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1.  Booster vaccination of pre-school children with reduced-antigen-content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine co-administered with measles-mumps-rubella-varicella vaccine 
Background: Pertussis occurs in older children, adolescents and adults due to waning immunity after primary vaccination. Booster vaccination for pre-school children has been recommended in Italy since 1999. In this study (NCT00871000), the immunogenicity, safety and reactogenicity of a booster dose of reduced-antigen content diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (dTpa-IPV; GSK Biologicals Boostrix™-Polio; 3-component pertussis) vs. full-strength DTPa-IPV vaccine (sanofi-pasteur—MSD Tetravac™; 2-component pertussis) was evaluated in pre-school Italian children.
 
Methods: Healthy children aged 5–6 y primed in a routine vaccination setting with three doses of DTPa-based vaccines were enrolled and randomized (1:1) in this phase IIIb, booster study to receive a single dose of dTpa-IPV or DTPa-IPV; the MMRV vaccine was co-administered. Antibody concentrations/titers against diphtheria, tetanus, pertussis and poliovirus 1–3 were measured before and one month post-booster. Reactogenicity and safety was assessed.
Results: 305 subjects were enrolled of whom 303 (dTpa-IPV = 151; DTPa-IPV = 152) received booster vaccination. One month post-booster, all subjects were seroprotected/seropositive for anti-diphtheria, anti-tetanus, anti-PT, anti-FHA and anti-poliovirus 1–3; 99.3% of dTpa-IPV and 60.4% of DTPa-IPV subjects were seropositive for anti-PRN; 98–100% of subjects were seropositive against MMRV antigens post-booster. Pain at the injection site (dTpa-IPV: 63.6%; DTPa-IPV: 63.2%) and fatigue (dTpa-IPV: 26.5%; DTPa-IPV: 23.7%) were the most commonly reported solicited local and general symptoms, during the 4-d follow-up period. No SAEs or fatalities were reported.
Conclusions: The reduced-antigen-content dTpa-IPV vaccine was non-inferior to full-strength DTPa-IPV vaccine with respect to immunogenicity. The vaccine was well-tolerated and can be confidently used as a booster dose in pre-school children.
doi:10.4161/hv.18650
PMCID: PMC3426082  PMID: 22327497
pre-school; MMRV; diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine; Italy; 2 + 1 schedule
2.  Parental confidence in measles, mumps and rubella vaccine: evidence from vaccine coverage and attitudinal surveys. 
BACKGROUND: The measles, mumps and rubella (MMR) vaccine has been the focus of considerable adverse publicity in recent years. AIM: To describe recent trends in parental attitudes to, and coverage of, MMR vaccine. DESIGN OF STUDY: Routine surveillance of vaccine coverage and cross-sectional surveys of parental attitudes. SETTING: All health authorities in England (vaccine coverage) and 132 enumeration districts in England (attitude survey). METHOD: Quarterly MMR vaccine coverage for all resident children in England at two years of age was requested from computerised child health information systems. Data was also obtained from 26 English health authorities/trusts on MMR coverage at 16 months of age. The proportion of mothers who believed that MMR vaccine was safe or carried only a slight risk, and the proportion who intended to fully vaccinate any future children, was obtained from biannual interviews with a national representative sample of over 1000 mothers of children under three years of age. RESULTS: Vaccine coverage at two years of age fell 8.6% (95% confidence interval [CI] = 8.4 to 8.8) between April and June 1995 and between April and June 2001. In September 2001, 67% of mothers reported that the MMR vaccine was safe or carried only a slight risk and 92% of mothers agreed with the statement: 'If I had another child in the future I would have them fully immunised against all childhood diseases'. CONCLUSIONS: Despite considerable adverse publicity, the fall in MMR coverage has been relatively small, mothers' attitudes to MMR remain positive, and most continue to seek advice on immunisation from health professionals. As the vast majority of mothers are willing to have future children fully immunised, we believe that health professionals should be able to use the available scientific evidence to help to maintain MMR coverage.
PMCID: PMC1314443  PMID: 12434960
3.  Validity of Parent-Reported Vaccination Status for Adolescents Aged 13–17 Years: National Immunization Survey-Teen, 2008 
Public Health Reports  2011;126(Suppl 2):60-69.
Objective
The validity of parent-reported adolescent vaccination histories has not been assessed. This study evaluated the validity of parent-reported adolescent vaccination histories by a combination of immunization card and recall, and by recall only, compared with medical provider records.
