scholarly journals Model-informed target product profiles of long acting-injectables for use as seasonal malaria prevention

2021 ◽  
Author(s):  
Lydia Burgert ◽  
Theresa Reiker ◽  
Monica Golumbeanu ◽  
Joerg J. Moehrle ◽  
Melissa A. Penny
Keyword(s):  
Simulation Analysis ◽  
Selection Process ◽  
Malaria Incidence ◽  
Protective Efficacy ◽  
Malaria Prevention ◽  
Transmission Season ◽  
Quantitative Evidence ◽  
Trade Offs ◽  
Seasonal Malaria Chemoprevention ◽  
Long Acting

Seasonal malaria chemoprevention (SMC) has proven highly efficacious in reducing malaria incidence. However, the continued success of SMC is threatened by the spread of resistance against one of its main preventive ingredients, Sulfadoxine-Pyrimethamine(SP), operational challenges in delivery, and incomplete adherence to the regimens. Via a simulation study with an individual-based model of malaria dynamics, we provide quantitative evidence to assess long-acting injectables (LAIs) as potential alternatives to SMC. We explored the predicted impact of a range of novel preventive LAIs as a seasonal prevention tool in children aged three months to five years old during late-stage clinical trials and at implementation. LAIs were co-administered with a blood-stage clearing drug once at the beginning of the transmission season. We found the establishment of non-inferiority of LAIs to standard 3 or 4 rounds of SMC with SP-amodiaquine was challenging in clinical trial stages due to high intervention deployment coverage. However, our analysis of implementation settings where the achievable SMC coverage was much lower, LAIs with fewer visits per season are potential suitable replacements to SMC. Suitability as a replacement with higher impact is possible if the duration of protection of LAIs covered the duration of the transmission season. Furthermore, optimizing LAIs coverage and protective efficacy half-life via simulation analysis in settings with an SMC coverage of 60% revealed important trade-offs between protective efficacy decay and deployment coverage. Our analysis additionally highlights that for seasonal deployment for LAIs, it will be necessary to investigate the protective efficacy decay as early as possible during clinical development to ensure a well-informed candidate selection process.

scholarly journals Nutritional status in young children prior to the malaria transmission season in Burkina Faso and Mali, and its impact on the incidence of clinical malaria

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mariken de Wit ◽  
Matthew Cairns ◽  
Yves Daniel Compaoré ◽  
Issaka Sagara ◽  
Irene Kuepfer ◽  
...  
Keyword(s):  
Young Children ◽  
Nutritional Status ◽  
Burkina Faso ◽  
Malaria Transmission ◽  
Malaria Incidence ◽  
Clinical Malaria ◽  
High Coverage ◽  
Transmission Season ◽  
Malaria Transmission Season ◽  
Seasonal Malaria Chemoprevention

Abstract Background Malaria and malnutrition remain major problems in Sahel countries, especially in young children. The direct effect of malnutrition on malaria remains poorly understood, and may have important implications for malaria control. In this study, nutritional status and the association between malnutrition and subsequent incidence of symptomatic malaria were examined in children in Burkina Faso and Mali who received either azithromycin or placebo, alongside seasonal malaria chemoprevention. Methods Mid-upper arm circumference (MUAC) was measured in all 20,185 children who attended a screening visit prior to the malaria transmission season in 2015. Prior to the 2016 malaria season, weight, height and MUAC were measured among 4149 randomly selected children. Height-for-age, weight-for-age, weight-for-height, and MUAC-for-age were calculated as indicators of nutritional status. Malaria incidence was measured during the following rainy seasons. Multivariable random effects Poisson models were created for each nutritional indicator to study the effect of malnutrition on clinical malaria incidence for each country. Results In both 2015 and 2016, nutritional status prior to the malaria season was poor. The most prevalent form of malnutrition in Burkina Faso was being underweight (30.5%; 95% CI 28.6–32.6), whereas in Mali stunting was most prevalent (27.5%; 95% CI 25.6–29.5). In 2016, clinical malaria incidence was 675 per 1000 person-years (95% CI 613–744) in Burkina Faso, and 1245 per 1000 person-years (95% CI 1152–1347) in Mali. There was some evidence that severe stunting was associated with lower incidence of malaria in Mali (RR 0.81; 95% CI 0.64–1.02; p = 0.08), but this association was not seen in Burkina Faso. Being moderately underweight tended to be associated with higher incidence of clinical malaria in Burkina Faso (RR 1.27; 95% CI 0.98–1.64; p = 0.07), while this was the case in Mali for moderate wasting (RR 1.27; 95% CI 0.98–1.64; p = 0.07). However, these associations were not observed in severely affected children, nor consistent between countries. MUAC-for-age was not associated with malaria risk. Conclusions Both malnutrition and malaria were common in the study areas, high despite high coverage of seasonal malaria chemoprevention and long-lasting insecticidal nets. However, no strong or consistent evidence was found for an association between any of the nutritional indicators and the subsequent incidence of clinical malaria.

