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IntroductionLeptospirosis, caused by Leptospira interrogans, is a neglected zoonotic disease that poses a significant global health risk to both humans and animals. The rise of antimicrobial resistance and the inefficacy of existing vaccines highlight the urgent need for new preventive strategies.MethodsAn immunoinformatics approach was employed to design a multi-epitope subunit vaccine (MESV) against leptospirosis. B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were selected from five key Leptospira proteins. These epitopes were fused with a heparin-binding hemagglutinin (HBHA) adjuvant and appropriate linkers to construct the broad-spectrum vaccine. The physicochemical properties of the vaccine were assessed, including antigenicity, immunogenicity, allergenicity, and conservation. The vaccine’s 3D structure was modeled, optimized, and validated. Molecular docking, molecular dynamics simulations, and MM-GBSA analysis were performed to assess the vaccine's binding interactions with Toll-like receptors (TLR2 and TLR4). Immune simulations and in silico cloning were also conducted to evaluate the vaccine’s immune response and expression potential.ResultsThe MESV demonstrated high antigenicity, immunogenicity, non-allergenicity, and conservation across different Leptospira strains. Population coverage analysis revealed that T-cell epitopes significantly interacted with HLA molecules, covering 95.7% of the global population. Molecular docking showed strong and stable binding with TLR2 and TLR4, with binding energies of -1,357.1 kJ/mol and -1,163.7 kJ/mol, respectively. Molecular dynamics simulations and MM-GBSA analysis confirmed the stability of these interactions and accurately calculated the intermolecular binding free energies. Immune simulations indicated robust B and T cell responses, and in silico cloning demonstrated that the vaccine could be successfully expressed in E. coli.DiscussionThese findings suggest that MESV is a promising candidate for leptospirosis prevention, providing robust immune responses and broad population coverage. However, further in vivo studies are necessary to validate its efficacy and safety.

Nipah virus, a zoonotic virus from the family Paramyxoviridae has led to significant loss of lives till date with the most recent outbreak in India reported in Kerala. The virus has a considerably high mortality rate along with lack of characteristic symptoms which results in the delay of the virus detection. No specific vaccine is available for the virus although monoclonal antibody treatment has been seen to be effective along with favipiravir. The high mortality and complications caused by the virus underscores the necessity to develop alternative modes of vaccination. One such method has been designed in this study using peptide cocktail consisting of the immunologically important epitopes for use as vaccine. The human leucocytic antigens that are used for the study were analyzed for their presence in various ethnic Indian populations. This study may serve as a new avenue for development of more efficient peptide cocktail vaccines in recent future based on the population genetics and ethnicity. [ABSTRACT FROM AUTHOR]

Background Ideally health insurance aims to provide financial security, promote social inclusion, and ensure equitable access to quality healthcare services for all households. Community-based health insurance has been operating in Ethiopia since 2011. However, its nationwide impact on universal health coverage has not yet been evaluated despite several studies being conducted. Objective We evaluated the impact of Ethiopia’s community-based health insurance (2012–2021) on universal health coverage. Methods On 27 August 2022, searches were conducted in Scopus, Hinari, PubMed, Google Scholar, and Semantic Scholar. Twenty-three studies were included. We used the Joana Briggs Institute checklists to assess the risk of bias. We included cross-sectional and mixed studies with low and medium risk. The data were processed in Microsoft Excel and analyzed using RevMan-5. The impact was measured first on insured households and then on insured versus uninsured households. We used a random model to measure the effect estimates (odds ratios) with a p value < 0.05 and a 95% CI. Results The universal health coverage provided by the scheme was 45.6% (OR = 1.92, 95% CI: 1.44–2.58). Being a member of the scheme increased universal health coverage by 24.8%. The healthcare service utilization of the beneficiaries was 64.5% (OR = 1.95, 95% CI: 1.29–2.93). The scheme reduced catastrophic health expenditure by 79.4% (OR = 4.99, 95% CI: 1.27–19.67). It yielded a 92% (OR = 11.58, 95% CI: 8.12–16.51) perception of health service quality. The health-related quality of life provided by it was 63% (OR = 1.71, 95% CI: 1.50–1.94). Its population coverage was 40.1% (OR = 0.64, 95% CI: 0.41–1.02). Conclusion Although the scheme had positive impacts on health service issues by reducing catastrophic costs, the low universal health coverage on a limited population indicates that Ethiopia should move to a broader national scheme that covers the entire population.

Abstract Background There is a strong and wide consensus that Pakistan must pursue universal health coverage (UHC) attainment as the driving force for achieving sustainable development goals by 2030. Nevertheless, several institutional and socioeconomic challenges may hinder the progress toward UHC. Main body It is important that the health system of Pakistan must be transformed to strengthen all three dimensions of UHC i.e. maximizing the population covered, increasing the range of services offered, and reducing the cost-sharing. To make UHC dream a reality in Pakistan, there are some pre-requisites to meet upfront: a) budgetary allocation for health as percentage of GDP must be increased; b) health system’s readiness especially in the public sector ought to improve in terms of human resource and availability of essential services; c) safety nets for health must continue regardless of the change in the political regimes; d) decrease the reliance on donors’ funding; and e) accountability to be ensured across the board for service providers, managers, administrators and policymakers in the health system. Conclusion COVID-19 pandemic has revealed some major gaps in the health system’s capacity to deliver equitable healthcare, which is a cornerstone to achieving the UHC agenda. The priority-setting process will need to be aligned with the SDGs to ensure that the agenda for action towards 2030 is comprehensively addressed and successfully accomplished preferably before, but hopefully not beyond the targeted dates.

ObjectiveThis study aimed to explore the current state of governance of full population coverage of health insurance in China and its influencing factors to provide empirical references for countries with similar social backgrounds as China.MethodsA cross-sectional quantitative study was conducted nationwide between 22 January 2020 and 26 January 2020, with descriptive statistics, analysis of variance, and logistic regression models via SPSS 25.0 to analyze the effectiveness and influencing factors of the governance of full population coverage of health insurance in China.ResultsThe effectiveness of the governance relating to the total population coverage of health insurance was rated as good by 59% of the survey respondents. According to the statistical results, the governance of the public's ability to participate in insurance (OR = 1.516), the degree of information construction in the medical insurance sector (OR = 2.345), the government's governance capacity (OR = 4.284), and completeness of the government's governance tools (OR = 1.370) were all positively correlated (p < 0.05) on the governance effect of the whole population coverage of health insurance.ConclusionsThe governance of Chinese health insurance relating to the total population coverage is effective. To effectively improve the effectiveness of the governance relating to the total population coverage of health insurance, health insurance information construction, governance capacity, and governance tools should be the focus of governance to further improve the accurate expansion of and increase the coverage of health insurance.

