Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children

BackgroundTwo rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries.MethodsFrom February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8–59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 − odds ratio of vaccination) × 100%.ResultsTotally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls.ConclusionsBoth vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.     

Barriers and activities to implementing or expanding influenza vaccination programs in low- and middle-income countries: A global survey

IntroductionDespite considerable global burden of influenza, few low- and middle-income countries (LMICs) have national influenza vaccination programs. This report provides a systematic assessment of barriers to and activities that support initiating or expanding influenza vaccination programs from the perspective of in-country public health officials.MethodsPublic health officials in LMICs were sent a web-based survey to provide information on barriers and activities to initiating, expanding, or maintaining national influenza vaccination programs. The survey primarily included Likert-scale questions asking respondents to rank barriers and activities in five categories.ResultsOf 109 eligible countries, 62% participated. Barriers to influenza vaccination programs included lack of data on cost-effectiveness of influenza vaccination programs (87%) and on influenza disease burden (84%), competing health priorities (80%), lack of public perceived risk from influenza (79%), need for better risk communication tools (77%), lack of financial support for influenza vaccine programs (75%), a requirement to use only WHO-prequalified vaccines (62%), and young children require two vaccine doses (60%). Activities for advancing influenza vaccination programs included educating healthcare workers (97%) and decision-makers (91%) on the benefits of influenza vaccination, better estimates of influenza disease burden (91%) and cost of influenza vaccination programs (89%), simplifying vaccine introduction by focusing on selected high-risk groups (82%), developing tools to prioritize target populations (80%), improving availability of influenza diagnostic testing (79%), and developing collaborations with neighboring countries for vaccine procurement (74%) and regulatory approval (73%). Responses varied by country region and income status.ConclusionsLocal governments and key international stakeholders can use the results of this survey to improve influenza vaccination programs in LMICs, which is a critical component of global pandemic preparedness for influenza and other pathogens such as coronaviruses. Additionally, strategies to improve global influenza vaccination coverage should be tailored to country income level and geographic location.     

Cost-effectiveness analysis of the implementation of a National Immunization Program for rotavirus vaccination in a country with a low rotavirus gastroenteritis-related mortality: A South Korean study

Rotavirus is a leading cause of severe gastroenteritis among children younger than 5 years in South Korea. Two rotavirus vaccines (RVs), pentavalent human-bovine reassortant vaccine (Rotateq®; RV5) and attenuated human strain originated monovalent vaccine (Rotarix®; RV1), have been available for voluntary vaccination using out-of-pocket payment since 2007 and 2008, respectively. Yet, RVs are not included in the National Immunization Program (NIP), partly because of the low associated mortality rate. We assessed the cost-effectiveness of RVs to assist the evidence-based decision-making process for NIP implementation in South Korea. Using a transparent age-structured static cohort model, we simulated the experience of ten annual birth cohorts of South Korean children from 2018 to 2027. Model inputs included rotavirus gastroenteritis (RVGE) incidence and mortality rates, RVGE treatment costs, vaccine coverage and timeliness, and vaccine effectiveness and price. The incremental costs of including RVs in the NIP compared to no vaccination were 59,662,738 USD and 152,444,379 USD for RV1 and RV5, respectively. The introduction of RV1 and RV5 can prevent 4799 disability-adjusted life years (DALYs) and 5068 DALYs. From the societal perspective, the incremental cost-effectiveness ratios (ICERs) for adopting RV into the NIP versus no vaccination were 12,432 USD per DALY averted for RV1 and 30,081 USD per DALY averted for RV 5. The weighted average for the ICERs of the two vaccines computed using the market share of each vaccine in the current voluntary use as a weight, was 21,698 USD per DALY averted. The estimated ICER was below 1 × gross domestic product per capita (30,000 USD), which has been a commonly used willingness-to-pay threshold for health care technology assessment in South Korea, suggesting that introducing RVs into the NIP would be cost-effective.     

