Vaccine. 2003 Sep 8;21(25-26):3954-60.
Unintended events following immunization with MMR: a
Jefferson T, Price D, Demicheli V, Bianco E; European Research
Program for Improved Vaccine Safety Surveillance (EUSAFEVAC)
Reparto Epidemiologia Clinica, Istituto Superiore di Sanita, Viale
Regina Elena, 299-00161 Rome, Italy. email@example.com
Public debate over the safety of the trivalent measles, mumps and
rubella (MMR) vaccine and the drop in vaccination rates in several
countries persists despite its almost universal use and accepted
effectiveness. We carried out a systematic review to assess the
evidence of unintended effects (beneficial or harmful) associated with
MMR and the applicability of systematic reviewing methods to the field
of safety evaluation. Eligible studies were comparative prospective or
retrospective on healthy individuals up to 15 years of age, carried out
or published by 2003. We identified 120 articles satisfying our
inclusion criteria and included 22. MMR is associated with a lower
incidence of upper respiratory tract infections, a higher incidence of
irritability, similar incidence of other adverse effects compared to
placebo and is likely to be
associated with benign thrombocytopenic purpura (TP), parotitis, joint and limb complaints and aseptic
meningitis (mumps Urabe strain-containing MMR). Exposure to MMR
is unlikely to be associated with Crohn's disease, ulcerative colitis,
autism or aseptic meningitis (mumps Jeryl-Lynn strain-containing MMR).
The design and reporting of safety outcomes in MMR vaccine studies,
both pre- and post-marketing, are largely inadequate. The evidence of
adverse events following immunization with MMR cannot be separated from
its role in preventing the target diseases.
PMID: 12922131 [PubMed - in process]
Br J Clin Pharmacol. 2003 Jan;55(1):107-11.
MMR vaccine and idiopathic thrombocytopaenic
Black C, Kaye JA, Jick H.
Department of Public Health, Aberdeen University, Aberdeen, UK.
AIMS: To estimate the relationship between idiopathic thrombocytopaenic
purpura (ITP) and the measles, mumps and rubella (MMR) vaccination in
children; calculating the relative risk estimate for ITP with in 6
weeks after MMR vaccination and the attributable risk of ITP within 6
weeks after MMR vaccination. METHODS: Using the General Practice
Research Database we identified children with a first-time diagnosis of
ITP from a base population of children aged less than 6 years between
January 1988 and December 1999. After describing the characteristics of
all the children identified with ITP, we focused on cases aged 13-24
months to perform a population-based, case-control analysis to estimate
the relative risk of developing ITP within 6 weeks after MMR
vaccination. We also calculated the risk of ITP attributable to the MMR
vaccination. RESULTS: Sixty-three children with a first time diagnosis
of ITP were identified; 23 cases were between 13 and 24 months old. The
relative risk estimate for ITP within 6 weeks after MMR vaccination,
compared to the combined group of unvaccinated children and children
vaccinated with MMR more than 26 weeks previously was 6.3 (95% CI
1.3-30.1). The attributable risk of developing ITP within 6 weeks after
MMR vaccination was estimated to be 1 in 25,000 vaccinations (95%
confidence interval 21,300, 89,400). CONCLUSION: This study confirms the increased risk
within 6 weeks after MMR
vaccination. However, the attributable risk of ITP within 6 weeks after MMR vaccination is
PMID: 12534647 [PubMed - indexed for MEDLINE]
Mol Immunol. 2003 Jul;39(17-18):1105-7.
Immune thrombocytopenic purpura in childhood: a
Moussalem M, Yassine N.
Pediatric Hematology-Oncology Division, Saint Georges Hospital
affiliated with Balamand University, Beirut, Lebanon.
