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1.  Estimating vaccination coverage using parental recall, vaccination cards, and medical records. 
Public Health Reports  1998;113(6):521-526.
OBJECTIVE: To compare estimates based on vaccination cards, parental recall, and medical records of the percentages of children up-to-date on vaccinations for diphtheria, tetanus, and pertussis; polio; and measles, mumps, and rubella. METHOD: The authors analyzed parent interview and 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: Only one-third of children had vaccination cards; based on medical records, these children had higher up-to-date coverage at 24 months of age than did children without cards. For individual vaccines, only two-thirds of parents could provide information to calculate coverage rates; however, almost all provided enough information to estimate coverage for the primary series. For each vaccine and the series, parental recall estimates were at least 17 percentage points higher than estimates from medical records. For children without vaccination cards whose parents could not provide coverage information, up-to-date rates based on medical records were consistently lower than for children with cards or with parents who provided coverage information. CONCLUSIONS: Population-based vaccine coverage surveys that rely on vaccination cards or parental recall or both may overestimate vaccination coverage.
PMCID: PMC1308435  PMID: 9847923
2.  Vaccination coverage and its determinants among migrant children in Guangdong, China 
BMC Public Health  2014;14:203.
Guangdong province attracted more than 31 million migrants in 2010. But few studies were performed to estimate the complete and age-appropriate immunization coverage and determine risk factors of migrant children.
1610 migrant children aged 12–59 months from 70 villages were interviewed in Guangdong. Demographic characteristics, primary caregiver’s knowledge and attitude toward immunization, and child’s immunization history were obtained. UTD and age-appropriate immunization rates for the following five vaccines and the overall series (1:3:3:3:1 immunization series) were assessed: one dose of BCG, three doses of DTP, OPV and HepB, one dose of MCV. Risk factors for not being UTD for the 1:3:3:3:1 immunization series were explored.
For each antigen, the UTD immunization rate was above 71%, but the age-appropriate immunization rates for BCG, HepB, OPV, DPT and MCV were only 47.8%, 45.1%, 47.1%, 46.8% and 37.2%, respectively. The 1st dose was most likely to be delayed within them. For the 1:3:3:3:1 immunization series, the UTD immunization rate and age-appropriate immunization rate were 64.9% and 12.4% respectively. Several factors as below were significantly associated with UTD immunization. The primary caregiver’s determinants were their occupation, knowledge and attitude toward immunization. The child’s determinants were sex, Hukou, birth place, residential buildings and family income.
Alarmingly low immunization coverage of migrant children should be closely monitored by NIISS. Primary caregiver and child’s determinants should be considered when taking measures. Strategies to strengthen active out-reach activities and health education for primary caregivers needed to be developed to improve their immunization coverage.
PMCID: PMC3938078  PMID: 24568184
Up-to-date; Age-appropriate immunization; Immunization coverage; Risk factor; Migrant children
3.  Immunization Milestones: A More Comprehensive Picture of Age-Appropriate Vaccination 
A challenge facing immunization registries is developing measures of childhood immunization coverage that contain more information for setting policy than present vaccine series up-to-date (UTD) rates. This study combined milestone analysis with provider encounter data to determine when children either do not receive indicated immunizations during medical encounters or fail to visit providers. Milestone analysis measures immunization status at key times between birth and age 2, when recommended immunizations first become late. The immunization status of a large population of children in the Oregon ALERT immunization registry and in the Oregon Health Plan was tracked across milestone ages. Findings indicate that the majority of children went back and forth with regard to having complete age-appropriate immunizations over time. We also found that immunization UTD rates when used alone are biased towards relating non-UTD status to a lack of visits to providers, instead of to provider visits on which recommended immunizations are not given.
PMCID: PMC2874993  PMID: 20508852
4.  Failure to vaccinate children against measles during the second year of life. An analysis of immunization practices in two Tennessee county health departments. 
Public Health Reports  1976;91(2):133-137.
