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BMC Infectious Diseases Mar 2020The objectives of this review were to evaluate the effect of age at administration of the first dose of a measles-containing vaccine (MCV1) on protection against measles... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The objectives of this review were to evaluate the effect of age at administration of the first dose of a measles-containing vaccine (MCV1) on protection against measles and on antibody response after one- and two-dose measles vaccinations.
METHODS
We conducted a systematic review of the PubMed/MEDLINE, Embase, Web of Science and Cochrane databases (1964-2017) to identify observational studies estimating vaccine effectiveness and/or measles attack rates by age at first vaccination as well as experimental studies comparing seroconversion by age at first vaccination. Random effect models were used to pool measles risk ratios (RR), measles odds ratios (OR) and seroconversion RR of MCV1 administered at < 9, 9-11 or ≥ 15 months compared with 12 or 12-14 months of age.
RESULTS
We included 41 and 67 studies in the measles protection and immunogenicity analyses. Older age at MCV1, from 6 to ≥15 months, improved antibody response and measles protection among one-dose recipients. Pooled measles RR ranged from 3.56 (95%CI: 1.28, 9.88) for MCV1 at < 9 months to 0.48 (95%CI: 0.36, 0.63) for MCV1 at ≥15 months, both compared to 12-14 months. Pooled seroconversion RR ranged from 0.93 (95%CI: 0.90, 0.96) for MCV1 at 9-11 months to 1.03 (95%CI: 1.00, 1.06) for MCV1 at ≥15 months, both compared to 12 months. After a second dose, serological studies reported high seropositivity regardless of age at administration of MCV1 while epidemiological data based on few studies suggested lower protection with earlier age at MCV1.
CONCLUSIONS
Earlier age at MCV1 decreases measles protection and immunogenicity after one dose and might still have an impact on vaccine failures after two doses of measles vaccine. While two-dose vaccination coverage is most critical to interrupt measles transmission, older age at first vaccination may be necessary to keep the high level of population immunity needed to maintain it.
Topics: Age Factors; Aged; Humans; Immunization Schedule; Infant; Measles; Measles Vaccine; Observational Studies as Topic; Odds Ratio
PubMed: 32223757
DOI: 10.1186/s12879-020-4870-x -
Journal of Epidemiology and Global... Mar 2020Europe has experienced a major resurgence of measles in recent years, despite the availability and free access to a safe, effective, and affordable vaccination measles,...
BACKGROUND AND OBJECTIVES
Europe has experienced a major resurgence of measles in recent years, despite the availability and free access to a safe, effective, and affordable vaccination measles, mumps and rubella vaccine (MMR). The main driver for this is suboptimal vaccine coverage. The three objectives of this study are to synthesize and critically assess parental attitudes and beliefs toward MMR uptake, to develop strategies and policy recommendations to effectively improve MMR vaccine uptake accordingly, and ultimately to identify areas for further research.
METHODS
A systematic review was conducted using primary studies from PubMed, Medline, Embase, and Scopus published between 2011 and April 2019. Inclusion criteria comprised primary studies in English conducted in Europe and studying parental attitudes and behavior regarding MMR uptake. Data were extracted using an inductive grounded theory approach.
RESULTS
In all, 20 high-quality studies were identified. Vaccine hesitancy or refusal were mainly due to concerns about vaccine safety, effectiveness, perception of measles risk and burden, mistrust in experts, and accessibility. Factors for MMR uptake included a sense of responsibility toward child and community health, peer judgement, trust in experts and vaccine, and measles severity. Anthroposophical and Gypsy, Roma, and Traveler populations presented unique barriers such as accessibility.
CONCLUSION
A multi-interventional, evidence-based approach is vital to improve confidence, competence, and convenience of measles vaccination uptake. Healthcare professionals need an understanding of individual contextual attitudes and barriers to MMR uptake to tailor effective communication. Effective surveillance is needed to identify under-vaccinated populations for vaccination outreach programs to improve accessibility and uptake.
Topics: Europe; Health Knowledge, Attitudes, Practice; Humans; Measles; Measles Vaccine; Parents; Patient Acceptance of Health Care; Qualitative Research; Vaccination
PubMed: 32175710
DOI: 10.2991/jegh.k.191117.001 -
Vaccine Mar 2020Serious adverse reactions after immunization are rare but do occur. In very rare instances, cases with fatal outcome have been reported. These reports can have a huge...
BACKGROUND
Serious adverse reactions after immunization are rare but do occur. In very rare instances, cases with fatal outcome have been reported. These reports can have a huge impact and even more so when due to an immunization error. The aim of this study is to systematically review immunization errors with fatal outcomes in EudraVigilance.
