Explore the vast range of titles available.

Recent advances in mosquito eradication and antimalarial treatments have reduced the malaria burden only modestly. An effective malaria vaccine remains a high priority, but its development has several challenges. Among many potential candidates, the RTS,S/AS01 vaccine (Mosquirix ) remains the leading candidate. This review aims to understand the advances in the RTS,S/AS01 vaccine, and future comments regarding the vaccine's effectiveness in malaria eradication. Literature review for the past five decades was performed searching PubMed, EMBASE Ovid, and Cochrane Library, with using the following search items: (\"malaria\" OR \"WHO's malaria\" OR \"Plasmodium falciparum\" OR \"RTS,S\" OR \"RTS,S/AS01\" OR \"RTS,S/AS02\" OR \"pre-erythrocytic malaria\" OR \"circumsporozoite\" OR \"Mosquirix\") AND (\"vaccine\" OR \"vaccination\"). RTS,S/AS01, a recombinant pre-erythrocytic vaccine containing surface-protein (circumsporozoite) antigen, is safe, well-tolerated, and immunogenic in children. Three doses, along with a booster, have a modest efficacy of about 36% in children (age 5-17 months) and about 26% in infants (age 6-12 weeks) against clinical malaria during a 48-month follow-up. However, the efficacy varies among population subgroups and with the parasite strain, it reduces without a booster and offers protection for a limited duration. Because of its potential cost-effectiveness and positive public health effect, the vaccine is being investigated in a pilot program for mortality benefits and broader deployment. The RTS,S/AS01 vaccine prevents malaria; however, it should be considered another addition to the malaria-control program and not as an eradication tool because of its relatively low to modest efficacy.

Background While Ghana has a good track record in the Expanded Programme on Immunization, there are substantial challenges with regards to subsequent vaccinations, particularly after the first year of life of the child. Given that the last dose of the RTS, S/AS01 E vaccine against malaria is administered at 24 months, there is a high likelihood of default. Hence, it is imperative to understand the dynamics and reasons for the defaults to enable the development of effective implementation strategies. This study explored why caregivers default on the RTS, S/AS01 E vaccine from the perspective of health service providers and caregivers. Methods This study employed an exploratory, descriptive approach. Using a purposive sampling technique, caregivers who defaulted and health service providers directly involved in the planning and delivery of the RTS, S/AS01 E vaccine at the district level were recruited. A total of five health service providers and 30 mothers (six per FGD) participated in this study. Data analysis was done using NVivo-12 following Collaizi’s thematic framework for qualitative analysis. The study relies on the Standards for Reporting Qualitative Research. Results Reasons for defaulting included the overlap of timing of the last dose and the child starting school, disrespectful attitudes of some health service providers, concerns about adverse side effects and discomforts, travel out of the implementing district, the perception that the vaccines are too many, and lack of support from partners. Conclusion To reduce the occurrence of defaulting on the RTS, S/AS01 E  vaccine programme, stakeholders must reconsider the timing of the last dose of the vaccine. The schedule of the RTS, S/AS01 E vaccine should be aligned with the established EPI schedule of Ghana. This will significantly limit the potential of defaults, particularly for the last dose. Also, the findings from this study underscore a need to encourage male partner involvement in the RTS, S/AS01 E vaccine programme. Health promotion programmes could be implemented to raise caregivers’ awareness of potential adverse reactions and discomforts—this is necessary to prepare the caregiver for the vaccine process psychologically.

The international GNSS service (IGS) real-time service (RTS) provides orbit and clock corrections for the global navigation satellite system (GNSS) via the internet. RTS is widely used for real-time, precise positioning and its data is transmitted via the internet. Intermittent data loss can occur and cause positioning accuracy degradation. RTS data has a discontinuity when the issue of data (IOD) changes every two hours. If the signal loss occurs immediately after the IOD change, then the performance of the RTS prediction degrades significantly. We propose an adjustment method to make the RTS data across the IOD change, which makes it possible to use long RTS data for building a prediction model. The proposed adjustment method is combined with a long-short-term memory (LSTM) network to improve long-period prediction accuracy. Experiments with GPS and RTS were performed to evaluate the RTS orbit prediction accuracy. The LSTM with the IOD adjustment outperforms other polynomial prediction methods, and the positioning accuracy with the predicted RTS orbit correction shows a significant improvement.

