Variations in CCL3L gene cluster sequence and non-specific gene copy numbers

<p>Abstract</p> <p>Background</p> <p>Copy number variations (CNVs) of the gene CC chemokine ligand 3-like1 (<it>CCL3L1</it>) have been implicated in HIV-1 susceptibility, but the association has been inconsistent. <it>CCL3L1 </it>shares homology with a cluster of genes localized to chromosome 17q12, namely <it>CCL3</it>, <it>CCL3L2</it>, and, <it>CCL3L3</it>. These genes are involved in host defense and inflammatory processes. Several CNV assays have been developed for the <it>CCL3L1 </it>gene.</p> <p>Findings</p> <p>Through pairwise and multiple alignments of these genes, we have shown that the homology between these genes ranges from 50% to 99% in complete gene sequences and from 70-100% in the exonic regions, with <it>CCL3L1 </it>and <it>CCL3L3 </it>being identical. By use of MEGA 4 and BioEdit, we aligned sense primers, anti-sense primers, and probes used in several previously described assays against pre-multiple alignments of all four chemokine genes. Each set of probes and primers aligned and matched with overlapping sequences in at least two of the four genes, indicating that previously utilized RT-PCR based CNV assays are not specific for only <it>CCL3L1</it>. The four available assays measured median copies of 2 and 3-4 in European and African American, respectively. The concordance between the assays ranged from 0.44-0.83 suggesting individual discordant calls and inconsistencies with the assays from the expected gene coverage from the known sequence.</p> <p>Conclusions</p> <p>This indicates that some of the inconsistencies in the association studies could be due to assays that provide heterogenous results. Sequence information to determine CNV of the three genes separately would allow to test whether their association with the pathogenesis of a human disease or phenotype is affected by an individual gene or by a combination of these genes.</p

The Field-Testing of a Novel Integrated Mapping Protocol for Neglected Tropical Diseases

Neglected tropical diseases (NTDs) cause significant physical debilitation, lowered economic productivity, and social ostracism for afflicted individuals. Five NTDs with available preventive chemotherapy: lymphatic filariasis (LF), trachoma, schistosomiasis, onchocerciasis and the three soil-transmitted helminths (STH); have been targeted for control or elimination, but resource constraints in endemic countries have impeded progress toward these goals. We have developed an integrated mapping protocol, Integrated Threshold Mapping (ITM) for use by Ministries of Health to decide where public health interventions for NTDs are needed. We compared this protocol to the World Health Organizations disease-specific mapping protocols in Mali and Senegal. Results from both methodologies indicated the same public health interventions for trachoma, LF and STH, while the ITM methodology resulted in a more targeted intervention for schistosomiasis. Our study suggests that the integrated methodology, which is also less expensive and logistically more feasible to implement, could replace disease-specific mapping protocols in resource-poor NTD-endemic countries

Identifying characteristics that enable resilient immunisation programmes: a scoping review

Objectives: The COVID-19 pandemic highlighted the fragility of immunisation programmes and resulted in a significant reduction in vaccination rates, with increasing vaccine-preventable disease outbreaks consequently reported. These vulnerabilities underscore the importance of resilient immunisation programmes to ensure optimal performance during crises. To date, a framework for assessing immunisation programme resilience does not exist. We conducted a scoping review of immunisation programmes during times of crisis to identify factors that characterise resilient immunisation programmes, which may inform an Immunisation Programme Resilience Tool. Design: Scoping review design followed the Arksey and O’Malley framework, and manuscript reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. Data sources: CINAHL, CENTRAL, Embase, Google Scholar, MEDLINE, PsycINFO and Web of Science and databases were searched between 1 January 2011 and 2 September 2023. Citation searching of identified studies was also performed. Eligibility criteria: We included primary empirical peer-reviewed studies that discussed the resilience of immunisation programme to crises, shocks or disruptions. Data extraction and synthesis: Two independent reviewers screened records and performed data extraction. We extracted data on study location and design, crisis description, and resilience characteristics discussed, and identified evidence gaps in the literature. Findings were synthesised using tabulation and an evidence gap map. Results: Thirty-seven studies met the eligibility criteria. These studies captured research conducted across six continents, with most concentrated in Africa, Asia and Europe. One study had a randomised controlled trial design, while 36 studies had observational designs (15 analytical and 21 descriptive). We identified five characteristics of resilient immunisation programmes drawing on the Health System Resilience Index (Integration, Awareness, Resource Availability and Access, Adaptiveness and Self-regulation) and several evidence gaps in the literature. Conclusions: To our knowledge, no immunisation programme resilience tool exists. We identified factors from the Health System Resilience Index coupled with factors identified through primary empirical evidence, which may inform development of an immunisation programme resilience tool