Methods
We analyzed data from the 2008 National Immunization Survey-Teen. Parents of adolescents aged 13–17 years reported their child's vaccination history either by immunization card and recall (n=3,661) or by recall only (n=12,822) for the hepatitis B (Hep B), measles-mumps-rubella (MMR), varicella (VAR), tetanus-diphtheria/tetanus-diphtheria-acellular pertussis (Td/Tdap), meningococcal conjugate (MCV4), and quadrivalent human papillomavirus (HPV4) (for girls only) vaccines. We validated parental report with medical records.
Results
Among the immunization card/recall group, vaccines with >20% false-positive reports included MMR (32.3%) and Td/Tdap (36.9%); vaccines with >20% false-negative reports included VAR (35.2%), MCV4 (36.0%), and Tdap (41.9%). Net bias ranged from −25.0 to −0.1 percentage points. Kappa values ranged from 0.22 to 0.92. Among the recall-only group, vaccines with >20% false-positive reports included Hep B (33.9%), MMR (61.4%), VAR (26.2%), and Td/Tdap (60.6%); vaccines with >20% false-negative reports included Hep B (58.9%), MMR (33.7%), VAR (51.6%), Td/Tdap (25.5%), Tdap (50.3%) MCV4 (63.0%), and HPV4 (20.5%). Net bias ranged from −46.0 to 0.5 percentage points. Kappa values ranged from 0.03 to 0.76.
Conclusions
Validity of parent-reported vaccination histories varies by type of report and vaccine. For recently recommended vaccines, false-negative rates were substantial and higher than false-positive rates, resulting in net underreporting of vaccination rates by both the immunization card/recall and recall-only groups. Provider validation of parent-reported vaccinations is needed for valid surveillance of adolescent vaccination coverage.
PMCID: PMC3113431  PMID: 21812170
4.  A case-control study of autism and mumps-measles-rubella vaccination using the general practice research database: design and methodology 
BMC Public Health  2001;1:2.
Background
An association between mumps-measles-rubella (MMR) vaccination and the onset of symptoms typical of autism has recently been suggested. This has led to considerable concern about the safety of the vaccine.
Methods
A matched case-control study using data derived form the United Kingdom General Practice Research Database. Children with a possible diagnosis of autism will be identified from their electronic health records. All diagnoses will be validated by a detailed review of hospital letters and by using information derived from a parental questionnaire. Ten controls per case will be selected from the database. Conditional logistic regression will be used to assess the association between MMR vaccination and autism. In addition case series analyses will be undertaken to estimate the relative incidence of onset of autism in defined time intervals after vaccination. The study is funded by the United Kingdom Medical Research Council.
Discussion
Electronic health databases offer tremendous opportunities for evaluating the adverse effects of vaccines. However there is much scope for bias and confounding. The rigorous validation of all diagnoses and the collection of additional information by parental questionnaire in this study are essential to minimise the possibility of misleading results.
doi:10.1186/1471-2458-1-2
PMCID: PMC29106  PMID: 11231881
5.  Deficiencies in current childhood immunization indicators. 
Public Health Reports  1998;113(6):527-532.
OBJECTIVE: To investigate "up-to-date" and "age-appropriate" indicators of preschool vaccination status and their implications for vaccination policy. METHODS: The authors analyzed medical records data from the Baltimore Immunization Study for 525 2-year-olds born from August 1988 through March 1989 to mothers living in low-income Census tracts of the city of Baltimore. RESULTS: While only 54% of 24-month-old children were up-to-date for the primary series, indicators of up-to-date coverage were consistently higher, by 37 or more percentage points, than corresponding age-appropriate indicators. Almost 80% of children who failed to receive the first dose of DTP or OPV age-appropriately failed to be up-to-date by 24 months of age for the primary series. CONCLUSIONS: Age-appropriate immunization indicators more accurately reflect adequacy of protection for preschoolers than up-to-date indicators at both the individual and population levels. Age-appropriate receipt of the first dose of DTP should be monitored to identify children likely to be underimmunized. Age-appropriate indicators should also be incorporated as vaccination coverage estimators in population-based surveys and as quality of care indicators for managed care organizations. These changes would require accurate dates for each vaccination and support the need to develop population-based registries.
PMCID: PMC1308436  PMID: 9847924
6.  Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners 
Western Journal of Medicine  2001;174(6):387-390.
