Population Coverage Research Articles

Lessons Learned from the COVID-19 Pandemic: Simulation of the Tuberculosis Epidemic as a Function of Population Coverage with Screening

The COVID-19 pandemic has led to the discontinuation of many support programs for tuberculosis patients worldwide, and lower coverage of population with screening for tuberculosis.The objective: To build a model describing the spread of tuberculosis depending on the population coverage with preventive screening, and to obtain a long-term forecast of the infection spread using this model.Subjects and Methods. We analyzed official statistical data on incidence, mortality, preventive screening coverage (PSC), and revalence of sputum smear-positive tuberculosis in the Russian Federation from 2008 to 2021. The model was built up based on fluctuations in those rates in 2020, when there was a sharp reduction in tuberculosis control interventions due to the COVID-19 pandemic. Statistical analysis was performed using the R Software (v.4.2.1).Results. A simple mathematical model describing the dependence of incidence and sputum smear-positive tuberculosis in the current year on sputum smear-positive tuberculosis in the past year and population coverage with preventive screening in the current and past years was built up. The adjusted coefficient of determination of the model (adjusted R-squared) was 0.9969, which meant that the model contained almost no random components. It showed that tuberculosis cases missed due to low population coverage with preventive screening lead to future spread of tuberculous infection and a significant increase in the number of new tuberculosis cases. Comparison of projected rates and data for 2022 demontrated correct formation of models. However, the projected rates were slightly higher than the actual rates for 2022 due to the influence of factors other than the population coverage with preventive screening for tuberculosis.Conclusions. The findings demonstrate the need for mass screening of the population in the context of significant spread of tuberculosis infection for timely detection of patients with sputum smear-positive tuberculosis.

Exploring dengue genome to design effective multi epitope-based peptide vaccine by immunoinformatics approach against all serotypes of dengue virus

Dengue fever is an acute tropical disease that is spread by Aedes species mosquitoes. It is a virus-mediated illness that causes headaches, fever, severe joint and muscle pain, swollen glands (lymphadenopathy), and rashes. Every year, 390 million people around the world suffer from it and ∼20 % die from cases that are left untreated. The virus is transmitted to humans by mosquito bites of infected Aedes species. When it gets into the body, its envelope protein attaches to the host cell surface receptor and initiates the viral infection cycle by the formation of a smooth coat with icosahedral symmetry. Due to its high mutation-prone nature and differences in protein sequences among serotypes, it is difficult to develop a stable vaccine suitable against all serotypes. In this study, a software-based vaccinology approach was used to design a vaccine construct against the envelope protein of all four subtypes of the dengue virus. This construct was designed by joining two epitopes of the protein. One epitope was taken from the envelope protein of DEN-2 which was conserved for DEN-1, DEN-2, and DEN-3, and another epitope from the same protein of DEN-4 serotype as the sequence composition of the protein is slightly different in these two groups of serotypes. Here, firstly 18 epitopes for dengue virus-1, 2, 3, and 12 epitopes for dengue virus-4 were retrieved based on the highest combined score of NetCTL server analysis of human leukocyte antigen (HLA) supertypes. Among them, the epitope MAILGDTAW has shown 100 % conservancy in strains of dengue virus 1, 2, 3, and KLRIKGMSY, TTAKEVALL, TPRSPSVEV, FRKGSSIGK, KTWLVHKQW have shown 100 % conservancy in dengue virus 4. In population coverage analysis, MAILGDTAW has shown 88.63 % and FRKGSSIGK has shown 90.72 % (highest among other DEN-4 epitopes) population coverage of the entire world population. These two epitopes along with their 15-mer extensions (MHCII binding peptides) were found as non-allergen and non-toxic. Finally, the two different 15-mer extensions (to get 100 % sequence conservancy) of the epitope MAILGDTAW and the 15-mer extension of the epitope FRKGSSIGK were put together using an EAAAK linker to construct the multi-epitope vaccine. In-vivo analysis of the proposed vaccine construct would aid in the development of a functional immune response that would eradicate dengue complications worldwide.

