers
the onset of either ulcerative colitis/proctitis or Crohn's disease.
This study was performed to address concerns raised by others regarding
whether MMR is associated with an increased risk for either IBD or nonspecific
colitis.1, 2 Because MMR coverage
in the US pediatric population is currently greater than 90% and vaccination
with MMR is generally required for school attendance, a link with a serious
chronic condition such as IBD would understandably raise widespread concern
and would lead to questions about the safety of the currently recommended
vaccination schedule for children. In the first study to suggest a possible
association,1 a cohort of children aged 10
to 24 months were enrolled in a 1964 United Kingdom Medical Research Council
vaccine trial of the Schwarz strain (derived from the Enders-Edmonston B strain)
and followed through 1994. Children in this cohort were compared with a group
of presumably nonvaccinated children in the National Child Development Study,
a longitudinal study of children born in a single week in 1958. Among vaccinated
children, the rate of reported Crohn's disease was 3-fold higher (relative
risk [RR], 3.01; 95% CI, 1.45-6.23), and ulcerative colitis 2.5-fold higher
(RR, 2.53; 95% CI, 1.15-5.58), than in the National Child Development Study
comparison group.
These findings by Thompson et al1 were
questioned most seriously because the method of disease ascertainment differed
considerably between the 2 cohorts.3, 4
The ascertainment of disease among the vaccinated children relied on questions
specifically focused on gastrointestinal disease, while the unvaccinated group
was asked about long-standing illnesses or disabilities. In addition, follow-up
among the vaccinated group was approximately half that of the unvaccinated
cohort, raising the possibility for biased response rates related to disease
status. As a result, it was not clear whether the observed relationship between
measles vaccine and IBD was due to the vaccine itself or to study design limitations.
The study by Wakefield et al2 did not
look specifically at IBD but focused on a group of 12 children with a complex
of nonspecific colitis, ileolymphoid hyperplasia, and pervasive developmental
disability, in which most but not all reported that symptoms began following
vaccination with an MCV. Of these 12 children, 6 had gastrointestinal symptoms,
and 11 had abnormal histological findings in ileum and colon biopsy specimens
(most commonly of nonspecific colitis and lymphoid hyperplasia). This study
was questioned owing to lack of specification of the source population, making
it impossible to determine whether vaccination was more common among these
cases than among a comparable set of children without disease. Because MMR
is given to approximately 600 000 children yearly in the United Kingdom,
some cases of disease will likely follow vaccine temporally, although not
necessarily as a result of cause and effect.7
Others questioned whether the gastrointestinal findings were unusual or represented
nonspecific findings common in the age group studied.8
Several other studies have subsequently addressed the risk for IBD following
MCV. A case-control study by Feeney et al9
from the United Kingdom looked at 140 patients with IBD born after 1968, matched
to 280 controls by age, sex, and location. No increased risk was found for
either Crohn's disease (OR, 1.08; 95% CI, 0.6-1.9) or ulcerative colitis (OR,
0.84; 95% CI, 0.4-1.6) among children receiving measles vaccine compared with
unvaccinated children. Other data by Morris et al10
on a national longitudinal study of children born in the United Kingdom found
no increased risk for Crohn's disease or ulcerative colitis by age 25 to 26
years associated with measles vaccination. Only sparse details were reported,
but there were no significantly increased risks (Crohn's disease: RR, 1.21;
95% CI, 0.5-2.9; ulcerative colitis: RR, 1.31; 95% CI, 0.47-3.7; and IBD:
RR, 1.25; 95% CI, 0.64-2.43).
Multiple ecological analyses have also shown no apparent increase in
IBD following the introduction of, or increased use of, MMR. In one study,
Miller and Waight11 used computerized hospital
discharge statistics from 1992 through 1996 to look for evidence of an increase
in Crohn's disease subsequent to a 1994 national measles-rubella vaccination
campaign aimed at school-aged children. Although the follow-up time was limited
to only the first 16 months following vaccination, there was no apparent increase
in the rate of hospital admissions for Crohn's disease and hence no suggestion
that MMR triggered the onset of symptoms as suggested in the study by Wakefield
et al.2
In a second study, Pebody et al12 used
Finnish data and contrasted the rate of Crohn's disease with the proportion
of the population receiving measles vaccine. Although there was an increase
over time in the proportion of the population receiving 1 or more doses of
measles virus vaccine, the rate of Crohn's disease remained stable among 2
age groups of children and adolescents aged 0 to 14 years and adolescents
and young adults aged 15 to 24 years. Finally, a study by Hermon-Taylor et
al13 contrasted the annual incidence of Crohn's
disease at 3 United Kingdom centers (south Wales, Derby, and northeast Scotland)
with the introduction of measles vaccine and MMR. In this study there was
a marked rise in the rate of Crohn's disease over the study period, but the
increased rate of disease predated introduction of the measles vaccine by
approximately 20 years.
