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Dermatology Online Journal Mar 2020New treatment options for warts include intralesional wart injection with agents such as vitamin D, measles, mumps, and rubella (MMR) vaccine antigen, Bacillus...
BACKGROUND
New treatment options for warts include intralesional wart injection with agents such as vitamin D, measles, mumps, and rubella (MMR) vaccine antigen, Bacillus Calmette-Guerin (BCG) antigen, and candida antigen but there have been limited studies to compare their efficacies.
OBJECTIVE
The purpose of this systematic review is to compare the efficacy and safety of injectable agents used for the treatment of warts.
METHODS
A PubMed search included terms "intralesional wart therapy," "wart injection" and "verruca injection." Articles reviewed were published over 10 years.
RESULTS
A total of 43 articles were reviewed; 30 covered studies with more than 10 participants and 13 were case reports, case series, and reviews. In comparison studies intralesional agents have equal or superior efficacy (66%-94.9%) compared to first-line salicylic acid or cryotherapy (65.5-76.5%). One advantage of intralesional injections is the rate of complete resolution of distant warts.
LIMITATIONS
Each study varied in their agents, treatment interval, and treatment dose, making comparisons difficult.
CONCLUSIONS
Intralesional wart injections are safe, affordable, and efficacious treatments for warts. Physicians should consider intralesional injections for patients with refractory warts, multiple warts, or warts in sensitive areas.
Topics: Aminolevulinic Acid; Anti-Bacterial Agents; Antiviral Agents; BCG Vaccine; Bacterial Vaccines; Humans; Injections, Intralesional; Interferon-alpha; Mycobacterium; Tuberculin; Vitamin D; Warts
PubMed: 32609439
DOI: No ID Found -
The Cochrane Database of Systematic... Apr 2020Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Measles, mumps, rubella, and varicella (chickenpox) are serious diseases that can lead to serious complications, disability, and death. However, public debate over the safety of the trivalent MMR vaccine and the resultant drop in vaccination coverage in several countries persists, despite its almost universal use and accepted effectiveness. This is an update of a review published in 2005 and updated in 2012.
OBJECTIVES
To assess the effectiveness, safety, and long- and short-term adverse effects associated with the trivalent vaccine, containing measles, rubella, mumps strains (MMR), or concurrent administration of MMR vaccine and varicella vaccine (MMR+V), or tetravalent vaccine containing measles, rubella, mumps, and varicella strains (MMRV), given to children aged up to 15 years.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase (1974 to 2 May 2019), the WHO International Clinical Trials Registry Platform (2 May 2019), and ClinicalTrials.gov (2 May 2019).
SELECTION CRITERIA
We included randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), interrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only ecological method (COEM) studies, self-controlled case series (SCCS) studies, person-time cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) studies, assessing any combined MMR or MMRV / MMR+V vaccine given in any dose, preparation or time schedule compared with no intervention or placebo, on healthy children up to 15 years of age.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the methodological quality of the included studies. We grouped studies for quantitative analysis according to study design, vaccine type (MMR, MMRV, MMR+V), virus strain, and study settings. Outcomes of interest were cases of measles, mumps, rubella, and varicella, and harms. Certainty of evidence of was rated using GRADE.
MAIN RESULTS
We included 138 studies (23,480,668 participants). Fifty-one studies (10,248,159 children) assessed vaccine effectiveness and 87 studies (13,232,509 children) assessed the association between vaccines and a variety of harms. We included 74 new studies to this 2019 version of the review. Effectiveness Vaccine effectiveness in preventing measles was 95% after one dose (relative risk (RR) 0.05, 95% CI 0.02 to 0.13; 7 cohort studies; 12,039 children; moderate certainty evidence) and 96% after two doses (RR 0.04, 95% CI 0.01 to 0.28; 5 cohort studies; 21,604 children; moderate certainty evidence). The effectiveness in preventing cases among household contacts or preventing transmission to others the children were in contact with after one dose was 81% (RR 0.19, 95% CI 0.04 to 0.89; 3 cohort studies; 151 children; low certainty evidence), after two doses 85% (RR 0.15, 95% CI 0.03 to 0.75; 3 cohort studies; 378 children; low certainty evidence), and after three doses was 96% (RR 0.04, 95% CI 0.01 to 0.23; 2 cohort studies; 151 children; low certainty evidence). The effectiveness (at least one dose) in preventing measles after exposure (post-exposure prophylaxis) was 74% (RR 0.26, 95% CI 0.14 to 0.50; 2 cohort studies; 283 children; low certainty evidence). The effectiveness of Jeryl Lynn containing MMR vaccine in preventing mumps was 72% after one dose (RR 0.24, 95% CI 0.08 to 0.76; 6 cohort studies; 9915 children; moderate certainty evidence), 86% after two doses (RR 0.12, 95% CI 0.04 to 0.35; 5 cohort studies; 7792 children; moderate certainty evidence). Effectiveness in preventing cases among household contacts was 74% (RR 0.26, 95% CI 0.13 to 0.49; 3 cohort studies; 1036 children; moderate certainty evidence). Vaccine effectiveness against rubella is 89% (RR 0.11, 95% CI 0.03 to 0.42; 1 cohort study; 1621 children; moderate certainty evidence). Vaccine effectiveness against varicella (any severity) after two doses in children aged 11 to 22 months is 95% in a 10 years follow-up (rate ratio (rr) 0.05, 95% CI 0.03 to 0.08; 1 RCT; 2279 children; high certainty evidence). Safety There is evidence supporting an association between aseptic meningitis and MMR vaccines containing Urabe and Leningrad-Zagreb mumps strains, but no evidence supporting this association for MMR vaccines containing Jeryl Lynn mumps strains (rr 1.30, 95% CI 0.66 to 2.56; low certainty evidence). The analyses provide evidence supporting an association between MMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile seizures normally occur in 2% to 4% of healthy children at least once before the age of 5. The attributable risk febrile seizures vaccine-induced is estimated to be from 1 per 1700 to 1 per 1150 administered doses. The analyses provide evidence supporting an association between MMR vaccination and idiopathic thrombocytopaenic purpura (ITP). However, the risk of ITP after vaccination is smaller than after natural infection with these viruses. Natural infection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The attributable risk is estimated about 1 case of ITP per 40,000 administered MMR doses. There is no evidence of an association between MMR immunisation and encephalitis or encephalopathy (rate ratio 0.90, 95% CI 0.50 to 1.61; 2 observational studies; 1,071,088 children; low certainty evidence), and autistic spectrum disorders (rate ratio 0.93, 95% CI 0.85 to 1.01; 2 observational studies; 1,194,764 children; moderate certainty). There is insufficient evidence to determine the association between MMR immunisation and inflammatory bowel disease (odds ratio 1.42, 95% CI 0.93 to 2.16; 3 observational studies; 409 cases and 1416 controls; moderate certainty evidence). Additionally, there is no evidence supporting an association between MMR immunisation and cognitive delay, type 1 diabetes, asthma, dermatitis/eczema, hay fever, leukaemia, multiple sclerosis, gait disturbance, and bacterial or viral infections.
