Le paludisme urbain à Yaoundé (Cameroun) : 2. Etude entomologique dans deux quartiers peu urbanisés

International audienceA one year entomological survey was carried out to precise the malaria vectors and the malaria transmission in Yaounde, the Cameroon capital (800,000 inhabitants). The study was done in two districts not yet fully urbanized: Nkol Bikok and Nkol Bisson. The latter is located at the periphery and has a pool. Anopheles gambiae was the only human malaria vector. Its agressivity for man depended on the urbanization of the district. Annual man biting rate was 284 in Nkol Bikok and 1,813 in Nkol Bisson. The densities were maximum in May-June and in October-November, corresponding to the end of the short and long rainy seasons. The presence of A. gambiae was permanent except in August-September in Nkol Bikok. In Nkol Bisson the density was higher in the houses near the pool. The yearly inoculation rate (h) was 14 in Nkol Bikok and 30 in Nkol Bisson. The vectorial transmission was observed in may in Nkol Bikok and during four months (June, August, January, February) in Nkol Bisson. These entomological data showed clearly that malaria transmission actually occurred in Yaounde and that the probability to receive at least one infected anopheline bite per year was very near to 1 for inhabitants unprotected against mosquito bites.Une étude longitudinale basée sur la capture des moustiques sur sujets humains s'est déroulée pendant un an dans deux quartiers de la ville de Yaoundé, l'un est situé à la périphérie de la ville (Nkol Bisson) et l'autre est plus central (Nkol Bikok). Ces deux quartiers présentent encore un caractère périurbain mais ils sont en pleine urbanisation. Le vecteur du paludisme humain identifé est Anopheles gambiae. Sa densité agressive pour l'homme (ma) est variable selon le degré d'urbanisation des quartiers : forte en Zone périphérique (ma annuel = I 813) et faible en zone centrale (ma annuel = 284). Cette densité est importante de mai à juin et d'octobre 6 novembre, c'est-à-dire à la fin de la petite et de la grande saison des pluies. Le taux d'inoculation (h) varie comme les densités agressives : h annuel = 30 en zone périphérique contre 14 en zone centrale. La transmission vectorielle est notable seulement pendant un mois (mai) à Nkol Bikok et pendant quatre mois (juin, août, janvier, février) à Nkol Bisson. Le risque quotidien d'au moins une inoculation par A. gambiae est environ deux fois plus élevé en zone périphérique qu'en zone centrale

Anthropophilic mosquitoes and malaria transmission at Edea, Cameroon

International audienceAn entomological study was carried out during 1990 in the town of Edea in the south of Cameroon to study anthropophilic mosquitoes with special reference to malaria transmission. Man-biting mosquitoes were caught regularly during one night each month in two different districts: Bilalang which is a well planned suburb with 160 houses on a hill-top, provided with a piped water supply; and Pongo which is a densely urbanised suburb in a valley. From 188 man-nights 1030 mosquitoes were collected, comprising 700 Culex quinquefasciatus (68%), 262 Anopheles gambiae (25%) and others species (7%) belonging to the genus Anopheles, Mansonia, Culex and Aedes. The estimated annual biting rates of mosquitoes were 811 bites per man in Bilalang and 2,866 in Pongo. The estimated yearly malaria inoculation rates were 3.8 and 30.2 infective bites per man in Bilalang and Pongo, respectively. In different parts of Pongo district much variation existed; extreme values of the estimated yearly inoculation rate were zero and 86.3 in two houses 200 m apart, located on the top of a hill and in the bottom of a valley, respectively. This study is one of the first conducted on malaria transmission in a moderate sized African town; it shows that the mosquito populations are typically urban and differ greatly from rural ones

Aspirin as an adjuvant treatment for cancer:feasibility results from the Add-Aspirin randomised trial

