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BMJ (Clinical Research Ed.) Oct 2016To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus. (Review)
Review
OBJECTIVE
To identify and characterise non-specific immunological effects after routine childhood vaccines against BCG, measles, diphtheria, pertussis, and tetanus.
DESIGN
Systematic review of randomised controlled trials, cohort studies, and case-control studies.
DATA SOURCES
Embase, PubMed, Cochrane library, and Trip searched between 1947 and January 2014. Publications submitted by a panel of experts in the specialty were also included.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
All human studies reporting non-specific immunological effects after vaccination with standard childhood immunisations. Studies using recombinant vaccines, no vaccine at all, or reporting only vaccine specific outcomes were excluded. The primary aim was to systematically identify, assemble, and review all available studies and data on the possible non-specific or heterologous immunological effects of BCG; measles; mumps, measles, and rubella (MMR); diphtheria; tetanus; and pertussis vaccines.
RESULTS
The initial search yielded 11 168 references; 77 manuscripts met the inclusion criteria for data analysis. In most included studies (48%) BCG was the vaccine intervention. The final time point of outcome measurement was primarily performed (70%) between one and 12 months after vaccination. There was a high risk of bias in the included studies, with no single study rated low risk across all assessment criteria. A total of 143 different immunological variables were reported, which, in conjunction with differences in measurement units and summary statistics, created a high number of combinations thus precluding any meta-analysis. Studies that compared BCG vaccinated with unvaccinated groups showed a trend towards increased IFN-γ production in vitro in the vaccinated groups. Increases were also observed for IFN-γ measured after BCG vaccination in response to in vitro stimulation with microbial antigens from Candida albicans, tetanus toxoid, Staphylococcus aureas, lipopolysaccharide, and hepatitis B. Cohort studies of measles vaccination showed an increase in lymphoproliferation to microbial antigens from tetanus toxoid and C albicans Increases in immunogenicity to heterologous antigens were noted after diphtheria-tetanus (herpes simplex virus and polio antibody titres) and diphtheria-tetanus-pertussis (pneumococcus serotype 14 and polio neutralising responses) vaccination.
CONCLUSIONS
The papers reporting non-specific immunological effects had heterogeneous study designs and could not be conventionally meta-analysed, providing a low level of evidence quality. Some studies, such as BCG vaccine studies examining in vitro IFN-γ responses and measles vaccine studies examining lymphoproliferation to microbial antigen stimulation, showed a consistent direction of effect suggestive of non-specific immunological effects. The quality of the evidence, however, does not provide confidence in the nature, magnitude, or timing of non-specific immunological effects after vaccination with BCG, diphtheria, pertussis, tetanus, or measles containing vaccines nor the clinical importance of the findings.
Topics: BCG Vaccine; Case-Control Studies; Child, Preschool; Communicable Disease Control; Diphtheria; Diphtheria-Tetanus-Pertussis Vaccine; Female; Humans; Immunization; Infant; Male; Measles; Measles Vaccine; Measles-Mumps-Rubella Vaccine; Randomized Controlled Trials as Topic; Tetanus; Tuberculosis; United Kingdom; Vaccination; Whooping Cough
PubMed: 27737830
DOI: 10.1136/bmj.i5225 -
The Journal of Adolescent Health :... Oct 2016Vaccination strategies are among the most successful and cost-effective public health strategies for preventing disease and death. Until recently, most of the existing... (Review)
Review
Vaccination strategies are among the most successful and cost-effective public health strategies for preventing disease and death. Until recently, most of the existing immunization programs targeted infants and children younger than 5 years which have successfully resulted in reducing global infant and child mortality. Adolescent immunization has been relatively neglected, leaving a quarter of world's population underimmunized and hence vulnerable to a number of preventable diseases. In recent years, a large number of programs have been launched to increase the uptake of different vaccines in adolescents; however, the recommended vaccination coverage among the adolescent population overall remains very low, especially in low- and middle-income countries. Adolescent vaccination has received significantly more attention since the advent of the human papillomavirus (HPV) vaccine in 2006. However, only half of the adolescent girls in the United States received a single dose of HPV vaccine while merely 43% and 33% received two and three doses, respectively. We systematically reviewed literature published up to December 2014 and included 23 studies on the effectiveness of interventions to improve immunization coverage among adolescents. Moderate-quality evidence suggested an overall increase in vaccination coverage by 78% (relative risk: 1.78; 95% confidence interval: 1.41-2.23). Review findings suggest that interventions including implementing vaccination requirement in school, sending reminders, and national permissive recommendation for adolescent vaccination have the potential to improve immunization uptake. Strategies to improve coverage for HPV vaccines resulted in a significant decrease in the prevalence of HPV by 44% and genital warts by 33%; however, the quality of evidence was low. Analysis from single studies with low- or very low-quality evidence suggested significant decrease in varicella deaths, measles incidence, rubella susceptibility, and incidence of pertussis while the impact was nonsignificant for incidence of mumps with their respective vaccines. Further rigorous evidence is needed to evaluate the effectiveness of strategies to improve immunization uptake among adolescents from low- and middle-income countries.