In many Tennessee counties, children under the care of health departments have low measles vaccination levels. An immunization survey and a health department record audit of 2-year-olds were undertaken in two counties to determine the reasons for this situation. The results indicated that faulty clinic procedures played a large part in the failure to vaccinate against measles. Nearly half of the unvaccinated 2-year-olds with health department records had been present in the health department clinic at the appropriate age for measles vaccination; the remainder had dropped out of the well-child program before their first birthday. Emphasis on tuberculin skin testing and delay in the administration of the basic series of DTP immunizations correlated with the failure to vaccinate against measles. For more than half of the children who attended the clinic after their first birthday, no reason was recorded for the failure to vaccinate them against measles. Improved clinic procedures could bring measles vaccination levels within the acceptable range. These procedures would include new methods for correcting immunization delinquency, simultaneous tuberculin skin testing and measles vaccination of children without a history of tuberculosis exposure, emphasis on vaccinating at-risk groups, and more convenient vaccination clinic hours.
PMCID: PMC1438513  PMID: 822461
5.  Risk factors for delay in age-appropriate vaccination. 
Public Health Reports  2004;119(2):144-155.
OBJECTIVE: To estimate the risk factors of children experiencing delay in age-appropriate vaccination using a nationally representative population of children, and to compare risk factors for vaccination delay with those based on up-to-date vaccination status models. METHODS: The authors compared predictors of delay in age-appropriate vaccination with those for children who were not up-to-date, using a nationally representative sample of children from five years of pooled data (1992-1996) from the National Health Interview Survey (NHIS) Immunization Supplement. Duration of delay was calculated for the DTP4, Polio3, MMR1 doses and 4:3:1 series using age-appropriate vaccination standards; up-to-date status (i.e., whether or not a dose was received) was also determined. Adjusted odds ratios were estimated using multivariate logistic regression for models of vaccination delay and up-to-date vaccination status. RESULTS: Absence of a two-parent household, large family size, parental education, Medicaid enrollment, absence of a usual provider, no insurance coverage, and households without a telephone were significantly related to increased odds of a child experiencing vaccination delay (p < or = 0.05). CONCLUSIONS: Many of the risk factors observed in models of vaccination delay were not found to be significant in risk models based upon up-to-date status. Consequently, risk models of delays in age-appropriate vaccination may foster identification of children at increased risk for inadequate vaccination. Populations at increased risk of inadequate vaccination can be more clearly identified through risk models of delays in age-appropriate vaccination.
PMCID: PMC1497606  PMID: 15192901
6.  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
7.  Timeliness of Immunizations of Children in a Medicaid Primary Care Case Management Managed Care Program 
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.
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.
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.
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
8.  Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial 
Archives of Disease in Childhood  2012;97(8):685-691.
Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants.
2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit.
Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls.
Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.
PMCID: PMC3409557  PMID: 22331681
9.  Immunization coverage and predictive factors for complete and age-appropriate vaccination among preschoolers in Athens, Greece: a cross- sectional study 
BMC Public Health  2013;13:908.
In Greece, several new childhood vaccines were introduced recently but were reimbursed gradually and at different time points. The aim of this study was to assess immunization coverage and identify factors influencing complete and age-appropriate vaccination among children attending public nurseries in the municipal district of Athens.
A cross-sectional study, using stratified sampling was performed. Immunization history was obtained from vaccination booklets. Demographic and socioeconomic data were obtained from school registries and telephone interviews. Vaccination rates were estimated by sample weighted proportions while associations between complete and age-appropriate immunization and potential determinants by logistic regression analysis.
A total of 731 children (mean age: 46, median: 48, range: 10–65 months) were included. Overall immunization coverage with traditional vaccines (DTP, polio, Hib, HBV, 1st dose MMR) was satisfactory, exceeding 90%, but the administration of booster doses was delayed (range: 33.7- 97.4%, at 60 months of age). Complete vaccination rates were lower for new vaccines (Men C, PCV7, varicella, hepatitis A), ranging between 61-92%. In addition, a significant delay in timely administration of Men C, PCV7, as well as HBV was noted (22.9%, 16.0% and 27.7% at 12 months of age, respectively). Child’s age was strongly associated with incomplete vaccination with all vaccines (p< 0.001), while as immigrant status was a predictor of incomplete (p=0.034) and delayed vaccination (p<0.001) with traditional vaccines. Increasing household size and higher maternal education were negatively associated with the receipt of all and newly licensed vaccines, respectively (p=0.035).
Our findings highlight the need to monitor uptake of new vaccines and improve age- appropriate administration of booster doses as well as early vaccination against hepatitis B. Immigrant status, increased household size and high maternal education may warrant targeted intervention.