BACKGROUND: Preclinical, epidemiological, and randomised data indicate that aspirin might prevent tumour development and metastasis, leading to reduced cancer mortality, particularly for gastro-oesophageal and colorectal cancer. Randomised trials evaluating aspirin use after primary radical therapy are ongoing. We present the pre-planned feasibility analysis of the run-in phase of the Add-Aspirin trial to address concerns about toxicity, particularly bleeding after radical treatment for gastro-oesophageal cancer.METHODS: The Add-Aspirin protocol includes four phase 3 randomised controlled trials evaluating the effect of daily aspirin on recurrence and survival after radical cancer therapy in four tumour cohorts: gastro-oesophageal, colorectal, breast, and prostate cancer. An open-label run-in phase (aspirin 100 mg daily for 8 weeks) precedes double-blind randomisation (for participants aged under 75 years, aspirin 300 mg, aspirin 100 mg, or matched placebo in a 1:1:1 ratio; for patients aged 75 years or older, aspirin 100 mg or matched placebo in a 2:1 ratio). A preplanned analysis of feasibility, including recruitment rate, adherence, and toxicity was performed. The trial is registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN74358648) and remains open to recruitment.FINDINGS: After 2 years of recruitment (October, 2015, to October, 2017), 3494 participants were registered (115 in the gastro-oesophageal cancer cohort, 950 in the colorectal cancer cohort, 1675 in the breast cancer cohort, and 754 in the prostate cancer cohort); 2719 (85%) of 3194 participants who had finished the run-in period proceeded to randomisation, with rates consistent across tumour cohorts. End of run-in data were available for 2253 patients; 2148 (95%) of the participants took six or seven tablets per week. 11 (0·5%) of the 2253 participants reported grade 3 toxicity during the run-in period, with no upper gastrointestinal bleeding (any grade) in the gastro-oesophageal cancer cohort. The most frequent grade 1-2 toxicity overall was dyspepsia (246 [11%] of 2253 participants).INTERPRETATION: Aspirin is well-tolerated after radical cancer therapy. Toxicity has been low and there is no evidence of a difference in adherence, acceptance of randomisation, or toxicity between the different cancer cohorts. Trial recruitment continues to determine whether aspirin could offer a potential low cost and well tolerated therapy to improve cancer outcomes.FUNDING: Cancer Research UK, The National Institute for Health Research Health Technology Assessment Programme, The MRC Clinical Trials Unit at UCL.</p

Structure and lipid binding properties of the kindlin-3 pleckstrin homology domain

Kindlins co-activate integrins alongside talin. They possess, like talin, a FERM domain comprising F0-F3 subdomains, but with a pleckstrin homology (PH) domain inserted in the F2 subdomain that enables membrane association. We present the crystal structure of murine kindlin-3 PH domain determined at 2.23Å resolution and characterise its lipid binding using biophysical and computational approaches. Molecular dynamics (MD) simulations suggest flexibility in the PH domain loops connecting β-strands forming the putative phosphatidylinositol phosphate (PtdInsP) binding site. Simulations with PtdInsP-containing bilayers reveal that the PH domain associates with PtdInsP molecules mainly via the positively charged surface presented by the β1-β2 loop and that it binds with somewhat higher affinity to PtdIns(3,4,5)P3 compared to PtdIns(4,5)P2. Surface plasmon resonance (SPR) with lipid headgroups immobilised and the PH domain as analyte indicate affinities of 300 μM for PtdIns(3,4,5)P3 and 1mM for PtdIns(4,5)P2. In contrast, SPR studies with immobilised PH domain and lipid nanodiscs as analyte show affinities of 0.40 µM for PtdIns(3,4,5)P3 and no affinity for PtdIns(4,5)P2 when the inositol phosphate constitutes 5% of the total lipids (~5 molecules per nanodisc). Reducing the PtdIns(3,4,5)P3 composition to 1% abolishes nanodisc binding to the PH domain, as does site-directed mutagenesis of two lysines within the β1-β2 loop. Binding of PtdIns(3,4,5)P3 by a canonical PH domain, Grp1, is not similarly influenced by SPR experimental design. These data suggest a role for PtdIns(3,4,5)P3 clustering in the binding of some PH domains and not others, highlighting the importance lipid mobility and clustering for the biophysical assessment of protein-membrane interactions

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Les moustiques et la transmission du paludisme dans un village traditionnel du bloc forestier sud-camerounais

Les auteurs présentent les résultats de trois enquêtes transversales, concernant la faune culicidienne et la transmission du paludisme, effectuées dans un village de forêt équatoriale. Trois genres culicidiens ont été collectés à chaque enquête : #Anopheles, #Mansonia, #Culex. Les anophèles vecteurs de paludisme sont, par ordre d'importance numérique : #An. moucheti, #An. gambiae, et #An. funestus. Les densités anophéliennes ont été faibles. Ces densités ont été constantes pour #An. funestus$ mais pas pour les deux autres espèces. La transmission du paludisme, quoique seulement observée en avril et en juillet, doit être permanente. Elle apparaît relativement homogène dans tout le village. (Résumé d'auteur