PubMed: 27664595
DOI: 10.1016/j.jadohealth.2016.07.005 -
International Journal of Public Health Sep 2016Despite the availability of vaccines and the existence of public vaccination recommendations, outbreaks of vaccine-preventable childhood diseases still cause public... (Review)
Review
OBJECTIVES
Despite the availability of vaccines and the existence of public vaccination recommendations, outbreaks of vaccine-preventable childhood diseases still cause public health debate. The objective of this systematic review was to provide an overview of the current epidemiology and economic burden of measles, mumps, pertussis, and varicella in Germany.
METHODS
We systematically reviewed studies published since 2000. The literature search was conducted using PubMed and EMBASE. Also, we used German notification data to give an up-to-date overview of the epidemiology of the four diseases under consideration.
RESULTS
Thirty-six studies were included in our review. Results suggest that there is still considerable morbidity due to childhood diseases in Germany. Studies providing cost estimates are scarce. Comparative analyses of different data sources (notification data vs. claims data) revealed a potential underestimation of incidence estimates when using notification data. Furthermore, several studies showed regional differences in incidence of some of the diseases under consideration.
CONCLUSIONS
Our findings underline the need for improved vaccination and communication strategies targeting all susceptible age and risk groups on a national and local level.
Topics: Chickenpox; Chickenpox Vaccine; Germany; Humans; Incidence; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Vaccines, Combined; Virus Diseases; Whooping Cough
PubMed: 27488917
DOI: 10.1007/s00038-016-0842-8 -
Vaccine Oct 2016Important investments were made in countries for the polio eradication initiative. On 25 September 2015, a major milestone was achieved when Nigeria was removed from the... (Review)
Review
BACKGROUND
Important investments were made in countries for the polio eradication initiative. On 25 September 2015, a major milestone was achieved when Nigeria was removed from the list of polio-endemic countries. Routine Immunization, being a key pillar of polio eradication initiative needs to be strengthened to sustain the gains made in countries. For this, there is a huge potential on building on the use of polio infrastructure to contribute to RI strengthening.
METHODS
We reviewed estimates of immunization coverage as reported by the countries to WHO and UNICEF for three vaccines: BCG, DTP3 (third dose of diphtheria-tetanus toxoid- pertussis), and the first dose of measles-containing vaccine (MCV1).We conducted a systematic review of best practices documents from eight countries which had significant polio eradication activities.
RESULTS
Immunization programmes have improved significantly in the African Region. Regional coverage for DTP3 vaccine increased from 51% in 1996 to 77% in 2014. DTP3 coverage increased >3 folds in DRC (18-80%) and Nigeria from 21% to 66%; and >2 folds in Angola (41-87%), Chad (24-46%), and Togo (42-87%). Coverage for BCG and MCV1 increased in all countries. Of the 47 countries in the region, 18 (38%) achieved a national coverage for DTP3 ⩾90% for 2years meeting the Global Vaccine Action (GVAP) target. A decrease was noted in the Ebola-affected countries i.e., Guinea, Liberia and Sierra Leone.
CONCLUSIONS
PEI has been associated with increased spending on immunization and the related improvements, especially in the areas of micro planning, service delivery, program management and capacity building. Continued efforts are needed to mobilize international and domestic support to strengthen and sustain high-quality immunization services in African countries. Strengthening RI will in turn sustain the gains made to eradicate poliovirus in the region.