Background: There is a strong and wide consensus that Pakistan must pursue universal health coverage (UHC) attainment as the driving force for achieving sustainable development goals by 2030. Nevertheless, several institutional and socioeconomic challenges may hinder the progress toward UHC. Main body: It is important that the health system of Pakistan must be transformed to strengthen all three dimensions of UHC i.e. maximizing the population covered, increasing the range of services offered, and reducing the cost-sharing. To make UHC dream a reality in Pakistan, there are some pre-requisites to meet upfront: a) budgetary allocation for health as percentage of GDP must be increased; b) health system's readiness especially in the public sector ought to improve in terms of human resource and availability of essential services; c) safety nets for health must continue regardless of the change in the political regimes; d) decrease the reliance on donors' funding; and e) accountability to be ensured across the board for service providers, managers, administrators and policymakers in the health system. Conclusion: COVID-19 pandemic has revealed some major gaps in the health system's capacity to deliver equitable healthcare, which is a cornerstone to achieving the UHC agenda. The priority-setting process will need to be aligned with the SDGs to ensure that the agenda for action towards 2030 is comprehensively addressed and successfully accomplished preferably before, but hopefully not beyond the targeted dates. [ABSTRACT FROM AUTHOR]

Ideally health insurance aims to provide financial security, promote social inclusion, and ensure equitable access to quality healthcare services for all households. Community-based health insurance has been operating in Ethiopia since 2011. However, its nationwide impact on universal health coverage has not yet been evaluated despite several studies being conducted. We evaluated the impact of Ethiopia's community-based health insurance (2012–2021) on universal health coverage. On 27 August 2022, searches were conducted in Scopus, Hinari, PubMed, Google Scholar, and Semantic Scholar. Twenty-three studies were included. We used the Joana Briggs Institute checklists to assess the risk of bias. We included cross-sectional and mixed studies with low and medium risk. The data were processed in Microsoft Excel and analyzed using RevMan-5. The impact was measured first on insured households and then on insured versus uninsured households. We used a random model to measure the effect estimates (odds ratios) with a p value < 0.05 and a 95% CI. The universal health coverage provided by the scheme was 45.6% (OR = 1.92, 95% CI: 1.44–2.58). Being a member of the scheme increased universal health coverage by 24.8%. The healthcare service utilization of the beneficiaries was 64.5% (OR = 1.95, 95% CI: 1.29–2.93). The scheme reduced catastrophic health expenditure by 79.4% (OR = 4.99, 95% CI: 1.27–19.67). It yielded a 92% (OR = 11.58, 95% CI: 8.12–16.51) perception of health service quality. The health-related quality of life provided by it was 63% (OR = 1.71, 95% CI: 1.50–1.94). Its population coverage was 40.1% (OR = 0.64, 95% CI: 0.41–1.02). Although the scheme had positive impacts on health service issues by reducing catastrophic costs, the low universal health coverage on a limited population indicates that Ethiopia should move to a broader national scheme that covers the entire population. [ABSTRACT FROM AUTHOR]

BackgroundDelivering essential health services through non-governmental organizations (NGOs) could facilitate moving toward universal health coverage (UHC), especially in low- and middle-income countries. This study investigates the viewpoints of Iranian health system experts and executive stakeholders on the role of NGOs in moving toward UHC.MethodWe conducted 33 semi-structured interviews with health policymakers, NGO representatives at the national and provincial level, and other key informants and analyzed using content analyses methods, using MAXQDA 12. The inductive-deductive approach was used for qualitative data analyses.ResultBased on the thematic analysis of interviews and document reviews, nine main themes and one hundred and five sub-themes were identified. Each theme was categorized based on NGO-, society-, and government-related factors.ConclusionRecognizing the critical role of NGOs and their contribution in moving toward UHC is essential, particularly in the local context. Collaboration between NGO stakeholders and the government could facilitate moving toward UHC.

T cell immunity, such as CD4 and/or CD8 T cell responses, plays a vital role in controlling the virus infection and pathological damage. Several studies have reported SARS-CoV-2 proteins could serve as ideal vaccine candidates against SARS-CoV-2 infection by activating the T cell responses. In the current study, based on the SARS-CoV-2 sequence and distribution of host human leukocyte antigen (HLA), we predicted the possible epitopes for the vaccine against SARS-CoV-2 infections. Firstly, the current study retrieved the SARS-CoV-2 S and N protein sequences from the NCBI Database. Then, using the Immune Epitope Database Analysis Resource, we predicted the CTL epitopes of the SARS-CoV-2 S and N proteins according to worldwide frequency distributions of HLA-A, -B, and -C alleles (>1%). Our results predicted 90 and 106 epitopes of N and S proteins, respectively. Epitope cluster analysis showed 16 and 34 respective clusters of SARS-CoV-2 N and S proteins, which covered 95.91% and 96.14% of the global population, respectively. After epitope conservancy analysis, 8 N protein epitopes and 6 S protein epitopes showed conservancy within two SARS-CoV-2 types. Of these 14 epitopes, 13 could cover SARS coronavirus and Bat SARS-like coronavirus. The remaining epitope (KWPWYIWLGF1211-1220) could cover MERS coronavirus. Finally, the 14-epitope combination could vaccinate 89.60% of all individuals worldwide. Our results propose single or combined CTL epitopes predicted in the current study as candidates for vaccines to effectively control SARS-CoV-2 infection and development.

BackgroundMass anti-malarial administration has been proposed as a key component of the malaria elimination strategy in South East Asia. The success of this approach depends on the local malaria epidemiology, nature of the anti-malarial regimen and population coverage. Community engagement is used to promote population coverage but little research has systematically analysed its impact. This systematic review examines population coverage and community engagement in programmes of mass anti-malarial drug administration.MethodsThis review builds on a previous review that identified 3049 articles describing mass anti-malarial administrations published between 1913 and 2011. Further search and application of a set of criteria conducted in the current review resulted in 51 articles that were retained for analysis. These 51 papers described the population coverage and/or community engagement in mass anti-malarial administrations. Population coverage was quantitatively assessed and a thematic analysis was conducted on the community engagement activities.ResultsThe studies were conducted in 26 countries: in diverse healthcare and social contexts where various anti-malarial regimens under varied study designs were administered. Twenty-eight articles reported only population coverage; 12 described only community engagement activities; and 11 community engagement and population coverage. Average population coverage was 83% but methods of calculating coverage were frequently unclear or inconsistent. Community engagement activities included providing health education and incentives, using community structures (e.g. existing hierarchies or health infrastructure), mobilizing human resources, and collaborating with government at some level (e.g. ministries of health). Community engagement was often a process involving various activities throughout the duration of the intervention.ConclusionThe mean population coverage was over 80% but incomplete reporting of calculation methods limits conclusions and comparisons between studies. Various community engagement activities and approaches were described, but many articles contained limited or no details. Other factors relevant to population coverage, such as the social, cultural and study context were scarcely reported. Further research is needed to understand the factors that influence population coverage and adherence in mass anti-malarial administrations and the role community engagement activities and approaches play in satisfactory participation.