Public health impact and return on investment of Belgium’s pediatric immunization program

ObjectiveWe evaluated the public health impact and return on investment of Belgium’s pediatric immunization program (PIP) from both healthcare-sector and societal perspectives.MethodsWe developed a decision analytic model for 6 vaccines routinely administered in Belgium for children aged 0–10 years: DTaP-IPV-HepB-Hib, DTaP-IPV, MMR, PCV, rotavirus, and meningococcal type C. We used separate decision trees to model each of the 11 vaccine-preventable pathogens: diphtheria, tetanus, pertussis, poliomyelitis, Haemophilus influenzae type b, measles, mumps, rubella, Streptococcus pneumoniae, rotavirus, and meningococcal type C; hepatitis B was excluded because of surveillance limitations. The 2018 birth cohort was followed over its lifetime. The model projected and compared health outcomes and costs with and without immunization (based on vaccine-era and pre–vaccine era disease incidence estimates, respectively), assuming that observed reductions in disease incidence were fully attributable to vaccination. For the societal perspective, the model included productivity loss costs associated with immunization and disease in addition to direct medical costs. The model estimated discounted cases averted, disease-related deaths averted, life-years gained, quality-adjusted life-years gained, costs (2020 euros), and an overall benefit–cost ratio. Scenario analyses considered alternate assumptions for key model inputs.ResultsAcross all 11 pathogens, we estimated that the PIP prevented 226,000 cases of infections and 200 deaths, as well as the loss of 7,000 life-years and 8,000 quality-adjusted life-years over the lifetime of a birth cohort of 118,000 children. The PIP was associated with discounted vaccination costs of €91 million from the healthcare-sector perspective and €122 million from the societal perspective. However, vaccination costs were more than fully offset by disease-related costs averted, with the latter amounting to a discounted €126 million and €390 million from the healthcare-sector and societal perspectives, respectively. As a result, pediatric immunization was associated with overall discounted savings of €35 million and €268 million from the healthcare-sector and societal perspectives, respectively; every €1 invested in childhood immunization resulted in approximately €1.4 in disease-related cost savings to the health system and €3.2 in cost savings from a societal perspective for Belgium’s PIP. Estimates of the value of the PIP were most sensitive to changes in input assumptions for disease incidence, productivity losses due to disease-related mortality, and direct medical disease costs.ConclusionBelgium’s PIP, which previously had not been systematically assessed, provides large-scale prevention of disease-related morbidity and premature mortality, and is associated with net savings to health system and society. Continued investment in the PIP is warranted to sustain its positive public health and financial impact

A review of factors influencing vaccination policies and programs for older adults globally

Policies and programs to increase vaccine coverage rates among adults 50 years of age or older are limited and vaccine uptake is often suboptimal. Our review evaluated evidence on the effectiveness and success of adult-targeted vaccination interventions and identified literature gaps. Literature was retrieved (2021) from PubMed, Embase, and Google Scholar databases. Outcomes assessed included data on an intervention’s effectiveness and impact on vaccine uptake. Interventions were characterized thematically: affordability (n = 9), awareness (n = 25), and vaccination access (n = 6); and included influenza, pneumococcal, tetanus-containing, and herpes zoster vaccines. Interactive interventions directed toward patients, including provider-led educational initiatives and provider recommendations showed more positive associations than less interactive interventions, such as posters and reminder-recall letters. Provider interventions, including awareness campaigns, incentives, affordability efforts, or vaccination site expansion generally showed positive associations. Combining interventions was found to be successful across several studies. Barriers and interventions varied for population subgroups, therefore, tailoring programs is critical