Topics: Africa; BCG Vaccine; Diphtheria-Tetanus-Pertussis Vaccine; Disease Eradication; Global Health; Humans; Immunization Programs; Measles Vaccine; Nigeria; Poliomyelitis; Poliovirus Vaccine, Oral; Practice Guidelines as Topic; Togo; United Nations; Vaccination Coverage; World Health Organization
PubMed: 27396492
DOI: 10.1016/j.vaccine.2016.05.062 -
The Cochrane Database of Systematic... Jun 2016More than 7.5 million children younger than age five living in low- and middle-income countries die every year. The World Health Organization (WHO) developed the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
More than 7.5 million children younger than age five living in low- and middle-income countries die every year. The World Health Organization (WHO) developed the integrated management of childhood illness (IMCI) strategy to reduce mortality and morbidity and to improve quality of care by improving the delivery of a variety of curative and preventive medical and behavioral interventions at health facilities, at home, and in the community.
OBJECTIVES
To evaluate the effects of programs that implement the IMCI strategy in terms of death, nutritional status, quality of care, coverage with IMCI deliverables, and satisfaction of beneficiaries.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), including the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; MEDLINE; EMBASE, Ovid; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), EbscoHost; the Latin American Caribbean Health Sciences Literature (LILACS), Virtual Health Library (VHL); the WHO Library & Information Networks for Knowledge Database (WHOLIS); the Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Science; Population Information Online (POPLINE); the WHO International Clinical Trials Registry Platform (WHO ICTRP); and the Global Health, Ovid and Health Management, ProQuest database. We performed searches until 30 June 2015 and supplemented these by searching revised bibliographies and by contacting experts to identify ongoing and unpublished studies.
SELECTION CRITERIA
We sought to include randomised controlled trials (RCTs) and controlled before-after (CBA) studies with at least two intervention and two control sites evaluating the generic IMCI strategy or its adaptation in children younger than age five, and including at minimum efforts to improve health care worker skills for case management. We excluded studies in which IMCI was accompanied by other interventions including conditional cash transfers, food supplementation, and employment. The comparison group received usual health services without provision of IMCI.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened searches, selected trials, and extracted, analysed and tabulated data. We used inverse variance for cluster trials and an intracluster co-efficient of 0.01 when adjustment had not been made in the primary study. We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation Working Group) approach to assess the certainty of evidence.
MAIN RESULTS
Two cluster-randomised trials (India and Bangladesh) and two controlled before-after studies (Tanzania and India) met our inclusion criteria. Strategies included training of health care staff, management strengthening of health care systems (all four studies), and home visiting (two studies). The two studies from India included care packages targeting the neonatal period.One trial in Bangladesh estimated that child mortality may be 13% lower with IMCI, but the confidence interval (CI) included no effect (risk ratio (RR) 0.87, 95% CI 0.68 to 1.10; 5090 participants; low-certainty evidence). One CBA study in Tanzania gave almost identical estimates (RR 0.87, 95% CI 0.72 to 1.05; 1932 participants).One trial in India examined infant and neonatal mortality by implementing the integrated management of neonatal and childhood illness (IMNCI) strategy including post-natal home visits. Neonatal and infant mortality may be lower in the IMNCI group compared with the control group (infant mortality hazard ratio (HR) 0.85, 95% CI 0.77 to 0.94; neonatal mortality HR 0.91, 95% CI 0.80 to 1.03; one trial, 60,480 participants; low-certainty evidence).We estimated the effect of IMCI on any mortality measured by combining infant and child mortality in the one IMCI and the one IMNCI trial. Mortality may be reduced by IMCI (RR 0.85, 95% CI 0.78 to 0.93; two trials, 65,570 participants; low-certainty evidence).Two trials (India, Bangladesh) evaluated nutritional status and noted that there may be little or no effect on stunting (RR 0.94, 95% CI 0.84 to 1.06; 5242 participants, two trials; low-certainty evidence) and there is probably little or no effect on wasting (RR 1.04, 95% CI 0.87 to 1.25; two trials, 4288 participants; moderate-certainty evidence).The Tanzania CBA study showed similar results.Investigators measured quality of care by observing prescribing for common illnesses at health facilities (727 observations, two studies; very low-certainty evidence) and by observing prescribing by lay health care workers (1051 observations, three studies; very low-certainty evidence). We could not confirm a consistent effect on prescribing at health facilities or by lay health care workers, as certainty of the evidence was very low.For coverage of IMCI deliverables, we examined vaccine and vitamin A coverage, appropriate care seeking, and exclusive breast feeding. Two trials (India, Bangladesh) estimated vaccine coverage for measles and reported that there is probably little or no effect on measles vaccine coverage (RR 0.92, 95% CI 0.80 to 1.05; two trials, 4895 participants; moderate-certainty evidence), with similar effects seen in the Tanzania CBA study. Two studies measured the third dose of diphtheria, pertussis, and tetanus vaccine; and two measured vitamin A coverage, all providing little or no evidence of increased coverage with IMCI.Four studies (2 from India, and 1 each from Tanzania and Bangladesh) reported appropriate care seeking and derived information from careful questioning of mothers about recent illness. Some studies on effects of IMCI may report better care seeking behavior, but others do not report this.All four studies recorded maternal responses on exclusive breast feeding. They provided mixed results and very low-certainty evidence. Therefore, we do not know whether IMCI impacts exclusive breast feeding.No studies reported on the satisfaction of mothers and service users.