Cost-effectiveness of sub-national geographically targeted vaccination programs: A systematic review

Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing administrative costs create logistic and financial challenges, especially in resource-limited settings. Sub-national geographic targeting of vaccination programs is a potential strategy for governments to reduce the impact of infectious disease outbreaks while optimizing resource allocation and reducing costs, promoting sustainability of critically important national immunization plans. We conducted a systematic review of peer-reviewed literature to identify studies that investigated the cost-effectiveness of geographically targeted sub-national vaccination programs, either through routine immunization or supplementary immunization activities. A total of 16 studies were included in our review, covering nine diseases of interest: cholera, dengue, enterotoxigenic Escherichia coli (ETEC), hepatitis A, Japanese encephalitis, measles, rotavirus, Shigella and typhoid fever. All studies modelled cost-effectiveness of geographically targeted vaccination. Despite the variation in study design, disease focus and country context, studies generally found that in countries where a heterogenous burden of disease exists, sub-national geographic targeting of vaccination programs in areas of high disease burden was more cost-effective than a non-targeted strategy. Sensitivity analysis revealed that cost-effectiveness was most sensitive to variations in vaccine price, vaccine efficacy, mortality rate, administrative and operational costs, discount rate, and treatment costs. This systematic review identified several key characteristics related to geographic targeting of vaccination, including the vaccination strategy used, variations in modelling parameters and their impact on cost-effectiveness. Additional research and guidance is needed to support the appropriateness and feasibility of geographically targeted vaccination and to determine what country context would make this a viable complement to routine immunization programs.     

Developing a manufacturing process to deliver a cost effective and stable liquid human rotavirus vaccine

Despite solid evidence of the success of rotavirus vaccines in saving children from fatal gastroenteritis, more than 82 million infants worldwide still lack access to a rotavirus vaccine. The main barriers to global rotavirus vaccine coverage include cost, manufacturing capacity and suboptimal efficacy in low- and lower-middle income countries. One vaccine candidate with the potential to address the latter is based on the novel, naturally attenuated RV3 strain of rotavirus, RV3-BB vaccine administered in a birth dose strategy had a vaccine efficacy against severe rotavirus gastroenteritis of 94% at 12 months of age in infants in Indonesia. To further develop this vaccine candidate, a well-documented and low-cost manufacturing process is required. A target fully loaded cost of goods (COGs) of ≤$3.50 per course of three doses was set based on predicted market requirements. COGs modelling was leveraged to develop a process using Vero cells in cell factories reaching high titers, reducing or replacing expensive reagents and shortening process time to maximise output. Stable candidate liquid formulations were developed allowing two-year storage at 2–8 °C. In addition, the formulation potentially renders needless the pretreatment of vaccinees with antacid to ensure adequate gastric acid neutralization for routine oral vaccination. As a result, the formulation allows small volume dosing and reduction of supply chain costs. A dose ranging study is currently underway in Malawi that will inform the final clinical dose required. At a clinical dose of ≤6.3 log₁₀ FFU, the COGs target of ≤$3.50 per three dose course was met. At a clinical dose of 6.5 log₁₀ FFU, the final manufacturing process resulted in a COGs that is substantially lower than the current average market price, 2.44 USD per dose. The manufacturing and formulation processes were transferred to BioFarma in Indonesia to enable future RV3-BB vaccine production.     

Economic evaluation of the introduction of rotavirus vaccine in Hong Kong

BackgroundRotavirus is a common cause of severe gastroenteritis in young children in Hong Kong (HK) with a high economic burden. This study aimed to evaluate the cost-effectiveness of introducing rotavirus vaccination into the HK Government’s Childhood Immunisation Programme (CIP) and to include the potential protective effect of the vaccine against seizures.MethodsA decision-support model was customised to estimate the potential impact, cost-effectiveness and benefit-risk of rotavirus vaccination in children below 5 years over the period 2020–2029 in HK. Two doses of Rotarix® and three doses of RotaTeq® were each compared to no vaccination. Rotavirus treatment costs were calculated from a governmental health sector perspective (i.e., costs of public sector treatment) and an overall health sector perspective (both governmental and patient, i.e., costs of public sector treatment, private sector treatment, transport and diapers). We ran probabilistic and deterministic uncertainty analyses.ResultsIntroduction of rotavirus vaccination in HK could prevent 49,000 (95% uncertainty interval: ~44,000–54,000) hospitalisations of rotavirus gastroenteritis and seizures and result in ~50 (95% uncertainty interval: ~25–85) intussusception hospitalisations, over the period 2020–2029 (a benefit-risk ratio of ~1000:1), compared to a scenario with no public or private sector vaccine use. The discounted vaccination cost would be US$51–57 million over the period 2020–2029 based on per-course prices of US$72 (Rotarix®) or US$78 (RotaTeq®), but this would be offset by discounted treatment cost savings of US$70 million (government) and US$127 million (governmental and patient health sector). There was a greater than 94% probability that the vaccine could be cost-saving irrespective of the vaccine product or perspective considered. All deterministic ‘what-if’ scenarios were cost-saving from an overall health sector perspective (governmental and patient).ConclusionsRotavirus vaccination is likely to be cost-saving and have a favourable benefit-risk profile in HK. Based on the assumptions made, our analysis supports its introduction into CIP.     

