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International Journal of Epidemiology Aug 2019In some countries that have introduced oral rotavirus vaccines, a small but elevated risk of intussusception-a rare bowel disorder-has been reported. Updated estimates...
Update on the global epidemiology of intussusception: a systematic review of incidence rates, age distributions and case-fatality ratios among children aged <5 years, before the introduction of rotavirus vaccination.
BACKGROUND
In some countries that have introduced oral rotavirus vaccines, a small but elevated risk of intussusception-a rare bowel disorder-has been reported. Updated estimates on the global epidemiology of intussusception are needed to help predict the potential number of intussusception cases that could be caused by the vaccine in different settings.
METHODS
We estimated incidence rates, age distributions and case-fatality ratios (CFRs) for intussusception hospital admissions among children aged <5 years, before the introduction of rotavirus vaccines. We included all articles identified in a systematic review between January 2002 and January 2018, and contacted authors for more granular unpublished data on age distributions.
RESULTS
We identified 128 articles containing 227 country datasets (61 age distributions, 71 incidence rates and 95 CFRs). The median age of intussusception ranged from 29 weeks in Africa (83% of cases in the first year of life) to 70 weeks in the Western Pacific region (35% of cases in the first year of life). The median (range) annual incidence of intussusception hospital admissions per 100 000 aged <1 year ranged from 34 (13-56) in Africa to 90 (9-380) in the Western Pacific region. We found extreme differences between the CFRs in Africa (1 death in every 10 hospital admissions) and the rest of the world (fewer than 1 death in every 100-2000 hospital admissions).
CONCLUSION
Intussusception epidemiology varies by country and region. Understanding and recognizing these differences will be important when assessing the potential number of intussusception cases associated with rotavirus vaccines.
Topics: Age Distribution; Child, Preschool; Hospitalization; Humans; Incidence; Infant; Intussusception; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 30879038
DOI: 10.1093/ije/dyz028 -
The Lancet. Infectious Diseases Feb 2019Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance is uncertain.
METHODS
We did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. We searched Ovid-MEDLINE and Embase for trials published until Oct 23, 2017. Inclusion criteria for meta-analysis were two or more studies per intervention category and available seroconversion data. We did random-effects meta-analyses to produce summary relative risk (RR) estimates. This study is registered with PROSPERO (CRD42017060608).
FINDINGS
Of 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. 22 different interventions were assessed for oral poliovirus vaccine (OPV), oral rotavirus vaccine (RVV), oral cholera vaccine (OCV), and oral typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by 4 weeks (RR 1·37, 95% CI 1·16-1·62) and OPV seroconversion was increased with monovalent or bivalent OPV compared with trivalent OPV (RR 1·51, 95% CI 1·20-1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95% CI 1·00-1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95% CI 1·00-1·26). There was no evidence of effect for anthelmintics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses, or vaccine buffering.
INTERPRETATION
Most strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the gap in oral vaccine efficacy are urgently required.
FUNDING
Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and WHO Polio Research Committee.
Topics: Administration, Oral; Adolescent; Adult; Child; Child, Preschool; Cholera; Cholera Vaccines; Female; Humans; Immunogenicity, Vaccine; Infant; Infant, Newborn; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Salmonella typhi; Seroconversion; Treatment Outcome; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination; Vibrio cholerae; Young Adult
PubMed: 30712836
DOI: 10.1016/S1473-3099(18)30602-9 -
Open Forum Infectious Diseases Nov 2018Gastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus... (Review)
Review
BACKGROUND
Gastroenteritis caused by rotavirus accounts for considerable morbidity in young children. We aimed to assess the vaccine effectiveness (VE) of the oral rotavirus vaccine , as measured by laboratory-confirmed rotavirus infection after referral to hospital and/or emergency departments in children aged <5 years with gastroenteritis.
METHODS
We performed a systematic search for peer-reviewed studies conducted in real-life settings published between 2006 and 2016 and a meta-analysis to calculate the overall VE, which was further discriminated through stratified analyses.
RESULTS
The overall VE estimate was 69% (95% confidence interval [CI], 62% to 75%); stratified analyses revealed a non-negligible impact of factors such as study design and socioeconomic status. Depending on the control group, VE ranged from 63% (95% CI, 52% to 72%) to 81% (95% CI, 69% to 88%) for unmatched and matched rotavirus test-negative controls. VE varied with socioeconomic status: 81% (95% CI, 74% to 86%) in high-income countries, 54% (95% CI, 39% to 65%) in upper-middle-income countries, and 63% (95% CI, 50% to 72%) in lower-middle-income countries. Age, rotavirus strain, and disease severity were also shown to impact VE, but to a lesser extent.