Introduction of an Efficient Multiepitopic Vaccine Against Different SARS -CoV -2 Strains: Reverse Vaccinology

Introduction: In recent years, COVID -19 has been recognized as a health threat. Despite vaccination, people still get the disease because the new variants have mutations in their genomes that allow them to bind to host receptors and evade the immune system’s responses. Therefore, the main aim of this study was to use bioinformatics tools to introduce a rapid and practical vaccine to fight against these diverse mutations in different SARS -CoV-2 strains. Method: To epitopes mapping, 32 different spike protein variants were retrieved. We then used the Immune Epitope Database (IEDB), NetCTL, and NetMHCIIpan to predict T and B cell epitopes. The vaccine based on protected epitopes was evaluated in terms of antigenicity, allergenicity, toxicity, solubility, physicochemical properties, population coverage, and secondary structure with relevant servers. Modeling using Robetta and docking with Toll -like receptor (TLR3) were performed using Cluspro, PatchDock, and FireDock, respectively. Results: After detailed evaluations, all the results confirmed the optimal quality of the vaccine. According to further investigations, this structure is similar to native proteins and there is a stable and strong interaction between the vaccine and the receptor. Based on molecular dynamics simulation, structural compactness and stability in binding were also observed. In addition, the immune simulation showed that the vaccine can stimulate immune responses similar to real conditions. Finally, codon optimization and in silico cloning confirmed efficient expression in Escherichia coli . Conclusion: Based on the obtained results, the designed multi -epitope vaccine can serve as a prophylactic candidate against SARS -CoV-2.

CMAIS-WOA: An Improved WOA with Chaotic Mapping and Adaptive Iterative Strategy

This paper proposes an improved whale optimization algorithm with chaotic mapping and adaptive iteration strategy (CMAIS-WOA). This algorithm addresses the issues of the WOA algorithm that is prone to local optimal solutions with low stability. CMAIS-WOA utilizes chaotic mapping to enhance the diversity and coverage of the initial population. Also, it adaptively adjusts the weight values based on the current distribution of whale populations and the fitness of search agents. In addition, CMAIS-WOA uses an improved nonlinear convergence factor to adjust the breadth-first and depth-first search during the optimization process. The performance of the proposed CMAIS-WOA is evaluated by using 13 classical benchmark functions and IEEE CEC2014 test suite. The experimental results show that CMAIS-WOA effectively improves the stability of the optimal solution and helps the algorithm to approach the global optimal solution. The method proposed in this paper contributes to the field of optimization which solves problems more powerfully and efficiently.

Hard-to-reach population groups in administrative sources: main challenges and future work

The paper deals with the concept and the definitions of hard-to-reach groups and the ways of capturing them in administrative sources, providing a detailed discussion of the meaning of hard-to-reach in the context of administrative sources and in relation to the traditional hard-to-count groups in censuses and surveys. The review of country practices shows that hard-to-reach populations in administrative data can be interpreted in different ways and that their definition is dependent on countries’ circumstances, though there are two main reasons for identifying a group as hard-to-reach in administrative sources. One of the interpretations is selecting some groups, typically considered difficult to reach with traditional survey methods (such as homeless, illegal immigrants or indigenous people) and then trying to capture them in registers to overcome the challenges of traditional field collection or to get more complete information. At first glance, administrative data might offer the potential to improve frame coverage for some target populations, but may also lead to other hard-to-reach or “hidden” populations for different population groups. Indeed, another interpretation refers to the incompleteness of registers or linked administrative databases, which makes some groups, such as children or elders, hard-to-reach and hence describe with data, due to time lag in reporting of some events or to other accuracy problems with the source itself. The paper summarizes the experience of national statistical offices in accessing hard-to-reach groups and describes problems and challenges in capturing them. It also proposes further possible work to improve access to hard-to-reach groups using administrative data.

Availability of basic first aid training for cardiac arrest for people with disabilities

Aim. Basic first aid digital training for cardiac arrest opens up opportunities for mass dissemination of knowledge, popularization and motivation of the population to provide assistance, and can also replace the theoretical part of classroom training, reducing the cost of training. However, due to poor design, such training may not be available to people with disabilities (PWD), who constitute a large population of more than one billion potential participants in first aid. The aim was to study the digital accessibility (web accessibility) of massive open online courses in cardiopulmonary resuscitation (CPR) for PWD.Material and methods. A search was carried out for free English-language online courses teaching the principles and rules of providing first aid in cardiac arrest. In addition, the digital content of online courses was assessed for compliance with the international Web Content Accessibility Guidelines (WCAG) 2.1.Results. All basic CPR online courses analyzed (n=28) were characterized by poor web accessibility. For each course, between 26,9% and 51,3% of the WCAG 2.1 guideline success criteria were not met. All courses have web accessibility errors related to text contrast and visual issues, lack of alternative text descriptions for non-text content, missing abbreviations, and web page layout issues that prevent the use of assistive technologies (such as text-to-speech software). Overall, none of the courses meet all of the criteria for the minimum acceptable level of compliance with WCAG 2.1 guidelines. The discovered problems of web accessibility can serve as serious, sometimes insurmountable barriers to the mastery of courses by students (including older people) with visual impairments, hearing loss, motor, cognitive and neurological disorders.Conclusion. All free mass online courses on basic CPR have deficiencies in the availability of digital content, which significantly complicate the learning of educational materials by PWD. The development of uniform guidelines for accessible educational content, along with the intensification of research and the implementation of organizational and methodological measures to ensure the availability of educational resources on first aid for various categories of the population, should help create equal opportunities for quality training. In addition, this should significantly expand the population coverage with training, and increase the frequency and effectiveness of first aid.

