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.     

Barriers to vaccination in Latin America: A systematic literature review

Current vaccination coverage rates in Latin America and the Caribbean (LAC) are lower than the region-wide rates set by the Pan American Health Organization. To improve vaccination uptake, it is crucial to identify barriers to vaccination. We conducted a systematic literature review to identify the key barriers to vaccination in the LAC region, and to classify and quantify factors affecting vaccination coverage using the barrier categories outlined by the Strategic Advisory Group of Experts (SAGE) working group. We mapped knowledge gaps in the understanding of region-specific and population-specific vaccine hesitancy. Nine databases (Medline via PubMed, Web of Science, LILACS, MedCarib, SciELO, Scopus, PATH, SAGE Online and Google Scholar) were searched for articles published in English, Spanish and Portuguese up to 15 July 2017. A total of 6867 articles were identified of which 75 were included in the review. Majority of the articles were quantitative in nature and nearly half from Brazil. Many other countries in LAC have limited published evidence on barriers to vaccination. The most commonly investigated target population was parents (of children <8 years of age [yoa] and adolescents 9–10 yoa) but there was a balance in the number of publications that reported on influenza, childhood and human papillomavirus vaccination. There was limited direct evidence which reported insights on the new generation of childhood vaccines (pneumococcal or meningococcal vaccines) or studies targeting adolescents and pregnant women. Among the SAGE barrier categories, ‘individual/group influences’ were the most frequently reported barrier category (68%) followed by ‘contextual influences’ (47%). Adverse socioeconomic factors, a low level of education, lack of awareness of diseases and their vaccines, religious and cultural beliefs are commonly cited as obstacles to vaccination acceptance. Additional evidence is needed to fully understand the barriers to vaccination for different target populations, countries in the region and specific vaccine types.     

Varicella-zoster-virus vaccination of immunosuppressed children with inflammatory bowel disease or autoimmune hepatitis: A prospective observational study

Background and aimsChildren with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS).MethodsThis prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response.ResultsA total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3–16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination.All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn’s disease the day after vaccination.The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078).ConclusionsVZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).     

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.     

COVID-19 vaccination hesitancy in people affected by diabetes and strategies to increase vaccine compliance: A systematic narrative review and meta-analysis

IntroductionPeople affected by diabetes are at higher risk for complications from certain vaccine-preventable diseases. Suboptimal vaccination coverages are reported in this population sub-group. The purpose of this study is to estimate the proportion of diabetic patients who express hesitation to the COVID-19 vaccine worldwide.MethodsSeven studies were included in the meta-analysis and systematic review, selected from scientific articles available in the MEDLINE/PubMed, Google Scholar and Scopus databases from 2020 to 2022. The following terms were used for the search strategy: (adherence OR hesitancy OR compliance OR attitude) AND (covid* OR SARS*) AND (vaccin* OR immun*) AND (diabet*).ResultsThe vaccine hesitation rate among persons with diabetes was 27.8 % (95 %CI = 15.6–41.9 %). In the comparison of vaccine hesitancy between sexes and educational status, the RRs were 0.90 (95 %CI = 0.71–1.15) and 0.88 (95 %CI = 0.76–1.02), respectively. The main reasons of unwillingness were lack of information, opinion that the vaccine was unsafe or not efficient, and fear of adverse events.ConclusionsIn order to achieve a high vaccination coverage, multifactorial approach is needed, which requires major social, scientific and health efforts. The success of the vaccination campaign in this population depends on the capillarity and consistency of the interventions implemented.     