Though it has passed over 30 years, Korea's community-based health insurance (CBHI) expansion can provide useful policy implications to developing countries with similar conditions, that is, lack of fiscal resources, health infrastructure, and medical resources to expand coverage to the informal sector. We summarized three groups of success factors through in-depth interviews and narrative analysis: system design, system operation, and public perception of the system. Korean CBHI could expand to the informal sector with the same system design as the formal sector such as mandatory enrolment, compulsory designation of medical service providers along with the low-benefit, low-contribution, and a low-payment system. However, expansion to the informal sector was somewhat different, as the CBHI exercised and operated the scheme with flexibility, semi-autonomy and leadership to fit for local context in terms of operation. Moreover, cultural factors that encouraged public awareness and increased participation significantly contributed in appealing to the informal sector. Overall, the systemic, operational, and cultural factors interacted with each other and created a synergy effect that local members in the informal sector found attractive. [ABSTRACT FROM AUTHOR]

Mucormycosis is a group of infections, caused by multiple fungal species, which affect many human organs and is lethal in immunocompromised patients. During the COVID-19 pandemic, the current wave of mucormycosis is a challenge to medical professionals as its effects are multiplied because of the severity of COVID-19 infection. The variant of concern, Omicron, has been linked to fatal mucormycosis infections in the US and Asia. Consequently, current postdiagnostic treatments of mucormycosis have been rendered unsatisfactory. In this hour of need, a preinfection cure is needed that may prevent lethal infections in immunocompromised individuals. This study proposes a potential vaccine construct targeting mucor and rhizopus species responsible for mucormycosis infections, providing immunoprotection to immunocompromised patients. The vaccine construct, with an antigenicity score of 0.75 covering, on average, 92–98% of the world population, was designed using an immunoinformatics approach. Molecular interactions with major histocompatibility complex-1 (MHC-I), Toll-like receptors-2 (TLR2), and glucose-regulated protein 78 (GRP78), with scores of −896.0, −948.4, and −925.0, respectively, demonstrated its potential to bind with the human immune receptors. It elicited a strong predicted innate and adaptive immune response in the form of helper T (Th) cells, cytotoxic T (TC) cells, B cells, natural killer (NK) cells, and macrophages. The vaccine cloned in the pBR322 vector showed positive amplification, further solidifying its stability and potential. The proposed construct holds a promising approach as the first step towards an antimucormycosis vaccine and may contribute to minimizing postdiagnostic burdens and failures. [ABSTRACT FROM AUTHOR]

Background: Community engagement has increasingly received attention in malaria research and programme interventions, particularly as countries aim for malaria elimination. Although community engagement strategies and activities are constantly developing, little is known about how those who implement research or programmes view community engagement. This article explores the perspectives of researchers and policy makers in the Greater Mekong Sub-region (GMS) on community engagement for malaria control and elimination. Methods: Semi-structured interviews were conducted among 17 policymakers and 15 senior researchers working in the field of malaria. All interviews were audio-recorded and transcribed in English. Transcribed data were analysed using deductive and inductive approaches in QSR NVivo. Themes and sub-themes were generated. Results: Researchers and policymakers emphasized the importance of community engagement in promoting participation in malaria research and interventions. Building trust with the community was seen as crucial. Respondents emphasized involving authority/leadership structures and highlighted the need for intense and participatory engagement. Geographic remoteness, social, cultural, and linguistic diversity were identified as barriers to meaningful engagement. Local staff were described as an essential 'connect' between researchers or policymakers and prospective participants. Sharing information with community members, using various strategies including creative and participatory methods were highlighted. Conclusions: Policymakers and researchers involved in malaria prevention and control in the GMS viewed community engagement as crucial for promoting participation in research or programmatic interventions. Given the difficulties of the 'last mile' to elimination, sustained investment in community engagement is needed in isolated areas of the GMS where malaria transmission continues. Involving community-based malaria workers is ever more critical to ensure the elimination efforts engage hard-to-reach populations in remote areas of GMS. [ABSTRACT FROM AUTHOR]

Pertussis vaccine is produced from physicochemically inactivated toxin for many years. Recent advancements in immunoinformatics [N. Tomar and R. K. De, “Immunoinformatics: an integrated scenario,” Immunology, vol. 131, no. 2, pp. 153–168, 2010] and structural bioinformatics can provide a new multidisciplinary approach to overcome the concerns including unwanted antibodies and incomplete population coverage. In this study we focused on solving the challenging issues by designing a multi-epitope vaccine (MEV) using rational bioinformatics analyses. The frequencies of All HLA DP, DQ, and DR alleles were evaluated in almost all countries. Strong binder surface epitopes on the pertussis toxin were selected based on our novel filtration strategy. Finally, the population coverage of MEV was determined in the candidate country. Filtration steps yielded 312 strong binder epitopes. Finally, 8 surface strong binder epitopes were selected as candidate epitopes. The population coverage of the MEV in France and the world was 98 and 100 percent, respectively. Our algorithm successfully filtered many unwanted strong binder epitopes. Considering the HLA type of all individuals in a country, we theoretically provided the maximum chance to all humans to be vaccinated efficiently. Application of a MEV would be led to production of highly efficient target specific antibodies, significant reduction of unwanted antibodies, and avoid possible raising of auto-antibodies as well. [ABSTRACT FROM AUTHOR]

Autoimmune diseases (ADs) could occur due to infectious diseases and vaccination programs. Since millions of people are expected to be infected with SARS-CoV-2 and vaccinated against it, autoimmune consequences seem inevitable. Therefore, we have investigated the whole proteome of the SARS-CoV-2 for its ability to trigger ADs. In this regard, the entire proteome of the SARS-CoV-2 was chopped into more than 48000 peptides. The produced peptides were searched against the entire human proteome to find shared peptides with similar experimentally confirmed T-cell and B-cell epitopes. The obtained peptides were checked for their ability to bind to HLA molecules. The possible population coverage was calculated for the most potent peptides. The obtained results indicated that the SARS-CoV-2 and human proteomes share 23 peptides originated from ORF1ab polyprotein, nonstructural protein NS7a, Surface glycoprotein, and Envelope protein of SARS-CoV-2. Among these peptides, 21 peptides had experimentally confirmed equivalent epitopes. Amongst, only nine peptides were predicted to bind to HLAs with known global allele frequency data, and three peptides were able to bind to experimentally confirmed HLAs of equivalent epitopes. Given the HLAs which have already been reported to be associated with ADs, the ESGLKTIL, RYPANSIV, NVAITRAK, and RRARSVAS were determined to be the most harmful peptides of the SARS-CoV-2 proteome. It would be expected that the COVID-19 pandemic and the vaccination against this pathogen could significantly increase the ADs incidences, especially in populations harboring HLA-B*08:01, HLA-A*024:02, HLA-A*11:01 and HLA-B*27:05. The Southeast Asia, East Asia, and Oceania are at higher risk of AD development.

