Landscape quality and brownfield regeneration: a community investigation approach inspired by landscape preference studies

Peer reviewe

Efficacy and safety of single 40 mg/kg oral praziquantel in the treatment of schistosomiasis in preschool-age versus school-age children:An individual participant data meta-analysis

Better knowledge of the efficacy and safety of single 40 mg/kg oral praziquantel in preschool-age children is required, should preventive chemotherapy programs for schistosomiasis be expanded to include this age group.; We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6-14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs).; Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool- and school-age children using a general linear model of individual-participant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up.; There is no indication that single 40 mg/kg oral praziquantel would be less efficacious and safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety

A call to action for Universal Health Coverage – Why we need to address gender inequities in the Neglected Tropical Diseases community

The UN’s Sustainable Development Goals (SDGs) and pledge to leave no one behind have raised the importance of ensuring equitable health outcomes and healthcare delivery. Multisectoral approaches to tackling neglected tropical diseases (NTDs), including prevention, diagnosis, treatment, and healthcare, have had a limited focus on gender. Yet, gender roles and relations shape vulnerability to NTDs, access to prevention and treatment, and experience of living with NTDs [1]. Understanding the similarities and differences of disease vulnerability and experience between genders can support NTD actors to deliver equitable prevention, diagnosis, and treatment services. The NTD community, including researchers and practitioners, needs to better understand these dynamics and take action to advance gender equality, meet the NTD roadmap 2020 goals, and contribute towards the SDGs and universal health coverage (UHC). The UHC movement is advocating for clear action to address the gender determinants of health. This viewpoint synthesizes evidence from a discussion paper [2] developed by the UN Development Programme (UNDP) and TDR (Special Programme for Research and Training in Tropical Diseases sponsored by UNICEF, UNDP, World Bank, and WHO) in partnership with the Liverpool School of Tropical Medicine to support governments and nongovernment organizations to understand how to recognize and address gender inequities within NTD programs and improve delivery through gender analysis

Global birth defects app: An innovative tool for describing and coding congenital anomalies at birth in low resource settings

BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The “basic” version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The “surveillance” version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The “basic” version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance” version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care

Evaluation of Two Strategies for Community-Based Safety Monitoring during Seasonal Malaria Chemoprevention Campaigns in Senegal, Compared with the National Spontaneous Reporting System.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine has been introduced in 12 African countries. Additional strategies for safety monitoring are needed to supplement national systems of spontaneous reporting that are known to under represent the incidence of adverse reactions. OBJECTIVES: This study aimed to determine if adverse event (AE) reporting could be improved using a smartphone application provided to village health workers, or by active follow-up using a symptom card provided to caregivers. METHODS: Two strategies to improve reporting of AEs during SMC campaigns were evaluated, in comparison with the national system of spontaneous reporting, in 11 health post areas in Senegal. In each health post, an average of approximately 4000 children under 10 years of age received SMC treatment each month for 3 months during the 2015 malaria transmission season-a total of 134,000 treatments. In three health posts (serving approximately 14,000 children), caregivers were encouraged to report any adverse reactions to the nurse at the health post or to a community health worker (CHW) in their village, who had been trained to use a smartphone application to report the event (enhanced spontaneous reporting). In two health posts (approximately 10,000 children), active follow-up of children at home was organized after each SMC campaign to ask about AEs that caregivers had been asked to record on a symptom card (active surveillance). Six health posts (approximately 23,000 children) followed the national system of spontaneous reporting using the national reporting (yellow) form. Each AE report was assessed by a panel to determine likely association with SMC drugs. RESULTS: The incidence of reported AEs was 2.4, 30.6, and 21.6 per 1000 children treated per month, using the national system, enhanced spontaneous reporting, and active surveillance, respectively. The most commonly reported symptoms were vomiting, fever, and abdominal pain. The incidence of vomiting, known to be caused by amodiaquine, was similar using both innovative methods (10/1000 in the first month, decreasing to 2.5/1000 in the third month). Despite increased surveillance, no serious adverse drug reactions were detected. CONCLUSION: Training CHWs in each village and health facility staff to report AEs using a mobile phone application led to much higher reporting rates than through the national system. This approach is feasible and acceptable, and could be further improved by strengthening laboratory investigation and the collection of control data immediately prior to SMC campaigns

C-reactive protein as a potential biomarker for disease progression in dengue: a multi-country observational study.