AUTHORS' CONCLUSIONS
The mix of interventions examined in research studies evaluating the IMCI strategy varies, and some studies include specific inputs to improve neonatal health. Most studies were conducted in South Asia. Implementing the integrated management of childhood illness strategy may reduce child mortality, and packages that include interventions for the neonatal period may reduce infant mortality. IMCI may have little or no effect on nutritional status and probably has little or no effect on vaccine coverage. Maternal care seeking behavior may be more appropriate with IMCI, but study results have been mixed, providing evidence of very low certainty about whether IMCI has effects on adherence to exclusive breast feeding.
Topics: Bangladesh; Breast Feeding; Child Health Services; Child Mortality; Child, Preschool; Controlled Before-After Studies; Delivery of Health Care, Integrated; Developing Countries; Disease Management; Health Personnel; House Calls; Humans; India; Infant; Infant Mortality; Program Evaluation; Quality Improvement; Randomized Controlled Trials as Topic; Tanzania
PubMed: 27378094
DOI: 10.1002/14651858.CD010123.pub2 -
Human Vaccines & Immunotherapeutics Jul 2016Low measles, mumps and rubella (MMR) immunization levels in European children highlight the importance of identifying determinants of parental vaccine uptake to... (Meta-Analysis)
Meta-Analysis Review
Low measles, mumps and rubella (MMR) immunization levels in European children highlight the importance of identifying determinants of parental vaccine uptake to implement policies for increasing vaccine compliance. The aim of this paper is to identify the main factors associated with partial and full MMR vaccination uptake in European parents, and combine the different studies to obtain overall quantitative measures. This activity is included within the ESCULAPIO project, funded by the Italian Ministry of Health. ORs and CIs were extracted, sources of heterogeneity explored and publication bias assessed. Forty-five papers were retrieved for the qualitative study, 26 of which were included in the meta-analysis. The following factors were associated with lower MMR vaccine uptake: misleading knowledge, beliefs and perceptions on vaccines (OR 0.57, CI 0.37-0.87); negative attitudes and behaviors toward vaccination (OR 0.71, CI 0.52-0.98); demographic characteristics, such as different ethnicity in Southern populations (OR 0.44, CI 0.31-0.61), higher child's age (OR 0.80, CI 0.76-0.85); low socio-economic status (OR 0.64, CI 0.51-0.80), especially low income (OR 0.39, CI 0.25-0.60) and education (OR 0.64, CI 0.48-0.84), high number of children (OR 0.54, CI 0.42-0.69), irregular marital status (OR 0.80, CI 0.66-0.96). The factors explaining heterogeneity were country location, administration modality, collection setting and responses reported on MMR alone or in combination. Findings from this study suggest policy makers to focus communication strategies on providing better knowledge, correct beliefs and perceptions on vaccines, and improving attitudes and behaviors in parents; and to target policies to people of ethnic minority from Southern Europe, low educated and deprived, with higher number of children and non-married marital status.