CONCLUSIONS
This meta-analysis of real-world studies showed that is effective in helping to prevent hospitalizations and/or emergency department visits due to rotavirus infection.
PubMed: 30539038
DOI: 10.1093/ofid/ofy292 -
Human Vaccines & Immunotherapeutics 2019National pediatric vaccination programs have been introduced in Latin America (LatAm) to reduce the burden of diseases due to pathogens such as rotavirus, Haemophilus...
BACKGROUND
National pediatric vaccination programs have been introduced in Latin America (LatAm) to reduce the burden of diseases due to pathogens such as rotavirus, Haemophilus influenzae type b (Hib) and pneumococcus. Vaccination health benefits may extend to unvaccinated populations by reducing pathogen transmission. Understanding herd effect is important for implementation and assessment of vaccination programs. The objective was to conduct a systematic review of published epidemiological evidence of herd effect with Hib, rotavirus and pneumococcal conjugate vaccines (PCV) in LatAm.
METHODS
Searches were conducted in PubMed, Virtual Health Library (VHL), SciELO and SCOPUS databases, for studies reporting data on herd effect from Hib, rotavirus and PCV vaccination in LatAm, without age restriction. Searches were limited to articles published in English, Spanish or Portuguese (1990-2016). After screening and full-text review, articles meeting the selection criteria were included to be critically appraised following criteria for observational and interventional studies. The presence of a herd effect was defined as a significant decrease in incidence of disease, hospitalization, or mortality.
RESULTS
3,465 unique articles were identified, and 23 were included (Hib vaccine n = 5, PCV n = 8, rotavirus vaccine n = 10). Most studies included children and/or adolescents (age range varied between studies). Studies in adults, including older adults (aged > 65 years), were limited. Few studies reported statistically significant reductions in disease incidence in age groups not targeted for vaccination. Hib-confirmed meningitis hospitalization decreased in children but herd effect could not be quantified. Some evidence of herd effect was identified for PCV and rotavirus vaccine in unvaccinated children. Evidence for herd effects due to PCV in adults was limited.
CONCLUSION
After introduction of Hib, PCV and rotavirus vaccination in LatAm, reductions in morbidity/mortality have been reported in children not targeted for vaccination. However, due to methodological limitations (e.g. short post-vaccination periods and age range studied), there is currently insufficient evidence to quantify the herd effect in adult populations. More research and higher quality surveillance is needed to characterize herd effect of these vaccines in LatAm.
Topics: Bacterial Capsules; Haemophilus Vaccines; Humans; Immunity, Herd; Immunization Programs; Latin America; Pneumococcal Vaccines; Rotavirus Vaccines; Vaccination
PubMed: 30230953
DOI: 10.1080/21645515.2018.1514225 -
Human Vaccines & Immunotherapeutics 2018We performed a systematic review to evaluate factors affecting uptake of rotavirus vaccine amongst physicians, parents and health system. We identified 15 studies that...
We performed a systematic review to evaluate factors affecting uptake of rotavirus vaccine amongst physicians, parents and health system. We identified 15 studies that met the inclusion criteria from 790 screened studies published between Jan 2005 to Jan 2016. Perceived severity of rotavirus disease, efficacy of vaccine and recommendation by health authorities positively influenced uptake of vaccine amongst health care providers. Routine and timely vaccination with routine vaccines and availability of rotavirus vaccine in public health programme facilitated uptake. Family income, parental education and employment status positively influenced the decision to vaccinate by parents. Concerns about safety, high cost, additional workload and logistic problems in acquiring vaccine stocks were perceived as barriers. Improved awareness regarding the rotavirus vaccination amongst public and scientific community and strengthening of public health system for better and timely immunisation coverage are important factors to maximize uptake of rotavirus vaccine in India.
PubMed: 29913110
DOI: 10.1080/21645515.2018.1489190 -
Cost Effectiveness and Resource... 2018Cost-effectiveness analysis (CEA) is frequently used as an input for guiding priority setting in health. However, CEA seldom incorporates information about trade-offs... (Review)
Review
BACKGROUND
Cost-effectiveness analysis (CEA) is frequently used as an input for guiding priority setting in health. However, CEA seldom incorporates information about trade-offs between total health gains and equity impacts of interventions. This study investigates to what extent equity considerations have been taken into account in CEA in low- and middle-income countries (LMICs), using rotavirus vaccination as a case study.
METHODS
Specific equity-related indicators for vaccination were first mapped to the Guidance on Priority Setting in Health Care (GPS-Health) checklist criteria. Economic evaluations of rotavirus vaccine in LMICs identified via a systematic review of the literature were assessed to explore the extent to which equity was considered in the research objectives and analysis, and whether it was reflected in the evaluation results.