Objectives To estimate changes in the risk of autism and assess the relation of autism to the mumps, measles, and rubella (MMR) vaccine. Design Time-trend analysis of data from the UK general practice research database. Setting General practices in the United Kingdom. Participants Children aged 12 years or younger diagnosed with autism between 1988 and 1999, with further analysis of boys aged 2 to 5 years born between 1988 and 1993. Main outcome measures Annual and age-specific incidence for first recorded diagnoses of autism (that is, when the diagnosis of autism was first recorded) in the children aged 12 years or younger; annual birth cohort-specific risk of autism diagnosed in the 2- to 5-year-old boys; and coverage (prevalence) of MMR vaccination in the same birth cohorts. Results The incidence of newly diagnosed autism increased 7-fold, from 0.3/10,000 person-years in 1988 to 2.1/10,000 person-years in 1999. The peak incidence was among 3- and 4-year-olds, and 83% (254/305) of cases were in boys. In an annual birth-cohort analysis of 114 boys born between 1988 and 1993, the risk of autism in 2- to 5-year-old boys increased nearly 4-fold over time, from 8/10,000 (95% confidence interval [CI], 4-14/10,000) for boys born in 1988 to 29/10,000 (95% CI, 20-43/10,000) for boys born in 1993. For the same annual birth cohorts, the prevalence of MMR vaccination was more than 95%. Conclusions Because the incidence of autism among 2- to 5-year-olds increased markedly among boys born in each year separately from 1988 to 1993 while MMR vaccine coverage was more than 95% for successive annual birth cohorts, the data provide evidence that no correlation exists between the prevalence of MMR vaccination and the rapid increase in the risk of autism over time. The explanation for the marked increase in risk of the diagnosis of autism in the past decade remains uncertain.
PMCID: PMC1071423
7.  Mumps, measles, and rubella vaccine and the incidence of autism recorded by general practitioners: a time trend analysis 
BMJ : British Medical Journal  2001;322(7284):460-463.
Objective
To estimate changes in the risk of autism and assess the relation of autism to the mumps, measles, and rubella (MMR) vaccine.
Design
Time trend analysis of data from the UK general practice research database (GPRD).
Setting
General practices in the United Kingdom.
Subjects
Children aged 12 years or younger diagnosed with autism 1988-99, with further analysis of boys aged 2 to 5 years born 1988-93.
Main outcome measures
Annual and age specific incidence for first recorded diagnoses of autism (that is, when the diagnosis of autism was first recorded) in the children aged 12 years or younger; annual, birth cohort specific risk of autism diagnosed in the 2 to 5 year old boys; coverage (prevalence) of MMR vaccination in the same birth cohorts.
Results
The incidence of newly diagnosed autism increased sevenfold, from 0.3 per 10 000 person years in 1988 to 2.1 per 10 000 person years in 1999. The peak incidence was among 3 and 4 year olds, and 83% (254/305) of cases were boys. In an annual birth cohort analysis of 114 boys born in 1988-93, the risk of autism in 2 to 5 year old boys increased nearly fourfold over time, from 8 (95% confidence interval 4 to 14) per 10 000 for boys born in 1988 to 29 (20 to 43) per 10 000 for boys born in 1993. For the same annual birth cohorts the prevalence of MMR vaccination was over 95%.
Conclusions
Because the incidence of autism among 2 to 5 year olds increased markedly among boys born in each year separately from 1988 to 1993 while MMR vaccine coverage was over 95% for successive annual birth cohorts, the data provide evidence that no correlation exists between the prevalence of MMR vaccination and the rapid increase in the risk of autism over time. The explanation for the marked increase in risk of the diagnosis of autism in the past decade remains uncertain.
PMCID: PMC26561  PMID: 11222420
8.  Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status 
Journal of Korean Medical Science  2011;26(6):711-719.
This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea.
doi:10.3346/jkms.2011.26.6.711
PMCID: PMC3102862  PMID: 21655054
Health Surveys; Interview; Telephone; Vaccination
9.  Illness after measles-mumps-rubella vaccination. 
OBJECTIVES: To provide accurate information on the common sequelae of measles-mumps-rubella (MMR) vaccination and to compare post-vaccine symptoms in children vaccinated at 13 and 15 months. DESIGN: Prospective cluster randomized controlled trial. SETTING: Twenty-two family practices in southwestern Ontario. PATIENTS: All 376 infants who were due to receive MMR vaccine in the next year, 253 (67.3%) successfully completed the study. INTERVENTION: MMR vaccine administered at 13 months by half of the family physicians and at 15 months by the remaining half. OUTCOME MEASURES: Family physician's physical findings in children 7 days and 30 days after vaccine; reported illnesses by mothers in a daily diary in the month before and after vaccination and medical records of visits to family physicians and hospital admissions in the month before and after vaccination. RESULTS: Compared with the incidence rates in the corresponding weeks before vaccination, the rates of lymphadenopathy (23.8%) and fever (16.8%) were higher 1 week afterward and the rate of rash (26.9%) was higher 7 to 14 days afterward. Fewer health problems were reported in the third and fourth weeks after vaccination than in the corresponding weeks beforehand. Hospital admissions after vaccination were no more frequent than those before once cause and time of admission were taken into account. The two age groups did not differ in any of the outcomes. CONCLUSIONS: Mothers should be informed about the possibility of increased physical findings in the weeks after MMR vaccination, especially lymphadenopathy, nasal discharge and rash. Since the occurrence of sequelae does not seem to differ significantly between 13-month-old recipients and 15-month-old recipients, it should not influence the decision of when to administer the vaccine.