Generation of a bank of clinical-grade, HLA-homozygous iPSC lines with high coverage of the Spanish population

BackgroundInduced pluripotent stem cell (iPSC)-derived cell therapies are an interesting new area in the field of regenerative medicine. One of the approaches to decrease the costs of iPSC-derived therapies is the use of allogenic homozygous human leukocyte antigen (HLA)-matched donors to generate iPSC lines and to build a clinical-grade iPSC bank covering a high percentage of the Spanish population.MethodsThe Spanish Stem Cell Transplantation Registry was screened for cord blood units (CBUs) homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes. Seven donors were selected with haplotypes covering 21.37% of the haplotypes of the Spanish population. CD34-positive hematopoietic progenitors were isolated from the mononuclear cell fraction of frozen cord blood units from each donor by density gradient centrifugation and further by immune magnetic labeling and separation using purification columns. Purified CD34 + cells were reprogrammed to iPSCs by transduction with the CTS CytoTune-iPS 2.1 Sendai Reprogramming Kit.ResultsThe iPSCs generated from the 7 donors were expanded, characterized, banked and registered. Master cell banks (MCBs) and working cell banks (WCBs) from the iPSCs of each donor were produced under GMP conditions in qualified clean rooms.ConclusionsHere, we present the first clinical-grade, iPSC haplobank in Spain made from CD34 + cells from seven cord blood units homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes within the Spanish population. We describe their generation by transduction with Sendai viral vectors and their GMP-compliant expansion and banking. These haplolines will constitute starting materials for advanced therapy medicinal product development (ATMP).

THE RATIONALITY OF URBAN FINANCIAL NETWORK LAYOUT BASED ON POI DATA

Abstract. Financial outlets are branches or business outlets of financial institutions such as banks, investment and finance companies and insurance companies in cities, which are used to provide a variety of financial services and businesses. The location of financial outlets is usually determined on the basis of factors such as population density, commercial areas, residential areas and transportation convenience. As an important carrier of urban financial services, the rationality of the layout of financial outlets can reflect the financial needs and behavioral patterns of people in the city. Urban functional area is a product after urbanization, different from urban land use type which focuses on the classification of urban land use through natural conditions, urban functional area mainly analyzes the internal spatial structure of the city, focusing on the discernment of the dominant functions within the built-up area of the city. By categorizing urban functions such as residence, commercial service and industry, the spatial distribution of urban functions can be grasped to provide support for urban planning and development. Urban functional areas can reveal human behavior patterns, needs and preferences in different areas. The current research on financial outlets mainly focuses on the accessibility and coverage of financial outlets, and researchers treat financial outlets as spatially undifferentiated points, ignoring the problem of spatial heterogeneity of financial outlets within different functional zones. When studying the rationality of the layout of urban financial outlets, considering different functional zones within the city can better meet the financial needs of residents, enterprises and institutions in the region and improve the accessibility and convenience of financial services. Analyzing the comprehensive service capacity of financial outlets within different functional areas is obviously insufficient in the current study, which is not conducive to the configuration planning of financial outlets and the promotion of the accessibility of urban financial services. The wide application of Point of Interest (POI) data in spatial analysis provides a new perspective for the study of urban financial outlets, for this reason, this paper analyzes and researches the current situation and rationality of the spatial layout of financial outlets based on POI data, under the perspective of the functional areas of the city, and combined with the population travel vitality index. The Term Frequency-Inverse Document Frequency (TF-IDF) algorithm is used to process the POI data to generate the urban functional area, on the basis of which the travel vitality index in the city is calculated by combining the population coverage and road network density, so as to judge the reasonableness of the layout of urban financial outlets. This helps us to better understand the behavioral decision-making process and social interaction of human beings about financial life in the city, and provides guidance and decision-making support for urban financial layout planning, financial public services and financial policies.