Immune thrombocytopenic purpura (ITP), due to the production of
antiplatelet antibodies, is the most prevalent etiology of
thrombocytopenia in children and a frequent cause of consultation for
the pediatrician. We review here a series of Lebanese pediatric
patients presenting with ITP and we discuss the relevant
characteristics of the group. STUDY: A retrospective chart analysis was
performed for 40 hospitalized or out-patient children presenting with
ITP between January 1998 and December 2001. All cases except two had a
diagnosis confirmed by bone marrow aspirate. Patients were equally
distributed between the sexes with a mean age of 56 months. More than
half of the patients had an episode of fever 2 days to 8 weeks prior to
the diagnosis. For 42% of them, the disease appeared in the months
between January and March. Ten percent presented with epistaxis but all
of these had a platelet count less than 12,000. One-third of the
patients had received immunization 2-8 weeks before the diagnosis, with
one patient having a relapse 4 weeks after mumps-measles-rubella (MMR)
immunization, which was 1 year after the initial cure. Initial
treatment consisted of either steroids or intravenous polyvalent
immunoglobulin in 58 and 36% of the cases, respectively. None of the
patients had life-threatening hemorrhage. Only 10% of the patients
developed chronic ITP (unremitting after 6 months). CONCLUSION: ITP is
generally a benign disease in infancy and childhood. Certain
characteristics of ITP in this series, such as the seasonal variation
and the post-vaccine ITP, will need to be better defined in larger
prospective studies. Optimal treatment will eventually be targeted
towards a better delineation of the disease phenotype.
PMID: 12835086 [PubMed - indexed for MEDLINE]
Arch Dis Child. 2001 Mar;84(3):227-9.
Idiopathic thrombocytopenic purpura and MMR
Miller E, Waight P, Farrington CP, Andrews N, Stowe J, Taylor
Immunisation Division, Public Health Laboratory Service Communicable
Disease Surveillance Centre, Colindale, London NW9 5EQ, UK.
A CAUSAL ASSOCIATION BETWEEN
MEASLES: mumps-rubella (MMR) vaccine and idiopathic
thrombocytopenic purpura (ITP) was confirmed using immunisation/hospital admission record linkage. The
absolute risk within six weeks of immunisation was 1 in 22 300 doses, with two of every
three cases occurring in the six week post-immunisation period being caused by MMR. Children
before MMR had no vaccine
PMID: 11207170 [PubMed - indexed for MEDLINE]
Therapie. 1996 Nov-Dec;51(6):677-80.
[Thrombocytopenic purpura after isolated or combined
vaccination against measles, mumps and rubella]
[Article in French]
Autret E, Jonville-Bera AP, Galy-Eyraud C, Hessel L.
Service de Pharmacologie Clinique, Hopital Bretonneau, Tours,
A retrospective epidemiological survey was conducted to evaluate the
incidence and characteristics of thrombocytopenic purpura (TP) reported
in France following measles, mumps or rubella vaccination with
monovalent or multivalent vaccines. Sixty cases of TP were reported i.e
an incidence/100,000 doses of 0.23 and 0.17 for measles or rubella
vaccines respectively given alone, to 0.87 for combined measles-rubella
vaccine and 0.95 for MMR vaccine. The mean age was 21 +/- 12 months and
the delay of diagnosis was 16 +/- 6 days after vaccination.
Thrombopenia was severe (mean platelet count: 8000 +/- 6000/mm3) and
always associated with purpura. The immediate outcome was favourable in
89.5 per cent of cases. Vaccine-associated TP appears to be similar to acute childhood
idiopathic thrombocytopenic purpura but the clear temporal relationship between
MMR vaccination and the occurrence of TP make a causal relationship highly
plausible. Acute TP seems a rare complication of measles-rubella
and MMR vaccination but clinicians had to be informed of the
possibility of their occurrence. Acute TP following vaccination should
be reported by physicians to their Regional Drug Surveillance
PMID: 9164004 [PubMed - indexed for MEDLINE]
J Am Board Fam Pract. 1996 Jan-Feb;9(1):53-5.
Acute idiopathic thrombocytopenic purpura following
combined vaccination against measles, mumps, and
Chang SK, Farrell DL, Dougan K, Kobayashi B.