Autoimmune diseases (ADs) could occur due to infectious diseases and vaccination programs. Since millions of people are expected to be infected with SARS-CoV-2 and vaccinated against it, autoimmune consequences seem inevitable. Therefore, we have investigated the whole proteome of the SARS-CoV-2 for its ability to trigger ADs. In this regard, the entire proteome of the SARS-CoV-2 was chopped into more than 48000 peptides. The produced peptides were searched against the entire human proteome to find shared peptides with similar experimentally confirmed T-cell and B-cell epitopes. The obtained peptides were checked for their ability to bind to HLA molecules. The possible population coverage was calculated for the most potent peptides. The obtained results indicated that the SARS-CoV-2 and human proteomes share 23 peptides originated from ORF1ab polyprotein, nonstructural protein NS7a, Surface glycoprotein, and Envelope protein of SARS-CoV-2. Among these peptides, 21 peptides had experimentally confirmed equivalent epitopes. Amongst, only nine peptides were predicted to bind to HLAs with known global allele frequency data, and three peptides were able to bind to experimentally confirmed HLAs of equivalent epitopes. Given the HLAs which have already been reported to be associated with ADs, the ESGLKTIL, RYPANSIV, NVAITRAK, and RRARSVAS were determined to be the most harmful peptides of the SARS-CoV-2 proteome. It would be expected that the COVID-19 pandemic and the vaccination against this pathogen could significantly increase the ADs incidences, especially in populations harboring HLA-B*08:01, HLA-A*024:02, HLA-A*11:01 and HLA-B*27:05. The Southeast Asia, East Asia, and Oceania are at higher risk of AD development. [ABSTRACT FROM AUTHOR]

• Population coverage of an HIV-1 vaccine targeting the PCSs was studied. • Targeting all 12-PCSs or a subset of the PCSs shows broad population coverage. • Coverage ranged from ~ 70% to ~ 100% for all 12-PCSs, Gag-PCSs, or Pol-PCSs. • There was no significant difference in population coverage between epitope sets. Development of an effective HIV-1 vaccine has been a great challenge faced by the research community. Recently a novel strategy targeting the viral protease cleavage sites (PCSs) has been tested and shown promising results. This T cell-based vaccine strategy depends on individuals expressing certain HLA class I molecules and since each population has unique distributions of HLA class I alleles, population coverage analysis is required to assess feasibility. Utilizing the validated CD8 T cell epitope data from previous studies we conducted coverage analysis of an HIV-1 vaccine targeting the sequences surrounding all 12-PCSs, Gag-PCSs, and Pol-PCSs. The population coverage, average epitope hit, and minimum number of epitopes recognized by 90% of the population (PC90) was compiled for 66 countries and 16 geographical regions using the web tool provided by "Immune Epitope Database and Analysis Resource". Our analysis shows that the coverage for an HIV-1 vaccine targeting sequences surrounding all 12 PCSs, 5 PCSs in Gag or 6 PCSs in Pol can cover ~ 70% to ~ 100% of the populations analyzed. There was no statistical difference in population coverages for the majority of populations examined when comparing the CD8 T cell epitope sets (12-PCSs, Gag-PCSs, and Pol-PCSs). As expected, vaccines targeting more sequences will have more CD8 T cell epitopes, as the mean average epitope hit for the 12-PCSs, Gag-PCSs, and Pol-PCSs across all countries studied was 9.45, 4.76, and 4.74, respectively, and across all geographical regions was 9.76, 4.99, and 4.92, respectively. The average PC90 for the 12-PCSs, Gag-PCSs, and Pol-PCSs across all countries studied was 2.53, 1.31, and 1.41, respectively, and across all geographical regions was 2.24, 1.23, and 1.29, respectively. Thus, vaccines targeting sequences surrounding the HIV-1 PCSs can cover broad populations; however, whether targeting a subset of the PCSs is sufficient to prevent acquisition requires further preclinical investigation. [ABSTRACT FROM AUTHOR]

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Whipple's disease is one of the rare maladies in terms of spread but very fatal one as it is linked with many disorders (like Gastroenteritis, Endocarditis etc.). Also, current regimens include less effective drugs which require long duration follows up. This exploratory study was conducted to commence the investigation for crafting multi target epitope vaccine against its bacterial pathogen Tropheryma whipplei. The modern bioinformatics tools like VaxiJen, NETMHCII PAN 3.2, ALLERGEN-FP, PATCH-DOCK, TOXIC-PRED, MHCPRED and IEDB were deployed, which makes the study more intensive in analyzing proteome of T. whipplei as these methods are based on robust result generating statistical algorithms ANN, HMM, and ML. This Immuno-Informatics approach leads us in the prediction of two epitopes: VLMVSAFPL and IRYLAALHL interacting with 4 and 6 HLA DRB1 alleles of MHC Class II respectively. VLMVSAFPL epitope is a part of DNA-directed RNA polymerase subunit beta, and IRYLAALHL epitope is a part of membranous protein insertase YidC of this bacterium. Molecular-Docking and Molecular-Simulation analysis yields the perfect interaction based on Atomic contact energy, binding scores along with RMSD values (0 to 1.5 Ǻ) in selection zone. The IEDB (Immune epitope database) population coverage analysis exhibits satisfactory relevance with respect to world population. [ABSTRACT FROM AUTHOR]