Timeliness and factors associated with rotavirus vaccine uptake among Australian Aboriginal and non-Aboriginal children: A record linkage cohort study

ObjectivesRotavirus vaccines (RV), included in Australia’s National Immunisation Program from mid-July 2007, are unique in strict time limits for administration. Here, we report on timeliness of RV uptake, compare cumulative RV coverage to age 12 months with DTPa, and assess factors associated with receipt of RV among Aboriginal and non-Aboriginal children.MethodsBirth records for 681,456 children born in two Australian states in 2007–2012 were probabilistically linked to national immunisation records. We assessed on-time coverage (defined as receipt of vaccine dose between 4 days prior to scheduled date and the recommended upper limit) for RV and compared this to diphtheria-tetanus-pertussis (DTPa) vaccine. Logistic regression modelling was used to assess independent determinants of receipt of RV.ResultsCompared to non-Aboriginal infants, on-time RV coverage was lower for all doses among Aboriginal infants. Post the upper age limit of RV dose2, DTPa dose2 coverage increased by 9–16% to ≥90%, whereas RV coverage remained around 77% (Aboriginal) and 85% (non-Aboriginal). Compared to first-born children, the adjusted odds of receiving ≥1 RV dose if born to a mother with ≥3 previous births was 0.30 (95%CI: 0.27–0.34) among Aboriginal, and 0.53 (95%CI: 0.51–0.55) among non-Aboriginal children. Prematurity (<33 weeks), low birthweight (<1500 g), maternal age <20 years, maternal smoking during pregnancy and living in a disadvantaged area were independently associated with decreased vaccine uptake.ConclusionsAboriginal children are at greater risk of rotavirus disease than non-Aboriginal children and delayed vaccine receipt is substantially higher. Although specific programs targeting groups at risk of delayed vaccination might improve RV coverage, relaxation of upper age restrictions is most readily implementable, and its overall risk-benefit should be evaluated.     

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review

BackgroundHepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known.MethodsWe conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence.ResultsOf 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3–5 years for two-dose programs. Vaccine efficacy was >98% over 0.1–7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively.ConclusionExperience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.     

Developing communication tools on rotavirus vaccination to support family paediatricians in Italy

BackgroundUniversal rotavirus (RV) vaccination for newborns was introduced in Italy in 2018, but national vaccination coverage is still suboptimal. Effective communication between the family paediatrician (FP) and parents/caregivers is essential to promote vaccination acceptance. This project aimed to support FPs in communicating RV vaccination to parents/caregivers through the development and implementation of demonstrative videos and training modules.MethodsA working group composed of two FPs, two communication professionals, a medical expert from GSK and a clinical psychologist, was formed to establish the key scientific information to be communicated to parents/caregivers and develop the demonstrative videos. Four videos depicting four communication styles (I to IV) were developed based on the Social Styles Theory. Thirty FPs were then asked to pilot test the videos and provide feedback. In addition, two training modules with scientific information were developed to learn how to respond to parents’/caregivers’ objections.ResultsA total of 23 FPs provided feedback after using one or more videos at least five times. Twenty FPs (87.0 %) used mostly-one style, and most (60.0 %) used Style IV. Overall, the feedback was positive, as the majority of FPs (82.6 %, n = 19/23) indicated that the proposed videos were ‘useful’ or ‘extremely useful’ for introducing the RV vaccination to parents/caregivers in their actual practice. Based on this feedback, shorter versions of each video were also produced, and two training modules were developed to support FPs in responding to parental objections. Most FPs 75 % (n = 9/12) found Module 1 ‘very useful’, and all found Module 2 ‘very useful’ (100 %, n = 12/12).ConclusionsThe communication tools developed were well appreciated by the FPs and are expected to support FPs in communicating RV vaccination thereby increasing its coverage. Practicing RV communication may also prove beneficial for FPs to communicate other critical topics to parents/caregivers.     