Reverse vaccinology and immunoinformatics approach to design a chimeric epitope vaccine against Orientia tsutsugamushi

Scrub typhus is a vector-borne infectious disease caused by Orientia tsutsugamushi and it is reportedly associated with up to 20 % of hospitalized cases of febrile illnesses. The major challenge of vaccine development is the lack of identified antigens that can induce both heterotypic and homotypic immunity including the production of antibodies, cytotoxic T lymphocyte, and helper T lymphocytes. We employed a comprehensive immunoinformatic prediction algorithm to identify immunogenic epitopes of the 56-kDa type-specific cell membrane surface antigen and surface cell antigen A of O. tsutsugamushi to select potential candidates for developing vaccines and diagnostic assays. We identified 35 linear and 29 continuous immunogenic B-cell epitopes and 51 and 27 strong-binding T-cell epitopes of major histocompatibility complex class I and class II molecules, respectively, in the conserved and variable regions of the 56-kDa type-specific surface antigen. The predicted B- and T-cell epitopes were used to develop immunogenic multi-epitope candidate vaccines and showed to elicit a broad-range of immune protection. A stable interactions between the multi-epitope vaccines and the host fibronectin protein were observed using docking and simulation methods. Molecular dynamics simulation studies demonstrated that the multi-epitope vaccine constructs and fibronectin docked models were stable during simulation time. Furthermore, the multi-epitope vaccine exhibited properties such as antigenicity, non-allergenicity and ability to induce interferon gamma production and had strong associations with their respective human leukocyte antigen alleles of world-wide population coverage. A correlation of immune simulations and the in-silico predicted immunogenic potential of multi-epitope vaccines implicate for further investigations to accelerate designing of epitope-based vaccine candidates and chimeric antigens for development of serological diagnostic assays for scrub typhus.

Global Cardiac Surgical Volume and Gaps: Trends, Targets, and Way Forward

BackgroundMore than 1 million cardiac surgical procedures are estimated to occur yearly. Little is known about country-level procedural estimates and volumes needed to provide adequate population coverage. We evaluated annual cardiac procedural volumes for high-income countries and present target volumes for countries to work toward as part of universal health coverage agendas. MethodsAcademic and gray literature was searched for total annual volumes for high-income countries for all cardiac surgery, coronary artery bypass grafting (CABG), valvular surgery, and congenital heart surgery between 2010 and 2021. Matched populations were obtained from the World Bank World Development Indicators. Volume targets by country income group were proposed on the basis of published expert opinion and adjusted for cardiovascular disease burdens. ResultsAn average total cardiac surgical volume of 123.2 per 100,000 population per year was performed in high-income countries (36.7 CABG, 30.8 valvular, 7.9 congenital). Unadjusted annual volume targets per 100,000 population for low- and middle-income countries are 61.6 cardiac surgical procedures, 18.3 CABGs, 15.4 valvular surgical procedures, and 4.0 congenital heart operations. Adjusted for cardiovascular disease burdens, total cardiac surgical volume targets are 86.1 procedures per 100,000 population per year for upper-middle-income countries, 55.1 for lower-middle-income countries, and 40.2 for low-income countries. ConclusionsTarget annual procedural volumes present opportunities to strategically work toward expanding cardiac surgical capacity to meet the needs of countries’ populations. These targets may guide country-specific targets, which should be optimized through the expert opinion and lived experiences of local health care professionals and the context-specific population needs.

Self-reported participation in cervical cancer screening among Polish women in 2004-2019.

We aimed to assess self-reported participation in cervical cancer screening among Polish women between 2004 and 2019 and to identify the groups with the lowest participation rate. Data on declared participation in cervical cancer screening were obtained from the European Health Interview Survey from 2004 to 2019. In 2019, 86.7% of Polish women aged ≥ 15 years declared that they had ever undergone a Pap test. Compared to 2004, the coverage of ever-screened women improved by 16.6 percentage points. The proxy population coverage was 72.9%. The highest proportion of women who underwent a Pap smear in the last three years was observed among those aged 35-44 years and 25-34 years (84.0% and 83.2%, respectively), and the lowest among women aged ≥ 75 years (20.5%). The proportion screened within the last three years also varied by education (up to lower secondary education 26.4%, up to post-secondary non-tertiary education 62.8%, and the highest level of education 83.7%), urbanization (large cities 66.7%, suburbs, and smaller cities 62.8%, and rural areas 59.0%), income (poorest households 42.5%, wealthiest households 70.6%), and declared health status (best 68.9%, worst 41.4%). The lowest participation in screening was observed in the southeastern regions and the highest in the northwestern regions of Poland. In Poland, in 2019, the approximate coverage of cervical cancer screening was high compared to other European countries and has improved over the last 15 years. A complete screening registry is required to confirm questionnaire-based self-reported data. Targeted interventions should be implemented to address low participation in the identified regions and socioeconomic groups.