Topics: Europe; Health Knowledge, Attitudes, Practice; Humans; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Parents; Patient Acceptance of Health Care; Rubella; Vaccination
PubMed: 27163657
DOI: 10.1080/21645515.2016.1151990 -
Medicine Nov 2015A combined measles-mumps-rubella-varicella (MMRV) vaccine is expected to facilitate universal immunization against these 4 diseases. This study was undertaken to... (Meta-Analysis)
Meta-Analysis Review
A combined measles-mumps-rubella-varicella (MMRV) vaccine is expected to facilitate universal immunization against these 4 diseases. This study was undertaken to synthesize current research findings of the immunogenicity and safety of MMRV in healthy children.We searched PubMed, Embase, BIOSIS Previews, Web of Science, Cochrane Library, and other databases through September 9, 2014. Eligible randomized controlled trials (RCTs) were selected and collected independently by 2 reviewers. Meta-analysis was conducted using Stata 12.0 and RevMan 5.3.Twenty-four RCTs were included in qualitative synthesis. Nineteen RCTs compared single MMRV dose with measles-mumps-rubella vaccine with or without varicella vaccine (MMR + V/MMR). Similar seroconversion rates of these 4 viruses were found between comparison groups. There were comparable geometric mean titers (GMTs) against mumps and varicella viruses between MMRV group and MMR + V/MMR group. MMRV group achieved enhanced immune response to measles component, with GMT ratio of 1.66 (95% confidence interval [CI] 1.48, 1.86; P < 0.001) for MMRV versus MMR and 1.62 (95% CI 1.51, 1.70; P < 0.001) for MMRV versus MMR + V. Meanwhile, immune response to rubella component in MMRV group was slightly reduced, GMT ratios were 0.81 (95% CI 0.78, 0.85; P < 0.001) and 0.79 (95% CI 0.76, 0.83; P < 0.001), respectively. Well tolerated safety profiles were demonstrated except higher incidence of fever (relative risks 1.12-1.60) and measles/rubella-like rash (relative risks 1.44-1.45) in MMRV groups.MMRV had comparable immunogenicity and overall safety profiles to MMR + V/MMR in healthy children based on current evidence.
Topics: Chickenpox; Chickenpox Vaccine; Child; Humans; Measles; Measles-Mumps-Rubella Vaccine; Rubella; Vaccination; Vaccines, Combined
PubMed: 26554769
DOI: 10.1097/MD.0000000000001721 -
Human Vaccines & Immunotherapeutics 2014A number of Japanese encephalitis (JE) vaccines have been used for preventing Japanese encephalitis around the world. We here reviewed the immunogenicity and safety of... (Review)
Review
A number of Japanese encephalitis (JE) vaccines have been used for preventing Japanese encephalitis around the world. We here reviewed the immunogenicity and safety of the currently available Japanese encephalitis vaccines. We searched Pubmed, Embase, Web of Science, the Cochrane Library and other online databases up to March 25, 2014 for studies focusing on currently used JE vaccines in any language. The primary outcomes were the seroconversion rate against JEV and adverse events. Meta-analysis was performed for the primary outcome when available. A total of 51 articles were included. Studies were grouped on the basic types of vaccines. This systematic review led to 2 aspects of the conclusions. On one hand, all the currently available JE vaccines are safe and effective. On the other hand, the overall of JE vaccine evaluation is disorganized, the large variation in study designs, vaccine types, schedules, doses, population and few hand-to-hand trails, make direct comparisons difficult. In order to make a more evidence-based decision on optimizing the JE vaccine, it is warranted to standardize the JE vaccine evaluation research.
Topics: Animals; Clinical Trials as Topic; Humans; Japanese Encephalitis Vaccines; Vaccination
PubMed: 25668666
DOI: 10.4161/21645515.2014.980197 -
The Cochrane Database of Systematic... Nov 2014A range of strategies are used to communicate with parents, caregivers and communities regarding child vaccination in order to inform decisions and improve vaccination... (Review)
Review
BACKGROUND
A range of strategies are used to communicate with parents, caregivers and communities regarding child vaccination in order to inform decisions and improve vaccination uptake. These strategies include interventions in which information is aimed at larger groups in the community, for instance at public meetings, through radio or through leaflets. This is one of two reviews on communication interventions for childhood vaccination. The companion review focuses on face-to-face interventions for informing or educating parents.