METHODS
This was a case-series analysis of Individual Case Safety Reports (ICSRs) reporting immunization errors and a fatal outcome. To determine the level of certainty of a causal association between the immunization errors and fatal outcomes two independent reviewers assessed all ICSRs using the WHO tool "Causality assessment of an Adverse Event Following Immunization (AEFI)". In accordance with the tool, the ICSRs were classified as consistent, indeterminate, inconsistent/coincidental, or unclassifiable. In addition, we estimated the contribution of reported errors to the fatal outcomes as large, moderate, small, none, or unclassifiable using a classification developed for this study.
RESULTS
A total of 154 ICSRs met the inclusion criteria. Vaccines reported most frequently were pneumococcal (33), rabies (27) and influenza vaccines (24). Most frequently reported errors were non-compliance with recommended schedules of immunization (63). The most frequently reported vaccine-error combination was rabies vaccines and non-compliance with a recommended schedule of immunization (23). Twelve cases were classified as consistent with causal association and had a large error contribution. These cases concerned a cluster of six cases reporting incorrect handling of multi-dose vials containing measles vaccine and six cases reporting administration of live-attenuated vaccines to immunocompromised patients.
DISCUSSION
In this study, we showed that fatal outcomes following immunization errors are very rare. Four key issues were the importance of: (1) quality control of multi-dose vaccines, (2) screening patients for immunocompromising factors, (3) education on the importance of adherence, and (4) measures to improve distinction between vaccines and medicines.
Topics: Adverse Drug Reaction Reporting Systems; Causality; Humans; Vaccination; Vaccines
PubMed: 32147297
DOI: 10.1016/j.vaccine.2020.02.074 -
The Journal of Dermatological Treatment Dec 2021Warts can be difficult to treat and progressing to chronic and resistant disease. Several studies have reported the successful application of mumps-measles-rubella (MMR)... (Meta-Analysis)
Meta-Analysis
Intralesional measles-mumps-rubella is associated with a higher complete response in cutaneous warts: a systematic review and meta-analysis of randomized controlled trial including GRADE qualification.
INTRODUCTION
Warts can be difficult to treat and progressing to chronic and resistant disease. Several studies have reported the successful application of mumps-measles-rubella (MMR) vaccine resulting in clearance of warts immunomodulation and induction of immune system.
METHODS
We performed a comprehensive search on the role of intralesional MMR in warts from several electronic databases. Complete response is defined as complete clearance of warts lesion.
RESULTS
There were a total of 425 subjects from five studies. Intralesional injection of MMR was associated with an increased complete response (OR 9.43 [5.78, 15.37], < .001; : 5%, = .38). Subgroup analysis on patients receiving injection for every 2 weeks for a maximum of five injections revealed an OR of 11.70 [6.40, 21.38], < .001; : 20%, = .29. Patients receiving intralesional MMR were associated with a lower partial response (OR 0.54 [0.33, 0.88], = .01; : 0%, = .66). Intralesional MMR was associated with a reduced no-response (OR 0.16 [0.06, 0.43], < .001; : 69%, = .01). Funnel plot analysis for complete response was asymmetrical, indicating the risk of publication bias. There were statistically significant small-study effects for intralesional MMR on complete response upon analysis using Harbord's test ( = .047). Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment showed that intralesional MMR injection has high level of certainty (quality of evidence) for complete response in warts with an absolute increase of 505 per 1000.
CONCLUSION
Intralesional MMR injection was associated with a higher complete response and lower no-response with a high level of certainty.
Topics: Humans; Injections, Intralesional; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Randomized Controlled Trials as Topic; Rubella; Warts
PubMed: 31985307
DOI: 10.1080/09546634.2020.1716931 -
Vaccines Dec 2019The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant... (Review)
Review
The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence on the safety of vaccine co-administrations in children by performing a systematic literature review of studies assessing the safety of vaccine co-administrations in children between 1999 and 2019, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty studies compared co-administered vaccines versus the same vaccines administered separately. The most frequently studied vaccines included quadrivalent meningococcal conjugate (MenACWY) vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines, diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, inactivated poliovirus and type b conjugate (DTaP-HepB-IPV/Hib) vaccine, measles, mumps, and rubella (MMR) vaccine, and pneumococcal conjugate 7-valent (PCV7) or 13-valent (PCV13) vaccines. Of this, 16% (n = 8) of the studies reported significantly more adverse events following immunization (AEFI) while in 10% (n = 5) significantly fewer adverse events were found in the co-administration groups. Statistically significant differences between co-administration and separate administration were found for 16 adverse events, for 11 different vaccine co-administrations. In general, studies briefly described safety and one-third of studies lacked any statistical assessment of AEFI. Overall, the evidence on the safety of vaccine co-administrations compared to separate vaccine administrations is inconclusive and there is a paucity of large post-licensure studies addressing this issue.