A Phase III,multicenter, randomized,double-blind,active comparator-controlled study to evaluate the safety,tolerability, and immunogenicity of V114 compared with PCV13 in healthy infants (PNEU-PED-EU-1)

BackgroundV114 (15-valent pneumococcal conjugate vaccine [PCV]) contains all serotypes in 13-valent PCV (PCV13) and additional serotypes 22F and 33F. This study evaluated safety and immunogenicity of V114 compared with PCV13 in healthy infants, and concomitant administration with DTPa–HBV–IPV/Hib and rotavirus RV1 vaccines.MethodsV114 and PCV13 were administered in a 2+1 schedule at 2, 4, and 11–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series (PPS), immediately prior to a toddler dose, and 30 days post-toddler dose (PTD). Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for the two additional serotypes.Results1184 healthy infants 42–90 days of age were randomized 1:1 to V114 (n = 591) or PCV13 (n = 593). Proportions of participants with solicited AEs and serious AEs were comparable between vaccination groups. V114 met pre-specified non-inferiority criteria for all 13 shared serotypes, based on the difference in proportions of participants with serotype-specific IgG concentrations ≥0.35 μg/mL (response rate; lower bound of two-sided 95% confidence interval [CI] >−10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5), and pre-specified superiority criteria for serotypes 22F and 33F (lower bound of two-sided 95% CI >10.0 for response rates and >2.0 for GMC ratios). Antibody responses to DTPa–HBV–IPV/Hib and RV1 vaccines met pre-specified non-inferiority criteria, based on antigen-specific response rates to DTPa–HBV–IPV/Hib and anti-rotavirus IgA geometric mean titers.ConclusionsAfter a 2+1 schedule, V114 elicited non-inferior immune responses to 13 shared serotypes and superior responses to the two additional serotypes compared with PCV13, with comparable safety profile. These results support the routine use of V114 in infants.Trial registration: ClinicalTrials.gov: NCT04031846; EudraCT: 2018-003787-31     

Hexavalent vaccines: What can we learn from head-to-head studies?

BackgroundThree hexavalent vaccines against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib) are licensed in Europe: Infanrix hexa (DT3aP-HBV-IPV/Hib), Hexyon (DT2aP-HBV-IPV-Hib) and Vaxelis (DT5aP-HBV-IPV-Hib).MethodsA systematic literature search was performed in various electronic databases to identify published peer-reviewed head-to-head studies comparing any licensed hexavalent vaccine to another.ResultsPredefined inclusion criteria were met by 12 articles. Individual studies concluded that the 3 hexavalent vaccines have acceptable safety profiles although some significant differences were observed in their reactogenicity profiles. The immunogenicity of DT2aP-HBV-IPV-Hib and DT5aP-HBV-IPV-Hib was non-inferior versus DT3aP-HBV-IPV/Hib. Some differences in immune responses to common antigens were observed, but their clinical relevance was not established. Anti-filamentous hemagglutinin (FHA) from pertussis and anti-polyribosylribitol phosphate (PRP) from Hib antibody concentrations tended to be higher, and anti-HBV and anti-pertussis toxin (PT) from pertussis antibody concentrations lower in DT2aP-HBV-IPV-Hib versus DT3aP-HBV-IPV/Hib vaccinees. Anti-PT and post-primary anti-PRP antibody concentrations tended to be higher, and anti-HBV, anti-FHA, anti-pertactin from pertussis and post-booster anti-PRP antibody concentrations lower in DT5aP-HBV-IPV-Hib versus DT3aP-HBV-IPV/Hib recipients. Slightly lower immune responses towards most vaccine antigens were observed with 2 + 1 versus 3 + 1 schedules post-primary vaccination, suggesting that 2 + 1 schedules should only be considered in countries with very high vaccination coverage.ConclusionAlthough the licensed hexavalent vaccines are generally considered similar, analyses of immunogenicity data from head-to-head trials highlighted differences that could be related to differences in composition and formulation. In addition, the demonstrated non-inferiority of the immunogenicity of the more recent vaccines versus DT3aP-HBV-IPV/Hib does not allow a full bridging to similar efficacy, effectiveness and safety. The availability of DT3aP-HBV-IPV/Hib over > 20 years allowed to collect a wealth of data on its long-term immunogenicity, safety and effectiveness in clinical and post-marketing studies, and makes it a key pillar of pediatric immunization.     