PMCID: PMC3850659  PMID: 24083352
Vaccination coverage; Age-appropriate immunization; Predictive factors; Conjugated pneumococcal vaccine; Conjugated meningococcal C vaccine; Varicella vaccine; Greece
10.  The delayed immunization of children of migrant farm workers in South Carolina. 
Public Health Reports  1990;105(3):317-320.
A study was conducted to evaluate the immunization status of migrant farm worker children in South Carolina. Results of this study indicate that the children receive their immunizations at times which are significantly later than the recommended schedule. The first, second, third, and fourth oral poliomyelitis vaccine (OPV) doses are being given approximately 10, 15, 23, and 32 months late, respectively. Diphtheria, pertussis, tetanus vaccine (DPT) is likewise late with the first, second, third, and fourth doses occurring 9, 14, 20, and 26 months late. The fifth booster dose in both series was timed properly. The mumps, measles, rubella vaccine (MMR) is approximately 28 months late, on average. An evaluation of antibody status of 41 migrant farm worker children (5-10 years old) revealed that, even with aberrant patterns of administration, all children had adequate antibody titers. These data indicate that, although adequate levels of protection are reached with the pattern of immunization that migrant farm worker children have, there are large groups of children that are unprotected early in life when they are most susceptible to these diseases.
PMCID: PMC1579997  PMID: 2113693
11.  Do Beliefs of Inner-City Parents About Disease and Vaccine Risks Affect Immunization? 
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.
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.
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.
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
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.  Vaccine-associated Paralytic Poliomyelitis : A Case Report of Flaccid Monoparesis after Oral Polio Vaccine 
Journal of Korean Medical Science  2007;22(2):362-364.
This report describes a case of acute flaccid paralysis after administration of oral polio vaccine (OPV). A 4 month-old male patient with the decreased movement of left lower extremity for 1 month was transferred to the Department of Pediatrics. He received OPV with DTaP at 2 months of age. Flaccid paralysis was detected 4 weeks after OPV immunization. Attempts to isolate Sabin-like viruses in the two stool and CSF samples failed because those specimens were collected more than 2 month after the onset of paralysis. Hypotonic monoparesis (GIV/V), hypotonia and atrophy on the left lower extremity, and ipsilateral claw foot persisted for more than 18 months, while we followed him with rehabilitation therapy. This is the first case of officially approved, recipient vaccine-associated paralytic poliomyelitis in Korea.
PMCID: PMC2693609  PMID: 17449951
Poliovirus vaccine; Poliomyelitis
14.  Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau: an observational cohort study 
BMJ Open  2012;2(6):e001509.
The WHO aims for 90% coverage of the Expanded Program on Immunization (EPI), which in Guinea-Bissau included BCG vaccine at birth, three doses of diphtheria−tetanus−pertussis vaccine (DTP) and oral polio vaccine (OPV) at 6, 10 and 14 weeks and measles vaccine (MV) at 9 months when this study was conducted. The WHO assesses coverage by 12 months of age. The sequence of vaccines may have an effect on child mortality, but is not considered in official statistics or assessments of programme performance. We assessed vaccination coverage and frequency of out-of-sequence vaccinations by 12 and 24 months of age.
Observational cohort study.
Setting and participants
The Bandim Health Project's (BHP) rural Health and Demographic Surveillance site covers 258 randomly selected villages in all regions of Guinea-Bissau. Villages are visited biannually and vaccination cards inspected to ascertain vaccination status. Between 2003 and 2009 vaccination status by 12 months of age was assessed for 5806 children aged 12–23 months; vaccination status by 24 months of age was assessed for 3792 children aged 24–35 months.
Outcome measures
Coverage of EPI vaccinations and frequency of out-of-sequence vaccinations.
Half of 12-month-old children and 65% of 24-month-old children had completed all EPI vaccinations. Many children received vaccines out of sequence: by 12 months of age 54% of BCG-vaccinated children had received DTP with or before BCG and 28% of measles-vaccinated children had received DTP with or after MV. By 24 months of age the proportion of out-of-sequence vaccinations was 58% and 35%, respectively, for BCG and MV.