Ending risk-group HBV vaccination for MSM after the introduction of universal infant HBV vaccination: A mathematical modelling study

BackgroundRisk-group HBV vaccination for men who have sex with men (MSM) was introduced in the Netherlands in 2002, followed by universal infant vaccination in 2011, that will enable termination of risk-group vaccination over time. The introduction of pre-exposure prophylaxis (PrEP) for HIV prevention might result in increased HBV testing and vaccination against HBV. The aim of this study was to investigate the impact of the transition from risk-group to universal HBV vaccination, accounting for improvements in HBV testing and treatment, as well as the introduction of PrEP.MethodsWe developed a mathematical model for HBV transmission among MSM. Universal vaccination was modelled by assigning some MSM (5–15% in 2028 increasing to 80–90% in 2033 and thereafter) to be vaccinated when they become sexually active. We investigated different scenarios assuming 0.5% extra vaccination rate and 0.5% extra testing rate due to PrEP consultations; and 5% of HIV-negative MSM on PrEP, that will reduce the probability of HBV acquisition by 88%.ResultsUniversal vaccination resulted in a reduction of 24% (interquartile range; 22–25%) of the total number of HBV infections among MSM estimated to occur from 2020 to 2070. With universal vaccination, terminating risk-group vaccination in 2030 or 2040 resulted in 30% or 10% more HBV infections over 2020–2070, respectively, compared to continuation of risk-group vaccination until 2070. With PrEP and continued risk-group vaccination, the total number of HBV infections over 2020–2070 was reduced by 13%.ConclusionsUniversal HBV vaccination can lead to a major reduction in HBV incidence among MSM in the future. The reduction becomes smaller when ending risk-group HBV vaccination, but larger by PrEP use for HIV prevention. Efforts to keep high levels of HBV vaccination, testing, and treatment have to be continued in the coming decades in order to eliminate HBV as a health threat for MSM.     

Modelling a cost-effective vaccination strategy for the prevention of varicella and herpes zoster infection: A systematic review

BackgroundVaricella zoster virus (VZV) and its re-emergence as herpes zoster (HZ) is associated with significant morbidity and mortality. While studies show that VZV vaccination is effective in reducing VZV incidence, many decision makers have not added VZV to their vaccination schedule, largely due to uncertainty surrounding the effect of VZV vaccination on HZ incidence (exogenous boosting, EB), and the cost-effectiveness (CE) of vaccination.MethodsA systematic review was conducted to identify the current published evidence of CE of VZV vaccination strategies where both VZV and HZ incidence were modelled.ResultsSix studies (one published in 2003 and five between 2010 and 2019), were identified with all conducting cost-utility analysis using a dynamic transmission modelling approach and assuming EB. All predicted that mass infant VZV vaccination would rapidly reduce VZV incidence, but HZ incidence would increase. Compared with no-vaccination, the CE of VZV vaccination strategies ranged from higher costs and poorer outcomes (dominated), towards CE (incremental cost-effectiveness ratios of between $7,000 to $61,000 USD), or lower cost and better outcomes (dominant). However, without EB, HZ incidence immediately dropped below pre-vaccination levels making VZV vaccination quickly CE and/or dominant to a no vaccination strategy.ConclusionsCurrent models are sensitive to assumptions of EB suggesting that future studies consider an agent-based modelling approach to address the individual nature of variables that determine the infectiousness of VZV.     

Efficacy,immunogenicity, and safety of available vaccines in children on biologics: A systematic review and meta-analysis