PMCID: PMC1485961  PMID: 8242506
10.  Do Beliefs of Inner-City Parents About Disease and Vaccine Risks Affect Immunization? 
Objective.
The objective of this study was to understand how low income, inner-city parents of preschool children think about childhood diseases and prevention and the impact that this has on late receipt of vaccines.
Methods.
Parents of all children born between 1/1/91 and 5/31/95, whose child received medical assistance and their health care at one of four inner-city, primary care clinics in Pittsburgh, PA., completed a telephone interview and gave consent for a vaccine record review. The main outcome measures were lateness for first and third diphtheria and tetanus toxoids and pertussis vaccines (DTP) and not receiving at least 4 DTP, 3 polio virus containing and 1 measles, mumps and rubella (MMR) doses by 19 months.
Results.
483 parents participated. Fifteen percent of children were late for the first DTP, 52% for the third DTP and, 40% had not received at least 4 DTP, 3 polio and 1 MMR by 19 months of age. Statistically significant factors associated with lateness at 19 months included: having three or more children, having two children, beliefs regarding the severity of immunization side effects and, being African American.
Conclusions.
The results of this study indicate that a combination of life circumstances as well as cognitive factors were associated with late immunization.
PMCID: PMC2568314
Immunization behavior; parental beliefs; health communication; health behavior; health disparities
11.  The Association Between Intentional Delay of Vaccine Administration and Timely Childhood Vaccination Coverage 
Public Health Reports  2010;125(4):534-541.
SYNOPSIS
Objectives
We evaluated the association between intentional delay of vaccine administration and timely vaccination coverage.
Methods
We used data from 2,921 parents of 19- to 35-month-old children that included parents' reports of intentional delay of vaccine administration. Timely vaccination was defined as administration with ≥4 doses of diphtheria, tetanus, and pertussis; ≥3 doses of polio vaccine; ≥1 dose of measles, mumps, and rubella vaccine; ≥3 doses of Haemophilus influenzae type b vaccine; ≥3 doses of hepatitis B vaccine; and ≥1 dose of varicella vaccine by 19 months of age, as reported by vaccination providers.
Results
In all, 21.8% of parents reported intentionally delaying vaccinations for their children. Among parents who intentionally delayed, 44.8% did so because of concerns about vaccine safety or efficacy and 36.1% delayed because of an ill child. Children whose parents intentionally delayed were significantly less likely to receive all vaccines by 19 months of age than children whose parents did not delay (35.4% vs. 60.1%, p<0.05). Parents who intentionally delayed were significantly more likely to have heard or read unfavorable information about vaccines than parents who did not intentionally delay (87.6% vs. 71.9%, p<0.05). Compared with parents who intentionally delayed only because their child was ill, parents who intentionally delayed only because of vaccine safety or efficacy concerns were significantly more likely to seek additional information about their decision from the Internet (11.4% vs. 1.1%, p<0.05), and significantly less likely to seek information from a doctor (73.9% vs. 93.9%, p<0.05).
Conclusions
Intentionally delayed vaccine doses are not uncommon. Children whose parents delay vaccinations may be at increased risk of not receiving all recommended vaccine doses by 19 months of age and are more vulnerable to vaccine-preventable diseases. Providers should consider strategies such as educational materials that address parents' vaccine safety and efficacy concerns to encourage timely vaccination.
PMCID: PMC2882604  PMID: 20597453
12.  Do beliefs of inner-city parents about disease and vaccine risks affect immunization? 
OBJECTIVE: The objective of this study was to understand how low income, inner-city parents of preschool children think about childhood diseases and prevention and the impact that this has on late receipt of vaccines. METHODS: Parents of all children born between January 1, 1991, and May 31, 1995, whose child received medical assistance and health care at one of four inner-city, primary care clinics in Pittsburgh, PA, completed a telephone interview and gave consent for a vaccine record review. The main outcome measures were lateness for first and third diphtheria and tetanus toxoids and pertussis vaccines (DTP) and not receiving at least four DTP, three polio virus containing and one measles, mumps and rubella (MMR) doses by 19 months. RESULTS: A total of 483 parents participated. Fifteen percent of children were late for the first DTP, 52% for the third DTP, and 40% had not received at least four DTP, three polio and one MMR by 19 months of age. Statistically significant factors associated with lateness at 19 months included: having three or more children, having two children, beliefs regarding the severity of immunization side effects, and being African American. CONCLUSIONS: The results of this study indicate that a combination of life circumstances, as well as cognitive factors were associated with late immunization.