High−precision and robust localization is critical for intelligent vehicle and transportation systems, while the sensor signal loss or variance could dramatically affect the localization performance. The vehicle localization problem in an environment with Global Navigation Satellite System (GNSS) signal errors is investigated in this study. The error state Kalman filtering (ESKF) and Rauch–Tung–Striebel (RTS) smoother are integrated using the data from Inertial Measurement Unit (IMU) and GNSS sensors. A segmented RTS smoothing algorithm is proposed in order to estimate the error state, which is typically close to zero and mostly linear, which allows more accurate linearization and improved state estimation accuracy. The proposed algorithm is evaluated using simulated GNSS signals with and without signal errors. The simulation results demonstrate its superior accuracy and stability for state estimation. The designed ESKF algorithm yielded an approximate 3% improvement in long straight line and turning scenarios compared to classical EKF algorithm. Additionally, the ESKF−RTS algorithm exhibited a 10% increase in the localization accuracy compared to the ESKF algorithm. In the double turning scenarios, the ESKF algorithm resulted in an improvement of about 50% in comparison to the EKF algorithm, while the ESKF−RTS algorithm improved by about 50% compared to the ESKF algorithm. These results indicated that the proposed ESKF−RTS algorithm is more robust and provides more accurate localization.

Background Following a 30-year development process, RTS,S/AS01 E (GSK, Belgium) is the first malaria vaccine to reach Phase IV assessments. The World Health Organization-commissioned Malaria Vaccine Implementation Programme (MVIP) is coordinating the delivery of RTS,S/AS01 E through routine national immunization programmes in areas of 3 countries in sub-Saharan Africa. The first doses were given in the participating MVIP areas in Malawi on 23 April, Ghana on 30 April, and Kenya on 13 September 2019. The countries participating in the MVIP have little or no baseline incidence data on rare diseases, some of which may be associated with immunization, a deficit that could compromise the interpretation of possible adverse events reported following the introduction of a new vaccine in the paediatric population. Further, effects of vaccination on malaria transmission, existing malaria control strategies, and possible vaccine-mediated selective pressure on Plasmodium falciparum variants, could also impact long-term malaria control. To address this data gap and as part of its post-approval commitments, GSK has developed a post-approval plan comprising of 4 complementary Phase IV studies that will evaluate safety, effectiveness and impact of RTS,S/AS01 E through active participant follow-up in the context of its real-life implementation. Methods EPI-MAL-002 (NCT02374450) is a pre-implementation safety surveillance study that is establishing the background incidence rates of protocol-defined adverse events of special interest. EPI-MAL-003 (NCT03855995) is an identically designed post-implementation safety and vaccine impact study. EPI-MAL-005 (NCT02251704) is a cross-sectional pre- and post-implementation study to measure malaria transmission intensity and monitor the use of other malaria control interventions in the study areas, and EPI-MAL-010 (EUPAS42948) will evaluate the P. falciparum genetic diversity in the periods before and after vaccine implementation. Conclusion GSK’s post-approval plan has been designed to address important knowledge gaps in RTS,S/AS01 E vaccine safety, effectiveness and impact. The studies are currently being conducted in the MVIP areas. Their implementation has provided opportunities and posed challenges linked to conducting large studies in regions where healthcare infrastructure is limited. The results from these studies will support ongoing evaluation of RTS,S/AS01 E ’s benefit-risk and inform decision-making for its potential wider implementation across sub-Saharan Africa. Graphic abstract

Background A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01 E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. Methods In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01 E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01 E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01 E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. Results The overall protective efficacy from RTS,S/AS01 E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2–3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. Conclusions The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. Trial registration The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218

This paper introduces a proposed method for identifying the left and right Returns to Scales (RTS) and the overall RTS of frontier units based on the theoretical framework of data envelopment analysis (DEA). This paper first proposes an alternative definition for Left RTS (L-RTS) and Right RTS (R-RTS) of frontier units and then by focusing on this definition, provides two new DEA models to present a proposed method for identifying the L-RTS and R-RTS of frontier units. The major advantages of these two models include that they are feasible in all situations. Also, these models are capable to properly and accurately identify frontier units and their type of L-RTS and R-RTS, without any plurality in their judgment. The proposed method is compared -theoretically and experimentally- with other methods presented in the literature. Moreover, the theoretical correlation between the concepts of overall RTS and L&R-RTS of frontier units is analyzed. Then, this analysis is used to propose an alternative method for categorizing overall RTS of frontier units. Experimental application of this method shows that the results of evaluation of overall RTS of frontier units obtained by the proposed method is completely consistent with the results of the method presented by Banker and Thrall (Eur J Oper Res 62(1):74–84, 1992). The proposed methods in this paper can be easily used by the existing codes of DEA.