The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are |$80\hbox{--} 90\%$| identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Abstract Background In the current scenario, designing of world-wide effective malaria vaccine against Plasmodium falciparum remain challenging despite the significant progress has been made in last few decades. Conventional vaccinology (isolate, inactivate and inject) approaches are time consuming, laborious and expensive; therefore, the use of computational vaccinology tools are imperative, which can facilitate the design of new and promising vaccine candidates. Results In current investigation, initially 5548 proteins of P. falciparum genome were carefully chosen for the incidence of signal peptide/ anchor using SignalP4.0 tool that resulted into 640 surface linked proteins (SLP). Out of these SLP, only 17 were predicted to contain GPI-anchors using PredGPI tool in which further 5 proteins were considered as malarial antigenic adhesins by MAAP and VaxiJen programs, respectively. In the subsequent step, T cell epitopes of 5 genome derived predicted antigenic adhesins (GDPAA) and 5 randomly selected known malarial adhesins (RSKMA) were analysed employing MHC class I and II tools of IEDB analysis resource. Finally, VaxiJen scored T cell epitopes from each antigen were considered for prediction of population coverage (PPC) analysis in the world-wide population including malaria endemic regions. The validation of the present in silico strategy was carried out by comparing the PPC of combined (MHC class I and II) predicted epitope ensemble among GDPAA (99.97%), RSKMA (99.90%) and experimentally known epitopes (EKE) of P. falciparum (97.72%) pertaining to world-wide human population. Conclusions The present study systematically screened 5 potential protective antigens from P. falciparum genome using bioinformatics tools. Interestingly, these GDPAA, RSKMA and EKE of P. falciparum epitope ensembles forecasted to contain highly promiscuous T cell epitopes, which are potentially effective for most of the world-wide human population with malaria endemic regions. Therefore, these epitope ensembles could be considered in near future for novel and significantly effective vaccine candidate against malaria.

Mucormycosis is a group of infections, caused by multiple fungal species, which affect many human organs and is lethal in immunocompromised patients. During the COVID-19 pandemic, the current wave of mucormycosis is a challenge to medical professionals as its effects are multiplied because of the severity of COVID-19 infection. The variant of concern, Omicron, has been linked to fatal mucormycosis infections in the US and Asia. Consequently, current postdiagnostic treatments of mucormycosis have been rendered unsatisfactory. In this hour of need, a preinfection cure is needed that may prevent lethal infections in immunocompromised individuals. This study proposes a potential vaccine construct targeting mucor and rhizopus species responsible for mucormycosis infections, providing immunoprotection to immunocompromised patients. The vaccine construct, with an antigenicity score of 0.75 covering, on average, 92–98% of the world population, was designed using an immunoinformatics approach. Molecular interactions with major histocompatibility complex-1 (MHC-I), Toll-like receptors-2 (TLR2), and glucose-regulated protein 78 (GRP78), with scores of −896.0, −948.4, and −925.0, respectively, demonstrated its potential to bind with the human immune receptors. It elicited a strong predicted innate and adaptive immune response in the form of helper T (Th) cells, cytotoxic T (TC) cells, B cells, natural killer (NK) cells, and macrophages. The vaccine cloned in the pBR322 vector showed positive amplification, further solidifying its stability and potential. The proposed construct holds a promising approach as the first step towards an antimucormycosis vaccine and may contribute to minimizing postdiagnostic burdens and failures.

Aeromedical retrieval is an essential component of contemporary emergency care systems. However, in many locations, ground emergency medical services are dispatched to the scene of an incident first to assess the patient and then call for a helicopter if needed. The time to definitive care therefore includes the helicopter's flight to the scene, flight to the trauma center, and nonflying time. Mission ground time (MGT) includes the time required to get the helicopter airborne, as well as time spent at the scene, packaging and loading the casualty into the aircraft. Estimates of MGT typically vary from 10 to 30 min. The impact of MGT duration on population coverage—the number of residents that could be taken to a trauma center within a set time—is not known. The aim of this study was to compare population coverage for different durations of MGT in a single state. Coverage was calculated using elliptical coverage areas ("isochrones") based on the location of helicopter bases and Level I and Level II trauma centers. The calculations were performed using Microsoft Excel, assuming a cruising speed of 133 knots (246 km/h), and mapped using arcGIS. The access time threshold was set at 60 min, and we evaluated MGTs of 10, 15, 20, 25, and 30 min. MGT has a marked impact on population coverage. The effect is, furthermore, not linear. When considering the state's three Level I trauma centers, decreasing MGT from 30 to 10 min increased population coverage from 61.2% to 84.2%. When also considering Level II centers, decreasing MGT from 30 min to 10 min increased coverage by 20%. Elliptical isochrones, with allowance for MGT, provide realistic estimates of population coverage. MGT significantly impacts the proportion of the population that can be taken to a Level I and/or Level II Trauma Center within a set time. The impact is not linear, reflecting the uneven distribution of the population. Consideration should be given to minimizing MGT to preserve the benefits of aeromedical retrieval. [ABSTRACT FROM AUTHOR]

Background: China and Vietnam have made impressive progress towards universal health coverage (UHC) through government-led health insurance reforms. We compared the different pathways used to achieve UHC, to identify the lessons other countries can learn from China and Vietnam.Methods: This was a mixed method study which included a literature review, in-depth interviews and secondary data analysis. We conducted a literature search in English and Chinese databases, and reviewed policy documents from internal contacts. We conducted semi-structured interviews with 16 policy makers, government bureaucrats, health insurance scholars in China and Vietnam. Secondary data was collected from National Health Statistics Reports, Health Insurance Statistical Reports and National Health Household Surveys carried out in both countries. We used population insurance coverage, insurance policies, reimbursement rates, number of households experiencing catastrophic heath expenditure (CHE) and incidence of impoverishment due to health expenditure (IHE) to measure the World Health Organization's three dimensions of UHC: population coverage, service coverage, and financial coverage.Results: China has increased population coverage through strong political commitment and extensive government financial subsidies to expand coverage. Vietnam expanded population coverage gradually, by prioritizing the poor and the near-poor in an incremental way. In China, insurance service packages varied across regions and schemes and were greatly determined by financial contributions, resulting in limited service coverage in less developed areas. Vietnam focused on providing a comprehensive and universal service packages for all enrollees thereby approaching UHC in a more equitable manner. CHE rate decreased in Vietnam but increased in China between 2003 and 2008. While Vietnam has decreased the CHE gap between urban and rural populations, China suffers from persistent disparities among population income levels and geographic location. CHE and CHE rates were still high in lower income groups.Conclusion: Political commitment, sustainable financial sources and administrative capacity are strong driving factors in achieving UHC through health insurance reform. Health insurance schemes need to consider covering essential health services for all beneficiaries and providing government subsidies for vulnerable populations' in order to help achieve health for all. [ABSTRACT FROM AUTHOR]