Five years of post-validation surveillance of lymphatic filariasis in Thailand

BackgroundThe World Health Organization (WHO) validated Thailand in 2017 as having eliminated lymphatic filariasis (LF) as a public health problem with recommendations for continued surveillance. This article describes measures and progress made in Thailand with post-validation surveillance (PVS) of LF from 2018 until 2022.MethodsThe implementation unit (IU) is a sub-village in 11 former LF endemic provinces. Human blood surveys are targeted in 10% of IUs each year. In Wuchereria bancrofti areas, filaria antigen test strips (FTS) are used, and in Brugia malayi areas, antibody test kits (Filaria DIAG RAPID) are used. Positive cases are confirmed by thick blood film (TBF) and polymerase chain reaction (PCR). Vector surveys for mosquito species identification and dissection for microfilaria (Mf)/filarial larvae are done in 1% of IUs where human blood surveys are conducted. Human blood surveys using FTS are conducted among migrants in five provinces. Surveillance of cats is done in areas that previously recorded > 1.0% Mf rate among cats. Morbidity management and disability prevention (MMDP) are done every 2 years in LF-endemic areas where chronic disease patients reside.ResultsFrom 2018 to 2022, in a total of 357 IUs in 11 provinces, human blood surveys were conducted in 145 IUs (41%) with an average population coverage of 81%. A total of 22,468 FTS and 27,741 FilariaDIAG RAPID were performed. 27 cases were detected: 3 cases of W. bancrofti in Kanchanaburi province and 24 cases of B. malayi in Narathiwat province. 4 cases of W. bancrofti were detected in two provinces through routine public health surveillance. Vector surveys in 47 IUs detected B. malayi Mf filarial larvae only in Narathiwat province. Chronic LF patients reduced from 114 in 2017 to 76 in 2022. Surveys among 7633 unregistered migrants yielded 12 cases of W. bancrofti. Mf rate among cats in Narathiwat province declined from 1.9% in 2018 to 0.7% in 2022. MMDP assessments revealed gaps in healthcare provider’s management of chronic cases due to staff turnover.ConclusionsIn 2022, after 5 years of PVS, Thailand re-surveyed 41% of its previously endemic IUs and demonstrated ongoing transmission in only one province of Narathiwat, where Mf prevalence is below the WHO provisional transmission threshold of 1%. This study highlights the importance of continued disease surveillance measures and vigilance among health care providers in LF receptive areas.Graphical

#309 : Menstrual Pain Related Endometriosis in Indonesia: Assessing Information Access Gap Through Social Media

Background and Aims: In Indonesian culture, most of us forced by wrong believed that menstrual pain is something normal and not a sign of pathology. While most Indonesian women in the past have a little access to gain the right information about menstrual pain that contribute to the delay treatment. In this era of social media like Instagram. Some use for seeking medical information like menstrual pain related to endometriosis symptoms. This study aims to know the role of social media to give Indonesian woman an access to gain right information about menstrual pain as one of endometriosis symptoms in Bahasa. Method: We searched several Bahasa hashtags “nyerihaid” and “nyerimenstruasi” (menstrual pain), “nyeriendometriosis” (endometriosis pain), “endometriosisinindonesia” (endometriosis in Indonesia). Results: We found that “nyerihaid” as the most common symptoms of endometriosis resulting to the most uploaded posts (156.196 posts) and “nyerimenstruasi” (3487 posts). Most of the information were related to herbal and other products marketing information that claimed can reduce menstrual pain (80.45%) and recipes for herbal mixture (5.45%). The reliable information sources about menstrual pain from health practitioner only (14.14%). For “nyeriendometriosis” has only (15 posts) and all from reliable health practitioner sources (100%). For “endometriosisinindonesia” (1120 posts), we found reliable information sources from health practitioners and health facility (54.05%), that consist of personal account (37.84%) and business account (16.22%). We also found endometriosis community forum information (17.57%) and herbal product marketing information (28.37%). Conclusion: Our study shows social media as an effective platform to educate woman about menstrual pain related to endometriosis, considering the coverage of population in Indonesian geographical barrier. Yet this potency of social media for educating and empowering woman in Bahasa using common symptoms like menstrual pain from the reliable sources is still very limited.