A number of studies have attempted to find evidence of persistent measles
virus genome in pathology specimens obtained from patients with IBD. These
investigations were prompted by a report of measles virus nucleocapsid protein
found in 13 of 15 patients with Crohn's disease.14
Most subsequent studies by Afzal et al15 on
19 patients with IBD, by Chadwick et al16 on
20 cases, and by Iizuka et al17 on 21 cases
have failed to replicate these findings, arguing that measles virus genome
is not present in the gut mucosa of patients with Crohn's disease or ulcerative
colitis. However, a recent study by Kawashima et al18
detected measles genomic RNA in peripheral mononuclear cells in 1 of 8 cases
of Crohn's disease and 1 of 3 with ulcerative colitis but no measles RNA in
8 subjects with subacute sclerosing panencephalitis, systemic lupus erythematosus,
or HIV (human immunodeficiency virus) infection. This latter study did not
examine intestinal pathology specimens.
There are some unique aspects to our study that deserve mention. First,
previous studies of the relationship between measles vaccination and IBD have
been conducted on populations outside of the United States. This is the first
study of MMR and other MCVs and IBD used historically and presently in the
United States. Second, that we did not find a relationship between MMR vaccine
and IBD argues against the suggestion that concurrent exposure to measles
and mumps antigens increases the risk for IBD19
and against the need to deliver these vaccinations as individual antigens.20 Third, this study uses information from a population-based
group of HMO members and was therefore likely free from the biases that might
occur in a study that relied on self-referred patients or patients studied
specifically because symptoms might have occurred following vaccination. Finally,
our study included only patients enrolled from (or shortly after) birth up
to the time of disease or the similar age for controls, and we reviewed each
patient's medical record to ascertain vaccination status. Consequently, the
completeness and quality of information on the timing and type of vaccine
received is likely to be good. Because we were able to ascertain the timing
of the first symptoms and date of first diagnosis of disease from the outpatient
medical records at each HMO, we were able to calculate an unbiased relationship
between receipt of vaccination and disease onset.
There are some limitations to our study. We included only patients with
a physician diagnosis (usually a gastroenterologist) of IBD, and we have the
inherent limitations of diagnostic accuracy in a retrospective study. We have
little information on children or adults who had nonspecific colitis that
did not eventually lead to a diagnosis of IBD. Nevertheless, our study provides
evidence against the hypothesis that MMR or other MCV leads to IBD. Another
limitation to our study concerned power. We were able to effectively rule
out associations larger than 2-fold between ever being vaccinated with MMR
and developing IBD and associations larger than 3-fold between vaccination
with other MCV and IBD. However, we had a limited sample size from which to
look at the independent associations between vaccination and either Crohn's
disease or ulcerative colitis (Table 2)
or at the relationship between timing of vaccination early in life and subsequent
risk for Crohn's disease or ulcerative colitis (Table 3).
There has been recent interest in the role of early exposure to measles
virus and subsequent risk for development of IBD. A few studies have suggested
that intrauterine or early-in-life exposure to infectious agents or measles
virus may lead to an increased risk for IBD.21, 22
Although we collected information on intrauterine and early-in-life measles
exposure, we did not identify any mothers of case or control subjects who
were noted to have first trimester measles infection. In addition, only 1
case of IBD and 2 controls had had measles infection. These small numbers
precluded analysis of the relationship between measles infection and subsequent
development of IBD; however, if such a risk does exist, the magnitude must
be too small to identify accurately with a study of our size.
Finally, it is important to recognize that the apparent protective effect
against IBD of primary vaccination with MMR after 18 months of age was not
an a priori hypothesis of ours, and a similar finding was not seen among children
vaccinated after age 18 months with other MCV. If subsequent studies are conducted
on the relationship between IBD and primary vaccination, attention should
be paid to the risk among children vaccinated after age 18 months with MMR.
In conclusion, our study of IBD using a population-based sample of cases
from 4 large HMOs did not find evidence of an elevated risk for disease following
vaccination with MMR or other MCV.
AUTHOR INFORMATION
Accepted for publication December 28, 2000.
This study was supported by contract 200-95-0947 (the VSD [Vaccine Safety
Datalink] project) from the Centers for Disease Control and Prevention.