Department of Family Practice and Community Health, University of
Hawaii John A. Burns School of Medicine, Honolulu, USA.
PMID: 8770810 [PubMed - indexed for MEDLINE]
Lancet. 1995 Mar 4;345(8949):567-9.
A new method for active surveillance of adverse
events from diphtheria/tetanus/pertussis and measles/mumps/rubella
Farrington P, Pugh S, Colville A, Flower A, Nash J, Morgan-Capner
P, Rush M, Miller E.
Public Health Laboratory Service Statistics Unit, Communicable
Disease Surveillance Center, London, UK.
We describe a new method for active post-marketing surveillance of
vaccine safety based on patient records. We studied the association
between diphtheria/tetanus/pertussis (DTP) vaccination and febrile
convulsion, and between measles/mumps/rubella (MMR) vaccination and
febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in
five district health authorities in England by linking vaccination
records with computerised hospital admission records. We found an
increased relative incidence for convulsions 0-3 days after DTP
vaccination. The effect was limited to the third dose of vaccine for
which the attributable risk (all ages) was 1 in 12,500 doses.
Completion of vaccination by 4 months instead of 10 months after the
change in the UK to an accelerated immunisation schedule may have
resulted in a 4-fold decrease in febrile convulsions attributable to
DTP vaccine. 67% of admissions for a convulsion 6-11 days after MMR
vaccination were attributable to the measles component of the vaccine
(risk 1 in 3000 doses). An excess of admissions for a convulsion
15-35 days after MMR vaccination was found only for vaccines
containing the Urabe mumps strain (1 in 2600 Urabe doses).
There was a causal
association between MMR vaccination and ITP resulting in admission 15-35 days
subsequently; there was no evidence of a mumps strain-specific
effect. The estimated absolute risk of 1 in 24,000 doses was 5 times
that calculated from cases passively reported by clinicians. This
finding emphasises the need for active surveillance of
adverse events. The record linkage method that we used is an
effective way to identify vaccine-attributable adverse events.
PMID: 7619183 [PubMed - indexed for MEDLINE]
Arch Pediatr Adolesc Med. 1994 Mar;148(3):326-7.
Exacerbation of chronic idiopathic thrombocytopenic
purpura following measles-mumps-rubella immunization.
Drachtman RA, Murphy S, Ettinger LJ.
Division of Pediatric Hematology-Oncology, UMDNJ-Robert Wood Johnson
Medical School, New Brunswick.
PMID: 8130872 [PubMed - indexed for MEDLINE]
Acta Paediatr. 1993 Mar;82(3):267-70.
Acute thrombocytopenic purpura following measles,
mumps and rubella vaccination. A report on 23 patients.
Nieminen U, Peltola H, Syrjala MT, Makipernaa A, Kekomaki R.
Finnish Red Cross Blood Transfusion Service, Helsinki.
thrombocytopenic purpura developed shortly after
measles-mumps-rubella vaccination in 23 of approximately 700,000
children immunized over a period of seven years. The mean
interval from inoculation to the onset of purpura was 19 days. Bone
marrow aspirates obtained from 13 patients showed increased or normal
amounts of megakaryocytes. Platelet survival time was markedly
shortened in the two patients studied. Fifteen patients recovered (the
platelet count exceeded 100 x 10(9)/l) in one month, five in two months
and two in six months. Increase in platelet-associated immunoglobulin
was detected in 10 of 15 patients. Circulating antiplatelet
autoantibodies (AAb) against glycoprotein IIb/IIIa were detected in 5
of 15 patients. The findings are compatible with an autoimmune
mechanism triggered by immune response to measles-mumps-rubella
vaccination. As evaluated by the clinical course and the presence of
AAb, post-vaccination thrombocytopenic purpura appears to be
indistinguishable from childhood acute idiopathic thrombocytopenic
PMID: 8495082 [PubMed - indexed for MEDLINE]
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