scholarly journals Identifying an optimal dihydroartemisinin-piperaquine dosing regimen for malaria prevention in young Ugandan children

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Erika Wallender ◽  
Ali Mohamed Ali ◽  
Emma Hughes ◽  
Abel Kakuru ◽  
Prasanna Jagannathan ◽  
...  
Keyword(s):  
Malaria Incidence ◽  
Protective Efficacy ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Malaria Prevention ◽  
Incidence Data ◽  
Resistance Selection ◽  
Mixed Effects Modeling ◽  
Malnourished Children ◽  
Dosing Regimens

AbstractIntermittent preventive treatment (IPT) with dihydroartemisinin-piperaquine (DP) is highly protective against malaria in children, but is not standard in malaria-endemic countries. Optimal DP dosing regimens will maximize efficacy and reduce toxicity and resistance selection. We analyze piperaquine (PPQ) concentrations (n = 4573), malaria incidence data (n = 326), and P. falciparum drug resistance markers from a trial of children randomized to IPT with DP every 12 weeks (n = 184) or every 4 weeks (n = 96) from 2 to 24 months of age (NCT02163447). We use nonlinear mixed effects modeling to establish malaria protective PPQ levels and risk factors for suboptimal protection. Compared to DP every 12 weeks, DP every 4 weeks is associated with 95% protective efficacy (95% CI: 84–99%). A PPQ level of 15.4 ng/mL reduces the malaria hazard by 95%. Malnutrition reduces PPQ exposure. In simulations, we show that DP every 4 weeks is optimal across a range of transmission intensities, and age-based dosing improves malaria protection in young or malnourished children.

scholarly journals Health education through mass media announcements by loudspeakers about malaria care: prevention and practice among people living in a malaria endemic area of northern Myanmar

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Pyae Linn Aung ◽  
Tepanata Pumpaibool ◽  
Than Naing Soe ◽  
Jessica Burgess ◽  
Lynette J. Menezes ◽  
...  
Keyword(s):  
Intervention Group ◽  
Malaria Prevention ◽  
Care Seeking ◽  
Endemic Region ◽  
Post Intervention ◽  
Chi Square ◽  
Transmission Season ◽  
Baseline Knowledge ◽  
Peak Transmission

Abstract Background Interventions to raise community awareness about malaria prevention and treatment have used various approaches with little evidence on their efficacy. This study aimed to determine the effectiveness of loudspeaker announcements regarding malaria care and prevention practices among people living in the malaria endemic villages of Banmauk Township, Sagaing Region, Myanmar. Methods Four villages among the most malaria-burdened areas were randomly selected: two villages were assigned as the intervention group, and two as the control. Prior to the peak transmission season of malaria in June 2018, a baseline questionnaire was administered to 270 participants from randomly selected households in the control and intervention villages. The loudspeaker announcements broadcasted health messages on malaria care and prevention practices regularly at 7:00 pm every other day. The same questionnaire was administered at 6-month post intervention to both groups. Descriptive statistics, Chi-square, and the t-test were utilized to assess differences between and within groups. Results Participants across the control and intervention groups showed similar socio-economic characteristics; the baseline knowledge, attitude and practice mean scores were not significantly different between the groups. Six months after the intervention, improvements in scores were observed at p-value < 0.001 in both groups, however; the increase was greater among the intervention group. The declining trend of malaria was also noticed during the study period. In addition, more than 75% of people expressed positive opinions of the intervention. Conclusions The loudspeaker intervention was found to be feasible and effective, as shown by the significant improvement in scores related to prevention and care-seeking practices for malaria as well as reduced malaria morbidity. Expanding the intervention to a larger population in this endemic region and evaluating its long-term effectiveness are essential in addition to replicating this in other low-resource malaria endemic regions.