In rural Guinea-Bissau vaccination coverage by 12 months of age was low, but continued to increase beyond 12 months of age. More than half of all children received vaccinations out of sequence. This highlights the need to improve vaccination services.
PMCID: PMC3532986  PMID: 23166127
15.  Measles vaccination coverage estimates from surveys, clinic records, and immune markers in oral fluid and blood: a population-based cross-sectional study 
BMC Public Health  2013;13:1211.
Recent outbreaks of measles and polio in low-income countries illustrate that conventional methods for estimating vaccination coverage do not adequately identify susceptible children. Immune markers of protection against vaccine-preventable diseases in oral fluid (OF) or blood may generate more accurate measures of effective vaccination history, but questions remain about whether antibody surveys are feasible and informative tools for monitoring immunization program performance compared to conventional vaccination coverage indicators. This study compares six indicators of measles vaccination status, including immune markers in oral fluid and blood, from children in rural Bangladesh and evaluates the implications of using each indicator to estimate measles vaccination coverage.
A cross-sectional population-based study of children ages 12–16 months in Mirzapur, Bangladesh, ascertained measles vaccination (MCV1) history from conventional indicators: maternal report, vaccination card records, ‘card + history’ and EPI clinic records. Oral fluid from all participants (n = 1226) and blood from a subset (n = 342) were tested for measles IgG antibodies as indicators of MCV1 history and compared to conventional MCV1 coverage indicators.
Maternal report yielded the highest MCV1 coverage estimates (90.8%), followed by EPI records (88.6%), and card + history (84.2%). Seroprotection against measles by OF (57.3%) was significantly lower than other indicators, even after adjusting for incomplete seroconversion and assay performance (71.5%). Among children with blood results, 88.6% were seroprotected, which was significantly higher than coverage by card + history and OF serostatus but consistent with coverage by maternal report and EPI records. Children with vaccination cards or EPI records were more likely to have a history of receiving MCV1 than those without cards or records. Despite similar MCV1 coverage estimates across most indicators, within-child agreement was poor for all indicators.
Measles IgG antibodies in OF was not a suitable immune marker for monitoring measles vaccination coverage in this setting. Because agreement between conventional MCV1 indicators was mediocre, immune marker surveillance with blood samples could be used to validate conventional MCV1 indicators and generate adjusted results that can be compared across indicators.
PMCID: PMC3890518  PMID: 24359402
Immunization; Vaccination; Immune marker; Surveillance; Measles; Oral fluid; Vaccination card; Maternal report; Bangladesh
16.  Achieving comprehensive childhood immunization: an analysis of obstacles and opportunities in The Gambia 
Health Policy and Planning  2013;29(2):193-203.
Introduction Immunization is a vital component in the drive to decrease global childhood mortality, yet challenges remain in ensuring wide coverage of immunization and full immunization, particularly in low- and middle-income countries. This study assessed immunization coverage and the determinants of immunization in a semi-rural area in The Gambia.
Methods Data were drawn from the Farafenni Health and Demographic Surveillance System. Children born within the surveillance area between January 2000 and December 2010 were included. Main outcomes assessed included measles, BCG and DTP vaccination status and full immunization by 12 months of age as reported on child healthcards. Predictor variables were evaluated based on a literature review and included gender, ethnicity, area of residence, household wealth and mother’s age.
Results Of the 7363 children included in the study, immunization coverage was 73% (CI 72–74) for measles, 86% (CI 86–87) for BCG, 79% (CI 78–80) for three doses of DTP and 52% (CI 51–53) for full immunization. Coverage was significantly associated with area of residence and ethnicity, with children in urban areas and of Mandinka ethnicity being least likely to be fully immunized.
Conclusions Despite high levels of coverage of many individual vaccines, delivery of vaccinations later in the schedule and achieving high coverage of full immunization remain challenges, even in a country with a committed childhood immunization programme, such as The Gambia. Our data indicate areas for targeted interventions by the national Expanded Programme of Immunization.
PMCID: PMC3944881  PMID: 23426974
The Gambia; immunization; socio-demographic; determinants; child
17.  Determinants of third dose of diphtheria–tetanus–pertussis (DTP) completion among children who received DTP1 at rural immunization centres in Pakistan: a cohort study 
In Pakistan, a high proportion of children fail to complete third dose of diphtheria-tetanus-pertussis (DTP3) after having received the first dose (DTP1). A cohort study was conducted to identify the factors predicting three doses of diphtheria–tetanus–pertussis (DTP3) completion among children who have received DTP1 at six centres of Expanded Programme on Immunization (EPI) in rural Pakistan.