Vaccinations are essential for preventing infectious diseases in children with chronic diseases as they have increased risk of infection from frequent use of biologics. Response to immunizations in this group is not well known.ObjectiveA systematic review was performed to evaluate three primary outcomes: efficacy; immunogenicity; and safety of vaccines in children with chronic conditions treated with biologics.MethodsThe protocol for our systematic review and meta-analysis was registered and published with PROSPERO. We searched electronic bibliographic databases for studies published from 2009 to 2019, focusing on vaccinations in children with chronic conditions treated with biologics.ResultsWe retrieved 532 records. Thirty-one full-text articles were selected, and 14 were included in the meta-analysis. No significant publication bias was found. Efficacy: limited data are available regarding the efficacy of vaccination, as most studies have focused on immunogenicity as surrogate outcome for efficacy. Immunogenicity: patients receiving anti-TNF-alpha therapy had a statistically significant risk of poor seroconversion (p = 0.028) and seroprotection by the serotype B influenza vaccine [inflammatory bowel disease (IBD) p = 0.013; juvenile idiopathic arthritis (JIA) p = 0.004]. We found adequate responses with H1N1 and H3N2 serotypes. Few studies existed for pneumococcal, hepatitis A virus, hepatitis B virus, varicella-zoster virus, Measles Mumps Rubella virus, and multiple vaccine administration. Safety: vaccine administration was not associated with serious side effects, but JIA patients on anti-TNF alpha therapy had a statistically significant risk of presenting with myalgia or arthralgia postinfluenza vaccine (p = 0.014).ConclusionsMore evidence concerning efficacy, immunogenicity, and safety of vaccinations is needed to guide physicians in the vaccine decision process for this pediatric population.     

Ten-year follow-up on efficacy,immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine or one dose of monovalent varicella vaccine: Results from five East European countries

BackgroundWe assessed the 10-year efficacy, immunogenicity and safety of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV) or one dose of a monovalent varicella vaccine (V) in children from Czech Republic, Lithuania, Poland, Romania and Slovakia.MethodsThis was a phase IIIB follow-up of an observer-blind, randomized, controlled trial (NCT00226499). In phase A, healthy children aged 12–22 months from 10 European countries were randomized in a 3:3:1 ratio to receive two doses of MMRV (MMRV group), one dose of MMR followed by one dose of V (MMR + V group), or two doses of MMR (MMR; control group), 42 days apart. Vaccine efficacy (VE) against varicella (confirmed by viral DNA detection or epidemiological link and clinical assessment) was calculated with 95% confidence intervals using Cox proportional hazards regression model. Immunogenicity was assessed as seropositivity rates and geometric mean concentrations (GMCs). Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded.ResultsA total of 3705 children were vaccinated (1590, MMRV group; 1586, MMR + V group; 529, MMR group). There were 663 confirmed varicella cases (47, MMRV group; 349, MMR + V group; 267, MMR group). VE ranged between 95.4% (Lithuania) and 97.4% (Slovakia) in the MMRV group and between 59.3% (Lithuania) and 74% (Slovakia) in the MMR + V group. At year 10, seropositivity rates were 99.5%–100% in the MMRV group, 98%–100% in the MMR + V group and 50%–100% in the MMR control group, and the anti-VZV antibody GMCs were comparable between MMRV and MMR + V groups. The occurrence of solicited and unsolicited AEs was similar across groups and no SAE was considered as vaccination-related. No new safety concerns were identified.ConclusionsOur results indicated that two doses of varicella zoster virus-containing vaccine provided better protection than one dose against varicella and induced antibody responses that persisted 10 years post-vaccination.     

Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis

BackgroundThe relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID.MethodsPubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis.ResultsSix observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2–66.6; female, 9.0–67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2–85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45–0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43–0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41–0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47–0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3–73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1–42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination.ConclusionsCOVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.     

Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis

BackgroundSerotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease.MethodsWe performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data.ResultsTwo published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2–75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7–76.9%]). No heterogeneity was observed.ConclusionsCurrently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.     

Dynamics of G2P[4] strain evolution and rotavirus vaccination: A review of evidence for Rotarix

