Developing the agenda for European Union collaboration on non-communicable diseases research in Sub-Saharan Africa

<p>Abstract</p> <p>Background</p> <p>Health research is increasing in Africa, but most resources are currently chanelled towards infectious diseases and health system development. While infectious diseases remain a heavy burden for some African countries, non-communicable diseases (NCDs) account for more than half of all deaths globally and WHO predicts 27% increase in NCDs in Africa over the next decade. We present findings of a European-Africa consultation on the research agenda for NCDs.</p> <p>Methods</p> <p>A workshop was held in Yaoundé, Cameroon, organized by the Network for the Coordination and Advancement of Sub-Saharan Africa-European Union Science and Technology Cooperation (CAAST-Net). Drawing on initial presentations, a small expert group from academic, clinical, public-health and administrative positions considered research needs in Africa for cardiovascular disease, cancer and diabetes.</p> <p>Results</p> <p>Research in Africa can draw from different environmental and genetic characteristics to understand the causes of the disease, while economic and social factors are important in developing relevant strategies for prevention and treatment. The suggested research needs include better methods for description and recording, clinical studies, understanding cultural impacts, prevention strategies, and the integrated organisation of care. Specific fields proposed for research are listed.</p> <p>Conclusions</p> <p>Our paper contributes to transparency in the process of priority-setting for health research in Africa. Although the European Union Seventh Framework Research Programme prioritises biomedical and clinical research, research for Africa should also address broader social and cultural research and intervention research for greatest impact. Research policy leaders in Africa must engage national governments and international agencies as well as service providers and research communities. None can act effectively alone. Bringing together the different stakeholders, and feeding the results through to the European Union research programme is a valuable contribution of CAAST-Net.</p

Use of HRP-2-based rapid diagnostic test for Plasmodium falciparum malaria: assessing accuracy and cost-effectiveness in the villages of Dielmo and Ndiop, Senegal

Background: In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck (R)). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck (R) compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP. Methods: A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT. Results: A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700(sic) per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs. Conclusions: A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable

Assessment of the relative success of sporozoite inoculations in individuals exposed to moderate seasonal transmission

Background: The time necessary for malaria parasite to re-appear in the blood following treatment (re-infection time) is an indirect method for evaluating the immune defences operating against pre-erythrocytic and early erythrocytic malaria stages. Few longitudinal data are available in populations in whom malaria transmission level had also been measured. Methods: One hundred and ten individuals from the village of Ndiop (Senegal), aged between one and 72 years, were cured of malaria by quinine (25 mg/day oral Quinimax T in three equal daily doses, for seven days). Thereafter, thick blood films were examined to detect the reappearance of Plasmodium falciparum every week, for 11 weeks after treatment. Malaria transmission was simultaneously measured weekly by night collection of biting mosquitoes. Results: Malaria transmission was on average 15.3 infective bites per person during the 77 days follow up. The median reappearance time for the whole study population was 46.8 days, whereas individuals would have received an average one infective bite every 5 days. At the end of the follow-up, after 77 days, 103 of the 110 individuals (93.6%; CI 95% [89.0-98.2]) had been re-infected with P. falciparum. The median reappearance time ('re-positivation') was longer in subjects with patent parasitaemia at enrolment than in parasitologically-negative individuals (58 days vs. 45.9; p = 0.03) and in adults > 30 years than in younger subjects (58.6 days vs. 42.7; p = 0.0002). In a multivariate Cox PH model controlling for the sickle cell trait, G6PD deficiency and the type of habitat, the presence of parasitaemia at enrolment and age >= 30 years were independently predictive of a reduced risk of re-infection (PH = 0.5 [95% CI: 0.3-0.9] and 0.4; [95% CI: 0.2-0.6] respectively). Conclusion: Results indicate the existence of a substantial resistance to sporozoites inoculations, but which was ultimately overcome in almost every individual after 2 1/2 months of natural challenges. Such a study design and the results obtained suggest that, despite a small sample size, this approach can contribute to assess the impact of intervention methods, such as the efficacy vector-control measures or of malaria pre-erythrocytic stages vaccines

An Exhaustive, Non-Euclidean, Non-Parametric Data Mining Tool for Unraveling the Complexity of Biological Systems – Novel Insights into Malaria

Complex, high-dimensional data sets pose significant analytical challenges in the post-genomic era. Such data sets are not exclusive to genetic analyses and are also pertinent to epidemiology. There has been considerable effort to develop hypothesis-free data mining and machine learning methodologies. However, current methodologies lack exhaustivity and general applicability. Here we use a novel non-parametric, non-euclidean data mining tool, HyperCube®, to explore exhaustively a complex epidemiological malaria data set by searching for over density of events in m-dimensional space. Hotspots of over density correspond to strings of variables, rules, that determine, in this case, the occurrence of Plasmodium falciparum clinical malaria episodes. The data set contained 46,837 outcome events from 1,653 individuals and 34 explanatory variables. The best predictive rule contained 1,689 events from 148 individuals and was defined as: individuals present during 1992–2003, aged 1–5 years old, having hemoglobin AA, and having had previous Plasmodium malariae malaria parasite infection ≤10 times. These individuals had 3.71 times more P. falciparum clinical malaria episodes than the general population. We validated the rule in two different cohorts. We compared and contrasted the HyperCube® rule with the rules using variables identified by both traditional statistical methods and non-parametric regression tree methods. In addition, we tried all possible sub-stratified quantitative variables. No other model with equal or greater representativity gave a higher Relative Risk. Although three of the four variables in the rule were intuitive, the effect of number of P. malariae episodes was not. HyperCube® efficiently sub-stratified quantitative variables to optimize the rule and was able to identify interactions among the variables, tasks not easy to perform using standard data mining methods. Search of local over density in m-dimensional space, explained by easily interpretable rules, is thus seemingly ideal for generating hypotheses for large datasets to unravel the complexity inherent in biological systems