We analyzed a cohort of mother–child pairs enrolled at DTP1 between November 2005 and May 2006 in the standard care group of a larger randomized controlled trial. Data were collected from mothers on a structured questionnaire at enrolment, and each child was followed up at clinic visits for 90 days to record dates of DTP2 and DTP3. Multivariable log-binomial regression analysis was performed to identify the independent predictors of DTP3 completion.
Only 39% (149/378) of enrolled children completed DTP3 during the follow-up period. After adjusting for the centre of enrolment in multivariable analysis, DTP3 completion was higher among children who were ≤60 days old at enrolment [adjusted risk ratio (Adj. RR) 1.39, 95% confidence interval (CI): 1.06–1.82], who were living in a household with monthly household income >Rs. 3000 (US$ 50) (Adj. RR 1.76, 95% CI: 1.16–2.65), and who were living ≤10 min away from EPI centre (Adj. RR 1.31, 95% CI: 1.04–1.66).
Interventions targeting childhood immunization dropouts should focus on bringing more children to EPI centres on-time for initial immunization. Relocation of existing EPI centres and creation of new EPI centres at appropriate locations may decrease the travel time to the EPI centres and result in fewer immunization dropouts.
PMCID: PMC2858790  PMID: 19930140
childhood immunization; Expanded Programme on Immunization; dropouts; determinants; cohort study; Pakistan
18.  Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid 
Serogroup B Neisseria meningitidis (MenB) is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis) after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT) was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization). Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine), its use should be restricted to outbreaks of meningococcal disease.
PMCID: PMC3854364  PMID: 23369971
Serological memory; Antibody recall response; Booster immunization
19.  Sex-Differential Effect on Infant Mortality of Oral Polio Vaccine Administered with BCG at Birth in Guinea-Bissau. A Natural Experiment 
PLoS ONE  2008;3(12):e4056.
The policy to provide oral polio vaccine (OPV) at birth was introduced in low-income countries to increase coverage. The effect of OPV at birth on overall child mortality was never studied. During a trial of vitamin A supplementation (VAS) at birth in Guinea-Bissau, OPV was not available during several periods. We took advantage of this “natural experiment” to test the effect on mortality of receiving OPV at birth.
Between 2002 and 2004, the VAS trial randomised normal-birth-weight infants to 50,000 IU VAS or placebo administered with BCG. Provision of OPV at birth was not part of the trial, but we noted whether the infants received OPV or not. OPV was missing during several periods in 2004. We used Cox proportional hazards models to compute mortality rate ratios (MRR) of children who had received or not received OPV at birth.
Principal Findings
A total of 962 (22.1%) of the 4345 enrolled children did not receive OPV at birth; 179 children died within the first year of life. Missing OPV at birth was associated with a tendency for decreased mortality (adjusted MRR = 0.69 (95% CI = 0.46–1.03)), the effect being similar among recipients of VAS and placebo. There was a highly significant interaction between OPV at birth and sex (p = 0.006). Not receiving OPV at birth was associated with a weak tendency for increased mortality in girls (1.14 (0.70–1.89)) but significantly decreased mortality in boys (0.35 (0.18–0.71)).
In our study OPV at birth had a sex-differential effect on mortality. Poliovirus is almost eradicated and OPV at birth contributes little to herd immunity. A randomised study of the effect of OPV at birth on overall mortality in both sexes is warranted.
PMCID: PMC2605256  PMID: 19112511
20.  Impact of the introduction of pneumococcal conjugate vaccine on immunization coverage among infants 
BMC Pediatrics  2005;5:43.
The introduction of pneumococcal conjugate vaccine (PCV) to the U.S. recommended childhood immunization schedule in the year 2000 added three injections to the number of vaccinations a child is expected to receive during the first year of life. Surveys have suggested that the addition of PCV has led some immunization providers to move other routine childhood vaccinations to later ages, which could increase the possibility of missing these vaccines. The purpose of this study was to evaluate whether introduction of PCV affected immunization coverage for recommended childhood vaccinations among 13-month olds in four large provider groups.