Rotavirus (RV) gastroenteritis is a vaccine-preventable disease that creates high medical and economic burden in both developed and developing countries. Worldwide, more than 100 countries have introduced RV vaccines in their national immunization programs, and the remarkable impact of reducing the burden of severe childhood gastroenteritis has been unequivocally demonstrated. Currently, 2 oral vaccines (Rotarix, GSK and RotaTeq, Merck) are widely utilized. Recent temporary increases in the relative prevalence of G2P[4] RV strains have been observed in countries implementing RV vaccination. This comprehensive literature review aims to provide an insight on RV genotype evolution in the context of mass vaccination with Rotarix, particularly in the case of G2P[4]. In the post-vaccine era, strain surveillance data indicated temporal and spatial changes in countries both with and without RV vaccination programs. Annual fluctuations in G2P[4] prevalence seem to occur naturally, with no substantial differences between countries using Rotarix, RotaTeq or mixed vaccination programs. Moreover, Rotarix has been shown to be efficacious and effective against gastroenteritis caused by non-vaccine strains, including G2P[4]. These data indicate that shifts in RV genotype distribution are likely to constitute an inherent process of virus evolution to infect the human gut. Following RV vaccine introduction, incidences of RV gastroenteritis declined dramatically and mass vaccination will likely maintain this status, despite possible fluctuations in the relative distribution of genotypes. There is no conclusive evidence of unusual burst of new or vaccine-escape strains since global RV vaccines use. The emergence of strains with a potential to increase the current burden of RV disease should be continuously monitored and can only be established by exhaustive characterization of strains, including whole genomic sequencing. Given the natural fluctuations in RV strains over time, caution is advised when interpreting temporal changes in RV strain dynamics, as they could mistakenly be attributed to vaccination.     

Cost-effectiveness of human papillomavirus vaccination in girls living in Latin American countries: A systematic review and meta-analysis

BackgroundCervical cancer is a major public health problem in Latin America. Cost-effectiveness studies help stakeholders with decisions regarding human papillomavirus (HPV) vaccination programs, one of the main prevention measures. Our objective was to synthesize the results of cost-effectiveness studies of HPV vaccination in girls, to understand factors influencing cost-effectiveness in the region.MethodsWe systematically searched databases as well as repositories from conferences, Ministries of Health and Health Technology Assessment offices. Incremental cost-effectiveness ratios (ICERs) were extracted, with data converted to international dollars (I$) and inflated to 2019 values. We used the gross domestic product per capita as threshold for judging the cost-effectiveness of vaccination. We calculated the geometric mean ICER by type of vaccine, whether screening (cytology or HPV test) was used as comparator, effectiveness measure, perspective, source of funding, year of cost, and country.ResultsWe found 24 studies. Despite the methodological differences, most studies concluded that HPV vaccination of girls in Latin American countries was either cost-saving or cost-effective. The mean ICER was I$ 3,804 for the bivalent vaccine, I$ 640 for the quadrivalent and I$ 358 for a generic HPV-16/18 vaccine. The mean ICER was lower in the studies that used HPV DNA test instead of cytology (I$ 122 vs I$ 1,841) as comparator; used the societal perspective (I$ 235 vs. I$ 1,986); were funded by non-profit sources instead of by pharmaceutical industry (I$ 421 vs. I$ 2,676); and used costs obtained prior to 2008 (I$ 365 vs I$ 1,415). We observed great variation in the mean ICERs by effectiveness measure (I$ 402 for per disability adjusted life years, I$ 461 for life year saved, and I$ 1,795 for quality adjusted life years).ConclusionsMost studies concluded that HPV vaccination of girls in Latin America countries was cost-saving or cost-effective, despite heterogeneity between models.     

Body mass index and vaccine responses following influenza vaccination during pregnancy