scholarly journals Estimating the local spatio‐temporal distribution of malaria from routine health information systems in areas of low health care access and reporting

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Elizabeth Hyde ◽  
Matthew H. Bonds ◽  
Felana A. Ihantamalala ◽  
Ann C. Miller ◽  
Laura F. Cordier ◽  
...  
Keyword(s):  
Health Care ◽  
Access To Health Care ◽  
Malaria Incidence ◽  
Universal Access ◽  
Surveillance Systems ◽  
Passive Surveillance ◽  
Transmission Season ◽  
Access To Health ◽  
Spatio Temporal ◽  
Geographic Access To Care

Abstract Background Reliable surveillance systems are essential for identifying disease outbreaks and allocating resources to ensure universal access to diagnostics and treatment for endemic diseases. Yet, most countries with high disease burdens rely entirely on facility-based passive surveillance systems, which miss the vast majority of cases in rural settings with low access to health care. This is especially true for malaria, for which the World Health Organization estimates that routine surveillance detects only 14% of global cases. The goal of this study was to develop a novel method to obtain accurate estimates of disease spatio-temporal incidence at very local scales from routine passive surveillance, less biased by populations' financial and geographic access to care. Methods We use a geographically explicit dataset with residences of the 73,022 malaria cases confirmed at health centers in the Ifanadiana District in Madagascar from 2014 to 2017. Malaria incidence was adjusted to account for underreporting due to stock-outs of rapid diagnostic tests and variable access to healthcare. A benchmark multiplier was combined with a health care utilization index obtained from statistical models of non-malaria patients. Variations to the multiplier and several strategies for pooling neighboring communities together were explored to allow for fine-tuning of the final estimates. Separate analyses were carried out for individuals of all ages and for children under five. Cross-validation criteria were developed based on overall incidence, trends in financial and geographical access to health care, and consistency with geographic distribution in a district-representative cohort. The most plausible sets of estimates were then identified based on these criteria. Results Passive surveillance was estimated to have missed about 4 in every 5 malaria cases among all individuals and 2 out of every 3 cases among children under five. Adjusted malaria estimates were less biased by differences in populations’ financial and geographic access to care. Average adjusted monthly malaria incidence was nearly four times higher during the high transmission season than during the low transmission season. By gathering patient-level data and removing systematic biases in the dataset, the spatial resolution of passive malaria surveillance was improved over ten-fold. Geographic distribution in the adjusted dataset revealed high transmission clusters in low elevation areas in the northeast and southeast of the district that were stable across seasons and transmission years. Conclusions Understanding local disease dynamics from routine passive surveillance data can be a key step towards achieving universal access to diagnostics and treatment. Methods presented here could be scaled-up thanks to the increasing availability of e-health disease surveillance platforms for malaria and other diseases across the developing world.

A Spectral Optimization Algorithm for Multi-Objective Prototype Selection

1995 ◽  
Author(s):  
Andy Dong ◽  
Alice M. Agogino
Keyword(s):  
Optimization Algorithm ◽  
Parametric Design ◽  
Selection Process ◽  
Objective Evaluation ◽  
Design Synthesis ◽  
Multi Objective ◽  
Trade Offs ◽  
Spectral Optimization ◽  
The Right ◽  
Selection Of

Abstract In design synthesis, engineering prototypes make an ideal representation medium for preliminary designs. Unlike parametric design wherein a pre-specified design is parametrically varied, design synthesis demands artistic creativity and engineering experience to transform the previously known components, relationships and designs into a new form. The process compels the designer to ascertain which prototypes will, in some sense, best satisfy the design task. The challenge in this assignment lies in selecting the “right” design prototype. This selection process typically entails an objective evaluation of different designs that perform the same functions or have similar intended behavior and comparing trade-offs between alternate designs. This paper introduces a multi-objective spectral optimization algorithm for the selection of design prototypes based upon their functional representations. The optimization algorithm returns an index of rank, scoring the functional similarity of the proposed design to the goal design. Two illustrative examples apply the algorithm to the selection of a heat fin and beam.