Influenza in Latin America: A report from the Global Influenza Initiative (GII)

The Global Influenza Initiative (GII) is a global expert group that aims to raise acceptance and uptake of influenza vaccines globally and provides recommendations and strategies to address challenges at local, national, regional, and global levels. This article provides a consolidated estimation of disease burden in Latin America, currently lacking in published literature, and delivers the GII recommendations specific to Latin America that provide guidance to combat existing vaccination challenges.While many countries worldwide, especially in the tropics and subtropics, do not have a seasonal influenza policy, 90% of Latin American countries have a seasonal influenza policy in place. Local governments in the Latin American countries and The Pan American Health Organization’s Technical Advisory Group on Vaccine-preventable Diseases play a major role in improving the vaccination coverage and reducing the overall disease burden. Influenza seasonality poses the biggest challenge in deciding on optimal timing for vaccination in Latin America, as in temperate climates seasonal influenza activity peaks during the winter months (November–February and May–October) in the northern and southern hemispheres, respectively, while in the tropics and subtropical regions it usually occurs throughout the year, but especially during the rainy season. Besides this, vaccine mismatch with circulating strains, misconception concerning influenza vaccine effectiveness, and poor disease and vaccine awareness among the public are also key challenges that need to be overcome. Standardization of clinical case definitions is important across all Latin American countries. Surveillance (mostly passive) has improved substantially in the Latin American countries over the past decade, but more is still required to better understand the disease burden and help inform policies.     

Development of a cumulative metric of vaccination adherence behavior and its application among a cohort of 12-month-olds in western Kenya

ObjectivesThe timely receipt of the recommended vaccination regimen, i.e. vaccination maintenance, is an underexplored, but important, indicator of public health. There is currently no standardized method for quantifying cumulative vaccination maintenance, however, and no simple way to explore predictors of adherence to vaccination schedules. We therefore sought to (1) develop a Vaccination Maintenance Score (VMS) and (2) apply this score to determine the predictors of vaccination behavior among infants in western Kenya (n = 245).MethodsWomen in western Kenya were enrolled during pregnancy and surveyed repeatedly through one year postpartum. Data were collected on a range of sociodemographic and health indicators and vaccinations. For each infant, we analyzed receipt of 11 vaccines recommended by the Kenyan Ministry of Health. We operationalized VMS as the total number of vaccines received on schedule. Vaccines that were not received or received off schedule were scored 0. VMS was modeled using multivariable tobit regression models.ResultsWe found that 85.7% of infants were fully immunized, but only 42.4% had optimal VMS, i.e. scored 11. The median (IQR) VMS was 10 (3). In multivariable regression, each one-point increase in maternal quality of life score (range: 0–32) was associated with a 0.22-point increase in VMS; each additional child in the household was associated with a 0.34-point increase in VMS; and initiating breastfeeding at birth was associated a 2.01-point increase in VMS.ConclusionsCoverage of the recommended vaccinations (85.7%) was nearly twice as high as cumulative timely receipt (42.4%). The VMS satisfies a need for a location-specific but easily adaptable metric of vaccination adherence behavior. It can be used to complement traditional methods of vaccination coverage and timeliness to better understand underlying behaviors that influence vaccination events, and thereby inform interventions to improve vaccination rates and decrease the burden of vaccine-preventable disease.Clinical Trial RegistrationNCT02974972 and NCT02979418.     