PMCID: PMC2594140  PMID: 12392046
13.  Reasons for non-uptake of measles, mumps, and rubella catch up immunisation in a measles epidemic and side effects of the vaccine. 
BMJ : British Medical Journal  1995;310(6995):1629-1632.
OBJECTIVE--To investigate the reasons for poor uptake of immunisation (non-immunisation) and the possible side effects of measles, mumps, and rubella vaccine in a catch up immunisation campaign during a community outbreak of measles. DESIGN--Descriptive study of reasons for non-immunisation and retrospective cohort study of side effects of the vaccine. SETTING--Secondary schools in South Glamorgan. SUBJECTS--Random cluster sample of the parents of 500 children targeted but not immunised and a randomised sample of 2866 of the children targeted. MAIN OUTCOME MEASURES--Reasons for non-immunisation; symptoms among immunised and non-immunised children. RESULTS--Immunisation coverage of the campaign was only 43.4% (7633/17,595). The practical problems experienced included non-return of consent forms (6698/17,595), refusal of immunisation (2061/10,897 forms returned), and absence from school on day of immunisation (1203/8836 children with consent for immunisation). The most common reasons cited for non-immunisation were previous measles infection (145/232), previous immunisation against measles (78/232), and concern about side effects (55/232). Symptoms were equally common among immunised and non-immunised subjects. However, significantly more immunised boys than non-immunised boys reported fever (relative risk 2.31 (95% confidence interval 1.36 to 3.93)), rash (2.00 (1.10 to 3.64), joint symptoms (1.58; 1.05 to 2.38), and headache (1.31 (1.04 to 1.65)). CONCLUSIONS--Many of the objections raised by parents could be overcome by emphasising that primary immunisation does not necessarily confer immunity and that diagnosis of measles is unreliable. Measles, mumps, and rubella vaccine is safe in children aged 11-15.
PMCID: PMC2550008  PMID: 7795447
14.  Ethnicity as a correlate of the uptake of the first dose of mumps, measles and rubella vaccine 
The aim of this study was to investigate whether a relationship exists between ethnicity and uptake of the first dose of mumps, measles and rubella (MMR1) vaccination, and to study important factors influencing the parental decision about vaccination. Examination of routine data on uptake of MMR1 vaccine among children living in the London borough of Brent, North West London, for associations with ethnicity was carried out. Six focus group interviews were held and a questionnaire on factors related to immunisation by convenience samples of mothers from Asian, Afro‐Caribbean and White backgrounds was completed. The routine data reported MMR1 vaccine status for 6444 children living in Brent who were aged between 18 months and 3 years on 1 December 2003. A total of 37 mothers took part in the 6 focus group sessions. Significantly higher coverage by MMR1 vaccine in the Asian population (87.1%) compared with Afro‐Caribbeans (74.7%) and the White group (57.5%) was noticed. The qualitative data revealed clear differences between the ethnic groups with respect to awareness of the controversy surrounding MMR vaccination (related to use of English‐language media) and influence of grandparents and health professionals in decisions about immunisation. A multiple logistic regression model showed that although coverage of MMR vaccination increased with increasing socioeconomic status, there was no evidence of a statistically significant interaction between socioeconomic status and ethnicity. An important association between ethnicity and uptake of MMR1 vaccine is observed. This has implications for efforts to improve the currently inadequate levels of MMR vaccination across the population as a whole.
doi:10.1136/jech.2005.045633
PMCID: PMC2660004  PMID: 17699534
15.  Economic benefits of a routine second dose of combined measles, mumps and rubella vaccine in Canada 
OBJECTIVE:
To evaluate the potential economic benefits of a program for a second routine dose of combined measles, mumps and rubella (MMR) vaccine, administered to children in Canada.
DESIGN:
Both published and unpublished data from the United States and Canada were incorporated into a linear model. This information was supplemented with opinions on probability and resource use from interviews with a Canadian panel of physicians and practitioners. The province of Quebec was used as a model for resource use and costs.
MATERIAL AND METHODS:
Data were based on a vaccination program for Canadian children at 18 months, with an estimated annual birth cohort of 400,000. Further data were also collected for the lifetime costs of complications arising from these diseases or from vaccination, for both patients and family caregivers.