PubMed: 31906218
DOI: 10.3390/vaccines8010012 -
Vaccine Jan 2020In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We...
BACKGROUND
In settings where measles has been eliminated, vaccine-derived immunity may in theory wane more rapidly due to a lack of immune boosting by circulating measles virus. We aimed to assess whether measles vaccine effectiveness (VE) waned over time, and if so, whether differentially in measles-eliminated and measles-endemic settings.
METHODS
We performed a systematic literature review of studies that reported VE and time since vaccination with measles-containing vaccine (MCV). We extracted information on case definition (clinical symptoms and/or laboratory diagnosis), method of vaccination status ascertainment (medical record or vaccine registry), as well as any biases which may have arisen from cold chain issues and a lack of an age at first dose of MCV. We then used linear regression to evaluate VE as a function of age at first dose of MCV and time since MCV.
RESULTS
After screening 14,782 citations, we identified three full-text articles from measles-eliminated settings and 33 articles from measles-endemic settings. In elimination settings, two-dose VE estimates increased as age at first dose of MCV increased and decreased as time since MCV increased; however, the small number of studies available limited interpretation. In measles-endemic settings, one-dose VE increased by 1.5% (95% CI 0.5, 2.5) for every month increase in age at first dose of MCV. We found no evidence of waning VE in endemic settings.
CONCLUSIONS
The paucity of data from measles-eliminated settings indicates that additional studies and approaches (such as studies using proxies including laboratory correlates of protection) are needed to answer the question of whether VE in measles-eliminated settings wanes. Age at first dose of MCV was the most important factor in determining VE. More VE studies need to be conducted in elimination settings, and standards should be developed for information collected and reported in such studies.
Topics: Age Factors; Humans; Immunization Schedule; Infant; Measles; Measles Vaccine; Measles virus; Randomized Controlled Trials as Topic; Treatment Outcome; Vaccination
PubMed: 31732326
DOI: 10.1016/j.vaccine.2019.10.090 -
The Journal of Infectious Diseases Apr 2020Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence...
BACKGROUND
Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection.
METHODS
We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria.
RESULTS
We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold.
CONCLUSIONS
Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold.
Topics: Antibodies, Viral; Humans; Measles; Measles Vaccine; Serologic Tests
PubMed: 31674648
DOI: 10.1093/infdis/jiz380 -
Human Vaccines & Immunotherapeutics Mar 2020Children who had received MMR as the most recent vaccine had a pooled 35% (95%CI: 12-53%) lower risk for hospitalization due to any infectious disease, compared to... (Meta-Analysis)
Meta-Analysis
Non-specific effects of MMR vaccines on infectious disease related hospitalizations during the second year of life in high-income countries: a systematic review and meta-analysis.
Children who had received MMR as the most recent vaccine had a pooled 35% (95%CI: 12-53%) lower risk for hospitalization due to any infectious disease, compared to children who had received DTaP as the most recent vaccine (three studies, 1,919,192 children). The effect was stronger for respiratory tract infections than for gastrointestinal infections. Two studies investigated MMR alone, compared to concurrent administration of MMR and DTaP vaccines. Here, the pooled estimate for reduction in risk of hospitalization for any infectious disease was smaller and not significant (15%; 95%CI: -9% to 34%). Risk of bias was serious to critical in all studies. Moreover, two of the five studies demonstrated a significantly reduced risk for a control outcome (hospitalization for injuries), strongly indicating healthy vaccinee bias or residual confounding. The available evidence is insufficient to support a change in current vaccination schedules.