BACKGROUND: Dengue infection can cause a wide spectrum of clinical outcomes. The severe clinical manifestations occur sufficiently late in the disease course, during day 4-6 of illness, to allow a window of opportunity for risk stratification. Markers of inflammation may be useful biomarkers. We investigated the value of C-reactive protein (CRP) measured early on illness days 1-3 to predict dengue disease outcome and the difference in CRP levels between dengue and other febrile illnesses (OFI). METHOD: We performed a nested case-control study using the clinical data and samples collected from the IDAMS-consortium multi-country study. This was a prospective multi-center observational study that enrolled almost 8000 participants presenting with a dengue-like illness to outpatient facilities in 8 countries across Asia and Latin America. Predefined severity definitions of severe and intermediate dengue were used as the primary outcomes. A total of 281 cases with severe/intermediate dengue were compared to 836 uncomplicated dengue patients as controls (ratio 1:3), and also 394 patients with OFI. RESULTS: In patients with confirmed dengue, median (interquartile range) of CRP level within the first 3 days was 30.2 mg/L (12.4-61.2 mg/L) (uncomplicated dengue, 28.6 (10.5-58.9); severe or intermediate dengue, 34.0 (17.4-71.8)). Higher CRP levels in the first 3 days of illness were associated with a higher risk of severe or intermediate outcome (OR 1.17, 95% CI 1.07-1.29), especially in children. Higher CRP levels, exceeding 30 mg/L, also associated with hospitalization (OR 1.37, 95% CI 1.14-1.64) and longer fever clearance time (HR 0.84, 95% CI 0.76-0.93), especially in adults. CRP levels in patients with dengue were higher than patients with potential viral infection but lower than patients with potential bacterial infection, resulting in a quadratic association between dengue diagnosis and CRP, with levels of approximately 30 mg/L associated with the highest risk of having dengue. CRP had a positive correlation with total white cell count and neutrophils and negative correlation with lymphocytes, but did not correlate with liver transaminases, albumin, or platelet nadir. CONCLUSIONS: In summary, CRP measured in the first 3 days of illness could be a useful biomarker for early dengue risk prediction and may assist differentiating dengue from other febrile illnesses

Des propriétés non-thrombogènes peuvent être conférées à des surfaces polymères

Doctorat en sciences chimiques -- UCL, 199

Contribution de l'activité sécrétoire de l'adipocyte au syndrome plurimétabolique

