Longitudinal estimation of Plasmodium falciparum prevalence in relation to malaria prevention measures in six sub-Saharan African countries.

BACKGROUND: Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. METHODS: This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013. Participants were enrolled in a 2:1:1 ratio according to age category: 6 months-4 years, 5-19 years, and ≥ 20 years, respectively, per year and per centre. All sites carried out surveys 1-3 while survey 4 was conducted only in 3 sites. Surveys were usually performed during the peak malaria parasite transmission season, in one home visit, when medical history and malaria risk factors/prevention measures were collected, and a blood sample taken for rapid diagnostic test, microscopy, and haemoglobin measurement. PfPR was estimated by site and age category. RESULTS: Overall, 6401 (survey 1), 6411 (survey 2), 6400 (survey 3), and 2399 (survey 4) individuals were included in the analyses. In the 6 months-4 years age group, the lowest prevalence (assessed using microscopy) was observed in 2 Tanzanian centres (4.6% for Korogwe and 9.95% for Bagamoyo) and Lambaréné, Gabon (6.0%), while the highest PfPR was recorded for Nanoro, Burkina Faso (52.5%). PfPR significantly decreased over the 3 years in Agogo (Ghana), Kombewa (Kenya), Lilongwe (Malawi), and Bagamoyo (Tanzania), and a trend for increased PfPR was observed over the 4 surveys for Kintampo, Ghana. Over the 4 surveys, for all sites, PfPR was predominantly higher in the 5-19 years group than in the other age categories. Occurrence of fever and anaemia was associated with high P. falciparum parasitaemia. Univariate analyses showed a significant association of anti-malarial treatment in 4 surveys (odds ratios [ORs]: 0.52, 0.52, 0.68, 0.41) and bed net use in 2 surveys (ORs: 0.63, 0.68, 1.03, 1.78) with lower risk of malaria infection. CONCLUSION: Local PfPR differed substantially between sites and age groups. In children 6 months-4 years old, a significant decrease in prevalence over the 3 years was observed in 4 out of the 8 study sites. Trial registration Clinical Trials.gov identifier: NCT01190202:NCT. GSK Study ID numbers: 114001

Patient-specific biokinetics evaluation based on multiple SPECT images or hybrid planar/SPECT technique using OEDIPE 3D personalized dosimetry software: development and application

International audienceBackground:With the development of targeted radionuclide therapy, it has become increasingly necessary to develop comprehensive tools to compute 3D personalized dosimetry accounting for patient-specific biokinetics. For that purpose new functionalities were developed in OEDIPE software, to insure compatibility with different sets of patient images (multiple 3D images, multiple planar/SPECT images).Materiel & Method:Two new processes of image analyses were implemented and adapted to multiple time-point 3D images (SPECT/CT or PET/CT), and multiple planar images associated to a single SPECT/CT. Both processes enable recovering time-activity data for each volume of interest (VOI). A biokinetic module was developed to fit time-activity curves (TACs) to the obtained data and to calculate the cumulated activity in the VOIs. To evaluate the robustness of these developments, multiple SPECT/CT and planar images of a JASZCZAK phantom containing I-131 were consecutively acquired at different time-points. Cumulated activity of I-131 was estimated in each sphere using: (i) the SPECT/CT images only, and (ii) the planar series associated to one SPECT/CT out of the six available images, to quantify the influence of the selected time-point at which the SPECT was acquired. Results were compared with the known cumulated activity. To test the clinical applicability of these developments, cumulated activities in lesions and in the lungs of a patient treated for differentiated thyroid cancer were estimated using four planar images and a SPECT/CT scan acquired after I-131 administration. Whole-body retention data combined with SPECT activities were used to generate biokinetic data to compare with.Results:Activities and cumulated activities estimated using OEDIPE in the phantom spheres agreed well with the reference values for both approaches. Results obtained for the patient were similar with those derived from the method based on the whole-body retention data combined with SPECT activities.Conclusion:These new features of OEDIPE allow automatic evaluation of patient-specific biokinetics from different series of patient images, enabling efficient patient-specific internal dosimetry without the need for external software to estimate the cumulated activities in different VOIs.Keywords:targeted radionuclide therapy (TRT); radiopharmaceutical therapy (RPT); patient-specific biokinetics; 3D personalized internal dosimetry; Monte Carlo-based radiation transport code; OEDIPE dosimetric software; hybrid planar-SPECT dosimetr

Design of a Phase III cluster randomized trial to assess the efficacy and safety of a malaria transmission blocking vaccine.