Nipah virus was first appeared in Malaysian 1998, which further found be outburst in neighbor countries i.e. Bangladesh, Singapore, and India. Currently there is no effective drug or vaccine available only supportive care and prevention are way to manage it. Epitope based vaccine could be the best way to cure Nipah virus infection. In this study, the proteome of Nipah virus was retrieve from UniProt database and were subjected to check for allergenicity using Allergen FP v.1.0 tool. NetMHCII 2.3 server screened epitopes from non-allergen proteins and Vaxijen tool was used to identify the most antigenic epitopes binds with MHC class II molecules. Two potent T cell epitopes LLFVFGPNL and KYKIKSNPL were found, which binds with HLA-DRB1*01:01 and HLA-DRB1*07:01 MHC class II alleles. PepstrMod and Swiss-Model server were used to build 3D structure model of epitopes and alleles, respectively. Further identified epitopes were docked with HLA alleles using AutoDock vina tool to confirm binding ability. The epitopes LLFVFGPNL and KYKIKSNPL had binding affinity of − 8.1 kcal/mol and − 5.7 kcal/mol with HLA-DRB1*01:01 and HLA-DRB1*07:01 alleles, respectively. Solidity of predicted epitope—allele docked complex were evaluating by molecular dynamics simulation.HLA distribution analysis was performed for predicted epitopes using the population coverage tool of Immune Epitope Database (IEDB). These predicted epitopes cover maximum number of populations in India as well as worldwide. Therefore, these epitopes could be potent vaccine candidates to counter Nipah virus by testing in wet lab. [ABSTRACT FROM AUTHOR]

Background: In order to conduct a probability business survey, a high quality sampling frame of enterprises is needed.

Background: This study aimed to provide tailored transferrable lessons for expanding population coverage through a descriptive lens by reviewing the population coverage policies, reforms and strategies in selected nations. Methods: In this comparative short communication, 14 countries with different status of population coverage and political economy that had successful experiences with coverage expansion were selected and categorized in four groups to study their approaches to reach Universal Health Coverage (UHC). Results: Although each country needs to tailor its policies and reforms based on its own contextual factors, the legal right of citizens to social security and health protection are enshrined in most countries' Constitution. Some countries adapted political and economic reforms to evolve their Social Health Insurance schemes. National laws to push governments to adapt UHC as a national strategy for ensuring that every resident is enrolled in health insurance schemes are key policies to reach UHC. Conclusion: A series of reforms are required to provide total population coverage through various approaches. To create an effective insurance coverage, physical merger of all insurance funds is not necessarily required. Further, the share of GDP for health is not a definite indicator to reach UHC. Finally, strong political commitment and citizens’ participation are the key issues in reaching UHC, while considering the poorest, remote and neglected population really matters.

Background: The design of an epitope-based vaccine against diphtheria toxin (DT) originated from the idea that many strong binder epitopes may be structurally located in the depth of DT. Subsequently, many ineffective antibodies may be produced by the presentation of those epitopes to T and B lymphocytes. The other critical issue is the population coverage of a vaccine that has been neglected in traditional vaccines.

Screening of HLA class II epitope-based peptides as potential vaccine candidates is one of the most rational approach for vaccine development against Hendra virus (HeV) infection, for which currently there is no successful vaccine in practice. In this study, screening of epitopes from HeV proteins viz matrix, glycoprotein, nucleocapsid, fusion, C protein, V protein, W protein and polymerase, followed by highest binding affinity & molecular dynamic simulation of selected T-cell epitopes with their corresponding HLA class II alleles has been done. The server ProPred facilitates the binding prediction of HLA class II allele specific epitopes from the antigenic protein sequences of HeV. PEPstrMOD server was used for PDB structure modeling of the screened epitopes and MODELLER was used for HLA alleles modeling. We docked the selected T-cell epitopes with their corresponding HLA allele structures using the AutoDock 4.2 tool. Further the selected docked complex structures were optimized by NAnoscale Molecular Dynamics program (NAMD) at 5 ps, with the CHARMM-22 force field parameter incorporated in Visual Molecular Dynamics (VMD 1.9.2) and complex structure stability was evaluated by calculating RMSD values. Epitopes IRIFVPATN (Nucleocapsid), MRNLLSQSL (Nucleocapsid), VRRAGKYYS (Matrix) and VRLKCLLCG (Fusion) proteins have shown considerable binding with DRB1*0806, DRB1*1304, DRB1*0701 and DRB1*0301 HLA class II allele respectively. Toxicity, antigenicity and population coverage of epitopes IRIFVPATN, MRNLLSQSL, VRRAGKYYS and VRLKCLLCG were analyzed by Toxin Pred, Vexijen and IEDB tool, respectively. The potential T-cell epitopes can be utilized in designing comprehensive epitope-based vaccines and diagnostic kits against Hendra virus after further in-vivo studies. [ABSTRACT FROM AUTHOR]

Background: The state of Tamil Nadu in India is one of the states with better health indicators in the country. With an ambition to provide still better health care to the residents of the state, the possibilities of the journey towards UHC are analyzed. Objectives: To explore the possibilities of using the existing Chief Minister's Comprehensive Health Insurance Scheme (CMCHISTN) as base to reach Universal Health Coverage (UHC) in Tamil Nadu. Methods: The various dimensions of UHC namely people, benefit, and financial protection are analyzed considering the present status in the state particularly the Chief Minister's Comprehensive Health Insurance Scheme and matched with future needs to reach UHC in Tamil Nadu. This provides the vital indications in success towards UHC. Results and conclusion: The gap between the existing modalities under CMCHSITN and requirements for UHC are within the reachable level. With additional resources and effort, it is possible to reach UHC in Tamil Nadu in the near future. CMCHISTN is one of the best available options for reaching UHC in Tamil Nadu.

Background: In the current scenario, designing of world-wide effective malaria vaccine against Plasmodium falciparum remain challenging despite the significant progress has been made in last few decades. Conventional vaccinology (isolate, inactivate and inject) approaches are time consuming, laborious and expensive; therefore, the use of computational vaccinology tools are imperative, which can facilitate the design of new and promising vaccine candidates. Results: In current investigation, initially 5548 proteins of P. falciparum genome were carefully chosen for the incidence of signal peptide/ anchor using SignalP4.0 tool that resulted into 640 surface linked proteins (SLP). Out of these SLP, only 17 were predicted to contain GPI-anchors using PredGPI tool in which further 5 proteins were considered as malarial antigenic adhesins by MAAP and VaxiJen programs, respectively. In the subsequent step, T cell epitopes of 5 genome derived predicted antigenic adhesins (GDPAA) and 5 randomly selected known malarial adhesins (RSKMA) were analysed employing MHC class I and II tools of IEDB analysis resource. Finally, VaxiJen scored T cell epitopes from each antigen were considered for prediction of population coverage (PPC) analysis in the world-wide population including malaria endemic regions. The validation of the present in silico strategy was carried out by comparing the PPC of combined (MHC class I and II) predicted epitope ensemble among GDPAA (99.97%), RSKMA (99.90%) and experimentally known epitopes (EKE) of P. falciparum (97.72%) pertaining to world-wide human population. Conclusions: The present study systematically screened 5 potential protective antigens from P. falciparum genome using bioinformatics tools. Interestingly, these GDPAA, RSKMA and EKE of P. falciparum epitope ensembles forecasted to contain highly promiscuous T cell epitopes, which are potentially effective for most of the world-wide human population with malaria endemic regions. Therefore, these epitope ensembles could be considered in near future for novel and significantly effective vaccine candidate against malaria. [ABSTRACT FROM AUTHOR]