In this retrospective cohort study, we analyzed computerized data on vaccinations for 33,319 children in four large provider groups before and after the introduction of PCV. The primary outcome was whether the child was up to date for all non-PCV recommended vaccinations at 13 months of age. Logistic regression was used to evaluate the association between PCV introduction and the primary outcome. The secondary outcome was the number of days spent underimmunized by 13 months. The association between PCV introduction and the secondary outcome was evaluated using a two-part modelling approach using logistic and negative binomial regression.
Overall, 93% of children were up-to-date at 13 months, and 70% received all non-PCV vaccinations without any delay. Among the entire study population, immunization coverage was maintained or slightly increased from the pre-PCV to post-PCV periods. After multivariate adjustment, children born after PCV entered routine use were less likely to be up-to-date at 13 months in one provider group (Group C: OR = 0.5; 95% CI: 0.3 – 0.8) and were less likely to have received all vaccine doses without any delay in two Groups (Group B: OR = 0.4, 95% CI: 0.3 – 0.6; Group C: OR = 0.5, 95% CI: 0.4 – 0.7). This represented 3% fewer children in Group C who were up-to-date and 14% (Group C) to 16% (Group B) fewer children who spent no time underimmunized at 13 months after PCV entered routine use compared to the pre-PCV baseline. Some disruptions in immunization delivery were also observed concurrent with temporary recommendations to suspend the birth dose of hepatitis B vaccine, preceding the introduction of PCV.
These findings suggest that the introduction of PCV did not harm overall immunization coverage rates in populations with good access to primary care. However, we did observe some disruptions in the timely delivery of other vaccines coincident with the introduction of PCV and the suspension of the birth dose of hepatitis B vaccine. This study highlights the need for continued vigilance in coming years as the U.S. introduces new childhood vaccines and policies that may change the timing of existing vaccines.
PMCID: PMC1314888  PMID: 16313673
21.  Related Factors of Age-Appropriate Immunization among Urban-Rural Children Aged 24-35 Months in a 2005 Population-Based Survey in Nonsan, Korea 
Yonsei Medical Journal  2010;52(1):104-112.
This study was aimed to determine the status and related factors of age-appropriate immunization among urban-rural children aged 24-35 months in a 2005 population-based survey in Nonsan, Korea.
Materials and Methods
We conducted household survey and provider check using questionnaire and checklist to obtain data on immunization status for children, aged 24-35 months. Age-appropriate immunization was defined as status of receiving the fourth diphtheria-tetanus-pertussis (4 DTP), 3 Polio, the first measles-mumps-rubella (1 MMR) doses, and the 4 : 3 : 1 series.
Age-appropriate immunization rates were 51.7% for 4 DPT, 88.0% for 3 Polio, 87.9% for 1 MMR, and 50.3% for the 4 : 3 : 1 series. First-born children, lower perceived barrier scores, and higher perception of immunization data were significantly related to age-appropriate immunization.
The findings indicated that age-appropriate immunization rate could be improved by implementing reminder/recall service and providing the knowledge about immunization. Identification and consideration related factors would improve immunization rate and age-appropriate immunization.
PMCID: PMC3017684  PMID: 21155042
Related factors; age-appropriate immunization; DPT; Polio; MMR
22.  Real-time Polymerase Chain Reaction Analysis of Sewage Samples to Determine Oral Polio Vaccine Circulation Duration and Mutation After Mexican National Immunization Weeks 
Oral polio vaccine (OPV) can mutate and cause outbreaks of paralytic poliomyelitis with prolonged replication. After poliovirus eradication, global use of inactivated polio vaccine (IPV) may be needed until all OPV stops circulating. Mexico, where children receive routine IPV but where OPV is given only during biannual national immunization weeks (NIWs), provides a natural setting to study duration of OPV circulation in a community primarily vaccinated with IPV.
One-liter sewage samples from four separate arroyos (creeks) near Orizaba, Mexico, were collected monthly for 12 months. Concentrated sewage underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3 and their variants containing the serotype-specific point mutation in the 5′ untranslated region associated with neurovirulence.