OBJECTIVES
To assess the effects of interventions aimed at communities to inform and/or educate people about vaccination in children six years and younger.
SEARCH METHODS
We searched CENTRAL, MEDLINE, EMBASE and five other databases up to July 2012. We searched for grey literature in the Grey Literature Report and OpenGrey. We also contacted authors of included studies and experts in the field. There were no language, date or settings restrictions.
SELECTION CRITERIA
Individual or cluster-randomised and quasi-randomised controlled trials, interrupted time series (ITS) and repeated measures studies, and controlled before-and-after (CBA) studies. We included interventions aimed at communities and intended to inform and/or educate about vaccination in children six years and younger, conducted in any setting. We defined interventions aimed at communities as those directed at a geographic area, and/or interventions directed to groups of people who share at least one common social or cultural characteristic. Primary outcomes were: knowledge among participants of vaccines or vaccine-preventable diseases and of vaccine service delivery; child immunisation status; and unintended adverse effects. Secondary outcomes were: participants' attitudes towards vaccination; involvement in decision-making regarding vaccination; confidence in the decision made; and resource use or cost of intervention.
DATA COLLECTION AND ANALYSIS
Two authors independently reviewed the references to identify studies for inclusion. We extracted data and assessed risk of bias in all included studies.
MAIN RESULTS
We included two cluster-randomised trials that compared interventions aimed at communities to routine immunisation practices. In one study from India, families, teachers, children and village leaders were encouraged to attend information meetings where they received information about childhood vaccination and could ask questions. In the second study from Pakistan, people who were considered to be trusted in the community were invited to meetings to discuss vaccine coverage rates in their community and the costs and benefits of childhood vaccination. They were asked to develop local action plans and to share the information they had been given and continue the discussions in their communities.The trials show low certainty evidence that interventions aimed at communities to inform and educate about childhood vaccination may improve knowledge of vaccines or vaccine-preventable diseases among intervention participants (adjusted mean difference 0.121, 95% confidence interval (CI) 0.055 to 0.189). These interventions probably increase the number of children who are vaccinated. The study from India showed that the intervention probably increased the number of children who received vaccinations (risk ratio (RR) 1.67, 95% CI 1.21 to 2.31; moderate certainty evidence). The study from Pakistan showed that there is probably an increase in the uptake of both measles (RR 1.63, 95% CI 1.03 to 2.58) and DPT (diptheria, pertussis and tetanus) (RR 2.17, 95% CI 1.43 to 3.29) vaccines (both moderate certainty evidence), but there may be little or no difference in the number of children who received polio vaccine (RR 1.01, 95% CI 0.97 to 1.05; low certainty evidence). There is also low certainty evidence that these interventions may change attitudes in favour of vaccination among parents with young children (adjusted mean difference 0.054, 95% CI 0.013 to 0.105), but they may make little or no difference to the involvement of mothers in decision-making regarding childhood vaccination (adjusted mean difference 0.043, 95% CI -0.009 to 0.097).The studies did not assess knowledge among participants of vaccine service delivery; participant confidence in the vaccination decision; intervention costs; or any unintended harms as a consequence of the intervention. We did not identify any studies that compared interventions aimed at communities to inform and/or educate with interventions directed to individual parents or caregivers, or studies that compared two interventions aimed at communities to inform and/or educate about childhood vaccination.
AUTHORS' CONCLUSIONS
This review provides limited evidence that interventions aimed at communities to inform and educate about early childhood vaccination may improve attitudes towards vaccination and probably increase vaccination uptake under some circumstances. However, some of these interventions may be resource intensive when implemented on a large scale and further rigorous evaluations are needed. These interventions may achieve most benefit when targeted to areas or groups that have low childhood vaccination rates.'
Topics: Child; Child, Preschool; Health Education; Health Knowledge, Attitudes, Practice; Humans; India; Infant; Information Dissemination; Pakistan; Parents; Randomized Controlled Trials as Topic; Vaccination
PubMed: 25408540
DOI: 10.1002/14651858.CD010232.pub2 -
The Cochrane Database of Systematic... Apr 2014Measles outbreaks continue to occur in countries with high vaccination coverage. Passive immunisation is generally considered to prevent measles in someone who is not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Measles outbreaks continue to occur in countries with high vaccination coverage. Passive immunisation is generally considered to prevent measles in someone who is not immune and has been exposed to infection. Estimates of effectiveness have varied and no minimum effective dose has been determined.