Background: Brazil's national oral health policy, established in 2004, is considered the largest public policy in this segment worldwide. Objective: To analyze the National Oral Health Policy of Brazil under the theory of the cycle of public policies. Methods: This was a qualitative study based on the policy cycle, which sought to analyze the cycle of the Brazilian National Oral Health Policy. Two methods were used to collect the data: the documentary analysis and the performance of semi-structured interviews. Results: Although the oral health problems of the Brazilian population have long been recognized, it was in 2003 that a window of opportunity was opened for this topic to occupy the agenda of priorities of the Federal Government. Established in 2004, the policy has advanced in coverage of basic and specialized services in the national territory, serving priority populations. From the year 2016, however, one can perceive its stagnation given the Brazilian political-economic conjuncture. Conclusions: The results of the interventions show a considerable improvement in the oral health indicators; and an increase in the population coverage served by oral health services and services, facts that recommend the continuity of the policy. [ABSTRACT FROM AUTHOR]

H56/AERAS-456 + IC31 (H56), composed of two early secretion proteins, Ag85B and ESAT-6, and a latency associated protein, Rv2660, and the IC31 Intercell adjuvant, is a new fusion subunit vaccine candidate designed to induce immunity against both new infection and reactivation of latent tuberculosis infection. Efficacy of subunit vaccines may be affected by the diversity of vaccine antigens among clinical strains and the extent of recognition by the diverse HLA molecules in the recipient population. Although a previous study showed the conservative nature of Ag85B- and ESAT-6-encoding genes, genetic diversity of Rv2660c that encodes RV2660 is largely unknown. The population coverage of H56 as a whole yet remains to be assessed. The present study was conducted to address these important knowledge gaps. DNA sequence analysis of Rv2660c found no variation among 83 of the 84 investigated clinical strains belonging to four genetic lineages. H56 was predicted to have as high as 99.6% population coverage in the South Africa population using the Immune Epitope Database (IEDB) Population Coverage Tool. Further comparison of H56 population coverage between South African Blacks and Caucasians based on the phenotypic frequencies of binding MHC Class I and Class II supertype alleles found that all of the nine MHC-I and six of eight MHC-II human leukocyte antigen (HLA) supertype alleles analyzed were significantly differentially expressed between the two subpopulations. This finding suggests the presence of race-specific functional binding motifs of MHC-I and MHC-II HLA alleles, which, in turn, highlights the importance of including diverse populations in vaccine clinical evaluation. In conclusion, H56 vaccine is predicted to have a promising population coverage in South Africa; this study demonstrates the utility of integrating comparative genomics and bioinformatics in bridging animal and clinical studies of novel TB vaccines. [ABSTRACT FROM AUTHOR]

Malaria is a global health burden, and a major cause of mortality and morbidity in Africa. Here we designed a putative malaria epitope ensemble vaccine by selecting an optimal set of pathogen epitopes. From the IEDB database, 584 experimentally-verified CD8+ epitopes and 483 experimentally-verified CD4+ epitopes were collected; 89% of which were found in 8 proteins. Using the PVS server, highly conserved epitopes were identified from variability analysis of multiple alignments of Plasmodium falciparum protein sequences. The allele-dependent binding of epitopes was then assessed using IEDB analysis tools, from which the population protection coverage of single and combined epitopes was estimated. Ten conserved epitopes from four well-studied antigens were found to have a coverage of 97.9% of the world population: 7 CD8+ T cell epitopes (LLMDCSGSI, FLIFFDLFLV, LLACAGLAYK, TPYAGEPAPF, LLACAGLAY, SLKKNSRSL, and NEVVVKEEY) and 3 CD4+ T cell epitopes (MRKLAILSVSSFLFV, KSKYKLATSVLAGLL and GLAYKFVVPGAATPYE). The addition of four heteroclitic peptides − single point mutated epitopes − increased HLA binding affinity and raised the predicted world population coverage above 99%. [ABSTRACT FROM AUTHOR]

Introduction: While CD8+ T cells (cytotoxic T lymphocytes, CTLs) play important roles in immunity against Mycobacterium tuberculosis, only a small number of human leukocyte differentiation antigen (HLA) class I-restricted CTL epitopes for TB have been identified. The current study evaluates CTL epitopes of Rv3117 and Rv3120 proteins, two newly found M. tuberculosis region-diffference-5 (RD5)-encoded antigens, and their population coverage. Methodology: The amino acid sequences of the two proteins were subjected to epitope analysis under HLA-A2, A3 and B7 supertype restriction using NetCTL, SYFPEITHI, BIMAS, NetCTLPan, IEDB, NetMHC and NetMHCPan prediction online servers. Results: Eight RD5-encoded CTL epitopes were identified in the two proteins and the average population coverage of these epitopes was 87.2% among populations worldwide. Conclusion: These CTL epitopes that were identified in silico and may have potential use for CD8+ T cell-mediated TB vaccine design. [ABSTRACT FROM AUTHOR]

Payesh2010; 9: 173-187Accepted for publication: 1 July 2007[EPub a head of print-25 May 2010] Objective(s): Contribute to a better understanding of the Iranian health financing system and draw some useful clues for policy makers are the aim of the study.Methods: We interviewed a purposeful sample of 25 participants from 7 main actors in Iranian health Insurance system in late 2007. We asked about three main tasks of health financing system: revenue collection, Risk Pooling and Purchasing and used a model suggested by Guy Carrin to design the study and the framework method for the analysis.Results: Unknown insured rate, Regressive financing and, non transparent financial flow, Fragmented system and non compulsory insurance, Nonscientific designed BP, non health oriented and expensive payment system, uncontrolled demands and defect in administrative efficiency are seven themes which explain the defects of current universal coverage in Iran.Conclusion: A long term systematic approach plan is required in any reform in Iran’s health financing system. The plan should aim to respond the above problems systematically.