In silico analysis of HLA-1 and HLA-2 recognition of a designed recombinant human papillomavirus vaccine based on L1 protein HPV subtype 45

BackgroundHuman leukocyte antigen (HLA) can bind and present the processed antigenic peptide derived from the vaccine to the T cell receptor, and this capability is crucial in determining the effectivity of the vaccine to terminate virus-infected cells, activate macrophages, and induce B cells to produce antibodies. A recombinant vaccine candidate based on protein L1 HPV45 was designed and analysed whether it is recognisable by T cells through the binding of their epitopes to HLAs. MethodsThe study consisted of two parts: part one was the analysis of the L1 recombinant protein binding to HLA-1 and 2 epitopes, whereas part two was the distribution analysis of HPV-linked HLA allele. HLA allele sets found at high frequency in the general population and in specific Indonesian population were listed for the binding analysis of the recombinant L1 HPV45 protein. In part one, immunoepitope servers from IEDB were used to predict the binding of the designed proteins to HLA alleles. The prediction method for MHC-I binding prediction was the NetMHCpan EL 4.1 whilst for MHC-II binding prediction was the Consensus approach. Antigenicity analysis for each peptide was conducted using VaxiJen 2.0 with the threshold 1.0 to select the highly antigenic peptides, and positions of these epitopes in the secondary and tertiary structure of the recombinant protein were also predicted. The percent population coverage of the alleles capable of binding to these epitopes worldwide was also estimated. In part two, the worldwide distribution and frequency of HPV-related HLA-1 and 2 were studied. ResultTwo highly antigenic peptides (EEYDLQFIF and KLKFWTVDLK) were recognised by high-frequency HLA-1 alleles in both, the general and Western Javanese. In addition to these two epitopes, a few more peptides are also recognised by the high-frequency Western Javanese HLA-1 alleles, which are not in Weiskopf’s list of high-frequency HLA-1 alleles in the general population. Analysis of the highly antigenic epitopes binding to HLA-DRB1 alleles in general (YIKGTSANM) and Western Javanese (LRRRPTIGP) populations showed that these peptide cores associate to HLA-DRB1*04, albeit the different sub-types, due to the presence of different allele in each population group. Analysis of the epitopes and the positive binding alleles showed on average 25.65% population coverage. ConclusionThe recombinant vaccine candidate based on protein L1 HPV45 is presumed to contain highly antigenic peptides that can bind to high-frequency HLA-1 and 2 alleles present in general and Western Javanese populations. It was expected that the protein is capable of eliciting T cell-mediated responses in both populations; however, in vitro study is needed to prove the protectiveness of the designed recombinant protein.

Exploring structural antigens of yellow fever virus to design multi-epitope subunit vaccine candidate by utilizing an immuno-informatics approach

BackgroundYellow fever is a mosquito-borne viral hemorrhagic disease transmitted by several species of virus-infected mosquitoes endemic to tropical regions of Central and South America and Africa. Earlier in the twentieth century, mass vaccination integrated with mosquito control was implemented to eradicate the yellow fever virus. However, regular outbreaks occur in these regions which pose a threat to travelers and residents of Africa and South America. There is no specific antiviral therapy, but there can be an effective peptide-based vaccine candidate to combat infection caused by the virus. Therefore, the study aims to design a multi-epitope-based subunit vaccine (MESV) construct against the yellow fever virus to reduce the time and cost using reverse vaccinology (RV) approach. MethodsYellow fever virus contains 10,233 nucleotides that encode for 10 proteins (C, prM, E, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) including 3 structural and 7 non-structural proteins. Structural proteins—precursor membrane protein (prM) and envelope protein (E)—were taken as a target for B cell and T cell epitope screening. Further, various immunoinformatics approaches were employed to FASTA sequences of structural proteins to retrieve B cell and T cell epitopes. MESV was constructed from these epitopes based on allergenicity, antigenicity and immunogenicity, toxicity, conservancy, and population coverage followed by structure prediction. The efficacy of the MESV construct to bind with human TLR-3, TLR-4, and TLR-8 were evaluated using molecular docking and simulation studies. Finally, in-silico cloning of vaccine construct was performed withpBR322 Escherichia coli expression system using codon optimization. ResultsPredicted epitopes evaluated and selected for MESV construction were found stable, non-allergenic, highly antigenic, and global population coverage of 68.03% according to in-silico analysis. However, this can be further tested in in-vitro and in-vivo investigations. Epitopes were sequentially merged to construct a MESV consisting of 393 amino acids using adjuvant and linkers. Molecular docking and simulation studies revealed stable and high-affinity interactions. Furthermore, in-silico immune response graphs showed effective immune response generation. Finally, higher CAI value ensured high gene expression of vaccine in the host cell. ConclusionThe designed MESV construct in the present in-silico study can be effective in generating an immune response against the yellow fever virus. Therefore, to prevent yellow fever, it can be an effective vaccine candidate. However, further downstream, in-vitro study is required.