OUTCOME MEASURES:
Outcomes were reviewed from the perspectives of a provincial ministry of health (direct medical costs) and of society (all direct and indirect medical and nonmedical costs).
RESULTS:
It was estimated that a second dose of MMR vaccine administered at 18 months of age would prevent 9200 cases of measles, 6120 cases of mumps and 1960 cases of rubella, producing a savings of $6.34 for every dollar spent from the ministry of health perspective, and $3.25 from the societal perspective.
CONCLUSIONS:
A routine second dose immunization with MMR vaccine would result in considerable cost savings in Canada.
PMCID: PMC3250895  PMID: 22346520
Benefit-cost; Economics; Measles; Mumps; Rubella; Second dose vaccine
16.  Measles-Mumps-Rubella Vaccine and the Development of Autism or Inflammatory Bowel Disease: The Controversy Should End 
Vaccines have been administered to millions of individuals, usually infants and children, with few serious adverse effects. In 1998 a report suggested that there may be a link between the measles-mumps-rubella vaccine and the development of behavioral abnormalities (i.e., autism) and inflammatory bowel disease in children. This report generated considerable media and political attention, which many feared would result in a decreased willingness of parents to immunize their children against these contagious diseases. Over the past decade, an increasing number of healthcare practitioners have been credentialed to administer vaccinations. Therefore, it is imperative for all medical professionals to understand the controversy surrounding this issue and to be able to appropriately educate and advise parents accordingly. This review article evaluated the primary and secondary literature pertaining to this topic and concluded that the available epidemiological and scientific evidence does not support a causal association between the MMR vaccine and autism or inflammatory bowel disease.
doi:10.5863/1551-6776-8.3.187
PMCID: PMC3469143  PMID: 23118678
Measles-Mumps-Rubella; MMR; vaccine; autism; inflammatory bowel disease
17.  Randomised controlled trial of the use of a modified postal reminder card on the uptake of measles vaccination 
Archives of Disease in Childhood  1998;79(2):136-140.
OBJECTIVE—To determine whether rewording postal reminder cards according to the "health belief model", a theory about preventive health behaviour, would help to improve measles vaccination rates.
DESIGN—A randomised controlled trial, with blind assessment of outcome status. Parents of children due for their first measles vaccination were randomised to one of two groups, one receiving the health belief model reminder card, the other receiving the usual, neutrally worded card. The proportion of children subsequently vaccinated in each group over a five week period was ascertained from clinical (provider based) records.
SETTING—A local government operated public vaccination clinic.
PARTICIPANTS—Parents of 259 children due for measles vaccination.
MAIN RESULTS—The proportion of children vaccinated in the health belief model card group was 79% compared with 67% of those sent the usual card (95% CI, 2% to 23%), a modest but important improvement.
CONCLUSION—This study illustrates how the effectiveness of a minimal and widely practised intervention to promote vaccination compliance can be improved with negligible additional effort.


PMCID: PMC1717666  PMID: 9797594
18.  Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen. 
Infection and Immunity  1986;51(3):784-787.
We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6-month intervals. The immune responses to the combination of HB vaccine and DTP-polio vaccines were similar to the immune responses observed after administration of each vaccine alone. In addition, no adverse reactions were noted. These experimental trials also demonstrated that with a DTP-polio vaccine containing 30Lf of tetanus and diphtheria toxoids, two doses given at 6-month intervals are sufficient to provide a satisfactory immune response. In the case of pertussis and HB vaccines; however, a third dose is necessary.
PMCID: PMC260966  PMID: 2936684
19.  Effect of reminder notices on the timeliness of early childhood immunizations 
Paediatrics & Child Health  1999;4(6):400-405.
OBJECTIVE:
To determine whether reminder notices would improve the timeliness of toddler-age vaccinations.
DESIGN:
Prospective, randomized, controlled trial.
POPULATION STUDIED:
Two convenience cohorts of 320 children due to receive either measles-mumps-rubella (MMR) vaccine (at 12 months of age) or diphtheria-pertussis-tetanus (DPT)-inactivated polio (IPV)- Haemophilus influenzae type b (Hib) booster vaccine (at 18 months of age).
SETTING:
Suburban community.
INTERVENTIONS:
Parents of the identified children were randomly assigned either to a group to receive a reminder notice of pending vaccinations or a control group that did not receive a notice at a ratio of 1:1. Immunization uptake was assessed eights weeks after the initial due date for vaccination.