Obesity belongs to a cluster of metabolic abnormalities (insulin resistance, type 2 diabetes, hypertension, dyslipidemia and hypofibrinolysis) leading to an increased risk for cardiovascular disease. These related disorders are components of the metabolic syndrome. It has become clear from epidemiological studies that some increase in the adipose tissue mass antedates the development of other metabolic disorders. However, the cellular and molecular basis of this connection is still elusive Adipocytes synthesize and release a variety of peptides which may have regulatory properties. I have studied three of these peptides : leptin, PAI-1 and adiponectin. Leptin controls whole-body energy homeostasis while PAI-1 and adiponectin play a role in atherothrombosis, PAI-1 being a risk factor for and adiponectin a protective factor against cardiovascular disease. In obese subjects, plasma levels of leptin and PAI-1are increased while those of adiponectin are reduced. I have examined whether endocrine abnormalities associated with the Metabolic Syndrome could contribute to altered production of leptin, PAI-1 and adiponectin by adipose tissue and subsequently to altered plasma levels of these “adipopeptide”. To this end, I have investigated the hormonal regulation of genes encoding leptin, PAI-1 and adiponectin in explants of human adipose tissue. For leptin and PAI-1, I have also measured the secretion in the medium. Glucocorticoids stimulated the transcription of the ob gene, which encodes leptin. Interestingly, ob gene and leptin responses to glucocorticoids were more pronounced in omental adipose tissue from obese subjects as compared to lean ones. These results suggest that this hyperresponsiveness to glucocorticoids could contribute to the metabolic abnormalities associated with central obesity. If this hyperresponsiveness also turned out to be true in subcutaneous fat, hyperleptinemia in obesity would reflect not only a resistance to central receptors, but also a primary alteration of Adipocytes (i.e. abnormal steroid response). Insulin added to the medium for up to 48h had no stimulatory effect on leptin production and even inhibited the stimulation by dexaméthasone. This effect of insulin was not due to a lowering of intracellular cAMP levels, because the addition of (Bu)2-cAMP to the medium also decreased the accumulation of ob mARN and leptin. I also provided evidence for a reciprocal regulation of PAI-1 by dexaméthasone (positive effector) and cAMP/catecholamines (negative effectors) in explants of human adipose tissue. These changes were reproduced in isolated fat cells and involved mainly pretranslational mechanisms. Insulin was indirectly stimulatory on PAU-1 gene expression as it partly reversed the inhibitory effect of catecholamines. The stimulation by glucocorticoids and insulin, and the impaired inhibition by catecholamines could contribute to enhances PAI-1 production by adipose tissue and to high plasma levels of PAI-1 associated with central obesity, and thereby lay be a link between this disorder and cardiovascular disease. Finally, I studied the hormonal regulation of the apM1 gene, which encodes adiponectin. The expression of this gene was negatively regulated by glucocorticoids and cAMP and positively regulated by insulin and IGF1 in human adipose tissue. This regulation could again contribute to the variations of adiponectin plasma levels and explain the paradoxical decrease of an adipose-specific protein in insulin-resistant patients with obesity and/or the Metabolic Syndrome and the subsequent risk for cardiovascular disease. I also found that adipose tissue may regulate its own production of adiponectin by releasing a factor that destabilizes apM1 mARN. In conclusion, adipose tissue may play a key role in the pathogenesis of the Metabolic Syndrome through the production of a variety of regulatory peptides. These peptides may influence several organs/tissues, thereby promoting metabolic or maintain the Metabolic Syndrome by altering the production of some of these adipose peptidesL’obésité pourrait être un facteur déterminant, si pas causal, dans l’association de diverses anomalies métaboliques prédictives de maladies cardiovasculaires (insulinorésistance, diabète de type 2, hypertension artérielle, dyslipidémie et hypofibrinolyse). L’ensemble constitue le syndrome plurimétabolique dont les mécanismes cellulaires et moléculaires restent encore mal connus. Le tissu adipeux s’est révélé capable de sécréter un grand nombre de molécules bio-actives et pourrait, peut-être par ce biais, être impliqué dans la pathogénie de ce syndrome. Trois des molécules synthétisées par l’adipocyte font l’objet de cette thèse : la leptine, le PAI-1 et l’adiponectine. La première intervient dans le contrôle de l’homéostasie énergétique et les deux autres dans les phénomènes d’athérothrombose, le PAI-1 étant un facteur de risque et l’adiponectine un facteur protecteur vis-à-vis des maladies cardiovasculaires. Les taux plasmatiques de leptine et de PAI-1 sont augmentés chez les sujets obèses tandis que ceux d’adiponectine sont diminués. j’ai recherché si certaines anomalies hormonales accompagnant le syndrome plurimétabolique (augmentation du turn-over des glucocorticoïdes, hyperinsulinisme/insulinorésistance, altération de la réponse aux catécholamines…) pouvaient, dans une certaine mesure, expliquer les variations de production des peptides adipocytaires précités, contribuant, par là, aux vibrations de leurs taux circulants. Dans ce but, j’ai étudié la régulation hormonales des gènes codant la leptine, le PAI-1 et l’adiponectine dans des explants de tissu adipeux humain. Pour les deux premiers facteurs, la sécrétion dans le milieu de culture a été mesurée en parallèle. L’expression du gène ob, qui encode la leptine, est régulée de manière aigüe par un certain nombre d’hormones. Mes résultats ont montré que les glucocorticoïdes stimulent sa transcription tandis que l’AMPc l’inhibe. La réponse du gène ob et de la sécrétion de leptine aux glucocorticoïdes était exacerbée dans le tissu adipeux omental des sujets obèses, et pourrait ainsi favoriser les anomalies métaboliques associées à l’obésité abdominale. Par ailleurs, si cette hyperréactivité aux glucocorticoïdes se vérifiait aussi pour le tissu sous-cutané, ce mécanisme pourrait de manière plus générale contribuer à l’hyperleptinémie du sujet obèse. J’ai également montré que l’insuline, à court terme, n’a pas d’effet stimulateur direct sur la synthèse de leptine et prévient même la stimulation par la dexaméthasone. Cet effet de l’insuline ne dépendait pas d’une diminution des concentrations intracellulaires en AMPc, car l’addition de (Bu)2-cAMP abaissait aussi les taux d’ARNm ob et de leptine. J’ai montré que la dexaméthasone stimule et que les catécholamines inhibent la production de PAI-1 par des explants de tissu adipeux. Cet effet était reproduit dans des cultures d’adipocytes isolés et impliquait des mécanismes prétraductionnels. De plus, l’insuline levait partiellement l’inhibition du gène PAI-1 induite par les catécholamines pourrait conduire, chez l’obèse, à l’augmentation de production de PAI-1 par le tissu adipeux et par là, à celle des taux plasmatiques, favorisant ainsi le développement des maladies cardiovasculaires. Finalement, j’ai étudié la régulation hormonale du gène apM1 qui code l’adiponectine. J’ai trouvé que l’expression du gène apM1 dans le tissu adipeux humain est régulée négativement par les glucocorticoïdes et l’AMPc, et positivement par l’insuline et l’IGF1. A nouveau, cette régulation hormonale pourrait contribuer aux variations des taux circulants d’adiponectine et expliquer la diminution observée chez les sujets insulinorésistants, obèses ou présentant un syndrome plurimétabolique, diminution favorisant les pathologies cardiovasculaires associées. Le tissu adipeux lui-même pourrait autoréguler les taux d’adiponectine en libérant un facteur déstabilisant les ARNm apM1. EN conclusion, le tissu adipeux serait un acteur important dans l’étiologie du syndrome plurimétabolique via la production de différents peptides. Ceux-ci peuvent agir (localement ou de manière plus systémique) sur différentes tissus et favoriser ainsi certaines perturbations métaboliques ou hormonales. Inversement, l’environnement hormonal/métabolique particulier qui s’associe à l’obésité pourrait contribuer à perpétuer ce syndrome en modulant la production de certaines peptides adipocytaireThèse de doctorat en sciences biomédicales (endocrinologie et nutrition) -- UCL, 200

Mise au point d'un modèle in vitro de la barrière épithéliale intestinale humaine : application à l'étude de l'absorption du fer et de sa régulation

Doctorat en sciences chimiques -- UCL, 199