PP147 What Does Real World Evidence (RWE) Offer Health Technology Assessment (HTA) Procedures In Australia?

IntroductionMedical device health technology assessment (HTA) in Australia is largely coordinated by the Medical Services Advisory Committee (MSAC). Its remit to improve the public’s health by deciding where to allocate public healthcare funding, can be enhanced by considering real world evidence (RWE). Existing data sources have limitations that can be addressed through RWE, including coverage of Australian patient populations who may not meet trial eligibility criteria, and long-term follow-up through data linkage and datasets. We partnered with a university to explore what information could be gained from an analysis of linked administrative patient data, with a view to addressing current evidence gaps and/or limitations. The findings can be used as a source of local data to define patient populations, estimate actual costs of care, and enable more comprehensive economic modeling to inform medical device HTA.MethodsThe University-developed New South Wales Cardiovascular Cohort dataset, comprising person-level longitudinal NSW administrative data for all patients admitted to hospital with a cardiovascular diagnosis from 2001 onwards, linked to national Medicare Benefits Schedule and Pharmaceutical Benefits Scheme claims data, was interrogated.ResultsWorking with RWE is resource intensive in terms of time and costs. The potential of these data was revealed as the research progressed. It was possible to continually refine the data analyzed and reported,as well as expand the data requested. Varied expertise is required to accurately analyze the administrative datasets, particularly clinical classification skills and expertise in methods for causal inference using observational data. Findings from this study will enable the refinement of information for MSAC submissions, including identifying the most relevant patient population and reporting comprehensive costs, beyond an admitted hospital setting. The data will enhance engagement with clinicians and refine messaging, for example regarding patient risk factors.ConclusionsRWE enhances Australian HTA applications. Local data, extended periods of time and insights not apparent from a focus on admitted hospital episodes can be revealed. Data can be refined during the process for specificity and applicability.

Immunoinformatics-aided rational design of multiepitope-based peptide vaccine (MEBV) targeting human parainfluenza virus 3 (HPIV-3) stable proteins

BackgroundHuman parainfluenza viruses (HPIVs) are common RNA viruses responsible for respiratory tract infections. Human parainfluenza virus 3 (HPIV-3) is particularly pathogenic, causing severe illnesses with no effective vaccine or therapy available. ResultsThe current study employed a systematic immunoinformatic/reverse vaccinology approach to design a multiple epitope-based peptide vaccine against HPIV-3 by analyzing the virus proteome. On the basis of a number of therapeutic features, all three stable and antigenic proteins with greater immunological relevance, namely matrix protein, hemagglutinin neuraminidase, and RNA-directed RNA polymerase L, were chosen for predicting and screening suitable T-cell and B-cell epitopes. All of our desired epitopes exhibited no homology with human proteins, greater population coverage (99.26%), and high conservancy among reported HPIV-3 isolates worldwide. All of the T- and B-cell epitopes are then joined by putative ligands, yielding a 478-amino acid-long final construct. Upon computational refinement, validation, and thorough screening, several programs rated our peptide vaccine as biophysically stable, antigenic, allergenic, and non-toxic in humans. The vaccine protein demonstrated sufficiently stable interaction as well as binding affinity with innate immune receptors TLR3, TLR4, and TLR8. Furthermore, codon optimization and virtual cloning of the vaccine sequence in a pET32a (+) vector showed that it can be readily expressed in the bacterial system. ConclusionThe in silico designed HPIV-3 vaccine demonstrated potential in evoking an effective immune response. This study paves the way for further preclinical and clinical evaluation of the vaccine, offering hope for a future solution to combat HPIV-3 infections.

Cross-Regional Data Initiative for the Assessment and Development of Treatment for Neurological and Mental Disorders.

To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN). An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives. The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK. The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.

Evaluating effective measles vaccine coverage in the Malaysian population accounting for between-dose correlation and vaccine efficacy

BackgroundMalaysia introduced the two dose measles-mumps-rubella (MMR) vaccine in 2004 as part of its measles elimination strategy. However, despite high historical coverage of MCV1 and MCV2, Malaysia continues to report high measles incidence. This study suggests a novel indicator for investigating population immunity against measles in the Malaysian population.MethodsWe define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia’s routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia’s measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters.ResultsThis study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia.ConclusionThe persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases.