Topics: Child; Communicable Diseases; Developed Countries; Diphtheria-Tetanus-Pertussis Vaccine; Hospitalization; Humans; Infant; Measles-Mumps-Rubella Vaccine
PubMed: 31625797
DOI: 10.1080/21645515.2019.1663119 -
Journal of Travel Medicine Mar 2020Pregnant travellers and their offspring are vulnerable to severe outcomes following a wide range of infections. Vaccine-preventable diseases can have a particularly... (Meta-Analysis)
Meta-Analysis
Pregnant travellers and their offspring are vulnerable to severe outcomes following a wide range of infections. Vaccine-preventable diseases can have a particularly severe course in pregnant women, but little is known about the safety of travel vaccines in pregnant women. We performed a systematic review of all published literature concerning the safety of vaccines frequently given to travellers such as yellow fever, MMR (mumps, measles and rubella), influenza, Tdap (tetanus, diphtheria and pertussis), meningococcus, hepatitis A and B, rabies, polio, typhoid fever, tick-borne encephalitis and Japanese encephalitis vaccines. We included case series, cohort studies and randomized controlled trials (RCTs). For the meta-analysis, we included only RCTs that compared the administration of a vaccine to placebo or to no vaccine. Outcome measures included severe systemic adverse events, maternal outcomes related to the course of pregnancy, neonatal outcomes and local adverse events. We calculated the risk ratio and its 95% confidence interval as the summary measure. The safety of influenza vaccine is supported by high-quality evidence. For Tdap vaccine, no evidence of any harm was found in the meta-analysis of RCTs. A slight increase in chorioamnionitis rate was reported in 3 out of 12 observational studies. However, this small possible risk is far outweighed by a much larger benefit in terms of infant morbidity and mortality. Meningococcal vaccines are probably safe during pregnancy, as supported by RCTs comparing meningococcal vaccines to other vaccines. Data from observational studies support the safety of hepatitis A, hepatitis B and rabies vaccines, as well as that of the live attenuated yellow fever vaccine. We found little or no data about the safety of polio, typhoid, Japanese encephalitis, tick-borne encephalitis and MMR vaccines during pregnancy.
Topics: Female; Humans; Pregnancy; Travel Medicine; Travel-Related Illness; Vaccination; Vaccines
PubMed: 31616947
DOI: 10.1093/jtm/taz074 -
The Lancet. Infectious Diseases Nov 2019Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vaccinating infants with a first dose of measles-containing vaccine (MCV1) before 9 months of age in high-risk settings has the potential to reduce measles-related morbidity and mortality. However, there is concern that early vaccination might blunt the immune response to subsequent measles vaccine doses. We systematically reviewed the available evidence on the effect of MCV1 administration to infants younger than 9 months on their immune responses to subsequent MCV doses.
METHODS
For this systematic review and meta-analysis, we searched for randomised and quasi-randomised controlled trials, outbreak investigations, and cohort and case-control studies without restriction on publication dates, in which MCV1 was administered to infants younger than 9 months. We did the literature search on June 2, 2015, and updated it on Jan 14, 2019. We included studies reporting data on strength or duration of humoral and cellular immune responses, and on vaccine efficacy or vaccine effectiveness after two-dose or three-dose MCV schedules. Our outcome measures were proportion of seropositive infants, geometric mean titre, vaccine efficacy, vaccine effectiveness, antibody avidity index, and T-cell stimulation index. We used random-effects meta-analysis to derive pooled estimates of the outcomes, where appropriate. We assessed the methodological quality of included studies using Grading of Recommendation Assessment, Development and Evaluation (GRADE) guidelines.
FINDINGS
Our search retrieved 1156 records and 85 were excluded due to duplication. 1071 records were screened for eligibility, of which 351 were eligible for full-text screening and 21 were eligible for inclusion in the review. From 13 studies, the pooled proportion of infants seropositive after two MCV doses, with MCV1 administered before 9 months of age, was 98% (95% CI 96-99; I=79·8%, p<0·0001), which was not significantly different from seropositivity after a two-dose MCV schedule starting later (p=0·087). Only one of four studies found geometric mean titres after MCV2 administration to be significantly lower when MCV1 was administered before 9 months of age than at 9 months of age or later. There was insufficient evidence to determine an effect of age at MCV1 administration on antibody avidity. The pooled vaccine effectiveness estimate derived from two studies of a two-dose MCV schedule with MCV1 vaccination before 9 months of age was 95% (95% CI 89-100; I=12·6%, p=0·29). Seven studies reporting on measles virus-specific cellular immune responses found that T-cell responses and T-cell memory were sustained, irrespective of the age of MCV1 administration. Overall, the quality of evidence was moderate to very low.
INTERPRETATION
Our findings suggest that administering MCV1 to infants younger than 9 months followed by additional MCV doses results in high seropositivity, vaccine effectiveness, and T-cell responses, which are independent of the age at MCV1, supporting the vaccination of very young infants in high-risk settings. However, we also found some evidence that MCV1 administered to infants younger than 9 months resulted in lower antibody titres after one or two subsequent doses of MCV than when measles vaccination is started at age 9 months or older. The clinical and public-health relevance of this immunity blunting effect are uncertain.
FUNDING
WHO.
Topics: Age Factors; Antibodies, Viral; Female; Humans; Immunity, Cellular; Immunity, Humoral; Immunization Schedule; Infant; Male; Measles; Measles Vaccine; Measles virus; T-Lymphocytes; Treatment Outcome
PubMed: 31548081
DOI: 10.1016/S1473-3099(19)30396-2