Validation of parental reports of rotavirus vaccination of their children compared to the national immunization registry

BackgroundThe introduction of rotavirus vaccines into national immunization programs necessitates vaccine effectiveness evaluations. Parental report of vaccination status is a simple and accessible source of information; however, its validity is unclear.AimsTo validate parental reports of rotavirus immunization compared to documentation of vaccination in national immunization registry, and to assess vaccine effectiveness by each method.MethodsParents of 1272 children aged 2–59 months from northern Israel hospitalized for gastroenteritis in 2011–2015 were interviewed on the sociodemographics and rotavirus vaccination status of their child. Rotavirus immunization status based on parental report was compared to that documented in the national immunization registry, which was considered the gold standard. Stool samples collected from patients were tested for rotavirus antigen by immunochromotgraphy. In a rotavirus test-negative case-control study, vaccination history was compared between children found positive for rotavirus and those who tested negative. Vaccine effectiveness for ≥ 1 dose vs. zero doses was calculated as: (1-adjusted odds ratio) * 100.ResultsThe sensitivity and specificity of parental report of their child's immunization with a rotavirus vaccine were 97% (95% CI 96–98), and 75% (95% CI 65–82), respectively. Kappa coefficient was 0.69 (p < 0.001) for the agreement between the two methods. Rotavirus vaccine effectiveness was 72% (95% CI 54–84) when using parental report of rotavirus immunization and 79% (95% CI 62–88) when using the registry.ConclusionParental report of their child's immunization with a rotavirus vaccine demonstrated high sensitivity, although the specificity was relatively low. Vaccine effectiveness was similar regardless of method used to determine rotavirus immunization status. Parental report of vaccination status can be useful in vaccine effectiveness assessment.     

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies

BackgroundNeither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines.MethodsWe collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated.ResultsAmong 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes.ConclusionsVaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.     

An innovative housing-related measure for individual socioeconomic status and human papillomavirus vaccination coverage: A population-based cross-sectional study

BackgroundHuman papillomavirus (HPV) is a known cause of anogenital (eg, cervical) and oropharyngeal cancers. Despite availability of effective HPV vaccines, US vaccination-completion rates remain low. Evidence is conflicting regarding the association of socioeconomic status (SES) and HPV vaccination rates. We assessed the association between SES, defined by an individual validated Housing-based Index of Socioeconomic Status (HOUSES), and HPV vaccination status.MethodsWe conducted a cross-sectional study of children/adolescents 9–17 years as of December 31, 2016, living in southeastern Minnesota by using a health-record linkage system to identify study-eligible children/adolescents, vaccination dates, and home addresses matched to HOUSES data. We analyzed the relationship between HPV vaccination status and HOUSES using multivariable Poisson regression models stratifying by age, sex, race, ethnicity, and county.ResultsOf 20,087 study-eligible children/adolescents, 19,363 (96.4%) were geocoded and HOUSES measures determined. In this cohort, 57.9% did not receive HPV vaccination, 15.8% initiated (only), and 26.3% completed the series. HPV vaccination-initiation and completion rates increased over higher SES HOUSES quartiles (P < .001). Rates of HPV vaccination initiation versus unvaccinated increased across HOUSES quartiles in multivariable analysis adjusted for age, sex, race, ethnicity, and county (1st quartile, referent; 2nd quartile, 0.97 [0.87–1.09]; 3rd quartile, 1.05 [0.94–1.17]; 4th quartile, 1.15 [1.03–1.28]; test for trend, P = .002). HOUSES was a stronger predictor of HPV vaccination completion versus unvaccinated (1st quartile referent; 2nd quartile, 1.06 [0.96–1.16]; 3rd quartile, 1.12 [1.03–1.23]; 4th quartile, 1.32 [1.21–1.44]; test for trend, P < .001). Significant interactions were shown for HPV vaccination initiation by HOUSES for sex (P = .009) and age (P = .006).ConclusionThe study showed disparities in HPV vaccination by SES, with the highest HOUSES quartiles associated with increased rates of initiating and even greater likelihood of completing the series. HOUSES data may be used to target and tailor HPV vaccination interventions to undervaccinated populations.     