OPV was detected 3, 4, 5, and 7 months after the May 2010 NIW, but was not detected at 6 or 8 months. A second and third NIW occurred in February 2011 and May 2011, and OPV was detected in the sewage monthly after both of these NIW through July 2011 when collection stopped. The OPV detected was primarily serotype 2 and predominantly contained the point mutations in the 5′ untranslated region associated with increased neurovirulence.
OPV was detected in sewage as late as 7 months after an NIW in a Mexican community primarily vaccinated with IPV, but was not detected at 8 months, suggesting that OPV circulation may have ceased. These data suggest that in communities with high vaccination rates, 1 or 2 years of IPV administration after OPV cessation could be sufficient to prevent outbreaks of paralytic poliomyelitis from vaccine-derived strains.
PMCID: PMC3529100  PMID: 23667738
Polio; OPV; Mexico; Sewage; PCR
23.  The effect of vitamin A supplementation administered with missing vaccines during national immunization days in Guinea-Bissau 
Background WHO recommends high-dose Vitamin A supplementation (VAS) at vaccination contacts after 6 months of age. It has not been studied whether the effect of VAS on mortality depends on the type of vaccine. We have hypothesized that VAS administered with measles vaccine (MV) is more beneficial than VAS with diphtheria–tetanus–pertussis (DTP) vaccine. We assessed the effect of VAS administered with different vaccines during national immunization days (NIDs).
Methods In 2003, VAS was distributed during NIDs in Guinea-Bissau. Children 6 months or older were given VAS, and if they were missing vaccines, these were often given as well. We compared survival between children who had received VAS alone, VAS with DTP or DTP + MV, or VAS with MV. We also compared the survival between participants and non-participants. We followed 6- to 17-month old children until 18 months of age and analysed survival in Cox models.
Results Twenty of 982 VAS-recipients died during follow-up. The mortality rate ratio (MRR) for VAS with DTP + MV or VAS with DTP was 3.43 (1.36–8.61) compared with VAS only. There were no deaths among those who received VAS with MV alone (P = 0.0005 for homogeneity of VAS effects). Children who received VAS with DTP had higher mortality than non-participants who did not receive VAS [MRR = 3.04 (1.31–7.07)].
Conclusion The study design does not allow for definite conclusions. However, the results are compatible with our a priori hypothesis that VAS is more beneficial when given with MV and potentially harmful when given with DTP. Randomized trials testing the impact on mortality of the current WHO policy seem warranted.
PMCID: PMC2639368  PMID: 18796481
Vitamin A; diphtheria–tetanus–pertussis vaccine; measles vaccine; child mortality; low income populations
24.  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
25.  Socioeconomic inequalities and vaccination coverage: results of an immunisation coverage survey in 27 Brazilian capitals, 2007–2008 
Since 1988, Brazil's Unified Health System has sought to provide universal and equal access to immunisations. Inequalities in immunisation may be examined by contrasting vaccination coverage among children in the highest versus the lowest socioeconomic strata. The authors examined coverage with routine infant immunisations from a survey of Brazilian children according to socioeconomic stratum of residence census tract.
The authors conducted a household cluster survey in census tracts systematically selected from five socioeconomic strata, according to average household income and head of household education, in 26 Brazilian capitals and the federal district. The authors calculated coverage with recommended vaccinations among children until 18 months of age, according to socioeconomic quintile of residence census tract, and examined factors associated with incomplete vaccination.
Among 17 295 children with immunisation cards, 14 538 (82.6%) had received all recommended vaccinations by 18 months of age. Among children residing in census tracts in the highest socioeconomic stratum, 77.2% were completely immunised by 18 months of age versus 81.2%–86.2% of children residing in the four census tract quintiles with lower socioeconomic indicators (p<0.01). Census tracts in the highest socioeconomic quintile had significantly lower coverage for bacille Calmette-Guérin, oral polio and hepatitis B vaccines than those with lower socioeconomic indicators. In multivariable analysis, higher birth order and residing in the highest socioeconomic quintile were associated with incomplete vaccination. After adjusting for interaction between socioeconomic strata of residence census tract and household wealth index, only birth order remained significant.
Evidence from Brazilian capitals shows success in achieving high immunisation coverage among poorer children. Strategies are needed to reach children in wealthier areas.
PMCID: PMC3433223  PMID: 22268129
Epidemiology; ethnicity; health status; health policy; surveillance

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