An Analytic Framework for the Prediction of Gvl Minor Histocompatibility Antigens to Prevent or Treat Post-Transplant Relapse

The therapeutic effect of allo-HSCT relies on T cell alloreactivity driven by genetic nonidentity between donor and recipient (D-R) pairs. In the setting of HLA-matched transplants, endogenous proteins in recipient cells differing from those of the donor due to genetic polymorphisms, can provide distinct HLA-binding peptides, serving as minor histocompatibility antigens (mHAgs). Hematopoietically-restricted mHAgs represent ideal targets to separate graft-versus-leukemia (GvL) from graft-versus-host-disease (GvHD) effects. To date,however, the quest for optimal GvL mHAgs has resulted in the identification of only a handful of targets, raising concerns on the clinical feasibility of their targeting. We hypothesized that systematic mHAg prediction from whole-exome sequencing (WES) of D-R pairs could help identifying novel candidate mHAgs with an acceptable safety profile for therapeutical targeting. We focused on AML/MDS, the most common indications for allo-HSCT in adults. To capture the transcriptional heterogeneity of malignant myeloid cells, we applied a single-cell based classifier to define genes expressed by leukemic cells in the Beat AML cohort, and then removed those expressed in non-hemopoietic tissues, per the GTEx RNA and protein database. Similarly, a broader set of pan-hematopoietic genes was defined starting from the expression profiles of 18 mature hematopoietic lineages and hematopoietic stem and precursor cells. Through this process, we identified 259 genes with preferential expression in AML and 615 broadly expressed in the hematopoietic compartment. We applied this analytical pipeline to WES from 220 HLA-matched D-R pairs transplanted at DFCI. To discover mHAgs with optimal GvL potential, we focused on the subgroup of 45 patients with long-term survival in the absence of both relapse and GvHD requiring systemic treatment (i.e. GvHD-free/relapse-free survival [GRFS]). For these patients experiencing purely GvL, we analyzed the individual repertoire of predicted GvL mHAgs, and found 86 SNPs recurring in ≥5 GRFS patients. These GvL SNPs were enriched in the subgroup of GRFS patients versus those without GRFS, suggesting that their overrepresentation was not dictated by high allelic frequency in the overall cohort. Using the median number of recurring GvL mHAgs in the GRFS subgroup (‘GRFS mHAgs‘) as a cutoff to stratify the entire study cohort, we found that a higher GRFS mHAg load was associated with a protective effect against relapse ( p=0.009) and conferred a benefit in 2-year overall survival ( p=0.03). Furthermore, HLA class I immunopeptidome analysis of 5 AML cell lines revealed evidence of presentation for 10 epitopes predicted from genes in the overall GvL filter, two of which were also part of the GRFS mHAg set. Given the limited size and lack of ethnic diversity of our discovery cohort (composed mainly of patients of European ancestry), we used genomic data from the 1000 Genomes project to estimate the feasibility of targeting our GRFS mHAg set in a broader population via in silico modeling of allo-HSCT. We simulated 2270 D-R pairs from 844 individuals across 5 populations of disparate ancestry (AFR, EAS, EUR, SAS, and AMR), mirroring a typical URD search in the NMDP registry. To gauge the feasibility of generating personalized mHAg-specific immunotherapy (i.e. cancer vaccines, adoptive cellular therapy) based on the GRFS mHAg set, we estimated that a 10-SNP design (i.e., the number of GRFS SNPs used for correlative analyses in our discovery cohort) would be possible for ~90% of the 1000 Genomes simulated cohort (EUR: 99%, EAS: 72%, SAS: 91%, AFR: 69%, AMR: 74%). Through a similar process, we calculated population coverage simulating a T cell-based approach targeting ≥1 epitope from the GRFS mHAg set. First, we identified 18 HLA alleles that could ensure ~99% coverage across diverse ethnic backgrounds. Second, for each HLA allele, the 3 most frequently predicted (and with highest agretopicity) epitopes from the GRFS SNP set were selected, defining a pool of 54 epitopes. We thus calculated that ≥1 epitopes could be potentially targeted for 81% of the simulated D-R pairs (EUR: 91%, EAS: 78%, SAS: 71%, AFR: 62%, and AMR:85%). Overall, we developed a robust approach to identify novel GvL mHAgs, which could form the basis for systematic personalized immunotherapy following allo-HSCT.