Resolving Senegal's crisis of renewable natural resources: A framework for policy development

The renewable natural resources (RNR) of Senegal form the basis of socioeconomic development for the population of this Sahelian country of West Africa. However, because of the current maladapted policies and practices, these resources are in a crisis that has led to a major degradation of the socioeconomic and environmental conditions. To solve these socioeconomic and environmental problems, many solutions have been developed and implemented. However, because of their disregard for both socioeconomic and traditional cultural values, these attempted solutions have often contributed to the problems. To resolve this crisis, Senegal needs to adopt a new integrated management approach along with new integrated natural resources tenure and decentralization policies. Considering the country's limited economic means, the urgent need for policy change, and the necessary progressive implementation of a new policy, this new natural resources policy will need to be developed incrementally. It should take into account the existing policies and examine different alternatives from the current ecological, economic, and sociocultural situation

MODULATION DE L'EXPRESSION DU GENE DE L'INSULINE LIKE - GROWTH FACTOR - 1 (IGF-1) PAR LES TECHNOLOGIES ANTISENS ET TRIPLE HELICE (APPROCHE POUR UNE IMMUNOTHERAPIE CELLULAIRE DE TUMEURS CEREBRALES (DOCTORAT : ONCO-IMMUNOLOGIE))

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Identification of Vietnamese Flea Species and Their Associated Microorganisms Using Morphological, Molecular, and Protein Profiling

International audienceFleas are obligatory blood-sucking ectoparasites of medical and veterinary importance. The identification of fleas and associated flea-borne microorganisms, therefore, plays an important role in controlling and managing these vectors. Recently, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has been reported as an innovative and effective approach to the identification of arthropods, including fleas. This study aims to use this technology to identify ethanol-preserved fleas collected in Vietnam and to use molecular biology to search for microorganisms associated with these fleas. A total of 502 fleas were collected from wild and domestic animals in four provinces in Vietnam. Morphological identification led to the recognition of five flea species, namely Xenopsylla cheopis, Xenopsylla astia, Pulex irritans, Ctenocephalides canis, and Ctenocephalides felis. The cephalothoraxes of 300 individual, randomly selected fleas were tested using MALDI-TOF MS and molecular analysis for the identification and detection of microorganisms. A total of 257/300 (85.7%) of the obtained spectra from the cephalothoraxes of each species were of good enough quality to be used for our analyses. Our laboratory MALDI-TOF MS reference database was upgraded with spectra achieved from five randomly selected fleas for every species of Ctenocephalides canis and Ctenocephalides felis. The remaining spectra were then queried against the upgraded MALDI-TOF MS database, which showed 100% correspondence between morphology and MALDI-TOF MS identification for two flea species (Ctenocephalides canis and Ctenocephalides felis). The MS spectra of the remaining species (three P. irritans, five X. astia, and two X. cheopis) were visually generated low-intensity MS profiles with high background noise that could not be used to update our database. Bartonella and Wolbachia spp. were detected in 300 fleas from Vietnam using PCR and sequencing with primers derived from the gltA gene for Bartonella and the 16S rRNA gene for Wolbachia, including 3 Bartonella clarridgeiae (1%), 3 Bartonella rochalimae (1%), 1 Bartonella coopersplainsensis (0.3%), and 174 Wolbachia spp. endosymbionts (58%)

IGF-I: from diagnostic to triple-helix gene therapy of solid tumors.

Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, including brain. IGF-I is also expressed at high levels in some nervous system-derived tumors, especially in glioblastoma. When using IGF-I as a diagnostic marker, 17 different tumors are considered as expressing the IGF-I gene. Malignant glioma, the most common human brain cancer, is usually fatal. Average survival is less than one year. Our strategy of gene therapy for the treatment of gliomas and other solid tumors is based on: 1) diagnostic using IGF-I gene expression as a differential marker, and 2) application of "triple-helix anti-IGF-I " therapy. In the latter approach, tumor cells are transfected with a vector, which encodes an oligoribonucleotide - an RNA strand containing oligopurine sequence which might be capable of forming a triple helix with an oligopurine and/or oligopyrimidine sequence of the promotor of IGF-I gene (RNA-IGF-I DNA triple helix). Human tumor cells transfected in vitro become down-regulated in the production of IGF-I and present immunogenic (MHC-I and B7 expression) and apoptotic characteristics. Similar results were obtained when IGF-I antisense strategy was applied. In both strategies the transfected cells reimplanted in vivo lose tumorigenicity and elicit tumor specific immunity which leads to elimination of established tumors

The Geographical Study of Anopheline Densities on a Small Space, using Satellite Imagery and Geographical Information Systems

International audienceTo predict the spatial distribution of anopheles in the Dielmo village (located in the southeastern part of Senegal), we used residual fauna collected from 104 different rooms during four separate trips conducted in 1994 and 1995. Thanks Generalized Estimating Equations, we were able to identify factors influencing the distribution of Anopheles in the village. Several variables, such as the number of persons sleeping in the room, population density around the hut, construction materials, presence of mosquito nets, were found to be significant, while many spatial variables relevant to the scale of a region (vegetation index, distance to larval sites...) were not found to be significant on the village level. As a result, it became clear that it is difficult to correctly predict the anopheline density for each house even with precise spatial data created with Satellite imagery and Geographical Information Systems (GIS). This work highlights the complexity of the geographical study of anopheline density and its limits on a small space