AUTHORS' CONCLUSIONS
Existing evidence on the safety and effectiveness of MMR/MMRV vaccines support their use for mass immunisation. Campaigns aimed at global eradication should assess epidemiological and socioeconomic situations of the countries as well as the capacity to achieve high vaccination coverage. More evidence is needed to assess whether the protective effect of MMR/MMRV could wane with time since immunisation.
Topics: Adolescent; Age Factors; Autistic Disorder; Chickenpox Vaccine; Child; Child, Preschool; Clinical Trials as Topic; Crohn Disease; Epidemiologic Studies; Humans; Infant; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Purpura, Thrombocytopenic; Rubella; Seizures, Febrile; Vaccines, Attenuated
PubMed: 32309885
DOI: 10.1002/14651858.CD004407.pub4 -
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 -
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 -
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 -
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 -
The Lancet. Infectious Diseases Nov 2019Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Measles is an important cause of death in children, despite the availability of safe and cost-saving measles-containing vaccines (MCVs). The first MCV dose (MCV1) is recommended at 9 months of age in countries with ongoing measles transmission, and at 12 months in countries with low risk of measles. To assess whether bringing forward the age of MCV1 is beneficial, we did a systematic review and meta-analysis of the benefits and risks of MCV1 in infants younger than 9 months.
METHODS
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, Proquest, Global Health, the WHO library database, and the WHO Institutional Repository for Information Sharing database, and consulted experts. We included 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 assessed: proportion of infants seroconverted, geometric mean antibody titre, avidity, cellular immunity, duration of immunity, vaccine efficacy, vaccine effectiveness, and safety. We used random-effects models to derive pooled estimates of the endpoints, where appropriate. We assessed methodological quality using the Grading of Recommendations, Assessment, Development, and Evaluation guidelines.
FINDINGS
Our search identified 1156 studies, of which 1071 were screened for eligibility. 351 were eligible for full-text screening, and data from 56 studies that met all inclusion criteria were used for analysis. The proportion of infants who seroconverted increased from 50% (95% CI 29-71) for those vaccinated with MCV1 at 4 months of age to 85% (69-97) for those were vaccinated at 8 months. The pooled geometric mean titre ratio for infants aged 4-8 months vaccinated with MCV1 compared with infants vaccinated with MCV1 at age 9 months or older was 0·46 (95% CI 0·33-0·66; I=99·9%, p<0·0001). Only one study reported on avidity and suggested that there was lower avidity and a shorter duration of immunity following MCV1 administration at 6 months of age than at 9 months of age (p=0·0016) or 12 months of age (p<0·001). No effect of age at MCV1 administration on cellular immunity was found. One study reported that vaccine efficacy against laboratory-confirmed measles virus infection was 94% (95% CI 74-98) in infants vaccinated with MCV1 at 4·5 months of age. The pooled vaccine effectiveness of MCV1 in infants younger than 9 months against measles was 58% (95% CI 9-80; I=84·9%, p<0·0001). The pooled vaccine effectiveness estimate from within-study comparisons of infants younger than 9 months vaccinated with MCV1 were 51% (95% CI -44 to 83; I=92·3%, p<0·0001), and for those aged 9 months and older at vaccination it was 83% (76-88; I=93·8%, p<0·0001). No differences in the risk of adverse events after MCV1 administration were found between infants younger than 9 months and those aged 9 months of older. Overall, the quality of evidence ranged from moderate to very low.
INTERPRETATION
MCV1 administered to infants younger than 9 months induces a good immune response, whereby the proportion of infants seroconverted increases with increased age at vaccination. A large proportion of infants receiving MCV1 before 9 months of age are protected and the vaccine is safe, although higher antibody titres and vaccine effectiveness are found when MCV1 is administered at older ages. Recommending MCV1 administration to infants younger than 9 months for those at high risk of measles is an important step towards reducing measles-related mortality and morbidity.
FUNDING
WHO.
Topics: Age Factors; Antibodies, Viral; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Immunity, Cellular; Immunization Schedule; Infant; Male; Measles; Measles Vaccine; Measles virus; Risk Assessment; Treatment Outcome
PubMed: 31548079
DOI: 10.1016/S1473-3099(19)30395-0