Background and AimsInfluenza vaccination is recommended by the World Health Organisation for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza infection. Various factors can influence vaccine immunogenicity, with obesity being one factor implicated in varied responses. This study aimed to investigate the impact of body mass index (BMI) on vaccine responses following influenza vaccination during pregnancy.MethodsPregnant women attending the Women’s and Children’s Hospital in South Australia during 2014–2016 were invited to participate. Participant’s clinical and demographic factors were recorded prior to administration of licensed seasonal influenza vaccination. Blood samples were collected before and one month post-vaccination to measure antibody responses by haemagglutination inhibition (HI) assay. Seroprotection was defined as a post-vaccination HI titre ≥ 1:40. Regression models assessed associations with failure to achieve seroprotective antibodies to H1, H3, and B influenza strains.ResultsA total of 96 women were enrolled in the study at a median gestation of 22 weeks with a BMI range of 18–49 kg/m². Paired sera samples were available for 90/96 (94%). Most pregnant women (72/90, 80%) demonstrated seroprotective antibody titres to all three influenza vaccine antigens (A(H1N1)pdm09, A(H3N2), B/Yamagata) following vaccination. Compared with women with BMI < 30 kg/m², those with high BMI were less likely to fail to achieve seroprotective antibodies, however this was not statistically significant (RR 0.42, 95% CI 0.11–1.68; p = 0.22). A greater proportion of women vaccinated during their second (47/53, 93%) or third trimester (18/25, 72%) demonstrated seroprotection to all three vaccine antigens following vaccination compared with women vaccinated during their first trimester (7/12, 58%).ConclusionHigh BMI did not impair seroprotection levels following influenza vaccination in pregnant women. Gestation at vaccination may be an important consideration for optimising vaccine protection for pregnant women and their newborns. Further assessment of first trimester influenza vaccine responses is warranted.     

A systematic review of pneumococcal conjugate vaccine impact on pneumococcal nasopharyngeal colonisation density in children under 5 years of age

BackgroundHigh pneumococcal carriage density has been associated with severe pneumonia in some settings. The impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal carriage density has been variable. The aim of this systematic literature review is to describe the effect of PCV7, PCV10 and PCV13 on pneumococcal colonisation density in children under five years old.MethodsWe included peer reviewed English literature published between 2000 and 2021 to identify relevant articles using Embase, Medline and PubMed. Original research articles of any study design in countries where PCV has been introduced/studied were included. Quality (risk) assessment was performed using tools developed by the National Heart Brain and Lung Institute for inclusion in this review. We used a narrative synthesis to present results.ResultsTen studies were included from 1941 articles reviewed. There were two randomised controlled trials, two cluster randomised trials, one case control study, one retrospective cohort study and four cross sectional studies. Three studies used semiquantitative culture methods to determine density while the remaining studies used quantitative molecular techniques. Three studies reported an increase in density and three studies found a decrease in density among vaccinated compared with unvaccinated children. Four studies found no effect. There was considerable heterogeneity in the study populations, study design and laboratory methods.ConclusionThere was no consensus regarding the impact of PCV on pneumococcal nasopharyngeal density. We recommend the use of standardised methods to evaluate PCV impact on density.     

Incidence of herpes zoster among varicella-vaccinated children,by number of vaccine doses and simultaneous administration of measles,mumps, and rubella vaccine

IntroductionChildren may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration.MethodsIn six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003–2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR.ResultsAmong 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups.ConclusionsHZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.     

Response to hepatitis B vaccination is co-determined by HLA-DPA1 and -DPB1

Background and aimsNo report explored the combined effects of HLA-DPA1 and -DPB1 with long-term response to hepatitis B (HB) vaccination (HBVac). The specific aims of the study were to assess the combined effects and relative contributions of DPA1 and DPB1 genes.MethodsThe cases were 152 adolescents who had undetectable (<1.0 mIU/mL) post-booster anti-HBs titers and the controls were adolescents who had residual anti-HBs ≥ 10 mIU/mL at aged 16 years (n = 207) or had detectable (≥1.0 mIU/mL) anti-HBs titers after booster HBVac (n = 481). HLA-DPA1 and -DPB1 genotypes were determined by sequence-based typing.ResultsHLA-DPA1*01:03:01 was correlated with lower ORs of undetectable anti-HBs titers, while -DPA1*02:02:02 and -DPB1*05:01:01 were correlated with higher ORs. The ORs for HLA-DPA1*01:03:01-DPB1*05:01:01 and DPA1*02:02:02-DPB1*protective combinatory types were significantly less than 1.0. As compared with subjects who had no protective allele, the adjusted ORs (95% CI) were 0.545 (0.328–0.906), 0.350 (0.174–0.702), and 0.122 (0.058–0.257), for subjects who had protective alleles on DPA1only, DPB1 only, and both genes, respectively. Analyses of amino acid polymorphisms showed that subjects who carried Arg81-Pro158-Val191-Pro259α + Met234β and Gln62-Arg82α + Met234β combinations had 4.3-to-4.6 folds of risks.ConclusionBoth DPA1 and DPB1 genes contribute to the persistence of immunological response to primary infantile HBVac. The effects of HLA-DP risk alleles were dominated by the protective alleles and there were significant gene-gene interactions. Our findings provide evidences for the design of more potent HB vaccine.     