Background In October 2021, the World Health Organization (WHO) recommended the RTS,S/AS01 E (RTS,S) malaria vaccine for the prevention of Plasmodium falciparum malaria in children living in endemic areas informed by evidence from the subnational pilot introduction and evaluation in Ghana, Kenya, and Malawi as part of the WHO-coordinated Malaria Vaccine Implementation Programme (MVIP). With the global vaccine supply boosted by the pre-qualification of a second malaria vaccine, R21/Matrix-M (R21), in October 2023, many endemic countries (20 as of April 2025) have introduced malaria vaccines into their national childhood immunization and malaria control programmes. More endemic countries are expected to introduce or scale up malaria vaccines in 2025 and beyond. This paper summarizes key operational lessons from the pilot countries to facilitate the introduction and scale-up of malaria vaccination in other countries. Methods Pilot areas were identified, in part, based on local malaria epidemiology. RTS,S was initially introduced in randomly selected areas, while other areas served as comparators until the four-dose schedule vaccine was scaled up following the WHO recommendation in 2021. In Ghana and Kenya, the vaccine was administered at ages 6, 7, 9, and 24 months (Ghana switched to administer the fourth dose at age 18 months in 2023), and Malawi chose a schedule of 5, 6, 7, and 22 months. Results Vaccination coverage improved over time, reaching about 80% for the first dose and around 75% for the third dose by 2023 in the initial pilot areas. Implementation challenges included an inadequate understanding of age eligibility among healthcare workers during the early phase of introduction, low fourth dose coverage (with a median coverage of 46% in 2023 across the three countries), and disruptions to service delivery caused by disease outbreaks and other natural disasters. Health stakeholders and caregivers attested to the positive impact of introducing the malaria vaccine, including a reduction in malaria hospitalizations and the strengthening of the National Immunization Programme (NIP) through routine immunization refresher training and supportive supervision. Conclusions The pilot highlighted lessons for malaria vaccine introduction: (1) clearly outlined roles and responsibilities of key stakeholders including NIP and National Malaria Programme (NMP); (2) appropriate approach to vaccine introduction launch, communication, and demand generation to enhance vaccine uptake; (3) flexibility with dose scheduling to optimize coverage; and (4) updated data collection tools for accurate documentation, and data quality.

AbstractsBackgroundEnsuring rapid and precise mortality prediction in patients with traumatic brain injury (TBI) at the emergency department (ED) is paramount in patient triage and enhancing their outcomes. We aimed to estimate and compare the predictive power of the Trauma Rating Index in Age, Glasgow Coma Scale, Respiratory rate, and Systolic blood pressure score (TRIAGES) and Revised Trauma Score (RTS) for 24-h in-hospital mortality in patients with isolated TBI. MethodsWe conducted a retrospective single-center study analyzing clinical data from 1156 patients with isolated acute TBI treated in the ED of the Affiliated Hospital of Nantong University from January 1, 2020, to December 31, 2020. We calculated each patient's TRIAGES and RTS scores and estimated their predictive value for short-term mortality using receiver operating characteristic (ROC) curves. Results87 patients (7.53%) died within 24 h of admission. The non-survival group had higher TRIAGES and lower RTS than the survival group. Compared to non-survivors, survivors exhibited higher Glasgow Coma Scale scores (GCS) with a median score of 15 (12, 15) compared to a median score of 4.0 (3.0, 6.0). The crude and adjusted odds ratios (ORs) for TRIAGES were 1.79, 95% CI (1.62 to 1.98) and 1.79, 95% CI (1.60 to 2.00), respectively. The crude and adjusted ORs for RTS were 0.39, 95% CI (0.33 to 0.45) and 0.40, 95% CI (0.34 to 0.47), respectively. The area under the ROC (AUROC) curve of TRIAGES, RTS, and GCS was 0.865 (0.844 to 0.884), 0.863 (0.842 to 0.882), and 0.869 (0.830 to 0.909), respectively. The optimal cut-off values for predicting 24-h in-hospital mortality were 3 for TRIAGES, 6.08 for RTS, and 8 for GCS. The subgroup analysis showed a higher AUROC in TRIAGES (0.845) compared to GCS (0.836) and RTS (0.829) among patients aged 65 and above, although the difference was not statistically significant. ConclusionsTRIAGES and RTS have shown promising efficacy in predicting 24-h in-hospital mortality in patients with isolated TBI, with comparable performance to GCS. However, improving the comprehensiveness of assessment does not necessarily translate into an overall increase in predictive ability.