scholarly journals FEATURE FILTERING AND SELECTION FOR DRY MATTER ESTIMATION ON PERENNIAL RYEGRASS: A CASE STUDY OF VEGETATION INDICES

2019 ◽  
Vol XLII-2/W13 ◽  
pp. 1827-1831 ◽  
Author(s):  
G. T. Alckmin ◽  
L. Kooistra ◽  
A. Lucieer ◽  
R. Rawnsley
Keyword(s):  
Feature Selection ◽  
Perennial Ryegrass ◽  
Dry Matter ◽  
Selection Process ◽  
Vegetation Indices ◽  
Robust Model ◽  
Trade Offs ◽  
Initial Dataset ◽  
High Degree

<p><strong>Abstract.</strong> Vegetation indices (VIs) have been extensively employed as a feature for dry matter (DM) estimation. During the past five decades more than a hundred vegetation indices have been proposed. Inevitably, the selection of the optimal index or subset of indices is not trivial nor obvious. This study, performed on a year-round observation of perennial ryegrass (n&amp;thinsp;=&amp;thinsp;900), indicates that for this response variable (i.e. kg.DM.ha<sup>&amp;minus;1</sup>), more than 80% of indices present a high degree of collinearity (correlation&amp;thinsp;&amp;gt;&amp;thinsp;|0.8|.) Additionally, the absence of an established workflow for feature selection and modelling is a handicap when trying to establish meaningful relations between spectral data and biophysical/biochemical features. Within this case study, an unsupervised and supervised filtering process is proposed to an initial dataset of 97 VIs. This research analyses the effects of the proposed filtering and feature selection process to the overall stability of final models. Consequently, this analysis provides a straightforward framework to filter and select VIs. This approach was able to provide a reduced feature set for a robust model and to quantify trade-offs between optimal models (i.e. lowest root mean square error &amp;ndash; RMSE&amp;thinsp;=&amp;thinsp;412.27&amp;thinsp;kg.DM.ha<sup>&amp;minus;1</sup>) and tolerable models (with a smaller number of features &amp;ndash; 4 VIs and within 10% of the lowest RMSE.)</p>

scholarly journals Effect of Interventions to Reduce Malaria Incidence Among Military Personnel on Active Duty: Study Protocol for a Cluster Randomised Controlled Trial of the Impact of Etofenprox-treated Uniforms, Permethrin-treated Uniforms and DEET Insect Repellent

2021 ◽  
Author(s):  
Daniel Msellemu ◽  
Amanda Ross ◽  
Lucky Temu ◽  
Irene Moshi ◽  
Lorenz Hofer ◽  
...  
Keyword(s):  
Military Personnel ◽  
Malaria Infection ◽  
Malaria Incidence ◽  
Protective Efficacy ◽  
Controlled Trial ◽  
Active Duty ◽  
Insect Repellent ◽  
Insect Repellents ◽  
Cluster Randomised ◽  
The Impact

Abstract Background: While there is strong evidence that permethrin-treated clothing and topical insect repellents are protective against insect bites, there are few studies assessing the impact on malaria infection. This study will evaluate the impact of the protective efficacy of bite prevention methods on the incidence of malaria infection among military personnel in an operational setting. Permethrin-treated uniforms will be compared to etofenprox-treated uniforms, with both clothing treatments used in conjunction with DEET insect repellent. An additional study arm will test permethrin uniforms with placebo lotion to determine if there is any additional protective effect of using DEET with insecticide-treated clothing. Method: A cluster randomised double-blind placebo-controlled trial is planned to evaluate the effectiveness of the interventions on preventing malaria infections in soldiers on active duty at Mgambo National Service Camp in Tanga, Tanzania. The arms are (1) permethrin-treated uniform with 30% DEET liposome formula; (2) permethrin-treated uniform with placebo lotion; (3) candidate insect repellent system, i.e., etofenprox-treated uniform with 30% DEET liposome formula; and (4) placebo, i.e., untreated uniforms with placebo lotion. The primary outcome is the incidence of Plasmodium falciparum malaria infection detected by polymerase chain reaction (PCR) by active case detection using surveys every 2 weeks for 12 months. Rapid diagnostic tests will be used for diagnosis of participants with symptoms. The unit of randomisation will be combania: companies formed by recruits aged 18 to 25 years; combania do activities together and sleep in the same dormitory. Unequal randomisation will be used to optimise statistical power for the primary comparison between permethrin-treated uniforms with DEET and etofenprox-treated uniforms with DEET. Discussion: This trial will estimate the effects of permethrin with DEET compared to those of the new fabric treatment etofenprox with DEET and any additional effect of using DEET. The results will inform strategies to protect military personnel and civilians who have more outdoor or occupational malaria exposure than the general public. Trial registration: clinicaltrials.gov Registration number NCT02938975.