Vaccine Safety Datalink Team
National Immunization Program, Centers for Disease
Control and Prevention, Atlanta, Ga: Frank DeStefano, MD, MPH; Robert
T. Chen, MD; John Glasser, PhD, MPH; Philip H. Rhodes, PhD; Piotr Kramarz,
MD; Thomas Verstraeten, MD; David Walker, MPH; Catherine Okoro
Group Health Cooperative, Seattle, Wash: Robert
S. Thompson, MD; Robert L. Davis, MD, MPH; Lisa A. Jackson, MD, MPH; Patti
Benson, MPH; William Barlow, PhD; Kari Bohlke, ScD; Paula Lee Poy; David Rubanowice;
Ann Zavitkovsky, MPH; Jo Ann Habakangas; Darren Malais; Wendy Rogers; Christi
Hanson; Onchee Yu, MS; Viviana Rebolledo
Kaiser Permanente Northwest Region, Portland, Ore: John P. Mullooly, PhD; Julie E. Maher, PhD; Sheila Weinman, PhD;
Lois Drew, BA; Jill Mesa; Kim Olson; Heather Houston, RN; Colleen Chun, MD;
Steven Gancher, MD; John A. Pearson, MD; Jerry Slepak, MD; Alan Bauck, BS;
Teresa Kimes, MS; Joseph Murphy, BA; Nadia Redmond, MSPH; Karen Riedlinger,
MPH; Carol Sullivan; Gayle Thomas-Monk
Kaiser Permanente of Northern California, Oakland: Steven B. Black, MD; Henry R. Shinefield, MD; Paula Ray, MPH; Edwin
Lewis, MPH; Bruce H. Fireman, MA; Joan Schwalbe; Ajit De Silva; Patti Hallam
Center for Vaccine Research, Harbor-UCLA Medical Center,
Torrance, Calif: Joel I. Ward, MD; Connie M. Vadheim, PhD; Hang Lee,
PhD; Jennie Jing, MA; Nancy Goff
Southern California Kaiser Permanente, Los Angeles: S. Michael Marcy, MD; Marlene Lugg, DrPH
Center for Biologics Evaluation and Research, Food
and Drug Administration, Rockville, Md: M. Miles Braun, MD, MPH; Robert
P. Wise, MD, MPH; Robert Ball, MD, MPH
Division of Vaccine Injury Compensation, Health Resources
and Services Administration, Rockville: Vito Caserta, MD, MPH; Geoffrey
Evans, MD
From the Departments of Pediatrics (Dr Davis), University of Washington
School of Medicine, and Epidemiology (Dr Davis), University of Washington
School of Public Health, Seattle, and the Center for Health Studies (Drs Davis,
Bohlke, and Thompson and Ms Benson), Group Health Cooperative, Seattle; the
Vaccine Safety and Development Branch (Drs Kramarz, Destefano, and Chen),
National Immunization Program, Centers for Disease Control and Prevention,
Atlanta, Ga; the Center for Health Research (Dr Mullooly), Northwest Kaiser
Permanente, Portland, Ore; the Division of Research (Drs Black and Shinefield
and Mr Lewis), Kaiser Permanente of Northern California, Oakland; the UCLA
Center for Vaccine Research (Dr Ward and Ms Eriksen), Harbor-UCLA Medical
Center, Torrance; and the Kaiser-UCLA Vaccine Research Group (Dr Marcy), Southern
California Kaiser Permanente, Panorama City.
Corresponding author and reprints: Robert L. Davis, MD, MPH, Immunization
Studies Program, Center for Health Studies Group Health Cooperative, 1730
Minor Ave, Suite 1600, Seattle, WA 98101-1448.
REFERENCES
| |
1. Thompson NP, Montgomery SM, Pounder RE, Wakefield AJ. Is measles vaccination a risk factor for inflammatory bowel disease? Lancet. 1995;345:1071-1074.
FULL TEXT
|
ISI
| PUBMED
2. Wakefield AJ, Murch SH, Anthony A, et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive
developmental disorder in children. Lancet. 1998;351:637-641.
FULL TEXT
|
ISI
| PUBMED
3. Farrington P, Miller E. Measles vaccination as a risk factor for inflammatory bowel disease
[letter]. Lancet. 1995;345:1362.
FULL TEXT
|
ISI
| PUBMED
4. Patriarca PA, Beeler JA. Measles vaccination and inflammatory bowel disease. Lancet. 1995;345:1062-1063.
FULL TEXT
|
ISI
| PUBMED
5. Thomas DR, Salmon R, King J. Rates of first measles-mumps-rubella immunisation in Wales (UK) [letter]. Lancet. 1998;351:1927.