Prevalence of indications for adult hepatitis A vaccination among hepatitis A outbreak-associated cases,Three US States, 2016–2019

BackgroundSafe and effective hepatitis A vaccines have been recommended in the United States for at-risk adults since 1996; however, adult vaccination coverage is low.MethodsAmong a random sample of adult outbreak-associated hepatitis A cases from three states that were heavily affected by person-to-person hepatitis A outbreaks, we assessed the presence of documented Advisory Committee on Immunization Practices (ACIP) indications for hepatitis A vaccination, hepatitis A vaccination status, and whether cases that were epidemiologically linked to an outbreak-associated hepatitis A case had received postexposure prophylaxis (PEP).ResultsOverall, 74.1% of cases had a documented ACIP indication for hepatitis A vaccination. Fewer than 20% of epidemiologically linked cases received PEP.ConclusionsEfforts are needed to increase provider awareness of and adherence to ACIP childhood and adult hepatitis A vaccination and PEP recommendations in order to stop the current person-to-person hepatitis A outbreaks and prevent similar outbreaks in the future.     

Hepatitis A antibody persistence 8 and 10 years after 1-dose and 2-dose vaccination in children from Panama

BackgroundHepatitis A virus (HAV) remains a global public health concern, which is potentially growing in Latin America, due to an expected shift from high to intermediate endemicity levels. The use of HAV vaccines in pediatric national immunization programs (NIPs), either as a 2-dose or a 1-dose schedule, has been explored in Latin American countries; however, evidence demonstrating long-term protection in this population is limited in the region. We evaluated long-term antibody persistence following a 1-dose partial series and the recommended 2-dose schedule used in Panama’s pediatric NIP.MethodsTwo independent cross-sectional serological surveys were conducted at year 8 (Y8) and Y10 following vaccination under the NIP with 1 or 2 doses of an inactivated HAV vaccine (Havrix, GSK). Seropositivity (anti-HAV antibody concentration ≥ 15 mIU/mL) rates and antibody geometric mean concentrations (GMCs) were assessed at each serosurvey. Non-inferiority of 1 dose versus 2 doses was also explored.ResultsThis study (NCT02712359) included 600 and 599 children at Y8 and Y10 post-vaccination, respectively. Seropositivity rates were 74.3% (95% confidence interval [CI]: 69.0; 79.2) and 97.7% (95% CI: 95.3; 99.1) at Y8 and 71.9% (95% CI: 66.4; 76.9) and 96.3% (95% CI: 93.5; 98.2) at Y10, in the 1-dose and 2-dose groups, respectively. Antibody GMCs were lower in the 1-dose versus the 2-dose group in both surveys. Non-inferiority was not demonstrated since the lower limit of the 2-sided 95% CI for the between-group difference in seropositivity rates (1-dose minus 2-dose) was < ?10%.ConclusionAnti-HAV antibody persistence was observed in lower percentages of children receiving 1 dose versus 2 doses of Havrix, at 8 and 10 years post-vaccination in Panama. Further investigations are needed to confirm antibody persistence and conclude on the protection afforded beyond 10 years in the pediatric population in Latin America.