Vaccines interrupting Plasmodium falciparum malaria transmission targeting sexual, sporogonic, or mosquito-stage antigens (SSM-VIMT) are currently under development to reduce malaria transmission. An international group of malaria experts was established to evaluate the feasibility and optimal design of a Phase III cluster randomized trial (CRT) that could support regulatory review and approval of an SSM-VIMT. The consensus design is a CRT with a sentinel population randomly selected from defined inner and buffer zones in each cluster, a cluster size sufficient to assess true vaccine efficacy in the inner zone, and inclusion of ongoing assessment of vaccine impact stratified by distance of residence from the cluster edge. Trials should be conducted first in areas of moderate transmission, where SSM-VIMT impact should be greatest. Sample size estimates suggest that such a trial is feasible, and within the range of previously supported trials of malaria interventions, although substantial issues to implementation exist

In vitro activity of ferroquine against artemisinin-based combination therapy (ACT)-resistant Plasmodium falciparum isolates from Cambodia

International audienceBackgroundCambodia is the epicentre of resistance emergence for virtually all antimalarial drugs. Selection and spread of parasites resistant to artemisinin-based combination therapy (ACT) is a major threat for malaria elimination, hence the need to renew the pool of effective treatments.ObjectivesTo determine whether ACT resistance haplotypes could have an effect on ferroquine in vitro antimalarial activity.MethodsIn vitro susceptibility to ferroquine was measured for 80 isolates from Cambodia characterized for their molecular resistance profile to artemisinin, piperaquine and mefloquine.ResultsAmong the 80 isolates tested, the overall median (IQR) IC50 of ferroquine was 10.9 nM (8.7–18.3). The ferroquine median (IQR) IC50 was 8.9 nM (8.1–11.8) for Pfk13 WT parasites and was 12.9 nM (9.5–20.0) for Pfk13 C580Y parasites with no amplification of Pfpm2 and Pfmdr1 genes. The median (IQR) IC50 of ferroquine for Pfk13 C580Y parasites with amplification of the Pfpm2 gene was 17.2 nM (14.5–20.5) versus 9.1 nM (7.9–10.7) for Pfk13 C580Y parasites with amplification of the Pfmdr1 gene.ConclusionsFerroquine exerts promising efficacy against ACT-resistant isolates. Whereas Pfpm2 amplification was associated with the highest parasite tolerance to ferroquine, the susceptibility range observed was in accordance with those measured in ACT resistance-free areas. This enables consideration of ferroquine as a relevant therapeutic option against ACT-resistant malaria

Aligning new interventions with developing country health systems : target product profiles, presentation, and clinical trial design

Abstract Many new interventions are being created to address health problems of the developing world. However, many developing countries have fragile health systems and find it difficult to accommodate change. Consequently, it is essential that new interventions are well aligned with health systems and their users. Establishing target product profiles (TPPs) is a critical, early step towards tailoring interventions to suit both of these constituencies. Specific analyses can help identify and establish relevant TPP criteria such as optimal formulation, presentation and packaging. Clinical trials for a new intervention should be designed to address both TPP-specific questions and anticipated use of the intervention in target countries. Examples are provided from research on malaria vaccines that are also applicable to other new public health intervention

Environmental transition: overview of actions to reduce the environmental footprint of astronomy

National audienceTo keep current global warming below 1.5 • C compared with the pre-industrial era, measures must be taken as quickly as possible in all spheres of society. Astronomy must also make its contribution. In this proceeding, and during the workshop to which it refers, different levers of actions are discussed through various examples: individual efforts, laboratory-level actions, impact evaluation and mitigation in major projects, institutional level, and involvement through collectives

Environmental transition: overview of actions to reduce the environmental footprint of astronomy

National audienceTo keep current global warming below 1.5 • C compared with the pre-industrial era, measures must be taken as quickly as possible in all spheres of society. Astronomy must also make its contribution. In this proceeding, and during the workshop to which it refers, different levers of actions are discussed through various examples: individual efforts, laboratory-level actions, impact evaluation and mitigation in major projects, institutional level, and involvement through collectives

Environmental transition: overview of actions to reduce the environmental footprint of astronomy

National audienceTo keep current global warming below 1.5 • C compared with the pre-industrial era, measures must be taken as quickly as possible in all spheres of society. Astronomy must also make its contribution. In this proceeding, and during the workshop to which it refers, different levers of actions are discussed through various examples: individual efforts, laboratory-level actions, impact evaluation and mitigation in major projects, institutional level, and involvement through collectives