RESULTS:
Information was obtained for 224 children in the MMR group and 227 children in the DPT-IPV-Hib booster group. MMR uptake within eight weeks of the due date was about 90% in both the test and control groups, probably because of publicity surrounding a local college-based measles outbreak. In the DPT-IPV-Hib group, reminder notices had no effect; the uptake rates within eight weeks of the due date were 73.7% to 75.2%. Delays in immunization resulted mostly from parents’ scheduling problems and provider-recommended delays. More than half of the parents whose child had delayed immunization did not recall receiving the reminder notice.
CONCLUSIONS:
Mailed reminders did not increase on-time immunization rates in the second year of a child’s life. A telephone call or a more memorable reminder notice may be better suited to catch the attention of parents.
PMCID: PMC2827742  PMID: 20212950
Childhood; Immunization; Reminder notice
20.  Safety of measles, mumps and rubella vaccination in juvenile idiopathic arthritis 
Annals of the Rheumatic Diseases  2007;66(10):1384-1387.
Objective
To assess the effect of measles, mumps and rubella (MMR) vaccination on disease activity in children with juvenile idiopathic arthritis (JIA).
Methods
A retrospective observational multicentre cohort study was performed in 314 patients with JIA, born between 1989 and 1996. Disease activity and medication use were compared during the period of 6 months before vaccination versus 6 months after vaccination. Disease activity was measured by joint counts, the Physician's global assessment scale and erythrocyte sedimentation rate. Next, we compared disease activity in patients vaccinated between 8 and 9 years of age with the activity in patients who had not been vaccinated at this time (who received MMR between the ages of 9 and 10 years).
Results
No increase in disease activity or medication use was seen in the 6 months after MMR vaccination (n = 207), including in patients using methotrexate (n = 49). No overt measles infections were noted. When disease activity in vaccinated patients (n = 108) was compared with activity in those not yet vaccinated (n = 86), there were no significant differences.
Conclusions
The MMR booster vaccination does not seem to aggravate disease activity in JIA. This indicates that the most patients with JIA can be vaccinated safely with the MMR vaccine. A prospective study is recommended.
doi:10.1136/ard.2006.063586
PMCID: PMC1994321  PMID: 17284544
measles; mumps and rubella vaccination; juvenile idiopathic arthritis; methotrexate; disease activity parameters; flares
21.  Short term evaluation of a rural immunization program in Nigeria. 
BACKGROUND: Immunization remains the primary strategy in both the control and prevention of common childhood diseases, particularly in the developing world. Immunization and preprimary health care services were commenced in a rural community in Nigeria in 1998, when vaccine coverage for all Expanded Program on Immunization (EPI) diseases (tuberculosis, polio, diphtheria, pertussis, tetanus, measles, and hepatitis B) was considerably low with only 43% of children fully immunized. METHODS: Children aged 0-2 years and living in a rural community were recruited into the study. Data on vaccination history was collected by both vaccination card and maternal history. Three hundred and twenty-seven children were recruited into the study. Study participants were vaccinated for EPI diseases. Hepatitis-B vaccine was administered at birth, and a combined diphtheria and tetanus toxoids, and pertussis whole cell vaccine (DTP) plus hepatitis-B vaccine was administered in a single injection after six weeks. RESULTS AND CONCLUSIONS: Two years after the program was started, immunization coverage rates were 94% for BCG, 88% for DTP (third dose), and 82% for measles. All antigens showed significant improvements from baseline values (p < 0.0001). Eighty four percent of children were fully immunized against all six diseases, compared with 43% at the commencement (p < 0.0001). Hepatitis-B coverage (three doses) was 58%. The vaccination program has significantly improved vaccination coverage and could be a model for under served, non-industrialized communities.
PMCID: PMC2594432  PMID: 12760613
22.  The contribution of single antigen measles, mumps and rubella vaccines to immunity to these infections in England and Wales 
Archives of Disease in Childhood  2007;92(9):786-789.
Objective
To obtain information on the use of single antigen measles, mumps and rubella vaccines to improve estimates of population immunity and help predict outbreaks.
Design
We requested information from providers of single antigen vaccines and from the Medicine and Healthcare products Regulatory Agency on requests for importation of single antigen measles and mumps vaccines.
Setting
England and Wales.
Main outcome measures
Number of doses of single measles, mumps and rubella vaccine, by age of child (in months), year given and area of residence, and number of children who have received all three single vaccinations.
Results
Of 27 providers identified, 13 held single site clinics: nine were individual general practitioners and five held clinics at multiple sites. Data were received from 9/27 (33%) providers operating 40/74 (54%) clinic sites. We received information on 60 768 vaccinations administered by single vaccine providers and 269 917 doses requested for importation. For children born in 2001/2002, the minimum estimates for the proportion who received single measles vaccine are 1.7% in 2001 and 2.1% in 2002, with a reasonable maximum estimate of 5.6% over the 2 years. For single mumps vaccine, the minimum estimates are 0.3% in 2001 and 0.02% in 2002, with a maximum estimate of 4.0%.