RESULTS
The mapping process resulted in 18 unique indicators. Under the 'disease and intervention' criteria, severity of illness was incorporated in 75% of the articles, age distribution of the disease in 70%, and presence of comorbidities in 5%. For the 'social groups' criteria, relative coverage reflecting wealth-based coverage inequality was taken into account in 30% of the articles, geographic location in 27%, household income level in 8%, and sex at birth in 5%. For the criteria of 'protection against the financial and social effects of ill health', age weighting was incorporated in 43% of the articles, societal perspective in 58%, caregiver's loss of productivity in 45%, and financial risk protection in 5%. Overall, some articles incorporated the indicators in their model inputs (20%) while the majority (80%) presented results (costs, health outcomes, or incremental cost-effectiveness ratios) differentiated according to the indicators. Critically, less than a fifth (17%) of articles incorporating indicators did so due to an explicit study objective related to capturing equity considerations. Most indicators were increasingly incorporated over time, with a notable exception of age-weighting of DALYs.
CONCLUSION
Integrating equity criteria in CEA can help policy-makers better understand the distributional impact of health interventions. This study illustrates how equity considerations are currently being incorporated within CEA of rotavirus vaccination and highlights the components of equity that have been used in studies in LMICs. Areas for further improvement are identified.
PubMed: 29796012
DOI: 10.1186/s12962-018-0102-2 -
Human Vaccines & Immunotherapeutics 2018An estimated 215,000 children died of rotavirus infections in 2013, accounting for 37% of diarrhea-related deaths worldwide, 92% of which occurred in low and...
An estimated 215,000 children died of rotavirus infections in 2013, accounting for 37% of diarrhea-related deaths worldwide, 92% of which occurred in low and lower-middle income countries. Since 2009 the World Health Organization (WHO) recommends the use of rotavirus vaccines in all national immunization programs. This review compares rotavirus vaccine (RV) introductions and vaccine coverage by region, country income status and Gavi-eligibility from 2006-2016. Gross National Income data from the World Bank and surviving infant population from United Nations Population Division was obtained for 2016. Data from WHO were collected on rotavirus vaccine coverage, national immunization schedules, and new vaccine introductions for 2016 while estimated rotavirus deaths were collected for 2013, the last year of available WHO data. As of December 2016, the majority of countries (57%, 110/194) had not introduced universal rotavirus vaccine despite WHO's 2009 recommendation to do so. Countries in the WHO African region had the greatest proportion of introductions (37%, 31/84) by December 2016 and a great majority of these (77%, 24/31) were supported by new vaccine introduction (NVI) grants from Gavi. Almost half (48%) of global introductions were in low and lower-middle income Gavi-eligible and Gavi-graduating countries. Conversely, countries in the Southeast Asia WHO region and those not eligible for Gavi NVI support have been slow to introduce rotavirus vaccine. High-income countries, on average, had poorer rotavirus vaccine coverage compared to low and lower-middle income countries. The over-representation of African countries within the Gavi subset and high estimated rotavirus deaths in these African countries, likely explains why introduction efforts have been focused in this region. While much progress has been made with the integration and implementation of rotavirus vaccine into national immunization programs, 110 countries representing 69% of the global birth cohort had yet to introduce the vaccine by December 2016.
Topics: Capital Financing; Disease Transmission, Infectious; Global Health; Humans; Immunization Programs; Infant; Rotavirus Infections; Rotavirus Vaccines; Vaccination Coverage
PubMed: 29787334
DOI: 10.1080/21645515.2018.1470725 -
The American Journal of Tropical... Apr 2018Two rotavirus vaccines, RotaTeq and Rotarix, are licensed for global use; however, the protection they confer to unvaccinated individuals through indirect effects... (Meta-Analysis)
Meta-Analysis
Two rotavirus vaccines, RotaTeq and Rotarix, are licensed for global use; however, the protection they confer to unvaccinated individuals through indirect effects remains unknown. We systematically reviewed the literature and quantified indirect rotavirus vaccine effectiveness (VE) for preventing rotavirus hospitalization in children aged less than 5 years. From 148 identified abstracts, 14 studies met our eligibility criteria. In our main analysis using a random-effects model, indirect rotavirus VE was 48% (95% confidence interval [CI]: 39-55%). In a subgroup analysis by country income level, indirect VE was greater in high-income countries (52%; 95% CI: 43-60%) than in low- and middle-income countries (LMICs) (25%; 95% CI: 5-41%). In a sensitivity analysis using a quality-effects model, the indirect VE in LMICs was not statistically significant (25%; 95% CI: 0-44%). Our findings highlight the importance of increasing rotavirus vaccine coverage, particularly in LMICs where evidence for indirect VE is limited and rotavirus burden is high.