OBJECTIVES
To assess the effectiveness and safety of intramuscular injection or intravenous infusion of immunoglobulins (passive immunisation) for preventing measles when administered to exposed susceptible people before the onset of symptoms.
SEARCH METHODS
We searched CENTRAL (2013, Issue 7), MEDLINE (1946 to July week 5, 2013), CINAHL (1981 to August 2013) and EMBASE (1974 to August 2013).
SELECTION CRITERIA
We included randomised controlled trials (RCTs), quasi-RCTs and prospective, controlled (cohort) studies if: participants were susceptible and exposed to measles, polyclonal immunoglobulins derived from human sera or plasma were administered intramuscularly or intravenously as the only intervention in at least one group and the number of subsequent measles cases was measured. We excluded studies of other sources of immunoglobulins.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and critically appraised the included studies. We attempted to contact study authors for missing information. We described the results of studies not included in meta-analyses.
MAIN RESULTS
We included one RCT, two quasi-RCTs and 10 cohort studies (3925 participants). No studies were rated as low risk of bias for all criteria. Critical appraisal was constrained by a lack of information in most studies. The overall quality of the evidence was moderate.Seven studies (1432 participants) assessed cases of measles after immunoglobulin versus no treatment. Heterogeneity was explained by subgrouping according to the blood product used as an approximation of dose of immunoglobulin. When given within seven days of exposure, immunoglobulins were effective at preventing measles: gamma globulin (risk ratio (RR) 0.17, 95% confidence interval (CI) 0.08 to 0.36), convalescent serum (RR 0.21, 95% CI 0.15 to 0.29 to RR 0.49, 95% CI 0.44 to 0.54) and adult serum (RR 0.52, 95% CI 0.45 to 0.59). The differences in the effectiveness of different blood products were supported by studies not included in the meta-analysis and by two studies (702 participants) that found gamma globulin more effective than serum (RR 0.56, 95% CI 0.46 to 0.69).Based on three studies (893 participants) immunoglobulin was effective at preventing death due to measles compared to no treatment (RR 0.24, 95% CI 0.13 to 0.44).Two studies included measles vaccine alone among the intervention groups. Meta-analysis could not be undertaken. Both studies suggested the vaccine was more effective than gamma globulin.No serious adverse events were observed in any of the included studies, although reporting of adverse events was poor overall. Non-serious adverse events included transient fever, rash, muscle stiffness, local redness and induration.
AUTHORS' CONCLUSIONS
Passive immunisation within seven days of exposure is effective at preventing measles, with the risk for non-immune people up to 83% less than if no treatment is given. Given an attack rate of 45 per 1000 (per the control group of the most recent included study), gamma globulin compared to no treatment has an absolute risk reduction (ARR) of 37 per 1000 and a number needed to treat to benefit (NNTB) of 27. Given an attack rate of 759 per 1000 (per the attack rate of the other included study assessing gamma globulin), the ARR of gamma globulin compared to no treatment is 629 and the NNTB is two.It seems the dose of immunoglobulin administered impacts on effectiveness. A minimum effective dose of measles-specific antibodies could not be identified.Passive immunisation is effective at preventing deaths from measles, reducing the risk by 76% compared to no treatment. Whether the benefits of passive immunisation vary among subgroups of non-immune exposed people could not be determined.Due to a paucity of evidence comparing vaccine to passive immunisation, no firm conclusions can be drawn regarding relative effectiveness.The included studies were not specifically designed to detect adverse events.Future research should consider the effectiveness of passive immunisation for preventing measles in high-risk populations such as pregnant women, immunocompromised people and infants. Further efforts should be made to determine the minimum effective dose of measles-specific antibodies for post-exposure prophylaxis and the relative effectiveness of vaccine compared to immunoglobulin.
Topics: Cohort Studies; Humans; Immunization, Passive; Measles; Post-Exposure Prophylaxis; Randomized Controlled Trials as Topic; gamma-Globulins
PubMed: 24687262
DOI: 10.1002/14651858.CD010056.pub2