Conclusion
The contribution of single vaccines to immunity is small in comparison to that of the combined measles, mumps and rubella vaccine (MMR). For recent birth cohorts this contribution could increase routine coverage for measles‐containing vaccines by around 2%, still below the level of immunity required to sustain elimination.
doi:10.1136/adc.2006.109223
PMCID: PMC2084043  PMID: 17412744
measles vaccine; mumps vaccine; rubella vaccine; MMR vaccine; vaccination coverage
23.  Joint and limb symptoms in children after immunisation with measles, mumps, and rubella vaccine. 
BMJ : British Medical Journal  1992;304(6834):1075-1078.
OBJECTIVE--To assess whether the combined measles, mumps, and rubella vaccine increases the incidence of joint and limb symptoms in young children. DESIGN--Comparison of six week recalled incidence of symptoms in two groups of children: children who had been immunised at the start of the six weeks, and children eligible for immunisation but who had not received it. SETTING--South Manchester Health Authority. SUBJECTS--2658 children immunised during July 1989-February 1990 and 2359 not yet immunised. Questionnaires were returned for 1846 immunised children and 1075 not immunised. MAIN OUTCOME MEASURE--Recalled rate of joint and limb episodes determined by postal questionnaire and later by clinical follow up. RESULTS--Compared with non-immunised children the immunised group had an increased incidence of new episodes (relative risk 1.6 (95% confidence interval (1.2 to 2.1)) and first ever episodes, though this was not significant (1.7 (0.3 to 3.5)). The risk of first episodes was increased in girls (3.5 (1.1 to 12.2)) but not in boys (1.0 (0.4 to 2.6)). Similarly, an increased risk was seen in children aged under 5 (12.0 (1.6 to 92.3)) but not in older children (0.7 (0.3 to 1.5)). Most episodes were mild and self limiting, but three immunised children required hospital referral. CONCLUSION--Measles, mumps, and rubella vaccine is associated with an increased risk of episodes of joint and limb symptoms, especially in girls and children under 5. The risk of frank arthritis is substantially less than after wild rubella infection.
PMCID: PMC1881909  PMID: 1586818
24.  Timeliness of immunizations of children in a Medicaid primary care case management managed care program. 
OBJECTIVE: This study assessed the timeliness of immunization for children in a Medicaid managed care primary care case management program controlling for patient and provider predictors of immunization status. METHODS: Using administrative data and patient medical records, up-to-date (UTD) and age appropriate immunization (AAI) status were reviewed for 5598 children. The 4:3:1 immunization series (four diphtheria, pertussis, tetanus vaccinations; three polio vaccinations; and one measles, mumps, rubella vaccination) was the standard. RESULTS: Childhood immunization rates were low when assessed using strict adherence to vaccination recommendations. At age 18 months, 28.3% were classified as UTD, and 6.3% were classified as AAI. Compared to children not up-to-date, UTD children were more likely to have public rather than private providers, to have had older mothers, and less likely to have been African American. Among UTD children, AAI children were more likely to reside in urban areas. CONCLUSIONS: Low-income children continue to be under-immunized, even under a managed care initiative. Health care providers and child health advocates need to continue pressure for programs that will increase adherence to nationally recommended guidelines.
PMCID: PMC2594144  PMID: 12392047
25.  Timeliness of Immunizations of Children in a Medicaid Primary Care Case Management Managed Care Program 
Objective.
This study assessed the timeliness of immunization for children in a Medicaid managed care primary care case management program controlling for patient and provider predictors of immunization status.
Methods.
Using administrative data and patient medical records, up-to-date (UTD) and age appropriate immunization (AAI) status were reviewed for 5,598 children. The 4:3:1 immunization series (4 diphtheria, pertussis, tetanus vaccinations; 3 polio vaccinations; and one measles, mumps, rubella vaccination) was the standard.
Results.
Childhood immunization rates were low when assessed using strict adherence to vaccination recommendations. At age 18 months, 28.3% were classified as UTD, and 6.3% were classified as AAI. Compared to children not up-to-date, UTD children were more likely to have public rather than private providers, to have had older mothers, and less likely to have been African-American. Among UTD children, AAI children were more likely to reside in urban areas.
Conclusions.
Low-income children continue to be under-immunized, even under a managed care initiative. Health care providers and child health advocates need to continue pressure for programs that will increase adherence to nationally recommended guidelines.
PMCID: PMC2568310
Medicaid; managed care; immunization; children

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