Topics: Child, Preschool; Hospitalization; Humans; Income; Infant; Infant, Newborn; Rotavirus Infections; Rotavirus Vaccines
PubMed: 29436336
DOI: 10.4269/ajtmh.17-0705 -
Vaccine Dec 2017The objectives of this review were to identify vaccine economic evaluations that include herd immunity and describe the methodological approaches used. (Review)
Review
OBJECTIVE
The objectives of this review were to identify vaccine economic evaluations that include herd immunity and describe the methodological approaches used.
METHODS
We used Kim and Goldie's search strategy from a systematic review (1976-2007) of modelling approaches used in vaccine economic evaluations and additionally searched PubMed/MEDLINE and Embase for 2007-2015. Studies were classified according to modelling approach used. Methods for estimating herd immunity effects were described, in particular for the static models.
RESULTS
We identified 625 economic evaluations of vaccines against human-transmissible diseases from 1976 to 2015. Of these, 172 (28%) included herd immunity. While 4% of studies included herd immunity in 2001, 53% of those published in 2015 did this. Pneumococcal, human papilloma and rotavirus vaccines represented the majority of studies (63%) considering herd immunity. Ninety-five of the 172 studies utilised a static model, 59 applied a dynamic model, eight a hybrid model and ten did not clearly state which method was used. Relatively crude methods and assumptions were used in the majority of the static model studies.
CONCLUSION
The proportion of economic evaluations using a dynamic model has increased in recent years. However, 55% of the included studies used a static model for estimating herd immunity. Values from a static model can only be considered reliable if high quality surveillance data are incorporated into the analysis. Without this, the results are questionable and they should only be included in sensitivity analysis.
Topics: Cost-Benefit Analysis; Humans; Immunity, Herd; Immunization Programs; Models, Economic; Pneumococcal Vaccines; Rotavirus Vaccines; Vaccination
PubMed: 29146380
DOI: 10.1016/j.vaccine.2017.10.024 -
PharmacoEconomics Jan 2018In low- and middle-income countries, budget impact is an important criterion for funding new interventions, particularly for large public health investments such as new...
Capturing Budget Impact Considerations Within Economic Evaluations: A Systematic Review of Economic Evaluations of Rotavirus Vaccine in Low- and Middle-Income Countries and a Proposed Assessment Framework.
BACKGROUND
In low- and middle-income countries, budget impact is an important criterion for funding new interventions, particularly for large public health investments such as new vaccines. However, budget impact analyses remain less frequently conducted and less well researched than cost-effectiveness analyses.
OBJECTIVE
The objective of this study was to fill the gap in research on budget impact analyses by assessing (1) the quality of stand-alone budget impact analyses, and (2) the feasibility of extending cost-effectiveness analyses to capture budget impact.
METHODS
We developed a budget impact analysis checklist and scoring system for budget impact analyses, which we then adapted for cost-effectiveness analyses, based on current International Society for Pharmacoeconomics and Outcomes Research Task Force recommendations. We applied both budget impact analysis and cost-effectiveness analysis checklists and scoring systems to examine the extent to which existing economic evaluations provide sufficient evidence about budget impact to enable decision making. We used rotavirus vaccination as an illustrative case in which low- and middle-income countries uptake has been limited despite demonstrated cost effectiveness. A systematic literature review was conducted to identify economic evaluations of rotavirus vaccine in low- and middle-income countries published between January 2000 and February 2017. We critically appraised the quality of budget impact analyses, and assessed the extension of cost-effectiveness analyses to provide useful budget impact information.
RESULTS
Six budget impact analyses and 60 cost-effectiveness analyses were identified. Budget impact analyses adhered to most International Society for Pharmacoeconomics and Outcomes Research recommendations, with key exceptions being provision of undiscounted financial streams for each budget period and model validation. Most cost-effectiveness analyses could not be extended to provide useful budget impact information; cost-effectiveness analyses also rarely presented undiscounted annual costs, or estimated financial streams during the first years of programme scale-up.
CONCLUSIONS
Cost-effectiveness analyses vastly outnumber budget impact analyses of rotavirus vaccination, despite both being critical for policy decision making. Straightforward changes to the presentation of cost-effectiveness analyses results could facilitate their adaptation into budget impact analyses.
Topics: Budgets; Cost-Benefit Analysis; Decision Making; Developing Countries; Health Policy; Humans; Policy Making; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 28905279
DOI: 10.1007/s40273-017-0569-2