Diarrhoeal diseases due to Shigellosis account for deaths of ~1.5 million children every year in developing countries. Outer membrane proteins (OMPs) of Gram negative bacteria have been shown to be excellent subunit vaccine candidates against various pathogens. However, effective immune response can be generated using specific immunogenic determinants or peptides instead of whole protein or pathogen. In the present study, we chose six OMPs of Shigella flexneri 2a to predict peptides with good antigenic potential. Various tools were used in a systematic flow to predict B- and T-cell epitopes. Stringent selection criteria were used for epitope screening to ensure generation of both arms of immunity. These epitopes are predicted to be effective against a significantly large population of the diarrhoea afflicted countries in Southeast Asia. Most of the predicted epitopes are located towards the outer exposed region of proteins. The epitopes were docked with respective MHC Class I and II molecules to study peptide-MHC interactions. In conclusion, we have predicted an epitope ensemble against Shigellosis which can be experimentally validated for its immunogenic efficacy. We also propose a systematic workflow for immune-optimization to design effective peptide vaccines. [ABSTRACT FROM AUTHOR]

Melioidosis is a serious infectious diseases affecting multi-organ system in humans with high mortality rate. The disease is caused by the bacterium, Burkholderia pseudomallei and it is intrinsically resistant to many antibiotics. Thus, there is an urgent need for protective vaccine against B. pseudomallei ; which may reduce morbidity and mortality in endemic areas. The identification of peptides that bind to major histocompatibility complex II class helps in understanding the nature of immune response and identifying T-cell epitopes for the design of new vaccines. Previous studies indicate that, ompA, bipB, fliC and groEL proteins of B. pseudomallei stimulate CD4+ T-cell immune response and act as protective immunogens. However, the data for CD4+ T-cell epitopes of these immunogenic proteins are very limited. Hence, in this present study we attempted to identify CD4+ T-cell epitopes in B. pseudomallei immunogenic proteins using in silico approaches. We did population coverage analysis for these identified epitopic core sequences to identify individuals in endemic areas expected to respond to a given set of these epitopes on the basis of HLA genotype frequencies. We observed that eight epitopic core sequences, two from each immunogenic protein, were associated with the maximum number of HLA-DR binding alleles. These eight peptides are found to be immunogenic in more than 90% of population in endemic areas considered. Thus, these eight peptides containing epitopic core sequences may act as probable vaccine candidates and they may be considered for the development of epitope-based vaccines for melioidosis. [ABSTRACT FROM AUTHOR]

Scientists are rigorously looking for an efficient vaccine against the current pandemic due to the SARS-CoV-2 virus. The reverse vaccinology approach may provide us with significant therapeutic leads in this direction and further determination of T-cell/B-cell response to antigen. In the present study, we conducted a population coverage analysis referring to the diverse Indian population. From the Immune epitope database (IEDB), HLA- distribution analysis was performed to find the most promiscuous T-cell epitope out of In silico determined epitope of Spike protein from SARS-CoV-2. Epitopes were selected based on their binding affinity with the maximum number of HLA alleles belonging to the highest population coverage rate values for the chosen geographical area in India. 404 cleavage sites within the 1288 amino acids sequence of spike glycoprotein were determined by NetChop proteasomal cleavage prediction suggesting the presence of adequate sites in the protein sequence for cleaving into appropriate epitopes. For population coverage analysis, 179 selected epitopes present the projected population coverage up to 97.45% with 56.16 average hit and 15.07 pc90. 54 epitopes are found with the highest coverage among the Indian population and highly conserved within the given spike RBD domain sequence. Among all the predicted epitopes, 9-mer TRFASVYAW and RFDNPVLPF along with 12-mer LLAGTITSGWTF and VSQPFLMDLEGK epitopes are observed as the best due to their decent docking score and best binding affinity to corresponding HLA alleles during MD simulations. Outcomes from this study could be critical to design a vaccine against SARS-CoV-2 for a different set of populations within the country.Communicated by Ramaswamy H. Sarma.

Background: There is an emerging global consensus on the importance of universal health coverage (UHC), but no unanimity on the conceptual definition and scope of UHC, whether UHC is achievable or not, how to move towards it, common indicators for measuring its progress, and its long-term sustainability. This has resulted in various interpretations of the concept, emanating from different disciplinary perspectives. This paper discusses the various dimensions of UHC emerging from these interpretations and argues for the need to pay attention to the complex interactions across the various components of a health system in the pursuit of UHC as a legal human rights issue. Discussion: The literature presents UHC as a multi-dimensional concept, operationalized in terms of universal population coverage, universal financial protection, and universal access to quality health care, anchored on the basis of health care as an international legal obligation grounded in international human rights laws. As a legal concept, UHC implies the existence of a legal framework that mandates national governments to provide health care to all residents while compelling the international community to support poor nations in implementing this right. As a humanitarian social concept, UHC aims at achieving universal population coverage by enrolling all residents into health-related social security systems and securing equitable entitlements to the benefits from the health system for all. As a health economics concept, UHC guarantees financial protection by providing a shield against the catastrophic and impoverishing consequences of out-of-pocket expenditure, through the implementation of pooled prepaid financing systems. As a public health concept, UHC has attracted several controversies regarding which services should be covered: comprehensive services vs. minimum basic package, and priority disease-specific interventions vs. primary health care. Summary: As a multi-dimensional concept, grounded in international human rights laws, the move towards UHC in LMICs requires all states to effectively recognize the right to health in their national constitutions. It also requires a human rights-focused integrated approach to health service delivery that recognizes the health system as a complex phenomenon with interlinked functional units whose effective interaction are essential to reach the equilibrium called UHC. [ABSTRACT FROM AUTHOR]

Detecting statistically significant trends in incidence with cancer registries data not only depends on the size of their covered population but also on the levels of incidence rates, duration of diagnostic period and type of temporal variation. We simulated sample sizes of newly diagnosed cases based on a variety of plausible levels of cancer rates and scenarios of changing trends over a period of about 30 years. Each simulated set of cases was then analysed with joinpoint regression models. The power was derived as the relative frequency of the simulation runs where the p -value of the coefficient was less than 0.05 under the alternative model. In case of a decreasing trend with no change of direction (join), an Annual Percentage Change ( APC ) of 1% for an average rate of 10 per 100,000 is detectable in populations of half a million inhabitants or more with a nominal power of 80%. In a model with one joinpoint followed by an increasing trend, the minimum detectable APC increases, and an APC of about 2%, can be detected only with populations of at least 2 million. For analyses requiring a larger sample size than the actual covered population, alternative organisational strategies should be considered, such as an extension of population coverage or data pooling and merging from registries with comparable data. (i.e. when heterogeneity across merging registries is low or acceptable for the specific study question). [ABSTRACT FROM AUTHOR]