ISI
| PUBMED
6. Begg N, Ramsay M, White J, Bozoky Z. Media dents confidence in MMR vaccine. BMJ. 1998;316:561.
FREE FULL TEXT
7. Chen RT, DeStefano F. Vaccine adverse events: causal or coincidental? Lancet. 1998;351:611-614.
FULL TEXT
|
ISI
| PUBMED
8. Richmond P, Goldblatt D. Autism, inflammatory bowel disease, and MMR vaccine [letter]. Lancet. 1998;351:1355-1356.
FULL TEXT
9. Feeney M, Clegg A, Winwood P, Snook J. A case-control study of measles vaccination and inflammatory bowel
disease. Lancet. 1997;350:764-766.
FULL TEXT
|
ISI
| PUBMED
10. Morris DL, Montgomery SM, Ebrahim S, Pounder RE. Measles vaccination and inflammatory bowel disease in the 1970 British
cohort study. Gut. 1997;41(suppl 3):A37.
11. Miller E, Waight P. Measles, measles vaccination and Crohn's's disease second immunisation
has not affected incidence in England [letter]. BMJ. 1998;316:1745.
FREE FULL TEXT
12. Pebody RG, Paunio M, Ruutu P. Measles, measles vaccination, and Crohn's disease: Crohn's disease
has not increased in Finland [letter]. BMJ. 1998;316:1745-1746.
13. Hermon-Taylor J, Ford J, Sumar N, Millar D, Doran T, Tizard M. Measles virus and Crohn's disease [letter]. Lancet. 1995;345:922-923.
PUBMED
14. Wakefield AJ, Pittilo RM, Sim R, et al. Evidence of persistent measles virus infection in Crohn's disease. J Med Virol. 1993;39:345-353.
ISI
| PUBMED
15. Afzal MA, Minor PD, Begley J, et al. Absence of measles-virus genome in inflammatory bowel disease [letter]. Lancet. 1998;351:646-647.
FULL TEXT
|
ISI
| PUBMED
16. Chadwick N, Bruce IJ, Schepelmann S, Pounder RE, Wakefield AJ. Measles virus RNA is not detected in inflammatory bowel disease using
hybrid capture and reverse transcription followed by the polymerase chain
reaction. J Med Virol. 1998;55:305-311.
FULL TEXT
|
ISI
| PUBMED
17. Iizuka M, Nakagomi O, Chiba M, Ueda S, Masamune O. Absence of measles virus in Crohn's disease [letter]. Lancet. 1995;345:199.
ISI
| PUBMED
18. Kawashima H, Mori T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A. Detection and sequencing of measles virus from peripheral mononuclear
cells from patients with inflammatory bowel disease and autism. Dig Dis Sci. 2000;45:723-729.
FULL TEXT
|
ISI
| PUBMED
19. Montgomery SM, Morris DL, Pounder RE, Wakefield AJ. Paramyxovirus infections in childhood and subsequent inflammatory bowel
disease. Gastroenterology. 1999;116:796-803.
FULL TEXT
|
ISI
| PUBMED
20. Measles, MMR, and autism: the confusion continues [editorial]. Lancet. 2000;355:1379.
FULL TEXT
|
ISI
| PUBMED
21. Ekbom A, Wakefield AJ, Zack M, Adami HO. Perinatal measles infection and subsequent Crohn's disease. Lancet. 1994;344:508-510.
FULL TEXT
|
ISI
| PUBMED
22. Ekbom A, Adami HO, Helmick CG, Jonzon A, Zack MW. Perinatal risk factors for inflammatory bowel disease: a case-control
study. Am J Epidemiol. 1990;132:1111-1119.
FREE FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
MMR vaccine and Crohn's disease: ecological study of hospital admissions in England, 1991 to 2002
Seagroatt
BMJ 2005;330:1120-1121.
FULL TEXT
Crohn's disease, ulcerative colitis, and measles vaccine in an English population, 1979-1998
Seagroatt and Goldacre
J. Epidemiol. Community Health 2003;57:883-887.
ABSTRACT
| FULL TEXT
Increased Risk of Seizures Following DTP and MMR Vaccine Is Not Associated with Any Long-Term Adverse Consequences
Millichap and Rathore
AAP Grand Rounds 2001;6:54-55.
FULL TEXT
Active Immunization in the United States: Developments over the Past Decade
Dennehy
Clin. Microbiol. Rev. 2001;14:872-908.
ABSTRACT
| FULL TEXT
Guillain-Barre Syndrome Not Related to MMR
Rathore
AAP Grand Rounds 2001;5:46-47.
FULL TEXT
|