Variability in non-core vaccination rates of dogs and cats in veterinary clinics across the United States

Vaccination guidelines for dogs and cats indicate that core vaccines (for dogs, rabies, distemper, adenovirus, parvovirus; for cats, feline parvovirus, herpes virus-1, calicivirus) are essential to maintain health, and that non-core vaccines be administered according to a clinician’s assessment of a pet’s risk of exposure and susceptibility to infection. A reliance on individual risk assessment introduces the potential for between-practice inconsistencies in non-core vaccine recommendations. A study was initiated to determine non-core vaccination rates of dogs (Leptospira, Borrelia burgdorferi, Bordetella bronchiseptica, canine influenza virus) and cats (feline leukemia virus) in patients current for core vaccines in veterinary practices across the United States. Transactional data for 5,531,866 dogs (1,670 practices) and 1,914,373 cats (1,661 practices) were retrieved from practice management systems for the period November 1, 2016 through January 1, 2020, deidentified and normalized. Non-core vaccination status was evaluated in 2,798,875 dogs and 788,772 cats that were core-vaccine current. Nationally, median clinic vaccination rates for dogs were highest for leptospirosis (70.5%) and B. bronchiseptica (68.7%), and much lower for canine influenza (4.8%). In Lyme-endemic states, the median clinic borreliosis vaccination rate was 51.8%. Feline leukemia median clinic vaccination rates were low for adult cats (34.6%) and for kittens and 1-year old cats (36.8%). Individual clinic vaccination rates ranged from 0 to 100% for leptospirosis, B. bronchiseptica and feline leukemia, 0–96% for canine influenza, and 0–94% for borreliosis. Wide variation in non-core vaccination rates between clinics in similar geographies indicates that factors other than disease risk are driving the use of non-core vaccines in pet dogs and cats, highlighting a need for veterinary practices to address gaps in patient protection. Failure to implement effective non-core vaccination strategies leaves susceptible dogs and cats unprotected against vaccine-preventable diseases.     

Prophylactic and therapeutic vaccine against Pseudomonas aeruginosa keratitis using bacterial membrane vesicles

PurposePseudomonas aeruginosa (P. aeruginosa) infection is one of the major causes of keratitis. However, effective prophylactic and therapeutic vaccines against P. aeruginosa keratitis have yet to be developed. In this study, we explored the use of P. aeruginosa membrane vesicles (MVs) as a prophylactic vaccine as well as the use of immune sera derived from P. aeruginosa MV-immunized animals as a treatment for P. aeruginosa corneal infections in C57BL/6 mice.MethodsC57BL/6 mice were intramuscularly immunized with P. aeruginosa MVs; the mouse corneas were then scarified and topically infected with several P. aeruginosa strains, followed by determination of corneal clinical score and corneal bacterial load. Next, immune sera derived from P. aeruginosa MV-immunized ICR mice were administered intraperitoneally to naïve C57BL/6 mice, followed by topical P. aeruginosa challenge. Finally, the immune sera were also used as a topical treatment in the mice with established P. aeruginosa corneal infections.ResultsP. aeruginosa-specific IgG and IgA antibodies induced by intramuscular immunization were detected not only in the sera but also in the eye-wash solution. Both active and passive immunization significantly inhibited P. aeruginosa corneal infection. Finally, topical treatment with immune sera in the mice with established P. aeruginosa corneal infections notably decreased the corneal clinical score and corneal bacterial load.ConclusionsP. aeruginosa keratitis can be attenuated by vaccination of P. aeruginosa MVs and topical application of P. aeruginosa MV-specific immune sera.     

The utilisation of vaccines in humanitarian crises, 2015–2019: A review of practice

BackgroundThe risk factors that emerge with the onset and protraction of humanitarian crises leave populations at a heightened risk of excess morbidity and mortality from vaccine-preventable diseases (VPDs). There is currently little clarity on which vaccines are being used in crises throughout the world, and whether vaccination decisions correspond to local disease threats. This review aimed to collect and analyse such information.MethodsWe reviewed vaccination services from January 2015 to June 2019 across all 25 humanitarian responses that had an activated coordination mechanism during this period. A range of online sources and informants within the humanitarian sector were consulted to compile data on which vaccines were provided in each crisis, and the modality and timing of vaccine provision. The package of vaccination services since the start of each crisis was then compared with local disease burden (baseline + excess due to crisis-emergent risk factors).ResultsThe range of vaccines used in humanitarian crises appears limited. When offered, vaccines were primarily delivered through the pre-existing routine schedule, with few supplementary actions taken in recognition of the need for rapidly enhancing population immunity. Vaccine packages mostly did not address the actual range of VPDs that likely accounted for substantial disease risk.ConclusionsThis review suggests inconsistencies and inequities in vaccine provision to crisis-affected populations. A consistent, standardised and broader approach to vaccine use in crises is needed.