Drivers of and barriers to routine adult vaccination: A systematic literature review

We performed a systematic literature review in PubMed and Embase (2016–2021) to investigate the drivers of and barriers to routine vaccination in adults aged 50 and older globally. A thematic assessment identified three categories across 61 publications: sociodemographic, health-related, and attitudinal. The most common sociodemographic determinants (factors identified in studies; n = 47) associated with vaccination uptake were economic status, age, education, and household composition, which had mixed effects on vaccine uptake. For health-related determinants (n = 27), individuals with comorbidities and health care consumption were the most common factors, both increased vaccine uptake. The most common attitudinal factors (n = 42) were self-efficacy, provider or other’s recommendations, and vaccine-preventable disease awareness; across studies, all attitude factors had a positive effect, unlike the sociodemographic and health status categories. Findings suggest that patient and provider awareness and education campaigns are effective ways to increase uptake of routine vaccinations in older adults

Attitudes and Beliefs around the Value of Vaccination in the United States

Despite the benefits of immunization, differences in attitudes persist toward vaccines. We captured individuals’ perceptions of vaccines and vaccination across the United States (US) to inform vaccine-related policy development. A survey was completed by 5000 respondents from 10 states. Respondents were screened for inclusion, which included individuals ≥ 18 years of age that had received a vaccine or were unvaccinated but indicated a favorable or neutral attitude towards vaccinations. Participants were excluded if they indicated they did not support the idea of vaccinations. Questions explored perceptions of vaccines for all age groups. Among unvaccinated individuals, the most common concerns were about safety (38%). Most respondents (95%) highlighted the importance of state immunization programs for disease prevention. Access to health and immunization records and immunization information systems were important to 96% and 88% of respondents, respectively, for future health planning. Doctors and healthcare professionals (HCPs) were considered trusted sources for vaccine information (95%). Overall, respondents recognized the importance of vaccination, but documented concerns among the unvaccinated indicated a need for greater promotion regarding vaccine safety. Doctors and HCPs, as trusted information sources, should continue to and increasingly advocate for the importance of immunization to increase vaccine uptake

Vaccine uptake and barriers to vaccination among at-risk adult populations in the US

To reduce morbidity and mortality associated with vaccine-preventable diseases (VPD), it is imperative that vaccination programs are implemented and prioritized throughout all stages of life across all populations. This study aimed to determine vaccine uptake and barriers to vaccination against VPDs among at-risk adult populations in the United States. We conducted a systematic literature review for articles published between January 2010 and June 2020 and identified 153 publications. The review identified 17 at-risk populations. Vaccine uptake was suboptimal among many populations, with factors including age, gender, and disease severity, associated with uptake. This review identified several barriers that impact vaccine uptake among at-risk populations, with concerns over safety, vaccine costs, lack of insurance, and lack of provider recommendation commonly reported across populations. Embracing a national life-course immunization framework that integrates developing policies, guidelines, and education would be a step to addressing these barriers

Burden of vaccine-preventable diseases among at-risk adult populations in the US

Life-course immunization holds significant benefit for population health by reducing the burden of vaccine-preventable diseases (VPD) through vaccinating individuals at different stages and circumstances in life. The study aimed to determine the epidemiologic, clinical, economic, and societal burden of VPDs among at-risk adult subpopulations in the United States. A systematic literature review was conducted for articles published between January 2010 and June 2020, which identified 72 publications. There was heterogeneity in available epidemiology data, with the prevalence of VPDs ranging from 1.1% to 68.7%. Where the disease burden was described, outcomes were typically worse among high-risk subpopulations than in the general population. Several VPDs, including herpes zoster, meningococcal, and pneumococcal infections were associated with increased costs. This review suggests that subpopulations may not frequently interact with the healthcare system, or their risk factors may not be recognized by healthcare providers, and therefore individuals may not be appropriately targeted for vaccination