scholarly journals Cubesat Antenna Analysis and Design: Are you using the right computational electromagnetic tool?

2021 ◽  
Vol 10 (2) ◽  
pp. 1-18
Author(s):  
I. Latachi ◽  
T. Rachidi ◽  
M. Karim
Keyword(s):  
Selection Process ◽  
Critical Role ◽  
Antenna System ◽  
Antenna Design ◽  
Design Processes ◽  
Analysis And Design ◽  
Trade Offs ◽  
Development Costs ◽  
Communication Links ◽  
The Right

Antenna systems play a critical role in establishing wireless communication links and sustaining remote sensing requirements for Cubesat applications. In addition to the usual antenna design requirements, Cubesat-based spacecrafts impose additional stringent constraints related to the on-board available space, power consumption and development costs. To develop optimal antenna prototypes while considering all these constraints and decrease trial and error related costs, computational electromagnetics (CEM) simulation tools are used. The accuracy of simulation results depends to a great extent on the choice of the appropriate CEM tool for the particular antenna problem to be analyzed; ergo, identifying and answering key questions about design objectives and requirements is necessary for informed decision-making throughout the selection and design processes. However, this could be quite challenging because of existing gaps both in the practitioners’ knowledge about different CEM tools capabilities, limitations, and design know-how. This is especially true for non-specialists such as students and academics involved in student driven Cubesat projects. Therefore, the rationale of this manuscript is to bridge those gaps and clarify some common misconception commonly encountered during the selection and design processes. In that regard, first, an overview of existing antenna configurations commonly used in Cubesat communications is provided. Next, antenna design general workflow is presented. Then, capabilities and limitations of different CEM solving methods are presented. After that, CEM software selection process trade-offs and possible sources of errors are discussed from a practical viewpoint. Finally, a case study of Masat-1 antenna system design is presented as practical example.

scholarly journals Targeting hotspots to reduce transmission of malaria in Senegal: modeling of the effects of human mobility

2018 ◽  
Author(s):  
Kankoé Sallah ◽  
Roch Giorgi ◽  
El Hadj Ba ◽  
Martine Piarroux ◽  
Renaud Piarroux ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Malaria Incidence ◽  
Human Mobility ◽  
Scaling Up ◽  
Intervention Strategies ◽  
Control Measures ◽  
Transmission Season ◽  
Targeted Interventions ◽  
Additional Control ◽  
Mathematical Simulations

AbstractBackgroundIn central Senegal malaria incidences have declined in recent years in response to scaling-up of control measures, but now remains stable, making elimination improbable. Additional control measures are needed to reduce transmission.MethodsBy using a meta-population mathematical model, we evaluated chemotherapy interventions targeting stable malaria hotspots, using a differential equation framework and incorporating human mobility, and fitted to weekly malaria incidences from 45 villages, over 5 years. Three simulated approaches for selecting intervention targets were compared: a) villages with at least one malaria case during the low transmission season of the previous year; b) villages ranked highest in terms of incidence during the high transmission season of the previous year; c) villages ranked based on the degree of connectivity with adjacent populations.ResultsOur mathematical modeling, taking into account human mobility, showed that the intervention strategies targeting hotspots should be effective in reducing malaria incidence in both treated and untreated areas.ConclusionsMathematical simulations showed that targeted interventions allow increasing malaria elimination potential.

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